44 research outputs found

    Meeting Report: Hazard Assessment for Nanoparticles—Report from an Interdisciplinary Workshop

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    In this report we present the findings from a nanotoxicology workshop held 6–7 April 2006 at the Woodrow Wilson International Center for Scholars in Washington, DC. Over 2 days, 26 scientists from government, academia, industry, and nonprofit organizations addressed two specific questions: what information is needed to understand the human health impact of engineered nanoparticles and how is this information best obtained? To assess hazards of nanoparticles in the near-term, most participants noted the need to use existing in vivo toxicologic tests because of their greater familiarity and interpretability. For all types of toxicology tests, the best measures of nanoparticle dose need to be determined. Most participants agreed that a standard set of nanoparticles should be validated by laboratories worldwide and made available for benchmarking tests of other newly created nanoparticles. The group concluded that a battery of tests should be developed to uncover particularly hazardous properties. Given the large number of diverse materials, most participants favored a tiered approach. Over the long term, research aimed at developing a mechanistic understanding of the numerous characteristics that influence nanoparticle toxicity was deemed essential. Predicting the potential toxicity of emerging nanoparticles will require hypothesis-driven research that elucidates how physicochemical parameters influence toxic effects on biological systems. Research needs should be determined in the context of the current availability of testing methods for nanoscale particles. Finally, the group identified general policy and strategic opportunities to accelerate the development and implementation of testing protocols and ensure that the information generated is translated effectively for all stakeholders

    A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA–based Regulation of Viral Processes

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    Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA–RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA–RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA–based interaction spanning ∼3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes

    Convergence in insulin resistance between very severely obese and lean women at the end of pregnancy

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    AIMS: Disrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity. Our aim was to study metabolism in such pregnancies. METHODS: We recruited a longitudinal cohort of very severely obese (n = 190) and lean (n = 118) glucose-tolerant women for anthropometric and metabolic measurements at early, mid and late gestation and postpartum. In case–control studies of very severely obese and lean women we measured glucose and glycerol turnover during low- and high-dose hyperinsulinaemic–euglycaemic clamps (HEC) at early and late pregnancy and in non-pregnant women (each n = 6–9) and body fat distribution by MRI in late pregnancy (n = 10/group). RESULTS: Although greater glucose, insulin, NEFA and insulin resistance (HOMA-IR), and greater weight and % fat mass (FM) was observed in very severely obese vs lean participants, the degree of worsening was attenuated in the very severely obese individuals with advancing gestation, with no difference in triacylglycerol (TG) concentrations between very severely obese and lean women at term. Enhanced glycerol production was observed in early pregnancy only in very severely obese individuals, with similar intrahepatic FM in very severely obese vs lean women by late gestation. Offspring from obese mothers were heavier (p = 0.04). CONCLUSIONS/INTERPRETATION: Pregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women. Increased glycerol production is confined to obese women in early pregnancy and obese and lean individuals have similar intrahepatic FM by term. When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3708-3) contains peer-reviewed but unedited supplementary material, which is available to authorised users

    Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

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    Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/μL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence

    Impact of electrical contacts design and materials on the stability of Ti superconducting transition shape

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    The South Pole Telescope SPT-3G camera utilizes Ti/Au transition edge sensors (TESs). A key requirement for these sensors is reproducibility and long-term stability of the superconducting (SC) transitions. Here, we discuss the impact of electrical contacts design and materials on the shape of the SC transitions. Using scanning electron microscope, atomic force microscope, and optical differential interference contrast microscopy, we observed the presence of unexpected defects of morphological nature on the titanium surface and their evolution in time in proximity to Nb contacts. We found direct correlation between the variations of the morphology and the SC transition shape. Experiments with different diffusion barriers between TES and Nb leads were performed to clarify the origin of this problem. We have demonstrated that the reproducibility of superconducting transitions can be significantly improved by preventing diffusion processes in the TES–leads contact areas

    Performance and characterization of the SPT-3G digital frequency-domain multiplexed readout system using an improved noise and crosstalk model

