FN Thomson Reuters Web of Science™ VR 1.0 PT B AU Zenilman, JM Deal, CD AF Zenilman, Jonathan M. Deal, Carolyn D. BE Stanberry, LR Rosenthal, SL TI Gonorrhea: Epidemiology, Control, and Prevention SO SEXUALLY TRANSMITTED DISEASES: VACCINES, PREVENTION, AND CONTROL, 2ND EDITION LA English DT Article; Book Chapter ID SEXUALLY-TRANSMITTED-DISEASES; NEISSERIA-GONORRHOEAE; GONOCOCCAL URETHRITIS; CHLAMYDIA-TRACHOMATIS; HUMAN-EXPERIMENTATION; PARTNER NOTIFICATION; ANTIGEN-SPECIFICITY; IMMUNE-RESPONSE; UNITED-STATES; RISK-FACTORS C1 [Zenilman, Jonathan M.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Deal, Carolyn D.] NIAID, Bethesda, MD 20892 USA. RP Zenilman, JM (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NR 57 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-12-415756-9; 978-0-12-391059-2 PY 2013 BP 411 EP 426 DI 10.1016/B978-0-12-391059-2.00016-4 PG 16 WC Infectious Diseases SC Infectious Diseases GA BA3SW UT WOS:000334784500017 ER PT J AU Bernstein, MB Ohri, N Hodge, JW Garg, M Bodner, W Kalnicki, S Dicker, AP Guha, C AF Bernstein, Michael B. Ohri, Nitin Hodge, James W. Garg, Madhur Bodner, William Kalnicki, Shalom Dicker, Adam P. Guha, Chandan TI Prostate-specific antigen bounce predicts for a favorable prognosis following brachytherapy: a meta-analysis SO JOURNAL OF CONTEMPORARY BRACHYTHERAPY LA English DT Article DE brachytherapy; prostate cancer; PSA bounce ID EXTERNAL-BEAM RADIATION; DOSE-RATE BRACHYTHERAPY; PSA BOUNCE; PERMANENT SEED; CANCER PATIENTS; RADIOTHERAPY; KINETICS; IMPLANT AB Purpose: Controversy exists whether the prostate-specific antigen (PSA) bounce phenomenon following definitive radiation for prostate cancer has prognostic significance. Here, we perform a meta-analysis to determine the association between PSA bounce and biochemical control after brachytherapy alone. Material and methods: We reviewed Medline, EMBASE, and CENTRAL citations through February 2012. Studies that recorded biochemical failure rates in bouncers and non-bouncers were included. Hazard ratios describing the impact of bounce on biochemical failure were extracted directly from the studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. A random effects model was used in cases of significant effect heterogeneity (p < 0.10 using Q test). Results: The final analysis included 3011 patients over 6 studies treated with brachytherapy. Meta-analysis revealed that patients experiencing PSA bounce after brachytherapy, conferred a decreased risk of biochemical failure (random effects model HR = 0.42, 95% CI: 0.30-0.59; p < 0.001). Conclusions: Our meta-analysis determined that PSA bounce predicts for improved biochemical control following brachytherapy. To our knowledge, this is the first study describing this effect. C1 [Bernstein, Michael B.; Garg, Madhur; Bodner, William; Kalnicki, Shalom; Guha, Chandan] Albert Einstein Coll Med, Dept Radiat Oncol, Montefiore Med Ctr, Bronx, NY 10461 USA. [Ohri, Nitin; Dicker, Adam P.] Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19107 USA. [Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Guha, C (reprint author), Albert Einstein Coll Med, Dept Pathol, Dept Radiat Oncol, Montefiore Med Ctr, Mazer Bldg,Room 620,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM cguha@montefiore.org RI Hodge, James/D-5518-2015; OI Hodge, James/0000-0001-5282-3154; Dicker, Adam/0000-0003-0733-3337 NR 25 TC 3 Z9 3 U1 1 U2 1 PU TERMEDIA PUBLISHING HOUSE LTD PI POZNAN PA WENEDOW ST 9-1, POZNAN, 61-614, POLAND SN 1689-832X EI 2081-2841 J9 J CONTEMP BRACHYTHER JI J. Contemp. Brachytherapy PY 2013 VL 5 IS 4 BP 210 EP 214 DI 10.5114/jcb.2013.38875 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AK3VT UT WOS:000338353800002 PM 24474969 ER PT B AU Gadlin, H Bennett, LM AF Gadlin, Howard Bennett, L. Michelle BA Bammer, G BF Bammer, G TI Interdisciplinarity without Borders SO DISCIPLINING INTERDISCIPLINARITY: INTEGRATION AND IMPLEMENTATION SCIENCES FOR RESEARCHING COMPLEX REAL-WORLD PROBLEMS LA English DT Editorial Material; Book Chapter C1 [Gadlin, Howard] Natl Inst Hlth, Ctr Cooperat Resolut, Bethesda, MD 20892 USA. [Gadlin, Howard] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Gadlin, Howard] Univ Calif Los Angeles, UCLA Conflict Mediat Program, Los Angeles, CA 90024 USA. [Gadlin, Howard] Univ Calif Los Angeles, Ctr Study & Resolut Interethn Interracial Conflic, Los Angeles, CA 90024 USA. [Bennett, L. Michelle] NHLBI, NIH, Bethesda, MD 20892 USA. RP Gadlin, H (reprint author), Natl Inst Hlth, Ctr Cooperat Resolut, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AUSTRALIAN NATL UNIV PI CANBERRA ACT PA P O BOX 4, 2600 CANBERRA ACT, AUSTRALIA BN 978-1-922144-27-0; 978-1-922144-28-7 PY 2013 BP 417 EP 426 PG 10 WC Social Issues; Social Sciences, Interdisciplinary SC Social Issues; Social Sciences - Other Topics GA BA5VP UT WOS:000337035700054 ER PT S AU Birnbaum, LS DeVito, MJ AF Birnbaum, Linda S. DeVito, Michael J. BE Rose, M Fernandes, A TI Persistent organic pollutants and toxic metals in foods Foreword SO PERSISTENT ORGANIC POLLUTANTS AND TOXIC METALS IN FOODS SE Woodhead Publishing Series in Food Science Technology and Nutrition LA English DT Editorial Material; Book Chapter C1 [Birnbaum, Linda S.; DeVito, Michael J.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Birnbaum, LS (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2042-8049 BN 978-0-85709-891-7; 978-0-85709-245-8 J9 WOODHEAD PUBL FOOD S JI Woodhead Publ. Food Sci. Technol. Nutr. PY 2013 IS 247 BP XXIII EP XXIV D2 10.1533/9780857098917 PG 2 WC Environmental Sciences; Food Science & Technology SC Environmental Sciences & Ecology; Food Science & Technology GA BA4PQ UT WOS:000336101200001 ER PT J AU Fernandez, EV Price, DK Figg, WD AF Fernandez, Elena V. Price, Douglas K. Figg, William D. TI Prostate cancer progression attributed to autonomic nerve development Potential for therapeutic prevention of localized and metastatic disease SO CANCER BIOLOGY & THERAPY LA English DT Article DE primary tumor development; autonomic nervous system; prostate cancer; metastasis; beta 2-beta 3-adrenergic receptors; stromal cholinergic muscarinic receptor type 1 ID PERINEURAL INVASION; BREAST-CANCER; MORTALITY; SURVIVAL; BLOCKERS AB In a study recently published in Science, Magnon et al. show that both the sympathetic and parasympathetic components of the autonomic nervous system play an integral part in the development and dissemination of prostate cancer (PCa). Inhibition of the sympathetic nervous system (SNS) and disruption of the adrenergic receptors, specifically Ard beta 2, resulted in the prevention of primary PCa tumor development in mice. The authors found that inhibition of the SNS is only successful in preventing murine tumor development if completed early enough, and the parasympathetic nervous system (PNS) predominates in later stages of PCa. Inhibition of the PNS by way of the cholinergic receptor, muscarinic 1 (Chrm1), caused mice to develop less metastases to the pelvic lymph nodes, intestines, and bones. A PCa progression scheme has been outlined where initial tumor engraftment is controlled by the SNS but then becomes less prominent than the PNS, which promotes metastasis. The investigators showed the dependence of the autonomic nervous system on development of PCa and present opportunities for prevention; further studies are needed to confirm these results in humans. C1 [Fernandez, Elena V.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA. [Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA. EM figgw@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 10 TC 1 Z9 1 U1 2 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PY 2013 VL 14 IS 11 BP 1005 EP 1006 AR PII 26339 DI 10.4161/cbt.26339 PG 2 WC Oncology SC Oncology GA AD7YG UT WOS:000333482800003 PM 24025357 ER PT J AU Li, Y Konicki, WS Wright, JT Suggs, C Xue, H Kuehl, MA Kulkarni, AB Gibson, CW AF Li, Yong Konicki, William S. Wright, J. Timothy Suggs, Cynthia Xue, Hui Kuehl, Melissa A. Kulkarni, Ashok B. Gibson, Carolyn W. TI Mouse Genetic Background Influences the Dental Phenotype SO CELLS TISSUES ORGANS LA English DT Article DE Genetic background; Enamel; Dentin; Amelogenesis imperfecta; Amelogenin ID LINKED AMELOGENESIS IMPERFECTA; MODIFIER GENES; ENAMEL; MICE; MUTATION; DEFECTS; HUMANS; MMP20; AIH1; EXPRESSION AB Dental enamel covers the crown of the vertebrate tooth and is considered to be the hardest tissue in the body. Enamel develops during secretion of an extracellular matrix by ameloblast cells in the tooth germ, prior to eruption of the tooth into the oral cavity. Secreted enamel proteins direct mineralization patterns during the maturation stage of amelogenesis as the tooth prepares to erupt. The amelogenins are the most abundant enamel proteins and are required for normal enamel development. Phenotypic differences were observed between incisors from individual Amelx (amelogenin) null mice that had a mixed 129xC57BL/6J genetic background and between inbred wild-type (WT) mice with different genetic backgrounds (C57BL/6J, C3H/HeJ, FVB/NJ). We hypothesized that this could be due to modifier genes, as human patients with a mutation in an enamel protein gene causing the enamel defect amelogenesis imperfecta (AI) can also have varied appearance of dentitions within a kindred. Enamel density measurements varied for all WT inbred strains midway during incisor development. Enamel thickness varied between some WT strains, and, unexpectedly, dentin density varied extensively between incisors and molars of all WT and Amelx null strains studied. WTFVB/NJ incisors were more similar to those of Amelx null mice than to those of the other WT strains in terms of incisor height/width ratio and pattern of enamel mineralization. Strain-specific differences led to the conclusion that modifier genes may be implicated in determining both normal development and severity of enamel appearance in Al mouse models and may in future studies be related to phenotypic heterogeneity within human Al kindreds reported in the literature. (C) 2014 S. Karger AG, Basel C1 [Li, Yong; Konicki, William S.; Xue, Hui; Kuehl, Melissa A.; Gibson, Carolyn W.] Univ Penn, Dept Anat & Cell Biol, Sch Dent Med, Philadelphia, PA 19104 USA. [Wright, J. Timothy; Suggs, Cynthia] Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC USA. [Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Gene Transfer Core, NIH, Bethesda, MD USA. [Xue, Hui] Fourth Mil Med Univ, Sch Stomatol, Dept Orthodont, Xian 710032, Peoples R China. RP Gibson, CW (reprint author), Univ Penn, Dept Anat & Cell Biol, Sch Dent Med, 240 S 40th St, Philadelphia, PA 19104 USA. EM cgibson@dental.upenn.edu FU National Institute of Dental Research [R01-DE011089] FX We acknowledge and thank J. Bartlett for communicating unpublished data and thank M. Pugach, E. Everett and J. Li for discussions of the data and concepts. We appreciate the care provided by the Penn Dental Medicine vivarium staff. This work was supported by funding from the National Institute of Dental Research (R01-DE011089). NR 55 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 EI 1422-6421 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2013 VL 198 IS 6 BP 448 EP 456 DI 10.1159/000360157 PG 9 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA AI4GS UT WOS:000336824300005 PM 24732779 ER PT S AU Lam, KH Zheng, F Li, Y Zhou, QF Shung, KK AF Lam, Kwok Ho Zheng, Fan Li, Ying Zhou, Qifa Shung, K. Kirk GP IEEE TI Zebrafish Egg Manipulation Using Ultrasound Microbeam SO 2013 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) SE IEEE International Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE International Ultrasonics Symposium (IUS) CY JUL 21-25, 2013 CL Prague, CZECH REPUBLIC SP IEEE DE Ultrasonic transducer; Zebrafish egg; microbeam; organism manipulation ID TRANSDUCERS; MOLECULES; TWEEZERS AB 60-MHz lithium niobate single crystal single-element ultrasonic transducers with an f-number (f#) of 0.6 were developed for acoustic microbeam applications. The f# of the transducer is the smallest ever reported on the study of single beam acoustic tweezers. With tightly focused ultrasound microbeam, a single Zebrafish egg as large as similar to 1.6 mm diameter was demonstrated to be manipulated two dimensionally in water. This is for the first time that the utilization of acoustic microbeam for manipulating such large organism is reported. The preliminary result shows the ultrasound microbeam is versatile that can manipulate the particles or organisms not only in micron scale, but also in millimeter scale. Besides, the demonstration also suggests the potential of ultrasound microbeam for organism sorting applications. C1 [Lam, Kwok Ho] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. RP Lam, KH (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. RI Lam, K.H./B-7765-2014 OI Lam, K.H./0000-0003-1456-9049 FU NIH [R01-EB12058, P41-EB02182] FX This work has been supported by NIH Grant Nos. R01-EB12058 and P41-EB02182. NR 10 TC 1 Z9 1 U1 1 U2 6 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-5719 BN 978-1-4673-5686-2 J9 IEEE INT ULTRA SYM PY 2013 BP 303 EP 305 DI 10.1109/ULTSYM.2013.0078 PG 3 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BA5IA UT WOS:000336665300078 ER PT J AU Jung, H Choi, H Shung, KK AF Jung, Hayong Choi, Hojong Shung, K. Kirk GP IEEE TI Wideband Portable Power Amplifier Design for Very High Frequency Ultrasonic Transducer Applications SO 2013 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) SE IEEE International Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE International Ultrasonics Symposium (IUS) CY JUL 21-25, 2013 CL Prague, CZECH REPUBLIC SP IEEE DE Ultrasound; Power Amplifier; Transducer AB This paper describes the design of Class A wideband power amplifier (PA) for very high frequency ultrasonic transducer applications with power field-effect transistor (FET). The PA is a one-stage common-source amplifier with 28 V supply voltage. The measured gain of the PA is 15.8 similar to 17.8 dB in the range of 100 to 250 MHz and current consumption of the PA is 0.3 similar to 0.4 A. The measured 3rd-order input and output inter-modulation points (IIP3 and OIP3) of the PA are 12.25 dBm and 27.25 dBm, respectively and the measured noise figure of the PA is 2.14 similar to 2.98 dB in the range of 80 similar to 120MHz. C1 [Jung, Hayong; Choi, Hojong; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. RP Jung, H (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. NR 13 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-5686-2 J9 IEEE INT ULTRA SYM PY 2013 BP 1556 EP 1559 DI 10.1109/ULTSYM.2013.0397 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BA5IA UT WOS:000336665300395 ER PT J AU Choi, HJ Jung, HY Chen, RM Shung, KK AF Choi, Hojong Jung, Hayong Chen, Ruimin Shung, K. Kirk GP IEEE TI Harmonic Distortion Reduction Technique of the Power Amplifier for Very High Frequency Ultrasonic Transducer Applications SO 2013 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) SE IEEE International Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE International Ultrasonics Symposium (IUS) CY JUL 21-25, 2013 CL Prague, CZECH REPUBLIC SP IEEE DE Power Amplifier; MOSFET; Ultrasound Systems; Harmonic Distortion; Dynamic Range AB Power amplifiers are used to trigger the transducers in order to generate the acoustic waves into the desired target. The resolution of the ultrasound imaging systems is related with the sensitivity of the transducers so the high voltage output signals of the power amplifiers are required to be used to drive the transducers. Therefore, a linear power amplifier is more attractive choice because of its higher dynamic range of the output signals. The novel pre-distortion circuit using the passive resistor, capacitor and inductor components with a power MOSFET device was designed to enhance the dynamic range of the power amplifiers. The dynamic range of the power amplifiers is defined as the characteristic to amplify an input signal with less distortion. This characteristic can be improved by reducing the harmonic distortion components of the high voltage signals produced by the power amplifiers. C1 [Choi, Hojong; Jung, Hayong; Chen, Ruimin; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. RP Choi, H (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. NR 13 TC 0 Z9 0 U1 1 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-5686-2 J9 IEEE INT ULTRA SYM PY 2013 BP 1560 EP 1562 DI 10.1109/ULTSYM.2013.0398 PG 3 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BA5IA UT WOS:000336665300396 ER PT S AU Sun, X Chen, X AF Sun, X. Chen, X. BE Park, K TI Synergistically integrated nanomaterials for multimodal cancer cell imaging SO BIOMATERIALS FOR CANCER THERAPEUTICS: DIAGNOSIS, PREVENTION AND THERAPY SE Woodhead Publishing Series in Biomaterials LA English DT Article; Book Chapter DE multimodality imaging; multifunctional nanoparticles; exogenous modalities; endogenous contrast ID IRON-OXIDE NANOPARTICLES; UP-CONVERSION NANOPROBES; DRUG-DELIVERY; MAGNETIC-RESONANCE; QUANTUM DOTS; GOLD NANOPARTICLES; AU-FE3O4 NANOPARTICLES; CARBON NANOTUBES; CONTRAST AGENTS; LIVE CELLS AB This chapter discusses the recent progress in the design and synthesis of nanomaterials (NM)-based multimodality cancer imaging agents. Multimodal imaging methods, which allow synergistic advantages over any single modality, provide important tools for comprehensive cancer imaging. NM-based multimodal platforms with unique physicochemical properties have shown their superiority in cancer diagnostics. In this chapter, we have divided the imaging agent preparation techniques into two main categories: integrating additional imaging labels into existing nano-vehicle via either surface modification, or function loading and synthesis of NMs with multimodal endogenous contrast. We also mentioned a design concept of sequential injection of different agents. Examples include the techniques we and others have developed, with emphasis on how these designs benefit the diagnostic effect. We believe that the emergence of NM-based multimodality imaging agents allows synergistically improving the efficiency and effectiveness of cancer diagnostics. C1 [Sun, X.; Chen, X.] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Chen, X (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov NR 82 TC 0 Z9 0 U1 0 U2 3 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2049-9485 BN 978-0-85709-676-0; 978-0-85709-664-7 J9 WOODH PUBL SER BIOM PY 2013 VL 66 BP 165 EP 187 DI 10.1533/9780857096760.3.165 PG 23 WC Materials Science, Biomaterials; Pharmacology & Pharmacy SC Materials Science; Pharmacology & Pharmacy GA BA2UA UT WOS:000333901400009 ER PT S AU Gallahan, D AF Gallahan, Dan BE Enderling, H Almog, N Hlatky, L TI Systems Biology of Tumor Dormancy Foreword SO SYSTEMS BIOLOGY OF TUMOR DORMANCY SE Advances in Experimental Medicine and Biology LA English DT Editorial Material; Book Chapter C1 NCI, Div Canc Biol, NIH, Bethesda, MD 20892 USA. RP Gallahan, D (reprint author), NCI, Div Canc Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-1444-5; 978-1-4614-1445-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 734 BP V EP VII D2 10.1007/978-1-4614-1445-2 PG 3 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BA2XQ UT WOS:000333981300001 ER PT S AU Smed-Sorensen, A Lore, K AF Smed-Sorensen, Anna Lore, Karin BE Wu, L Schwartz, O TI Targeting Dendritic Cells for Improved HIV-1 Vaccines SO HIV INTERACTIONS WITH DENDRITIC CELLS: INFECTION AND IMMUNITY SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID IMMUNODEFICIENCY-VIRUS TYPE-1; EPIDERMAL LANGERHANS CELLS; TOLL-LIKE RECEPTORS; BLOOD MONONUCLEAR-CELLS; IN-VIVO; CROSS-PRESENTATION; RECOMBINANT ADENOVIRUS; ANTIGEN PRESENTATION; INNATE IMMUNITY; GAG PROTEIN AB As dendritic cells (DCs) have the unique capacity to activate antigen-naive T cells they likely play a critical role in eliciting immune responses to vaccines. DCs are therefore being explored as attractive targets for vaccines, but understanding the interaction of DCs and clinically relevant vaccine antigens and adjuvants is a prerequisite. The HIV-1/AIDS epidemic continues to be a significant health problem, and despite intense research efforts over the past 30 years a protective vaccine has not yet been developed. A common challenge in vaccine design is to find a vaccine formulation that best shapes the immune response to protect against and/or control the given pathogen. Here, we discuss the importance of understanding the diversity, anatomical location and function of different human DC subsets in order to identify the optimal target cells for an HIV-1 vaccine. We review human DC interactions with some of the HIV-1 vaccine antigen delivery vehicles and adjuvants currently utilized in preclinical and clinical studies. Specifically, the effects of distinctly different vaccine adjuvants in terms of activation of DCs and improving DC function and vaccine efficacy are discussed. The susceptibility and responses of DCs to recombinant adenovirus vectors are reviewed, as well as the strategy of directly targeting DCs by using DC marker-specific monoclonal antibodies coupled to an antigen. C1 [Smed-Sorensen, Anna] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden. [Lore, Karin] Karolinska Inst, Ctr Infect Med, Dept Med, S-17177 Stockholm, Sweden. [Lore, Karin] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Smed-Sorensen, A (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Nobels Vag 16, S-17177 Stockholm, Sweden. EM anna.smed.sorensen@ki.se NR 158 TC 4 Z9 4 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-1-4614-4433-6; 978-1-4614-4432-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 762 BP 263 EP 288 DI 10.1007/978-1-4614-4433-6_10 D2 10.1007/978-1-4614-4433-6 PG 26 WC Immunology; Virology SC Immunology; Virology GA BA3GE UT WOS:000334216300011 PM 22975879 ER PT S AU Aguda, BD AF Aguda, Baltazar D. BE Schmitz, U Wolkenhauer, O Vera, J TI Modeling microRNA-Transcription Factor Networks in Cancer SO MICRORNA CANCER REGULATION: ADVANCED CONCEPTS, BIOINFORMATICS AND SYSTEMS BIOLOGY TOOLS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Mathematical modeling; Feedback loops; Feedforward loops; miR-17-92; E2F; Myc; p53; Cancer zone; Qualitative network ID STEM-CELLS; GLIOBLASTOMA-MULTIFORME; SIGNALING PATHWAYS; RESTRICTION POINT; TUMOR-SUPPRESSOR; NANOG EXPRESSION; GENE-EXPRESSION; C-MYC; DIFFERENTIATION; P53 AB An increasing number of transcription factors (TFs) and microRNAs (miRNAs) is known to form feedback loops (FBLs) of interactions where a TF positively or negatively regulates the expression of a miRNA, and the miRNA suppresses the translation of the TF messenger RNA. FBLs are potential sources of instability in a gene regulatory network. Positive FBLs can give rise to switching behaviors while negative FBLs can generate periodic oscillations. This chapter presents documented examples of FBLs and their relevance to stem cell renewal and differentiation in gliomas. Feed-forward loops (FFLs) are only discussed briefly because they do not affect network stability unless they are members of cycles. A primer on qualitative network stability analysis is given and then used to demonstrate the network destabilizing role of FBLs. Steps in model formulation and computer simulations are illustrated using the miR-17-92/Myc/E2F network as an example. This example possesses both negative and positive FBLs. C1 NCI, Neurooncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Aguda, BD (reprint author), NCI, Neurooncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM agudabd@mail.nih.gov NR 60 TC 18 Z9 20 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-94-007-5590-1; 978-94-007-5589-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 774 BP 149 EP 167 DI 10.1007/978-94-007-5590-1_9 D2 10.1007/978-94-007-5590-1 PG 19 WC Oncology; Mathematical & Computational Biology SC Oncology; Mathematical & Computational Biology GA BA3GC UT WOS:000334214300010 PM 23377973 ER PT S AU Farag, AA AF Farag, Amal A. BE Farag, AA TI Performance Evaluation of Geometric Feature Descriptors With Application to Classification of Small-Size Lung Nodules in Low Dose CT SO PROCEEDINGS OF 3RD INTERNATIONAL CONFERENCE ON MULTIMEDIA TECHNOLOGY (ICMT-13) SE Advances in Intelligent Systems Research LA English DT Proceedings Paper CT 3rd International Conference on Multimedia Technology (ICMT) CY NOV 29-DEC 01, 2013 CL Guangzhou, PEOPLES R CHINA SP Ningbo Univ DE feature descriptors; SIFT; SURF; LBP; deformable objects; object classifications; lung nodules ID SCALE AB Object modeling is a multifaceted and active area of research in image analysis, manufacturing, and computational geometry. In image analysis, the focus of this paper, objects may be described in terms of their shape and appearance. Geometric features that are invariant to scale, rotation and translation are essential for proper modeling of shape. Deformable random objects, common in biomedical imaging, do not carry distinct features and suffer from multiple sources of uncertainty, including resolution, size, location and occlusion. Registration involves generating the transformation parameters for mapping a source to a target, while categorization involves matching entities into classes. Both processes, involve mapping attributes of objects with respect to each other, and robust features together with proper similarity measures are keys for good performance. This article examines the issues of features, similarity measures for registration and categorization of small-size deformable random objects; a case study of lung nodules in chest CT is used as an example. We show that feature descriptors capturing textural contents are more effective for these types of objects. The paper includes survey and evaluations of several modern feature descriptors that have been introduced in the computer vision and image analysis literature. C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Farag, AA (reprint author), NIH, Dept Radiol, Bldg 10, Bethesda, MD 20892 USA. EM amal.aly1@gmail.com NR 8 TC 0 Z9 0 U1 0 U2 0 PU ATLANTIS PRESS PI PARIS PA 29 AVENUE LAVMIERE, PARIS, 75019, FRANCE SN 1951-6851 BN 978-90-78677-89-5 J9 ADV INTEL SYS RES PY 2013 VL 84 BP 32 EP 39 PG 8 WC Engineering, Electrical & Electronic SC Engineering GA BA4EM UT WOS:000335511000006 ER PT S AU Zeng, XK Chauhan, C Hou, SX AF Zeng, Xiankun Chauhan, Chhavi Hou, Steven X. BE Hime, G Abud, H TI Stem Cells in the Drosophila Digestive System SO TRANSCRIPTIONAL AND TRANSLATIONAL REGULATION OF STEM CELLS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Drosophila; Gastric stem cells; Intestinal stem cells; Midgut; Renal and nephric stem cells ID CONTROLS SELF-RENEWAL; MALPIGHIAN TUBULES; POSTEMBRYONIC DEVELOPMENT; BACTERIAL-INFECTION; SIGNALING PATHWAY; SMALL-INTESTINE; HORMONE ACTION; PROLIFERATION; DIVISION; NOTCH AB Adult stem cells maintain tissue homeostasis by continuously replenishing damaged, aged and dead cells in any organism. Five types of region and organ-specific multipotent adult stem cells have been identified in the Drosophila digestive system: intestinal stem cells (ISCs) in the posterior midgut; hindgut intestinal stem cells (HISCs) at the midgut/hindgut junction; renal and nephric stem cells (RNSCs) in the Malpighian Tubules; type I gastric stem cells (GaSCs) at foregut/midgut junction; and type II gastric stem cells (GSSCs) at the middle of the midgut. Despite the fact that each type of stem cell is unique to a particular organ, they share common molecular markers and some regulatory signaling pathways. Due to the simpler tissue structure, ease of performing genetic analysis, and availability of abundant mutants, Drosophila serves as an elegant and powerful model system to study complex stem cell biology. The recent discoveries, particularly in the Drosophila ISC system, have greatly advanced our understanding of stem cell self-renewal, differentiation, and the role of stem cells play in tissue homeostasis/regeneration and adaptive tissue growth. C1 [Zeng, Xiankun; Chauhan, Chhavi; Hou, Steven X.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP Hou, SX (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. EM hous@mail.nih.gov NR 59 TC 4 Z9 4 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0065-2598 BN 978-94-007-6621-1; 978-94-007-6620-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 786 BP 63 EP 78 DI 10.1007/978-94-007-6621-1_5 D2 10.1007/978-94-007-6621-1 PG 16 WC Cell Biology; Developmental Biology; Medicine, Research & Experimental SC Cell Biology; Developmental Biology; Research & Experimental Medicine GA BA2AW UT WOS:000333215400005 PM 23696352 ER PT J AU Stewart, R Lombardo, FL Albanese, E AF Stewart, R. Lombardo, F. L. Albanese, E. TI DEMENTIA AND LOWER BLOOD PRESSURE IN SEVEN LOW AND MIDDLE INCOME COUNTRIES: THE 10/66 CROSS-SECTIONAL SURVEYS SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Stewart, R.] Kings Coll London, Inst Psychiat, Hlth Serv & Populat Res Dept, London WC2R 2LS, England. [Lombardo, F. L.] Italian Natl Inst Hlth, Natl Ctr Epidemiol, Rome, Italy. [Albanese, E.] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2013 VL 28 SU 1 MA 1430 PG 1 WC Psychiatry SC Psychiatry GA AG5LN UT WOS:000335460601168 ER PT J AU Anderson, E Spindler, J Boltz, V Shao, W Uldrick, T Rehm, C Kearney, M Mellors, J Coffin, J Maldarelli, F AF Anderson, E. Spindler, J. Boltz, V. Shao, W. Uldrick, T. Rehm, C. Kearney, M. Mellors, J. Coffin, J. Maldarelli, F. TI Persistent elevation in HIV viraemia during cART with identical WT sequences imply expansion of a clonal source SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 [Anderson, E.; Spindler, J.; Boltz, V.; Kearney, M.; Maldarelli, F.] NCI Frederick Natl Lab, Frederick, MD USA. [Shao, W.] SAIC Frederick Natl Lab, Frederick, MD USA. [Uldrick, T.] NCI, Bethesda, MD 20892 USA. [Rehm, C.] NIAID, Bethesda, MD 20892 USA. [Mellors, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Coffin, J.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 SU 1 BP A24 EP A24 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500020 ER PT J AU Boltz, VF Shao, W Kearney, MF Mellors, JW Maldarelli, F Coffin, JM AF Boltz, V. F. Shao, W. Kearney, M. F. Mellors, J. W. Maldarelli, F. Coffin, J. M. TI In vitro analysis of PCR founder effects in Illumina sequencing SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 [Boltz, V. F.; Kearney, M. F.; Maldarelli, F.] NCI, Bethesda, MD 20892 USA. [Mellors, J. W.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Coffin, J. M.] Tufts Univ, Medford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 SU 1 BP A44 EP A44 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500040 ER PT J AU Chung, S Miller, JT Lapkouski, M Tian, L Yang, W Le Grice, SFJ AF Chung, S. Miller, J. T. Lapkouski, M. Tian, L. Yang, W. Le Grice, S. F. J. TI Examining the role of C-terminal domain of HIV-1 reverse transcriptase p51 subunit in positioning and hydrolysis of RNA/DNA hybrids SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 [Chung, S.; Miller, J. T.; Le Grice, S. F. J.] NCI Frederick, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Lapkouski, M.; Tian, L.; Yang, W.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 SU 1 BP A35 EP A35 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500031 ER PT J AU Dilley, KA Nikolaitchik, OA Burdick, R Chen, J Galli, A Pathak, VK Hu, WS AF Dilley, K. A. Nikolaitchik, O. A. Burdick, R. Chen, J. Galli, A. Pathak, V. K. Hu, W-S TI The recognition of the HIV-1 dimeric RNA genome nucleates virus assembly SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 [Dilley, K. A.; Nikolaitchik, O. A.; Burdick, R.; Chen, J.; Galli, A.; Pathak, V. K.; Hu, W-S] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Galli, A.] Univ Copenhagen, Copenhagen Hepatitis Program C, Hvidovre, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 SU 1 BP A63 EP A63 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500055 ER PT J AU Grossman, Z Avidor, B Mor, Z Turner, D Levy, I Ram, D Anis, E Maldarelli, F AF Grossman, Z. Avidor, B. Mor, Z. Turner, D. Levy, I. Ram, D. Anis, E. Maldarelli, F. TI Subtype B HIV transmission groups in Israel detected by Bayesian phylogenetics are composed predominantly of men who have sex with men (MSM) with recent HIV infection SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 [Grossman, Z.] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Avidor, B.; Turner, D.] Sourasky Med Ctr, Tel Aviv, Israel. [Mor, Z.] Minist Hlth, Publ Hlth Serv, Ramle Dept Hlth, Jerusalem, Israel. [Levy, I.] Sheba Med Ctr, Ramat Gan, Israel. [Ram, D.] Minist Hlth, Publ Hlth Serv, Natl HIV Reference Lab, Tel Hashomer, Israel. [Ram, D.] Minist Hlth, Publ Hlth Serv, Dept Epidemiol, Jerusalem, Israel. [Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 SU 1 BP A82 EP A82 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500069 ER PT J AU Holmes, EC AF Holmes, E. C. TI RNA virus evolution: a guide for the perplexed SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia. [Holmes, E. C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Holmes, E. C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 SU 1 BP A5 EP A5 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500004 ER PT J AU Kearney, MF Anderson, EM Kline, C Kordella, D Shao, W Smith, L Coomer, C Spindler, J Lifson, JD Mellors, JW Coffin, JM Ambrose, Z AF Kearney, M. F. Anderson, E. M. Kline, C. Kordella, D. Shao, W. Smith, L. Coomer, C. Spindler, J. Lifson, J. D. Mellors, J. W. Coffin, J. M. Ambrose, Z. TI Virus populations in plasma and tissues are well-mixed in RT-SHIV-infected macaques SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 [Kearney, M. F.; Anderson, E. M.; Kordella, D.; Smith, L.; Coomer, C.; Spindler, J.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Kline, C.; Mellors, J. W.; Ambrose, Z.] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA USA. [Shao, W.] NCI, Adv Biomed Comp Ctr, SAIC, Frederick, MD 21701 USA. [Lifson, J. D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Coffin, J. M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 SU 1 BP A26 EP A26 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500022 ER PT J AU Larder, BA Revell, AD Wang, D Hamers, R Tempelman, H Barth, R Wensing, AMJ Morrow, C Wood, R van Sighem, A Reiss, P Nelson, M Emery, S Montaner, JM Lane, HC AF Larder, B. A. Revell, A. D. Wang, D. Hamers, R. Tempelman, H. Barth, R. Wensing, A. M. J. Morrow, C. Wood, R. van Sighem, A. Reiss, P. Nelson, M. Emery, S. Montaner, J. M. Lane, H. C. CA RDI Study Grp TI Accurate prediction of response to HIV therapy without a genotype: a potential tool for therapy optimization in resource-limited settings SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 [Larder, B. A.; Revell, A. D.; Wang, D.] HIV Resistance Response Database Initiat RDI, London, England. [Hamers, R.] Univ Amsterdam, Acad Med Ctr, PharmAccess Fdn, NL-1105 AZ Amsterdam, Netherlands. [Tempelman, H.] Ndlovu Care Grp, Elandsdoorn, South Africa. [Barth, R.; Wensing, A. M. J.] Univ Med Ctr, Utrecht, Netherlands. [Morrow, C.; Wood, R.] Desmond Tutu HIV Ctr, Cape Town, South Africa. [van Sighem, A.; Reiss, P.] Stichting HIV Monitoring, Amsterdam, Netherlands. [Nelson, M.] Chelsea & Westminster Hosp, London, England. [Emery, S.] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia. [Montaner, J. M.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Lane, H. C.] NIAID, Bethesda, MD 20892 USA. RI Emery, Sean/H-4920-2013 OI Emery, Sean/0000-0001-6072-8309 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 SU 1 BP A20 EP A20 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500016 ER PT J AU Liang, D Das, B Zheng, X Boltz, VF Kearney, MF Robin, D Tran, B Stephens, R Yang, J Huang, DW Lempicki, RA AF Liang, D. Das, B. Zheng, X. Boltz, V. F. Kearney, M. F. Robin, D. Tran, B. Stephens, R. Yang, J. Huang, D. W. Lempicki, R. A. TI Evaluation of three next-generation sequencing platforms on low frequency HIV drug resistant variants detection SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 [Liang, D.; Das, B.; Zheng, X.; Yang, J.; Huang, D. W.; Lempicki, R. A.] SAIC Frederick Inc, Lab Immunopathogenesis & Bioinformat, Frederick, MD USA. [Robin, D.] SAIC Frederick Inc, Virus Isolat & Serol Lab, Frederick, MD USA. [Tran, B.] SAIC Frederick Inc, Adv Technol Program, Frederick, MD USA. [Stephens, R.] SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD USA. [Boltz, V. F.; Kearney, M. F.] NCI, HIV Drug Resistance Program, Frederick Natl Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 SU 1 BP A42 EP A42 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500038 ER PT J AU Dallal, CM Stone, RA Cauley, JA Ness, RB Vogel, VG Fentiman, IS Fowke, JH Krogh, V Loft, S Meilahn, EN Muti, P Olsen, A Overvad, K Sieri, S Tjonneland, A Ursin, G Wellejus, A Taioli, E AF Dallal, Cher M. Stone, Roslyn A. Cauley, Jane A. Ness, Roberta B. Vogel, Victor G. Fentiman, Ian S. Fowke, Jay H. Krogh, Vittorio Loft, Steffen Meilahn, Elaine N. Muti, Paola Olsen, Anja Overvad, Kim Sieri, Sabina Tjonneland, Anne Ursin, Giske Wellejus, Anja Taioli, Emanuela TI Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Article DE Epidemiology; Estrogen metabolite ratio; Menopause ID ENDOGENOUS ESTRADIOL METABOLITES; PROGESTERONE-RECEPTOR STATUS; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; MASS-SPECTROMETRY; SEX-HORMONES; RISK-FACTORS; 16-ALPHA-HYDROXYESTRONE; CELLS; RATIO AB Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), and their ratio (2:16 alpha-OHE1) in relation to breast cancer risk. Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status. Results: Higher premenopausal 2:16 alpha-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI = 0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16 alpha-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003). Conclusions: Premenopausal urinary 2:16 alpha-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16 alpha-OHE1 overall, although obesity may modify associations with 2-OHE1. C1 [Dallal, Cher M.; Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Stone, Roslyn A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX USA. [Vogel, Victor G.] Geisinger Med Ctr, Geisinger Canc Inst, Danville, PA 17822 USA. [Fentiman, Ian S.] Guys Hosp, London SE1 9RT, England. [Fowke, Jay H.] Vanderbilt Univ, Med Ctr, Div Epidemiol, Nashville, TN USA. [Krogh, Vittorio; Sieri, Sabina] Fdn IRCCS Ist Nazl Tumori, Nutr Epidemiol Unit, Milan, Italy. [Loft, Steffen; Wellejus, Anja] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark. [Meilahn, Elaine N.] Virginia Polytech Inst & State Univ, Coll Vet Med, Marion DuPont Scott Equine Med Ctr, Leesburg, VA USA. [Muti, Paola] Italian Natl Canc Inst Regina Elena, Rome, Italy. [Olsen, Anja; Tjonneland, Anne] Danish Canc Soc, Res Ctr, Unit Diet Genes & Environm, Copenhagen, Denmark. [Overvad, Kim] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, Aarhus, Denmark. [Ursin, Giske] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Taioli, Emanuela] Hofstra North Shore LIJ Sch Med, Dept Populat Hlth, Manhasset, NY USA. RP Dallal, CM (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, EPS, 6120 Execut Blvd,Suite 550,Rm 5010, Bethesda, MD 20892 USA. EM cher.dallal@nih.gov RI Krogh, Vittorio/K-2628-2016; Sieri, Sabina/K-4667-2016 OI Krogh, Vittorio/0000-0003-0122-8624; Cauley, Jane A/0000-0003-0752-4408; Sieri, Sabina/0000-0001-5201-172X FU National Institutes of Health [R25 CA057703]; ECNIS grant from the European Union [FOOD-CT-2005-513943] FX This work was partly supported by the National Institutes of Health training grant [R25 CA057703] to C.M.D. Part of this work was also performed in relation to the Molecular Epidemiology of Cancer Database under the ECNIS grant from the European Union (FOOD-CT-2005-513943). NR 53 TC 3 Z9 3 U1 0 U2 2 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 EI 1724-6008 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD JAN-MAR PY 2013 VL 28 IS 1 BP 3 EP 16 DI 10.5301/JBM.2012.9353 PG 14 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA AG1LF UT WOS:000335176000002 PM 22865302 ER PT S AU Suhasini, AN Brosh, RM AF Suhasini, Avvaru N. Brosh, Robert M., Jr. BE Spies, M TI DNA Helicases Associated with Genetic Instability, Cancer, and Aging SO DNA HELICASES AND DNA MOTOR PROTEINS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID NUCLEOTIDE EXCISION-REPAIR; SISTER-CHROMATID EXCHANGES; ROTHMUND-THOMSON SYNDROME; WERNER-SYNDROME HELICASE; BLOOMS-SYNDROME HELICASE; ANEMIA GROUP J; FANCONI-ANEMIA; HOMOLOGOUS RECOMBINATION; XERODERMA-PIGMENTOSUM; CHARGE-TRANSPORT AB DNA helicases have essential roles in the maintenance of genomic stability. They have achieved even greater prominence with the discovery that mutations in human helicase genes are responsible for a variety of genetic disorders and are associated with tumorigenesis. A number of missense mutations in human helicase genes are linked to chromosomal instability diseases characterized by age-related disease or associated with cancer, providing incentive for the characterization of molecular defects underlying aberrant cellular phenotypes. In this chapter, we discuss some examples of clinically relevant missense mutations in various human DNA helicases, particularly those of the Iron-Sulfur cluster and RecQ families. Clinically relevant mutations in the XPD helicase can lead to Xeroderma pigmentosum, Cockayne's syndrome, Trichothiodystrophy, or COFS syndrome. FANCJ mutations are associated with Fanconi anemia or breast cancer. Mutations of the Fe-S helicase ChlR1 (DDX11) are linked to Warsaw Breakage syndrome. Mutations in the RecQ helicases BLM and WRN are linked to the cancer-prone disorder Bloom's syndrome and premature aging condition Werner syndrome, respectively. RECQL4 mutations can lead to Rothmund-Thomson syndrome, Baller-Gerold syndrome, or RAPADILINO. Mutations in the Twinkle mitochondrial helicase are responsible for several neuromuscular degenerative disorders. We will discuss some insights gained from biochemical and genetic studies of helicase variants, and highlight some hot areas of helicase research based on recent developments. C1 [Suhasini, Avvaru N.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. EM BroshR@grc.nia.nih.gov NR 108 TC 14 Z9 15 U1 4 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-1-4614-5037-5; 978-1-4614-5036-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 973 BP 123 EP 144 DI 10.1007/978-1-4614-5037-5_6 D2 10.1007/978-1-4614-5037-5 PG 22 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA BA1OK UT WOS:000332746700007 ER PT J AU Schmiedt, J Peters, A Saunders, R Maier, A Leopold, D Schmid, M AF Schmiedt, J. Peters, A. Saunders, R. Maier, A. Leopold, D. Schmid, M. TI Blindsight: insights from neuronal responses in macaque V4 after V1 injury SO PERCEPTION LA English DT Meeting Abstract C1 [Schmiedt, J.; Schmid, M.] ESI, Schmid Lab, Leonberg, Germany. [Peters, A.; Saunders, R.; Leopold, D.] NIMH, Bethesda, MD USA. [Maier, A.] Vanderbilt Univ, Dept Psychol, Nashville, TN USA. EM joscha.schmiedt@esi-frankfurt.de NR 0 TC 0 Z9 0 U1 0 U2 3 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 EI 1468-4233 J9 PERCEPTION JI Perception PY 2013 VL 42 SU S BP 163 EP 163 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA AF7NE UT WOS:000334901000508 ER PT J AU Horowitz, T AF Horowitz, T. TI Does chemotherapy lead to a visual search deficit? SO PERCEPTION LA English DT Meeting Abstract C1 [Horowitz, T.] NCI, NIH, Bethesda, MD 20892 USA. EM todd.horowitz@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 EI 1468-4233 J9 PERCEPTION JI Perception PY 2013 VL 42 SU S BP 214 EP 214 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA AF7NE UT WOS:000334901000667 ER PT J AU Tsui, Y Horowitz, T Thornton, TM AF Tsui, Y. Horowitz, T. Thornton, T. M. TI Planning Search for Multiple Targets using the iPad SO PERCEPTION LA English DT Meeting Abstract C1 [Tsui, Y.; Thornton, T. M.] Swansea Univ, Psychol Dept, Swansea, W Glam, Wales. [Horowitz, T.] NCI, NIH, Bethesda, MD 20892 USA. EM yyt@ianthornton.com NR 0 TC 1 Z9 1 U1 0 U2 1 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 EI 1468-4233 J9 PERCEPTION JI Perception PY 2013 VL 42 SU S BP 217 EP 217 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA AF7NE UT WOS:000334901000675 ER PT S AU Shinohara, RT Crainiceanu, CS Caffo, BS Reich, DS AF Shinohara, Russell T. Crainiceanu, Ciprian S. Caffo, Brian S. Reich, Daniel S. GP IEEE TI Information Criteria for Dynamic Contrast-Enhanced Magnetic Resonance Imaging SO 2013 3RD INTERNATIONAL WORKSHOP ON PATTERN RECOGNITION IN NEUROIMAGING (PRNI 2013) SE International Workshop on Pattern Recognition in Neuroimaging LA English DT Proceedings Paper CT 3rd International Workshop on Pattern Recognition in NeuroImaging (PRNI) CY JUN 22-24, 2013 CL Philadelphia, PA SP Siemens, Univ Penn, MICCAI, IEEE, IEEE Comp Soc DE functional principal components analysis; dynamic contrast-enhanced MRI; information criteria AB Inflammatory lesions form in the brain and spinal cord of patients with multiple sclerosis (MS). In many active MS lesions, blood flows abnormally into the white matter of the brain due to breakdown of the blood-brain barrier (BBB), which is know to be associated with morbidity and disability. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows quantitative study of blood flow and permeability dynamics throughout the brain. In our study, we observe 15 patients who undergo DCE-MRI periodically throughout a year. In this paper, we design and study spatiotemporal parameters of interest that cannot be obtained by visual inspection. Examples of such parameters are the rate and maximum intensity observed in regions of interest. We develop semiparametric methods for this quantification of BBB disruption at each visit. C1 [Shinohara, Russell T.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Crainiceanu, Ciprian S.; Caffo, Brian S.; Reich, Daniel S.] Johns Hopkins Univ, Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Shinohara, Russell T.; Reich, Daniel S.] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Translat Neuroradiol Unit, Bethesda, MD 20892 USA. RP Shinohara, RT (reprint author), Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. EM rshi@mail.med.upenn.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2330-9989 BN 978-0-7695-5061-9 J9 INT WORKSHOP PATTERN PY 2013 BP 37 EP 41 DI 10.1109/PRNI.2013.19 PG 5 WC Computer Science, Interdisciplinary Applications; Neuroimaging SC Computer Science; Neurosciences & Neurology GA BA2WL UT WOS:000333958600010 ER PT B AU Ngamsirijit, W AF Ngamsirijit, Wuttigrai GP IEEE TI Using Capacity Flexibility Model for Responsive Tourism Logistics: The Case of Pattaya City SO 2013 IEEE INTERNATIONAL CONFERENCE ON SERVICE OPERATIONS AND LOGISTICS, AND INFORMATICS (SOLI) LA English DT Proceedings Paper CT IEEE International Conference on Service Operations and Logistics, and Informatics (SOLI) CY JUL 28-30, 2013 CL Dongguan, PEOPLES R CHINA SP IEEE DE Tourism logistics; Responsiveness; Capacity flexibility AB An evolution of tourist behavior and an introduction of new tourist attractions lead to more land dispersion and higher level of accessibility needs. The development of modern tourism logistics must be carefully conducted to achieve performance of responsiveness by leveraging existing infrastructure and facilities, especially in tourism city with constrained capacities. Regarding to this, the public transport can be considered potential means of tourism logistics development. This paper firstly explores current travel situations and future requirements for Pattaya tourism and investigates specific public transport services in Pattaya city. It also conducts an assessment of the performance in responding travel needs of tourism by using the Capacity Flexibility Model. The model is based on an optimization technique and is developed for selecting the most flexible and efficient vehicle routes and directions among various locations or destinations. The results from the analysis can provide insights for properly designing tourism logistics operations and obtain appropriate vehicle routes and travel patterns suitable for travel conditions of Pattaya city. In addition, this study can be employed as a framework for managers in designing the responsive logistics and operations and making decision regarding transportation choices in both tourism and industrial contexts. C1 NIDA, Sch Human Resource Dev, Bangkok, Thailand. RP Ngamsirijit, W (reprint author), NIDA, Sch Human Resource Dev, Bangkok, Thailand. EM wuttigrai.n@gmail.com NR 3 TC 0 Z9 0 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-0530-0; 978-1-4799-0529-4 PY 2013 BP 404 EP 407 PG 4 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BA2UB UT WOS:000333901500078 ER PT J AU Rosenfeld, S AF Rosenfeld, Simon GP IEEE TI Critical Junction: Nonlinear Dynamics, Swarm Intelligence and Cancer Research SO PROCEEDINGS OF THE 2013 IEEE SYMPOSIUM ON COMPUTATIONAL INTELLIGENCE IN BIOINFORMATICS AND COMPUTATIONAL BIOLOGY (CIBCB) LA English DT Proceedings Paper CT 10th Annual IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology (CIBCB) CY APR 16-19, 2013 CL Singapore, SINGAPORE SP IEEE, IEEE Computat Intelligence Soc DE Global Consensus Theorem; Swarm Intelligence; Biomolecular Networks; Carcinogenesis ID CHEMICAL IMPLEMENTATION; AGGREGATION BEHAVIOR; PATTERN-FORMATION; NEURAL-NETWORKS; COMPETITION; DECISION; SYSTEMS; ROBOTS; OSCILLATIONS; MACHINES AB Complex biological systems manifest a large variety of emergent phenomena among which prominent roles belong to self-organization and swarm intelligence. Despite astoundingly wide repertoire of observed forms, there are comparatively simple rules governing evolution of large systems towards self-organization, in general, and towards swarm intelligence, in particular. In this work, an attempt is made to outline general guiding principles in exploration of a wide range of seemingly dissimilar phenomena observed in large communities of individuals devoid of any personal intelligence and interacting with each other through simple stimulus-response rules. Mathematically, these guiding principles are well captured by the Global Consensus Theorem (GCT) allowing for unified approach to such diverse systems as biological networks, communities of social insects, robotic communities, microbial communities, communities of somatic cells, to social networks, and to many other systems. The GCT provides a conceptual basis for understanding the emergent phenomena of self-organization occurring in large communities without involvement of a supervisory authority, without system-wide informational infrastructure, and without mapping of general plan of action onto cognitive/behavioral faculties of its individual members. Cancer onset and proliferation serves as an important example of application of these conceptual approaches. A growing body of evidence confirms the premise that disruption of quorum sensing, an important aspect of swarm intelligence, plays a key role in carcinogenesis. Other aspects of swarm intelligence, such as collective memory, adaptivity (a form of learning from experience) and ability for self-repair are the key for understanding biological robustness and acquired chemoresistance. Yet another aspects of swarm intelligence, such as division of labor and competitive differentiation, may be helpful in understanding of cancer compartmentalization and tumor heterogeneity. C1 NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Rosenfeld, S (reprint author), NCI, Canc Prevent Div, Bethesda, MD 20892 USA. EM sr212a@nih.gov NR 36 TC 0 Z9 0 U1 1 U2 6 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-5875-0 PY 2013 BP 206 EP 211 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Computer Science; Mathematical & Computational Biology GA BA2TU UT WOS:000333898800030 ER PT J AU Raiten, DJ Raghavan, R Kraemer, K AF Raiten, Daniel J. Raghavan, Ramkripa Kraemer, Klaus TI Biomarkers in Growth SO ANNALS OF NUTRITION AND METABOLISM LA English DT Editorial Material DE Biomarkers; Growth; Stunting; Biomarkers in growth ID MIDDLE-INCOME COUNTRIES; GLYCINE; UNDERNUTRITION; TRANSPORTERS; BIRTH; AGE AB Background: The current approaches to assess growth are limited to anthropometry, are insensitive and nonspecific, and do not enable an improved understanding of how nutrition might impact growth. Consequently, new tools to develop better standards of care and programs to address ongoing concerns about nutrition and health are needed. Methods: The Biomarkers of Nutrition for Development (BOND) project is designed to support the discovery, development, and use of current and new biomarkers of nutritional exposure, status, function, and effect. The Biomarkers in Growth (BIG) project was initiated as a BOND program to develop a roadmap for moving the nutrition and growth agenda forward. The first step in this project was a session jointly organized by the BOND Secretariat and Sight and Life at the 20th International Congress on Nutrition in Granada, Spain. Results: The BIG session outlined current approaches to evaluating growth and understanding of the role of nutrition in linear growth, body composition, and long-term health outcomes and the potential role of systems biology in the assessment of the nutrition-growth relationship. Conclusion: The session presentations and deliberations highlighted the need for a concerted effort to address the critical gaps in our understanding of the biology and assessment of growth. (C) 2014 S. Karger AG, Basel C1 [Raiten, Daniel J.; Raghavan, Ramkripa] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Kraemer, Klaus] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Kraemer, Klaus] Sight & Life, Basel, Switzerland. RP Raiten, DJ (reprint author), 6100 Execut Blvd, Bethesda, MD 20892 USA. EM raitend@mail.nih.gov NR 11 TC 2 Z9 2 U1 1 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 IS 4 BP 293 EP 297 DI 10.1159/000357572 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AD8KT UT WOS:000333515600005 PM 24457286 ER PT S AU Bagci, U Mollura, DJ AF Bagci, Ulas Mollura, Daniel J. BE Mori, K Sakuma, I Sato, Y Barillot, C Navab, N TI Denoising PET Images Using Singular Value Thresholding and Stein's Unbiased Risk Estimate SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION (MICCAI 2013), PT III SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 16th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) CY SEP 22-26, 2013 CL Nagoya Univ, Nagoya, JAPAN SP Nagoya Convent & Visitors Bur, Murata Sci Fdn, Daiko Fdn, Japan Soc Comp Aided Surg, Sci Council Japan, Nagoya Univ, Informat & Commun Headquarters, Nagoya Univ, Grad Sch Informat Sci HO Nagoya Univ DE PET; Denoising; Singular Value Thresholding; Stein Risk Estimate AB Image denoising is an important pre-processing step for accurately quantifying functional morphology and measuring activities of the tissues using PET images. Unlike structural imaging modalities, PET images have two difficulties: (1) the Gaussian noise model does not necessarily fit into PET imaging because the exact nature of noise propagation in PET imaging is not well known, and (2) PET images are low resolution; therefore, it is challenging to denoise them while preserving structural information. To address these two difficulties, we introduce a novel methodology for denoising PET images. The proposed method uses the singular value thresholding concept and Stein's unbiased risk estimate to optimize a soft thresholding rule. Results, obtained from 40 MRI-PET images, demonstrate that the proposed algorithm is able to denoise PET images successfully, while still maintaining the quantitative information. C1 [Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Bagci, U (reprint author), NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM ulas.bagci@nih.gov OI Bagci, Ulas/0000-0001-7379-6829 NR 9 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-40760-4; 978-3-642-40759-8 J9 LECT NOTES COMPUT SC PY 2013 VL 8151 BP 115 EP 122 PG 8 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA2LH UT WOS:000333633500015 ER PT S AU Liu, YX Sadowski, SM Weisbrod, AB Kebebew, E Summers, RM Yao, JH AF Liu, Yixun Sadowski, Samira M. Weisbrod, Allison B. Kebebew, Electron Summers, Ronald M. Yao, Jianhua BE Mori, K Sakuma, I Sato, Y Barillot, C Navab, N TI Multimodal Image Driven Patient Specific Tumor Growth Modeling SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION (MICCAI 2013), PT III SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 16th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) CY SEP 22-26, 2013 CL Nagoya Univ, Nagoya, JAPAN SP Nagoya Convent & Visitors Bur, Murata Sci Fdn, Daiko Fdn, Japan Soc Comp Aided Surg, Sci Council Japan, Nagoya Univ, Informat & Commun Headquarters, Nagoya Univ, Grad Sch Informat Sci HO Nagoya Univ ID DIFFUSION AB Personalized tumor growth model using clinical imaging data is valuable in tumor staging and therapy planning. In this paper, we build a patient specific tumor growth model based on longitudinal dual phase CT and FDG-PET. We propose a reaction-advection-diffusion model integrating cancerous cell proliferation, infiltration, metabolic rate and extracellular matrix biomechanical response. We then develop a scheme to bridge our model with multimodal radiologic images through intracellular volume fraction (ICVF) and Standardized Uptake Value (SUV). The model was evaluated by comparing the predicted tumors with the observed tumors in terms of average surface distance (ASD), root mean square difference (RMSD) of the ICVF map, the average ICVF difference (AICVFD) of tumor surface and the tumor relative volume difference (RVD) on six patients with pathologically confirmed pancreatic neuroendocrine tumors. The ASD between the predicted tumor and the reference tumor was 2.5 +/- 0.7 mm, the RMSD was 4.3 +/- 0.6%, the AICVFD was 2.6 +/- 0.8%, and the RVD was 7.7 +/- 1.9%. C1 [Liu, Yixun; Summers, Ronald M.; Yao, Jianhua] NIH, Bethesda, MD 20892 USA. RP Liu, YX (reprint author), NIH, Bethesda, MD 20892 USA. NR 8 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-40760-4; 978-3-642-40759-8 J9 LECT NOTES COMPUT SC PY 2013 VL 8151 BP 283 EP 290 PG 8 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA2LH UT WOS:000333633500036 ER PT S AU Reiter, DA Spencer, RG AF Reiter, David A. Spencer, Richard G. BE Garrido, L Beckmann, N TI Applications of MRI and MRS in Cartilage Therapeutics and Tissue Engineering SO NEW APPLICATIONS OF NMR IN DRUG DISCOVERY AND DEVELOPMENT SE New Developments in NMR LA English DT Article; Book Chapter ID LOW-INTENSITY ULTRASOUND; AUTOLOGOUS CHONDROCYTE IMPLANTATION; HOLLOW-FIBER BIOREACTOR; MULTIEXPONENTIAL T-2 RELAXATION; MAGNETIC-RESONANCE MICROSCOPY; HUMAN ARTICULAR CHONDROCYTES; AGGRECAN GENE-EXPRESSION; OXYGEN MAPPING EPROM; FIXED CHARGE-DENSITY; OSTEOCHONDRAL DEFECTS C1 [Reiter, David A.] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA. [Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21225 USA. RP Reiter, DA (reprint author), NIA, Clin Res Branch, NIH, 3001 S Hanover St,5th Floor, Baltimore, MD 21225 USA. EM reiterda@mail.nih.gov NR 111 TC 1 Z9 1 U1 2 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2044-253X BN 978-1-84973-766-1; 978-1-84973-444-8 J9 NEW DEV NMR PY 2013 IS 2 BP 376 EP 404 DI 10.1039/9781849737661-00376 D2 10.1039/9781849737661 PG 29 WC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA BA0RS UT WOS:000332124100016 ER PT J AU Szymczak, S Malley, J Franke, A AF Szymczak, Silke Malley, James Franke, Andre TI Comparison of Variable Selection Methods in Random Forests for Genomic Data Sets SO HUMAN HEREDITY LA English DT Meeting Abstract CT 42nd European Mathematical Genetics Meeting (EMGM) CY APR 01-02, 2014 CL Cologne, GERMANY C1 [Szymczak, Silke; Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Malley, James] NIH, Ctr Informat Technol, Bethesda, MD USA. EM s.szymczak@ikmb.uni-kiel.de RI Szymczak, Silke/C-6625-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2013 VL 76 IS 2 BP 88 EP 89 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA AD6BD UT WOS:000333337100012 ER PT S AU Wang, SJ McKenna, M Wei, ZS Liu, JM Liu, P Summers, RM AF Wang, Shijun McKenna, Matthew Wei, Zhuoshi Liu, Jiamin Liu, Peter Summers, Ronald M. BE Mori, K Sakuma, I Sato, Y Barillot, C Navab, N TI Visual Phrase Learning and Its Application in Computed Tomographic Colonography SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION (MICCAI 2013), PT I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 16th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) CY SEP 22-26, 2013 CL Nagoya Univ, Nagoya, JAPAN SP Nagoya Convent & Visitors Bur, Murata Sci Fdn, Daiko Fdn, Japan Soc Comp Aided Surg, Sci Council Japan, Nagoya Univ, Informat & Commun Headquarters, Nagoya Univ, Grad Sch Informat Sci HO Nagoya Univ AB In this work, we propose a visual phrase learning scheme to learn an optimal visual composite of anatomical components/parts from CT colonography images for computer-aided detection. The key idea is to utilize the anatomical parts of human body from medical images and associate them with biological targets of interest (organs, cancers, lesions, etc.) for joint detection and recognition. These anatomical parts of the human body are not necessarily near each other regarding their physical locations, and they serve more like a human body navigation system for detection and recognition. To show the effectiveness of the proposed learning scheme, we applied it to two sub-problems in computed tomographic colonography: teniae detection and classification of colorectal polyp candidates. Experimental results showed its efficacy. C1 [Wang, Shijun; McKenna, Matthew; Wei, Zhuoshi; Liu, Jiamin; Liu, Peter; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Wang, SJ (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C224, Bethesda, MD 20892 USA. EM rms@nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-40811-3; 978-3-642-40810-6 J9 LECT NOTES COMPUT SC PY 2013 VL 8149 BP 243 EP 250 PG 8 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA2DH UT WOS:000333330700031 ER PT S AU Liu, JF Wang, SJ Yao, JH Linguraru, MG Summers, RM AF Liu, Jianfei Wang, Shijun Yao, Jianhua Linguraru, Marius George Summers, Ronald M. BE Mori, K Sakuma, I Sato, Y Barillot, C Navab, N TI Manifold Diffusion for Exophytic Kidney Lesion Detection on Non-contrast CT Images SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION (MICCAI 2013), PT I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 16th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) CY SEP 22-26, 2013 CL Nagoya Univ, Nagoya, JAPAN SP Nagoya Convent & Visitors Bur, Murata Sci Fdn, Daiko Fdn, Japan Soc Comp Aided Surg, Sci Council Japan, Nagoya Univ, Informat & Commun Headquarters, Nagoya Univ, Grad Sch Informat Sci HO Nagoya Univ DE Kidney lesion detection; computed tomographic colonography; manifold diffusion; extracolonic finding; Riemannian manifold ID COLONOGRAPHY; SHAPE AB Kidney lesions are important extracolonic findings at computed tomographic colonography (CTC). However, kidney lesion detection on non-contrast CTC images poses significant challenges due to low image contrast with surrounding tissues. In this paper, we treat the kidney surface as manifolds in Riemannian space and present an intrinsic manifold diffusion approach to identify lesion-caused protrusion while simultaneously removing geometrical noise on the manifolds. Exophytic lesions (those that deform the kidney surface) are detected by searching for surface points with local maximum diffusion response and using the normalized cut algorithm to extract them. Moreover, multi-scale diffusion response is a discriminative feature descriptor for the subsequent classification to reduce false positives. We validated the proposed method and compared it with a baseline method using shape index on CTC datasets from 49 patients. Free-response receiver operating characteristic analysis showed that at 7 false positives, the proposed method achieved 87% sensitivity while the baseline method achieved only 22% sensitivity. The proposed method showed far fewer false positives compared with the baseline method which makes it feasible for clinical practice. C1 [Liu, Jianfei; Wang, Shijun; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Linguraru, Marius George] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediatr Surg Innovat, Washington, DC 20010 USA. RP Liu, JF (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-40811-3; 978-3-642-40810-6 J9 LECT NOTES COMPUT SC PY 2013 VL 8149 BP 340 EP 347 PG 8 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA2DH UT WOS:000333330700043 ER PT S AU Kadoury, S Abi-Jaoudeh, N Valdes, PA AF Kadoury, Samuel Abi-Jaoudeh, Nadine Valdes, Pablo A. BE Mori, K Sakuma, I Sato, Y Barillot, C Navab, N TI 7 Higher-Order CRF Tumor Segmentation with Discriminant Manifold Potentials SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION (MICCAI 2013), PT I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 16th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) CY SEP 22-26, 2013 CL Nagoya Univ, Nagoya, JAPAN SP Nagoya Convent & Visitors Bur, Murata Sci Fdn, Daiko Fdn, Japan Soc Comp Aided Surg, Sci Council Japan, Nagoya Univ, Informat & Commun Headquarters, Nagoya Univ, Grad Sch Informat Sci HO Nagoya Univ ID MODEL AB The delineation of tumor boundaries in medical images is an essential task for the early detection, diagnosis and follow-up of cancer. However accurate segmentation remains challenging due to presence of noise, inhomogeneity and high appearance variability of malignant tissue. In this paper, we propose an automatic segmentation approach using fully-connected higher-order conditional random fields (HOCRF) where potentials are computed within a discriminant Grassmannian manifold. First, the framework learns within-class and between-class similarity distributions from a training set of images to discover the optimal manifold discrimination between normal and pathological tissues. Second, the conditional optimization scheme computes non-local pairwise as well as pattern-based higher-order potentials from the manifold subspace to recognize regions with similar labelings and incorporate global consistency in the inference process. Our HOCRF framework is applied in the context of metastatic liver tumor segmentation in CT images. Compared to state of the art methods, our method achieves better performance on a group of 30 liver tumors and can deal with highly pathological cases. C1 [Kadoury, Samuel] Ecole Polytech, Med, Montreal, PQ H3C 3A7, Canada. [Abi-Jaoudeh, Nadine] Natl Inst Hlth, Rad & Imaging Sci, Bethesda, MD 20892 USA. [Valdes, Pablo A.] Dartmouth Coll, Hanover, NH 03755 USA. RP Kadoury, S (reprint author), Ecole Polytech, Med, Montreal, PQ H3C 3A7, Canada. NR 13 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-40811-3; 978-3-642-40810-6 J9 LECT NOTES COMPUT SC PY 2013 VL 8149 BP 719 EP 726 PG 8 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA2DH UT WOS:000333330700090 ER PT S AU Asman, AJ Smith, SA Reich, DS Landman, BA AF Asman, Andrew J. Smith, Seth A. Reich, Daniel S. Landman, Bennett A. BE Mori, K Sakuma, I Sato, Y Barillot, C Navab, N TI Robust GM/WM Segmentation of the Spinal Cord with Iterative Non-local Statistical Fusion SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION (MICCAI 2013), PT I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 16th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) CY SEP 22-26, 2013 CL Nagoya Univ, Nagoya, JAPAN SP Nagoya Convent & Visitors Bur, Murata Sci Fdn, Daiko Fdn, Japan Soc Comp Aided Surg, Sci Council Japan, Nagoya Univ, Informat & Commun Headquarters, Nagoya Univ, Grad Sch Informat Sci HO Nagoya Univ DE Spinal Cord Parcellation; Multi-Atlas Segmentation; Non-local Correspondence Models; Registration Refinement ID MAGNETIC-RESONANCE IMAGES; MULTIPLE-SCLEROSIS; REGISTRATION; COMBINATION; MATTER AB New magnetic resonance imaging (MRI) sequences are enabling clinical study of the in vivo spinal cord's internal structure. Yet, low contrast-to-noise ratio, artifacts, and imaging distortions have limited the applicability of tissue segmentation techniques pioneered elsewhere in the central nervous system. Recently, methods have been presented for cord/non-cord segmentation on MRI and the feasibility of gray matter/white matter tissue segmentation has been evaluated. To date, no automated algorithms have been presented. Herein, we present a non-local multi-atlas framework that robustly identifies the spinal cord and segments its internal structure with submillimetric accuracy. The proposed algorithm couples non-local fusion with a large number of slice-based atlases (as opposed to typical volumetric ones). To improve performance, the fusion process is interwoven with registration so that segmentation information guides registration and vice versa. We demonstrate statistically significant improvement over state-of-the-art benchmarks in a study of 67 patients. The primary contributions of this work are (1) innovation in non-volumetric atlas information, (2) advancement of label fusion theory to include iterative registration/segmentation, and (3) the first fully automated segmentation algorithm for spinal cord internal structure on MRI. C1 [Asman, Andrew J.; Landman, Bennett A.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Smith, Seth A.; Landman, Bennett A.] Vanderbilt Univ, Inst Imaging Sci, Nashville, TN 37235 USA. [Reich, Daniel S.] Natl Inst Hlth, Translat Neuroradiol Unit, Bethesda, MD 37235 USA. RP Asman, AJ (reprint author), Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. EM andrew.j.asman@vanderbilt.edu; seth.smith@vanderbilt.edu; daniel.reich@nih.gov; bennett.landman@vanderbilt.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU NIH [1R21NS064534, 1R03EB012461, 2R01EB006136, R01EB006193]; NIH/NINDS Intramural Research Program FX Supported in part by NIH 1R21NS064534, 1R03EB012461, 2R01EB006136, R01EB006193, and the NIH/NINDS Intramural Research Program. NR 18 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-40811-3; 978-3-642-40810-6 J9 LECT NOTES COMPUT SC PY 2013 VL 8149 BP 759 EP 767 PG 9 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA2DH UT WOS:000333330700095 ER PT J AU Khare, R Li, J Lu, ZY AF Khare, Ritu Li, Jiao Lu, Zhiyong GP IEEE TI Toward Creating a Gold Standard of Drug Indications from FDA Drug Labels SO 2013 IEEE INTERNATIONAL CONFERENCE ON HEALTHCARE INFORMATICS (ICHI 2013) LA English DT Proceedings Paper CT 1st IEEE International Conference on Healthcare Informatics (ICHI) CY SEP 09-11, 2013 CL Philadelphia, PA SP IEEE, IEEE Comp Soc DE annotation; drug indication; expert curation; gold standard AB Having quick access to trustworthy drug-disease relationships (which drug(s) are approved for treating or preventing which disease(s)) is one of the top information needs of health providers, consumers, and researchers. This paper presents a semi-automatic approach that can lead to the creation of a gold standard of drugs and their indications. As our system input, we use the DailyMed, which houses the most current drug labels submitted to FDA by pharmaceutical companies. Extraction of specific indications from FDA labels is a challenging problem that requires distinguishing indications from other disease mentions. In response, we first identify the candidate indications from drug labels using UMLS resources and BioNLP tools, and then rely on expert judgments to validate those pre-computed indications through an interactive Web interface. For preliminary analysis, we recruited two experts to manually annotate 100 labels of frequently sought human prescription drugs at PubMed Health. We find that the resultant expert-curated gold standard on drugs and their indications is high-quality (precision=97%, recall=94%), and differs from existing resources in that it is factual, structured, and dose-form specific. The study findings suggest the feasibility of the proposed method toward building a comprehensive resource of drug indications. C1 [Khare, Ritu; Lu, Zhiyong] US Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Li, Jiao] Chinese Acad Med Sci, Inst Med Informat, Beijing 100020, Peoples R China. RP Khare, R (reprint author), US Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM ritu.khare@nih.gov; li.jiao@imicams.ac.cn; zhiyong.lu@nih.gov RI Lu, Zhiyong/H-3622-2016 OI Lu, Zhiyong/0000-0001-9998-916X FU NIH; National Library of Medicine; National Key Technology R&D Program of China [2013BAI06B01] FX This research was supported by the Intramural Research Program of the NIH, National Library of Medicine, the National Key Technology R&D Program of China (Grant No. 2013BAI06B01), and the Peking Union Medical College Youth Fund. The authors would like to thank the two human annotators, Zanmei Li and Yujing Ji. NR 14 TC 1 Z9 1 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-0-7695-5089-3 PY 2013 BP 30 EP 35 DI 10.1109/ICHI.2013.11 PG 6 WC Medical Informatics SC Medical Informatics GA BA1QP UT WOS:000332894400004 ER PT J AU Borovikov, E Vajda, S Lingappa, G Antani, S Thoma, G AF Borovikov, Eugene Vajda, Szilard Lingappa, Girish Antani, Sameer Thoma, George GP IEEE TI Face matching for post-disaster family reunification SO 2013 IEEE INTERNATIONAL CONFERENCE ON HEALTHCARE INFORMATICS (ICHI 2013) LA English DT Proceedings Paper CT 1st IEEE International Conference on Healthcare Informatics (ICHI) CY SEP 09-11, 2013 CL Philadelphia, PA SP IEEE, IEEE Comp Soc ID RAPID OBJECT DETECTION AB The National Library of Medicine (NLM) has developed People Locator (TM)(PL), a Web-based system for family reunification in cases of a natural or man-made disaster. PL accepts photos and brief text meta-data (name, age, etc.) of missing or found persons. Searchers may query PL with text information, but text data is often incomplete or inconsistent. Adding an image-based search capability, i.e., matching faces in query photos to those already stored in the system, would significantly benefit the user experience. We report on our face matching R&D that aims to provide robust face localization and matching on digital photos of variable quality. In this article, we review relevant research and present our approach to robust near-duplicate image detection as well as face matching. We describe the integration of our face matching system with PL, report on its performance, and compare it to other publicly available face recognition systems. In contrast to these systems that have many good quality well-illuminated sample images for each person, our algorithms are hampered by the lack of training examples for individual faces, as those are unlikely in a disaster setting. C1 [Borovikov, Eugene; Vajda, Szilard; Lingappa, Girish; Antani, Sameer; Thoma, George] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. RP Borovikov, E (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20892 USA. EM FaceMatch@NIH.gov OI Antani, Sameer/0000-0002-0040-1387 NR 36 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-0-7695-5089-3 PY 2013 BP 131 EP 140 DI 10.1109/ICHI.2013.23 PG 10 WC Medical Informatics SC Medical Informatics GA BA1QP UT WOS:000332894400016 ER PT J AU Xue, ZY Antan, S Long, LR Demner-Fushman, D Thoma, GR AF Xue, Zhiyun Antan, Sameer Long, L. Rodney Demner-Fushman, Dina Thoma, George R. GP IEEE TI Classification of CT figures in biomedical articles based on body segments SO 2013 IEEE INTERNATIONAL CONFERENCE ON HEALTHCARE INFORMATICS (ICHI 2013) LA English DT Proceedings Paper CT 1st IEEE International Conference on Healthcare Informatics (ICHI) CY SEP 09-11, 2013 CL Philadelphia, PA SP IEEE, IEEE Comp Soc DE figure classification; content-based image retrieval; CT image classification; biomedical article retrieval ID FEATURES; RETRIEVAL AB Figures in biomedical articles provide important information that can be utilized to enrich user experience in biomedical article retrieval. One method to improve retrieval performance is to categorize figures into various modalities. We have previously used a hierarchical classification strategy that significantly improves retrieval performance. In this paper, we extend the hierarchy and add body segment classification, i.e., classifying the figures in CT (computed tomography) modality into different body segments, such as head, abdomen, pelvis, or thorax. To address the large variety of article images, we extracted a wide set of feature types (feature vector length of 2321) and applied a multi-class SVM classifier. Feature selection was applied to reduce the feature vector to length 50. Evaluation of the proposed method on a dataset consisting of 2465 figures from a subset of open access biomedical articles from the National Library of Medicine's (NLM) Pub Med Central repository achieves classification accuracy of over 90%. This demonstrates its effectiveness and potential to become a vital component in biomedical document retrieval systems such as OpenI, a multimodal biomedical literature search system developed at NLM. C1 [Xue, Zhiyun; Antan, Sameer; Long, L. Rodney; Demner-Fushman, Dina; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Xue, ZY (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-0-7695-5089-3 PY 2013 BP 264 EP 268 DI 10.1109/ICHI.2013.17 PG 5 WC Medical Informatics SC Medical Informatics GA BA1QP UT WOS:000332894400032 ER PT B AU Hook, SS Farrell, D Hinkal, GW Ptak, K Grodzinski, P Panaro, NJ AF Hook, Sara S. Farrell, Dorothy Hinkal, George W. Ptak, Krzystzof Grodzinski, Piotr Panaro, Nicholas J. BE Liang, XJ TI Innovative Treatments for Cancer: The Impact of Delivering siRNAs, Chemotherapies, and Preventative Agents Using Nanoformulations SO NANOPHARMACEUTICS: THE POTENTIAL APPLICATION OF NANOMATERIALS LA English DT Article; Book Chapter DE Cancer; nanotechnology; siRNA; neutraceuticals; vaccine; chemotherapeutics ID METASTATIC BREAST-CANCER; LIPOSOME-ENCAPSULATED DOXORUBICIN; MESOPOROUS SILICA NANOPARTICLES; CHRONIC MYELOID-LEUKEMIA; CONVENTIONAL DOXORUBICIN; PROSTATE-CANCER; REDUCED CARDIOTOXICITY; 1ST-LINE TREATMENT; MULTICENTER TRIAL; CARBON NANOTUBES AB A multi-disciplinary approach to research epitomized by the emerging field of cancer nanotechnology can catalyze scientific developments and enable clinical translation beyond what we currently utilize. Engineers, chemists, and physical scientists are teaming up with cancer biologists and clinical oncologists to attack the vast array of cancer malignancies using materials at the nanoscale. We discuss how nanoformulations are enabling the targeted, efficient, delivery of not only genetic therapies such silencing RNAs, but also conventional cytotoxic agents and small molecules which results in decreased systemic toxicity and improved therapeutic index. As preventative approaches, there are various imaging agents and devices are being developed for screening purposes as well as new formulations of sunscreens, neutraceuticals, and cancer vaccines. The goal then of incorporating nanotechnology into clinical applications is to achieve new and more effective ways of diagnosing, treating, and preventing cancer to ultimately change the lives of patients worldwide. C1 [Hook, Sara S.; Farrell, Dorothy; Hinkal, George W.; Ptak, Krzystzof; Grodzinski, Piotr] NCI, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. [Panaro, Nicholas J.] NCI Frederick, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA. RP Grodzinski, P (reprint author), NCI, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. EM grodzinp@mail.nih.gov NR 53 TC 0 Z9 0 U1 0 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4368-67-4; 978-981-4368-66-7 PY 2013 BP 1 EP 19 PG 19 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Materials Science, Biomaterials; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Materials Science; Pharmacology & Pharmacy GA BA2AS UT WOS:000333214900002 ER PT B AU Xu, Y Jia, L AF Xu, Yan Jia, Lee BE Liang, XJ TI Nanoscaled Proteomic Analysis SO NANOPHARMACEUTICS: THE POTENTIAL APPLICATION OF NANOMATERIALS LA English DT Article; Book Chapter DE Nanoproteomics; proteomics; analytical technologies; nanomaterials; gold nanoparticles; single-walled carbon nanotubes; multiple-walled carbon nanotubes; MALDI-TOF-MS ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; CYSTEINE-CONTAINING PEPTIDES; CARBON NANOTUBES; GOLD NANOPARTICLES; LIQUID-CHROMATOGRAPHY; CAPILLARY-ELECTROPHORESIS; ENERGY-TRANSFER; POLYMERIC NANOPARTICLES; MAGNETIC NANOPARTICLES; PROTEIN ADSORPTION AB Global proteomics research is currently hampered by the extremely complexity of the proteome and the absence of techniques like the polymerase chain reaction in genomics which enables multiplication of a single protein molecule. Since all the existing analytical technologies cannot overcome the detection limit and the dynamic concentration barrier, development of improved analytical technologies at nanoscale, ideally those that could recognize single protein molecule in the presence of high abundant of others, is a high priority for proteomics. In this chapter, we will show the state-of-the-art of nanoproteomics, i.e., the application of nanotechnologies to proteomics. Various nanomaterials including carbon nanomaterials, magnetic nanoparticles, silica nanoparticles, polymer and copolymer nanoparticles, metal and metal oxide nanoparticles have been used to improve sensitivity, specificity, and repeatability of proteomic analysis especially when the multidimensional separation system coupled with MALDI-TOF-MS is used. Among them, gold nanoparticles (GNPs) and carbon nanotubes (CNTs) are the two most important nanomaterials: while GNPs are frequently utilized for enzyme immobilization, high throughput bioassay, selection of target-peptides and target-protein, CNTs including single-walled carbon nanotubes (SWCNTs) and mutiple-walled carbon nanotubes (MWCNTs) have wide applications to electronic sensor, sensitive immunodetection, nanobiocatalysis, affinity probes, MALDI matrices, protein digestion, peptides enrichment and analysis. In perspectives, a deep understanding of the structures and property of nanomaterials and interdisciplinary applications of nanotechnology to proteomics will certainly be revolutionary and intellectually rewarding. C1 [Xu, Yan] UCLA Olymp Analyt Lab, Los Angeles, CA USA. [Jia, Lee] NCI, Dev Therapeut Program, DCTD, NIH, Bethesda, MD 20892 USA. RP Xu, Y (reprint author), UCLA Olymp Analyt Lab, Los Angeles, CA USA. EM yanxu@mednet.ucla.edu NR 91 TC 0 Z9 0 U1 1 U2 5 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4368-67-4; 978-981-4368-66-7 PY 2013 BP 65 EP 81 PG 17 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Materials Science, Biomaterials; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Materials Science; Pharmacology & Pharmacy GA BA2AS UT WOS:000333214900005 ER PT B AU Gupta, K Yavlovich, A Puri, A Blumenthal, R AF Gupta, Kshitij Yavlovich, Amichai Puri, Anu Blumenthal, Robert BE Liang, XJ TI Tumor Targeting Potential of Lipid-Based Nano-Pharmaceuticals (LNPs) SO NANOPHARMACEUTICS: THE POTENTIAL APPLICATION OF NANOMATERIALS LA English DT Article; Book Chapter DE Lipid-based nanoparticles; drug delivery; tumor cell surface targeting; tumor vasculature targeting ID RECEPTOR-MEDIATED ENDOCYTOSIS; LONG-CIRCULATING LIPOSOMES; STERICALLY STABILIZED LIPOSOMES; SINGLE-CHAIN FV; FOLATE-CONJUGATED LIPOSOMES; LARGE UNILAMELLAR LIPOSOMES; HUMAN-LEUKEMIA CELLS; IN-VIVO; DRUG-DELIVERY; MONOCLONAL-ANTIBODY AB Nanoparticle-mediated targeted drug delivery has become the modality of interest for cancer/tumor therapy as it reduces the undesirable delivery to normal cells and improves efficacy of the pharmaceuticals. Among all the nanosystems, lipid-based nano-pharmaceuticals (LNPs) have been most extensively studied for cancer therapy. Doxil formulation was the first LNP that has been approved for cancer treatment. When conjugated with ligands, LNPs can be targeted to tumor cells. This chapter focuses on the targeting potential of LNPs for cancer therapy. We will discuss the advantages of enhanced permeability and retention (EPR) effect (passive targeting) for preferential tumor accumulation of LNPs, the importance of pegylation to avoid reticulo-endothelial system uptake and active targeting strategies using various targeting ligands that can be coupled to the LNP surface to target the tumor region (tumor cells/tumor vasculature). Targeted LNPs show higher binding affinity, greater intracellular localization and thereby increased cancer cell killing in comparison to non targeted LNPs. However, contrasting reports exist that pose challenges to the notion that targeted LNPs are advantageous. Recent trends have also demonstrated the concept of dual targeting that simultaneously homes LNPs to receptors on the tumor cells and biomarkers expressed on the tumor vasculature. In addition, targeting with multiple ligands on the LNPs has also been explored. These approaches may prove to be a better answer for next generation of LNPs for delivery of anti-cancer agents. However, more extensive studies are required to get their clinical approval in anti-cancer therapy. C1 [Gupta, Kshitij; Yavlovich, Amichai; Puri, Anu; Blumenthal, Robert] Frederick Natl Lab Canc Res, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD USA. RP Blumenthal, R (reprint author), Frederick Natl Lab Canc Res, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD USA. EM blumenthalr@mail.nih.gov NR 156 TC 0 Z9 0 U1 1 U2 4 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4368-67-4; 978-981-4368-66-7 PY 2013 BP 83 EP 113 PG 31 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Materials Science, Biomaterials; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Materials Science; Pharmacology & Pharmacy GA BA2AS UT WOS:000333214900006 ER PT B AU Shan, L Gu, XB Wang, P AF Shan, Liang Gu, Xinbin Wang, Paul BE Liang, XJ TI Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging SO NANOPHARMACEUTICS: THE POTENTIAL APPLICATION OF NANOMATERIALS LA English DT Article; Book Chapter DE MRI (magnetic resonance imaging); nanoparticle; molecular imaging ID IRON-OXIDE NANOPARTICLES; POSITRON-EMISSION-TOMOGRAPHY; TRANSFERRIN RECEPTOR GENE; IN-VIVO; BREAST-CANCER; TUMOR MICROENVIRONMENT; DRUG DEVELOPMENT; CELL TRACKING; RGD PEPTIDES; THERAPY AB Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, http://www.ncbi.nlm.nih.gov/books/NBK5330/), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI. C1 [Shan, Liang; Wang, Paul] Howard Univ, Dept Radiol, Mol Imaging Lab, Washington, DC 20059 USA. [Shan, Liang] NIH, MICAD, Bethesda, MD USA. [Gu, Xinbin] Howard Univ, Dept Oral Diagnost Serv, Washington, DC USA. RP Wang, P (reprint author), Howard Univ, Dept Radiol, Mol Imaging Lab, Washington, DC 20059 USA. EM pwang@howard.edu NR 95 TC 0 Z9 0 U1 0 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4368-67-4; 978-981-4368-66-7 PY 2013 BP 275 EP 292 PG 18 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Materials Science, Biomaterials; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Materials Science; Pharmacology & Pharmacy GA BA2AS UT WOS:000333214900012 ER PT B AU Yin, JJ Zhao, BZ Xia, QS Fu, PP AF Yin, Jun-Jie Zhao, Baozhong Xia, Qingsu Fu, Peter P. BE Liang, XJ TI Electron Spin Resonance Spectroscopy for Studying the Generation and Scavenging of Reactive Oxygen Species by Nanomaterials SO NANOPHARMACEUTICS: THE POTENTIAL APPLICATION OF NANOMATERIALS LA English DT Article; Book Chapter DE Electron spin resonance; nanomaterials; reactive oxygen species; free radical ID SINGLET OXYGEN; LIPID-PEROXIDATION; OXIDATIVE STRESS; FREE-RADICALS; CONCENTRATION PRODUCTS; POLYHYDROXYLATED C-60; UVA PHOTOIRRADIATION; WHEAT ANTIOXIDANTS; CANCER-THERAPY; IN-VITRO AB One fundamental mechanism widely described for nanotoxicity involves oxidative damage due to generation of free radicals and other reactive oxygen species. Indeed, the ability of nanoscale materials to facilitate the transfer of electrons, and thereby promote oxidative damage or in some instances provide antioxidant protection, may be a fundamental property of these materials. Any assessment of a nanoscale material's safety must therefore consider the potential for toxicity arising from oxidative damage. Therefore, rapid and predictive methods are needed to assess oxidative damage elicited by nanoscale materials. The use of electron spin resonance (ESR) to study free radical related bioactivity of nanomaterials has several advantages for free radical determination and identification. Specifically it can directly assess antioxidant quenching or prooxidant generation of relevant free radicals and reactive oxygen species. In this chapter, we have reported some nonclassical behaviors of the electron spin relaxation properties of unpaired electrons in different fullerenes and the investigation of anti/prooxidant activity by various types of nanomaterials using ESR. In addition, we have reviewed the mechanisms of free radical formation photosensitized by different nanomaterials. This chapter also included the use of spin labels, spin traps and ESR oximetry to systematically examine the enzymatic mimetic activities of nanomaterials. C1 [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Zhao, Baozhong; Fu, Peter P.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. [Xia, Qingsu] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM junjie.yin@fda.hhs.gov NR 86 TC 1 Z9 1 U1 0 U2 4 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4368-67-4; 978-981-4368-66-7 PY 2013 BP 375 EP 400 PG 26 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Materials Science, Biomaterials; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Materials Science; Pharmacology & Pharmacy GA BA2AS UT WOS:000333214900015 ER PT J AU Scott, DA Mills, M Black, A Cantwell, M Campbell, A Cardwell, CR Porter, S Donnelly, M AF Scott, David A. Mills, Moyra Black, Amanda Cantwell, Marie Campbell, Anna Cardwell, Chris R. Porter, Sam Donnelly, Michael TI Multidimensional rehabilitation programmes for adult cancer survivors SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; INCREASE PHYSICAL-ACTIVITY; BASE-LINE CHARACTERISTICS; ACTIVE-FOR-LIFE; PROSTATE-CANCER; FRESH START; SELF-MANAGEMENT; PROJECT LEAD AB Background Multidimensional rehabilitation programmes (MDRPs) have developed in response to the growing number of people living with and surviving cancer. MDRPs comprise a physical component and a psychosocial component. Studies of the effectiveness of these programmes have not been reviewed and synthesised. Objectives To conduct a systematic review of studies examining the effectiveness of MDRPs in terms of maintaining or improving the physical and psychosocial well-being of adult cancer survivors. Search methods We conducted electronic searches in theCochraneCentralRegister ofControlledTrials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsychINFO up to February 2012. Selection criteria Selection criteria focused on randomised controlled trials (RCTs) of multidimensional interventions for adult cancer survivors. Interventions had to include a physical component and a psychosocial component and to have been carried out on two or more occasions following completion of primary cancer treatment. Outcomes had to be assessed using validated measures of physical health and psychosocial well-being. Non-English language papers were included. Data collection and analysis Pairs of review authors independently selected trials, rated their methodological quality and extracted relevant data. Although meta-analyses of primary and secondary endpoints were planned there was a high level of study heterogeneity and only one common outcome measure (SF-36) could be statistically synthesised. In addition, we conducted a narrative analysis of interventions, particularly in terms of inspecting and identifying intervention components, grouping or categorising interventions and examining potential common links and outcomes. Main results Twelve RCTs (comprising 1669 participants) met the eligibility criteria. We judged five studies to have a moderate risk of bias and assessed the remaining seven as having a high risk of bias. It was possible to include SF-36 physical health component scores from five studies in a meta-analysis. Participating in a MDRP was associated with an increase in SF-36 physical health component scores (mean difference (MD) 2.22, 95% confidence interval (CI) 0.12 to 4.31, P = 0.04). The findings from the narrative analysis suggested that MDRPs with a single domain or outcome focus appeared to be more successful than programmes with multiple aims. In addition, programmes that comprised participants with different types of cancer compared to cancer site-specific programmes were more likely to show positive improvements in physical outcomes. The most effective mode of service delivery appeared to be face-to-face contact supplemented with at least one follow-up telephone call. There was no evidence to indicate that MDRPs which lasted longer than six months improved outcomes beyond the level attained at six months. In addition, there was no evidence to suggest that services were more effective if they were delivered by a particular type of health professional. Authors' conclusions There is some evidence to support the effectiveness of brief, focused MDRPs for cancer survivors. Rigorous and methodologically sound clinical trials that include an economic analysis are required. C1 [Scott, David A.] Queens Univ Belfast, Ctr Hlth Improvement, Belfast BT9 7BL, Antrim, North Ireland. [Mills, Moyra] Northern Hlth & Social Care Trust, Ballymena, Antrim, North Ireland. [Black, Amanda] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Cantwell, Marie] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Publ Hlth, Canc Epidemiol & Hlth Serv Res Grp, Belfast BT9 7BL, Antrim, North Ireland. [Campbell, Anna] Univ Dundee, Inst Sport & Exercise, Dundee, Scotland. [Cardwell, Chris R.; Donnelly, Michael] Queens Univ Belfast, Ctr Publ Hlth, Belfast BT9 7BL, Antrim, North Ireland. [Porter, Sam] Queens Univ Belfast, Sch Nursing & Midwifery, Belfast BT9 7BL, Antrim, North Ireland. RP Scott, DA (reprint author), Queens Univ Belfast, Ctr Med Biol, Ctr Hlth Improvement, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland. EM david.scott@qub.ac.uk OI Cardwell, Chris/0000-0002-2689-4335 FU RD Office NI, UK; NI Public Health Agency Health and Social Care Research and Development Division Cochrane Review Training Fellowship; Cochrane Fellowship FX MM was funded via a NI Public Health Agency Health and Social Care Research and Development Division Cochrane Review Training Fellowship. DS conducted the final searches and completed the review. DS, MM, MB, AC, CC, KG and MD were involved in the development of the review and in pairs they identified eligible studies, conducted quality assessments of eligible studies and extracted data from the original studies. CC provided statistical advice. MD supervised the conduct and completion of the review.; External sources; R&D Office NI, UK. Two-year Cochrane Fellowship NR 76 TC 8 Z9 8 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2013 IS 3 AR CD007730 DI 10.1002/14651858.CD007730.pub2 PG 47 WC Medicine, General & Internal SC General & Internal Medicine GA 116MC UT WOS:000316885700008 PM 23543556 ER PT J AU Roche, B Rohani, P Dobson, AP Guegan, JF AF Roche, Benjamin Rohani, Pejman Dobson, Andy P. Guegan, Jean-Francois TI The Impact of Community Organization on Vector-Borne Pathogens SO AMERICAN NATURALIST LA English DT Article DE community epidemiology; emerging vector-borne diseases; community ecology; mathematical modeling ID WEST-NILE-VIRUS; LYME-DISEASE RISK; INFECTIOUS-DISEASES; BIODIVERSITY; TRANSMISSION; ECOLOGY; CALIFORNIA; DIVERSITY; EMERGENCE; POPULATION AB Vector-borne zoonotic disease agents, which are known to often infect multiple species in the wild, have been identified as an emerging threat to human health. Understanding the ecology of these pathogens is especially timely, given the continued anthropogenic impacts on biodiversity. Here, we integrate empirical scaling laws from community ecology within a theoretical reservoir-vector-pathogen framework to study the transmission consequences of host community structure and diversity within large assemblages. We show that heterogeneity in susceptibility of the reservoir species promotes transmission "dilution," while a greater vector species richness "amplifies" it. These contrasting transmission impacts of vector and reservoir communities can yield very different epidemiological patterns. We demonstrate that vector and reservoir species richness can explain per se most of the pathogen transmission observed for West Nile virus in different parts of the United States, giving empirical support for the validity of these opposing theoretically predicted effects. We conclude that, in the context of disease emergence, the integration of a community perspective can provide critical insights into the understanding of pathogen transmission in wildlife. C1 [Roche, Benjamin] Ctr IRD France, IRD UPMC 209, UMI, Unite Modelisat Math & Informat Syst Complexes UM, F-93143 Bondy, France. [Roche, Benjamin; Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [Roche, Benjamin; Guegan, Jean-Francois] Univ Montpellier I, Ctr IRD Montpellier, CNRS, IRD,Unite Mixte Rech UMR Malad Infect & Vecteurs, F-34394 Montpellier 5, France. [Roche, Benjamin; Guegan, Jean-Francois] Univ Montpellier 2, Ctr IRD Montpellier, CNRS, IRD,Unite Mixte Rech UMR Malad Infect & Vecteurs, F-34394 Montpellier 5, France. [Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. [Dobson, Andy P.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Guegan, Jean-Francois] French Sch Publ Hlth, Interdisciplinary Ctr Biodivers Climate Change &, Montpellier, France. RP Roche, B (reprint author), Ctr IRD France, IRD UPMC 209, UMI, Unite Modelisat Math & Informat Syst Complexes UM, F-93143 Bondy, France. EM benjamin.roche@ird.fr OI Roche, Benjamin/0000-0001-7975-4232; Dobson, Andy/0000-0002-9678-1694 FU Institut de Recherche pour le Developpement; CNRS; French School of Public Health; EU [GOCE2003010284 EDEN]; Laboratoire d'Excellence Centre d'Etude de la Biodiversite Amazonienne [ANR-10-LABX-25-01]; Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX We sincerely acknowledge the reviewers and the many colleagues who reviewed and improved the manuscript. In particular, we thank T. Ben Ari, M. Choisy, J. Drake, C. Lebarbenchon, K. Magori, and A. Park as well as the Rohani and King laboratories at the University of Michigan for their helpful comments. B. R. and J.-F.G. are sponsored by the Institut de Recherche pour le Developpement, CNRS, and the French School of Public Health and acknowledge support from the EDEN (Emerging Diseases in a Changing European Environment) project (EU grant GOCE2003010284 EDEN). This publication is cataloged by the EDEN Steering Committee as EDEN089 (http://www.eden-fp6project.net/). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. This work is a contribution from the DIVERSITAS-EcoHealth Alliance-ecoHEALTH research working group. J.-F.G. is supported by Laboratoire d'Excellence Centre d'Etude de la Biodiversite Amazonienne (grant ANR-10-LABX-25-01). P. R. is supported by the Research and Policy in Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security, and by the Fogarty International Center, National Institutes of Health. NR 43 TC 21 Z9 21 U1 6 U2 138 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0003-0147 EI 1537-5323 J9 AM NAT JI Am. Nat. PD JAN PY 2013 VL 181 IS 1 BP 1 EP 11 DI 10.1086/668591 PG 11 WC Ecology; Evolutionary Biology SC Environmental Sciences & Ecology; Evolutionary Biology GA 055VI UT WOS:000312445500004 PM 23234841 ER PT J AU Acker, MA Pagani, FD Stough, WG Mann, DL Jessup, M Kormos, R Slaughter, MS Baldwin, T Stevenson, L Aaronson, KD Miller, L Naftel, D Yancy, C Rogers, J Teuteberg, J Starling, RC Griffith, B Boyce, S Westaby, S Blume, E Wearden, P Higgins, R Mack, M AF Acker, Michael A. Pagani, Francis D. Stough, Wendy Gattis Mann, Douglas L. Jessup, Mariell Kormos, Robert Slaughter, Mark S. Baldwin, Timothy Stevenson, Lynne Aaronson, Keith D. Miller, Leslie Naftel, David Yancy, Clyde Rogers, Joseph Teuteberg, Jeffrey Starling, Randall C. Griffith, Bartley Boyce, Steven Westaby, Stephen Blume, Elizabeth Wearden, Peter Higgins, Robert Mack, Michael TI Statement Regarding the Pre and Post Market Assessment of Durable, Implantable Ventricular Assist Devices in the United States: Executive Summary SO CIRCULATION-HEART FAILURE LA English DT Article DE AHA Scientific Statements; heart-assist device; heart failure ID CLINICAL-TRIAL DESIGN; CARDIOVASCULAR DEVICES; MEDICAL DEVICES; HEART-FAILURE; SURVEILLANCE; SUPPORT; FDA AB The incorporation of complex medical device tech-nologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients with advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and the Interagency Registry of Mechanically Assisted Circulatory Support. C1 [Acker, Michael A.] Univ Penn, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. [Pagani, Francis D.] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. [Stough, Wendy Gattis] Campbell Univ Coll Pharm & Hlth Sci, Buies Creek, NC USA. [Mann, Douglas L.] Washington Univ, Cardiovasc Div, St Louis, MO USA. [Jessup, Mariell] Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Kormos, Robert] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Slaughter, Mark S.] Univ Louisville, Div Cardiothorac Surg, Louisville, KY 40292 USA. [Baldwin, Timothy] NHLBI, Bethesda, MD 20892 USA. [Stevenson, Lynne] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Aaronson, Keith D.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Miller, Leslie] Univ S Florida, Dept Cardiovasc Sci, Tampa, FL USA. [Naftel, David] Univ Alabama Birmingham, Dept Cardiothorac Surg, Birmingham, AL USA. [Yancy, Clyde] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA. [Rogers, Joseph] Duke Univ, Div Cardiol, Durham, NC USA. [Teuteberg, Jeffrey] Univ Pittsburgh Med Ctr, Inst Heart & Vasc, Pittsburgh, PA USA. [Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA. [Griffith, Bartley] Univ Maryland, Div Cardiac Surg, Baltimore, MD 21201 USA. [Boyce, Steven] Washington Hosp Ctr, MedStar Heart Inst, Dept Cardiac Surg, Washington, DC 20010 USA. [Westaby, Stephen] John Radcliffe Hosp, Oxford Heart Ctr, Oxford OX3 9DU, England. [Blume, Elizabeth] Bostons Childrens Hosp, Dept Cardiol, Boston, MA USA. [Wearden, Peter] Childrens Hosp Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA 15213 USA. [Higgins, Robert] Ohio State Univ, Div Cardiac Surg, Columbus, OH 43210 USA. [Mack, Michael] Med City Dallas Hosp, Dallas, TX USA. RP Acker, MA (reprint author), Hosp Univ Penn, 3400 Spruce St,6 Silverstein Pavil, Philadelphia, PA 19104 USA. EM michael.acker@uphs.upenn.edu RI Stough, Wendy/R-4287-2016; OI Stough, Wendy/0000-0001-8290-1205; Mann, Douglas /0000-0002-2516-0145 NR 14 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2013 VL 6 IS 1 BP 145 EP 150 DI 10.1161/HHF.0b013e318279f55d PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA8YI UT WOS:000331380500024 PM 23149496 ER PT J AU Acker, MA Pagani, FD Stough, WG Mann, DL Jessup, M Kormos, R Slaughter, MS Baldwin, T Stevenson, L Aaronson, KD Miller, L Naftel, D Yancy, C Rogers, J Teuteberg, J Starling, RC Griffith, B Boyce, S Westaby, S Blume, E Wearden, P Higgins, R Mack, M AF Acker, Michael A. Pagani, Francis D. Stough, Wendy Gattis Mann, Douglas L. Jessup, Mariell Kormos, Robert Slaughter, Mark S. Baldwin, Timothy Stevenson, Lynne Aaronson, Keith D. Miller, Leslie Naftel, David Yancy, Clyde Rogers, Joseph Teuteberg, Jeffrey Starling, Randall C. Griffith, Bartley Boyce, Steven Westaby, Stephen Blume, Elizabeth Wearden, Peter Higgins, Robert Mack, Michael TI Statement Regarding the Pre and Post Market Assessment of Durable, Implantable Ventricular Assist Devices in the United States SO CIRCULATION-HEART FAILURE LA English DT Article DE AHA Scientific Statements; heart-assist device; heart failure ID ADVANCED HEART-FAILURE; INTERMACS ANNUAL-REPORT; CLINICAL-TRIAL DESIGN; CONTINUOUS-FLOW; CARDIOVASCULAR DEVICES; MEDICAL DEVICES; CARDIAC-RESYNCHRONIZATION; DESTINATION THERAPY; SUPPORT; OUTCOMES AB The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients who have advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and Interagency Registry of Mechanically Assisted Circulatory Support. C1 [Acker, Michael A.] Univ Penn, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. [Pagani, Francis D.] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. [Stough, Wendy Gattis] Campbell Univ Coll Pharm & Hlth Sci, Buies Creek, NC USA. [Mann, Douglas L.] Washington Univ, Cardiovasc Div, St Louis, MO USA. [Jessup, Mariell] Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Kormos, Robert] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Slaughter, Mark S.] Univ Louisville, Div Cardiothorac Surg, Louisville, KY 40292 USA. [Baldwin, Timothy] NHLBI, Bethesda, MD 20892 USA. [Stevenson, Lynne] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Aaronson, Keith D.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Miller, Leslie] Univ S Florida, Dept Cardiovasc Sci, Tampa, FL USA. [Naftel, David] Univ Alabama Birmingham, Dept Cardiothorac Surg, Birmingham, AL USA. [Yancy, Clyde] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA. [Rogers, Joseph] Duke Univ, Div Cardiol, Durham, NC USA. [Teuteberg, Jeffrey] Univ Pittsburgh Med Ctr, Inst Heart & Vasc, Pittsburgh, PA USA. [Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA. [Griffith, Bartley] Univ Maryland, Div Cardiac Surg, Baltimore, MD 21201 USA. [Boyce, Steven] Washington Hosp Ctr, MedStar Heart Inst, Dept Cardiac Surg, Washington, DC 20010 USA. [Westaby, Stephen] John Radcliffe Hosp, Oxford Heart Ctr, Oxford OX3 9DU, England. [Blume, Elizabeth] Bostons Childrens Hosp, Dept Cardiol, Boston, MA USA. [Wearden, Peter] Childrens Hosp Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA 15213 USA. [Higgins, Robert] Ohio State Univ, Div Cardiac Surg, Columbus, OH 43210 USA. [Mack, Michael] Med City Dallas Hosp, Dallas, TX USA. RP Acker, MA (reprint author), Hosp Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA. EM michael.acker@uphs.upenn.edu RI Stough, Wendy/R-4287-2016 OI Stough, Wendy/0000-0001-8290-1205 NR 36 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2013 VL 6 IS 1 BP E1 EP E11 DI 10.1161/HHF.0b013e318279f6b5 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA8YI UT WOS:000331380500001 PM 23149497 ER PT J AU Pongpiachan, S AF Pongpiachan, Siwatt TI Fingerprint of Carcinogenic Semi-Volatile Organic Compounds (SVOCs) during Bonfire Night SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE PAHs; alkanes; cholestanes; hopanes; bonfire night ID POLYCYCLIC AROMATIC-HYDROCARBONS; VOLUME AIR SAMPLER; VERTICAL-DISTRIBUTION; SOURCE APPORTIONMENT; PARTICLE; PARTICULATE; THAILAND; PHASE; URBAN; BIRMINGHAM AB It is well known that increased incidences of lung, skin, and bladder cancers are associated with occupational exposure to PAHs. Animal studies show that certain PAHs also can affect the hematopoietic and immune systems and can produce reproductive, neurologic, and developmental effects. As a consequence, several studies have been attempted to investigate the fate of PAHs in atmospheric environment during the past decades. However, there is still a lack of information in regard to the atmospheric concentration of PAHs during the "Bon Fire Night". In this study, twenty-three polycyclic aromatic hydrocarbons and twenty-eight aliphatics were identified and quantified in the PM10 and vapour range in Birmingham (27th November 2001-19th January 2004). The measured concentrations of total particulate and vapour (P+V) PAHs were consistently higher at the BROS in both winter and summer. Arithmetic mean total (P+V) PAH concentrations were 51.04+/-47.62 ng m(-3) and 22.30+/-19.18 ng m(-3) at the Bristol Road Observatory Site (BROS) and Elms Road Observatory Site (EROS) respectively. In addition arithmetic mean total (P+V) B[a]P concentrations at the BROS were 0.47+/-0.39 ng m(-3) which exceeded the EPAQS air quality standard of 0.25 ng m(-3). On the other hand, the arithmetic mean total (P+V) aliphatics were 81.80+/-69.58 ng m(-3) and 48.00+/-35.38 ng m(-3) at the BROS and EROS in that order. The lowest average of CPI and C-max measured at the BROS supports the idea of traffic emissions being a principle source of SVOCs in an urban atmosphere. The annual trend of PAHs was investigated by using an independent t-test and one-way independent ANOVA analysis. Generally, there is no evidence of a significant decline of heavier MW PAHs from the two data sets, with only Ac, Fl, Ph, An, 2-MePh, 1+9-MePh, Fluo and B[b+j+k]F showing a statistically significant decline (p<0.05). A further attempt for statistical analysis had been conducted by dividing the data set into three groups (i.e. 2000, 2001-2002 and 2003-2004). For lighter MW compounds a significant level of decline was observed by using one-way independent ANOVA analysis. Since the annual mean of O-3 measured in Birmingham City Centre from 2001 to 2004 increased significantly (p<0.05), it may be possible to attribute the annul reduction of more volatile PAHs to the enhanced level of annual average O-3. By contrast, the heavier MW PAHs measured at the BROS did not show any significant annual reduction, implying the difficulties of 5- and 6-ring PAHs to be subject to photochemical decomposition. The deviation of SVOCs profile measured at the EROS was visually confirmed during the "Bonfire Night" festival closest to the 6th November 2003. In this study, the atmospheric PAH concentrations were generally elevated on this day with concentrations of Fl, Ac, B[a]A, B[b+j+k]F, Ind and B[g,h,i]P being particularly high. C1 NIDA, Sch Social & Environm Dev, Ctr Res & Dev Disaster Prevent & Management, Bangkok, Thailand. RP Pongpiachan, S (reprint author), NIDA, Sch Social & Environm Dev, Ctr Res & Dev Disaster Prevent & Management, Bangkok, Thailand. EM pongpiajun@gmail.com NR 39 TC 0 Z9 0 U1 1 U2 14 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2013 VL 14 IS 5 BP 3243 EP 3254 DI 10.7314/APJCP.2013.14.5.3243 PG 12 WC Oncology SC Oncology GA AB0HU UT WOS:000331473400096 PM 23803111 ER PT J AU Pongpiachan, S Choochuay, C Chonchalar, J Kanchai, P Phonpiboon, T Wongsuesat, S Chomkhae, K Kittikoon, I Hiranyatrakul, P Cao, J Thamrongthanyawong, S AF Pongpiachan, Siwatt Choochuay, Chomsri Chonchalar, Jittiphan Kanchai, Panatda Phonpiboon, Tidarat Wongsuesat, Sornsawan Chomkhae, Kanokwan Kittikoon, Itthipon Hiranyatrakul, Phoosak Cao, Junji Thamrongthanyawong, Sombat TI Chemical Characterisation of Organic Functional Group Compositions in PM2.5 Collected at Nine Administrative Provinces in Northern Thailand during the Haze Episode in 2013 SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE PM2.5; FTIR; PCA; incremental lifetime exposure; northern provinces of Thailand ID POLYCYCLIC AROMATIC-HYDROCARBONS; VERTICAL-DISTRIBUTION; PARTICLE-SIZE; PAHS; FINE; POLLUTION; AEROSOLS; BANGKOK; RANGE; PHASE AB Along with rapid economic growth and enhanced agricultural productivity, particulate matter emissions in the northern cities of Thailand have been increasing for the past two decades. This trend is expected to continue in the coming decade. Emissions of particulate matter have brought about a series of public health concerns, particularly chronic respiratory diseases. It is well known that lung cancer incidence among northern Thai women is one of the highest in Asia (an annual age-adjusted incidence rate of 37.4 per 100,000). This fact has aroused serious concern among the public and the government and has drawn much attention and interest from the scientific community. To investigate the potential causes of this relatively high lung cancer incidence, this study employed Fourier transform infrared spectroscopy (FTIR) transmission spectroscopy to identify the chemical composition of the PM2.5 collected using Quartz Fibre Filters (QFFs) coupled with MiniVol (TM) portable air samplers (Airmetrics). PM2.5 samples collected in nine administrative provinces in northern Thailand before and after the "Haze Episode" in 2013 were categorised based on three-dimensional plots of a principal component analysis (PCA) with Varimax rotation. In addition, the incremental lifetime exposure to PM2.5 of both genders was calculated, and the first derivative of the FTIR spectrum of individual samples is here discussed. C1 [Pongpiachan, Siwatt; Choochuay, Chomsri; Chonchalar, Jittiphan; Kanchai, Panatda; Phonpiboon, Tidarat; Wongsuesat, Sornsawan; Thamrongthanyawong, Sombat] NIDA, Sch Social & Environm Dev, NIDA Res Ctr Disaster Prevent Management, Bethesda, MD 20892 USA. [Chomkhae, Kanokwan; Kittikoon, Itthipon; Hiranyatrakul, Phoosak] Bara Sci Co Ltd, Bangkok, Thailand. [Cao, Junji] Chinese Acad Sci IEECAS, SKLLQG, Inst Earth Environm, Xian, Peoples R China. RP Pongpiachan, S (reprint author), NIDA, Sch Social & Environm Dev, NIDA Res Ctr Disaster Prevent Management, Bethesda, MD 20892 USA. EM pongpiajun@gmail.com RI Cao, Junji/D-3259-2014 OI Cao, Junji/0000-0003-1000-7241 FU National Institute of Development Administration (NIDA) Research Center FX This project was financed by National Institute of Development Administration (NIDA) Research Center. The author acknowledges Assist. Prof. Dr. Torpong Kreetachart from School of Energy and Environment (SEEN), University of Phayao for their contributions on laboratory works. The authors thank the kind support from Pollution Control Department, Ministry of Natural Resources and Environment for providing meteorological data. NR 28 TC 4 Z9 4 U1 3 U2 40 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2013 VL 14 IS 6 BP 3653 EP 3661 DI 10.7314/APJCP.2013.14.6.3653 PG 9 WC Oncology SC Oncology GA AB0YG UT WOS:000331517700046 PM 23886161 ER PT S AU Collins, PL Fearns, R Graham, BS AF Collins, Peter L. Fearns, Rachel Graham, Barney S. BE Anderson, LJ Graham, BS TI Respiratory Syncytial Virus: Virology, Reverse Genetics, and Pathogenesis of Disease SO CHALLENGES AND OPPORTUNITIES FOR RESPIRATORY SYNCYTIAL VIRUS VACCINES SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID SMALL HYDROPHOBIC PROTEIN; REPLICATION IN-VITRO; TRANSCRIPTION ELONGATION-FACTOR; POLARIZED EPITHELIAL-CELLS; OPEN READING FRAME; M2 MESSENGER-RNA; NF-KAPPA-B; P-PROTEIN; VIRAL REPLICATION; MATRIX PROTEIN AB Human respiratory syncytial virus (RSV) is an enveloped, nonsegmented negative-strand RNA virus of family Paramyxoviridae. RSV is the most complex member of the family in terms of the number of genes and proteins. It is also relatively divergent and distinct from the prototype members of the family. In the past 30 years, we have seen a tremendous increase in our understanding of the molecular biology of RSV based on a succession of advances involving molecular cloning, reverse genetics, and detailed studies of protein function and structure. Much remains to be learned. RSV disease is complex and variable, and the host and viral factors that determine tropism and disease are poorly understood. RSV is notable for a historic vaccine failure in the 1960s involving a formalin-inactivated vaccine that primed for enhanced disease in RSV naive recipients. Live vaccine candidates have been shown to be free of this complication. However, development of subunit or other protein-based vaccines for pediatric use is hampered by the possibility of enhanced disease and the difficulty of reliably demonstrating its absence in preclinical studies. C1 [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Fearns, Rachel] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Room 6517,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. EM pcollins@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000372-25] NR 131 TC 29 Z9 29 U1 6 U2 18 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-38919-1; 978-3-642-38918-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 372 BP 3 EP 38 DI 10.1007/978-3-642-38919-1_1 D2 10.1007/978-3-642-38919-1 PG 36 WC Immunology; Respiratory System; Virology SC Immunology; Respiratory System; Virology GA BJU63 UT WOS:000330592500002 PM 24362682 ER PT S AU Anderson, LJ Graham, BS AF Anderson, Larry J. Graham, Barney S. BE Anderson, LJ Graham, BS TI Challenges and Opportunities for Respiratory Syncytial Virus Vaccines Preface SO CHALLENGES AND OPPORTUNITIES FOR RESPIRATORY SYNCYTIAL VIRUS VACCINES SE Current Topics in Microbiology and Immunology LA English DT Editorial Material; Book Chapter C1 [Anderson, Larry J.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Anderson, Larry J.] Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Anderson, LJ (reprint author), Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-38919-1; 978-3-642-38918-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 372 BP V EP VII D2 10.1007/978-3-642-38919-1 PG 3 WC Immunology; Respiratory System; Virology SC Immunology; Respiratory System; Virology GA BJU63 UT WOS:000330592500001 ER PT S AU McLellan, JS Ray, WC Peeples, ME AF McLellan, Jason S. Ray, William C. Peeples, Mark E. BE Anderson, LJ Graham, BS TI Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins SO CHALLENGES AND OPPORTUNITIES FOR RESPIRATORY SYNCYTIAL VIRUS VACCINES SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID SMALL HYDROPHOBIC PROTEIN; ANTIBODY-MEDIATED RESTRICTION; FUSION F GLYCOPROTEIN; REPLICATION IN-VITRO; 2 DISTINCT SITES; MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODY; ATTACHMENT PROTEIN; EPITHELIAL-CELLS; RSV INFECTION AB The two major glycoproteins on the surface of the respiratory syncytial virus (RSV) virion, the attachment glycoprotein (G) and the fusion glycoprotein (F), control the initial phases of infection. G targets the ciliated cells of the airways, and F causes the virion membrane to fuse with the target cell membrane. The F protein is the major target for antiviral drug development, and both G and F glycoproteins are the antigens targeted by neutralizing antibodies induced by infection. In this chapter, we review the structure and function of the RSV surface glycoproteins, including recent X-ray crystallographic data of the F glycoprotein in its pre- and postfusion conformations, and discuss how this information informs antigen selection and vaccine development. C1 [McLellan, Jason S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Ray, William C.] Nationwide Childrens Hosp, Res Inst, Battelle Ctr Math Med, Columbus, OH USA. [Peeples, Mark E.] Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, Columbus, OH 43205 USA. RP Peeples, ME (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, Columbus, OH 43205 USA. EM Mark.Peeples@nationwidechildrens.org FU NIAID NIH HHS [AI095684, AI093848, R01 AI093848, R01 AI095684, R56 AI095684] NR 103 TC 34 Z9 38 U1 3 U2 13 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-38919-1; 978-3-642-38918-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 372 BP 83 EP 104 DI 10.1007/978-3-642-38919-1_4 D2 10.1007/978-3-642-38919-1 PG 22 WC Immunology; Respiratory System; Virology SC Immunology; Respiratory System; Virology GA BJU63 UT WOS:000330592500005 PM 24362685 ER PT S AU Choi, EH Lee, HJ Chanock, SJ AF Choi, Eun Hwa Lee, Hoan Jong Chanock, Stephen J. BE Anderson, LJ Graham, BS TI Human Genetics and Respiratory Syncytial Virus Disease: Current Findings and Future Approaches SO CHALLENGES AND OPPORTUNITIES FOR RESPIRATORY SYNCYTIAL VIRUS VACCINES SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID MESSENGER-RNA EXPRESSION; GENOME-WIDE ASSOCIATION; IMMUNE-RESPONSE; BINDING LECTIN; YOUNG-CHILDREN; INFECTION; BRONCHIOLITIS; SUSCEPTIBILITY; POLYMORPHISMS; SEVERITY AB Infection with respiratory syncytial virus (RSV) can result in a wide spectrum of pulmonary manifestations, from mild upper respiratory symptoms to severe bronchiolitis and pneumonia. Although there are several known risk factors for severe RSV disease, namely, premature birth, chronic lung disease, congenital heart disease, and T cell immunodeficiency, the majority of young children who develop severe RSV disease are otherwise healthy children. Genetic susceptibility to RSV infection is emerging as a complex trait, in which many different host genetic variants contribute to risk for distinct disease manifestations. Initially, host genetic studies focused on severe RSV disease using the candidate gene approach to interrogate common single nucleotide polymorphisms (SNPs). Many studies have reported genetic associations between severe RSV bronchiolitis and SNPs in genes within plausible biological pathways, such as in innate host defense genes (SPA, SPD, TLR4, and VDR), cytokine or chemokine response genes (CCR5, IFN, IL6, IL10, TGFB1), and altered Th1/Th2 immune responses (IL4, IL13). Due to the complexity of RSV susceptibility, genome studies done on a larger scale, such as genome-wide association studies have certainly identified more of the host factors that contribute to the development of severe RSV bronchiolitis or excessive pathology. Furthermore, whole-genome approaches can reveal robust associations between genetic markers and RSV disease susceptibility. Recent introduction of 'exome' genotyping or sequencing, which specifically analyzes the majority of coding variants, should be fruitful in sufficiently large, well-powered studies. The advent of new genomic technologies together with improved computational tools offer the promise of interrogating the host genome in search of genetic factors, rare, uncommon, or common that should give new insights into the underlying biology of susceptibility to or protection from severe RSV infection. Careful assessment of novel pathways and further identification of specific genes could identify new approaches for vaccine development and perhaps lead to effective risk modeling. C1 [Choi, Eun Hwa; Lee, Hoan Jong] Seoul Natl Univ, Coll Med, Dept Pediat, Seoul 110769, South Korea. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov NR 65 TC 10 Z9 10 U1 3 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-38919-1; 978-3-642-38918-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 372 BP 121 EP 137 DI 10.1007/978-3-642-38919-1_6 D2 10.1007/978-3-642-38919-1 PG 17 WC Immunology; Respiratory System; Virology SC Immunology; Respiratory System; Virology GA BJU63 UT WOS:000330592500007 PM 24362687 ER PT S AU Malloy, AMW Falsey, AR Ruckwardt, TJ AF Malloy, Allison M. W. Falsey, Ann R. Ruckwardt, Tracy J. BE Anderson, LJ Graham, BS TI Consequences of Immature and Senescent Immune Responses for Infection with Respiratory Syncytial Virus SO CHALLENGES AND OPPORTUNITIES FOR RESPIRATORY SYNCYTIAL VIRUS VACCINES SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID AGE-RELATED DIFFERENCES; T-CELL RESPONSES; INNATE IMMUNITY; ADAPTIVE IMMUNITY; ELDERLY PERSONS; SERUM ANTIBODY; RSV INFECTION; CTL RESPONSES; HUMAN INFANTS; HUMAN NEWBORN AB Infants in the first 6 months of life and older adults (>65 years of age) are disproportionately burdened with respiratory syncytial virus (RSV)-associated morbidity and mortality. While other factors play a role in the risk these groups assume, shortcomings of the immune response make a substantial contribution to the predisposition to severe disease. Ineffectual antibody production with misdirected cytokine responses and excess inflammation in the airways are common to both groups. However, the mechanisms underlying these immune responses differ between infants and older adults and need to be better understood. Preventative approaches to decreasing the burden of disease are preferable to therapeutic intervention and effective vaccination strategies will need to target the strengths of the immune responses in these populations. C1 [Malloy, Allison M. W.; Ruckwardt, Tracy J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Falsey, Ann R.] Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. RP Falsey, AR (reprint author), Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. EM ann.falsey@viahealth.org NR 83 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-38919-1; 978-3-642-38918-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 372 BP 211 EP 231 DI 10.1007/978-3-642-38919-1_11 D2 10.1007/978-3-642-38919-1 PG 21 WC Immunology; Respiratory System; Virology SC Immunology; Respiratory System; Virology GA BJU63 UT WOS:000330592500012 PM 24362692 ER PT S AU Karron, RA Buchholz, UJ Collins, PL AF Karron, Ruth A. Buchholz, Ursula J. Collins, Peter L. BE Anderson, LJ Graham, BS TI Live-Attenuated Respiratory Syncytial Virus Vaccines SO CHALLENGES AND OPPORTUNITIES FOR RESPIRATORY SYNCYTIAL VIRUS VACCINES SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID INACTIVATED INFLUENZA VACCINES; AFRICAN-GREEN MONKEYS; TEMPERATURE-SENSITIVE MUTANTS; T-CELL RESPONSES; RSV VACCINE; REVERSE GENETICS; ADULT VOLUNTEERS; YOUNG-CHILDREN; SENDAI-VIRUS; SUBGROUP-B AB Live-attenuated respiratory syncytial virus (RSV) vaccines offer several advantages for immunization of infants and young children: (1) they do not cause vaccine-associated enhanced RSV disease; (2) they broadly stimulate innate, humoral, and cellular immunity, both systemically and locally in the respiratory tract; (3) they are delivered intranasally; and (4) they replicate in the upper respiratory tract of young infants despite the presence of passively acquired maternally derived RSV neutralizing antibody. This chapter describes early efforts to develop vaccines through the classic methods of serial cold-passage and chemical mutagenesis, and recent efforts using reverse genetics to derive attenuated derivatives of wild-type (WT) RSV and to develop parainfluenza vaccine vectors that express RSV surface glycoproteins. C1 [Karron, Ruth A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21218 USA. [Buchholz, Ursula J.; Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Karron, RA (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21218 USA. EM rkarron@jhsph.edu FU Intramural NIH HHS [Z01 AI000372-25]; NIAID NIH HHS [HHSN272200900010C]; PHS HHS [HHSN272200900010C] NR 66 TC 34 Z9 34 U1 2 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-38919-1; 978-3-642-38918-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 372 BP 259 EP 284 DI 10.1007/978-3-642-38919-1_13 D2 10.1007/978-3-642-38919-1 PG 26 WC Immunology; Respiratory System; Virology SC Immunology; Respiratory System; Virology GA BJU63 UT WOS:000330592500014 PM 24362694 ER PT S AU Graham, BS Anderson, LJ AF Graham, Barney S. Anderson, Larry J. BE Anderson, LJ Graham, BS TI Challenges and Opportunities for Respiratory Syncytial Virus Vaccines SO CHALLENGES AND OPPORTUNITIES FOR RESPIRATORY SYNCYTIAL VIRUS VACCINES SE Current Topics in Microbiology and Immunology LA English DT Editorial Material; Book Chapter ID CORYZA AGENT CCA; INFANTS; RECOVERY; CHIMPANZEES; ILLNESS AB Respiratory syncytial virus (RSV) causes a significant proportion of the global burden of respiratory disease. Here we summarize the conclusions of a series of chapters written by investigators describing and interpreting what is known about the virology, clinical manifestations, immunity, pathogenesis, and epidemiology of RSV relevant to vaccine development. Several technological and conceptual advances have recently occurred that make RSV vaccine development more feasible, and this collected knowledge is intended to help inform and organize the future contributions of funding agencies, scientists, regulatory agencies, and policy makers that will be needed to achieve the goal of a safe, effective, and accessible vaccine to prevent RSV-associated disease. C1 [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Anderson, Larry J.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Anderson, Larry J.] Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU Intramural NIH HHS NR 12 TC 24 Z9 25 U1 1 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-38919-1; 978-3-642-38918-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 372 BP 391 EP 404 DI 10.1007/978-3-642-38919-1_20 D2 10.1007/978-3-642-38919-1 PG 14 WC Immunology; Respiratory System; Virology SC Immunology; Respiratory System; Virology GA BJU63 UT WOS:000330592500021 PM 24362701 ER PT J AU Chawla, LS Davison, DL Brasha-Mitchell, E Koyner, JL Arthur, JM Shaw, AD Tumlin, JA Trevino, SA Kimmel, PL Seneff, MG AF Chawla, Lakhmir S. Davison, Danielle L. Brasha-Mitchell, Ermira Koyner, Jay L. Arthur, John M. Shaw, Andrew D. Tumlin, James A. Trevino, Sharon A. Kimmel, Paul L. Seneff, Michael G. TI Development and Standardization of a Furosemide Stress Test to Predict the Severity of Acute Kidney Injury SO CRITICAL CARE LA English DT Article ID ACUTE-RENAL-FAILURE; REPLACEMENT THERAPY; BIOMARKERS; AKI; DIURETICS; RAT; METAANALYSIS; INITIATION; DIAGNOSIS; BINDING AB Introduction: In the setting of early acute kidney injury (AKI), no test has been shown to definitively predict the progression to more severe stages. Methods: We investigated the ability of a furosemide stress test (FST) (one-time dose of 1.0 or 1.5 mg/kg depending on prior furosemide-exposure) to predict the development of AKIN Stage-III in 2 cohorts of critically ill subjects with early AKI. Cohort 1 was a retrospective cohort who received a FST in the setting of AKI in critically ill patients as part of Southern AKI Network. Cohort 2 was a prospective multicenter group of critically ill patients who received their FST in the setting of early AKI. Results: We studied 77 subjects; 23 from cohort 1 and 54 from cohort 2; 25 (32.4%) met the primary endpoint of progression to AKIN-III. Subjects with progressive AKI had significantly lower urine output following FST in each of the first 6 hours (p<0.001). The area under the receiver operator characteristic curves for the total urine output over the first 2 hours following FST to predict progression to AKIN-III was 0.87 (p = 0.001). The ideal-cutoff for predicting AKI progression during the first 2 hours following FST was a urine volume of less than 200mls(100ml/hr) with a sensitivity of 87.1% and specificity 84.1%. Conclusions: The FST in subjects with early AKI serves as a novel assessment of tubular function with robust predictive capacity to identify those patients with severe and progressive AKI. Future studies to validate these findings are warranted. C1 [Chawla, Lakhmir S.; Davison, Danielle L.; Brasha-Mitchell, Ermira; Seneff, Michael G.] George Washington Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, Washington, DC 20037 USA. [Chawla, Lakhmir S.] George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. [Koyner, Jay L.; Trevino, Sharon A.] Univ Chicago, Dept Med, Sect Nephrol, Chicago, IL 60637 USA. [Arthur, John M.] Med Univ S Carolina, Dept Med, CSB Div Nephrol 829, Charleston, SC USA. [Shaw, Andrew D.] Duke Univ, Durham VAMC, Dept Anesthesiol, Durham, NC 27710 USA. [Tumlin, James A.] Univ Tennessee, Coll Med Chattanooga, Renal Div, Chattanooga, TN 37404 USA. [Kimmel, Paul L.] Natl Inst Diabet Digest & Kidney Dis, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20817 USA. RP Chawla, LS (reprint author), George Washington Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, 900 23rd St, Washington, DC 20037 USA. EM minkchawla@gmail.com FU National Institutes of Health, NIDDK, NIH [R01 DK080234]; [K23DK081616] FX The SAKInet portion of this study was funded by National Institutes of Health, NIDDK, NIH grant number R01 DK080234. JLK was supported by K23DK081616. The investigators would like to thank all of the nurses and support staff of the George Washington University Hospital Jack Zimmerman Intensive Care Unit for their assistance in all of our clinical research. The investigators would also like to acknowledge Christina Seneff and Lindita Shelu for their assistance in conducting this study. The authors would like to thank Oscar Medaless, Dan Barker, Welshi Ladde, Astra Fudgeri, and Gary R Snyder for reviewing the manuscript and offering suggestions. LSC and JAT would like to thank Robert Safirstein for his input into the development of this protocol. NR 33 TC 40 Z9 41 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 5 AR R207 DI 10.1186/cc13015 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA AB1HA UT WOS:000331540900024 PM 24053972 ER PT J AU Hirschfeld, S Ward, RM AF Hirschfeld, Steven Ward, Robert M. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI History of Children and the Development of Regulations at the FDA SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter C1 [Hirschfeld, Steven] Inst Child Hlth & Human Dev, USPHS Rapid Deployment Force 1, Eunice Kennedy Shriver Natl, Bethesda, MD 20892 USA. [Ward, Robert M.] Univ Utah, Dept Clin Pharmacol, Salt Lake City, UT USA. RP Hirschfeld, S (reprint author), Inst Child Hlth & Human Dev, USPHS Rapid Deployment Force 1, Eunice Kennedy Shriver Natl, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 6 EP 15 D2 10.1002/9781118312087 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800003 ER PT J AU Zajicek, A AF Zajicek, Anne BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Drug Delivery Challenges for the Pediatric Patient: Novel Forms for Consideration SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID ORALLY DISINTEGRATING TABLETS; CONTROLLED-RELEASE; SUSTAINED-RELEASE; MINI-TABLETS; FORMULATION; BIOAVAILABILITY; NANOPARTICLES; POLYMERS; CHILDREN; LIQUID C1 Uniformed Serv Univ Hlth Sci, Obstet & Pediat Pharmacol & Therapeut Branch, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20814 USA. RP Zajicek, A (reprint author), Uniformed Serv Univ Hlth Sci, Obstet & Pediat Pharmacol & Therapeut Branch, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20814 USA. NR 40 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 576 EP 582 D2 10.1002/9781118312087 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800047 ER PT J AU Park, JW Zhao, L Cheng, SY AF Park, Jeong Won Zhao, Li Cheng, Sheue-Yann TI Inhibition of estrogen-dependent tumorigenesis by the thyroid hormone receptor beta in xenograft models SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Thyroid hormone receptor beta; tumor suppressor; tumorigenesis; STAT signaling; MCF-7 cells ID BREAST-CANCER PATIENTS; CLEAR-CELL CARCINOMA; NUCLEAR RECEPTORS; TRIIODOTHYRONINE LEVELS; POSTMENOPAUSAL WOMEN; PITUITARY-TUMOR; TR-BETA; EXPRESSION; GENE; PATHWAY AB Association studies suggest that thyroid hormone receptor beta (TR beta) could function as a tumor suppressor in breast cancer development, but unequivocal evidence is still lacking. To understand the role of TR beta in breast tumor development, we adopted the gain-of-function approach by stably expressing the THRB gene in a human breast cancer cell line, MCF-7 (MCF-7-TR beta). Parental MCF-7 cells express the estrogen receptor, but not TRs. MCF-7 cells, stably expressing only the selectable marker, the Neo gene, were also generated as control for comparison (MCF-7-Neo cells). Cell-based studies indicate that the estrogen (E2)-dependent growth of MCF-7 cells was inhibited by the expression of TR beta in the presence of the thyroid hormone (T3). In a xenograft mouse model, large tumors rapidly developed after inoculation of MCF-7-Neo cells in athymic mice. In contrast, markedly smaller tumors (98% smaller) were found when MCF-7-TR beta cells were inoculated in athymic mice, indicating that TR beta inhibited the E2-dependent tumor growth of MCF-7 cells. Further detailed molecular analysis showed that TR beta acted to activate apoptosis and decrease proliferation of tumor cells, resulting in inhibition of tumor growth. The TR beta-mediated inhibition of tumor growth was elucidated via down-regulation of the JAK-STAT-cyclin D pathways. This in vivo evidence shows that TR beta could act as a tumor suppressor in breast tumorigenesis. The present study provides new insights into the role of TR in breast cancer. C1 [Park, Jeong Won; Zhao, Li; Cheng, Sheue-Yann] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Gene Regulat Sect, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural Research Program at the Center for Cancer Research, National Cancer Institute, National Institutes of Health FX The present research was supported by the Intramural Research Program at the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 50 TC 10 Z9 10 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2013 VL 3 IS 3 BP 302 EP 311 PG 10 WC Oncology SC Oncology GA AA4LT UT WOS:000331067800006 PM 23841029 ER PT J AU Du, Q Yan, WS Burton, VH Hewitt, SM Wang, LM Hu, N Taylor, PR Armani, MD Mukherjee, S Emmert-Buck, MR Tangrea, MA AF Du, Qiang Yan, Wusheng Burton, Victoria H. Hewitt, Stephen M. Wang, Lemin Hu, Nan Taylor, Philip R. Armani, Michael D. Mukherjee, Sumana Emmert-Buck, Michael R. Tangrea, Michael A. TI Validation of esophageal squamous cell carcinoma candidate genes from high-throughput transcriptomic studies SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Expression microdissection; esophageal squamous cell carcinoma; RNAscope; immunoblot ID EXPRESSION MICRODISSECTION; CANCER; CORNULIN AB In a recent study, a unique gene expression signature was observed when comparing esophageal squamous cell carcinoma (ESCC) epithelial cells to normal esophageal epithelial cells using laser capture microdissection (LCM) and cDNA microarray technology. To validate the expression of several intriguing genes from that study (KRT17, cornulin, CD44, and EpCAM), we employed two new technologies, expression microdissection (xMD) for high-throughput microdissection facilitating protein analysis and RNAscope for the evaluation of low abundant transcripts in situ. For protein measurements, xMD technology was utilized to specifically procure sufficient tumor and normal epithelium from frozen human tissue for immunoblot analysis of KRT17 (CK17) and cornulin. A novel in situ hybridization method (RNAscope) was used to determine the transcript level of two relatively low expressed genes, CD44 and EpCAM in both individual formalin-fixed paraffin-embedded (FFPE) tissue sections and in an ESCC tissue microarray (TMA). The results successfully confirmed the initial expression pattern observed for all four genes, potentially implicating them in the pathogenesis of ESCC. Additionally, the study provides important methodological information on the overall process of candidate gene validation. C1 [Du, Qiang; Yan, Wusheng; Armani, Michael D.; Mukherjee, Sumana; Emmert-Buck, Michael R.; Tangrea, Michael A.] NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Burton, Victoria H.; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Appl Mol Pathol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Lemin; Hu, Nan; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM buckm@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported by the intramural program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. M.R.E.-B. and M.A.T. are inventors on NIH held patents covering expression microdissection and are entitled to receive royalty-based payments through the NIH technology transfer program. NR 17 TC 7 Z9 7 U1 0 U2 1 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2013 VL 3 IS 4 BP 402 EP 410 PG 9 WC Oncology SC Oncology GA AA4MJ UT WOS:000331069400006 PM 23977449 ER PT J AU Rodrigo, L Blanco, I Bobes, J de Serres, FJ AF Rodrigo, Luis Blanco, Ignacio Bobes, Julio de Serres, Frederick J. TI Remarkable prevalence of coeliac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; SPANISH VERSION; LYMPHOCYTIC DUODENOSIS; HEALTH-STATUS; SYMPTOMS; CRITERIA; PAIN; CLASSIFICATION; QUESTIONNAIRE; METAANALYSIS AB Introduction: Irritable bowel syndrome (IBS) and fibromyalgia syndrome (FMS) are two common central sensitization disorders frequently associated in the same patient, and some of these patients with IBS plus FMS (IBS/FMS) could actually be undiagnosed of coeliac disease (CD). The present study was an active case finding for CD in two IBS cohorts, one constituted by IBS/FMS subjects and the other by people with isolated IBS. Methods: A total of 104 patients (89.4% females) fulfilling the 1990 ACR criteria for FMS and the Rome III criteria for IBS classification and 125 unrelated age- and sex-matched IBS patients without FMS underwent the following studies: haematological, coagulation and biochemistry tests, serological and genetic markers for CD (i.e., tissue transglutaminase 2 (tTG-2) and major histocompatibility complex HLA-DQ2/HLA-DQ8), multiple gastric and duodenal biopsies, FMS tender points (TPs), Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ), 36-Item Short Form Health Survey (SF-36) and Visual Analogue Scales (VASs) for tiredness and gastrointestinal complaints. Results: As a whole, IBS/FMS patients scored much worse in quality of life and VAS scores than those with isolated IBS (P < 0.001). Seven subjects (6.7%) from the IBS/FMS group displayed HLA-DQ2/HLA-DQ8 positivity, high tTG-2 serum levels and duodenal villous atrophy, concordant with CD. Interestingly enough, these seven patients were started on a gluten-free diet (GFD), showing a remarkable improvement in their digestive and systemic symptoms on follow-up. Conclusions: The findings of this screening indicate that a non-negligible percentage of IBS/FMS patients are CD patients, whose symptoms can improve and in whom long-term CD-related complications might possibly be prevented with a strict lifelong GFD. C1 [Rodrigo, Luis] Cent Univ Hosp Asturias HUCA, ES-33006 Oviedo, Principality Of, Spain. [Blanco, Ignacio] FICYT, Biomed Res Off Principal Asturias, ES-33009 Oviedo, Principality Of, Spain. [Bobes, Julio] Univ Oviedo, Dept Med, Psychiat Area, ES-33006 Oviedo, Principality Of, Spain. [de Serres, Frederick J.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Rodrigo, L (reprint author), Cent Univ Hosp Asturias HUCA, Celestino Villamil S-N, ES-33006 Oviedo, Principality Of, Spain. EM lrodrigosaez@gmail.com NR 46 TC 9 Z9 9 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2013 VL 15 IS 6 AR R201 DI 10.1186/ar4391 PG 12 WC Rheumatology SC Rheumatology GA 302TW UT WOS:000330628800027 PM 24283458 ER PT J AU Vincent, A Benzo, RP Whipple, MO McAllister, SJ Erwin, PJ Saligan, LN AF Vincent, Ann Benzo, Roberto P. Whipple, Mary O. McAllister, Samantha J. Erwin, Patricia J. Saligan, Leorey N. TI Beyond pain in fibromyalgia: insights into the symptom of fatigue SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; TRANSCRANIAL MAGNETIC STIMULATION; CONTROLLED CLINICAL-TRIALS; PATIENT-REPORTED OUTCOMES; SELF-MANAGEMENT PROGRAM; CHRONIC WIDESPREAD PAIN; CROSS-SECTIONAL SURVEY; LONG-TERM MAINTENANCE AB Fatigue is a disabling, multifaceted symptom that is highly prevalent and stubbornly persistent. Although fatigue is a frequent complaint among patients with fibromyalgia, it has not received the same attention as pain. Reasons for this include lack of standardized nomenclature to communicate about fatigue, lack of evidence-based guidelines for fatigue assessment, and a deficiency in effective treatment strategies. Fatigue does not occur in isolation; rather, it is present concurrently in varying severity with other fibromyalgia symptoms such as chronic widespread pain, unrefreshing sleep, anxiety, depression, cognitive difficulties, and so on. Survey-based and preliminary mechanistic studies indicate that multiple symptoms feed into fatigue and it may be associated with a variety of physiological mechanisms. Therefore, fatigue assessment in clinical and research settings must consider this multi-dimensionality. While no clinical trial to date has specifically targeted fatigue, randomized controlled trials, systematic reviews, and meta-analyses indicate that treatment modalities studied in the context of other fibromyalgia symptoms could also improve fatigue. The Outcome Measures in Rheumatology (OMERACT) Fibromyalgia Working Group and the Patient Reported Outcomes Measurement Information System (PROMIS) have been instrumental in propelling the study of fatigue in fibromyalgia to the forefront. The ongoing efforts by PROMIS to develop a brief fibromyalgia-specific fatigue measure for use in clinical and research settings will help define fatigue, allow for better assessment, and advance our understanding of fatigue. C1 [Vincent, Ann] Mayo Clin, Fibromyalgia & Chron Fatigue Clin, Rochester, MN 55905 USA. [Vincent, Ann; Whipple, Mary O.; McAllister, Samantha J.] Mayo Clin, Div Gen Internal Med, Rochester, MN 55905 USA. [Benzo, Roberto P.] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. [Erwin, Patricia J.] Mayo Clin, Lib Publ Serv, Rochester, MN 55905 USA. [Saligan, Leorey N.] Natl Inst Nurs Res, Div Intramural Res, Bethesda, MD 20892 USA. RP Vincent, A (reprint author), Mayo Clin, Fibromyalgia & Chron Fatigue Clin, Rochester, MN 55905 USA. EM vincent.ann@mayo.edu FU Center for Translational Science Activities (CTSA) at Mayo Clinic; National Center for Research Resources (NCRR); National Institutes of Health (NIH) [RR024150] FX This study was supported in part by the Center for Translational Science Activities (CTSA) at Mayo Clinic. This center is funded in part by a grant from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) (RR024150). Its contents are solely the NR 155 TC 16 Z9 16 U1 7 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2013 VL 15 IS 6 AR 221 DI 10.1186/ar4395 PG 14 WC Rheumatology SC Rheumatology GA 302TW UT WOS:000330628800058 PM 24289848 ER PT J AU Fernandez-Ayala, DJM Guerra, I Jimenez-Gancedo, S Cascajo, MV Gavilan, A DiMauro, S Hirano, M Briones, P Artuch, R De Cabo, R Salviati, L Navas, P AF Fernandez-Ayala, Daniel J. M. Guerra, Ignacio Jimenez-Gancedo, Sandra Cascajo, Maria V. Gavilan, Angela DiMauro, Salvatore Hirano, Michio Briones, Paz Artuch, Rafael De Cabo, Rafael Salviati, Leonardo Navas, Placido TI Survival transcriptome in the coenzyme Q(10) deficiency syndrome is acquired by epigenetic modifications: a modelling study for human coenzyme Q(10) deficiencies SO BMJ OPEN LA English DT Article ID MITOCHONDRIAL DISEASE; CEREBELLAR-ATAXIA; GENE-EXPRESSION; FOLLOW-UP; SUPPLEMENTATION; ENCEPHALOMYOPATHY; BIOSYNTHESIS; FIBROBLASTS; METHYLATION; MICROARRAY AB Objectives: Coenzyme Q(10) (CoQ(10)) deficiency syndrome is a rare condition that causes mitochondrial dysfunction and includes a variety of clinical presentations as encephalomyopathy, ataxia and renal failure. First, we sought to set up what all have in common, and then investigate why CoQ(10) supplementation reverses the bioenergetics alterations in cultured cells but not all the cellular phenotypes. Design Modelling study: This work models the transcriptome of human CoQ(10) deficiency syndrome in primary fibroblast from patients and study the genetic response to CoQ(10) treatment in these cells. Setting: Four hospitals and medical centres from Spain, Italy and the USA, and two research laboratories from Spain and the USA. Participants: Primary cells were collected from patients in the above centres. Measurements: We characterised by microarray analysis the expression profile of fibroblasts from seven CoQ(10)-deficient patients (three had primary deficiency and four had a secondary form) and aged-matched controls, before and after CoQ(10) supplementation. Results were validated by Q-RT-PCR. The profile of DNA (CpG) methylation was evaluated for a subset of gene with displayed altered expression. Results: CoQ(10)-deficient fibroblasts (independently from the aetiology) showed a common transcriptomic profile that promotes cell survival by activating cell cycle and growth, cell stress responses and inhibiting cell death and immune responses. Energy production was supported mainly by glycolysis while CoQ(10) supplementation restored oxidative phosphorylation. Expression of genes involved in cell death pathways was partially restored by treatment, while genes involved in differentiation, cell cycle and growth were not affected. Stably demethylated genes were unaffected by treatment whereas we observed restored gene expression in either non-methylated genes or those with an unchanged methylation pattern. Conclusions: CoQ(10) deficiency induces a specific transcriptomic profile that promotes cell survival, which is only partially rescued by CoQ(10) supplementation. C1 [Fernandez-Ayala, Daniel J. M.; Guerra, Ignacio; Jimenez-Gancedo, Sandra; Cascajo, Maria V.; Gavilan, Angela; Navas, Placido] Univ Pablo Olavide, Ctr Andaluz Biol Desarrollo CABD CSIC, Seville, Spain. [Fernandez-Ayala, Daniel J. M.; Guerra, Ignacio; Jimenez-Gancedo, Sandra; Cascajo, Maria V.; Gavilan, Angela; Briones, Paz; Artuch, Rafael; Navas, Placido] Inst Salud Carlos III, CIBERER, Seville, Spain. [DiMauro, Salvatore; Hirano, Michio] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Briones, Paz] Corp Sanitaria Clin, Inst Bioquim Clin, Barcelona, Spain. [Artuch, Rafael] Hosp St Joan de Deu, Dept Clin Biochem, Barcelona, Spain. [De Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Salviati, Leonardo] Univ Padua, Clin Genet Unit, Dept Woman & Child Hlth, Padua, Italy. RP Navas, P (reprint author), Univ Pablo Olavide, Ctr Andaluz Biol Desarrollo CABD CSIC, Seville, Spain. EM Leonardo.salviati@unipd.it; pnavas@upo.es RI Salviati, Leonardo/L-1007-2016; OI Salviati, Leonardo/0000-0001-5642-9963; Fernandez-Ayala, Daniel Jose Moreno/0000-0001-8176-1431; de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Spanish Ministerio de Sanidad (FIS) [PI11/00078, PI11/02350]; National Institutes of Health (NIH, USA) [1R01HD057543]; Junta de Andalucia (Spanish Regional Government) [CTS-3988]; Telethon (Italy) [GGP09207]; Fondazione CARIPARO FX This work was supported by the following funders: Spanish Ministerio de Sanidad (FIS) grant numbers PI11/00078 and PI11/02350; National Institutes of Health (NIH, USA) grant number 1R01HD057543; Junta de Andalucia (Spanish Regional Government) grant number CTS-3988; Telethon (Italy) grant number GGP09207; and from a grant from Fondazione CARIPARO. NR 34 TC 4 Z9 4 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2013 VL 3 IS 3 AR e002524 DI 10.1136/bmjopen-2012-002524 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 301VP UT WOS:000330560500070 ER PT J AU Mann, AG Mangtani, P Russell, CA Whittaker, JC AF Mann, Andrea G. Mangtani, Punam Russell, Colin A. Whittaker, John C. TI The impact of targeting all elderly persons in England and Wales for yearly influenza vaccination: excess mortality due to pneumonia or influenza and time trend study SO BMJ OPEN LA English DT Article ID PRACTICE-RESEARCH-DATABASE; EFFICACY; COVERAGE; DECLINE; DEATHS; PEOPLE; COHORT; HEALTH; POLICY; VIRUS AB Objective: To investigate the impact on mortality due to pneumonia or influenza of the change from risk-based to age group-based targeting of the elderly for yearly influenza vaccination in England and Wales. Design: Excess mortality estimated using time series of deaths registered to pneumonia or influenza, accounting for seasonality, trend and artefacts. Non-excess mortality plotted as proxy for long-term trend in mortality. Setting: England and Wales. Participants: Persons aged 65-74 and 75+ years whose deaths were registered to underlying pneumonia or influenza between 1975/1976 and 2004/2005. Outcome measures: Multiplicative effect on average excess pneumonia and influenza deaths each winter in the 4-6 winters since age group-based targeting of vaccination was introduced (in persons aged 75+ years from 1998/1999; in persons aged 65+ years from 2000/2001), estimated using multivariable regression adjusted for temperature, antigenic drift and vaccine mismatch, and stratified by dominant circulating influenza subtype. Trend in baseline weekly pneumonia and influenza death rates. Results: There is a suggestion of lower average excess mortality in the six winters after age group-based targeting began compared to before, but the CI for the 65-74 years age group includes no difference. Trend in baseline pneumonia and influenza mortality shows an apparent downward turning point around 2000 for the 65-74 years age group and from the mid-1990s in the 75+ years age group. Conclusions: There is weakly supportive evidence that the marked increases in vaccine coverage accompanying the switch from risk-based to age group-based targeting of the elderly for yearly influenza vaccination in England and Wales were associated with lower levels of pneumonia and influenza mortality in older people in the first 6 years after age group-based targeting began. The possible impact of these policy changes is observed as weak evidence for lower average excess mortality as well as a turning point in baseline mortality coincident with the changes. C1 [Mann, Andrea G.; Mangtani, Punam] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, Dept Infect Dis Epidemiol, London WC1, England. [Russell, Colin A.] Univ Cambridge, Dept Zool, Cambridge, England. [Russell, Colin A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Whittaker, John C.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, Dept Noncommunicable Dis Epidemiol, London WC1, England. [Whittaker, John C.] GlaxoSmithKline, Med Res Ctr, Stat Platforms & Technol, Stevenage, Herts, England. RP Mann, AG (reprint author), London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, Dept Infect Dis Epidemiol, London WC1, England. EM andrea.mann@lshtm.ac.uk OI Russell, Colin/0000-0002-2113-162X FU National Institute of Health Research, UK [RDA06/068] FX This work was supported by a Researcher Development Award to AGM from the National Institute of Health Research, UK (fellowship grant number RDA06/068). NR 57 TC 2 Z9 2 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2013 VL 3 IS 8 AR e002743 DI 10.1136/bmjopen-2013-002743 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 301VX UT WOS:000330561300046 ER PT S AU Ma, BY Nussinov, R AF Ma, Buyong Nussinov, Ruth BE Klinman, J HammesSchiffer, S TI Structured Crowding and Its Effects on Enzyme Catalysis SO DYNAMICS IN ENZYME CATALYSIS SE Topics in Current Chemistry LA English DT Review; Book Chapter DE Allostery; Conformational selection; Energy landscape; Enzymatics; Macromolecular crowding; Protein dynamics ID GLYCOGEN-PHOSPHORYLASE-B; ALPHA-CHYMOTRYPSIN; ESCHERICHIA-COLI; MOLECULAR-DYNAMICS; CONFORMATIONAL SELECTION; CHEMICAL GLYCOSYLATION; BIOCHEMICAL REACTIONS; GLOBULAR-PROTEINS; HIV-1 PROTEASE; ACTIVE-SITE AB Macromolecular crowding decreases the diffusion rate, shifts the equilibrium of protein-protein and protein-substrate interactions, and changes protein conformational dynamics. Collectively, these effects contribute to enzyme catalysis. Here we describe how crowding may bias the conformational change and dynamics of enzyme populations and in this way affect catalysis. Crowding effects have been studied using artificial crowding agents and in vivo-like environments. These studies revealed a correlation between protein dynamics and function in the crowded environment. We suggest that crowded environments be classified into uniform crowding and structured crowding. Uniform crowding represents random crowding conditions created by synthetic particles with a narrow size distribution. Structured crowding refers to the highly coordinated cellular environment, where proteins and other macromolecules are clustered and organized. In structured crowded environments the perturbation of protein thermal stability may be lower; however, it may still be able to modulate functions effectively and dynamically. Dynamic, allosteric enzymes could be more sensitive to cellular perturbations if their free energy landscape is flatter around the native state; on the other hand, if their free energy landscape is rougher, with high kinetic barriers separating deep minima, they could be more robust. Above all, cells are structured; and this holds both for the cytosol and for the membrane environment. The crowded environment is organized, which limits the search, and the crowders are not necessarily inert. More likely, they too transmit allosteric effects, and as such play important functional roles. Overall, structured cellular crowding may lead to higher enzyme efficiency and specificity. C1 [Ma, Buyong; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21702 USA. EM mabuyong@mail.nih.gov; ruthnu@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU PHS HHS [HHSN261200800001E] NR 110 TC 9 Z9 9 U1 6 U2 30 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0340-1022 BN 978-3-642-38962-7; 978-3-642-38961-0 J9 TOP CURR CHEM JI Top. Curr. Chem. PY 2013 VL 337 BP 123 EP 137 DI 10.1007/128_2012_316 D2 10.1007/978-3-642-38962-7 PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA BA0DT UT WOS:000331047400006 PM 23571857 ER PT S AU Hayman, DTS Gurley, ES Pulliam, JRC Field, HE AF Hayman, David T. S. Gurley, Emily S. Pulliam, Juliet R. C. Field, Hume E. BE Mackenzie, JS Jeggo, M Daszak, P Richt, JA TI The Application of One Health Approaches to Henipavirus Research SO ONE HEALTH: THE HUMAN-ANIMAL-ENVIRONMENT INTERFACES IN EMERGING INFECTIOUS DISEASES: THE CONCEPT AND EXAMPLES OF A ONE HEALTH APPROACH SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID EQUINE MORBILLIVIRUS PNEUMONIA; NIPAH VIRUS; PTEROPUS-VAMPYRUS; HENDRA VIRUS; FRUIT BATS; ENCEPHALITIS OUTBREAK; WEST-AFRICA; TRANSMISSION; BANGLADESH; INFECTION AB Henipaviruses cause fatal infection in humans and domestic animals. Transmission from fruit bats, the wildlife reservoirs of henipaviruses, is putatively driven (at least in part) by anthropogenic changes that alter host ecology. Human and domestic animal fatalities occur regularly in Asia and Australia, but recent findings suggest henipaviruses are present in bats across the Old World tropics. We review the application of the One Health approach to henipavirus research in three locations: Australia, Malaysia and Bangladesh. We propose that by recognising and addressing the complex interaction among human, domestic animal and wildlife systems, research within the One Health paradigm will be more successful in mitigating future human and domestic animal deaths from henipavirus infection than alternative single-discipline approaches. C1 [Hayman, David T. S.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. [Gurley, Emily S.] Icddr B, Dhaka 1212, Bangladesh. [Hayman, David T. S.; Pulliam, Juliet R. C.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA. [Pulliam, Juliet R. C.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. [Pulliam, Juliet R. C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Field, Hume E.] Queensland Ctr Emerging Infect Dis, Dept Agr Fisheries & Forestry, Brisbane, Qld 4108, Australia. RP Hayman, DTS (reprint author), Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. EM davidtshayman@gmail.com; egurley@icddrb.org; pulliam@ufl.edu; Hume.Field@deedi.qld.gov.au RI Pulliam, Juliet/A-6516-2008; Gurley, Emily/B-7903-2010 OI Pulliam, Juliet/0000-0003-3314-8223; Gurley, Emily/0000-0002-8648-9403 FU Wellcome Trust NR 48 TC 0 Z9 1 U1 3 U2 17 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-36889-9; 978-3-642-36888-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 365 BP 155 EP 170 DI 10.1007/82_2012_276 D2 10.1007/978-3-642-36889-9 PG 16 WC Immunology; Microbiology SC Immunology; Microbiology GA BJT58 UT WOS:000330226900009 PM 23160861 ER PT J AU Groft, SC Rubinstein, YR AF Groft, S. C. Rubinstein, Y. R. TI New and Evolving Rare Diseases Research Programs at the National Institutes of Health SO PUBLIC HEALTH GENOMICS LA English DT Article DE Biospecimens; Common data elements; Orphan drugs; Patient advocacy groups; Patient registries; Rare and genetic diseases research; Research network; Undiagnosed diseases ID INFORMED-CONSENT; PATIENT REGISTRY AB Research emphasis on rare diseases and orphan products remains a major focus of the research Institutes and Centers of National Institutes of Health (NIH). NIH provides more than USD 31 billion annually in biomedical research and research support. This research is the basis of many of the health advances in rare and common diseases. Numerous efforts and a major emphasis by the public and private sector initiatives have resulted in an increase of interventions and diagnostics for rare diseases. Newer translational research programs provide a more systematic and coordinated approach to rare diseases research and orphan products development. The approach that is offered requires extensive public-private partnerships with the pharmaceutical industry, contract research organizations, philanthropic foundations, medical and scientific advisory boards, patient advocacy groups, the academic research community, research and regulatory scientists, government funding agencies, and the public. Each program is unique and requires lengthy planning and collaborative efforts to reach programmatic goals. (C) 2013 S. Karger AG, Basel C1 [Groft, S. C.; Rubinstein, Y. R.] NIH, Natl Ctr Adv Translat Sci, Off Rare Dis Res, Bethesda, MD 20892 USA. RP Rubinstein, YR (reprint author), NIH, Natl Ctr Adv Translat Sci, Off Rare Dis Res, Bethesda, MD 20892 USA. EM rubinsty@mail.nih.gov NR 25 TC 5 Z9 5 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2013 VL 16 IS 6 BP 259 EP 267 DI 10.1159/000355929 PG 9 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 302NQ UT WOS:000330611600002 PM 24503586 ER PT S AU Yassine, HM Lee, CW Saif, YM AF Yassine, Hadi M. Lee, Chang-Won Saif, Yehia M. BE Richt, JA Webby, RJ TI Interspecies Transmission of Influenza A Viruses Between Swine and Poultry SO SWINE INFLUENZA SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID TURKEY BREEDER HENS; AVIAN INFLUENZA; UNITED-STATES; GENETIC REASSORTMENT; SOUTHEASTERN CHINA; MOLECULAR-BASIS; PIGS; INFECTION; SUSCEPTIBILITY; CHICKENS AB The special susceptibility of pigs to infection with avian and mammalian influenza viruses, the close proximity of pigs and poultry farms, and applied human practices in raising and trading of farm animals/farm animal products, provide opportunities for genetic exchange and interspecies transmission of influenza A viruses. Although only H1 and H3 influenza subtypes have widely circulated and caused disease in pig populations worldwide, H9 subtype is being continuously detected in pigs in Asia, plus sporadic infections with highly pathogenic H5-avian influenza viruses. On the other hand, swine viruses are continuously isolated from poultry species, especially turkeys, causing economic losses in poultry production. The viral and host factors contributing to influenza transmission between pigs and poultry are poorly defined. In addition, surveillance programs for influenza viruses in both species, especially pigs, are rarely implemented, and thus, leaving many questions about influenza unanswered. In this review, we summarize early and recent findings about influenza transmission between swine and poultry with emphasis on the role of turkeys. C1 [Yassine, Hadi M.; Lee, Chang-Won; Saif, Yehia M.] Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, Wooster, OH 44691 USA. [Yassine, Hadi M.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Saif, YM (reprint author), Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, 1680 Madison Ave, Wooster, OH 44691 USA. EM saif.1@osu.eud NR 65 TC 5 Z9 5 U1 0 U2 10 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-36871-4; 978-3-642-36870-7 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 370 BP 227 EP 240 DI 10.1007/82_2011_180 D2 10.1007/978-3-642-36871-4 PG 14 WC Public, Environmental & Occupational Health; Infectious Diseases; Virology SC Public, Environmental & Occupational Health; Infectious Diseases; Virology GA BJU59 UT WOS:000330591000013 PM 22167468 ER PT S AU Alexander, W Dudley, PA Di Francesco, V AF Alexander, William Dudley, Peter A. Di Francesco, Valentina BE Katze, MG TI Introduction: Embracing Complexity in Infectious Disease Research SO SYSTEMS BIOLOGY SE Current Topics in Microbiology and Immunology LA English DT Editorial Material; Book Chapter C1 [Alexander, William; Dudley, Peter A.; Di Francesco, Valentina] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Alexander, W (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM vdifrancesco@niaid.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-33099-5; 978-3-642-33098-8 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2013 VL 363 BP XI EP XIV D2 10.1007/978-3-642-33099-5 PG 4 WC Mathematical & Computational Biology; Immunology; Microbiology SC Mathematical & Computational Biology; Immunology; Microbiology GA BJU56 UT WOS:000330590200002 ER PT S AU Kindrachuk, J Napper, S AF Kindrachuk, Jason Napper, Scott BE Horvatovich, P Bischoff, R TI Sample Preparation and Profiling: Probing the Kinome for Biomarkers and Therapeutic Targets: Peptide Arrays for Global Phosphorylation Mediated Signal Transduction SO COMPREHENSIVE BIOMARKER DISCOVERY AND VALIDATION FOR CLINICAL APPLICATION SE RSC Drug Discovery Series LA English DT Article; Book Chapter ID PROTEIN-KINASE ACTIVATION; HUMAN MONKEYPOX; DRUG-THERAPY; IN-VITRO; RECEPTOR; PATHOGENESIS; INHIBITION; CELLS; PHOSPHOPROTEOME; DISCOVERY C1 [Kindrachuk, Jason] NIAID, Emerging Viral Pathogens Sect, NIH, Bethesda, MD 20892 USA. [Napper, Scott] Univ Saskatchewan, Dept Biochem, Saskatoon, SK S7N 5E5, Canada. [Napper, Scott] Univ Saskatchewan, Saskatoon, SK S7N 5E3, Canada. RP Kindrachuk, J (reprint author), NIAID, Emerging Viral Pathogens Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM napper@usask.ca NR 77 TC 4 Z9 4 U1 0 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2041-3203 BN 978-1-84973-436-3; 978-1-84973-422-6 J9 RSC DRUG DISCOV JI RSC Drug Discov. PY 2013 IS 33 BP 162 EP 195 DI 10.1039/9781849734363-00162 D2 10.1039/9781849734363 PG 34 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BHW83 UT WOS:000326878400007 ER PT S AU Niemann, CU Jones, J Wiestner, A AF Niemann, Carsten U. Jones, Jade Wiestner, Adrian BE Malek, S TI Towards Targeted Therapy of Chronic Lymphocytic Leukemia SO ADVANCES IN CHRONIC LYMPHOCYTIC LEUKEMIA SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE BCR (B cell antigen receptor); Microenvironment; Targeted therapy; Lymphocytosis; Ibrutinib (PCI-32765); idelalisib (GS-1101, CAL-101); Everolimus (RAD001); Navitoclax (ABT-263); ABT-199; Lenalidomide; Dasatinib (BMS-354825); Fostamatinib (R788); BTK (Bruton's tyrosine kinase); SYK (spleen tyrosine kinase); LYN; PI3K (phosphatidylinositol 3 kinase); mTOR (mammalian target of rapamycin); BCL-2 ID B-CELL-RECEPTOR; TYROSINE KINASE INHIBITOR; LYN-DEFICIENT MICE; PROGRESSION-FREE SURVIVAL; NON-HODGKIN-LYMPHOMA; CLL CELLS; ANTIGEN RECEPTOR; MAMMALIAN TARGET; AUTOIMMUNE-DISEASE; PHASE-II AB The B cell antigen receptor (BCR) and its downstream pathways are pivotal in the pathogenesis of chronic lymphocytic leukemia (CLL). Recently, inhibitors of kinases in the BCR pathway have shown promising clinical activity in CLL. Based upon these results, the treatment paradigm for CLL will likely undergo major changes. The kinases essential for BCR signal transduction, which are emerging as targets for CLL treatment, and the specific inhibitors under development are the focus of this chapter. In particular, the BTK inhibitor ibrutinib and the PI3K inhibitor idelalisib (GS-1101) are two evolving targeted therapies with the most mature clinical data. C1 [Niemann, Carsten U.; Jones, Jade; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM wiestnera@mail.nih.gov RI Niemann, Carsten/P-3497-2015 OI Niemann, Carsten/0000-0001-9880-5242 NR 162 TC 6 Z9 7 U1 0 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-8050-1; 978-1-4614-8051-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 792 BP 259 EP 291 DI 10.1007/978-1-4614-8051-8_12 D2 10.1007/978-1-4614-8051-8 PG 33 WC Oncology SC Oncology GA BJS51 UT WOS:000329985100013 PM 24014301 ER PT J AU Danhauer, SC Legault, C Bandos, H Kidwell, K Costantino, J Vaughan, L Avis, NE Rapp, S Coker, LH Naughton, M Naylor, C Terracciano, A Shumaker, S AF Danhauer, Suzanne C. Legault, Claudine Bandos, Hanna Kidwell, Kelley Costantino, Joseph Vaughan, Leslie Avis, Nancy E. Rapp, Steve Coker, Laura H. Naughton, Michelle Naylor, Cecile Terracciano, Antonio Shumaker, Sally TI Positive and negative affect, depression, and cognitive processes in the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) Trial SO AGING NEUROPSYCHOLOGY AND COGNITION LA English DT Article DE Positive affect; Negative affect; Depression; Cognition; Women's health ID PRIMARY-CARE PATIENTS; GERIATRIC DEPRESSION; BREAST-CANCER; EXECUTIVE DYSFUNCTION; VERBAL MEMORY; OLDER-ADULTS; LATE-LIFE; SYMPTOMS; MOOD; DECLINE AB Objectives: This study examined the relationship between positive and negative affect, depressive symptoms, and cognitive performance. Methods: The sample consisted of 1479 non-demented, postmenopausal women (mean age = 67 years) at increased risk of breast cancer enrolled in the National Surgical Adjuvant Breast and Bowel Project's Study of Tamoxifen and Raloxifene. At each annual visit, women completed a standardized neuropsychological battery and self-report measures of affect and depression. Data from three visits were used in linear mixed models for repeated measures using likelihood ratio tests. Separate analyses were performed to relate positive/negative affect and depression to each cognitive measure. Results: Higher positive affect was associated with better letter fluency (p = .006) and category fluency (p < .0001). Higher negative affect was associated with worse global cognitive function (p < .0001), verbal memory (CVLT List B; p = .002), and spatial ability (p < .0001). Depressive symptoms were negatively associated with verbal knowledge (p = .004), figural memory (p < .0001), and verbal memory (p's = .0001). Discussion: Findings are consistent with some prior research demonstrating a link between positive affect and increased verbal fluency and between depressive symptoms and decreased memory. The most novel finding shows that negative affect is related to decreased global cognition and visuospatial ability. Overall, this research in a large, longitudinal sample supports the notion that positive affect is related to increases and negative affect to decreases in performance on distinct cognitive measures. C1 [Danhauer, Suzanne C.; Legault, Claudine; Vaughan, Leslie; Avis, Nancy E.; Rapp, Steve; Coker, Laura H.; Naughton, Michelle; Naylor, Cecile; Shumaker, Sally] Wake Forest Sch Med, Winston Salem, NC USA. [Bandos, Hanna; Kidwell, Kelley; Costantino, Joseph] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Terracciano, Antonio] NIA, Baltimore, MD 21224 USA. RP Danhauer, SC (reprint author), Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM danhauer@wakehealth.edu NR 62 TC 3 Z9 3 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1382-5585 EI 1744-4128 J9 AGING NEUROPSYCHOL C JI Aging Neuropsychol. Cogn. PY 2013 VL 20 IS 5 BP 532 EP 552 DI 10.1080/13825585.2012.747671 PG 21 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 298SB UT WOS:000330343600003 ER PT J AU Rehm, J Hingson, R AF Rehm, Juergen Hingson, Ralph TI Measuring the Burden Alcohol's Evolving Impact on Individuals, Families, and Society SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Editorial Material C1 [Rehm, Juergen] Ctr Addict & Mental Hlth, Social & Epidemiol Res Dept, Toronto, ON, Canada. [Rehm, Juergen] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01062 Dresden, Germany. [Hingson, Ralph] Natl Inst Alcohol Abuse & Alcoholism, Natl Inst Hlth, Div Epidemiol & Prevent Res, Rockville, MD USA. RP Rehm, J (reprint author), Ctr Addict & Mental Hlth, Social & Epidemiol Res Dept, Toronto, ON, Canada. NR 6 TC 4 Z9 4 U1 0 U2 4 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2013 VL 35 IS 2 BP 117 EP 118 PG 2 WC Substance Abuse SC Substance Abuse GA 300TG UT WOS:000330486300001 PM 24881319 ER PT J AU Hingson, R Rehm, J AF Hingson, Ralph Rehm, Juergen TI Measuring the Burden: Alcohol's Evolving Impact SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Article DE Alcohol use consumption; alcohol use frequency; alcohol use pattern; alcohol burden; public health impact; burden of disease; morbidity; mortality; disease; measurement; outcomes; specificity of measurement; sensitivity of measurement ID GLOBAL BURDEN; UNITED-STATES; CONSUMPTION; RISK; DISEASE; QUANTIFICATION; DEPENDENCE; HEALTH; AGE AB Measuring the impact of alcohol consumption on morbidity and mortality depends on the accurate measurement of alcohol exposure, risk relationships, and outcomes. A variety of complicating factors make it difficult to measure these elements. This article reviews these factors and provides an overview of the articles that make up this special issue on current research examining alcohol's role in the burden of disease. These topics include estimating alcohol consumption as well as alcohol-related morbidity and mortality in various demographic groups, and the burden of alcohol use disorders. C1 [Rehm, Juergen] Ctr Addict & Mental Hlth, Social & Epidemiol Res Dept, Toronto, ON, Canada. [Rehm, Juergen] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Rehm, Juergen] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01062 Dresden, Germany. [Hingson, Ralph] Natl Inst Alcohol Abuse & Alcoholism, Natl Inst Hlth, Div Epidemiol & Prevent Res, Rockville, MD 20852 USA. RP Hingson, R (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Natl Inst Hlth, Div Epidemiol & Prevent Res, Rockville, MD 20852 USA. NR 49 TC 2 Z9 2 U1 2 U2 8 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2013 VL 35 IS 2 BP 122 EP 127 PG 6 WC Substance Abuse SC Substance Abuse GA 300TG UT WOS:000330486300002 PM 24881320 ER PT J AU Hilton, M AF Hilton, Michael TI APIS: The NIAAA Alcohol Policy Information System SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Editorial Material C1 Natl Inst Alcohol Abuse & Alcoholism, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. RP Hilton, M (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2013 VL 35 IS 2 BP 184 EP 185 PG 2 WC Substance Abuse SC Substance Abuse GA 300TG UT WOS:000330486300009 PM 24881326 ER PT J AU White, A Hingson, R AF White, Aaron Hingson, Ralph TI The Burden of Alcohol Use Excessive Alcohol Consumption and Related Consequences Among College Students SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Article DE Alcohol consumption; alcohol use, abuse, and dependence; alcohol burden; alcohol effects and consequences; harmful drinking; underage drinking; binge drinking; college student; risk factors; genetic factors; environmental factors; social norms; parental attitude; Greek organization; athletes; community environment; academic performance; injury; sexual assault; overdose; memory blackout; brain function; cognitive deficits; death; accessibility; availability; affordability; survey; data collection; data analysis ID RANDOMIZED CONTROLLED-TRIAL; NORMS MARKETING CAMPAIGNS; LEGAL DRINKING AGE; INDUCED MEMORY BLACKOUTS; HIGH-RISK DRINKING; FACE-TO-FACE; BINGE-DRINKING; OUTLET DENSITY; PUBLIC-HEALTH; BLOOD-ALCOHOL AB Research shows that multiple factors influence college drinking, from an individual's genetic susceptibility to the positive and negative effects of alcohol, alcohol use during high school, campus norms related to drinking, expectations regarding the benefits and detrimental effects of drinking, penalties for underage drinking, parental attitudes about drinking while at college, whether one is member of a Greek organization or involved in athletics, and conditions within the larger community that determine how accessible and affordable alcohol is. Consequences of college drinking include missed classes and lower grades, injuries, sexual assaults, overdoses, memory blackouts, changes in brain function, lingering cognitive deficits, and death. This article examines recent findings about the causes and consequences of excessive drinking among college students relative to their non-college peers and many of the strategies used to collect and analyze relevant data, as well as the inherent hurdles and limitations of such strategies. C1 [White, Aaron] Natl Inst Alcohol Abuse & Alcoholism, Coll & Underage Drinking Prevent Res, Bethesda, MD 20892 USA. [Hingson, Ralph] Natl Inst Alcohol Abuse & Alcoholism, Div Epidemiol & Prevent Res, Bethesda, MD USA. RP White, A (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Coll & Underage Drinking Prevent Res, Bethesda, MD 20892 USA. NR 180 TC 32 Z9 32 U1 13 U2 53 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2013 VL 35 IS 2 BP 201 EP 218 PG 18 WC Substance Abuse SC Substance Abuse GA 300TG UT WOS:000330486300012 PM 24881329 ER PT J AU Willenbring, ML AF Willenbring, Mark L. TI Gaps in Clinical Prevention and Treatment for Alcohol Use Disorders Costs, Consequences, and Strategies SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Article DE Alcohol use, abuse, and dependence; heavy drinking; alcohol use disorders (AUDs); alcohol-related problems; alcohol burden; burden of disease; morbidity; mortality; prevention; treatment; prevention; strategy; treatment strategy; screening and brief intervention; primary care; cost-effectiveness of AOD health services ID INTEGRATED OUTPATIENT TREATMENT; PRIMARY-CARE; INPATIENT SETTINGS; UNITED-STATES; BRIEF INTERVENTION; DRINKING BEHAVIOR; NATURAL RECOVERY; CONTROLLED-TRIAL; FOLLOW-UP; DEPENDENCE AB Heavy drinking causes significant morbidity, premature mortality, and other social and economic burdens on society, prompting numerous prevention and treatment efforts to avoid or ameliorate the prevalence of heavy drinking and its consequences. However, the impact on public health of current selective (i.e., clinical) prevention and treatment strategies is unclear. Screening and brief counseling for at-risk drinkers in ambulatory primary care has the strongest evidence for efficacy, and some evidence indicates this approach is cost-effective and reduces excess morbidity and dysfunction. Widespread implementation of screening and brief counseling of nondependent heavy drinkers outside of the medical context has the potential to have a large public health impact. For people with functional dependence, no appropriate treatment and prevention approaches currently exist, although such strategies might be able to prevent or reduce the morbidity and other harmful consequences associated with the condition before its eventual natural resolution. For people with alcohol use disorders, particularly severe and recurrent dependence, treatment studies have shown improvement in the short term. However, there is no compelling evidence that treatment of alcohol use disorders has resulted in reductions in overall disease burden. More research is needed on ways to address functional alcohol dependence as well as severe and recurrent alcohol dependence. C1 [Willenbring, Mark L.] Natl Inst Alcohol Abuse & Alcoholism, St Paul, MN USA. [Willenbring, Mark L.] Alltyr Transforming Treatment Addict, St Paul, MN USA. RP Willenbring, ML (reprint author), Natl Inst Alcohol Abuse & Alcoholism, St Paul, MN USA. NR 45 TC 1 Z9 1 U1 6 U2 11 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2013 VL 35 IS 2 BP 238 EP 243 PG 6 WC Substance Abuse SC Substance Abuse GA 300TG UT WOS:000330486300015 PM 24881332 ER PT J AU Breslow, RA Mukamal, KJ AF Breslow, Rosalind A. Mukamal, Kenneth J. TI Measuring the Burden-Current and Future Research Trends Results From the NIAAA Expert Panel on Alcohol and Chronic Disease Epidemiology SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Article DE NIAAA Expert Panel on Alcohol and Chronic Disease Epidemiology; alcohol consumption; alcohol burden; chronic disease; risk factors; epidemiology; research; diabetes; cardiovascular disease; cancer; stroke; liver disease; genetic factors; eating behaviors; clinical trials ID CORONARY-HEART-DISEASE; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; PROSPECTIVE COHORT; DRINKING PATTERNS; ISCHEMIC-STROKE; POSTMENOPAUSAL WOMEN; INSULIN SENSITIVITY; JOINT ASSOCIATION; NATIONAL-HEALTH AB Alcohol has a significant impact on health and well-being, from the beneficial aspects of moderate drinking to the detrimental effects of alcoholism. The broad implications of alcohol use on public health have been addressed through a wide range of epidemiological and clinical studies, many of which are described in this issue of Alcohol Research: Current Reviews. Where chronic disease is involved, alcohol use can be a risk factor that not only affects the onset of various chronic diseases but also exacerbates the ongoing extent and severity of those diseases. Lifestyle choices and genetic influences also contribute to, or help to alleviate, that risk. C1 [Breslow, Rosalind A.] Natl Inst Alcohol Abuse & Alcoholism, Natl Inst Hlth, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. [Mukamal, Kenneth J.] Harvard Univ, Sch Med, Div Gen Med & Primary Care, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Breslow, RA (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Natl Inst Hlth, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. NR 53 TC 4 Z9 4 U1 1 U2 5 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2013 VL 35 IS 2 BP 250 EP 259 PG 10 WC Substance Abuse SC Substance Abuse GA 300TG UT WOS:000330486300017 PM 24881334 ER PT J AU Zheng, L Bosch, RJ Chan, ES Read, S Kearney, M Margolis, DM Mellors, JW Eron, JJ Gandhi, RT AF Zheng, Lu Bosch, Ronald J. Chan, Ellen S. Read, Sarah Kearney, Mary Margolis, David M. Mellors, John W. Eron, Joseph J. Gandhi, Rajesh T. CA AIDS Clinical Trials Grp ACTG A524 TI Predictors of residual viraemia in patients on long-term suppressive antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Article ID IMMUNE ACTIVATION; HIV BURDEN; T-CELLS; GUT; INFECTION; TRIALS; PLASMA; RNA AB Background: HIV-1-infected individuals with plasma RNA<50 copies/ml on antiretroviral therapy (ART) may have residual, low-level viraemia detectable by PCR assays that are able to detect a single copy of viral RNA (single-copy assay [SCA]). The clinical predictors of residual viraemia in patients on long-term suppressive ART are not yet fully understood. Methods: We evaluated factors associated with residual viraemia in patients on suppressive ART who underwent screening for a raltegravir intensification trial (ACTG A5244). The screened population was HIV-1-infected adults receiving ART for >= 12 months with pre-ART HIV-1 RNA>100,000 copies/ml and on-therapy RNA levels below detection limits of commercial assays for >= 6 months. Results: Of 103 patients eligible for analysis, the median age was 46 years and the median duration of viral suppression was 4.8 years. 62% had detectable viraemia (> 0.2 copies/ml) by SCA (median 0.2 copies/ml, IQR < 0.2-1.8). Younger patients had lower HIV-1 RNA levels than older individuals (r=0.27, P=0.005). Patients with virological suppression on ART for 2 years or less had higher residual viraemia than those with suppression for > 2 years (median 2.3 versus 0.2 copies/ml; P=0.016). Conclusions: Among HIV-1-infected patients with pre-ART HIV-1 RNA>100,000 copies/ml, residual viraemia was detectable in the majority (62%) despite many years of suppressive ART. Higher level viraemia was associated with older age and < 2 years of virological suppression on ART. These findings should help in the selection of candidates for clinical trials of interventions designed to eliminate residual viraemia. C1 [Zheng, Lu; Bosch, Ronald J.; Chan, Ellen S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Read, Sarah] NIAID, Bethesda, MD 20892 USA. [Kearney, Mary] NCI, Frederick, MD 21701 USA. [Margolis, David M.; Eron, Joseph J.] Univ N Carolina, Chapel Hill, NC USA. [Mellors, John W.] Univ Pittsburgh, Pittsburgh, PA USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gandhi, Rajesh T.] Ragon Inst, Boston, MA USA. RP Zheng, L (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM szheng@sdac.harvard.edu OI Margolis, David/0000-0001-5714-0002 FU National Institute of Allergy and Infectious Diseases [U01AI068636, AI 06834]; NIH [R01 AI066992-04A1, G08LM008830-01]; Harvard University Center for AIDS Research [NIH 2P30 AI060354-06]; Tobira; GSK/ViiV through the University of North Carolina; [NIH U01 AI 694722] FX The project was supported by award number U01AI068636 from the National Institute of Allergy and Infectious Diseases. The project was also supported by a grant from the National Institute of Allergy and Infectious Diseases to the Statistical and Data Analysis Center (AI 06834). RTG is supported by NIH R01 AI066992-04A1 and NIH G08LM008830-01 and by grants to the AIDS Clinical Trials Group (NIH U01 AI 694722) and the Harvard University Center for AIDS Research (NIH 2P30 AI060354-06). The results of this analysis were previously presented at the XVII International AIDS Conference (Mexico City, Mexico) on 3-8 August 2008.; JWM is a consultant for Gilead Sciences and RFS Pharma and owns shares in RFS Pharma. JJE is a consultant for Merck, GSK/ViiV, Gilead, Tibotec and Bristol-Myers Squibb. He also receives research support from Tobira and GSK/ViiV through the University of North Carolina. NR 14 TC 7 Z9 7 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 IS 1 BP 39 EP 43 DI 10.3851/IMP2323 PG 5 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 287XP UT WOS:000329575900005 PM 22914318 ER PT J AU Falk, RT Brinton, LA Dorgan, JF Fuhrman, BJ Veenstra, TD Xu, X Gierach, GL AF Falk, Roni T. Brinton, Louise A. Dorgan, Joanne F. Fuhrman, Barbara J. Veenstra, Timothy D. Xu, Xia Gierach, Gretchen L. TI Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested case-control study SO BREAST CANCER RESEARCH LA English DT Article ID SEX-HORMONES; WOMEN; CARCINOGENESIS; ESTRADIOL; REPRODUCIBILITY; RELIABILITY; MECHANISMS AB Introduction: Elevated levels of circulating estrogens are linked to breast cancer risk among postmenopausal women but little is known about the importance of estrogen metabolism. A recently developed liquid chromatography tandem mass spectrometry-based method (LC-MS/MS) measuring a panel of 15 estrogen metabolites (EM) has been evaluated in one study, linking high levels of 2-pathway metabolites relative to the parent estrogens to reduced breast cancer risk. We analyzed this panel of EM in a nested case-control study of postmenopausal breast cancer. Methods: Between 1977 and 1987, 6,915 women provided blood samples to the Columbia Missouri Serum Bank and were followed for incident breast cancer through December 2002. We studied 215 postmenopausal breast cancer cases and 215 matched controls who were postmenopausal and not using exogenous hormones at the time of blood draw. EM were examined individually, grouped by pathway (hydroxylation at the C-2, C-4 or C-16 positions of the steroid ring) and by ratios of the groupings. Logistic regression models controlling for matching and breast cancer risk factors were used to calculate quartile-specific odds ratios (ORs) and 95% CIs. Results: Significant elevated risks were not observed for individual EM, except for quartiles of 16-epiestriol (P trend = 0.07). The OR for total EM, the parent estrogens estrone and estradiol, and 2-pathway catechol EM (2-hydroxyestrone and 2-hydroxyestradiol) were elevated but the trends were not statistically significant. Among 2-pathway metabolites, risks for the highest levels of 2-hydroxyestrone-3-methyl ether and 2-methoxyestradiol were reduced; ORs for women in the highest versus lowest quartiles were 0.57 (95% CI = 0.33 to 0.99) and 0.53 (95% CI = 0.30 to 0.96), respectively. Overall, women with higher levels of 2-pathway EM had a reduced risk of breast cancer, which remained after accounting for levels of parent EM, 4-pathway EM and 16-pathway EM (all trends, P <0.11). Conclusions: Women with more extensive hydroxylation along the 2-pathway may have a reduced risk of postmenopausal breast cancer. Further studies are needed to clarify the risks for specific EM and complex patterns of estrogen metabolism. This will require aggregation of EM results from several studies. C1 [Falk, Roni T.; Brinton, Louise A.; Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Dorgan, Joanne F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Fuhrman, Barbara J.] Univ Arkansas Med Sci, Dept Epidemiol, Fay W Boozman Coll Publ Hlth, Little Rock, AR 72205 USA. [Veenstra, Timothy D.; Xu, Xia] SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Falk, RT (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20852 USA. EM falkr@mail.nih.gov RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016; OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522; Fuhrman, Barbara/0000-0002-1777-9888 NR 21 TC 38 Z9 38 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 2 AR R34 DI 10.1186/bcr3416 PG 14 WC Oncology SC Oncology GA 302NU UT WOS:000330612000017 PM 23607871 ER PT J AU Yin, XD Xiang, TX Li, LL Su, XW Shu, XS Luo, XR Huang, JB Yuan, Y Peng, WY Oberst, M Kelly, K Ren, GS Tao, Q AF Yin, Xuedong Xiang, Tingxiu Li, LiLi Su, Xianwei Shu, Xingsheng Luo, Xinrong Huang, Jianbo Yuan, Ying Peng, Weiyan Oberst, Michael Kelly, Kathleen Ren, Guosheng Tao, Qian TI DACT1, an antagonist to Wnt/beta-catenin signaling, suppresses tumor cell growth and is frequently silenced in breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID BETA-CATENIN; METHYLATION PATTERNS; EPIGENETICS; CARCINOMA; PATHWAY; HDPR1; DNA; ESOPHAGEAL; MECHANISM; DAPPER1 AB Introduction: Aberrant activation of Wnt/beta-catenin signaling plays an important role in the pathogenesis of breast cancer. DACT1 (Dapper/Frodo) has been identified as involved in antagonizing Wnt/beta-catenin signaling through interacting with Dishevelled (Dvl), a central mediator of Wnt signaling, whereas its role in breast tumorigenesis remains unclear. Methods: We examined DACT1 expression in breast cancer cell lines and primary tumors with semiquantitative or quantitative RT-PCR and immunochemistry, and further evaluated the promoter methylation of DACT1 with methylation-specific PCR (MSP). We also explored the tumor-suppressive functions of DACT1 in vivo and in vitro, and its related mechanism in breast cancer. Results: We identified DACT1 as a methylated target in our breast cancer epigenome study. Here, we further investigated DACT1 expression in multiple breast cell lines and primary tumors, and further studied its function and molecular mechanisms. We found that DACT1 expression was silenced in eight (88.9%) of nine breast cancer cell lines, and its protein levels were obviously reduced in breast tumors compared with paired surgical-margin tissues. Promoter CpG methylation of DACT1 was detected in five (55.6%) of nine breast cancer cell lines and 40 (29.9%) of 134 primary tumors, but not in surgical-margin tissues and normal breast tissues. Demethylation treatment of breast cancer cell lines restored DACT1 expression along with promoter demethylation, suggesting that an epigenetic mechanism mediates DACT1 silencing in breast cancer. Functional assays showed that ectopic expression of DACT1 could inhibit breast tumor cell proliferation in vivo and in vitro through inducing apoptosis, and further suppress tumor cell migration through antagonizing the Wnt/beta-catenin signaling pathway. Conclusions: Our study demonstrates that DACT1 could function as a tumor suppressor but was frequently downregulated in breast cancer. C1 [Yin, Xuedong; Xiang, Tingxiu; Luo, Xinrong; Huang, Jianbo; Yuan, Ying; Peng, Weiyan; Ren, Guosheng; Tao, Qian] Chongqing Med Univ, Affiliated Hosp 1, Mol Oncol & Epigenet Lab, Chongqing 400016, Peoples R China. [Li, LiLi; Su, Xianwei; Shu, Xingsheng; Tao, Qian] Chinese Univ Hong Kong, Sir YK Pao Ctr Canc, Dept Clin Oncol, Canc Epigenet Lab, Shatin, Hong Kong, Peoples R China. [Li, LiLi; Su, Xianwei; Shu, Xingsheng; Tao, Qian] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China. [Li, LiLi; Su, Xianwei; Shu, Xingsheng; Tao, Qian] CUHK Shenzhen Res Inst, Shatin, Hong Kong, Peoples R China. [Oberst, Michael; Kelly, Kathleen] NCI, Signal Transduct Sect, NIH, Bethesda, MD 20892 USA. [Tao, Qian] Dalian Med Univ, Ctr Canc, Dalian 116044, Peoples R China. RP Ren, GS (reprint author), Chongqing Med Univ, Affiliated Hosp 1, Mol Oncol & Epigenet Lab, 1 Youyi Rd, Chongqing 400016, Peoples R China. EM rgs726@163.com; qtao@clo.cuhk.edu.hk FU National Natural Science Foundation of China [31171243, 81072148, 81172582]; Natural Science Foundation of Chongqing [2010BB5101]; Group Research Scheme of The Chinese University of Hong Kong [3110085] FX We thank Dr. Sun Y. Rha for some breast cancer cell lines. This study was supported by National Natural Science Foundation of China (31171243, 81072148, and 81172582), Natural Science Foundation of Chongqing (2010BB5101) and the Group Research Scheme of The Chinese University of Hong Kong (3110085). NR 34 TC 17 Z9 21 U1 2 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 2 AR R23 DI 10.1186/bcr3399 PG 12 WC Oncology SC Oncology GA 302NU UT WOS:000330612000006 PM 23497530 ER PT J AU Abu-Asab, MS Salazar, J Tuo, JS Chan, CC AF Abu-Asab, Mones S. Salazar, Jose Tuo, Jingsheng Chan, Chi-Chao TI Systems Biology Profiling of AMD on the Basis of Gene Expression SO JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MACULAR DEGENERATION; DISEASE AB Genetic pathways underlying the initiation and progression of age-related macular degeneration (AMD) have not been yet sufficiently revealed, and the correlations of AMD's genotypes, phenotypes, and disease spectrum are still awaiting resolution. We are tackling both problems with systems biology phylogenetic parsimony analysis. Gene expression data (GSE29801: NCBI, Geo) of macular and extramacular specimens of the retinas and retinal pigment epithelium (RPE) choroid complexes representing dry AMD without geographic atrophy (GA), choroidal neovascularization (CNV), GA, as well as pre-AMD and subclinical pre-AMD were polarized against their respective normal specimens and then processed through the parsimony program MIX to produce phylogenetic cladograms. Gene lists from cladograms' nodes were processed in Genomatix GePS to reveal the affected signaling pathway networks. Cladograms exposed a highly heterogeneous transcriptomic profiles within all the conventional phenotypes. Moreover, clades and nodal synapomorphies did not support the classical AMD phenotypes as valid transcriptomal genotypes. Gene lists defined by cladogram nodes showed that the AMD-related deregulations occurring in the neural retina were different from those in RPE-choroidal tissue. Our analysis suggests a more complex transcriptional profile of the phenotypes than expected. Evaluation of the disease in much earlier stages is needed to elucidate the initial events of AMD. C1 [Abu-Asab, Mones S.; Salazar, Jose; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Abu-Asab, MS (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mones@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 NR 20 TC 5 Z9 5 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2013 AR 453934 DI 10.1155/2013/453934 PG 7 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA 303GX UT WOS:000330663600001 ER PT S AU Farag, AA Graham, JH Farag, AA AF Farag, Amal A. Graham, James H. Farag, Aly A. GP IEEE TI DEFORMABLE MODELS FOR RANDOM SMALL-SIZE OBJECTS: CASE OF LUNG NODULES IN CT TOMOGRAPHY SO 2013 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING (ICASSP) SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech, and Signal Processing (ICASSP) CY MAY 26-31, 2013 CL Vancouver, CANADA SP Inst Elect & Elect Engineers, Inst Elect & Elect Engineers Signal Proc Soc ID TIME AB Deformable models are common in image modeling and analysis. Random objects provide major challenges as shapes and appearances are hard to quantify; hence, formulation of deformable models are much harder to construct and validate. In this paper, we examine the effect of randomness on building the shape and appearance models for small-size lung nodules (<= 1cm) which appear in computed tomography (CT) of the human chest. We devise an approach for annotation, which lends a standard mechanism for building traditional active appearance (AAM), active shape (ASM) and active tensor models (ATM). We illustrate the effectiveness of AAM for nodule detection. C1 [Farag, Amal A.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Bldg 10, Bethesda, MD 20892 USA. [Graham, James H.; Farag, Aly A.] Univ Louisville, Comp Vis & Image Proc Lab, Louisville, KY USA. RP Farag, AA (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Bldg 10, Bethesda, MD 20892 USA. EM Amal.aly1@gmail.com; james.graham@louisville.edu; aly.farag@louisville.edu NR 12 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4799-0356-6 J9 INT CONF ACOUST SPEE PY 2013 BP 1090 EP 1093 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BJQ19 UT WOS:000329611501053 ER PT J AU Hoon, M AF Hoon, Mark TI NPPB IS CRITICAL FOR ITCH SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 [Hoon, Mark] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2013 VL 93 IS 5 BP 606 EP 606 PG 1 WC Dermatology SC Dermatology GA 298ME UT WOS:000330327200038 ER PT S AU Court, DL Gan, JH Liang, YH Shaw, GX Tropea, JE Costantino, N Waugh, DS Ji, XH AF Court, Donald L. Gan, Jianhua Liang, Yu-He Shaw, Gary X. Tropea, Joseph E. Costantino, Nina Waugh, David S. Ji, Xinhua BE Bassler, BL Lichten, M Schupbach, G TI RNase III: Genetics and Function; Structure and Mechanism SO ANNUAL REVIEW OF GENETICS, VOL 47 SE Annual Review of Genetics LA English DT Review; Book Chapter DE global gene regulation; dsRNA binding; dsRNA processing; bacteriophage; CRISPR; Dicer ID DOUBLE-STRANDED-RNA; COLI RIBONUCLEASE-III; 16S RIBOSOMAL-RNA; ESCHERICHIA-COLI; MESSENGER-RNA; BACTERIOPHAGE-LAMBDA; ANTISENSE RNA; INT GENE; ELONGATION-FACTOR; HUMAN DICER AB RNase III is a global regulator of gene expression in Escherichia coli that is instrumental in the maturation of ribosomal and other structural RNAs. We examine here how RNase III itself is regulated in response to growth and other environmental changes encountered by the cell and how, by binding or processing double-stranded RNA (dsRNA) intermediates, RNase III controls the expression of genes. Recent insight into the mechanism of dsRNA binding and processing, gained from structural studies of RNase III, is reviewed. Structural studies also reveal new cleavage sites in the enzyme that can generate longer 3' overhangs. C1 [Court, Donald L.; Gan, Jianhua; Liang, Yu-He; Shaw, Gary X.; Tropea, Joseph E.; Costantino, Nina; Waugh, David S.; Ji, Xinhua] NCI, Ctr Canc Res, Frederick, MD 21702 USA. RP Court, DL (reprint author), NCI, Ctr Canc Res, Frederick, MD 21702 USA. EM courtd@mail.nih.gov; ganj@mail.nih.gov; liangyh@mail.nih.gov; shawg@mail.nih.gov; costantn@mail.nih.gov; tropeajo@mail.nih.gov; waughd@mail.nih.gov; jix@mail.nih.gov FU Intramural NIH HHS NR 134 TC 31 Z9 31 U1 2 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4197 BN 978-0-8243-1247-3 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2013 VL 47 BP 405 EP + DI 10.1146/annurev-genet-110711-155618 PG 35 WC Genetics & Heredity SC Genetics & Heredity GA BJR48 UT WOS:000329816000018 PM 24274754 ER PT B AU Antani, S You, D Simpson, M Rahman, M Demner-Fushman, D Thoma, G AF Antani, Sameer You, Daekeun Simpson, Matthew Rahman, Mahmudur Demner-Fushman, Dina Thoma, George GP IS&T TI The Role of Image Modality and Visual Characteristics in Archiving Biomedical Images SO ARCHIVING 2013: FINAL PROGRAM AND PROCEEDINGS LA English DT Proceedings Paper CT 10th IS&T Archiving Conference CY APR 02-05, 2013 CL Natl Archives & Records Adm Bldg, Washington, DC SP Soc Imag Sci & Technol, Natl Archives & Records Adm, Cinevation, JVC, MAMA HO Natl Archives & Records Adm Bldg AB Imaging in biomedicine has seen an explosive growth in recent decades. Clinicians can offer better diagnosis, and scientists and the lay public often better understand complex biomedical concepts through visual means. Typically, patient identifiers are used for archiving and indexing images' metadata in the clinical setting, and bibliographic citation data are used in library collections, such as the open access biomedical research articles from the U.S. National Library of Medicine's (NLM) PubMed Central (R) (PMC) repository. Automatically detected image modality and visual image characteristics can offer valuable addition to these traditional textual metadata for archiving and indexing visual material. Example image modalities include computerized tomography (CT), X-ray, magnetic resonance imaging (MRI), ultrasound, photographs, illustrations, charts, graphs, and sketches. The open-access biomedical literature in PMC is a source for OpenI (pronounced Open "eye"), a multimodal biomedical information retrieval system developed at the NLM that enables users to search for and retrieve relevant images and text. Our methods were evaluated in an international benchmarking forum in which we achieve a classification accuracy exceeding 90% at the highest level of a hierarchically organized image modality taxonomy, and 63.2% at the leaf level. C1 [Antani, Sameer; You, Daekeun; Simpson, Matthew; Rahman, Mahmudur; Demner-Fushman, Dina; Thoma, George] NIH, Natl Lib Med, Bethesda, MD 20892 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 10 TC 0 Z9 0 U1 0 U2 3 PU SOC IMAGING SCIENCE & TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA BN 978-0-89208-304-6 PY 2013 BP 31 EP 35 PG 5 WC Computer Science, Information Systems; Information Science & Library Science; Imaging Science & Photographic Technology SC Computer Science; Information Science & Library Science; Imaging Science & Photographic Technology GA BJT36 UT WOS:000330142700008 ER PT B AU Gallagher, ME AF Gallagher, Marie E. GP IS&T TI Improving Software Sustainability: Lessons Learned from Profiles in Science SO ARCHIVING 2013: FINAL PROGRAM AND PROCEEDINGS LA English DT Proceedings Paper CT 10th IS&T Archiving Conference CY APR 02-05, 2013 CL Natl Archives & Records Adm Bldg, Washington, DC SP Soc Imag Sci & Technol, Natl Archives & Records Adm, Cinevation, JVC, MAMA HO Natl Archives & Records Adm Bldg AB The Profiles in Science (R) digital library features digitized surrogates of historical items selected from the archival collections of the U.S. National Library of Medicine as well as collaborating institutions. In addition, it contains a database of descriptive, technical and administrative metadata. It also contains various software components that allow creation of the metadata, management of the digital items, and access to the items and metadata through the Profiles in Science Web site [1]. The choices made building the digital library were designed to maximize the sustainability and long-term survival of all of the components of the digital library [2]. For example, selecting standard and open digital file formats rather than proprietary formats increases the sustainability of the digital files [3]. Correspondingly, using non-proprietary software may improve the sustainability of the software either through in-house expertise or through the open source community. Limiting our digital library software exclusively to open source software or to software developed in-house has not been feasible. For example, we have used proprietary operating systems, scanning software, a search engine, and office productivity software. We did this when either lack of essential capabilities or the cost-benefit trade-off favored using proprietary software. We also did so knowing that in the future we would need to replace or upgrade some of our proprietary software, analogous to migrating from an obsolete digital file format to a new format as the technological landscape changes. Since our digital library's start in 1998, all of its software has been upgraded or replaced, but the digitized items have not yet required migration to other formats. Technological changes that compelled us to replace proprietary software included the cost of product licensing, product support, incompatibility with other software, prohibited use due to evolving security policies, and product abandonment. Sometimes these changes happen on short notice, so we continually monitor our library's software for signs of endangerment. We have attempted to replace proprietary software with suitable in-house or open source software. When the replacement involves a standalone piece of software with a nearly equivalent version, such as replacing a commercial HTTP server with an open source HTTP server, the replacement is straightforward. Recently we replaced software that functioned not only as our search engine but also as the backbone of the architecture of our Web site. In this paper, we describe the lessons learned and the pros and cons of replacing this software with open source software. C1 [Gallagher, Marie E.] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU SOC IMAGING SCIENCE & TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA BN 978-0-89208-304-6 PY 2013 BP 74 EP 79 PG 6 WC Computer Science, Information Systems; Information Science & Library Science; Imaging Science & Photographic Technology SC Computer Science; Information Science & Library Science; Imaging Science & Photographic Technology GA BJT36 UT WOS:000330142700017 ER PT B AU Misra, D Thoma, GR AF Misra, Dharitri Thoma, George R. GP IS&T TI Use of Descriptive Metadata as a Knowledgebase for Analyzing Data in Large Textual Collections SO ARCHIVING 2013: FINAL PROGRAM AND PROCEEDINGS LA English DT Proceedings Paper CT 10th IS&T Archiving Conference CY APR 02-05, 2013 CL Natl Archives & Records Adm Bldg, Washington, DC SP Soc Imag Sci & Technol, Natl Archives & Records Adm, Cinevation, JVC, MAMA HO Natl Archives & Records Adm Bldg AB Descriptive metadata, such as an article's title, authors, institutional affiliations, keywords and date of publication, collected either manually or automatically from documents contents, is often used to search and retrieve relevant documents in an archived collection. This metadata, especially for a large text corpus such as a biomedical collection, may encapsulate patterns, trends, and other valuable information, usually revealed by using specialized data analysis software to answer specific questions. A more useful, generalized approach is to repurpose this metadata to serve as a knowledgebase to answer appropriate semantic queries. At the US National Library of Medicine (NLM), we recently archived a large biomedical collection comprising annual conference proceedings containing research findings on cholera, conducted between the years 1960-2011 under the "US-Japan Cooperative Medical Science Program" (CMSP). This program was established to address health problems in Southeast Asia and other developing countries. An R&D information management system developed at NLM, called "System for the Preservation of Electronic Resources" (SPER), automatically extracted descriptive metadata from this text corpus and built a DSpace-based archive for accessing the conference articles. SPER also used this metadata to get detailed information regarding the CMSP research community, timelines of important drugs and discoveries and international collaboration, etc., using special purpose data analysis software. In this paper, we describe the occurrence and extraction of metadata from the CMSP document set, and present an alternative approach in which this metadata is used to build a knowledgebase to support semantic queries about the CMSP Program. Specifically, we show the OWL-based hierarchical ontology model created to represent the CMSP Program with its publications, participants and international collaboration over time. We discuss the technique used to convert the extracted metadata from relational database tables to OWL/RDF assertions suitable for supporting semantic queries. We show examples of queries performed against this CMSP knowledgebase, and discuss some scalability issues. Finally we describe how this approach could be customized for other large textual collections, including one from the Food and Drug Administration previously archived by the SPER system. C1 [Misra, Dharitri; Thoma, George R.] Natl Lib Med, Bethesda, MD USA. NR 5 TC 0 Z9 0 U1 1 U2 5 PU SOC IMAGING SCIENCE & TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA BN 978-0-89208-304-6 PY 2013 BP 193 EP 199 PG 7 WC Computer Science, Information Systems; Information Science & Library Science; Imaging Science & Photographic Technology SC Computer Science; Information Science & Library Science; Imaging Science & Photographic Technology GA BJT36 UT WOS:000330142700041 ER PT J AU Carpenter, AW Reighard, KP Saavedra, JE Schoenfisch, MH AF Carpenter, Alexis W. Reighard, Katelyn P. Saavedra, Joseph E. Schoenfisch, Mark H. TI O-2-Protected diazeniumdiolate-modified silica nanoparticles for extended nitric oxide release from dental composites SO BIOMATERIALS SCIENCE LA English DT Article ID FUNCTIONALIZATION; XEROGELS; ADHESION; DELIVERY AB O-2-Protected N-diazeniumdiolate-based silanes were grafted onto mesoporous silica nanoparticles to yield a scaffold with an NO payload of 2.4 mu mol NO per mg and NO release half-life of 23 d. Adhesion of Streptococcus mutans to dental restorative materials doped with these NO-releasing particles was reduced by 3-log compared to controls. C1 [Carpenter, Alexis W.; Reighard, Katelyn P.; Schoenfisch, Mark H.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Saavedra, Joseph E.] NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21702 USA. RP Carpenter, AW (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA. EM schoenfisch@unc.edu FU National Science Foundation [DMR 1104892]; Eastman Chemical Company (Kingsport, TN); Federal funds from the National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported by a National Science Foundation grant (DMR 1104892). A. W. C. gratefully acknowledges a graduate research fellowship from Eastman Chemical Company (Kingsport, TN). This project was also funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The authors thank Dr. Luiz Pimenta of the UNC School of Dentistry for providing dental composite materials and equipment. NR 26 TC 10 Z9 10 U1 2 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2047-4830 EI 2047-4849 J9 BIOMATER SCI-UK JI Biomater. Sci. PY 2013 VL 1 IS 5 BP 456 EP 459 DI 10.1039/c3bm00153a PG 4 WC Materials Science, Biomaterials SC Materials Science GA 295RX UT WOS:000330134300001 PM 23930221 ER PT J AU Proctor, LM Chhibba, S McEwen, J Peterson, J Wellington, C Baker, C Giovanni, M McInnes, P Lunsford, RD AF Proctor, Lita M. Chhibba, Shaila McEwen, Jean Peterson, Jane Wellington, Chris Baker, Carl Giovanni, Maria McInnes, Pamela Lunsford, R. Dwayne BE Fredricks, DN TI THE NIH HUMAN MICROBIOME PROJECT SO HUMAN MICROBIOTA: HOW MICROBIAL COMMUNITIES AFFECT HEALTH AND DISEASE LA English DT Article; Book Chapter ID HUMAN INTESTINAL MICROBIOTA; IMMUNE-SYSTEM; BODY HABITATS; BIRTH COHORT; GUT; DIVERSITY; DISEASE; BACTERIA; RISK; LIFE C1 [Proctor, Lita M.; Chhibba, Shaila; McEwen, Jean; Peterson, Jane; Wellington, Chris] NHGRI, NIH, Bethesda, MD 20892 USA. [Baker, Carl] NIAMS, NIH, Bethesda, MD USA. [Giovanni, Maria] NIAID, NIH, Bethesda, MD 20892 USA. [McInnes, Pamela] NIDCR, NIH, Bethesda, MD 20892 USA. [Lunsford, R. Dwayne] NIDCR, Microbiol Program, Integrat Biol & Infect Dis Branch, Div Extramural Res,NIH, Bethesda, MD 20892 USA. RP Proctor, LM (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 49 TC 2 Z9 2 U1 0 U2 12 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-47989-6 PY 2013 BP 1 EP 50 D2 10.1002/9781118409855 PG 50 WC Microbiology; Virology SC Microbiology; Virology GA BJO88 UT WOS:000329433600002 ER PT J AU Kraushaar, DC Zhao, KJ AF Kraushaar, Daniel C. Zhao, Keji TI The Epigenomics of Embryonic Stem Cell Differentiation SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE Epigenomics; chromatin; embryonic stem cells; differentiation ID HISTONE VARIANT H3.3; CORE TRANSCRIPTIONAL NETWORK; CHROMATIN REMODELING COMPLEX; RNA-POLYMERASE-II; SELF-RENEWAL; GENE-EXPRESSION; DEVELOPMENTAL REGULATORS; DEACETYLASE COMPLEX; FATE DETERMINATION; H3K4 METHYLATION AB Embryonic stem cells (ESCs) possess an open and highly dynamic chromatin landscape, which underlies their plasticity and ultimately maintains ESC pluripotency. The ESC epigenome must not only maintain the transcription of pluripotency-associated genes but must also, through gene priming, facilitate rapid and cell type-specific activation of developmental genes upon lineage commitment. Trans-generational inheritance ensures that the ESC chromatin state is stably transmitted from one generation to the next; yet at the same time, epigenetic marks are highly dynamic, reversible and responsive to extracellular cues. Once committed to differentiation, the ESC epigenome is remodeled and resolves into a more compact chromatin state. A thorough understanding of the role of chromatin modifiers in ESC fate and differentiation will be important if they are to be used for therapeutic purposes. Recent technical advances, particularly in next-generation sequencing technologies, have provided a genome-scale view of epigenetic marks and chromatin modifiers. More affordable and faster sequencing platforms have led to a comprehensive characterization of the ESC epigenome and epigenomes of differentiated cell types. In this review, we summarize and discuss the recent progress that has highlighted the central role of histone modifications, histone variants, DNA methylation and chromatin modifiers in ESC pluripotency and ESC fate. We provide a detailed and comprehensive discussion of genome-wide studies that are pertinent to our understanding of mammalian development. C1 [Kraushaar, Daniel C.; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Kraushaar, DC (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM daniel.kraushaar@nih.gov; zhaok@nhlbi.nih.gov FU Division of Intramural Research, NHLBI, NIH FX The research in the authors' laboratory was supported by the Division of Intramural Research, NHLBI, NIH. NR 116 TC 15 Z9 19 U1 1 U2 14 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2013 VL 9 IS 10 BP 1134 EP 1144 DI 10.7150/ijbs.7998 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 295NB UT WOS:000330121700013 PM 24339734 ER PT J AU Tesauro, M Campia, U Iantorno, M AF Tesauro, Manfredi Campia, Umberto Iantorno, Micaela TI Obesity-Related Metabolic Syndrome and Vascular Complications SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Editorial Material ID RISK-FACTORS; CARDIOVASCULAR RISK; INSULIN-RESISTANCE; CHILDREN; ASSOCIATION C1 [Tesauro, Manfredi] Univ Roma Tor Vergata, Dipartimento Med Sistemi, I-00133 Rome, Italy. [Campia, Umberto] MedStar Heart Inst, Washington, DC 20009 USA. [Campia, Umberto] MedStar Cardiovasc Res Network, Washington, DC 20009 USA. [Iantorno, Micaela] NIH, Dept Crit Care Med, Bethesda, MD 20852 USA. RP Tesauro, M (reprint author), Univ Roma Tor Vergata, Dipartimento Med Sistemi, I-00133 Rome, Italy. EM mtesauro@tiscali.it NR 12 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 EI 1687-8345 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2013 AR 534056 DI 10.1155/2013/534056 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299EQ UT WOS:000330378800001 ER PT J AU Staudt, LM AF Staudt, Louis M. TI New Lymphoma Therapies Inspired by Functional and Structural Genomics SO ONCOLOGIST LA English DT Meeting Abstract C1 [Staudt, Louis M.] NCI, Ctr Canc Genom, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 4 BP S2 EP S2 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700005 ER PT J AU El-Maouche, D Mehta, SH Sutcliffe, CG Higgins, Y Torbenson, MS Moore, RD Thomas, DL Sulkowski, MS Brown, TT AF El-Maouche, Diala Mehta, Shruti H. Sutcliffe, Catherine G. Higgins, Yvonne Torbenson, Michael S. Moore, Richard D. Thomas, David L. Sulkowski, Mark S. Brown, Todd T. TI Vitamin D deficiency and its relation to bone mineral density and liver fibrosis in HIV-HCV coinfection SO ANTIVIRAL THERAPY LA English DT Article ID CHRONIC HEPATITIS-C; SERUM 25-HYDROXYVITAMIN D; US GENERAL-POPULATION; AFRICAN-AMERICANS; D SUPPLEMENTATION; COHORT; WOMEN; OSTEOPOROSIS; PREVALENCE; FRACTURE AB Background: Fractures and cirrhosis are major causes of morbidity and mortality among HIV-HCV-coinfected individuals. It is not known whether vitamin D deficiency is associated with these outcomes. Methods: Between 2005 and 2007, 116 HIV-HCV-coinfected individuals underwent dual-energy X-ray absorptiometry within 1 year of a liver biopsy. 25-Hydroxyvitamin D (25OHD) and parathyroid hormone were measured from archived samples. Low bone mineral density (BMD) was defined as BMD >= 2 standard deviations lower than age-, sex- and race-matched controls (Z-score <=-2.0) at the total hip, femoral neck or lumbar spine. Histological fibrosis staging was assessed according to the METAVIR system (0 [no fibrosis] to 4 [cirrhosis]). Results: The cohort was 87% African-American and 63% male. The median age (IQR) was 49.9 years (46.5-53.3). A total of 89% had a CD4(+) T-cell count >200 cells/mm(3) and 64% were receiving HAART. The median 25OHD was 19 ng/ml (IQR 11.0-26.0). Hypovitaminosis D (25OHD <= 15 ng/ml) was present in 41% and secondary hyperparathyroidism, defined by parathyroid hormone >65 pg/ml, was present in 24%. In total, 27% had low BMD (Z-score <=-2) at the spine, femoral neck or total hip, and 39% had significant hepatic fibrosis (METAVIR >= 2). In multivariate analysis, vitamin D deficiency was not associated with significant fibrosis or with BMD at any site. Conclusions: Vitamin D deficiency was highly prevalent in this mostly African-American HIV-HCV-coinfected population, but was not related to BMD or liver disease severity. These data suggest that efforts to increase vitamin D levels in this population may not improve bone or liver outcomes. C1 [El-Maouche, Diala] NIDDK, NIH, Bethesda, MD 20892 USA. [Mehta, Shruti H.; Sutcliffe, Catherine G.; Moore, Richard D.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Higgins, Yvonne; Torbenson, Michael S.; Moore, Richard D.; Thomas, David L.; Sulkowski, Mark S.; Brown, Todd T.] Johns Hopkins Sch Med, Baltimore, MD 21218 USA. RP Brown, TT (reprint author), Johns Hopkins Sch Med, Baltimore, MD 21218 USA. EM tbrown27@jhmi.edu OI El-Maouche, Diala/0000-0002-0936-2249 FU National Institutes of Health [R01 DA11602, R01 AA16893, K24 DA00432, R37 013806, R01DA016065, R01A1093520]; National Center for Research Resources (NCRR) [UL1 RR 025005] FX This work was supported by grants from the National Institutes of Health: R01 DA11602, R01 AA16893, K24 DA00432 (RDM), R37 013806 (DLT), R01DA016065 (MSS) and R01A1093520 (TTB).; The project described was supported by grant number UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Road-map for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. NR 24 TC 7 Z9 7 U1 0 U2 3 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 IS 2 BP 237 EP 242 DI 10.3851/IMP2264 PG 6 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 290LP UT WOS:000329759300012 PM 22910231 ER PT B AU Yadav, H Jain, S Yadav, M AF Yadav, H. Jain, S. Yadav, M. BE Watson, RR Preedy, VR TI Probiotics and Diabetes/Obesity Health Implications SO BIOACTIVE FOOD AS DIETARY INTERVENTIONS FOR DIABETES SE Bioactive Foods in Chronic Disease States LA English DT Article; Book Chapter ID LACTOBACILLUS-CASEI; LACTOCOCCUS-LACTIS; MILK WHEY; IN-VITRO; RATS; STRESS; MICE; ACIDOPHILUS; CHOLESTEROL; PRODUCTS C1 [Yadav, H.; Jain, S.] NIH, Bethesda, MD 20892 USA. [Yadav, M.] Coll Profess Studies, Datia, Madhya Pradesh, India. RP Yadav, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397762-5; 978-0-12-397153-1 J9 BIOACT FOOD CHRON PY 2013 BP 307 EP 317 DI 10.1016/B978-0-12-397153-1.00029-9 PG 11 WC Endocrinology & Metabolism; Food Science & Technology; Nutrition & Dietetics SC Endocrinology & Metabolism; Food Science & Technology; Nutrition & Dietetics GA BJM04 UT WOS:000329030300028 ER PT B AU Alekel, DL Weaver, CM Ronis, MJJ Ward, WE AF Alekel, D. L. Weaver, C. M. Ronis, M. J. J. Ward, W. E. BE Watson, RR Preedy, VR TI Nutritional Influences on Bone Health and Overview of Methods SO BIOACTIVE FOOD AS DIETARY INTERVENTIONS FOR THE AGING POPULATION SE Bioactive Foods in Chronic Disease States LA English DT Article; Book Chapter ID ESTROGEN-RECEPTOR-BETA; HORMONE-REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; EARLY POSTMENOPAUSAL WOMEN; CALCIUM-METABOLISM; VITAMIN-D; MINERAL DENSITY; SOY PROTEIN; DIETARY-PROTEIN; UNITED-STATES C1 [Alekel, D. L.] NIH, Bethesda, MD 20892 USA. [Weaver, C. M.] Purdue Univ, W Lafayette, IN 47907 USA. [Ronis, M. J. J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Ronis, M. J. J.] Arkansas Childrens Nutr Ctr, Little Rock, AR USA. [Ward, W. E.] Brock Univ, St Catharines, ON L2S 3A1, Canada. RP Alekel, DL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 56 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397761-8; 978-0-12-397155-5 J9 BIOACT FOOD CHRON PY 2013 BP 357 EP 370 DI 10.1016/B978-0-12-397155-5.00096-9 PG 14 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA BJL94 UT WOS:000329024500027 ER PT B AU Alekel, DL AF Alekel, D. L. BE Watson, RR Preedy, VR TI Skeletal Impact of Soy Protein and Soy Isoflavones in Humans SO BIOACTIVE FOOD AS DIETARY INTERVENTIONS FOR THE AGING POPULATION SE Bioactive Foods in Chronic Disease States LA English DT Article; Book Chapter ID BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; EARLY POSTMENOPAUSAL WOMEN; PLACEBO-CONTROLLED TRIAL; HIP FRACTURE; CHINESE WOMEN; DOUBLE-BLIND; PREMENOPAUSAL WOMEN; LIFE-STYLE; BIOLOGIC CONTRIBUTORS C1 NIH, Bethesda, MD 20892 USA. RP Alekel, DL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397761-8; 978-0-12-397155-5 J9 BIOACT FOOD CHRON PY 2013 BP 371 EP 382 DI 10.1016/B978-0-12-397155-5.00105-7 PG 12 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA BJL94 UT WOS:000329024500028 ER PT J AU Calafat, AM Koch, HM Swan, SH Hauser, R Goldman, LR Lanphear, BP Longnecker, MP Rudel, RA Teitelbaum, SL Whyatt, RM Wolff, MS AF Calafat, Antonia M. Koch, Holger M. Swan, Shanna H. Hauser, Russ Goldman, Lynn R. Lanphear, Bruce P. Longnecker, Matthew P. Rudel, Ruthann A. Teitelbaum, Susan L. Whyatt, Robin M. Wolff, Mary S. TI Misuse of blood serum to assess exposure to bisphenol A and phthalates SO BREAST CANCER RESEARCH LA English DT Letter C1 [Calafat, Antonia M.] Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. [Koch, Holger M.] Inst Ruhr Univ Bochum, Inst Prevent & Occupat Med German Social Accid In, D-44789 Bochum, Germany. [Swan, Shanna H.; Teitelbaum, Susan L.; Wolff, Mary S.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Geol, Boston, MA 02115 USA. [Goldman, Lynn R.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC 20037 USA. [Lanphear, Bruce P.] British Columbia Childrens Hosp, Vancouver, BC V5Z 3ES, Canada. [Longnecker, Matthew P.] NIEHS, Res Triangle Pk, NC 27709 USA. [Rudel, Ruthann A.] Silent Spring Inst, Durham, MA 02458 USA. [Whyatt, Robin M.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. RP Wolff, MS (reprint author), Icahn Sch Med Mt Sinai, Dept Prevent Med, 1 Gustave L Levy Pl,Box 1057, New York, NY 10029 USA. EM mary.wolff@mssm.edu RI Koch, Holger/B-3277-2011; OI Koch, Holger/0000-0002-8328-2837; Longnecker, Matthew/0000-0001-6073-5322 FU NIEHS NIH HHS [U01 ES019454] NR 6 TC 38 Z9 38 U1 3 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 5 AR 403 DI 10.1186/bcr3494 PG 2 WC Oncology SC Oncology GA 290NA UT WOS:000329763800041 PM 24083327 ER PT J AU Ma, HY Lu, YN Marchbanks, PA Folger, SG Strom, BL McDonald, JA Simon, MS Weiss, LK Malone, KE Burkman, RT Sullivan-Halley, J Deapen, DM Press, MF Bernstein, L AF Ma, Huiyan Lu, Yani Marchbanks, Polly A. Folger, Suzanne G. Strom, Brian L. McDonald, Jill A. Simon, Michael S. Weiss, Linda K. Malone, Kathleen E. Burkman, Ronald T. Sullivan-Halley, Jane Deapen, Dennis M. Press, Michael F. Bernstein, Leslie TI Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women SO BREAST CANCER RESEARCH LA English DT Article ID PROGESTERONE-RECEPTOR; REPRODUCTIVE EXPERIENCES; PROLIFERATIVE ACTIVITY; ENDOCRINE THERAPY; SURVIVAL; RECURRENCE; TAMOXIFEN; BIOMARKERS; CARCINOMA; PATHOLOGY AB Introduction: The association of breast cancer patients' mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality. Methods: We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalinfixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of ER examined here included the percentage of tumor cell nuclei positively stained for ER, ER Histo (H)-score, and a score based on an adaptation of an equation presented by Cuzick and colleagues, which combines weighted values of ER H-score, percentage of tumor cell nuclei positively stained for the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) results. This is referred to as the ER/PR/HER2 score. Results: After controlling for age at diagnosis, race, study site, tumor stage, and histologic grade in multivariable Cox proportional hazards regression models, both percentage of tumor cell nuclei positively stained for ER (Ptrend = 0.0003) and the ER H-score (Ptrend = 0.0004) were inversely associated with breast cancer-specific mortality risk. The ER/PR/HER2 score was positively associated with breast cancer-specific mortality risk in women with ER + tumor (Ptrend = 0.001). Analyses by race revealed that ER positivity was associated with reduced risk of breast cancer-specific mortality in white women and black women. The two quantitative measures for ER alone provided additional discrimination in breast cancer-specific mortality risk only among white women with ER + tumors (both Ptrend = 0.01) while the ER/PR/HER2 score provided additional discrimination for both white women (Ptrend = 0.01) and black women (Ptrend = 0.03) with ER + tumors. Conclusions: Our data support quantitative immunohistochemical measures of ER, especially the ER/PR/HER2 score, as a more precise predictor for breast cancer-specific mortality risk than a simple determination of ER positivity. C1 [Ma, Huiyan; Lu, Yani; Sullivan-Halley, Jane; Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Marchbanks, Polly A.; Folger, Suzanne G.; McDonald, Jill A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA 30333 USA. [Strom, Brian L.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Simon, Michael S.] Wayne State Univ, Dept Oncol, Karmanos Canc Inst, Detroit, MI 48201 USA. [Weiss, Linda K.] NCI, Canc Ctr Branch, Bethesda, MD 20892 USA. [Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Burkman, Ronald T.] Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA 01199 USA. [Deapen, Dennis M.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. [Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. RP Ma, HY (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. EM hma@coh.org FU National Institute for Child Health and Human Development [NO1-HD-3-3175]; National Cancer Institute [K05-CA136967]; National Institute of Child Health and Human Development; National Cancer Institute, NIH FX The authors would like to thank Dr Karen Petrosyan, Armine Arakelyan, Hasmik Toumaian, and Judith Udove for technical assistance in the performance of the immunohistochemical assays for this study. They would also like to thank collaborators who contributed to the development and conduct of the Women's CARE Study but who did not directly contribute to the current study. This work was supported by National Institute for Child Health and Human Development grant NO1-HD-3-3175 and National Cancer Institute grant K05-CA136967. Data collection for the Women's CARE Study was supported by the National Institute of Child Health and Human Development and National Cancer Institute, NIH, through contracts with Emory University (N01-HD-3-3168), Fred Hutchinson Cancer Research Center (N01-HD-2-3166), Karmanos Cancer Institute at Wayne State University (N01-HD-3-3174), University of Pennsylvania (NO1-HD-3-3276), and University of Southern California (N01-HD-3-3175) and Interagency Agreement with Centers for Disease Control and Prevention (Y01-HD-7022). Collection of cancer incidence data in LA County by University of Southern California was supported by California Department of Health Services as part of statewide cancer reporting program mandated by California Health and Safety Code, Section 103885. Support for use of SEER cancer registries through contracts N01-CN-65064 (Detroit) and N01-PC-67010 (LA). Biomarker determination and analyses were supported by a contract from the National Institute of Child Health and Human Development (NO1-HD-3-3175) and a grant from the Breast Cancer Research Foundation (MFPress). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. NR 37 TC 4 Z9 4 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 5 AR R90 DI 10.1186/bcr3486 PG 12 WC Oncology SC Oncology GA 290NA UT WOS:000329763800018 PM 24070170 ER PT J AU Nichols, HB Trentham-Dietz, A Newcomb, PA Egan, KM Titus, LJ Hampton, JM Visvanathan, K AF Nichols, Hazel B. Trentham-Dietz, Amy Newcomb, Polly A. Egan, Kathleen M. Titus, Linda J. Hampton, John M. Visvanathan, Kala TI Pre-diagnosis oophorectomy, estrogen therapy and mortality in a cohort of women diagnosed with breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID HORMONE REPLACEMENT THERAPY; RECREATIONAL PHYSICAL-ACTIVITY; BRCA2 MUTATION CARRIERS; OVARIAN CONSERVATION; BILATERAL OOPHORECTOMY; POSTMENOPAUSAL WOMEN; NURSES HEALTH; ALL-CAUSE; RISK; HYSTERECTOMY AB Introduction: Pre-diagnosis oophorectomy and estrogen therapy could impact mortality due to breast cancer and cardiovascular disease (CVD) among breast cancer survivors. Elective bilateral oophorectomy at the time of hysterectomy for benign conditions is not uncommon among US women. Methods: We examined the association between pre-diagnosis total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) and both overall and cause-specific mortality in the Collaborative Breast Cancer Studies cohort. Medical history and prior estrogen use were collected during standardized telephone interviews. Vital status, including date and cause of death, was obtained by linkage with the National Death Index. Multivariate hazard ratios (HR) and 95% confidence intervals (CI) for cause-specific mortality were calculated using Cox proportional hazards regression. Results: Seventeen percent (N = 1,778) of breast cancer survivors (mean age at diagnosis = 63.5) reported pre-diagnosis TAHBSO. During follow-up (mean = 9.5 years), 2,856 deaths occurred, including 1,060 breast cancer deaths and 459 CVD deaths. Breast cancer deaths occurred a median of 5.1 years after diagnosis; CVD deaths occurred further from diagnosis (median = 9.7 years). Women who reported pre-diagnosis TAHBSO had a 16% decrease in all-cause mortality (HR = 0.84; 95% CI: 0.76, 0.92) compared to those with an intact uterus and ovaries. This overall decrease reflected a 27% lower breast cancer mortality among women who never used postmenopausal hormones (HR = 0.73; CI: 0.55, 0.96) and 43% lower CVD risk among women who reported using estrogen (HR = 0.57; CI: 0.39, 0.83) after TAHBSO. Conclusions: Information on prior TAHBSO and estrogen use can inform risk of death from both breast cancer and cardiovascular disease among breast cancer survivors. C1 [Nichols, Hazel B.; Visvanathan, Kala] Natl Inst Environm Hlth Sci, Epidemiol Branch, Durham, NC 27709 USA. [Trentham-Dietz, Amy] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA. [Trentham-Dietz, Amy; Hampton, John M.] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53726 USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Egan, Kathleen M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Titus, Linda J.] Dartmouth Med Sch, Lebanon, NH 03756 USA. [Visvanathan, Kala] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. RP Nichols, HB (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, 111 T W Alexander Dr,Res Triangle Pk, Durham, NC 27709 USA. EM nicholshb@niehs.nih.gov FU National Cancer Institute at the National Institutes of Health [CA47147, CA47305, CA069664, CA009314, CA111948] FX This works was supported by grants from the National Cancer Institute at the National Institutes of Health (CA47147, CA47305, CA069664, CA009314, CA111948). NR 44 TC 1 Z9 1 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 5 AR R99 DI 10.1186/bcr3560 PG 10 WC Oncology SC Oncology GA 290NA UT WOS:000329763800027 PM 24152546 ER PT J AU Razzaghi, H Troester, MA Gierach, GL Olshan, AF Yankaskas, BC Millikan, RC AF Razzaghi, Hilda Troester, Melissa A. Gierach, Gretchen L. Olshan, Andrew F. Yankaskas, Bonnie C. Millikan, Robert C. TI Association between mammographic density and basal-like and luminal A breast cancer subtypes SO BREAST CANCER RESEARCH LA English DT Article DE Mammographic density; Breast cancer; Subtypes; Basal-like; Epidemiology ID ESTROGEN-RECEPTOR STATUS; BODY-MASS INDEX; TUMOR CHARACTERISTICS; RISK-FACTORS; MOLECULAR SUBTYPES; PARENCHYMAL PATTERNS; POSTMENOPAUSAL WOMEN; MULTIETHNIC COHORT; RECORD LINKAGE; ETHNIC-GROUPS AB Introduction: Mammographic density is a strong risk factor for breast cancer overall, but few studies have examined the association between mammographic density and specific subtypes of breast cancer, especially aggressive basal-like breast cancers. Because basal-like breast cancers are less frequently screen-detected, it is important to understand how mammographic density relates to risk of basal-like breast cancer. Methods: We estimated associations between mammographic density and breast cancer risk according to breast cancer subtype. Cases and controls were participants in the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). A total of 491 cases had mammograms within five years prior to and one year after diagnosis and 528 controls had screening or diagnostic mammograms close to the dates of selection into CBCS. Mammographic density was reported to the CMR using Breast Imaging Reporting and Data System categories. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 1 and 2 (HER1 and HER2), and cytokeratin 5/6 (CK5/6) were assessed by immunohistochemistry and dichotomized as positive or negative, with ER+ and/or PR+, and HER2-tumors classified as luminal A and ER-, PR-, HER2-, HER1+ and/or CK5/6+ tumors classified as basal-like breast cancer. Triple negative tumors were defined as negative for ER, PR and HER2. Of the 491 cases 175 were missing information on subtypes; the remaining cases included 181 luminal A, 17 luminal B, 48 basal-like, 29 ER-/PR-/HER2+, and 41 unclassified subtypes. Odds ratios comparing each subtype to all controls and case-case odds ratios comparing mammographic density distributions in basal-like to luminal A breast cancers were estimated using logistic regression. Results: Mammographic density was associated with increased risk of both luminal A and basal-like breast cancers, although estimates were imprecise. The magnitude of the odds ratio associated with mammographic density was not substantially different between basal-like and luminal A cancers in case-control analyses and case-case analyses (case-case OR = 1.08 (95% confidence interval: 0.30, 3.84)). Conclusions: These results suggest that risk estimates associated with mammographic density are not distinct for separate breast cancer subtypes (basal-like/triple negative vs. luminal A breast cancers). Studies with a larger number of basal-like breast cancers are needed to confirm our findings. C1 [Razzaghi, Hilda; Troester, Melissa A.; Olshan, Andrew F.; Millikan, Robert C.] Univ N Carolina, Dept Epidemiol, Gillings Global Sch Publ Hlth, Chapel Hill, NC 27514 USA. [Troester, Melissa A.; Olshan, Andrew F.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Yankaskas, Bonnie C.] Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC 27514 USA. [Razzaghi, Hilda] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30345 USA. RP Razzaghi, H (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Global Sch Publ Hlth, Chapel Hill, NC 27514 USA. EM hrazzaghi@cdc.gov RI Gierach, Gretchen/E-1817-2016 OI Gierach, Gretchen/0000-0002-0165-5522 FU Intramural Research Program of the NIH; National Cancer Institute; National Institute Breast Cancer and the Environment Research Program [5U01ES019472-02]; NCI [5R01CA138255]; SPORE in Breast Cancer [5P50CA058233] FX The authors are grateful to Jessica Tse and Robert Christopher Allis for their assistance with data management and data analysis for this manuscript. This research was supported (in part) by the Intramural Research Program of the NIH and the National Cancer Institute. MAT was supported by the National Institute Breast Cancer and the Environment Research Program 5U01ES019472-02 and NCI grant 5R01CA138255. MAT is also supported by a SPORE in Breast Cancer 5P50CA058233. NR 76 TC 6 Z9 7 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 5 AR R76 DI 10.1186/bcr3470 PG 10 WC Oncology SC Oncology GA 290NA UT WOS:000329763800004 PM 24008056 ER PT J AU Whipple, RA Vitolo, MI Boggs, AE Charpentier, MS Thompson, K Martin, SS AF Whipple, Rebecca A. Vitolo, Michele I. Boggs, Amanda E. Charpentier, Monica S. Thompson, Keyata Martin, Stuart S. TI Parthenolide and costunolide reduce microtentacles and tumor cell attachment by selectively targeting detyrosinated tubulin independent from NF-kappa B inhibition SO BREAST CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; BREAST-CANCER CELLS; MESENCHYMAL TRANSITION; MICROTUBULE STABILITY; ANTICANCER DRUGS; IN-VITRO; PACLITAXEL; EXPRESSION; GROWTH; ACTIVATION AB Introduction: Detyrosinated tubulin, a post-translational modification of a-tubulin and a hallmark of stable microtubules, has gained recent attention given its association with tumor progression, invasiveness, and chemoresistance. We also recently reported that epithelial-to-mesenchymal transition (EMT) promotes tubulin detyrosination through tubulin tyrosine ligase (TTL) suppression. Furthermore, detyrosinated tubulin-enriched membrane protrusions, termed microtentacles (McTN), facilitate tumor cell reattachment to endothelial layers. Given the induction of EMT associated with inflammation and cancer progression, we tested anti-inflammatory nuclear factor-kappaB (NF-kappa B) inhibitors on a panel of human breast carcinoma cells to examine their effects on detyrosinated tubulin to identify more specific tubulin-directed anti-cancer treatments. Methods: Using metastatic human breast carcinoma cells MDA-MB-157, MDA-MB-436, and Bt-549, we measured the impact of NF-kappa B inhibitors parthenolide, costunolide, and resveratrol on detyrosinated tubulin using protein expression analysis and immunofluorescence. A luciferase reporter assay and a viability screen were performed to determine if the effects were associated with their NF-kappa B inhibitory properties or were a result of apoptosis. Realtime monitoring of cell-substratum attachment was measured utilizing electrical impedance across microelectronic sensor arrays. We compared the selectivity of the NF-kappa B inhibitors to specifically target detyrosinated tubulin with traditional tubulin-targeted therapeutics, paclitaxel and colchicine, throughout the study. Results: Sesquiterpene lactones, parthenolide and costunolide, selectively decrease detyrosinated tubulin independent of their inhibition of NF-kappa B. Live-cell scoring of suspended cells treated with parthenolide and costunolide show reduction in the frequency of microtentacles and inhibition of reattachment. Structural analysis shows that parthenolide and costunolide can decrease detyrosinated microtubules without significantly disrupting the overall microtubule network or cell viability. Paclitaxel and colchicine display indiscriminate disruption of the microtubule network. Conclusions: Our data demonstrate that selective targeting of detyrosinated tubulin with parthenolide and costunolide can reduce McTN frequency and inhibit tumor cell reattachment. These actions are independent of their effects on NF-kappa B inhibition presenting a novel anti-cancer property and therapeutic opportunity to selectively target a stable subset of microtubules in circulating tumor cells to reduce metastatic potential with less toxicity in breast cancer patients. C1 [Whipple, Rebecca A.; Vitolo, Michele I.; Thompson, Keyata; Martin, Stuart S.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA. [Vitolo, Michele I.; Martin, Stuart S.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Boggs, Amanda E.; Charpentier, Monica S.; Martin, Stuart S.] Univ Maryland, Sch Med, Program Mol Med, Baltimore, MD 21201 USA. RP Martin, SS (reprint author), Univ Maryland, Sch Med, Marlene & Stewart Greenebaum NCI Canc Ctr, Bressler Bldg,Rm 10-29,22 S Greene St, Baltimore, MD 21201 USA. EM ssmartin@som.umaryland.edu FU National Cancer Institute [R01-CA154624, R01-124704]; Susan G. Komen Foundation [KG100240]; Era of Hope Scholar award from the Department of Defense [BC100675] FX This research was supported by R01-CA154624 and R01-124704 from the National Cancer Institute, KG100240 from the Susan G. Komen Foundation and an Era of Hope Scholar award from the Department of Defense (BC100675). NR 45 TC 11 Z9 11 U1 2 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 5 AR R83 DI 10.1186/bcr3477 PG 12 WC Oncology SC Oncology GA 290NA UT WOS:000329763800011 PM 24028602 ER PT J AU Wang, DD Zhang, HY Liang, J Li, X Feng, XB Wang, H Hua, BZ Liu, BJ Lu, LW Gilkeson, GS Silver, RM Chen, WJ Shi, ST Sun, LY AF Wang, Dandan Zhang, Huayong Liang, Jun Li, Xia Feng, Xuebing Wang, Hong Hua, Bingzhu Liu, Bujun Lu, Liwei Gilkeson, Gary S. Silver, Richard M. Chen, Wanjun Shi, Songtao Sun, Lingyun TI Allogeneic Mesenchymal Stem Cell Transplantation in Severe and Refractory Systemic Lupus Erythematosus: 4 Years of Experience SO CELL TRANSPLANTATION LA English DT Article DE Mesenchymal stem cells (MSCs); Lupus erythematosus; Transplantation; Clinical remission ID UMBILICAL-CORD; STROMAL CELLS; MYOCARDIAL-INFARCTION; DISEASE-ACTIVITY; DOSE-ESCALATION; MRL/LPR MICE; DOUBLE-BLIND; DIFFERENTIATION; INFECTIONS; NEPHRITIS AB Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitors and are capable of differentiating into several tissues of mesenchymal origin. We have shown that bone marrow-derived MSCs from both SLE patients and lupus-prone MRL/lpr mice are defective structurally and functionally. Here we observe the long-term safety and efficacy of allogeneic MSC transplantation (MSCT) in treatment-resistant SLE patients. Eighty-seven patients with persistently active SLE who were refractory to standard treatment or had life-threatening visceral involvement were enrolled. Allogeneic bone marrow or umbilical cord-derived MSCs were harvested and infused intravenously (1 x 106 cells/kg of body weight). Primary outcomes were rates of survival, disease remission and relapse, as well as transplantation-related adverse events. Secondary outcomes included SLE disease activity index (SLEDAI) and serologic features. During the 4-year follow-up and with a mean follow-up period of 27 months, the overall rate of survival was 94% (82/87). Complete clinical remission rate was 28% at 1 year (23/83), 31% at 2 years (12/39), 42% at 3 years (5/12), and 50% at 4 years (3/6). Rates of relapse were 12% (10/83) at 1 year, 18% (7/39) at 2 years, 17% (2/12) at 3 years, and 17% (1/6) at 4 years. The overall rate of relapse was 23% (20/87). Disease activity declined as revealed by significant changes in the SLEDAI score, levels of serum autoantibodies, albumin, and complements. A total of five patients (6%) died after MSCT from non-treatment-related events in the 4-year follow-up, and no transplantation-related adverse event was observed. Allogeneic MSCT resulted in the induction of clinical remission and improvement in organ dysfunction in drug-resistant SLE patients. C1 [Wang, Dandan; Zhang, Huayong; Liang, Jun; Li, Xia; Feng, Xuebing; Wang, Hong; Hua, Bingzhu; Liu, Bujun; Sun, Lingyun] Nanjing Univ, Affiliated Drum Tower Hosp, Sch Med, Dept Rheumatol & Immunol, Nanjing 210008, Jiangsu, Peoples R China. [Lu, Liwei] Univ Hong Kong, Ctr Infect & Immunol, Dept Pathol & Microbiol, Hong Kong, Hong Kong, Peoples R China. [Gilkeson, Gary S.; Silver, Richard M.] Med Univ S Carolina, Div Rheumatol, Charleston, SC 29425 USA. [Chen, Wanjun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. [Shi, Songtao] Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90089 USA. RP Sun, LY (reprint author), Nanjing Univ, Affiliated Drum Tower Hosp, Sch Med, Dept Rheumatol & Immunol, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China. EM lingyunsun2001@yahoo.com.cn FU Major International (Regional) Joint Research Project [81120108021]; National Natural Science Foundation of China [30972736, 81273304]; Jiangsu Province Natural Science Foundation [BK2009034]; Jiangsu Province Kejiao Xingwei Program; Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health FX Dr. Sun's work was supported by the Major International (Regional) Joint Research Project (No. 81120108021), National Natural Science Foundation of China (No. 30972736, No. 81273304), Jiangsu Province Natural Science Foundation (BK2009034), and Jiangsu Province Kejiao Xingwei Program. This work was supported in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health (Dr. Chen). The authors declare no conflict of interest. NR 35 TC 54 Z9 64 U1 1 U2 8 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2013 VL 22 IS 12 BP 2267 EP 2277 DI 10.3727/096368911X582769 PG 11 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 293PS UT WOS:000329986100006 PM 24388428 ER PT S AU Ghann, WE Kim, YS Xu, S Lu, X Smith, MF Gullapalli, R Fleiter, T Brechbiel, MW Daniel, MC AF Ghann, William E. Kim, Young-Seung Xu, Su Lu, Xin Smith, Mark F. Gullapalli, Rao Fleiter, Thorsten Brechbiel, Martin W. Daniel, Marie-Christine BE Cullum, BM McLamore, ES TI Bifunctional Gold Nanoparticles for Targeted Dual-Imaging of Angiotensin Converting Enzyme SO SMART BIOMEDICAL AND PHYSIOLOGICAL SENSOR TECHNOLOGY X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Smart Biomedical and Physiological Sensor Technology X CY MAY 01-02, 2013 CL Baltimore, MD SP SPIE DE Gold nanoparticles; MRI; CT contrast agent; lisinopril; ACE; Gadolinium ID RAY COMPUTED-TOMOGRAPHY; CONTRAST AGENT; LISINOPRIL; SIZE AB The aim of nanodiagnostics is to identify disease at its earliest stage, particularly at the molecular level. Nanoparticle-based molecular imaging has set a unique platform for cellular tracking, targeted diagnostic studies, and image-monitored therapy. In the preclinical setting, several modalities, such as fluorescence, positron emission tomography (PET), magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound imaging are used for imaging of the cardiovascular system. Although this conventional imaging describes the extent and severity of cardiovascular diseases such as atherosclerosis or ischemia, molecular imaging is needed to identifying precursors of disease development and progression. Bringing multimodality capability to molecular imaging will harness the complimentary abilities of different techniques, thus optimizing the overall resolution and sensitivity of the resulting scans. The enhanced imaging details will permit more precise diagnosis and control of treatments. In this paper, we present the synthesis and characterization of a dual-imaging contrast agent based on bifunctional gold nanoparticles designed for the targeting of tissue ACE (angiotensin-converting enzyme) and monitoring of cardiovascular diseases. Lisinopril (an ACE inhibitor) was selected as the targeting agent and derivatized with thioctic acid for a stronger anchoring onto gold nanoparticles. A Gd(DOTA) complex was chosen as the MRI tag. The gold core serves as the CT contrast agent. The new nanoprobes prepared not only possess the ability to target tissue ACE but also provided bimodal imaging capabilities (CT and MRI). This bimodal molecular imaging will improve the ability to accurately target diseased tissue at a very early stage, thus diagnosing and then treating patients in the most efficient way. C1 [Ghann, William E.; Daniel, Marie-Christine] Univ Maryland Baltimore Cty, Dept Chem & Biochem, 1000 Hilltop Circle, Baltimore, MD 21250 USA. [Kim, Young-Seung; Brechbiel, Martin W.] NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. [Xu, Su; Lu, Xin; Smith, Mark F.; Gullapalli, Rao; Fleiter, Thorsten] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Baltimore, MD 21201 USA. RP Ghann, WE (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem, 1000 Hilltop Circle, Baltimore, MD 21250 USA. NR 25 TC 0 Z9 0 U1 0 U2 9 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9510-5 J9 PROC SPIE PY 2013 VL 8719 AR UNSP 87190U DI 10.1117/12.2016219 PG 9 WC Engineering, Biomedical; Optics; Physics, Applied SC Engineering; Optics; Physics GA BJQ21 UT WOS:000329624600020 ER PT J AU Benavente, OR Hart, RG McClure, LA Pergola, PE Conwit, R AF Benavente, O. R. Hart, R. G. McClure, L. A. Pergola, P. E. Conwit, R. CA SPS3 Investigators TI Effects of Blood Pressure Targets in Patients with Recent Lacunar Stroke: Results of the SPS3 Trial SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Benavente, O. R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Hart, R. G.] McMaster Univ, Hamilton, ON, Canada. [McClure, L. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Pergola, P. E.] Univ Texas San Antonio, San Antonio, TX USA. [Conwit, R.] NINDS, NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 34 EP 34 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600041 ER PT J AU Cheng, B Brinkmann, M Forkert, ND Treszl, A Ebinger, M Kohrmann, M Wu, O Kang, DW Liebeskind, DS Tourdias, T Singer, OC Christensen, S Luby, M Gerloff, C Thomalla, G AF Cheng, B. Brinkmann, M. Forkert, N. D. Treszl, A. Ebinger, M. Koehrmann, M. Wu, O. Kang, D. W. Liebeskind, D. S. Tourdias, T. Singer, O. C. Christensen, S. Luby, M. Gerloff, C. Thomalla, G. CA STIR & VISTA Imaging Investigators TI Quantitative measurements of relative fluid-attenuated inversion recovery (FLAIR) signal intensities in acute stroke do not improve accuracy of estimation of lesion age SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Cheng, B.; Brinkmann, M.; Gerloff, C.; Thomalla, G.] Klin & Poliklin Neurol Kopf & Neurozentrum, Hamburg, Germany. [Forkert, N. D.] Unversite Klinikum Hamburg Eppendorf, Inst Computat Neurosci, Hamburg, Germany. [Treszl, A.] Unversite Klinikum Hamburg Eppendorf, Inst Med Biometrie & Epidemiol, Hamburg, Germany. [Ebinger, M.] Charite, Ctr Schlaganfallforsch Berlin, D-13353 Berlin, Germany. [Koehrmann, M.] Univ Erlangen Nurnberg, Neurol Klin, D-91054 Erlangen, Germany. [Wu, O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula MartinosCtr Biomed Imaging,Dept Radiol, Boston, MA USA. [Kang, D. W.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea. [Liebeskind, D. S.] Univ Calif Oakland, Dept Neurol, Oakland, CA USA. [Tourdias, T.] Univ Bordeaux, Serv NeuroImagerie Diagnost Therapeut, CHU Bordeaux, Bordeaux, France. [Singer, O. C.] Univ Klinikum Erlangen Nurnberg, Kliniken Neuroradiol, Erlangen, Germany. [Christensen, S.] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic, Australia. [Luby, M.] Inst Neurol Disorders & Stroke, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 44 EP 44 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600052 ER PT J AU Ginsberg, MD Palesch, YY Hill, MD Martin, RH Moy, CS Barsan, WG Ryckborst, KJ Tamariz, D Waldman, BD AF Ginsberg, M. D. Palesch, Y. Y. Hill, M. D. Martin, R. H. Moy, C. S. Barsan, W. G. Ryckborst, K. J. Tamariz, D. Waldman, B. D. CA ALIAS Trial Investigators TI THE ALBUMIN IN ACUTE STROKE (ALIAS) PART 2 CLINICAL TRIAL - A RANDOMIZED MULTICENTER INVESTIGATION OF ALBUMIN- NEUROPROTECTION FOR ACUTE ISCHEMIC STROKE. 