206 research outputs found

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3â€Č-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

    ϒ production in p–Pb collisions at √sNN=8.16 TeV

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    ϒ production in p–Pb interactions is studied at the centre-of-mass energy per nucleon–nucleon collision √sNN = 8.16 TeV with the ALICE detector at the CERN LHC. The measurement is performed reconstructing bottomonium resonances via their dimuon decay channel, in the centre-of-mass rapidity intervals 2.03 < ycms < 3.53 and −4.46 < ycms < −2.96, down to zero transverse momentum. In this work, results on the ϒ(1S) production cross section as a function of rapidity and transverse momentum are presented. The corresponding nuclear modification factor shows a suppression of the ϒ(1S) yields with respect to pp collisions, both at forward and backward rapidity. This suppression is stronger in the low transverse momentum region and shows no significant dependence on the centrality of the interactions. Furthermore, the ϒ(2S) nuclear modification factor is evaluated, suggesting a suppression similar to that of the ϒ(1S). A first measurement of the ϒ(3S) has also been performed. Finally, results are compared with previous ALICE measurements in p–Pb collisions at √sNN = 5.02 TeV and with theoretical calculations.publishedVersio

    (Anti-)deuteron production in pp collisions at 1as=13TeV

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    The study of (anti-)deuteron production in pp collisions has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. In this paper the production of (anti-)deuterons is studied as a function of the charged particle multiplicity in inelastic pp collisions at s=13 TeV using the ALICE experiment. Thanks to the large number of accumulated minimum bias events, it has been possible to measure (anti-)deuteron production in pp collisions up to the same charged particle multiplicity (d Nch/ d \u3b7 3c 26) as measured in p\u2013Pb collisions at similar centre-of-mass energies. Within the uncertainties, the deuteron yield in pp collisions resembles the one in p\u2013Pb interactions, suggesting a common formation mechanism behind the production of light nuclei in hadronic interactions. In this context the measurements are compared with the expectations of coalescence and statistical hadronisation models (SHM)

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

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    Measurements of the inclusive J/psi yield as a function of charged-particle pseudorapidity density dN(ch)/d eta in pp collisions at root s = 13 TeV with ALICE at the LHC are reported. The J/psi meson yield is measured at midrapidity (vertical bar y vertical bar <0.9) in the dielectron channel, for events selected based on the charged-particle multiplicity at midrapidity (vertical bar eta vertical bar <1) and at forward rapidity (-3.7 <eta <-1.7 and 2.8 <eta <5.1); both observables are normalized to their corresponding averages in minimum bias events. The increase of the normalized J/psi yield with normalized dN(ch)/d eta 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. (C) 2020 European Organization for Nuclear Research. Published by Elsevier B.V.Peer reviewe

    First measurement of Ωc0 production in pp collisions at s=13 TeV

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    The inclusive production of the charm–strange baryon 0 c is measured for the first time via its hadronic √ decay into −π+ at midrapidity (|y| &lt;0.5) in proton–proton (pp) collisions at the centre-of-mass energy s =13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 &lt; pT &lt; 12 GeV/c. The pT dependence of the 0 c-baryon production relative to the prompt D0-meson and to the prompt 0 c-baryon production is compared to various models that take different hadronisation mechanisms into consideration. In the measured pT interval, the ratio of the pT-integrated cross sections of 0 c and prompt + c baryons multiplied by the −π+ branching ratio is found to be larger by a factor of about 20 with a significance of about 4σ when compared to e+e− collisions

    Elliptic flow of charged particles at midrapidity relative to the spectator plane in Pb–Pb and Xe–Xe collisions

