1,801 research outputs found

    4 '-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN

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    Pantothenate kinase-associated neurodegeneration (PKAN) is an inborn error of CoA metabolism causing dystonia, parkinsonism, and brain iron accumulation. Lack of a good mammalian model has impeded studies of pathogenesis and development of rational therapeutics. We took a new approach to investigating an existing mouse mutant of Pank2 and found that isolating the disease-vulnerable brain revealed regional perturbations in CoA metabolism, iron homeostasis, and dopamine metabolism and functional defects in complex I and pyruvate dehydrogenase. Feeding mice a CoA pathway intermediate, 4 '-phosphopantetheine, normalized levels of the CoA-, iron-, and dopamine-related biomarkers as well as activities of mitochondrial enzymes. Human cell changes also were recovered by 4 '-phosphopantetheine. We can mechanistically link a defect in CoA metabolism to these secondary effects via the activation of mitochondrial acyl carrier protein, which is essential to oxidative phosphorylation, iron-sulfur cluster biogenesis, and mitochondrial fatty acid synthesis. We demonstrate the fidelity of our model in recapitulating features of the human disease. Moreover, we identify pharmacodynamic biomarkers, provide insights into disease pathogenesis, and offer evidence for 4 '-phosphopantetheine as a candidate therapeutic for PKAN

    Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

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    The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum

    Complete Genome Sequences of Cluster A Mycobacteriophages BobSwaget, Fred313, KADY, Lokk, MyraDee, Stagni, and StepMih

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    Seven mycobacteriophages from distinct geographical locations were isolated, using Mycobacterium smegmatis mc2155 as the host, and then purified and sequenced. All of the genomes are related to cluster A mycobacteriophages, BobSwaget and Lokk in subcluster A2; Fred313, KADY, Stagni, and StepMih in subcluster A3; and MyraDee in subcluster A18, the first phage to be assigned to that subcluster

    Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at √S^{S}NN = 5.02 TeV

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    The second-order Fourier coefficients (υ2_{2}) characterizing the azimuthal distributions of Υ(1S) and Υ(2S) mesons produced in PbPb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV are studied. The Υmesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb1^{-1}. The scalar product method is used to extract the υ2_{2} coefficients of the azimuthal distributions. Results are reported for the rapidity range |y| < 2.4, in the transverse momentum interval 0 < pT_{T} < 50 GeV/c, and in three centrality ranges of 10–30%, 30–50% and 50–90%. In contrast to the J/ψ mesons, the measured υ2_{2} values for the Υ mesons are found to be consistent with zero

    Search for the lepton flavor violating decay τ → 3μ in proton-proton collisions at s \sqrt{\mathrm{s}} = 13 TeV

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    Results are reported from a search for the lepton flavor violating decay τ → 3μ in proton-proton collisions at s \sqrt{\mathrm{s}} = 13 TeV. The data sample corresponds to an integrated luminosity of 33.2 fb1^{-1} recorded by the CMS experiment at the LHC in 2016. The search exploits τ leptons produced in both W boson and heavy-flavor hadron decays. No significant excess above the expected background is observed. An upper limit on the branching fraction B(τ → 3μ) of 8.0 x 108^{-8} at 90% confidence level is obtained, with an expected upper limit of 6.9 x 108^{-8}

    Erratum to: Search for dark matter produced in association with a leptonically decaying Z{\mathrm{Z}} boson in proton–proton collisions at s=13TeV\sqrt{s}=13\,\text {Te}\text {V}

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    Search for invisible decays of the Higgs boson produced via vector boson fusion in proton-proton collisions at s\sqrt{s} = 13 TeV

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    A search for invisible decays of the Higgs boson produced via vector boson fusion (VBF) has been performed with 101  fb1^{-1} of proton-proton collisions delivered by the LHC at s\sqrt{s} =13  TeV and collected by the CMS detector in 2017 and 2018. The sensitivity to the VBF production mechanism is enhanced by constructing two analysis categories, one based on missing transverse momentum and a second based on the properties of jets. In addition to control regions with Z and W boson candidate events, a highly populated control region, based on the production of a photon in association with jets, is used to constrain the dominant irreducible background from the invisible decay of a Z boson produced in association with jets. The results of this search are combined with all previous measurements in the VBF topology, based on data collected in 2012 (at s\sqrt{s} =8  TeV), 2015, and 2016, corresponding to integrated luminosities of 19.7, 2.3, and 36.3  fb1^{-1}, respectively. The observed (expected) upper limit on the invisible branching fraction of the Higgs boson is found to be 0.18 (0.10) at the 95% confidence level, assuming the standard model production cross section. The results are also interpreted in the context of Higgs-portal models

    Observation of the Bc+_\mathrm{c}^+ Meson in Pb-Pb and pp Collisions at sNN\sqrt{s_{\mathrm{NN}}} = 5.02 TeV and Measurement of its Nuclear Modification Factor

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    The Bc+_\mathrm{c}^+ meson is observed for the first time in heavy ion collisions. Data from the CMS detector are used to study the production of the Bc+_\mathrm{c}^+ meson in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a center-of-mass energy per nucleon pair of sNN\sqrt{s_{\mathrm{NN}}} = 5.02 TeV , via the Bc+_\mathrm{c}^+ → (J/ψ → μ+^+μ^−+^+νμ decay. The Bc+_\mathrm{c}^+ nuclear modification factor, derived from the PbPb-to-pp ratio of production cross sections, is measured in two bins of the trimuon transverse momentum and of the PbPb collision centrality. The Bc+_\mathrm{c}^+meson is shown to be less suppressed than quarkonia and most of the open heavy-flavor mesons, suggesting that effects of the hot and dense nuclear matter created in heavy ion collisions contribute to its production. This measurement sets forth a promising new probe of the interplay of suppression and enhancement mechanisms in the production of heavy-flavor mesons in the quark-gluon plasma

    First Search for Exclusive Diphoton Production at High Mass with Tagged Protons in Proton-Proton Collisions at √s = 13 TeV

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    Measurement of the B0^{0}s_{s} → μ+^{+} μ^{-} decay properties and search for the B0^{0} → μ+^{+}μ^{-} decay in proton-proton collisions at √s = 13 TeV

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