454 research outputs found

    Wars2 is a determinant of angiogenesis.

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    Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary density. Mitochondrial tryptophanyl-tRNA synthetase (Wars2), encoding an L53F protein variant within the ATP-binding motif, is prioritized as the candidate at the locus by integrating genomic data sets. WARS2(L53F) has low enzyme activity and inhibition of WARS2 in endothelial cells reduces angiogenesis. In the zebrafish, inhibition of wars2 results in trunk vessel deficiencies, disordered endocardial-myocardial contact and impaired heart function. Inhibition of Wars2 in the rat causes cardiac angiogenesis defects and diminished cardiac capillary density. Our data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart that may have translational relevance given the association of WARS2 with common human diseases

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Measurement of the Splitting Function in &ITpp &ITand Pb-Pb Collisions at root&ITsNN&IT=5.02 TeV

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    Data from heavy ion collisions suggest that the evolution of a parton shower is modified by interactions with the color charges in the dense partonic medium created in these collisions, but it is not known where in the shower evolution the modifications occur. The momentum ratio of the two leading partons, resolved as subjets, provides information about the parton shower evolution. This substructure observable, known as the splitting function, reflects the process of a parton splitting into two other partons and has been measured for jets with transverse momentum between 140 and 500 GeV, in pp and PbPb collisions at a center-of-mass energy of 5.02 TeV per nucleon pair. In central PbPb collisions, the splitting function indicates a more unbalanced momentum ratio, compared to peripheral PbPb and pp collisions.. The measurements are compared to various predictions from event generators and analytical calculations.Peer reviewe

    Search for anomalous couplings in boosted WW/WZ -> l nu q(q)over-bar production in proton-proton collisions at root s=8TeV

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    Electroweak production of two jets in association with a Z boson in proton-proton collisions root s =13 TeV

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    A measurement of the electroweak (EW) production of two jets in association with a Z boson in proton-proton collisions at root s = 13 TeV is presented, based on data recorded in 2016 by the CMS experiment at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lljj final state with l including electrons and muons, and the jets j corresponding to the quarks produced in the hard interaction. The measured cross section in a kinematic region defined by invariant masses m(ll) > 50 GeV, m(jj) > 120 GeV, and transverse momenta P-Tj > 25 GeV is sigma(EW) (lljj) = 534 +/- 20 (stat) fb (syst) fb, in agreement with leading-order standard model predictions. The final state is also used to perform a search for anomalous trilinear gauge couplings. No evidence is found and limits on anomalous trilinear gauge couplings associated with dimension-six operators are given in the framework of an effective field theory. The corresponding 95% confidence level intervals are -2.6 <cwww/Lambda(2) <2.6 TeV-2 and -8.4 <cw/Lambda(2) <10.1 TeV-2. The additional jet activity of events in a signal-enriched region is also studied, and the measurements are in agreement with predictions.Peer reviewe

    Bose-Einstein correlations of charged hadrons in proton-proton collisions at s\sqrt s = 13 TeV

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    Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at s \sqrt{s} = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at s \sqrt{s} = 7 TeV, as well as with theoretical predictions.[graphic not available: see fulltext]Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at s=\sqrt{s} = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at s=\sqrt{s} = 7 TeV, as well as with theoretical predictions

    Search for dark matter in events with a leptoquark and missing transverse momentum in proton-proton collisions at 13 TeV

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    A search is presented for dark matter in proton-proton collisions at a center-of-mass energy of root s= 13 TeV using events with at least one high transverse momentum (p(T)) muon, at least one high-p(T) jet, and large missing transverse momentum. The data were collected with the CMS detector at the CERN LHC in 2016 and 2017, and correspond to an integrated luminosity of 77.4 fb(-1). In the examined scenario, a pair of scalar leptoquarks is assumed to be produced. One leptoquark decays to a muon and a jet while the other decays to dark matter and low-p(T) standard model particles. The signature for signal events would be significant missing transverse momentum from the dark matter in conjunction with a peak at the leptoquark mass in the invariant mass distribution of the highest p(T) muon and jet. The data are observed to be consistent with the background predicted by the standard model. For the first benchmark scenario considered, dark matter masses up to 500 GeV are excluded for leptoquark masses m(LQ) approximate to 1400 GeV, and up to 300 GeV for m(LQ) approximate to 1500 GeV. For the second benchmark scenario, dark matter masses up to 600 GeV are excluded for m(LQ) approximate to 1400 GeV. (C) 2019 The Author(s). Published by Elsevier B.V.Peer reviewe

    Search for an L-mu - L-tau gauge boson using Z -> 4 mu events in proton-proton collisions at root s=13 TeV

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    A search for a narrow Z' gauge boson with a mass between 5 and 70 GeV resulting from an L-mu - L-tau U (1) local gauge symmetry is reported. Theories that predict such a particle have been proposed as an explanation of various experimental discrepancies, including the lack of a dark matter signal in direct-detection experiments, tension in the measurement of the anomalous magnetic moment of the muon, and reports of possible lepton flavor universality violation in B meson decays. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV is used, corresponding to an integrated luminosity of 77.3 fb(-1) recorded in 2016 and 2017 by the CMS detector at the LHC. Events containing four muons with an invariant mass near the standard model Z boson mass are analyzed, and the selection is further optimized to be sensitive to the events that may contain Z -> Z'mu mu -> 4 mu decays. The event yields are consistent with the standard model predictions. Upper limits of 10(-8)-10(-7) at 95% confidence level are set on the product of branching fractions B(Z -> Z'mu mu)B(Z' -> mu mu), depending on the Z' mass, which excludes a Z' boson coupling strength to muons above 0.004-0.3. These are the first dedicated limits on L-mu - L-tau models at the LHC and result in a significant increase in the excluded model parameter space. The results of this search may also be used to constrain the coupling strength of any light Z' gauge boson to muons. (C) 2019 The Author(s). Published by Elsevier B.V.Peer reviewe

    Azimuthal separation in nearly back-to-back jet topologies in inclusive 2-and 3-jet events in pp collisions at root s=13TeV

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    A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, Delta phi(12), is presented. The measurement considers events where the two leading jets are nearly collinear ("back-to-back") in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 35.9 fb(-1) are used. Predictions based on calculations using matrix elements at leading-order and next-to-leading-order accuracy in perturbative quantum chromodynamics supplemented with leading-log parton showers and hadronization are generally in agreement with themeasurements. Discrepancies between the measurement and theoretical predictions are as large as 15%, mainly in the region 177 degrees <Delta phi(12) <180 degrees. The 2- and 3-jet measurements are not simultaneously described by any of models.Peer reviewe
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