2: PRIMARY AND SECONDARY EFFICACY OUTCOMES SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Ginsberg, M. D.; Tamariz, D.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Palesch, Y. Y.; Martin, R. H.; Waldman, B. D.] Med Univ S Carolina, Charleston, SC USA. [Hill, M. D.; Ryckborst, K. J.] Univ Calgary, Calgary, AB, Canada. [Moy, C. S.] Natl Inst Neurol Disorders & Stroke, Rockville, MD USA. [Barsan, W. G.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 107 EP 107 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600143 ER PT J AU Ginsberg, MD Hill, MD Palesch, YY Martin, RH Moy, CS Barsan, WG Ryckborst, KJ Tamariz, D Waldman, BD AF Ginsberg, M. D. Hill, M. D. Palesch, Y. Y. Martin, R. H. Moy, C. S. Barsan, W. G. Ryckborst, K. J. Tamariz, D. Waldman, B. D. CA ALIAS Trial Investigators TI THE ALBUMIN IN ACUTE STROKE (ALIAS) PART 2 CLINICAL TRIAL - A RANDOMIZED MULTICENTER INVESTIGATION OF ALBUMIN-NEUROPROTECTION FOR ACUTE ISCHEMIC STROKE. 1: RATIONALE, TRIAL DESIGN AND SAFETY OUTCOMES SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Ginsberg, M. D.; Tamariz, D.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Hill, M. D.; Ryckborst, K. J.] Univ Calgary, Calgary, AB, Canada. [Palesch, Y. Y.; Martin, R. H.; Waldman, B. D.] Med Univ S Carolina, Charleston, SC USA. [Moy, C. S.] Natl Inst Neurol Disorders & Stroke, Rockville, MD USA. [Barsan, W. G.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 107 EP 107 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600142 ER PT J AU Field, TS Patton, KL McClure, LA Sussman, CR White, CL Pergola, PE Cervantes-Arriaga, A Conwit, RA Hart, RG Benavente, OR AF Field, T. S. Patton, K. L. McClure, L. A. Sussman, C. R. White, C. L. Pergola, P. E. Cervantes-Arriaga, A. Conwit, R. A. Hart, R. G. Benavente, O. R. CA SPS3 Investigators TI The Impact of Blood Pressure Variability on Stroke Recurrence: The SPS3 trial SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Field, T. S.; Benavente, O. R.] Univ British Columbia, Brain Res Ctr, Vancouver Stroke Program, Vancouver, BC V5Z 1M9, Canada. [Patton, K. L.; McClure, L. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Sussman, C. R.] Vanderbilt Univ, Nashville, TN 37235 USA. [White, C. L.; Pergola, P. E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Cervantes-Arriaga, A.] Natl Inst Neurol & Neurosurg, Neurodegenerat Res Unit, Mexico City, DF, Mexico. [Conwit, R. A.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Hart, R. G.] McMaster Univ, Hamilton, ON L8S 4L8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 111 EP 111 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600150 ER PT J AU Mohr, JP Stapf, C Moskowitz, AJ Parides, MK Moquete, E Young, WL Moy, CS Vicaut, E AF Mohr, J. P. Stapf, C. Moskowitz, A. J. Parides, M. K. Moquete, E. Young, W. L. Moy, C. S. Vicaut, E. CA 35 Ctr North South Amer Europe TI ARUBA (A Randomized trial of Unruptured Brain Arteriovenous malformations) SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Mohr, J. P.] NYC, Neurol Inst, New York, NY USA. [Stapf, C.; Vicaut, E.] Hop Lariboisiere, AP HP, F-75475 Paris, France. [Moskowitz, A. J.; Parides, M. K.; Moquete, E.] Mt Sinai Med Ctr, InCHOIR, New York, NY 10029 USA. [Young, W. L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Moy, C. S.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 191 EP 191 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600269 ER PT J AU Phan, TG Demchuk, A Srikanth, V Silver, B Patel, S Barber, PA Levine, SR Hill, M AF Phan, T. G. Demchuk, A. Srikanth, V. Silver, B. Patel, S. Barber, P. A. Levine, S. R. Hill, M. CA NINDS Rt-PA Stroke Study Grp TI Relating ASPECTS infarct location to stroke disability in the NINDS rt-PA trial: proof of concept study using penalized logistic regression SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Phan, T. G.; Srikanth, V.] Stroke & Aging Res, Clayton, Vic, Australia. [Demchuk, A.; Barber, P. A.; Hill, M.] Hotchkiss Brain Inst, Calgary, AB, Canada. [Silver, B.] Brown Univ, Providence, RI 02912 USA. [Patel, S.] Wayne State, Henry Ford Hosp, Detroit, MI USA. [Levine, S. R.] State Univ New York, Brooklyn, NY USA. [NINDS Rt-PA Stroke Study Grp] NINDS Rt PA Stroke Study Grp, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 407 EP 407 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092601226 ER PT J AU Conforto, AB Mello, EA Anjos, SM Conti, J Andrade, KN Rodrigues, W Cohen, LG AF Conforto, A. B. Mello, E. A. Anjos, S. M. Conti, J. Andrade, K. N. Rodrigues, W., Jr. Cohen, L. G. TI Effects of low-frequency repetitive magnetic stimulation of the unaffected hemisphere on cortical excitability in the subacute phase after stroke SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Conforto, A. B.; Mello, E. A.; Anjos, S. M.; Conti, J.; Andrade, K. N.; Rodrigues, W., Jr.] Univ Sao Paulo, Hosp Clin, Sao Paulo, Brazil. [Cohen, L. G.] NINDS, Human Cort Physiol & Stroke Rehabil Sect, Bethesda, MD 20892 USA. RI DOS ANJOS, SARAH/G-9277-2015 OI DOS ANJOS, SARAH/0000-0002-7792-862X NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 853 EP 853 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092602522 ER PT J AU Wang, YJ Subramanian, P Shen, DF Tuo, JS Becerra, SP Chan, CC AF Wang, Yujuan Subramanian, Preeti Shen, Defen Tuo, Jingsheng Becerra, S. Patricia Chan, Chi-Chao TI Pigment epithelium-derived factor reduces apoptosis and pro-inflammatory cytokine gene expression in a murine model of focal retinal degeneration SO ASN NEURO LA English DT Article DE age-related macular degeneration; apoptosis; inflammation; neuroprotection; pigment epithelium-derived factor; retina ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; FACTOR PEDF; CCL2/CX3CR1-DEFICIENT MICE; PHOTORECEPTOR DEGENERATION; INTERPHOTORECEPTOR MATRIX; CELLS; IDENTIFICATION; LESIONS; NEOVASCULARIZATION AB AMD (age-related macular degeneration) is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor) is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults. We studied the effects of PEDF on focal retinal lesions in DKO rd8 (Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)]) mice, a model for progressive, focal rd (retinal degeneration). First, we found a significant decrease in PEDF transcript expression in DKO rd8 mouse retina and RPE (retinal pigment epithelium) than WT (wild-type, C57BL/6N). Next, cultured DKO rd8 RPE cells secreted lower levels of PEDF protein in the media than WT. Then the right eyes of DKO rd8 mice were injected intravitreously with recombinant human PEDF protein (1 mu g), followed by a subconjunctival injection of PEDF (3 mu g) 4 weeks later. The untreated left eyes served as controls. The effect of PEDF was assessed by fundoscopy, ocular histopathology and A2E {[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E, 3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl) 1E,3E,5E,7E-hexatrienyl]-pyridinium} levels, as well as apoptotic and inflammatory molecules. The PEDF-treated eyes showed slower progression or attenuation of the focal retinal lesions, fewer and/or smaller photoreceptor and RPE degeneration, and significantly lower A2E, relative to the untreated eyes. In addition, lower expression of apoptotic and inflammatory molecules were detected in the PEDF-treated than untreated eyes. Our results establish that PEDF potently stabilizes photoreceptor degeneration via suppression of both apoptotic and inflammatory pathways. The multiple beneficial effects of PEDF represent a novel approach for potential AMD treatment. C1 [Wang, Yujuan; Shen, Defen; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Yujuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China. [Subramanian, Preeti; Becerra, S. Patricia] NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI wang, yujuan/C-8428-2016 FU National Eye Institute Intramural Research Program FX This work was supported by the National Eye Institute Intramural Research Program. NR 61 TC 17 Z9 17 U1 1 U2 6 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 1759-0914 J9 ASN NEURO JI ASN Neuro PY 2013 VL 5 IS 5 AR e00126 DI 10.1042/AN20130028 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 286EZ UT WOS:000329450200002 PM 24160756 ER PT J AU Stofanko, M Han, JC Elsea, SH Pena, HB Goncalves-Dornelas, H Pena, SDJ AF Stofanko, Martin Han, Joan C. Elsea, Sarah H. Pena, Heloisa B. Goncalves-Dornelas, Higgor Junho Pena, Sergio Danilo TI Rapid and Inexpensive Screening of Genomic Copy Number Variations Using a Novel Quantitative Fluorescent PCR Method SO DISEASE MARKERS LA English DT Article ID DELINEATION; DELETIONS; REGION; GENES AB Detection of human microdeletion and microduplication syndromes poses significant burden on public healthcare systems in developing countries. With genome-wide diagnostic assays frequently inaccessible, targeted low-cost PCR-based approaches are preferred. However, their reproducibility depends on equally efficient amplification using a number of target and control primers. To address this, the recently described technique called Microdeletion/Microduplication Quantitative Fluorescent PCR (MQF-PCR) was shown to reliably detect four human syndromes by quantifying DNA amplification in an internally controlled PCR reaction. Here, we confirm its utility in the detection of eight human microdeletion syndromes, including the more common WAGR, Smith-Magenis, and Potocki-Lupski syndromes with 100% sensitivity and 100% specificity. We present selection, design, and performance evaluation of detection primers using variety of approaches. We conclude that MQF-PCR is an easily adaptable method for detection of human pathological chromosomal aberrations. C1 [Stofanko, Martin; Pena, Heloisa B.; Goncalves-Dornelas, Higgor; Junho Pena, Sergio Danilo] GENE Nucleo Genet Med, BR-30130909 Belo Horizonte, MG, Brazil. [Han, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Metab & Neuroendocrinol, NIH, Bethesda, MD 20892 USA. [Elsea, Sarah H.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Sch Med, Richmond, VA 23298 USA. [Elsea, Sarah H.] Virginia Commonwealth Univ, Dept Pediat, Sch Med, Richmond, VA 23298 USA. [Elsea, Sarah H.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Junho Pena, Sergio Danilo] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG, Brazil. RP Pena, SDJ (reprint author), GENE Nucleo Genet Med, Ave Afonso Pena 3111,9th Floor, BR-30130909 Belo Horizonte, MG, Brazil. EM spena@gene.com.br FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [401983/2010-2]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [ZIAHD008898] FX The authors thank Conselho Nacional de Desenvolvimento Cientifico e Tecnologico Grant no. 401983/2010-2 for providing financial funding for this work. The research was also supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIAHD008898). We thank PRISMS (SMS support group) and the patients and their families for their participation and support of research. NR 18 TC 0 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0278-0240 EI 1875-8630 J9 DIS MARKERS JI Dis. Markers PY 2013 BP 589 EP 594 DI 10.1155/2013/704917 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 286EO UT WOS:000329449100001 PM 24288428 ER PT J AU Kraushaar, DC Jin, WF Maunakea, A Abraham, B Ha, M Zhao, KJ AF Kraushaar, Daniel C. Jin, Wenfei Maunakea, Alika Abraham, Brian Ha, Misook Zhao, Keji TI Genome-wide incorporation dynamics reveal distinct categories of turnover for the histone variant H3.3 SO GENOME BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; NUCLEOSOME STABILITY; STEM-CELLS; CHROMATIN; REPLICATION; DEPOSITION; REGIONS; ELONGATION AB Background: Nucleosomes are present throughout the genome and must be dynamically regulated to accommodate binding of transcription factors and RNA polymerase machineries by various mechanisms. Despite the development of protocols and techniques that have enabled us to map nucleosome occupancy genome-wide, the dynamic properties of nucleosomes remain poorly understood, particularly in mammalian cells. The histone variant H3.3 is incorporated into chromatin independently of DNA replication and requires displacement of existing nucleosomes for its deposition. Here, we measure H3.3 turnover at high resolution in the mammalian genome in order to present a genome-wide characterization of replication-independent H3.3-nucleosome dynamics. Results: We developed a system to study the DNA replication-independent turnover of nucleosomes containing the histone variant H3.3 in mammalian cells. By measuring the genome-wide incorporation of H3.3 at different time points following epitope-tagged H3.3 expression, we find three categories of H3.3-nucleosome turnover in vivo: rapid turnover, intermediate turnover and, specifically at telomeres, slow turnover. Our data indicate that H3.3-containing nucleosomes at enhancers and promoters undergo rapid turnover that is associated with active histone modification marks including H3K4me1, H3K4me3, H3K9ac, H3K27ac and the histone variant H2A. Z. The rate of turnover is negatively correlated with H3K27me3 at regulatory regions and with H3K36me3 at gene bodies. Conclusions: We have established a reliable approach to measure turnover rates of H3.3-containing nucleosomes on a genome-wide level in mammalian cells. Our results suggest that distinct mechanisms control the dynamics of H3.3 incorporation at functionally different genomic regions. C1 [Kraushaar, Daniel C.; Jin, Wenfei; Maunakea, Alika; Abraham, Brian; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Ha, Misook] Samsung Elect Corp, Samsung Adv Inst Technol, Yongin 446712, Gyeonggi Do, South Korea. RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov FU Division of Intramural Research, NHLBI, NIH, USA FX We thank the NHLBI DNA Sequencing Core facility for sequencing the ChIP-Seq and RNA-Seq libraries. The work is supported by the Division of Intramural Research, NHLBI, NIH, USA. NR 53 TC 37 Z9 37 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2013 VL 14 IS 10 AR R121 DI 10.1186/gb-2013-14-10-r121 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 285IN UT WOS:000329387500014 PM 24176123 ER PT J AU Maraia, RJ Arimbasseri, AG AF Maraia, Richard J. Arimbasseri, Aneeshkumar G. TI It's Sno'ing on Pol III at nuclear pores SO GENOME BIOLOGY LA English DT Editorial Material ID RNA-POLYMERASE III; TRANSCRIPTION; EXPRESSION; ELEMENTS; GENES AB Integral nuclear pore proteins associate with subsets of snoRNA and tRNA genes transcribed by RNA polymerase III and promote 3 ' transcript processing in nematodes. C1 [Maraia, Richard J.; Arimbasseri, Aneeshkumar G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov OI Arimbasseri, Gopalakrishnan Aneeshkumar/0000-0001-5266-2688 NR 10 TC 1 Z9 1 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2013 VL 14 IS 10 AR 137 DI 10.1186/gb4137 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 285IN UT WOS:000329387500017 PM 24176203 ER PT J AU Taher, L Smith, RP Kim, MJ Ahituv, N Ovcharenko, I AF Taher, Leila Smith, Robin P. Kim, Mee J. Ahituv, Nadav Ovcharenko, Ivan TI Sequence signatures extracted from proximal promoters can be used to predict distal enhancers SO GENOME BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; GENOMIC REGULATORY BLOCKS; TISSUE-SPECIFIC ENHANCERS; OPEN-ACCESS DATABASE; LIVER-X-RECEPTOR; GENE-EXPRESSION; CHIP-SEQ; VERTEBRATE GENOMES; MAMMALIAN GENOMES; CONTROL ELEMENTS AB Background: Gene expression is controlled by proximal promoters and distal regulatory elements such as enhancers. While the activity of some promoters can be invariant across tissues, enhancers tend to be highly tissue-specific. Results: We compiled sets of tissue-specific promoters based on gene expression profiles of 79 human tissues and cell types. Putative transcription factor binding sites within each set of sequences were used to train a support vector machine classifier capable of distinguishing tissue-specific promoters from control sequences. We obtained reliable classifiers for 92% of the tissues, with an area under the receiver operating characteristic curve between 60% (for subthalamic nucleus promoters) and 98% (for heart promoters). We next used these classifiers to identify tissue-specific enhancers, scanning distal non-coding sequences in the loci of the 200 most highly and lowly expressed genes. Thirty percent of reliable classifiers produced consistent enhancer predictions, with significantly higher densities in the loci of the most highly expressed compared to lowly expressed genes. Liver enhancer predictions were assessed in vivo using the hydrodynamic tail vein injection assay. Fifty-eight percent of the predictions yielded significant enhancer activity in the mouse liver, whereas a control set of five sequences was completely negative. Conclusions: We conclude that promoters of tissue-specific genes often contain unambiguous tissue-specific signatures that can be learned and used for the de novo prediction of enhancers. C1 [Taher, Leila; Ovcharenko, Ivan] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Taher, Leila] Univ Rostock, Inst Biostat & Informat Med & Ageing Res, D-18057 Rostock, Germany. [Smith, Robin P.; Kim, Mee J.; Ahituv, Nadav] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA. [Smith, Robin P.; Kim, Mee J.; Ahituv, Nadav] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA. RP Ahituv, N (reprint author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA. EM nadav.ahituv@ucsf.edu; ovcharen@nih.gov OI Ahituv, Nadav/0000-0002-7434-8144 FU Intramural Research Program of the NIH, National Library of Medicine (IO); NIGMS [GM61390]; NICHD [R01HD059862]; NHGRI [1R01HG005058, 1R01HG006768]; NIDDK [1R01DK090382]; NINDS [1R01NS079231]; Simons Foundation (SFARI) [256769]; CIHR fellowship in hepatology; NIH [T32 GM007175]; Amgen Research Excellence in Bioengineering and Therapeutic Sciences Fellowship; QBC Fellowship FX This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine (IO). NA is supported in part by NIGMS award number GM61390, NICHD grant number R01HD059862, NHGRI grant numbers 1R01HG005058 and 1R01HG006768, NIDDK grant number 1R01DK090382, NINDS award number 1R01NS079231 and the Simons Foundation (SFARI # 256769). RPS is supported in part by a CIHR fellowship in hepatology. MJK was supported in part by NIH training grant T32 GM007175, the Amgen Research Excellence in Bioengineering and Therapeutic Sciences Fellowship and the QBC Fellowship. We are grateful to Marcelo Nobrega and John Westlund from the University of Chicago for productive discussions and assistance with the analysis of preliminary data. NR 105 TC 10 Z9 10 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2013 VL 14 IS 10 AR R117 DI 10.1186/gb-2013-14-10-r117 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 285IN UT WOS:000329387500010 PM 24156763 ER PT B AU Wlodawer, A Gustchina, A James, MNG AF Wlodawer, Alexander Gustchina, Alla James, Michael N. G. BE Rawlings, ND Salvesen, GS TI Catalytic Pathways of Aspartic Peptidases SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID X-RAY; CRYSTALLOGRAPHIC ANALYSIS; CRYSTAL-STRUCTURE; HIV-1 PROTEASE; PH-DEPENDENCE; 3RD DOMAIN; MECHANISM; PROTEINASES; INHIBITOR; PEPSIN C1 [Wlodawer, Alexander; Gustchina, Alla] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. [James, Michael N. G.] Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada. RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM wlodawer@nih.gov; gustchia@mail.nih.gov; michael.james@ualberta.ca NR 39 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 19 EP 26 DI 10.1016/B978-0-12-382219-2.00002-8 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545100004 ER PT B AU Kervinen, J Wlodawer, A AF Kervinen, Jukka Wlodawer, Alexander BE Rawlings, ND Salvesen, GS TI Phytepsin SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID PLANT ASPARTIC PROTEINASE; CYNARA-CARDUNCULUS L; CATHEPSIN-D; HYDROLYTIC SPECIFICITY; ANTIMICROBIAL ACTIVITY; PROTEOLYTIC ACTIVITIES; ACID SPHINGOMYELINASE; ARABIDOPSIS-THALIANA; DISEASE RESISTANCE; PROTEASE FUNCTIONS C1 [Kervinen, Jukka] Cephalon Inc, W Chester, PA 19380 USA. [Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Kervinen, J (reprint author), Cephalon Inc, 145 Brandywine Pkwy, W Chester, PA 19380 USA. EM jukkakervinen@comcast.net; wlodawer@nih.gov NR 80 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 118 EP 124 DI 10.1016/B978-0-12-382219-2.00023-5 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545100025 ER PT B AU Cawley, NX Loh, YP AF Cawley, Niamh X. Loh, Y. Peng BE Rawlings, ND Salvesen, GS TI Yapsin 1 SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID ASPARTIC PROTEASE 3; PROOPIOMELANOCORTIN CONVERTING-ENZYME; HUMAN PARATHYROID-HORMONE; SACCHAROMYCES-CEREVISIAE; PROCESSING ENZYMES; SHARED FUNCTIONS; PLASMA-MEMBRANE; FUNCTIONAL-ROLE; CELL-SURFACE; IN-VIVO C1 [Cawley, Niamh X.; Loh, Y. Peng] NICHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Cawley, NX (reprint author), NICHD, Cellular Neurobiol Sect, NIH, 49 Convent Dr,MSC 4880,Room 5A22, Bethesda, MD 20892 USA. EM cawleyn@mail.nih.gov; ypl@codon.nih.gov NR 38 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 176 EP 180 DI 10.1016/B978-0-12-382219-2.00038-7 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545100040 ER PT B AU Cawley, NX Loh, YP AF Cawley, Niamh X. Loh, Y. Peng BE Rawlings, ND Salvesen, GS TI Yapsin A SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID PROOPIOMELANOCORTIN CONVERTING-ENZYME; LOBE SECRETORY VESICLES; RAT INTERMEDIATE; PROCESSING ENZYMES; ASPARTIC PROTEASE; PRO-OPIOCORTIN; PITUITARY; PROENKEPHALIN; YEAST; PURIFICATION C1 [Cawley, Niamh X.; Loh, Y. Peng] NICHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Cawley, NX (reprint author), NICHD, Cellular Neurobiol Sect, NIH, 49 Convent Dr,MSC 4880,Room 5A22, Bethesda, MD 20892 USA. EM cawleyn@mail.nih.gov; ypl@codon.nih.gov NR 18 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 183 EP 184 DI 10.1016/B978-0-12-382219-2.00040-5 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545100042 ER PT B AU Tozser, J Menendez-Arias, L Oroszlan, S AF Toezser, Jozsef Menendez-Arias, Luis Oroszlan, Stephen BE Rawlings, ND Salvesen, GS TI Equine Infectious Anemia Virus Retropepsin SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID RETROVIRAL PROTEASES; CLEAVAGE SITES; AMINO-ACID; PROTEINASE; SUBSTRATE; INHIBITOR; REQUIREMENTS; EXPRESSION; GAG C1 [Toezser, Jozsef] Univ Debrecen, Res Ctr Mol Med, Med & Hlth Sci Ctr, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. [Menendez-Arias, Luis] UAM, CSIC, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain. [Oroszlan, Stephen] NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. RP Tozser, J (reprint author), Univ Debrecen, Res Ctr Mol Med, Med & Hlth Sci Ctr, Dept Biochem & Mol Biol, Egyet Ter 1, H-4012 Debrecen, Hungary. EM tozser@med.unideb.hu; lmenendez@cbm.uam.es; oroszlan98@yahoo.com RI Menendez Arias, Luis/N-7447-2016 OI Menendez Arias, Luis/0000-0002-1251-6640 NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 207 EP 210 DI 10.1016/B978-0-12-382219-2.00047-8 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545100049 ER PT B AU Menendez-Arias, L Tozser, J Oroszlan, S AF Menendez-Arias, Luis Toezser, Jozsef Oroszlan, Stephen BE Rawlings, ND Salvesen, GS TI Mouse Mammary Tumor Virus Retropepsin SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID AMINO-ACID PREFERENCES; RETROVIRAL PROTEASES; GAG; PROTEIN; PURIFICATION; TRANSLATION; SEQUENCE; EVENTS; SITE C1 [Menendez-Arias, Luis] UAM, CSIC, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain. [Toezser, Jozsef] Univ Debrecen, Med & Hlth Sci Ctr, Res Ctr Mol Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. [Oroszlan, Stephen] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Menendez-Arias, L (reprint author), UAM, CSIC, Ctr Biol Mol Severo Ochoa, C Nicolas Cabrera,1,Campus Cantoblanco, Madrid 28049, Spain. EM lmenendez@cbm.uam.es; tozser@med.unideb.hu; oroszlan98@yahoo.com RI Menendez Arias, Luis/N-7447-2016 OI Menendez Arias, Luis/0000-0002-1251-6640 NR 17 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 223 EP 226 DI 10.1016/B978-0-12-382219-2.00052-1 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545100054 ER PT B AU Menendez-Arias, L Tozser, J Oroszlan, S AF Menendez-Arias, Luis Toezser, Jozsef Oroszlan, Stephen BE Rawlings, ND Salvesen, GS TI Moloney Murine Leukemia Virus Retropepsin SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID AMBER TERMINATION CODON; AMINO-ACID PREFERENCES; RETROVIRAL PROTEASES; IMMUNODEFICIENCY-VIRUS; PROTEOLYTIC FACTOR; GAG GENE; MEMBRANE-FUSION; VIRAL-PROTEINS; MATURE FORM; R-PEPTIDE C1 [Menendez-Arias, Luis] UAM, CSIC, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain. [Toezser, Jozsef] Univ Debrecen, Dept Biochem & Mol Biol, Res Ctr Mol Med, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary. [Oroszlan, Stephen] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Menendez-Arias, L (reprint author), UAM, CSIC, Ctr Biol Mol Severo Ochoa, C Nicolas Cabrera,1 Campus Cantoblanco, Madrid 28049, Spain. EM lmenendez@cbm.uam.es; tozser@med.unideb.hu; oroszlan98@yahoo.com RI Menendez Arias, Luis/N-7447-2016 OI Menendez Arias, Luis/0000-0002-1251-6640 NR 39 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 226 EP 230 DI 10.1016/B978-0-12-382219-2.00053-3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545100055 ER PT B AU Sang, QXA Shi, YB AF Sang, Qing-Xiang Amy Shi, Yun-Bo BE Rawlings, ND Salvesen, GS TI Matrix Metallopeptidase-18/Collagenase 4 SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID IMPLICATES DISTINCT FUNCTIONS; HUMAN NEUTROPHIL COLLAGENASE; HUMAN FIBROBLAST COLLAGENASE; XENOPUS-LAEVIS; SUBSTRATE-SPECIFICITY; METALLOPROTEINASES; SKIN; METAMORPHOSIS; PURIFICATION; EXPRESSION C1 [Sang, Qing-Xiang Amy] Florida State Univ, Dept Chem, Tallahassee, FL 32306 USA. [Sang, Qing-Xiang Amy] Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. [Shi, Yun-Bo] NICHD, UMM, LME, NIH, Bethesda, MD 20892 USA. RP Sang, QXA (reprint author), Florida State Univ, Dept Chem, Tallahassee, FL 32306 USA. EM sang@chem.fsu.edu; Shi@helix.nih.gov NR 19 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 744 EP 747 DI 10.1016/B978-0-12-382219-2.00155-1 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545101021 ER PT B AU Eisen, AZ Sarkar, SK Neuman, KC Goldberg, GI AF Eisen, Arthur Z. Sarkar, Susanta K. Neuman, Keir C. Goldberg, Gregory I. BE Rawlings, ND Salvesen, GS TI Matrix Metallopeptidase 9/Gelatinase B SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID HUMAN NEUTROPHIL GELATINASE; HIGH-AFFINITY BINDING; MYELIN BASIC-PROTEIN; IV COLLAGENASE; TUMOR PROGRESSION; TISSUE INHIBITOR; PROGELATINASE-B; HUMAN-SKIN; IN-VITRO; LATENT MATRIX-METALLOPROTEINASE-9 C1 [Eisen, Arthur Z.] Washington Univ, Sch Med, Dept Med, Div Dermatol, St Louis, MO 63110 USA. [Sarkar, Susanta K.; Neuman, Keir C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Goldberg, Gregory I.] Washington Univ, Sch Med, Dept Med, Div Dermatol,Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Eisen, AZ (reprint author), Washington Univ, Sch Med, Dept Med, Div Dermatol, St Louis, MO 63110 USA. EM AEISEN@dom.wustl.edu; sarkarsk@mail.nih.gov; neumankc@mail.nih; Goldberg@DOM.wustl.edu RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 NR 113 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 754 EP 763 DI 10.1016/B978-0-12-382219-2.00157-5 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545101023 ER PT B AU Leppla, SH AF Leppla, Stephen H. BE Rawlings, ND Salvesen, GS TI Anthrax Lethal Factor SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID PROTEIN-KINASE KINASE; BACILLUS-ANTHRACIS; MONOCLONAL-ANTIBODIES; TOXIN COMPONENTS; FACTOR CLEAVES; IN-VIVO; MACROPHAGES; SUSCEPTIBILITY; INHIBITORS; DISCOVERY C1 NIAID, Lab Bacterial Dis, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Lab Bacterial Dis, 33 North Dr,Bldg 33,Room 1W20B, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov NR 43 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 1257 EP 1261 DI 10.1016/B978-0-12-382219-2.00282-9 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545102004 ER PT B AU Rozanov, M AF Rozanov, Mikhail BE Rawlings, ND Salvesen, GS TI Tymovirus Endopeptidase SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID YELLOW MOSAIC-VIRUS; PAPAIN-LIKE PROTEINASE; STRAND RNA VIRUSES; COMPLETE SEQUENCE; CLEAVAGE SITE; IDENTIFICATION; EXPRESSION; PROTEASE; CYSTEINE; METHYLTRANSFERASE C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Rozanov, M (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM rozanov@ncbi.nlm.nih.gov NR 21 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 2229 EP 2232 DI 10.1016/B978-0-12-382219-2.00496-8 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545103068 ER PT B AU Marcotrigiano, J Soukhodolets, KE Rice, CM AF Marcotrigiano, Joseph Soukhodolets, Karen E. Rice, Charles M. BE Rawlings, ND Salvesen, GS TI Hepatitis C Virus Endopeptidase 2 SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID ZINC-BINDING SITE; SERINE PROTEINASE; NS2/3 PROTEASE; PRECURSOR PROTEIN; CRYSTAL-STRUCTURE; NS2-3 PROTEASE; IN-VITRO; CLEAVAGE; NS3; PESTIVIRUSES C1 [Marcotrigiano, Joseph; Rice, Charles M.] Rockefeller Univ, Lab Virol & Infect Dis, Ctr Study Hepatitis C, New York, NY 10021 USA. [Soukhodolets, Karen E.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Marcotrigiano, J (reprint author), Rockefeller Univ, Lab Virol & Infect Dis, Ctr Study Hepatitis C, 1230 York Ave, New York, NY 10021 USA. EM Rice@mail.rockefeller.edu RI Marcotrigiano, Joseph /K-6697-2016 OI Marcotrigiano, Joseph /0000-0003-0346-3353 NR 35 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 2472 EP 2476 DI 10.1016/B978-0-12-382219-2.00552-4 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545103119 ER PT B AU Paetzel, M Woodgate, R AF Paetzel, Mark Woodgate, Roger BE Rawlings, ND Salvesen, GS TI UmuD and UmuD ' Proteins SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID BACTERIAL SIGNAL PEPTIDASE; FAMILY DNA-POLYMERASES; SER-LYS DYAD; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; SOS MUTAGENESIS; ULTRAVIOLET-LIGHT; RECA PROTEIN; Y-FAMILY; INTERMOLECULAR CLEAVAGE C1 [Paetzel, Mark] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. [Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. RP Paetzel, M (reprint author), Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. EM mpaetzel@sfu.ca; woodgate@nih.gov NR 65 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 3487 EP 3492 DI 10.1016/B978-0-12-382219-2.00773-0 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545105078 ER PT B AU Maurizi, MR AF Maurizi, Michael R. BE Rawlings, ND Salvesen, GS TI Endopeptidase Clp SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID ATP-DEPENDENT PROTEASE; N-END RULE; ESCHERICHIA-COLI CLPP; SSRA-TAGGED PROTEINS; DEGRADATION MACHINE; CRYSTAL-STRUCTURE; HSP100 CHAPERONE; TAGGING SYSTEM; MU-TRANSPOSASE; SUBSTRATE C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, Bldg 37,Room 1B09, Bethesda, MD 20892 USA. EM maurizim@mail.nih.gov NR 62 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 3593 EP 3599 DI 10.1016/B978-0-12-382219-2.00794-8 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545105099 ER PT B AU Adam, Z Clarke, AK Maurizi, MR AF Adam, Zach Clarke, Adrian K. Maurizi, Michael R. BE Rawlings, ND Salvesen, GS TI Clp Endopeptidase Homologs in Plants and Animals SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID ATP-DEPENDENT PROTEASE; ESCHERICHIA-COLI CLPP; HUMAN MITOCHONDRIAL CLPP; SACCHAROMYCES-CEREVISIAE; FUNCTIONAL IMPLICATIONS; BACTERIAL CLPX; PIM1 PROTEASE; CHLOROPLAST; ARABIDOPSIS; COMPLEX C1 [Adam, Zach] Hebrew Univ Jerusalem, Inst Plant Sci, IL-76100 Rehovot, Israel. [Clarke, Adrian K.] Gothenburg Univ, Inst Bot, S-40530 Gothenburg, Sweden. [Maurizi, Michael R.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Adam, Z (reprint author), Hebrew Univ Jerusalem, Inst Plant Sci, IL-76100 Rehovot, Israel. EM zach@agri.huji.ac.il; Adrian.Clarke@botinst.gu.se; mmaurizi@helix.nih.gov NR 42 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 3600 EP 3605 DI 10.1016/B978-0-12-382219-2.00795-X PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545105100 ER PT J AU Tot, M Opsenica, DM Mitric, M Burnett, JC Gomba, L Bavari, S Solaja, BA AF Tot, Miklos Opsenica, Dejan M. Mitric, Milena Burnett, James C. Gomba, Laura Bavari, Sina Solaja, Bogdan A. TI New 9-aminoacridine derivatives as inhibitors of botulinum neurotoxins and P. falciparum malaria SO JOURNAL OF THE SERBIAN CHEMICAL SOCIETY LA English DT Article DE antiviral; BoNT/A; BoNT/B; antimalarial; aminoacridine ID PLASMODIUM-FALCIPARUM; IN-VITRO; ANTIMALARIAL ACTIVITY; ACRIDINE HYBRIDS; NEUROTRANSMITTER RELEASE; CHLOROQUINE-RESISTANT; PROTEASE INHIBITORS; PARALLEL SYNTHESIS; SEROTYPE-A; TOXIN AB Steroidal and adamantane aminoacridine derivatives were prepared and tested as both botulinum neurotoxin (BoNT) inhibitors and antimalarials.. Steroid-bound acridines provided good potency against both the BoNT/A and BoNT/B light chains (LCs). The observed inhibition of the BoNT/B LC by ca. 50 % is the highest attained inhibitory activity against this serotype by acridine-based compounds to date. With respect to the antimalarial activity, the adamantane acridines were the most potent derivatives (IC50 = 6-9 nM, SI>326), indicating that an adamantyl group is a better carrier than a steroidal motif for this indication. C1 [Tot, Miklos; Mitric, Milena; Solaja, Bogdan A.] Univ Belgrade, Fac Chem, Belgrade 11158, Serbia. [Opsenica, Dejan M.] Univ Belgrade, Inst Chem Technol & Met, Belgrade 11000, Serbia. [Burnett, James C.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Gomba, Laura] US Army Med Res Inst Infect Dis, Dept Bacteriol, Frederick, MD 21702 USA. [Bavari, Sina] US Army Med Res Inst Infect Dis, Frederick, MD 21702 USA. RP Solaja, BA (reprint author), Univ Belgrade, Fac Chem, Studentski Trg 16,POB 51, Belgrade 11158, Serbia. EM bsolaja@chem.bg.ac.rs OI Solaja, Bogdan/0000-0002-9975-2725 FU National Institute of Allergy and Infectious Diseases (USA) [5-U01AI082051-02]; Ministry of Education, Science and Technological Development of the Republic of Serbia [172008]; Serbian Academy of Sciences and Arts; National Cancer Institute, National Institutes of Health (USA) [HHSN261200800001E] FX This research was supported by National Institute of Allergy and Infectious Diseases (USA) grant 5-U01AI082051-02, by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. 172008) and the Serbian Academy of Sciences and Arts. Furthermore, for J.C.B., in compliance with SAIC-Frederick, Inc. contractual requirements: this project was funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health (USA), under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services (USA), or the US Army, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government, or the US Army. B.S. is grateful to WRAIR for providing the in vitro antimalarial results. NR 71 TC 3 Z9 3 U1 0 U2 3 PU SERBIAN CHEMICAL SOC PI BELGRADE PA KARNEGIJEVA 4, 11 120 BELGRADE, SERBIA SN 0352-5139 J9 J SERB CHEM SOC JI J. Serb. Chem. Soc. PY 2013 VL 78 IS 12 BP 1847 EP 1864 DI 10.2298/JSC130924112T PG 18 WC Chemistry, Multidisciplinary SC Chemistry GA 283QD UT WOS:000329261200003 ER PT S AU Sawitzke, JA Thomason, LC Bubunenko, M Li, XT Costantino, N Court, DL AF Sawitzke, James A. Thomason, Lynn C. Bubunenko, Mikhail Li, Xintian Costantino, Nina Court, Donald L. BE Lorsch, J TI Recombineering: Using Drug Cassettes to Knock out Genes in vivo SO LABORATORY METHODS IN ENZYMOLOGY: CELL, LIPID AND CARBOHYDRATE SE Methods in Enzymology LA English DT Review; Book Chapter ID ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; BACTERIA; SYSTEM AB A 'gene knockout' or 'knockout' is a mutation that inactivates a gene function. These mutations are very useful for classical genetic studies as well as for modern techniques including functional genomics. In the past, knockouts of bacterial genes were often made by transposon mutagenesis. In this case, laborious screens are required to find a knockout in the gene of interest. Knockouts of other organisms have traditionally been made by first using in vitro genetic engineering to modify genes contained on plasmids or bacterial artificial chromosomes (BACs) and later moving these modified constructs to the organism of interest by cell culture techniques. Other methods utilizing a combination of genetic engineering and in vivo homologous recombination were inefficient at best. Recombineering provides a new way to generate knockout mutations directly on the bacterial chromosome or to modify any plasmid or BAC in vivo as a prelude to making knockouts in other organisms. The constructs are designed to the base pair and are not dependent on suitable restriction sites. A drug cassette can be placed anywhere within a gene or the open reading frame of the gene can be replaced with the drug cassette. Either way, the desired construct is selected for. C1 [Sawitzke, James A.; Bubunenko, Mikhail; Li, Xintian; Costantino, Nina; Court, Donald L.] NCI, Mol Control & Genet Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Thomason, Lynn C.; Bubunenko, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Sawitzke, JA (reprint author), NCI, Mol Control & Genet Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA. EM sawitzkj@mail.nih.gov NR 15 TC 3 Z9 3 U1 2 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-420067-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 533 BP 79 EP 102 DI 10.1016/B978-0-12-420067-8.00007-6 PG 24 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJN43 UT WOS:000329254800007 PM 24182919 ER PT S AU Sawitzke, JA Thomason, LC Bubunenko, M Li, XT Costantino, N Court, DL AF Sawitzke, James A. Thomason, Lynn C. Bubunenko, Mikhail Li, Xintian Costantino, Nina Court, Donald L. BE Lorsch, J TI Recombineering: Highly Efficient in vivo Genetic Engineering using Single-strand Oligos SO LABORATORY METHODS IN ENZYMOLOGY: CELL, LIPID AND CARBOHYDRATE SE Methods in Enzymology LA English DT Review; Book Chapter ID ESCHERICHIA-COLI; BACTERIA; REPAIR; SYSTEM; DNA AB Recombineering provides the ability to make rapid, precise, and inexpensive genetic alterations to any DNA sequence, either in the chromosome or cloned onto a vector that replicates in E. coli (or other recombineering-proficient bacteria), and to do so in a highly efficient manner. Complicated genetic constructs that are impossible to make with in vitro genetic engineering can be created in days with recombineering. Recombineering with single-strand DNA (ssDNA) can be used to create single or multiple clustered point mutations, small or large (up to 10kb) deletions, and small (10-20 base) insertions such as sequence tags. Using optimized conditions, point mutations can be made with such high frequencies that they can be found without selection. This technology excels at creating both directed and random mutations. C1 [Sawitzke, James A.; Bubunenko, Mikhail; Li, Xintian; Costantino, Nina; Court, Donald L.] NCI, Mol Control & Genet Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Thomason, Lynn C.; Bubunenko, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Sawitzke, JA (reprint author), NCI, Mol Control & Genet Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA. EM sawitzkj@mail.nih.gov NR 13 TC 6 Z9 6 U1 2 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-420067-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 533 BP 157 EP 177 DI 10.1016/B978-0-12-420067-8.00010-6 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJN43 UT WOS:000329254800010 PM 24182922 ER PT S AU Sengupta, P Lippincott-Schwartz, J AF Sengupta, Prabuddha Lippincott-Schwartz, Jennifer BE Perez, F Stephens, DJ TI Photohighlighting Approaches to Access Membrane Dynamics of the Golgi Apparatus SO METHODS FOR ANALYSIS OF GOLGI COMPLEX FUNCTION SE Methods in Cell Biology LA English DT Review; Book Chapter ID LIVING CELLS; SECRETORY PATHWAY; FLUORESCENT PROTEINS; IN-VIVO; TRANSPORT; ER; COMPLEX; MAINTENANCE; TRAFFICKING; MICROSCOPY AB By providing quantitative, visual data of live cells, fluorescent protein-based microscopy techniques are furnishing novel insights into the complexities of membrane trafficking pathways and organelle dynamics In this chapter, we describe experimental protocols employing fluorescent protein-based photohighlighting techniques to quantify protein movement into and out of the Golgi apparatus, an organelle that serves as the central sorting and processing station of the secretory pathway. The methods allow kinetic characteristics of Golgi-associated protein trafficking to be deciphered, which can help clarify how the Golgi maintains itself as a steady-state structure despite a continuous flux of secretory cargo passing into and out of this organelle. The guidelines presented in this chapter can also be applied to examine the dynamics of other intracellular organelle systems, elucidating mechanisms for how proteins are maintained in specific organelles and/or circulated to other destinations within the cell. C1 [Sengupta, Prabuddha; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Sengupta, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. OI Sengupta, Prabuddha/0000-0001-7094-6967 FU Intramural NIH HHS [Z99 HD999999] NR 28 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-417164-0 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2013 VL 118 BP 217 EP 234 DI 10.1016/B978-0-12-417164-0.00013-6 PG 18 WC Cell Biology SC Cell Biology GA BJN49 UT WOS:000329255400014 PM 24295309 ER PT J AU Gregg, EW Ali, MK Moore, BA Pavkov, ME Devlin, HM Garfield, S Mangione, CM AF Gregg, Edward W. Ali, Mohammed K. Moore, Bernice A. Pavkov, Meda E. Devlin, Heather M. Garfield, Sanford Mangione, Carol M. TI The Importance of Natural Experiments in Diabetes Prevention and Control and the Need for Better Health Policy Research SO PREVENTING CHRONIC DISEASE LA English DT Editorial Material ID UNITED-STATES; PREVALENCE C1 [Pavkov, Meda E.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Gregg, Edward W.; Ali, Mohammed K.; Moore, Bernice A.; Devlin, Heather M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Garfield, Sanford] NIH, Bethesda, MD 20892 USA. [Mangione, Carol M.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Pavkov, ME (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, 4770 Buford Hwy NE,MS K10, Atlanta, GA USA. EM mpavkov@cdc.gov NR 10 TC 3 Z9 3 U1 0 U2 0 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2013 VL 10 AR UNSP 120145 DI 10.5888/pcd10.120145 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 285IY UT WOS:000329388600014 ER PT B AU Nussenblatt, RB Marincola, FM AF Nussenblatt, Robert B. Marincola, Francesco M. BE Mittra, J Milne, CP TI Emerging Concepts in Biomarker Discovery: Cancer Immunotherapy and Degenerative Disease of the Eye as Model Systems SO TRANSLATIONAL MEDICINE: THE FUTURE OF THERAPY? LA English DT Article; Book Chapter ID HEPATITIS-C VIRUS; VERSUS-HOST-DISEASE; GENE-EXPRESSION; MACULAR DEGENERATION; TRANSLATIONAL MEDICINE; IMMUNE-RESPONSES; NONINFECTIOUS UVEITIS; ALLOGRAFT-REJECTION; METASTATIC MELANOMA; COLORECTAL-CANCER C1 [Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. [Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol, CC CHI FOCIS Ctr Excellence, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM nussenblattr@nei.nih.gov NR 122 TC 0 Z9 0 U1 0 U2 0 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-981-4364-84-3; 978-981-4316-99-6 PY 2013 BP 129 EP 161 PG 33 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA BJH98 UT WOS:000328280400007 ER PT S AU Novikova, SI Richman, DM Supekar, K Barnard-Brak, L Hall, D AF Novikova, S. I. Richman, D. M. Supekar, K. Barnard-Brak, L. Hall, D. BE Urbano, RC TI NDAR: A Model Federal System for Secondary Analysis in Developmental Disabilities Research SO USING SECONDARY DATASETS TO UNDERSTAND PERSONS WITH DEVELOPMENTAL DISABILITIES AND THEIR FAMILIES SE International Review of Research in Developmental Disabilities LA English DT Article; Book Chapter ID ABERRANT BEHAVIOR CHECKLIST; AUTISM SPECTRUM DISORDERS; SELF-INJURIOUS-BEHAVIOR; EXECUTIVE FUNCTIONS; MISSING DATA; CHILDREN; CLASSIFICATION; INDIVIDUALS; SEVERITY; ADHD AB The National Database for Autism Research (NDAR) is a human-subject data repository on tens of thousands of research participants. Approved researchers have access to an unprecedented volume of item-level clinical, genomic, and imaging data. Data are shared quickly using both a common data standard and innovative tools for experiment definition, which provide the level of detail needed for efficient use of the repository. As described, early adopters have used it to conduct secondary data analysis. Now, with an ever-increasing volume of research data being made available, and new methods for data query, data download, and computation in place, this initiative is becoming vital to those interested in scientific discovery in autism or is being used as a model by other research communities. C1 [Novikova, S. I.; Hall, D.] OMNITEC Solut Inc, NIMH, Natl Database Autism Res, Rockville, MD USA. [Richman, D. M.; Barnard-Brak, L.] Texas Tech Univ, Lubbock, TX 79409 USA. [Supekar, K.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Novikova, SI (reprint author), OMNITEC Solut Inc, NIMH, Natl Database Autism Res, Rockville, MD USA. EM svetlana.novikova@nih.gov NR 45 TC 3 Z9 3 U1 3 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 2211-6095 BN 978-0-12-407760-7 J9 INT REV RES DEV DISA JI Int. Rev. Res. Dev. Disabil. PY 2013 VL 45 BP 123 EP 153 DI 10.1016/B978-0-12-407760-7.00003-7 PG 31 WC Education, Special; Psychology, Multidisciplinary SC Education & Educational Research; Psychology GA BJN47 UT WOS:000329255200004 ER PT J AU Uvarova, EA Belavin, PA Permyakova, NV Zagorskaya, AA Nosareva, OV Kakimzhanova, AA Deineko, EV AF Uvarova, Elena A. Belavin, Pavel A. Permyakova, Natalya V. Zagorskaya, Alla A. Nosareva, Olesya V. Kakimzhanova, Almagul A. Deineko, Elena V. TI Oral Immunogenicity of Plant-Made Mycobacterium tuberculosis ESAT6 and CFP10 SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID VACCINE; BCG; ANTIGENS; SUBUNIT; PROTEIN AB Two lines of transgenic carrot plants producing Mycobacterium tuberculosis proteins (ESAT6 and CFP10) have been constructed. The target proteins are present in carrot storage roots at a level not less than 0.056% of the total storage protein (TSP) for ESAT6 and 0.002% of TSP for CFP10. As has been shown, oral immunization of mice induces both the cell-mediated and humoral immunities. These data suggest that the proteins in question are appropriate as a candidate edible vaccine against tuberculosis. C1 [Uvarova, Elena A.; Belavin, Pavel A.; Permyakova, Natalya V.; Zagorskaya, Alla A.; Nosareva, Olesya V.; Deineko, Elena V.] Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk 630090, Russia. [Nosareva, Olesya V.] State Res Ctr Virol & Biotechnol Vector, Koltsov 630559, Novosibirsk Obl, Russia. [Kakimzhanova, Almagul A.] Natl Ctr Biotechnol, Astana 010000, Kazakhstan. RP Deineko, EV (reprint author), Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Pr Lavrentieva 10, Novosibirsk 630090, Russia. EM deineko@bionet.nsc.ru RI Deyneko, Elena/N-7685-2014; OI Kakimzhanova, Almagul/0000-0002-7797-6867 NR 30 TC 6 Z9 7 U1 1 U2 9 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 316304 DI 10.1155/2013/316304 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 280KA UT WOS:000329026900001 ER PT J AU Danforth, DN AF Danforth, David N., Jr. TI Disparities in breast cancer outcomes between Caucasian and African American women: a model for describing the relationship of biological and nonbiological factors SO BREAST CANCER RESEARCH LA English DT Review ID PROGESTERONE-RECEPTOR STATUS; CYCLE REGULATORY PROTEINS; P53 GENE-MUTATIONS; RACIAL-DIFFERENCES; WHITE WOMEN; ESTROGEN-RECEPTOR; UNITED-STATES; TUMOR CHARACTERISTICS; RACIAL/ETHNIC GROUPS; BLACK-WOMEN AB Breast cancer is the most common malignancy in women in the United States but significant disparities exist for African American women compared to Caucasian women. African American women present with breast cancer at a younger age and with a greater incidence under the age of 50 years, develop histologically more aggressive tumors that are at a more advanced stage at presentation, and have a worse disease-free and overall survival than Caucasian women. The biological characteristics of the primary tumor play an important role in determining the outcome of the disparity, and significant differences have been identified between African American and Caucasian breast cancer in steroid receptor and growth factor receptor content, mutations in cell cycle components, chromosomal abnormalities, and tumor suppressor and other cancer genes. The consequences of the biological factors are influenced by a variety of nonbiological factors, including socioeconomic, health care access, reproductive, and confounding factors. The nonbiological factors may act directly to enhance (or inhibit) the consequences of the biological changes, indirectly to facilitate outcome of the disparity, or as a cofounding factor, driving the association between the biological factors and the disparity. The prevention and management of the disparities will require an understanding of the relationship of biological and nonbiological factors. The present review was undertaken to promote this understanding by describing the biological basis of the four major disparities - early age of onset, more advanced stage of disease, more aggressive histologic changes, and worse survival - and the important relationship to the nonbiological factors. A model is proposed to provide a comprehensive view of this relationship, with the goal of facilitating an understanding of each disparity and the issues that need to be addressed to eliminate the disparity. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Danforth, DN (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM david_danforth@nih.gov FU Intramural Research Program of the NCI, NIH FX I would like to thank Dr Jennifer Loud, Clinical Genetics Branch, and Dr Worta J McCaskill-Stevens, Community Oncology and Prevention Trials Research Group, National Cancer Institute, NIH, for their helpful suggestions in preparation of the manuscript. This research was supported by the Intramural Research Program of the NCI, NIH. NR 98 TC 22 Z9 22 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 3 AR 208 DI 10.1186/bcr3429 PG 15 WC Oncology SC Oncology GA 279CQ UT WOS:000328937600020 PM 23826992 ER PT J AU Godfrey, AC Xu, ZL Weinberg, CR Getts, RC Wade, PA DeRoo, LA Sandler, DP Taylor, JA AF Godfrey, Ashley C. Xu, Zongli Weinberg, Clarice R. Getts, Robert C. Wade, Paul A. DeRoo, Lisa A. Sandler, Dale P. Taylor, Jack A. TI Serum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort SO BREAST CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; CIRCULATING MICRORNAS; DIFFERENTIAL EXPRESSION; TAMOXIFEN RESISTANCE; MICROARRAY ANALYSIS; DOWN-REGULATION; MESSENGER-RNAS; BIOMARKERS; CELLS; IDENTIFICATION AB Introduction: MicroRNAs (miRNAs) are small, non-coding, single-stranded RNAs between 18-22 nucleotides long that regulate gene expression. Expression of miRNAs is altered in tumor compared to normal tissue; there is some evidence that these changes may be reflected in the serum of cancer cases compared to healthy individuals. This has yet to be examined in a prospective study where samples are collected before diagnosis. Methods: We used Affymetrix arrays to examine serum miRNA expression profiles in 410 participants in the Sister Study, a prospective cohort study of 50,884 women. All women in the cohort had never been diagnosed with breast cancer at the time of enrollment. We compared global miRNA expression patterns in 205 women who subsequently developed breast cancer and 205 women who remained breast cancer-free. In addition within the case group we examined the association of miRNA expression in serum with different tumor characteristics, including hormone status (ER, PR, and HER-2) and lymph node status. Results: Overall, 414 of 1,105 of the human miRNAs on the chip were expressed above background levels in 50 or more women. When the average expression among controls was compared to cases using conditional logistic regression, 21 miRNAs were found to be differentially expressed (P <=. 05). Using qRT-PCR on a small, independent sample of 5 cases and 5 controls we verified overexpression of the 3 highest expressing miRNAs among cases, miR-18a, miR-181a, and miR-222; the differences were not statistically significant in this small set. The 21 differentially expressed miRNAs are known to target at least 82 genes; using the gene list for pathway analysis we found enrichment of genes involved in cancer-related processes. In a separate case-case analyses restricted to the 21 miRNAs, we found 7 miRNAs with differential expression for women whose breast tumors differed by HER-2 expression, and 10 miRNAs with differential expression by nodal status. Conclusions: miRNA levels in serum show a number of small differences between women who later develop cancer versus those who remain cancer-free. C1 [Godfrey, Ashley C.; Wade, Paul A.; Taylor, Jack A.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Xu, Zongli; DeRoo, Lisa A.; Sandler, Dale P.; Taylor, Jack A.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Weinberg, Clarice R.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Getts, Robert C.] Genisphere LLC, Hatfield, PA 19440 USA. RP Taylor, JA (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM taylor@niehs.nih.gov OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398; Sandler, Dale/0000-0002-6776-0018 FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences FX We thank Dan Scharf at Westat (Rockville, MD, USA) for sample selection and batch and chip lot designation of the samples and Carol Messler at SSS for pulling and delivering the serum samples. We are especially grateful to Robert (Bob) Getts and Jessica Bowers at Genisphere and Keith Jones and Radharani Duttagupta at Affymetrix for their help and advice in pilot studies and troubleshooting, and we want to thank Bob Getts and Jessica Bowers for doing all of the sample labeling. All of the array hybridization and scanning was carried out by Precision Biomarkers Resources, and we would especially like to thank both David Paul and Jason Monroe at Precision Biomarkers Resources for their help with this project. This work was funded by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 62 TC 35 Z9 36 U1 2 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2013 VL 15 IS 3 AR R42 DI 10.1186/bcr3428 PG 10 WC Oncology SC Oncology GA 279CQ UT WOS:000328937600006 PM 23705859 ER PT J AU Randall, TA Perera, L London, RE Mueller, GA AF Randall, Thomas A. Perera, Lalith London, Robert E. Mueller, Geoffrey A. TI Genomic, RNAseq, and Molecular Modeling Evidence Suggests That the Major Allergen Domain in Insects Evolved from a Homodimeric Origin SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE SDMA; molecular modeling; genome; gene family; tandem duplication; synteny; ortholog; gene expression; RNAseq; Bla g 1; ANG12; allergen ID AEDES-AEGYPTI; BLATTELLA-GERMANICA; DRAFT GENOME; COCKROACH; SEQUENCE; INSIGHTS; PROTEIN; ADAPTATIONS; MOSQUITO; VECTOR AB The major allergen domain (MA) is widely distributed in insects. The crystal structure of a single Bla g 1 MA revealed a novel protein fold in which the fundamental structure was a duplex of two subsequences (monomers), which had diverged over time. This suggested that the evolutionary origin of the MA structure may have been a homodimer of this smaller subsequence. Using publicly available genomic data, the distribution of the basic unit of this class of proteins was determined to better understand its evolutionary history. The duplication and divergence is examined at three distinct levels of resolution: 1) within the orders Diptera and Hymenoptera, 2) within one genus Drosophila, and 3) within one species Aedes aegypti. Within the family Culicidae, we have found two separate occurrences of monomers as independent genes. The organization of the gene family in A. aegypti shows a common evolutionary origin for its monomer and several closely related MAs. Molecular modeling of the A. aegypti monomer with the unique Bla g 1 fold confirms the distant evolutionary relationship and supports the feasibility of homodimer formation from a single monomer. RNAseq data for A. aegypti confirms that the monomer is expressed in the mosquito similar to other A. aegypti MAs after a blood meal. Together, these data support the contention that the detected monomer shares similar functional characteristics to related MAs in other insects. An extensive search for this domain outside of Insecta confirms that the MAs are restricted to insects. C1 [Randall, Thomas A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Perera, Lalith; London, Robert E.; Mueller, Geoffrey A.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. RP Mueller, GA (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. EM Mueller3@niehs.nih.gov OI Randall, Thomas/0000-0002-4605-7606 FU National Institute of Environmental Health Sciences, National Institutes of Health [Z01-ES102885-01, Z01-ES043010-28] FX The authors thank Jim Mason and Lee Pedersen for a critical reading of the manuscript. This research was supported by Research Project Number Z01-ES102885-01 to R. E. L. and Z01-ES043010-28 to L. P. in the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. NR 54 TC 4 Z9 4 U1 5 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2013 VL 5 IS 12 BP 2344 EP 2358 DI 10.1093/gbe/evt182 PG 15 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 283MO UT WOS:000329250400008 PM 24253356 ER PT J AU Byun, SA Singh, S AF Byun, S. Ashley Singh, Sarabdeep TI Protein Subcellular Relocalization Increases the Retention of Eukaryotic Duplicate Genes SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE duplicate genes; protein subceulluar relocalization; genome evolution; death rates ID EVOLUTION; SEQUENCE; GENOME; MODELS; SPECIFICITY; VERTEBRATES; REVEALS; ENSEMBL; PLANTS AB Gene duplication is widely accepted as a key evolutionary process, leading to new genes and novel protein functions. By providing the raw genetic material necessary for functional expansion, the mechanisms that involve the retention and functional diversification of duplicate genes are one of the central topics in evolutionary and comparative genomics. One proposed source of retention and functional diversification is protein subcellular relocalization (PSR). PSR postulates that changes in the subcellular location of eukaryotic duplicate proteins can positively modify function and therefore be beneficial to the organism. As such, PSR would promote retention of those relocalized duplicates and result in significantly lower death rates compared with death rates of nonrelocalized duplicate pairs. We surveyed both relocalized and nonrelocalized duplicate proteins from the available genomes and proteomes of 59 eukaryotic species and compared their relative death rates over a Ks range between 0 and 1. Using the Cox proportional hazard model, we observed that the death rates of relocalized duplicate pairs were significantly lower than the death rates of the duplicates without relocalization in most eukaryotic species examined in this study. These observations suggest that PSR significantly increases retention of duplicate genes and that it plays an important, but currently underappreciated, role in the evolution of eukaryotic genomes. C1 [Byun, S. Ashley] Fairfield Univ, Dept Biol, Fairfield, CT 06824 USA. [Singh, Sarabdeep] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Byun, SA (reprint author), Fairfield Univ, Dept Biol, Fairfield, CT 06824 USA. EM sbyun@fairfield.edu RI Singh, Sarabdeep/D-7881-2017 FU Fairfield University's Science Institute; Intramural Research Program of the National Institutes of Health [NLM ZIA LM000097-13] FX The authors thank the following people and institutions for their assistance: A. Vilella (European Bioinformatics Institute) for advice on MySQL queries of the Ensembl databases; S. McKay (iPlant Collaborative; Cold Spring Harbor Laboratory) for assistance with bioinformatics and high performance computing; O. Kohlbacher for discussions on the use of MultiLoc2, and the NIH Fellows Editorial Board for editorial assistance. They thank the Broad and Genome Institutes (Washington University) for permission to use some of their unpublished genomes for this analysis. They also thank E. Koonin, M. Lynch, J. Zhang, R. Geeta, S. Phelan, and A. Fernandez for their helpful suggestions to this manuscript as well as the anonymous reviewers for their thoughtful, insightful comments. This work was supported by the Fairfield University's Science Institute and, in part, by the Intramural Research Program of the National Institutes of Health, NLM ZIA LM000097-13. NR 50 TC 2 Z9 2 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2013 VL 5 IS 12 BP 2402 EP 2409 DI 10.1093/gbe/evt183 PG 8 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 283MO UT WOS:000329250400013 PM 24265504 ER PT J AU Adam, RD Dahlstrom, EW Martens, CA Bruno, DP Barbian, KD Ricklefs, SM Hernandez, MM Narla, NP Patel, RB Porcella, SF Nash, TE AF Adam, Rodney D. Dahlstrom, Eric W. Martens, Craig A. Bruno, Daniel P. Barbian, Kent D. Ricklefs, Stacy M. Hernandez, Matthew M. Narla, Nirmala P. Patel, Rima B. Porcella, Stephen F. Nash, Theodore E. TI Genome Sequencing of Giardia lamblia Genotypes A2 and B Isolates (DH and GS) and Comparative Analysis with the Genomes of Genotypes A1 and E (WB and Pig) SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE genotype; parasitology; diplomonad; synteny; heterozygosity ID BAYESIAN PHYLOGENETIC INFERENCE; MOLECULAR EPIDEMIOLOGY; CHILDREN; INFECTION; ANTIGENS; REARRANGEMENTS; BANGLADESH; REDUCTION; EVOLUTION; DIARRHEA AB Giardia lamblia (syn G. intestinalis, G. duodenalis) is the most common pathogenic intestinal parasite of humans worldwide and is a frequent cause of endemic and epidemic diarrhea. G. lamblia is divided into eight genotypes (A-H) which infect a wide range of mammals and humans, but human infections are caused by Genotypes A and B. To unambiguously determine the relationship among genotypes, we sequenced GS and DH (Genotypes B and A2) to high depth coverage and compared the assemblies with the nearly completed WB genome and draft sequencing surveys of Genotypes E (P15; pig isolate) and B (GS; human isolate). Our results identified DH as the smallest Giardia genome sequenced to date, while GS is the largest. Our open reading frame analyses and phylogenetic analyses showed that GS was more distant from the other three genomes than any of the other three were from each other. Whole-genome comparisons of DH_A2 and GS_B with the optically mapped WB_A1 demonstrated substantial synteny across all five chromosomes but also included a number of rearrangements, inversions, and chromosomal translocations that were more common toward the chromosome ends. However, the WB_A1/GS_B alignment demonstrated only about 70% sequence identity across the syntenic regions. Our findings add to information presented in previous reports suggesting that GS is a different species of Giardia as supported by the degree of genomic diversity, coding capacity, heterozygosity, phylogenetic distance, and known biological differences from WB_A1 and other G. lamblia genotypes. C1 [Adam, Rodney D.; Narla, Nirmala P.; Patel, Rima B.] Univ Arizona, Dept Med, Coll Med, Tucson, AZ 85721 USA. [Adam, Rodney D.; Narla, Nirmala P.; Patel, Rima B.] Univ Arizona, Dept Immunobiol, Coll Med, Tucson, AZ 85721 USA. [Dahlstrom, Eric W.; Martens, Craig A.; Bruno, Daniel P.; Barbian, Kent D.; Ricklefs, Stacy M.; Hernandez, Matthew M.; Porcella, Stephen F.] NIAID, Res Technol Sect, Genom Unit, NIH,US Dept HHS, Hamilton, MT USA. [Nash, Theodore E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Adam, RD (reprint author), Univ Arizona, Dept Med, Coll Med, Tucson, AZ 85721 USA. EM adamr@u.arizona.edu FU National Institute of Allergy and Infectious Diseases, US National Institutes of Health FX The following are the contributions of the authors: R. D. A., coordinated the manuscript writing and other parts of the genome effort E. W. D., comparative genomic analysis of the Giardia genomes; and contributed to writing and editing the paper; C. A. M., GS_B and DH_A2 assembly, GS_B and DH_A2 heterozygosity analysis; D. P. B., 3 kb and 8 kb paired-end library prep for 454 sequencing of GS_B; 8 kb library paired-end library prep for 454 sequencing of DH_A2; K. D. B., DNA extraction of trophozoites; S. M. R., 3 kb, 6 kb, and 8 kb paired-end library prep for 454 sequencing of DH_A2; M. M. H., sample preparation for the libraries to be sequenced; N.P.N., Giardia heterozygosity and vsp gene analysis; R. B. P., Giardia vsp gene analysis; S. F. P., directed the genome sequencing efforts and contributed to writing and editing the paper; T.E.N., originated and supported the project, suggested analyses, and contributed to writing and editing the paper. This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health. NR 50 TC 18 Z9 18 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2013 VL 5 IS 12 BP 2498 EP 2511 DI 10.1093/gbe/evt197 PG 14 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 283MO UT WOS:000329250400021 PM 24307482 ER PT J AU Ferreira, Z Hurle, B Andres, AM Kretzschmar, WW Mullikin, JC Cherukuri, PF Cruz, P Gonder, MK Stone, AC Tishkoff, S Swanson, WJ Green, ED Clark, AG Seixas, S AF Ferreira, Zelia Hurle, Belen Andres, Aida M. Kretzschmar, Warren W. Mullikin, James C. Cherukuri, Praveen F. Cruz, Pedro Gonder, Mary Katherine Stone, Anne C. Tishkoff, Sarah Swanson, Willie J. Green, Eric D. Clark, Andrew G. Seixas, Susana CA NISC Comparative Sequencing TI Sequence Diversity of Pan troglodytes Subspecies and the Impact of WFDC6 Selective Constraints in Reproductive Immunity SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE WFDC; natural selection; chimpanzees; serine protease inhibitor; reproduction; innate immunity ID HUMAN SEMINAL PLASMA; HUMAN GENOME; HAPLOTYPE RECONSTRUCTION; CHIMPANZEE POPULATIONS; PHYLOGENETIC ANALYSIS; MOLECULAR EVOLUTION; DEMOGRAPHIC HISTORY; MAXIMUM-LIKELIHOOD; STATISTICAL-METHOD; SEMEN COAGULUM AB Recent efforts have attempted to describe the population structure of common chimpanzee, focusing on four subspecies: Pan troglodytes verus, P. t. ellioti, P. t. troglodytes, and P. t. schweinfurthii. However, few studies have pursued the effects of natural selection in shaping their response to pathogens and reproduction. Whey acidic protein (WAP) four-disulfide core domain (WFDC) genes and neighboring semenogelin (SEMG) genes encode proteins with combined roles in immunity and fertility. They display a strikingly high rate of amino acid replacement (d(N)/d(S)), indicative of adaptive pressures during primate evolution. In human populations, three signals of selection at the WFDC locus were described, possibly influencing the proteolytic profile and antimicrobial activities of the male reproductive tract. To evaluate the patterns of genomic variation and selection at the WFDC locus in chimpanzees, we sequenced 17 WFDC genes and 47 autosomal pseudogenes in 68 chimpanzees (15 P. t. troglodytes, 22 P. t. verus, and 31 P. t. ellioti). We found a clear differentiation of P. t. verus and estimated the divergence of P. t. troglodytes and P. t. ellioti subspecies in 0.173 Myr; further, at the WFDC locus we identified a signature of strong selective constraints common to the three subspecies in WFDC6-a recent paralog of the epididymal protease inhibitor EPPIN. Overall, chimpanzees and humans do not display similar footprints of selection across the WFDC locus, possibly due to different selective pressures between the two species related to immune response and reproductive biology. C1 [Ferreira, Zelia; Hurle, Belen; Green, Eric D.] NHGRI, NIH, Bethesda, MD 20892 USA. [Ferreira, Zelia; Seixas, Susana] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Oporto, Portugal. [Ferreira, Zelia] Univ Porto, Fac Sci, Dept Zool & Anthropol, P-4100 Oporto, Portugal. [Ferreira, Zelia] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA. [Andres, Aida M.] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Leipzig, Germany. [Kretzschmar, Warren W.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Mullikin, James C.; Cherukuri, Praveen F.; Cruz, Pedro; NISC Comparative Sequencing] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Rockville, MD USA. [Gonder, Mary Katherine] Drexel Univ, Dept Biol, Philadelphia, PA USA. [Stone, Anne C.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. [Tishkoff, Sarah] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Tishkoff, Sarah] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Swanson, Willie J.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Clark, Andrew G.] Cornell Univ, Dept Biol Mol Biol & Genet, Ithaca, NY 14853 USA. RP Ferreira, Z (reprint author), Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA. EM zferreir@pitt.edu RI Andres, Aida/B-4088-2014; Seixas, Susana /I-5084-2013; OI Andres, Aida/0000-0002-8590-9672; Seixas, Susana /0000-0002-7035-7422; Kretzschmar, Warren/0000-0002-2575-0807 FU Intramural Research Program of the National Human Genome Research Institute; Portuguese Foundation for Science and Technology (FCT); European Social Funds (COMPETE-FEDER); national funds of the Portuguese Ministry of Education and Science (POPH-QREN) [SFRH/BD/45907/2008]; NSF [0755823]; NIH [HD057974, DP1 ES022577]; Wellcome Trust Centre for Human Genetics [WT097307]; FCT; [PTDC/BEX-GMG/0242/2012] FX The authors acknowledge Anh-Dao Nguyen for the help inferring the ancestral allele state of each SNP and Riverside Zoo, Sunset Zoo, Lincoln Park Zoo, the Primate Foundation of Arizona, New Iberia Research Center, and Texas Biomed for sample donation. The authors would also like to thank John Kiyang and Felix Lanekster of the Limbe Wildlife Centre for sample collection. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute, by the Portuguese Foundation for Science and Technology (FCT), financed by the European Social Funds (COMPETE-FEDER) and national funds of the Portuguese Ministry of Education and Science (POPH-QREN) fellowship SFRH/BD/45907/2008 to Z.F., grant PTDC/BEX-GMG/0242/2012 to S. S., NSF Grant 0755823 to M. K. G., NIH grants HD057974 to W.J.S. and DP1 ES022577 to S. A. T., and by the Wellcome Trust Centre for Human Genetics (WT097307) to W. W. K. IPATIMUP is an Associated Laboratory of the Portuguese Ministry of Education and Science and is partially supported by FCT. NR 73 TC 2 Z9 2 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2013 VL 5 IS 12 BP 2512 EP 2523 DI 10.1093/gbe/evt198 PG 12 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 283MO UT WOS:000329250400022 PM 24356879 ER PT J AU Rapp, SR Espeland, MA Manson, JE Resnick, SM Bryan, NR Smoller, S Coker, LH Phillips, LS Stefanick, ML Sarto, GE AF Rapp, Stephen R. Espeland, Mark A. Manson, Joann E. Resnick, Susan M. Bryan, Nick R. Smoller, Sylvia Coker, Laura H. Phillips, Lawrence S. Stefanick, Marcia L. Sarto, Gloria E. CA Women's Hlth Initiative Memory TI EDUCATIONAL ATTAINMENT, MRI CHANGES, AND COGNITIVE FUNCTION IN OLDER POSTMENOPAUSAL WOMEN FROM THE WOMEN'S HEALTH INITIATIVE MEMORY STUDY SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE cognition; MRI; cognitive reserve; aging; women; WHIMS ID PROBABLE ALZHEIMERS-DISEASE; RESERVE HYPOTHESIS; RISK-FACTORS; DEMENTIA; DECLINE; OCCUPATION; ASSOCIATION; POPULATION; PROGRESSION; MORTALITY AB The relationship between neuropathology and clinically manifested functional and cognitive deficits is complex. Clinical observations of individuals with greater neuropathology who function better than some individuals with less neuropathology are common and puzzling. Educational attainment, a proxy for "cognitive reserve," may help to explain this apparent contradiction. The objective of this study is to determine if educational attainment is correlated with cognitive decline, brain lesion volume, and total brain atrophy. One thousand three hundred ninety of the 7,479 community-dwelling women 65 years of age and older enrolled in the Women's Health Initiative Memory Study, two parallel randomized, placebo-controlled clinical trials comparing unopposed and opposed postmenopausal hormone therapy with placebo, were studied. Study participants received annual assessments of global cognitive function with the Modified Mini Mental State exam. One thousand sixty-three participants also received supplemental neurocognitive battery and neuroimaging studies. Magnetic resonance imaging was used to calculate total ischemic lesion and brain volumes. Incident cases of probable dementia and mild cognitive impairment were centrally adjudicated. After adjustment for total lesion and total brain volumes (atrophy), higher educational attainment predicted better cognitive performance (p < 0.001). Following conversion to dementia/MCI, higher education predicted steeper declines in cognitive function (p < 0.001). Thus, higher educational attainment was associated with a delay in diagnosis of dementia/MCI in the face of a growing neuropathological load. C1 [Rapp, Stephen R.; Espeland, Mark A.; Coker, Laura H.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA. [Manson, Joann E.] Harvard Univ, Sch Med, Boston, MA USA. [Resnick, Susan M.] NIA, Baltimore, MD 21224 USA. [Bryan, Nick R.] Univ Penn, Philadelphia, PA 19104 USA. [Smoller, Sylvia] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Phillips, Lawrence S.] Emory Univ, Sch Med, Atlanta, GA USA. [Stefanick, Marcia L.] Stanford Univ, Palo Alto, CA 94304 USA. [Sarto, Gloria E.] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53706 USA. RP Rapp, SR (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Psychiat & Behav Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM srapp@wakehealth.edu FU Wyeth Pharmaceuticals, Inc., St. Davids, PA; National Heart, Lung and Blood Institute; National Heart, Lung, and Blood Institute of the National Institutes of Health, U.S. Department of Health and Human Services; Department of Health and Human Services; National Institute on Aging [NO1-AG-1-2106]; NIA, NIH FX The Women's Health Initiative Memory Study was initially funded by Wyeth Pharmaceuticals, Inc., St. Davids, PA, with sustaining support from the National Heart, Lung and Blood Institute which also funded the Women's Health Initiative Magnetic Resonance Imaging Study. The Women's Health Initiative is funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health, U.S. Department of Health and Human Services. Wyeth Pharmaceuticals provided the study drug and the placebo to the WHI trial. The Women's Health Initiative Study of Cognitive Aging was supported by the Department of Health and Human Services and the National Institute on Aging, NO1-AG-1-2106, and in part, by the Intramural Research Program, NIA, NIH. NR 55 TC 8 Z9 9 U1 3 U2 4 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-2174 EI 1541-3527 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2013 VL 46 IS 2 BP 121 EP 143 DI 10.2190/PM.46.2.a PG 23 WC Psychiatry SC Psychiatry GA 280MT UT WOS:000329035200001 PM 24552037 ER PT J AU Peters, E Klein, W Kaufman, A Meilleur, L Dixon, A AF Peters, Ellen Klein, William Kaufman, Annette Meilleur, Louise Dixon, Anna TI More Is Not Always Better: Intuitions About Effective Public Policy Can Lead to Unintended Consequences SO SOCIAL ISSUES AND POLICY REVIEW LA English DT Article ID MEDICAL DECISION-MAKING; RANDOMIZED CONTROLLED-TRIAL; PRESCRIPTION DRUG BENEFIT; NEW-YORK-CITY; OUTCOME SATISFACTION; DIETARY-SUPPLEMENTS; SELF-DETERMINATION; HEALTH-INSURANCE; RISK PERCEPTION; PRIMARY-CARE AB Public policy decisions often appear based on an assumption that providing more options, more information, and greater decision-making autonomy to consumers will produce better outcomes. We examine reasons why this "more-is-better" approach exists based on the psychological literature. Although better outcomes can result from informed consumer choice, we argue that more options, information, and autonomy can also lead to unintended negative consequences. We use mostly health-related policies and guidelines from the United States and elsewhere as exemplars. We consider various psychological mechanisms that cause these unintended consequences including cognitive overload, affect, and anticipated regret, information salience and availability, and trust in governments as authoritative information providers. We also point toward potential solutions based on psychological research that may reduce the negative unintended consequences of a "more-is-better" approach. C1 [Peters, Ellen; Meilleur, Louise] Ohio State Univ, Columbus, OH 43206 USA. [Klein, William] NCI, Behav Res Program, Bethesda, MD 20892 USA. [Kaufman, Annette] NCI, Bethesda, MD 20892 USA. [Dixon, Anna] Kings Fund, London, England. RP Peters, E (reprint author), Ohio State Univ, Dept Psychol, 1835 Neil Ave, Columbus, OH 43206 USA. EM peters.498@osu.edu FU Intramural NIH HHS [Z99 CA999999] NR 176 TC 11 Z9 11 U1 8 U2 21 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1751-2395 EI 1751-2409 J9 SOC ISS POLICY REV JI Soc. Issue Policy Rev. PD JAN PY 2013 VL 7 IS 1 BP 114 EP 148 DI 10.1111/j.1751-2409.2012.01045.x PG 35 WC Social Issues; Psychology, Social SC Social Issues; Psychology GA 280YG UT WOS:000329066100005 PM 24000291 ER PT J AU Tuo, JS Wei, L Hu, N AF Tuo, Jingsheng Wei, Lai Hu, Nan TI Genetic/Epigenetic Modulation, Ocular Diseases, and Therapeutic Prospective SO JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material C1 [Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wei, Lai] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China. [Hu, Nan] Nantong Univ, Affiliated Hosp, Inst Eye, Nantong, Peoples R China. RP Tuo, JS (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM tuoj@nei.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2013 AR 980608 DI 10.1155/2013/980608 PG 2 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA 276PZ UT WOS:000328763500001 ER PT J AU Machado-Vieira, R Zarate, CA AF Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. TI Next-generation strategies in animal model research to translate preclinical discoveries into better treatments for circuit-centered psychiatric dimensions SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Editorial Material ID PERSPECTIVES; DEPRESSION C1 [Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Machado-Vieira, R (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 6 TC 1 Z9 1 U1 1 U2 1 PU ASSOC BRASILEIRA PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP 04039-032 A, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PY 2013 VL 35 SU 2 BP S75 EP S76 DI 10.1590/1516-4446-2013-1132 PG 2 WC Psychiatry SC Psychiatry GA 277CF UT WOS:000328795300002 PM 24271228 ER PT J AU Oliveira, CJ Anatriello, E de Miranda-Santos, IK Francischetti, IM Sa-Nunes, A Ferreira, BR Ribeiro, JMC AF Oliveira, C. J. Anatriello, E. de Miranda-Santos, I. K. Francischetti, I. M. Sa-Nunes, A. Ferreira, B. R. Ribeiro, J. M. C. TI Proteome of Rhipicephalus sanguineus tick saliva induced by the secretagogues pilocarpine and dopamine SO TICKS AND TICK-BORNE DISEASES LA English DT Article DE Proteome; Tick saliva; Rhipicephalus sanguineus; Dopamine; Pilocarpine ID MOUNTAIN-SPOTTED-FEVER; HUMAN SERUM PROTEOME; LONE STAR TICK; BROWN DOG TICK; IXODES-SCAPULARIS; MASS-SPECTROMETRY; CYCLOPHILIN-A; SIALOSTATIN-L; GLANDS; INHIBITOR AB One dimensional gel electrophoresis was used to separate proteins from the saliva of Rhipicephalus sanguineus female ticks fed on rabbits. Gel slices were subjected to tryptic digestion and analyzed by reversed-phase HPLC followed by MS/MS analysis. The data were compared to a database of salivary proteins of the same tick and to the predicted proteins of the host. Saliva was obtained by either pilocarpine or dopamine stimulation of partially fed ticks. Electrophoretic separations of both yielded products that were identified by mass spectrometry, although the pilocarpine-derived sample was of much better quality. The majority of identified proteins were of rabbit origin, indicating the recycling of the host proteins in the tick saliva, including hemoglobin, albumin, haptoglobin, transferring, and a plasma serpin. The few proteins found that were previously associated with parasitism and blood feeding include 2 glycine-rich, cement-like proteins, 2 lipocalins, and a thyropin protease inhibitor. Among other of the 19 tick proteins identified, albeit with undefined roles, were SPARC and cyclophilin A. This catalog provides a resource that can be mined for secreted molecules that play a role in tick-host interactions. Published by Elsevier GmbH. C1 [Oliveira, C. J.] Univ Fed Triangulo Mineiro, Inst Biol & Nat Sci, BR-38025180 Uberaba, MG, Brazil. [Anatriello, E.; de Miranda-Santos, I. K.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil. [Francischetti, I. M.; Ribeiro, J. M. C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Sa-Nunes, A.] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Expt Immunol Lab, BR-05508900 Sao Paulo, Brazil. [Ferreira, B. R.] Univ Sao Paulo, Ribeirao Preto Sch Nursing, Dept Maternal & Child & Publ Hlth Nursing, BR-14049900 Ribeirao Preto, SP, Brazil. RP Ribeiro, JMC (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2E-32,Twinbrook 3 Bldg,, Bethesda, MD 20892 USA. EM jribeiro@nih.gov RI Ferreira, Beatriz/C-2003-2012; Ribeiro, Jose/J-7011-2015; Anatriello, Elen/N-1429-2015; de Miranda Santos, Isabel/D-5261-2016; Sa-Nunes, Anderson/D-8667-2012; de Miranda Santos, Isabel/B-7597-2012; OI Ferreira, Beatriz/0000-0002-6781-2236; Sa-Nunes, Anderson/0000-0002-1859-4973; de Miranda Santos, Isabel/0000-0002-0438-4430; Ribeiro, Jose/0000-0002-9107-0818 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [2009/53645-3, 2007/50869-2, 2006/54985-4]; Brazilian National Science Foundation-CNPq [559603/2009-6, 471946/2010-9]; Fundacao de Amparo a Pesquisa do Estado de Minas Gerais- FAPEMIG; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP through grant 2009/53645-3 to IKMS, and scholarships to EA (2007/50869-2) and CJFO (2006/54985-4); by the Brazilian National Science Foundation-CNPq through grants 559603/2009-6 and 471946/2010-9 to IKMS, Fundacao de Amparo a Pesquisa do Estado de Minas Gerais- FAPEMIG and the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank the Research Technology Branch under Dr. Robert Hohman for preparing the gel and mass spectrometric data collection and analysis, and to the NIAID intramural editor Brenda Rae Marshall for assistance. NR 56 TC 14 Z9 14 U1 0 U2 11 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1877-959X EI 1877-9603 J9 TICKS TICK-BORNE DIS JI Ticks Tick-Borne Dis. PY 2013 VL 4 IS 6 BP 469 EP 477 DI 10.1016/j.ttbdis.2013.05.001 PG 9 WC Infectious Diseases; Microbiology; Parasitology SC Infectious Diseases; Microbiology; Parasitology GA 277CL UT WOS:000328795900001 PM 24029695 ER PT S AU Farag, AA AF Farag, Amal A. GP IEEE TI A Variational Approach for Small-Size Lung Nodule Segmentation SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Lung Nodule; Level Sets; Shape Priors ID SMALL PULMONARY NODULES; CT IMAGES AB This paper describes a novel variational approach for segmentation of small-size lung nodules which may be detected in low dose CT (LDCT) scans. These nodules do not possess distinct shape or appearance characteristics; hence, their segmentation is enormously difficult, especially at small size (<= 1cm). Variational methods hold promise in these scenarios despite the difficulties in estimation of the energy function parameters and the convergence. The proposed method is analytic and has a clear implementation strategy for LDCT scans. We show the effectiveness of the algorithm for segmenting various types of nodules regardless of their location in the lung tissue. C1 NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Farag, AA (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10 Room 1C224D MSC 1182, Bethesda, MD 20892 USA. EM amal.aly1@gmail.com NR 12 TC 5 Z9 5 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 81 EP 84 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100021 ER PT S AU Beliveau, P Cheriet, F Anderson, SA Taylor, J Berul, S Arai, AE Hsu, LY AF Beliveau, Pascale Cheriet, Farida Anderson, Stasia A. Taylor, Joni Berul, Stephen Arai, Andrew E. Hsu, Li-Yueh GP IEEE TI TEXTURAL ANALYSIS OF DIFFUSE MYOCARDIAL FIBROSIS IN AGING RATS: A LATE GADOLINIUM ENHANCEMENT MAGNETIC RESONANCE IMAGING STUDY SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Texture analysis; diffuse fibrosis; non-ischemic cardiomyopathies; gadolinium; cardiac MRI; age ID CLASSIFICATION; HEART AB Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging has been shown to identify myocardial fibrosis secondary to myocardial infarction at nearly a cellular level. The purpose of this study is to assess diffuse myocardial fibrosis in aging hearts using LGE CMR imaging and histological staining as a reference. We present a quantitative approach to compare the amount of myocardial fibrosis between young (6-week-old) and elderly (2-year-old) rats. We hypothesize that 3D texture analysis of the high resolution MR images can characterize the level of diffuse fibrosis present in the myocardium and discriminate between the two age groups. Our results show the elderly hearts have an apparent increase of myocardial fibrosis in the histological slices stained with picrosirius red, which were qualitatively compared to the young group. The CMR quantification also shows a significant increase of myocardial fibrosis in the elderly group compared to the young rats. Furthermore, receiver operating characteristic curve analysis shows texture features derived from the MR images can distinguish between the two age groups better than signal intensity of the MR images. Our results suggest that texture analysis may improve the ability of detecting diffuse myocardial fibrosis in LGE CMR images. C1 [Beliveau, Pascale; Anderson, Stasia A.; Taylor, Joni; Berul, Stephen; Arai, Andrew E.; Hsu, Li-Yueh] NHLBI, NIH, Bethesda, MD 20892 USA. RP Beliveau, P (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 1 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 109 EP 112 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100028 ER PT S AU Wei, ZS Zhang, WD Liu, JF Wang, SJ Yao, JH Summers, RM AF Wei, Zhuoshi Zhang, Weidong Liu, Jianfei Wang, Shijun Yao, Jianhua Summers, Ronald M. GP IEEE TI COMPUTER-AIDED DETECTION OF COLITIS ON COMPUTED TOMOGRAPHY USING A VISUAL CODEBOOK SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE CT; colon; colitis; visual codebook ID CT AB Colitis is inflammation of the colon that is frequently associated with infection and immune compromise. In this paper, we propose an automatic method for colitis detection in abdominal CT scans. We first used a visual codebook constructed by clustering feature vectors from a set of training image patches to detect the suspicious colitis regions. The initial detections included false detection points located in various organs including muscle, kidney and liver. We reduced the false positives by applying masks of these regions obtained from whole-organ segmentation. We tested our method on a CT dataset with 20 cases of colitis and 15 non-colitis cases. Average detected lesion volume for positive cases is 205ml; for negative cases is 97ml. Sixteen out of the 22 positive cases were correctly identified, yielding a sensitivity of 72.7%; 4 out of 15 negative cases were incorrectly identified, yielding a specificity of 73.3%. C1 [Wei, Zhuoshi; Zhang, Weidong; Liu, Jianfei; Wang, Shijun; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Wei, ZS (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. NR 14 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 141 EP 144 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100036 ER PT S AU Cheng, RD Bernardo, M Senseney, J Bokinsky, A Gandler, W Turkbey, B Pohida, T Choyke, P McAuliffe, MJ AF Cheng, Ruida Bernardo, Marcelino Senseney, Justin Bokinsky, Alexandra Gandler, William Turkbey, Baris Pohida, Thomas Choyke, Peter McAuliffe, Matthew J. GP IEEE TI SEGMENTATION AND SURFACE RECONSTRUCTION MODEL OF PROSTATE MRI TO IMPROVE PROSTATE CANCER DIAGNOSIS SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Prostate Segmentation; Registration; Surface Reconstruction AB This work presents a MRI prostate segmentation and surface reconstruction model that facilities the validation of multiparametric MRI with histopathology slides from radical prostatectomy specimens and targeted biopsy specimens. Application of this technique combines image processing and computer aided design to provide a generalized solution to construct a high resolution 3D prostate surface from MRI images in three orthogonal views with non-isotropic voxel resolution. The performance of the segmentation is evaluated with 45 MR image datasets, yielding an average segmentation accuracy of 90%. C1 [Cheng, Ruida; Senseney, Justin; Gandler, William; Pohida, Thomas; McAuliffe, Matthew J.] NIH, Image Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. [Bernardo, Marcelino] Natl Canc Inst, Mol Imaging Program, Bethesda, MD USA. [Bernardo, Marcelino; Turkbey, Baris; Choyke, Peter] Frederick Natl Lab, SAIC Frederick, Frederick, MD USA. [Bokinsky, Alexandra] Geometr Tools Inc, Chapel Hill, NC USA. RP Cheng, RD (reprint author), NIH, Image Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 185 EP 189 PG 5 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100047 ER PT S AU Zhang, WD Liu, JM Yao, JH Summers, RM AF Zhang, Weidong Liu, Jiamin Yao, Jianhua Summers, Ronald M. GP IEEE TI AUTOMATIC ANATOMICAL LABELING OF ABDOMINAL ARTERIES FOR SMALL BOWEL EVALUATION ON 3D CT SCANS SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE anatomical labeling; small bowel evaluation; image segmentation ID IMAGES AB While segmentation of the small bowel on CT scans is helpful for diagnosis and surgery planning, it is challenging to reproducibly identify specific locations within the small bowel. Assigning anatomical names to the individual mesenteric arteries supplying the small bowel may enable more precise lesion localization. It also enables registration of the small bowel from CT scans before and after surgery. In this study, an automated anatomical labeling method was introduced for the mesenteric arterial vasculature. After segmenting the mesenteric vascular tree, features including blood vessel size, direction, relative position and branching pattern were calculated. Known anatomic names were assigned to the major abdominal arteries, and names encoding order and direction were assigned to the arteries arising from the superior mesenteric artery. Five CT scans were analyzed and experimental results showed 73% recall and 79% precision rate. To our knowledge, this is the first reported method to label the smaller branches of the mesenteric vasculature and will have applications for diagnosis and treatment of small bowel disease. C1 [Zhang, Weidong; Liu, Jiamin; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Zhang, WD (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. NR 11 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 210 EP 213 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100053 ER PT S AU Liu, YX Sadowski, SM Weisbrod, AB Kebebew, E Summers, RM Yao, JH AF Liu, Yixun Sadowski, Samira M. Weisbrod, Allison B. Kebebew, Electron Summers, Ronald M. Yao, Jianhua GP IEEE TI TUMOR GROWTH MODELING BASED ON DUAL PHASE CT AND FDG-PET SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Tumor growth; image driven; reaction-diffusion model; metabolic rate; intracellular volume fraction ID DIFFUSION AB In this paper, we presented a method to deal with tumor growth prediction using multimodality non-invasive clinical imaging data. We developed a reaction-diffusion tumor growth model that (1) relates cell metabolic rate and tumor growth, and (2) is driven by clinical imaging data. The metabolic rate was incorporated into the model through cell proliferation rate of the model via energy conservation law. FDG-PET scan was employed to provide non-invasive measurement of the metabolic rate. To bridge the gap between the model prediction and the clinical observation, we introduced intracellular volume fraction (ICVF) using dual phase CT scans to link them. The patient specific model parameters were estimated by minimizing the deviation between the predicted ICVF and the measured ICVF with deformation corrected. The experiment was conducted on two pancreatic neuroendocrine tumors. The average surface distance between the predicted tumor and the reference tumor was 2.1 mm and 2.7 mm, respectively, and the mean square difference of the ICVF map was 5.4% and 3.8%, respectively. C1 [Liu, Yixun; Summers, Ronald M.; Yao, Jianhua] NIH, Clin Image Proc Serv, Bethesda, MD 20892 USA. [Sadowski, Samira M.; Weisbrod, Allison B.; Kebebew, Electron] NIH, Natl Canc Ctr, Endocrine Oncol Branch, Bethesda, MD 20892 USA. RP Liu, YX (reprint author), NIH, Clin Image Proc Serv, Bethesda, MD 20892 USA. NR 14 TC 1 Z9 1 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 394 EP 397 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100099 ER PT S AU Liu, JF Wang, SJ Linguraru, MG Yao, JH Summers, RM AF Liu, Jianfei Wang, Shijun Linguraru, Marius George Yao, Jianhua Summers, Ronald M. GP IEEE TI AUGMENTING TUMOR SENSITIVE MATCHING FLOW TO IMPROVE DETECTION AND SEGMENTATION OF OVARIAN CANCER METASTASES WITHIN A PDE FRAMEWORK SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Ovarian cancer metastases; tumor sensitive matching flow; tumor segmentation ID IMAGES; LIVER; CT AB The detection and segmentation of ovarian cancer metastases have potentially great clinical impact on women's healthcare. We recently developed a tumor sensitive matching flow (TSMF) technique to locate metastases by juxtaposing the roles of matching and classification within a PDE framework. This paper further augments the TSMF approach by integrating 1) shape index to measure metastasis-caused deformation, 2) Gaussian mixture model to describe metastasis intensity distribution, 3) total variation (TV) flow to enhance metastasis regions, and 4) TSMF vector displacements to control the amount of level-set propagation. The method was validated on contrast-enhanced CT data from 30 patients, of which 15 have 37 metastases in total. The true positive rate was 87% compared to 76% in our earlier work. Moreover, the false positive rate per patients was dropped to 1.1 from 4.2 in our earlier work. The metastasis segmentation achieved a Dice coefficient of 80.0 +/- 7.2%. All these experimental results demonstrated that shape index, Gaussian mixture model, TV flow, and TSMF-constrained level set propagation substantially improve the accuracy of metastasis detection and segmentation. C1 [Liu, Jianfei; Wang, Shijun; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Liu, JF (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. FU Intramural Research Program of the National Institutes of Health, Clinical Center FX This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center. NR 13 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 652 EP 655 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100163 ER PT S AU Xu, ZY Bagci, U Foster, B Mollura, DJ AF Xu, Ziyue Bagci, Ulas Foster, Brent Mollura, Daniel J. GP IEEE TI A HYBRID MULTI-SCALE APPROACH TO AUTOMATIC AIRWAY TREE SEGMENTATION FROM CT SCANS SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Airway tree segmentation; fuzzy connectivity; multi-scale vesselness; grayscale morphological reconstruction; region growing AB Airway structure and morphology is commonly related to inflammatory and infectious lung diseases, and often analyzed non-invasively through high resolution computed tomography (CT) scans. Conventionally, most airway related feature characterization on these scans is performed manually, but is often too labor intensive and time consuming for routine clinical practice. Therefore, semi-and fully-automatic airway segmentation algorithms are crucial for the diagnosis of these conditions. A fundamental challenge in airway tree segmentation is highly variable intensity levels within the lumen, which often causes a segmentation method to leak into adjacent lung parenchyma through blurred airway walls or soft boundaries. In this paper, we present a new hybrid multi-scale airway segmentation approach to solve these problems through proposing a new fuzzy connectivity based algorithm combining multiple features to identify airways at different scales. The performance of the proposed method was qualitatively and quantitatively evaluated on pulmonary CT images from human patients with diverse diseases with promising results. C1 [Xu, Ziyue; Bagci, Ulas; Foster, Brent; Mollura, Daniel J.] NIH, CIDI, Radiol & Imaging Sci Dept, Bethesda, MD 20892 USA. RP Xu, ZY (reprint author), NIH, CIDI, Radiol & Imaging Sci Dept, Bethesda, MD 20892 USA. EM ziyue.xu@nih.gov OI Bagci, Ulas/0000-0001-7379-6829 NR 8 TC 6 Z9 6 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 1308 EP 1311 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100327 ER PT S AU Foster, B Bagci, U Luna, B Dey, B Bishai, W Jain, S Xu, ZY Mollura, DJ AF Foster, Brent Bagci, Ulas Luna, Brian Dey, Bappaditya Bishai, William Jain, Sanjay Xu, Ziyue Mollura, Daniel J. GP IEEE TI Robust Segmentation and Accurate Target Definition for Positron Emission Tomography Images Using Affinity Propagation SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE PET Segmentation; Affinity Propagation; Thresholding; Image Segmentation; Target Definition AB Distributed inflammation in infectious diseases cause variable uptake regions in positron emission tomography (PET) images. Due to this distributed nature of immuno-pathology and associated PET uptake, intensity based methods are much better suited over region based methods for segmentation. The most commonly used intensity based segmentation is thresholding, but it has a major drawback of a lack of consensus on the selection of the thresholding value. We propose a method to select an optimal thresholding value by utilizing a novel similarity metric between the data points along the gray-level histogram of the image then using Affinity Propagation (AP) to cluster the intensities based on this metric. This method is tested against the PET images of rabbits infected with tuberculosis with distributed uptakes with promising results. C1 [Foster, Brent; Bagci, Ulas; Xu, Ziyue; Mollura, Daniel J.] NIH, CIDI, Bldg 10, Bethesda, MD 20892 USA. [Luna, Brian; Dey, Bappaditya; Bishai, William; Jain, Sanjay] Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. RP Foster, B (reprint author), NIH, CIDI, Bldg 10, Bethesda, MD 20892 USA. OI Dey, Bappaditya/0000-0003-2728-4683; Bagci, Ulas/0000-0001-7379-6829 FU CIDI; National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Biomedical Imaging and Bioengineering (NIBIB); NIH [OD006492]; HHMI; NIAD [R01AI079590, R01A1035272] FX This research is supported by CIDI, the intramural research program of the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB). Dr. Jain acknowledges the NIH Directors New Innovator Award (OD006492). The rabbit infection study is funded by HHMI, NIAD R01AI079590, and R01A1035272. NR 7 TC 4 Z9 5 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 1461 EP 1464 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100365 ER PT S AU Candemir, S Palaniappan, K Akgul, YS AF Candemir, Sema Palaniappan, Kannappan Akgul, Yusuf Sinan GP IEEE TI MULTI-CLASS REGULARIZATION PARAMETER LEARNING FOR GRAPH CUT IMAGE SEGMENTATION SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc AB One of the first steps of computer-aided systems is robustly detect the anatomical boundaries. Literature has several successful energy minimization based algorithms which are applied to medical images. However, these algorithms depend on parameters which need to be tuned for a meaningful solution. One of the important parameters is the regularization parameter (lambda) which is generally estimated in an ad-hoc manner and is used for the whole data set. In this paper we claim that lambda can be learned by local features which hold the regional characteristics of the image. We propose a lambda estimation system which is modeled as a multi-class classification scheme. We demonstrate the performance of the approach within graph cut segmentation framework via qualitative results on chest x-rays. Experimental results indicate that predicted parameters produce better segmentation results. C1 [Candemir, Sema; Akgul, Yusuf Sinan] NIH, Lister Hill Natl Ctr Biomed Commun, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. [Palaniappan, Kannappan] Univ Missouri, Dept Comp Sci, Columbia, MO 65211 USA. RP Candemir, S (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 22 TC 3 Z9 3 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 1473 EP 1476 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100368 ER PT J AU Armstrong, N Schupf, N Grafman, J Huey, ED AF Armstrong, Nicole Schupf, Nicole Grafman, Jordan Huey, Edward D. TI Caregiver Burden in Frontotemporal Degeneration and Corticobasal Syndrome SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Caregiver burden; Frontotemporal degeneration; Corticobasal syndrome; Frontal Systems Behavior Scale; Zarit Burden Interview ID QUALITY-OF-LIFE; ALZHEIMERS-DISEASE; BEHAVIORAL VARIANT; DIAGNOSTIC-CRITERIA; DEMENTIA PATIENTS; SYMPTOMS; IMPACT; DISTRESS; SPOUSAL AB Background and Aims: Caregiver stress is often a serious problem when caring for a patient with frontal lobe dysfunction. Methods: A total of 102 caregivers of both patients with frontotemporal degeneration and corticobasal syndrome completed the Frontal Systems Behavior Scale (FrSBe) and the Zarit Burden Interview (ZBI). To analyze the association between apathy or disinhibition (or both) and caregiver burden, the effects of the total FrSBe and the apathy and disinhibition subscales of the FrSBE on the total ZBI score were assessed with logistic regressions and t tests. Results: Total FrSBE score and the apathy FrSBE subscore predicted caregiver burden. Apathy occurred without disinhibition, and the two occurred together, but disinhibition without apathy was very rare. Conclusions: Disinhibition without apathy occurred very rarely. Apathy was more associated with caregiver burden than disinhibition. (C) 2013 S. Karger AG, Basel C1 [Armstrong, Nicole] Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Schupf, Nicole; Huey, Edward D.] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [Schupf, Nicole; Huey, Edward D.] Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Grafman, Jordan; Huey, Edward D.] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Bethesda, MD USA. RP Huey, ED (reprint author), Taub Inst Res Alzheimers Dis & Aging Brain, 630 West 168th St,19th Floor, New York, NY 10032 USA. EM edh2126@columbia.edu OI Grafman, Jordan H./0000-0001-8645-4457 FU NIA NIH HHS [P50 AG008702, T32 AG000247]; NINDS NIH HHS [R01 NS076837, R00 NS060766] NR 33 TC 2 Z9 2 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2013 VL 36 IS 5-6 BP 310 EP 318 DI 10.1159/000351670 PG 9 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 270OT UT WOS:000328328800005 PM 24022248 ER PT J AU Kang, YS Park, YG Lee, BS Park, HS AF Kang, Yeoun-Seung Park, Yoon-Ghil Lee, Bum-Suk Park, Hyung-Soon TI Biomechanical evaluation of wrist-driven flexor hinge orthosis in persons with spinal cord injury SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE biomechanics; efficiency; finger motion; hand function; mechanical operating model; pinch force; spinal cord injury; three-point prehension; wrist-driven flexor hinge orthosis; wrist extensor muscles ID FUNCTIONAL ELECTRICAL-STIMULATION; PARALYZED HAND; FOLLOW-UP; TETRAPLEGIA; TENODESIS; STRENGTH; SPLINT; MOTION; GRIP; DEVIATION AB The wrist-driven flexor hinge orthosis (WDFHO) is a device used to restore hand function in persons with tetraplegic spinal cord injury by furnishing three-point prehension. We assessed the effectiveness and biomechanical properties of the WDFHO in 24 persons with cervical 6 or 7 tetraplegia who have severely impaired hand function. This study introduces a mechanical operating model to assess the efficiency of the WDFHO. Experimental results showed that pinch force increased significantly (p < 0.001) after using the WDFHO and was found to positively correlate with the strength of wrist extensor muscles (r = 0.41, p < 0.001). However, when the strength of the wrist extensors acting on the WDFHO was greater, the reciprocal wrist and finger motion that generates three-point prehension was less effective (r = 0.79, p < 0.001). Reliable and valid biomechanical evaluation of the WDFHO could improve our understanding of its biomechanics. C1 [Kang, Yeoun-Seung; Park, Hyung-Soon] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Park, Yoon-Ghil] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Seoul, South Korea. [Lee, Bum-Suk] Natl Rehabil Hosp, Seoul, South Korea. [Park, Hyung-Soon] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea. RP Park, HS (reprint author), Korea Adv Inst Sci & Technol, Dept Mech Engn, 291 Daehak Ro, Taejon 305701, South Korea. EM hyungspark@kaist.ac.kr RI Park, Hyung-Soon/B-3334-2010 OI Park, Hyung-Soon/0000-0003-4274-7420 FU Intramural Research Program of the National Institutes of Health Clinical Center FX This material was based on work supported by the Intramural Research Program of the National Institutes of Health Clinical Center. NR 44 TC 1 Z9 1 U1 0 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2013 VL 50 IS 8 BP 1129 EP 1137 DI 10.1682/JRRD.2012.10.0189 PG 9 WC Rehabilitation SC Rehabilitation GA 270GX UT WOS:000328308000013 PM 24458899 ER PT J AU Wankhede, DP Kumar, K Singh, P Sinha, AK AF Wankhede, Dhammaprakash Pandhari Kumar, Kundan Singh, Pallavi Sinha, Alok Krishna TI Involvement of mitogen activated protein kinase kinase 6 in UV induced transcripts accumulation of genes in phytoalexin biosynthesis in rice SO RICE LA English DT Article DE MAPKK; Magnaporthe oryzae; Phytoalexins; Rice; UV ID CATHARANTHUS-ROSEUS; MOMILACTONES; EXPRESSION; DEFENSE; STRESS; LEAVES; PLANTS; BLAST AB Ultra violet radiation leads to accumulation of phytoalexins (PA) in rice (Oryza sativa) which are typically accumulated when the plants are infected with rice blast pathogen Magnaporthe oryzae. Although extensive works have been done in elucidating phytoalexin biosynthesis, UV stress signal transduction leading to accumulations of rice phytoalexin is largely unknown. In the present study, the involvement of mitogen activated protein kinase (MAPK) cascade has been shown in UV induced regulation of genes in phytoalexin biosynthesis in rice. UV induced activation of MAPK and expression of PA biosynthesis genes were shown to be inhibited with staurosporin and MAPK inhibitors. Transcript regulation studies and kinase assays indicated involvement of OsMKK6 in the process. Transgenic rice overexpressing constitutive active OsMKK6 (EE) exhibited higher expression of genes of PA biosynthesis pathway upon UV stress and also upon infection with M. oryzae. These results suggest a key role of OsMKK6 in regulation of UV responsive expression of genes of PA biosynthesis in rice. This study will help to elucidate the intricate signalling components of UV leading to phytoalexins biosynthesis in rice. C1 [Wankhede, Dhammaprakash Pandhari; Kumar, Kundan; Singh, Pallavi; Sinha, Alok Krishna] NHGRI, New Delhi, India. RP Sinha, AK (reprint author), NHGRI, Aruna Asaf Ali Rd, New Delhi, India. EM alok@nipgr.ac.in FU National Institute of Plant Genome Research, New Delhi, India from the Department of Biotechnology, Government of India; University Grants Commission, India; Council of Scientific and Industrial Research FX This work was supported by the core grants of National Institute of Plant Genome Research, New Delhi, India from the Department of Biotechnology, Government of India. DPW and KK acknowledge University Grants Commission, India while PS thanks Council of Scientific and Industrial Research for the fellowships. Authors thank Dr. T. R. Sharma of National Research Centre on Plant Molecular Biology, New Delhi for providing the facilities for carrying out Magnaporthe oryzae infection in rice. NR 23 TC 2 Z9 2 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1939-8425 EI 1939-8433 J9 RICE JI Rice PY 2013 VL 6 AR 35 DI 10.1186/1939-8433-6-35 PG 8 WC Agronomy SC Agriculture GA 270VV UT WOS:000328348200001 PM 24295067 ER PT B AU Reiner, O Gerlitz, G AF Reiner, O. Gerlitz, G. BE Rubenstein, JLR Rakic, P TI Nucleokinesis SO COMPREHENSIVE DEVELOPMENTAL NEUROSCIENCE: CELLULAR MIGRATION AND FORMATION OF NEURONAL CONNECTIONS LA English DT Article; Book Chapter ID DOUBLECORTIN-LIKE-KINASE; NUCLEAR-MEMBRANE PROTEIN; TANGENTIALLY MIGRATING NEURONS; MICROTUBULE-ASSOCIATED PROTEIN; DEVELOPING CEREBRAL-CORTEX; EARLY EMBRYONIC LETHALITY; CENTRAL-NERVOUS-SYSTEM; SPINDLE POLE BODY; CYTOPLASMIC DYNEIN; C-ELEGANS C1 [Reiner, O.] Weizmann Inst Sci, IL-76100 Rehovot, Israel. [Gerlitz, G.] NCI, NIH, Bethesda, MD 20892 USA. RP Reiner, O (reprint author), Weizmann Inst Sci, IL-76100 Rehovot, Israel. RI Reiner, Orly/E-9455-2010 OI Reiner, Orly/0000-0001-7560-9599 NR 210 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-397347-4; 978-0-12-397266-8 PY 2013 BP 261 EP 279 DI 10.1016/B978-0-12-397266-8.00026-0 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BIE42 UT WOS:000327883200015 ER PT J AU Foster, BL Nociti, FH Somerman, MJ AF Foster, Brian L. Nociti, Francisco H., Jr. Somerman, Martha J. BE Huang, GTJ Thesleff, I TI TOOTH ROOT DEVELOPMENT SO STEM CELLS IN CRANIOFACIAL DEVELOPMENT AND REGENERATION LA English DT Article; Book Chapter ID STEM-CELL COMPARTMENT; MECHANICAL-PROPERTIES; CHEMICAL-COMPOSITION; CEMENTUM FORMATION; MOUSE INCISORS; IN-VITRO; MICE; DIFFERENTIATION; MORPHOGENESIS; EXPRESSION C1 [Foster, Brian L.; Nociti, Francisco H., Jr.; Somerman, Martha J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Nociti, Francisco H., Jr.] Univ Estadual Campinas, Sch Dent, Sao Paulo, Brazil. RP Foster, BL (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. RI Foster, Brian/H-8375-2015 OI Foster, Brian/0000-0003-3444-0576 NR 64 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-27923-6 PY 2013 BP 153 EP 177 D2 10.1002/9781118498026 PG 25 WC Cell & Tissue Engineering; Developmental Biology SC Cell Biology; Developmental Biology GA BIF26 UT WOS:000327996200009 ER PT J AU Lombaert, IMA Hoffman, MP AF Lombaert, Isabelle M. A. Hoffman, Matthew P. BE Huang, GTJ Thesleff, I TI STEM CELLS IN SALIVARY GLAND DEVELOPMENT AND REGENERATION SO STEM CELLS IN CRANIOFACIAL DEVELOPMENT AND REGENERATION LA English DT Article; Book Chapter ID RAT SUBMANDIBULAR-GLAND; PROGENITOR CELLS; PARASYMPATHETIC INNERVATION; BRANCHING MORPHOGENESIS; STEM/PROGENITOR CELLS; PANCREATIC LINEAGES; MAMMARY-GLAND; MICE; IRRADIATION; DAMAGE C1 [Lombaert, Isabelle M. A.; Hoffman, Matthew P.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Lombaert, IMA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 59 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-1-118-27923-6 PY 2013 BP 271 EP 284 D2 10.1002/9781118498026 PG 14 WC Cell & Tissue Engineering; Developmental Biology SC Cell Biology; Developmental Biology GA BIF26 UT WOS:000327996200015 ER PT J AU Francisci, S Yabroff, KR Gigli, A Mariotto, A Mezzetti, M Lipscomb, J AF Francisci, Silvia Yabroff, K. Robin Gigli, Anna Mariotto, Angela Mezzetti, Maura Lipscomb, Joseph TI Advancing the science of cancer cost measurement: challenges and opportunities SO ANNALI DELL ISTITUTO SUPERIORE DI SANITA LA English DT Article DE cost-effectiveness; phase of care; incidence; prevalence; targeted therapy ID UP-TO-DATE; PROSTATE-CANCER; UNITED-STATES; COLORECTAL-CANCER; SURVIVAL ANALYSIS; PATIENT SURVIVAL; PERIOD ANALYSIS; FUTURE BURDEN; REGISTRY DATA; POPULATION AB Objectives. Cancer accounts for a major proportion of national health expenditures, which are expected to increase in the future. This paper aims to identify major challenges with estimating cancer related costs, and discuss international comparisons, and recommendations for future research. Methods. It starts from the experience of an international workshop aimed at comparing cancer burden evaluation methods, improving results comparability, discussing strengths and criticisms of different approaches. Results. Three methodological themes necessary to inform the analysis are identified and discussed: data availability; costs definition; epidemiological measures. Conclusions. Cost evaluation is applied to cancer control interventions and is relevant for public health planners. Despite their complexity, international comparisons are fundamental to improve, generalize and extend cost evaluation to different contexts. C1 [Francisci, Silvia] Ist Super Sanita, Ctr Nazl Epidemiol Sorveglianza & Promoz Salute, I-00161 Rome, Italy. [Yabroff, K. Robin] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Gigli, Anna] CNR, Ist Ric Popolaz & Polit Sociali, Rome, Italy. [Mariotto, Angela] NCI, Bethesda, MD 20892 USA. [Mezzetti, Maura] Univ Roma Tor Vergata, Rome, Italy. [Lipscomb, Joseph] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Lipscomb, Joseph] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. RP Francisci, S (reprint author), Ist Super Sanita, Ctr Nazl Epidemiol Sorveglianza & Promoz Salute, Via Giano della Bella 34, I-00161 Rome, Italy. EM silvia.francisci@iss.it OI Gigli, Anna/0000-0003-4929-505X NR 44 TC 1 Z9 1 U1 1 U2 5 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0021-2571 J9 ANN I SUPER SANITA JI Ann. Ist. Super. Sanita PY 2013 VL 49 IS 1 BP 73 EP 78 DI 10.4415/ANN_13_01_12 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 261WM UT WOS:000327695300012 PM 23535133 ER PT J AU Maver, A Hristovski, D Rindflesch, TC Peterlin, B AF Maver, Ales Hristovski, Dimitar Rindflesch, Thomas C. Peterlin, Borut TI Integration of Data from Omic Studies with the Literature-Based Discovery towards Identification of Novel Treatments for Neovascularization in Diabetic Retinopathy SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID DIFFERENTIALLY EXPRESSED GENES; MICROARRAY DATA; BIOCONDUCTOR; METAANALYSIS; CAUCASIANS; KNOWLEDGE; IDENTIFY; BIOLOGY AB Diabetic retinopathy (DR) is a secondary complication of diabetes associated with retinal neovascularization and represents the leading cause of blindness in the adult population in the developed world. Despite research efforts, the nature of pathogenetic processes leading to DR is still unknown, making development of novel effective treatments difficult. Advances in omic technologies now offer unprecedented insight into global molecular alterations in DR, but identification of novel treatments based on massive amounts of data generated in omic studies still represents a considerable challenge. For this reason, we attempted to facilitate discovery of novel treatments for DR by complementing the interpretation of omic results using the vast body of information existing in the published literature with the literature-based discovery (LBD) approaches. To achieve this, we collected data from transcriptomic studies performed on retinal tissue from animal models of DR, performed a meta-analysis of these datasets and identified altered genes and pathways. Using the SemBT LBD framework, we have determined which therapies could regulate perturbed pathways or that could stabilize the gene expression alterations in DR. We show that by using this approach, we not only could reidentify drugs currently in use or in clinical trials, but also could indicate novel treatment directions for ameliorating neovascularization processes in DR. C1 [Maver, Ales; Peterlin, Borut] Univ Med Ctr Ljubljana, Dept Obstet & Gynecol, Inst Med Genet, Ljubljana 1000, Slovenia. [Hristovski, Dimitar] Fac Med, Inst Biostat & Med Informat, Ljubljana 1000, Slovenia. [Rindflesch, Thomas C.] NIH, Natl Lib Med, Bethesda, MD 20894 USA. RP Peterlin, B (reprint author), Univ Med Ctr Ljubljana, Dept Obstet & Gynecol, Inst Med Genet, 3 Slajmerjeva St, Ljubljana 1000, Slovenia. EM borut.peterlin@guest.arnes.si RI peterlin, borut/C-6086-2011; OI peterlin, borut/0000-0001-7824-4978; Hristovski, Dimitar/0000-0001-6908-0246 NR 30 TC 2 Z9 2 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 848952 DI 10.1155/2013/848952 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 265PS UT WOS:000327964700001 ER PT S AU Davis, GE Kim, DJ Meng, CX Norden, PR Speichinger, KR Davis, MT Smith, AO Bowers, SLK Stratman, AN AF Davis, George E. Kim, Dae Joong Meng, Chun-Xia Norden, Pieter R. Speichinger, Katherine R. Davis, Matthew T. Smith, Annie O. Bowers, Stephanie L. K. Stratman, Amber N. BE Baudino, TA TI Control of Vascular Tube Morphogenesis and Maturation in 3D Extracellular Matrices by Endothelial Cells and Pericytes SO CELL-CELL INTERACTIONS: METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Endothelial cells; Pericytes; 3D matrices; Cell-cell interaction; Vascular tube morphogenesis ID 3-DIMENSIONAL COLLAGEN MATRIX; LUMEN FORMATION; MOLECULAR-MECHANISMS; CAPILLARY LUMEN; STABILIZATION; TUBULOGENESIS; VASCULOGENESIS; ANGIOGENESIS; REQUIRES; CDC42 AB An important advance using in vitro EC tube morphogenesis and maturation models has been the development of systems using serum-free defined media. Using this approach, the growth factors and cytokines which are actually necessary for these events can be determined. The first model developed by our laboratory was such a system where we showed that phorbol ester was needed in order to promote survival and tube morphogenesis in 3D collagen matrices. Recently, we have developed a new system in which the hematopoietic stem cell cytokines, stem cell factor (SCF), interleukin-3 (IL-3), and stromal derived factor-1 alpha (SDF-1 alpha) were added in conjunction with FGF-2 to promote human EC tube morphogenesis in 3D collagen matrices under serum-free defined conditions. This new model using SCF, IL-3, SDF-1 alpha, and FGF-2 also works well following the addition of pericytes where EC tube formation occurs, pericytes are recruited to the tubes, and vascular basement membrane matrix assembly occurs following EC-pericyte interactions. In this chapter, we describe several in vitro assay models that we routinely utilize to investigate the molecular requirements that are critical to EC tube formation and maturation events in 3D extracellular matrix environments. C1 [Davis, George E.; Kim, Dae Joong; Meng, Chun-Xia; Norden, Pieter R.; Speichinger, Katherine R.; Davis, Matthew T.; Smith, Annie O.; Bowers, Stephanie L. K.] Univ Missouri, Sch Med, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA. [Davis, George E.; Kim, Dae Joong; Meng, Chun-Xia; Norden, Pieter R.; Speichinger, Katherine R.; Davis, Matthew T.; Smith, Annie O.; Bowers, Stephanie L. K.] Dalton Cardiovasc Res Ctr, Columbia, MO USA. [Davis, George E.] Univ Missouri, Sch Med, Dept Pathol & Anat Sci, Columbia, MO USA. [Stratman, Amber N.] