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1.
  • Ablikim, M., et al. (författare)
  • Measurements of (XcJ)-> K+K-K+K- decays
  • 2006
  • Ingår i: Physics Letters B. - 0370-2693. ; 642:3, s. 197-202
  • Tidskriftsartikel (refereegranskat)abstract
    • Using 14M psi(2S) events taken with the BESII detector, chi(cJ) -> 2(K+K-) decays are studied. For the four-kaon final state, the branching fractions are B(chi(c0,1,2) ->.2(K+K-)) = (3.48 +/- 0.23 +/- 0.47) x 10(-3), (0.70 +/- 0.13 +/- 0.10) x 10(-3), and (2.17 +/- 0.20 +/- 0.31) x 10(-3). For the phi K+K- final state, the branching fractions, which are measured for the first time, are B(chi(c0,1,2) -> phi K+K-) = (1.03 +/- 0.22 +/- 0.15) x 10(-3), (0.46 +/- 0.16 +/- 0.06) x 10(-3), and (1.67 +/- 0.26 +/- 0.24) x 10(-4). For the phi phi final state, B(chi(c0,2) -> phi phi) = (0.94 +/- 0.21 +/- 0.13) x 10(-3) and (1.70 +/- 0.30 +/- 0.25) x 10(-3).
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3.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - 0028-0836. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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4.
  • Deng, Min, et al. (författare)
  • Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
  • 2013
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 45:6, s. 697-
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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6.
  • Albrechtsen, A., et al. (författare)
  • Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
  • 2013
  • Ingår i: Diabetologia. - Springer. - 0012-186X. ; 56:2, s. 298-310
  • Tidskriftsartikel (refereegranskat)abstract
    • Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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7.
  • Lange, Leslie A, et al. (författare)
  • Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.
  • 2014
  • Ingår i: American journal of human genetics. - CELL PRESS. - 0002-9297 .- 1537-6605. ; 94:2, s. 233-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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8.
  • Zhang, Guojie, et al. (författare)
  • Comparative genomics reveals insights into avian genome evolution and adaptation
  • 2014
  • Ingår i: Science. - 0036-8075. ; 346:6215, s. 1311-1320
  • Tidskriftsartikel (refereegranskat)abstract
    • Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.
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10.
  • Zhang, Y, et al. (författare)
  • Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China
  • 2013
  • Ingår i: Chinese Science Bulletin. - 1001-6538. ; 58:34, s. 4182-4189
  • Tidskriftsartikel (refereegranskat)abstract
    • Asthma, rhinitis and eczema (allergic or non-allergic) have increased throughout the world during the last decades, especially among children. Changes in the indoor environment are suspected to be important causes. China has experienced a dramatic change in indoor environmental exposures during the past two decades. However, such changes and their associations with children's asthma and other health aspects have not been thoroughly studied. China, Children, Homes, Health (CCHH), Phase I, was a cross-sectional questionnaire survey of 48219 children 1-8 years old in 10 Chinese cities during 2010-2012. The questionnaire includes the International Study of Asthma and Allergies in Childhood (ISAAC) core health questions and additional questions regarding housing, life habits and outdoor environment. In health analyses, children aged 3-6 years old were included. The prevalences of doctor diagnosed asthma varied from 1.7% to 9.8% (mean 6.8%), a large increase from 0.91% in 1999 and 1.50% in 2000. The prevalence of wheeze, rhinitis and atopic eczema (last 12 months) varied from 13.9% to 23.7%, 24.0% to 50.8% and 4.8% to 15.8%, respectively. Taiyuan had the lowest prevalences of all illnesses and Shanghai the highest, except for wheeze-where the highest value was for Urumqi. We found (1) no obvious association between disease prevalences and ambient PM10 concentrations and (2) higher prevalences of disease in humid climates with hot summers and cold winters, but with no centrally heated buildings. Associations between the diseases and economic status as indexed by Gross Domestic Product (GDP) requires further study.
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