631 research outputs found

    Enumerating Pathways of Proton Abstraction Based on a Spatial and Electrostatic Analysis of Residues in the Catalytic Site

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    The pathways of proton abstraction (PA), a key aspect of most catalytic reactions, is often controversial and highly debated. Ultrahigh-resolution diffraction studies, molecular dynamics, quantum mechanics and molecular mechanic simulations are often adopted to gain insights in the PA mechanisms in enzymes. These methods require expertise and effort to setup and can be computationally intensive. We present a push button methodology – Proton abstraction Simulation (PRISM) – to enumerate the possible pathways of PA in a protein with known 3D structure based on the spatial and electrostatic properties of residues in the proximity of a given nucleophilic residue. Proton movements are evaluated in the vicinity of this nucleophilic residue based on distances, potential differences, spatial channels and characteristics of the individual residues (polarity, acidic, basic, etc). Modulating these parameters eliminates their empirical nature and also might reveal pathways that originate from conformational changes. We have validated our method using serine proteases and concurred with the dichotomy in PA in Class A β-lactamases, both of which are hydrolases. The PA mechanism in a transferase has also been corroborated. The source code is made available at www.sanchak.com/prism

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Clinical associations and prognostic value of MRI-visible perivascular spaces in patients with ischemic stroke or TIA: a pooled analysis

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    BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH

    Measurement of fiducial and differential W+W- production cross-sections at √s=13 TeV with the ATLAS detector

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    A measurement of fiducial and differential cross-sections for W+W- production in proton–proton collisions at s=13 TeV with the ATLAS experiment at the Large Hadron Collider using data corresponding to an integrated luminosity of 36.1 fb - 1 is presented. Events with one electron and one muon are selected, corresponding to the decay of the diboson system as WW→ e±νμ∓ν. To suppress top-quark background, events containing jets with a transverse momentum exceeding 35 GeV are not included in the measurement phase space. The fiducial cross-section, six differential distributions and the cross-section as a function of the jet-veto transverse momentum threshold are measured and compared with several theoretical predictions. Constraints on anomalous electroweak gauge boson self-interactions are also presented in the framework of a dimension-six effective field theory

    Search for top-philic heavy resonances in pp collisions at s=13 TeV with the ATLAS detector

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    A search for the associated production of a heavy resonance with a top-quark or a top-antitop-quark pair, and decaying into a tt¯ pair is presented. The search uses the data recorded by the ATLAS detector in pp collisions at s=13 TeV at the Large Hadron Collider during the years 2015–2018, corresponding to an integrated luminosity of 139 fb-1. Events containing exactly one electron or muon are selected. The two hadronically decaying top quarks from the resonance decay are reconstructed using jets clustered with a large radius parameter of R=1. The invariant mass spectrum of the two top quark candidates is used to search for a resonance signal in the range of 1.0 TeV to 3.2 TeV. The presence of a signal is examined using an approach with minimal model dependence followed by a model-dependent interpretation. No significant excess is observed over the background expectation. Upper limits on the production cross section times branching ratio at 95% confidence level are provided for a heavy Z′ boson based on a simplified model, for Z′ mass between 1.0 TeV and 3.0 TeV. The observed (expected) limits range from 21 (14) fb to 119 (86) fb depending on the choice of model parameters

    A precise measurement of the Z-boson double-differential transverse momentum and rapidity distributions in the full phase space of the decay leptons with the ATLAS experiment at s=8 TeV

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    This paper presents for the first time a precise measurement of the production properties of the Z boson in the full phase space of the decay leptons. This is in contrast to the many previous precise unfolded measurements performed in the fiducial phase space of the decay leptons. The measurement is obtained from proton–proton collision data collected by the ATLAS experiment in 2012 at s=8 TeV at the LHC and corresponding to an integrated luminosity of 20.2 fb-1. The results, based on a total of 15.3 million Z-boson decays to electron and muon pairs, extend and improve a previous measurement of the full set of angular coefficients describing Z-boson decay. The double-differential cross-section distributions in Z-boson transverse momentum pT and rapidity y are measured in the pole region, defined as 80<mℓℓ<100 GeV, over the range |y|<3.6. The total uncertainty of the normalised cross-section measurements in the peak region of the pT distribution is dominated by statistical uncertainties over the full range and increases as a function of rapidity from 0.5–1.0% for |y|<2.0 to 2-7% at higher rapidities. The results for the rapidity-dependent transverse momentum distributions are compared to state-of-the-art QCD predictions, which combine in the best cases approximate N4LL resummation with N3LO fixed-order perturbative calculations. The differential rapidity distributions integrated over pT are even more precise, with accuracies from 0.2–0.3% for |y|<2.0 to 0.4–0.9% at higher rapidities, and are compared to fixed-order QCD predictions using the most recent parton distribution functions. The agreement between data and predictions is quite good in most cases
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