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Davis, GE (reprint author), Univ Missouri, Sch Med, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA. RI Meng, Chunxia/G-7583-2016 OI Meng, Chunxia/0000-0001-8197-439X FU NHLBI NIH HHS [HL105606, HL87308, HL79460] NR 21 TC 8 Z9 8 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-604-7; 978-1-62703-603-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1066 BP 17 EP 28 DI 10.1007/978-1-62703-604-7_2 D2 10.1007/978-1-62703-604-7 PG 12 WC Cell Biology SC Cell Biology GA BIE11 UT WOS:000327799400003 PM 23955730 ER PT S AU Hardwick, JP Eckman, K Lee, YK Abdelmegeed, MA Esterle, A Chilian, WM Chiang, JY Song, BJ AF Hardwick, James P. Eckman, Katie Lee, Yoon Kwang Abdelmegeed, Mohamed A. Esterle, Andrew Chilian, William M. Chiang, John Y. Song, Byoung-Joon BE Webb, DR TI Eicosanoids in Metabolic Syndrome SO IMMUNOPHARMACOLOGY SE Advances in Pharmacology LA English DT Article; Book Chapter ID FATTY LIVER-DISEASE; ACID-BINDING PROTEIN; ENDOPLASMIC-RETICULUM STRESS; SOLUBLE EPOXIDE HYDROLASE; NECROSIS-FACTOR-ALPHA; ADIPOSE-TISSUE INFLAMMATION; B-4 OMEGA-HYDROXYLASE; DIET-INDUCED OBESITY; VERY-LONG-CHAIN; INSULIN-RESISTANCE AB Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism. The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS. C1 [Hardwick, James P.; Eckman, Katie; Lee, Yoon Kwang; Chilian, William M.; Chiang, John Y.] Northeast Ohio Med Univ NEOMED, Dept Integrat Med Sci, Rootstown, OH USA. [Esterle, Andrew] Akron Gen Med Ctr, Dept Orthoped Surg, Akron, OH USA. [Abdelmegeed, Mohamed A.; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD USA. RP Hardwick, JP (reprint author), Northeast Ohio Med Univ NEOMED, Dept Integrat Med Sci, Rootstown, OH USA. EM jph@neomed.edu OI Chiang, John/0000-0001-9360-7650 FU Intramural NIH HHS [Z99 AA999999, ZIA AA000036-26]; NHLBI NIH HHS [HL32788, R01 HL032788]; NIDDK NIH HHS [DK44442, DK58379, R01 DK044442, R01 DK058379, R01 DK093774, R01DK093774, R37 DK058379, R56 DK044442]; PHS HHS [R0183366, RCIHL100828] NR 269 TC 15 Z9 15 U1 1 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-12-405184-3; 978-0-12-404717-4 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2013 VL 66 BP 157 EP 266 DI 10.1016/B978-0-12-404717-4.00005-6 PG 110 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BID60 UT WOS:000327731500006 PM 23433458 ER PT J AU Eldridge, RC Doubeni, CA Fletcher, RH Zauber, AG Corley, DA Doria-Rose, VP Goodman, M AF Eldridge, Ronald C. Doubeni, Chyke A. Fletcher, Robert H. Zauber, Ann G. Corley, Douglas A. Doria-Rose, V. Paul Goodman, Michael TI Uncontrolled confounding in studies of screening effectiveness: an example of colonoscopy SO JOURNAL OF MEDICAL SCREENING LA English DT Article ID FECAL-OCCULT-BLOOD; COLORECTAL-CANCER MORTALITY; RANDOMIZED CONTROLLED TRIAL; FATAL COLON-CANCER; RISK-FACTORS; FOLLOW-UP; REDUCED RISK; LIFE-STYLE; ASSOCIATION; POPULATION AB Objective: To estimate the expected magnitude of error produced by uncontrolled confounding from health behaviours in observational medical record-based studies evaluating effectiveness of screening colonoscopy. Methods: We used data from the prospective National Institutes of Health American Association of Retired Persons (NIH-AARP) Diet and Health Study to assess the impact of health behaviour related factors (lifestyle, education, and use of non-steroidal anti-inflammatory drugs [NSAID]) on the association between colonoscopy and colorectal cancer (CRC) mortality. We first examined the difference between adjusted and unadjusted results within the cohort data, and then estimated a broader range of likely confounding errors based on the Breslow-Day approach that uses prevalence of confounders among persons with and without exposure, and the rate ratio reflecting the association between these confounders and the outcome of interest. As dietary factors and habits are often inter-correlated, we combined these variables (physical activity, body mass index, waist-to-hip ratio, alcohol consumption, and intakes of red meat, processed meat, fibre, milk, and calcium) into a "healthy lifestyle score" (HLS). Results: The estimated error (a ratio of biased-to-true result) attributable to confounding by HLS was 0.959-0.997, indicating less than 5% departure from the true effect of colonoscopy on CRC mortality. The corresponding errors ranged from 0.970 to 0.996 for NSAID, and from 0.974 to 1.006 for education (all <= 3% difference). The results for other CRC screening tests were similar. Conclusion: Health behaviour-related confounders, either alone or in combination, seem unlikely to strongly affect the association between colonoscopy and CRC mortality in observational studies of CRC screening. C1 [Eldridge, Ronald C.; Goodman, Michael] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Doubeni, Chyke A.] Univ Penn, Dept Family Med & Community Hlth, Perelman Sch Med, Philadelphia, PA 19104 USA. [Fletcher, Robert H.] Harvard Univ, Sch Med, Dept Populat Hlth, Boston, MA USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Corley, Douglas A.] Kaiser Permanente, Div Res, Oakland, CA USA. [Doria-Rose, V. Paul] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Goodman, M (reprint author), Emory Univ, Sch Publ Hlth, Dept Epidemiol, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM mgoodm2@emory.edu OI Doubeni, Chyke/0000-0001-7495-0285; Doria-Rose, Vincent/0000-0002-8802-5143 FU National Cancer Institute of the National Institutes of Health [U01CA151736] FX This work was supported by grant # U01CA151736 from the National Cancer Institute of the National Institutes of Health. NR 40 TC 3 Z9 3 U1 2 U2 5 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 EI 1475-5793 J9 J MED SCREEN JI J. Med. Screen. PY 2013 VL 20 IS 4 BP 198 EP 207 DI 10.1177/0969141313508282 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265IE UT WOS:000327943300006 PM 24144847 ER PT J AU Ahn, H Hernandez-Andrade, E Romero, R Ptwardhan, M Goncalves, LF Aurioles-Garibay, A Garcia, M Hassan, SS Yeo, L AF Ahn, Hyunyoung Hernandez-Andrade, Edgar Romero, Roberto Ptwardhan, Manasi Goncalves, Luis F. Aurioles-Garibay, Alma Garcia, Maynor Hassan, Sonia S. Yeo, Lami TI Mirror Artifacts in Obstetric Ultrasound: Case Presentation of a Ghost Twin during the Second-Trimester Ultrasound Scan SO FETAL DIAGNOSIS AND THERAPY LA English DT Article DE Ultrasound physics; Twin gestation; Abdominal heterotopic pregnancy; Diagnostic error ID IMAGE ARTIFACT; EARLY-PREGNANCY; BASIC PHYSICS; ARTERY; MISINTERPRETATION; SONOGRAPHY; APPEARANCE; RELEVANCE; US AB Mirror artifacts are produced by the reflection of ultrasound waves after they propagate through a structure and encounter a strong and smooth interface capable of acting as a mirror. Ultrasound waves bounce back and forth between the mirroring interface and the reflective object and then eventually return to the transducer. The typical display of the mirror artifact consists of two similar structures separated and at similar distances from the reflective interface. We report a mirror artifact in a patient with a singleton gestation at 18 weeks. The image was interpreted as consistent with a twin gestation using transabdominal and transvaginal ultrasound. The differential diagnosis consisted of an abdominal heterotopic pregnancy. The presence of synchronized but opposite movements of both fetuses, and the blurred image of the second fetus, suggested a mirror artifact. The reflective surface was created by the interface located between a distended rectosigmoid filled with gas and the posterior uterine wall. Mirror artifacts can lead to diagnostic errors. This case illustrates how a distended rectosigmoid colon can generate an image that simulates either a twin gestation or an abdominal heterotopic pregnancy. Copyright (C) 2013 S. Karger AG, Basel C1 [Ahn, Hyunyoung; Hernandez-Andrade, Edgar; Romero, Roberto; Ptwardhan, Manasi; Aurioles-Garibay, Alma; Garcia, Maynor; Hassan, Sonia S.; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA. [Ahn, Hyunyoung; Hernandez-Andrade, Edgar; Ptwardhan, Manasi; Aurioles-Garibay, Alma; Garcia, Maynor; Hassan, Sonia S.; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Goncalves, Luis F.] Oakland Univ, William Beaumont Sch Med, Dept Obstet & Gynecol, Rochester, MI 48063 USA. [Goncalves, Luis F.] Oakland Univ, William Beaumont Sch Med, Dept Radiol, Rochester, MI 48063 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, Department of Health and Human Services [HHSN275201300006C] FX This project has been funded in whole or in part with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201300006C. NR 25 TC 0 Z9 0 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-3837 EI 1421-9964 J9 FETAL DIAGN THER JI Fetal Diagn. Ther. PY 2013 VL 34 IS 4 BP 248 EP 252 DI 10.1159/000353702 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 260FK UT WOS:000327580200008 PM 24071724 ER PT J AU Balamurugan, K Sterneck, E AF Balamurugan, Kuppusamy Sterneck, Esta TI The Many Faces of C/EBP delta and their Relevance for Inflammation and Cancer SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE C/EBP; transcription factor; cell signaling; inflammation; cancer ID BINDING-PROTEIN-DELTA; ACUTE LUNG INJURY; SMOOTH-MUSCLE-CELLS; PROINFLAMMATORY GENE-EXPRESSION; MAMMARY EPITHELIAL-CELLS; ACTIVATED RECEPTOR-GAMMA; FACTOR-ALPHA RECEPTOR; GROWTH-FACTOR-BETA; ADIPOCYTE DIFFERENTIATION; TRANSCRIPTION FACTORS AB The CCAAT/enhancer binding protein delta (CEBPD, C/EBP delta) is a transcription factor that modulates many biological processes including cell differentiation, motility, growth arrest, proliferation, and cell death. The diversity of C/EBP delta's functions depends in part on the cell type and cellular context and can have opposing outcomes. For example, C/EBP delta promotes inflammatory signaling, but it can also inhibit pro-inflammatory pathways, and in a mouse model of mammary tumorigenesis, C/EBP delta reduces tumor incidence but promotes tumor metastasis. This review highlights the multifaceted nature of C/EBP delta's functions, with an emphasis on pathways that are relevant for cancer and inflammation, and illustrates how C/EBP delta emerged from the shadow of its family members as a fascinating "jack of all trades." Our current knowledge on C/EBP delta indicates that, rather than being essential for a specific cellular process, C/EBP delta helps to interpret a variety of cues in a cell-type and context-dependent manner, to adjust cellular functions to specific situations. Therefore, insights into the roles and mechanisms of C/EBP delta signaling can lead to a better understanding of how the integration of different signaling pathways dictates normal and pathological cell functions and physiology. C1 [Balamurugan, Kuppusamy; Sterneck, Esta] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Sterneck, E (reprint author), NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Ft Detrick, MD 21702 USA. EM sternecg@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute FX The authors are supported by the Intramural Research Program of the NIH, National Cancer Institute. We are grateful to Drs. Peter Johnson, Howard Young, and Ju-Ming Wang for helpful discussion and critical comments on the manuscript, and Allen Kane for preparation of the figures. We apologize for not citing all the publications in the field and welcome feedback. NR 177 TC 25 Z9 25 U1 3 U2 10 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2013 VL 9 IS 9 BP 917 EP 933 DI 10.7150/ijbs.7224 PG 17 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 261XJ UT WOS:000327697700006 PM 24155666 ER PT J AU Wang, RH Xu, XL Kim, HS Xiao, Z Deng, CX AF Wang, Rui-Hong Xu, Xiaoling Kim, Hyun-Seok Xiao, Zhen Deng, Chu-Xia TI SIRT1 Deacetylates FOXA2 and Is Critical for Pdx1 Transcription and beta-Cell Formation SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE SIRT1; FOXA2; PDX1; insulin ID NUCLEAR FACTOR 3-BETA; STIMULATED INSULIN-SECRETION; CALORIE RESTRICTION; PANCREAS DEVELOPMENT; MAMMALIAN SIRTUINS; IN-VIVO; MICE; GENE; EXPRESSION; MOUSE AB Pancreas duodenum homeobox 1 (PDX1) is essential for pancreas development and beta-cell formation; however more studies are needed to clearly illustrate the precise mechanism regarding spatiotemporal regulation of Pdx1 expression during beta-cell formation and development. Here, we demonstrate that SIRT1, FOXA2 and a number of proteins form a protein complex on the promoter of the Pdx1 gene. SIRT1 and PDX1 are expressed in the same set of cells during beta-cell differentiation and maturation. Pancreas-specific disruption of SIRT1 diminished PDX1 expression and impaired islet development. Consequently, SIRT1 mutant mice develop progressive hyperglycemia, glucose intolerance, and insulin insufficiency, which directly correlate with the extent of SIRT1 deletion. We further show that SIRT1 interacts with and deacetylates FOXA2 on the promoter of the Pdx1gene, and positively regulates its transcription. These results uncover an essential role of SIRT1 in beta-cell formation by maintaining expression of PDX1 and its downstream genes, and identify pancreas-specific SIRT1 mutant mice as a relevant model for studying insulin insufficiency. C1 [Wang, Rui-Hong; Xu, Xiaoling; Kim, Hyun-Seok; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Xiao, Zhen] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA FX We thank Dr. Douglas Melton for PDX1-Cre mice, and Dr. Kenneth S. Zaret for GFP-FOXA2 expression vector. We thank Drs. Oksana Gavrilova, Tyler J. Lahusen, Cuiling Li, and Cuiying Xiao for technical assistance. We also thank the members of the Deng lab for critical review of the manuscript. This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA. NR 66 TC 11 Z9 12 U1 1 U2 3 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2013 VL 9 IS 9 BP 934 EP 946 DI 10.7150/ijbs.7529 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 261XJ UT WOS:000327697700007 PM 24163589 ER PT J AU Fang, CG Man, YG Cuttitta, F Stetler-Stevenson, W Salomon, D Mazar, A Kulesza, P Rosen, S Avital, I Stojadinovic, A Jewett, A Jiang, B Mulshine, J AF Fang, Changge Man, Yan-Gao Cuttitta, Frank Stetler-Stevenson, William Salomon, David Mazar, Andrew Kulesza, Piotr Rosen, Steve Avital, Itzhak Stojadinovic, Alexander Jewett, Anahid Jiang, Bin Mulshine, James TI Novel Phenotypic Fluorescent Three-Dimensional Co-Culture Platforms for Recapitulating Tumor in vivo Progression and for Personalized Therapy SO JOURNAL OF CANCER LA English DT Article DE 3D co-culture platform; in vivo; tumor ID CELL LUNG-CANCER; HUMAN-BREAST-CANCER; STEM-CELLS; SPHEROID MODEL; COLLAGEN GEL; MULTICELLULAR SPHEROIDS; GENE-EXPRESSION; NUDE-MICE; RAT; CULTURE AB Because three-dimensional (3D) in vitro models are more accurate than 2D cell culture models and faster and cheaper than animal models, they have become a prospective trend in the biomedical and pharmaceutical fields, especially for personalized and targeted therapies. Because appropriate 3D models can be customized to mimic the in vivo microenvironment wherein various cell populations grow within an intricate but well organized extracellular matrix (ECM), they can accurately recapitulate physiological and pathophysiological progressions. The majority of cancers are carcinomas, which originate from epithelial cells, and dynamically interact with non-malignant cells including stromal cells (fibroblasts), vascular cells (endothelial cells and pericytes), immune cells (macrophages and mast cells), and the ECM. Employing a tumor monoclonal colony, tumor xenograft or patient cancer biopsy into an in vivo-like microenvironment, the native signaling pathways, cell-cell and cell-matrix interactions, and cell phenotypes are preserved and our fluorescent phenotypic 3D co-culture platforms can then accurately recapitulate the tumor in vivo scenario including tumor induced angiogenesis, tumor growth, and metastasis. In this paper, we describe a robust and standardized method to co-culture a tumor colony or biopsy with different cell populations, e. g., endothelial cells, immune cells, pericytes, etc. The procedures for recovering cells from the co-culture for molecular analyses, imaging, and analyzing are also described. We selected ECM solubilized extract derived from Engelbreth-Holm-Swam sarcoma cells. Because the 3D co-culture platforms can provide drug chemosensitivity data within 9 days that is equivalent to the results generated from mouse tumor xenograft models in 50 days, the 3D co-culture platforms are more accurate, efficient, and cost-effective and may replace animal models in the near future to predict drug efficacy, personalize therapies, prevent drug resistance, and improve the quality of life. C1 [Fang, Changge] Adv Personalized Diagnost, Alexandria, VA 22303 USA. [Man, Yan-Gao; Avital, Itzhak; Stojadinovic, Alexander] Bon Secours Hlth Syst, Bon Secours Canc Inst, Richmond, VA USA. [Cuttitta, Frank] Sci Segues LLC, Adamstown, MD 21710 USA. [Stetler-Stevenson, William] NCI, Extracellular Matrix Pathol Sect, Ctr Canc Res, ATC, Bethesda, MD 20892 USA. [Salomon, David] NCI, Tumor Growth Factor Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD USA. [Mazar, Andrew] Northwestern Univ, Chem Life Proc Inst, Chicago, IL 60611 USA. [Kulesza, Piotr] Northwestern Univ, Pathol Core Facil, Chicago, IL 60611 USA. [Rosen, Steve] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Jewett, Anahid] Univ Calif Los Angeles, Sch Med & Dent, Div Oral Biol & Med, Tumor Immunol Lab, Los Angeles, CA USA. [Jiang, Bin] Nanjing Univ, Affiliated Hosp 3, Univ Chinese Med, Nanjing 210008, Jiangsu, Peoples R China. [Mulshine, James] Rush Univ, Rush Med Coll, Chicago, IL 60612 USA. RP Fang, CG (reprint author), Adv Personalized Diagnost, 6006 Bangor Dr, Alexandria, VA 22303 USA. EM changgefang@hotmail.com RI Stetler-Stevenson, William/H-6956-2012; Cuttitta, Frank/B-4758-2016 OI Stetler-Stevenson, William/0000-0002-5500-5808; NR 73 TC 4 Z9 5 U1 2 U2 11 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2013 VL 4 IS 9 BP 755 EP 763 DI 10.7150/jca.7813 PG 9 WC Oncology SC Oncology GA 260HU UT WOS:000327586400007 PM 24312145 ER PT J AU Chan, ESL Liu, HL Fernandez, P Luna, A Perez-Aso, M Bujor, AM Trojanowska, M Cronstein, BN AF Chan, Edwin S. L. Liu, Hailing Fernandez, Patricia Luna, Alex Perez-Aso, Miguel Bujor, Andreea M. Trojanowska, Maria Cronstein, Bruce N. TI Adenosine A(2A) receptors promote collagen production by a Fli1-and CTGF-mediated mechanism SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE Fibrosis; fibroblast; scleroderma ID TISSUE GROWTH-FACTOR; HUMAN DERMAL FIBROBLASTS; TRANSCRIPTION FACTOR FLI1; PROTEIN-ASSOCIATED FACTOR; INDUCIBLE FACTOR-I; FACTOR-BETA; ECTO-5'-NUCLEOTIDASE CD73; PHARMACOLOGICAL BLOCKADE; SYSTEMIC-SCLEROSIS; SIGNALING PATHWAY AB Introduction: Adenosine, acting through the A(2A) receptor, promotes tissue matrix production in the skin and the liver and induces the development of dermal fibrosis and cirrhosis in murine models. Since expression of A(2A) receptors is increased in scleroderma fibroblasts, we examined the mechanisms by which the A(2A) receptor produces its fibrogenic effects. Methods: The effects of A(2A) receptor ligation on the expression of the transcription factor, Fli1, a constitutive repressor for the synthesis of matrix proteins, such as collagen, is studied in dermal fibroblasts. Fli1 is also known to repress the transcription of CTGF/CCN2, and the effects of A(2A) receptor stimulation on CTGF and TGF-beta 1 expression are also examined. Results: A(2A) receptor occupancy suppresses the expression of Fli1 by dermal fibroblasts. A(2A) receptor activation induces the secretion of CTGF by dermal fibroblasts, and neutralization of CTGF abrogates the A(2A) receptor-mediated enhancement of collagen type I production. A(2A)R activation, however, resulted in a decrease in TGF-beta 1 protein release. Conclusions: Our results suggest that Fli1 and CTGF are important mediators of the fibrogenic actions of adenosine and the use of small molecules such as adenosine A(2A) receptor antagonists may be useful in the therapy of dermal fibrosis in diseases such as scleroderma. C1 [Chan, Edwin S. L.; Liu, Hailing; Fernandez, Patricia; Luna, Alex; Perez-Aso, Miguel; Cronstein, Bruce N.] NYU, Sch Med, Dept Med, New York, NY 10016 USA. [Fernandez, Patricia] NCI, NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [Bujor, Andreea M.; Trojanowska, Maria] Boston Univ, Sch Med, Arthrit Ctr, Dept Med, Boston, MA 02118 USA. RP Chan, ESL (reprint author), NYU, Sch Med, Dept Med, 550 1st Ave, New York, NY 10016 USA. EM Edwin.Chan@nyumc.org FU National Institutes of Health [AR057544, AR56672, AR54897, AR42334]; Scleroderma Foundation; NYU-HHC CTSI [UL1RR029893] FX This study was funded by grants from the National Institutes of Health AR057544 (EC), AR56672 and AR54897, (BC), AR42334 (MT), the Scleroderma Foundation (EC). In addition this work was supported by the NYU-HHC CTSI (UL1RR029893). The authors thank EUSTAR (EULAR Scleroderma Trials and Research Group), in particular, Dr. Oliver Distler, Dr. Tatiana Nevskaja and Prof. Marco Matucci-Cerinic for their help and participation in these studies. NR 42 TC 16 Z9 16 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2013 VL 15 IS 3 AR R58 DI 10.1186/ar4229 PG 11 WC Rheumatology SC Rheumatology GA 258CK UT WOS:000327436400001 PM 23663495 ER PT J AU Chu, XK Tuo, JS Chan, CC AF Chu, Xi K. Tuo, Jingsheng Chan, Chi-Chao TI Genetics of age-related macular degeneration: application to drug design SO FUTURE MEDICINAL CHEMISTRY LA English DT Editorial Material DE age-related macular degeneration; anti-VEGF; CFH; gene therapy; HTRA1; ARMS2; inflammation; siRNA ID RANIBIZUMAB; BEVACIZUMAB; VEGF; CFH C1 [Chu, Xi K.; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,Room 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU Intramural NIH HHS [ZIA EY000418-09] NR 20 TC 1 Z9 1 U1 0 U2 9 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 EI 1756-8927 J9 FUTURE MED CHEM JI Future Med. Chem. PD JAN PY 2013 VL 5 IS 1 BP 13 EP 15 DI 10.4155/fmc.12.187 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 254SY UT WOS:000327188500004 PM 23256807 ER PT S AU Lauretani, F Maggio, M Ruggiero, C Ceda, GP Ferrucci, L AF Lauretani, F. Maggio, M. Ruggiero, C. Ceda, G. P. Ferrucci, L. BE Watson, RR TI Vitamin D in health of seniors SO HANDBOOK OF VITAMIN D IN HUMAN HEALTH: PREVENTION, TREATMENT AND TOXICITY SE Human Health Handbooks LA English DT Article; Book Chapter DE vitamin D deficiency; mortality; sarcopenia; falls; older persons ID RANDOMIZED CONTROLLED-TRIALS; PARATHYROID-HORMONE LEVELS; SERUM 25-HYDROXYVITAMIN D; CARDIOVASCULAR-DISEASE; PHYSICAL PERFORMANCE; OLDER-ADULTS; D DEFICIENCY; CALCIUM SUPPLEMENTATION; HYPOVITAMINOSIS-D; HEART-FAILURE AB Vitamin D is a hormone with multiple biological activities that are essential for normal functioning of many biological systems including bone, skeletal muscle, brain and heart. The estimated worldwide prevalence of vitamin D deficiency among the elderly is of about 50% and, because of the demographic expansion, vitamin D deficiency is becoming very important for public health. Vitamin D status has been studied in all continents and most countries over the world. Vitamin D deficiency in adults is highly prevalent especially in the Middle-East and Asia. In this chapter, we explore potential mechanism which vitamin D could influence the muscle-skeletal system and increase risk of falling. In particular, we propose an array of mechanisms for the increased risk of falling secondary to low vitamin D. These mechanisms can be directly or indirectly related to sarcopenia (defined as reduced muscle mass with age in older persons) - and are implicated in the genesis of osteoporotic fractures. Although we mention all therapeutic options for treatment of vitamin D deficiency, we recognize that in a recent Cochrane review addressing the relationship between vitamin D and mortality, only low vitamin D3 levels were significantly associated with high risk of death whereas vitamin D2, alfacalcidol, or calcitriol were not. Therefore, the treatment of choice for vitamin D deficiency should be cholecalciferol, also known as vitamin D3. Supplementation with 1000 IU per day still remains the treatment of choice of vitamin D supplementation. C1 [Lauretani, F.] Univ Hosp Parma, Geriatr Rehabil Dept, Lab Movement Anal, Geriatr Unit, I-43126 Parma, Italy. [Maggio, M.; Ceda, G. P.] Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43126 Parma, Italy. [Ruggiero, C.] Univ Perugia, Dept Clin & Expt Med, Inst Gerontol & Geriatr, I-06156 Perugia, Italy. [Ferrucci, L.] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD USA. RP Lauretani, F (reprint author), Univ Hosp Parma, Geriatr Rehabil Dept, Lab Movement Anal, Geriatr Unit, Via Gramsci 14, I-43126 Parma, Italy. EM flauretani@ao.pr.it NR 57 TC 0 Z9 0 U1 1 U2 5 PU WAGENINGEN ACAD PUBL PI WAGENINGEN PA POSTBUS 220, 6700 AE WAGENINGEN, NETHERLANDS SN 2212-375X BN 978-90-8686-765-3; 978-90-8686-210-8 J9 HUM HEALT HANDB PY 2013 IS 4 BP 39 EP 52 D2 10.3920/978-908686-765-3 PG 14 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BIC84 UT WOS:000327428200002 ER PT J AU Harding, JD AF Harding, John D. TI Progress in Genetics and Genomics of Nonhuman Primates SO ILAR JOURNAL LA English DT Editorial Material ID CALORIC RESTRICTION; MACACA-MULATTA; RHESUS-MONKEYS; LINKAGE MAP; DISEASE; INFORMATION; DIVERGENCE; SEQUENCE; HEALTH C1 [Harding, John D.] NIH, Div Comparat Med, Bethesda, MD 20892 USA. RP Harding, JD (reprint author), NIH, Div Comparat Med, ORIP, DPCPSI, 6701 Democracy Blvd,MSC 4874, Bethesda, MD 20892 USA. EM hardingj@mail.nih.gov NR 38 TC 1 Z9 1 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 EI 1930-6180 J9 ILAR J JI ILAR J. PY 2013 VL 54 IS 2 BP 77 EP 81 DI 10.1093/ilar/ilt051 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 248EE UT WOS:000326675700001 PM 24174433 ER PT J AU Berezovskaya, F Karev, G AF Berezovskaya, F. Karev, G. TI Bifurcation Approach to Analysis of Travelling Waves in Some Taxis-Cross-Diffusion Models SO MATHEMATICAL MODELLING OF NATURAL PHENOMENA LA English DT Article DE traveling wave solutions; wave system; bifurcation diagram; taxis; cross-diffusion; Keller-Segel model; FitzHugh-Nagumo equations ID REINFORCED RANDOM-WALKS; NAGUMO EQUATIONS; NERVE AXON; CHEMOTAXIS; STABILITY; IMPULSES; DYNAMICS; FRONTS; FAMILY; CELLS AB An overview of recently obtained authors' results on traveling wave solutions of some classes of PDEs is presented. The main aim is to describe all possible travelling wave solutions of the equations. The analysis was conducted using the methods of qualitalive and bifurcation analysis in order to study the phase-parameter space of the corresponding wave systems of ODEs. In the first part we analyze the wave dynamic modes of populations described by the "growth taxis - diffusion" polynomial models. It is shown that "suitable" nonlinear taxis can affect the wave front sets and generate non-monotone waves, such as trains and pulses, which represent the exact solutions of the model system. Parametric critical points whose neighborhood displays the full spectrum of possible model wave regimes are identified; the wave mode systematization is given in the form of bifurcation diagrams. In the second part we study a modified version of the FitzHugh-Naguirto equations, which model the spatial propagation of neuron firing. We assume that this propagation is (at least, partially) caused by the cross-diffusion connection between the potential and recovery variables. We show that the cross-diffusion version of the model, besides giving rise to the typical fast travelling wave solution exhibited in the original "diffusion" FitzHugh-Nagumo equations, additionally gives rise to a slow traveling wave solution. We analyze all possible traveling wave solutions of the model and show that there exists a. threshold of the cross-diffusion coefficient (for a given speed of propagation), which bounds the area where "normal" impulse propagation is possible. In the third part We describe all possible wave solutions for a class of PDEs with cross-diffusion, which fall in a general class of the classical Keller-Segel models describing chemotaxis. Conditions for existence of front-impulse, impulse-front, and front-front traveling wave solutions are formulated. In particular, we show that a lion-isolated singular point in the ODE wave system implies existence of free-boundary fronts. C1 [Berezovskaya, F.] Howard Univ, Washington, DC 20059 USA. [Karev, G.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Karev, G (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM fberezovskaya@howard.edu NR 71 TC 0 Z9 0 U1 1 U2 2 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0973-5348 EI 1760-6101 J9 MATH MODEL NAT PHENO JI Math. Model. Nat. Phenom. PY 2013 VL 8 IS 3 BP 133 EP 153 DI 10.1051/mmnp/20138309 PG 21 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications; Multidisciplinary Sciences SC Mathematical & Computational Biology; Mathematics; Science & Technology - Other Topics GA 252RR UT WOS:000327027900009 ER PT S AU Mirigian, M Mukherjee, K Bane, SL Sackett, DL AF Mirigian, Matthew Mukherjee, Kamalika Bane, Susan L. Sackett, Dan L. BE Correia, JJ Wilson, L TI Measurement of In Vitro Microtubule Polymerization by Turbidity and Fluorescence SO MICROTUBULES, IN VITRO, 2ND EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID TUBULIN POLYMERIZATION; PROBE; MECHANISM; KINETICS; INVITRO; AGENTS AB Tubulin polymerization may be conveniently monitored by the increase in turbidity (optical density, or OD) or by the increase in fluorescence intensity of diamidino-phenylindole. The resulting data can be a quantitative measure of microtubule (MT) assembly, but some care is needed in interpretation, especially of OD data. Buffer formulations used for the assembly reaction significantly influence the polymerization, both by altering the critical concentration for polymerization and by altering the exact polymer produced-for example, by increasing the production of sheet polymers in addition to MT. Both the turbidity and the fluorescence methods are useful for demonstrating the effect of MT-stabilizing or -destabilizing additives. C1 [Mirigian, Matthew; Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA. [Mukherjee, Kamalika; Bane, Susan L.] SUNY Binghamton, Dept Chem, Binghamton, NY USA. RP Mirigian, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA. RI Bane, Susan/C-1414-2013 OI Bane, Susan/0000-0002-4270-6314 NR 23 TC 2 Z9 2 U1 1 U2 18 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-407888-8; 978-0-12-407757-7 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2013 VL 115 BP 215 EP 229 DI 10.1016/B978-0-12-407757-7.00014-1 PG 15 WC Cell Biology SC Cell Biology GA BIC49 UT WOS:000327397400015 PM 23973075 ER PT J AU Babu, S Nutman, TB AF Babu, Subash Nutman, Thomas B. BE Kennedy, MW Harnett, W TI Influence of Nematodes on Mycobacterium tuberculosis and Related Mycobacteriae: From Disease Outcome to Immune Responses SO PARASITIC NEMATODES: MOLECULAR BIOLOGY, BIOCHEMISTRY AND IMMUNOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID CALMETTE-GUERIN VACCINATION; HUMAN LYMPHATIC FILARIASIS; PARASITE-SPECIFIC ANERGY; HUMAN DENDRITIC CELLS; CD4(+) T-CELLS; BANCROFTIAN FILARIASIS; HELMINTH-PARASITES; BRUGIA-MALAYI; SCHISTOSOMA-MANSONI; LATENT TUBERCULOSIS C1 [Babu, Subash] Natl Inst Hlth, Int Ctr Excellence Res, Madras, Tamil Nadu, India. [Nutman, Thomas B.] NIAID, Bethesda, MD 20892 USA. RP Babu, S (reprint author), Natl Inst Hlth, Int Ctr Excellence Res, Madras, Tamil Nadu, India. EM sbabu@niaid.nih.gov; TNUTMAN@niaid.nih.gov NR 100 TC 0 Z9 0 U1 1 U2 1 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-84593-759-1 PY 2013 BP 130 EP 143 D2 10.1079/9781845937591.0000 PG 14 WC Parasitology SC Parasitology GA BIA47 UT WOS:000327141000009 ER PT B AU Schug, TT Howard, SG Taylor, KW Heindel, JJ AF Schug, Thaddeus T. Howard, Sarah G. Taylor, Kyla W. Heindel, Jerrold J. BE Weiss, B TI Obesity and Diabetes: Role of Environmental Chemical Exposures SO AGING AND VULNERABILITY TO ENVIRONMENTAL CHEMICALS: AGE-RELATED DISORDERS AND THEIR ORIGINS IN ENVIRONMENTAL EXPOSURES SE Issues in Toxicology LA English DT Article; Book Chapter ID PERSISTENT ORGANIC POLLUTANTS; ENDOCRINE DISRUPTING CHEMICALS; BISPHENOL-A CONCENTRATION; BETA-CELL AUTOIMMUNITY; INSULIN-RESISTANCE; AIR-POLLUTION; DEVELOPMENTAL EXPOSURE; SERUM CONCENTRATIONS; PESTICIDE EXPOSURE; ANIMAL-MODELS C1 [Schug, Thaddeus T.; Heindel, Jerrold J.] NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. [Howard, Sarah G.] Collaborat Hlth & Environm, Bolinas, CA 94924 USA. [Taylor, Kyla W.] NIEHS, Off Hlth Assessment & Translat, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Schug, TT (reprint author), NIEHS, Div Extramural Res & Training, POB 12233, Res Triangle Pk, NC 27709 USA. EM heindelj@NIEHS.NIH.GOV NR 209 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND BN 978-1-84973-466-0; 978-1-84973-418-9 J9 ISSUES TOXICOL PY 2013 VL 16 BP 201 EP 240 DI 10.1039/9781849734660-00201 D2 10.1039/9781849734660 PG 40 WC Chemistry, Multidisciplinary; Toxicology SC Chemistry; Toxicology GA BHW88 UT WOS:000326880400010 ER PT B AU White, SS Fenton, SE AF White, Sally S. Fenton, Suzanne E. BE Weiss, B TI Breast Cancer - Importance of Life Stage with Respect to Environmental Influences SO AGING AND VULNERABILITY TO ENVIRONMENTAL CHEMICALS: AGE-RELATED DISORDERS AND THEIR ORIGINS IN ENVIRONMENTAL EXPOSURES SE Issues in Toxicology LA English DT Article; Book Chapter ID MAMMARY-GLAND DEVELOPMENT; AFRICAN-AMERICAN WOMEN; ATOMIC-BOMB SURVIVORS; COLLABORATIVE REANALYSIS; MAMMOGRAPHIC DENSITY; ALCOHOL-CONSUMPTION; PROSPECTIVE COHORT; CIGARETTE-SMOKING; DIETARY PATTERNS; DIOXIN EXPOSURE C1 [White, Sally S.] NIEHS, NTP Labs Branch, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Fenton, Suzanne E.] NIEHS, NTP Labs Branch, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP White, SS (reprint author), NIEHS, NTP Labs Branch, Div Natl Toxicol Program, NIH, 111 TW Alexander Dr,Bldg 101,MD E1-08, Res Triangle Pk, NC 27709 USA. EM fentonse@niehs.nih.gov NR 105 TC 0 Z9 0 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND BN 978-1-84973-466-0; 978-1-84973-418-9 J9 ISSUES TOXICOL PY 2013 VL 16 BP 293 EP 330 DI 10.1039/9781849734660-00293 D2 10.1039/9781849734660 PG 38 WC Chemistry, Multidisciplinary; Toxicology SC Chemistry; Toxicology GA BHW88 UT WOS:000326880400013 ER PT S AU Hill, VK Gartner, JJ Samuels, Y Goldstein, AM AF Hill, Victoria K. Gartner, Jared J. Samuels, Yardena Goldstein, Alisa M. BE Chakravarti, A Green, E TI The Genetics of Melanoma: Recent Advances SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 14 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE germline susceptibility; somatic mutations; driver mutations; high risk; low risk ID GENOME-WIDE ASSOCIATION; CUTANEOUS MALIGNANT-MELANOMA; FREQUENT SOMATIC MUTATIONS; POPULATION-BASED SAMPLE; BASAL-CELL CARCINOMA; N-RAS MUTATIONS; UVEAL MELANOMA; MC1R VARIANTS; METASTATIC MELANOMA; BRAF MUTATIONS AB Cutaneous malignant melanoma results from the interplay of genetic, host, and environmental factors. Genetic factors implicated in melanoma etiology include inherited high-, intermediate-, and low-risk susceptibility genes as well as numerous somatic mutations in melanoma tumors. CDKN2A is the major high-risk melanoma susceptibility gene identified to date. Recent identification of low-risk loci has been accomplished predominantly through genome-wide association studies. Whole-exome and whole-genome studies have identified numerous genes somatically altered in melanoma tumors and highlighted a higher mutation load in melanoma tumors compared with those in other cancers. This higher load is believed to be attributable to the preponderance of cytosine-to-thymine nucleotide substitutions as a result of UV radiation exposure. Technological advances, particularly next-generation sequencing, have increased the opportunities for germline and somatic gene discovery in melanoma and are opening up new avenues for understanding melanoma pathogenesis as well as leading to new opportunities for treatment. C1 [Hill, Victoria K.; Gartner, Jared J.; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. [Goldstein, Alisa M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Hill, VK (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM yardena.samuels@weizmann.ac.il; goldstea@mail.nih.gov FU Intramural NIH HHS NR 148 TC 37 Z9 37 U1 3 U2 14 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3714-8 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2013 VL 14 BP 257 EP 279 DI 10.1146/annurev-genom-091212-153429 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA BHU05 UT WOS:000326658500012 PM 23875803 ER PT S AU Panagiotou, OA Willer, CJ Hirschhorn, JN Ioannidis, JPA AF Panagiotou, Orestis A. Willer, Cristen J. Hirschhorn, Joel N. Ioannidis, John P. A. BE Chakravarti, A Green, E TI The Power of Meta-Analysis in Genome-Wide Association Studies SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 14 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE variance explained; gene discovery; sample size; common variants; rare variants; missing heritability; consortium ID NON-SYNONYMOUS VARIANTS; COMMON VARIANTS; GENETIC-VARIATION; BLOOD-PRESSURE; COMPLEX TRAITS; HUMAN HEIGHT; MISSING HERITABILITY; BIOLOGICAL PATHWAYS; PARKINSON-DISEASE; CROHNS-DISEASE AB Meta-analysis of multiple genome-wide association (GWA) studies has become common practice over the past few years. The main advantage of this technique is the maximization of power to detect subtle genetic effects for common traits. Moreover, one can use meta-analysis to probe and identify heterogeneity in the effect sizes across the combined studies. In this review, we systematically appraise and evaluate the characteristics of GWA meta-analyses with 10,000 or more subjects published up to June 2012. We provide an overview of the current landscape of variants discovered by GWA meta-analyses, and we discuss and assess with extrapolations from empirical data the value of larger meta-analyses for the discovery of additional genetic associations and new biology in the future. Finally, we discuss some emerging logistical and practical issues related to the conduct of meta-analysis of GWA studies. C1 [Panagiotou, Orestis A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. [Willer, Cristen J.] Univ Michigan, Sch Med, Dept Internal Med, Dept Human Genet, Ann Arbor, MI 48109 USA. [Willer, Cristen J.] Univ Michigan, Sch Med, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Boston, MA 02115 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Hlth Res & Policy, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Panagiotou, OA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM orestis.panagiotou@nih.gov; cristen@umich.edu; joelh@broadinstitute.org; jioannid@stanford.edu RI Panagiotou, Orestis/I-5934-2015; OI Panagiotou, Orestis/0000-0001-9604-8380; Willer, Cristen/0000-0001-5645-4966 FU NHLBI NIH HHS [R00 HL094535]; NIDDK NIH HHS [R01 DK075787, R01DK07587] NR 102 TC 33 Z9 34 U1 1 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3714-8 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2013 VL 14 BP 441 EP 465 DI 10.1146/annurev-genom-091212-153520 PG 25 WC Genetics & Heredity SC Genetics & Heredity GA BHU05 UT WOS:000326658500020 PM 23724904 ER PT S AU You, D Simpson, M Antani, S Demner-Fushman, D Thoma, GR AF You, Daekeun Simpson, Matthew Antani, Sameer Demner-Fushman, Dina Thoma, George R. BE Zanibbi, R Couasnon, B TI Annotating Image ROIs with Text Descriptions for Multimodal Biomedical Document Retrieval SO DOCUMENT RECOGNITION AND RETRIEVAL XX SE Proceedings of SPIE LA English DT Proceedings Paper CT 20th Conference on Document Recognition and Retrieval (DRR) held as part of the IS and T/SPIE Symposium on Electronic Imaging CY FEB 05-07, 2013 CL San Francisco, CA SP Soc Imaging Sci & Technol, SPIE, Qualcomm Inc, Google Inc DE Biomedical image analysis; biomedical article retrieval; content-based image retrieval; image overlay recognition; figure caption analysis ID THIN-SECTION CT AB Regions of interest (ROIs) that are pointed to by overlaid markers (arrows, asterisks, etc.) in biomedical images are expected to contain more important and relevant information than other regions for biomedical article indexing and retrieval. We have developed several algorithms that localize and extract the ROIs by recognizing markers on images. Cropped ROIs then need to be annotated with contents describing them best. In most cases accurate textual descriptions of the ROIs can be found from figure captions, and these need to be combined with image ROIs for annotation. The annotated ROIs can then be used to, for example, train classifiers that separate ROIs into known categories (medical concepts), or to build visual ontologies, for indexing and retrieval of biomedical articles. We propose an algorithm that pairs visual and textual ROIs that are extracted from images and figure captions, respectively. This algorithm based on dynamic time warping (DTW) clusters recognized pointers into groups, each of which contains pointers with identical visual properties (shape, size, color, etc.). Then a rule-based matching algorithm finds the best matching group for each textual ROI mention. Our method yields a precision and recall of 96% and 79%, respectively, when ground truth textual ROI data is used. C1 [You, Daekeun; Simpson, Matthew; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20894 USA. RP You, D (reprint author), NIH, Natl Lib Med, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9431-3 J9 PROC SPIE PY 2013 VL 8658 AR 86580D DI 10.1117/12.2005937 PG 11 WC Optics; Imaging Science & Photographic Technology SC Optics; Imaging Science & Photographic Technology GA BHV52 UT WOS:000326744400012 ER PT S AU You, D Simpson, M Antani, S Demner-Fushman, D Thoma, GR AF You, Dakeun Simpson, Matthew Antani, Sameer Demner-Fushman, Dina Thoma, George R. BE Zanibbi, R Couasnon, B TI A Robust Pointer Segmentation in Biomedical Images Toward Building a Visual Ontology for Biomedical Article Retrieval SO DOCUMENT RECOGNITION AND RETRIEVAL XX SE Proceedings of SPIE LA English DT Proceedings Paper CT 20th Conference on Document Recognition and Retrieval (DRR) held as part of the IS and T/SPIE Symposium on Electronic Imaging CY FEB 05-07, 2013 CL San Francisco, CA SP Soc Imaging Sci & Technol, SPIE, Qualcomm Inc, Google Inc DE Biomedical image analysis; biomedical article retrieval; content-based image retrieval; image overlay segmentation; image binarization AB Pointers (arrows and symbols) are frequently used in biomedical images to highlight specific image regions of interest (ROIs) that are mentioned in figure captions and/or text discussion. Detection of pointers is the first step toward extracting relevant visual features from ROIs and combining them with textual descriptions for a multimodal (text and image) biomedical article retrieval system. Recently we developed a pointer recognition algorithm based on an edge-based pointer segmentation method, and subsequently reported improvements made on our initial approach involving the use of Active Shape Models (ASM) for pointer recognition and region growing-based method for pointer segmentation. These methods contributed to improving the recall of pointer recognition but not much to the precision. The method discussed in this article is our recent effort to improve the precision rate. Evaluation performed on two datasets and compared with other pointer segmentation methods show significantly improved precision and the highest F-1 score. C1 [You, Dakeun; Simpson, Matthew; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20894 USA. RP You, D (reprint author), NIH, Natl Lib Med, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 9 TC 2 Z9 2 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9431-3 J9 PROC SPIE PY 2013 VL 8658 AR 86580Q DI 10.1117/12.2005934 PG 9 WC Optics; Imaging Science & Photographic Technology SC Optics; Imaging Science & Photographic Technology GA BHV52 UT WOS:000326744400025 ER PT S AU Zhang, XL Zou, J Le, DX Thoma, GR AF Zhang, Xiaoli Zou, Jie Le, Daniel X. Thoma, George R. BE Zanibbi, R Couasnon, B TI Combining discriminative SVM models for the improved recognition of investigator names in medical articles SO DOCUMENT RECOGNITION AND RETRIEVAL XX SE Proceedings of SPIE LA English DT Proceedings Paper CT 20th Conference on Document Recognition and Retrieval (DRR) held as part of the IS and T/SPIE Symposium on Electronic Imaging CY FEB 05-07, 2013 CL San Francisco, CA SP Soc Imaging Sci & Technol, SPIE, Qualcomm Inc, Google Inc DE Investigator Names; Support Vector Machine (SVM); Structural SVM AB Investigators are people who are listed as members of corporate organizations but not entered as authors in an article. Beginning with journals published in 2008, investigator names are required to be included in a new bibliographic field in MEDLINE citations. Automatic extraction of investigator names is necessary due to the increase in collaborative biomedical research and consequently the large number of such names. We implemented two discriminative SVM models, i.e., SVM and structural SVM, to identify named entities such as the first and last names of investigators from online medical journal articles. Both approaches achieve good performance at the word and name chunk levels. We further conducted an error analysis and found that SVM and structural SVM can offer complementary information about the patterns to be classified. Hence, we combined the two independently trained classifiers where the SVM is chosen as a base learner with its outputs enhanced by the predictions from the structural SVM. The overall performance especially the recall rate of investigator name retrieval exceeds that of the standalone SVM model. C1 [Zhang, Xiaoli; Zou, Jie; Le, Daniel X.; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Zhang, XL (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM zhangxiaol@mail.nih.gov NR 34 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9431-3 J9 PROC SPIE PY 2013 VL 8658 AR 865815 DI 10.1117/12.2007336 PG 11 WC Optics; Imaging Science & Photographic Technology SC Optics; Imaging Science & Photographic Technology GA BHV52 UT WOS:000326744400040 ER PT J AU DuMouchel, W Ryan, PB Schuemie, MJ Madigan, D AF DuMouchel, William Ryan, Patrick B. Schuemie, Martijn J. Madigan, David TI Evaluation of Disproportionality Safety Signaling Applied to Healthcare Databases SO DRUG SAFETY LA English DT Article ID EVENT REPORTING SYSTEM; PHARMACOVIGILANCE; PERFORMANCE; GENERATION; ALGORITHMS; RATIOS; DRUGS AB Objective To evaluate the performance of a disproportionality design, commonly used for analysis of spontaneous reports data such as the FDA Adverse Event Reporting System database, as a potential analytical method for an adverse drug reaction risk identification system using healthcare data. Research Design We tested the disproportionality design in 5 real observational healthcare databases and 6 simulated datasets, retrospectively studying the predictive accuracy of the method when applied to a collection of 165 positive controls and 234 negative controls across 4 outcomes: acute liver injury, acute myocardial infarction, acute kidney injury, and upper gastrointestinal bleeding. Measures We estimate how well the method can be expected to identify true effects and discriminate from false findings and explore the statistical properties of the estimates the design generates. The primary measure was the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results For each combination of 4 outcomes and 5 databases, 48 versions of disproportionality analysis (DPA) were carried out and the AUC computed. The majority of the AUC values were in the range of 0.35 < AUC <0.6, which is considered to be poor predictive accuracy, since the value AUC = 0.5 would be expected from mere random assignment. Several DPA versions achieved AUC of about 0.7 for the outcome Acute Renal Failure within the GE database. The overall highest DPA version across all 20 outcome-database combinations was the Bayesian Information Component method with no stratification by age and gender, using first occurrence of outcome and with assumed time-at-risk equal to duration of exposure + 30d, but none were uniformly optimal. The relative risk estimates for the negative control drugevent combinations were very often biased either upward or downward by a factor of 2 or more. Coverage probabilities of confidence intervals from all methods were far below nominal. Conclusions The disproportionality methods that we evaluated did not discriminate true positives from true negatives using healthcare data as they seem to do using spontaneous report data. C1 [DuMouchel, William] Oracle Hlth Sci, Burlington, MA USA. [DuMouchel, William] Oracle Hlth Sci Global Business Unit, Tucson, AZ 85718 USA. [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [DuMouchel, William; Ryan, Patrick B.; Schuemie, Martijn J.; Madigan, David] Fdn Natl Inst Hlth, Bethesda, MD USA. RP DuMouchel, W (reprint author), Oracle Hlth Sci Global Business Unit, 7164 N Mercer Spring Pl, Tucson, AZ 85718 USA. EM bill.dumouchel@oracle.com FU Foundation for the National Institutes of Health (FNIH); Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration; FNIH; Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Dr. DuMouchel is an employee of Oracle Health Sciences. Drs. Ryan and Schuemie are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Drs. Schuemie and Madigan have received grants from FNIH.; This article was published in a supplement sponsored by the Foundation for the National Institutesof Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed byOlaf H. Klungel who received a small honorarium to cover out-ofpocket expenses. S.J.W.E hasreceived travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECTproject.from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under GrantAgreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kindcontribution. NR 23 TC 4 Z9 4 U1 3 U2 8 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S123 EP S132 DI 10.1007/s40264-013-0106-y PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900012 PM 24166229 ER PT J AU Hartzema, AG Reich, CG Ryan, PB Stang, PE Madigan, D Welebob, E Overhage, JM AF Hartzema, Abraham G. Reich, Christian G. Ryan, Patrick B. Stang, Paul E. Madigan, David Welebob, Emily Overhage, J. Marc TI Managing Data Quality for a Drug Safety Surveillance System SO DRUG SAFETY LA English DT Article ID HEALTH-CARE DATABASES; ACUTE-RENAL-FAILURE; COMMON DATA MODEL; MYOCARDIAL-INFARCTION; ADMINISTRATIVE DATA; ICD-9-CM CODES; CLAIMS DATA; VALIDATION; VALIDITY; PHARMACOEPIDEMIOLOGY AB Objective The objective of this study is to present a data quality assurance program for disparate data sources loaded into a Common Data Model, highlight data quality issues identified and resolutions implemented. Background The Observational Medical Outcomes Partnership is conducting methodological research to develop a system to monitor drug safety. Standard processes and tools are needed to ensure continuous data quality across a network of disparate databases, and to ensure that procedures used to extract-transform-load (ETL) processes maintain data integrity. Currently, there is no consensus or standard approach to evaluate the quality of the source data, or ETL procedures. Methods We propose a framework for a comprehensive process to ensure data quality throughout the steps used to process and analyze the data. The approach used to manage data anomalies includes: (1) characterization of data sources; (2) detection of data anomalies; (3) determining the cause of data anomalies; and (4) remediation. Findings Data anomalies included incomplete raw dataset: no race or year of birth recorded. Implausible data: year of birth exceeding current year, observation period end date precedes start date, suspicious data frequencies and proportions outside normal range. Examples of errors found in the ETL process were zip codes incorrectly loaded, drug quantities rounded, drug exposure length incorrectly calculated, and condition length incorrectly programmed. Conclusions Complete and reliable observational data are difficult to obtain, data quality assurance processes need to be continuous as data is regularly updated; consequently, processes to assess data quality should be ongoing and transparent. C1 [Hartzema, Abraham G.] Univ Florida, Coll Pharm, Gainesville, FL 32610 USA. [Reich, Christian G.] AstraZeneca, Waltham, MA USA. [Ryan, Patrick B.; Stang, Paul E.] Janssen Res & Dev LLC, Titusville, NJ USA. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [Overhage, J. Marc] Siemens Hlth Serv, Malvern, PA USA. [Hartzema, Abraham G.; Reich, Christian G.; Ryan, Patrick B.; Stang, Paul E.; Madigan, David; Welebob, Emily; Overhage, J. Marc] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Hartzema, AG (reprint author), Univ Florida, Coll Pharm, Gainesville, FL 32610 USA. EM Hartzema@ufl.edu OI Overhage, Joseph/0000-0003-0223-0195 FU Foundation for the National Institutes of Health (FNIH); Abbott, Amgen Inc.; AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc.; Merck Co. FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Talceda. Drs. Schuemie, Stang, and Ryan are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Dr. Reich is an employee of AstraZeneca. Drs. Schuemie, Madigan and Hartzema have received funding previously from FNIH. J. Marc Overhage and Emily Welebob have no conflicts of interest to declare.; The authors thank and acknowledge the contributions of the OMOP Distributed Research Partners in phases of this research, who were supported by a grant from FNIH. Assistance with writing and manuscript preparation was provided by Ken Scholz, PhD, with financial support from FNIH.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMIPROTECT project from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 47 TC 6 Z9 6 U1 0 U2 1 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S49 EP S58 DI 10.1007/s40264-013-0098-7 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900006 PM 24166223 ER PT J AU Madigan, D Schuemie, MJ Ryan, PB AF Madigan, David Schuemie, Martijn J. Ryan, Patrick B. TI Empirical Performance of the Case-Control Method: Lessons for Developing a Risk Identification and Analysis System SO DRUG SAFETY LA English DT Article ID SAFETY AB Background Considerable attention now focuses on the use of large-scale observational healthcare data for understanding drug safety. In this context, analysts utilize a variety of statistical and epidemiological approaches such as case control, cohort, and self-controlled methods. The operating characteristics of these methods are poorly understood. Objective Establish the operating characteristics of the case control method for large scale observational analysis in drug safety. Research Design We empirically evaluated the case control approach in 5 real observational healthcare databases and 6 simulated datasets. We retrospectively studied the predictive accuracy of the method when applied to a collection of 165 positive controls and 234 negative controls across 4 outcomes: acute liver injury, acute myocardial infarction, acute kidney injury, and upper gastrointestinal bleeding. Results In our experiment, the case control method provided weak discrimination between positive and negative controls. Furthermore, the method yielded positively biased estimates and confidence intervals that had poor coverage properties. Conclusions For the four outcomes we examined, the case control method may not be the method of choice for estimating potentially harmful effects of drugs. C1 [Madigan, David] Columbia Univ, Dept Stat, New York, NY 10027 USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ USA. [Madigan, David; Schuemie, Martijn J.; Ryan, Patrick B.] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Madigan, D (reprint author), Columbia Univ, Dept Stat, 1255 Amsterdam Ave, New York, NY 10027 USA. EM david.madigan@columbia.edu FU Foundation for the National Institutes of Health (FNIH); Office of Medical Policy; Center for Drug Evaluation and Research; Food and Drug Administration; Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Drs. Ryan and Schuemie are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Drs. Schuemie and Madigan have both received a grant previously from FNIH.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project from the Innovative Medicines Initiative Joint Undertaking (www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 13 TC 11 Z9 11 U1 1 U2 8 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S73 EP S82 DI 10.1007/s40264-013-0105-z PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900008 PM 24166225 ER PT J AU Noren, GN Bergvall, T Ryan, PB Juhlin, K Schuemie, MJ Madigan, D AF Noren, G. Niklas Bergvall, Tomas Ryan, Patrick B. Juhlin, Kristina Schuemie, Martijn J. Madigan, David TI Empirical Performance of the Calibrated Self-Controlled Cohort Analysis Within Temporal Pattern Discovery: Lessons for Developing a Risk Identification and Analysis System SO DRUG SAFETY LA English DT Article ID ADVERSE DRUG-REACTIONS; LONGITUDINAL DATABASES; SAFETY SURVEILLANCE; PHARMACOVIGILANCE; DESIGN AB Background Observational healthcare data offer the potential to identify adverse drug reactions that may be missed by spontaneous reporting. The self-controlled cohort analysis within the Temporal Pattern Discovery framework compares the observed-to-expected ratio of medical outcomes during post-exposure surveillance periods with those during a set of distinct pre-exposure control periods in the same patients. It utilizes an external control group to account for systematic differences between the different time periods, thus combining within- and between-patient confounder adjustment in a single measure. Objectives To evaluate the performance of the calibrated self-controlled cohort analysis within Temporal Pattern Discovery as a tool for risk identification in observational healthcare data. Research Design Different implementations of the calibrated self-controlled cohort analysis were applied to 399 drug-outcome pairs (165 positive and 234 negative test cases across 4 health outcomes of interest) in 5 real observational databases (four with administrative claims and one with electronic health records). Measures Performance was evaluated on real data through sensitivity/specificity, the area under receiver operator characteristics curve (AUC), and bias. Results The calibrated self-controlled cohort analysis achieved good predictive accuracy across the outcomes and databases under study. The optimal design based on this reference set uses a 360 days surveillance period and a single control period 180 days prior to new prescriptions. It achieved an average AUC of 0.75 and AUC >0.70 in all but one scenario. A design with three separate control periods performed better for the electronic health records database and for acute renal failure across all data sets. The estimates for negative test cases were generally unbiased, but a minor negative bias of up to 0.2 on the RR-scale was observed with the configurations using multiple control periods, for acute liver injury and upper gastrointestinal bleeding. Conclusions The calibrated self-controlled cohort analysis within Temporal Pattern Discovery shows promise as a tool for risk identification; it performs well at discriminating positive from negative test cases. The optimal parameter configuration may vary with the data set and medical outcome of interest. C1 [Noren, G. Niklas; Bergvall, Tomas; Juhlin, Kristina] WHO Collaborating Ctr Int Drug Monitoring, Uppsala Monitoring Ctr, Uppsala, Sweden. [Noren, G. Niklas] Stockholm Univ, Dept Math, S-10691 Stockholm, Sweden. [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [Ryan, Patrick B.; Schuemie, Martijn J.; Madigan, David] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Noren, GN (reprint author), WHO Collaborating Ctr Int Drug Monitoring, Uppsala Monitoring Ctr, Uppsala, Sweden. EM niklas.noren@who-umc.org FU Foundation for the National Institutes of Health (FNIH); Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration; FNIH [NOREN11OMOP]; Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Dr. Ryan is an employee of Janssen Research and Development, and a past employee of GlaxoSmithKline, but does not receive compensation for his work with OMOP. Dr. Schuemie has become an employee of Janssen Research and Development since completing the work described here. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Drs. Schuemie and Madigan receive funding from FNIH. Dr. Noren, Mr. Bergvall and Ms. Juhlin were partially funded by FNIH grant NOREN11OMOP. The authors appreciate the thoughtful feedback from I. Ralph Edwards at the Uppsala Monitoring Centre, the OMOP Research Investigators, Executive Board, and Advisory Boards. No compensation was given for the reviews.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 23 TC 7 Z9 7 U1 1 U2 9 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S107 EP S121 DI 10.1007/s40264-013-0095-x PG 15 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900011 PM 24166228 ER PT J AU Overhage, JM Ryan, PB Schuemie, MJ Stang, PE AF Overhage, J. Marc Ryan, Patrick B. Schuemie, Martijn J. Stang, Paul E. TI Desideratum for Evidence Based Epidemiology SO DRUG SAFETY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIALS; CORONARY-HEART-DISEASE; POSTMENOPAUSAL ESTROGEN; CARDIOVASCULAR-DISEASE; ORAL BISPHOSPHONATES; EXTERNAL VALIDITY; RISK; METAANALYSIS; FRACTURES; PROGESTIN AB Background There is great variation in choices of method and specific analytical details in epidemiological studies, resulting in widely varying results even when studying the same drug and outcome in the same database. Not only does this variation undermine the credibility of the research but it limits our ability to improve the methods. Methods In order to evaluate the performance of methods and analysis choices we used standard references and a literature review to identify 164 positive controls (drug outcome pairs believed to represent true adverse drug reactions), and 234 negative controls (drug outcome pairs for which we have confidence there is no direct causal relationship). We tested 3,748 unique analyses (methods in combination with specific analysis choices) that represent the full range of approaches to adjusting for confounding in five large observational datasets on these controls. We also evaluated the impact of increasingly specific outcome definitions, and performed a replication study in six additional datasets. We characterized the performance of each method using the area under the receiver operator curve (AUC), bias, and coverage probability. In addition, we developed simulated datasets that closely matched the characteristics of the observational datasets into which we inserted data consistent with known drug outcome relationships in order to measure the accuracy of estimates generated by the analyses. Discussion We expect the results of this systematic, empirical evaluation of the performance of these analyses across a moderate range of outcomes and databases to provide important insights into the methods used in epidemiological studies and to increase the consistency with which methods are applied, thereby increasing the confidence in results and our ability to systematically improve our approaches. C1 [Overhage, J. Marc] Siemens Hlth Serv, Malvern, PA USA. [Overhage, J. Marc] Siemens Med Solut USA Inc, Malvern, PA 19355 USA. [Ryan, Patrick B.; Stang, Paul E.] Janssen Res & Dev LLC, Titusville, NJ USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Overhage, J. Marc; Ryan, Patrick B.; Schuemie, Martijn J.; Stang, Paul E.] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Overhage, JM (reprint author), Siemens Med Solut USA Inc, 51 Valley Stream Pkwy,MC B9K, Malvern, PA 19355 USA. EM marc.overhage@siemens.com OI Overhage, Joseph/0000-0003-0223-0195 NR 58 TC 14 Z9 14 U1 1 U2 5 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S5 EP S14 DI 10.1007/s40264-013-0102-2 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900002 PM 24166219 ER PT J AU Reich, CG Ryan, PB Schuemie, MJ AF Reich, Christian G. Ryan, Patrick B. Schuemie, Martijn J. TI Alternative Outcome Definitions and Their Effect on the Performance of Methods for Observational Outcome Studies SO DRUG SAFETY LA English DT Article ID ACUTE KIDNEY INJURY; RELATIVE RISK; MISCLASSIFICATION; BIAS AB Background A systematic risk identification system has the potential to test marketed drugs for important Health Outcomes of Interest or HOI. For each HOT, multiple definitions are used in the literature, and some of them are validated for certain databases. However, little is known about the effect of different definitions on the ability of methods to estimate their association with medical products. Objectives Alternative definitions of HOI were studied for their effect on the performance of analytical methods in observational outcome studies. Methods A set of alternative definitions for three HOT were defined based on literature review and clinical diagnosis guidelines: acute kidney injury, acute liver injury and acute myocardial infarction. The definitions varied by the choice of diagnostic codes and the inclusion of procedure codes and lab values. They were then used to empirically study an array of analytical methods with various analytical choices in four observational healthcare databases. The methods were executed against predefined drug-HOT pairs to generate an effect estimate and standard error for each pair. These test cases included positive controls (active ingredients with evidence to suspect a positive association with the outcome) and negative controls (active ingredients with no evidence to expect an effect on the outcome). Three different performance metrics where used: (i) Area Under the Receiver Operator Characteristics (ROC) curve (AUC) as a measure of a method's ability to distinguish between positive and negative test cases, (ii) Measure of bias by estimation of distribution of observed effect estimates for the negative test pairs where the true effect can be assumed to be one (no relative risk), and (iii) Minimal Detectable Relative Risk (MDRR) as a measure of whether there is sufficient power to generate effect estimates. Results In the three outcomes studied, different definitions of outcomes show comparable ability to differentiate true from false control cases (AUC) and a similar bias estimation. However, broader definitions generating larger outcome cohorts allowed more drugs to be studied with sufficient statistical power. Conclusions Broader definitions are preferred since they allow studying drugs with lower prevalence than the more precise or narrow definitions while showing comparable performance characteristics in differentiation of signal vs. no signal as well as effect size estimation. C1 [Reich, Christian G.] AstraZeneca PLC, Waltham, MA 02451 USA. [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Reich, Christian G.; Ryan, Patrick B.; Schuemie, Martijn J.] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Reich, CG (reprint author), AstraZeneca PLC, 35 Gatehouse Dr, Waltham, MA 02451 USA. EM reich@omop.org FU Foundation for the National Institutes of Health (FNIH); Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration; Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Merck & Co., Novartis Pharmaceuticals Corporation, Pfizer, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-Aventis, Schering-Plough Corporation, and Takeda. Dr. Reich is an employee of AstraZeneca. Drs. Ryan and Schuemie are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Dr. Schuemie has previously received a grant from FNIH.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-ofpocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project from the Innovative Medicines Initiative Joint Undertaking (http:ftww.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 17 TC 12 Z9 12 U1 0 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S181 EP S193 DI 10.1007/s40264-013-0111-1 PG 13 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900017 PM 24166234 ER PT J AU Reich, CG Ryan, PB Suchard, MA AF Reich, Christian G. Ryan, Patrick B. Suchard, Marc A. TI The Impact of Drug and Outcome Prevalence on the Feasibility and Performance of Analytical Methods for a Risk Identification and Analysis System SO DRUG SAFETY LA English DT Article ID SAMPLE-SIZE; TRIALS; POWER AB Background A systematic risk identification system has the potential to study all marketed drugs. However, the rates of drug exposure and outcome occurrences in observational databases, the database size and the desired risk detection threshold determine the power and therefore limit the feasibility of the application of appropriate analytical methods. Drugs vary dramatically for these parameters because of their prevalence of indication, cost, time on the market, payer formularies, market pressures and clinical guidelines. Objectives Evaluate (i) the feasibility of a risk identification system based on commercially available observational databases, (ii) the range of drugs that can be studied for certain outcomes, (iii) the influence of underpowered drug-outcome pairs on the performance of analytical methods estimating the strength of their association and (iv) the time required from the introduction of a new drug to accumulate sufficient data for signal detection. Methods As part of the Observational Medical Outcomes Partnership experiment, we used data from commercially available observational databases and calculated the minimal detectable relative risk of all pairs of marketed drugs and eight health outcomes of interest. We then studied an array of analytical methods for their ability to distinguish between pre-determined positive and negative drug-outcome test pairs. The positive controls contained active ingredients with evidence of a positive association with the outcome, and the negative controls had no such evidence. As a performance measure we used the area under the receiver operator characteristics curve (AUC). We compared the AUC of methods using all test pairs or only pairs sufficiently powered for detection of a relative risk of 1.25. Finally, we studied all drugs introduced to the market in 2003-2008 and determined the time required to achieve the same minimal detectable relative risk threshold. Results The performance of methods improved after restricting them to fully powered drug-outcome pairs. The availability of drug-outcome pairs with sufficient power to detect a relative risk of 1.25 varies enormously among outcomes. Depending on the market uptake, drugs can generate relevant signals in the first month after approval, or never reach sufficient power. Conclusion The incidence of drugs and important outcomes determines sample size and method performance in estimating drug-outcome associations. Careful consideration is therefore necessary to choose databases and outcome definitions, particularly for newly introduced drugs. C1 [Reich, Christian G.] AstraZeneca PLC, Waltham, MA 02451 USA. [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, UCLA Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. [Reich, Christian G.; Ryan, Patrick B.; Suchard, Marc A.] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Reich, CG (reprint author), AstraZeneca PLC, 35 Gatehouse Dr, Waltham, MA 02451 USA. EM reich@omop.org FU Foundation for the National Institutes of Health (FNIH); FNIH; Innovative Medicines Initiative Joint Undertaking [115004] FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, Glaxo-SmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Novartis Pharmaceuticals, Pfizer, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, SanofiAventis, Schering-Plough, and Takeda. Dr. Reich is an employee of AstraZeneca. Dr. Ryan is an employee of Janssen Research and Development. Dr. Suchard received a grant previously from the FNIH.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the PNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project.from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 17 TC 4 Z9 4 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S195 EP S204 DI 10.1007/s40264-013-0112-0 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900018 PM 24166235 ER PT J AU Ryan, PB Schuemie, MJ AF Ryan, Patrick B. Schuemie, Martijn J. TI Evaluating Performance of Risk Identification Methods Through a Large-Scale Simulation of Observational Data SO DRUG SAFETY LA English DT Article ID BIAS AB Background There has been only limited evaluation of statistical methods for identifying safety risks of drug exposure in observational healthcare data. Simulations can support empirical evaluation, but have not been shown to adequately model the real-world phenomena that challenge observational analyses. Objectives To design and evaluate a probabilistic framework (OSIM2) for generating simulated observational healthcare data, and to use this data for evaluating the performance of methods in identifying associations between drug exposure and health outcomes of interest. Research Design Seven observational designs, including case control, cohort, self-controlled case series, and self-controlled cohort design were applied to 399 drug-outcome scenarios in 6 simulated datasets with no effect and injected relative risks of 1.25, 1.5, 2, 4, and 10, respectively. Subjects Longitudinal data for 10 million simulated patients were generated using a model derived from an administrative claims database, with associated demographics, periods of drug exposure derived from pharmacy dispensings, and medical conditions derived from diagnoses on medical claims. Measures Simulation validation was performed through descriptive comparison with real source data. Method performance was evaluated using Area Under ROC Curve (AUC), bias, and mean squared error. Results OSIM2 replicates prevalence and types of confounding observed in real claims data. When simulated data are injected with relative risks (RR) >= 2, all designs have good predictive accuracy (AUC > 0.90), but when RR < 2, no methods achieve 100 % predictions. Each method exhibits a different bias profile, which changes with the effect size. Conclusions OSIM2 can support methodological research. Results from simulation suggest method operating characteristics are far from nominal properties. C1 [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ 08560 USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Ryan, Patrick B.; Schuemie, Martijn J.] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Ryan, PB (reprint author), Janssen Res & Dev LLC, 1125 Trenton Harbourton Rd,Room K30205,POB 200, Titusville, NJ 08560 USA. EM ryan@omop.org FU Foundation for the National Institutes of Health (FNIH); Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration; UBC/ProSanos; FNIH; Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Drs. Ryan and Schuemie are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. This work was supported by UBC/ProSanos for implementing OSIM2 through funding by FNIH. The authors thank Susan Gruber for the OSIM2 assessment she shared with the OMOP Statistics working group.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement Was guest edited by Stephen J.W. Evans. Tt was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 17 TC 10 Z9 10 U1 1 U2 9 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S171 EP S180 DI 10.1007/s40264-013-0110-2 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900016 PM 24166233 ER PT J AU Ryan, PB Stang, PE Overhage, JM Suchard, MA Hartzema, AG DuMouchel, W Reich, CG Schuemie, MJ Madigan, D AF Ryan, Patrick B. Stang, Paul E. Overhage, J. Marc Suchard, Marc A. Hartzema, Abraham G. DuMouchel, William Reich, Christian G. Schuemie, Martijn J. Madigan, David TI A Comparison of the Empirical Performance of Methods for a Risk Identification System SO DRUG SAFETY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE DATA; CARDIOVASCULAR EVENTS; CONTROL DESIGNS; CASE-CROSSOVER; SAFETY; INHIBITORS; ROFECOXIB; EXPOSURE AB Background Observational healthcare data offer the potential to enable identification of risks of medical products, and the medical literature is replete with analyses that aim to accomplish this objective. A number of established analytic methods dominate the literature but their operating characteristics in real-world settings remain unknown. Objectives To compare the performance of seven methods (new user cohort, case control, self-controlled case series, self-controlled cohort, disproportionality analysis, temporal pattern discovery, and longitudinal gamma poisson shrinker) as tools for risk identification in observational healthcare data. Research Design The experiment applied each method to 399 drug-outcome scenarios (165 positive controls and 234 negative controls across 4 health outcomes of interest) in 5 real observational databases (4 administrative claims and 1 electronic health record). Measures Method performance was evaluated through Area Under the receiver operator characteristics Curve (AUC), bias, mean square error, and confidence interval coverage probability. Results Multiple methods offer strong predictive accuracy, with AUC > 0.70 achievable for all outcomes and databases with more than one analytical approach. Selfcontrolled methods (self-controlled case series, temporal pattern discovery, self-controlled cohort) had higher predictive accuracy than cohort and case control methods across all databases and outcomes. Methods differed in the expected value and variance of the error distribution. All methods had lower coverage probability than the expected nominal properties. Conclusions Observational healthcare data can inform risk identification of medical product effects on acute liver injury, acute myocardial infarction, acute renal failure and gastrointestinal bleeding. However, effect estimates from all methods require calibration to address inconsistency in method operating characteristics. Further empirical evaluation is required to gauge the generalizability of these findings to other databases and outcomes. C1 [Ryan, Patrick B.; Stang, Paul E.] Janssen Res & Dev LLC, Titusville, NJ 08560 USA. [Overhage, J. Marc] Siemens Hlth Serv, Malvern, PA USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath & Human Genet, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, UCLA Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. [Hartzema, Abraham G.] Univ Florida, Coll Pharm, Gainesville, FL USA. [DuMouchel, William] Oracle Hlth Sci, Burlington, MA USA. [Reich, Christian G.] AstraZeneca, Waltham, MA USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [Ryan, Patrick B.; Stang, Paul E.; Overhage, J. Marc; Suchard, Marc A.; Hartzema, Abraham G.; DuMouchel, William; Reich, Christian G.; Schuemie, Martijn J.; Madigan, David] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Ryan, PB (reprint author), Janssen Res & Dev LLC, 1125 Trenton Harbourton Rd,Room K30205,POB 200, Titusville, NJ 08560 USA. EM ryan@omop.org OI Overhage, Joseph/0000-0003-0223-0195 FU Foundation for the National Institutes of Health (FNIH); Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration; FNIH; Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Drs. Ryan, Stang and Schuemie are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Drs. Schuemie, Suchard, Madigan, and Hartzema have received a grant previously from FNIH. Dr. DuMouchel is an employee of Oracle Health Sciences. Dr. Overhage is an employee of Siemens. Christian Reich is an employee of Astra-Zeneca.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 40 TC 17 Z9 18 U1 0 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S143 EP S158 DI 10.1007/s40264-013-0108-9 PG 16 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900014 PM 24166231 ER PT J AU Ryan, PB Schuemie, MJ Madigan, D AF Ryan, Patrick B. Schuemie, Martijn J. Madigan, David TI Empirical Performance of a Self-Controlled Cohort Method: Lessons for Developing a Risk Identification and Analysis System SO DRUG SAFETY LA English DT Article AB Background Observational healthcare data offer the potential to enable identification of risks of medical products, but appropriate methodology has not yet been defined. The self-controlled cohort method, which compares the post-exposure outcome rate with the pre-exposure rate among an exposed cohort, has been proposed as a potential approach for risk identification but its performance has not been fully assessed. Objectives To evaluate the performance of the self-controlled cohort method as a tool for risk identification in observational healthcare data. Research Design The method was applied to 399 drug-outcome scenarios (165 positive controls and 234 negative controls across 4 health outcomes of interest) in 5 real observational databases (4 administrative claims and 1 electronic health record) and in 6 simulated datasets with no effect and injected relative risks of 1.25, 1.5, 2, 4, and 10, respectively. Measures Method performance was evaluated through area under ROC curve (AUC), bias, and coverage probability. Results The self-controlled cohort design achieved strong predictive accuracy across the outcomes and databases under study, with the top-performing settings exceeding AUC >0.76 in all scenarios. However, the estimates generated were observed to be highly biased with low coverage probability. Conclusions If the objective for a risk identification system is one of discrimination, the self-controlled cohort method shows promise as a potential tool for risk identification. However, if a system is intended to generate effect estimates to quantify the magnitude of potential risks, the self-controlled cohort method may not be suitable, and requires substantial calibration to be properly interpreted under nominal properties. C1 [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ 08560 USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [Ryan, Patrick B.; Schuemie, Martijn J.; Madigan, David] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Ryan, PB (reprint author), Janssen Res & Dev LLC, 1125 Trenton Harbourton Rd,Room K30205,POB 200, Titusville, NJ 08560 USA. EM ryan@omop.org FU Foundation for the National Institutes of Health; Pharmaceutical Research Manufacturers of America (PhRMA); Office of Medical Policy; Center for Drug Evaluation and Research; Food and Drug Administration; Foundation for the National Institutes of Health (FNIH); Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Drs. Ryan and Schuemie are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Drs. Schuemie and Madigan have received funding from FNIH.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMIPROTECT project from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 15 TC 9 Z9 9 U1 1 U2 8 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S95 EP S106 DI 10.1007/s40264-013-0101-3 PG 12 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900010 PM 24166227 ER PT J AU Ryan, PB Schuemie, MJ Gruber, S Zorych, I Madigan, D AF Ryan, Patrick B. Schuemie, Martijn J. Gruber, Susan Zorych, Ivan Madigan, David TI Empirical Performance of a New User Cohort Method: Lessons for Developing a Risk Identification and Analysis System SO DRUG SAFETY LA English DT Article ID MEDICAL PRODUCT-SAFETY; HEALTH-CARE DATA; PROPENSITY SCORE; LOGISTIC-REGRESSION; ACTIVE SURVEILLANCE; MONITORING-SYSTEM; DESIGN; BIAS; ADJUSTMENT; PHARMACOEPIDEMIOLOGY AB Background Observational healthcare data offer the potential to enable identification of risks of medical products, but appropriate methodology has not yet been defined. The new user cohort method, which compares the post-exposure rate among the target drug to a referent comparator group, is the prevailing approach for many pharmacoepidemiology evaluations and has been proposed as a promising approach for risk identification but its performance in this context has not been fully assessed. Objectives To evaluate the performance of the new user cohort method as a tool for risk identification in observational healthcare data. Research Design The method was applied to 399 drug-outcome scenarios (165 positive controls and 234 negative controls across 4 health outcomes of interest) in 5 real observational databases (4 administrative claims and 1 electronic health record) and in 6 simulated datasets with no effect and injected relative risks of 1.25, 1.5, 2, 4, and 10, respectively. Measures Method performance was evaluated through Area Under ROC Curve (AUC), bias, and coverage probability. Results The new user cohort method achieved modest predictive accuracy across the outcomes and databases under study, with the top-performing analysis near AUC >0.70 in most scenarios. The performance of the method was particularly sensitive to the choice of comparator population. For almost all drug-outcome pairs there was a large difference, either positive or negative, between the true effect size and the estimate produced by the method, although this error was near zero on average. Simulation studies showed that in the majority of cases, the true effect estimate was not within the 95 % confidence interval produced by the method. Conclusion The new user cohort method can contribute useful information toward a risk identification system, but should not be considered definitive evidence given the degree of error observed within the effect estimates. Careful consideration of the comparator selection and appropriate calibration of the effect estimates is required in order to properly interpret study findings. C1 [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Gruber, Susan] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [Ryan, Patrick B.; Schuemie, Martijn J.; Zorych, Ivan; Madigan, David] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Ryan, PB (reprint author), 1125 Trenton Harbourton Rd,Room K30205,POB 200, Titusville, NJ 08560 USA. EM ryan@omop.org FU Foundation for the National Institutes of Health (FNIH); Office of Medical Policy; Center for Drug Evaluation and Research; Food and Drug Administration; FNTH; Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKlin,e, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Drs. Ryan and Schuemie are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Drs. Schuemie and Madigan have previously received funding from FNTH. Susan Gruber and Ivan Zorych have no conflicts of interest to declare.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received honoraria to cover out-ofpocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP712007-2013) and EFPIA companies' in kind contribution. NR 46 TC 13 Z9 13 U1 1 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S59 EP S72 DI 10.1007/s40264-013-0099-6 PG 14 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900007 PM 24166224 ER PT J AU Ryan, PB Schuemie, MJ Welebob, E Duke, J Valentine, S Hartzema, AG AF Ryan, Patrick B. Schuemie, Martijn J. Welebob, Emily Duke, Jon Valentine, Sarah Hartzema, Abraham G. TI Defining a Reference Set to Support Methodological Research in Drug Safety SO DRUG SAFETY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SEROTONIN REUPTAKE INHIBITORS; POPULATION-BASED COHORT; ACUTE-RENAL-FAILURE; ACUTE LIVER-INJURY; UPPER GASTROINTESTINAL COMPLICATIONS; MEDICAL OUTCOMES PARTNERSHIP; MYOCARDIAL-INFARCTION; GENERAL-POPULATION; SIGNAL-DETECTION AB Background Methodological research to evaluate the performance of methods requires a benchmark to serve as a referent comparison. In drug safety, the performance of analyses of spontaneous adverse event reporting databases and observational healthcare data, such as administrative claims and electronic health records, has been limited by the lack of such standards. Objectives To establish a reference set of test cases that contain both positive and negative controls, which can serve the basis for methodological research in evaluating methods performance in identifying drug safety issues. Research Design Systematic literature review and natural language processing of structured product labeling was performed to identify evidence to support the classification of drugs as either positive controls or negative controls for four outcomes: acute liver injury, acute kidney injury, acute myocardial infarction, and upper gastrointestinal bleeding. Results Three-hundred and ninety-nine test cases comprised of 165 positive controls and 234 negative controls were identified across the four outcomes. The majority of positive controls for acute kidney injury and upper gastrointestinal bleeding were supported by randomized clinical trial evidence, while the majority of positive controls for acute liver injury and acute myocardial infarction were only supported based on published case reports. Literature estimates for the positive controls shows substantial variability that limits the ability to establish a reference set with known effect sizes. Conclusions A reference set of test cases can be established to facilitate methodological research in drug safety. Creating a sufficient sample of drug-outcome pairs with binary classification of having no effect (negative controls) or having an increased effect (positive controls) is possible and can enable estimation of predictive accuracy through discrimination. Since the magnitude of the positive effects cannot be reliably obtained and the quality of evidence may vary across outcomes, assumptions are required to use the test cases in real data for purposes of measuring bias, mean squared error, or coverage probability. C1 [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ 08560 USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Duke, Jon] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Duke, Jon] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. [Valentine, Sarah; Hartzema, Abraham G.] Univ Florida, Coll Pharm, Gainesville, FL USA. [Ryan, Patrick B.; Schuemie, Martijn J.; Welebob, Emily; Hartzema, Abraham G.] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Ryan, PB (reprint author), Janssen Res & Dev LLC, 1125 Trenton Harbourton Rd,Room K30205,POB 200, Titusville, NJ 08560 USA. EM ryan@omop.org FU Foundation for the National Institutes of Health (FNIH); Office of Medical Policy; Center for Drug Evaluation and Research; Food and Drug Administration; FNIH; FNM; Innovative Medicines Initiative Joint Undertaking [Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Drs. Ryan and Schuemie are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Drs. Duke, Schuemie and Hartzema have previously received funding from FNIH. Emily Welebob and Sarah Valentine have no conflicts of interest to declare.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-ofpocket expenses. S.J.W.E has received travel funding from the FNM to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project.from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 85 TC 28 Z9 29 U1 0 U2 5 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S33 EP S47 DI 10.1007/s40264-013-0097-8 PG 15 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900005 PM 24166222 ER PT J AU Schuemie, MJ Madigan, D Ryan, PB AF Schuemie, Martijn J. Madigan, David Ryan, Patrick B. TI Empirical Performance of LGPS and LEOPARD: Lessons for Developing a Risk Identification and Analysis System SO DRUG SAFETY LA English DT Article ID SAFETY SIGNAL-DETECTION; DRUG; DATABASES; COHORT AB Background The availability of large-scale observational healthcare data allows for the active monitoring of safety of drugs, but research is needed to determine which statistical methods are best suited for this task. Recently, the Longitudinal Gamma Poisson Shrinker (LGPS) and Longitudinal Evaluation of Observational Profiles of Adverse events Related to Drugs (LEOPARD) methods were developed specifically for this task. LGPS applies Bayesian shrinkage to an estimated incidence rate ratio, and LEOPARD aims to detect and discard associations due to protopathic bias. The operating characteristics of these methods still need to be determined. Objective Establish the operating characteristics of LGPS and LEOPARD for large scale observational analysis in drug safety. Research Design We empirically evaluated LGPS and LEOPARD in five real observational healthcare databases and six simulated datasets. We retrospectively studied the predictive accuracy of the methods when applied to a collection of 165 positive control and 234 negative control drug-outcome pairs across four outcomes: acute liver injury, acute myocardial infarction, acute kidney injury, and upper gastrointestinal bleeding. Results In contrast to earlier findings, we found that LGPS and LEOPARD provide weak discrimination between positive and negative controls, although the use of LEOPARD does lead to higher performance in this respect. Furthermore, the methods produce biased estimates and confidence intervals that have poor coverage properties. Conclusions For the four outcomes we examined, LGPS and LEOPARD may not be the designs of choice for risk identification. C1 [Schuemie, Martijn J.] Erasmus Univ, Med Ctr Rotterdam, Dept Med Informat, NL-3000 CA Rotterdam, Netherlands. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ USA. [Schuemie, Martijn J.; Madigan, David; Ryan, Patrick B.] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Schuemie, MJ (reprint author), Erasmus Univ, Med Ctr Rotterdam, Dept Med Informat, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM m.schuemie@erasmusmc.nl FU Foundation for the National Institutes of Health; Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration; Foundation for the National Institutes of Health (FNIH); Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Drs. Schuemie and Ryan are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration. Dr. Madigan has no conflicts of interest to declare.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project.from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 18 TC 7 Z9 7 U1 2 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S133 EP S142 DI 10.1007/s40264-013-0107-x PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900013 PM 24166230 ER PT J AU Schuemie, MJ Gini, R Coloma, PM Straatman, H Herings, RMC Pedersen, L Innocenti, F Mazzaglia, G Picelli, G van der Lei, J Sturkenboom, MCJM AF Schuemie, Martijn J. Gini, Rosa Coloma, Preciosa M. Straatman, Huub Herings, Ron M. C. Pedersen, Lars Innocenti, Francesco Mazzaglia, Giampiero Picelli, Gino van der Lei, Johan Sturkenboom, Miriam C. J. M. TI Replication of the OMOP Experiment in Europe: Evaluating Methods for Risk Identification in Electronic Health Record Databases SO DRUG SAFETY LA English DT Article ID CARE DATABASES AB Background The Observational Medical Outcomes Partnership (OMOP) has just completed a large scale empirical evaluation of statistical methods and analysis choices for risks identification in longitudinal observational healthcare data. This experiment drew data from four large US health insurance claims databases and one US electronic health record (EHR) database, but it is unclear to what extend the findings of this study apply to other data sources. Objective To replicate the OMOP experiment in six European ERR databases. Research Design Six databases of the EU-ADR (Exploring and Understanding Adverse Drug Reactions) database network participated in this study: Aarhus (Denmark), ARS (Italy), HealthSearch (Italy), IPCI (the Netherlands), Pedianet (Italy), and Pharmo (the Netherlands). All methods in the OMOP experiment were applied to a collection of 165 positive and 234 negative control drug outcome pairs across four outcomes: acute liver injury, acute myocardial infarction, acute kidney injury, and upper gastrointestinal bleeding. Area under the receiver operator characteristics curve (AUC) was computed per database and for a combination of all six databases using metaanalysis for random effects. We provide expected values of estimation error as well, based on negative controls. Results Similarly to the US experiment, high predictive accuracy was found (AUC >0.8) for some analyses. Selfcontrolled designs, such as self-controlled case series, IC temporal pattern discovery and self-controlled cohort achieved higher performance than other methods, both in terms of predictive accuracy and observed bias. Conclusions The major findings of the recent OMOP experiment were also observed in the European databases. C1 [Schuemie, Martijn J.; Gini, Rosa; Coloma, Preciosa M.; Herings, Ron M. C.; van der Lei, Johan; Sturkenboom, Miriam C. J. M.] Erasmus Univ, Med Ctr, Dept Med Informat, NL-3000 CA Rotterdam, Netherlands. [Gini, Rosa; Innocenti, Francesco] Agenzia Reg Sanita Toscana, Florence, Italy. [Straatman, Huub; Herings, Ron M. C.] PHARMO Inst, Utrecht, Netherlands. [Pedersen, Lars] Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark. [Innocenti, Francesco; Mazzaglia, Giampiero] Italian Coll Gen Practitioners, Florence, Italy. [Picelli, Gino] Soc Serv Telemat SRL, Pedianet, Padua, Italy. [Schuemie, Martijn J.] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Schuemie, MJ (reprint author), Erasmus Univ, Med Ctr, Dept Med Informat, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM m.schuemie@erasmusmc.nl FU Foundation for the National Institutes of Health [STUR11OMOP]; Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration; Foundation for the National Institutes of Health (FNIH); Innovative Medicines Initiative Joint Undertaking [115004]; European Union's Seventh Framework Programme FX The authors wish to acknowledge the Observational Medical Outcomes Partnership (OMOP) investigators for their help in running the OMOP methods in the EU-ADR environment. The study was funded by The Foundation for the National Institutes of Health, grant STUR11OMOP. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration, has become an employee of Janssen Research & Development since completing this research, and is an OMOP investigator. OMOP is funded by the Foundation for the National Institutes of Health through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Mr. Straatman and Dr. Herings are employees of the PHARMO Institute for Drug Outcomes Research, which performs financially supported studies for several pharmaceutical companies. All other authors declare to have no conflicts of interests to declare. Dr. Sturkenboom is an employee of the Erasmus University Medical Center, and coordinates studies that are financially supported by several pharmaceutical companies (Novartis, Pfizer, Eli Lilly, Boehringer), none related to this study.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI-PROTECT project.from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 18 TC 12 Z9 12 U1 2 U2 9 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S159 EP S169 DI 10.1007/s40264-013-0109-8 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900015 PM 24166232 ER PT J AU Stang, PE Ryan, PB Overhage, JM Schuemie, MJ Hartzema, AG Welebob, E AF Stang, Paul E. Ryan, Patrick B. Overhage, J. Marc Schuemie, Martijn J. Hartzema, Abraham G. Welebob, Emily TI Variation in Choice of Study Design: Findings from the Epidemiology Design Decision Inventory and Evaluation (EDDIE) Survey SO DRUG SAFETY LA English DT Article ID ORAL BISPHOSPHONATES; RISK; DATABASES; DISEASE; CANCER; DRUGS AB Background Researchers using observational data to understand drug effects must make a number of analytic design choices that suit the characteristics of the data and the subject of the study. Review of the published literature suggests that there is a lack of consistency even when addressing the same research question in the same database. Objective To characterize the degree of similarity or difference in the method and analysis choices made by observational database research experts when presented with research study scenarios. Research Design On-line survey using research scenarios on drug-effect studies to capture method selection and analysis choices that follow a dependency branching based on response to key questions. Subjects Voluntary participants experienced in epidemiological study design solicited for participation through registration on the Observational Medical Outcomes Partnership website, membership in particular professional organizations, or links in relevant newsletters. Measures Description (proportion) of respondents selecting particular methods and making specific analysis choices based on individual drug-outcome scenario pairs. The number of questions/decisions differed based on stem questions of study design, time-at-risk, outcome definition, and comparator. Results There is little consistency across scenarios, by drug or by outcome of interest, in the decisions made for design and analyses in scenarios using large healthcare databases. The most consistent choice was the cohort study design but variability in the other critical decisions was common. C1 [Stang, Paul E.; Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ USA. [Overhage, J. Marc] Siemens Hlth Serv, Malvern, PA USA. [Schuemie, Martijn J.] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands. [Hartzema, Abraham G.] Univ Florida, Coll Pharm, Gainesville, FL USA. [Stang, Paul E.; Ryan, Patrick B.; Overhage, J. Marc; Schuemie, Martijn J.; Welebob, Emily] Fdn Natl Inst Hlth, Bethesda, MD USA. RP Stang, PE (reprint author), 1125 Trenton Harbourton Rd,Room K30205,200, Titusville, NJ 08560 USA. EM pstang@its.jnj.com OI Overhage, Joseph/0000-0003-0223-0195 FU Foundation for the National Institutes of Health (FNIH); IMI PROTECT [115004]; European Union's Seventh Framework Programme; EFPIA FX The Observational Medical Outcomes Partnership is funded by the Foundation for the National Institutes of Health (FNIH) through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Bioden Idec, Bristol-Myers Squibb, Eli Lilly & Company, Glaxo-SmithKline, Janssen Research and Development, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America (PhRMA), Roche, Sanofi-aventis, Schering-Plough Corporation, and Takeda. Drs. Stang, Schuemie and Ryan are employees of Janssen Research and Development. Dr. Schuemie received a fellowship from the Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration and has become an employee of Janssen Research & Development since completing this research.; This article was published in a supplement sponsored by the Foundation for the National Institutes of Health (FNIH). The supplement was guest edited by Stephen J.W. Evans. It was peer reviewed by Olaf H. Klungel who received a small honorarium to cover out-of-pocket expenses. S.J.W.E has received travel funding from the FNIH to travel to the OMOP symposium and received a fee from FNIH for the review of a protocol for OMOP. O.H.K has received funding for the IMI PROTECT project.from the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. NR 20 TC 5 Z9 5 U1 1 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PY 2013 VL 36 SU 1 BP S15 EP S25 DI 10.1007/s40264-013-0103-1 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 249GO UT WOS:000326765900003 PM 24166220 ER PT J AU Mansky, PJ Wallerstedt, DB Sannes, TS Stagl, J Johnson, LL Blackman, MR Grem, JL Swain, SM Monahan, BP AF Mansky, Patrick J. Wallerstedt, Dawn B. Sannes, Timothy S. Stagl, Jamie Johnson, Laura Lee Blackman, Marc R. Grem, Jean L. Swain, Sandra M. Monahan, Brian P. TI NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID VISCUM-ALBUM L.; GALACTOSIDE-SPECIFIC LECTIN; CELL-MEDIATED CYTOTOXICITY; BLOOD MONONUCLEAR-CELLS; NECROSIS FACTOR-ALPHA; IN-VITRO; COMPLEMENTARY TREATMENT; EUROPEAN MISTLETOE; CANCER-PATIENTS; GENE-EXPRESSION AB Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m(2) and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone. C1 [Mansky, Patrick J.] Bellin Hlth, Canc Team, Green Bay, WI 54313 USA. [Mansky, Patrick J.; Johnson, Laura Lee] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Wallerstedt, Dawn B.] Samuelli Inst, Alexandria, VA USA. [Sannes, Timothy S.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. [Stagl, Jamie] Univ Miami, Miami, FL USA. [Blackman, Marc R.] Georgetown Univ, Sch Med, Vet Affairs Med Ctr, Res Serv 151, Washington, DC USA. [Blackman, Marc R.] Georgetown Univ, Sch Med, Dept Med, Washington, DC USA. [Grem, Jean L.] Univ Nebraska Med Ctr, Omaha, NE USA. [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. [Monahan, Brian P.] Uniformed Serv Univ Hlth Sci, Dept Med, Hematol & Med Oncol Div, Bethesda, MD 20814 USA. RP Mansky, PJ (reprint author), Bellin Hlth, Canc Team, 1580 Commanche Ave, Green Bay, WI 54313 USA. EM manpaj@bellin.org OI Jacobs, Jamie M./0000-0001-9740-624X; Swain, Sandra/0000-0002-1320-3830 FU Intramural Research Programs of the NIH; NCCAM; NCI FX The authors would like to acknowledge the help and advice of Drs. Agnes Nguyenpho, FDA; Maria Merino, Laboratory of Pathology, NCI; Alex Ling, Diagnostic Imaging Department, Clinical Center, NIH; and Julia T. Arnold, NCCAM. They greatly appreciate the technical assistance of Howard Baldwin, NCCAM, and the support of Drs. Dieter Schlodder and Juergen Schierholz as well as Sabine Rieger from Helixor GmbH. The authors also thank the NIH and NNMC fellows, nurses, pharmacy staff, and all the patients who made it possible to conduct this study. This research was supported, in part, by the Intramural Research Programs of the NIH, NCCAM, and NCI and was done at the Intramural Research Program of the National Center for Complementary and Alternative Medicine, National Institutes of Health. Conclusions drawn and recommendations for future directions made are the opinions of the authors and do not represent the view of the National Center for Complementary and Alternative Medicine, The Department of the Navy, Department of Defense, or the National Cancer Institute. Mistletoe extract (Helixor A) was provided by Helixor GmbH, Rosenfeld, Germany, which also supported the mistletoe lectin analyses. NR 45 TC 7 Z9 7 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2013 AR 964592 DI 10.1155/2013/964592 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 252AG UT WOS:000326976000001 ER PT J AU Gursel, M Klinman, DM Gursel, I AF Gursel, Mayda Klinman, Dennis M. Gursel, Ihsan TI Plasmacytoid Dendritic Cell Response to CpG ODN Correlates with CXCL16 Expression and Is Inhibited by ox-LDL SO MEDIATORS OF INFLAMMATION LA English DT Article ID CHEMOKINE LIGAND-16; SCAVENGER RECEPTOR; T-CELLS; B-CELL; DNA; ACTIVATION; INDUCTION; IDENTIFICATION; DISINTEGRIN; SUBSETS AB Structurally distinct classes of synthetic CpG oligonucleotides (ODN) differentially activate human immune cells. K-type ODN trigger plasmacytoid dendritic cells (pDCs) to differentiate and produce TNF alpha. In contrast, D-type ODN stimulate large amounts of IFN alpha secretion from pDCs. The cell-surface receptor CXCL16 was previously shown to influence the nature and specificity of CpG ODN-induced immune activation. Here, we evaluated the expression and function of CXCL16 on pDC from healthy volunteers. We report that increased CXCL16 expression correlated with enhanced in vitro response exclusively to D-type CpG ODN. Conversely, enzymatic digestion of the receptor resulted in a decrease in IFN alpha production. Moreover, ox-LDL presence significantly inhibited D-ODN mediated IFN alpha production by pDCs. Coculture of enriched pDCs with the CXCR6 expressing Jurkat T cells decreased the activation threshold of these cells responding to D-ODN, suggesting that CXCL16/CXCR6 interaction may play an important role in modifying the response of pDCs to environmental danger signals. C1 [Gursel, Mayda] Middle E Tech Univ, Dept Biol Sci, TR-06800 Ankara, Turkey. [Klinman, Dennis M.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. [Gursel, Ihsan] Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey. RP Gursel, M (reprint author), Middle E Tech Univ, Dept Biol Sci, TR-06800 Ankara, Turkey. EM mgursel@metu.edu.tr OI Gursel, Ihsan/0000-0003-3761-1166; Gursel, Mayda/0000-0003-0044-9054 NR 27 TC 0 Z9 0 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 EI 1466-1861 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2013 AR 312590 DI 10.1155/2013/312590 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 253CA UT WOS:000327058200001 ER PT J AU Krueger, AB Dehdashti, SJ Southall, N Marugan, JJ Ferrer, M Li, XN Ford, HL Zheng, W Zhao, R AF Krueger, Aaron B. Dehdashti, Seameen J. Southall, Noel Marugan, Juan J. Ferrer, Marc Li, Xueni Ford, Heide L. Zheng, Wei Zhao, Rui TI Identification of a Selective Small-Molecule Inhibitor Series Targeting the Eyes Absent 2 (Eya2) Phosphatase Activity SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE phosphatase; Eyes Absent 2; Eya2; Eya2 inhibitor; Six1 ID EPITHELIAL-MESENCHYMAL TRANSITION; PROTEIN-TYROSINE PHOSPHATASES; BRANCHIOOTORENAL SYNDROME; TRANSCRIPTION FACTOR; SCREENING ASSAYS; BREAST-CANCER; SIX1; METASTASIS; CARCINOMA; SURVIVAL AB Eya proteins are essential coactivators of the Six family of homeobox transcription factors and also contain a unique protein tyrosine phosphatase activity, belonging to the haloacid dehalogenase family of phosphatases. The phosphatase activity of Eya is important for a subset of Six1-mediated transcription, making this a unique type of transcriptional control. It is also responsible for directing cells to the repair instead of apoptosis pathway upon DNA damage. Furthermore, the phosphatase activity of Eya is critical for transformation, migration, invasion, and metastasis of breast cancer cells. Thus, inhibitors of the Eya phosphatase activity may be antitumorigenic and antimetastatic, as well as sensitize cancer cells to DNA damage-inducing therapies. In this article, we identified a previously unknown chemical series using high-throughput screening that inhibits the Eya2 phosphatase activity with IC(50)s ranging from 1.8 to 79 mu M. Compound activity was confirmed using an alternative malachite green assay and H2AX, a known Eya substrate. Importantly, these Eya2 phosphatase inhibitors show specificity and do not significantly inhibit several other cellular phosphatases. Our studies identify the first selective Eya2 phosphatase inhibitors that can potentially be developed into chemical probes for functional studies of Eya phosphatase or into anticancer drugs in the future. C1 [Krueger, Aaron B.; Li, Xueni; Ford, Heide L.; Zhao, Rui] Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA. [Dehdashti, Seameen J.; Southall, Noel; Marugan, Juan J.; Ferrer, Marc; Zheng, Wei] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Ford, Heide L.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA. [Ford, Heide L.] Univ Colorado, Sch Med, Dept Ob Gyn, Aurora, CO 80045 USA. RP Zhao, R (reprint author), Univ Colorado, Sch Med, Dept Biochem & Mol Genet, POB 6511,Mailstop 8101, Aurora, CO 80045 USA. EM wzheng@mail.nih.gov; Rui.Zhao@ucdenver.edu RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014 OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research, National Institutes of Health, through NIH [R03DA030559]; Department of Defense [BC084105]; AACR/BCRF (American Association for Cancer Research and Breast Cancer Research Foundation); State of Colorado; Colorado Bioscience Discovery and Evaluation Grant FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research, National Institutes of Health, through a grant from the NIH (R03DA030559) to R.Z. and H.L.F. Additional support for this work comes from a Department of Defense Synergistic Idea Award (BC084105), an AACR/BCRF (American Association for Cancer Research and Breast Cancer Research Foundation) grant, a State of Colorado Proof of Concept grant, and a Colorado Bioscience Discovery and Evaluation Grant to R.Z. and H.L.F. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 8 Z9 9 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 EI 1552-454X J9 J BIOMOL SCREEN JI J. Biomol. Screen PD JAN PY 2013 VL 18 IS 1 BP 85 EP 96 DI 10.1177/1087057112453936 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 059GT UT WOS:000312693100008 PM 22820394 ER PT B AU Mora, KE Cohen, JD Morgan, NY Yu, PP Geller, HM AF Mora, Keshia E. Cohen, Joshua D. Morgan, Nicole Y. Yu, Panpan Geller, Herbert M. GP IEEE TI Microfluidic deposition of chondroitin sulfate proteoglycan surface gradients for neural cell culture SO 2013 MICROSYSTEMS FOR MEASUREMENT AND INSTRUMENTATION (MAMNA) LA English DT Proceedings Paper CT MAMNA Spring Symposium on Microsystems for Measurement and Instrumentation CY MAY 14, 2013 CL Natl Inst Standards & Technol, Gaithersburg, MD SP Mid Atlantic Micro Nano Alliance HO Natl Inst Standards & Technol DE microfluidics; gradients; chondroitin sulfate proteoglycans; axon guidance ID NEURITE OUTGROWTH; GUIDANCE; GROWTH AB After injury, regeneration of the central nervous system (CNS) is inhibited by the secretion of repulsive guidance cues that mediate axon growth and guidance. These repulsive cues are perceived as spatial gradients of neurons. Microfluidic systems can enable studies of neuron response to spatial gradients, by generating precise and reproducible surface gradients of guidance cues. Understanding neuron response to these gradients could provide valuable information for therapies seeking to promote regeneration in the CNS. Here we report on the successful use of a microfluidic gradient generator to deposit spatially-extended and uniform surface gradients of one repulsive guidance cue, chondroitin sulfate proteoglycans (CSPGs). The patterned substrates are compatible with high-quality culture of large numbers of primary neurons, and initial findings indicate that neuron growth and guidance are responsive to the deposited CSPGs. C1 [Mora, Keshia E.; Cohen, Joshua D.; Morgan, Nicole Y.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Yu, Panpan; Geller, Herbert M.] Natl Heart Lung & Blood Inst Natl Inst Hlth, Bethesda, MD USA. RP Mora, KE (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. FU Intramural Research Program at National Institute of Biomedical Imaging and Bioengineering; National Heart, Lung and Blood Institute FX This research was funded by the Intramural Research Program at the National Institute of Biomedical Imaging and Bioengineering and the National Heart, Lung and Blood Institute. NR 10 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-0221-7; 978-1-4799-0220-0 PY 2013 BP 20 EP 23 PG 4 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA BHT00 UT WOS:000326596700005 ER PT J AU Bae, KT Tao, C Wang, JH Kaya, D Wu, ZY Bae, JT Chapman, AB Torres, VE Grantham, JJ Mrug, M Bennett, WM Flessner, MF Landsittel, DP AF Bae, Kyongtae T. Tao, Cheng Wang, Jinhong Kaya, Diana Wu, Zhiyuan Bae, Junu T. Chapman, Arlene B. Torres, Vicente E. Grantham, Jared J. Mrug, Michal Bennett, William M. Flessner, Michael F. Landsittel, Doug P. CA Consortium Radiologic Imaging Stud TI Novel Approach to Estimate Kidney and Cyst Volumes Using Mid-Slice Magnetic Resonance Images in Polycystic Kidney Disease SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Kidney; Polycystic kidney disease; Kidney volume; Renal cysts; Magnetic resonance imaging ID CONSORTIUM; PROGRESSION; COHORT; CRISP; ADPKD; MRI AB Objective: To evaluate whether kidney and cyst volumes can be accurately estimated based on limited area measurements from magnetic resonance (MR) images of patients with autosomal dominant polycystic kidney disease (ADPKD). Materials and Methods: MR coronal images of 178 ADPKD participants from the Consortium for Radiologic Imaging Studies of ADPKD (CRISP) were analyzed. For each MR image slice, we measured kidney and renal cyst areas using stereology and region-based thresholding methods, respectively. The kidney and cyst 'observed' volumes were calculated by summing up the area measurements of all the slices covering the kidney. To estimate the volume, we selected a coronal mid-slice in each kidney and multiplied its area by the total number of slices ('PANK2' for kidney and 'PANC2' for cyst). We then compared the kidney and cyst volumes predicted from PANK2 and PANC2, respectively, to the corresponding observed volumes, using a linear regression analysis. Results: The kidney volume predicted from PANK2 correlated extremely well with the observed kidney volume (R-2 = 0.994 for the right kidney and 0.991 for the left kidney). The linear regression coefficient multiplier to PANK2 that best fit the kidney volume was 0.637 (95% CI: 0.629-0.644) for the right kidney and 0.624 (95% CI: 0.616-0.633) for the left kidney. The correlation between the cyst volume predicted from PANC2 and the observed cyst volume was also very high (R-2 = 0.984 for the right kidney and 0.967 for the left kidney). The least squares linear regression coefficient for PANC2 was 0.637 (95% CI: 0.624-0.649) for the right kidney and 0.608 (95% CI: 0.591-0.625) for the left kidney. Conclusion: Kidney and cyst volumes can be closely approximated by multiplying the product of the mid-slice area measurement and the total number of slices in the coronal MR images of ADPKD kidneys by 0.61-0.64. This information will help save processing time needed to estimate total kidney and cyst volumes of ADPKD kidneys. (C) 2013 S. Karger AG, Basel C1 [Bae, Kyongtae T.; Tao, Cheng; Wang, Jinhong; Kaya, Diana; Wu, Zhiyuan; Bae, Junu T.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15213 USA. [Landsittel, Doug P.] Univ Pittsburgh, Sch Med, Dept Internal Med, Pittsburgh, PA 15213 USA. [Chapman, Arlene B.] Emory Univ, Sch Med, Dept Internal Med, Atlanta, GA USA. [Torres, Vicente E.] Mayo Coll Med, Dept Internal Med, Rochester, MN USA. [Grantham, Jared J.] Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA. [Mrug, Michal] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL USA. [Bennett, William M.] Legacy Good Samaritan Hosp, Portland, OR USA. [Flessner, Michael F.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. RP Bae, KT (reprint author), Univ Pittsburgh, Sch Med, Dept Radiol, Presbyterian South Tower,Room 3950,200 Lothrop St, Pittsburgh, PA 15213 USA. EM baek@upmc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [DK056943, DK056956, DK056957, DK056961]; National Center for Research Resources General Clinical Research Centers at each institution [RR000039, RR00585, RR23940, RR000032]; National Center for Research Resources Clinical and Translational Science Awards [RR025008, RR024150, RR033179, RR025777, UL1TR000165, RR024153, UL1TR000005] FX The CRISP study is supported by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (DK056943, DK056956, DK056957, DK056961), by the National Center for Research Resources General Clinical Research Centers at each institution (RR000039, Emory University; RR00585, Mayo College of Medicine; RR23940, Kansas University Medical Center; RR000032, University of Alabama at Birmingham), and the National Center for Research Resources Clinical and Translational Science Awards at each institution (RR025008, Emory; RR024150, Mayo College of Medicine; RR033179, Kansas University Medical Center; RR025777 and UL1TR000165, University of Alabama at Birmingham; RR024153 and UL1TR000005, University of Pittsburgh School of Medicine). The investigators are indebted to the radiologists, radiology technologists, imaging engineers, and study coordinators in CRISP. NR 9 TC 10 Z9 10 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2013 VL 38 IS 4 BP 333 EP 341 DI 10.1159/000355375 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 240YR UT WOS:000326134100009 PM 24107679 ER PT S AU Gottesman, S AF Gottesman, Susan BE Gottesman, S TI Annual Review of Microbiology Volume 67, 2013 Introduction SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 67 SE Annual Review of Microbiology LA English DT Editorial Material; Book Chapter C1 NCI, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1167-4 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2013 VL 67 BP V EP V PG 1 WC Microbiology SC Microbiology GA BHU49 UT WOS:000326686400001 ER PT S AU Decker, KB Hinton, DM AF Decker, Kimberly B. Hinton, Deborah M. BE Gottesman, S TI Transcription Regulation at the Core: Similarities Among Bacterial, Archaeal, and Eukaryotic RNA Polymerases SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 67 SE Annual Review of Microbiology LA English DT Review; Book Chapter DE sigma; TBP; TFIIB; activation; promoter ID TATA-BINDING PROTEIN; ESCHERICHIA-COLI SIGMA(70); RAY CRYSTAL-STRUCTURE; PROMOTER OPEN COMPLEX; STRUCTURAL BASIS; INITIATION COMPLEX; GENE-REGULATION; FACTOR-B; PREINITIATION COMPLEX; ANGSTROM RESOLUTION AB Multisubunit RNA polymerases are complex protein machines that require a specificity factor for the recognition of a specific transcription start site. Although bacterial sigma factors are thought to be quite different from the specificity factors employed in higher organisms, a comparison of the sigma/RNA polymerase structures with recent structures of eukaryotic Pol II together with TFIIB highlights significant functional similarities. Other work reveals that both bacterial and eukaryotic promoters are composed of modular elements that are used in different combinations. Bacteria, archaea, and eukaryotes also utilize similar strategies to alter core promoter specificity, from specificity factor exchange to the employment of activators that bind close to or overlap core promoter sequences, directing the transcriptional machinery to a new start site. Here we examine the details of core promoter recognition in bacteria that reveal the transcriptional similarities throughout biology. C1 [Decker, Kimberly B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Microbial Pathogenesis, NIH, Bethesda, MD 20892 USA. [Hinton, Deborah M.] NIDDK, Gene Express & Regulat Sect, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Decker, KB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Microbial Pathogenesis, NIH, Bethesda, MD 20892 USA. EM dhinton@helix.nih.gov FU Intramural NIH HHS NR 130 TC 22 Z9 22 U1 4 U2 35 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1167-4 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2013 VL 67 BP 113 EP 139 DI 10.1146/annurev-micro-092412-155756 PG 27 WC Microbiology SC Microbiology GA BHU49 UT WOS:000326686400007 PM 23768203 ER PT S AU Kraus, A Groveman, BR Caughey, B AF Kraus, Allison Groveman, Bradley R. Caughey, Byron BE Gottesman, S TI Prions and the Potential Transmissibility of Protein Misfolding Diseases SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 67 SE Annual Review of Microbiology LA English DT Review; Book Chapter DE prion; TSE; amytrophic lateral sclerosis; Alzheimer's; Parkinson's; Huntington's; transmissibility; protein misfolding ID CHRONIC WASTING DISEASE; BETA-AMYLOID FIBRILS; AMYOTROPHIC-LATERAL-SCLEROSIS; TO-NEURON TRANSMISSION; STATE NMR-SPECTROSCOPY; SCRAPIE PRION; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; HYDROGEN/DEUTERIUM EXCHANGE; SUPEROXIDE DISMUTASE-1 AB Prions, or infectious proteins, represent a major frontier in the study of infectious agents. The prions responsible for mammalian transmissible spongiform encephalopathies (TSEs) are due primarily to infectious self-propagation of misfolded prion proteins. TSE prion structures remain ill-defined, other than being highly structured, self-propagating, and often fibrillar protein multimers with the capacity to seed, or template, the conversion of their normal monomeric precursors into a pathogenic form. Purified TSE prions usually take the form of amyloid fibrils, which are self-seeding ultrastructures common to many serious protein misfolding diseases such as Alzheimer's, Parkinson's, Huntington's and Lou Gehrig's (amytrophic lateral sclerosis). Indeed, recent reports have now provided evidence of prion-like propagation of several misfolded proteins from cell to cell, if not from tissue to tissue or individual to individual. These findings raise concerns that various protein misfolding diseases might have spreading, prion-like etiologies that contribute to pathogenesis or prevalence. C1 [Kraus, Allison; Groveman, Bradley R.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Kraus, A (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM bcaughey@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000580-18, Z01 AI000580-19] NR 144 TC 36 Z9 37 U1 4 U2 29 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1167-4 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2013 VL 67 BP 543 EP 564 DI 10.1146/annurev-micro-092412-155735 PG 22 WC Microbiology SC Microbiology GA BHU49 UT WOS:000326686400027 PM 23808331 ER PT J AU Balakrishnan, B Dai, H Janisse, J Romero, R Kannan, S AF Balakrishnan, Bindu Dai, Hui Janisse, James Romero, Roberto Kannan, Sujatha TI Maternal Endotoxin Exposure Results in Abnormal Neuronal Architecture in the Newborn Rabbit SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Maternal intrauterine inflammation; Dendrites; Dendritic spine; Cerebral palsy; Neuronal injury; Perinatal brain injury; Thalamus ID NEONATAL SEROTONIN DEPLETION; PERIVENTRICULAR LEUKOMALACIA; CEREBRAL-PALSY; RETROSPLENIAL CORTEX; WHITE-MATTER; INTRAUTERINE INFLAMMATION; MICROGLIAL ACTIVATION; COGNITIVE DEFICITS; PYRAMIDAL NEURONS; MOTOR DEFICITS AB Maternal intrauterine inflammation/infection is a potential risk factor for the development of neurologic disorders such as cerebral palsy (CP) in preterm and term infants. CP is associated with white matter and grey matter injury. In the current study, we used a rabbit model of CP in which pregnant rabbits are administered intrauterine injections of the endotoxin lipopolysaccharide. We then investigated the extent of neuronal damage in the newborn kit brain. We observed an overall decrease in the number of MAP2-stained neurons and an increase in Fluoro-Jade C-stained cells in the anterior thalamus of 1-day-old rabbit brain. We also observed an overall decrease in the number of branching points and spine density in the retrosplenial cortex, a major output region of the anterior thalamus that is involved in cognition and memory. The loss of spines and dendritic atrophy in the retrosplenial cortex may be caused by loss of presynaptic input from the thalamus. Our study indicates that the cognitive impairments seen in patients with CP may be related to the degeneration of neurons and abnormal arborization of the thalamic and cortical neurons. (C) 2013 S. Karger AG, Basel C1 [Balakrishnan, Bindu; Kannan, Sujatha] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Balakrishnan, Bindu; Dai, Hui; Kannan, Sujatha] Wayne State Univ, Sch Med, Dept Pediat, Childrens Hosp Michigan, Detroit, MI 48201 USA. [Janisse, James] Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. RP Kannan, S (reprint author), Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, 1800 Orleans St, Baltimore, MD 21218 USA. EM skannan3@jhmi.edu FU NICHD, NIH; Perinatology Research Branch, Eunice Kennedy Shriver NICHD, NIH, DHHS; [1K08HD050652]; [R01 HD069562] FX This study was supported in part by 1K08HD050652, R01 HD069562, NICHD, NIH, and the Perinatology Research Branch, Eunice Kennedy Shriver NICHD, NIH, DHHS. NR 60 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 EI 1421-9859 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2013 VL 35 IS 5 BP 396 EP 405 DI 10.1159/000353156 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 244BU UT WOS:000326362900005 PM 23988854 ER PT J AU Pinsky, PF Gierada, DS Nath, H Kazerooni, EA Amorosa, J AF Pinsky, Paul F. Gierada, David S. Nath, Hrudaya Kazerooni, Ella A. Amorosa, Judith TI ROC Curves for Low-Dose CT in the National Lung Screening Trial SO JOURNAL OF MEDICAL SCREENING LA English DT Article DE ROC curve; AUC; lung cancer; CT screening ID CANCER AB The National Lung Screening Trial (NLST) reported a 20% reduction in lung cancer specific mortality using low-dose chest CT (LDCT) compared with chest radiograph (CXR) screening. The high number of false positive screens with LDCT (around 25%) raises concerns. NLST radiologists reported LDCT screens as either positive or not positive, based primarily on the presence of a 4+ mm non-calcified lung nodule (NCN). They did not explicitly record a propensity score for lung cancer. However, by using maximum NCN size, or alternatively, radiologists' recommendations for diagnostic follow-up categorized hierarchically, surrogate propensity scores (PSSZ and PSFR) were created. These scores were then used to compute ROC curves, which determine possible operating points of sensitivity versus false positive rate (1-Specificity). The area under the ROC curve (AUC) was 0.934 and 0.928 for PSFR and PSSZ, respectively; the former was significantly greater than the latter. With the NLST definition of a positive screen, sensitivity and specificity of LDCT was 93.1% and 76.5%, respectively. With cutoffs based on PSFR, a specificity of 92.4% could be achieved while only lowering sensitivity to 86.9%. Radiologists using LDCT have good predictive ability; the optimal operating point for sensitivity and specificity remains to be determined. C1 [Pinsky, Paul F.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Gierada, David S.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Nath, Hrudaya] Univ Alabama Birmingham, Birmingham, AL USA. [Kazerooni, Ella A.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Amorosa, Judith] Canc Inst New Jersey, New Brunswick, NJ USA. RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr,Room 5E212, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 7 TC 0 Z9 0 U1 0 U2 2 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 EI 1475-5793 J9 J MED SCREEN JI J. Med. Screen. PY 2013 VL 20 IS 3 BP 165 EP 168 DI 10.1177/0969141313500666 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 247VW UT WOS:000326652000006 PM 24009092 ER PT J AU Lindberg, DAB Ball, MJ AF Lindberg, D. A. B. Ball, M. J. TI Morris F. Collen at 100: A Tribute to "The Father of Medical Informatics" SO METHODS OF INFORMATION IN MEDICINE LA English DT Editorial Material C1 [Lindberg, D. A. B.] Natl Lib Med, Bethesda, MD USA. [Ball, M. J.] IBM Res, Healthcare Informat, Baltimore, MD USA. RP Lindberg, DAB (reprint author), Natl Lib Med, Bethesda, MD USA. EM lindberg@nlm.nih.gov; marionball@us.ibm.com NR 4 TC 0 Z9 0 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2013 VL 52 IS 5 BP 371 EP 373 PG 3 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 245RG UT WOS:000326480900001 PM 24114266 ER PT J AU Li, J Lu, Z AF Li, J. Lu, Z. TI Developing Topic-specific Search Filters for PubMed with Click-through Data SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Information retrieval; PubMed search filter; PubMed log analysis; clinical topic ID SYSTEMATIC REVIEWS; MEDLINE; RETRIEVAL; INFORMATION; STRATEGIES; QUERIES; EMBASE; MESH AB Objectives: Search filters have been developed and demonstrated for better information access to the immense and ever-growing body of publications in the biomedical domain. However, to date the number of filters remains quite limited because the current filter development methods require significant human efforts in manual document review and filter term selection. In this regard, we aim to investigate automatic methods for generating search filters. Methods: We present an automated method to develop topic-specific filters on the basis of users' search logs in PubMed. Specifically, for a given topic, we first detect its relevant user queries and then include their corresponding clicked articles to serve as the topic-relevant document set accordingly. Next, we statistically identify informative terms that best represent the topic-relevant, document set using a background set composed of topic irrelevant articles. Lastly, the selected representative terms are combined with Boolean operators and evaluated on benchmark datasets to derive the final filter with the best performance. Results: We applied our method to develop filters for four clinical topics: nephrology, diabetes, pregnancy, and depression. For the nephrology filter, our method obtained performance comparable to the state of the art (sensitivity of 91,3%, specificity of 98.7%, precision of 94.6%, and accuracy of 97.2%). Similarly, high-performing results (over 90% in all measures) were obtained for the other three search filters. Conclusion: Based on PubMed click-through data, we successfully developed a high-performance method for generating topic-specific search filters that is significantly more efficient than existing manual methods. All data sets (topic-relevant and irrelevant document sets) used in this study and a demonstration system are publicly available at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/downloads/CQ_filter/ C1 [Li, J.] Chinese Acad Med Sci, Inst Med Informat & Lib, Beijing 100730, Peoples R China. [Li, J.; Lu, Z.