7 research outputs found

    An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease

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    Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD risk and related endophenotypes in females carrying the Apolipoprotein E (APOE)-ε4 genotype; the association is stronger in Chinese than in European-descent populations. Human and mouse transcriptome and immunohistochemical studies showed that rs1921622/sST2 regulates amyloid-beta (Aβ) pathology through the modulation of microglial activation and Aβ clearance. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD

    Measurement of electrons from semileptonic heavy-flavour hadron decays at midrapidity in pp and Pb–Pb collisions at √sNN = 5.02 TeV

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    The differential invariant yield as a function of transverse momentum (pT) of electrons from semileptonic heavy-flavour hadron decays was measured at midrapidity in central (0–10%), semi-central (30–50%) and peripheral (60–80%) lead–lead (Pb–Pb) collisions at √sNN = 5.02 TeV in the pT intervals 0.5–26 GeV/c (0–10% and 30–50%) and 0.5–10 GeV/c (60–80%). The production cross section in proton–proton (pp) collisions at √s = 5.02 TeV was measured as well in 0.5 < pT < 10 GeV/c and it lies close to the upper band of perturbative QCD calculation uncertainties up to pT = 5 GeV/c and close to the mean value for larger pT. The modification of the electron yield with respect to what is expected for an incoherent superposition of nucleon–nucleon collisions is evaluated by measuring the nuclear modification factor RAA. The measurement of the RAA in different centrality classes allows in-medium energy loss of charm and beauty quarks to be investigated. The RAA shows a suppression with respect to unity at intermediate pT, which increases while moving towards more central collisions. Moreover, the measured RAA is sensitive to the modification of the parton distribution functions (PDF) in nuclei, like nuclear shadowing, which causes a suppression of the heavy-quark production at low pT in heavy-ion collisions at LHC

    Multiplicity dependence of K*(892)0 and ϕ(1020) production in pp collisions at t √s=13 TeV

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    The striking similarities that have been observed between high-multiplicity proton-proton (pp) collisions and heavy-ion collisions can be explored through multiplicity-differential measurements of identified hadrons in pp collisions. With these measurements, it is possible to study mechanisms such as collective flow that determine the shapes of hadron transverse momentum (pT) spectra, to search for possible modifications of the yields of short-lived hadronic resonances due to scattering effects in an extended hadron-gas phase, and to investigate different explanations provided by phenomenological models for enhancement of strangeness production with increasing multiplicity. In this paper, these topics are addressed through measurements of the K∗(892)0 and φ(1020) mesons at midrapidity in pp collisions at √s = 13 TeV as a function of the charged-particle multiplicity. The results include the pT spectra, pT-integrated yields, mean transverse momenta, and the ratios of the yields of these resonances to those of longer-lived hadrons. Comparisons with results from other collision systems and energies, as well as predictions from phenomenological models, are also discussed

    Measuring KS0K± interactions using Pb–Pb collisions at √sNN=2.76 TeV

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    We present the first ever measurements of femtoscopic correlations between the K0 S and K± particles. The analysis was performed on the data from Pb–Pb collisions at √sNN = 2.76 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for K0 SK− are found to be equal within the experimental uncertainties to those for K0 SK+. Comparing the results of the present study with those from published identical-kaon femtoscopic studies by ALICE, mass and coupling parameters for the a0 resonance are tested. Our results are also compatible with the interpretation of the a0 having a tetraquark structure instead of that of a diquar

    Multiplicity dependence of inclusive J/ψ production at midrapidity in pp collisions at √s=13 TeV

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    Measurements of the inclusive J/ψ yield as a function of charged-particle pseudorapidity density dNch/dη in pp collisions at √s = 13 TeV with ALICE at the LHC are reported. The J/ψ meson yield is measured at midrapidity (|y| < 0.9) in the dielectron channel, for events selected based on the charged-particle multiplicity at midrapidity (|η| < 1) and at forward rapidity (−3.7 < η < −1.7 and 2.8 < η < 5.1); both observables are normalized to their corresponding averages in minimum bias events. The increase of the normalized J/ψ yield with normalized dNch/dη is significantly stronger than linear and dependent on the transverse momentum. The data are compared to theoretical predictions, which describe the observed trends well, albeit not always quantitatively

    Direct observation of the dead-cone effect in quantum chromodynamics

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    At particle collider experiments, elementary particle interactions with large momentum transfer produce quarks and gluons (known as partons) whose evolution is governed by the strong force, as described by the theory of quantum chromodynamics (QCD) [1]. The vacuum is not transparent to the partons and induces gluon radiation and quark pair production in a process that can be described as a parton shower [2]. Studying the pattern of the parton shower is one of the key experimental tools in understanding the properties of QCD. This pattern is expected to depend on the mass of the initiating parton, through a phenomenon known as the dead-cone effect, which predicts a suppression of the gluon spectrum emitted by a heavy quark of mass m and energy E, within a cone of angular size m/E around the emitter [3]. A direct observation of the dead-cone effect in QCD has not been possible until now, due to the challenge of reconstructing the cascading quarks and gluons from the experimentally accessible bound hadronic states. Here we show the first direct observation of the QCD dead-cone by using new iterative declustering techniques [4, 5] to reconstruct the parton shower of charm quarks. This result confirms a fundamental feature of QCD, which is derived more generally from its origin as a gauge quantum field theory. Furthermore, the measurement of a dead-cone angle constitutes the first direct experimental observation of the non-zero mass of the charm quark, which is a fundamental constant in the standard model of particle physics.The direct measurement of the QCD dead cone in charm quark fragmentation is reported, using iterative declustering of jets tagged with a fully reconstructed charmed hadron.In particle collider experiments, elementary particle interactions with large momentum transfer produce quarks and gluons (known as partons) whose evolution is governed by the strong force, as described by the theory of quantum chromodynamics (QCD). These partons subsequently emit further partons in a process that can be described as a parton shower which culminates in the formation of detectable hadrons. Studying the pattern of the parton shower is one of the key experimental tools for testing QCD. This pattern is expected to depend on the mass of the initiating parton, through a phenomenon known as the dead-cone effect, which predicts a suppression of the gluon spectrum emitted by a heavy quark of mass mQm_{\rm{Q}} and energy EE, within a cone of angular size mQm_{\rm{Q}}/EE around the emitter. Previously, a direct observation of the dead-cone effect in QCD had not been possible, owing to the challenge of reconstructing the cascading quarks and gluons from the experimentally accessible hadrons. We report the direct observation of the QCD dead cone by using new iterative declustering techniques to reconstruct the parton shower of charm quarks. This result confirms a fundamental feature of QCD. Furthermore, the measurement of a dead-cone angle constitutes a direct experimental observation of the non-zero mass of the charm quark, which is a fundamental constant in the standard model of particle physics

    Progression of Geographic Atrophy in Age-related Macular Degeneration

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