Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women

Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2

Improved Measurement of the dˉ/uˉ\bar d / \bar u Asymmetry in the Nucleon Sea

Measurements of the ratio of Drell-Yan yields from an 800 \rm{GeV/c} proton beam incident on liquid hydrogen and deuterium targets are reported. Approximately 360,000 Drell-Yan muon pairs remained after all cuts on the data. From these data, the ratio of anti-down ($\bar{d}$) to anti-up ($\bar{u}$) quark distributions in the proton sea is determined over a wide range in Bjorken-$x$. These results confirm previous measurements by E866 and extend them to lower $x$. From these data, $(\bar{d}-\bar{u})$ and $\int(\bar{d}-\bar{u})dx$ are evaluated for $0.015<x<0.35$. These results are compared with parameterizations of various parton distribution functions, models and experimental results from NA51, NMC, and HERMES.Comment: 17 pages, 15 figure

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%