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Lu, Z (reprint author), NCBI NLM NIH, 8600 Rockville Pike,Bldg 38A,Room 1003A, Bethesda, MD 20894 USA. EM zhiyong.lu@nih.gov FU National Institutes of Health, National Library of Medicine; National Key Technology R&D Program of China [2013BAI06B01]; Peking Union Medical College Youth Fund FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine, the National Key Technology R&D Program of China (Grant No. 2013BAI06B01), and the Peking Union Medical College Youth Fund. The authors would like to thank Chih-Hsuan Wei for implementing a demonstration system for our work, Drs. W John Wilbur, Won Kim, Sun Kim and Rezarta Islamaj Dogan for their helpful comments and discussion on this work, and Bethany Harris for proofreading our manuscript. NR 37 TC 1 Z9 1 U1 1 U2 3 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2013 VL 52 IS 5 BP 395 EP 402 DI 10.3414/ME12-01-0054 PG 8 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 245RG UT WOS:000326480900004 PM 23666447 ER PT J AU Cho, HY Kwak, MK Pi, JB AF Cho, Hye-Youn Kwak, Mi-Kyoung Pi, Jingbo TI Nrf2 in Host Defense: Over the Rainbow SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Editorial Material ID TRANSCRIPTION FACTOR NRF2; MICE C1 [Cho, Hye-Youn] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Kwak, Mi-Kyoung] Catholic Univ Korea, Coll Pharm, Puchon 420743, Gyeonggi Do, South Korea. [Pi, Jingbo] Hamner Inst Hlth Sci, Inst Chem Safety Sci, Res Triangle Pk, NC 27709 USA. RP Cho, HY (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA. EM cho2@niehs.nih.gov NR 10 TC 0 Z9 0 U1 1 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 EI 1942-0994 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2013 DI 10.1155/2013/975839 PG 3 WC Cell Biology SC Cell Biology GA 249FS UT WOS:000326763100001 ER PT S AU Combs, GF Trumbo, PR McKinley, MC Milner, J Studenski, S Kimura, T Watkins, SM Raiten, DJ AF Combs, Gerald F., Jr. Trumbo, Paula R. McKinley, Michelle C. Milner, John Studenski, Stephanie Kimura, Takeshi Watkins, Steven M. Raiten, Daniel J. GP Annals NY Acad Sci TI Biomarkers in nutrition: new frontiers in research and application SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE biomarkers; nutrition; nutrients ID SELENIUM SUPPLEMENTATION; CANCER PREVENTION; ADULTS; TRIAL; MALNUTRITION; SARCOPENIA AB Nutritional biomarkers-biochemical, functional, or clinical indices of nutrient intake, status, or functional effects-are needed to support evidence-based clinical guidance and effective health programs and policies related to food, nutrition, and health. Such indices can reveal information about biological or physiological responses to dietary behavior or pathogenic processes, and can be used to monitor responses to therapeutic interventions and to provide information on interindividual differences in response to diet and nutrition. Many nutritional biomarkers are available; yet there has been no formal mechanism to establish consensus regarding the optimal biomarkers for particular nutrients and applications. C1 [Combs, Gerald F., Jr.] USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. [Trumbo, Paula R.] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. [McKinley, Michelle C.] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland. [Milner, John] NCI, NIH, US Dept Hlth & Human Serv, Rockville, MD USA. [Studenski, Stephanie] Univ Pittsburgh, Pittsburgh, PA USA. [Kimura, Takeshi] Ajinomoto Co Inc, Tokyo, Japan. [Watkins, Steven M.] Tethys Biosci Inc, Emeryville, CA USA. [Raiten, Daniel J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept Hlth & Human Serv, Rockville, MD USA. RP Combs, GF (reprint author), USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. EM annals@nyas.org FU Medical Research Council [MR/K023241/1] NR 26 TC 8 Z9 8 U1 2 U2 13 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1278 BP 1 EP 10 DI 10.1111/nyas.12069 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHO53 UT WOS:000326100700001 PM 23488557 ER PT S AU Davis, M Boekelheide, K Boverhof, DR Eichenbaum, G Hartung, T Holsapple, MP Jones, TW Richard, AM Watkins, PB AF Davis, Myrtle Boekelheide, Kim Boverhof, Darrell R. Eichenbaum, Gary Hartung, Thomas Holsapple, Michael P. Jones, Thomas W. Richard, Ann M. Watkins, Paul B. GP Annals NY Acad Sci TI The new revolution in toxicology: The good, the bad, and the ugly SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE toxicology; pharmaceuticals; testing ID PRECLINICAL SAFETY EVALUATION; FETAL TESTIS XENOGRAFTS; LYMPH-NODE ASSAY; IN-VITRO; GENE-EXPRESSION; CARDIOVASCULAR-DISEASE; PREDICTIVE TOXICOLOGY; ANTICANCER DRUGS; RISK-ASSESSMENT; TOXICITY AB In 2007, the United States National Academy of Sciences issued a report entitled Toxicity Testing in the 21st Century: A Vision and a Strategy. The report reviewed the state of the science and outlined a strategy for the future of toxicity testing. One of the more significant components of the vision established by the report was an emphasis on toxicity testing in human rather than animal systems. In the context of drug development, it is critical that the tools used to accomplish this strategy are maximally capable of evaluating human risk. Since 2007, many advances toward implementation of this vision have been achieved, particularly with regard to safety assessment of new chemical entities intended for pharmaceutical use. C1 [Davis, Myrtle] NCI, NIH Bethesda, Div Canc Treatment & Diag, Toxicol & Pharmacol Branch,Dev Therapeut Program, Rockville, MD 20852 USA. [Boekelheide, Kim] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Boverhof, Darrell R.] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. [Eichenbaum, Gary] Johnson & Johnson Pharmaceut R&D LLC, Dept Drug Safety Sci, Raritan, NJ USA. [Hartung, Thomas] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Holsapple, Michael P.] Battelle Mem Inst, Columbus, OH 43201 USA. [Jones, Thomas W.] Eli Lilly & Co, Dept Toxicol & Pathol, Indianapolis, IN 46285 USA. [Richard, Ann M.] US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA. [Watkins, Paul B.] Hamner Univ North Carolina, Inst Drug Safety Sci, Res Triangle Pk, NC 27711 USA. RP Davis, M (reprint author), NCI, NIH Bethesda, Div Canc Treatment & Diag, Toxicol & Pharmacol Branch,Dev Therapeut Program, Rockville, MD 20852 USA. EM davismillinm@mail.nih.gov OI Eichenbaum, Gary/0000-0002-2318-6042 NR 59 TC 7 Z9 8 U1 6 U2 20 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1278 BP 11 EP 24 DI 10.1111/nyas.12086 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHO53 UT WOS:000326100700002 PM 23488558 ER PT J AU Ashour, F Raiten, D AF Ashour, F. Raiten, D. TI ADDRESSING CROSS-CUTTING ISSUES SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE Biomarkers; INSPIRE; nutrition; inflammation C1 [Ashour, F.; Raiten, D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 4 EP 4 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548201008 ER PT J AU Darnton-Hill, I Raiten, D AF Darnton-Hill, I. Raiten, D. TI ROADMAP FOR BOND: A PANEL DISCUSSION OF PHASE 1 AND OPPORTUNITIES FOR PHASE II SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE Biomarkers; BOND; BOND phase I; BOND phase II; growth; micronutrients C1 [Darnton-Hill, I.] Univ Sydney, Boden Inst Obes Nutr Exercise & Eating Disorders, Sydeny, Australia. [Raiten, D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 4 EP 5 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548201009 ER PT J AU Raiten, D Raghavan, R AF Raiten, D. Raghavan, R. TI BOND OVERVIEW AND SUMMARY OF EXPERT PANEL REPORTS SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE BOND; biomarkers; micronutrients C1 [Raiten, D.; Raghavan, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 5 EP 5 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548201011 ER PT J AU Raghavan, R Raiten, D AF Raghavan, R. Raiten, D. TI DEMO OF BOND WEBSITE AND QUERY BASED SYSTEM SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE BOND; BOND website; Query Based System; QBS and micronutrients C1 [Raghavan, R.; Raiten, D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 6 EP 6 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548201012 ER PT J AU Rabadan-Diehl, C AF Rabadan-Diehl, C. TI THE NIH NHLBI/UHG CENTERS OF EXCELLENCE: A MODEL FOR INTERNATIONAL RESEARCH COLLABORATION SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE Child heaalth; Infectious diseases; Research collaboration; The National Heart; Lung and Blood Institute C1 [Rabadan-Diehl, C.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 47 EP 47 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548201100 ER PT J AU Raiten, D AF Raiten, D. TI OVERVIEW OF THE IRON AND MALARIA PROJECT SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE Biomarkers; iron; malaria C1 [Raiten, D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 86 EP 87 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548201182 ER PT J AU Jankovic, N Geelen, A Kampman, E de Groot, CP Pikhart, H Huangfu, P Bofetta, P Bueno-de-Mesquita, HB Kee, F O'Doherty, M Franco, OH Hooven van den, EH Rooij van, F Trichopoulou, A Orfanos, P Tjonneland, A Gonzalez, CA Hallmanns, G Peeters, PH Park, Y Pajak, A Malyutina, S Kubinova, R Feskens, EJ AF Jankovic, N. Geelen, A. Kampman, E. de Groot, C. P. Pikhart, H. Huangfu, P. Bofetta, P. Bueno-de-Mesquita, H. B. Kee, F. O'Doherty, M. Franco, O. H. Hooven van den, E. H. Rooij van, F. Trichopoulou, A. Orfanos, P. Tjonneland, A. Gonzalez, C. A. Hallmanns, G. Peeters, P. H. Park, Y. Pajak, A. Malyutina, S. Kubinova, R. Feskens, E. J. TI ASSOCIATION BETWEEN A HEALTHY DIET ACCORDING TO WHO GUIDELINES AND ALL-CAUSE MORTALITY IN EUROPEAN AND AMERICAN ELDERLY, THE CHANCES PROJECT SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE CHANCES; Ageing; Cohort; diet; mortality C1 [Jankovic, N.; Geelen, A.; Kampman, E.; de Groot, C. P.; Feskens, E. J.] Wageningen Univ, Div Human Nutr, NL-6700 EV Wageningen, Netherlands. [Pikhart, H.; Huangfu, P.] UCL, Dept Epidemiol & Publ Hlth, London, England. [Bofetta, P.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bueno-de-Mesquita, H. B.] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Kee, F.; O'Doherty, M.] Queens Univ Belfast, Sch Med & Dent, Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland. [Franco, O. H.; Hooven van den, E. H.; Rooij van, F.] Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Trichopoulou, A.] Hellen Hlth Fdn, Athens, Greece. [Trichopoulou, A.; Orfanos, P.] Univ Athens, Sch Med, WHO Collaborating Ctr Food & Nutr Policies, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece. [Tjonneland, A.] Danish Canc Soc, Res Ctr, Copenhagen, Denmark. [Gonzalez, C. A.] Catalan Inst Oncol, Unit Nutr Environm & Canc, Canc Epidemiol Res Program, Barcelona, Spain. [Hallmanns, G.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Peeters, P. H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Park, Y.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Pajak, A.] Jagiellonian Univ, Dept Epidemiol & Populat Studies, Krakow, Poland. [Malyutina, S.] Russian Acad Med Sci, Siberian Branch, Inst Internal Med, Novosibirsk, Russia. [Kubinova, R.] Natl Publ Hlth Inst, Prague, Czech Republic. RI Geelen, Anouk/P-5041-2014; Kampman, E./H-8057-2014 OI Geelen, Anouk/0000-0003-1799-4075; NR 0 TC 0 Z9 0 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 234 EP 234 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548201487 ER PT J AU Vandevijvere, S Lobstein, T Lee, A Albert, J Krebs-Smith, S Swinburn, B Monteiro, C AF Vandevijvere, S. Lobstein, T. Lee, A. Albert, J. Krebs-Smith, S. Swinburn, B. Monteiro, C. TI THE INFORMAS FRAMEWORK FOR MONITORING AND BENCHMARKING DIET QUALITY GLOBALLY: A STEP-BASED APPROACH SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE Food environments; benchmarking; diet quality; ultra-processed C1 [Vandevijvere, S.; Swinburn, B.] Univ Auckland, Dept Epidemiol & Biostat, Sch Populat Hlth, Auckland 1, New Zealand. [Lee, A.] Queensland Univ Technol, Sch Publ Hlth & Social Work, Brisbane, Qld 4001, Australia. [Krebs-Smith, S.] NCI, Bethesda, MD 20892 USA. [Monteiro, C.] Univ Sao Paulo, Dept Nutr, Sch Publ Hlth, BR-05508 Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 251 EP 251 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548201520 ER PT J AU Carrasco-Benso, MP Gomez-Abellan, P Bel-Monte, FS Garaulet, M Fox, CS AF Carrasco-Benso, M. P. Gomez-Abellan, P. Saez Bel-Monte, F. Garaulet, M. Fox, C. S. TI THE MEASUREMENT OF HOUNSFIELD UNITS ON COMPUTED TOMOGRAPHY IMAGES AS A METHOD TO ASSESS FAT QUALITY SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE Computed-tomography; visceral-fat; adipose-tissue C1 [Carrasco-Benso, M. P.; Gomez-Abellan, P.; Garaulet, M.] Univ Murcia, Dept Physiol, Murcia, Spain. [Saez Bel-Monte, F.] Univ Murcia, Serv Res Support, Murcia, Spain. [Fox, C. S.] Harvard Univ, Framingham Heart Study, NHLBI, Sch Med, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 448 EP 448 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548202098 ER PT J AU Eysteinsdottir, T Halldorsson, TI Thorsdottir, I Sigurdsson, G Sigurdsson, S Harris, T Launer, LJ Gudnason, V Gunnarsdottir, I Steingrimsdottir, L AF Eysteinsdottir, T. Halldorsson, T. I. Thorsdottir, I. Sigurdsson, G. Sigurdsson, S. Harris, T. Launer, L. J. Gudnason, V. Gunnarsdottir, I. Steingrimsdottir, L. TI MILK CONSUMPTION THROUGHOUT LIFE IS ASSOCIATED WITH BONE MINERAL DENSITY IN ELDERLY MEN AND WOMEN SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Eysteinsdottir, T.; Halldorsson, T. I.; Thorsdottir, I.; Gunnarsdottir, I.; Steingrimsdottir, L.] Univ Iceland, Unit Nutr Res, Reykjavik, Iceland. [Eysteinsdottir, T.; Halldorsson, T. I.; Thorsdottir, I.; Sigurdsson, S.; Gunnarsdottir, I.; Steingrimsdottir, L.] Landspitali Natl Univ Hosp, Reykjavik, Iceland. [Halldorsson, T. I.; Thorsdottir, I.; Gunnarsdottir, I.; Steingrimsdottir, L.] Univ Iceland, Fac Food Sci & Human Nutr, Sch Hlth Sci, Reykjavik, Iceland. [Sigurdsson, G.; Sigurdsson, S.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Sigurdsson, G.] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland. [Harris, T.; Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015; Gunnarsdottir, Ingibjorg/L-9371-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084; NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 789 EP 789 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548202793 ER PT J AU Byrd-Bredbenner, C Quick, V White, A Brown, O Colby, S Shoff, S Lohse, B Greene, G Horacek, T Kidd, T AF Byrd-Bredbenner, C. Quick, V. White, A. Brown, O. Colby, S. Shoff, S. Lohse, B. Greene, G. Horacek, T. Kidd, T. TI EAT, SLEEP, WORK, PLAY: RELATIONSHIPS AMONG HEALTH-RELATED BEHAVIORS OF YOUNG ADULTS BY WEIGHT STATUS SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE young adults; health; behaviors; sleep C1 [Byrd-Bredbenner, C.] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Quick, V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [White, A.] Univ Maine, Orono, ME USA. [Brown, O.] Auburn Univ, Dept Nutr Dietet & Hospitality Management, Auburn, AL 36849 USA. [Colby, S.] Univ Tennessee, Dept Nutr, Knoxville, TN 37996 USA. [Shoff, S.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Lohse, B.] Penn State Univ, University Pk, PA 16802 USA. [Greene, G.] Univ Rhode Isl Kingston, Dept Nutr & Food Sci, Kingston, RI USA. [Horacek, T.] Syracuse Univ, Dept Publ Hlth Food Studies & Nutr, Syracuse, NY USA. [Kidd, T.] Kansas State Univ, Dept Human Nutr, Manhattan, KS 66506 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 EI 1421-9697 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2013 VL 63 SU 1 BP 863 EP 864 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 219YR UT WOS:000324548203128 ER PT S AU Zarate, C Duman, RS Liu, G Sartori, S Quiroz, J Murck, H AF Zarate, Carlos Duman, Ronald S. Liu, Guosong Sartori, Simone Quiroz, Jorge Murck, Harald GP NYAS TI New paradigms for treatment-resistant depression SO ANNALS REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE depression; SSRI; SNRI; ketamine; glutamate antagonist; NMDA; scopolamine; magnesium; glutamine; CP-AMPA ID ELEMENT-BINDING PROTEIN; PREFRONTAL CORTEX; MAJOR DEPRESSION; NMDA RECEPTOR; GLUTAMINE-SYNTHETASE; SYNAPTIC PLASTICITY; BRAIN MAGNESIUM; KETAMINE; ACTIVATION; EXPRESSION AB Clinical depression is a serious mental disorder characterized by low mood, anhedonia, loss of interest in daily activities, and other symptoms, and is associated with severe consequences including suicide and increased risk of cardiovascular events. Depression affects nearly 15% of the population. The standard of care for the last 50 years has focused on monoamine neurotransmitters, including such treatments as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, these treatments have significant limitations: they can take weeks before showing mood-altering effects, and only one to two out of ten patients shows clinical effects beyond those associated with placebo. A major paradigm shift in research into the treatment of depression is underway, based on promising results with the glutamatergic NMDA receptor antagonist ketamine. Further research has demonstrated the significance of glutamatergic pathways in depression and the association of this system with the stress pathway and magnesium homeostasis. Treatment with NMDA receptor antagonists and magnesium have shown the ability to sprout new synaptic connections and reverse stress-induced neural changes, opening up promising new territory for the development of drugs to meet the unmet need in patients with clinical depression. C1 [Zarate, Carlos] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Zarate, Carlos] US Dept HHS, Bethesda, MD USA. [Duman, Ronald S.] Yale Univ, Sch Med, Dept Psychiat & Neurobiol, New Haven, CT USA. [Liu, Guosong] Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China. [Sartori, Simone] Univ Innsbruck, Dept Pharmacol & Toxicol, A-6020 Innsbruck, Austria. [Quiroz, Jorge] Roche, Neurosci Translat Med, Child & Adult Psychiat, Nutley, NJ USA. [Murck, Harald] Covance, Princeton, NJ 08540 USA. [Murck, Harald] Univ Marburg, Psychiat Clin, Marburg, Germany. RP Murck, H (reprint author), Covance, Neurosci Med & Sci Serv, 206 Carnegie Ctr, Princeton, NJ 08540 USA. EM Harald.Murck@Covance.com FU Intramural NIH HHS [Z99 MH999999]; NIMH NIH HHS [R01 MH093897, R37 MH045481] NR 49 TC 37 Z9 39 U1 3 U2 27 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-931-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1292 BP 21 EP 31 DI 10.1111/nyas.12223 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHO45 UT WOS:000326096800002 PM 23876043 ER PT S AU Metifiot, M Marchand, C Pommier, Y AF Metifiot, Mathieu Marchand, Christophe Pommier, Yves BE DeClercq, E TI HIV Integrase Inhibitors: 20-Year Landmark and Challenges SO ANTIVIRAL AGENTS SE Advances in Pharmacology LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL DNA INTEGRATION; SMALL-MOLECULE INHIBITORS; TYPE-1 INTEGRASE; STRAND TRANSFER; VIRAL-DNA; IN-VITRO; POLY(ADP-RIBOSE) POLYMERASE-1; REVERSE-TRANSCRIPTASE; PEPTIDE INHIBITORS AB Since the discovery of HIV as the cause for AIDS 30 years ago, major progress has been made, including the discovery of drugs that now control the disease. Here, we review the integrase (IN) inhibitors from the discovery of the first compounds 20 years ago to the approval of two highly effective IN strand transfer inhibitors (INSTIs), raltegravir (Isentress) and elvitegravir (Stribild), and the promising clinical activity of dolutegravir. After summarizing the molecular mechanism of action of the INSTIs as interfacial inhibitors, we discuss the remaining challenges. Those include: overcoming resistance to clinical INSTIs, long-term safety of INSTIs, cost of therapy, place of the INSTIs in prophylactic treatments, and the development of new classes of inhibitors (the LEDGINs) targeting IN outside its catalytic site. We also discuss the role of chromatin and host DNA repair factor for the completion of integration. C1 [Metifiot, Mathieu; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov NR 115 TC 24 Z9 24 U1 0 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-12-405537-7; 978-0-12-405880-4 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2013 VL 67 BP 75 EP 105 DI 10.1016/B978-0-12-405880-4.00003-2 PG 31 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA BHP67 UT WOS:000326268400004 PM 23885999 ER PT J AU Persani, L Sherman, S Nelson, L AF Persani, Luca Sherman, Stephanie Nelson, Lawrence BE Trounson, A Gosden, R EichenlaubRitter, U TI Genetic basis for primary ovarian insufficiency SO BIOLOGY AND PATHOLOGY OF THE OOCYTE: ROLE IN FERTILITY, MEDICINE, AND NUCLEAR REPROGRAMMING, 2ND EDITION LA English DT Article; Book Chapter ID EARLY EMBRYONIC-DEVELOPMENT; TRANSCRIPTION FACTOR FOXL2; DNA POLYMERASE-GAMMA; TURNER-SYNDROME; AUTOIMMUNE OOPHORITIS; PREMUTATION CARRIERS; CLASSIC GALACTOSEMIA; PREMATURE MENOPAUSE; ADDISONS-DISEASE; GONADAL-FUNCTION C1 [Persani, Luca] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. [Persani, Luca] IRCCS Ist Auxol Italiano, Div Endocrine & Metab Dis, Milan, Italy. [Sherman, Stephanie] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Nelson, Lawrence] NICHHD, Intramural Res Program Reprod & Adult Endocrinol, Integrat Reprod Med Grp, NIH, Bethesda, MD 20892 USA. RP Persani, L (reprint author), Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. NR 91 TC 1 Z9 1 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-02190-7 PY 2013 BP 394 EP 408 D2 10.1017/CBO9781139135030 PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BHP17 UT WOS:000326228300035 ER PT J AU Kamoun, M Kearns, J Prak, EL Clarke, WR Ecklund, DJ Eggerman, T Bridges, N Naji, A AF Kamoun, Malek Kearns, Jane Prak, Eline Luning Clarke, William R. Ecklund, Dixie J. Eggerman, Thomas Bridges, Nancy Naji, Ali CA CIT Investigators TI INCIDENCE OF HLA ANTIBODIES AFTER ISLET CELL TRANSPLANTATION: INITIAL RESULTS OF THE CLINICAL ISLET TRANSPLANTATION (UT) CONSORTIUM TRIAL. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics (ASHI) CY NOV 17-21, 2013 CL Chicago, IL SP Amer Soc Histocompatibil & Immunogenet C1 [Kamoun, Malek; Kearns, Jane; Prak, Eline Luning; Naji, Ali] Univ Penn, Philadelphia, PA 19104 USA. [Clarke, William R.] Univ Iowa, Iowa City, IA USA. [Ecklund, Dixie J.] Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA. [Eggerman, Thomas] NIDDK, NIH, Bethesda, MD USA. [Bridges, Nancy] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 EI 1879-1166 J9 HUM IMMUNOL JI Hum. Immunol. PY 2013 VL 74 SU S BP 15 EP 15 PG 1 WC Immunology SC Immunology GA 239YC UT WOS:000326060900019 ER PT J AU Yuan, Y Adams, SD Dinauer, DM Rosenau, CM Uribe, MR Flegel, WA AF Yuan, Yao Adams, Sharon D. Dinauer, David M. Rosenau, Christopher M. Uribe, Marcela R. Flegel, Willy A. TI KIR mRNA EXPRESSION IN PBMC AND ENRICHED NK CELLS ASSAYED BY QUANTITATIVE REAL-TIME PCR. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics (ASHI) CY NOV 17-21, 2013 CL Chicago, IL SP Amer Soc Histocompatibil & Immunogenet C1 [Yuan, Yao; Adams, Sharon D.; Uribe, Marcela R.; Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 EI 1879-1166 J9 HUM IMMUNOL JI Hum. Immunol. PY 2013 VL 74 SU S BP 119 EP 119 PG 1 WC Immunology SC Immunology GA 239YC UT WOS:000326060900161 ER PT J AU Lindberg, DAB AF Lindberg, Donald A. B. TI Native voices: native peoples' concepts of health and illness SO INTERNATIONAL JOURNAL OF CIRCUMPOLAR HEALTH LA English DT Article C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Lindberg, DAB (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. EM carson@nlm.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1239-9736 EI 2242-3982 J9 INT J CIRCUMPOL HEAL JI Int. J. Circumpolar Health PY 2013 VL 72 SU 1 BP 106 EP 107 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 235LZ UT WOS:000325721900017 ER PT J AU Pierce-Bulger, M AF Pierce-Bulger, Marilyn TI SIDS risk reduction: The Healthy Native Babies Project SO INTERNATIONAL JOURNAL OF CIRCUMPOLAR HEALTH LA English DT Article ID INFANT-DEATH-SYNDROME C1 NICHD Healthy Native Babies Project & Southcent F, Alaska Consultant, Anchorage, AK USA. RP Pierce-Bulger, M (reprint author), NICHD Healthy Native Babies Project & Southcent F, Alaska Consultant, Anchorage, AK USA. EM marilynp@pioneerconsulting.biz NR 4 TC 0 Z9 0 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1239-9736 EI 2242-3982 J9 INT J CIRCUMPOL HEAL JI Int. J. Circumpolar Health PY 2013 VL 72 SU 1 BP 393 EP 394 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 235LZ UT WOS:000325721900122 ER PT S AU Freeman, LA AF Freeman, Lita A. BE Freeman, LA TI Cloning Full-Length Transcripts and Transcript Variants Using 5 ' and 3 ' RACE SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE RT-PCR; RNA; cDNA; RACE; 5 ' UTR; 3 ' UTR; mRNA; Noncoding RNA; Cloning; Sequencing ID GENE-EXPRESSION; MESSENGER-RNA; CAP ANALYSIS; IDENTIFICATION; WIDESPREAD; COMPLEXITY; PROMOTERS AB Gene transcripts and transcript variants must be cloned to characterize gene function and regulation. However, obtaining full-length cDNAs with accurate sequences from the 5' end through to the 3' end can be challenging. Here we describe a reverse-transcriptase-based method for obtaining full-length cDNAs using the SMARTer ("Switching Mechanism At RNA Termini") RACE technology developed by Clontech. RNA is isolated from the tissue of interest and annealed to a primer (a modified oligo(dT) primer for polyA+ transcripts; random hexamers or a gene-specific primer for polyA-transcripts). A modi fied MMLV-reverse transcriptase uses the primer to initiate cDNA synthesis from RNA transcript(s) annealed to the primer and continues cDNA synthesis (reverse transcription) towards the 5' end of the transcript(s). Importantly, this reverse transcriptase possesses terminal transferase activity, so when it reaches the 5' end of a transcript it adds a 3-5 residue "tail" to the newly synthesized cDNA strand. Included in the reverse transcriptase reaction mix is an oligonucleotide containing a sequence tag as well as a terminal series of modi fied bases that anneal to the 3-5 residue tail on the newly synthesized cDNA. The reverse transcriptase proceeds from the end of the transcript onwards into the modi fied bases and the rest of the sequence-tagged oligo. The newly synthesized cDNA now has a sequence tag attached to it and can be used as a template for PCR, with one primer complementary to the sequence tag and the second primer specific to the gene of interest. The fragment can be cloned and sequenced or just sequenced directly. If high-quality, undegraded RNA is used, obtaining the true 5' end of a transcript is greatly enhanced. In combination with 3' RACE, full-length transcripts are easily cloned. This method provides sequence information on important regulatory regions, such as 5' and 3' UTRs and flanking regions, and is ideal for detecting transcript variants, including those with alternative transcriptional start sites, alternative splicing, and/or alternative polyadenylation. C1 NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Freeman, LA (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 25 TC 1 Z9 1 U1 1 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 3 EP 17 DI 10.1007/978-1-60327-369-5_1 D2 10.1007/978-1-60327-369-5 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300002 PM 23912980 ER PT S AU Freeman, LA AF Freeman, Lita A. BE Freeman, LA TI Lipoproteins and Cardiovascular Disease Methods and Protocols Preface SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter C1 NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Freeman, LA (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP V EP V D2 10.1007/978-1-60327-369-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300001 ER PT S AU Raghavachari, N AF Raghavachari, Nalini BE Freeman, LA TI Microarray Technology: Basic Methodology and Application in Clinical Research for Biomarker Discovery in Vascular Diseases SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Microarrays; Amplification; Globins; Whole blood; PBMC; Biomarkers; Gene chips; Affymetrix; Hybridization; Gene expression ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PROFILES; SICKLE-CELL-DISEASE; BLOOD-SAMPLES; RNA AB Microarray technology is a novel tool in molecular biology, capable of quantitating hundreds or thousands of gene transcripts from a given cell or tissue sample simultaneously. A microarray has thousands of DNA fragments or oligonucleotides of known sequence arrayed in a known sequence of rows and columns on a chip. Hybridization of sample RNA that has been reverse-transcribed and labeled enables the detection and quantitation of specific transcripts. The ability to quantitate systemic gene changes in normal vs. diseased states has led to significant progress in many biomedical disciplines, including lipoprotein and atherosclerosis research, and can be used for discovery of diagnostic/prognostic and predictive biomarkers and to test the effectiveness of potential therapeutic agents. The design and analysis of microarray experiments present some unique problems to clinical medicine due to inherent issues related to biological sample procurement and processing, sensitivity and specificity of the assay, reliability and reproducibility of data, and applicability of the technology in multicenter-based clinical studies. This chapter will provide details on the methodologies that address these problems for successful microarray-based transcriptome analysis of tissues, whole blood, cell subpopulations, and cultured cells. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Raghavachari, N (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 13 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 47 EP 84 DI 10.1007/978-1-60327-369-5_3 D2 10.1007/978-1-60327-369-5 PG 38 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300004 PM 23912982 ER PT S AU Freeman, LA AF Freeman, Lita A. BE Freeman, LA TI Northern Analysis of Gene Expression SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE RNA; Gene expression; Hybridization; Transcription; Alternative splicing; Alternative promoters; Lipoproteins ID ATHEROSCLEROSIS; OVEREXPRESSION; CHOLESTEROL; LIPOPROTEINS; ACCUMULATION; MICE AB Northern analysis detects and quantitates full-length RNA transcripts by hybridizing a labeled sequence-specific probe to RNA fractionated by size and blotted onto a membrane. The first step in Northern analysis is RNA extraction from the tissue(s) of interest, followed by RNA denaturation and electrophoresis to separate all RNA transcripts in the tissue by size. The size-fractionated RNA is then transferred (blotted) onto a membrane. The membrane is incubated with a labeled probe complementary to the sequence of interest. Stringent washing removes nonspecifically bound probe and leaves labeled probe bound specifically to the transcript(s) of interest on the membrane. Northern analysis provides information on gene transcript sizes and abundance and the presence of alternative splice variants or transcription initiation sites. Northern analysis can also confirm the presence or absence of specific exons within a given transcript. The method is medium throughput, as multiple samples can be analyzed side by side with relatively little effort. Finally, any potential PCR amplification artifacts are completely avoided using this methodology. Northern analysis offers a unique view of a gene's transcripts and provides novel insight into gene expression. C1 NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Freeman, LA (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 13 TC 1 Z9 1 U1 4 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 85 EP 121 DI 10.1007/978-1-60327-369-5_4 D2 10.1007/978-1-60327-369-5 PG 37 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300005 PM 23912983 ER PT S AU Youngblood, V Taylor, JG AF Youngblood, Victoria Taylor, James G. BE Freeman, LA TI Sequencing PCR-Amplified DNA in Lipoprotein and Cardiovascular Disease Research SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE PCR; DNA sequencing; Automated Sanger sequencing; Single-nucleotide variant; Mutation; Genetic variant; Automation ID COLORECTAL CANCERS; HUMAN BREAST; HUMAN GENOME; POLYMORPHISMS; HDL AB The discovery of novel genetic variants and mutations in lipoprotein and cardiovascular disease research requires DNA sequencing. Large-scale genomics facilities will increasingly accomplish this with a combination of "next-generation" DNA sequencing methodologies. However, laboratories with limited access to these emerging technologies can still support focused genomic studies with the use of automated Sanger sequencing. Here, we describe two robust methods for medium-throughput DNA sequencing from PCR-amplified fragments of genomic DNA. C1 [Youngblood, Victoria; Taylor, James G.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. RP Youngblood, V (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS NR 17 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 139 EP 155 DI 10.1007/978-1-60327-369-5_6 D2 10.1007/978-1-60327-369-5 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300007 PM 23912985 ER PT S AU Diaw, L Youngblood, V Taylor, JG AF Diaw, Lena Youngblood, Victoria Taylor, James G. BE Freeman, LA TI Introduction to Next-Generation Nucleic Acid Sequencing in Cardiovascular Disease Research SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Next-generation sequencing; DNA; Single nucleotide polymorphism; Mutation; Genetic variant; Gene expression ID MYELOID-LEUKEMIA GENOME; SINGLE DNA-MOLECULES; IDENTIFICATION; NANOPORE; ATTACHMENT; MUTATIONS; HDL AB The identification of new genomic paradigms in lipoprotein and cardiovascular diseases will be accelerated by the application of the recent technological advances in nucleic acid sequencing. Presently, large-scale genomics facilities are equipped to accomplish this objective with a combination of "next-generation" DNA sequencing chemistries, largely focused on assembling massively parallel sequence reads corresponding to complete genes, entire exomes, or whole genomes from populations of individuals. In the future, individual laboratories will also use this emerging technology for focused genomic studies with the use of a combination of next-generation sequencing and automated Sanger sequencing. In particular, next-generation sequencing will play an increasingly important role when applied to chromatin immunoprecipitation, RNA transcriptome analysis, and studies of human genetic variation and mutation in carefully phenotyped healthy and disease populations. In this chapter, a brief overview of recent technological advances in next-generation nucleic acid sequencing is presented, with emphasis on practical application to clinical studies in cardiovascular diseases. C1 [Diaw, Lena; Youngblood, Victoria; Taylor, James G.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. RP Diaw, L (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Taylor, James/0000-0002-4421-1809 NR 47 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 157 EP 179 DI 10.1007/978-1-60327-369-5_7 D2 10.1007/978-1-60327-369-5 PG 23 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300008 PM 23912986 ER PT S AU Liu, CY AF Liu, Chengyu BE Freeman, LA TI Strategies for Designing Transgenic DNA Constructs SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Transgene; DNA construct; Position effects; BAC; Plasmid; Overexpression; Insulator; siRNA; Recombinase; Cre-loxP; FLP-FRT; Conditional; Inducible; Animal model ID BACTERIAL ARTIFICIAL CHROMOSOMES; SITE-SPECIFIC RECOMBINATION; GREEN FLUORESCENT PROTEIN; GENE-EXPRESSION; MAMMALIAN-CELLS; CRE RECOMBINASE; NERVOUS-SYSTEM; GERMLINE TRANSMISSION; ESCHERICHIA-COLI; RNA INTERFERENCE AB Generation and characterization of transgenic mice are important elements of biomedical research. In recent years, transgenic technology has become more versatile and sophisticated, mainly because of the incorporation of recombinase-mediated conditional expression and targeted insertion, site-specific endonuclease-mediated genome editing, siRNA-mediated gene knockdown, various inducible gene expression systems, and fluorescent protein marking and tracking techniques. Site-specific recombinases (such as PhiC31) and engineered endonucleases (such as ZFN and Talen) have significantly enhanced our ability to target transgenes into specific genomic loci, but currently a great majority of transgenic mouse lines are continuingly being created using the conventional random insertion method. A major challenge for using this conventional method is that the genomic environment at the integration site has a substantial influence on the expression of the transgene. Although our understanding of such chromosomal position effects and our means to combat them are still primitive, adhering to some general guidelines can significantly increase the odds of successful transgene expression. This chapter first discusses the major problems associated with transgene expression, and then describes some of the principles for using plasmid and bacterial artificial chromosomes (BACs) for generating transgenic constructs. Finally, the strategies for conducting each of the major types of transgenic research are discussed, including gene overexpression, promoter characterization, cell-lineage tracing, mutant complementation, expression of double or multiple transgenes, siRNA knockdown, and conditional and inducible systems. C1 NHLBI, iPSC & Genome Engn Core, NIH, Bethesda, MD 20892 USA. RP Liu, CY (reprint author), NHLBI, iPSC & Genome Engn Core, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIC HL005907-04, ZIC HL005907-02, Z99 HL999999, ZIC HL005907-05, ZIC HL005907-03] NR 81 TC 3 Z9 3 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 183 EP 201 DI 10.1007/978-1-60327-369-5_8 D2 10.1007/978-1-60327-369-5 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300009 PM 23912987 ER PT S AU Liu, CY Du, YB Xie, W Gui, CY AF Liu, Chengyu Du, Yubin Xie, Wen Gui, Changyun BE Freeman, LA TI Purification of Plasmid and BAC Transgenic DNA Constructs SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Transgenic; BAC; Plasmid; DNA purification; Microinjection ID MOUSE MODELS; MICE; ATHEROSCLEROSIS; EXPRESSION AB Pronuclear microinjection is the most used method for generating transgenic mice. The quality of DNA to be microinjected is a key determinant of the success rate of this method. DNA purity is a critical factor because trace amounts of many substances, when microinjected into the pronucleus of the fertilized egg, can kill or prevent the further development of the embryo. Avoiding all contaminants is not a trivial issue, because most transgenic fragments need to be purified from agarose gels. Small particles and viscous materials in the DNA solution can also dramatically reduce the efficiency of microinjection because they tend to clog the injection needles. DNA shearing or breakage during purification and microinjection is also a potential problem, particularly when linearized bacterial artificial chromosomes (BAC) DNAs are used. The overall quantity and the final DNA concentration are also important considerations, because egg pronuclei are very sensitive to the amount of foreign DNA. In this chapter, we first discuss the general guidelines and cautions for preparing microinjection-quality DNA, and then describe in detail two protocols, one for gel purification of transgenic fragments from plasmid vectors and the other for isolating high-quality BAC DNA from bacteria. C1 [Liu, Chengyu; Du, Yubin; Xie, Wen; Gui, Changyun] NHLBI, iPSC & Genome Engn Core, NIH, Bethesda, MD 20892 USA. RP Liu, CY (reprint author), NHLBI, iPSC & Genome Engn Core, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIC HL005907-03, Z99 HL999999, ZIC HL005907-04, ZIC HL005907-02, ZIC HL005907-05] NR 10 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 203 EP 215 DI 10.1007/978-1-60327-369-5_9 D2 10.1007/978-1-60327-369-5 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300010 PM 23912988 ER PT S AU Liu, CY Xie, W Gui, CY Du, YB AF Liu, Chengyu Xie, Wen Gui, Changyun Du, Yubin BE Freeman, LA TI Pronuclear Microinjection and Oviduct Transfer Procedures for Transgenic Mouse Production SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Microinjection; Pronuclear; Transgenic; Embryo transfer ID BETA-GLOBIN GENE; LENTIVIRAL VECTORS; GERM-LINE; EXPRESSION; TRANSMISSION; INTEGRATION; INJECTION; ZYGOTES; EGGS; MICE AB Transgenic mouse technology is a powerful method for studying gene function and creating animal models of human diseases. Currently, the most widely used method for generating transgenic mice is the pronuclear microinjection method. In this method, a transgenic DNA construct is physically microinjected into the pronucleus of a fertilized egg. The injected embryos are subsequently transferred into the oviducts of pseudopregnant surrogate mothers. A portion of the mice born to these surrogate mothers will harbor the injected foreign gene in their genomes. These procedures are technically challenging for most biomedical researchers. Inappropriate experimental procedures or suboptimal equipment setup can substantially reduce the efficiency of transgenic mouse production. In this chapter, we describe in detail our microinjection setup as well as our standard microinjection and oviduct transfer procedures. C1 [Liu, Chengyu; Xie, Wen; Gui, Changyun; Du, Yubin] NHLBI, iPSC & Genome Engn Core, NIH, Bethesda, MD 20892 USA. RP Liu, CY (reprint author), NHLBI, iPSC & Genome Engn Core, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIC HL005907-03, ZIC HL005907-05, Z99 HL999999, ZIC HL005907-02, ZIC HL005907-04] NR 10 TC 8 Z9 8 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 217 EP 232 DI 10.1007/978-1-60327-369-5_10 D2 10.1007/978-1-60327-369-5 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300011 PM 23912989 ER PT S AU Vaisman, BL AF Vaisman, Boris L. BE Freeman, LA TI Genotyping of Transgenic Animals by Real-Time Quantitative PCR with TaqMan Probes SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Genotype or genotyping; Real-time PCR; DNA isolation; Transgenes; Calibration standards AB Real-time quantitative PCR (qPCR) is a fast, sensitive, specific, and quantitative method for genotyping transgenic animals. Accurate quantitation of the number of transgenes helps to identify founders and to create and maintain pure lines of transgenic mice, thus reducing experimental variability. Here we describe an accurate method of genotyping using real-time quantitative PCR with primers and MGB TaqMan probes from Life Technologies. The first step in quantitating copy number is isolation of genomic DNA. To accurately compare the copies per genome (c/g) of a transgene in different mice, genomic DNA must be prepared by the same method for all the mice, with sample DNA and calibration standards dissolved in the same buffer. This chapter describes several "tried and true" methods, including an automatic system that isolates 16 samples at once in just 35-45 min, yielding DNA of excellent quality. Next, genomic DNA must be quantitated accurately so that similar amounts of DNA are added to each well. A fluorescent assay that is selective for dsDNA over RNA circumvents interference from RNA contamination and ensures more accurate DNA quantitation than A(260) measurements. It is also very important to use appropriate calibration standards for accurate quantitation of transgene copy number. The best calibrator is the DNA fragment used for microinjection, mixed with normal mouse DNA in such a way that the transgene is present in a range of concentrations spanning the expected copy number in the transgenic mice. This chapter provides guidelines and sample calculations for preparing calibration standards that will accurately reflect the number of transgenes in the mice being tested. Finally, guidelines for preparing primers and TaqMan probes and techniques to prepare and run a 384-well plate smoothly and without errors are presented. C1 NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Vaisman, BL (reprint author), NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 233 EP 251 DI 10.1007/978-1-60327-369-5_11 D2 10.1007/978-1-60327-369-5 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300012 PM 23912990 ER PT S AU Vaisman, BL Remaley, AT AF Vaisman, Boris L. Remaley, Alan T. BE Freeman, LA TI Measurement of Lecithin-Cholesterol Acyltransferase Activity with the Use of a Peptide-Proteoliposome Substrate SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE LCAT activity; Proteoliposomes storage; Apolipoprotein A-I mimetic peptides ID LECITHINCHOLESTEROL ACYLTRANSFERASE; LCAT DEFICIENCY; ATHEROSCLEROSIS; TRANSPORT; HDL AB Lecithin-cholesterol acyltransferase (LCAT) is the major enzyme responsible for the esterification of free cholesterol on plasma lipoproteins, which is a key step in the reverse cholesterol transport pathway. The measurement of plasma LCAT activity not only is important in the diagnosis of patients with genetic or acquired LCAT deficiency but is also valuable in calculating cardiovascular risk, as well as in research studies of lipoprotein metabolism. In this chapter, we describe a convenient LCAT assay based on the use of an apoA-I mimetic peptide. The proteoliposome substrate used in this assay for LCAT is easily made with the peptide and can be stored by deep freezing without significant loss of activity. C1 [Vaisman, Boris L.] NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA. [Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. RP Vaisman, BL (reprint author), NHLBI, Lipoprot Metab Sect, Cardiovasc Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 343 EP 352 DI 10.1007/978-1-60327-369-5_16 D2 10.1007/978-1-60327-369-5 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300017 PM 23912995 ER PT S AU Freeman, LA AF Freeman, Lita A. BE Freeman, LA TI Native-Native 2D Gel Electrophoresis for HDL Subpopulation Analysis SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE HDL subpopulations; Apolipoprotein A-I; alpha-Particles; beta-Particles; HDL particles; 2D gel electrophoresis; Lipoproteins ID CORONARY-HEART-DISEASE; ESTER TRANSFER PROTEIN; DEFICIENCY; LIPOPROTEINS; INHIBITION AB High-density lipoproteins (HDLs) are a heterogeneous mixture of lipoprotein particles with densities ranging from 1.063 to 1.021 g/ml. The various lipoprotein particles present in HDL have not yet been completely characterized, largely due to methodological difficulties. Asztalos and Schaefer have developed a powerful native-native 2D gel method to analyze HDL subpopulations with high resolution. In this technique, native HDL particles present in plasma are separated electrophoretically by charge in the first dimension and then by size in the second dimension. The native particles in the gel are then transferred onto a membrane using traditional Western blotting techniques. After probing the membrane with, for example, apoA-I antibodies, subpopulations of HDL particles containing apoA-I can be visualized. Traditionally, midi-sized native gels are poured manually in the laboratory and running, blotting, and probing the gels is a tricky and laborious procedure that involves the use of I-125-labeled antibodies. Here we present a streamlined native-native 2D gel electrophoresis and blotting method using minigels. Traditional antibody incubation and chemiluminescent methods can be used for detection and use of I-125 is not required. This update of the Asztalos and Schaefer native-native 2D gel protocol renders the procedure more accessible to the nonspecialist. C1 NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Freeman, LA (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 17 TC 8 Z9 8 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 353 EP 367 DI 10.1007/978-1-60327-369-5_17 D2 10.1007/978-1-60327-369-5 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300018 PM 23912996 ER PT S AU Freeman, LA AF Freeman, Lita A. BE Freeman, LA TI Western Blots SO LIPOPROTEINS AND CARDIOVASCULAR DISEASE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE HDL Western; LDL Western; Apolipoprotein Western; apoB-100 Western ID SEPARATION AB Western analysis of apolipoproteins, lipoproteins, and proteins involved in lipoprotein metabolism can be challenging due to their size, hydrophobic nature, and, in some cases, low abundance. Here we describe a Western blotting method that has been used successfully for many proteins involved in lipoprotein metabolism, as well as intact LDL or HDL particles. Proteins or lipoprotein particles separated by gel electrophoresis are transferred to a PVDF membrane in a Hoefer TE22 transfer tank with Tris-Glycine-SDS-Methanol transfer buffer. The membrane is blocked with 3 % BSA/5 % milk to prevent nonspecific binding of antibody to the membrane and is then incubated with primary antibody that binds specifically to the protein of interest. After washing away unbound primary antibody, the membrane is then incubated with an HRP-labeled secondary antibody that binds primary antibody. After washing away unbound secondary antibody, the membrane is then incubated with a substrate for HRP, generating a chemiluminescent signal at the location of the protein of interest. The protein is visualized by exposing the membrane to an autoradiography film or an imaging device. Information on the use of several human antibodies, including apoA-I, A-II, apoB, apoC-II, apoC-III, apoD, apoL1, apoM, PON1, SAA, ABCA1, nitrotyrosine, and LCAT, is provided. This method can be used for Western blotting of virtually any protein as well as native lipoprotein particles. C1 NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Freeman, LA (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 4 Z9 4 U1 1 U2 14 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-369-5; 978-1-60327-368-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1027 BP 369 EP 385 DI 10.1007/978-1-60327-369-5_18 D2 10.1007/978-1-60327-369-5 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BHJ32 UT WOS:000325615300019 PM 23912997 ER PT S AU Wang, E Bedognetti, D Tomei, S Marincola, FM AF Wang, Ena Bedognetti, Davide Tomei, Sara Marincola, Francesco M. BE Finn, OJ Schuler, G TI Common pathways to tumor rejection SO RENAISSANCE OF CANCER IMMUNOTHERAPY SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 7th International Cancer Vaccine Symposium on Renaissance of Cancer Immunotherapy (ICVS) CY SEP 09-11, 2012 CL Florence, ITALY SP Hasumi Int Res Fdn DE cancer immunotherapy; melanoma; rejection; autoimmunity ID IMMUNE RESPONSIVENESS; MELANOMA METASTASES; CANCER; IMMUNOTHERAPY; INTERFERON; THERAPY; DISEASE AB The control of tumor growth by the host's immunosurveillance is centered on the activation of interferon (IFN) pathways. In particular, direct study of tumors by various groups has uncovered an IFN-gamma-related signature whose presence is consistently associated with better prognosis, predisposition to respond to immunotherapy, and, in its extrememanifestation, the acute phases of tumor rejection. Together, and related to the IFN-gamma-associated signature, a cluster of genes are coordinately expressed that we refer to as the immunologic constant of rejection (ICR). Activation of ICR components is observed in all forms of immune-mediated, tissue-specific destruction, including autoimmunity, allograft rejection, graft-versus-host disease, and killing of affected cells during the acute phases of infection that leads to clearance of pathogens. Thus, tumor rejection is a facet of a general and conserved mechanism that favors (tumor rejection, clearance of pathogen) or encumbers (graft rejection, autoimmunity) the organism. Here, we summarize progress in the understanding of its genesis, outline the difficulties, and propose a strategy for understanding the causes of tumor rejection. C1 [Wang, Ena; Bedognetti, Davide; Tomei, Sara; Marincola, Francesco M.] NIH, Clin Ctr & Trans NIH Ctr Human Immunol CHI, Dept Transfus Med, IDIS, Bethesda, MD USA. [Bedognetti, Davide] Univ Genoa, Dept Oncol Biol Genet DOBIG, Genoa, Italy. [Bedognetti, Davide] Natl Inst Canc Res, Genoa, Italy. [Bedognetti, Davide] Univ Genoa, Dept Internal Med DiMI, Genoa, Italy. [Tomei, Sara; Marincola, Francesco M.] Sidra Med & Res Ctr, Chief Res Off, Doha, Qatar. RP Marincola, FM (reprint author), Sidra Med & Res Ctr, POB 26999, Doha, Qatar. EM fmarincola@mail.cc.nih.gov OI Bedognetti, Davide/0000-0002-5857-773X NR 22 TC 10 Z9 10 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-895-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1284 BP 75 EP 79 DI 10.1111/nyas.12063 PG 5 WC Oncology; Immunology SC Oncology; Immunology GA BHO59 UT WOS:000326108000014 PM 23651198 ER PT S AU Fielding, RA Gunstad, J Gustafson, DR Heymsfield, SB Kral, JG Launer, LJ Penninger, J Phillips, DIW Scarmeas, N AF Fielding, Roger A. Gunstad, John Gustafson, Deborah R. Heymsfield, Steven B. Kral, John G. Launer, Lenore J. Penninger, Josef Phillips, David I. W. Scarmeas, Nikolaos GP Annals New York Acad Sci TI The paradox of overnutrition in aging and cognition SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE overnutrition; obesity; cognitive decline; Alzheimer's disease; sarcopenia ID AGE-RELATED DISEASE; ALZHEIMERS-DISEASE; OBESITY; WOMEN; RISK AB Populations of many countries are becoming increasingly overweight and obese, driven largely by excessive calorie intake and reduced physical activity; greater body mass is accompanied by epidemic levels of comorbid metabolic diseases. At the same time, individuals are living longer. The combination of aging and the increased prevalence of metabolic disease is associated with increases in aging-related comorbid diseases such as Alzheimer's disease, cerebrovascular dementia, and sarcopenia. Here, correlative and causal links between diseases of overnutrition and diseases of aging and cognition are explored. C1 [Fielding, Roger A.] Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA USA. [Gunstad, John] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Gustafson, Deborah R.] Suny Downstate Med Ctr, Dept Neurol, Brooklyn, NY 11203 USA. [Gustafson, Deborah R.] Univ Gothenburg, Neuropsychiat Epidemiol Res Unit, Gothenburg, Sweden. [Heymsfield, Steven B.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Kral, John G.] Suny Downstate Med Ctr, Dept Surg & Med, Brooklyn, NY 11203 USA. [Launer, Lenore J.] Natl Inst Aging, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD USA. [Penninger, Josef] Austrian Acad Sci, Inst Mol Biotechnol, A-1010 Vienna, Austria. [Phillips, David I. W.] Univ Southampton, Lifecourse Epidemiol Unit, Southampton, Hants, England. [Scarmeas, Nikolaos] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. [Scarmeas, Nikolaos] Univ Athens, Athens, Greece. RP Kral, JG (reprint author), Suny Downstate Med Ctr, Dept Surg, 450 Clarkson Ave,Box 40, Brooklyn, NY 11203 USA. EM jkral@downstate.edu RI Penninger, Josef/I-6860-2013 OI Penninger, Josef/0000-0002-8194-3777 FU Intramural NIH HHS [Z01 AG007420-01] NR 17 TC 8 Z9 8 U1 1 U2 16 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-930-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1287 BP 31 EP 43 DI 10.1111/nyas.12138 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHL82 UT WOS:000325809400003 PM 23682739 ER PT S AU Christakos, S Hewison, M Gardner, DG Wagner, CL Sergeev, IN Rutten, E Pittas, AG Boland, R Ferrucci, L Bikle, DD AF Christakos, Sylvia Hewison, Martin Gardner, David G. Wagner, Carol L. Sergeev, Igor N. Rutten, Erica Pittas, Anastassios G. Boland, Ricardo Ferrucci, Luigi Bikle, Daniel D. GP Annals New York Acad Sci TI Vitamin D: beyond bone SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE vitamin D; cancer; immunity; pregnancy; obesity; diabetes; pulmonary disease; muscle; aging; cognitive function ID OBSTRUCTIVE PULMONARY-DISEASE; SERUM 25-HYDROXYVITAMIN D; D-RECEPTOR; 1,25-DIHYDROXYVITAMIN D-3; SKELETAL-MUSCLE; D SUPPLEMENTATION; DOUBLE-BLIND; D DEFICIENCY; CALCIUM; WOMEN AB In recent years, vitamin D has been received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries and the identification of extraskeletal effects of vitamin D, suggesting unexpected benefits of vitamin D in health and disease, beyond bone health. The possibility of extraskeletal effects of vitamin D was first noted with the discovery of the vitamin D receptor (VDR) in tissues and cells that are not involved in maintaining mineral homeostasis and bone health, including skin, placenta, pancreas, breast, prostate and colon cancer cells, and activated T cells. However, the biological significance of the expression of the VDR in different tissues is not fully understood, and the role of vitamin D in extraskeletal health has been a matter of debate. This report summarizes recent research on the roles for vitamin D in cancer, immunity and autoimmune diseases, cardiovascular and respiratory health, pregnancy, obesity, erythropoiesis, diabetes, muscle function, and aging. C1 [Christakos, Sylvia] UMDNJ New Jersey, Sch Med, Dept Biochem & Mol Biol, Newark, NJ USA. [Hewison, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthopaed Surg, Los Angeles, CA 90095 USA. [Gardner, David G.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Gardner, David G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Wagner, Carol L.] Med Univ S Carolina, Dept Pediat, Div Neonatol, Charleston, SC 29425 USA. [Sergeev, Igor N.] S Dakota State Univ, Dept Hlth & Nutrit Sci, Brookings, SD 57007 USA. [Rutten, Erica] Ciro, Ctr Expertise Chron Organ Failure, Horn, Netherlands. [Pittas, Anastassios G.] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA. [Boland, Ricardo] Univ Nacl Sur, Dept Biol Bioquim & Farm, RA-8000 Bahia Blanca, Buenos Aires, Argentina. [Ferrucci, Luigi] Natl Inst Hlth, Natl Inst Aging, Longitudinal Studies Sect, Baltimore, MD USA. [Bikle, Daniel D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bikle, Daniel D.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Bikle, Daniel D.] VA Med Ctr, San Francisco, CA USA. RP Christakos, S (reprint author), UMDNJ New Jersey, Sch Med, Dept Biochem & Mol Biol, Newark, NJ USA. EM annals@nyas.org FU Abbott Nutrition Health Institute FX The conference "Vitamin D: Beyond Bone," presented by the Sackler Institute for Nutrition Science at the New York Academy of Sciences, was sponsored by an unrestricted educational grant from Abbott Nutrition Health Institute. NR 59 TC 78 Z9 82 U1 2 U2 29 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-930-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1287 BP 45 EP 58 DI 10.1111/nyas.12129 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHL82 UT WOS:000325809400004 PM 23682710 ER PT J AU Graubard, BI Sirken, MG AF Graubard, Barry I. Sirken, Monroe G. TI Estimating Sibling Recurrence Risk in Population Sample Surveys SO HUMAN HEREDITY LA English DT Article DE Counting rule; Network estimation; Sampling errors; Diabetes ID GENETICALLY COMPLEX TRAITS; AFFECTED RELATIVE PAIRS; LINKAGE STRATEGIES; ASCERTAINMENT BIAS; PARAMETERS AB Background/Aims: Sibling recurrence risk (SRR) is a measure of familial aggregation of a disease and is often used in family-based studies in genetic epidemiology to indicate the existence of possible genes conferring susceptibility of disease. Estimating SRR requires information about the disease status of sibships of families with two or more siblings where at least one is affected. Since family-based studies are not usually random samples, estimates of SRR derived from these studies may be biased. Network sampling used in survey research offers a way to ascertain the disease status of sibships from interviewed individuals in household survey samples, in order to obtain (approximately) unbiased estimators of SRR and its related SRR ratio (SRR divided by the prevalence of disease). Methods: Two methods of ascertaining sibships of affected families are considered: in one method the siblings' affected status is reported by an individual, regardless of the individual's affected status, and in the other method only affected individuals can report their siblings' affected status. Network estimators of SRR and SRR ratio and estimators of their standard errors are provided. Results: Reported diabetes for siblings from the 1976 National Health Interview is used to illustrate the estimation methods. The SRR ratio for diabetes among living siblings was 5.79% [relative standard error (RSE) = 5.12%], and for living or deceased siblings, it was 7.66% (RSE = 3.76%). Conclusions: Network sampling estimators can provide population estimates of SRR and SRR ratio for diseases such as diabetes. copyright (C) 2013 S . Karger AG, Basel C1 [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Sirken, Monroe G.] Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Graubard, BI (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,7-E140, Bethesda, MD 20892 USA. EM graubarb@mail.nih.gov NR 20 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2013 VL 76 IS 1 BP 18 EP 27 DI 10.1159/000351737 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 239FX UT WOS:000326009100003 PM 23921823 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI Epiphany in a Hamburger SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 1 EP 10 PG 10 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700003 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI Paul Lauterbur and the Invention of MRI Foreword SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Editorial Material; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP VII EP IX PG 3 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700001 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI Portrait of a Scientist as a Young Man SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 11 EP 25 PG 15 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700004 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI Paul Lauterbur and the Invention of MRI Prologue SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Editorial Material; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP XIII EP + PG 16 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700002 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI Study, Work, and War SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 27 EP 45 PG 19 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700005 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI Early Breakthroughs SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 47 EP 65 PG 19 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700006 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI The 1960s: Stony Brook, Stanford, and Spectrometers SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 67 EP 84 PG 18 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700007 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI The First Fruitful Weeks SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 85 EP 106 PG 22 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700008 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI The Worldwide Laboratory SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 107 EP 124 PG 18 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700009 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI Baby Grows Up SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 125 EP 151 PG 27 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700010 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI Among the Corn Fields SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 153 EP 178 PG 26 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700011 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI The End and the Beginning SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 179 EP 196 PG 18 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700012 ER PT B AU Becker, ED AF Becker, Edwin D. BA Dawson, MJ BF Dawson, MJ TI Paul Lauterbur and the Invention of MRI Epilogue SO PAUL LAUTERBUR AND THE INVENTION OF MRI LA English DT Editorial Material; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31670-5; 978-0-262-01921-7 PY 2013 BP 197 EP 200 PG 4 WC History & Philosophy Of Science SC History & Philosophy of Science GA BHM21 UT WOS:000325879700013 ER PT S AU Singh, R Liu, Y Kango-Singh, M Nevo, E AF Singh, Ram Liu, Ying Kango-Singh, Madhuri Nevo, Eviatar BE Turksen, K TI Genetic, Immunofluorescence Labeling, and In Situ Hybridization Techniques in Identification of Stem Cells in Male and Female Germline Niches SO STEM CELL NICHE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Drosophila; Testis; Ovary; Germline stem cells; Niches ID SOMATIC SUPPORT CELLS; DROSOPHILA TESTIS; SELF-RENEWAL; JAK-STAT; TUMOR-SUPPRESSOR; SCREEN REVEALS; MAINTENANCE; DIFFERENTIATION; OVARY; DIVISION AB Stem cells have an enormous capacity of self-renewal, as well as the ability to differentiate into specialized cell types. Proper control of these two properties of stem cells is crucial for animal development, growth control, and reproduction. Germline stem cells (GSCs) are a self-renewing population of germ cells, which generate haploid gametes (sperms or oocyte) that transmit genetic information from generation to generation. In Drosophila testis and ovary, GSCs are anchored around the niche cells. The cap cells cluster in females and hub cells in males act as a niche to control GSC behavior. With highly sophisticated genetic techniques in Drosophila, tremendous progress has been made in understanding the interactions between stem cells and niches at cellular and molecular levels. Here, we provide details of genetic, immunofluorescence labeling, and in situ hybridization techniques in identification and characterization of stem cells in Drosophila male and female germline niches. C1 [Singh, Ram; Liu, Ying] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. [Kango-Singh, Madhuri] Univ Dayton, Dept Biol, Ctr Tissue Regenerat & Engn Dayton TREND, Dayton, OH 45469 USA. [Nevo, Eviatar] Univ Haifa, Inst Evolut, IL-31999 Haifa, Israel. RP Singh, R (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. RI Liu, Ying /K-8883-2016; Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X NR 61 TC 0 Z9 0 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-507-1; 978-1-62703-508-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1035 BP 9 EP 23 DI 10.1007/978-1-62703-508-8_2 D2 10.1007/978-1-62703-508-8 PG 15 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA BHK49 UT WOS:000325716600003 ER PT S AU Mishra, PK Kuypers, NJ Singh, R Leiberh, ND Chavali, V Tyagi, SC AF Mishra, Paras Kumar Kuypers, Nicholas John Singh, Ram Leiberh, Noel Diaz Chavali, Vishalakshi Tyagi, Suresh C. BE Turksen, K TI Cardiac Stem Cell Niche, MMP9, and Culture and Differentiation of Embryonic Stem Cells SO STEM CELL NICHE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Stem cell; MMP9; TIMP-4; Differentiation; Extracellular matrix; Cardiomyocytes ID ACUTE MYOCARDIAL-INFARCTION; SUBSTRATE ELASTICITY; PROGENITOR CELLS; HEMATOPOIETIC STEM; HEART; THERAPY; CARDIOMYOCYTES; PROLIFERATION; DYSFUNCTION; ABLATION AB Embryonic stem cells (ESC) are totipotent, self-renewing, and clonogenic, having potential to differentiate into a wide variety of cell types. Due to regenerative capability, it has tremendous potential for treating myocardial infarction (death of myocardial tissue) and type 1 diabetes (death of pancreatic beta cells). Understanding the components regulating ESC differentiation is the key to unlock the regenerative potential of ESC-based therapies. Both the stiffness of extracellular matrix (ECM) and surrounding niche/microenvironment play pivotal roles in ESC differentiation. Matrix metalloproteinase-9 (MMP9) induces fibrosis that causes stiffness of the ECM and impairs differentiation of cardiac stem cells into cardiomyocytes. Here, we describe the method of ESC culture and differentiation, and the expression of MMP9 and its inhibitor, tissue inhibitor of metalloproteinase-4 (TIMP4) in differentiating ESC. C1 [Mishra, Paras Kumar] Univ Nebraska Med Ctr, Dept Cellular & Integrat Physiol, Omaha, NE USA. [Kuypers, Nicholas John] Univ Louisville, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA. [Singh, Ram] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. [Leiberh, Noel Diaz; Tyagi, Suresh C.] Univ Louisville, Sch Med, Dept Physiol & Biophys, Louisville, KY 40292 USA. [Chavali, Vishalakshi] Univ Nebraska Med Ctr, Omaha, NE USA. RP Mishra, PK (reprint author), Univ Nebraska Med Ctr, Dept Cellular & Integrat Physiol, Omaha, NE USA. RI Singh, Shree Ram/B-7614-2008; OI Singh, Shree Ram/0000-0001-6545-583X; Mishra, Paras Kumar/0000-0002-7810-9239 FU Intramural NIH HHS [Z99 CA999999]; NHLBI NIH HHS [HL-108621, HL-74185, HL113281, R01 HL074185, R01 HL108621, R01 HL113281] NR 35 TC 4 Z9 4 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-507-1; 978-1-62703-508-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1035 BP 153 EP 163 DI 10.1007/978-1-62703-508-8_13 D2 10.1007/978-1-62703-508-8 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA BHK49 UT WOS:000325716600014 PM 23959989 ER PT S AU Veech, RL AF Veech, Richard L. GP Annals New York Acad Sci TI Ketone esters increase brown fat in mice and overcome insulin resistance in other tissues in the rat SO UNDERSTANDING ADIPOGENESIS AND FUNCTIONS OF BROWN FAT SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE ketones; insulin resistance; mitochondria; Alzheimer's disease ID ADIPOSE-TISSUE; ALZHEIMERS-DISEASE; KETOGENIC DIET; PYRUVATE-DEHYDROGENASE; UNCOUPLING PROTEIN-1; BETA-HYDROXYBUTYRATE; COGNITIVE DECLINE; GENETIC RISK; MOUSE MODEL; METABOLISM AB Brown adipose tissue (BAT) is classically activated by sympathetic nervous stimulation resulting from exposure to cold. Feeding a high-fat diet also induces development of brown fat, but is decreased by caloric restriction. Blood ketone bodies, which function as alternative energy substrates to glucose, are increased during caloric restriction. Here we discuss the unexpected observation that feeding an ester of ketone bodies to the mouse, which increases blood ketone body concentrations, results in an activation of brown fat. The mechanism of this activation of brown fat is similar to that occurring from cold exposure in that cyclic adenosine monophosphate (AMP) levels are increased as are levels of the transcription factor cyclic AMP-responsive element-binding protein, which is also increased by ketone ester feeding. Other effects of feeding ketone esters, in addition to their ability to induce brown fat, are discussed such as their ability to overcome certain aspects of insulin resistance and to ameliorate the accumulation of amyloid and phosphorylated tau protein in brain, and improve cognitive function, in a triple transgenic mouse model of Alzheimer's disease. C1 NIAAA, Lab Metab Control, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Veech, RL (reprint author), NIAAA, Lab Metab Control, NIH, Dept Hlth & Human Serv, 5625 Fishers Lane, Rockville, MD 20852 USA. EM rveech@mail.nih.gov FU Intramural NIH HHS [ZIA AA000110-15] NR 39 TC 5 Z9 5 U1 5 U2 11 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1302 BP 42 EP 48 DI 10.1111/nyas.12222 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA BHM40 UT WOS:000325920200006 PM 23909803 ER PT S AU Kanchanawong, P Waterman, CM AF Kanchanawong, Pakorn Waterman, Clare M. BE Coutts, AS TI Localization-Based Super-Resolution Imaging of Cellular Structures SO ADHESION PROTEIN PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Super-resolution microscopy; Focal adhesions; Localization microscopy; TIRF; PALM; Single molecules; Photoswitchable fluorophores; Photoactivatable fluorescent proteins ID OPTICAL RECONSTRUCTION MICROSCOPY; FLUORESCENCE MICROSCOPY; PROTEIN; RESOLUTION; PERFORMANCE; PROBES; BLINKING; SAMPLES; SYSTEM; CELLS AB Fluorescence microscopy allows direct visualization of fluorescently tagged proteins within cells. However, the spatial resolution of conventional fluorescence microscopes is limited by diffraction to similar to 250 nm, prompting the development of super-resolution microscopy which offers resolution approaching the scale of single proteins, i.e., similar to 20 nm. Here, we describe protocols for single molecule localization-based super-resolution imaging, using focal adhesion proteins as an example and employing either photoswitchable fluorophores or photoactivatable fluorescent proteins. These protocols should also be easily adaptable to imaging a broad array of macromolecular assemblies in cells whose components can be fluorescently tagged and assemble into high density structures. C1 [Kanchanawong, Pakorn] Natl Univ Singapore, Mechanobiol Inst, Dept Bioengn, Singapore 117548, Singapore. [Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. RP Kanchanawong, P (reprint author), Natl Univ Singapore, Mechanobiol Inst, Dept Bioengn, Singapore 117548, Singapore. OI Waterman, Clare/0000-0001-6142-6775 FU Intramural NIH HHS [Z99 HL999999] NR 38 TC 1 Z9 1 U1 1 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-538-5; 978-1-62703-537-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1046 BP 59 EP 84 DI 10.1007/978-1-62703-538-5_4 D2 10.1007/978-1-62703-538-5 PG 26 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BHJ76 UT WOS:000325641400005 PM 23868582 ER PT S AU Ziolkowska, NE Roll-Mecak, A AF Ziolkowska, Natasza E. Roll-Mecak, Antonina BE Coutts, AS TI In Vitro Microtubule Severing Assays SO ADHESION PROTEIN PROTOCOLS, 3RD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Cytoskeleton; Microtubule; Tubulin; Severing; Depolymerization; Spastin; Katanin; AAA ATPase ID SPASTIC PARAPLEGIA PROTEIN; CAENORHABDITIS-ELEGANS; STABLE MICROTUBULES; SPINDLE LENGTH; KATANIN; DROSOPHILA; XENOPUS; DYNAMICS; SUBUNIT; ENZYMES AB Microtubules are rigid and highly dynamic cellular polymers essential for intracellular transport, cell division and differentiation. Their stability is tightly regulated by a vast array of cellular factors. In vitro microtubule assays have proven to be powerful tools for deciphering the mechanism of microtubule dynamics regulators such as molecular motors and microtubule associated proteins. In this chapter we focus on microtubule severing enzymes that use the energy of ATP hydrolysis to introduce internal breaks in the microtubule lattice. We present a detailed protocol for a light microscopy based in vitro microtubule severing assay that was instrumental in the identification and characterization of these enzymes. C1 [Ziolkowska, Natasza E.] NINDS, Cell Biol & Biophys Unit, Bethesda, MD 20892 USA. [Roll-Mecak, Antonina] NHLBI, Cell Biol & Biophys Unit, Ctr Biophys, NINDS, Bethesda, MD 20892 USA. RP Ziolkowska, NE (reprint author), NINDS, Cell Biol & Biophys Unit, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 33 TC 4 Z9 4 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-538-5; 978-1-62703-537-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1046 BP 323 EP 334 DI 10.1007/978-1-62703-538-5_19 D2 10.1007/978-1-62703-538-5 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BHJ76 UT WOS:000325641400020 PM 23868597 ER PT S AU Sun, YN Yolitz, J Wang, C Spangler, E Zhan, M Zou, SG AF Sun, Yaning Yolitz, Jason Wang, Cecilia Spangler, Edward Zhan, Ming Zou, Sige BE Tollefsbol, TO TI Aging Studies in Drosophila Melanogaster SO BIOLOGICAL AGING: METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Aging; Drosophila melanogaster; Lifespan; Reproduction; Locomotor activity; Mitochondrial function; Oxidative stress; Starvation ID LIFE-SPAN; DIETARY RESTRICTION; STARVATION RESISTANCE; OXIDATIVE STRESS; AGE; REPRODUCTION; LONGEVITY; EXTENSION; FECUNDITY; SELECTION AB Drosophila is a genetically tractable system ideal for investigating the mechanisms of aging and developing interventions for promoting healthy aging. Here we describe methods commonly used in Drosophila aging research. These include basic approaches for preparation of diets and measurements of lifespan, food intake, and reproductive output. We also describe some commonly used assays to measure changes in physiological and behavioral functions of Drosophila in aging, such as stress resistance and locomotor activity. C1 [Sun, Yaning; Yolitz, Jason; Spangler, Edward; Zou, Sige] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Wang, Cecilia] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Zhan, Ming] Methodist Hosp, Weill Cornell Med Coll, Res Inst, Dept Syst Med & Bioengn, Houston, TX 77030 USA. RP Sun, YN (reprint author), NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. FU Intramural NIH HHS [Z01 AG000365-03] NR 61 TC 3 Z9 3 U1 2 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-556-9; 978-1-62703-555-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1048 BP 77 EP 93 DI 10.1007/978-1-62703-556-9_7 D2 10.1007/978-1-62703-556-9 PG 17 WC Cell Biology SC Cell Biology GA BHJ15 UT WOS:000325584400008 PM 23929099 ER PT J AU Chatterji, S Alonso, J Petukhova, MV Vilagut, G Glantz, M Khalaf, MS AF Chatterji, Somnath Alonso, Jordi Petukhova, Maria V. Vilagut, Gemma Glantz, Meyer Khalaf, Mohammad Salih BE Alonso, J Chatterji, S He, Y TI Disability associated with common mental and physical disorders SO BURDENS OF MENTAL DISORDERS: GLOBAL PERSPECTIVES FROM THE WHO WORLD MENTAL HEALTH SURVEYS LA English DT Article; Book Chapter ID TERM PSYCHOTIC DISORDERS; ASSESSMENT SCHEDULE 2.0; QUALITY-OF-LIFE; HEALTH; RISK C1 [Chatterji, Somnath] WHO, Multicountry Studies Hlth Stat & Informat Syst HS, CH-1211 Geneva, Switzerland. [Alonso, Jordi] IMIM Inst Hosp Mar Invest Med, Epidemiol & Publ Hlth Program, Barcelona, Spain. [Alonso, Jordi] Pompeu Fabra Univ UPF, Barcelona, Spain. [Alonso, Jordi; Vilagut, Gemma] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain. [Petukhova, Maria V.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Vilagut, Gemma] IMIM Inst Hosp Mar Invest Med, Hlth Serv Res Grp, Barcelona, Spain. [Glantz, Meyer] NIDA, DESPR, Bethesda, MD 20892 USA. [Khalaf, Mohammad Salih] Ibn Seena Teaching Hosp, Day Care & Rehabil Ctr, Mosul, Iraq. RP Chatterji, S (reprint author), WHO, Multicountry Studies Hlth Stat & Informat Syst HS, CH-1211 Geneva, Switzerland. NR 22 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-01928-7 PY 2013 BP 186 EP 194 PG 9 WC Psychology, Clinical; Health Policy & Services SC Psychology; Health Care Sciences & Services GA BGZ97 UT WOS:000324772500014 ER PT J AU Sterky, FH Pernold, K Harvey, BK Lindqvist, E Hoffer, BJ Olson, L AF Sterky, Fredrik H. Pernold, Karin Harvey, Brandon K. Lindqvist, Eva Hoffer, Barry J. Olson, Lars TI Glial Cell Line-Derived Neurotrophic Factor Partially Ameliorates Motor Symptoms Without Slowing Neurodegeneration in Mice With Respiratory Chain-Deficient Dopamine Neurons SO CELL TRANSPLANTATION LA English DT Article DE Glial cell line-derived neurotrophic factor (GDNF); Mitochondria; Parkinson's disease (PD); Trophic support; Gene therapy ID ADENOASSOCIATED VIRAL VECTOR; PARKINSONS-DISEASE; IN-VIVO; RAT MODEL; TYROSINE-HYDROXYLASE; NIGROSTRIATAL SYSTEM; DOWN-REGULATION; VIRUS VECTORS; GENE-TRANSFER; GDNF AB Degeneration of midbrain dopamine neurons causes the striatal dopamine deficiency responsible for the hallmark motor symptoms of Parkinson's disease (PD). Intraparenchymal delivery of neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), is a possible future therapeutic approach. In animal PD models, GDNF can both ameliorate neurodegeneration and promote recovery of the dopamine system following a toxic insult. However, clinical studies have generated mixed results, and GDNF has not been efficacious in genetic animal models based on alpha-synuclein overexpression. We have tested the response to GDNF in a genetic mouse PD model with progressive degeneration of dopamine neurons caused by mitochondrial impairment. We find that GDNF, delivered to the striatum by either an adeno-associated virus or via miniosmotic pumps, partially alleviates the progressive motor symptoms without modifying the rate of neurodegeneration. These behavioral changes are accompanied by increased levels of dopamine in the rnidbrain, but not in striatum. At high levels, GDNF may instead reduce striatal dopamine levels. These results demonstrate the therapeutic potential of GDNF in a progressively impaired dopamine system. C1 [Sterky, Fredrik H.] Karolinska Inst, Dept Lab Med, SE-17177 Stockholm, Sweden. [Sterky, Fredrik H.; Pernold, Karin; Lindqvist, Eva; Olson, Lars] Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden. [Harvey, Brandon K.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Hoffer, Barry J.] Case Western Reserve Univ, Sch Med, Dept Neurosurg, Cleveland, OH USA. RP Olson, L (reprint author), Karolinska Inst, Dept Neurosci, Retzius Vag 8, SE-17177 Stockholm, Sweden. EM lars.olson@ki.se FU National Institutes of Health-Karolinska Institute Graduate Partnership Program for the Neurosciences; Swedish Research Council; Swedish Brain Power; Parkinson Foundation; Karolinska Institutet; US Public Health Service (National Institute on Drug Abuse, Intramural Research Program) [R01NS070825] FX This work was supported by the National Institutes of Health-Karolinska Institute Graduate Partnership Program for the Neurosciences (F.H.S.), the Swedish Research Council, Swedish Brain Power, the Parkinson Foundation, the Karolinska Institutet, and US Public Health Service (National Institute on Drug Abuse, Intramural Research Program and R01NS070825). L.O. is a shareholder in a company that holds commercial rights to MitoPark mice. NR 45 TC 1 Z9 1 U1 0 U2 3 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2013 VL 22 IS 9 BP 1529 EP 1539 DI 10.3727/096368912X657693 PG 11 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 230AM UT WOS:000325309000003 PM 23051605 ER PT S AU Miranda, TB Voss, TC Hager, GL AF Miranda, Tina B. Voss, Ty C. Hager, Gordon L. BE ShavTal, Y TI High-Throughput Fluorescence-Based Screen to Identify Factors Involved in Nuclear Receptor Recruitment to Response Elements SO IMAGING GENE EXPRESSION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nuclear receptor; Glucocorticoid receptor; siRNA screen; Chromatin ID COREPRESSOR AB The glucocorticoid receptor is an inducible transcription factor which plays important roles in many physiological processes. Upon activation, GR interacts with regulatory elements and modulates the expression of genes. Although GR is widely expressed in multiple tissues, its binding sites within chromatin and the genes it regulates are tissue specific. Many accessory proteins and cofactors are thought to play a role in dictating GR's function; however, mechanisms involved in targeting GR to specific sites in the genome are not well understood. Here we describe a high-throughput fluorescence-based method to identify factors involved in GR loading at response elements. This screen utilizes a genetically engineered cell line that contains 200 repeats of a glucocorticoid response promoter and expresses GFP-tagged GR. Upon treatment with corticosteroids, GFP-GR forms a steady-state distribution at the promoter array, and its concentration at this focal point can be quantitatively determined. This system provides a novel approach to identify activities important for GR loading at its response element using siRNA libraries to target factors that enhance or inhibit receptor localization. C1 [Miranda, Tina B.; Voss, Ty C.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Miranda, TB (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 8 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-526-2; 978-1-62703-525-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1042 BP 3 EP 12 DI 10.1007/978-1-62703-526-2_1 D2 10.1007/978-1-62703-526-2 PG 10 WC Genetics & Heredity; Radiology, Nuclear Medicine & Medical Imaging SC Genetics & Heredity; Radiology, Nuclear Medicine & Medical Imaging GA BHJ25 UT WOS:000325611900002 PM 23979996 ER PT S AU Ferguson, ML Larson, DR AF Ferguson, Matthew L. Larson, Daniel R. BE ShavTal, Y TI Measuring Transcription Dynamics in Living Cells Using Fluctuation Analysis SO IMAGING GENE EXPRESSION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Fluorescence fluctuation spectroscopy; Fluorescence correlation spectroscopy; FCS; Transcription; MS2; PP7; Single molecule; Imaging; RNA; Stochastic ID FLUORESCENCE CORRELATION SPECTROSCOPY; GENE-EXPRESSION; MESSENGER-RNA; MICROSCOPY; YEAST; LOCALIZATION AB Single-cell studies of gene regulation suggest that transcription dynamics play a fundamental role in determining expression heterogeneity within a population. In addition, the three-dimensional organization of the nucleus seems to both reflect and influence expression patterns in the cell. Therefore, to gain a holistic understanding of transcriptional regulation, it is necessary to develop methods for studying transcription of single genes in living cells with high spatial and temporal resolution. In this chapter, we describe a recently developed approach for visualizing and quantifying pre-mRNA synthesis at a single active gene in the nucleus. The approach is based on the high-affinity interaction between MS2/PP7 bacteriophage coat proteins and RNA hairpins which are transcribed by the gene of interest. The MS2/PP7 coat protein is fused to a fluorescent protein and binds the nascent mRNA, allowing for detection of single transcription events in the fluorescence microscope. By time-lapse fluorescence imaging and quantitative image analysis, one can generate a time trace of fluorescence intensity at the site of transcription. By temporal autocorrelation analysis, one can determine enzymatic activities of RNAP such as initiation rate and elongation rate. In this protocol, we summarize the experimental concept, design, and execution for real-time observation of transcription in living cells. C1 [Ferguson, Matthew L.; Larson, Daniel R.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ferguson, ML (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Ferguson, Matthew/C-4140-2014; Larson, Daniel/B-9829-2008 OI Ferguson, Matthew/0000-0003-0760-757X; Larson, Daniel/0000-0001-9253-3055 FU Intramural NIH HHS NR 30 TC 2 Z9 2 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-526-2; 978-1-62703-525-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1042 BP 47 EP 60 DI 10.1007/978-1-62703-526-2_4 D2 10.1007/978-1-62703-526-2 PG 14 WC Genetics & Heredity; Radiology, Nuclear Medicine & Medical Imaging SC Genetics & Heredity; Radiology, Nuclear Medicine & Medical Imaging GA BHJ25 UT WOS:000325611900005 PM 23979999 ER PT S AU Mazza, D Ganguly, S McNally, JG AF Mazza, Davide Ganguly, Sourav McNally, James G. BE ShavTal, Y TI Monitoring Dynamic Binding of Chromatin Proteins In Vivo by Single-Molecule Tracking SO IMAGING GENE EXPRESSION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Single-molecule tracking; Microscopy; Transcription factor; DNA binding ID CORRELATION SPECTROSCOPY; FLUORESCENCE; CELLS; MICROSCOPY; KINETICS; LEVEL; FRAP AB Single-molecule fluorescence microscopy has been used for decades to quantify macromolecular dynamics occurring in specimens that are in direct contact with a coverslip. This has permitted in vitro analysis of single-molecule motion in various biochemically reconstituted systems as well as in vivo studies of single-molecule motion on cell membranes. More recently, thanks to improvements in fluorescent tags and microscopes, it has been possible to follow individual molecules inside thicker specimens such as the nucleus of living cells. This has enabled a detailed description of the live-cell binding of nuclear proteins to DNA. In this protocol we describe a method to quantify intranuclear binding using single-molecule tracking (SMT). C1 [Mazza, Davide] Osped San Raffaele, Ist Sci, Ctr Expt Imaging, Bethesda, MD USA. [Mazza, Davide] Univ Vita Salute San Raffaele, Bethesda, MD USA. [Ganguly, Sourav; McNally, James G.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Mazza, D (reprint author), Osped San Raffaele, Ist Sci, Ctr Expt Imaging, Bethesda, MD USA. RI Ganguly, Sourav/A-8931-2011; Mazza, Davide/R-5340-2016 OI Ganguly, Sourav/0000-0003-1002-9002; Mazza, Davide/0000-0003-2776-4142 NR 24 TC 3 Z9 3 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-526-2; 978-1-62703-525-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1042 BP 117 EP 137 DI 10.1007/978-1-62703-526-2_9 D2 10.1007/978-1-62703-526-2 PG 21 WC Genetics & Heredity; Radiology, Nuclear Medicine & Medical Imaging SC Genetics & Heredity; Radiology, Nuclear Medicine & Medical Imaging GA BHJ25 UT WOS:000325611900010 PM 23980004 ER PT S AU Waybright, TJ Chan, KC Veenstra, TD Xiao, Z AF Waybright, Timothy J. Chan, King C. Veenstra, Timothy D. Xiao, Zhen BE Fulton, KM Twine, SM TI Preparation of the Low Molecular Weight Serum Proteome for Mass Spectrometry Analysis SO IMMUNOPROTEOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Low molecular weight proteome; Mass spectrometry; Strong cation exchange; Human serum; Liquid chromatography; Protein depletion ID BIOMARKER DISCOVERY; CANCER; ENRICHMENT; BLOOD AB The discovery of viable biomarkers or indicators of disease states is complicated by the inherent complexity of the chosen biological specimen. Every sample, whether it is serum, plasma, urine, tissue, cells, or a host of others, contains thousands of large and small components, each interacting in multiple ways. The need to concentrate on a group of these components to narrow the focus on a potential biomarker candidate becomes, out of necessity, a priority, especially in the search for immune-related low molecular weight serum biomarkers. One such method in the field of proteomics is to divide the sample proteome into groups based on the size of the protein, analyze each group, and mine the data for statistically significant items. This chapter details a portion of this method, concentrating on a method for fractionating and analyzing the low molecular weight proteome of human serum. C1 [Waybright, Timothy J.; Chan, King C.; Veenstra, Timothy D.; Xiao, Zhen] SAIC Frederick, Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. RP Waybright, TJ (reprint author), SAIC Frederick, Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. FU PHS HHS [HHSN261200800001E] NR 15 TC 0 Z9 0 U1 1 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-589-7; 978-1-62703-588-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1061 BP 279 EP 289 DI 10.1007/978-1-62703-589-7_17 D2 10.1007/978-1-62703-589-7 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA BHJ20 UT WOS:000325605100018 PM 23963944 ER PT S AU Huang, JX Ling, A Summers, RM Yao, JH AF Huang, Jiaxin Ling, Alexander Summers, Ronald M. Yao, Jianhua BE Law, MY Boonn, WW TI Integration of PACS and CAD Systems using DICOMDIR and Open-Source Tools SO MEDICAL IMAGING 2013: ADVANCED PACS-BASED IMAGING INFORMATICS AND THERAPEUTIC APPLICATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Advanced PACS-Based Imaging Informatics and Therapeutic Applications CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE CAD; PACS; integration; DICOMDIR; open-source; clinical efficiency; time saving workflow ID INFORMATION-SYSTEMS AB The advancements of the last 30 years have made picture archiving and communication system (PACS) an indispensable technology to improve the delivery and management of clinical imaging services. Similarly, the maturation of algorithms and computer aided detection (CAD) systems has enhanced the interpretation and diagnosis of radiographical images. However, the lack of integration between the two systems inhibits the rate of development and application of these recent innovations in reaching the clinical users of PACS. We aim to enhance the clinical efficiency of CAD systems by developing an accessible, fully automated, user-friendly, and integrated linkage of CAD and PACS systems. This is the first integration initiative to take advantage of DICOMDIR file and its ability to index DICOM files, allowing images outside of PACS to be viewed within PACS. In this demonstration, the CAD system evaluates CT chest exams to detect lesions in the ribs and produces whole rib map images, screenshots, and detection report. A script executes the rib CAD system and creates a DICOMDIR file using, DCMTK., an open-source DICOM toolkit. We evaluated our system on thirty 5mm slice thickness and thirty 2mm slice thickness image studies and demonstrated a time saving efficiency of 93s +/- 14s and 221s +/- 17s per exam, respectively, compared to the current non-integrated workflow of using CAD systems. The advantages of this system are that it is easy to implement, requires no additional workstation and training, and allows CAD results to be viewed in PACS without disrupting radiology workflow, while maintaining the independence of both technologies. C1 [Huang, Jiaxin; Yao, Jianhua] NIH, Clin Ctr, Clin Image Proc Serv Lab, Bldg 10,MSC 1182, Bethesda, MD 20892 USA. [Huang, Jiaxin; Ling, Alexander; Summers, Ronald M.; Yao, Jianhua] NIH, Clin Ctr, Radiol Imaging Sci, Bethesda, MD 20892 USA. [Summers, Ronald M.] NIH, Clin Ctr, Imaging Biomarkers & Comp Aided Diagnosis Lab, Bethesda, MD 20892 USA. RP Huang, JX (reprint author), NIH, Clin Ctr, Clin Image Proc Serv Lab, Bldg 10,MSC 1182, Bethesda, MD 20892 USA. EM JYao@cc.nih.gov FU Intramural Research Program of the National Institutes of Health, Clinical Center FX The authors would like to acknowledge Te Chen, MS, and Sue Powell, PhD, for their assistance in testing and evaluating the CAD-PACS integrated system. This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center. NR 11 TC 0 Z9 0 U1 0 U2 6 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9448-1 J9 PROC SPIE PY 2013 VL 8674 AR 86740V DI 10.1117/12.2001560 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHG83 UT WOS:000325369900027 ER PT S AU You, D Rahman, MM Antani, S Demner-Fushman, D Thoma, GR AF You, Daekeun Rahman, Md Mahmudur Antani, Sameer Demner-Fushman, Dina Thoma, George R. BE Law, MY Boonn, WW TI Text- and Content-based Biomedical Image Modality Classification SO MEDICAL IMAGING 2013: ADVANCED PACS-BASED IMAGING INFORMATICS AND THERAPEUTIC APPLICATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Advanced PACS-Based Imaging Informatics and Therapeutic Applications CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE biomedical article retrieval; modality classification; content-based image retrieval; feature extraction AB Image modality classification is an important task toward achieving high performance in biomedical image and article retrieval. Imaging modality captures information about its appearance and use. Examples include X-ray, MRI, Histopathology, Ultrasound, etc. Modality classification reduces the search space in image retrieval. We have developed and evaluated several modality classification methods using visual and textual features extracted from images and text data, such as figure captions, article citations, and MeSH (R). Our hierarchical classification method using multimodal (mixed textual and visual) and several class-specific features achieved the highest classification accuracy of 63.2%. The performance was among the best in ImageCLEF2012 evaluation. C1 [You, Daekeun; Rahman, Md Mahmudur; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20894 USA. RP You, D (reprint author), NIH, Natl Lib Med, Bethesda, MD 20894 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9448-1 J9 PROC SPIE PY 2013 VL 8674 AR 86740L DI 10.1117/12.2007932 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHG83 UT WOS:000325369900018 ER PT S AU Skelton, J Gower, LH McGough, A Labosky, PA AF Skelton, Jennifer Gower, Linda H. McGough, Anne Labosky, Patricia A. BE Allen, IC TI Transgenic Mouse Models SO MOUSE MODELS OF ALLERGIC DISEASE, METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Mice; Transgenics; Microinjection; Pronuclear injection; Animal models ID BETA-GLOBIN GENE; THYMIDINE KINASE; GERM-LINE; MICE; TRANSFORMATION; INJECTION; DNA AB The generation of transgenic mouse models has been a powerful technique for several decades and is still widely used. There have been many manuals and general reviews of this technology. This chapter is designed to be a "how-to" resource with detailed specifics. C1 [Skelton, Jennifer; Gower, Linda H.; McGough, Anne] Vanderbilt Univ, Med Ctr, Ctr Stem Cell Biol, Nashville, TN 37203 USA. [Labosky, Patricia A.] NIH, Off Strateg Coordinat, Div Program Coordinat Planning & Strateg Initiat, Off Director, Bethesda, MD 20892 USA. RP Skelton, J (reprint author), Vanderbilt Univ, Med Ctr, Ctr Stem Cell Biol, Nashville, TN 37203 USA. NR 6 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-495-1; 978-1-62703-496-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1032 BP 1 EP 17 DI 10.1007/978-1-62703-496-8_1 D2 10.1007/978-1-62703-496-8 PG 17 WC Immunology SC Immunology GA BHK48 UT WOS:000325715900002 PM 23943440 ER PT S AU Nakano, H Cook, DN AF Nakano, Hideki Cook, Donald N. BE Allen, IC TI Pulmonary Antigen Presenting Cells: Isolation, Purification, and Culture SO MOUSE MODELS OF ALLERGIC DISEASE, METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Antigen presenting cells; Dendritic cells; Macrophages; Monocytes; Lung; Lymph nodes; Gradient centrifugation; Flow cytometry; Autofluorescence; Sorting; Culture ID DENDRITIC CELLS; FLOW-CYTOMETRY; RESPONSES AB Antigen presenting cells (APCs) such as dendritic cells (DCs) and macrophages comprise a relatively small fraction of leukocytes residing in lymphoid and non-lymphoid tissues. Accordingly, functional analyses of these cells have been hampered by low cell yields. Also, alveolar macrophages share several physical properties with DCs, and this has complicated efforts to prepare pure populations of lung APCs. To overcome these difficulties, we have developed improved flow cytometry-based methods to analyze and purify APCs from the lung and its draining lymph nodes (LNs). In this chapter, we describe these methods in detail, as well as methods for culturing APCs and characterizing their interactions with T cells. C1 [Nakano, Hideki; Cook, Donald N.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Nakano, H (reprint author), NIEHS, Lab Resp Biol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS NR 14 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-495-1; 978-1-62703-496-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1032 BP 19 EP 29 DI 10.1007/978-1-62703-496-8_2 D2 10.1007/978-1-62703-496-8 PG 11 WC Immunology SC Immunology GA BHK48 UT WOS:000325715900003 PM 23943441 ER PT S AU Dyer, KD Garcia-Crespo, KE Percopo, CM Sturm, EM Rosenberg, HF AF Dyer, Kimberly D. Garcia-Crespo, Katia E. Percopo, Caroline M. Sturm, Eva M. Rosenberg, Helene F. BE Allen, IC TI Protocols for Identifying, Enumerating, and Assessing Mouse Eosinophils SO MOUSE MODELS OF ALLERGIC DISEASE, METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Piece-meal degranulation (PMD); Eosinophil peroxidase (EPO); Major basic protein (MBP); Eotaxin; Ribonuclease; IL5-R alpha; CCR3 ID TRANSGENIC MICE; FLOW-CYTOMETRY; EX-VIVO AB Eosinophils are prominent in allergic diseases, and their effector functions are studied in numerous gene-deleted and transgenic mouse models. However, mouse eosinophils and human eosinophils are not structurally or functionally equivalent, and assays designed to evaluate the properties of human eosinophils may or may not be reliable or effective in experiments targeting their murine counterparts. In this chapter, we emphasize methods focused on detection, isolation, and functional assessment of eosinophils from mouse tissue and present a protocol that promotes the growth and differentiation of eosinophils from unselected mouse bone marrow progenitors. Overall, these protocols provide a scaffold on which the relative contributions of mouse eosinophils can be evaluated. C1 [Dyer, Kimberly D.; Garcia-Crespo, Katia E.; Percopo, Caroline M.; Sturm, Eva M.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Dyer, KD (reprint author), NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI000941] NR 17 TC 5 Z9 5 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-495-1; 978-1-62703-496-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1032 BP 59 EP 77 DI 10.1007/978-1-62703-496-8_5 D2 10.1007/978-1-62703-496-8 PG 19 WC Immunology SC Immunology GA BHK48 UT WOS:000325715900006 PM 23943444 ER PT S AU Cyphert, JM AF Cyphert, Jaime M. BE Allen, IC TI Bilateral Vagotomy as a Tool for Determining Autonomic Involvement in Airway Responses in Mouse Models of Asthma SO MOUSE MODELS OF ALLERGIC DISEASE, METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Vagus nerve; Autonomic nervous system; Lung mechanics; Asthma ID TACHYKININS; NERVES AB This chapter describes the use of bilateral vagotomy as a tool for determining autonomic regulation of airway responses to the exogenous bronchoconstrictor thromboxane mimetic U46619 in an acute model of asthma in the mouse. Mice receive a sensitization of ovalbumin (OVA) and adjuvant followed by 3 days of OVA aerosol to induce allergic airway disease characterized by bronchoalveolar lavage (BAL) eosinophilia, increased mucus production, and elevated IgE and IL-13. Using a small animal ventilator (Flexi-vent) and the forced oscillatory technique fit to the constant phase model of the lung, a variety of features associated with human asthma can be evaluated in mouse models. For example, this protocol describes the methods to evaluate central and peripheral airway mechanics, airway resistance (R-aw) and tissue damping (G), and tissue elastance (H) in response to U46619. The contribution of autonomic nerves in this response is determined by severing both the left and right vagus nerves prior to aerosol challenge. C1 NIEHS, Matrix Biol Branch, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Cyphert, JM (reprint author), NIEHS, Matrix Biol Branch, Lab Resp Biol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 13 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-495-1; 978-1-62703-496-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1032 BP 219 EP 227 DI 10.1007/978-1-62703-496-8_17 D2 10.1007/978-1-62703-496-8 PG 9 WC Immunology SC Immunology GA BHK48 UT WOS:000325715900018 PM 23943456 ER PT J AU Rogers, ZR Alter, BP AF Rogers, Zora R. Alter, Blanche P. BE DeAlarcon, PA Werner, EJ Christensen, RD TI Bone marrow failure syndromes SO NEONATAL HEMATOLOGY: PATHOGENESIS, DIAGNOSIS, AND MANAGEMENT OF HEMATOLOGIC PROBLEMS, 2ND EDITION LA English DT Article; Book Chapter ID SHWACHMAN-DIAMOND-SYNDROME; CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA; STEM-CELL TRANSPLANTATION; FANCONI-ANEMIA; DYSKERATOSIS-CONGENITA; MOLECULAR PATHOGENESIS; BLACKFAN ANEMIA; ABSENT RADII; DIAGNOSIS; NEUTROPENIA C1 [Rogers, Zora R.] Univ Texas SW Med Ctr Dallas, Div Pediat Hematol Oncol, Dallas, TX 75390 USA. [Rogers, Zora R.] Childrens Med Ctr, Hematol Program, Dallas, TX 75235 USA. [Rogers, Zora R.] Childrens Med Ctr, Bone Marrow Failure Program, Dallas, TX 75235 USA. [Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Rogers, ZR (reprint author), Univ Texas SW Med Ctr Dallas, Div Pediat Hematol Oncol, Dallas, TX 75390 USA. NR 47 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-11931-3 PY 2013 BP 47 EP 64 PG 18 WC Hematology; Pediatrics SC Hematology; Pediatrics GA BHH72 UT WOS:000325463000007 ER PT S AU Tian, WH Dong, XY Wu, XB Wu, ZJ AF Tian, Wenhong Dong, Xiaoyan Wu, Xiaobing Wu, Zhijian BE Kolpashchikov, DM Gerasimova, YV TI High-Throughput Functional MicroRNA Profiling Using Recombinant AAV-Based MicroRNA Sensor Arrays SO NUCLEIC ACID DETECTION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE miRNA; miRNA activity; high-throughput; miRNA Asensor array ID HERPES-SIMPLEX-VIRUS; ADENOASSOCIATED VIRUS; EXPRESSION; STABILITY; CANCER AB There is a lack of methods for high-throughput functional microRNA (miRNA) profiling. In this chapter, we describe a recombinant adeno-associated virus-based miRNA sensor array (miRNA Asensor array), which is able to profile functional miRNAs in cultured cells. The preparation of an miRNA Asensor array and its usage are discussed. C1 [Tian, Wenhong] Jilin Univ, Coll Life Sci, Changchun 130023, Jilin, Peoples R China. [Dong, Xiaoyan; Wu, Xiaobing] Beijing FivePlus Mol Med Inst, Beijing, Peoples R China. [Wu, Zhijian] NEI, Unit Ocular Gene Therapy, NIH, Bethesda, MD 20892 USA. RP Tian, WH (reprint author), Jilin Univ, Coll Life Sci, Changchun 130023, Jilin, Peoples R China. FU Intramural NIH HHS [ZIA EY000443-07] NR 19 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-535-4; 978-1-62703-534-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1039 BP 261 EP 277 DI 10.1007/978-1-62703-535-4_21 D2 10.1007/978-1-62703-535-4 PG 17 WC Chemistry, Multidisciplinary; Genetics & Heredity SC Chemistry; Genetics & Heredity GA BHJ28 UT WOS:000325613800022 PM 24026702 ER PT S AU Teriete, P Pinkerton, AB Cosford, NDP AF Teriete, Peter Pinkerton, Anthony B. Cosford, Nicholas D. P. BE Millan, JL TI Inhibitors of Tissue-Nonspecific Alkaline Phosphatase (TNAP): From Hits to Leads SO PHOSPHATASE MODULATORS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Absorption; distribution; metabolism; excretion, and toxicity (ADME/T); High-throughput screening (HTS); Hit-to-lead; Inhibitor design; Medicinal chemistry; Pharmacokinetics (PK); Pharmacophore; Rational design; Structure-activity relationship (SAR) ID DRUG DISCOVERY; PHARMACOPHORE MODEL; ASSAY; SOLUBILITY; BINDING; POTENT AB The optimization of active hits, commonly derived from high-throughput screening campaigns (see Chapters 2 and 4), into promising small-molecule lead compounds is one of the fundamental steps in early drug discovery. Directions taken during this stage can have important consequences reaching through lead optimization into preclinical development and beyond. Considering the ever-increasing costs of preclinical as well as clinical development phases (DiMasi et al., J Health Econ 22:151-185, 2003) the choices made at the early stages of drug discovery can have a real impact on the likelihood of the best lead becoming a viable candidate (Bleicher et al., Nat Rev Drug Discov 2:369-378, 2003). Thus it is important to utilize proven and robust methodologies to turn promising hits into suitable lead series with propitious characteristics. Here, we describe such an approach using the example of a tissue-nonspecific alkaline phosphatase (see Chapter 3) inhibitor developed in our group (Sidique et al., Bioorg Med Chem Lett 19:222-225, 2009). C1 [Teriete, Peter; Pinkerton, Anthony B.; Cosford, Nicholas D. P.] NCI, Designated Canc Ctr, Sanford Burnham Med Res Inst, La Jolla, CA USA. RP Teriete, P (reprint author), NCI, Designated Canc Ctr, Sanford Burnham Med Res Inst, La Jolla, CA USA. RI Teriete, Peter/N-3331-2014; OI Teriete, Peter/0000-0003-3692-9308; Pinkerton, Anthony/0000-0003-4571-152X NR 28 TC 3 Z9 3 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-562-0; 978-1-62703-561-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1053 BP 85 EP 101 DI 10.1007/978-1-62703-562-0_5 D2 10.1007/978-1-62703-562-0 PG 17 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BHI05 UT WOS:000325475800006 PM 23860648 ER PT B AU Colloca, L Flaten, MA Meissner, K AF Colloca, Luana Flaten, Magne Arve Meissner, Karin BE Colloca, L Flaten, MA Meissner, K TI PLACEBO AND PAIN FROM BENCH TO BEDSIDE Preface SO PLACEBO AND PAIN: FROM BENCH TO BEDSIDE LA English DT Editorial Material; Book Chapter C1 [Colloca, Luana] NIH, NCCAM, Bethesda, MD 20892 USA. [Colloca, Luana] NIMH, NIH, Bethesda, MD 20892 USA. [Colloca, Luana] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Flaten, Magne Arve] Norwegian Univ Sci & Technol, Dept Psychol, N-7034 Trondheim, Norway. [Meissner, Karin] Univ Munich, Inst Med Psychol, D-80539 Munich, Germany. RP Colloca, L (reprint author), NIH, NCCAM, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397931-5; 978-0-12-397928-5 PY 2013 BP IX EP IX PG 1 WC Anesthesiology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA BHG58 UT WOS:000325348000001 ER PT B AU Colloca, L AF Colloca, Luana BE Colloca, L Flaten, MA Meissner, K TI How Placebo Responses are Formed: From Bench to Bedside SO PLACEBO AND PAIN: FROM BENCH TO BEDSIDE LA English DT Article; Book Chapter ID IRRITABLE-BOWEL-SYNDROME; SYNDROME IBS PATIENTS; ASTHMATIC SUBJECTS; AIRWAY REACTIVITY; ANALGESIA; NOCEBO; EXPECTANCY; PAIN; MECHANISMS; ACTIVATION C1 [Colloca, Luana] NIH, NCCAM, Bethesda, MD 20892 USA. [Colloca, Luana] NIMH, NIH, Bethesda, MD 20892 USA. [Colloca, Luana] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Colloca, L (reprint author), NIH, NCCAM, Bldg 10, Bethesda, MD 20892 USA. NR 82 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397931-5; 978-0-12-397928-5 PY 2013 BP 137 EP 148 DI 10.1016/B978-0-12-397928-5.00014-3 PG 12 WC Anesthesiology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA BHG58 UT WOS:000325348000015 ER PT B AU Flaten, MA Meissner, K Colloca, L AF Flaten, Magne Arve Meissner, Karin Colloca, Luana BE Colloca, L Flaten, MA Meissner, K TI Methodologic Aspects of Placebo Research SO PLACEBO AND PAIN: FROM BENCH TO BEDSIDE LA English DT Article; Book Chapter ID DECISION THEORY ANALYSIS; ASTHMATIC SUBJECTS; AIRWAY REACTIVITY; NOCEBO RESPONSES; PAIN; ANALGESIA; EXPECTATION; SUGGESTION; MECHANISMS; D' C1 [Flaten, Magne Arve] Norwegian Univ Sci & Technol, Dept Psychol, N-7034 Trondheim, Norway. [Meissner, Karin] Univ Munich, Inst Med Psychol, D-80539 Munich, Germany. [Colloca, Luana] NIH, NCCAM, Bethesda, MD 20892 USA. [Colloca, Luana] NIMH, NIH, Bethesda, MD 20892 USA. [Colloca, Luana] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Flaten, MA (reprint author), Norwegian Univ Sci & Technol, Dept Psychol, N-7034 Trondheim, Norway. NR 58 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397931-5; 978-0-12-397928-5 PY 2013 BP 149 EP 157 DI 10.1016/B978-0-12-397928-5.00015-5 PG 9 WC Anesthesiology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA BHG58 UT WOS:000325348000016 ER PT B AU Jonas, WB Crawford, C Meissner, K Colloca, L AF Jonas, Wayne B. Crawford, Cindy Meissner, Karin Colloca, Luana BE Colloca, L Flaten, MA Meissner, K TI The Wound that Heals: Placebo, Pain and Surgery SO PLACEBO AND PAIN: FROM BENCH TO BEDSIDE LA English DT Article; Book Chapter ID LOW-BACK-PAIN; PERCUTANEOUS MYOCARDIAL LASER; MAMMARY-ARTERY LIGATION; CONTROLLED-TRIAL; DOUBLE-BLIND; RANDOMIZED-TRIAL; VERTEBRAL FRACTURES; NEUROPATHIC PAIN; ANGINA-PECTORIS; SHAM PROCEDURES C1 [Jonas, Wayne B.; Crawford, Cindy] Samueli Inst, Alexandria, VA 22314 USA. [Meissner, Karin] Univ Munich, Inst Med Psychol, D-80539 Munich, Germany. [Colloca, Luana] NCCAM, Bethesda, MD 20892 USA. [Colloca, Luana] NIMH, NIH, Bethesda, MD 20892 USA. [Colloca, Luana] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Jonas, WB (reprint author), Samueli Inst, Alexandria, VA 22314 USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397931-5; 978-0-12-397928-5 PY 2013 BP 227 EP 233 DI 10.1016/B978-0-12-397928-5.00022-2 PG 7 WC Anesthesiology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA BHG58 UT WOS:000325348000023 ER PT B AU Colloca, L Miller, FG AF Colloca, Luana Miller, Franklin G. BE Colloca, L Flaten, MA Meissner, K TI Placebo and Nocebo: Ethical Challenges and Solutions SO PLACEBO AND PAIN: FROM BENCH TO BEDSIDE LA English DT Article; Book Chapter ID TRIALS COMPARING PLACEBO; CLINICAL-PRACTICE; INFORMED-CONSENT; QUESTIONNAIRE SURVEY; ADVERSE EVENTS; NO TREATMENT; PAIN; ANALGESIA; VERTEBROPLASTY; INTERVENTIONS C1 [Colloca, Luana] NIH, NCCAM, Bethesda, MD 20892 USA. [Colloca, Luana] NIMH, NIH, Bethesda, MD 20892 USA. [Colloca, Luana; Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Colloca, L (reprint author), NIH, NCCAM, Bldg 10, Bethesda, MD 20892 USA. NR 71 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397931-5; 978-0-12-397928-5 PY 2013 BP 277 EP 286 DI 10.1016/B978-0-12-397928-5.00027-1 PG 10 WC Anesthesiology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA BHG58 UT WOS:000325348000028 ER PT B AU Lejuez, CW Reynolds, EK Aklin, WM Frueh, C AF Lejuez, C. W. Reynolds, Elizabeth K. Aklin, Will M. Frueh, Christopher BE Prinstein, MJ TI Applying for NIH Grants SO PORTABLE MENTOR: EXPERT GUIDE TO A SUCCESSFUL CAREER IN PSYCHOLOGY, SECOND EDITION LA English DT Article; Book Chapter C1 [Lejuez, C. W.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Lejuez, C. W.] Univ Maryland, Ctr Addict Personal & Emot Res, College Pk, MD 20742 USA. [Reynolds, Elizabeth K.] Johns Hopkins Univ, Sch Med, Div Child & Adolescent Psychiat, Baltimore, MD USA. [Aklin, Will M.] NIDA, Behav & Integrat Treatment Branch, Div Clin Neurosci, Bethesda, MD 20892 USA. [Frueh, Christopher] Univ Hawaii, Div Social Sci, Hilo, HI 96720 USA. [Frueh, Christopher] Menninger Clin, Houston, TX USA. RP Lejuez, CW (reprint author), Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. EM clejuez@psyc.umd.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-3993-6 PY 2013 BP 319 EP 331 DI 10.1007/978-1-4614-3994-3_24 D2 10.1007/978-1-4614-3994-3 PG 13 WC Education & Educational Research; Psychology, Multidisciplinary SC Education & Educational Research; Psychology GA BHB83 UT WOS:000324895600025 ER PT J AU Krieger, FV Leibenluft, E Stringaris, A Polanczyk, GV AF Krieger, Fernanda Valle Leibenluft, Ellen Stringaris, Argyris Polanczyk, Guilherme V. TI Irritability in children and adolescents: past concepts, current debates, and future opportunities SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Article DE Irritability; disruptive behavior; mood; dysregulation; children; adolescents ID SEVERE MOOD DYSREGULATION; OPPOSITIONAL DEFIANT DISORDER; PEDIATRIC BIPOLAR DISORDER; LONGITUDINAL COURSE; CONTROLLED-TRIAL; YOUTH; PSYCHOPATHOLOGY; CHILDHOOD; MANIA; PREVALENCE AB Irritability is defined as a low threshold to experience anger in response to frustration. It is one of the most common symptoms in youth and is part of the clinical presentation of several disorders. Irritability can present early in life and is a predictor of long-term psychopathology; yet, the diagnostic status of irritability is a matter of intense debate. In the present article, we address two main components of the debate regarding irritability in youth: the misdiagnosis of chronic irritability as pediatric bipolar disorder, and the proposal of a new diagnosis in the DSM-5, disruptive mood dysregulation disorder, whose defining symptoms are chronic irritability and temper outbursts. C1 [Krieger, Fernanda Valle; Polanczyk, Guilherme V.] Univ Sao Paulo, Dept Psychiat, BR-05403903 Sao Paulo, Brazil. [Krieger, Fernanda Valle; Polanczyk, Guilherme V.] Conselho Nacl Desenvolvimento Cientif & Tecnol CN, Natl Sci & Technol Inst Dev Psychiat Children & A, Brasilia, DF, Brazil. [Krieger, Fernanda Valle; Stringaris, Argyris] Kings Coll London, Inst Psychiat, London, England. [Leibenluft, Ellen] NIMH, Emot & Dev Branch, Dept Hlth & Human Serv HHS, Bethesda, MD 20892 USA. [Polanczyk, Guilherme V.] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. [Polanczyk, Guilherme V.] Univ Sao Paulo, Res Support Ctr Neurodev & Mental Hlth, Sao Paulo, Brazil. RP Krieger, FV (reprint author), Univ Sao Paulo, Inst Psiquiatria, Rua Dr Ovidio Pires Campos,785,1 Andar,Sala 1C015, BR-05403903 Sao Paulo, Brazil. EM fvkrieger@gmail.com RI Polanczyk, Guilherme/C-2345-2012 OI Polanczyk, Guilherme/0000-0003-2311-3289 FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil FX This study was supported by a PhD scholarship received by the first author from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil. NR 54 TC 5 Z9 5 U1 5 U2 20 PU ASSOC BRASILEIRA PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP 04039-032 A, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PY 2013 VL 35 SU 1 BP S32 EP S39 DI 10.1590/1516-4446-2013-S107 PG 8 WC Psychiatry SC Psychiatry GA 235SX UT WOS:000325742100005 PM 24142126 ER PT J AU Rapoport, JL AF Rapoport, Judith L. TI Perspectives on child and adolescent psychiatry from Brazil SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Editorial Material ID COMORBIDITY SURVEY REPLICATION; BRAIN-DEVELOPMENT; MENTAL-DISORDERS; ONSET C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 MH002581-17] NR 12 TC 0 Z9 0 U1 2 U2 3 PU ASSOC BRASILEIRA PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP 04039-032 A, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PY 2013 VL 35 SU 1 BP S2 EP S2 DI 10.1590/1516-4446-2013-S102 PG 1 WC Psychiatry SC Psychiatry GA 235SX UT WOS:000325742100002 PM 24142124 ER PT J AU Salum, GA DeSousa, DA do Rosario, MC Pine, DS Manfro, GG AF Salum, Giovanni Abrahao DeSousa, Diogo Araujo do Rosario, Maria Conceicao Pine, Daniel Samuel Manfro, Gisele Gus TI Pediatric anxiety disorders: from neuroscience to evidence-based clinical practice SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Article DE Child; adolescent; anxiety disorders; obsessive-compulsive disorder ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; REPLICATION-ADOLESCENT SUPPLEMENT; GENOME-WIDE ASSOCIATION; PSYCHIATRIC-ASSESSMENT CAPA; RANDOMIZED CONTROLLED-TRIAL; GENE-ENVIRONMENT INTERPLAY; RESEARCH DOMAIN CRITERIA; TEST-RETEST RELIABILITY; SUBSTANCE USE DISORDER AB The objective of this narrative review of the literature is to describe the epidemiology, etiology, pathophysiology, diagnosis, and treatment of pediatric anxiety disorders. We aim to guide clinicians in understanding the biology of anxiety disorders and to provide general guidelines for the proper diagnoses and treatment of these conditions early in life. Anxiety disorders are prevalent, associated with a number of negative life outcomes, and currently under-recognized and under-treated. The etiology involves both genes and environmental influences modifying the neural substrate in a complex interplay. Research on pathophysiology is still in its infancy, but some brain regions, such as the amygdala and the prefrontal cortex, have been implicated in fear and anxiety. Current practice is to establish diagnosis based purely on clinical features, derived from clinical interviews with the child, parents, and teachers. Treatment is effective using medication, cognitive behavioral therapy, or a combination of both. An introduction to the neuroscience behind anxiety disorders combined with an evidence-based approach may help clinicians to understand these disorders and treat them properly in childhood. C1 [Salum, Giovanni Abrahao; DeSousa, Diogo Araujo; Manfro, Gisele Gus] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Anxiety Disorders Outpatient Program Child & Adol, Porto Alegre, RS, Brazil. [Salum, Giovanni Abrahao; Manfro, Gisele Gus] Univ Fed Rio Grande do Sul, Grad Program Med Sci Psychiat, Porto Alegre, RS, Brazil. [Salum, Giovanni Abrahao; do Rosario, Maria Conceicao; Manfro, Gisele Gus] Conselho Nacl Desenvolvimento Cientif & Tecnol CN, Natl Sci & Technol Inst Dev Psychiat Children & A, Sao Paulo, Brazil. [do Rosario, Maria Conceicao] Univ Fed Sao Paulo UNIFESP, Dept Psychiat, Child & Adolescent Psychiat Unit, Sao Paulo, Brazil. [Pine, Daniel Samuel] NIMH, Intramural Res Program Emot & Dev Branch, Bethesda, MD 20892 USA. RP Salum, GA (reprint author), Hosp Clin Porto Alegre, Rua Ramiro Barcelos 2350-2202, BR-90035003 Porto Alegre, RS, Brazil. EM gsalumjr@gmail.com RI Salum, Giovanni/A-7849-2010; DeSousa, Diogo/D-1605-2016 OI Salum, Giovanni/0000-0002-7537-7289; DeSousa, Diogo/0000-0003-4112-6649 FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); CNPq; FAPERGS; Fundo de Incentivo a Pesquisa - Hospital de Clinicas de Porto Alegre - FIPE-HCPA FX Giovanni Abrahao Salum receives a post-doctoral fellowship from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) and Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS). Diogo Araujo DeSouza receives a doctoral fellowship from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). Maria Conceicao do Rosario receives research support from Brazilian government institutions (CNPq) and has worked in the last 5 years as a speaker for the companies Novartis and Shire. Daniel Pine declares no potential conflicts of interest. Gisele Gus Manfro receives research support from Brazilian government institutions (CNPq, FAPERGS and Fundo de Incentivo a Pesquisa - Hospital de Clinicas de Porto Alegre - FIPE-HCPA). NR 201 TC 7 Z9 8 U1 9 U2 21 PU ASSOC BRASILEIRA PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP 04039-032 A, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PY 2013 VL 35 SU 1 BP S3 EP S21 DI 10.1590/1516-4446-2013-S108 PG 19 WC Psychiatry SC Psychiatry GA 235SX UT WOS:000325742100003 PM 24142122 ER PT S AU Lee, IH Yun, J Finkel, T AF Lee, In Hye Yun, Jeanho Finkel, Toren BE Hirschey, MD TI The Emerging Links Between Sirtuins and Autophagy SO SIRTUINS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Autophagy; p62; LC3; Autophagosome; Atg; Keima ID SIRT1; DEACETYLASE; MICE AB Evidence suggests a role for acetylation and deacetylation in regulating autophagy. In this chapter, we describe the methods useful for understanding this important connection. In particular, we discuss methods for the measurements of sirtuin deacetylase activity, in vivo acetylation detection, and the common assays used to monitor both autophagy and the more selective process of mitophagy. C1 [Lee, In Hye; Yun, Jeanho; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Yun, Jeanho] Dong A Univ, Coll Med, Dept Biochem, Pusan, South Korea. [Yun, Jeanho] Dong A Univ, Coll Med, Mitochondria Hub Regulat Ctr, Pusan, South Korea. RP Lee, IH (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA HL005012-18] NR 12 TC 3 Z9 3 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-637-5; 978-1-62703-636-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1077 BP 259 EP 271 DI 10.1007/978-1-62703-637-5_17 D2 10.1007/978-1-62703-637-5 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA BHK08 UT WOS:000325690400018 PM 24014412 ER PT S AU Curtis, J de Cabo, R AF Curtis, Jessica de Cabo, Rafael BE Hirschey, MD TI Utilizing Calorie Restriction to Evaluate the Role of Sirtuins in Healthspan and Lifespan of Mice SO SIRTUINS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Sirtuins; Calorie restriction; Lifespan; Healthspan ID DIETARY RESTRICTION; GLUCOSE-HOMEOSTASIS; INSULIN-SECRETION; RHESUS-MONKEYS; SIRT1; METABOLISM; SURVIVAL; PROTECTS; IMPACT; DAMAGE AB Calorie restriction is the most powerful method currently known to delay aging-associated disease and extend lifespan. Use of this technique in combination with genetic models has led to identification of key metabolic regulators of lifespan. Limiting energy availability by restricting caloric intake leads to redistribution of energy expenditure and storage. The signaling required for these metabolic changes is mediated in part by the sirtuins at both the posttranslational and transcriptional levels, and consequently, sirtuins are recognized as instigating factors in the regulation of lifespan. This family of class III protein deacetylases is responsible for directing energy regulation based on NAD(+) availability. However, there are many effectors of NAD(+) availability, and hence sirtuin action, that should be considered when performing experiments using calorie restriction. The methods outlined in this chapter are intended to provide a guide to help the aging community to use and interpret experimental calorie restriction properly. The importance of healthspan and the use of repeated measures to assess metabolic health during lifespan experiments are strongly emphasized. C1 [Curtis, Jessica; de Cabo, Rafael] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Curtis, J (reprint author), NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS NR 28 TC 5 Z9 5 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-637-5; 978-1-62703-636-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1077 BP 303 EP 311 DI 10.1007/978-1-62703-637-5_20 D2 10.1007/978-1-62703-637-5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA BHK08 UT WOS:000325690400021 PM 24014415 ER PT S AU Blair, RJR White, SF Meffert, H Hwang, S AF Blair, R. James R. White, Stuart F. Meffert, Harma Hwang, Soonjo BE Vilarroya, O Tobena, A TI Emotional learning and the development of differential moralities: implications from research on psychopathy SO SOCIABILITY, RESPONSIBILITY, AND CRIMINALITY: FROM LAB TO LAW SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 2nd Barcelona Social Brain Conference on Neuroethics - From Lab to Law-A Scientific Scrutiny of Sociability, Responsibility and Criminality CY NOV 12-13, 2012 CL Barcelona, SPAIN ID CALLOUS-UNEMOTIONAL TRAITS; DISRUPTIVE BEHAVIOR DISORDERS; VENTROMEDIAL PREFRONTAL CORTEX; FEARFUL EXPRESSIONS; VOCAL EXPRESSIONS; RESPONSE REVERSAL; NEURAL BASIS; AMYGDALA; TENDENCIES; JUDGMENTS AB In this paper, we will argue that (1) four classes of norm can be distinguished from a neuro-cognitive perspective; (2) learning the prohibitive power of these norms relies on relatively independent emotional systems; (3) individuals with psychopathy show selective impairment for one of these emotional learning systems and two classes of norm: care based and justice based; and (4) while emotional learning systems are necessary for appropriate moral development/reasoning, they are not sufficient for moral development/reasoning. C1 [Blair, R. James R.; White, Stuart F.; Meffert, Harma; Hwang, Soonjo] NIMH, NIH, Dept Hlth & Human Serv, Sect Affect Cognit Neurosci, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), Natl Inst Mental Health Psychiat, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM JamesBlair@mail.nih.gov OI Meffert, Harma/0000-0002-7298-7276 FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health [1-ZIA-MH002860-08] FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health under Grant number 1-ZIA-MH002860-08. NR 57 TC 3 Z9 3 U1 4 U2 19 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-872-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1299 BP 36 EP 41 DI 10.1111/nyas.12169 PG 6 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA BHM53 UT WOS:000325924700005 PM 25684831 ER PT J AU Johnson, JL Beamer, K AF Johnson, Jeannette L. Beamer, Keola TI An Indigenous Narrative of Resilience: Malama ko Aloha SO SUBSTANCE USE & MISUSE LA English DT Article DE Hawaiian; resilience; storytelling; indigenous ID NATIVE HAWAIIAN YOUTH; DRUG-USE; AMERICAN-INDIANS; SUBSTANCE-ABUSE; OWN WORDS; ADVERSITY; COMMUNITY; HEALTH; ADOLESCENTS; PSYCHOLOGY AB Many indigenous cultures use storytelling as the foundation for the transmission of important cultural information. Stories passed down from generation to generation sometimes teach, record history, provide examples, or inform. One important function of storytelling is the transmission of stories about cultural resilience illustrating how a cultural group has kept strong in the face of adversity. This article shows how storytelling in the Hawaiian culture has been used for this purpose and how the Beamer family has served as the master storytellers of their culture, keeping the culture and traditions alive through their music, dance, and stories. C1 [Johnson, Jeannette L.] NIA, NIH, Bethesda, MD 20892 USA. [Beamer, Keola] Starscape Mus, Lahaina, HI USA. RP Johnson, JL (reprint author), NIA, 7201 Wisconsin Blvd,Suite 2C212, Bethesda, MD 20892 USA. EM JJ1951@gmail.com NR 71 TC 2 Z9 2 U1 5 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2013 VL 48 IS 13 BP 1369 EP 1376 DI 10.3109/10826084.2013.814998 PG 8 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 230RP UT WOS:000325360400009 PM 24087870 ER PT S AU Cheung, HH Rennert, OM Lee, TL AF Cheung, Hoi-Hung Rennert, Owen M. Lee, Tin-Lap BE Lee, TL Luk, ACS TI Detection of Epigenetic Alterations Using Tiling Arrays SO TILING ARRAYS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Tiling array; MeDIP; Methylome; Epigenetic alteration AB The epigenetic status of cancer cells is a consequence of the neoplastic transformation of their normal counterpart. Epigenetic changes directly influence gene expression and chromatin organization, which consequently leads to escape from the tumor-suppression mechanisms. Global mapping for specific epigenetic modifications (e.g., DNA methylation) of the entire genome is required to reveal epigenetic hotspots associated with a cancer type/stage. DNA tiling arrays may be applied for genome-wide analysis of different epigenetic marks. Tiling arrays are high-density DNA microarrays that can be custom-made to survey regions of interest (e.g., gene promoters) or permit whole-genome analysis. To identify the genomic alterations associated with testicular cancers we used tiling arrays to profile their methylome. We successfully identified numerous epigenetically modified loci that arose as a consequence of tumor progression. C1 [Cheung, Hoi-Hung] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, Bethesda, MD USA. [Rennert, Owen M.] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Lee, Tin-Lap] Chinese Univ Hong Kong, Sch Biomed Sci, Reprod Endocrinol & Dev Program, Shatin, Hong Kong, Peoples R China. RP Cheung, HH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, Bethesda, MD USA. RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 NR 6 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-607-8; 978-1-62703-606-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1067 BP 79 EP 86 DI 10.1007/978-1-62703-607-8_6 D2 10.1007/978-1-62703-607-8 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA BHJ27 UT WOS:000325613400007 PM 23975787 ER PT S AU Cheung, HH Claus, J Singh, S Sastry, C Rennert, OM Chan, WY Lee, TL AF Cheung, Hoi-Hung Claus, Janek Singh, Sumeeta Sastry, Chandan Rennert, Owen M. Chan, Wai-Yee Lee, Tin-Lap BE Lee, TL Luk, ACS TI Mapping Genomic Features of Tiling Microarray Data by TileMapper SO TILING ARRAYS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Annotations; Genomics; ChIP-chip; MeDIP; Transcriptome ID NONCODING RNAS; CHROMOSOME-22 AB The recent revolution of genomics techniques has allowed the detection of various sequence features and biological variations on whole-genome scale. However, these high-resolution data present significant challenges for experimental biologists to understand and analyze. The conventional way is to use genome browsers to locate and visualize regions of interest. But it lacks user-friendly data mining functionality. Here we present a protocol that allows rapid annotation of genomic coordinate data by using TileMapper. Interesting biological annotations from large-scale genomic data, such as transcriptome analysis, chromatin immunoprecipitation on chip, or methylated DNA immunoprecipitation (MeDIP) studies generated from the tiling microarrays and other platforms, could be analyzed without requiring computational skills. The outputs are saved in tabulated format, which permit flexible and simple processing in spreadsheet software, or to be exported to other pipelines for subsequent analysis. C1 [Cheung, Hoi-Hung] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, Bethesda, MD USA. [Claus, Janek; Singh, Sumeeta; Sastry, Chandan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Informat Technol, NIH, Bethesda, MD USA. [Rennert, Owen M.] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Chan, Wai-Yee] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin Genom, NIH, Bethesda, MD USA. [Lee, Tin-Lap] Chinese Univ Hong Kong, Sch Biomed Sci, Reprod Endocrinol & Dev Program, Shatin, Hong Kong, Peoples R China. RP Cheung, HH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, Bethesda, MD USA. RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 NR 5 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-607-8; 978-1-62703-606-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1067 BP 225 EP 233 DI 10.1007/978-1-62703-607-8_14 D2 10.1007/978-1-62703-607-8 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA BHJ27 UT WOS:000325613400015 PM 23975795 ER PT J AU Revell, AD Alvarez-Uria, G Wang, DC Pozniak, A Montaner, JS Lane, HC Larder, BA AF Revell, Andrew D. Alvarez-Uria, Gerardo Wang, Dechao Pozniak, Anton Montaner, Julio S. Lane, H. Clifford Larder, Brendan A. TI Potential Impact of a Free Online HIV Treatment Response Prediction System for Reducing Virological Failures and Drug Costs after Antiretroviral Therapy Failure in a Resource-Limited Setting SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID COMPUTATIONAL MODELS; GENOTYPE; RESISTANCE; ACCUMULATION; AFRICA; TOOL AB Objective. Antiretroviral drug selection in resource-limited settings is often dictated by strict protocols as part of a public health strategy. The objective of this retrospective study was to examine if the HIV-TRePS online treatment prediction tool could help reduce treatment failure and drug costs in such settings. Methods. The HIV-TRePS computational models were used to predict the probability of response to therapy for 206 cases of treatment change following failure in India. The models were used to identify alternative locally available 3-drug regimens, which were predicted to be effective. The costs of these regimens were compared to those actually used in the clinic. Results. The models predicted the responses to treatment of the cases with an accuracy of 0.64. The models identified alternative drug regimens that were predicted to result in improved virological response and lower costs than those used in the clinic in 85% of the cases. The average annual cost saving was $364 USD per year (41%). Conclusions. Computational models that do not require a genotype can predict and potentially avoid treatment failure and may reduce therapy costs. The use of such a system to guide therapeutic decision-making could confer health economic benefits in resource-limited settings. C1 [Revell, Andrew D.; Wang, Dechao; Larder, Brendan A.] HIV Resistance Response Database Initiat RDI, London N1 7DH, England. [Alvarez-Uria, Gerardo] RDT Hosp, Bathalapalli 515661, AP, India. [Pozniak, Anton] Chelsea & Westminster Hosp, London SW10 9NH, England. [Montaner, Julio S.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Lane, H. Clifford] NIAID, Bethesda, MD 20892 USA. RP Revell, AD (reprint author), HIV Resistance Response Database Initiat RDI, 14 Union Sq, London N1 7DH, England. EM andrewrevell@hivrdi.org FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institute of Allergy and Infectious Diseases FX The RDI data and study group wishes to thank all the following individuals and institutions for providing the data used in training and testing its models. Cohorts: Peter Reiss and Ard van Sighem (ATHENA, the Netherlands); Julio Montaner and Richard Harrigan (BC Center for Excellence in HIV & AIDS, Canada); Tobias Rinke de Wit, Raph Hamers and Kim Sigaloff (PASER-M cohort, The Netherlands); Brian Agan; Vincent Marconi and Scott Wegner (US Department of Defense); Wataru Sugiura (National Institute of Health, Japan); Maurizio Zazzi (MASTER, Italy); Adrian Streinu-Cercel (National Institute of Infectious Diseases); Professor Dr. Matei Bals, (Bucharest, Romania); Gerardo Alvarez-Uria (VFHCS, India). Clinics: Jose Gatell and Elisa Lazzari (University Hospital, Barcelona, Spain); Brian Gazzard, Mark Nelson, Anton Pozniak, and Sundhiya Mandalia (Chelsea and Westminster Hospital, London, UK); Lidia Ruiz and Bonaventura Clotet (Fundacion IrsiCaixa, Badelona, Spain); Schlomo Staszewski (Hospital of the Johann Wolfgang Goethe-University, Frankfurt, Germany); Carlo Torti (University of Brescia); Cliff Lane and Julie Metcalf (National Institutes of Health Clinic, Rockville, USA); Maria-Jesus Perez-Elias (Instituto Ramon y Cajal de Investigacion Sanitaria, Madrid, Spain); Andrew Carr, Richard Norris, and Karl Hesse (Immunology B Ambulatory Care Service, St. Vincent's Hospital, Sydney, NSW, Australia); Dr Emanuel Vlahakis (Taylor's Square Private Clinic, Darlinghurst, NSW, Australia); Hugo Tempelman and Roos Barth (Ndlovu Care Group, Elandsdoorn, South Africa), Carl Morrow and Robin Wood (Desmond Tutu HIV Centre, Cape Town, South Africa); Luminita Ene ("Dr. Victor Babes" Hospital for Infectious and Tropical Diseases, Bucharest, Romania); Clinical trials: Sean Emery and David Cooper (CREST); Carlo Torti (GenPherex); John Baxter (GART, MDR); Laura Monno and Carlo Torti (PhenGen); Jose Gatell and Bonventura Clotet (HAVANA); Gaston Picchio and Marie-Pierre deBethune (DUET 1 & 2 and POWER 3); Maria-Jesus Perez-Elias (RealVirfen). This paper has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract no. HHSN261200800001E. This research was supported by the National Institute of Allergy and Infectious Diseases. NR 21 TC 2 Z9 2 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 579741 DI 10.1155/2013/579741 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 231IY UT WOS:000325411200001 ER PT J AU Laje, G McMahon, FJ AF Laje, Gonzalo McMahon, Francis J. BE Mann, JJ McGrath, PJ Roose, SP TI Pharmacogenetics and mood disorders SO CLINICAL HANDBOOK FOR THE MANAGEMENT OF MOOD DISORDERS LA English DT Article; Book Chapter ID STAR-ASTERISK-D; EMERGENT SUICIDAL IDEATION; GENOME-WIDE ASSOCIATION; ANTIDEPRESSANT TREATMENT RESPONSE; SEQUENCED TREATMENT ALTERNATIVES; GENE PROMOTER POLYMORPHISM; MAJOR DEPRESSIVE DISORDER; STEVENS-JOHNSON-SYNDROME; ELEMENT-BINDING PROTEIN; SEROTONIN TRANSPORTER C1 [Laje, Gonzalo] George Washington Univ, Washington, DC 20052 USA. [McMahon, Francis J.] NIMH, Bethesda, MD 20892 USA. RP Laje, G (reprint author), George Washington Univ, Washington, DC 20052 USA. NR 70 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-02463-2 PY 2013 BP 368 EP 379 D2 10.1017/CBO9781139175869 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BGN18 UT WOS:000323552500029 ER PT J AU McCaffery, JM Papandonatos, GD Huggins, GS Peter, I Erar, B Kahn, SE Knowler, WC Lipkin, EW Kitabchi, AE Wagenknecht, LE Wing, RR AF McCaffery, Jeanne M. Papandonatos, George D. Huggins, Gordon S. Peter, Inga Erar, Bahar Kahn, Steven E. Knowler, William C. Lipkin, Edward W. Kitabchi, Abbas E. Wagenknecht, Lynne E. Wing, Rena R. CA Genetic Subgrp Look AHEAD Look AHEAD Res Grp TI Human Cardiovascular Disease IBC Chip-Wide Association with Weight Loss and Weight Regain in the Look AHEAD Trial SO HUMAN HEREDITY LA English DT Article DE Type 2 diabetes; Obesity; Weight loss; Diet; Genetics ID DIABETES PREVENTION PROGRAM; SALT EXPORT PUMP; BODY-MASS INDEX; FAMILIAL INTRAHEPATIC CHOLESTASIS; LIFE-STYLE INTERVENTION; OBESITY-RELATED TRAITS; ADIPOSE-TISSUE; CLINICAL-TRIAL; RISK-FACTORS; GENE AB Background/Aims:The present study identified genetic predictors of weight change during behavioral weight loss treatment. Methods: Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) on the Illumina CARe iSelect (IBC) chip (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost at year 1. Results: Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified (p < 2.96E-06). ABCB11 rs484066 was associated with 1.16 kg higher weight per minor allele at year 1, whereas TNFRSF11A, or RANK, rs17069904 was associated with 1.70 kg lower weight per allele at year 1. Conclusions: This study, the largest to date on genetic predictors of weight loss and regain, indicates that SNPs within ABCB11, related to bile salt transfer, and TNFRSF11A, implicated in adipose tissue physiology, predict the magnitude of weight loss during behavioral intervention. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment. (C) 2013 S. Karger AG, Basel C1 [McCaffery, Jeanne M.; Wing, Rena R.] Brown Univ, Miriam Hosp, Weight Control & Diabet Res Ctr, Dept Psychiat & Human Behav, Providence, RI USA. [McCaffery, Jeanne M.; Wing, Rena R.] Brown Univ, Brown Med Sch, Providence, RI 02912 USA. [Papandonatos, George D.; Erar, Bahar] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Huggins, Gordon S.] Mol Cardiol Res Inst, MCRI Ctr Translat Genom, Tufts Med Ctr, Boston, MA USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Lipkin, Edward W.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Knowler, William C.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ USA. [Kitabchi, Abbas E.] Univ Tennessee, Ctr Hlth Sci, Div Endocrinol Diabet & Metab, Memphis, TN 38163 USA. [Wagenknecht, Lynne E.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. RP McCaffery, JM (reprint author), Miriam Hosp, Weight Control & Diabet Res Ctr, 196 Richmond St, Providence, RI 02903 USA. EM jeanne_mccaffery@brown.edu RI Papandonatos, George/J-2328-2014; OI Papandonatos, George/0000-0001-6770-932X; Kahn, Steven/0000-0001-7307-9002 FU Department of Health and Human Services through National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR0021140]; University of Pittsburgh General Clinical Research Center (GCRC) [M01RR000056]; Clinical Translational Research Center (CTRC); Clinical and Translational Science Award [UL1 RR 024153]; NIH [DK 046204]; VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C. Bartter General Clinical Research Center [M01RR01346] FX This study was supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135 and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women's Health, and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the IHS or other funding sources.; Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (GCRC) (M01RR000056); the Clinical Translational Research Center (CTRC) funded by the Clinical and Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs, and the Frederic C. Bartter General Clinical Research Center (M01RR01346). NR 67 TC 8 Z9 8 U1 0 U2 16 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2013 VL 75 IS 2-4 BP 160 EP 174 DI 10.1159/000353181 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 229BE UT WOS:000325236000011 PM 24081232 ER PT J AU Yu, CR Dambuza, IM Lee, YJ Frank, GM Egwuagu, CE AF Yu, Cheng-Rong Dambuza, Ivy M. Lee, Yong-Jun Frank, Gregory M. Egwuagu, Charles E. TI STAT3 Regulates Proliferation and Survival of CD8(+) T Cells: Enhances Effector Responses to HSV-1 Infection, and Inhibits IL-10(+) Regulatory CD8(+) T Cells in Autoimmune Uveitis SO MEDIATORS OF INFLAMMATION LA English DT Article ID FORKHEAD TRANSCRIPTION FACTORS; IN-VIVO; STAT3-DEFICIENT MICE; GENERATION; RECEPTOR; DIFFERENTIATION; ACTIVATION; EXPRESSION; CONTRIBUTE; IL-2 AB STAT3 regulates CD4(+) T cell survival and differentiation. However, its effects on CD8(+) T cells are not well understood. Here, we show that in comparison to WT CD8(+) T cells, STAT3-deficient CD8(+) T cells exhibit a preactivated memory-like phenotype, produce more IL-2, proliferate faster, and are more sensitive to activation-induced cell death (AICD). The enhanced proliferation and sensitivity to AICD correlated with downregulation of class-O forkhead transcription factors (FoxO1, FoxO3A), p21(waf1), p27(KIP1), Bcl-2, OX-40, and upregulation of FasL, Bax, and Bad. We examined whether STAT3-deficient CD8(+) T cells can mount effective response during herpes simplex virus (HSV-1) infection and experimental autoimmune uveitis (EAU). Compared to WT mice, HSV-1-infected STAT3-deficient mice (STAT3KO) produced less IFN-gamma and virus-specific KLRG-1(+) CD8(+) T cells. STAT3KO mice are also resistant to EAU and produced less IL-17-producing Tc17 cells. Resistance of STAT3KO to EAU correlated with marked expansion of IL-10-producing regulatory CD8(+) T cells (CD8-Treg) implicated in recovery from autoimmune encephalomyelitis. Thus, increases of IL-6-induced STAT3 activation observed during inflammation may inhibit expansion of CD8-Tregs, thereby impeding recovery from uveitis. These results suggest that STAT3 is a potential therapeutic target for upregulating CD8(+) T cell-mediated responses to viruses and suggest the successful therapeutic targeting of STAT3 as treatment for uveitis, derived, in part, from promoting CD8-Treg expansion. C1 [Yu, Cheng-Rong; Dambuza, Ivy M.; Lee, Yong-Jun; Egwuagu, Charles E.] Natl Inst Allergy & Viral Dis, Mol Immunol Sect, NEI, NIH, Bethesda, MD 20892 USA. [Frank, Gregory M.] Natl Inst Allergy & Viral Dis, Cellular Biol & Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), Natl Inst Allergy & Viral Dis, Mol Immunol Sect, NEI, NIH, Bldg 10,Room 10N109A,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov NR 32 TC 6 Z9 6 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2013 AR 359674 DI 10.1155/2013/359674 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 230GH UT WOS:000325324600001 ER PT J AU Wu, MC Forbes, JG Wang, K AF Wu, Ming-Chya Forbes, Jeffrey G. Wang, Kuan TI Correlated vibrations in ion-pair dynamics in mechanoactivation identify functional domains of force-dependent titin kinase SO SOFT MATTER LA English DT Article ID MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; ARC REPRESSOR; TIME-SERIES; SALT BRIDGE; PROTEINS; RECOGNITION; ACTIVATION; BEHAVIOR AB Titin kinase is a mechanoenzyme, whose activity is activated by mechanical stretching and binding of calcium sensors. Stretching causes local and global conformational changes of secondary structures and complex movements of ion pairs and transient formations of salt bridges. This paper applies the adaptive time series analysis approach to study the mechanical responses of ion-pair movements to stretch unfolding through steered molecular dynamics (SMD) simulations, focusing on the ion-pair dynamics of mechanoactivation obtained from the SMD trajectories. Temporal correlation analysis of the ion-pair time series shows that the activation process involves changes of secondary structure. Spectral analysis defined several groups and subgroups of the ion pairs with vibrational damping/resonance in the scale of similar to 0.5 angstrom, corresponding to vibrational modes of chemical bonds. Examination of these groups revealed the locations or neighboring structures of the autoinhibitory loop, ATP binding cleft, catalytic loop, and P+1 loop, all key functional domains of this kinase. We propose that the correlated vibrations of subgroups of ion pairs have significant correlations with functional domains, which can be used to identify, a priori, special functional and structural features of folded proteins. C1 [Wu, Ming-Chya] Natl Cent Univ, Res Ctr Adapt Data Anal, Chungli 32001, Taiwan. [Wu, Ming-Chya; Wang, Kuan] Acad Sinica, Inst Phys, Taipei 11529, Taiwan. [Forbes, Jeffrey G.; Wang, Kuan] NIAMSD, Muscle Prote & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Kuan] Acad Sinica, Inst Biol Chem, Nanomed Program, Taipei 11529, Taiwan. RP Wu, MC (reprint author), Natl Cent Univ, Res Ctr Adapt Data Anal, Chungli 32001, Taiwan. EM mcwu@ncu.edu.tw FU National Science Council of the Republic of China (Taiwan), NCTS of Taiwan [NSC 96-2112-M-008-021-MY3, 97-2627-B-008-004, 100-2112-M-008-003-MY3]; Nanomedicine Program of Academia Sinica; Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, DHHS FX This work was supported by the National Science Council of the Republic of China (Taiwan) under Grant no. NSC 96-2112-M-008-021-MY3, 97-2627-B-008-004, and 100-2112-M-008-003-MY3, NCTS of Taiwan, and the Nanomedicine Program of Academia Sinica. This work was also supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, DHHS. This study utilized the high performance computational capabilities of the Biowulf PC/Linux cluster at NIH (http://biowulf.nih.gov). NAMD was developed by the Theoretical and Computational Biophysics Group in the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. NR 56 TC 1 Z9 1 U1 2 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X J9 SOFT MATTER JI Soft Matter PY 2013 VL 9 IS 41 BP 9897 EP 9906 DI 10.1039/c3sm51539g PG 10 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 230VV UT WOS:000325372300021 ER PT J AU Bradigan, PS Hartel, LJ AF Bradigan, Pamela S. Hartel, Lynda J. BE Blessinger, K Hrycaj, P TI Organizational culture and leadership: exploring perceptions and relationships SO WORKPLACE CULTURE IN ACADEMIC LIBRARIES: THE EARLY 21ST CENTURY SE Chandos Information Professional Series LA English DT Article; Book Chapter DE accountability; coaching; collaboration; leadership; Mood Elevator; organizational culture; organizational health; Edgar Schein; Senn Delaney; subcultures AB Organizational culture plays a powerful role in the workplace. What issues are impacting the cultural dynamics of the workplace in today's academic library? What are the cultural challenges of the workplace facing library leaders? The authors provide definitions of organizational culture, consider the importance of subcultures, review the literature from corporate and academic perspectives, and explore a leader- and employee-driven approach to fostering a high-performing culture. Principles of organizational culture, including values, perceptions, organizational history, and employee leadership and accountability, are discussed. The authors present recommended leadership practices from the perspective of academic librarians actively engaged in rethinking culture to improve performance and outcomes. C1 [Bradigan, Pamela S.; Hartel, Lynda J.] Ohio State Univ, Columbus, OH 43210 USA. [Bradigan, Pamela S.; Hartel, Lynda J.] Ohio State Univ, Hlth Sci Lib, Columbus, OH 43210 USA. [Bradigan, Pamela S.] Natl Lib Med, Bethesda, MD 20894 USA. RI Hartel, Lynda/E-8138-2011 OI Hartel, Lynda/0000-0001-6359-9178 NR 0 TC 0 Z9 0 U1 0 U2 2 PU CHANDOS PUBL PI SAWSTON PA 80 HIGH ST, SAWSTON, CAMBRIDGE CB22 3HJ, ENGLAND BN 978-1-78063-368-8 J9 CHANDOS INF PROF SER PY 2013 BP 7 EP 19 D2 10.1533/9781780633688 PG 13 WC Information Science & Library Science SC Information Science & Library Science GA BGP57 UT WOS:000323721100002 ER PT S AU Dickler, HB McCoy, JP Nussenblatt, R Perl, S Schwartzberg, PA Tsang, JS Wang, E Young, NS AF Dickler, Howard B. McCoy, J. Philip Nussenblatt, Robert Perl, Shira Schwartzberg, Pamela A. Tsang, John S. Wang, Ena Young, Neil S. BE Rose, NR TI The National Institutes of Health Center for Human Immunology, Autoimmunity, and Inflammation: history and progress SO YEAR IN IMMUNOLOGY SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE human; immunology; autoimmunity; inflammation ID DOSE INTERLEUKIN-2; FLOW-CYTOMETRY AB The Center for Human Immunology, Autoimmunity, and Inflammation (CHI) is an exciting initiative of the NIH intramural program begun in 2009. It is uniquely trans-NIH in support (multiple institutes) and leadership (senior scientists from several institutes who donate their time). Its goal is an in-depth assessment of the human immune system using high-throughput multiplex technologies for examination of immune cells and their products, the genome, gene expression, and epigenetic modulation obtained from individuals both before and after interventions, adding information from in-depth clinical phenotyping, and then applying advanced biostatistical and computer modeling methods for mining these diverse data. The aim is to develop a comprehensive picture of the human "immunome" in health and disease, elucidate common pathogenic pathways in various diseases, identify and validate biomarkers that predict disease progression and responses to new interventions, and identify potential targets for new therapeutic modalities. Challenges, opportunities, and progress are detailed. C1 [Dickler, Howard B.; McCoy, J. Philip; Perl, Shira] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Dickler, Howard B.; McCoy, J. Philip; Perl, Shira] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Nussenblatt, Robert] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Schwartzberg, Pamela A.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Tsang, John S.] NIAID, Lab Syst Biol, Bethesda, MD 20892 USA. [Wang, Ena] NIH, Lab Serv Sect, Dept Transfus Med, Off Deputy Clin Care,Clin Ctr, Bethesda, MD 20892 USA. [Young, Neil S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, R (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 4 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1285 BP 133 EP 147 DI 10.1111/nyas.12101 PG 15 WC Immunology SC Immunology GA BHB56 UT WOS:000324886100010 PM 23692568 ER PT S AU Uhl, GR AF Uhl, George R. BE Uhl, GR TI Preface to Addiction Reviews SO ADDICTION REVIEWS SE Annals of the New York Academy of Sciences LA English DT Editorial Material; Book Chapter C1 NIH Intramural Res Program NIDA, Baltimore, MD USA. RP Uhl, GR (reprint author), NIH Intramural Res Program NIDA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1282 BP IV EP IV DI 10.1111/nyas.12100 PG 1 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA BHB03 UT WOS:000324841500001 ER PT S AU Contoreggi, C Lee, MR Chrousos, G AF Contoreggi, Carlo Lee, Mary R. Chrousos, George BE Uhl, GR TI Addiction and corticotropin-releasing hormone type 1 receptor antagonist medications SO ADDICTION REVIEWS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE corticotropin-releasing hormone; CRH antagonists; stress; addiction ID GENE-EXPRESSION ANALYSIS; CUE-INDUCED DRUG; MAJOR DEPRESSION; PSYCHOLOGICAL STRESS; SENSITIVE PERIODS; BINDING-KINETICS; SUICIDE BRAIN; COCAINE CUES; CRHR1 GENE; CRF FAMILY AB Derangements in corticotropin-releasing hormone (CRH) through its type 1 receptor (CRHR1) have been identified in many pathologic conditions. Preclinical models of addiction find that small-molecule antagonists of CRHR1 can limit induction, maintenance, and relapse to drugs of abuse. Neuropsychiatric clinical trials of CRHR1 antagonists have shown mixed efficacy; treatment of addictive disorders has not been established, but finding effective treatments for addictive disorders is critical. Establishing effectiveness for substance abuse treatment will require a different design approach than was used for depression and anxiety trials. Focusing on active versus passive outcome measures, such as resilience to external stressful stimuli, may provide signals in curbing craving and relapse. Study design should include measures of abstinence and drug exposure, but additional elements of stress prevention should also be incorporated. Agents that could provide preemptive protection from drug use and relapse are novel and untested. An understanding of the evolutionary significance of the stress system and preclinical models suggests that these agents may provide protection in this manner. Investigators designing future trials might refocus their understanding of addiction and treatment in this new direction. C1 [Contoreggi, Carlo] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Lee, Mary R.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Chrousos, George] Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, GR-11527 Athens, Greece. RP Contoreggi, C (reprint author), NIDA, Intramural Res Program, NIH, Johns Hopkins Bayview Med Ctr, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM ccontore@intra.nida.nih.gov NR 94 TC 3 Z9 3 U1 1 U2 6 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1282 BP 107 EP 118 DI 10.1111/nyas.12007 PG 12 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA BHB03 UT WOS:000324841500008 PM 23398379 ER PT J AU Thompson, JL AF Thompson, Jennifer L. TI Carfilzomib: A Second-Generation Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma SO ANNALS OF PHARMACOTHERAPY LA English DT Article ID SINGLE-AGENT CARFILZOMIB; OPEN-LABEL; BORTEZOMIB; ARM; CRITERIA; PHASE-2; PR-171 AB OBJECTIVE: To review and summarize data on carfilzomib, which was approved by the Food and Drug Administration (FDA) in July 2012 for the treatment of patients with relapsed and refractory multiple myeloma (MM) who received prior bortezomib and thalidomide or lenalidomide. DATA SOURCES: A literature search through PubMed was conducted through October 2012 using the terms carfilzomib, PR-171, proteasome inhibitor (PI), and MM. Data were also obtained through the American Society of Clinical Oncology and American Society of Hematology abstracts and FDA briefing documents. STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to human studies published in English. Priority was placed on trials of carfilzomib in relapsed and refractory MM. DATA SYNTHESIS: Carfilzomib is a new PI that differs in pharmacology and pharmacokinetics from bortezomib, the first-in-class PI. The FDA approval was based on efficacy data from a Phase 2 study of carfilzomib in patients with relapsed and refractory MM (n = 266). All patients had received prior bortezomib and 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients were treated with intravenous carfilzomib 20 mg/m(2) (cycle 1) followed by 27 mg/m(2) (cycles >= 2) on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. The overall response rate was 23.7% (18.7-29.4), with a median duration of response of 7.8 (5.6-9.2) months. Safety data from an integrated analysis reported thrombocytopenia, anemia, fatigue, nausea, and diarrhea as the most common adverse events, with minimal dose-limiting neutropenia or peripheral neuropathy (PN) (n = 526). The incidence of grade 3 or higher thrombocytopenia was 24.9%, while that of neutropenia was 11.9%, and the incidence of all grades of treatment-emergent PN was 13%. CONCLUSIONS: Carfilzomib is a safe and effective new treatment option for patients with relapsed MM refractory to bortezomib and thalidomide or lenalidomide. Randomized head-to-head trials with bortezomib will assist in formulary and treatment decisions in the context of PIs as a drug class. C1 NCI, Pharmaceut Management Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag,NIH, Rockville, MD USA. RP Thompson, JL (reprint author), NCI, Pharmaceut Management Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag,NIH, Rockville, MD USA. EM jennifer.thompson3@nih.gov NR 27 TC 31 Z9 33 U1 2 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 2013 VL 47 IS 1 BP 56 EP 62 DI 10.1345/aph.1R561 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 225RX UT WOS:000324981100014 PM 23300152 ER PT J AU Carrera, I Etcheverria, I Li, Y Fernandez-Novoa, L Lombardi, V Vigo, C Palacios, HH Benberin, VV Cacabelos, R Aliev, G AF Carrera, Ivan Etcheverria, Ignacio Li, Yi Fernandez-Novoa, Lucia Lombardi, Valter Vigo, Carmen Palacios, Hector H. Benberin, Valery V. Cacabelos, Ramon Aliev, Gjumrakch TI Immunocytochemical Characterization of Alzheimer Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-beta Vaccine SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID PRECURSOR-PROTEIN; MOUSE MODEL; IN-VIVO; PRESENILIN-1 TRANSGENES; MEMORY IMPAIRMENT; IMMUNE-RESPONSE; IMMUNIZATION; PATHOLOGY; DEPOSITION; PEPTIDE AB APP/PS1 double-transgenic mouse models of Alzheimer's disease (AD), which overexpress mutated forms of the gene for human amyloid precursor protein (APP) and presenilin 1 (PS1), have provided robust neuropathological hallmarks of AD-like pattern at early ages. This study characterizes immunocytochemical patterns of AD mouse brain as a model for human AD treated with the EB101 vaccine. In this novel vaccine, a new approach has been taken to circumvent past failures by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol). Our findings showed that administration of amyloid-beta(1-42) (A beta) and sphingosine-1-phosphate emulsified in liposome complex (EB101) to APP/PS1 mice before onset of A.. deposition (7 weeks of age) and/or at an older age (35 weeks of age) is effective in halting the progression and clearing the AD-like neuropathological hallmarks. Passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus) in the brain of treated mice was notably reduced. These results demonstrate that immunization with EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice. C1 [Carrera, Ivan; Etcheverria, Ignacio; Fernandez-Novoa, Lucia; Lombardi, Valter] EuroEspes Biotechnol, Dept Neurosci, La Coruna 15165, Spain. [Li, Yi] Texas A&M Univ Kingsville, Dept Human Sci, Kingsville, TX USA. [Vigo, Carmen] Atlas Pharmaceut, Sunnyvale, CA USA. [Palacios, Hector H.] NIA, NIH, Baltimore, MD 21224 USA. [Benberin, Valery V.] Med Ctr Adm, Astana, Kazakhstan. [Cacabelos, Ramon] Inst CNS Disorders & Genom Med, EuroEspes Biomed Res Ctr, La Coruna 15165, Spain. [Aliev, Gjumrakch] GALLY Int Biomed Res Consulting LLC, San Antonio, TX USA. [Aliev, Gjumrakch] Univ Atlanta, Dept Hlth Sci & Healthcare Adm, Atlanta, GA USA. RP Cacabelos, R (reprint author), Inst CNS Disorders & Genom Med, EuroEspes Biomed Res Ctr, La Coruna 15165, Spain. EM rcacabelos@euroespes.com; aliev03@gmail.com NR 68 TC 9 Z9 9 U1 1 U2 12 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 709145 DI 10.1155/2013/709145 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 222LW UT WOS:000324733500001 ER PT S AU Shi, YB AF Shi, Yun-Bo BE Rougvie, AE OConnor, MB TI Unliganded Thyroid Hormone Receptor Regulates Metamorphic Timing via the Recruitment of Histone Deacetylase Complexes SO DEVELOPMENTAL TIMING SE Current Topics in Developmental Biology LA English DT Review; Book Chapter ID RANA-CATESBEIANA TADPOLES; RETINOIC ACID RECEPTORS; INTESTINAL STEM-CELLS; XENOPUS-LAEVIS; AMPHIBIAN METAMORPHOSIS; POSTEMBRYONIC DEVELOPMENT; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; MEDIATED TRANSCRIPTION; COREPRESSOR COMPLEX AB Anuran metamorphosis involves a complex series of tissue transformations that change an aquatic tadpole to a terrestrial frog and resembles the postembryonic perinatal period in mammals. Thyroid hormone (TH) plays a causative role in amphibian metamorphosis and its effect is mediated by TH receptors (TRs). Molecular analyses during Xenopus development have shown that unliganded TR recruits histone deacetylase (HDAC)-containing N-CoR/SMRT complexes and causes histone deacetylation at target genes while liganded TR leads to increased histone acetylations and altered histone methylations at target genes. Transgenic studies involving mutant TR-cofactors have shown that corepressor recruitment by unliganded TR is required to ensure proper timing of the onset of metamorphosis while coactivator levels influence the rate of metamorphic progression. In addition, a number of factors that can influence cellular free TH levels appear to contribute the timing of metamorphic transformations of different organs by regulating the levels of unliganded vs. liganded TR in an organ-specific manner. Thus, the recruitment of HDAC-containing corepressor complexes by unliganded TR likely controls both the timing of the initiation of metamorphosis and the temporal regulation of organ-specific transformations. Similar mechanisms likely mediate TR function in mammals as the maturation of many organs during postembryonic development is dependent upon TH and resembles organ metamorphosis in amphibians. C1 NICHD, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHD, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. EM Shi@helix.nih.gov FU Intramural NIH HHS [ZIA HD001901-19] NR 116 TC 12 Z9 12 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0070-2153 BN 978-0-12-397275-0 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2013 VL 105 BP 275 EP 297 DI 10.1016/B978-0-12-396968-2.00010-5 PG 23 WC Developmental Biology SC Developmental Biology GA BGR91 UT WOS:000323925100011 PM 23962846 ER PT J AU Li, M Mazilu, D Horvath, KA AF Li, Ming Mazilu, Dumitru Horvath, Keith A. BE Kpodonu, J Bonan, R TI Real-time magnetic resonance imaging guidance in cardiac surgery SO ENDOVASCULAR AND HYBRID THERAPIES FOR STRUCTURAL HEART AND AORTIC DISEASE LA English DT Article; Book Chapter ID CARDIOPULMONARY BYPASS; CATHETER TRACKING; MRI; TSENSE C1 [Li, Ming; Mazilu, Dumitru] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. [Horvath, Keith A.] NHLBI, NIH Heart Ctr, Suburban Hosp, Cardiothorac Surg Res Program,NIH, Bethesda, MD 20892 USA. RP Li, M (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 26 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-0-470-65639-6 PY 2013 BP 253 EP 261 D2 10.1002/9781118504536 PG 9 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA BGS03 UT WOS:000323932300021 ER PT J AU Wolf, YI Snir, S Koonin, EV AF Wolf, Yuri I. Snir, Sagi Koonin, Eugene V. TI Stability along with Extreme Variability in Core Genome Evolution SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE evolutionary rate; universal genes; molecular clock; universal pacemaker of genome evolution ID OVERDISPERSED MOLECULAR CLOCK; EUKARYOTIC GENES; DROSOPHILA; ORTHOLOGY; DATABASE; SEARCH; RATES AB The shape of the distribution of evolutionary distances between orthologous genes in pairs of closely related genomes is universal throughout the entire range of cellular life forms. The near invariance of this distribution across billions of years of evolution can be accounted for by the Universal PaceMaker (UPM) model of genome evolution that yields a significantly better fit to the phylogenetic data than the Molecular Clock (MC) model. Unlike the MC, the UPM model does not assume constant gene-specific evolutionary rates but rather postulates that, in each evolving lineage, the evolutionary rates of all genes change (approximately) in unison although the pacemakers of different lineages are not necessarily synchronized. Here, we dissect the nearly constant evolutionary rate distribution by comparing the genome-wide relative rates of evolution of individual genes in pairs or triplets of closely related genomes from diverse bacterial and archaeal taxa. We show that, although the gene-specific relative rate is an important feature of genome evolution that explains more than half of the variance of the evolutionary distances, the ranges of relative rate variability are extremely broad even for universal genes. Because of this high variance, the gene-specific rate is a poor predictor of the conservation rank for any gene in any particular lineage. C1 [Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Snir, Sagi] Univ Haifa Mt Carmel, Dept Evolutionary & Environm Biol, Haifa, Israel. [Snir, Sagi] Univ Haifa Mt Carmel, Inst Evolut, Haifa, Israel. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov FU US Department of Health and Human Services; Yeshaya Horowitz Association through the Center for Complexity Science FX The authors thank Alex Lobkovsky for expert help with the statistical analysis. This work was supported by intramural funds of the US Department of Health and Human Services (to National Library of Medicine) to Y.I.W. and E. V. K. and by the Yeshaya Horowitz Association through the Center for Complexity Science to S.S. NR 31 TC 10 Z9 10 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2013 VL 5 IS 7 BP 1393 EP 1402 DI 10.1093/gbe/evt098 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 220OQ UT WOS:000324594500013 PM 23821522 ER PT J AU Hudecova, S Pacak, K Soltysova, A Krizanova, O AF Hudecova, Sona Pacak, Karel Soltysova, Andrea Krizanova, Olga TI NF-kappa B inhibition in pheochromocytoma cell lines causes apoptosis: A novel therapeutic option? SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Hudecova, Sona; Soltysova, Andrea; Krizanova, Olga] Slovak Acad Sci, Inst Mol Physiol & Genet, Bratislava 83334, Slovakia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PY 2013 VL 32 SU 1 MA 163 BP S20 EP S20 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 219LC UT WOS:000324507400064 ER PT S AU Tang, EG Arany, PR AF Tang, Elieza G. Arany, Praveen R. BE Hamblin, MR Arany, PR Carroll, JD TI Tissue Regeneration with Photobiomodulation SO MECHANISMS FOR LOW-LIGHT THERAPY VIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy VIII CY FEB 02, 2013 CL San Francisco, CA SP SPIE DE Photobiomodulation; Low level light therapy; tissue regeneration; wound healing ID LEVEL LASER THERAPY; LIGHT; ANGIOGENESIS; METAANALYSIS; NM AB Low level light therapy (LLLT) has been widely reported to reduce pain and inflammation and enhance wound healing and tissue regeneration in various settings. LLLT has been noted to have both stimulatory and inhibitory biological effects and these effects have been termed Photobiomodulation (PBM). Several elegant studies have shown the key role of Cytochrome C oxidase and ROS in initiating this process. The downstream biological responses remain to be clearly elucidated. Our work has demonstrated activation of an endogenous latent growth factor complex, TGF-beta 1, as one of the major biological events in PBM. TGF-beta 1 has critical roles in various biological processes especially in inflammation, immune responses, wound healing and stem cell biology. This paper overviews some of the studies demonstrating the efficacy of PBM in promoting tissue regeneration. C1 [Tang, Elieza G.; Arany, Praveen R.] NIDCR, Cell Regulat & Control Unit, NIH, Bethesda, MD 20892 USA. RP Arany, PR (reprint author), NIDCR, NIH, 30 Convent Dr,Room 3A-301, Bethesda, MD 20892 USA. EM Praveen.arany@nih.gov NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9338-5 J9 PROC SPIE PY 2013 VL 8569 AR UNSP 856907 DI 10.1117/12.2019284 PG 12 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BHA24 UT WOS:000324803700003 ER PT J AU Wansi, JD Devkota, KP Tshikalange, E Kuete, V AF Wansi, Jean Duplex Devkota, Krishna Prasad Tshikalange, Emmanuel Kuete, Victor BE Kuete, V TI Alkaloids from the Medicinal Plants of Africa SO MEDICINAL PLANT RESEARCH IN AFRICA: PHARMACOLOGY AND CHEMISTRY SE Elsevier Insights LA English DT Article; Book Chapter ID ACETYLCHOLINESTERASE INHIBITORY-ACTIVITY; AMARYLLIDACEAE ALKALOIDS; STEM BARK; FUROQUINOLINE ALKALOIDS; APORPHINE ALKALOIDS; NAPHTHYLISOQUINOLINE ALKALOIDS; PYRROLIZIDINE ALKALOIDS; ANTIPLASMODIAL ACTIVITY; BENZOPHENANTHRIDINE ALKALOIDS; ANTIBACTERIAL ACTIVITY C1 [Wansi, Jean Duplex] Univ Douala, Dept Chem, Douala, Cameroon. [Devkota, Krishna Prasad] Frederick Natl Lab Canc Res, Ctr Canc Res, Mol Targets Lab, Frederick, MD USA. [Tshikalange, Emmanuel] Univ Pretoria, Dept Plant Sci, ZA-0002 Pretoria, South Africa. [Kuete, Victor] Univ Dschang, Dept Biochem, Fac Sci, Dschang, Cameroon. RP Wansi, JD (reprint author), Univ Douala, Dept Chem, Douala, Cameroon. RI Tshikalange, Thilivhali Emmanuel/A-6590-2011; OI Tshikalange, Thilivhali Emmanuel/0000-0002-7454-1454; Kuete, Victor/0000-0002-1070-1236 NR 137 TC 5 Z9 5 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-405936-8 J9 ELSEV INSIGHT PY 2013 BP 557 EP 605 DI 10.1016/B978-0-12-405927-6.00014-X PG 49 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGT98 UT WOS:000324138400015 ER PT S AU Putney, JW AF Putney, James W. BE Prakriya, M TI Alternative Forms of the Store-Operated Calcium Entry Mediators, STIM1 and Orai1 SO STORE-OPERATED CALCIUM CHANNELS SE Current Topics in Membranes LA English DT Review; Book Chapter ID STROMAL INTERACTION MOLECULE-1; TYROSINE KINASE SYK; LOCAL CA2+ INFLUX; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; CHANNEL FUNCTION; GENE-EXPRESSION; DIRECT BINDING; CRAC CHANNELS; RELEASE AB Activation of phospholipase C results in release of intracellular Ca2+ and activation of Calf entry. Plasma membrane Ca2+ entry most commonly is signaled by the depletion of intracellular Ca2+ stores, a mechanism referred to as capacitative calcium entry or store-operated calcium entry (SOCE). The major players in the SOCE pathway are a Ca2+ sensor protein, STIM1, and a channel subunit, Orai1. STIM1 activates Orai channels by a mechanism that depends upon its colocalization with Orai at endoplasmic reticulum-plasma membrane junctions. Signaling proteins often occur in multiple forms with distinct properties and/or functions. Such forms arise by a number of mechanisms, including covalent modification, alternative splicing, and alternative translation initiation. This chapter summarizes and discusses recent work revealing alternative forms of STIM1 and Orai1, and the physiological consequences of these modified proteins. C1 NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Durham, NC USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Durham, NC USA. EM putney@niehs.nih.gov FU Intramural NIH HHS NR 61 TC 13 Z9 14 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 978-0-12-407870-3 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2013 VL 71 BP 109 EP 123 DI 10.1016/B978-0-12-407870-3.00005-6 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BGZ55 UT WOS:000324716400006 PM 23890113 ER PT S AU Cheng, KT Ong, HL Liu, XB Ambudkar, IS AF Cheng, Kwong Tai Ong, Hwei Ling Liu, Xibao Ambudkar, Indu S. BE Prakriya, M TI Contribution and Regulation of TRPC Channels in Store-Operated Ca2+ Entry SO STORE-OPERATED CALCIUM CHANNELS SE Current Topics in Membranes LA English DT Review; Book Chapter ID SMOOTH-MUSCLE-CELLS; STROMAL INTERACTION MOLECULE-1; RECEPTOR POTENTIAL CHANNEL-1; SALIVARY-GLAND CELLS; PLASMA-MEMBRANE; CALCIUM INFLUX; ENDOTHELIAL PERMEABILITY; CATION CHANNEL; ENDOPLASMIC-RETICULUM; CRAC CHANNELS AB Store-operated calcium entry (SOCE) is activated in response to depletion of the endoplasmic reticulum-Ca2+ stores following stimulation of plasma membrane receptors that couple to PIP2 hydrolysis and IP3 generation. Search for the molecular components of SOCE channels led to the identification of mammalian transient receptor potential canonical (TRPC) family of calcium-permeable channels (TRPC1-TRPC7), which are all activated in response to stimuli that result in PIP2 hydrolysis. While several TRPCs, including TRPC1, TRPC3, and TRPC4, have been implicated in SOCE, the data are most consistent for TRPC1. Extensive studies in cell lines and knockout mouse models have established the contribution of TRPC1 to SOCE. Furthermore, there is a critical functional interaction between TRPC1 and the key components of SOCE, STIM1, and Orai1, which determines the activation of TRPC1. Orai1-mediated Ca2+ entry is required for recruitment of TRPC1 and its insertion into surface membranes while STIM1 gates the channel. Notably, TRPC1 and Orai1 generate distinct patterns of Ca2+ signals in cells that are decoded for the regulation of specific cellular functions. Thus, SOCE appears to be a complex process that depends on temporal and spatial coordination of several distinct steps mediated by proteins in different cellular compartments. Emerging data suggest that, in many cell types;the net Ca2+ entry measured in response to store depletion is the result of the coordinated regulation of different calcium-permeable ion channels. Orai1 and STIM1 are central players in this process, and by mediating recruitment or activation of other Ca2+ channels, Orai1-CRAC function can elicit rapid changes in global and local [Ca2+](i) signals in cells. It is most likely that the type of channels and the [Ca2+](i) signature that are generated by this process reflect the physiological function of the cell that is regulated by Ca2+. C1 [Cheng, Kwong Tai; Ong, Hwei Ling; Liu, Xibao; Ambudkar, Indu S.] Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. RP Ambudkar, IS (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. EM indu.ambudkar@nih.gov FU Intramural NIH HHS [ZIA DE000438-26] NR 108 TC 60 Z9 64 U1 3 U2 20 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 978-0-12-407870-3 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2013 VL 71 BP 149 EP 179 DI 10.1016/B978-0-12-407870-3.00007-X PG 31 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BGZ55 UT WOS:000324716400008 PM 23890115 ER PT J AU Kapetanovic, IM AF Kapetanovic, Izet M. BE Preedy, VR TI Toxicity of Green Tea Polyphenols SO TEA IN HEALTH AND DISEASE PREVENTION LA English DT Article; Book Chapter ID EPIGALLOCATECHIN-GALLATE EGCG; CAMELLIA-SINENSIS; HEALTHY-INDIVIDUALS; HYDROGEN-PEROXIDE; CATECHINS; RATS; EXTRACT; SAFETY; HEPATOTOXICITY; CANCER C1 NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Kapetanovic, IM (reprint author), NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. NR 50 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-384938-0 PY 2013 BP 1435 EP 1447 DI 10.1016/B978-0-12-384937-3.00120-8 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BGQ97 UT WOS:000323833800121 ER PT S AU Narfstrom, K Deckman, KH Menotti-Raymond, M AF Narfstroem, Kristina Deckman, Koren Holland Menotti-Raymond, Marilyn BE Lewin, HA Roberts, RM TI Cats: A Gold Mine for Ophthalmology SO ANNUAL REVIEW OF ANIMAL BIOSCIENCES, VOL 1 SE Annual Review of Animal Biosciences LA English DT Article; Book Chapter DE eye; hereditary disease; molecular genetics; animal model; therapy ID HEREDITARY RETINAL DEGENERATION; DOMINANT RETINITIS-PIGMENTOSA; ROD-CONE DEGENERATION; MUCOPOLYSACCHARIDOSIS TYPE-VI; BETA-GLUCURONIDASE DEFICIENCY; MAROTEAUX-LAMY SYNDROME; PLURIPOTENT STEM-CELLS; ABYSSINIAN CATS; GENE-THERAPY; JOUBERT-SYNDROME AB Over 200 hereditary diseases have been identified and reported in the cat, several of which affect the eye, with homology to human hereditary disease. Compared with traditional murine models, the cat demonstrates more features in common with humans, including many anatomic and physiologic similarities, longer life span, increased size, and a genetically more heterogeneous background. The development of genomic resources in the cat has facilitated mapping and further characterization of feline models. During recent years, the wealth of knowledge in feline ophthalmology and neurophysiology has been extended to include new diseases of significant interest for comparative ophthalmology. This makes the cat an extremely valuable animal species to utilize for further research into disease processes affecting both cats and humans. This is especially true in the advancement and study of new treatment regimens and for extended therapeutic trials. Groups of feline eye diseases reviewed in the following are lysosomal storage disorders, congenital glaucoma, and neuroretinal degenerations. Each has important implications for human ophthalmic research. C1 [Narfstroem, Kristina] Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65201 USA. [Narfstroem, Kristina] RetVet KB, S-18593 Vaxholm, Sweden. [Deckman, Koren Holland] Gettysburg Coll, Dept Chem, Gettysburg, PA 17325 USA. [Menotti-Raymond, Marilyn] Frederick Natl Lab Canc Res, Lab Genom Divers, Frederick, MD 21702 USA. RP Narfstrom, K (reprint author), Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65201 USA. EM narfstromk@missouri.edu; kholland@gettysburg.edu; raymondm@mail.nih.gov NR 128 TC 4 Z9 4 U1 1 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 2165-8102 BN 978-0-8243-0001-2 J9 ANNU REV ANIM BIOSCI PY 2013 VL 1 BP 157 EP 177 DI 10.1146/annurev-animal-031412-103629 PG 21 WC Biotechnology & Applied Microbiology; Veterinary Sciences; Zoology SC Biotechnology & Applied Microbiology; Veterinary Sciences; Zoology GA BGM01 UT WOS:000323479900008 PM 25387015 ER PT S AU Lei, XG Weaver, JD Mullaney, E Ullah, AH Azain, MJ AF Lei, Xin Gen Weaver, Jeremy D. Mullaney, Edward Ullah, Abul H. Azain, Michael J. BE Lewin, HA Roberts, RM TI Phytase, a New Life for an "Old" Enzyme SO ANNUAL REVIEW OF ANIMAL BIOSCIENCES, VOL 1 SE Annual Review of Animal Biosciences LA English DT Article; Book Chapter DE animal; biotechnology; environment; food production; nutrition; phosphorus ID ASPERGILLUS-NIGER PHYTASE; ESCHERICHIA-COLI PHYTASE; SITE-DIRECTED MUTAGENESIS; BETA-PROPELLER PHYTASE; SOYBEAN MEAL DIETS; WHOLE-WHEAT BREAD; MYOINOSITOL HEXAKISPHOSPHATE PHOSPHOHYDROLASES; SUPPLEMENTAL MICROBIAL PHYTASE; OPTIMUM ACID-PHOSPHATASE; PHYTIC ACID AB Phytases are phosphohydrolytic enzymes that initiate stepwise removal of phosphate from phytate. Simple-stomached species such as swine, poultry, and fish require extrinsic phytase to digest phytate, the major form of phosphorus in plant-based feeds. Consequently, this enzyme is supplemented in these species' diets to decrease their phosphorus excretion, and it has emerged as one of the most effective and lucrative feed additives. This chapter provides a comprehensive review of the evolving course of phytase science and technology. It gives realistic estimates of the versatile roles of phytase in animal feeding, environmental protection, rock phosphorus preservation, human nutrition and health, and industrial applications. It elaborates on new biotechnology and existing issues related to developing novel microbial phytases as well as phytase-transgenic plants and animals. And it targets critical and integrated analyses on the global impact, novel application, and future demand of phytase in promoting animal agriculture, human health, and societal sustainability. C1 [Lei, Xin Gen] Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. [Weaver, Jeremy D.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Mullaney, Edward; Ullah, Abul H.] USDA ARS, New Orleans, LA 70124 USA. [Azain, Michael J.] Univ Georgia, Dept Anim Sci, Athens, GA 30602 USA. RP Lei, XG (reprint author), Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. EM XL20@cornell.edu; jdw25@cornell.edu; edwmull@gmail.com; abul.ullah@ars.usda.gov; mazain@uga.edu NR 183 TC 38 Z9 42 U1 6 U2 69 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 2165-8102 BN 978-0-8243-0001-2 J9 ANNU REV ANIM BIOSCI PY 2013 VL 1 BP 283 EP 309 DI 10.1146/annurev-animal-031412-103717 PG 27 WC Biotechnology & Applied Microbiology; Veterinary Sciences; Zoology SC Biotechnology & Applied Microbiology; Veterinary Sciences; Zoology GA BGM01 UT WOS:000323479900014 PM 25387021 ER PT S AU Krauzlis, RJ Lovejoy, LP Zenon, A AF Krauzlis, Richard J. Lovejoy, Lee P. Zenon, Alexandre BE Hyman, SE TI Superior Colliculus and Visual Spatial Attention SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 36 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE perception; pursuit; saccade; selection; neglect; eye movement ID PEDUNCULOPONTINE TEGMENTAL NUCLEUS; SACCADE TARGET SELECTION; IBOTENIC ACID LESIONS; CHICKS GALLUS-GALLUS; CORTICAL AREA MT; EYE-MOVEMENTS; OPTIC TECTUM; SUBSTANTIA-NIGRA; RHESUS-MONKEY; BASAL GANGLIA AB The superior colliculus (SC) has long been known to be part of the network of brain areas involved in spatial attention, but recent findings have dramatically refined our understanding of its functional role. The SC both implements the motor consequences of attention and plays a crucial role in the process of target selection that precedes movement. Moreover, even in the absence of overt orienting movements, SC activity is related to shifts of covert attention and is necessary for the normal control of spatial attention during perceptual judgments. The neuronal circuits that link the SC to spatial attention may include attention-related areas of the cerebral cortex, but recent results show that the SC's contribution involves mechanisms that operate independently of the established signatures of attention in visual cortex. These findings raise new issues and suggest novel possibilities for understanding the brain mechanisms that enable spatial attention. C1 [Krauzlis, Richard J.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Krauzlis, Richard J.] Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA. [Lovejoy, Lee P.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Lovejoy, Lee P.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Zenon, Alexandre] Catholic Univ Louvain, Inst Neurosci, B-1200 Brussels, Belgium. RP Krauzlis, RJ (reprint author), NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. EM richard.krauzlis@nih.gov OI Lovejoy, Lee/0000-0002-5732-9224 FU Intramural NIH HHS [Z99 EY999999, ZIA EY000511-01]; NIGMS NIH HHS [T32 GM007198]; NIMH NIH HHS [T32 MH020002] NR 97 TC 100 Z9 101 U1 4 U2 36 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2436-0 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2013 VL 36 BP 165 EP 182 DI 10.1146/annurev-neuro-062012-170249 PG 18 WC Neurosciences SC Neurosciences & Neurology GA BGR42 UT WOS:000323892300008 PM 23682659 ER PT S AU Bond, MR Hanover, JA AF Bond, Michelle R. Hanover, John A. BE Cousins, RJ TI O-GlcNAc Cycling: A Link Between Metabolism and Chronic Disease SO ANNUAL REVIEW OF NUTRITION, VOL 33 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE O-GlcNAc transferase (OGT); O-GlcNAcase (OGA); uridine diphospho-N-acetylglucosamine (UDP-GlcNAc); hexosamine biosynthetic pathway (HBP) ID EMBRYONIC STEM-CELLS; N-ACETYLGLUCOSAMINE TRANSFERASE; RNA-POLYMERASE-II; ESTROGEN-RECEPTOR-BETA; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE; INSULIN-RESISTANCE; CAENORHABDITIS-ELEGANS; PROTEIN MODIFICATION; ORAL GLUCOSAMINE AB To maintain homeostasis under variable nutrient conditions, cells rapidly and robustly respond to fluctuations through adaptable signaling networks. Evidence suggests that the O-linked N-acetylglucosamine (O-GlcNAc) posttranslational modification of serine and threonine residues functions as a critical regulator of intracellular signaling cascades in response to nutrient changes. O-GlcNAc is a highly regulated, reversible modification poised to integrate metabolic signals and acts to influence many cellular processes, including cellular signaling, protein stability, and transcription. This review describes the role O-GlcNAc plays in governing both integrated cellular processes and the activity of individual proteins in response to nutrient levels. Moreover, we discuss the ways in which cellular changes in O-GlcNAc status may be linked to chronic diseases such as type 2 diabetes, neurodegeneration, and cancers, providing a unique window through which to identify and treat disease conditions. C1 [Bond, Michelle R.; Hanover, John A.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Bond, MR (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM bondmr@mail.nih.gov; jah@helix.nih.gov FU Intramural NIH HHS NR 147 TC 61 Z9 63 U1 5 U2 37 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2833-7 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2013 VL 33 BP 205 EP 229 DI 10.1146/annurev-nutr-071812-161240 PG 25 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BGR40 UT WOS:000323891400010 PM 23642195 ER PT S AU Montaner, S Kufareva, I Abagyan, R Gutkind, JS AF Montaner, Silvia Kufareva, Irina Abagyan, Ruben Gutkind, J. Silvio BE Insel, PA TI Molecular Mechanisms Deployed by Virally Encoded G Protein-Coupled Receptors in Human Diseases SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 53, 2013 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE signal transduction; structure; virus-associated malignancies; chemokine receptors; constitutive activity; human viruses ID SARCOMA-ASSOCIATED HERPESVIRUS; BETA-CHEMOKINE RECEPTOR; MUSCLE-CELL MIGRATION; NF-KAPPA-B; HUMAN CYTOMEGALOVIRUS-INFECTION; EFFUSION LYMPHOMA-CELLS; ANGIOPOIETIN-LIKE 4; FRAME U12 ENCODES; KAPOSIS-SARCOMA; CONSTITUTIVE ACTIVITY AB G protein-coupled receptors (GPCRs) represent the largest family of cell surface molecules involved in signal transduction. Surprisingly, open reading frames for multiple GPCRs were hijacked in the process of coevolution between Herpesviridae family viruses and their human and mammalian hosts. Virally encoded GPCRs (vGPCRs) evolved as parts of viral genomes, and this evolution allowed the power of host GPCR signaling circuitries to be harnessed in order to ensure viral replicative success. Phylogenetically, vGPCRs are distantly related to human chemokine receptors, although they feature several unique characteristics. Here, we describe the molecular mechanisms underlying vGPCR-mediated viral pathogenesis. These mechanisms include constitutive activity, aberrant coupling to human G proteins and beta-arrestins, binding and activation by human chemokines, and dimerization with other GPCRs expressed in infected cells. The likely structural basis for these molecular events is described for the two closest viral homologs of human GPCRs. This information may aid in the development of novel targeted therapeutic strategies against viral diseases. C1 [Montaner, Silvia] Univ Maryland, Dept Pathol, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA. [Montaner, Silvia] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Kufareva, Irina; Abagyan, Ruben] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Gutkind, J. Silvio] NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. RP Montaner, S (reprint author), Univ Maryland, Dept Pathol, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA. EM smontaner@umaryland.edu; ikufareva@ucsd.edu; rabagyan@ucsd.edu; sg39v@nih.gov OI Kufareva, Irina/0000-0001-9083-7039 FU Intramural NIH HHS [ZIA DE000551-22]; NCI NIH HHS [R01 CA119911]; NIGMS NIH HHS [R01 GM071872, U01 GM094612] NR 131 TC 25 Z9 25 U1 0 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0453-9 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2013 VL 53 BP 331 EP 354 DI 10.1146/annurev-pharmtox-010510-100608 PG 24 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGH79 UT WOS:000323040100017 PM 23092247 ER PT J AU Holmes, A AF Holmes, Andrew BE Crusio, WE Sluyter, F Gerlai, RT Pietropaolo, S TI Strains, SNPs, and selected lines Genetic factors influencing variation in murine anxiety-like behavior SO BEHAVIORAL GENETICS OF THE MOUSE, VOL 1: GENETICS OF BEHAVIORAL PHENOTYPES SE Cambridge Handbooks in Behavioural Genetics LA English DT Article; Book Chapter ID QUANTITATIVE TRAIT LOCI; INBRED MOUSE STRAINS; TAIL-SUSPENSION TEST; ANIMAL-MODELS; TRYPTOPHAN HYDROXYLASE-2; PLASMA-CORTICOSTERONE; MICE; FEAR; DEPRESSION; SENSITIVITY C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NR 89 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-03481-5 J9 CAM HBK BEHAV GENET PY 2013 BP 155 EP 162 D2 10.1017/CBO9781139541022 PG 8 WC Behavioral Sciences; Genetics & Heredity SC Behavioral Sciences; Genetics & Heredity GA BGQ67 UT WOS:000323818800017 ER PT J AU Blanchard, DC Crawley, JN Arakawa, H Blanchard, RJ AF Blanchard, D. Caroline Crawley, Jacqueline N. Arakawa, Hiroyuki Blanchard, Robert J. BE Crusio, WE Sluyter, F Gerlai, RT Pietropaolo, S TI Social behaviors in wild and laboratory mice with a special emphasis on the C57BL/6J inbred strain SO BEHAVIORAL GENETICS OF THE MOUSE, VOL 1: GENETICS OF BEHAVIORAL PHENOTYPES SE Cambridge Handbooks in Behavioural Genetics LA English DT Article; Book Chapter ID IN-HOUSE MICE; MUS-MUSCULUS-DOMESTICUS; SCENT MARKING BEHAVIOR; VISIBLE BURROW SYSTEM; ANXIETY-LIKE BEHAVIOR; BTBR-T+TF/J MICE; MOUSE STRAINS; URINE MARKING; PLASMA-CORTICOSTERONE; RESOURCE DISTRIBUTION C1 [Blanchard, D. Caroline] Univ Hawaii, Pacific Biosci Res Ctr, John A Burns Sch Med, Honolulu, HI 96822 USA. [Blanchard, D. Caroline] Univ Hawaii, Dept Genet & Mol Biol, John A Burns Sch Med, Honolulu, HI 96822 USA. [Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. [Arakawa, Hiroyuki] NYU, Dept Psychol, Binghamton, NY USA. [Blanchard, Robert J.] Univ Hawaii, Pacific Biosci Res Ctr, Honolulu, HI 96822 USA. [Blanchard, Robert J.] Univ Hawaii, Dept Psychol, Honolulu, HI 96822 USA. RP Blanchard, DC (reprint author), Univ Hawaii, Pacific Biosci Res Ctr, John A Burns Sch Med, Honolulu, HI 96822 USA. NR 112 TC 2 Z9 2 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-03481-5 J9 CAM HBK BEHAV GENET PY 2013 BP 205 EP 217 D2 10.1017/CBO9781139541022 PG 13 WC Behavioral Sciences; Genetics & Heredity SC Behavioral Sciences; Genetics & Heredity GA BGQ67 UT WOS:000323818800022 ER PT J AU Chakraborty, S Mookherjee, S Sen, A Ray, K AF Chakraborty, Subhadip Mookherjee, Suddhasil Sen, Abhijit Ray, Kunal TI Analysis of COCH and TNFA Variants in East Indian Primary Open-Angle Glaucoma Patients SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID TUMOR-NECROSIS-FACTOR; ALPHA PROMOTER POLYMORPHISMS; TRABECULAR MESHWORK; GENE POLYMORPHISM; MULTIPLE-SCLEROSIS; LYMPHOTOXIN-ALPHA; RISK-FACTORS; ASSOCIATION; IDENTIFICATION; DEPOSITS AB Glaucoma represents a heterogeneous group of optic neuropathies with a complex genetic basis. It is the second-largest cause of blindness in the world that reduces vision without warning and often without symptoms. Among 3 major subtypes of glaucoma, primary open-angle glaucoma (POAG) is the most common form. The focus of this study is to understand the molecular basis of the disease among Indian patients with respect to two genes, Cochlin (COCH) and tumor necrosis factor alpha (TNFA), selected based on reports of possible association with POAG. The genes were screened in patients and controls by PCR and direct sequencing. Although two novel changes (-450 C/T and -79 G/G) were identified in the 5' upstream region of COCH, no causal variant could be identified in either gene. -450 C/T was detected in 3 patients and 2 controls and -79 G/C in a single patient. Further, we did not observe significant association with the promoter SNPs of TNFA that had been previously reported to be associated with POAG pathogenesis. Thus, our study suggests lack of association of both COCH and TNFA with POAG pathogenesis. C1 [Chakraborty, Subhadip; Mookherjee, Suddhasil; Ray, Kunal] Indian Inst Chem Biol, CSIR, Mol & Human Genet Div, Kolkata 700032, India. [Mookherjee, Suddhasil] NEI, NIH, Bethesda, MD 20892 USA. [Sen, Abhijit] Dristi Pradip, Kolkata 700068, India. [Ray, Kunal] Acad Sci & Innovat Res, New Delhi 110001, India. RP Ray, K (reprint author), Indian Inst Chem Biol, CSIR, Mol & Human Genet Div, 4 Raja SC Mullick Rd, Kolkata 700032, India. EM kunalray@gmail.com RI Ray, Kunal/E-6515-2011 OI Mookherjee, Suddhasil/0000-0003-2796-2659; Ray, Kunal/0000-0001-9989-1760 FU Council of Scientific and Industrial Research (CSIR), India [SIP-007, MLP-0016, NWP 004]; CSIR FX The authors are thankful to the donors who participated in this study, to Dr. Keya Sen for helping with clinical evaluation of patients along with Dr. A. Sen, and Ms Ananya Ray (University of Wisconsin, Madison, WI USA) for helping with language correction of the paper. This study was supported by grants SIP-007, MLP-0016, and NWP 004 from the Council of Scientific and Industrial Research (CSIR), India. S. M. and S. C. were supported by fellowships from CSIR. NR 42 TC 2 Z9 2 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 937870 DI 10.1155/2013/937870 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 215VJ UT WOS:000324238600001 ER PT S AU Ardeshirpour, Y Gandjbakhche, AH Najafizadeh, L AF Ardeshirpour, Yasaman Gandjbakhche, Amir H. Najafizadeh, Laleh BE Cohen, S TI Biophotonics Techniques for Structural and Functional Imaging, In Vivo SO BIOPHOTONICS IN PATHOLOGY: PATHOLOGY AT THE CROSSROADS SE Studies in Health Technology and Informatics LA English DT Article; Book Chapter ID NEAR-INFRARED SPECTROSCOPY; DIFFUSE OPTICAL TOMOGRAPHY; FLUORESCENCE MOLECULAR TOMOGRAPHY; INDEPENDENT COMPONENT ANALYSIS; MEASUREMENT DENSITY-FUNCTIONS; CEREBRAL OXYGENATION CHANGES; BENIGN BREAST-LESIONS; HUMAN BRAIN-FUNCTION; VISUAL-CORTEX; MOTOR-CORTEX AB In vivo optical imaging is being conducted in a variety of medical applications, including optical breast cancer imaging, functional brain imaging, endoscopy, exercise medicine, and monitoring the photodynamic therapy and progress of neoadjuvant chemotherapy. In the past three decades, in vivo diffuse optical breast cancer imaging has shown promising results in cancer detection, and monitoring the progress of neoadjuvant chemotherapy. The use of near infrared spectroscopy for functional brain imaging has been growing rapidly. In fluorescence imaging, the difference between autofluorescence of cancer lesions compared to normal tissues were used in endoscopy to distinguish malignant lesions from normal tissue or inflammation and in determining the boarders of cancer lesions in surgery. Recent advances in drugs targeting specific tumor receptors, such as monoclonal antibodies (mAb), has created a new demand for developing non-invasive in vivo imaging techniques for detection of cancer biomarkers, and for monitoring their down regulations during therapy. Targeted treatments, combined with new imaging techniques, are expected to potentially result in new imaging and treatment paradigms in cancer therapy. Similar approaches can potentially be applied for the characterization of other disease-related biomarkers. In this chapter, we provide a review of diffuse optical and fluorescence imaging techniques with their application in functional brain imaging and cancer diagnosis. C1 [Ardeshirpour, Yasaman; Gandjbakhche, Amir H.; Najafizadeh, Laleh] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Funct & Analyt Biophoton, NIH, Bethesda, MD USA. [Najafizadeh, Laleh] Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Rockville, MD USA. RP Gandjbakhche, AH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Funct & Analyt Biophoton, NIH, Bethesda, MD USA. EM gandjbaa@mail.nih.gov FU Intramural NIH HHS NR 166 TC 2 Z9 2 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-61499-234-9; 978-1-61499-233-2 J9 STUD HEALTH TECHNOL PY 2013 VL 185 BP 265 EP 297 DI 10.3233/978-1-61499-234-9-265 PG 33 WC Optics; Pathology SC Optics; Pathology GA BGV92 UT WOS:000324328800012 PM 23542939 ER PT S AU Spring, KR AF Spring, Kenneth R. BE Sluder, G Wolf, DE TI Cameras for Digital Microscopy SO DIGITAL MICROSCOPY, 4TH EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter AB This chapter reviews the fundamental characteristics of charge-coupled devices (CCDs) and related detectors, outlines the relevant parameters for their use in microscopy, and considers promising recent developments in the technology of detectors. Electronic imaging with a CCD involves three stages-interaction of a photon with the photosensitive surface, storage of the liberated charge, and readout or measurement of the stored charge. The most demanding applications in fluorescence microscopy may require as much as four orders of greater magnitude sensitivity. The image in the present-day light microscope is usually acquired with a CCD camera. The CCD is composed of a large matrix of photosensitive elements (often referred to as "pixels" shorthand for picture elements, which simultaneously capture an image over the entire detector surface. The light-intensity information for each pixel is stored as electronic charge and is converted to an analog voltage by a readout amplifier. This analog voltage is subsequently converted to a numerical value by a digitizer situated on the CCD chip, or very close to it. Several (three to six) amplifiers are required for each pixel, and to date, uniform images with a homogeneous background have been a problem because of the inherent difficulties of balancing the gain in all of the amplifiers. Complementary metal oxide semiconductor sensors also exhibit relatively high noise associated with the requisite high-speed switching. Both of these deficiencies are being addressed, and sensor performance is nearing that required for scientific imaging. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Spring, KR (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 1 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-407892-5 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2013 VL 114 BP 163 EP 178 DI 10.1016/B978-0-12-407761-4.00008-7 PG 16 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA BGR53 UT WOS:000323900000009 PM 23931507 ER PT J AU Petras, V Glushko, RJ Nomorosa, KJ Ekaterin, JJM Park, H Marimpietri, S AF Petras, Vivien Glushko, Robert J. Nomorosa, Karen Joy Ekaterin, J. J. M. Park, Hyunwoo Marimpietri, Sean BE Glushko, RJ TI Interactions with Resources SO DISCIPLINE OF ORGANIZING LA English DT Article; Book Chapter C1 [Petras, Vivien] Humboldt Univ, Sch Lib & Informat Sci, Berlin, Germany. [Petras, Vivien] GESIS Leibniz Inst Social Sci, Informat Syst R&D Dept, Cologne, Germany. [Glushko, Robert J.] Univ Calif Berkeley, Sch Informat, Berkeley, CA 94720 USA. [Glushko, Robert J.] Bell Labs, Murray Hill, NJ USA. [Park, Hyunwoo] Georgia Inst Technol, Atlanta, GA 30332 USA. [Park, Hyunwoo] Georgia Inst Technol, Tennenbaum Inst, Atlanta, GA 30332 USA. [Marimpietri, Sean] Natl Lib Med, Res Grp, Bethesda, MD 20894 USA. RP Petras, V (reprint author), Humboldt Univ, Sch Lib & Informat Sci, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-31396-4 PY 2013 BP 363 EP 400 PG 38 WC Information Science & Library Science SC Information Science & Library Science GA BGM36 UT WOS:000323496500011 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Alkaloids SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 1 EP 2 PG 2 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400004 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Amide Alkaloids SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID DNA STRAND SCISSION; NF-KAPPA-B; PIPER-CHABA; ACID-AMIDES; LONGUM; CELLS; CONSTITUENTS; APOPTOSIS; CANINUM; CANCER C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 47 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 2 EP 15 PG 14 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400005 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Lead Compounds from Medicinal Plants for the Treatment of Cancer Foreword SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Editorial Material; Book Chapter C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP IX EP XI PG 3 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400001 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Lead Compounds from Medicinal Plants for the Treatment of Cancer Foreword SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Editorial Material; Book Chapter C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP XIII EP XIV PG 2 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400002 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Lead Compounds from Medicinal Plants for the Treatment of Cancer Preface SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Editorial Material; Book Chapter C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP XV EP XV PG 1 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400003 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Indole Alkaloids and Derivatives SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID STRYCHNOS-NUX-VOMICA; DNA STRAND SCISSION; ISOLATED RAT AORTA; NAUCLEA-ORIENTALIS; WINCHIA-CALOPHYLLA; MELODINUS-HENRYI; CLAUSENA-HARMANDIANA; CELL-PROLIFERATION; CANCER-CELLS; ROOT BARK C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 74 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 16 EP 34 PG 19 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400006 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Isoquinoline Alkaloids and Derivatives SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID TETRAHYDROISOQUINOLINE-MONOTERPENE GLUCOSIDES; COCCULUS-TRILOBUS DC; INDIAN MEDICINAL-PLANTS; ALANGIUM-LAMARCKII THW; SANGUINARINE-INDUCED APOPTOSIS; SUPPRESSES TUMOR-GROWTH; MICROCARPA MAXIM. FEDDE; BREAST-CARCINOMA CELLS; ARISTOLOCHIA-MANSHURIENSIS; GONIOTHALAMUS-AMUYON C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 131 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 35 EP 66 PG 32 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400007 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Terpenoid Alkaloids SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID PACHYSANDRA-TERMINALIS SIEB; DIMERIC SESQUITERPENE THIOALKALOIDS; BIOACTIVE STEROIDAL ALKALOIDS; HEDGEHOG SIGNALING PATHWAY; FRIEDELIN-TYPE TRITERPENE; FACTOR-KAPPA-B; NEUTRAL CONSTITUENTS; NUPHAR-PUMILUM; DAPHNIPHYLLUM-GLAUCESCENS; IMMUNOSUPPRESSIVE ACTIVITY C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 51 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 67 EP 80 PG 14 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400008 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Other Alkaloids SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID CYTOTOXIC PHENANTHROINDOLIZIDINE ALKALOIDS; CHRONIC LYMPHOCYTIC-LEUKEMIA; POTENTIAL ANTICANCER AGENTS; FICUS-SEPTICA; CARCINOMA-CELLS; TYLOPHORINE DERIVATIVES; INHIBITORS FLAVOPIRIDOL; CYNANCHUM-VINCETOXICUM; DYSOXYLUM-ACUTANGULUM; KINASE INHIBITORS C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 55 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 81 EP 95 PG 15 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400009 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Terpenes SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 97 EP 99 PG 3 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400010 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Sesquiterpenes SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID NF-KAPPA-B; SIYEKUCAI IXERIS-CHINENSIS; ATRACTYLODES-MACROCEPHALA KOIDZ; PROSTATE-CANCER CELLS; FATTY-ACID SYNTHASE; B16 MELANOMA-CELLS; CURCUMA-WENYUJIN; BETA-ELEMENE; CACALIA-PILGERIANA; CYTOTOXIC ACTIVITY C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. RI Xia, Bo/P-9380-2016 NR 99 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 99 EP 128 PG 30 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400011 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Diterpenes SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID ORIDONIN INDUCES APOPTOSIS; CLERODENDRUM-KAICHIANUM HSU; JOLKINOLIDE-D PHARMACOPHORE; ENT-KAURANE DITERPENOIDS; LABDANE-TYPE DITERPENES; CELL-CYCLE PROGRESSION; MYELOID-LEUKEMIA CELLS; PROSTATE-CANCER CELLS; VITEX-ROTUNDIFOLIA L; NF-KAPPA-B C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 81 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 128 EP 146 PG 19 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400012 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Triterpenes SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID NF-KAPPA-B; PROSTATE-CANCER CELLS; ACID INDUCES APOPTOSIS; JAVANICA L MERR; QUINONE-METHIDE TRITERPENES; PROTOSTANE-TYPE TRITERPENES; CHINESE ALISMATIS RHIZOMA; DNA-POLYMERASE-BETA; HEPATOCELLULAR-CARCINOMA CELLS; CYCLOARTANE-TYPE TRITERPENOIDS C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 344 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 147 EP 265 PG 119 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400013 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Phenolics SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. OI Wiart, Christophe/0000-0003-2824-7286 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 267 EP 269 PG 3 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400014 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Benzopyrones SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID CELL-CYCLE ARREST; BREAST-CANCER CELLS; NF-KAPPA-B; HUMAN PROSTATE-CANCER; LEUKEMIA HL-60 CELLS; HUMAN HEPATOMA-CELLS; HEPATOCELLULAR-CARCINOMA CELLS; ENDOPLASMIC-RETICULUM STRESS; KAEMPFEROL INDUCES APOPTOSIS; APIGENIN-INDUCED-APOPTOSIS C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 187 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 269 EP 340 PG 72 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400015 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Quinones SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID ENDOPLASMIC-RETICULUM STRESS; MITOCHONDRIAL DEATH PATHWAY; EMODIN INDUCES APOPTOSIS; RHEIN-INDUCED APOPTOSIS; LUNG-CANCER CELLS; NF-KAPPA-B; NASOPHARYNGEAL CARCINOMA-CELLS; LAPACHONE-MEDIATED APOPTOSIS; JUGLANS-MANDSHURICA-MAXIM; GROWTH-FACTOR RECEPTOR C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 106 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 341 EP 368 PG 28 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400016 ER PT J AU Cragg, GM AF Cragg, Gordon M. BA Wiart, C BF Wiart, C TI Lignans SO LEAD COMPOUNDS FROM MEDICINAL PLANTS FOR THE TREATMENT OF CANCER LA English DT Article; Book Chapter ID NF-KAPPA-B; REGULATED GENE-EXPRESSION; CELL-CYCLE ARREST; MAGNOLIA-OBOVATA; CANCER CELLS; JUSTICIDIN-A; INDUCE APOPTOSIS; TUMOR-CELLS; HL-60 CELLS; ACTIVATION C1 NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 36 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398382-4 PY 2013 BP 369 EP 380 PG 12 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BGQ71 UT WOS:000323821400017 ER PT J AU Henrich, CJ Beutler, JA AF Henrich, Curtis J. Beutler, John A. TI Matching the power of high throughput screening to the chemical diversity of natural products SO NATURAL PRODUCT REPORTS LA English DT Review ID RECEPTOR EXPRESSION ENHANCEMENT; CELL-BASED ASSAY; DRUG-DISCOVERY; PLANT-EXTRACTS; MASS SPECTROMETRY; LEAD DISCOVERY; COMPOUND LIBRARIES; ANTICANCER AGENTS; STAPHYLOCOCCUS-AUREUS; BINDING-AFFINITY AB Application of high throughput screening technologies to natural product samples demands alterations in assay design as well as sample preparation in order to yield meaningful hit structures at the end of the campaign. C1 [Henrich, Curtis J.] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab, Frederick, MD 21702 USA. [Henrich, Curtis J.; Beutler, John A.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Beutler, JA (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM henrichcj@mail.nih.gov; beutlerj@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX We thank all former and current members of our laboratory for their contributions, and James McMahon, Barry O'Keefe and Kirk Gustafson for their thoughtful comments on the manuscript. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, and also was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 183 TC 21 Z9 21 U1 3 U2 69 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0265-0568 EI 1460-4752 J9 NAT PROD REP JI Nat. Prod. Rep. PY 2013 VL 30 IS 10 BP 1284 EP 1298 DI 10.1039/c3np70052f PG 15 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 218GT UT WOS:000324421500003 PM 23925671 ER PT J AU Sittampalam, GS AF Sittampalam, G. Sitta BE Christ, GJ Andersson, KE TI Enabling Drug Discovery Technologies for Regenerative Pharmacology SO REGENERATIVE PHARMACOLOGY LA English DT Article; Book Chapter ID GREEN-FLUORESCENT PROTEIN; PLURIPOTENT STEM-CELLS; DEFINED FACTORS; COMBINATORIAL; FIBROBLASTS; EXPRESSION; CHEMISTRY; BIOLOGY; FUTURE; GENE C1 NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. RP Sittampalam, GS (reprint author), NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. NR 62 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-89949-9 PY 2013 BP 190 EP 218 D2 10.1017/CBO9781139047357 PG 29 WC Cell & Tissue Engineering; Pharmacology & Pharmacy SC Cell Biology; Pharmacology & Pharmacy GA BGO63 UT WOS:000323648400011 ER PT J AU Sheets, L Gavino, A Callaghan, F Fontelo, P AF Sheets, L. Gavino, A. Callaghan, F. Fontelo, P. TI Do Language Fluency and Other Socioeconomic Factors Influence the Use of PubMed and MedlinePlus? SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Library information systems; access to information; diffusion of innovation; communication barriers; economic barriers ID HEALTH-CARE; COUNTRIES; SATISFACTION; INFORMATION; INTERNET; IMPACT AB Background: Increased usage of MedlinePlus by Spanish-speakers was observed after introduction of MedlinePlus in Spanish. This probably reflects increased usage of MEDLINE and PubMed by those with greater fluency in the language in which it is presented; but this has never been demonstrated in English speakers. Evidence that lack of English fluency deters international healthcare personnel from using PubMed could support the use of multi-language search tools like Babel-MeSH. Objectives: This study aims to measure the effects of language fluency and other socioeconomic factors on PubMed MEDLINE and MedlinePlus access by international users. Methods: We retrospectively reviewed server pageviews of PubMed and MedlinePlus from various periods of time, and analyzed them against country statistics on language fluency, GDP, literacy rate, Internet usage, medical schools, and physicians per capita, to determine whether they were associated. Results: We found fluency in English to be positively associated with pageviews of PubMed and MedlinePlus in countries with high literacy rates. Spanish was generally found to be positively associated with pageviews of MedlinePlus en Espanol. The other parameters also showed varying degrees of association with pageviews. Conclusions: After adjusting for the other factors investigated in this study, language fluency was a consistently significant predictor of the use of PubMed, MedlinePlus English and MedlinePlus en Espanol. This study may support the need for multi-language search tools and may increase access of health information resources from non-English speaking countries. C1 [Sheets, L.] Univ Missouri, Inst Informat, Columbia, MO 65211 USA. [Sheets, L.; Gavino, A.; Callaghan, F.; Fontelo, P.] Natl Lib Med, Bethesda, MD USA. RP Sheets, L (reprint author), Univ Missouri, Inst Informat, EBW 241, Columbia, MO 65211 USA. EM lincolnsheets@gmail.com OI Sheets, Lincoln/0000-0002-1586-1474 FU Intramural Research Program of the National Institutes of Health, National Library of Medicine, and Lister Hill National Center for Biomedical Communications FX The authors would like to thank Dennis Benson, PhD, of the National Center for Biotechnology Information, for several useful discussions. This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine, and Lister Hill National Center for Biomedical Communications. NR 27 TC 2 Z9 2 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2013 VL 4 IS 2 BP 170 EP 184 DI 10.4338/ACI-2013-01-RA-0006 PG 15 WC Medical Informatics SC Medical Informatics GA 208TG UT WOS:000323701800002 PM 23874356 ER PT J AU Pongpiachan, S Ho, KF Cao, JJ AF Pongpiachan, Siwatt Ho, Kin Fai Cao, Junji TI Estimation of Gas-Particle Partitioning Coefficients (K-p) of Carcinogenic Polycyclic Aromatic Hydrocarbons in Carbonaceous Aerosols Collected at Chiang-Mai, Bangkok and Hat-Yai, Thailand SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE Carbonaceous aerosols; vertical distribution; gas-particle partitioning coefficient (K-p) PAHs; Thailand ID SECONDARY ORGANIC-CARBON; POLYBROMINATED DIPHENYL ETHERS; DIESEL SOOT PARTICLES; RIVER DELTA REGION; ELEMENTAL CARBON; VERTICAL-DISTRIBUTION; CHEMICAL-COMPOSITION; SOURCE APPORTIONMENT; DIURNAL-VARIATIONS; URBAN ATMOSPHERE AB To assess environmental contamination with carcinogens, carbonaceous compounds, water-soluble ionic species and trace gaseous species were identified and quantified every three hours for three days at three different atmospheric layers at the heart of Chiang-Mai, Bangkok and Hat-Yai from December 2006 to February 2007. A DRI Model 2001 Thermal/Optical Carbon Analyzer with the IMPROVE thermal/optical reflectance (TOR) protocol was used to quantify the organic carbon (OC) and elemental carbon (EC) contents in PM10. Diurnal and vertical variability was also carefully investigated. In general, OC and EC mass concentration showed the highest values at the monitoring period of 21.00-00.00 as consequences of human activities at night bazaar coupled with reduction of mixing layer, decreased wind speed and termination of photolysis at nighttime. Morning peaks of carbonaceous compounds were observed during the sampling period of 06:00-09:00, emphasizing the main contribution of traffic emission in the three cities. The estimation of incremental lifetime particulate matter exposure (ILPE) raises concern of high risk of carbonaceous accumulation over workers and residents living close to the observatory sites. The average values of incremental lifetime particulate matter exposure (ILPE) of total carbon at Baiyoke Suit Hotel and Baiyoke Sky Hotel are approximately ten times higher than those air samples collected at Prince of Songkla University Hat-Yai campus corpse incinerator and fish-can manufacturing factory but only slightly higher than those of rice straw burning in Songkla province. This indicates a high risk of developing lung cancer and other respiratory diseases across workers and residents living in high buildings located in Pratunam area. Using knowledge of carbonaceous fractions in PM10, one can estimate the gas-particle partitioning of polycyclic aromatic hydrocarbons (PAHs). Dachs-Eisenreich model highlights the crucial role of adsorption in gas-particle partitioning of low molecular weight PAHs, whereas both absorption and adsorption tend to account for gas-particle partitioning of high molecular weight PAHs in urban residential zones of Thailand. Interestingly, the absorption mode alone plays a minor role in gas-particle partitioning of PAHs in Chiang-Mai, Bangkok and Hat-Yai. C1 [Pongpiachan, Siwatt] NIDA, NIDA Ctr Res & Dev Disaster Prevent & Management, Sch Social & Environm Dev, Bangkok 10240, Thailand. Chinese Acad Sci IEECAS, SKLLQG, Inst Earth Environm, Xian 710075, Peoples R China. RP Pongpiachan, S (reprint author), NIDA, NIDA Ctr Res & Dev Disaster Prevent & Management, Sch Social & Environm Dev, Bangkok 10240, Thailand. EM pongpiajun@gmail.com RI Loess, IEECAS/I-8075-2014; Ho, Kin Fai/E-6131-2011; Cao, Junji/D-3259-2014 OI Cao, Junji/0000-0003-1000-7241 FU Institute of Earth Environment, Chinese Academy of Sciences (IEECAS); National Institute of Development Administration (NIDA) FX This work was performed with the approval of National Research Council of Thailand (NRCT). Also with acknowledged support from Institute of Earth Environment, Chinese Academy of Sciences (IEECAS) and National Institute of Development Administration (NIDA). The authors acknowledge Dr. Surat Bualert and and laboratory works. NR 90 TC 4 Z9 4 U1 2 U2 20 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2013 VL 14 IS 4 BP 2461 EP 2476 DI 10.7314/APJCP.2013.14.4.2461 PG 16 WC Oncology SC Oncology GA 188NC UT WOS:000322198700055 PM 23725158 ER PT J AU Panlilio, LV Justinova, Z Goldberg, SR AF Panlilio, Leigh V. Justinova, Zuzana Goldberg, Steven R. BE Miller, PM TI Animal Models of Addiction: Cannabinoids SO BIOLOGICAL RESEARCH ON ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 2 LA English DT Article; Book Chapter ID ENDOCANNABINOID SYSTEM; CB1 RECEPTORS; BRAIN REWARD; DEPENDENCE; MARIJUANA C1 [Panlilio, Leigh V.; Justinova, Zuzana; Goldberg, Steven R.] NIDA, NIH, Baltimore, MD 21218 USA. RP Panlilio, LV (reprint author), NIDA, NIH, Baltimore, MD 21218 USA. RI Justinova, Zuzana/A-9109-2011 OI Justinova, Zuzana/0000-0001-5793-7484 NR 15 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398360-2 PY 2013 BP 69 EP 78 DI 10.1016/B978-0-12-398335-0.00008-X PG 10 WC Psychology, Biological; Behavioral Sciences; Substance Abuse; Neurosciences SC Psychology; Behavioral Sciences; Substance Abuse; Neurosciences & Neurology GA BGH99 UT WOS:000323053800009 ER PT J AU Le Foll, B Goldberg, SR AF Le Foll, Bernard Goldberg, Steven R. BE Miller, PM TI Effects of Nicotine in Animal Models of Drug Addiction Across Species SO BIOLOGICAL RESEARCH ON ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 2 LA English DT Article; Book Chapter ID CONDITIONED TASTE-AVERSION; RATS; BEHAVIOR; MECAMYLAMINE; REINFORCER; WITHDRAWAL; SEEKING C1 [Le Foll, Bernard] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Translat Addict Res Lab, Toronto, ON, Canada. [Le Foll, Bernard] Univ Toronto, Toronto, ON, Canada. [Goldberg, Steven R.] NIDA RP, DHHS, NIH, Preclin Pharmacol Sect, Baltimore, MD USA. RP Le Foll, B (reprint author), Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Translat Addict Res Lab, Toronto, ON, Canada. RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 NR 24 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398360-2 PY 2013 BP 89 EP 97 DI 10.1016/B978-0-12-398335-0.00010-8 PG 9 WC Psychology, Biological; Behavioral Sciences; Substance Abuse; Neurosciences SC Psychology; Behavioral Sciences; Substance Abuse; Neurosciences & Neurology GA BGH99 UT WOS:000323053800011 ER PT J AU Stark, JA Lu, HB Stein, EA AF Stark, Jennifer A. Lu, Hanbing Stein, Elliot A. BE Miller, PM TI Cocaine and Amphetamine Neuroimaging in Small Rodents SO BIOLOGICAL RESEARCH ON ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 2 LA English DT Article; Book Chapter ID FUNCTIONAL CONNECTIVITY; BRAIN; RAT C1 [Stark, Jennifer A.; Lu, Hanbing; Stein, Elliot A.] NIDA IRP, Neuroimaging Res Branch, Baltimore, MD USA. RP Stark, JA (reprint author), NIDA IRP, Neuroimaging Res Branch, Baltimore, MD USA. NR 10 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398360-2 PY 2013 BP 699 EP 710 DI 10.1016/B978-0-12-398335-0.00068-6 PG 12 WC Psychology, Biological; Behavioral Sciences; Substance Abuse; Neurosciences SC Psychology; Behavioral Sciences; Substance Abuse; Neurosciences & Neurology GA BGH99 UT WOS:000323053800069 ER PT J AU Foster, BL Chun, YHP Scheller, EL Lin, Z Novince, CM Paranjpe, A AF Foster, Brian L. Chun, Yong-Hee P. Scheller, Erica L. Lin, Zhao Novince, Chad M. Paranjpe, Avina TI Development, Disease, and Regeneration of Tissues in the Dental-Craniofacial Complex SO BIOMED RESEARCH INTERNATIONAL LA English DT Editorial Material C1 [Foster, Brian L.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Chun, Yong-Hee P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Scheller, Erica L.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48105 USA. [Lin, Zhao] Virginia Commonwealth Univ, Dept Periodont, Sch Dent, Richmond, VA 23298 USA. [Novince, Chad M.] Univ Washington, Dept Periodont, Sch Dent, Seattle, WA 98195 USA. [Paranjpe, Avina] Univ Washington, Dept Endodont, Sch Dent, Seattle, WA 98195 USA. RP Foster, BL (reprint author), NIAMSD, NIH, 9000 Rockville Pike Bldg 50,Room 4120, Bethesda, MD 20892 USA. EM brian.foster@nih.gov RI Foster, Brian/H-8375-2015; OI Foster, Brian/0000-0003-3444-0576; Scheller, Erica/0000-0002-1551-3816 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 836871 DI 10.1155/2013/836871 PG 3 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 215EI UT WOS:000324191900001 ER PT J AU Qian, Z Zhao, JJ Bai, X Tong, W Chen, Z Wei, HF Wang, QH Liu, SQ AF Qian, Zhong Zhao, Jingjing Bai, Xue Tong, Wei Chen, Zhen Wei, Hanfu Wang, Quanhui Liu, Siqi TI Thermal Stability of Glucokinases in Thermoanaerobacter tengcongensis SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID ATP-DEPENDENT GLUCOKINASE; ARCHAEON PYROCOCCUS-FURIOSUS; THERMOPHILIC ROK GLUCOKINASE; BROAD HEXOSE SPECIFICITY; HYPERTHERMOPHILIC ARCHAEON; SUGAR KINASES; EVOLUTIONARY RELATIONSHIPS; PROTEINS; PURIFICATION; HEXOKINASE AB In the genome of Thermoanaerobacter tengcongensis, three genes belonging to ROK (Repressor, ORF, and Kinase) family are annotated as glucokinases (GLKs). Using enzyme assays, the three GLKs were identified as ATP-dependent GLK (ATP-GLK), ADP-dependent GLK (ADP-GLK), and N-acetyl-glucosamine/mannosamine kinase (glu/man-NacK). The kinetic properties of the three GLKs such as K-m, K-max, optimal pH, and temperature were characterized, demonstrating that these enzymes performed the specific functions against varied substrates and under different temperatures. The abundance of ATP-GLK was attenuated when culture temperature was elevated and was almost undetectable at 80 degrees C, whereas the ADP-GLK abundance was insensitive to temperature changes. Using degradation assays, ATP-GLK was found to have significantly faster degradation than ADP-GLK at 80 degrees C. Co-immunoprecipitation results revealed that heat shock protein 60 (HSP60) could interact with ATP-GLK and ADP-GLK at 60 and 75 degrees C, whereas at 80 degrees C, the interaction was only effectively with ADP-GLK but not ATP-GLK. The functions of GLKs in T. tengcongensis are temperature dependent, likely regulated through interactions with HSP60. C1 [Qian, Zhong; Zhao, Jingjing; Bai, Xue; Tong, Wei; Chen, Zhen; Wang, Quanhui; Liu, Siqi] Chinese Acad Sci, Beijing Inst Genom, Beijing 100101, Peoples R China. [Qian, Zhong] NCI, Dev Genet Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Wei, Hanfu] Beijing Prote Innovat, Beijing 101318, Peoples R China. RP Wang, QH (reprint author), Chinese Acad Sci, Beijing Inst Genom, 1 Beichen West Rd, Beijing 100101, Peoples R China. EM wangqh@big.ac.cn; siqiliu@big.ac.cn FU Beijing Natural Science Foundation [5132023]; National Natural Science Foundation of China [30800023] FX This study was supported by Grants 5132023 from Beijing Natural Science Foundation and 30800023 from the National Natural Science Foundation of China. NR 33 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 646539 DI 10.1155/2013/646539 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 212HK UT WOS:000323973400001 ER PT J AU Lucas, HR Lee, JC AF Lucas, Heather R. Lee, Jennifer C. BE Brown, DR TI Emerging Role for Copper-Bound alpha-Synuclein in Parkinson's Disease Etiology SO BRAIN DISEASES AND METALLOPROTEINS LA English DT Article; Book Chapter ID METAL-CATALYZED OXIDATION; METHIONINE OXIDATION; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; PROTEIN OXIDATION; AMYLOID FIBRILS; LEWY BODIES; CATION-PI; IN-VITRO; BINDING C1 [Lucas, Heather R.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Lucas, HR (reprint author), NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 NR 103 TC 0 Z9 0 U1 0 U2 3 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-981-4364-07-2 PY 2013 BP 295 EP 326 PG 32 WC Biochemistry & Molecular Biology; Clinical Neurology SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BGL82 UT WOS:000323436700009 ER PT J AU Lin, YT Mattson, MP Yang, JL AF Lin, Yu-Ting Mattson, Mark P. Yang, Jenq-Lin TI Glucagon-Like Peptide-1 and its Analogue, Exendin-4, Enhance Base Excision DNA Repair Against Oxidative Damage to Protect Rat Cortical Neurons SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Lin, Yu-Ting; Yang, Jenq-Lin] Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Kaohsiung, Taiwan. [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 36 SU 1 BP 36 EP 37 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 211WD UT WOS:000323941400088 ER PT J AU Rotroff, DM Dix, DJ Houck, KA Knudsen, TB Martin, MT McLaurin, KW Reif, DM Crofton, KM Singh, AV Xia, MH Huang, RL Judson, RS AF Rotroff, Daniel M. Dix, David J. Houck, Keith A. Knudsen, Thomas B. Martin, Matthew T. McLaurin, Keith W. Reif, David M. Crofton, Kevin M. Singh, Amar V. Xia, Menghang Huang, Ruili Judson, Richard S. TI Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE androgen; endocrine; estrogen; high throughput; in vitro; ToxCast ID RAT UTEROTROPHIC BIOASSAY; PREGNANE X RECEPTOR; MALE WISTAR RATS; ESTROGEN-RECEPTOR; ANDROGEN RECEPTOR; THYROID-FUNCTION; OECD PROGRAM; PESTICIDES; CELLS; HORMONES AB BACKGROUND: Over the past 20 years, an increased focus on detecting environmental-chemicals that pose a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP; thus, processing these chemicals using current test batteries could require millions of dollars and decades. A need for increased throughput and efficiency motivated the development of methods using in vitro high throughput screening (HTS) assays to prioritize chemicals for EDSP Tier 1 screening (T1S). OBJECTIVE: In this study we used U. S. EPA ToxCast HTS assays for estrogen, androgen, steroidogenic, and thyroid-disrupting mechanisms to classify compounds and compare ToxCast results to in vitro and in vivo data from EDSP T1S assays. METHOD: We implemented an iterative model that optimized the ability of endocrine-related HTS assays to predict components of EDSP T1S and related results. Balanced accuracy was used as a measure of model performance. RESULTS: ToxCast estrogen receptor and androgen receptor assays predicted the results of relevant EDSP T1S assays with balanced accuracies of 0.91 (p < 0.001) and 0.92 (p < 0.001), respectively. Uterotrophic and Hershberger assay results were predicted with balanced accuracies of 0.89 (p < 0.001) and 1 (p < 0.001), respectively. Models for steroidogenic and thyroid-related effects could not be developed with the currently published ToxCast data. CONCLUSIONS: Overall, results suggest that current ToxCast assays can accurately identify chemicals with potential to interact with the estrogenic and androgenic pathways, and could help prioritize chemicals for EDSP T1S assays. C1 [Rotroff, Daniel M.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. [Rotroff, Daniel M.; Dix, David J.; Houck, Keith A.; Knudsen, Thomas B.; Martin, Matthew T.; McLaurin, Keith W.; Reif, David M.; Judson, Richard S.] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Crofton, Kevin M.] US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Singh, Amar V.] Lockheed Martin, Res Triangle Pk, NC USA. [Xia, Menghang; Huang, Ruili] NIH, Natl Ctr Adv Translat Sci, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Judson, RS (reprint author), US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, 109 TW Alexander Dr B205-01, Res Triangle Pk, NC 27711 USA. EM judson.richard@epa.gov RI Singh, Amar/K-4400-2013; Crofton, Kevin/J-4798-2015; OI Reif, David/0000-0001-7815-6767; Singh, Amar/0000-0003-3780-8233; Crofton, Kevin/0000-0003-1749-9971; Judson, Richard/0000-0002-2348-9633 NR 63 TC 46 Z9 46 U1 6 U2 66 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2013 VL 121 IS 1 BP 7 EP 14 DI 10.1289/ehp.1205065 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 208SE UT WOS:000323698700018 PM 23052129 ER PT J AU Zablotska, LB Bazyka, D Lubin, JH Gudzenko, N Little, MP Hatch, M Finch, S Dyagil, I Reiss, RF Chumak, VV Bouville, A Drozdovitch, V Kryuchkov, VP Golovanov, I Bakhanova, E Babkina, N Lubarets, T Bebeshko, V Romanenko, A Mabuchi, K AF Zablotska, Lydia B. Bazyka, Dimitry Lubin, Jay H. Gudzenko, Nataliya Little, Mark P. Hatch, Maureen Finch, Stuart Dyagil, Irina Reiss, Robert F. Chumak, Vadim V. Bouville, Andre Drozdovitch, Vladimir Kryuchkov, Victor P. Golovanov, Ivan Bakhanova, Elena Babkina, Nataliya Lubarets, Tatiana Bebeshko, Volodymyr Romanenko, Anatoly Mabuchi, Kiyohiko TI Radiation and the Risk of Chronic Lymphocytic and Other Leukemias among Chornobyl Cleanup Workers SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE Chernobyl nuclear accident; Chornobyl; Ukraine; chronic lymphocytic leukemia; leukemia; matched case-control study; radiation; radiation dose-response relationship; radiation-induced leukemia ID ATOMIC-BOMB SURVIVORS; CANCER INCIDENCE; HEMATOLOGICAL MALIGNANCIES; UKRAINIAN-AMERICAN; IONIZING-RADIATION; MULTIPLE-MYELOMA; URANIUM MINERS; DISORDERS; LYMPHOMA; EXPOSURE AB BACKGROUND: Risks of most types of leukemia from exposure to acute high doses of ionizing-radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear. OBJECTIVES: We estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation. METHODS: A nested case-control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986-2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose. RESULTS: We found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews < 2 years from start of chemo-therapy with an anomalous finding of ERR/Gy = -0.47 (95% CI: < -0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure. CONCLUSIONS: Exposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive. C1 [Zablotska, Lydia B.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA. [Bazyka, Dimitry; Gudzenko, Nataliya; Dyagil, Irina; Chumak, Vadim V.; Bakhanova, Elena; Babkina, Nataliya; Lubarets, Tatiana; Bebeshko, Volodymyr; Romanenko, Anatoly] Natl Res Ctr Radiat Med, Kiev, Ukraine. [Lubin, Jay H.; Little, Mark P.; Hatch, Maureen; Bouville, Andre; Drozdovitch, Vladimir; Mabuchi, Kiyohiko] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Finch, Stuart] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. [Reiss, Robert F.] Columbia Univ Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Reiss, Robert F.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Kryuchkov, Victor P.; Golovanov, Ivan] Burnasyan Fed Med Biophys Ctr, Moscow, Russia. RP Zablotska, LB (reprint author), Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, 3333 Calif St,Suite 280, San Francisco, CA 94118 USA. EM lydia.zablotska@ucsf.edu RI Chumak, Vadim/N-6960-2015; OI Chumak, Vadim/0000-0001-6045-9356; Bazyka, Dimitry/0000-0001-9982-5990; Little, Mark/0000-0003-0980-7567 FU National Cancer Institute (NCI) [CA132918, NO1-CP-21178]; National Cancer Institute (NCI) Division of Cancer Epidemiology and Genetics; National Institute of Allergy and Infectious Diseases (NIAID) [Y2-Al-5077]; NCI [Y3-CO-5117]; U.S. Department of Energy [HHSN 261 2004 55796C]; Nuclear Regulatory Commission; French Institute for Radiological Protection and Nuclear Safety FX We thank the staff of the National Research Center for Radiation Medicine (Kyiv, Ukraine), and especially study epidemiologists and interviewers, for their dedication and commitment to the success of the study. We express our deep appreciation of the work of the members of the International Hematology Panel: B.J. Bain, L. Peterson, P. McPhedran, S.N. Gaidukova, and D. F. Gluzman; likewise, the members of the Leukemia Advisory Group for their wise counsel: F. L. Wong, H. Checkoway, K. Eckerman, B. Chabner, and B. Cheson. We acknowledge G. R. Howe, one of the original principal investigators of the study, for his contributions to setting up this study and for his foresight in recognizing the future need for accurate cancer diagnosis information and his significant efforts to computerize the Ukrainian Cancer Registry. We also acknowledge the late E. Ron, who played a major role in the conduct of this study. We are greatly saddened by her death, and her wisdom and guidance will be greatly missed. We thank D. L. Preston for his review of the draft of the manuscript and helpful discussions. Funding for this study was provided by the National Cancer Institute (NCI grant CA132918 and contract NO1-CP-21178 to L.B.Z. and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics to J.H.L., M. P. L., M. H., A. B., V. D., and K. M.). Radiation dose reconstruction was partially supported by an intra-agency agreement between the National Institute of Allergy and Infectious Diseases (NIAID) and the NCI (NIAID agreement Y2-Al-5077 and NCI agreement Y3-CO-5117). At earlier stages of the study, the U.S. Department of Energy (contract HHSN 261 2004 55796C), the Nuclear Regulatory Commission, and the French Institute for Radiological Protection and Nuclear Safety contributed additional funding. NR 37 TC 31 Z9 36 U1 1 U2 12 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2013 VL 121 IS 1 BP 59 EP 65 DI 10.1289/ehp.1204996 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 208SE UT WOS:000323698700025 PM 23149165 ER PT J AU Humblet, O Korrick, SA Williams, PL Sergeyev, O Emond, C Birnbaum, LS Burns, JS Altshul, LM Patterson, DG Turner, WE Lee, MM Revich, B Hauser, R AF Humblet, Olivier Korrick, Susan A. Williams, Paige L. Sergeyev, Oleg Emond, Claude Birnbaum, Linda S. Burns, Jane S. Altshul, Larisa M. Patterson, Donald G., Jr. Turner, Wayman E. Lee, Mary M. Revich, Boris Hauser, Russ TI Genetic Modification of the Association between Peripubertal Dioxin Exposure and Pubertal Onset in a Cohort of Russian Boys SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE children; development; gene-environment interaction; PCBs; puberty; TCDD ID ARYL-HYDROCARBON RECEPTOR; GENOME-WIDE ASSOCIATION; TOXIC EQUIVALENCY FACTORS; ENVIRONMENT INTERACTIONS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; SERUM; AGE; MENARCHE; RAT; EXPRESSION AB BACKGROUND: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins. OBJECTIVES: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset. METHODS: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations. RESULTS: After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-alpha (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only to those with marginal genetic associations. CONCLUSIONS: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-alpha genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings. C1 [Humblet, Olivier; Korrick, Susan A.; Burns, Jane S.; Altshul, Larisa M.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Humblet, Olivier] Univ Calif San Francisco, Ctr Hlth & Community, San Francisco, CA 94143 USA. [Korrick, Susan A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Korrick, Susan A.] Harvard Univ, Sch Med, Boston, MA USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Sergeyev, Oleg] Samara State Med Univ, Dept Phys Educ & Hlth, Samara, Russia. [Sergeyev, Oleg] Chapaevsk Med Assoc, Chapaevsk, Russia. [Emond, Claude] BioSimulat Consulting Inc, Newark, DC USA. [Birnbaum, Linda S.] NIEHS, NCI, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Altshul, Larisa M.] Environm Hlth & Engn Inc, Needham, MA USA. [Patterson, Donald G., Jr.] EnviroSolut Consulting Inc, Jasper, GA USA. [Turner, Wayman E.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Lee, Mary M.] Univ Massachusetts, Sch Med, Dept Pediat, Pediat Endocrinol Div, Worcester, MA USA. [Lee, Mary M.] Univ Massachusetts, Sch Med, Dept Cell Biol, Pediat Endocrinol Div, Worcester, MA USA. [Revich, Boris] Russian Acad Sci, Inst Forecasting, Ctr Demog & Human Ecol, Moscow, Russia. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1405, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu RI Sergeyev, Oleg/H-8854-2013 OI Sergeyev, Oleg/0000-0002-5745-3348 FU U.S. Environmental Protection Agency [EPA R82943701]; National Institute of Environmental Health Sciences (NIEHS) [ES014370, ES00002, 5T32-ES07069-28]; Robert Wood Johnson Foundation Health & Society Scholars program from NIEHS/National Human Genome Research Institute [5T32ES016645-02] FX This work was funded by grants from the U.S. Environmental Protection Agency (EPA R82943701) and the National Institute of Environmental Health Sciences (NIEHS) (ES014370, ES00002, and 5T32-ES07069-28). O.H. was supported by the Robert Wood Johnson Foundation Health & Society Scholars program and grant 5T32ES016645-02 from NIEHS/National Human Genome Research Institute. M.M.L. is a member of the University of Massachusetts Diabetes and Endocrinology Research Center (DK32520). NR 48 TC 1 Z9 1 U1 1 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2013 VL 121 IS 1 BP 111 EP 117 DI 10.1289/ehp.1205278 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 208SE UT WOS:000323698700033 PM 23060366 ER PT J AU Birnbaum, LS AF Birnbaum, Linda S. TI Designing Safer Chemicals SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Birnbaum, Linda S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NIH, NTP, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Birnbaum, LS (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbaumls@niehs.nih.gov NR 2 TC 3 Z9 3 U1 1 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2013 VL 121 IS 1 BP A9 EP A9 DI 10.1289/ehp.1206349 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 208SE UT WOS:000323698700002 PM 23287533 ER PT J AU Carlin, DJ Rider, CV Woychik, R Birnbaum, LS AF Carlin, Danielle J. Rider, Cynthia V. Woychik, Rick Birnbaum, Linda S. TI Unraveling the Health Effects of Environmental Mixtures: An NIEHS Priority SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID CHEMICAL-MIXTURES; CONTAMINANTS; FUTURE C1 [Carlin, Danielle J.; Rider, Cynthia V.; Woychik, Rick; Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Carlin, DJ (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM danielle.carlin@nih.gov NR 13 TC 12 Z9 12 U1 0 U2 13 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2013 VL 121 IS 1 BP A6 EP A8 DI 10.1289/ehp.1206182 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 208SE UT WOS:000323698700001 PM 23409283 ER PT J AU Duffy, SQ AF Duffy, Sarah Q. BE Miller, PM TI Economic Analysis of Addiction Treatment Programs SO INTERVENTIONS FOR ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 3 LA English DT Article; Book Chapter ID SUBSTANCE-ABUSE SERVICES; COST-EFFECTIVENESS; HEALTH C1 NIDA, Bethesda, MD 20892 USA. RP Duffy, SQ (reprint author), NIDA, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398363-3 PY 2013 BP 599 EP 609 DI 10.1016/B978-0-12-398338-1.00062-2 PG 11 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BGI00 UT WOS:000323055000063 ER PT J AU Kaufman, A Hunt, Y AF Kaufman, Annette Hunt, Yvonne BE Miller, PM TI Impact of Tobacco Control Policies on Youth Smoking Rates SO INTERVENTIONS FOR ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 3 LA English DT Article; Book Chapter C1 [Kaufman, Annette; Hunt, Yvonne] NCI, Bethesda, MD 20892 USA. RP Kaufman, A (reprint author), NCI, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398363-3 PY 2013 BP 933 EP 944 DI 10.1016/B978-0-12-398338-1.00094-4 PG 12 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BGI00 UT WOS:000323055000095 ER PT J AU Walter, BA Valera, VA Pinto, PA Merino, MJ AF Walter, Beatriz A. Valera, Vladimir A. Pinto, Peter A. Merino, Maria J. TI Comprehensive microRNA Profiling of Prostate Cancer SO JOURNAL OF CANCER LA English DT Article DE microRNA; Prostate Cancer; biomarkers ID PROGNOSTIC-SIGNIFICANCE; EXPRESSION PROFILES; GLEASON GRADE; HETEROGENEITY; CARCINOMA; TUMORS; MIRNA; MEN AB MicroRNAs are small non-coding RNA molecules that have been shown to regulate the expression of genes linked to cancer. The relevance of microRNAs in the development, progression and prognosis of prostate cancer is not fully understood. It is also possible that these specific molecules may assist in the recognition of aggressive tumors and the development of new molecular targets. Our study investigated the importance of several microRNAs in cases of prostate cancer from 37 patients that were manually microdissected to obtain pure populations of tumor cells, normal epithelium and adjacent stroma. MicroRNA was extracted for PCR array profiling. Differentially expressed miRNAs for each case were used to compare tumor vs. normal epithelium and tumor- adjacent stroma samples. Loss of 18 miRNAs (e. g. miR-34c, miR-29b, miR-212 and miR-10b) and upregulation of miR-143 and miR-146b were significantly found in all the tumors in comparison with normal epithelium and/or stroma (p <= 0.001). A different signature was found in the high grade tumors (Gleason score >= 8) when compared with tumors Gleason score 6. Upregulation of miR-122, miR-335, miR-184, miR-193, miR-34, miR-138, miR-373, miR-9, miR-198, miR-144 and miR-215 and downregulation of miR-96, miR-222, miR-148, miR-92, miR-27, miR-125, miR-126, miR-27 were found in the high grade tumors. MicroRNA profiling in prostate cancer appears to have unique expression patterns in comparison with normal tissue. These differential expressed miRNAs may provide novel diagnostic and prognostic tools that will assist in the recognition of prostate cancers with aggressive behavior. C1 [Walter, Beatriz A.; Valera, Vladimir A.; Merino, Maria J.] NCI, Translat Surg Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Merino, MJ (reprint author), 10 Ctr Dr,Bldg 10 MSC Room 2B44, Bethesda, MD 20892 USA. EM mjmerino@mail.nih.gov NR 25 TC 83 Z9 83 U1 1 U2 17 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2013 VL 4 IS 5 BP 350 EP 357 DI 10.7150/jca.6394 PG 8 WC Oncology SC Oncology GA 206XJ UT WOS:000323559200001 PM 23781281 ER PT J AU Sekhar, SC Kasai, T Satoh, A Shigehiro, T Mizutani, A Murakami, H El-Aarag, BYA Salomon, DS Massaguer, A de Llorens, R Seno, M AF Sekhar, Sreeja C. Kasai, Tomonari Satoh, Ayano Shigehiro, Tsukasa Mizutani, Akifumi Murakami, Hiroshi El-Aarag, Bishoy Y. A. Salomon, David S. Massaguer, Anna de Llorens, Rafael Seno, Masaharu TI Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells SO JOURNAL OF CANCER LA English DT Article DE ErbB2; Caveolin-1; Antibody dependent cell mediated cytotoxicity (ADCC); internalization; Ec-eGFP; Trastuzumab ID CLATHRIN-INDEPENDENT ENDOCYTOSIS; RECEPTOR TYROSINE KINASES; ERBB RECEPTORS; MONOCLONAL-ANTIBODY; MEMBRANE DOMAINS; IN-VIVO; LIGAND; EXPRESSION; INTERNALIZATION; GELDANAMYCIN AB The oncogenic tyrosine kinase receptor ErbB2 is a prognostic factor and target for breast cancer therapeutics. In contrast with the other ErbB receptors, ErbB2 is hardly internalized by ligand induced mechanisms, indicating a prevalent surface expression. Elevated levels of ErbB2 in tumor cells are associated with its defective endocytosis and down regulation. Here we show that caveolin-1 expression in breast cancer derived SKBR-3 cells (SKBR-3/Cav-1) facilitates ligand induced ErbB2 endocytosis using an artificial peptide ligand EC-eGFP. Similarly, stimulation with humanized anti ErbB2 antibody Trastuzumab (Herceptin) was found to be internalized and co-localized with caveolin-1 in SKBR-3/Cav-1 cells. Internalized EC-eGFP and Trastuzumab in SKBR-3/Cav-1 cells were then delivered via caveolae to the caveolin-1 containing early endosomes. Consequently, attenuated Fc receptor mediated ADCC functions were observed when exposed to Trastuzumab and EC-Fc (EC-1 peptide conjugated to Fc part of human IgG). On the other hand, this caveolae dependent endocytic synergy was not observed in parental SKBR-3 cells. Therefore, caveolin-1 expression in breast cancer cells could be a predictive factor to estimate how cancer cells are likely to respond to Trastuzumab treatment. C1 [Sekhar, Sreeja C.; Kasai, Tomonari; Satoh, Ayano; Shigehiro, Tsukasa; Mizutani, Akifumi; Murakami, Hiroshi; Seno, Masaharu] Okayama Univ, Grad Sch Nat Sci & Technol, Div Chem & Biotechnol, Okayama 7008530, Japan. [El-Aarag, Bishoy Y. A.] Menoufia Univ, Fac Sci, Dept Chem, Menoufia, Egypt. [Salomon, David S.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. [Massaguer, Anna; de Llorens, Rafael] Girona Univ, Dept Biol, Biochem & Mol Biol Unit, Girona 17071, Spain. RP Kasai, T (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Div Chem & Biotechnol, Okayama 7008530, Japan. EM t-kasai@cc.okayama-u.ac.jp RI Massaguer, Anna/L-5993-2014; SENO, Masaharu /B-2092-2011; OI Massaguer, Anna/0000-0003-1312-593X; SENO, Masaharu /0000-0001-8547-6259; SATOH, Ayano/0000-0003-3736-1283 FU JSPS KAKENHI [24510151, 23650598] FX We thank Dr. Yoshiaki Iwasaki, M. D, PhD, Okayama University for his assistance to conduct ADCC experiments. This work was supported by JSPS KAKENHI Grant Numbers 24510151, 23650598. NR 49 TC 5 Z9 7 U1 3 U2 9 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2013 VL 4 IS 5 BP 391 EP 401 DI 10.7150/jca.6470 PG 11 WC Oncology SC Oncology GA 206XJ UT WOS:000323559200005 PM 23833684 ER PT J AU Fang, CG Avis, I Salomon, D Cuttitta, F AF Fang, Changge Avis, Ingalill Salomon, David Cuttitta, Frank TI Novel Phenotypic Fluorescent Three-Dimensional Platforms for High-throughput Drug Screening and Personalized Chemotherapy SO JOURNAL OF CANCER LA English DT Article DE Three-dimensional; Fluorescent; Angiogenesis; Metastasis; High-throughput; Drug screening; Personalized chemotherapy ID CAPILLARY ENDOTHELIAL-CELLS; TUMOR ANGIOGENESIS; CANCER METASTASIS; SPHEROID MODEL; MAST-CELLS; CULTURE; BIOLOGY; GROWTH; NEOVASCULARIZATION; DIFFERENTIATION AB We have developed novel phenotypic fluorescent three-dimensional co-culture platforms that efficiently and economically screen anti-angiogenic/anti-metastatic drugs on a high-throughput scale. Individual cell populations can be identified and isolated for protein/gene expression profiling studies and cellular movement/interactions can be tracked by time-lapse cinematography. More importantly, these platforms closely parallel the in vivo angiogenic and metastatic outcomes of a given tumor xenograft in the nude mouse model but, unlike in vivo models, our co-culture platforms produce comparable results in five to nine days. Potentially, by incorporating cancer patient biopsies, the co-culture platforms should greatly improve the effectiveness and efficiency of personalized chemotherapy. C1 [Fang, Changge] Adv Personalized Diagnost LLC, Alexandria, VA 22303 USA. [Fang, Changge; Avis, Ingalill; Cuttitta, Frank] NCI, Angiogenesis Core Facil, Adv Technol Ctr, Ctr Canc Res, Bethesda, MD 20892 USA. [Salomon, David] NCI, Tumor Growth Factor Sect, Lab Canc Prevent, Frederick, MD 21702 USA. RP Fang, CG (reprint author), Adv Personalized Diagnost LLC, 6006 Bangor Dr, Alexandria, VA 22303 USA. EM changgefang@hotmail.com RI Cuttitta, Frank/B-4758-2016 NR 50 TC 10 Z9 11 U1 0 U2 5 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2013 VL 4 IS 5 BP 402 EP 415 DI 10.7150/jca.6780 PG 14 WC Oncology SC Oncology GA 206XJ UT WOS:000323559200006 PM 23833685 ER PT J AU Wang, XY Zhou, ZJ Wang, ZY Xue, YX Zeng, Y Gao, JH Zhu, L Zhang, XZ Liu, G Chen, XY AF Wang, Xiaoyong Zhou, Zijian Wang, Zhiyong Xue, Yunxin Zeng, Yun Gao, Jinhao Zhu, Lei Zhang, Xianzhong Liu, Gang Chen, Xiaoyuan TI Gadolinium embedded iron oxide nanoclusters as T-1-T-2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery SO NANOSCALE LA English DT Article ID IN-VIVO; RNA INTERFERENCE; DNA DELIVERY; MAGNETIC NANOPARTICLES; NONVIRAL VECTOR; GENE; STRATEGIES; THERAPY; CANCER; POLYETHYLENIMINE AB This report illustrates a new strategy of designing a T-1-T-2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T-1-T-2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T-1-T-2 dual-modal MRI monitoring capability. C1 [Wang, Xiaoyong; Zhou, Zijian; Xue, Yunxin; Zeng, Yun; Gao, Jinhao; Zhu, Lei; Zhang, Xianzhong; Liu, Gang] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361102, Fujian, Peoples R China. [Zhou, Zijian; Gao, Jinhao] Xiamen Univ, State Key Lab Phys Chem Solid Surfaces, Key Lab Chem Biol Fujian Prov, Xiamen 361005, Peoples R China. [Zhou, Zijian; Gao, Jinhao] Xiamen Univ, Dept Biol Chem, Coll Chem & Chem Engn, Xiamen 361005, Peoples R China. [Liu, Gang] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Peoples R China. [Wang, Zhiyong] Chinese Acad Sci, Shenzhen Inst Adv Technol, Inst Biomed & Hlth Engn, Paul C Lauterbur Res Ctr Biomed Imaging, Shenzhen 518055, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Liu, G (reprint author), Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361102, Fujian, Peoples R China. EM gangliu.cmitm@xmu.edu.cn; shawn.chen@nih.gov RI Gao, Jinhao/F-5092-2010; Zhu, Lei/P-9786-2016; Zhang, Xianzhong/A-7754-2012 OI Gao, Jinhao/0000-0003-3215-7013; Zhu, Lei/0000-0002-1820-4795; Zhang, Xianzhong/0000-0002-1001-1884 FU Major State Basic Research Development Program of China (973 Program) [2013CB733802]; National Science Foundation of China (NSFC) [81101101, 51273165, 81201086, 81201190]; Key Project of Chinese Ministry of Education [212149]; Fundamental Research Funds for the Central Universities [2013121039]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported in part by the Major State Basic Research Development Program of China (973 Program) (no. 2013CB733802), National Science Foundation of China (NSFC) (81101101, 51273165, 81201086, 81201190), Key Project of Chinese Ministry of Education (212149), Fundamental Research Funds for the Central Universities (2013121039), and Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 34 TC 12 Z9 12 U1 1 U2 59 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2013 VL 5 IS 17 BP 8098 EP 8104 DI 10.1039/c3nr02797j PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 198YA UT WOS:000322958800056 PM 23884164 ER PT J AU Pagani, JH Wersinger, SR Young, WS AF Pagani, Jerome H. Wersinger, Scott R. Young, W. Scott, III BE Choleris, E Pfaff, DW Kavaliers, M TI The roles of vasopressin and oxytocin in aggression SO OXYTOCIN, VASOPRESSIN AND RELATED PEPTIDES IN THE REGULATION OF BEHAVIOR LA English DT Article; Book Chapter ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; V-1A RECEPTOR-BINDING; MEDIAL PREOPTIC AREA; GESTATIONAL COCAINE TREATMENT; MESSENGER RIBONUCLEIC-ACIDS; LATERAL SEPTAL VASOPRESSIN; CENTRAL-NERVOUS-SYSTEM; RAT SPINAL-CORD; MATERNAL AGGRESSION; GOLDEN-HAMSTERS C1 [Pagani, Jerome H.; Young, W. Scott, III] NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. [Wersinger, Scott R.] