695 research outputs found

    Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

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    Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH

    Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

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    A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κT = 0.25 and a relative decay width Γ/MT′ < 5%

    Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

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    A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level

    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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    Observation of Same-Sign WW Production from Double Parton Scattering in Proton-Proton Collisions at √s = 13 TeV

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    The first observation of the production of W±W± bosons from double parton scattering processes using same-sign electron-muon and dimuon events in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 138  fb−1 recorded at a center-of-mass energy of 13 TeV using the CMS detector at the CERN LHC. Multivariate discriminants are used to distinguish the signal process from the main backgrounds. A binned maximum likelihood fit is performed to extract the signal cross section. The measured cross section for production of same-sign W bosons decaying leptonically is 80.7±11.2(stat) +9.5−8.6(syst)±12.1(model)  fb, whereas the measured fiducial cross section is 6.28±0.81(stat)±0.69(syst)±0.37(model)  fb. The observed significance of the signal is 6.2 standard deviations above the background-only hypothesis

    Observation of four top quark production in proton-proton collisions at √s = 13 TeV

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    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

    Measurement of the differential tt\hbox {t}\overline{\hbox {t}} production cross section as a function of the jet mass and extraction of the top quark mass in hadronic decays of boosted top quarks

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    A measurement of the jet mass distribution in hadronic decays of Lorentz-boosted top quarks is presented. The measurement is performed in the lepton + jets channel of top quark pair production (tt¯) events, where the lepton is an electron or muon. The products of the hadronic top quark decay are reconstructed using a single large-radius jet with transverse momentum greater than 400GeV. The data were collected with the CMS detector at the LHC in proton-proton collisions and correspond to an integrated luminosity of 138fb−1. The differential tt¯ production cross section as a function of the jet mass is unfolded to the particle level and is used to extract the top quark mass. The jet mass scale is calibrated using the hadronic W boson decay within the large-radius jet. The uncertainties in the modelling of the final state radiation are reduced by studying angular correlations in the jet substructure. These developments lead to a significant increase in precision, and a top quark mass of 173.06±0.84GeV

    Search for a high-mass dimuon resonance produced in association with b quark jets at s \sqrt{s} = 13 TeV

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