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    Measurements of the elliptic flow coefficient relative to the collision plane defined by the spectator neutrons v2{ SP} in collisions of Pb ions at center-of-mass energy per nucleon–nucleon pair √ 2.76 TeV and Xe ions at √ sNN = sNN =5.44 TeV are reported. The results are presented for charged particles produced at midrapidity as a function of centrality and transverse momentum for the 5–70% and 0.2–6 GeV/c ranges, respectively. The ratio between v2{ SP} and the elliptic flow coefficient relative to the participant plane v2{4}, estimated using four-particle correlations, deviates by up to 20% from unity depending on centrality. This observation differs strongly from the magnitude of the corresponding eccentricity ratios predicted by the TRENTo and the elliptic power models of initial state fluctuations that are tuned to describe the participant plane anisotropies. The differences can be interpreted as a decorrelation of the neutron spectator plane and the reaction plane because of fragmentation of the remnants from the colliding nuclei, which points to an incompleteness of current models describing the initial state fluctuations. A significant transverse momentum dependence of the ratio v2{ SP}/v2{4} is observed in all but the most central collisions, which may help to understand whether momentum anisotropies at low and intermediate transverse momentum have a common origin in initial state f luctuations. The ratios of v2{ SP} and v2{4} to the corresponding initial state eccentricities for Xe–Xe and Pb–Pb collisions at similar initial entropy density show a difference of (7.0 ±0.9)%with an additional variation of +1.8% when including RHIC data in the TRENTo parameter extraction. These observations provide new experimental constraints for viscous effects in the hydrodynamic modeling of the expanding quark–gluon plasma produced in heavy-ion collisions at the LHC

    Compensation of piezoceramic bonding layer degradation for structural health monitoring

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    The compensation of the degradation of the bonding layer of piezoceramics used in structural health monitoring is addressed in this article. A simple admittance model is first used to measure and extract the variation of admittance parameters using the same acquisition chain which is used by the structural health monitoring system for damage monitoring. More precisely, the method uses measurable changes in physical transducer modal damping at frequencies around piezoceramic resonance to estimate the extent of degradation. Then, a finite element model is used to obtain calibration curves linking the variations in transducer modal damping to amplitude and phase of the ultrasonic signals generated or measured by the piezoceramics. Such calibration curves are obtained by simulating with the FEM the effect of varying the bonding layer coverage area and Young's modulus on (a) admittance and (b) amplitude and phase of the ultrasonic signals. From this, a signal correction factor is developed for the dominant bonding layer coverage area degradation failure mode to compensate for the changes in amplitude and phase of guided waves generated and measured by degraded piezoceramic transducers. The measured modal damping determines the amount of bonding layer degradation from the simulated modal damping calibration curves and then the quantified bonding layer degradation amount selects the amplitude and phase correction to be applied to measured signals from the calibration curves. The benefits of the signal correction factor are demonstrated below piezoceramic resonance to improve damage imaging and localization using the Embedded Ultrasonic Structural Radar algorithm (delay and sum method) when a single transducer in a sparse array of transducers fixed to an aluminum plate is damaged due to the close proximity of drop-weight impacts. Up to a certain damage extent, the signal correction factor could allow an extension of the service life of the structural health monitoring system. \ua9 The Author(s) 2013.Peer reviewed: YesNRC publication: Ye

    Comparison of metrics to monitor and compensate for piezoceramic debonding in structural health monitoring

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    This article investigates metrics to assess and compensate for the degradation of the adhesive layer of surface-bonded piezoceramic transducers for structural health-monitoring applications. Capacitance, resonance frequency, and modal damping parameters are derived from admittance curves using a lumped parameter model to monitor the degradation of the transducer adhesive layer. A pitch-catch configuration is then used to discriminate the effect of bonding degradation on actuation and sensing. It is shown that below the first mechanical resonance frequency of the piezoceramic transducers, the degradation causes a decrease in the amplitude of the transmitted and received signals, while above resonance, in addition to a decrease in the amplitude of the transmitted and received signals, a linear phase shift is observed. A signal-correction factor is proposed to adjust signals based on adhesive degradation evaluated using the measured modal damping. The benefits of the signal-correction factor are demonstrated in the frequency domain for both the A0 and S0 modes. \ua9 The Author(s) 2012.Peer reviewed: YesNRC publication: Ye
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