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. RP Pagani, JH (reprint author), NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 180 TC 4 Z9 4 U1 1 U2 6 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-19035-0 PY 2013 BP 193 EP 212 D2 10.1017/CBO9781139017855 PG 20 WC Behavioral Sciences; Pharmacology & Pharmacy SC Behavioral Sciences; Pharmacology & Pharmacy GA BGJ25 UT WOS:000323213300012 ER PT J AU Glantz, MD AF Glantz, Meyer D. BE Miller, PM Blume, AW Kavanagh, DJ Kampman, KM Bates, ME Larimer, ME Petry, NM DeWitte, P Ball, SA TI The Terminology of Addictive Behavior SO PRINCIPLES OF ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 1 LA English DT Article; Book Chapter ID DIAGNOSTIC SYSTEMS; DSM-V; COMORBIDITY C1 [Glantz, Meyer D.] NIDA, Bethesda, MD 20892 USA. [Glantz, Meyer D.] NIH, Bethesda, MD 20892 USA. RP Glantz, MD (reprint author), NIDA, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398361-9 PY 2013 BP 13 EP 22 DI 10.1016/B978-0-12-398336-7.00002-4 PG 10 WC Substance Abuse SC Substance Abuse GA BGG51 UT WOS:000322841800003 ER PT J AU Faden, VB Powell, PA AF Faden, Vivian B. Powell, Patricia A. BE Miller, PM Blume, AW Kavanagh, DJ Kampman, KM Bates, ME Larimer, ME Petry, NM DeWitte, P Ball, SA TI Epidemiology of Adolescent and Young Adult Alcohol, Tobacco, and Drug Use and Misuse in the United States SO PRINCIPLES OF ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 1 LA English DT Article; Book Chapter ID DEPENDENCE; DRINKING; ONSET; AGE C1 [Faden, Vivian B.; Powell, Patricia A.] NIAAA, Bethesda, MD USA. RP Faden, VB (reprint author), NIAAA, Bethesda, MD USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398361-9 PY 2013 BP 545 EP 562 DI 10.1016/B978-0-12-398336-7.00057-7 PG 18 WC Substance Abuse SC Substance Abuse GA BGG51 UT WOS:000322841800058 ER PT J AU Hingson, RW White, AM AF Hingson, Ralph W. White, Aaron M. BE Miller, PM Blume, AW Kavanagh, DJ Kampman, KM Bates, ME Larimer, ME Petry, NM DeWitte, P Ball, SA TI Costs and Consequences (Morbidity and Mortality) Associated with Adolescent and College Drinking and Related Problems SO PRINCIPLES OF ADDICTION: COMPREHENSIVE ADDICTIVE BEHAVIORS AND DISORDERS, VOL 1 LA English DT Article; Book Chapter ID HEAVY DRINKING; INTERVENTIONS; PREVENTION; STUDENTS; TRIAL C1 [Hingson, Ralph W.; White, Aaron M.] NIAAA, Bethesda, MD USA. RP Hingson, RW (reprint author), NIAAA, Bethesda, MD USA. NR 16 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398361-9 PY 2013 BP 605 EP 616 DI 10.1016/B978-0-12-398336-7.00062-0 PG 12 WC Substance Abuse SC Substance Abuse GA BGG51 UT WOS:000322841800063 ER PT J AU Shukla, SD Zakhari, S AF Shukla, Shivendra D. Zakhari, Samir TI Epigenetics-New Frontier for Alcohol Research SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Editorial Material ID HUMAN-DISEASE C1 [Shukla, Shivendra D.] Univ Missouri, Sch Med, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA. [Zakhari, Samir] NIAAA, Div Metab & Hlth Effects, Washington, DC USA. [Zakhari, Samir] Distilled Spirits Council US DISCUS, Washington, DC USA. RP Shukla, SD (reprint author), Univ Missouri, Sch Med, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA. NR 4 TC 3 Z9 4 U1 0 U2 1 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2013 VL 35 IS 1 BP 1 EP 2 PG 2 WC Substance Abuse SC Substance Abuse GA 210BO UT WOS:000323804500001 PM 24313159 ER PT J AU Zakhari, S AF Zakhari, Samir TI Alcohol Metabolism and Epigenetics Changes SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Article DE Alcohol consumption; alcohol metabolism; ethanol metabolism; alcohol-induced organ damage; disease; epigenetics; epigenetic mechanisms; epigenetic modifications; gene expression; DNA; DNA methylation; histone modification; histone acetylation ID APOPTOSIS-INDUCING FACTOR; CALORIE RESTRICTION; REDOX STATE; CELL-DEATH; RAT-LIVER; METHIONINE ADENOSYLTRANSFERASE; PERMEABILITY TRANSITION; S-ADENOSYLMETHIONINE; ETHANOL-CONSUMPTION; CIRCADIAN-RHYTHM AB Metabolites, including those generated during ethanol metabolism, can impact disease states by binding to transcription factors and/or modifying chromatin structure, thereby altering gene expression patterns. For example, the activities of enzymes involved in epigenetic modifications such as DNA and histone methylation and histone acetylation, are influenced by the levels of metabolites such as nicotinamide adenine dinucleotide (NAD), adenosine triphosphate (ATP), and S-adenosylmethionine (SAM). Chronic alcohol consumption leads to significant reductions in SAM levels, thereby contributing to DNA hypomethylation. Similarly, ethanol metabolism alters the ratio of NAD+ to reduced NAD (NADH) and promotes the formation of reactive oxygen species and acetate, all of which impact epigenetic regulatory mechanisms. In addition to altered carbohydrate metabolism, induction of cell death, and changes in mitochondrial permeability transition, these metabolism-related changes can lead to modulation of epigenetic regulation of gene expression. Understanding the nature of these epigenetic changes will help researchers design novel medications to treat or at least ameliorate alcohol-induced organ damage. C1 [Zakhari, Samir] NIAAA, Div Metab & Hlth Effects, Washington, DC USA. [Zakhari, Samir] Distilled Spirits Council US DISCUS, Washington, DC USA. RP Zakhari, S (reprint author), NIAAA, Div Metab & Hlth Effects, Washington, DC USA. NR 67 TC 24 Z9 27 U1 2 U2 14 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2013 VL 35 IS 1 BP 6 EP 16 PG 11 WC Substance Abuse SC Substance Abuse GA 210BO UT WOS:000323804500002 PM 24313160 ER PT J AU Percopo, CM AF Percopo, Caroline M. BE Lee, JJ Rosenberg, HF TI Isolation and Manipulation of Eosinophils from Human Peripheral Blood SO EOSINOPHILS IN HEALTH AND DISEASE LA English DT Article; Book Chapter ID HYPODENSE EOSINOPHILS; IMMUNOMAGNETIC BEADS; DENSITY GRADIENTS; PERCOLL GRADIENTS; PURIFICATION; SEPARATION; NEUTROPHILS; SELECTION; RELEASE; RESPOND C1 NIAID, Inflammat Immunobiol Sect, LAD, NIH, Bethesda, MD 20892 USA. RP Percopo, CM (reprint author), NIAID, Inflammat Immunobiol Sect, LAD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-394385-9 PY 2013 BP 46 EP 51 PG 6 WC Immunology SC Immunology GA BGG52 UT WOS:000322842400010 ER PT J AU Dyer, KD AF Dyer, Kimberly D. BE Lee, JJ Rosenberg, HF TI Culture and Characterization of Mouse Bone Marrow-Derived Eosinophils SO EOSINOPHILS IN HEALTH AND DISEASE LA English DT Article; Book Chapter ID ACTIVATING-FACTOR RECEPTOR; GM-CSF; DIFFERENTIATION FACTOR; PAF-RECEPTOR; EX-VIVO; IN-VIVO; MICE; INTERLEUKIN-5; EXPRESSION; PROMOTER C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Dyer, KD (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-394385-9 PY 2013 BP 64 EP 67 PG 4 WC Immunology SC Immunology GA BGG52 UT WOS:000322842400012 ER PT J AU Rosenberg, HF Dyer, KD Domachowske, JB AF Rosenberg, Helene F. Dyer, Kimberly D. Domachowske, Joseph B. BE Lee, JJ Rosenberg, HF TI Interactions of Eosinophils with Respiratory Virus Pathogens SO EOSINOPHILS IN HEALTH AND DISEASE LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; VACCINE-ENHANCED DISEASE; AIRWAY EPITHELIAL-CELLS; CORONAVIRUS SARS-COV; SYNCYTIAL VIRUS; INFLUENZA-VIRUS; PNEUMONIA VIRUS; HOST-DEFENSE; IN-VITRO; PULMONARY PATHOLOGY C1 [Rosenberg, Helene F.; Dyer, Kimberly D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Div Infect Dis, Syracuse, NY 13210 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 85 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-394385-9 PY 2013 BP 281 EP 290 PG 10 WC Immunology SC Immunology GA BGG52 UT WOS:000322842400040 ER PT J AU Nutman, TB AF Nutman, Thomas B. BE Lee, JJ Rosenberg, HF TI Immune Responses in Helminth Infections SO EOSINOPHILS IN HEALTH AND DISEASE LA English DT Article; Book Chapter ID REGULATORY T-CELLS; SCHISTOSOMA-MANSONI EGGS; ANTIGEN-PRESENTING CELLS; HELPER TYPE-2 RESPONSE; DENDRITIC CELLS; TH2 RESPONSES; BRUGIA-MALAYI; B-CELLS; LYMPHATIC FILARIASIS; CYTOKINE RESPONSES C1 NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nutman, TB (reprint author), NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 75 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-394385-9 PY 2013 BP 312 EP 320 PG 9 WC Immunology SC Immunology GA BGG52 UT WOS:000322842400044 ER PT J AU Prussin, C AF Prussin, Calman BE Lee, JJ Rosenberg, HF TI Eosinophil Cell-Cell Communication SO EOSINOPHILS IN HEALTH AND DISEASE LA English DT Editorial Material; Book Chapter ID TH2 IMMUNITY; INNATE; BASOPHILS; RESPONSES C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Prussin, C (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C207, Bethesda, MD 20892 USA. RI Fryer, Allison/F-2420-2014; OI Fryer, Allison/0000-0003-1712-9831; Prussin, Calman/0000-0002-3917-3326 NR 6 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-394385-9 PY 2013 BP 329 EP 331 DI 10.1016/B978-0-12-394385-9.00011-0 PG 3 WC Immunology SC Immunology GA BGG52 UT WOS:000322842400046 ER PT J AU Marini, JC Rajpar, MH AF Marini, Joan C. Rajpar, M. Helen BE Thakker, RV Whyte, MP Eisman, JA Igarashi, T TI Osteogenesis Imperfecta SO GENETICS OF BONE BIOLOGY AND SKELETAL DISEASE LA English DT Article; Book Chapter ID EPITHELIUM-DERIVED FACTOR; ALPHA-1(I) COLLAGEN GENE; TRIPLE-HELIX FORMATION; EHLERS-DANLOS-SYNDROME; BRITTLE BONE-DISEASE; CIS-TRANS-ISOMERASE; I COLLAGEN; MOUSE MODEL; ENDOPLASMIC-RETICULUM; CYCLOPHILIN-B C1 [Marini, Joan C.; Rajpar, M. Helen] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. RP Marini, JC (reprint author), NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. NR 101 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-387830-4 PY 2013 BP 257 EP 273 DI 10.1016/B978-0-12-387829-8.00017-2 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BGF11 UT WOS:000322631800018 ER PT J AU Weinstein, LS Collins, MT Spiegel, AM AF Weinstein, Lee S. Collins, Michael T. Spiegel, Allen M. BE Thakker, RV Whyte, MP Eisman, JA Igarashi, T TI G(s)alpha, Pseudohypoparathyroidism, Fibrous Dysplasia, and McCune-Albright Syndrome SO GENETICS OF BONE BIOLOGY AND SKELETAL DISEASE LA English DT Article; Book Chapter ID STIMULATORY G-PROTEIN; XL-ALPHA-S; PROGRESSIVE OSSEOUS HETEROPLASIA; HEREDITARY OSTEODYSTROPHY; GS-ALPHA; PRECOCIOUS PUBERTY; ACTIVATING MUTATIONS; PARATHYROID-HORMONE; AUTOSOMAL-DOMINANT; SKELETAL PROGENITORS C1 [Weinstein, Lee S.] NIDDK, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD USA. [Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Spiegel, Allen M.] Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Weinstein, LS (reprint author), NIDDK, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD USA. NR 99 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-387830-4 PY 2013 BP 425 EP 440 DI 10.1016/B978-0-12-387829-8.00027-5 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BGF11 UT WOS:000322631800028 ER PT S AU Giulianelli, S Molinolo, A Lanari, C AF Giulianelli, Sebastian Molinolo, Alfredo Lanari, Claudia BE Litwack, G TI Targeting Progesterone Receptors in Breast Cancer SO HORMONES AND BREAST CANCER SE Vitamins and Hormones LA English DT Review; Book Chapter ID EPIDERMAL-GROWTH-FACTOR; SPRAGUE-DAWLEY RATS; MEDROXYPROGESTERONE ACETATE MPA; ESTROGEN PLUS PROGESTIN; MAMMARY-TUMOR GROWTH; METHYL-N-NITROSOUREA; HEALTHY POSTMENOPAUSAL WOMEN; HORMONE-REPLACEMENT THERAPY; BALB/C FEMALE MICE; CELL-PROLIFERATION AB Hormone receptors represent the earliest biomarkers used in breast cancer not only as prognosis markers but, in addition, to decide treatment. However, mostly estrogen receptors have been used as therapeutic targets. There is compelling evidence indicating that progesterone receptors (PRs) play a hierarchical role in breast cancer growth and that they might be potentially used to improve the success of endocrine treatments. The two PR isoforms, PR-A and PR-B, play differential roles in regulating gene expression. Tumors overexpressing one or other PR isoform may respond different to endocrine treatment. In this chapter, we highlight the evidence regarding progestins as promoters or inhibitors of cell proliferation in order to understand the dual role of PR in regulating tumor growth, underscoring thus the need of biomarkers to identify which patients may benefit with an antiprogestin/progestin treatment. C1 [Giulianelli, Sebastian; Lanari, Claudia] Consejo Nacl Invest Cient & Tecn CONICET, Lab Hormonal Carcinogenesis, Inst Expt Biol & Med IBYME, Buenos Aires, DF, Argentina. [Molinolo, Alfredo] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Lanari, C (reprint author), Consejo Nacl Invest Cient & Tecn CONICET, Lab Hormonal Carcinogenesis, Inst Expt Biol & Med IBYME, Buenos Aires, DF, Argentina. EM lanari.claudia@gmail.com FU Intramural NIH HHS NR 154 TC 4 Z9 5 U1 0 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 978-0-12-416673-8 J9 VITAM HORM JI Vitam. Horm. PY 2013 VL 93 BP 161 EP 184 DI 10.1016/B978-0-12-416673-8.00009-5 PG 24 WC Biochemistry & Molecular Biology; Oncology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Oncology; Endocrinology & Metabolism GA BGG56 UT WOS:000322845500006 PM 23810006 ER PT J AU Xin, HW Ambe, CM Ray, S Kim, BK Koizumi, T Wiegand, GW Hari, D Mullinax, JE Jaiswal, KR Garfield, SH Stojadinovic, A Rudloff, U Thorgeirsson, SS Avital, I AF Xin, Hong-Wu Ambe, Chenwi M. Ray, Satyajit Kim, Bo-Kyu Koizumi, Tomotake Wiegand, Gordon W. Hari, Danielle Mullinax, John E. Jaiswal, Kshama R. Garfield, Susan H. Stojadinovic, Alexander Rudloff, Udo Thorgeirsson, Snorri S. Avital, Itzhak TI Wnt and the Cancer Niche: Paracrine Interactions with Gastrointestinal Cancer Cells Undergoing Asymmetric Cell Division SO JOURNAL OF CANCER LA English DT Article DE Cancer Stem Cells; Asymmetric Cell Division; Non-Random Chromosomal Cosegregation; Microenvironment ID LABEL-RETAINING CELLS; TEMPLATE DNA STRANDS; STEM-CELLS; CHROMOSOME SEGREGATION; IDENTIFICATION; LIVER; LESSONS; PROTECT; GENOME; LGR5 AB Objective: Stem-like cancer cells contribute to cancer initiation and maintenance. Stem cells can self-renew by asymmetric cell division (ACD). ACD with non-random chromosomal cosegregation (ACD-NRCC) is one possible self-renewal mechanism. There is a paucity of evidence supporting ACD-NRCC in human cancer. Our aim was to investigate ACD-NRCC and its potential interactions with the cancer niche (microenvironment) in gastrointestinal cancers. Design: We used DNA double and single labeling approaches with FACS to isolate live cells undergoing ACD-NRCC. Results: Gastrointestinal cancers contain rare subpopulations of cells capable of ACD-NRCC. ACD-NRCC was detected preferentially in subpopulations of cells previously suggested to be stem-like/tumor-initiating cancer cells. ACD-NRCC was independent of cell-to-cell contact, and was regulated by the cancer niche in a heat-sensitive paracrine fashion. Wnt pathway genes and proteins are differentially expressed in cells undergoing ACD-NRCC vs. symmetric cell division. Blocking the Wnt pathway with IWP2 (WNT antagonist) or siRNA-TCF4 resulted in suppression of ACD-NRCC. However, using a Wnt-agonist did not increase the relative proportion of cells undergoing ACD-NRCC. Conclusion: Gastrointestinal cancers contain subpopulations of cells capable of ACD-NRCC. Here we show for the first time that ACD-NRCC can be regulated by the Wnt pathway, and by the cancer niche in a paracrine fashion. However, whether ACD-NRCC is exclusively associated with stem-like cancer cells remains to be determined. Further study of these findings might generate novel insights into stem cell and cancer biology. Targeting the mechanism of ACD-NRCC might engender novel approaches for cancer therapy. C1 [Xin, Hong-Wu; Ambe, Chenwi M.; Ray, Satyajit; Kim, Bo-Kyu; Koizumi, Tomotake; Wiegand, Gordon W.; Hari, Danielle; Mullinax, John E.; Jaiswal, Kshama R.; Rudloff, Udo; Avital, Itzhak] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Garfield, Susan H.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Stojadinovic, Alexander] Walter Reed Natl Mil Med Ctr, Dept Surg, Div Surg Oncol, Bethesda, MD USA. [Stojadinovic, Alexander; Avital, Itzhak] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. [Avital, Itzhak] Bon Secours Canc Inst, Richmond, VA 23230 USA. RP Thorgeirsson, SS (reprint author), NCI, Ctr Excellence Integrat Canc Biol & Genom Chief, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, 37 Convent Dr MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. EM snor-ri_thorgeirsson@nih.gov; itzhak.avital@gmail.com RI Mullinax, John/L-2509-2014 FU NCI [1ZIABC011005] FX NCI grant 1ZIABC011005. NR 29 TC 3 Z9 3 U1 0 U2 7 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2013 VL 4 IS 6 BP 447 EP 457 DI 10.7150/jca.6896 PG 11 WC Oncology SC Oncology GA 206XL UT WOS:000323559600001 PM 23901343 ER PT J AU Srimaroeng, C Cecile, JP Walden, R Pritchard, JB AF Srimaroeng, Chutima Cecile, Jennifer Perry Walden, Ramsey Pritchard, John B. TI Regulation of Renal Organic Anion Transporter 3 (SLC22A8) Expression and Function by the Integrity of Lipid Raft Domains and their Associated Cytoskeleton SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE Renal organic anion transporter; Lipid rafts; Regulation; Transporters; Cytoskeleton ID PROTEIN-KINASE-C; BLOOD-BRAIN-BARRIER; PLASMA-MEMBRANE; RAT-KIDNEY; ACTIN CYTOSKELETON; PROXIMAL TUBULES; CHOLESTEROL; CAVEOLIN; TRAFFICKING; ACTIVATION AB Background/Aims: In humans and rodents, organic anion transporter 3 (Oat3) is highly expressed on the basolateral membrane of renal proximal tubules and mediates the secretion of exogenous and endogenous anions. Regulation of Oat3 expression and function has been observed in both expression system and intact renal epithelia. However, information on the local membrane environment of Oat3 and its role is limited. Lipid raft domains (LRD; cholesterol-rich domains of the plasma membrane) play important roles in membrane protein expression, function and targeting. In the present study, we have examined the role of LRDrich membranes and their associated cytoskeletal proteins on Oat3 expression and function. Methods: LRD-rich membranes were isolated from rat renal cortical tissues and from HEK-293 cells stably expressing human OAT3 (hOAT3) by differential centrifugation with triton X-100 extraction. Western blots were subsequently analyzed to determine protein expression. In addition, the effect of disruption of LRD-rich membranes was examined on functional Oat3 mediated estrone sulfate (ES) transport in rat renal cortical slices. Cytoskeleton disruptors were investigated in both hOAT3 expressing HEK-293 cells and rat renal cortical slices. Results: Lipid-enriched membranes from rat renal cortical tissues and hOAT3-expressing HEK-293 cells showed co-expression of rOat3/hOAT3 and several lipid raft-associated proteins, specifically caveolin 1 (Cav1), beta-actin and myosin. Moreover, immunohistochemistry in hOAT3-expressing HEK-293 cells demonstrated that these LRD-rich proteins co-localized with hOAT3. Potassium iodide (KI), an inhibitor of protein-cytoskeletal interaction, effectively detached cytoskeleton proteins and hOAT3 from plasma membrane, leading to redistribution of hOAT3 into non-LRDrich compartments. In addition, inhibition of cytoskeleton integrity and membrane trafficking processes significantly reduced ES uptake mediated by both human and rat Oat3. Cholesterol depletion by methyl-beta-cyclodextrin (M beta CD) also led to a dose dependent reduction Oat3 expression and ES transport by rat renal cortical slices. Moreover, the up-regulation of rOat3-mediated transport seen following insulin stimulation was completely prevented by M beta CD. Conclusion: We have demonstrated that renal Oat3 resides in LRD-rich membranes in proximity to cytoskeletal and signaling proteins. Disruption of LRD-rich membranes by cholesterol-binding agents or protein trafficking inhibitors altered Oat3 expression and regulation. These findings indicate that the integrity of LRD-rich membranes and their associated proteins are essential for Oat3 expression and function. Copyright (C) 2013 S. Karger AG, Basel C1 [Srimaroeng, Chutima] Chiang Mai Univ, Fac Med, Dept Physiol, Chiang Mai 50200, Thailand. [Srimaroeng, Chutima; Cecile, Jennifer Perry; Walden, Ramsey; Pritchard, John B.] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, Res Triangle Pk, NC USA. [Cecile, Jennifer Perry] Appalachian State Univ, Dept Chem, Boone, NC 28608 USA. RP Srimaroeng, C (reprint author), Chiang Mai Univ, Fac Med, Dept Physiol, 110 Intavaroros Rd, Chiang Mai 50200, Thailand. EM c.srimaroeng@gmail.com OI Srimaroeng, Chutima/0000-0002-5537-1023 FU Faculty of Medicine Endowment Fund; Faculty of Medicine; Chiang Mai University; Chiang Mai, Thailand; NIH, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA FX We wish to thank Drs. Timothy Lockwich for kindly providing detergent extraction of cell membrane protocol and Amy Aslamkhan for valuable suggestion in this manuscript. We also thank Mr. Chaya Vaddhanaphuti and Ms. Atcharaporn Ontawong for their assistance with manuscript preparation. This research was supported by the Faculty of Medicine Endowment Fund, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand and the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. NR 48 TC 2 Z9 2 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2013 VL 31 IS 4-5 BP 565 EP 578 DI 10.1159/000350077 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 195RD UT WOS:000322720400009 PM 23615001 ER PT J AU Vourganti, S Harbin, A Singer, EA Shuch, B Metwalli, AR Agarwal, PK AF Vourganti, Srinivas Harbin, Andrew Singer, Eric A. Shuch, Brian Metwalli, Adam R. Agarwal, Piyush K. TI Low Grade Micropapillary Urothelial Carcinoma, Does It Exist? - Analysis of Management and Outcomes from the Surveillance, Epidemiology and End Results (SEER) Database SO JOURNAL OF CANCER LA English DT Article DE bladder; carcinoma; grade; micropapillary; SEER ID TRANSITIONAL-CELL CARCINOMA; URINARY-BLADDER; VARIANT; CANCER AB Objective: To elucidate the oncologic behavior of Micropapillary Urothelial Bladder Carcinoma (MPBC), a rare aggressive variant histology. Methods: All MPBC patients in SEER 17 database were compared with those with traditional urothelial carcinoma (UC). Kaplan-Meier curves were used to determine OS and CSS. A Cox proportional hazards model (CPH) was constructed to test the effect of covariates on outcomes. Results: From 2001-2008, 120 MPBC patients were identified, 0.1% of all bladder cancer. MPBC presented with more high grade (86.1% vs. 38.7%, p<0.0001) and more high stage disease (40.8% NMI vs. 90.4% NMI, p < 0.0001) than UC. Low grade (LG) NMI MPBC had worse OS and CSS compared to LG UC (p=0.0037, p<0.0001 respectively), and did no better than high grade (HG) NMI MPBC. No difference was detected between HG NMI MPBC and HG NMI UC pts. A CPH model controlling for stage, grade, treatment, age, race, and sex detected no significant survival difference in MPBC vs. UC (HR 1.04, p=0.7966). For NMI MPBC (n=49), only 4 patients underwent definitive therapy, of whom none died of disease. However, in those not receiving definitive therapy (n=45), 7 cancer specific deaths occurred (15.6%). Conclusion: Controlling for stage and grade, no survival difference could be detected between MPBC and UC. Low grade NMI MPBC behaved similarly to both high grade MPBC and high grade UC. We propose that all MPBC (regardless of grade) be managed as high grade disease, and that strong consideration for definitive therapy should be given in all cases. C1 [Vourganti, Srinivas; Shuch, Brian; Metwalli, Adam R.; Agarwal, Piyush K.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Singer, Eric A.] UMDNJ Robert Wood Johnson Med Sch, Canc Inst New Jersey, Sect Urol Oncol, Piscataway, NJ 08854 USA. RP Vourganti, S (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 1W-5940,10 Ctr Dr, Bethesda, MD 20892 USA. OI Agarwal, Piyush/0000-0002-6042-6834 NR 16 TC 10 Z9 10 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2013 VL 4 IS 4 BP 336 EP 342 DI 10.7150/jca.6215 PG 7 WC Oncology SC Oncology GA 206XI UT WOS:000323558900001 PM 23678370 ER PT J AU Elshaer, SL Abdelsaid, MA Al-Azayzih, A Kumar, P Matragoon, S Nussbaum, JJ El-Remessy, AB AF Elshaer, Sally L. Abdelsaid, Mohammed A. Al-Azayzih, Ahmad Kumar, Parag Matragoon, Suraporn Nussbaum, Julian J. El-Remessy, Azza B. TI Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic Retinopathy SO JOURNAL OF DIABETES RESEARCH LA English DT Article ID P75 NEUROTROPHIN RECEPTOR; ENDOTHELIAL-CELLS; FACTOR BDNF; FACTOR NGF; IN-VITRO; NERVE; P75(NTR); APOPTOSIS; TISSUE; DEATH AB Proliferative diabetic retinopathy (PDR) is the leading cause of blindness in working age Americans. We demonstrated that diabetes disturbs the homeostasis of nerve growth factor (NGF) resulting in accumulation of its precursor proNGF. Increases in proNGF were positively correlated with progression of diabetic retinopathy, having the highest level in ocular fluids from PDR patients compared to nondiabetic patients. Here, we attempted to evaluate the contribution and the possible mechanism of proNGF to PDR. The angiogenic response of aqueous humor samples from PDR patients was examined in human retinal endothelial cells in the presence or absence of anti-proNGF antibody. Additional cultures were treated with mutant-proNGF in the presence of specific pharmacological inhibitors of TrkA and p75(NTR) receptors. PDR-aqueous humor samples exerted significant angiogenic response including cell proliferation, migration, and alignment into tube-like structures. These effects were significantly reduced by anti-proNGF antibody but not by IgG. Treatment of retinal endothelial cells with mutant-proNGF activated phosphorylation of TrkA and p38MAPK; however, it did not alter p75(NTR) expression. Inhibition of TrkA but not p75(NTR) significantly reduced mutant-proNGF-induced cell proliferation, cell migration, and tube formation. Taken together, these results provide evidence that proNGF can contribute to PDR at least in part via activation of TrkA. C1 [Elshaer, Sally L.; Abdelsaid, Mohammed A.; Al-Azayzih, Ahmad; Kumar, Parag; Matragoon, Suraporn; Nussbaum, Julian J.; El-Remessy, Azza B.] Univ Georgia, Ctr Pharm & Expt Therapeut, Augusta, GA 30912 USA. [Elshaer, Sally L.; Abdelsaid, Mohammed A.; Matragoon, Suraporn; Nussbaum, Julian J.; El-Remessy, Azza B.] Univ Georgia, Culver Vis Discovery Inst, Augusta, GA 30912 USA. [Elshaer, Sally L.; Abdelsaid, Mohammed A.; Al-Azayzih, Ahmad; Matragoon, Suraporn; El-Remessy, Azza B.] Charlie Norwood VA Med Ctr, Augusta, GA 30912 USA. [Abdelsaid, Mohammed A.] Georgia Reagents Univ, Dept Physiol, Bethesda, MD 20892 USA. [Kumar, Parag] Natl Inst Hlth Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. RP El-Remessy, AB (reprint author), Univ Georgia, Ctr Pharm & Expt Therapeut, 1120 15th St HM-1200, Augusta, GA 30912 USA. EM aelremessy@gru.edu OI Kumar, Parag/0000-0003-2757-8649 FU National Eye Institute [RO-1EY-022408]; JDRF [2-2008-149]; Vision Discovery Institute; American Heart Association; Egyptian Cultural and Education Bureau FX This work was supported by grants from the National Eye Institute (RO-1EY-022408), JDRF (2-2008-149), and Vision Discovery Institute to Azza B. El-Remessy, pre-doctoral fellowship from American Heart Association for Mohammed A. Abdelsaid and a scholarship from Egyptian Cultural and Education Bureau to Sally L. Elshaer. NR 58 TC 4 Z9 4 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6745 J9 J DIABETES RES JI J. Diabetes Res. PY 2013 AR 432659 DI 10.1155/2013/432659 PG 10 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA 205KI UT WOS:000323442700001 ER PT S AU Bryant, B Sari-Sarraf, H Wachtel, M Long, R Antani, S AF Bryant, Benjamin Sari-Sarraf, Hamed Wachtel, Mitchell Long, Rodney Antani, Sameer BE Gurcan, MN Madabhushi, A TI Fast GPU-based segmentation of H&E stained Squamous Epithelium from Multi-Gigapixel Tiled Virtual Slides SO MEDICAL IMAGING 2013: DIGITAL PATHOLOGY SE Proceedings of SPIE LA English DT Proceedings Paper CT 9th Conference on Digital Pathology at the SPIE Medical Imaging Symposium CY FEB 10-11, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE CIN; segmentation; GPU; CUDA; SVM AB The processing of multi-gigapixel virtual histology slides presents a computationally intensive and time consuming task. Common tiled TIFF slide formats, such as those used by Aperio [1], contain inherent header information that can be used to rapidly locate tissue regions for cervical intraepithelial neoplasia (CIN) diagnosis. Tiles used in these formats are individually compressed subsections of the virtual slide, whose compression ratio varies based on their individual content. This paper discusses a method that exploits this information to rapidly identify regions of interest in an iterative process to locate epithelial tissue. These regions are decompressed using a multi-core CPU, from which a Compute Unified Device Architecture (CUDA) enabled GPU rapidly generates features and Support Vector Machine (SVM) decisions. SVM classifier results are used in a post-processing scheme to remove apparently spurious misclassifications. The mean overall execution time when using a high-end desktop PC, together with a GTX 560 GPU, is roughly 3 seconds per gigapixel, while maintaining the area under an ROC curve above 0.9 when classifying squamous epithelium versus other tissues. C1 [Bryant, Benjamin; Sari-Sarraf, Hamed] Texas Tech Univ, Appl Vis Lab, Box 43102, Lubbock, TX 79409 USA. [Long, Rodney; Antani, Sameer] Natl Lib Med, Bethesda, MD 20894 USA. RP Bryant, B (reprint author), Texas Tech Univ, Appl Vis Lab, Box 43102, Lubbock, TX 79409 USA. OI Antani, Sameer/0000-0002-0040-1387 FU National Institutes of Health (NIH); National Library of Medicine (NLM); Lister Hill National Center for Biomedical Communications (LHNCBC) FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Library of Medicine (NLM), and Lister Hill National Center for Biomedical Communications (LHNCBC). NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9450-4 J9 PROC SPIE PY 2013 VL 8676 AR 86760X DI 10.1117/12.2007800 PG 10 WC Optics; Pathology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Pathology; Radiology, Nuclear Medicine & Medical Imaging GA BGH42 UT WOS:000322982800033 ER PT S AU Rosebrock, A Caban, JJ Figueroa, J Gierach, G Linville, L Hewitt, S Sherman, M AF Rosebrock, Adrian Caban, Jesus J. Figueroa, Jonine Gierach, Gretchen Linville, Laura Hewitt, Stephen Sherman, Mark BE Gurcan, MN Madabhushi, A TI Quantitative Analysis of TDLUs using Adaptive Morphological Shape Techniques SO MEDICAL IMAGING 2013: DIGITAL PATHOLOGY SE Proceedings of SPIE LA English DT Proceedings Paper CT 9th Conference on Digital Pathology at the SPIE Medical Imaging Symposium CY FEB 10-11, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE image processing; adaptive morphological shape; TDLU detection; acinidetection; clustering; breast cancer AB Within the complex branching system of the breast, terminal duct lobular units (TDLUs) are the anatomical location where most cancer originates. With aging, TDLUs undergo physiological involution, reflected in a loss of structural components (acini) and a reduction in total number. Data suggest that women undergoing benign breast biopsies that do not show age appropriate involution are at increased risk of developing breast cancer. To date, TDLU assessments have generally been made by qualitative visual assessment, rather by objective quantitative analysis. This paper introduces a technique to automatically estimate a set of quantitative measurements and use those variables to more objectively describe and classify TDLUs. To validate the accuracy of our system, we compared the computer-based morphological properties of 51 TDLUs in breast tissues donated for research by volunteers in the Susan G. Komen Tissue Bank and compared results to those of a pathologist, demonstrating 70% agreement. Secondly, in order to show that our method is applicable to a wider range of datasets, we analyzed 52 TDLUs from biopsies performed for clinical indications in the National Cancer Institute Breast Radiology and Study of Tissues (BREAST) STAMP project and obtained 82% correlation with visual assessment. Lastly, we demonstrate the ability to uncover novel measures when researching the structural properties of the acini by applying machine learning and clustering techniques. Through our study we found that while the number of acini per TDLU increase exponentially with the TDLU diameter, the average elongation and roundness remain constant. C1 [Rosebrock, Adrian] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. [Caban, Jesus J.] Natl Intrepid Ctr Excellence, Naval Med Ctr, Bethesda, MD 20889 USA. [Figueroa, Jonine; Gierach, Gretchen; Linville, Laura; Sherman, Mark] NCI, NIH, DCEG, Bethesda, MD 20892 USA. [Hewitt, Stephen; Sherman, Mark] NCI, NIH, AMPL, Bethesda, MD 20892 USA. RP Rosebrock, A (reprint author), Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. RI Gierach, Gretchen/E-1817-2016; OI Gierach, Gretchen/0000-0002-0165-5522; Hewitt, Stephen/0000-0001-8283-1788 FU U.S. National Cancer Institute FX This work was supported in part by the Intramural Research Program of the U.S. National Cancer Institute. NR 6 TC 4 Z9 4 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9450-4 J9 PROC SPIE PY 2013 VL 8676 AR 86760N DI 10.1117/12.2006619 PG 6 WC Optics; Pathology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Pathology; Radiology, Nuclear Medicine & Medical Imaging GA BGH42 UT WOS:000322982800023 ER PT S AU Cheng, R Turkbey, B Senseney, J Bernardo, M Bokinsky, A Gandler, W McCreedy, E Pohida, T Choyke, P McAuliffe, MJ AF Cheng, Ruida Turkbey, Baris Senseney, Justin Bernardo, Marcelino Bokinsky, Alexandra Gandler, William McCreedy, Evan Pohida, Thomas Choyke, Peter McAuliffe, Matthew J. BE Ourselin, S Haynor, DR TI 2D Registration Guided Models for Semi-automatic MRI Prostate Segmentation SO MEDICAL IMAGING 2013: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 10-12, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Segmentation; Registration; Prostate; MRI; Concurrency; MIPAV ID IMAGES; ATLAS AB Accurate segmentation of prostate magnetic resonance images (MRI) is a challenging task due to the variable anatomical structure of the prostate. In this work, two semi-automatic techniques for segmentation of T-2-weighted MRI images of the prostate are presented. Both models are based on 2D registration that changes shape to fit the prostate boundary between adjacent slices. The first model relies entirely on registration to segment the prostate. The second model applies Fuzzy-C means and morphology filters on top of the registration in order to refine the prostate boundary. Key to the success of the two models is the careful initialization of the prostate contours, which requires specifying three Volume of Interest (VOI) contours to each axial, sagittal and coronal image. Then, a fully automatic segmentation algorithm generates the final results with the three images. The algorithm performance is evaluated with 45 MR image datasets. VOI volume, 3D surface volume and VOI boundary masks are used to quantify the segmentation accuracy between the semi-automatic and expert manual segmentations. Both models achieve an average segmentation accuracy of 90%. The proposed registration guided segmentation model has been generalized to segment a wide range of T-2-weighted MRI prostate images. C1 [Cheng, Ruida; Senseney, Justin; Gandler, William; McCreedy, Evan; Pohida, Thomas; McAuliffe, Matthew J.] NIH, Image Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Cheng, R (reprint author), NIH, Image Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 2 Z9 2 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9443-6 J9 PROC SPIE PY 2013 VL 8669 AR 86692V DI 10.1117/12.2006225 PG 10 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGA04 UT WOS:000322020600099 ER PT S AU Liu, YX Liu, ST Lardo, AC Schuleri, K Nacif, MS Bluemke, DA Summers, RM Yao, JH AF Liu, Yixun Liu, Songtao Lardo, Albert C. Schuleri, Karl Nacif, Marcelo Souto Bluemke, David A. Summers, Ronald M. Yao, Jianhua BE Ourselin, S Haynor, DR TI Build 4-Dimensional Myocardial Model for Dynamic CT Images SO MEDICAL IMAGING 2013: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Processing CY FEB 10-12, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE 4D myocardial model; Finite Element Method; linear elastic membrane; dynamic CT; surface tracking ID SEGMENTATION; REGISTRATION; MRI AB 4D (3D + time) model is valuable in comprehensive assessment of cardiac functions. Usually, the generation of the 4D myocardial models involves myocardium segmentation, mesh generation and non-rigid registration (to build mesh node correspondence). In this paper, we present a method to simultaneously perform the above tasks. This method begins from a triangular surface model of the myocardium at the first phase of a cardiac cycle. Then, the myocardial surface is simulated as a linear elastic membrane, and evolves toward the next phase governed by an energy function while maintaining the mesh quality. Our preliminary experiments performed on dynamic CT images of the dog demonstrated the effectiveness of this method on both segmentation and mesh generation. The minimum average surface distance between the segmentation results of the proposed method and the ground truth can reach 0.72 +/- 0.55 mm, and the mesh quality measured by the aspect ratio of the triangle was less than 11.57 +/- 1.18. C1 [Liu, Yixun; Liu, Songtao; Lardo, Albert C.; Schuleri, Karl; Nacif, Marcelo Souto; Bluemke, David A.; Summers, Ronald M.; Yao, Jianhua] NIH, Bethesda, MD USA. RP Yao, JH (reprint author), NIH, Bethesda, MD USA. EM JYao@cc.nih.gov OI Bluemke, David/0000-0002-8323-8086 NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9443-6 J9 PROC SPIE PY 2013 VL 8669 AR 86691Q DI 10.1117/12.2007070 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGA04 UT WOS:000322020600060 ER PT J AU Willis, G Boeije, H AF Willis, Gordon Boeije, Hennie TI The Survey Field Needs a Framework for the Systematic Reporting of Questionnaire Development and Pretesting SO METHODOLOGY-EUROPEAN JOURNAL OF RESEARCH METHODS FOR THE BEHAVIORAL AND SOCIAL SCIENCES LA English DT Editorial Material C1 [Willis, Gordon] NCI, NIH, Bethesda, MD 20892 USA. [Boeije, Hennie] Univ Utrecht, Fac Social & Behav Sci, Dept Methodol & Stat, NL-3508 TC Utrecht, Netherlands. RP Willis, G (reprint author), NCI, 6130 Execut Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA. EM willisg@mail.nih.gov NR 0 TC 1 Z9 1 U1 3 U2 5 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 1614-1881 J9 METHODOLOGY-EUR JI Methodology PY 2013 VL 9 IS 3 BP 85 EP 86 DI 10.1027/1614-2241/a000070 PG 2 WC Social Sciences, Mathematical Methods; Psychology, Mathematical SC Mathematical Methods In Social Sciences; Psychology GA 200GY UT WOS:000323057300001 ER PT J AU Boeije, H Willis, G AF Boeije, Hennie Willis, Gordon TI The Cognitive Interviewing Reporting Framework (CIRF) Towards the Harmonization of Cognitive Testing Reports SO METHODOLOGY-EUROPEAN JOURNAL OF RESEARCH METHODS FOR THE BEHAVIORAL AND SOCIAL SCIENCES LA English DT Article DE cognitive interviewing; comparative effectiveness; questionnaire pretesting; standard report format; survey research; checklist AB Cognitive interviewing is an important qualitative tool for the testing, development, and evaluation of survey questionnaires. Despite the widespread adoption of cognitive testing, there remain large variations in the manner in which specific procedures are implemented, and it is not clear from reports and publications that have utilized cognitive interviewing exactly what procedures have been used, as critical details are often missing. Especially for establishing the effectiveness of procedural variants, it is essential that cognitive interviewing reports contain a comprehensive description of the methods used. One approach to working toward more complete reporting would be to develop and adhere to a common framework for reporting these results. In this article we introduce the Cognitive Interviewing Reporting Framework (CIRF), which applies a checklist approach, and which is based on several existing checklists for reviewing and reporting qualitative research. We propose that researchers apply the CIRF in order to test its usability and to suggest potential adjustments. Over the longer term, the CIRF can be evaluated with respect to its utility in improving the quality of cognitive interviewing reports. C1 [Boeije, Hennie] Univ Utrecht, Fac Social & Behav Sci, Dept Methodol & Stat, NL-3508 TC Utrecht, Netherlands. [Willis, Gordon] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Willis, G (reprint author), NCI, 6130 Execut Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA. EM willisg@mail.nih.gov NR 28 TC 11 Z9 11 U1 3 U2 16 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 1614-1881 J9 METHODOLOGY-EUR JI Methodology PY 2013 VL 9 IS 3 BP 87 EP 95 DI 10.1027/1614-2241/a000075 PG 9 WC Social Sciences, Mathematical Methods; Psychology, Mathematical SC Mathematical Methods In Social Sciences; Psychology GA 200GY UT WOS:000323057300002 ER PT J AU Willis, G Boeije, H AF Willis, Gordon Boeije, Hennie TI Reflections on the Cognitive Interviewing Reporting Framework Efficacy, Expectations, and Promise for the Future SO METHODOLOGY-EUROPEAN JOURNAL OF RESEARCH METHODS FOR THE BEHAVIORAL AND SOCIAL SCIENCES LA English DT Article DE cognitive interviewing; CIRF; qualitative methods; report-writing standards AB Based on the experiences of three research groups using and evaluating the Cognitive Interviewing Reporting Framework (CIRF), we draw conclusions about the utility of the CIRF as a guide to creating cognitive testing reports. Authors generally found the CIRF checklist to be usable, and that it led to a more complete description of key steps involved. However, despite the explicit direction by the CIRF to include a full explanation of major steps and features (e. g., research objectives and research design), the three cognitive testing reports tended to simply state what was done, without further justification. Authors varied in their judgments concerning whether the CIRF requires the appropriate level of detail. Overall, we believe that current cognitive interviewing practice will benefit from including, within cognitive testing reports, the 10 categories of information specified by the CIRF. Future use of the CIRF may serve to direct the overall research project from the start, and to further the goal of evaluation of specific cognitive interviewing procedures. C1 [Willis, Gordon] NCI, NIH, Bethesda, MD 20892 USA. [Boeije, Hennie] Univ Utrecht, Fac Social & Behav Sci, Dept Methodol & Stat, NL-3508 TC Utrecht, Netherlands. RP Willis, G (reprint author), NCI, 6130 Execut Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA. EM willisg@mail.nih.gov NR 8 TC 1 Z9 1 U1 2 U2 9 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 1614-1881 J9 METHODOLOGY-EUR JI Methodology PY 2013 VL 9 IS 3 BP 123 EP 128 DI 10.1027/1614-2241/a000074 PG 6 WC Social Sciences, Mathematical Methods; Psychology, Mathematical SC Mathematical Methods In Social Sciences; Psychology GA 200GY UT WOS:000323057300006 ER PT S AU Clements, IP Gnade, AG Rush, AD Patten, CD Twomey, MC Kravitz, AV AF Clements, Isaac P. Gnade, Andrew G. Rush, Alexander D. Patten, Craig D. Twomey, Mark C. Kravitz, Alexxai V. BE Mohanty, SK Thakor, NV TI Miniaturized LED sources for in vivo optogenetic experimentation SO OPTOGENETICS: OPTICAL METHODS FOR CELLULAR CONTROL SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optogenetics - Optical Methods for Cellular Control CY FEB 02-03, 2013 CL San Francisco, CA SP SPIE, Plexon Inc DE optogenetics; LED; commutator; miniaturized; optrode; in vivo; fiber optic rotary joint ID NEURAL CIRCUITRY; PERFORMANCE; NEURONS AB Recently developed optogenetics techniques have enabled researchers to modulate the activity of specific cell types. As a result, complex neural pathways previously regarded as black boxes can now be directly probed, yielding a steadily increasing understanding of the basic neural circuits that underlie health and disease. For in vivo experimentation, fiber-coupled lasers have traditionally been used to illuminate internal brain regions, via an optical fiber that penetrates through overlying tissue. Though able to deliver intense fiber-coupled light, lasers are costly, bulky, and face limitations in output beam stability and temporal precision during modulated outputs. For experiments on unrestricted, behaving animals, a laser-based system also necessitates the use of fiber optic rotary joints, which come with costs and limitations of their own. Here, we report and characterize an alternative light delivery solution, based on high intensity fiber-coupled LEDs that are miniaturized for placement on the end of custom electrical commutators. This design allows for enhanced control of output light and expanded capabilities for optical stimulation as well as simultaneous electrical neural recordings, as with an optrode array. Temporal response of light outputs and light stability during commutator rotation were assessed. The influence of high current optical control signals on adjacent neural recording channels was also explored. To validate the function of this LED based system in in vivo recording scenarios, chronic stimulation experiments were performed. C1 [Clements, Isaac P.; Gnade, Andrew G.; Rush, Alexander D.; Patten, Craig D.; Twomey, Mark C.] Plexon Inc, 6500 Greenville Ave Ste 730, Dallas, TX 75206 USA. [Kravitz, Alexxai V.] NIDDK, Natl Inst Hlth, Bethesda, MD 20914 USA. RP Clements, IP (reprint author), Plexon Inc, 6500 Greenville Ave Ste 730, Dallas, TX 75206 USA. NR 12 TC 0 Z9 0 U1 0 U2 8 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9355-2 J9 PROC SPIE PY 2013 VL 8586 AR 85860X DI 10.1117/12.2008080 PG 9 WC Genetics & Heredity; Optics SC Genetics & Heredity; Optics GA BGG91 UT WOS:000322901400016 ER PT S AU Mays, JW Ambatipudi, KS Bassim, CW Melvin, JE AF Mays, Jacqueline W. Ambatipudi, Kiran S. Bassim, Carol W. Melvin, James E. BE Southern, SO TI Emerging technologies for oral diagnostics: lessons from chronic graft-versus-host disease SO SENSING TECHNOLOGIES FOR GLOBAL HEALTH, MILITARY MEDICINE, AND ENVIRONMENTAL MONITORING III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Sensing Technologies for Global Health, Military Medicine, and Environmental Monitoring III CY APR 29-MAY 01, 2013 CL Baltimore, MD SP SPIE DE Saliva; oral disease; salivary gland; mass spectrometry; Graft-versus-Host Disease ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; SJOGRENS-SYNDROME; CLINICAL-TRIALS; BIOMARKERS; CRITERIA; THERAPY AB Saliva is a protein-rich oral fluid that contains information about systemic and oral-specific disease pathogenesis and diagnosis. Technologies are emerging to improve detection of protein components of human saliva for use not only in biomarker discovery, but also for the illumination of pathways involved in oral disease. These include the optimization of liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis of saliva in health and disease. Downstream of saliva component identification and validation comes the complex task of connecting salivary proteomic data to biological function, disease state, and other clinical patient information in a meaningful way. Augmentation of database information with biological expertise is crucial for effective analysis of potential biomarkers and disease pathways in order to improve diagnosis and identify putative therapeutic targets. This presentation will use LC-MS/MS analysis of saliva from chronic Graft-versus-Host disease (cGVHD) patients to illustrate these principles, and includes a discussion of the complex clinical and diagnostic issues related to proteomics and biomarker research in cGVHD. C1 [Mays, Jacqueline W.; Bassim, Carol W.; Melvin, James E.] Natl Inst Dent & Craniofacial Res, Dental Clin Res Core, NIH, Bethesda, MD 20892 USA. RP Mays, JW (reprint author), Natl Inst Dent & Craniofacial Res, Dental Clin Res Core, NIH, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9514-3 J9 PROC SPIE PY 2013 VL 8723 AR 87230F DI 10.1117/12.2020014 PG 7 WC Remote Sensing; Optics SC Remote Sensing; Optics GA BGL64 UT WOS:000323425300005 ER PT J AU Bates, ST Ahrendt, S Bik, HM Bruns, TD Caporaso, JG Cole, J Dwan, M Fierer, N Gu, D Houston, S Knight, R Leff, J Lewis, C Maestre, JP McDonald, D Nilsson, RH Porras-Alfaro, A Robert, V Schoch, C Scott, J Taylor, DL Parfrey, LW Stajich, JE AF Bates, Scott T. Ahrendt, Steven Bik, Holly M. Bruns, Thomas D. Caporaso, J. Gregory Cole, James Dwan, Michael Fierer, Noah Gu, Dai Houston, Shawn Knight, Rob Leff, Jon Lewis, Christopher Maestre, Juan P. McDonald, Daniel Nilsson, R. Henrik Porras-Alfaro, Andrea Robert, Vincent Schoch, Conrad Scott, James Taylor, D. Lee Parfrey, Laura Wegener Stajich, Jason E. TI Meeting Report: Fungal ITS Workshop (October 2012) SO STANDARDS IN GENOMIC SCIENCES LA English DT Article ID DATABASE; CLASSIFICATION; SEQUENCES C1 [Bates, Scott T.; Fierer, Noah; Leff, Jon] Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA. [Ahrendt, Steven; Gu, Dai; Stajich, Jason E.] Univ Calif Riverside, Dept Plant Pathol & Microbiol, Riverside, CA 92521 USA. [Bik, Holly M.] Univ Calif Davis, UC Davis Genome Ctr, Davis, CA 95616 USA. [Bruns, Thomas D.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. [Caporaso, J. Gregory] No Arizona Univ, Dept Comp Sci, Flagstaff, AZ 86011 USA. [Caporaso, J. Gregory] Argonne Natl Labs, Argonne, IL USA. [Cole, James] Michigan State Univ, Dept Microbiol & Mol Genetet, E Lansing, MI 48824 USA. [Dwan, Michael] TGen North, Ctr Microbi & Human Hlth, Flagstaff, AZ USA. [Houston, Shawn] Univ Minnesota, Minnesota Supercomp Inst, Minneapolis, MN USA. [Knight, Rob; McDonald, Daniel] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Knight, Rob; Parfrey, Laura Wegener] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. [Lewis, Christopher] Agr & Agri Food Canada, Eastern Cereals & Oilseed Res Ctr, Ottawa, ON, Canada. [Maestre, Juan P.] Univ Texas Austin, Dept Civil Architecture & Environm Engn, Austin, TX 78712 USA. [McDonald, Daniel] Univ Colorado, Biofrontiers Inst, Boulder, CO 80309 USA. [Nilsson, R. Henrik] Univ Gothenburg, Dept Biol & Environm Sci, Gothenburg, Sweden. [Porras-Alfaro, Andrea] Western Illinois Univ, Dept Biol Sci, Macomb, IL 61455 USA. [Robert, Vincent] Royal Netherlands Acad Arts & Sci, Cent Bureau Schimmelcultures, Utrecht, Netherlands. [Schoch, Conrad] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Scott, James] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Occupat & Environm Hlth, Toronto, ON, Canada. [Taylor, D. Lee] Univ Alaska, Inst Arctic Biol, Fairbanks, AK 99775 USA. RP Bates, ST (reprint author), Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA. RI Scott, James/A-8598-2011; Stajich, Jason/C-7297-2008; Knight, Rob/D-1299-2010; OI Scott, James/0000-0002-5073-0832; Stajich, Jason/0000-0002-7591-0020; Taylor, Donald/0000-0002-5985-9210; Porras-Alfaro, Andrea/0000-0002-9053-7973; Nilsson, Henrik/0000-0002-8052-0107 FU Paula Olsiewski; Alfred P. Sloan Foundation FX The workshop would not have been possible without the intellectual and financial support of Paula Olsiewski and the Alfred P. Sloan Foundation. We thank Jason Stajich, for organizing the meeting, as well as all the workshop participants for their valuable contributions. NR 17 TC 12 Z9 12 U1 0 U2 13 PU GENOMIC STAND CONSORT PI EAST LANSING PA MICHIGAN STATE UNIV, GEEO GARRITY, DEPT MICROBIOL, 6162 BIOMED & PHYS SCI BLDG, EAST LANSING, MI 48824 USA SN 1944-3277 J9 STAND GENOMIC SCI JI Stand. Genomic Sci. PY 2013 VL 8 IS 1 BP 118 EP 123 PG 6 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 203WP UT WOS:000323325500011 PM 23961317 ER PT J AU Saldutti, LP Beyer, BK Breslin, W Brown, TR Chapin, RE Campion, S Enright, B Faustman, E Foster, PMD Hartung, T Kelce, W Kim, JH Loboa, EG Piersma, AH Seyler, D Turner, KJ Yu, H Yu, XZ Sasaki, JC AF Saldutti, Louise Parks Beyer, Bruce K. Breslin, William Brown, Terry R. Chapin, Robert E. Campion, Sarah Enright, Brian Faustman, Elaine Foster, Paul M. D. Hartung, Thomas Kelce, William Kim, James H. Loboa, Elizabeth G. Piersma, Aldert H. Seyler, David Turner, Katie J. Yu, Hanry Yu, Xiaozhong Sasaki, Jennifer C. TI In Vitro Testicular Toxicity Models: Opportunities for Advancement via Biomedical Engineering Techniques SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE testicular toxicity; bioengineering; biomedical engineering; in vitro screening ID RAT SEMINIFEROUS TUBULES; MALE REPRODUCTIVE TOXICITY; SERTOLI-CELL FUNCTIONS; TRANSEPITHELIAL ELECTRICAL-RESISTANCE; ETHYLENE-GLYCOL MONOMETHYL; ORTHO-CRESYL PHOSPHATE; AGAR-CULTURE-SYSTEM; MALE GERM-CELLS; LEYDIG-CELLS; EXTRACELLULAR-MATRIX AB To address the pressing need for better in vitro testicular toxicity models, a workshop sponsored by the International Life Sciences Institute (ILSI), the Health and Environmental Science Institute (HESI), and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), was held at the Mt. Washington Conference Center in Baltimore, MD, USA on October 26-27, 2011. At this workshop, experts in testis physiology, toxicology, and tissue engineering discussed approaches for creating improved in vitro environments that would be more conducive to maintaining spermatogenesis and steroidogenesis and could provide more predictive models for testicular toxicity testing. This workshop report is intended to provide scientists with a broad overview of relevant testicular toxicity literature and to suggest opportunities where bioengineering principles and techniques could be used to build improved in vitro testicular models for safety evaluation. Tissue engineering techniques could, conceivably, be immediately implemented to improve existing models. However, it is likely that in vitro testis models that use single or multiple cell types will be needed to address such endpoints as accurate prediction of chemically induced testicular toxicity in humans, elucidation of mechanisms of toxicity, and identification of possible biomarkers of testicular toxicity. C1 [Saldutti, Louise Parks] Merck & Co Inc, Dept Dev & Reprod, West Point, PA USA. [Beyer, Bruce K.] Sanofi US Inc, Dept Disposit Safety & Anim Res Preclin Safety, Bridgewater, MA USA. [Breslin, William; Seyler, David] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Brown, Terry R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD USA. [Chapin, Robert E.; Campion, Sarah] Pfizer Inc, Global R&D, Dev & Reprod Toxicol Grp, Groton, CT USA. [Enright, Brian] AbbVie Inc, N Chicago, IL USA. [Faustman, Elaine] Univ Washington, Inst Risk Anal & Risk Commun, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Foster, Paul M. D.] NIEHS, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Hartung, Thomas] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, Baltimore, MD USA. [Hartung, Thomas] Univ Konstanz, Constance, Germany. [Kelce, William] Leading Edge PharmTox LLC, Durham, NC USA. [Kim, James H.] ILSI Hlth & Environm Sci Inst, Washington, DC USA. [Loboa, Elizabeth G.] Loboa UNC, Chapel Hill, NC USA. [Loboa, Elizabeth G.] N Carolina State Univ, Raleigh, NC 27695 USA. [Piersma, Aldert H.] RIVM, Ctr Hlth Protect, Bilthoven, Netherlands. [Piersma, Aldert H.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Turner, Katie J.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Yu, Hanry] Natl Univ Singapore, Physiol & Mechanobiol Inst, Singapore 117548, Singapore. [Yu, Hanry] ASTAR, Inst Bioengn & Nanotechnol, Singapore, Singapore. [Yu, Hanry] MIT, Cambridge, MA 02139 USA. [Yu, Xiaozhong] Univ Washington, Seattle, WA 98195 USA. [Sasaki, Jennifer C.] AstraZeneca, Global Safety Assessment, Waltham, MA USA. RP Saldutti, LP (reprint author), Merck & Co Inc, WP-45-119, West Point, PA USA. EM louise.saldutti@merck.com RI Yu, Hanry/C-1031-2013 OI Yu, Hanry/0000-0002-0339-3685 FU Doerenkamp-Zbinden Foundation FX a report of t4 - the transatlantic think tank for toxicology, a collaboration of the toxicologically oriented chairs in Baltimore, Konstanz, and Utrecht, sponsored by the Doerenkamp-Zbinden Foundation. The opinions expressed in this report are those of the participants as individuals and do not necessarily reflect the opinions of the organizations they are affiliated with; participants do not necessarily endorse all recommendations made. NR 223 TC 7 Z9 7 U1 0 U2 7 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2013 VL 30 IS 3 BP 353 EP 377 PG 25 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 197OR UT WOS:000322861000008 ER PT J AU Yang, CZ Huntoon, K Ksendzovsky, A Zhuang, ZP Lonser, RR AF Yang, Chunzhang Huntoon, Kristin Ksendzovsky, Alexander Zhuang, Zhengping Lonser, Russell R. TI Proteostasis Modulators Prolong Missense VHL Protein Activity and Halt Tumor Progression SO CELL REPORTS LA English DT Article ID HIPPEL-LINDAU-DISEASE; RENAL-CELL CARCINOMA; HYPOXIA-INDUCIBLE FACTORS; SUPPRESSOR GENE; GERMLINE MUTATIONS; UP-REGULATION; HEMANGIOBLASTOMAS; UBIQUITINATION; CHAPERONIN; INHIBITORS AB Although missense mutations of the von Hippel-Lindau disease (VHL) gene are the most common germline mutation underlying this heritable cancer syndrome, the mechanism of tumorigenesis is unknown. We found a quantitative reduction of missense mutant VHL protein (pVHL) in tumors associated with physiologic mRNA expression. Although mutant pVHL is unstable and degraded contemporarily with translation, it retains its E3 ligase function, including hypoxia-inducible factor degradation. The premature pVHL degradation is due to misfolding and imbalance of chaperonin binding. Histone deacetylase inhibitors (HDACIs) can modulate this pathway by inhibiting the HDAC-Hsp90 chaperone axis, stabilizing pVHL, and restoring activity comparable to wild-type protein, both in vitro and in animal models. Furthermore, HDACI-mediated stabilization of missense pVHL significantly attenuates the growth of 786-O rodent tumor model. These findings provide direct biological insight into VHL-associated tumors and elucidate a treatment paradigm for VHL. C1 [Yang, Chunzhang; Huntoon, Kristin; Ksendzovsky, Alexander; Zhuang, Zhengping; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), Ohio State Univ, Dept Neurol Surg, 410 West 10th Ave,N1047 Doan Hall, Columbus, OH 43210 USA. EM lonserr@ninds.nih.gov FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS) FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS) and a cooperative research and development agreement between NINDS and Lixte Biotechnology Holdings, Inc. NR 40 TC 16 Z9 16 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD JAN PY 2013 VL 3 IS 1 BP 52 EP 59 DI 10.1016/j.celrep.2012.12.007 PG 8 WC Cell Biology SC Cell Biology GA 184LO UT WOS:000321891400008 PM 23318261 ER PT J AU Yamane, A Robbiani, DF Resch, W Bothmer, A Nakahashi, H Oliveira, T Rommel, PC Brown, EJ Nussenzweig, A Nussenzweig, MC Casellas, R AF Yamane, Arito Robbiani, Davide F. Resch, Wolfgang Bothmer, Anne Nakahashi, Hirotaka Oliveira, Thiago Rommel, Philipp C. Brown, Eric J. Nussenzweig, Andre Nussenzweig, Michel C. Casellas, Rafael TI RPA Accumulation during Class Switch Recombination Represents 5 '-3 ' DNA-End Resection during the S-G2/M Phase of the Cell Cycle SO CELL REPORTS LA English DT Article ID REPLICATION PROTEIN-A; INDUCED CYTIDINE DEAMINASE; DOUBLE-STRAND BREAKS; RNA-POLYMERASE-II; SOMATIC HYPERMUTATION; CHROMOSOMAL TRANSLOCATIONS; V(D)J RECOMBINATION; B-CELLS; MISMATCH REPAIR; HOMOLOGOUS RECOMBINATION AB Activation-induced cytidine deaminase (AID) promotes chromosomal translocations by inducing DNA double-strand breaks (DSBs) at immunoglobulin (Ig) genes and oncogenes in the G1 phase. RPA is a single-stranded DNA (ssDNA)-binding protein that associates with resected DSBs in the S phase and facilitates the assembly of factors involved in homologous repair (HR), such as Rad51. Notably, RPA deposition also marks sites of AID-mediated damage, but its role in Ig gene recombination remains unclear. Here, we demonstrate that RPA associates asymmetrically with resected ssDNA in response to lesions created by AID, recombination-activating genes (RAG), or other nucleases. Small amounts of RPA are deposited at AID targets in G1 in an ATM-dependent manner. In contrast, recruitment in the S-G2/M phase is extensive, ATM independent, and associated with Rad51 accumulation. In the S-G2/M phase, RPA increases in nonhomologous-end-joining-deficient lymphocytes, where there is more extensive DNA-end resection. Thus, most RPA recruitment during class switch recombination represents salvage of unrepaired breaks by homology-based pathways during the S-G2/M phase of the cell cycle. C1 [Casellas, Rafael] NIH, NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Nussenzweig, Andre] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Brown, Eric J.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Brown, Eric J.] Univ Penn, Dept Canc Biol, Philadelphia, PA 19104 USA. [Nussenzweig, Andre] NIH, NCI, Lab Genome Integr, Bethesda, MD 20892 USA. RP Nussenzweig, MC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Genet Program, Boston, MA 02215 USA. EM nussen@rockefeller.edu; casellar@mail.nih.gov OI Rommel, Philipp/0000-0002-9790-4086; Oliveira, Thiago/0000-0002-2654-0879 FU NIAMS at the NIH FX We thank all members of the Casellas and Nussenzweig labs for helpful discussions, Matthias F. Muellenbeck, Jim Simone, Jeff Lay, and Gustavo Gutierrez for technical assistance. The work was supported in part by the intramural program of NIAMS at the NIH. This study utilized the high-performance computational capabilities of the Helix/Biowulf Systems at the National Institutes of Health, Bethesda, MD (http://helix.nih.gov). NR 82 TC 40 Z9 40 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD JAN PY 2013 VL 3 IS 1 BP 138 EP 147 DI 10.1016/j.celrep.2012.12.006 PG 10 WC Cell Biology SC Cell Biology GA 184LO UT WOS:000321891400016 PM 23291097 ER PT S AU Pluta, RM AF Pluta, Ryszard M. BE Zuccarello, M Clark, JF PyneGeithman, G Andaluz, N Hartings, JA Adeoye, OM TI Prolonged Intravenous Infusion of Sodium Nitrite Delivers Nitric Oxide (NO) in Humans SO CEREBRAL VASOSPASM: NEUROVASCULAR EVENTS AFTER SUBARACHNOID HEMORRHAGE SE Acta Neurochirurgica Supplementum LA English DT Proceedings Paper CT 11th International Conference on Cerebral Vasospasm: Neurovascular Events after Subarachnoid Hemorrhage CY JUL 21-23, 2011 CL Cincinnati, OH DE Nitric oxide; Nitrite; Vasospasm; Methemoglobin ID VIVO ISCHEMIA-REPERFUSION; SUBARACHNOID HEMORRHAGE; CEREBRAL VASOSPASM; HUMAN CIRCULATION; PRIMATE MODEL; REVERSAL AB In preclinical studies, infusion of sodium nitrite delivers nitric oxide (NO) as treatment of vasospasm after subarachnoid hemorrhage. We evaluated safety and toxicity of intravenous nitrite administration in healthy volunteers infused with increasing doses of sodium nitrite for 48 h. Twelve volunteers (5 men, 7 women; mean age was 38.8 years, range 27-56 years) participated in the study. The starting sodium nitrite dose was 4.2 mg/kg/h, and it was doubled for each subsequent volunteer up to a maximal dose of 533.8 mg/kg/h at which a clinically silent dose-limiting toxicity (DLT) was observed. Toxicity included a transient decrease of mean arterial blood pressure or asymptomatic increase of methemoglobin level above 5%. The maximal tolerated dose (MTD) was 267 mg/kg/h. S-Nitrosothiols increased significantly in plasma, confirming in vivo sodium nitrite reduction to NO and encouraging its use against vasospasm and ischemia-reperfusion injury to the brain, kidneys, liver, and heart. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA. RP Pluta, RM (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 5512 Pembroke Terrace, Bethesda, MD USA. EM rysiek@ninds.nih.gov FU Intramural NIH HHS NR 10 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-7091-1191-8 J9 ACTA NEUROCHIR SUPPL JI Acta Neurochir. Suppl. PY 2013 VL 115 BP 49 EP 51 DI 10.1007/978-3-7091-1192-5_11 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA BGF56 UT WOS:000322747200011 PM 22890643 ER PT S AU Pluta, RM Skopets, B Kralik, JD AF Pluta, Ryszard M. Skopets, Boris Kralik, Jerald D. BE Zuccarello, M Clark, JF PyneGeithman, G Andaluz, N Hartings, JA Adeoye, OM TI Relevance of Animal Models of Subarachnoid Hemorrhage for Examining Neurobehavioral Changes SO CEREBRAL VASOSPASM: NEUROVASCULAR EVENTS AFTER SUBARACHNOID HEMORRHAGE SE Acta Neurochirurgica Supplementum LA English DT Proceedings Paper CT 11th International Conference on Cerebral Vasospasm: Neurovascular Events after Subarachnoid Hemorrhage CY JUL 21-23, 2011 CL Cincinnati, OH DE SAH; Vasospasm; Animal models; Neurobehavior ID ANTERIOR COMMUNICATING ARTERY; CEREBRAL VASOSPASM; PREFRONTAL CORTEX; INTRACRANIAL ANEURYSM; RHESUS-MONKEYS; MEMORY; RATS; PERFORMANCE; AVOIDANCE; SURGERY AB Background and purpose: For many years survival and neurological functionality of patients were the main outcome measures after treatment of intracranial aneurysms. But, the variable outcomes of patients operated on in a delayed fashion or before the aneurysm rupture indicate that more precise measures are needed for assessment of not only the neurological but also the neuropsychological outcome. However, development and testing of such new tools requires better understanding of pathomechanisms of neurobehavioral changes evoked by aneurysmal subarachnoid hemorrhage (aSAH), which can be achieved using animal models. Methods: We reviewed and selected (1) animal models developed to investigate delayed cerebral vasospasm that could be useful for examining effects of brain injury evoked by aSAH and (2) a battery of neurobehavioral animal testing that can be used for assessment of patients after aSAH. Results: For every species used as an aSAH model, a battery of neurobehavioral test exists. Conclusion: Albeit some limitations must be recognized, research using animal models of SAH should continue to play a critical role in assessment of cognitive and behavioral functions after aSAH. C1 [Pluta, Ryszard M.] NINDS, NIH, Surg Neurol Branch, Bethesda, MD 20817 USA. RP Pluta, RM (reprint author), NINDS, NIH, Surg Neurol Branch, 5512 Pembroke Terrace, Bethesda, MD 20817 USA. EM rysiek@ninds.nih.gov FU Intramural NIH HHS NR 80 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-7091-1191-8 J9 ACTA NEUROCHIR SUPPL JI Acta Neurochir. Suppl. PY 2013 VL 115 BP 225 EP 232 DI 10.1007/978-3-7091-1192-5_41 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA BGF56 UT WOS:000322747200041 PM 22890673 ER PT J AU Humbard, MA Maupin-Furlow, JA AF Humbard, Matthew A. Maupin-Furlow, Julie A. TI Prokaryotic Proteasomes: Nanocompartments of Degradation SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Prokaryotic ubiquitin-like protein; Pupylation; Small archaeal modifier proteins; Sampylation ID UBIQUITIN-LIKE PROTEIN; HALOARCHAEON HALOFERAX-VOLCANII; MYCOBACTERIUM-TUBERCULOSIS PROTEASOME; ARCHAEAL MODIFIER PROTEINS; 20 S PROTEASOMES; THERMOPLASMA-ACIDOPHILUM; ACTIVATING NUCLEOTIDASE; 26S PROTEASOME; AAA-ATPASE; METHANOCALDOCOCCUS-JANNASCHII AB Proteasomes are self-compartmentalized energy-dependent proteolytic machines found in Archaea, Actinobacteria species of bacteria and eukaryotes. Proteasomes consist of two separate protein complexes, the core particle that hydrolyzes peptide bonds and an AAA+ ATPase domain responsible for the binding, unfolding and translocation of protein substrates into the core particle for degradation. Similarly to eukaryotes, proteasomes play a central role in protein degradation and can be essential in Archaea. Core particles associate with and utilize a variety of ATPase complexes to carry out protein degradation in Archaea. In actinobacterial species, such as Mycobacterium tuberculosis, proteasome-mediated degradation is associated with pathogenesis and does not appear to be essential. Interestingly, both actinobacterial species and Archaea use small proteins to covalently modify proteins, prokaryotic ubiquitin-like proteins (Pup) in Actinobacteria and ubiquitin-like small archaeal modifier proteins (SAMP) in Archaea. These modifications may play a role in proteasome targeting similar to the ubiquitin-proteasome system in eukaryotes. Copyright (C) 2013 S. Karger AG, Basel C1 [Humbard, Matthew A.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Maupin-Furlow, Julie A.] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA. RP Maupin-Furlow, JA (reprint author), Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA. EM jmaupin@ufl.edu FU Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., USA; National Institutes of Health [R01 GM57498]; Division of Chemical Sciences, Geosciences and Biosciences, Office of Basic Energy Sciences of the US Department of Energy [DE-FG02-05ER15650] FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., USA to M. A. H. and grants awarded to J.M.-F. through the National Institutes of Health (R01 GM57498) and the Division of Chemical Sciences, Geosciences and Biosciences, Office of Basic Energy Sciences of the US Department of Energy (Grant DE-FG02-05ER15650). NR 119 TC 4 Z9 4 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2013 VL 23 IS 4-5 BP 321 EP 334 DI 10.1159/000351348 PG 14 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 197YL UT WOS:000322888700007 PM 23920495 ER PT J AU Chio, A Logroscino, G Traynor, BJ Collins, J Simeone, JC Goldstein, LA White, LA AF Chio, A. Logroscino, G. Traynor, B. J. Collins, J. Simeone, J. C. Goldstein, L. A. White, L. A. TI Global Epidemiology of Amyotrophic Lateral Sclerosis: A Systematic Review of the Published Literature SO NEUROEPIDEMIOLOGY LA English DT Review DE Amyotrophic lateral sclerosis; Case ascertainment; Demographics; Diagnostic criteria; Epidemiology; Incidence; Prevalence; Temporal and age-related trends ID MOTOR-NEURON DISEASE; CAPTURE-RECAPTURE METHODOLOGY; SOUTH-EAST ENGLAND; HEXANUCLEOTIDE REPEAT; CLINICAL-FEATURES; REGGIO-EMILIA; KII PENINSULA; ALS INCIDENCE; HONG-KONG; POPULATION AB Background: Amyotrophic lateral sclerosis (ALS) is relatively rare, yet the economic and social burden is substantial. Having accurate incidence and prevalence estimates would facilitate efficient allocation of healthcare resources. Objective: To provide a comprehensive and critical review of the epidemiological literature on ALS. Methods: MEDLINE and EMBASE (1995-2011) databases of population-based studies on ALS incidence and prevalence reporting quantitative data were analyzed. Data extracted included study location and time, design and data sources, case ascertainment methods and incidence and/or prevalence rates. Medians and interquartile ranges (IQRs) were calculated, and ALS case estimates were derived using 2010 population estimates. Results: In all, 37 articles met the inclusion criteria. In Europe, the median incidence rate (/100,000 population) was 2.08 (IQR 1.47-2.43), corresponding to an estimated 15,355 (10,852-17,938) cases. Median prevalence (/100,000 population) was 5.40 (IQR 4.06-7.89), or 39,863 (29,971-58,244) prevalent cases. Conclusions: Disparity in rates among ALS incidence and prevalence studies may be due to differences in study design or true variations in population demographics such as age and geography, including environmental factors and genetic predisposition. Additional large-scale studies that use standardized case ascertainment methods are needed to more accurately assess the true global burden of ALS. copyright (C) 2013 S. Karger AG, Basel C1 [Chio, A.] Univ Turin, Rita Levi Montalcini Dept Neurosci, IT-10126 Turin, Italy. [Logroscino, G.] Univ Bari, Bari, Italy. [Traynor, B. J.] NIA, NIH, Bethesda, MD 20892 USA. [Collins, J.; Simeone, J. C.] United BioSource Corp, Lexington, MA USA. [Goldstein, L. A.] Sci Solut, United BioSource Corp Envis Grp, Southport, CT USA. [White, L. A.] Biogen Idec Inc, Weston, MA USA. RP Chio, A (reprint author), Univ Turin, Rita Levi Montalcini Dept Neurosci, Via Cherasco 15, IT-10126 Turin, Italy. EM adriano.chio@unito.it RI Traynor, Bryan/G-5690-2010; LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chio, Adriano/0000-0001-9579-5341 FU European Community [259867, 278611]; Biogen Idec FX This report and medical writing assistance was funded by Biogen Idec. The research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013; grant agreement Nos. 259867 and 278611 to A.C.). NR 80 TC 100 Z9 103 U1 8 U2 35 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 EI 1423-0208 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2013 VL 41 IS 2 BP 118 EP 130 DI 10.1159/000351153 PG 13 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 198RQ UT WOS:000322940400008 PM 23860588 ER PT J AU Perdivara, I Yamauchi, M Tomer, KB AF Perdivara, Irina Yamauchi, Mitsuo Tomer, Kenneth B. TI Molecular Characterization of Collagen Hydroxylysine O-Glycosylation by Mass Spectrometry: Current Status SO AUSTRALIAN JOURNAL OF CHEMISTRY LA English DT Review ID CYANOGEN-BROMIDE PEPTIDES; TRIPLE-HELICAL DOMAIN; OSTEOGENESIS IMPERFECTA; POSTTRANSLATIONAL MODIFICATIONS; LYSYL HYDROXYLASE-3; BASEMENT-MEMBRANE; REMNANT EPITOPES; CROSS-LINKING; GELATINASE-B; AMINO-ACID AB The most abundant proteins in vertebrates - the collagen family proteins - play structural and biological roles in the body. The predominant member, type I collagen, provides tissues and organs with structure and connectivity. This protein has several unique post-translational modifications that take place intra-and extra-cellularly. With growing evidence of the relevance of such post-translational modifications in health and disease, the biological significance of O-linked collagen glycosylation has recently drawn increased attention. However, several aspects of this unique modification - the requirement for prior lysyl hydroxylation as a substrate, involvement of at least two distinct glycosyl transferases, its involvement in intermolecular crosslinking - have made its molecular mapping and quantitative characterization challenging. Such characterization is obviously crucial for understanding its biological significance. Recent progress in mass spectrometry has provided an unprecedented opportunity for this type of analysis. This review summarizes recent advances in the area of O-glycosylation of fibrillar collagens and their characterization using state-of-the-art liquid chromatography-mass spectrometry-based methodologies, and perspectives on future research. The analytical characterization of collagen crosslinking and advanced glycation end-products are not addressed here. C1 [Perdivara, Irina; Tomer, Kenneth B.] NIEHS, Mass Spectrometry Grp, NIH, Res Triangle Pk, NC 27709 USA. [Yamauchi, Mitsuo] Univ N Carolina, Sch Dent, Chapel Hill, NC 27599 USA. RP Perdivara, I (reprint author), NIEHS, Mass Spectrometry Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM perdivarai@niehs.nih.gov FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [ES 050171]; NIH [AR060978] FX The authors would like to acknowledge the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Project no. ES 050171 to KBT) and the NIH funding grant AR060978 (MY). We would like to thank Dr Nancy Pleshko (Temple University, PA) for providing collagen samples, Drs Masahiko Terajima (University of North Carolina, NC) and Marnisa Sricholpech (Srinakarinwirot University, Bangkok, Thailand) for isolation and purification of collagen, and the NIEHS Protein Microcharacterization Facility for the assistance with the in-gel digests. NR 56 TC 6 Z9 6 U1 5 U2 13 PU CSIRO PUBLISHING PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA SN 0004-9425 J9 AUST J CHEM JI Aust. J. Chem. PY 2013 VL 66 IS 7 BP 760 EP 769 DI 10.1071/CH13174 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 188WC UT WOS:000322227000005 PM 25414518 ER PT J AU Jia, WL Qiu, KL He, MH Song, PF Zhou, Q Zhou, F Yu, Y Zhu, DD Nickerson, ML Wan, SQ Liao, XK Zhu, XQ Peng, SL Li, YR Wang, J Guo, GW AF Jia, Wenlong Qiu, Kunlong He, Minghui Song, Pengfei Zhou, Quan Zhou, Feng Yu, Yuan Zhu, Dandan Nickerson, Michael L. Wan, Shengqing Liao, Xiangke Zhu, Xiaoqian Peng, Shaoliang Li, Yingrui Wang, Jun Guo, Guangwu TI SOAPfuse: an algorithm for identifying fusion transcripts from paired-end RNA-Seq data SO GENOME BIOLOGY LA English DT Article ID SHORT READ ALIGNMENT; GENE FUSIONS; SEQUENCING DATA; PROSTATE-CANCER; BREAST-CANCER; IDENTIFICATION; RESOLUTION; ULTRAFAST; DISCOVERY; GENOME AB We have developed a new method, SOAPfuse, to identify fusion transcripts from paired-end RNA-Seq data. SOAPfuse applies an improved partial exhaustion algorithm to construct a library of fusion junction sequences, which can be used to efficiently identify fusion events, and employs a series of filters to nominate high-confidence fusion transcripts. Compared with other released tools, SOAPfuse achieves higher detection efficiency and consumed less computing resources. We applied SOAPfuse to RNA-Seq data from two bladder cancer cell lines, and confirmed 15 fusion transcripts, including several novel events common to both cell lines. SOAPfuse is available at http://soap.genomics.org.cn/soapfuse.html. C1 [Jia, Wenlong; Qiu, Kunlong; He, Minghui; Zhou, Quan; Wan, Shengqing; Li, Yingrui; Wang, Jun; Guo, Guangwu] BGI Tech Solut Co Ltd, Shenzhen 518083, Peoples R China. [Jia, Wenlong; Qiu, Kunlong; He, Minghui; Song, Pengfei; Zhou, Quan; Zhou, Feng; Yu, Yuan; Zhu, Dandan; Wan, Shengqing; Li, Yingrui; Wang, Jun; Guo, Guangwu] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Zhou, Quan] Univ Elect Sci & Technol China, Sch Life Sci & Technol, Chengdu 610054, Peoples R China. [Zhou, Feng] S China Univ Technol, Guangzhou Higher Educ Mega Ctr, Sch Biosci & Bioengn, Guangzhou 510006, Guangdong, Peoples R China. [Nickerson, Michael L.] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. [Liao, Xiangke; Zhu, Xiaoqian; Peng, Shaoliang] Natl Univ Def Technol, Sch Comp Sci, Changsha 410073, Hunan, Peoples R China. [Zhu, Xiaoqian; Peng, Shaoliang] Natl Univ Def Technol, State Key Lab High Performance Comp, Changsha 410073, Hunan, Peoples R China. [Wang, Jun] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, DK-1165 Copenhagen, Denmark. [Wang, Jun] Univ Copenhagen, Dept Biol, DK-1165 Copenhagen, Denmark. RP Guo, GW (reprint author), BGI Tech Solut Co Ltd, Shenzhen 518083, Peoples R China. EM guogw@genomics.org.cn RI Li, Yingrui/K-1064-2015; Wang, Jun/C-8434-2016; Wang, Jun/B-9503-2016 OI Wang, Jun/0000-0002-8540-8931; Wang, Jun/0000-0002-2113-5874 FU National Basic Research Program of China (973 program) [2011CB809200]; National High Technology Research and Development Program of China (863 Program) [2012AA02A201]; Shenzhen municipal government of China; local government of the Yantian District of Shenzhen FX This work was supported by the National Basic Research Program of China (973 program 2011CB809200), National High Technology Research and Development Program of China (863 Program, 2012AA02A201). This project was also funded by the Shenzhen municipal government of China and the local government of the Yantian District of Shenzhen. Thanks to Xueda Hu (BGI-shenzhen) for giving advice and supporting this project. Thanks to TianHe research and development team of National University of Defense Technology for testing, optimizing and deploying the software on TianHe series supercomputers. We thank D Kim (TopHat-Fusion group), SL Salzberg (TopHat-Fusion group), and A McPherson (deFuse group) for help on operating software. We also thank the FusionMap group for helpful comments on simulation data. NR 37 TC 33 Z9 35 U1 4 U2 26 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2013 VL 14 IS 2 AR R12 DI 10.1186/gb-2013-14-2-r12 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 191BY UT WOS:000322388800002 PM 23409703 ER PT S AU Summers, FA Zhao, BZ Ganini, D Mason, RP AF Summers, Fiona A. Zhao, Baozhong Ganini, Douglas Mason, Ronald P. BE Cadenas, E Packer, L TI Photooxidation of Amplex Red to Resorufin: Implications of Exposing the Amplex Red Assay to Light SO HYDROGEN PEROXIDE AND CELL SIGNALING, PT A SE Methods in Enzymology LA English DT Review; Book Chapter ID HYPOXIC PULMONARY VASOCONSTRICTION; INDUCED EGF-RECEPTOR; SMOOTH-MUSCLE-CELLS; HYDROGEN-PEROXIDE; REACTIVE OXYGEN; MITOCHONDRIA; H2O2; GENERATION; REDUCTASE AB The Amplex Red assay, a fluorescent assay for the detection of H2O2, relies on the reaction of H2O2 which, in the presence of horseradish peroxidase, oxidizes the colorless, nonfluorescent, Amplex Red with a 1:1 stoichiometry to form the colored, fluorescent resorufin. We have found that resorufin is artifactually formed when Amplex Red is exposed to light. This photochemistry is initiated by trace amounts of resorufin present in Amplex Red stock solutions. ESR spin-trapping studies have demonstrated that superoxide radical is an intermediate in this process. Oxygen consumption measurements further confirmed that superoxide and H2O2 were artifactually produced by the photooxidation of Amplex Red. The artifactual formation of resorufin was also significantly increased by the presence of superoxide dismutase or HRP. This photooxidation process leads to a less sensitive assay for H2O2 under ambient light exposure and potentially invalid measurements under high energy exposure such as UVA irradiation. In general, precautions should be taken to minimize exposure to light, including that from instrumental light, during measurement of oxidative stress with Amp lex Red. C1 [Summers, Fiona A.; Ganini, Douglas; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Zhao, Baozhong] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA. RP Mason, RP (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM mason4@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES050139-13] NR 25 TC 9 Z9 9 U1 2 U2 20 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-405883-5 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 526 BP 1 EP 17 DI 10.1016/B978-0-12-405883-5.00001-6 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGF16 UT WOS:000322680100002 PM 23791091 ER PT J AU Qiao, CY Zhang, K Jin, H Miao, LY Shi, C Liu, X Yuan, AL Liu, JZ Li, DW Zheng, CY Zhang, GR Li, XW Yang, B Sun, HC AF Qiao, Chunyan Zhang, Kai Jin, Han Miao, Leiying Shi, Ce Liu, Xia Yuan, Anliang Liu, Jinzhong Li, Daowei Zheng, Changyu Zhang, Guirong Li, Xiangwei Yang, Bai Sun, Hongchen TI Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE gene therapy; bone regeneration; biodegradable polymer; human BMP-2 ID GENE DELIVERY; PLGA MICROSPHERES; BMP-2 GENE; RELEASE; DEFECTS; REGENERATION; REPAIR; DRUG; RHBMP-2; SYSTEMS AB Repair of large bone defects is a major challenge, requiring sustained stimulation to continually promote bone formation locally. Bone morphogenetic protein 2 (BMP-2) plays an important role in bone development. In an attempt to overcome this difficulty of bone repair, we created a delivery system to slowly release human BMP-2 cDNA plasmid locally, efficiently transfecting local target cells and secreting functional human BMP-2 protein. For transfection, we used polyethylenimine (PEI) to create pBMP-2/PEI nanoparticles, and to ensure slow release we used poly(lactic-co-glycolic acid) (PLGA) to create microsphere encapsulated pBMP-2/PEI nanoparticles, PLGA@pBMP-2/PEI. We demonstrated that pBMP-2/PEI nanoparticles could slowly release from the PLGA@pBMP-2/PEI microspheres for a long period of time. The 3-15 mu m diameter of the PLGA@pBMP-2/PEI further supported this slow release ability of the PLGA@pBMP-2/PEI. In vitro transfection assays demonstrated that pBMP-2/PEI released from PLGA@pBMP-2/PEI could efficiently transfect MC3T3-E1 cells, causing MC3T3-E1 cells to secrete human BMP-2 protein, increase calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7 and I type collagen (COLL I), and finally induce MC3T3-E1 cell differentiation. Importantly, in vivo data from micro-computed tomography (micro-CT) and histological staining demonstrated that the human BMP-2 released from PLGA@pBMP-2/PEI had a long-term effect locally and efficiently promoted bone formation in the bone defect area compared to control animals. All our data suggest that our PLGA-nanoparticle delivery system efficiently and functionally delivers the human BMP-2 cDNA and has potential clinical application in the future after further modification. C1 [Qiao, Chunyan; Jin, Han; Shi, Ce; Liu, Xia; Yuan, Anliang; Liu, Jinzhong; Li, Daowei; Li, Xiangwei; Sun, Hongchen] Jilin Univ, Sch Stomatol, Dept Pathol, Changchun 130021, Peoples R China. [Zhang, Kai; Yang, Bai] Jilin Univ, Coll Chem, State Key Lab Supramol Struct & Mat, Changchun 130023, Peoples R China. [Miao, Leiying] Nanjing Univ, Sch Med, Inst Stomatol, Nanjing 210008, Jiangsu, Peoples R China. [Miao, Leiying] Nanjing Univ, Sch Med, Hosp Stomatol, Nanjing 210008, Jiangsu, Peoples R China. [Zheng, Changyu] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Zhang, Guirong] Jilin Univ, Sch Basic Med, Dept Biochem, Changchun 130023, Peoples R China. RP Sun, HC (reprint author), Jilin Univ, Sch Stomatol, Dept Pathol, Changchun 130021, Peoples R China. EM hcsun@jlu.edu.cn FU National Science Foundation of China [30830108, 81271111]; Doctoral Fund of Ministry of Education of China [233200801830063]; Science and Technology Development projects of Jilin Province [201101051]; Jilin Provincial Health Department research projects [2012S017]; Fundamental Research Project of the Central Universities, People's Republic of China FX This work was supported by the National Science Foundation of China (Grant No 30830108, 81271111), Doctoral Fund of Ministry of Education of China (Grant No 233200801830063), Science and Technology Development projects of Jilin Province (No 201101051), Jilin Provincial Health Department research projects (No 2012S017), and Fundamental Research Project of the Central Universities, People's Republic of China. NR 37 TC 21 Z9 23 U1 4 U2 40 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2013 VL 8 BP 2985 EP 2995 DI 10.2147/IJN.S45184 PG 11 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 198VX UT WOS:000322951900001 PM 23990717 ER PT J AU Koizumi, H AF Koizumi, Hidehiko TI Multiple modes of respiratory rhythm and pattern generation in the brainstem SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Koizumi, Hidehiko] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2013 VL 63 SU 1 BP S56 EP S56 PG 1 WC Physiology SC Physiology GA 190PH UT WOS:000322352200134 ER PT J AU Shiono, H Matsui, T Morimoto, A Okada, T Ito, Y AF Shiono, Hiroyuki Matsui, Takuya Morimoto, Atsuko Okada, Tadashi Ito, Yoichiro TI A Preparative Separation of Basophils and Eosinophils by a Continuous Flow-Through Density Gradient Cell Separation Method SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Shiono, Hiroyuki; Matsui, Takuya; Morimoto, Atsuko; Okada, Tadashi] Aichi Med Univ Med, Dept Physiol, Nagakute, Aichi, Japan. [Ito, Yoichiro] NIH, Bioseparat Technol Lab, Biochem & Biophys Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2013 VL 63 SU 1 BP S232 EP S232 PG 1 WC Physiology SC Physiology GA 190PH UT WOS:000322352200746 ER PT S AU Bandettini, PA Kundu, P Gonzalez-Castillo, J Misaki, M Guillod, P AF Bandettini, Peter A. Kundu, Prantik Gonzalez-Castillo, Javier Misaki, Masaya Guillod, Paul BE Weaver, JB Molthen, RC TI Characterizing and Utilizing fMRI Fluctuations, Patterns, and Dynamics SO MEDICAL IMAGING 2013: BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Biomedical Applications in Molecular, Structural, and Functional Imaging CY FEB 10-13, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE fMRI; resting state fMRI; functional connectivity; clustering; multi-echo EPI; physiologic fluctuations; blood oxygenation; fMRI decoding AB Functional MRI is fundamentally grounded in the hemodynamic response. With an increase in neuronal activity, blood flow increases, causing an increase in blood oxygenation, leading to an increase in transverse relaxation rate T2*. This increase in blood flow is slow and highly variable and shows a considerable spatial heterogeneity. In spite of these limitations, the hemodynamic response has been proven to be exquisitely sensitive to subtle differences in neuronal activity in time, over space, and between subjects. This paper is a brief review of my Keynote address describing some of the effort coming from my group that further demonstrates methods to robustly extract ever more information from both resting state fMRI and activation-induced fMRI. Specifically, I discuss 1) our new method to use multi-echo fMRI time series data collection to separate blood oxygen level dependent (BOLD) signal from non-BOLD signal, 2) activation of the whole brain obtained using a simple task and, importantly massive averaging and a model-free analysis approach, and 3) fMRI decoding of left vs right eye ocular dominance column activation with a timing offset as low as 100 ms. C1 [Bandettini, Peter A.; Kundu, Prantik; Gonzalez-Castillo, Javier; Misaki, Masaya; Guillod, Paul] NIH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Bandettini, PA (reprint author), NIH, Sect Funct Imaging Methods, Lab Brain & Cognit, 10 Ctr Dr Bethesda, Bethesda, MD 20892 USA. OI Kundu, Prantik/0000-0001-9367-3068; Gonzalez-Castillo, Javier/0000-0002-6520-5125 NR 3 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9446-7 J9 PROC SPIE PY 2013 VL 8672 AR 86720T DI 10.1117/12.2012737 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BFY76 UT WOS:000321907600028 ER PT S AU Liu, JF Wang, SJ Linguraru, MG Summers, RM AF Liu, Jianfei Wang, Shijun Linguraru, Marius George Summers, Ronald M. BE Novak, CL Aylward, S TI Robust Detection of Renal Calculi from Non-contract CT Images Using TV-flow and MSER Features SO MEDICAL IMAGING 2013: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Renal calculi detection; Total variation flow; Maximal stable extremal region; CT colonography ID EFFICIENT AB Renal calculi are one of the most painful urologic disorders causing 3 million treatments per year in the United States The objective of this paper is the automated detection of renal calculi from CT colonography (CTC) images on which. they are one of the major extracolonic findings. However, the primary purpose of the CTC protocols is not for th(e) detection of renal calculi, but for screening of colon cancer. The kidneys are imaged with significant amounts of noise in the non-contrast CTC images, which makes the detection of renal calculi extremely challenging. We propose a computer-aided diagnosis method to detect renal calculi in CTC images. It is built on three novel techniques: 1) tota(l) variation (TV) flow to reduce image noise while keeping calculi, 2) maximally stable extremal region (MSER) features to find calculus candidates, 3) salient feature descriptors based on intensity properties to train a support vector machin(e) classifier and filter false positives. We selected 23 CTC cases with 36 renal calculi to analyze the detection algorithm. The calculus size ranged from 1.0mm to 6.8mm. Fifteen cases were selected as the training dataset, and the remaining eight cases were used for the testing dataset. The area under the receiver operating characteristic curve (AUC) values were 0.92 in the training datasets and 0.93 in the testing datasets. The testing dataset confidence interval for AUC reported by ROCKIT was [0.8799, 0.9591] and the training dataset was [0.8974, 0.9642]. These encouraging result(s) demonstrated that our detection algorithm can robustly and accurately identify renal calculi from CTC images. C1 [Liu, Jianfei; Wang, Shijun; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Liu, JF (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9444-3 J9 PROC SPIE PY 2013 VL 8670 AR 867006 DI 10.1117/12.2008034 PG 7 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGC32 UT WOS:000322261500005 ER PT S AU Liu, JF Linguraru, MG Wang, SJ Summers, RM AF Liu, Jianfei Linguraru, Marius George Wang, Shijun Summers, Ronald M. BE Novak, CL Aylward, S TI Automatic Segmentation of Kidneys from Non-Contrast CT Images Using Efficient Belief Propagation SO MEDICAL IMAGING 2013: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Kidney segmentation; extracolonic finding; CT colonography; belief propagation; Markov random field ID GRAPH CUTS; FRAMEWORK AB CT colonography (CTC) can increase the chance of detecting high-risk lesions not only within the colon but anywhere in the abdomen with a low cost. Extracolonic findings such as calculi and masses are frequently found in the kidneys on CTC. Accurate kidney segmentation is an important step to detect extracolonic findings in the kidneys. However, non-contrast CTC images make the task of kidney segmentation substantially challenging because the intensity values of kidney parenchyma are similar to those of adjacent structures. In this paper, we present a fully automatic kidney segmentation algorithm to support extracolonic diagnosis from CTC data. It is built upon three major contributions: 1) localize kidney search regions by exploiting the segmented liver and spleen as well as body symmetry; 2) construct a probabilistic shape prior handling the issue of kidney touching other organs; 3) employ efficient belief propagation on the shape prior to extract the kidneys. We evaluated the accuracy of our algorithm on five non-contrast CTC datasets with manual kidney segmentation as the ground-truth. The Dice volume overlaps were 88%/89%, the root-mean-squared errors were 3.4 mm/2.8 mm, and the average surface distances were 2.1 mm/1.9 mm for the left/right kidney respectively. We also validated the robustness on 27 additional CTC cases, and 23 datasets were successfully segmented. In four problematic cases, the segmentation of the left kidney failed due to problems with the spleen segmentation. The results demonstrated that the proposed algorithm could automatically and accurately segment kidneys from CTC images, given the prior correct segmentation of the liver and spleen. C1 [Liu, Jianfei; Wang, Shijun; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Liu, JF (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 1 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9444-3 J9 PROC SPIE PY 2013 VL 8670 AR 867005 DI 10.1117/12.2007738 PG 6 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGC32 UT WOS:000322261500004 ER PT S AU Liu, P Wang, SJ Turkbey, B Grant, K Pinto, P Choyke, P Wood, BJ Summers, RM AF Liu, Peter Wang, Shijun Turkbey, Baris Grant, Kinzya Pinto, Peter Choyke, Peter Wood, Bradford J. Summers, Ronald M. BE Novak, CL Aylward, S TI A prostate cancer computer-aided diagnosis system using multimodal magnetic resonance imaging and targeted biopsy labels SO MEDICAL IMAGING 2013: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Prostate cancer imaging; multimodality analysis; statistical learning; computer-aided diagnosis; biopsy label; MRI AB We propose a new method for prostate cancer classification based on supervised statistical learning methods by integrating T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI images with targeted prostate biopsy results. In the first step of the method, all three imaging modalities are registered based on the image coordinates encoded in the DICOM images. In the second step, local statistical features are extracted in each imaging modality to capture intensity, shape, and texture information at every biopsy target. Finally, using support vector machines, supervised learning is conducted with the biopsy results to train a classification system that predicts the pathology of suspicious cancer lesions. The algorithm was tested with a dataset of 54 patients that underwent 164 targeted biopsies (58 positive, 106 negative). The proposed tri-modal MRI algorithm shows significant improvement over a similar approach that utilizes only T2-weighted MRI images (p=0.048). The areas under the ROC curve for these methods were 0.82 (95% CI: [0.71, 0.93]) and 0.73 (95% CI: [0.55, 0.84]), respectively. C1 [Liu, Peter; Wang, Shijun; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10 Room 1C224 MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov NR 8 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9444-3 J9 PROC SPIE PY 2013 VL 8670 AR 86701G DI 10.1117/12.2007927 PG 6 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGC32 UT WOS:000322261500050 ER PT S AU Munoz, HE Yao, JH Burns, JE Summers, RM AF Munoz, Hector E. Yao, Jianhua Burns, Joseph E. Summers, Ronald M. BE Novak, CL Aylward, S TI Detection of Vertebral Degenerative Disc Disease Based on Cortical Shell Unwrapping SO MEDICAL IMAGING 2013: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE degenerative disc disease; osteophytes; computer-aided detection ID OSTEOPHYTES AB Degenerative disc disease (DDD) can be identified as hyperdense regions of bone and osseous spur formation in the spine that become more prevalent with age. These regions can act as confounding factors in the search for alternative hyperdense foci such as neoplastic processes. We created a preliminary CAD system that detects DDD in the spine on CT images. After the spine is segmented, the cortical shell of each vertebral body is unwrapped onto a 2D map. Candidates are detected from the 2D map based on their intensity and gradient. The 2D detections are remapped into 3D space and a level set algorithm is applied to more fully segment the 3D lesions. Features generated from the unwrapped 2D map and 3D segmentation are combined to train a support vector machine (SVM) classifier. The classifier was trained on 20 cases with DDD, which were marked by a radiologist. The pre-SVM program detected 164/193 ground truth lesions. Preliminary results showed 69.65% sensitivity with a 95% confidence interval of (64.47%, 73.92%), at an average of 9.8 false positives per patient. C1 [Munoz, Hector E.; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Munoz, HE (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9444-3 J9 PROC SPIE PY 2013 VL 8670 AR 86700C DI 10.1117/12.2008063 PG 7 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGC32 UT WOS:000322261500011 ER PT S AU Yao, JH Liu, YX Chen, F Summers, RM Bhattacharyya, T AF Yao, Jianhua Liu, Yixun Chen, Foster Summers, Ronald M. Bhattacharyya, Timothy BE Novak, CL Aylward, S TI Computer Assisted Measurement of Femoral Cortex Thickening on Radiographs SO MEDICAL IMAGING 2013: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE femur cortex thickening; compute-assisted evaluation; quantitative analysis ID ALENDRONATE THERAPY; ATYPICAL FRACTURES; DIAPHYSIS AB Radiographic features such as femoral cortex thickening have been frequently observed with atypical subtrochanteric fractures. These features may be a valuable finding to help prevent fractures before they happen. The current practice of manual measurement is often subjective and inconsistent. We developed a semi-automatic tool to consistently measure and monitor the progress of femoral cortex thickening on radiographs. By placing two seed points on each side of the femur, the program automatically extracts the periosteal and endosteal layers of the cortical shell by active contour models and B-spline fitting. Several measurements are taken along the femur shaft, including shaft diameter, cortical thickness, and integral area for medial and lateral cortex. The experiment was conducted on 52 patient datasets. The semi-automatic measurements were validated against manual measurements on 52 patients and demonstrated great improvement in consistency and accuracy (p<0.001). C1 [Yao, Jianhua; Liu, Yixun; Summers, Ronald M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Ctr Clin, Bldg 10 Room 1C351 MSC 1182 10 Ctr Dr, Bethesda, MD 20892 USA. EM jyao@cc.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9444-3 J9 PROC SPIE PY 2013 VL 8670 AR 86703C DI 10.1117/12.2007605 PG 8 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGC32 UT WOS:000322261500116 ER PT S AU Zhang, WD Liu, JM Yao, JH Summers, RM AF Zhang, Weidong Liu, Jiamin Yao, Jianhua Summers, Ronald M. BE Novak, CL Aylward, S TI Segmenting the Thoracic, Abdominal and Pelvic Musculature on CT Scans Combining Atlas-based Model and Active Contour Model SO MEDICAL IMAGING 2013: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE muscle segmentation; atlas-based model; active contour model; CT ID IMAGES AB Segmentation of the musculature is very important for accurate organ segmentation, analysis of body composition, and localization of tumors in the muscle. In research fields of computer assisted surgery and computer-aided diagnosis (CAD), muscle segmentation in CT images is a necessary pre-processing step. This task is particularly challenging due to the large variability in muscle structure and the overlap in intensity between muscle and internal organs. This problem has not been solved completely, especially for all of thoracic, abdominal and pelvic regions. We propose an automated system to segment the musculature on CT scans. The method combines an atlas-based model, an active contour model and prior segmentation of fat and bones. First, body contour, fat and bones are segmented using existing methods. Second, atlas-based models are pre-defined using anatomic knowledge at multiple key positions in the body to handle the large variability in muscle shape. Third, the atlas model is refined using active contour models (ACM) that are constrained using the pre-segmented bone and fat. Before refining using ACM, the initialized atlas model of next slice is updated using previous atlas. The muscle is segmented using threshold and smoothed in 3D volume space. Thoracic, abdominal and pelvic CT scans were used to evaluate our method, and five key position slices for each case were selected and manually labeled as the reference. Compared with the reference ground truth, the overlap ratio of true positives is 91.1%+/- 3.5%, and that of false positives is 5.5%+/- 4.2%. C1 [Zhang, Weidong; Liu, Jiamin; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD USA. RP Zhang, WD (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD USA. NR 12 TC 1 Z9 1 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9444-3 J9 PROC SPIE PY 2013 VL 8670 AR 867008 DI 10.1117/12.2007970 PG 6 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGC32 UT WOS:000322261500007 ER PT J AU Lebovitz, E Burbelo, P AF Lebovitz, Evan E. Burbelo, Peter D. TI Commercial Multiplex Technologies for the Microbiological Diagnosis of Sepsis SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Review ID POLYMERASE-CHAIN-REACTION; BLOOD-STREAM INFECTIONS; REAL-TIME PCR; RIBOSOMAL-RNA GENE; LIGHTCYCLER SEPTIFAST TEST; RAPID ETIOLOGIC DIAGNOSIS; MICROARRAY-BASED ASSAY; SUSPECTED SEPSIS; MOLECULAR DIAGNOSIS; ANTIMICROBIAL THERAPY AB In patients with suspected sepsis, rapid and accurate diagnosis of the causative infectious agent is critical. Although clinicians often use empiric antimicrobial therapy until the blood cultures are available to potentially adjust treatment, this approach is often not optimum for patient care. Recently, several commercial molecular multiplex technologies have shown promise for fast and comprehensive diagnosis of microorganisms and their antimicrobial resistance signatures. While one class of multiplex technologies is directed at improving the speed and diagnostic information obtained from positive blood cultures, the other identifies the causative microorganisms directly from clinical blood samples. This review provides an overview of these molecular technologies and describes their performance capabilities compared to standard blood cultures and in some cases to each other. We discuss the current clinical impact, limitations, and likely futures advances these multiplex technologies may have in guiding the management of patients with sepsis. C1 [Lebovitz, Evan E.] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA. [Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Clin Dent Res Core, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Burbelo, P (reprint author), Natl Inst Dent & Craniofacial Res, Clin Dent Res Core, Ctr Clin, NIH, Bldg 10,Rm 5N102, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research; Clinical Center, NIH FX This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, and the Clinical Center, NIH. The views expressed in this review are those of the authors and do not necessarily represent the views of the National Institutes of Health or the United States Government. NR 73 TC 7 Z9 8 U1 0 U2 16 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1177-1062 EI 1179-2000 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PY 2013 VL 17 IS 4 BP 221 EP 231 DI 10.1007/s40291-013-0037-4 PG 11 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 186CQ UT WOS:000322019900002 PM 23636778 ER PT J AU Issaq, HJ Veenstra, TD AF Issaq, Haleem J. Veenstra, Timothy D. BE Issaq, HJ Veenstra, TD TI Biomarker Discovery: Study Design and Execution SO PROTEOMIC AND METABOLOMIC APPROACHES TO BIOMARKER DISCOVERY LA English DT Article; Book Chapter ID HUMAN SERUM PROTEOME; BLADDER-CANCER; MASS-SPECTROMETRY; KIDNEY CANCER; TUMOR-MARKERS; PLASMA; URINE; METABOLOMICS; DIAGNOSIS; SARCOSINE C1 [Issaq, Haleem J.; Veenstra, Timothy D.] Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. RP Issaq, HJ (reprint author), Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. NR 51 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394795-6 PY 2013 BP 1 EP 16 DI 10.1016/B978-0-12-394446-7.00001-7 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BFQ63 UT WOS:000320992200002 ER PT J AU Issaq, HJ Veenstra, TD AF Issaq, Haleem J. Veenstra, Timothy D. BE Issaq, HJ Veenstra, TD TI PROTEOMIC AND METABOLOMIC APPROACHES TO BIOMARKER DISCOVERY Preface SO PROTEOMIC AND METABOLOMIC APPROACHES TO BIOMARKER DISCOVERY LA English DT Editorial Material; Book Chapter C1 [Issaq, Haleem J.; Veenstra, Timothy D.] Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. RP Issaq, HJ (reprint author), Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394795-6 PY 2013 BP XI EP XII PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BFQ63 UT WOS:000320992200001 ER PT J AU Ye, XY Prieto, DA Chan, KC Wei, BR Blonder, J AF Ye, Xiaoying Prieto, DaRue A. Chan, King C. Wei, Bih-Rong Blonder, Josip BE Issaq, HJ Veenstra, TD TI Tissue Sample Preparation for Proteomic Analysis SO PROTEOMIC AND METABOLOMIC APPROACHES TO BIOMARKER DISCOVERY LA English DT Article; Book Chapter ID PARAFFIN-EMBEDDED TISSUES; TANDEM MASS-SPECTROMETRY; LASER CAPTURE MICRODISSECTION; RENAL-CELL CARCINOMA; BIOMARKER DISCOVERY; LIQUID-CHROMATOGRAPHY; MEMBRANE-PROTEINS; FROZEN TISSUE; CANCER-TISSUE; LC-MS C1 [Ye, Xiaoying; Prieto, DaRue A.; Chan, King C.; Blonder, Josip] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. [Wei, Bih-Rong] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Ye, XY (reprint author), Frederick Natl Lab Canc Res, SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. NR 45 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394795-6 PY 2013 BP 39 EP 50 DI 10.1016/B978-0-12-394446-7.00003-0 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BFQ63 UT WOS:000320992200004 ER PT J AU Van, QN AF Van, Que N. BE Issaq, HJ Veenstra, TD TI Current NMR Strategies for Biomarker Discovery SO PROTEOMIC AND METABOLOMIC APPROACHES TO BIOMARKER DISCOVERY LA English DT Article; Book Chapter ID NUCLEAR-MAGNETIC-RESONANCE; PATTERN-RECOGNITION METHODS; HIGH-RESOLUTION H-1-NMR; CHOLINE PHOSPHOLIPID-METABOLISM; TOTAL CORRELATION SPECTROSCOPY; COMPLEX MIXTURE ANALYSIS; BASE-LINE CORRECTION; MAS MR SPECTROSCOPY; HUMAN CANCER-CELLS; SIGNAL-TO-NOISE C1 Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. RP Van, QN (reprint author), Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. NR 195 TC 1 Z9 1 U1 2 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394795-6 PY 2013 BP 87 EP 117 DI 10.1016/B978-0-12-394446-7.00006-6 PG 31 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BFQ63 UT WOS:000320992200007 ER PT J AU Issaq, HJ Veenstra, TD AF Issaq, Haleem J. Veenstra, Timothy D. BE Issaq, HJ Veenstra, TD TI Sample Depletion, Fractionation, and Enrichment for Biomarker Discovery SO PROTEOMIC AND METABOLOMIC APPROACHES TO BIOMARKER DISCOVERY LA English DT Article; Book Chapter ID MASS-SPECTROMETRY; PROTEOME ANALYSIS; PHOSPHOPEPTIDES; IDENTIFICATION; PROTEINS; ELECTROPHORESIS; CHROMATOGRAPHY; TECHNOLOGY; SEPARATION; STRATEGY C1 [Issaq, Haleem J.; Veenstra, Timothy D.] Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. RP Issaq, HJ (reprint author), Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. NR 22 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394795-6 PY 2013 BP 237 EP 244 DI 10.1016/B978-0-12-394446-7.00015-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BFQ63 UT WOS:000320992200016 ER PT J AU Veenstra, TD Van, QN Fox, SD Issaq, HJ AF Veenstra, Timothy D. Van, Que N. Fox, Stephen D. Issaq, Haleem J. BE Issaq, HJ Veenstra, TD TI Protein and Metabolite Identification SO PROTEOMIC AND METABOLOMIC APPROACHES TO BIOMARKER DISCOVERY LA English DT Article; Book Chapter ID NUCLEAR-MAGNETIC-RESONANCE; TANDEM MASS-SPECTROMETRY; PULSED-FIELD GRADIENTS; CORRELATION SPECTROSCOPY; NMR-SPECTRA; NATURAL-ABUNDANCE; METABOLOMICS; METABONOMICS; MOLECULES; DATABASE C1 [Veenstra, Timothy D.; Van, Que N.; Fox, Stephen D.; Issaq, Haleem J.] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. RP Veenstra, TD (reprint author), Frederick Natl Lab Canc Res, SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. NR 52 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394795-6 PY 2013 BP 245 EP 258 DI 10.1016/B978-0-12-394446-7.00016-9 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BFQ63 UT WOS:000320992200017 ER PT J AU Bosley, AD Das, S Andresson, T AF Bosley, Allen D. Das, Sudipto Andresson, Thorkell BE Issaq, HJ Veenstra, TD TI A Role for Protein-Protein Interaction Networks in the Identification and Characterization of Potential Biomarkers SO PROTEOMIC AND METABOLOMIC APPROACHES TO BIOMARKER DISCOVERY LA English DT Article; Book Chapter ID HUMAN-DISEASE GENES; QUANTITATIVE MASS-SPECTROMETRY; MOLECULAR INTERACTION DATABASE; INTERACTION DATASETS; INTERACTION PARTNERS; ANALYSIS REVEALS; SYSTEMS BIOLOGY; GASTRIC-CANCER; LUNG-CANCER; EXPRESSION C1 [Bosley, Allen D.; Das, Sudipto; Andresson, Thorkell] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. RP Bosley, AD (reprint author), Frederick Natl Lab Canc Res, SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA. NR 72 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394795-6 PY 2013 BP 333 EP 347 DI 10.1016/B978-0-12-394446-7.00021-2 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BFQ63 UT WOS:000320992200022 ER PT B AU Meng, ZJ Veenstra, TD AF Meng, Zhaojing Veenstra, Timothy D. BE Issaq, HJ Veenstra, TD TI Mass Spectrometry-Based Approach for Protein Biomarker Verification SO PROTEOMIC AND METABOLOMIC APPROACHES TO BIOMARKER DISCOVERY LA English DT Article; Book Chapter ID MULTIPLEXED ABSOLUTE QUANTIFICATION; PERFORMANCE LIQUID-CHROMATOGRAPHY; CONCATENATED SIGNATURE PEPTIDES; PROSTATE-SPECIFIC ANTIGEN; POSTTRANSLATIONAL MODIFICATIONS; ISOTOPE-DILUTION; PLASMA-PROTEINS; PROTEOMICS; SERUM; DISCOVERY C1 [Meng, Zhaojing; Veenstra, Timothy D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Meng, ZJ (reprint author), SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USA. NR 56 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394795-6; 978-0-12-394446-7 PY 2013 BP 407 EP 424 DI 10.1016/B978-0-12-394446-7.00026-1 PG 18 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BFQ63 UT WOS:000320992200027 ER PT J AU Wu, CX Li, F Niu, G Chen, XY AF Wu, Chenxi Li, Fang Niu, Gang Chen, Xiaoyuan TI PET Imaging of Inflammation Biomarkers SO THERANOSTICS LA English DT Review DE Positron emission tomography; inflammation; molecular imaging; biomarker ID POSITRON-EMISSION-TOMOGRAPHY; TUMOR-ASSOCIATED MACROPHAGES; VASCULAR ADHESION PROTEIN-1; NECROSIS-FACTOR-ALPHA; TYPE-2 CANNABINOID RECEPTOR; IN-VIVO EVALUATION; PERIPHERAL BENZODIAZEPINE-RECEPTOR; TRAUMATIC BRAIN-INJURY; RHEUMATOID-ARTHRITIS; FDG-PET AB Inflammation plays a significant role in many disease processes. Development in molecular imaging in recent years provides new insight into the diagnosis and treatment evaluation of various inflammatory diseases and diseases involving inflammatory process. Positron emission tomography using F-18-FDG has been successfully applied in clinical oncology and neurology and in the inflammation realm. In addition to glucose metabolism, a variety of targets for inflammation imaging are being discovered and utilized, some of which are considered superior to FDG for imaging inflammation. This review summarizes the potential inflammation imaging targets and corresponding PET tracers, and the applications of PET in major inflammatory diseases and tumor associated inflammation. Also, the current attempt in differentiating inflammation from tumor using PET is also discussed. C1 [Wu, Chenxi; Li, Fang] CAMS, PUMCH, Dept Nucl Med, Beijing, Peoples R China. [Wu, Chenxi; Li, Fang] PUMC, Beijing, Peoples R China. [Wu, Chenxi; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Chen, XY (reprint author), CAMS, PUMCH, Dept Nucl Med, Beijing, Peoples R China. EM lifang@pumch.cn; shawn.chen@nih.gov FU Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 182 TC 39 Z9 40 U1 2 U2 34 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2013 VL 3 IS 7 BP 448 EP 466 DI 10.7150/thno.6592 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196RB UT WOS:000322792100001 PM 23843893 ER PT J AU Ho, DN Choi, KY Lee, SJ AF Ho, Don N. Choi, Ki Young Lee, Sung-Jong TI Bibliometric Analysis of Theranostics: Two Years in the Making SO THERANOSTICS LA English DT Article DE Theranostics; Bibliometric Analysis ID JOURNALS; IMPACT AB With the newly released impact factor from Thomson Reuters, we look at the first two years of the journal Theranostics under the scope of a new bibliometric designed for the analysis of emerging specialties and also for journals with a multidisciplinary approach. With this method, we are able to look at characteristics of an interdisciplinary field or a single journal subject area, and also, the bibliographic trends of their authors. We use this tool to examine authors from the journal Theranostics and compare them to similar authors in the field of theranostics, or theranosticians. Our document and co-citation analysis examines the growth and overlap of established knowledge networks with the incorporation of fields, topics, and disciplines; the quantification can also reflect the intellectual activity in combining leading edge developments in solidly grounded specialties. The quantification of junior authorship aims to gauge the promotion of fresh ideas and scientific development in the community, while productivity of overall authors is measured by citation analysis. C1 [Ho, Don N.; Choi, Ki Young; Lee, Sung-Jong] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. [Lee, Sung-Jong] Natl Res Fdn Korea, Taejon, South Korea. RP Lee, SJ (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. EM Chris@nrf.re.kr RI CHOI, KI YOUNG/Q-7177-2016 NR 9 TC 1 Z9 1 U1 2 U2 11 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2013 VL 3 IS 7 BP 527 EP 531 DI 10.7150/thno.7021 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196RB UT WOS:000322792100008 PM 23843900 ER PT S AU Long, EO Kim, HS Liu, DF Peterson, ME Rajagopalan, S AF Long, Eric O. Kim, Hun Sik Liu, Dongfang Peterson, Mary E. Rajagopalan, Sumati BE Littman, DR Yokoyama, WM TI Controlling Natural Killer Cell Responses: Integration of Signals for Activation and Inhibition SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 31 SE Annual Review of Immunology LA English DT Review; Book Chapter DE inhibitory receptor; licensing; major histocompatibility complex; signaling ID MHC CLASS-I; COMPLEX CLASS-I; RESTING NK CELLS; HUMAN CYTOMEGALOVIRUS-INFECTION; SLAM FAMILY RECEPTORS; LECTIN-LIKE RECEPTORS; HUMAN DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSE; CUTTING EDGE; TARGET-CELLS AB Understanding how signals are integrated to control natural killer (NK) cell responsiveness in the absence of antigen-specific receptors has been a challenge, but recent work has revealed some underlying principles that govern NK cell responses. NK cells use an array of innate receptors to sense their environment and respond to alterations caused by infections, cellular stress, and transformation. No single activation receptor dominates; instead, synergistic signals from combinations of receptors are integrated to activate natural cytotoxicity and cytokine production. Inhibitory receptors for major histocompatibility complex class I (MHC-I) have a critical role in controlling NK cell responses and, paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing. MHC-I-specific inhibitory receptors both block activation signals and trigger signals to phosphorylate and inactivate the small adaptor Crk. These different facets of inhibitory signaling are incorporated into a revocable license model for the reversible tuning of NK cell responsiveness. C1 [Long, Eric O.; Kim, Hun Sik; Liu, Dongfang; Peterson, Mary E.; Rajagopalan, Sumati] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Kim, Hun Sik] Univ Ulsan, Dept Med, Seoul 138736, South Korea. [Liu, Dongfang] Texas Childrens Hosp, Baylor Coll Med, Ctr Human Immunobiol, Houston, TX 77030 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM elong@nih.gov; hunkim@amc.seoul.kr; dongfanl@bcm.edu; mpeterson@niaid.nih.gov; sumi@nih.gov RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU National Institute of Allergy and Infectious Diseases FX We thank A. Hoofring for illustrations and I. Tassi and L. M. Thomas for comments. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. NR 202 TC 242 Z9 250 U1 3 U2 34 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3031-6 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2013 VL 31 BP 227 EP 258 DI 10.1146/annurev-immunol-020711-075005 PG 32 WC Immunology SC Immunology GA BFY00 UT WOS:000321861600009 PM 23516982 ER PT S AU Leng, EY Xu, S Pinto, PA Wood, BJ AF Leng, Ethan Y. Xu, Sheng Pinto, Peter A. Wood, Bradford J. BE Holmes, DR Yaniv, ZR TI Fully automated needle detection in transrectal ultrasound series for repeated prostate biopsies SO MEDICAL IMAGING 2013: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Transrectal ultrasound; needle detection; prostate; biopsy; machine learning; support vector machine ID ALGORITHM AB Needle identification in transrectal ultrasound (TRUS) guided prostate biopsy is important for documenting the positions of tissue samples, which can help physicians reach missed tumors in repeated biopsies. Due to the inherent high signal-to-noise ratio of ultrasound and the frequent occurrence of out-of-plane needle insertions that present indistinctly on TRUS images, robust needle identification is difficult. In this paper, we describe a novel method for the automatic detection and distance measurement of biopsy needles in TRUS that uses the concept of support vector machines (SVMs). Recorded frames are first retrospectively analyzed based on a series of quantifiable characteristics, and then a set of training examples are formed from both frames with insertions and those without. Using the training set, our algorithm is able to determine whether a given prospective frame contains a needle insertion. The algorithm has been evaluated retrospectively on TRUS video data with a total of more than 95,000 frames, and detected needle deployments with sensitivity and specificity of 98.4% and >99.9%, respectively. Furthermore, given the nature of an SVM model, the algorithm can be easily adapted for real-time applications. C1 [Leng, Ethan Y.] Rice Univ, 6320 Main St, Houston, TX 77005 USA. [Xu, Sheng; Pinto, Peter A.; Wood, Bradford J.] NIH, NIH Clin Ctr, Bethesda, MD 20892 USA. RP Leng, EY (reprint author), Rice Univ, 6320 Main St, Houston, TX 77005 USA. EM Ethan.Leng@rice.edu FU NIH Biomedical Engineering Summer Internship Program FX The corresponding author thanks the NIH Biomedical Engineering Summer Internship Program for providing the opportunity and financial support for this work. NR 5 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9445-0 J9 PROC SPIE PY 2013 VL 8671 AR 86711O DI 10.1117/12.2007392 PG 6 WC Engineering, Biomedical; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BFY70 UT WOS:000321905800059 ER PT S AU Li, M Abi-Jaoudeh, N Kapoor, A Kadoury, S Xu, S Noordhoek, N Radaelli, A Carelsen, B Wood, BJ AF Li, Ming Abi-Jaoudeh, Nadine Kapoor, Ankur Kadoury, Samuel Xu, Sheng Noordhoek, Niels Radaelli, Alessandro Carelsen, Bart Wood, Bradford J. BE Holmes, DR Yaniv, ZR TI Towards cone-beam CT thermometry SO MEDICAL IMAGING 2013: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE CBCT thermometry; temperature monitoring; RFA ablation; Wronskian change detector ID NON-INVASIVE THERMOMETRY; COMPUTED-TOMOGRAPHY; INTERVENTIONAL SUITE; FEASIBILITY; ABLATION; GUIDANCE; SCANNER AB Temperature monitoring and therefore the final treatment zone achieved during a cone-beam CT (CBCT) guided ablation can prevent overtreatment and undertreatment. A novel method is proposed to detect changes in consecutive CBCT images obtained from projection reconstructions during an ablation procedure. The possibility is explored of using this method to generate thermometry maps from CBCT images, which can be used as an input function for ablation treatment planning. This novel method uses a baseline and an intermittent CBCT scan, which are routinely acquired to confirm the needle position and monitor progress of the ablation. Accurate registration is required and assumed in vitro and ex vivo. A Wronskian change detector algorithm is applied on the compensated images to obtain a difference image between the intermittent and baseline scans. Finally, a thermal map created by applying a calibration determined experimentally is used to obtain the corresponding temperature at each pixel or voxel. We applied Wronskian change detector to detect the difference of two CBCT images, which have low signal to noise ratio, and calibrate Wronskian change model to temperature data using a gel phantom. We tested the temperature mapping with water and gel phantoms as well as pig shoulder. The experimental results show this method can detect temperature change within 5 degrees C for a voxel size of 1mm(3) (within clinical relevancy), and by consequence delineate the ablation zone. The preliminary experimental results show that CBCT thermometry is possible and promising, but may require pre-processing, such as registration for motion compensation between the baseline and intermittent scans. Further, quantitative evaluations have to be conducted for validation prior to clinical assessment and translation. CBCT is a widely available technology that could make thermometry clinically practical as an enabling component of iterative ablation treatment planning. C1 [Li, Ming] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Abi-Jaoudeh, Nadine; Kapoor, Ankur; Xu, Sheng; Wood, Bradford J.] NIH, Ctr Clin, Bethesda, MD USA. [Kadoury, Samuel] Philips Res North America, Briarcliff Manor, NY USA. [Kadoury, Samuel] Ecole Polytech Montreal, Montreal, PQ, Canada. [Noordhoek, Niels; Radaelli, Alessandro; Carelsen, Bart] Philips Healthcare, Veenpluis, Netherlands. RP Li, M (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. FU NIH Intramural Research Program; NIH Center for Interventional Oncology FX This study supported by the NIH Intramural Research Program and the NIH Center for Interventional Oncology. The NIH and Philips Healthcare have a Cooperative Research and Development Agreement and intellectual property in the field. NR 19 TC 0 Z9 0 U1 0 U2 5 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9445-0 J9 PROC SPIE PY 2013 VL 8671 AR 86711I DI 10.1117/12.2006851 PG 7 WC Engineering, Biomedical; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BFY70 UT WOS:000321905800053 ER PT S AU Liu, JF Subramanian, KR Yoo, TS AF Liu, Jianfei Subramanian, Kalpathi R. Yoo, Terry S. BE Holmes, DR Yaniv, ZR TI Towards Designing an Optical-Flow Based Colonoscopy Tracking Algorithm: A Comparative Study SO MEDICAL IMAGING 2013: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Colonoscopy Tracking; Optical Flow; Egomotion Estimation ID SCALE AB Automatic co-alignment of optical and virtual colonoscopy images can supplement traditional endoscopic procedures, by providing more complete information of clinical value to the gastroenterologist. In this work, we present a comparative analysis of our optical flow based technique for colonoscopy tracking, in relation to current state of the art methods, in terms of tracking accuracy, system stability, and computational efficiency. Our optical-flow based colonoscopy tracking algorithm starts with computing multi-scale dense and sparse optical flow fields to measure image displacements. Camera motion parameters are then determined from optical flow fields by employing a Focus of Expansion (FOE) constrained egomotion estimation scheme. We analyze the design choices involved in the three major components of our algorithm: dense optical flow, sparse optical flow, and egomotion estimation. Brox's optical flow method,1 due to its high accuracy, was used to compare and evaluate our multi-scale dense optical flow scheme. SIFT6 and Harris-affine features(7) were used to assess the accuracy of the multi-scale sparse optical flow, because of their wide use in tracking applications; the FOE-constrained egomotion estimation was compared with collinear,2 image deformationl and image derivative(4) based egomotion estimation methods, to understand the stability of our tracking system. Two virtual colonoscopy (VC) image sequences were used in the study, since the exact camera parameters(for each frame) were known; dense optical flow results indicated that Brox's method was superior to multi-scale dense optical flow in estimating camera rotational velocities, but the final tracking errors were comparable, viz., 6mm vs. 8mm after the VC camera traveled 110mm. Our approach was computationally more efficient, averaging 7.2 sec. vs. 38 sec. per frame. SIFT and Harris affine features resulted in tracking errors of up to 70mm, while our sparse optical flow error was 6mm. The comparison among egomotion estimation algorithms showed that our FOE-constrained egomotion estimation method achieved the optimal balance between tracking accuracy and robustness. The comparative study demonstrated that our optical-flow based colonoscopy tracking algorithm maintains good accuracy and stability for routine use in clinical practice. C1 [Liu, Jianfei] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Subramanian, Kalpathi R.] Univ N Carolina, Charlotte, NC 28223 USA. [Yoo, Terry S.] Natl Inst Hlth, Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20892 USA. RP Subramanian, KR (reprint author), Univ N Carolina, Dept Comp Sci, Charlotte Visualizat Ctr, 9201 Univ City Blvd, Charlotte, NC 28223 USA. EM jliu1@uncc.edu; krs@uncc.edu; yoo@nlm.