247 research outputs found

    GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways

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    Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively

    Measurement of the cross section of top quark-antiquark pair production in association with a W boson in proton-proton collisions at s \sqrt{s} = 13 TeV

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    The production of a top quark-antiquark pair in association with a W boson (ttˉW)(t\bar{t}W) is measured in proton-proton collisions at a center-of-mass energy of 13 TeV. The analyzed data was recorded by the CMS experiment at the CERN LHC and corresponds to an integrated luminosity of 138 fb1^{−1}. Events with two or three leptons (electrons and muons) and additional jets are selected. In events with two leptons, a multiclass neural network is used to distinguish between the signal and background processes. Events with three leptons are categorized based on the number of jets and of jets originating from b quark hadronization, and the lepton charges. The inclusive (ttˉW)(t\bar{t}W) production cross section in the full phase space is measured to be 868 ± 40(stat) ± 51(syst) fb. The (ttˉW)+(t\bar{t}W)+ and (ttˉW)(t\bar{t}W)− cross sections are also measured as 553 ± 30(stat) ± 30(syst) and 343 ± 26(stat) ± 25(syst) fb, respectively, and the corresponding ratio of the two cross sections is found to be 1.61±0.15(stat)0.05+0.07^{+0.07}_{−0.05}(syst). The measured cross sections are larger than but consistent with the standard model predictions within two standard deviations, and represent the most precise measurement of these cross sections to date

    Search for high-mass exclusive γγ → WW and γγ → ZZ production in proton-proton collisions at s \sqrt{s} = 13 TeV

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    Azimuthal anisotropy of dijet events in PbPb collisions at sNN \sqrt{s_{\textrm{NN}}} = 5.02 TeV

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    The path-length dependent parton energy loss within the dense partonic medium created in lead-lead collisions at a nucleon-nucleon center-of-mass energy of sNN−−−√ = 5.02 TeV is studied by determining the azimuthal anisotropies for dijets with high transverse momentum. The data were collected by the CMS experiment in 2018 and correspond to an integrated luminosity of 1.69 nb−1. For events containing back-to-back jets, correlations in relative azimuthal angle and pseudorapidity (η) between jets and hadrons, and between two hadrons, are constructed. The anisotropies are expressed as the Fourier expansion coefficients vn, n = 2–4 of these azimuthal distributions. The dijet vn values are extracted from long-range (1.5 < |∆η| < 2.5) components of these correlations, which suppresses the background contributions from jet fragmentation processes. Positive dijet v2 values are observed which increase from central to more peripheral events, while the v3 and v4 values are consistent with zero within experimental uncertainties

    A search for new physics in central exclusive production using the missing mass technique with the CMS detector and the CMS-TOTEM precision proton spectrometer

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    A generic search is presented for the associated production of a Z boson or a photon with an additional unspecified massive particle X, pp → pp + Z/γ + X, in proton-tagged events from proton–proton collisions at √s = 13 TeV, recorded in 2017 with the CMS detector and the CMS-TOTEM precision proton spectrometer. The missing mass spectrum is analysed in the 600–1600 GeV range and a fit is performed to search for possible deviations from the background expectation. No significant excess in data with respect to the background predictions has been observed. odelindependent upper limits on the visible production cross section of pp → pp + Z/γ + X are set

    Measurements of the Higgs boson production cross section and couplings in the W boson pair decay channel in proton-proton collisions at s=13TeV\sqrt{s}=13\,\text {Te\hspace{-.08em}V}

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    Production cross sections of the standard model Higgs boson decaying to a pair of W bosons are measured in proton-proton collisions at a center-of-mass energy of 13Te\hspace{-.08em}V. The analysis targets Higgs bosons produced via gluon fusion, vector boson fusion, and in association with a W or Z boson. Candidate events are required to have at least two charged leptons and moderate missing transverse momentum, targeting events with at least one leptonically decaying W boson originating from the Higgs boson. Results are presented in the form of inclusive and differential cross sections in the simplified template cross section framework, as well as couplings of the Higgs boson to vector bosons and fermions. The data set collected by the CMS detector during 2016–2018 is used, corresponding to an integrated luminosity of 138fb−1. The signal strength modifier μ, defined as the ratio of the observed production rate in a given decay channel to the standard model expectation, is measured to be μ=0.95+0.10−0.09. All results are found to be compatible with the standard model within the uncertainties

    Measurement of the Higgs boson inclusive and differential fiducial production cross sections in the diphoton decay channel with pp collisions at s \sqrt{s} = 13 TeV

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    The measurements of the inclusive and differential fiducial cross sections of the Higgs boson decaying to a pair of photons are presented. The analysis is performed using proton-proton collisions data recorded with the CMS detector at the LHC at a centre-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 137 fb1^{−1}. The inclusive fiducial cross section is measured to be σfidσ_{fid}=73.45.3+5.4^{+5.4}_{−5.3}(stat)2.2+2.4^{+2.4}_{−2.2}(syst) fb, in agreement with the standard model expectation of 75.4 ± 4.1 fb. The measurements are also performed in fiducial regions targeting different production modes and as function of several observables describing the diphoton system, the number of additional jets present in the event, and other kinematic observables. Two double differential measurements are performed. No significant deviations from the standard model expectations are observed

    Search for top squarks in the four-body decay mode with single lepton final states in proton-proton collisions at s \sqrt{s} = 13 TeV

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    A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark (t∼1), is presented. The search targets the four-body decay of the t∼1, which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino (χ∼01), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between m(t∼1) and m(χ∼01). The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for m(t∼1) − m(χ∼01) = 10 and 80 GeV, respectively

    Observation of τ Lepton Pair Production in Ultraperipheral Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV

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