73 research outputs found

    Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.

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    Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit in autism, intellectual disability, Lennox Gastaut and West Syndromes. Here, we investigated several such mutations using a near-complete, hybrid 3D model of the human NMDAR and studied their consequences with kinetic modelling and electrophysiology. The mutants revealed reductions in glutamate potency; increased receptor desensitisation; and ablation of voltage-dependent Mg block. In addition, we provide new views on Mg and NMDA channel blocker binding sites. We demonstrate that these mutants have significant impact on excitatory transmission in developing neurons, revealing profound changes that could underlie their associated neurological disorders. Of note, the NMDAR channel mutant GluN2B unusually allowed Mg permeation, whereas nearby N615I reduced Ca permeability. By identifying the binding site for an NMDAR antagonist that is used in the clinic to rescue gain-of-function phenotypes, we show that drug binding may be modified by some GluN2B disease-causing mutations

    Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC

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    Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators

    Search for supersymmetry at √s = 13 TeV in final states with jets and two same-sign leptons or three leptons with the ATLAS detector

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    A search for strongly produced supersymmetric particles is conducted using signatures involving multiple energetic jets and either two isolated leptons (e or μμ ) with the same electric charge or at least three isolated leptons. The search also utilises b-tagged jets, missing transverse momentum and other observables to extend its sensitivity. The analysis uses a data sample of proton–proton collisions at s√=13s=13 TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015 corresponding to a total integrated luminosity of 3.2 fb −1−1. No significant excess over the Standard Model expectation is observed. The results are interpreted in several simplified supersymmetric models and extend the exclusion limits from previous searches. In the context of exclusive production and simplified decay modes, gluino masses are excluded at 95%95% confidence level up to 1.1–1.3 TeV for light neutralinos (depending on the decay channel), and bottom squark masses are also excluded up to 540 GeV. In the former scenarios, neutralino masses are also excluded up to 550–850 GeV for gluino masses around 1 TeV

    Anatomy of the sign-problem in heavy-dense QCD

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    QCD at finite densities of heavy quarks is investigated using the density-of-states method. The phase factor expectation value of the quark determinant is calculated to unprecedented precision as a function of the chemical potential. Results are validated using those from a reweighting approach where the latter can produce a significant signalto-noise ratio. We confirm the particle–hole symmetry at low temperatures, find a strong sign problem at intermediate values of the chemical potential, and an inverse Silver Blaze feature for chemical potentials close to the onset value: here, the phase-quenched theory underestimates the density of the full theory

    Measurement of the photon identification efficiencies with the ATLAS detector using LHC Run-1 data

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    © 2016, CERN for the benefit of the ATLAS collaboration.The algorithms used by the ATLAS Collaboration to reconstruct and identify prompt photons are described. Measurements of the photon identification efficiencies are reported, using 4.9 fb- 1 of pp collision data collected at the LHC at s=7 TeV and 20.3 fb- 1 at s=8 TeV. The efficiencies are measured separately for converted and unconverted photons, in four different pseudorapidity regions, for transverse momenta between 10 GeV and 1.5 TeV. The results from the combination of three data-driven techniques are compared to the predictions from a simulation of the detector response, after correcting the electromagnetic shower momenta in the simulation for the average differences observed with respect to data. Data-to-simulation efficiency ratios used as correction factors in physics measurements are determined to account for the small residual efficiency differences. These factors are measured with uncertainties between 0.5% and 10% in 7 TeV data and between 0.5% and 5.6% in 8 TeV data, depending on the photon transverse momentum and pseudorapidity

    Search for squarks and gluinos in final states with jets and missing transverse momentum at root s=13 TeV with the ATLAS detector

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    Search for resonances in the mass distribution of jet pairs with one or two jets identified as <i>b</i> -jets in proton–proton collisions at √s = 13 TeV with the ATLAS detector