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9445-0 J9 PROC SPIE PY 2013 VL 8671 AR 867103 DI 10.1117/12.2007956 PG 7 WC Engineering, Biomedical; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BFY70 UT WOS:000321905800003 ER PT S AU Senseney, J Bokinsky, A Cheng, R McCreedy, E McAuliffe, MJ AF Senseney, Justin Bokinsky, Alexandra Cheng, Ruida McCreedy, Evan McAuliffe, Matthew J. BE Holmes, DR Yaniv, ZR TI Java Multi-histogram Volume Rendering Framework for Medical Images SO MEDICAL IMAGING 2013: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE GPU; Multi-histogram; rendering AB This work extends the multi-histogram volume rendering framework proposed by Kniss et al. [1] to provide rendering results based on the impression of overlaid triangles on a graph of image intensity versus gradient magnitude. The developed method of volume rendering allows for greater emphasis to boundary visualization while avoiding issues common in medical image acquisition. For example, partial voluming effects in computed tomography and intensity inhomogeneity of similar tissue types in magnetic resonance imaging introduce pixel values that will not reflect differing tissue types when a standard transfer function is applied to an intensity histogram. This new framework uses developing technology to improve upon the Kniss multi-histogram framework by using Java, the GPU, and MIPAV, an open-source medical image processing application, to allow multi-histogram techniques to be widely disseminated. The OpenGL view aligned texture rendering approach suffered from performance setbacks, inaccessibility, and usability problems. Rendering results can now be interactively compared with other rendering frameworks, surfaces can now be extracted for use in other programs, and file formats that are widely used in the field of biomedical imaging can be visualized using this multi-histogram approach. OpenCL and GLSL are used to produce this new multi-histogram approach, leveraging texture memory on the graphics processing unit of desktops to provide a new interactive method for visualizing biomedical images. Performance results for this method are generated and qualitative rendering results are compared. The resulting framework provides the opportunity for further applications in medical imaging, both in volume rendering and in generic image processing. C1 [Senseney, Justin; Cheng, Ruida; McCreedy, Evan; McAuliffe, Matthew J.] NIH, Imaging Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. [Senseney, Justin] WRNMMC, Natl Intrepid Ctr Excellence, Bethesda, MD 20889 USA. [Bokinsky, Alexandra] Geometr Tools Inc, Chapel Hill, NC 27510 USA. RP Senseney, J (reprint author), NIH, Imaging Sci Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9445-0 J9 PROC SPIE PY 2013 VL 8671 AR 86712J DI 10.1117/12.2006980 PG 7 WC Engineering, Biomedical; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BFY70 UT WOS:000321905800090 ER PT S AU Xu, S Kapoor, A Abi-Jaoudeh, N Imbesi, K Hong, CW Mazilu, D Sharma, K Venkatesan, AM Levy, E Wood, BJ AF Xu, Sheng Kapoor, Ankur Abi-Jaoudeh, Nadine Imbesi, Kimberly Hong, Cheng William Mazilu, Dumitru Sharma, Karun Venkatesan, Aradhana M. Levy, Elliot Wood, Bradford J. BE Holmes, DR Yaniv, ZR TI Percutaneous needle placement using laser guidance: a practical solution SO MEDICAL IMAGING 2013: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image-Guided Procedures, Robotic Interventions, and Modeling CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Medical robotics; Image guidance; Device tracking; Needle intervention; Laser AB In interventional radiology, various navigation technologies have emerged aiming to improve the accuracy of device deployment and potentially the clinical outcomes of minimally invasive procedures. While these technologies' performance has been explored extensively, their impact on daily clinical practice remains undetermined due to the additional cost and complexity, modification of standard devices (e.g. electromagnetic tracking), and different levels of experience among physicians. Taking these factors into consideration, a robotic laser guidance system for percutaneous needle placement is developed. The laser guidance system projects a laser guide line onto the skin entry point of the patient, helping the physician to align the needle with the planned path of the preoperative CT scan. To minimize changes to the standard workflow, the robot is integrated with the CT scanner via optical tracking. As a result, no registration between the robot and CT is needed. The robot can compensate for the motion of the equipment and keep the laser guide line aligned with the biopsy path in real-time. Phantom experiments showed that the guidance system can benefit physicians at different skill levels, while clinical studies showed improved accuracy over conventional freehand needle insertion. The technology is safe, easy to use, and does not involve additional disposable costs. It is our expectation that this technology can be accepted by interventional radiologists for CT guided needle placement procedures. C1 [Xu, Sheng; Abi-Jaoudeh, Nadine; Mazilu, Dumitru; Venkatesan, Aradhana M.; Levy, Elliot; Wood, Bradford J.] NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Kapoor, Ankur] Siemens Corp Res, Princeton, NJ 08540 USA. [Imbesi, Kimberly] Duke Univ, Durham, NC 27705 USA. [Hong, Cheng William] Cleveland Clin Fdn, Lerner Coll Med, Cleveland, OH 44195 USA. [Sharma, Karun] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Xu, S (reprint author), NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 1 U2 8 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9445-0 J9 PROC SPIE PY 2013 VL 8671 AR 867115 DI 10.1117/12.2007270 PG 6 WC Engineering, Biomedical; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Robotics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BFY70 UT WOS:000321905800040 ER PT J AU Jumpertz, R Venti, CA Le, DS Michaels, J Parrington, S Krakoff, J Votruba, S AF Jumpertz, Reiner Venti, Colleen A. Le, Duc Son Michaels, Jennifer Parrington, Shannon Krakoff, Jonathan Votruba, Susanne TI Food Label Accuracy of Common Snack Foods SO OBESITY LA English DT Article ID ENERGY-INTAKE; OVERWEIGHT; OBESITY; TRENDS; US AB Nutrition labels have raised awareness of the energetic value of foods, and represent for many a pivotal guideline to regulate food intake. However, recent data have created doubts on label accuracy. Objective: We tested label accuracy for energy and macronutrient content of prepackaged energy-dense snack food products. We measured "true" caloric content of 24 popular snack food products in the U.S. and determined macronutrient content in 10 selected items. Design and Methods: Bomb calorimetry and food factors were used to estimate energy content. Macronutrient content was determined according to Official Methods of Analysis. Calorimetric measurements were performed in our metabolic laboratory between April 20th and May 18th and macronutrient content was measured between September 28th and October 7th of 2010. Results and Conclusion: Serving size, by weight, exceeded label statements by 1.2% [median] (25th percentile -1.4, 75th percentile 4.3, P = 0.10). When differences in serving size were accounted for, metabolizable calories were 6.8 kcal (0.5, 23.5, P = 0.0003) or 4.3% (0.2, 13.7, P = 0.001) higher than the label statement. In a small convenience sample of the tested snack foods, carbohydrate content exceeded label statements by 7.7% (0.8, 16.7, P = 0.01); however fat and protein content were not significantly different from label statements (-12.8% [-38.6, 9.6], P = 0.23; 6.1% [-6.1, 17.5], P = 0.32). Carbohydrate content explained 40% and serving size an additional 55% of the excess calories. Among a convenience sample of energy-dense snack foods, caloric content is higher than stated on the nutrition labels, but overall well within FDA limits. This discrepancy may be explained by inaccurate carbohydrate content and serving size. C1 [Jumpertz, Reiner; Venti, Colleen A.; Michaels, Jennifer; Parrington, Shannon; Krakoff, Jonathan; Votruba, Susanne] NIDDK, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ 85016 USA. [Le, Duc Son] Nutr Ctr Ho Chi Minh City, Ho Chi Minh City, Vietnam. RP Votruba, S (reprint author), NIDDK, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ 85016 USA. EM votrubas@niddk.nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 17 TC 2 Z9 2 U1 2 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD JAN PY 2013 VL 21 IS 1 BP 164 EP 169 DI 10.1002/oby.20185 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 187AE UT WOS:000322086900053 PM 23505182 ER PT J AU Traurig, MT Orczewska, JI Ortiz, DJ Bian, L Marinelarena, AM Kobes, S Malhotra, A Hanson, RL Mason, CC Knowler, WC Bogardus, C Baier, LJ AF Traurig, Michael T. Orczewska, Julieanna I. Ortiz, Daniel J. Bian, Li Marinelarena, Alejandra M. Kobes, Sayuko Malhotra, Alka Hanson, Robert L. Mason, Clint C. Knowler, William C. Bogardus, Clifton Baier, Leslie J. TI Evidence for a Role of LPGAT1 in Influencing BMI and Percent Body Fat in Native Americans SO OBESITY LA English DT Article ID COA-DIACYLGLYCEROL ACYLTRANSFERASE-1; PIMA-INDIANS; TRIGLYCERIDE SYNTHESIS; GLUCOSE-METABOLISM; MICE; OBESITY; ENERGY; GENES; BIOSYNTHESIS; CARDIOLIPIN AB Objective: A genome-wide association study (GWAS) was recently completed in 1120 Pima Indians to identify loci that influence BMI. Among the top 100 signals were three variants that mapped within the lysophosphatidylglycerol acyltransferase 1 (LPGAT1) gene. LPGAT1 belongs to a large family of acyltransferases, which are involved in a variety of biological processes including pathways that regulate energy homeostasis and body weight. Therefore LPGAT1 was analyzed as a candidate gene for obesity in Pima Indians. Design and Methods: Variants (n = 26) located within and adjacent to LPGAT1 including a novel 27bp deletion in the 5'-untranslated region identified by sequencing were genotyped in a population-based sample of 3,391 full-heritage Pima Indians living in the Gila River Indian Community. Replication of selected variants was assessed in a second sample of 3,327 mixed-heritage Native Americans from the same community. Results: Variants with nominal associations with BMI in each of the two independent samples (tagged by rs112662024 and rs12058008) had associations of P = 1-4 x 10(-5) in the combined sample (n = 6718). A haplotype that includes the novel 27bp deletion, which does not occur in Caucasians, showed the strongest association with BMI in the full-heritage Pima Indians. In vitro functional studies provided suggestive evidence that this 27bp deletion may affect transcriptional or posttranscriptional regulation. Analysis of LPGAT1 cDNA from human preadipocytes identified an additional exon whose sequence could potentially serve as a mitochondrial targeting peptide. Conclusions: LPGAT1 is a novel gene that influences BMI in Native Americans. C1 [Traurig, Michael T.; Orczewska, Julieanna I.; Ortiz, Daniel J.; Bian, Li; Marinelarena, Alejandra M.; Kobes, Sayuko; Malhotra, Alka; Hanson, Robert L.; Mason, Clint C.; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. RP Baier, LJ (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. EM lbaier@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural Research Program of the National Institute of Diabetes and Kidney Diseases (NIDDK); American Diabetes Association [7-04-DCS-02] FX We thank all of the participants from the Gila River Indian Community for their cooperation. This research was supported by the Intramural Research Program of the National Institute of Diabetes and Kidney Diseases (NIDDK), and by a Distinguished Clinical Scientist award to Dr Clifton Bogardus from the American Diabetes Association (#7-04-DCS-02). NR 33 TC 8 Z9 8 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2013 VL 21 IS 1 BP 193 EP 202 DI 10.1038/oby.2012.161 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 187AE UT WOS:000322086900057 PM 23505186 ER PT J AU Abraham, SB Rubino, D Sinaii, N Ramsey, S Nieman, LK AF Abraham, S. B. Rubino, D. Sinaii, N. Ramsey, S. Nieman, L. K. TI Cortisol, Obesity, and the Metabolic Syndrome: A Cross-Sectional Study of Obese Subjects and Review of the Literature SO OBESITY LA English DT Review ID BODY-FAT DISTRIBUTION; PITUITARY-ADRENAL AXIS; MIDDLE-AGED MEN; PLASMA-CORTISOL; CARDIOVASCULAR RISK; INSULIN-RESISTANCE; CUSHINGS-SYNDROME; CENTRAL ADIPOSITY; PRODUCTION-RATES; BLOOD-PRESSURE AB Objective: Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome (MS). To evaluate these relationships, a cross-sectional study of 369 overweight and obese subjects and 60 healthy volunteers was performed and reviewed the previous literature. Design and Methods: Overweight and obese subjects had at least two other features of Cushing's syndrome. They underwent measurements representing cortisol dynamics (24 h urine cortisol excretion (UFC), bedtime salivary cortisol, 1 mg dexamethasone suppression test) and metabolic parameters (BMI, blood pressure (BP); fasting serum triglycerides, HDL, insulin, and glucose). Subjects also completed the Perceived Stress Scale (PSS). UFC, salivary cortisol, and weight from 60 healthy volunteers were analyzed. Results: No subject had Cushing's syndrome. UFC and dexamethasone responses were not associated with BMI or weight. However, salivary cortisol showed a trend to increase as BMI increased (P < 0.0001), and correlated with waist circumference (WC) in men (r(s) = 0.28, P = 0.02) and systolic BP in women (r(s) = 0.24, P = 0.0008). Post-dexamethasone cortisol levels were weak to moderately correlated with fasting insulin (r(s) = -0.31, P = 0.01) and HOMA-IR (r(s) = -0.31, P = 0.01) in men and systolic (r(s) = 0.18, P = 0.02) and diastolic BP (r(s) = 0.20, P = 0.009) in women. PSS results were higher in obese subjects than controls, but were not associated with cortisol or metabolic parameters. As expected, WC correlated with fasting insulin, HOMA-IR, and systolic BP (adjusted for BMI and gender; P < 0.01). Literature showed inconsistent relationships between cortisol and metabolic parameters. Conclusion: Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or MS. C1 [Abraham, S. B.; Nieman, L. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Rubino, D.; Ramsey, S.] Washington Ctr Weight Management & Res, Arlington, VA USA. [Rubino, D.; Ramsey, S.] George Washington Univ, Weight Management Program, Washington, DC USA. [Sinaii, N.] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Rubino, D (reprint author), Washington Ctr Weight Management & Res, Arlington, VA USA. EM drubino@wtmgmt.com FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported in part by the intramural program of The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 40 TC 42 Z9 44 U1 2 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD JAN PY 2013 VL 21 IS 1 BP E105 EP E117 DI 10.1002/oby.20083 PG 13 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 187AE UT WOS:000322086900015 PM 23505190 ER PT J AU Bose, S Krishnamoorthy, P Varanasi, A Nair, J Schutta, M Braunstein, S Iqbal, N Schwartz, S St Clair, C Master, SR Rader, DJ Reilly, MP Mehta, NN AF Bose, Subhasish Krishnamoorthy, Parasuram Varanasi, Ajay Nair, Jayamohan Schutta, Mark Braunstein, Seth Iqbal, Nayyar Schwartz, Stanley St Clair, Caitlin Master, Stephen R. Rader, Daniel J. Reilly, Muredach P. Mehta, Nehal N. TI Measurement of Waist Circumference Predicts Coronary Atherosclerosis Beyond Plasma Adipokines SO OBESITY LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; BEAM COMPUTED-TOMOGRAPHY; VISCERAL ADIPOSE-TISSUE; HEART-DISEASE EVENTS; ALL-CAUSE MORTALITY; BODY-MASS INDEX; ARTERY CALCIFICATION; METABOLIC SYNDROME; MYOCARDIAL-INFARCTION; ABDOMINAL ADIPOSITY AB Objective: The association of plasma adipokines beyond waist circumference (WC) with coronary artery calcification (CAC), a measure of subclinical atherosclerosis, is unknown. Design and Methods: Asymptomatic Caucasian individuals from two community-based cross-sectional studies (n = 1,285) were examined and multivariate analysis of traditional risk factors was performed, then WC and adipokines (adiponectin and leptin) were added. Incremental value of each was tested with likelihood ratio testing. Results: Beyond traditional risk factors, WC (Tobit regression ratio 1.69, P < 0.001) and plasma leptin (1.57, P < 0.001) but not plasma adiponectin (P = 0.75) were independently associated with CAC. In nested models, neither adiponectin (chi(2) = 0.76, P = 0.38) nor leptin (chi(2) = 1.32, P = 0.25) added value to WC beyond traditional risk factors, whereas WC added incremental value to adiponectin (chi(2) = 28.02, P < 0.0001) and leptin (chi(2) = 13.58, P = 0.0002). Conclusion: In the face of important biomarkers such as plasma adiponectin and leptin, WC remained a significant predictor of CAC beyond traditional risk factors underscoring the importance of WC measurement during cardiovascular risk assessment. C1 [Bose, Subhasish; Krishnamoorthy, Parasuram; Varanasi, Ajay; Nair, Jayamohan; St Clair, Caitlin; Rader, Daniel J.; Reilly, Muredach P.; Mehta, Nehal N.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Schutta, Mark; Braunstein, Seth; Iqbal, Nayyar; Schwartz, Stanley; Reilly, Muredach P.; Mehta, Nehal N.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Master, Stephen R.; Rader, Daniel J.; Reilly, Muredach P.; Mehta, Nehal N.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Master, Stephen R.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Reilly, Muredach P.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Reilly, Muredach P.] NHLBI, Bethesda, MD 20814 USA. RP Mehta, NN (reprint author), Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. EM nehal.mehta@nih.gov OI Krishnamoorthy, Parasuram/0000-0002-4560-7346 FU American College of Cardiology; National Psoriasis Foundation; [K23HL097151-01] FX Dr Mehta is supported by K23HL097151-01 and is a recipient of the American College of Cardiology Young Investigator Award for the Metabolic Syndrome and the National Psoriasis Foundation Award for Young Investigators. NR 40 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2013 VL 21 IS 1 BP E118 EP E123 DI 10.1002/oby.20086 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 187AE UT WOS:000322086900016 PM 23505191 ER PT J AU Pikilidou, MI Scuteri, A Morrell, C Lakatta, EG AF Pikilidou, M. I. Scuteri, A. Morrell, C. Lakatta, E. G. TI The Burden of Obesity on Blood Pressure is Reduced in Older Persons: The SardiNIA Study SO OBESITY LA English DT Article ID BODY-MASS INDEX; HYPERTENSION; AGE; ASSOCIATION; POPULATION; MORTALITY; GENDER AB Introduction: Being overweight or obese increases the risk of elevated blood pressure. However differences of their effects on blood pressure in different age groups are not clear. Objective: The aim of the present study was to evaluate differences of the effects of adiposity on the odds of having hypertension in different age groups. Design and Methods: Three thousand fifty-six subjects (1,532 women and 1,524 men) consist of the drug naive subjects from the SardiNIA study. Logistic regression models with backward elimination were used to determine and compare the association between categories of obesity on hypertension within young (<= 39), middle aged (40-59), and older (60+) subjects. Additional terms controlled for in the model were smoking and alcohol intake status. Results: The relationship of body mass index (BMI) on hypertension differed by age, as indicated by the significant interaction term of age with BMI (P < 0.01). Older subjects had higher odds of having hypertension than younger subjects but these odds were lower for obese than for lean subjects (OR 10.45, 95% CIs 4.58-23.85 in obese versus OR 33.89, 95% CIs 17.94-64.02 in lean subjects). A similar trend was also observed in middle aged subjects. Conclusions: This study shows that among men and women, older age was associated with a lesser effect of BMI on the odds of having hypertension. C1 [Pikilidou, M. I.; Scuteri, A.; Morrell, C.; Lakatta, E. G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Pikilidou, M. I.] Aristotle Univ Thessaloniki, AHEPA Hosp, Dept Internal Med 1, GR-54006 Thessaloniki, Greece. [Scuteri, A.] Cittadella Univ Monserrato, Consiglio Nazl Ric, INN, I-09042 Cagliari, Italy. [Morrell, C.] Loyola Univ Maryland, Baltimore, MD 21210 USA. RP Pikilidou, MI (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. EM pikilidou@gmail.com FU NIA [NO1-AG-1-2109]; Intramural Research Program of the NIH, National Institute on Aging (USA) FX The SardiNIA team was supported by Contract NO1-AG-1-2109 from the NIA. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (USA). NR 15 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2013 VL 21 IS 1 BP E10 EP E13 DI 10.1002/oby.20010 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 187AE UT WOS:000322086900001 PM 23404647 ER PT J AU Powell-Wiley, TM Ayers, CR de Lemos, JA Lakoski, SG Vega, GL Grundy, S Das, SR Banks-Richard, K Albert, MA AF Powell-Wiley, Tiffany M. Ayers, Colby R. de Lemos, James A. Lakoski, Susan G. Vega, Gloria L. Grundy, Scott Das, Sandeep R. Banks-Richard, Kamakki Albert, Michelle A. TI Relationship between Perceptions about Neighborhood Environment and Prevalent Obesity: Data from the Dallas Heart Study SO OBESITY LA English DT Article ID BODY-MASS INDEX; LOCAL FOOD ENVIRONMENT; PSYCHOSOCIAL STRESS; BUILT ENVIRONMENT; PHYSICAL-ACTIVITY; ATHEROSCLEROSIS; DISORDER; HEALTH; ADULTS; RISK AB Objectives: Although psychosocial stress can result in adverse health outcomes, little is known about how perceptions of neighborhood conditions, a measure of environment-derived stress, may impact obesity. The association between perceptions of neighborhood environment and obesity (defined as body mass index [BMI] >= 30 kg/m(2)) among 5,907 participants in the Dallas Heart Study, a multi-ethnic, probability-based sample of Dallas County residents was examined. Design and Methods: Participants were asked to respond to 18 questions about perceptions of their neighborhood. Factor analysis was used to identify three factors associated with neighborhood perceptions: neighborhood violence, physical environment, and social cohesion. Logistic regression analyses were performed to determine the relationship between each factor (higher quintile = more unfavorable perceptions) and the odds of obesity. Results: Decreasing age, income, and education associated with unfavorable overall neighborhood perceptions and unfavorable perceptions about specific neighborhood factors (P trend <0.05 for all). Increasing BMI was associated with unfavorable perceptions about physical environment (P trend <0.05) but not violence or social cohesion. After adjustment for race, age, sex, income, education, and length of residence, physical environment perception score in the highest quintile remained associated with a 25% greater odds of obesity (OR 1.25, [95% CI 1.03-1.50]). Predictors of obesity related to environmental perceptions included heavy traffic (OR 1.39, [1.17-1.64]), trash/litter in neighborhood (OR 1.27, [1.01-1.46]), lack of recreational areas (OR 1.21, [1.01-1.46]), and lack of sidewalks (OR 1.25, [95% CI 1.04-1.51]). Conclusions: Thus, unfavorable perceptions of environmental physical conditions are related to increased obesity. Efforts to improve the physical characteristics of neighborhoods, or the perceptions of those characteristics, may assist in the prevention of obesity in this community. C1 [Powell-Wiley, Tiffany M.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Powell-Wiley, Tiffany M.] NCI, Appl Res Program, Div Canc Control & Populat Studies, NIH, Bethesda, MD 20892 USA. [Ayers, Colby R.; de Lemos, James A.; Lakoski, Susan G.; Vega, Gloria L.; Grundy, Scott; Das, Sandeep R.; Banks-Richard, Kamakki] Univ Texas SW Med Ctr Dallas, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA. [de Lemos, James A.; Lakoski, Susan G.; Das, Sandeep R.; Banks-Richard, Kamakki] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Albert, Michelle A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Donald W Reynolds Ctr Cardiovasc Res,Div Cardiova, Boston, MA 02115 USA. [Albert, Michelle A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Donald W Reynolds Ctr Cardiovasc Res,Div Prevent, Boston, MA 02115 USA. RP Powell-Wiley, TM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM powelltm2@mail.nih.gov FU Ruth Kirschstein National Research Service Award from the National Institutes of Health [2-T32-HL007360-31]; Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health; National Institute of Health [RO1 AG038492]; Donald W. Reynolds Foundation (Las Vegas, NV); United States Public Health Service General Clinical Research Center from the National Institutes of Health/National Center Research Resources-Clinical Research [MO1-RR00633] FX Funding support for Dr. Powell-Wiley and Dr. Banks-Richard was provided by the Ruth Kirschstein National Research Service Award from the National Institutes of Health (#2-T32-HL007360-31). Dr. Powell-Wiley is currently funded by the Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. Dr. Albert is funded by the National Institute of Health (RO1 AG038492). Funding support for the Dallas Heart Study was provided by the Donald W. Reynolds Foundation (Las Vegas, NV) and the United States Public Health Service General Clinical Research Center grant #MO1-RR00633 from the National Institutes of Health/National Center Research Resources-Clinical Research. NR 31 TC 15 Z9 15 U1 2 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2013 VL 21 IS 1 BP E14 EP E21 DI 10.1002/oby.20012 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 187AE UT WOS:000322086900002 PM 23404728 ER PT S AU van Deventer, HE Soldin, SJ AF van Deventer, Hendrick E. Soldin, Steven J. BE Makowski, GS TI The Expanding Role of Tandem Mass Spectrometry in Optimizing Diagnosis and Treatment of Thyroid Disease SO ADVANCES IN CLINICAL CHEMISTRY, VOL 61 SE Advances in Clinical Chemistry LA English DT Review; Book Chapter ID FAMILIAL DYSALBUMINEMIC HYPERTHYROXINEMIA; FREE-THYROXINE ASSAY; CHRONIC-RENAL-FAILURE; NONTHYROIDAL ILLNESS; EQUILIBRIUM DIALYSIS; FREE TRIIODOTHYRONINE; HORMONE-BINDING; EARLY-PREGNANCY; SERUM-PROTEINS; NEUROPSYCHOLOGICAL DEVELOPMENT AB This review discusses the state-of-the-art measurement of free and total thyroid hormones in clinical laboratories. We highlight some of the limitations of currently used immunoassays and critically discuss physical separation methods for the measurement of free thyroid hormone. Physical separation methods, such as equilibrium dialysis or ultrafiltration, followed by tandem mass spectrometry for the measurement of free thyroid hormones offer many advantages, which we feel, can deepen our understanding of thyroid hormone metabolism and improve patient diagnosis and care. Problems with direct analogue immunoassay methods for FT4/FT3 as well as immunoassay methods for total T-3 at low T-3 concentrations and during pregnancy are highlighted. Improved diagnosis and patient management can be achieved utilizing tandem mass spectrometry for these measurements. C1 [van Deventer, Hendrick E.] Lancet Labs, Johannesburg, South Africa. [Soldin, Steven J.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Soldin, SJ (reprint author), NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA. EM soldinsj@cc.nih.gov FU Intramural NIH HHS NR 116 TC 9 Z9 9 U1 7 U2 19 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2423 BN 978-0-12-407827-7; 978-0-12-407680-8 J9 ADV CLIN CHEM JI Advan. Clin. Chem. PY 2013 VL 61 BP 127 EP 152 DI 10.1016/B978-0-12-407680-8.00005-1 PG 26 WC Medical Laboratory Technology SC Medical Laboratory Technology GA BFQ01 UT WOS:000320925300005 PM 24015601 ER PT J AU Birnbaum, LS DeVito, M AF Birnbaum, Linda S. DeVito, Michael BE Fowler, BA TI COMPUTATIONAL TOXICOLOGY METHODS AND APPLICATIONS FOR RISK ASSESSMENT Foreword SO COMPUTATIONAL TOXICOLOGY: METHODS AND APPLICATIONS FOR RISK ASSESSMENT LA English DT Editorial Material; Book Chapter ID PHARMACOKINETIC MODEL; TOXICITY; EXPOSURE; ASSAY C1 [Birnbaum, Linda S.; DeVito, Michael] NIEHS, Res Triangle Pk, NC 27709 USA. RP Birnbaum, LS (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-396508-0 PY 2013 BP IX EP XIV PG 6 WC Mathematical & Computational Biology; Toxicology SC Mathematical & Computational Biology; Toxicology GA BFR29 UT WOS:000321041500001 ER PT S AU Farmer, CA Aman, MG AF Farmer, Cristan A. Aman, Michael G. BE Hastings, RP Rojahn, J TI Pharmacological Intervention for Disruptive Behaviors in Intellectual and Developmental Disabilities: The Glass is Half Full SO INTERNATIONAL REVIEW OF RESEARCH IN DEVELOPMENTAL DISABILITIES: CHALLENGING BEHAVIOR, VOL 44 SE International Review of Research in Developmental Disabilities LA English DT Article; Book Chapter ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; PSYCHOTROPIC MEDICATION USE; OPEN-LABEL TRIAL; SELF-INJURIOUS-BEHAVIOR; PRADER-WILLI-SYNDROME; MENTAL-RETARDATION; DOUBLE-BLIND; RETROSPECTIVE ASSESSMENT; SUBAVERAGE INTELLIGENCE AB The use of psychotropic medicine for the treatment of disruptive behaviors such as irritability, attention-deficit hyperactivity disorder symptoms, and self-injury is more common in individuals with intellectual and developmental disabilities (IDD) than in neurotypical populations. With the exception of some atypical antipsychotics, few drugs carry clinical indications for such use. Thus, many children and adults with IDD receive "off-label" medication with varying degrees of empirical support for safety and efficacy. In this chapter, we review the literature on pharmacologic treatment of disruptive behavior in IDD between 2001 and 2010. We discuss several drug classes, including antipsychotics, antidepressants, psychostimulants, norepinephrine reuptake inhibitors, anticonvulsants, and glutamatergic agents. Due to the relative preponderance of research in samples with autism spectrum disorders, we present these separately from studies in general IDD samples. Overall, the research base is strongest for atypical antipsychotics and psychostimulants, and it is clear that the field has advanced between 2001 and 2010. Other drug classes have received relatively little research attention. We identify several areas in which the field can improve future research, including the study of combination treatments (e.g. cotherapy and medication plus behavioral). C1 [Farmer, Cristan A.] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. [Aman, Michael G.] Ohio State Univ, Nisonger Ctr UCEDD, Columbus, OH 43210 USA. RP Farmer, CA (reprint author), NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. EM farmerca@mail.nih.gov NR 121 TC 2 Z9 2 U1 0 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 2211-6095 BN 978-0-12-401725-2 J9 INT REV RES DEV DISA JI Int. Rev. Res. Dev. Disabil. PY 2013 VL 44 BP 281 EP 325 DI 10.1016/B978-0-12-401662-0.00009-9 PG 45 WC Education, Special; Psychology, Multidisciplinary SC Education & Educational Research; Psychology GA BFQ02 UT WOS:000320926000010 ER PT S AU Nishi, H Hashimoto, K Madej, T Panchenko, AR AF Nishi, Hafumi Hashimoto, Kosuke Madej, Thomas Panchenko, Anna R. BE Giraldo, J Ciruela, F TI Evolutionary, Physicochemical, and Functional Mechanisms of Protein Homooligomerization SO OLIGOMERIZATION IN HEALTH AND DISEASE SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID KINASE TYPE M2; COILED-COIL; QUATERNARY STRUCTURE; MYOFIBRILLAR MYOPATHY; DOMAIN INTERACTIONS; CRYSTALLINE STATE; OLIGOMERIC STATE; LEUCINE-ZIPPER; SH3 DOMAIN; HOT-SPOT AB Protein homooligomers afford several important benefits for the cell; they mediate and regulate gene expression, activity of many enzymes, ion channels, receptors, and cell cell adhesion processes. The evolutionary and physical mechanisms of oligomer formation are very diverse and are not well understood. Certain homooligomeric states may be conserved within protein subfamilies and between different subfamilies, therefore providing the specificity to particular substrates while minimizing interactions with unwanted partners. In addition, transitions between different oligomeric states may regulate protein activity and support the switch between different pathways. In this chapter, we summarize the biological importance of homooligomeric assemblies, physicochemical properties of their interfaces, experimental methods for their identification, their evolution, and role in human diseases. C1 [Nishi, Hafumi; Madej, Thomas; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Hashimoto, Kosuke] RIKEN, Om Sci Ctr, Yokohama, Kanagawa, Japan. RP Nishi, H (reprint author), Yokohama City Univ, Yokohama, Kanagawa 232, Japan. RI Ciruela, Francisco/A-5096-2013; OI Ciruela, Francisco/0000-0003-0832-3739; Nishi, Hafumi/0000-0002-0846-0330 FU Intramural NIH HHS [Z99 LM999999] NR 107 TC 10 Z9 10 U1 0 U2 16 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-386931-9 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2013 VL 117 BP 3 EP 24 DI 10.1016/B978-0-12-386931-9.00001-5 PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFV27 UT WOS:000321526600002 PM 23663963 ER PT J AU Cho, HY AF Cho, Hye-Youn TI Genomic Structure and Variation of Nuclear Factor (Erythroid-Derived 2)-Like 2 SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article ID INBRED MOUSE STRAINS; OBSTRUCTIVE PULMONARY-DISEASE; ANTIOXIDANT RESPONSE ELEMENTS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENE PROMOTER POLYMORPHISM; TRANSCRIPTION FACTOR NRF2; SQUAMOUS-CELL CARCINOMAS; LUNG-CANCER; OXIDATIVE STRESS; MOLECULAR-MECHANISMS AB High-density mapping of mammalian genomes has enabled a wide range of genetic investigations including the mapping of polygenic traits, determination of quantitative trait loci, and phylogenetic comparison. Genome sequencing analysis of inbred mouse strains has identified high-density single nucleotide polymorphisms (SNPs) for investigation of complex traits, which has become a useful tool for biomedical research of human disease to alleviate ethical and practical problems of experimentation in humans. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) encodes a key host defense transcription factor. This review describes genetic characteristics of human NRF2 and its homologs in other vertebrate species. NRF2 is evolutionally conserved and shares sequence homology among species. Compilation of publically available SNPs and other genetic mutations shows that human NRF2 is highly polymorphic with a mutagenic frequency of 1 per every 72 bp. Functional at-risk alleles and haplotypes have been demonstrated in various human disorders. In addition, other pathogenic alterations including somatic mutations and misregulated epigenetic processes in NRF2 have led to oncogenic cell survival. Comprehensive information from the current review addresses association of NRF2 variation and disease phenotypes and supports the new insights into therapeutic strategies. C1 NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Cho, HY (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA. EM cho2@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health of the National Institute of Environmental Health Sciences (NIEHS) FX The research related to this paper was supported by the Intramural Research Program of the National Institutes of Health of the National Institute of Environmental Health Sciences (NIEHS). Drs. Steven Kleeberger and Stephanie London at the NIEHS provided excellent critical review of this paper. The author thanks Mrs. Jacqui Marzec for her helpful comments and English editing. NR 77 TC 6 Z9 6 U1 0 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2013 AR UNSP 286524 DI 10.1155/2013/286524 PG 24 WC Cell Biology SC Cell Biology GA 189CT UT WOS:000322245400001 ER PT J AU Desai, SA AF Desai, Sanjay A. TI Insights Gained from P. falciparum Cultivation in Modified Media SO SCIENTIFIC WORLD JOURNAL LA English DT Review ID SURFACE ANION CHANNEL; RED-BLOOD-CELLS; HIGH-THROUGHPUT SCREEN; PLASMODIUM-FALCIPARUM; MALARIA PARASITES; HUMAN-PLASMA; NUTRITIONAL-REQUIREMENTS; CULTURE; ACID; GROWTH AB In vitro cultivation of Plasmodium falciparum, the agent of severe human malaria, has enabled advances in basic research and accelerated the development of new therapies. Since the introduction of in vitro parasite culture nearly 40 years ago, most workers have used a medium consisting of RPMI 1640 medium supplemented with lipids and hypoxanthine. While these standardized conditions yield robust parasite growth and facilitate comparison of results from different studies, they may also lead to implicit assumptions that limit future advances. Here, I review recent studies that used modified culture conditions to challenge these assumptions and explore parasite physiology. The findings are relevant to understanding in vivo parasite phenotypes and the prioritization of antimalarial targets. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 51 TC 2 Z9 2 U1 0 U2 8 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 SCI WORLD J JI Sci. World J. PY 2013 AR 363505 DI 10.1155/2013/363505 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 189DU UT WOS:000322248200001 ER PT J AU Coleman, K Weed, JL Schapiro, SJ AF Coleman, Kristine Weed, James L. Schapiro, Steven J. BE Conn, PM TI Environmental Enrichment for Animals Used in Research SO ANIMAL MODELS FOR THE STUDY OF HUMAN DISEASE LA English DT Article; Book Chapter ID SELF-INJURIOUS-BEHAVIOR; YEARLING RHESUS-MONKEYS; BIOMEDICAL-RESEARCH FACILITIES; PARROTS AMAZONA-AMAZONICA; MACAQUES MACACA-MULATTA; NONHUMAN-PRIMATES; LABORATORY MICE; INDIVIDUAL-DIFFERENCES; NESTING MATERIAL; CAPTIVE CHIMPANZEES C1 [Coleman, Kristine] Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Weed, James L.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. [Schapiro, Steven J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Schapiro, Steven J.] Univ Copenhagen, Copenhagen, Denmark. RP Coleman, K (reprint author), Oregon Natl Primate Res Ctr, Beaverton, OR USA. NR 238 TC 0 Z9 0 U1 2 U2 20 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-415912-9 PY 2013 BP 75 EP 94 DI 10.1016/B978-0-12-415894-8.00004-X PG 20 WC Biology; Medical Ethics SC Life Sciences & Biomedicine - Other Topics; Medical Ethics GA BFR75 UT WOS:000321100200005 ER PT J AU Schindler, CW Goldberg, SR AF Schindler, Charles W. Goldberg, Steven R. BE Conn, PM TI Animal Models of Reward Behavior SO ANIMAL MODELS FOR THE STUDY OF HUMAN DISEASE LA English DT Article; Book Chapter ID SEXUAL REINFORCEMENT; INTRAVENOUS COCAINE; RESPONSE SEQUENCES; FEMALE RATS; SELF; ACQUISITION; OPERANT; SCHEDULES; STIMULI; HYPOTHESIS C1 [Schindler, Charles W.; Goldberg, Steven R.] NIDA, Behav Neurosci Res Branch, Baltimore, MD USA. RP Schindler, CW (reprint author), NIDA, Behav Neurosci Res Branch, Baltimore, MD USA. NR 73 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-415912-9 PY 2013 BP 709 EP 726 DI 10.1016/B978-0-12-415894-8.00029-4 PG 18 WC Biology; Medical Ethics SC Life Sciences & Biomedicine - Other Topics; Medical Ethics GA BFR75 UT WOS:000321100200030 ER PT S AU Nussinov, R Tsai, CJ Ma, BY AF Nussinov, Ruth Tsai, Chung-Jung Ma, Buyong BE Dill, KA TI The Underappreciated Role of Allostery in the Cellular Network SO ANNUAL REVIEW OF BIOPHYSICS, VOL 42 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE cellular pathways; regulation; conformational selection; induced fit; protein dynamics; population shift ID NUCLEAR-MAGNETIC-RESONANCE; PROTEIN-KINASE CASCADE; DRUG DISCOVERY; CONFORMATIONAL SELECTION; SIGNAL-TRANSDUCTION; POPULATION-SHIFT; BINDING-SITES; MOLECULAR-DYNAMICS; ENERGY LANDSCAPES; TYROSINE KINASES AB Allosteric propagation results in communication between distinct sites in the protein structure; it also encodes specific effects on cellular pathways, and in this way it shapes cellular response. One example of long-range effects is binding of morphogens to cell surface receptors, which initiates a cascade of protein interactions that leads to genome activation and specific cellular action. Allosteric propagation results from combinations of multiple factors, takes place through dynamic shifts of conformational ensembles, and affects the equilibria of macromolecular interactions. Here, we (a) emphasize the well-known yet still underappreciated role of allostery in conveying explicit signals across large multimolecular assemblies and distances to specify cellular action; (b) stress the need for quantitation of the allosteric effects; and finally, (c) propose that each specific combination of allosteric effectors along the pathway spells a distinct function. The challenges are colossal; the inspiring reward will be predicting function, misfunction, and outcomes of drug regimes. C1 [Nussinov, Ruth; Tsai, Chung-Jung; Ma, Buyong] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. EM NussinoR@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; PHS HHS [HHSN261200800001E] NR 132 TC 68 Z9 68 U1 5 U2 47 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1842-0 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2013 VL 42 BP 169 EP 189 DI 10.1146/annurev-biophys-083012-130257 PG 21 WC Biophysics SC Biophysics GA BFW68 UT WOS:000321695700009 PM 23451894 ER PT J AU Wong, FC Boja, J Ho, B Kuhar, MJ Wong, DF AF Wong, Franklin C. Boja, John Ho, Beng Kuhar, Michael J. Wong, Dean F. TI Affinity Labeling of Membrane Receptors Using Tissue-Penetrating Radiations SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; H-3 PK 14105; PHOTOAFFINITY LIGAND; DOPAMINE-RECEPTORS; BINDING-SITES; CELL-DAMAGE; RAT-BRAIN; ULTRASOUND; PET; HEMATOPORPHYRIN AB Photoaffinity labeling, a useful in vivo biochemical tool, is limited when applied in vivo because of the poor tissue penetration by ultraviolet (UV) photons. This study investigates affinity labeling using tissue-penetrating radiation to overcome the tissue attenuation and irreversibly label membrane receptor proteins. Using X-ray (115 kVp) at low doses (<50 cGy or Rad), specific and irreversible binding was found on striatal dopamine transporters with 3 photoaffinity ligands for dopamine transporters, to different extents. Upon X-ray exposure (115 kVp), RTI-38 and RTI-78 ligands showed irreversible and specific binding to the dopamine transporter similar to those seen with UV exposure under other conditions. Similarly, gamma rays at higher energy (662 keV) also affect irreversible binding of photoreactive ligands to peripheral benzodiazepine receptors (by PK14105) and to the dopamine (D2) membrane receptors (by azidoclebopride), respectively. This study reports that X-ray and gamma rays induced affinity labeling of membrane receptors in a manner similar to UV with photoreactive ligands of the dopamine transporter, D2 dopamine receptor (D2R), and peripheral benzodiazepine receptor (PBDZR). It may provide specific noninvasive irreversible block or stimulation of a receptor using tissue-penetrating radiation targeting selected anatomic sites. C1 [Wong, Franklin C.; Ho, Beng] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wong, Franklin C.; Wong, Dean F.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA. [Boja, John; Kuhar, Michael J.] Natl Inst Drug Abuse, Addict Res Ctr, Baltimore, MD 21224 USA. [Boja, John] US Consumer Product Safety Commiss, Bethesda, MD 20814 USA. [Kuhar, Michael J.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Wong, Dean F.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Wong, Dean F.] Johns Hopkins Med Inst, Carey Business Sch, Baltimore, MD 21205 USA. RP Wong, FC (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. EM fwong@mdanderson.org OI Wong, Franklin/0000-0002-3449-5836 FU National Institutes of Health [RR00165] FX The authors acknowledge the logistic support of gamma rays irradiation from Raymond Meyn, Ph.D., of the Division of Radiation Oncology, University of Texas MD Anderson Cancer Center. The report work was partially supported by a research Grant RR00165 from the National Institutes of Health to Dr. Michael Kuhar. NR 24 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 503095 DI 10.1155/2013/503095 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 181BS UT WOS:000321643600001 ER PT J AU Ghosh, D Guha, R AF Ghosh, Debarchana (Debs) Guha, Rajarshi TI What are we 'tweeting' about obesity? Mapping tweets with topic modeling and Geographic Information System SO CARTOGRAPHY AND GEOGRAPHIC INFORMATION SCIENCE LA English DT Article DE mapping; social media; topic models; GIS; text mining; obesity AB Public health related tweets are difficult to identify in large conversational datasets like Twitter.com. Even more challenging is the visualization and analyses of the spatial patterns encoded in tweets. This study has the following objectives: how can topic modeling be used to identify relevant public health topics such as obesity on Twitter.com? What are the common obesity related themes? What is the spatial pattern of the themes? What are the research challenges of using large conversational datasets from social networking sites? Obesity is chosen as a test theme to demonstrate the effectiveness of topic modeling using Latent Dirichlet Allocation (LDA) and spatial analysis using Geographic Information System (GIS). The dataset is constructed from tweets (originating from the United States) extracted from Twitter.com on obesity-related queries. Examples of such queries are 'food deserts', 'fast food', and 'childhood obesity'. The tweets are also georeferenced and time stamped. Three cohesive and meaningful themes such as 'childhood obesity and schools', 'obesity prevention', and 'obesity and food habits' are extracted from the LDA model. The GIS analysis of the extracted themes show distinct spatial pattern between rural and urban areas, northern and southern states, and between coasts and inland states. Further, relating the themes with ancillary datasets such as US census and locations of fast food restaurants based upon the location of the tweets in a GIS environment opened new avenues for spatial analyses and mapping. Therefore the techniques used in this study provide a possible toolset for computational social scientists in general, and health researchers in specific, to better understand health problems from large conversational datasets. C1 [Ghosh, Debarchana (Debs)] Univ Connecticut, Dept Geog, Storrs, CT 06040 USA. [Guha, Rajarshi] NIH, Ctr Adv Translat Sci, Rockville, MD 20850 USA. RP Ghosh, D (reprint author), Univ Connecticut, Dept Geog, Storrs, CT 06040 USA. EM debarchana.ghosh@uconn.edu FU Intramural NIH HHS [ZIB TR000004-02] NR 20 TC 23 Z9 24 U1 2 U2 54 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1523-0406 J9 CARTOGR GEOGR INF SC JI Cartogr. Geogr. Inf. Sci. PY 2013 VL 40 IS 2 SI SI BP 90 EP 102 DI 10.1080/15230406.2013.776210 PG 13 WC Geography SC Geography GA 178MP UT WOS:000321452400004 PM 25126022 ER PT J AU Yavlovich, A Viard, M Gupta, K Sine, J Vu, M Blumenthal, R Tata, DB Puri, A AF Yavlovich, Amichai Viard, Mathias Gupta, Kshitij Sine, Jessica Vu, Mylinh Blumenthal, Robert Tata, Darrell B. Puri, Anu TI Low-visibility light-intensity laser-triggered release of entrapped calcein from 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine liposomes is mediated through a type I photoactivation pathway SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE visible laser-triggered payload release; photo-agents; photopolymerizable phospholipids; photodynamic actions; reactive oxygen species ID PHOTODYNAMIC THERAPY; BIOLOGICAL-SYSTEMS; LIPID-BILAYERS; SINGLET OXYGEN; SOLUTE RELEASE; CELLS; DELIVERY; PHOSPHATIDYLCHOLINE; VESICLES; MECHANISMS AB We recently reported on the physical characteristics of photo-triggerable liposomes containing dipalmitoylphosphatidylcholine (DPPC), and 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) carrying a photo agent as their payload. When exposed to a low-intensity 514 nm wavelength (continuous-wave) laser light, these liposomes were observed to release entrapped calcein green (Cal-G; Ex/Em 490/517 nm) but not calcein blue (Cal-B; Ex/Em 360/460 nm). In this study, we have investigated the mechanism for the 514 nm laser-triggered release of the Cal-G payload using several scavengers that are known specifically to inhibit either type I or type II photoreaction pathways. Liposomes containing DPPC:DC8,9PC: distearoylphosphatidylethanolamine (DSPE)-polyethylene glycol (PEG)-2000 (86:10:04 mole ratio) were loaded either with fluorescent (calcein) or nonfluorescent (H-3-inulin) aqueous markers. In addition, a non-photo-triggerable formulation (1-palmitoyl-2-oleoyl phosphatidylcholine [POPC]:DC8,9PC:DSPE-PEG2000) was also studied with the same payloads. The 514 nm wavelength laser exposure on photo-triggerable liposomes resulted in the release of Cal-G but not that of Cal-B or H-3-inulin, suggesting an involvement of a photoactivated state of Cal-G due to the 514 nm laser exposure. Upon 514 nm laser exposures, substantial hydrogen peroxide (H2O2, approximate to 100 mu M) levels were detected from only the Cal-G loaded photo-triggerable liposomes but not from Cal-B-loaded liposomes (<= 10 mu M H2O2). The Cal-G release from photo-triggerable liposomes was found to be significantly inhibited by ascorbic acid (AA), resulting in a 70%-80% reduction in Cal-G release. The extent of AA-mediated inhibition of Cal-G release from the liposomes also correlated with the consumption of AA. No AA consumption was detected in the 514 nm laser-exposed Cal B-loaded liposomes, thus confirming a role of photoactivation of Cal-G in liposome destabilization. Inclusion of 100 mM K3Fe(CN)(6) (a blocker of electron transfer) in the liposomes substantially inhibited Cal-G release, whereas inclusion of 10 mM sodium azide (a blocker of singlet oxygen of type II photoreaction) in the liposomes failed to block 514 nm laser-triggered Cal-G release. Taken together, we conclude that low-intensity 514 nm laser-triggered release of Cal-G from photo-triggerable liposomes involves the type I photoreaction pathway. C1 [Yavlovich, Amichai; Viard, Mathias; Gupta, Kshitij; Sine, Jessica; Vu, Mylinh; Blumenthal, Robert; Puri, Anu] NCI, Nanobiol Program, Ctr Canc Res, Ft Detrick, MD 21702 USA. [Viard, Mathias] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Tata, Darrell B.] US FDA, CDRH, OSEL, Div Phys, White Oak, MD USA. RP Puri, A (reprint author), NCI, Membrane Struct & Funct Sect, Nanobiol Program, Ctr Canc Res, Bldg 469,Room 216A, Ft Detrick, MD 21702 USA. EM puria@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This project was funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Alex Haber and Christopher Connor for their help with the experiments. NR 40 TC 2 Z9 2 U1 0 U2 16 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2013 VL 8 BP 2575 EP 2587 DI 10.2147/IJN.S44993 PG 13 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 185XI UT WOS:000322003800001 PM 23901274 ER PT S AU Maudsley, S Siddiqui, S Martin, B AF Maudsley, Stuart Siddiqui, Sana Martin, Bronwen BE Luttrell, LM TI Systems Analysis of Arrestin Pathway Functions SO MOLECULAR BIOLOGY OF ARRESTINS SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID PROTEIN-COUPLED RECEPTOR; DIFFERENTIALLY EXPRESSED GENES; 7 TRANSMEMBRANE RECEPTORS; BETA-ADRENERGIC-RECEPTOR; TACHYKININ NK2 RECEPTOR; GROWTH-FACTOR RECEPTOR; TERNARY COMPLEX MODEL; DIETARY ENERGY-INTAKE; FALSE DISCOVERY RATE; MASS-SPECTRAL DATA AB To fully appreciate the diversity and specificity of complex cellular signaling events, such as arrestin-mediated signaling from G protein-coupled receptor activation, a complex systems-level investigation currently appears to be the best option. A rational combination of transcriptomics, proteomics, and interactomics, all coherently integrated with applied next-generation bioinformatics, is vital for the future understanding of the development, translation, and expression of GPCR-mediated arrestin signaling events in physiological contexts. Through a more nuanced, systems-level appreciation of arrestin-mediated signaling, the creation of arrestin-specific molecular response "signatures" should be made simple and ultimately amenable to drug discovery processes. Arrestin-based signaling paradigms possess important aspects, such as its specific temporal kinetics and ability to strongly affect transcriptional activity, that make it an ideal test bed for next-generation of drug discovery bioinformatic approaches such as multi-parallel dose response analysis, data texturization, and latent semantic indexing-based natural language data processing and feature extraction. C1 [Maudsley, Stuart; Siddiqui, Sana] NIA, Receptor Pharmacol Unit, Baltimore, MD 21224 USA. [Martin, Bronwen] NIA, Metab Unit, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Baltimore, MD 21224 USA. FU Intramural NIH HHS NR 157 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-394440-5 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2013 VL 118 BP 431 EP 467 DI 10.1016/B978-0-12-394440-5.00017-6 PG 37 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFY19 UT WOS:000321874600018 PM 23764064 ER PT J AU Urbani, A De Canio, M Palmieri, F Sechi, S Bini, L Castagnola, M Fasano, M Modesti, A Roncada, P Timperio, AM Bonizzi, L Brunori, M Cutruzzola, F De Pinto, V Di Ilio, C Federici, G Folli, F Foti, S Gelfi, C Lauro, D Lucacchini, A Magni, F Messana, I Pandolfi, PP Papa, S Pucci, P Sacchetta, P AF Urbani, Andrea De Canio, Michele Palmieri, Ferdinando Sechi, Salvatore Bini, Luca Castagnola, Massimo Fasano, Mauro Modesti, Alessandra Roncada, Paola Timperio, Anna Maria Bonizzi, Luigi Brunori, Maurizio Cutruzzola, Francesca De Pinto, Vito Di Ilio, Carmine Federici, Giorgio Folli, Franco Foti, Salvatore Gelfi, Cecilia Lauro, Davide Lucacchini, Antonio Magni, Fulvio Messana, Irene Pandolfi, Pier Paolo Papa, Sergio Pucci, Piero Sacchetta, Paolo CA Italian Mt-HPP Study Grp-Italian P TI The mitochondrial Italian Human Proteome Project initiative (mt-HPP) SO MOLECULAR BIOSYSTEMS LA English DT Review ID ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASES; RESPIRATORY-CHAIN; FATIGUE-SYNDROME; DYSFUNCTION; CANCER; DNA; METABOLISM; STRESS; MUSCLE AB Mitochondria carry maternally inherited genetic material, called the mitochondrial genome (mtDNA), which can be defined as the 25th human chromosome. The chromosome-centric Human Proteome Project (c-HPP) has initially focused its activities addressing the characterization and quantification of the nuclear encoded proteins. Following the last International HUPO Congress in Boston (September 2012) it was clear that however small the mitochondrial chromosome is, it plays an important role in many biological and physiopathological functions. Mutations in the mtDNA have been shown to be associated with dozens of unexplained disorders and the information contained in the mtDNA should be of major relevance to the understanding of many human diseases. Within this paper we describe the Italian initiative of the Human Proteome Project dedicated to mitochondria as part of both programs: chromosome-centric (c-HPP) and Biology/Disease (B/D-HPP). The mt-HPP has finally shifted the attention of the HUPO community outside the nuclear chromosomes with the general purpose to highlight the mitochondrial processes influencing the human health. Following this vision and considering the large interest and evidence collected on the non-Mendelian heredity of Homo sapiens associated with mt-chromosome and with the microbial commensal ecosystem constituting our organism we may speculate that this program will represent an initial step toward other HPP initiatives focusing on human phenotypic heredity. C1 Univ Roma Tor Vergata, Dept Expt Med & Surg, I-00133 Rome, Italy. [De Canio, Michele] IRCCS Santa Lucia Fdn, Rome, Italy. [De Canio, Michele; Roncada, Paola; Bonizzi, Luigi] Univ Milan, Dipartimento Sci Vet & Sanita Pubbl, Milan, Italy. [Palmieri, Ferdinando] Univ Bari, Dept Biosci Biotechnol & Biopharmaceut, Bari, Italy. [Sechi, Salvatore] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. [Bini, Luca] Univ Siena, Dept Biotechnol, I-53100 Siena, Italy. [Castagnola, Massimo] Cattolica Univ, Biochem & Clin Biochem Inst, Rome, Italy. [Fasano, Mauro] Univ Insubria, Dept Theoret & Appl Sci, Busto Arsizio, Italy. [Modesti, Alessandra] Univ Florence, Dept Biochem, Florence, Italy. [Roncada, Paola] Ist Sperimentale Italiano L Spallanzani, Milan, Italy. [Timperio, Anna Maria] Univ Tuscia, Dept Ecol & Biol Sci, Viterbo, Italy. [Brunori, Maurizio; Cutruzzola, Francesca] Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy. [De Pinto, Vito] Univ Catania, Dept Biol Geol & Environm Sci, Catania, Italy. [Di Ilio, Carmine] CeSI Ctr Excellence Aging, Chieti, Italy. [Di Ilio, Carmine] Univ G dAnnunzio, Dept Expt & Clin Sci, Chieti, Italy. [Federici, Giorgio] IRCCS Children Hosp Bambino Gesu, Rome, Italy. [Folli, Franco] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Foti, Salvatore] Univ Catania, Dept Chem Sci, Catania, Italy. [Gelfi, Cecilia] SysBio Ctr Syst Biol, Milan, Italy. [Gelfi, Cecilia] SysBio Ctr Syst Biol, Rome, Italy. [Gelfi, Cecilia] IBFM CNR, Milan, Italy. [Lauro, Davide] Univ Roma Tor Vergata, Dept Syst Med, I-00133 Rome, Italy. [Lucacchini, Antonio] Univ Pisa, Dept Pharm, Pisa, Italy. [Magni, Fulvio] Bicocca Univ, Dept Expt Med, Milan, Italy. [Messana, Irene] Univ Cagliari, Dept Life & Environm Sci, Cagliari, Italy. [Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Papa, Sergio] CNR, Inst Biomembranes & Bioenerget, I-70126 Bari, Italy. [Pucci, Piero] Univ Naples Federico II, Dipartimento Sci Chim, Naples, Italy. [Urbani, Andrea; Sacchetta, Paolo] Univ G dAnnunzio, Dept Biomed Sci, Chieti, Italy. RP Urbani, A (reprint author), Univ G dAnnunzio, Dept Biomed Sci, Chieti, Italy. EM andrea.urbani@uniroma2.it RI Fasano, Mauro/A-7100-2008; Cutruzzola, Francesca/G-4052-2011; Roncada, Paola/C-5263-2013; Gelfi, Cecilia/L-1490-2016; Magni, Fulvio/A-7340-2014 OI PUCCI, Pietro/0000-0002-5885-1495; Brunori, Maurizio/0000-0002-7795-1635; Lauro, Davide/0000-0002-8597-4415; De Pinto, Vito/0000-0001-5513-2906; Foti, Salvatore/0000-0002-4007-6582; LUCACCHINI, ANTONIO/0000-0002-0917-4491; Bini, Luca/0000-0001-8951-2106; Fasano, Mauro/0000-0003-0628-5871; Cutruzzola, Francesca/0000-0002-4621-2135; Roncada, Paola/0000-0002-0114-5872; BONIZZI, LUIGI/0000-0002-9364-095X; Timperio, Anna Maria/0000-0001-8457-042X; folli, franco/0000-0001-9824-5222; Papa, Sergio/0000-0002-4417-1763; Gelfi, Cecilia/0000-0002-2996-6912; Magni, Fulvio/0000-0002-8663-0374 NR 36 TC 3 Z9 3 U1 0 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2013 VL 9 IS 8 BP 1984 EP 1992 DI 10.1039/c3mb70065h PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174ZV UT WOS:000321199100001 PM 23712443 ER PT J AU Chen, SH Liu, DB Wang, ZH Sun, XL Cui, DX Chen, XY AF Chen, Shouhui Liu, Dingbin Wang, Zhihua Sun, Xiaolian Cui, Daxiang Chen, Xiaoyuan TI Picomolar detection of mercuric ions by means of gold-silver core-shell nanorods SO NANOSCALE LA English DT Article ID ENHANCED RAMAN-SCATTERING; ULTRASENSITIVE DETECTION; COLORIMETRIC DETECTION; AQUEOUS-MEDIA; NANOPARTICLES; MERCURY(II); HG2+; SPECTROSCOPY; SENSITIVITY; MOLECULES AB We report an ultrasensitive and selective probe for detection of mercuric ions using gold-silver core-shell nanorods as the substrate of surface-enhanced Raman scattering. The detection limit of this probe for mercuric ions can be as low as 1 pM. The efficiency of this probe in complex samples was evaluated by allowing detection of spiked mercuric ions in river water and fish samples. C1 [Chen, Shouhui; Cui, Daxiang] Shanghai Jiao Tong Univ, Dept Bionanosci & Engn, Key Lab Thin Film & Microfabricat, Minist Educ,Inst Micronano Sci & Technol, Shanghai 200240, Peoples R China. [Chen, Shouhui; Liu, Dingbin; Wang, Zhihua; Sun, Xiaolian; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Cui, DX (reprint author), Shanghai Jiao Tong Univ, Dept Bionanosci & Engn, Key Lab Thin Film & Microfabricat, Minist Educ,Inst Micronano Sci & Technol, Shanghai 200240, Peoples R China. EM dxcui@sjtu.edu.cn; shawn.chen@nih.gov NR 29 TC 27 Z9 28 U1 7 U2 58 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 J9 NANOSCALE JI Nanoscale PY 2013 VL 5 IS 15 BP 6731 EP 6735 DI 10.1039/c3nr01603j PG 5 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 181NY UT WOS:000321675600011 PM 23793867 ER PT J AU Sun, ZC Huang, P Tong, G Lin, J Jin, A Rong, PF Zhu, L Nie, LM Niu, G Cao, F Chen, XY AF Sun, Zhongchan Huang, Peng Tong, Guang Lin, Jing Jin, Albert Rong, Pengfei Zhu, Lei Nie, Liming Niu, Gang Cao, Feng Chen, Xiaoyuan TI VEGF-loaded graphene oxide as theranostics for multi-modality imaging-monitored targeting therapeutic angiogenesis of ischemic muscle SO NANOSCALE LA English DT Article ID FIBROBLAST GROWTH FACTOR-2; PHOTOTHERMAL THERAPY; PHOTODYNAMIC THERAPY; GENE-THERAPY; MOUSE MODEL; PET; CANCER; INTEGRIN; NANOPARTICLES; DELIVERY AB Herein we report the design and synthesis of multifunctional VEGF-loaded IR800-conjugated graphene oxide (GO-IR800-VEGF) for multi-modality imaging-monitored therapeutic angiogenesis of ischemic muscle. The as-prepared GO-IR800-VEGF positively targets VEGF receptors, maintains an elevated level of VEGF in ischemic tissues for a prolonged time, and finally leads to remarkable therapeutic angiogenesis of ischemic muscle. Although more efforts are required to further understand the in vivo behaviors and the long-term toxicology of GO, our work demonstrates the success of using GO for efficient VEGF delivery in vivo by intravenous administration and suggests the great promise of using graphene oxide in theranostic applications for treating ischemic disease. C1 [Sun, Zhongchan; Cao, Feng] Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China. [Sun, Zhongchan; Huang, Peng; Lin, Jing; Rong, Pengfei; Zhu, Lei; Nie, Liming; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Huang, Peng; Lin, Jing] Shanghai Jiao Tong Univ, Res Inst Micro Nano Sci & Technol, Shanghai 200240, Peoples R China. [Tong, Guang] Fourth Mil Med Univ, Dept Cardiovasc Surg, Xijing Hosp, Xian 710032, Peoples R China. [Jin, Albert] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Zhu, Lei] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361005, Peoples R China. RP Niu, G (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; wind8828@gmail.com; shawn.chen@nih.gov RI Huang, Peng/H-9985-2013; Nie, Liming/F-7718-2016; Zhu, Lei/P-9786-2016; Huang, Peng/R-2480-2016; OI Zhu, Lei/0000-0002-1820-4795; Huang, Peng/0000-0003-3651-7813; Jin, Albert/0000-0003-3826-1081 FU National Key Basic Research Program (973 Project) [2010CB933901, 2012CB518101, 2013CB733802]; National Science Foundation of China [81272987, 31170961, 51102258, 81090274, 81227901]; Zhejiang Province Foundation [LY12H11011]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institutes of Health (NIH) FX This work was supported by the National Key Basic Research Program (973 Project) (2010CB933901, 2012CB518101 and 2013CB733802), the National Science Foundation of China (81272987, 31170961, 51102258, 81090274 and 81227901), Zhejiang Province Foundation (LY12H11011), the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and National Institutes of Health (NIH). NR 44 TC 24 Z9 24 U1 2 U2 32 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 J9 NANOSCALE JI Nanoscale PY 2013 VL 5 IS 15 BP 6857 EP 6866 DI 10.1039/c3nr01573d PG 10 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 181NY UT WOS:000321675600029 PM 23770832 ER PT J AU Janes, DE Elsey, RM Langan, EM Valenzuela, N Edwards, SV AF Janes, D. E. Elsey, R. M. Langan, E. M. Valenzuela, N. Edwards, S. V. TI Sex-Biased Expression of Sex-Differentiating Genes FOXL2 and FGF9 in American Alligators, Alligator mississippiensis SO SEXUAL DEVELOPMENT LA English DT Article DE Exaptation; Organogenesis; qPCR; Sex differentiation; Temperature-dependent sex determination; Thermosensitive period ID MOLECULAR-CLONING; EVOLUTION; TEMPERATURE; REPTILES; CHROMOSOMES; MECHANISMS; AROMATASE; SELECTION; REVERSAL; CHICKEN AB Across amniotes, sex-determining mechanisms exhibit great variation, yet the genes that govern sexual differentiation are largely conserved. Studies of evolution of sex-determining and sex-differentiating genes require an exhaustive characterization of functions of those genes such as FOXL2 and FGF9. FOXL2 is associated with ovarian development, and FGF9 is known to play a role in testicular organogenesis in mammals and other amniotes. As a step toward characterization of the evolutionary history of sexual development, we measured expression of FOXL2 and FGF9 across 3 developmental stages and 8 juvenile tissue types in male and female American alligators, Alligator mississippiensis. We report surprisingly high expression of FOXL2 before the stage of embryonic development when sex is determined in response to temperature, and sustained and variable expression of FGF9 in juvenile male, but not female tissue types. Novel characterization of gene expression in reptiles with temperature-dependent sex determination such as American alligators may inform the evolution of sex-determining and sex-differentiating gene networks, as they suggest alternative functions from which the genes may have been exapted. Future functional profiling of sex-differentiating genes should similarly follow other genes and other species to enable a broad comparison across sex-determining mechanisms. copyright (C) 2013 S. Karger AG, Basel C1 [Janes, D. E.; Edwards, S. V.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Elsey, R. M.] Rockefeller Wildlife Refuge, Louisiana Dept Wildlife & Fisheries, Grand Chenier, LA USA. [Langan, E. M.] Smithsonians Natl Zool Pk, Dept Pathol, Washington, DC USA. [Valenzuela, N.] Iowa State Univ, Dept Ecol Evolut & Organismal Biol, Ames, IA USA. RP Janes, DE (reprint author), Natl Inst Gen Med Sci, NIH, 45 Ctr Dr, Bethesda, MD 20892 USA. EM Daniel.janes@nih.gov OI Edwards, Scott/0000-0003-2535-6217; Valenzuela, Nicole/0000-0003-1148-631X FU National Institutes of Health, National Research Service Award [5F32GM072494]; National Science Foundation [MCB-0817687] FX Alligators were donated by Rockefeller State Wildlife Refuge in Grand Chenier, La., USA. All animal work was approved under Institutional Animal Care and Use Protocol No. 24-06. David Ottenheimer, David Gonzalez Arroyo, Portia Botchway, Randi Griffin, Chris Organ, Andrew Shedlock, Jae Hur, Courtney Stern, and Lewis Ward assisted with sample collection and benchwork. Funding was provided by a National Institutes of Health, National Research Service Award to D.E.J. (5F32GM072494) and by National Science Foundation Grant MCB-0817687 to N.V. and S.V.E. NR 40 TC 2 Z9 2 U1 0 U2 27 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-5425 J9 SEX DEV JI Sex. Dev. PY 2013 VL 7 IS 5 BP 253 EP 260 DI 10.1159/000350787 PG 8 WC Developmental Biology SC Developmental Biology GA 178RI UT WOS:000321464700004 PM 23689672 ER PT S AU Feldmann, F Feldmann, H AF Feldmann, F. Feldmann, H. BE Roth, JA Richt, JA Morozov, IA TI Ebola: Facing a New Transboundary Animal Disease? SO VACCINES AND DIAGNOSTICS FOR TRANSBOUNDARY ANIMAL DISEASES SE Developments in Biologicals LA English DT Proceedings Paper CT Workshop on Vaccines and Diagnostics for Transboundary Animal Diseases CY SEP 17-19, 2012 CL Ames, IA SP US Dept Homeland Secur Sci & Technol Directorate, Kansas State Univ, Coll Vet Med, DHS Ctr Excellence Emerg & Zoonot Anim Dis, Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Inst Int Cooperat Anim Biol, Benchmark Biolabs, Boehringer Ingelheim Vetmedica Inc, Pfizer Animal Hlth, Merial Ltd, World Org Anim Hlth, Int Alliance Biol Standardizat DE Ebola; hemorrhagic fever; pigs; livestock; diagnostics; vaccines ID VACCINES; VIRUS; TRANSMISSION; PIGS AB Ebola viruses are zoonotic pathogens with the potential of causing severe viral hemorrhagic fever in humans and nonhuman primates. Bats have been identified as a reservoir for Ebola viruses but it remains unclear if transmission to an end host involves intermediate hosts. Recently, one of the Ebola species has been found in Philippine pigs raising concerns regarding animal health and food safety. Diagnostics have so far focused on human application, but enhanced pig surveillance and diagnostics, particularly in Asia, for Ebola virus infections seem to be needed to establish reasonable guidelines for public and animal health and food safety. Livestock vaccination against Ebola seems currently not justified but proper preparedness may include experimental vaccine approaches. C1 [Feldmann, F.] NIAID, Off Operat Management, NIH, Rocky Mt Labs, Hamilton, MT USA. RP Feldmann, H (reprint author), NIAID, Virol Lab, DIR, NIH,Rocky Mt Labs, Hamilton, MT USA. EM feldmannh@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 18 TC 5 Z9 6 U1 1 U2 27 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 978-3-318-02365-7 J9 DEV BIOLOGICALS JI Dev. Biols PY 2013 VL 135 BP 201 EP 209 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA BFV96 UT WOS:000321592800021 PM 23689898 ER PT J AU Biesecker, BB Schwartz, MD Marteau, TM AF Biesecker, Barbara Bowles Schwartz, Marc D. Marteau, Theresa M. TI Enhancing Informed Choice to Undergo Health Screening: A Systematic Review SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Review DE prescreening interventions; health screening; randomized control trials; informed choice; systematic review ID RANDOMIZED CONTROLLED-TRIAL; PROSTATE-CANCER; DECISION-MAKING; PATIENT EDUCATION; COLORECTAL-CANCER; MAMMOGRAPHY; IMPACT; INTERVENTIONS; KNOWLEDGE; INFORMATION AB Objective: To assess the effectiveness of health screening interventions aimed at enhancing informed choice. Methods: Studies were selected if (1) they were randomized controlled trials conducted between January 1, 2000, and March 30, 2010, (2) participants in one arm underwent a prescreening intervention aimed at improving informed choice, and (3) informed choice was the primary outcome. Results: Eight studies that met the inclusion criteria involved screening for prostate, colorectal and breast cancer, and diabetes. Five of the 8 prescreening interventions led to greater informed choice. Conclusions: With researchers mindful of the limited number of studies, findings were encouraging, but conclusions regarding the most effective ways of facilitating informed choice for screening are at best tentative. C1 [Biesecker, Barbara Bowles] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Schwartz, Marc D.] Georgetown Univ, Lombardi Canc Ctr, Canc Control Program, Washington, DC USA. [Marteau, Theresa M.] Kings Coll London, Hlth Psychol Sect, Psychol Dept Guys, London WC2R 2LS, England. RP Biesecker, BB (reprint author), NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. EM barbarab@mail.nih.gov OI Marteau, Theresa/0000-0003-3025-1129 FU Intramural NIH HHS [Z99 HG999999] NR 34 TC 8 Z9 8 U1 3 U2 13 PU PNG PUBLICATIONS PI OAK RIDGE PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA SN 1945-7359 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PY 2013 VL 37 IS 3 BP 351 EP 359 DI 10.5993/AJHB.37.3.8 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175ES UT WOS:000321214000008 PM 23985182 ER PT J AU Hunsberger, JG Fessler, EB Chibane, FL Leng, Y Maric, D Elkahloun, AG Chuang, DM AF Hunsberger, Joshua G. Fessler, Emily B. Chibane, Fairouz L. Leng, Yan Maric, Dragan Elkahloun, Abdel G. Chuang, De-Maw TI Mood stabilizer-regulated miRNAs in neuropsychiatric and neurodegenerative diseases: identifying associations and functions SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Article DE microRNA; neuroprotection; glutamate excitotoxicity; lithium; valproic acid; mood stabilizers ID SPORADIC ALZHEIMERS-DISEASE; AUTISM SPECTRUM DISORDERS; MICRORNA EXPRESSION; VALPROIC ACID; PREFRONTAL CORTEX; HUNTINGTONS-DISEASE; ALPHA-SYNUCLEIN; DOWN-REGULATION; RAT MODEL; LITHIUM AB Identifying mechanisms to enhance neuroprotection holds tremendous promise in developing new treatments for neuropsychiatric and neurodegenerative diseases. We sought to determine the potential role for microRNAs (miRNAs) in neuroprotection following neuronal death. A neuronal culture system of rat cerebellar granule cells was used to examine miRNA expression changes following glutamate-induced excitotoxicity and neuroprotective treatments. Combination treatment with the mood stabilizers lithium and valproic acid provided near-complete protection from glutamate excitotoxicity. Numerous miRNAs were detected by microarrays to be regulated by the combined lithium and valproic acid treatment, and the following candidates were confirmed using real-time PCR: miR-34a, miR-147b, miR-182, miR-222, miR-495, and miR-690. We then verified the apoptotic actions of miR-34a mimic in a human neuroblastoma cell line (SH-SY5Y) under basal conditions and following endoplasmic reticulum stress. To gain insight into the function of these mood stabilizer-regulated miRNAs, we performed two separate analyses: a candidate approach using Ingenuity Pathway Analysis that was restricted to only our PCR-verified miRNAs, and a global approach using DIANA-mirPath that included all significantly regulated miRNAs. It was observed that the pathways associated with mood stabilizer-regulated miRNAs in our study (global approach) are strongly associated with pathways implicated in neuropsychiatric diseases such as schizophrenia. We also observed an overlap in the mood stabilizer-regulated miRNAs identified from our study along with dysregulated miRNAs in both neuropsychiatric and neurodegenerative disorders. We anticipate that these associations and overlaps implicate critical pathways and miRNAs in disease mechanisms for novel therapeutic treatments that may hold potential for many neurological diseases. C1 [Hunsberger, Joshua G.; Fessler, Emily B.; Chibane, Fairouz L.; Leng, Yan; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel G.] NHGRI, NIH, Bethesda, MD USA. [Maric, Dragan] NINDS, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, NIH, 10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA. EM hunsbergerj@mail.nih.gov; chuang@mail.nih.gov FU NIMH, NIH FX We would like to acknowledge the support of the Intramural Research Program of the NIMH, NIH. We would also like to acknowledge the technical support kindly provided by Weiwei Wu for microRNA array processing, and the editorial suggestions by Peter Leeds. NR 68 TC 20 Z9 20 U1 0 U2 7 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2013 VL 5 IS 4 BP 450 EP U113 PG 16 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA 172EP UT WOS:000320983100007 PM 23724168 ER PT J AU Weaver, JD Wang, HC Shears, SB AF Weaver, Jeremy D. Wang, Huanchen Shears, Stephen B. TI The kinetic properties of a human PPIP5K reveal that its kinase activities are protected against the consequences of a deteriorating cellular bioenergetic environment SO BIOSCIENCE REPORTS LA English DT Article DE bis-diphosphoinositol tetrakisphosphate; cellular energy homoeostasis; diphosphoinositol pentakisphosphate; diphosphoinositol polyphosphate; inositol pyrophosphate; inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) ID INOSITOL HEXAKISPHOSPHATE KINASE; DIPHOSPHOINOSITOL PENTAKISPHOSPHATE; HYPEROSMOTIC STRESS; ENERGY-METABOLISM; PYROPHOSPHATES; PHOSPHATE; POLYPHOSPHATES; PURIFICATION; TETRAKISPHOSPHATE; IDENTIFICATION AB We obtained detailed kinetic characteristics - stoichiometry, reaction rates, substrate affinities and equilibrium conditions - of human PPIP5K2 (diphosphoinositol pentakisphosphate kinase 2). This enzyme synthesizes 'high-energy' PP-InsPs (diphosphoinositol polyphosphates) by metabolizing InsP(6) (inositol hexakisphosphate) and 5-InsP(7) (5-diphosphoinositol 1,2,3,4,6-pentakisphosphate) to 1-InsP(7) (1-diphosphoinositol 2,3,4,5,6-pentakisphosphate) and InsP(8) (1,5-bis-diphosphoinositol 2,3,4,6-tetrakisphosphate), respectively. These data increase our insight into the PPIP5K2 reaction mechanism and clarify the interface between PPIP5K catalytic activities and cellular bioenergetic status. For example, stochiometric analysis uncovered non-productive, substrate-stimulated ATPase activity (thus, approximately 2 and 1.2 ATP molecules are utilized to synthesize each molecule of 1-InsP(7) and InsP(8), respectively). Impaired ATPase activity of a PPIP5K2-K248A mutant increased atomic-level insight into the enzyme's reaction mechanism. We found PPIP5K2 to be fully reversible as an ATP-synthase in vitro, but our new data contradict previous perceptions that significant 'reversibility' occurs in vivo. PPIP5K2 was insensitive to physiological changes in either [AMP] or [ATP]/[ADP] ratios. Those data, together with adenine nucleotide kinetics (ATP K-m = 20-40 mu M), reveal how insulated PPIP5K2 is from cellular bioenergetic challenges. Finally, the specificity constants for PPIP5K2 revise upwards by one-to-two orders of magnitude the inherent catalytic activities of this enzyme, and we show its equilibrium point favours 80-90% depletion of InsP(6)/5-InsP(7). C1 [Weaver, Jeremy D.; Wang, Huanchen; Shears, Stephen B.] NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM Shears@niehs.nih.gov FU National Institutes of Health/National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health/National Institute of Environmental Health Sciences. NR 56 TC 6 Z9 6 U1 1 U2 9 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0144-8463 J9 BIOSCIENCE REP JI Biosci. Rep. PY 2013 VL 33 BP 229 EP 242 AR UNSP e00022 DI 10.1042/BSR20120115 PN 2 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 175PV UT WOS:000321244100005 PM 23240582 ER PT J AU O'Connor, GM McVicar, DW AF O'Connor, Geraldine M. McVicar, Daniel W. TI The Yin-Yang of KIR3DL1/S1: Molecular Mechanisms and Cellular Function SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE Killer Immunoglobulin-like Receptors; Natural Killer Cells; Human Leukocyte Antigen; Innate Immunity ID IMMUNOGLOBULIN-LIKE RECEPTOR; MHC CLASS-I; HUMAN NK CELLS; NATURAL-KILLER-CELLS; VIRUS TYPE-1 INFECTION; IFN-GAMMA PRODUCTION; HEPATITIS-C-VIRUS; HLA-B; CUTTING EDGE; ANKYLOSING-SPONDYLITIS AB Killer Immunoglobulin-like Receptors (KIR) are a family of receptors expressed on natural killer (NK) and T-cell subsets. KIR3DL1 is a highly polymorphic receptor that binds to groups of HLA-A and HLA-B allotypes that express the Bw4 epitope. The variation in KIR3DL1 allotypes manifests at a number of levels. Most dramatically, a common allelic variant encodes an activating rather than an inhibitory receptor (KIR3DS1). In addition, sequence variants can affect both the frequency of expression within the NK cell population and the intensity of expression on a given cell. KIR3DL1 polymorphism also influences the interaction with HLA-Bw4 molecules, due to contacts with the HLA molecule itself and sensitivity to the presented peptide. A body of evidence from genetic association studies supports the biological significance not only of the interaction of KIR3DL1 with HLA-Bw4 but also the functional variation seen with different KIR3DL1 and HLA allotypes. In this review, we discuss our current understanding of KIR3DL1 function and our recent insights from the structure of the KIR3DL1 in complex with HLA. In addition, we will summarize our current understanding of KIR3DS1, including its ligand specificity and its role in immune responses. C1 [O'Connor, Geraldine M.; McVicar, Daniel W.] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. RP McVicar, DW (reprint author), NCI, Bldg 560 Rm 31-50, Frederick, MD 21702 USA. EM mcvicard@mail.nih.gov RI McVicar, Daniel/G-1970-2015 FU NIH, National Cancer Institute, Center for Cancer Research; National Institutes of Health FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This work was supported by the Intramural AIDS Targeted Antiviral Program of the National Institutes of Health. We thank Dr Steve Anderson for critical review of the manuscript. NR 74 TC 6 Z9 9 U1 0 U2 4 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2013 VL 33 IS 3 BP 203 EP 218 PG 16 WC Immunology SC Immunology GA 171ZD UT WOS:000320968400002 PM 23756244 ER PT S AU Mulkidjanian, AY Galperin, MY AF Mulkidjanian, Armen Y. Galperin, Michael Y. BE Beatty, JT TI A Time to Scatter Genes and a Time to Gather Them: Evolution of Photosynthesis Genes in Bacteria SO GENOME EVOLUTION OF PHOTOSYNTHETIC BACTERIA SE Advances in Botanical Research LA English DT Review; Book Chapter ID COMPLETE GENOME SEQUENCE; CANDIDATUS CHLORACIDOBACTERIUM THERMOPHILUM; ANOXYGENIC PHOTOTROPHIC BACTERIA; GREEN-SULFUR BACTERIUM; CYCLIC ELECTRON-TRANSPORT; ANOXIC GEOTHERMAL FIELDS; REACTION-CENTER COMPLEX; ZINC-SULFIDE; PHOTOSYSTEM-II; HELIOBACTERIUM-MODESTICALDUM AB Genome sequencing opened entirely new avenues for studying the evolution of photosynthesis. By systematically comparing sequences of photosynthesis-related genes and their products in phototrophic members of diverse bacterial lineages, it has become possible to delineate their common and distinct traits, analyse their evolutionary relationships, and reconstruct the likely scenarios for the overall evolution of the photosynthetic machinery. We consider here the comparative genomics data on the distribution of photosynthesis genes among certain representatives of six bacterial phyla, Acidobacteria, Chlorobi, Chloroflexi, Cyanobacteria, Firmicutes, and Proteobacteria and put these data in a broader geochemical context. We address the tentative nature of the first photosynthetic organisms, the driving forces behind their origin, and review the evidence for the early origin of abiogenic photosynthesis. C1 [Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, Osnabruck, Germany. [Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, Sch Bioengn & Bioinformat, Moscow, Russia. [Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia. [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, Osnabruck, Germany. EM amulkid@uos.de RI Mulkidjanian, Armen/J-8086-2013 OI Mulkidjanian, Armen/0000-0001-5844-3064 NR 160 TC 5 Z9 5 U1 0 U2 29 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND SN 0065-2296 BN 978-0-12-397923-0 J9 ADV BOT RES JI Adv. Bot. Res. PY 2013 VL 66 BP 1 EP 35 DI 10.1016/B978-0-12-397923-0.00001-1 PG 35 WC Plant Sciences SC Plant Sciences GA BFV93 UT WOS:000321592500002 ER PT J AU Delaney, KMH Axelrod, KC Buscetta, A Hassell, KL Adams-Graves, PE Seamon, C Kato, GJ Minniti, CP AF Delaney, Kara-Marie H. Axelrod, Karen C. Buscetta, Ashley Hassell, Kathryn L. Adams-Graves, Patricia E. Seamon, Catherine Kato, Gregory J. Minniti, Caterina P. TI LEG ULCERS IN SICKLE CELL DISEASE: CURRENT PATTERNS AND PRACTICES SO HEMOGLOBIN LA English DT Article DE Leg Ulcers; Sickle cell disease; Hydroxyurea (HU); Survey ID PULMONARY-HYPERTENSION; NATURAL-HISTORY; FOOT ULCERS; THERAPY; HYDROXYUREA; ANEMIA; ULCERATION; HEMOLYSIS; TRIAL; ZINC AB Leg ulcers are a debilitating complication of patients with sickle cell disease, and their frequency in North America was reported to be 2.5% by the Cooperative Study of Sickle Cell Disease more than 20 years ago. We sought to determine if the frequency of leg ulcers in sickle cell patients in the United States had declined and to assess which treatments providers use most commonly. We sent an e-mail survey to health professionals belonging to the national Sickle Cell Adult Provider Network. Responses were obtained from 31 of them (26.0%). Most of them (96.0%) reported having some patients with leg ulcers. Providers reported a total of 185 patients with active leg ulcers and 224 in the previous 5 years, for a total of 409 patients. Hb SS (homozygous sickle cell anemia) was the most common genotype of affected individuals, followed by Hb SC (double heterozygote for Hb S [beta 6(A3) Glu -> Val, GAG>GTG; HBB: c.20A>T] and Hb C [beta 6(A3) Glu -> Lys, GAG>AAG; HBB: c.19G>A]). Males showed a 2:1 predominance. Two-thirds of patients were treated with either hydroxyurea (HU) or transfusion therapy and most used compression stockings and topical therapies as directed by wound care services. We conclude that leg ulcers continue to be a debilitating complication of young adults with sickle cell disease, despite improved supportive care and the widespread use of disease modifying agents such HU and transfusion. While some providers offer office-based ulcer care, the majority prefer specialty consultation including podiatry, plastic surgery and dermatology. Despite their frequency, there is no clear consensus among providers as to the best treatment. C1 [Delaney, Kara-Marie H.; Axelrod, Karen C.; Buscetta, Ashley; Seamon, Catherine; Kato, Gregory J.; Minniti, Caterina P.] NHLBI, Bethesda, MD 20892 USA. [Hassell, Kathryn L.] Colorado Sickle Cell Ctr, Aurora, CO USA. [Adams-Graves, Patricia E.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. RP Minniti, CP (reprint author), NHLBI, Hematol Branch, 10 Ctr Dr,Bldg 10-CRC Room 5-5140, Bethesda, MD 20892 USA. EM minnitic@nhlbi.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [ZIA HL006162-01] NR 32 TC 18 Z9 19 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0363-0269 J9 HEMOGLOBIN JI Hemoglobin PY 2013 VL 37 IS 4 BP 325 EP 332 DI 10.3109/03630269.2013.789968 PG 8 WC Biochemistry & Molecular Biology; Hematology SC Biochemistry & Molecular Biology; Hematology GA 174IS UT WOS:000321149500003 PM 23600469 ER PT J AU Kuhrova, P Banas, P Best, RB Sponer, J Otyepka, M AF Kuehrova, Petra Banas, Pavel Best, Robert B. Sponer, Jiri Otyepka, Michal TI Computer folding of RNA tetraloops? Are we there yet? SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 [Kuehrova, Petra; Banas, Pavel; Otyepka, Michal] Palacky Univ, Dept Phys Chem, Fac Sci, Olomouc 77146, Czech Republic. [Kuehrova, Petra; Banas, Pavel; Otyepka, Michal] Palacky Univ, RCPTM, Olomouc 77146, Czech Republic. [Best, Robert B.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Sponer, Jiri; Otyepka, Michal] Acad Sci Czech Republic, Inst Biophys, CS-61265 Brno, Czech Republic. EM petra.kuhrova@upol.cz NR 2 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JAN 1 PY 2013 VL 31 SU 1 SI SI MA 42 BP 25 EP 26 DI 10.1080/07391102.2013.786475 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160VU UT WOS:000320149400043 ER PT J AU Haran, TE Senitzki, A Sharav, J Beno, I Rosenthal, K Jordan, JJ Menendez, D Resnick, MA AF Haran, Tali E. Senitzki, Alon Sharav, Jenia Beno, Itai Rosenthal, Karin Jordan, Jennifer J. Menendez, Daniel Resnick, Michael A. TI Binding and transactivation by the tumor suppression protein p53 are encoded in the differential structural properties of its response elements SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract ID SEQUENCES; REVEALS; RULES C1 [Haran, Tali E.; Senitzki, Alon; Sharav, Jenia; Beno, Itai; Rosenthal, Karin] Technion Israel Inst Technol, Dept Biol, IL-320003 Haifa, Israel. [Jordan, Jennifer J.; Menendez, Daniel; Resnick, Michael A.] NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. EM bitali@tx.technion.ac.il NR 3 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JAN 1 PY 2013 VL 31 SU 1 SI SI MA 60 BP 37 EP 38 DI 10.1080/07391102.2013.786494 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160VU UT WOS:000320149400061 ER PT J AU Cui, F Zhurkin, VB AF Cui, Feng Zhurkin, Victor B. TI Distinct nucleosome organization around p53 response elements associated with cell cycle arrest and apoptosis SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 [Cui, Feng] Rochester Inst Technol, Thomas H Gosnell Sch Life Sci, Rochester, NY 14623 USA. [Zhurkin, Victor B.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM fxcsbi@rit.edu; zhurkin@nih.gov NR 2 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JAN 1 PY 2013 VL 31 SU 1 SI SI MA 62 BP 39 EP 40 DI 10.1080/07391102.2013.786496 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160VU UT WOS:000320149400063 ER PT J AU Panyutin, IG Karamychev, VN Neumann, RD Mazur, S Appella, E Wang, DF Zhurkin, VB AF Panyutin, Igor G. Karamychev, Valery N. Neumann, Ronald D. Mazur, Sharlyn Appella, Ettore Wang, Difei Zhurkin, Victor B. TI Hoogsteen or not Hoogsteen? Iodine-125 radioprobing of the p53-induced DNA deformations SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract ID TETRAMER; COMPLEX C1 [Panyutin, Igor G.; Karamychev, Valery N.; Neumann, Ronald D.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Mazur, Sharlyn; Appella, Ettore; Wang, Difei; Zhurkin, Victor B.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM zhurkin@nih.gov RI Wang, Difei/E-7066-2010 NR 6 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JAN 1 PY 2013 VL 31 SU 1 SI SI MA 64 BP 41 EP 41 DI 10.1080/07391102.2013.786498 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160VU UT WOS:000320149400065 ER PT J AU Subramanian, HKK Bernard, SE Chiang, C Parker, SCJ Tullius, TD AF Subramanian, Hari K. K. Bernard, Sarah E. Chiang, Cheryl Parker, Stephen C. J. Tullius, Thomas D. TI Genome-wide mapping of DNA strand breaks in Saccharomyces cerevisiae SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 [Subramanian, Hari K. K.; Bernard, Sarah E.; Chiang, Cheryl; Tullius, Thomas D.] Boston Univ, Dept Chem, Boston, MA 02215 USA. [Parker, Stephen C. J.] NHGRI, NIH, Bethesda, MD 20892 USA. [Tullius, Thomas D.] Boston Univ, Program Bioinformat, Boston, MA 02215 USA. EM tullius@bu.edu RI Subramanian, Hari/I-8248-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JAN 1 PY 2013 VL 31 SU 1 SI SI MA 120 BP 76 EP 76 DI 10.1080/07391102.2013.786362 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160VU UT WOS:000320149400121 ER PT J AU Panchenko, A AF Panchenko, Anna TI Impact of cancer mutations on protein binding and activity SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 [Panchenko, Anna] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. EM panch@ncbi.nlm.nih.gov NR 3 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JAN 1 PY 2013 VL 31 SU 1 SI SI MA 179 BP 115 EP 116 DI 10.1080/07391102.2013.786421 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160VU UT WOS:000320149400180 ER PT J AU Kolanowski, AM Resnick, B Beck, C Grady, PA AF Kolanowski, Ann M. Resnick, Barbara Beck, Cornelia Grady, Patricia A. TI Advances in Nonpharmacological Interventions, 2011-2012 SO RESEARCH IN GERONTOLOGICAL NURSING LA English DT Editorial Material ID FUNCTION-FOCUSED CARE; NURSING-HOME; OLDER-ADULTS; ALZHEIMERS-DISEASE; RESIDENTS; OSTEOARTHRITIS; FEASIBILITY; TRIAL; SLEEP C1 [Kolanowski, Ann M.] Penn State Univ, Hartford Ctr Geriatr Nursing Excellence, Sch Nursing, University Pk, PA 16802 USA. [Resnick, Barbara] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Beck, Cornelia] Univ Arkansas Med Sci, Dept Nursing, Coll Med, Little Rock, AR 72205 USA. [Grady, Patricia A.] NINR, NIH, Bethesda, MD 20892 USA. RP Kolanowski, AM (reprint author), Penn State Univ, Hartford Ctr Geriatr Nursing Excellence, Sch Nursing, 106 Hlth & Human Dev East, University Pk, PA 16802 USA. EM amk20@psu.edu FU NINR NIH HHS [R01 NR012242] NR 19 TC 2 Z9 2 U1 1 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1940-4921 J9 RES GERONTOL NURS JI Res. Gerontol. Nurs. PD JAN PY 2013 VL 6 IS 1 BP 5 EP 8 DI 10.3928/19404921-20121204-03 PG 4 WC Nursing SC Nursing GA 173TX UT WOS:000321104600002 PM 23327595 ER PT J AU Huzurbazar, S Singh, S Schlueter, JA AF Huzurbazar, Snehalata Singh, Sarabdeep Schlueter, Jessica A. TI Statistical issues associated with modeling of synonymous mutation data SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE Bayesian models; truncation; discrete-continuous mixture distribution; distributional fit; Weibull ID GENOME DUPLICATIONS; EVOLUTION; DISTRIBUTIONS; PLANTS; GENES AB The explosion of data in evolutionary bioinformatics has led to sometimes ad hoc, incomplete and even inaccurate data analyses. Taking dS data, namely, data on synonymous substitutions per synonymous sites, we go through a statistical analysis for modeling the time since duplications of genes. We explore the shortcomings of previous analyses, especially with a view towards their effect on inference for the gene duplication process. We present a statistical analysis which respects the assumptions of the models and the integrity of the data, and emphasize that exploratory data analysis, formulation of a data model, its estimation and finally, assessment of the model are important steps in a complete data analysis. Furthermore, for dS data, we develop Bayesian discrete-continuous mixture models and present analyses using two genomes. C1 [Huzurbazar, Snehalata] Stat & Appl Math Sci Inst, Res Triangle Pk, NC 27709 USA. [Huzurbazar, Snehalata] Univ Wyoming, Dept Stat, Dept 3332, Laramie, WY 82071 USA. [Huzurbazar, Snehalata] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Singh, Sarabdeep] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Schlueter, Jessica A.] Univ N Carolina, Charlotte, NC 28223 USA. RP Huzurbazar, S (reprint author), Stat & Appl Math Sci Inst, 19 TW Alexander Dr,POB 14006, Res Triangle Pk, NC 27709 USA. EM Lata@uwyo.edu RI Singh, Sarabdeep/D-7881-2017 FU National Science Foundation [DMS-1100615, DMS-1127914] FX The three authors' research was supported by a grant to the University of Wyoming from the National Science Foundation under grant DMS-1100615. Huzurbazar's contribution was also based upon work partially supported by the National Science Foundation under Grant DMS-1127914 to the Statistical and Applied Mathematical Sciences Institute. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Huzurbazar and Singh thank David Liberles and Anke Konrad for introducing them to the study of gene duplications and evolutionary bioinformatics in general. All the authors thank the associate editor Vincent Plagnol and two anonymous reviewers for very helpful suggestions. NR 24 TC 0 Z9 0 U1 0 U2 2 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-6302 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2013 VL 12 IS 3 BP 361 EP 374 DI 10.1515/sagmb-2012-0033 PG 14 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 175QW UT WOS:000321247600005 PM 23629458 ER PT J AU Nakajima, T Sano, K Choyke, PL Kobayashi, H AF Nakajima, Takahito Sano, Kohei Choyke, Peter L. Kobayashi, Hisataka TI Improving the Efficacy of Photoimmunotherapy (PIT) using a Cocktail of Antibody Conjugates in a Multiple Antigen Tumor Model SO THERANOSTICS LA English DT Article DE photoimmunotherapy; monoclonal antibody; cocktail; micro-distribution; binding site barrier ID BINDING-SITE BARRIER; LABELED MONOCLONAL-ANTIBODIES; IN-VIVO; UVC IRRADIATION; CANCER-CELLS; GROWTH; PENETRATION; TRANSPORT; MICE AB Tumors are characterized by a high degree of diversity and heterogeneity in receptor expression. Monoclonal antibodies (mAbs) are an established therapeutic method of targeting cell surface receptors. However, high affinity antibodies targeting highly expressed receptors are often prevented from distributing evenly throughout the tumor due to the "binding site barrier" whereby antibody is trapped peripherally before it can reach deeper into the tumor that leads inhomogeneous micro-distribution. When employing armed antibodies it is important that the toxin (in this case, phototoxin) be distributed evenly to more effectively treat the cancer. By adding an additional antibody conjugate, targeting a secondary, unsaturated receptor with lower expression, a more uniform distribution of the phototoxin can be achieved. In this study, panitumumab (Pan) and basiliximab (Bas) were conjugated with the phthalocyanine dye, IRDye700DX (IR700). Upon exposure to near infrared light, these armed antibodies produce rapid cell death only when bound to their respective receptors, a treatment termed photo-immunotherapy (PIT). ATAC4 cells which demonstrate high expression of human epidermal growth factor receptor (EGFR) and low expression of interleukin-2 receptor-alpha (CD25) were treated by PIT using a cocktail of Pan-IR700 and Bas-IR700. An in vivo study showed that the cocktail Pan-Bas-IR700 resulted in significantly reduced tumor growth and prolonged survival in ATAC4 tumor-bearing mice compared with either Pan-IR700 or Bas-IR700 alone. In conclusion, a cocktail injection of two different antibody-IR700 conjugates created a more homogeneous microdistribution of antibody-conjugates resulting in enhanced therapeutic effects after PIT, compared to the use of either antibody-IR700 conjugate. C1 [Nakajima, Takahito; Sano, Kohei; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,RoomB3B69,MSC1088, Bethesda, MD 20892 USA. EM Koba-yash@mail.nih.gov FU Intramural Research Program of the U.S. NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the U.S. NIH, National Cancer Institute, Center for Cancer Research. NR 28 TC 34 Z9 34 U1 0 U2 8 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2013 VL 3 IS 6 BP 357 EP 365 DI 10.7150/thno.5908 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 173DK UT WOS:000321058100001 PM 23781283 ER PT J AU Rio, DE Rawlings, RR Woltz, LA Gilman, J Hommer, DW AF Rio, Daniel E. Rawlings, Robert R. Woltz, Lawrence A. Gilman, Jodi Hommer, Daniel W. TI Development of the Complex General Linear Model in the Fourier Domain: Application to fMRI Multiple Input-Output Evoked Responses for Single Subjects SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article ID TIME-SERIES ANALYSIS; STATISTICAL-ANALYSIS; SENSORY STIMULATION; FUNCTIONAL MRI; BRAIN; NOISE; IMAGE; ACTIVATION; INFERENCE AB A linear time-invariantmodel based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function. C1 [Rio, Daniel E.; Rawlings, Robert R.; Hommer, Daniel W.] NIAAA, Sect Brain Electrophysiol & Imaging, LCTS, NIH, Bethesda, MD 90034 USA. [Woltz, Lawrence A.] Synergy Res Inc, Monrovia, MD USA. [Gilman, Jodi] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Lab Neuroimaging & Genet, Charlestown, MA USA. RP Rio, DE (reprint author), NIAAA, Sect Brain Electrophysiol & Imaging, LCTS, NIH, 10 Ctr Dr,MSC 1540, Bethesda, MD 90034 USA. EM drio@nih.gov NR 44 TC 0 Z9 0 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2013 AR UNSP 645043 DI 10.1155/2013/645043 PG 16 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 169PE UT WOS:000320791500001 ER PT J AU Jo, HJ Gotts, SJ Reynolds, RC Bandettini, PA Martin, A Cox, RW Saad, ZS AF Jo, Hang Joon Gotts, Stephen J. Reynolds, Richard C. Bandettini, Peter A. Martin, Alex Cox, Robert W. Saad, Ziad S. TI Effective Preprocessing Procedures Virtually Eliminate Distance-Dependent Motion Artifacts in Resting State FMRI SO JOURNAL OF APPLIED MATHEMATICS LA English DT Article ID FUNCTIONAL CONNECTIVITY; MRI; REGRESSION AB Artifactual sources of resting-state (RS) FMRI can originate from head motion, physiology, and hardware. Of these sources, motion has received considerable attention and was found to induce corrupting effects by differentially biasing correlations between regions depending on their distance. Numerous corrective approaches have relied on the identification and censoring of high-motion time points and the use of the brain-wide average time series as a nuisance regressor to which the data are orthogonalized (Global Signal Regression, GSReg). We replicate the previously reported head-motion bias on correlation coefficients and then show that while motion can be the source of artifact in correlations, the distance-dependent bias is exacerbated by GSReg. Put differently, correlation estimates obtained after GSReg are more susceptible to the presence of motion and by extension to the levels of censoring. More generally, the effect of motion on correlation estimates depends on the preprocessing steps leading to the correlation estimate, with certain approaches performing markedly worse than others. For this purpose, we consider various models for RS FMRI preprocessing and show that the local white matter regressor (WMeLOCAL), a subset of ANATICOR, results in minimal sensitivity to motion and reduces by extension the dependence of correlation results on censoring. C1 [Jo, Hang Joon; Bandettini, Peter A.] NIMH, Sect Funct ImagingMethods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Gotts, Stephen J.; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Reynolds, Richard C.; Cox, Robert W.; Saad, Ziad S.] NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA. RP Jo, HJ (reprint author), NIMH, Sect Funct ImagingMethods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM joh21@mail.nih.gov RI JO, HANG JOON/D-1775-2011 OI JO, HANG JOON/0000-0002-9180-3831 FU NIMH; NINDS Intramural Research Programs of the NIH FX This study was greatly facilitated by the generous contribution of data by the authors of Power et al. 2012. The authors thank Kelly Barnes for helpful discussions. This research was supported by the NIMH and NINDS Intramural Research Programs of the NIH. NR 12 TC 26 Z9 26 U1 0 U2 13 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-757X J9 J APPL MATH JI J. Appl. Math. PY 2013 AR 935154 DI 10.1155/2013/935154 PG 9 WC Mathematics, Applied SC Mathematics GA 169TX UT WOS:000320804400001 ER PT J AU Galli, G Piaggi, P Mattingly, MS de Jonge, L Courville, AB Pinchera, A Santini, F Csako, G Cizza, G AF Galli, G. Piaggi, P. Mattingly, M. S. de Jonge, L. Courville, A. B. Pinchera, A. Santini, F. Csako, G. Cizza, G. CA Sleep Extension Study Grp TI Inverse relationship of food and alcohol intake to sleep measures in obesity SO NUTRITION & DIABETES LA English DT Article DE sleep apnea; public health; CPAP; epidemic ID GHRELIN LEVELS; DIETARY-FAT; ENERGY-EXPENDITURE; RISK-FACTORS; DURATION; DEPRIVATION; QUALITY; ADULTS; EPIDEMIC; APNEA AB BACKGROUND: Short sleep and weight gain are inversely related. Sleep deprivation acutely increases food intake but little is known about eating behavior in chronically sleep-deprived, obese individuals. OBJECTIVE: To characterize the relationship between sleep, food intake and alcohol consumption under free-living conditions in obese, chronically sleep-deprived individuals. DESIGN: Cross-sectional study of a cohort of obese men and premenopausal women. SUBJECTS: A total of 118 obese subjects (age: 40.3 +/- 6.7 years; 91 females/27 males; body mass index 38.7 +/- 6.4 kgm(-2)). MEASUREMENTS: Energy, macronutrient, alcohol and caffeine intake assessed by 3-day food records. Sleep duration estimated by actigraphy. Respiratory disturbance index assessed by a portable device. RESULTS: Subjects slept 360.7 +/- 50.2 min per night and had a total energy intake of 2279.1 +/- 689 kcal per day. Sleep duration and energy intake were inversely related (r = -0.230, P = 0.015). By extrapolation, each 30-min deficit per day in sleep duration would translate to an similar to 83 kcal per day increase in energy intake. In addition, sleep apnea was associated with a shift from carbohydrate to fat intake. Alcohol intake in subjects consuming >3.5 g of alcohol per day (N = 41) was inversely related to sleep duration (r = -0.472, P = 0.002). CONCLUSIONS: Shorter sleep duration and obstructive sleep apnea are associated with higher energy, fat and alcohol intakes in obese individuals. The importance of this study relies on the population studied, obese subjects with chronic sleep deprivation. These novel findings apply to the large segment of the US population who are obese and sleep-deprived. C1 [Galli, G.; Mattingly, M. S.; de Jonge, L.; Cizza, G.] NIDDK, Sect Neuroendocrinol Obes, DEOB, Bethesda, MD 20892 USA. [Galli, G.; Piaggi, P.; Pinchera, A.; Santini, F.] Univ Hosp Pisa, Dept Endocrinol, Pisa, Italy. [Piaggi, P.] Univ Pisa, Dept Energy & Syst Engn, Pisa, Italy. [Courville, A. B.] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA. [Csako, G.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Cizza, G (reprint author), NIDDK, Sect Neuroendocrinol Obes, DEOB, NIH, Bldg 10,CRC,Rm 6-3940, Bethesda, MD 20892 USA. EM cizzag@intra.niddk.nih.gov OI Piaggi, Paolo/0000-0003-2774-9161 FU National Institutes of Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [06-DK-0036]; Clinical Center, National Institutes of Health (NIH) FX This study was fully supported by the National Institutes of Health (NIH), Intramural Research Program: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This study was supported by the Intramural Program of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) and the Clinical Center, National Institutes of Health (NIH). This study was conducted under the NIDDK protocol 06-DK-0036 and is listed in ClinicalTrials.gov (identifier: NCT00261898). We would like to thank in alphabetical order the following colleagues for their scientific advice and critical suggestions in the development and conduct of the study protocol: Karim Calis, Janet Gershengorn, Gregor Hasler, Emmanuel Mignot, Susan Redline, Kristina I Rother, Terry Phillips, Nancy Sebring, Duncan Wallace, Robert Wesley, Elizabeth Wright. We would also like to thank the members of the study team: Peter Bailey, Laide Bello, Meredith Coyle, Paula Marincola, Patrick Michaels, Svetlana Primma, Angela Ramer, Rebecca Romero, Megan Sabo, Tanner Slayden, Sara Torvik, Sam Zuber, Elizabeth Widen and Lyda Williams. The bioinformatics support of Frank Pierce (Esprit Health) is gratefully acknowledged. Finally we are grateful to all of our enthusiastic study participants. NR 59 TC 9 Z9 9 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-4052 J9 NUTR DIABETES JI Nutr. Diabetes PD JAN PY 2013 VL 3 AR UNSP e58 DI 10.1038/nutd.2012.33 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 171IY UT WOS:000320920700001 PM 23357877 ER PT J AU Boskey, AL Verdelis, K Spevak, L Lukashova, L Beniash, E Yang, X Cabral, WA Marini, JC AF Boskey, Adele L. Verdelis, Kostas Spevak, Lyudmila Lukashova, Lyudmila Beniash, Elia Yang, Xu Cabral, Wayne A. Marini, Joan C. TI Mineral and Matrix Changes in Brtl/ plus Teeth Provide Insights into Mineralization Mechanisms SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID D-RESISTANT RICKETS; OSTEOGENESIS IMPERFECTA; MOUSE MODEL; DENTINOGENESIS IMPERFECTA; HELICAL DOMAIN; MURINE MODEL; I COLLAGEN; PHENOTYPE; ENAMEL; BONE AB The Brtl/+ mouse is a knock-in model for osteogenesis imperfecta type IV in which a Gly349Cys substitution was introduced into one COL1A1 allele. To gain insight into the changes in dentin structure and mineral composition in these transgenic mice, the objective of this study was to use microcomputed tomography (micro-CT), scanning electron microscopy (SEM), and Fourier transform infrared imaging (FTIRI) to analyze these structures at 2 and 6 months of age. Results, consistent with the dental phenotype in humans with type IVOI, showed decreased molar volume and reduced mineralized tissue volume in the teeth without changes in enamel properties. Increased acid phosphate content was noted at 2 and 6 months by FTIRI, and a trend towards altered collagen structure was noted at 2 but not 6 months in the Brtl/+ teeth. The increase in acid phosphate content suggests a delay in the mineralization process, most likely associated with the defect in the collagen structure. It appears that in the Brtl/+ teeth slow maturation of the mineralized structures allows correction of altered mineral content and acid phosphate distribution. C1 [Boskey, Adele L.; Spevak, Lyudmila; Lukashova, Lyudmila] Hosp Special Surg, Musculoskeletal Integr Program, New York, NY 10021 USA. [Verdelis, Kostas] Univ Pittsburgh, Sch Dent Med, Dept Endodont, Pittsburgh, PA 15261 USA. [Beniash, Elia; Yang, Xu] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Pittsburgh, PA 15261 USA. [Cabral, Wayne A.; Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. RP Boskey, AL (reprint author), Hosp Special Surg, Musculoskeletal Integr Program, 535 E 70th St, New York, NY 10021 USA. EM boskeya@hss.edu OI Boskey, Adele/0000-0002-6181-2219 FU NIH [DE04141, AR046121]; NICHD FX This work is supported by NIH Grants DE04141 and AR046121 (toAdele L. Boskey) and by the NICHD Intramural Funding to Joan C. Marini. NR 36 TC 3 Z9 3 U1 0 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 295812 DI 10.1155/2013/295812 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 162KF UT WOS:000320263200001 ER PT J AU Chen, DY Song, PS Hong, JS Chu, CL Pan, IH Chen, YM Lin, CH Lin, SH Lin, CC AF Chen, Der-Yuan Song, Pei-Shan Hong, Jau-Shyong Chu, Ching-Liang Pan, I-Horng Chen, Yi-Ming Lin, Ching-Hsiung Lin, Sheng-Hao Lin, Chi-Chen TI Dextromethorphan Inhibits Activations and Functions in Dendritic Cells SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; ADAPTIVE IMMUNE-RESPONSES; TOLL-LIKE-RECEPTORS; REGULATORY T-CELLS; SIGNALING PATHWAYS; OXIDATIVE STRESS; NADPH OXIDASE; CROSS-TALK; TNF-ALPHA; MATURATION AB Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-gamma secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-kappa B translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS- induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. C1 [Chen, Der-Yuan; Song, Pei-Shan; Lin, Sheng-Hao; Lin, Chi-Chen] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 402, Taiwan. [Chen, Der-Yuan] Natl Yang Ming Univ, Fac Med, Taipei 112, Taiwan. [Chen, Der-Yuan; Chen, Yi-Ming] Taichung Vet Gen Hosp, Div Allergy Immunol & Rheumatol, Taichung 407, Taiwan. [Hong, Jau-Shyong] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. [Chu, Ching-Liang] Natl Taiwan Univ, Grad Inst Immunol, Coll Med, Taipei 100, Taiwan. [Pan, I-Horng] Ind Technol Res Inst, Biomed Technol & Device Res Labs, Hsinchu 300, Taiwan. [Chen, Yi-Ming] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan. [Lin, Ching-Hsiung; Lin, Sheng-Hao] Changhua Christian Hosp, Div Chest Med, Dept Internal Med, Changhua 500, Taiwan. [Lin, Ching-Hsiung] Chang Jung Christian Univ, Dept Resp Care, Coll Hlth Sci, Tainan 711, Taiwan. [Lin, Ching-Hsiung] Chung Shan Med Univ, Sch Med, Taichung 402, Taiwan. [Lin, Chi-Chen] Taichung Vet Gen Hosp, Dept Med Res & Educ, Taichung 407, Taiwan. RP Lin, CC (reprint author), Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 402, Taiwan. EM lincc@dragon.nchu.edu.tw OI Chu, Ching-Liang/0000-0002-8463-526X; Chen, Yi-Ming/0000-0001-7593-3065 FU Taichung Veterans General Hospital Taichung, Taiwan [TCVGH-1017323D]; Ministry of Education, Taiwan under the ATU plan; STSP Grant [EG310815101] FX This study was supported by grants from the Taichung Veterans General Hospital Taichung, Taiwan (TCVGH-1017323D), by the Ministry of Education, Taiwan under the ATU plan (for C.C. Lin), and by STSP Grant EG310815101 (for C. L. Chu). NR 59 TC 6 Z9 6 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2013 AR 125643 DI 10.1155/2013/125643 PG 11 WC Immunology SC Immunology GA 162AU UT WOS:000320237400001 ER PT J AU Laiyemo, AO Doubeni, C Pinsky, PF Doria-Rose, VP Marcus, PM Schoen, RE Lanza, E Cross, AJ AF Laiyemo, Adeyinka O. Doubeni, Chyke Pinsky, Paul F. Doria-Rose, V. Paul Marcus, Pamela M. Schoen, Robert E. Lanza, Elaine Cross, Amanda J. TI Factors Associated with the Risk of Adenoma Recurrence in Distal and Proximal Colon SO DIGESTION LA English DT Article DE Adenomatous polyps; Colonoscopy; Advanced adenoma; Proximal adenoma; Distal adenoma ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLORECTAL-CANCER; NEGATIVE COLONOSCOPY; PREVENTION; TRIAL; CELECOXIB AB Background/Aims: Colonoscopy may be less effective in preventing cancer in the proximal colon. We evaluated whether risk factors for adenoma recurrence exhibit differential effect on adenoma recurrence by colon subsite. Methods: We examined the association of age, sex, body mass index, smoking status and use of nonsteroidal anti-inflammatory drugs (NSAIDs) on proximal and distal adenoma recurrence among 1,864 participants in the Polyp Prevention Trial. We used multinomial logistic regression models to calculate the relative risk ratios (RRR) and 95% CI. Results: 733 (39.3%) participants had adenoma recurrence (228 distal only, 369 proximal only and 136 synchronous proximal and distal adenoma). When compared to participants without adenoma recurrence, no factor was associated with an increased risk of distal only adenoma recurrence. Age 65-69 years (RRR = 1.47, 95% CI 1.00-2.16), age years (RRR = 2.24, 95% CI 1.57-3.20), and male sex (RRR = 1.73, 95% CI 1.32-2.27) were positively associated with proximal only adenoma recurrence. NSAIDs use was associated with a reduced risk of adenoma recurrence by similar magnitude in distal (RRR = 0.78, 95% CI 0.58-1.07) and proximal colon (RRR = 0.77,95% CI 0.60-1.00). Conclusions: We did not find any modifiable risk factor that differentially increases proximal as compared to distal adenoma recurrence to be clinically useful for targeted intervention. Copyright (C) 2013 S. Karger AG, Basel C1 [Laiyemo, Adeyinka O.] Howard Univ, Coll Med, Dept Med, Div Gastroenterol, Washington, DC 20060 USA. [Laiyemo, Adeyinka O.] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Pinsky, Paul F.] NCI, Early Detect Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Doria-Rose, V. Paul; Marcus, Pamela M.] NCI, Hlth Serv & Econ Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Lanza, Elaine] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cross, Amanda J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Doubeni, Chyke] Univ Massachusetts, Dept Family Med, Worcester, MA 01605 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Med & Epidemiol, Pittsburgh, PA USA. RP Laiyemo, AO (reprint author), Howard Univ, Coll Med, Dept Med, Div Gastroenterol, 2041 Georgia Ave NW, Washington, DC 20060 USA. EM adeyinka.laiyemo@howard.edu OI Doubeni, Chyke/0000-0001-7495-0285; Doria-Rose, Vincent/0000-0002-8802-5143 FU National Cancer Institute [5K01CA127118-03]; National Cancer Institute's new faculty recruitment supplement [5U54CA091431-09 S1]; Howard University Cancer Center; Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins University FX Funding was from the National Cancer Institute. No author has any financial interests that may be relevant to the submitted work. An abstract from this study was presented as an oral presentation during Digestive Diseases Week in Chicago in 2009.; Dr. Laiyemo is supported by the National Cancer Institute's new faculty recruitment supplement to the Comprehensive Minority Institution/Cancer Center Partnership between, Howard University Cancer Center and Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins University (5U54CA091431-09 S1).; Dr. Doubeni is supported by a mentored career development award (5K01CA127118-03) from the National Cancer Institute. NR 24 TC 6 Z9 6 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 J9 DIGESTION JI Digestion PY 2013 VL 87 IS 3 BP 141 EP 146 DI 10.1159/000346281 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 162WC UT WOS:000320295700002 PM 23548665 ER PT J AU Jang, H Connelly, L Arce, FT Ramachandran, S Lal, R Kagan, BL Nussinov, R AF Jang, Hyunbum Connelly, Laura Arce, Fernando Teran Ramachandran, Srinivasan Lal, Ratnesh Kagan, Bruce L. Nussinov, Ruth TI Alzheimer's disease: which type of amyloid-preventing drug agents to employ? SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID A-BETA OLIGOMERS; PROTEIN MISFOLDING DISEASES; ATOMIC-FORCE MICROSCOPY; FORMS ION CHANNELS; ALL-D-ENANTIOMER; LIPID-BILAYERS; PORE FORMATION; MEMBRANE FRAGMENTATION; SECONDARY STRUCTURE; CALCIUM-CHANNELS AB The current paradigm in the amyloid hypothesis brands small beta-amyloid (A beta) oligomers as the toxic species in Alzheimer's disease (AD). These oligomers are fibril-like; contain beta-sheet structure, and present exposed hydrophobic surface. Oligomers with this motif are capable of penetrating the cell membrane, gathering to form toxic ion channels. Current agents suppressing precursor A beta cleavage have only met partial success; and to date, those targeting the peptides and their assemblies in the aqueous environment of the extracellular space largely fail in clinical trials. One possible reason is failure to reach membrane-embedded targets of disease 'infected' cells. Here we provide an overview, point to the need to account for the lipid environment when aiming to prevent the formation of toxic channels, and propose a combination therapy to target the species spectrum. C1 [Jang, Hyunbum; Nussinov, Ruth] NCI, Ctr Canc Res, Nanobiol Program, Basic Sci Program,SAIC Frederick Inc, Frederick, MD 21702 USA. [Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA. [Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Mat Sci Program, La Jolla, CA 92093 USA. [Kagan, Bruce L.] Univ Calif Los Angeles, Dept Psychiat, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Kagan, BL (reprint author), Univ Calif Los Angeles, Dept Psychiat, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. EM bkagan@mednet.ucla.edu; nussinor@helix.nih.gov RI Ramachandran, Srinivasan/G-5300-2010 OI Ramachandran, Srinivasan/0000-0002-4912-0279 FU Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; NIH, Frederick National Lab, Center for Cancer Research; National Institutes of Health (National Institute on Aging ) [AG028709] FX We thank Dr Bertini for providing us with the coordinates of the A beta11-40 oligomer. This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. This research was supported [in part] by the Intramural Research Program of NIH, Frederick National Lab, Center for Cancer Research. This research was supported by the National Institutes of Health (National Institute on Aging AG028709 to RL). All simulations had been performed using the high-performance computational facilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 104 TC 24 Z9 24 U1 2 U2 35 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2013 VL 15 IS 23 BP 8868 EP 8877 DI 10.1039/c3cp00017f PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 148YN UT WOS:000319285000002 PM 23450150 ER PT J AU Bailey, JF Liebenberg, E Fields, AJ Mattison, JA Lotz, JC Kramer, PA AF Bailey, Jeannie F. Liebenberg, Ellen Fields, Aaron J. Mattison, Julie A. Lotz, Jeffrey C. Kramer, Patricia A. TI Relating posture to spinal osteoarthritis: histological evidence SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 82nd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-13, 2013 CL Knoxville, TN SP Amer Assoc Phys Anthropologists C1 [Bailey, Jeannie F.; Kramer, Patricia A.] Univ Washington, Seattle, WA 98195 USA. [Liebenberg, Ellen; Fields, Aaron J.; Lotz, Jeffrey C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mattison, Julie A.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2013 VL 150 SU 56 SI SI BP 71 EP 72 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 132BR UT WOS:000318043201034 ER PT J AU Feldblum, JT Wroblewski, EW Rudicell, RS Hahn, BH Pusey, AE Gilby, IC AF Feldblum, Joseph T. Wroblewski, Emily W. Rudicell, Rebecca S. Hahn, Beatrice H. Pusey, Anne E. Gilby, Ian C. TI Male chimpanzee aggression toward females: A test of the sexual coercion hypothesis. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 82nd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-13, 2013 CL Knoxville, TN SP Amer Assoc Phys Anthropologists C1 [Feldblum, Joseph T.; Pusey, Anne E.; Gilby, Ian C.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27706 USA. [Wroblewski, Emily W.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. [Rudicell, Rebecca S.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2013 VL 150 SU 56 SI SI BP 122 EP 122 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 132BR UT WOS:000318043201252 ER PT J AU Fourie, N Bernstein, R Porter, L Garber, P AF Fourie, Nicolaas Bernstein, Robin Porter, Leila Garber, Paul TI Hair cortisol concentrations in wild saddle back tamarins (Saguinus fuscicollis weddelli). SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 82nd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-13, 2013 CL Knoxville, TN SP Amer Assoc Phys Anthropologists C1 [Fourie, Nicolaas] NINR, NIH, Bethesda, MD 20892 USA. [Bernstein, Robin] George Washington Univ, Dept Anthropol, Washington, DC 20052 USA. [Porter, Leila] No Illinois Univ, Dept Anthropol, De Kalb, IL 60115 USA. [Garber, Paul] Univ Illinois, Dept Anthropol, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2013 VL 150 SU 56 SI SI BP 124 EP 125 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 132BR UT WOS:000318043201261 ER PT J AU Keller, MF Nalls, MA Singleton, A AF Keller, Margaux F. Nalls, Michael A. Singleton, Andrew TI Genome-wide associations for Parkinson's disease on the X chromosome. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 82nd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-13, 2013 CL Knoxville, TN SP Amer Assoc Phys Anthropologists C1 [Keller, Margaux F.] Temple Univ, Dept Biol Anthropol, Philadelphia, PA 19122 USA. [Keller, Margaux F.; Nalls, Michael A.; Singleton, Andrew] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2013 VL 150 SU 56 SI SI BP 164 EP 165 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 132BR UT WOS:000318043201430 ER PT J AU Schroepfer-Walker, KK Pusey, A Rudicell, RS Ramirez, MA Hahn, BH Wroblewski, E AF Schroepfer-Walker, Kara K. Pusey, Anne Rudicell, Rebecca S. Ramirez, Miguel A. Hahn, Beatrice H. Wroblewski, Emily TI Females select mates that are less related than expected among the Gombe chimpanzees. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 82nd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-13, 2013 CL Knoxville, TN SP Amer Assoc Phys Anthropologists C1 [Schroepfer-Walker, Kara K.; Pusey, Anne] Duke Univ, Durham, NC 27706 USA. [Rudicell, Rebecca S.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Ramirez, Miguel A.; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Ramirez, Miguel A.; Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wroblewski, Emily] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2013 VL 150 SU 56 SI SI BP 246 EP 246 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 132BR UT WOS:000318043202275 ER PT J AU Seraphin, SB Whitten, PL Sanchez, MM Winslow, JT AF Seraphin, Sally B. Whitten, Patricia L. Sanchez, M. Mar Winslow, James T. TI The neuroendocrinology, behavioral pharmacology and frontal neuroanatomy of dopamine in mother-reared and nursery-reared rhesus monkeys (Macaca mulatta). SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 82nd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-13, 2013 CL Knoxville, TN SP Amer Assoc Phys Anthropologists C1 [Seraphin, Sally B.; Whitten, Patricia L.] Emory Univ, Dept Anthropol, Lab Reprod Ecol & Environm Toxicol, Atlanta, GA 30322 USA. [Sanchez, M. Mar] Emory Univ, Dept Psychiat & Behav Sci, Sch Med, Atlanta, GA 30322 USA. [Winslow, James T.] NIMH, Nonhuman Primate Res Core, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2013 VL 150 SU 56 SI SI BP 250 EP 250 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 132BR UT WOS:000318043202294 ER PT J AU Wilson, ML Wroblewski, EE Mjungu, DC Kamenya, S Rudicell, RS Hahn, BH Pusey, AE AF Wilson, Michael L. Wroblewski, Emily E. Mjungu, Deus C. Kamenya, Shadrack Rudicell, Rebecca S. Hahn, Beatrice H. Pusey, Anne E. TI Trade-offs between intra-group reproductive competition and inter-group territorial competition in male chimpanzees. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 82nd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-13, 2013 CL Knoxville, TN SP Amer Assoc Phys Anthropologists C1 [Wilson, Michael L.] Univ Minnesota, Dept Anthropol, Minneapolis, MN 55455 USA. [Wilson, Michael L.] Univ Minnesota, Dept Ecol Evolut & Behav, Minneapolis, MN 55455 USA. [Wroblewski, Emily E.] Stanford Univ, Dept Biol Struct, Stanford, CA 94305 USA. [Mjungu, Deus C.; Kamenya, Shadrack] Jane Goodall Inst, Gombe Stream Res Ctr, Arlington, VA USA. [Rudicell, Rebecca S.] NIH, Vaccine Res Ctr, Bethesda, MD USA. [Hahn, Beatrice H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Pusey, Anne E.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2013 VL 150 SU 56 SI SI BP 293 EP 293 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 132BR UT WOS:000318043202480 ER EF