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    The third-generation South Pole Telescope camera (SPT-3G) improves upon its predecessor (SPTpol) by an order of magnitude increase in detectors on the focal plane. The technology used to read out and control these detectors, digital frequency-domain multiplexing (DfMUX), is conceptually the same as used for SPTpol, but extended to accommodate more detectors. A nearly 5× expansion in the readout operating bandwidth has enabled the use of this large focal plane, and SPT-3G performance meets the forecasting targets relevant to its science objectives. However, the electrical dynamics of the higher-bandwidth readout differ from predictions based on models of the SPTpol system due to the higher frequencies used and parasitic impedances associated with new cryogenic electronic architecture. To address this, we present an updated derivation for electrical crosstalk in higher-bandwidth DfMUX systems and identify two previously uncharacterized contributions to readout noise, which become dominant at high bias frequency. The updated crosstalk and noise models successfully describe the measured crosstalk and readout noise performance of SPT-3G. These results also suggest specific changes to warm electronics component values, wire-harness properties, and SQUID parameters, to improve the readout system for future experiments using DfMUX, such as the LiteBIRD space telescope

    Die Auswirkungen des 11. September 2001 auf die transatlantischen Beziehungen = The Effect of September 11, 2001 on the Transatlantic relationship. ZEI Discussion Paper: 2003, C 118

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    [Table of Contents]. "Rally the World" – Die Vereinigten Staaten von Amerika und die transatlantischen Beziehungen seit dem 11. September, by Andrew B. Denison; Das europäisch-amerikanische Verhältnis seit dem 11. September 2001, by Lothar Ruhl; Die transatlantischen Beziehungen seit dem 11. September, by Bassam Tibi

    Spatial cluster modelling

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    Research has generated a number of advances in methods for spatial cluster modelling in recent years, particularly in the area of Bayesian cluster modelling. Along with these advances has come an explosion of interest in the potential applications of this work, especially in epidemiology and genome research. In one integrated volume, this book reviews the state-of-the-art in spatial clustering and spatial cluster modelling, bringing together research and applications previously scattered throughout the literature. It begins with an overview of the field, then presents a series of chapters that illuminate the nature and purpose of cluster modelling within different application areas, including astrophysics, epidemiology, ecology, and imaging. The focus then shifts to methods, with discussions on point and object process modelling, perfect sampling of cluster processes, partitioning in space and space-time, spatial and spatio-temporal process modelling, nonparametric methods for clustering, and spatio-temporal cluster modelling. Many figures, some in full color, complement the text, and a single section of references cited makes it easy to locate source material. Leading specialists in the field of cluster modelling authored each chapter, and an introduction by the editors to each chapter provides a cohesion not typically found in contributed works. Spatial Cluster Modelling thus offers a singular opportunity to explore this exciting new field, understand its techniques, and apply them in your own research

    Shades of multilateralism U.S. perspectives on Europe's role in the war on terrorism

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    Der vorliegende Beitrag untersucht, inwiefern sich die sicherheitspolitische Rolle der Europaeer aus Sicht der USA seit dem 11. September 2001 veraendert hat und weiter veraendern muesste. Zunaechst erfolgt eine Definition der zentralen Begriffe dieses Artikels, wie z.B. Terrorismus, Zusammenarbeit und Partnerschaft. Danach erklaert der Autor kurz die us-amerikanische Aufstandsbekaempfungsstrategie. Im Anschluss daran wird auf die Rolle eingegangen, die die europaeischen Regierungen, aus Sicht der US-Administration, in der Welt haben. Auf dieser Basis werden die Auswirkungen auf die transatlantische Zusammenarbeit, unter besonderer Beruecksichtigung geopolitischer Interessen, analysiert. Im Mittelpunkt stehen dabei folgende drei Fragen: (1) Was ist der Unterschied zwischen Macht- und Kostenteilung? (2) Welche Beziehungen hat Europa zur Welt? (3) Wie gestalten sich die us-amerikanisch-europaeischen Beziehungen? Es wird deutlich, dass ein transatlantisches Antiterror-Netzwerk, das die Interessen beider Partner beruecksichtigt, sowohl fuer Europa als auch fuer die USA von Vorteil sein kann. (ICD)German title: Schattierungen des Multilateralismus: us-amerikanische Ansichten ueber die Rolle Europas im Krieg gegen den TerrorismusAvailable from http://www.zei.de/download/zei dp/dp c106 denison.pdf / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman
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