233 research outputs found

    Large Scale Comparative Codon-Pair Context Analysis Unveils General Rules that Fine-Tune Evolution of mRNA Primary Structure

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    BACKGROUND: Codon usage and codon-pair context are important gene primary structure features that influence mRNA decoding fidelity. In order to identify general rules that shape codon-pair context and minimize mRNA decoding error, we have carried out a large scale comparative codon-pair context analysis of 119 fully sequenced genomes. METHODOLOGIES/PRINCIPAL FINDINGS: We have developed mathematical and software tools for large scale comparative codon-pair context analysis. These methodologies unveiled general and species specific codon-pair context rules that govern evolution of mRNAs in the 3 domains of life. We show that evolution of bacterial and archeal mRNA primary structure is mainly dependent on constraints imposed by the translational machinery, while in eukaryotes DNA methylation and tri-nucleotide repeats impose strong biases on codon-pair context. CONCLUSIONS: The data highlight fundamental differences between prokaryotic and eukaryotic mRNA decoding rules, which are partially independent of codon usage

    Association between hepatitis B virus infection and metabolic syndrome: a retrospective cohort study in Shanghai, China

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    Background: Metabolic syndrome (MS) and hepatitis B (HBV) infection are two major public health problems in China. There are few studies about their association, and the results of these studies are contradictory. We conducted a retrospective cohort study to assess the association between MS and HBV in a Shanghai community-based cohort. Methods: Nine hundred seventy-six Shanghai residents were recruited from the Putuo community. 480 HBV infections were in exposed group and 496 non-infections in unexposed group. All metabolic-related parameters and hepatitis B serology were tested with routine biochemical or immunological methods. “Exposed” was defined by HBV infection represented by hepatitis B surface antigen (HBsAg) and without anti-virus treatment. “Unexposed” were subjects who didn’t infect with HBV (Represented by HBsAg) and no MS when they entered the cohort. MS was defined based on the updated National Cholesterol Education Program Adult Treatment Panel III criteria. The Cox proportional hazards model was used to estimate the hazard ratios (HR) and related 95% confidence intervals (95% CI) for the association between HBV infection and MS over a 20-year follow-up period. Results: Of 976 subjects recruited, 480 had latent HBV infection (exposed subjects). After adjusting for age, the crude HR was 2.46 (95% CI: 1.77, 3.41). After adjusting for potential risk factors of MS (age, gender, smoking, passive smoking, alcohol consumption, physical activity, and diet), the HR was 2.27 (95% CI: 1.52, 3.38). Conclusions: This 20-year follow-up retrospective cohort study in Shanghai showed a positive association between HBV infection and MS

    The structure and function of Alzheimer's gamma secretase enzyme complex

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    The production and accumulation of the beta amyloid protein (Aβ) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer’s disease (AD). A multi-subunit enzyme complex, referred to as gamma (γ) secretase, plays a pivotal role in the generation of Aβ from its parent molecule, the amyloid precursor protein (APP). Four core components (presenilin, nicastrin, aph-1, and pen-2) interact in a high-molecular-weight complex to perform intramembrane proteolysis on a number of membrane-bound proteins, including APP and Notch. Inhibitors and modulators of this enzyme have been assessed for their therapeutic benefit in AD. However, although these agents reduce Aβ levels, the majority have been shown to have severe side effects in pre-clinical animal studies, most likely due to the enzymes role in processing other proteins involved in normal cellular function. Current research is directed at understanding this enzyme and, in particular, at elucidating the roles that each of the core proteins plays in its function. In addition, a number of interacting proteins that are not components of γ-secretase also appear to play important roles in modulating enzyme activity. This review will discuss the structural and functional complexity of the γ-secretase enzyme and the effects of inhibiting its activity

    Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

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    This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

    Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

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    A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

    Accuracy versus precision in boosted top tagging with the ATLAS detector

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    Abstract The identification of top quark decays where the top quark has a large momentum transverse to the beam axis, known as top tagging, is a crucial component in many measurements of Standard Model processes and searches for beyond the Standard Model physics at the Large Hadron Collider. Machine learning techniques have improved the performance of top tagging algorithms, but the size of the systematic uncertainties for all proposed algorithms has not been systematically studied. This paper presents the performance of several machine learning based top tagging algorithms on a dataset constructed from simulated proton-proton collision events measured with the ATLAS detector at √ s = 13 TeV. The systematic uncertainties associated with these algorithms are estimated through an approximate procedure that is not meant to be used in a physics analysis, but is appropriate for the level of precision required for this study. The most performant algorithms are found to have the largest uncertainties, motivating the development of methods to reduce these uncertainties without compromising performance. To enable such efforts in the wider scientific community, the datasets used in this paper are made publicly available.</jats:p

    Combination and summary of ATLAS dark matter searches interpreted in a 2HDM with a pseudo-scalar mediator using 139 fb−1 of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si157.svg"><mml:mrow><mml:msqrt><mml:mrow><mml:mi>s</mml:mi></mml:mrow></mml:msqrt><mml:mo linebreak="goodbreak" linebreakstyle="after">=</mml:mo><mml:mn>13</mml:mn></mml:mrow></mml:math> TeV pp collision data

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    Results from a wide range of searches targeting different experimental signatures with and without missing transverse momentum ( ) are used to constrain a Two–Higgs-Doublet Model (2HDM) with an additional pseudo-scalar mediating the interaction between ordinary and dark matter (2HDM + a). The analyses use up to 139 fb−1 of proton–proton collision data at a centre-of-mass energy TeV recorded with the ATLAS detector at the Large Hadron Collider during 2015–2018. The results from three of the most sensitive searches are combined statistically. These searches target signatures with large and a leptonically decaying Z boson; large and a Higgs boson decaying to bottom quarks; and production of charged Higgs bosons in final states with top and bottom quarks, respectively. Constraints are derived for several common and new benchmark scenarios in the 2HDM + a
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