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

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 3′-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

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

Search for the associated production of the Higgs boson with a top-quark pair

A search for the standard model Higgs boson produced in association with a top-quark pair t t ¯ H (tt¯H) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb &#8722;1 and 19.7 fb &#8722;1 collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H &#8594; hadrons, H &#8594; photons, and H &#8594; leptons. The results are characterized by an observed t t ¯ H tt¯H signal strength relative to the standard model cross section, &#956; = &#963;/&#963; SM ,under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is &#956; = 2.8 ± 1.0 for a Higgs boson mass of 125.6 GeV

Measurement of prompt Jψ\psi pair production in pp collisions at \sqrt s = 7 Tev

Production of prompt J/ &#968; meson pairs in proton-proton collisions at s s&#8730; = 7 TeV is measured with the CMS experiment at the LHC in a data sample corresponding to an integrated luminosity of about 4.7 fb &#8722;1 . The two J/ &#968; mesons are fully reconstructed via their decays into &#956; + &#956; &#8722; pairs. This observation provides for the first time access to the high-transverse-momentum region of J/ &#968; pair production where model predictions are not yet established. The total and differential cross sections are measured in a phase space defined by the individual J/ &#968; transverse momentum ( p T J/ &#968; ) and rapidity (| y J/ &#968; |): | y J/ &#968; | 6.5 GeV/ c ; 1.2 4.5 GeV/ c . The total cross section, assuming unpolarized prompt J/ &#968; pair production is 1.49 ± 0.07 (stat) ±0.13 (syst) nb. Different assumptions about the J/ &#968; polarization imply modifications to the cross section ranging from &#8722;31% to +27%

Measurements of the t(t)Overbar charge asymmetry using the dilepton decay channel in pp collisions at root s=7 TeV

The tt¯ charge asymmetry in proton-proton collisions at s&#8730; = 7 TeV is measured using the dilepton decay channel (ee, e &#956; , or &#956;&#956; ). The data correspond to a total integrated luminosity of 5.0 fb &#8722;1 , collected by the CMS experiment at the LHC. The tt and lepton charge asymmetries, defined as the differences in absolute values of the rapidities between the reconstructed top quarks and antiquarks and of the pseudorapidities between the positive and negative leptons, respectively, are measured to be A C = &#8722;0 . 010 ± 0 . 017 (stat . ) ± 0 . 008 (syst . ) and AlepC = 0 . 009 ± 0 . 010 (stat . ) ± 0 . 006 (syst . ). The lepton charge asymmetry is also measured as a function of the invariant mass, rapidity, and transverse momentum of the tt¯ system. All measurements are consistent with the expectations of the standard model

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Charged-particle nuclear modification factors in PbPb and pPb collisions at √=sNN=5.02 TeV

The spectra of charged particles produced within the pseudorapidity window |η| < 1 at √ sNN = 5.02 TeV are measured using 404 µb −1 of PbPb and 27.4 pb−1 of pp data collected by the CMS detector at the LHC in 2015. The spectra are presented over the transverse momentum ranges spanning 0.5 < pT < 400 GeV in pp and 0.7 < pT < 400 GeV in PbPb collisions. The corresponding nuclear modification factor, RAA, is measured in bins of collision centrality. The RAA in the 5% most central collisions shows a maximal suppression by a factor of 7–8 in the pT region of 6–9 GeV. This dip is followed by an increase, which continues up to the highest pT measured, and approaches unity in the vicinity of pT = 200 GeV. The RAA is compared to theoretical predictions and earlier experimental results at lower collision energies. The newly measured pp spectrum is combined with the pPb spectrum previously published by the CMS collaboration to construct the pPb nuclear modification factor, RpA, up to 120 GeV. For pT > 20 GeV, RpA exhibits weak momentum dependence and shows a moderate enhancement above unity

Excimer laser deposition of apatite at room temperature on titanium substrates

Highly adhesive apatite films were deposited by pulse laser sputtering of apatite target on Ti substrates at room temperature. The model of laser ablation/deposition of multi-component solids was discussed to explain the observed differences in the properties of films obtained from apatite mineral, sintered hydrohyapatite, and bone tissue targets