51 research outputs found

    Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

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    A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

    NF-Y Dependent Epigenetic Modifications Discriminate between Proliferating and Postmitotic Tissue

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    The regulation of gene transcription requires posttranslational modifications of histones that, in concert with chromatin remodeling factors, shape the structure of chromatin. It is currently under intense investigation how this structure is modulated, in particular in the context of proliferation and differentiation. Compelling evidence suggests that the transcription factor NF-Y acts as a master regulator of cell cycle progression, activating the transcription of many cell cycle regulatory genes. However, the underlying molecular mechanisms are not yet completely understood. Here we show that NF-Y exerts its effect on transcription through the modulation of the histone “code”. NF-Y colocalizes with nascent RNA, while RNA polymerase II is I phosphorylated on serine 2 of the YSPTSPS repeats within its carboxyterminal domain and histones are carrying modifications that represent activation signals of gene expression (H3K9ac and PAN-H4ac). Comparing postmitotic muscle tissue from normal mice and proliferating muscles from mdx mice, we demonstrate by chromatin immunoprecipitation (ChIP) that NF-Y DNA binding activity correlates with the accumulation of acetylated histones H3 and H4 on promoters of key cell cycle regulatory genes, and with their active transcription. Accordingly, p300 is recruited onto the chromatin of NF-Y target genes in a NF-Y-dependent manner, as demonstrated by Re-ChIP. Conversely, the loss of NF-Y binding correlates with a decrease of acetylated histones, the recruitment of HDAC1, and a repressed heterochromatic state with enrichment of histones carrying modifications known to mediate silencing of gene expression (H3K9me3, H3K27me2 and H4K20me3). As a consequence, NF-Y target genes are downregulated in this context. In conclusion, our data indicate a role of NF-Y in modulating the structure and transcriptional competence of chromatin in vivo and support a model in which NF-Y-dependent histone “code” changes contribute to the proper discrimination between proliferating and postmitotic cells in vivo and in vitro

    Oral Rabies Vaccination in North America: Opportunities, Complexities, and Challenges

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    Steps to facilitate inter-jurisdictional collaboration nationally and continentally have been critical for implementing and conducting coordinated wildlife rabies management programs that rely heavily on oral rabies vaccination (ORV). Formation of a national rabies management team has been pivotal for coordinated ORV programs in the United States of America. The signing of the North American Rabies Management Plan extended a collaborative framework for coordination of surveillance, control, and research in border areas among Canada, Mexico, and the US. Advances in enhanced surveillance have facilitated sampling of greater scope and intensity near ORV zones for improved rabies management decision-making in real time. The value of enhanced surveillance as a complement to public health surveillance was best illustrated in Ohio during 2007, where 19 rabies cases were detected that were critical for the formulation of focused contingency actions for controlling rabies in this strategically key area. Diverse complexities and challenges are commonplace when applying ORV to control rabies in wild meso-carnivores. Nevertheless, intervention has resulted in notable successes, including the elimination of an arctic fox (Vulpes lagopus) rabies virus variant in most of southern Ontario, Canada, with ancillary benefits of elimination extending into Quebec and the northeastern US. Progress continues with ORV toward preventing the spread and working toward elimination of a unique variant of gray fox (Urocyon cinereoargenteus) rabies in west central Texas. Elimination of rabies in coyotes (Canis latrans) through ORV contributed to the US being declared free of canine rabies in 2007. Raccoon (Procyon lotor) rabies control continues to present the greatest challenges among meso-carnivore rabies reservoirs, yet to date intervention has prevented this variant from gaining a broad geographic foothold beyond ORV zones designed to prevent its spread from the eastern US. Progress continues toward the development and testing of new bait-vaccine combinations that increase the chance for improved delivery and performance in the diverse meso-carnivore rabies reservoir complex in the US

    Mortality Trends in Pacific Island States

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    Mortality is an essential measure of the health of populations. Examining mortality trends over time allows governments and development partners to better understand key priorities for intervention, whether health investments are having the desired impact, and how the health of the population is changing over time. This report examines mortality trends through measures of infant mortality rate (IMR) ‐ deaths in children aged <1 year per 1000 live births; under five mortality rate (U5MR) ‐ deaths in children aged less than 5 years per 1000 live births; and life expectancy (LE) ‐ average number of years a person could expect to live given the currentconditions for males and females. These are important development indicators, both for the health sector and in a broader development context

    Diabetes and obesity trends in Tonga over 40 years

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    Diabetes incidence and projections from prevalence surveys in Samoa over 1978–2013

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    OBJECTIVES: This study estimates type 2 diabetes (T2DM) incidence in Samoans aged 25-64 years from sequential, irregularly spaced, cross-sectional population prevalence surveys. METHODS: T2DM prevalence from eight population surveys conducted over 1978-2013 (n = 12,516) was adjusted for census region, sex, and 5-year age group to the nearest previous census. Annual T2DM incidence was calculated from adjusted prevalences (by sex), using birth cohorts constructed from age-period matrices. Projections of T2DM incidence to 2020 were estimated, based on various scenarios of population weight change using Poisson regression. RESULTS: Over 1978-2013, T2DM incidence was estimated to increase from 1.12 to 8.44 per 1000 person-years in men and from 2.55 to 8.04 per 1000 in women. Based on regression modeling, if mean population weight was stabilized from 2013, absolute incidence reductions of 0.9 per 1000 person-years (7% lower) are predicted in 2020, compared to the current period trend in weight gain. CONCLUSIONS: T2DM incidence can be calculated from irregularly conducted population risk factor surveys which may be useful in developing countries with limited resources

    Diabetes incidence and projections from prevalence surveys in Fiji

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    Background: Type 2 diabetes mellitus (T2DM) incidence is traditionally derived from cohort studies that are notalways feasible, representative, or available. The present study estimates T2DM incidence in Fijian adults from T2DMprevalence estimates assembled from surveys of 25–64 year old adults conducted over 30 years (n = 14,288).Methods: T2DM prevalence by five-year age group from five population-based risk factor surveys conducted over1980–2011 were variously adjusted for urban-rural residency, ethnicity, and sex to previous censuses (1976, 1986, 1996,2009) to improve representativeness. Prevalence estimates were then used to calculate T2DM incidence based on birthcohorts from the age-period (Lexis) matrix following the Styblo technique, first used to estimate annual risk oftuberculosis infection (incidence) from sequential Mantoux population surveys. Poisson regression of year, age,sex, and ethnicity strata (n = 160) was used to develop projections of T2DM prevalence and incidence to 2020based on various scenarios of population weight measured by body mass index (BMI) change.Results: T2DM prevalence and annual incidence increased in Fiji over 1980–2011. Prevalence was higher in Indiansand men than i-Taukei and women. Incidence was higher in Indians and women. From regression analyses, absolutereductions of 2.6 to 5.1% in T2DM prevalence (13–26% lower), and 0.5–0.9 per 1000 person-years in incidence (8–14%lower), could be expected in 2020 in adults if mean population weight could be reduced by 1–4 kg, compared to thecurrent period trend in weight gain.Conclusions: This is the first application of the Styblo technique to calculate T2DM incidence from population-basedprevalence surveys over time. Reductions in population BMI are predicted to reduce T2DM incidence and prevalence inFiji among adults aged 25–64 year
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