124 research outputs found

    Determination of alphaS from Hadronic Event Shapes in e+e- Annihilation at 192 < sqrt(s) < 208 GeV

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    Results are presented from a study of the structure of high energy hadronic events recorded by the L3 detector at sqrt(s)>192 GeV. The distributions of several event shape variables are compared to resummed O(alphaS^2) QCD calculations. We determine the strong coupling constant at three average centre-of-mass energies: 194.4, 200.2 and 206.2 GeV. These measurements, combined with previous L3 measurements at lower energies, demonstrate the running of alphaS as expected in QCD and yield alphaS(mZ) = 0.1227 +- 0.0012 +- 0.0058, where the first uncertainty is experimental and the second is theoretical

    A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance

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    Mucociliary clearance, the physiological process by which mammalian conducting airways expel pathogens and unwanted surface materials from the respiratory tract, depends on the coordinated function of multiple specialized cell types, including basal stem cells, mucus-secreting goblet cells, motile ciliated cells, cystic fibrosis transmembrane conductance regulator (CFTR)-rich ionocytes, and immune cells1,2. Bronchiectasis, a syndrome of pathological airway dilation associated with impaired mucociliary clearance, may occur sporadically or as a consequence of Mendelian inheritance, for example in cystic fibrosis, primary ciliary dyskinesia (PCD), and select immunodeficiencies3. Previous studies have identified mutations that affect ciliary structure and nucleation in PCD4, but the regulation of mucociliary transport remains incompletely understood, and therapeutic targets for its modulation are lacking. Here we identify a bronchiectasis syndrome caused by mutations that inactivate NIMA-related kinase 10 (NEK10), a protein kinase with previously unknown in vivo functions in mammals. Genetically modified primary human airway cultures establish NEK10 as a ciliated-cell-specific kinase whose activity regulates the motile ciliary proteome to promote ciliary length and mucociliary transport but which is dispensable for normal ciliary number, radial structure, and beat frequency. Together, these data identify a novel and likely targetable signaling axis that controls motile ciliary function in humans and has potential implications for other respiratory disorders that are characterized by impaired mucociliary clearance

    Synaptic processes and immune-related pathways implicated in Tourette syndrome.

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    Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS

    Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

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    Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

    Measurement of the CP-Violating Asymmetry Amplitude sin2β\beta

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    We present results on time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 million Y(4S) --> B Bbar decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B0 or B0bar from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta = 0.741 +/- 0.067 (stat) +/- 0.033 (syst) and |lambda| = 0.948 +/- 0.051 (stat) +/- 0.017 (syst). The magnitude of lambda is consistent with unity, in agreement with the Standard Model expectation of no direct CP violation in these modes

    Studies of Hadronic Event Structure in e+e- Annihilation from 30 GeV to 209 GeV with the L3 Detector

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    In this Report, QCD results obtained from a study of hadronic event structure in high energy e^+e^- interactions with the L3 detector are presented. The operation of the LEP collider at many different collision energies from 91 GeV to 209 GeV offers a unique opportunity to test QCD by measuring the energy dependence of different observables. The main results concern the measurement of the strong coupling constant, \alpha_s, from hadronic event shapes and the study of effects of soft gluon coherence through charged particle multiplicity and momentum distributions.Comment: To appear in Physics Report

    ATLAS detector and physics performance: Technical Design Report, 1

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    GW190814: gravitational waves from the coalescence of a 23 solar mass black hole with a 2.6 solar mass compact object

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    We report the observation of a compact binary coalescence involving a 22.2–24.3 Me black hole and a compact object with a mass of 2.50–2.67 Me (all measurements quoted at the 90% credible level). The gravitational-wave signal, GW190814, was observed during LIGO’s and Virgo’s third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network. The source was localized to 18.5 deg2 at a distance of - + 241 45 41 Mpc; no electromagnetic counterpart has been confirmed to date. The source has the most unequal mass ratio yet measured with gravitational waves, - + 0.112 0.009 0.008, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system. The dimensionless spin of the primary black hole is tightly constrained to �0.07. Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence. We estimate a merger rate density of 1–23 Gpc−3 yr−1 for the new class of binary coalescence sources that GW190814 represents. Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters. However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries

    The Physics of the B Factories

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