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    Searches for high-mass resonances in the dijet invariant mass spectrum with one or two jets identified as b -jets are performed using an integrated luminosity of 3.2 fb−1 of proton–proton collisions with a centre-of-mass energy of √s = 13 TeV recorded by the ATLAS detector at the Large Hadron Collider. No evidence of anomalous phenomena is observed in the data, which are used to exclude, at 95% credibility level, excited b* quarks with masses from 1.1 TeV to 2.1 TeV and leptophobic Z′ bosons with masses from 1.1 TeV to 1.5 TeV. Contributions of a Gaussian signal shape with effective cross sections ranging from approximately 0.4 to 0.001 pb are also excluded in the mass range 1.5–5.0 TeV

    Measurement of the transverse momentum and ϕ∗ηϕη∗ distributions of Drell–Yan lepton pairs in proton–proton collisions at s√=8s=8 TeV with the ATLAS detector

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    Distributions of transverse momentum p T and the related angular variable φ∗ η of Drell–Yan lepton pairs are measured in 20.3 fb−1 of proton–proton collisions at √s = 8 TeV with the ATLAS detector at the LHC. Measurements in electron-pair and muon-pair final states are corrected for detector effects and combined. Compared to previous measurements in proton–proton collisions at √s = 7 TeV, these new measurements benefit from a larger data sample and improved control of systematic uncertainties. Measurements are performed in bins of lepton-pair mass above, around and below the Z-boson mass peak. The data are compared to predictions from perturbative and resummed QCD calculations. For values of φ∗ η < 1 the predictions from the Monte Carlo generator ResBos are generally consistent with the data within the theoretical uncertainties. However, at larger values of φ∗ η this is not the case. Monte Carlo generators based on the parton-shower approach are unable to describe the data over the full range of p T while the fixed-order prediction of Dynnlo falls below the data at high values of p T . ResBos and the parton-shower Monte Carlo generators provide a much better description of the evolution of the φ∗ η and p T distributions as a function of lepton-pair mass and rapidity than the basic shape of the data. Conte

    Beam-induced and cosmic-ray backgrounds observed in the ATLAS detector during the LHC 2012 proton-proton running period

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    This paper discusses various observations on beam-induced and cosmic-ray backgrounds in the ATLAS detector during the LHC 2012 proton-proton run. Building on published results based on 2011 data, the correlations between background and residual pressure of the beam vacuum are revisited. Ghost charge evolution over 2012 and its role for backgrounds are evaluated. New methods to monitor ghost charge with beam-gas rates are presented and observations of LHC abort gap population by ghost charge are discussed in detail. Fake jets from colliding bunches and from ghost charge are analysed with improved methods, showing that ghost charge in individual radio-frequency buckets of the LHC can be resolved. Some results of two short periods of dedicated cosmic-ray background data-taking are shown; in particular cosmic-ray muon induced fake jet rates are compared to Monte Carlo simulations and to the fake jet rates from beam background. A thorough analysis of a particular LHC fill, where abnormally high background was observed, is presented. Correlations between backgrounds and beam intensity losses in special fills with very high β* are studied

    Measurements of top-quark pair differential cross-sections in the lepton plus jets channel in pp collisions at root s=8 TeV using the ATLAS detector

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    Measurements of normalized differential cross-sections of top-quark pair production are presented as a function of the top-quark, tt¯tt¯ system and event-level kinematic observables in proton–proton collisions at a centre-of-mass energy of s√=8TeVs=8TeV . The observables have been chosen to emphasize the tt¯tt¯ production process and to be sensitive to effects of initial- and final-state radiation, to the different parton distribution functions, and to non-resonant processes and higher-order corrections. The dataset corresponds to an integrated luminosity of 20.3 fb −1−1 , recorded in 2012 with the ATLAS detector at the CERN Large Hadron Collider. Events are selected in the lepton+jets channel, requiring exactly one charged lepton and at least four jets with at least two of the jets tagged as originating from a b-quark. The measured spectra are corrected for detector effects and are compared to several Monte Carlo simulations. The results are in fair agreement with the predictions over a wide kinematic range. Nevertheless, most generators predict a harder top-quark transverse momentum distribution at high values than what is observed in the data. Predictions beyond NLO accuracy improve the agreement with data at high top-quark transverse momenta. Using the current settings and parton distribution functions, the rapidity distributions are not well modelled by any generator under consideration. However, the level of agreement is improved when more recent sets of parton distribution functions are used
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