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Träfflista för sökning "WFRF:(Bernstein Charles N.) "

Sökning: WFRF:(Bernstein Charles N.)

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  • Tidskriftsartikel (refereegranskat)
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  • Tidskriftsartikel (refereegranskat)
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  • Drlica-Wagner, A. (författare)
  • SEARCH FOR GAMMA-RAY EMISSION FROM DES DWARF SPHEROIDAL GALAXY CANDIDATES WITH FERMI-LAT DATA
  • 2015
  • Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 809:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to their proximity, high dark-matter (DM) content, and apparent absence of non-thermal processes, Milky Way dwarf spheroidal satellite galaxies (dSphs) are excellent targets for the indirect detection of DM. Recently, eight new dSph candidates were discovered using the first year of data from the Dark Energy Survey (DES). We searched for gamma-ray emission coincident with the positions of these new objects in six years of Fermi Large Area Telescope data. We found no significant excesses of gamma-ray emission. Under the assumption that the DES candidates are dSphs with DM halo properties similar to the known dSphs, we computed individual and combined limits on the velocity-averaged DM annihilation cross section for these new targets. If the estimated DM content of these dSph candidates is confirmed, they will constrain the annihilation cross section to lie below the thermal relic cross section for DM particles with masses less than or similar to 20 GeV annihilating via the b (b) over bar or pi(+)pi(-) channels.
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  • Haiman, Christopher A., et al. (författare)
  • A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
  • 2011
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718. ; 43:12, s. 61-1210
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
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8.
  • Sampson, Joshua N., et al. (författare)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - 0027-8874 .- 1460-2105. ; 107:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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  • Purrington, Kristen S., et al. (författare)
  • Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
  • 2014
  • Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 35:5, s. 1012-1019
  • Tidskriftsartikel (refereegranskat)abstract
    • In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
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10.
  • Christmann, Benjamin S., et al. (författare)
  • Human seroreactivity to gut microbiota antigens
  • 2015
  • Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 136:5, s. 1378-1386
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although immune responses directed against antigens from the intestinal microbiota are observed in certain diseases, the normal human adaptive immune response to intestinal microbiota is poorly defined. Objective: Our goal was to assess the adaptive immune response to the intestinal microbiota present in 143 healthy adults and compare this response with the response observed in 52 children and their mothers at risk of having allergic disease. Methods: Human serum was collected from adults and children followed from birth to 7 years of age, and the serum IgG response to a panel of intestinal microbiota antigens was assessed by using a novel protein microarray. Results: Nearly every subject tested, regardless of health status, had serum IgG that recognized a common set of antigens. Seroreactivity to the panel of antigens was significantly lower in atopic adults. Healthy infants expressed the highest level of IgG seroreactivity to intestinal microbiota antigens. This adaptive response developed between 6 and 12 months of age and peaked around 2 years of age. Low IgG responses to certain clusters of microbiota antigens during infancy were associated with allergy development during childhood. Conclusions: There is an observed perturbation of the adaptive response to antigens from the microbiota in allergic subjects. These perturbations are observable even in childhood, suggesting that optimal stimulation of the adaptive immune system by the microbiota might be needed to prevent certain immune-mediated diseases.
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