12 research outputs found

    Measurement of event-shape observables in Z→ℓ+ℓ− events in pp collisions at √ s=7 TeV with the ATLAS detector at the LHC

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    Event-shape observables measured using charged particles in inclusive ZZ-boson events are presented, using the electron and muon decay modes of the ZZ bosons. The measurements are based on an integrated luminosity of 1.1fb−11.1 {\rm fb}^{-1} of proton--proton collisions recorded by the ATLAS detector at the LHC at a centre-of-mass energy s=7\sqrt{s}=7 TeV. Charged-particle distributions, excluding the lepton--antilepton pair from the ZZ-boson decay, are measured in different ranges of transverse momentum of the ZZ boson. Distributions include multiplicity, scalar sum of transverse momenta, beam thrust, transverse thrust, spherocity, and F\mathcal{F}-parameter, which are in particular sensitive to properties of the underlying event at small values of the ZZ-boson transverse momentum. The Sherpa event generator shows larger deviations from the measured observables than Pythia8 and Herwig7. Typically, all three Monte Carlo generators provide predictions that are in better agreement with the data at high ZZ-boson transverse momenta than at low ZZ-boson transverse momenta and for the observables that are less sensitive to the number of charged particles in the event.Comment: 36 pages plus author list + cover page (54 pages total), 14 figures, 4 tables, submitted to EPJC, All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2014-0

    SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

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    Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

    PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial

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    Background and Purpose-Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≄36.5°C. In the present trial, we aimed to confirm this finding. Methods-PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Results-Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Conclusions-Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed

    Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

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    We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery

    A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee

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    Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. METHODS: CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group. INTERPRETATION: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin

    Search for a heavy Standard Model Higgs boson in the channel H→ZZ→l+l−qqˉH\rightarrow ZZ\rightarrow l^{+}l^{-} q\bar{q} using the ATLAS detector

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    A search for a heavy Standard Model Higgs boson decaying via H->ZZ->llqq, where l=e,mu, is presented. The search is performed using a data set of pp collisions at sqrt(s)=7 TeV, corresponding to an integrated luminosity of 1.04 fb^-1 collected in 2011 by the ATLAS detector at the CERN LHC collider. No significant excess of events above the estimated background is found. Upper limits at 95% confidence level on the production cross section (relative to that expected from the Standard Model) of a Higgs boson with a mass in the range between 200 and 600 GeV are derived. Within this mass range, there is at present insufficient sensitivity to exclude a Standard Model Higgs boson. For a Higgs boson with a mass of 360 GeV, where the sensitivity is maximal, the observed and expected cross section upper limits are factors of 1.7 and 2.7, respectively, larger than the Standard Model prediction.Comment: 11 pages plus author list (26 pages total), 4 figures, 1 table, final version to appear in Physics Letters

    Charged-particle multiplicities in <i>pp</i> interactions at &#8730;s = 900 GeV measured with the ATLAS detector at the LHC

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    The first measurements from proton–proton collisions recorded with the ATLAS detector at the LHC are presented. Data were collected in December 2009 using a minimum-bias trigger during collisions at a centre-of-mass energy of 900 GeV. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity, and the relationship between mean transverse momentum and charged-particle multiplicity are measured for events with at least one charged particle in the kinematic range |η|&#60;2.5 and pT&#62;500 MeV. The measurements are compared to Monte Carlo models of proton–proton collisions and to results from other experiments at the same centre-of-mass energy. The charged-particle multiplicity per event and unit of pseudorapidity at η=0 is measured to be1.333&#177;0.003(stat.)&#177;0.040(syst.), which is 5–15% higher than the Monte Carlo models predict

    Search for Diphoton Events with Large Missing Transverse Energy in 7 TeV Proton-Proton Collisions with the ATLAS Detector

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    A search for diphoton events with large missing transverse energy is presented. The data were collected with the ATLAS detector in proton-proton collisions at √s=7  [square root of s=7] TeV at the CERN Large Hadron Collider and correspond to an integrated luminosity of 3.1  pb-1 [pb superscript -1]. No excess of such events is observed above the standard model background prediction. In the context of a specific model with one universal extra dimension with compactification radius R and gravity-induced decays, values of 1/R<729  GeV are excluded at 95% C. L., providing the most sensitive limit on this model to date.United States. Dept. of EnergyNational Science Foundation (U.S.

    Measurement of the isolated diphoton cross section in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

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    15 pages plus author list (27 pages total), 9 figures, 2 tables, submitted to Phys. Rev. DThe ATLAS experiment has measured the production cross-section of events with two isolated photons in the final state, in proton-proton collisions at sqrt(s) = 7 TeV. The full data set acquired in 2010 is used, corresponding to an integrated luminosity of 37 pb-1. The background, consisting of hadronic jets and isolated electrons, is estimated with fully data-driven techniques and subtracted. The differential cross-sections, as functions of the di-photon mass, total transverse momentum and azimuthal separation, are presented and compared to the predictions of next-to-leading-order QCD
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