Flavor Decomposition of the Polarized Quark Distributions in the Nucleon from Inclusive and Semi-inclusive Deep-inelastic Scattering

Spin asymmetries of semi-inclusive cross sections for the production of positively and negatively charged hadrons have been measured in deep-inelastic scattering of polarized positrons on polarized hydrogen and 3He targets, in the kinematic range 0.023<x<0.6 and 1 GeV^2<Q^2<10 GeV^2. Polarized quark distributions are extracted as a function of x for up $(u+u_bar) and down (d+d_bar) flavors. The up quark polarization is positive and the down quark polarization is negative in the measured range. The polarization of the sea is compatible with zero. The first moments of the polarized quark distributions are presented. The isospin non-singlet combination Delta_q_3 is consistent with the prediction based on the Bjorken sum rule. The moments of the polarized quark distributions are compared to predictions based on SU(3)_f flavor symmetry and to a prediction from lattice QCD.Comment: 14 pages, 6 figures (eps format), 10 tables in Latex New version contains tables of asymmetries and correlation matri

Plane-wave impulse approximation extraction of the neutron magnetic form factor from quasielastic 3He(e,e′) at Q2=0.3 to 0.6 (GeV/c)2

A high precision measurement of the transverse spin-dependent asymmetry AT′ in 3He(e,e′) quasielastic scattering was performed in Hall A at Jefferson Lab at values of the squared four-momentum transfer, Q2, between 0.1 and 0.6 (GeV/c)2. AT′ is sensitive to the neutron magnetic form factor, GMn. Values of GMn at Q2=0.1 and 0.2 (GeV/c)2, extracted using Faddeev calculations, were reported previously. Here, we report the extraction of GMn for the remaining Q2 values in the range from 0.3 to 0.6 (GeV/c)2 using a plane-wave impulse approximation calculation. The results are in good agreement with recent precision data from experiments using a deuterium target

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the

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

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Plane-wave impulse approximation extraction of the neutron magnetic form factor from quasielastic 3He(e,e′) at Q2=0.3 to 0.6 (GeV/c)2

A high precision measurement of the transverse spin-dependent asymmetry AT′ in 3He(e,e′) quasielastic scattering was performed in Hall A at Jefferson Lab at values of the squared four-momentum transfer, Q2, between 0.1 and 0.6 (GeV/c)2. AT′ is sensitive to the neutron magnetic form factor, GMn. Values of GMn at Q2=0.1 and 0.2 (GeV/c)2, extracted using Faddeev calculations, were reported previously. Here, we report the extraction of GMn for the remaining Q2 values in the range from 0.3 to 0.6 (GeV/c)2 using a plane-wave impulse approximation calculation. The results are in good agreement with recent precision data from experiments using a deuterium target

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

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

Extraction of the Neutron Magnetic Form Factor from Quasi-Elastic 3He(pol)(e(pol),e') at Q^2 = 0.1 - 0.6 (GeV/c)^2

We have measured the spin-dependent transverse asymmetry, A_T', in quasi-elastic inclusive electron scattering from polarized 3He with high precision at Q^2 = 0.1 to 0.6 (GeV/c)^2. The neutron magnetic form factor, GMn, was extracted at Q^2 = 0.1 and 0.2 (GeV/c)^2 using a non-relativistic Faddeev calculation that includes both final-state interactions (FSI) and meson-exchange currents (MEC). In addition, GMn was extracted at Q^2 = 0.3 to 0.6 (GeV/c)^2 using a Plane Wave Impulse Approximation calculation. The accuracy of the modeling of FSI and MEC effects was tested and confirmed with a precision measurement of the spin-dependent asymmetry in the breakup threshold region of the 3He(pol)(e(pol),e') reaction. The total relative uncertainty of the extracted GMn data is approximately 3%. Close agreement was found with other recent high-precision GMn data in this Q^2 range.Comment: Archival paper, 17 pages, 10 figures, 5 tables, submitted to Physical Review C. v2: shortened considerably, updated comparison to theor