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Sökning: WFRF:(Wieland Thomas)

  • Resultat 11-20 av 39
  • Föregående 1[2]34Nästa
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  • Reifarth, R., et al. (författare)
  • Nuclear astrophysics with radioactive ions at FAIR
  • 2016
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
  • Konferensbidrag (refereegranskat)abstract
    • The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
  • Tin, Adrienne, et al. (författare)
  • Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
  • 2019
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 51:10, s. 1459-1474
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.
  • Wang, Dongxue, et al. (författare)
  • A deep proteome and transcriptome abundance atlas of 29 healthy human tissues
  • 2019
  • Ingår i: Molecular Systems Biology. - : WILEY. - 1744-4292 .- 1744-4292. ; 15:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-, transcriptome- and proteome-wide measurements provide insights into how biological systems are regulated. However, fundamental aspects relating to which human proteins exist, where they are expressed and in which quantities are not fully understood. Therefore, we generated a quantitative proteome and transcriptome abundance atlas of 29 paired healthy human tissues from the Human Protein Atlas project representing human genes by 18,072 transcripts and 13,640 proteins including 37 without prior protein-level evidence. The analysis revealed that hundreds of proteins, particularly in testis, could not be detected even for highly expressed mRNAs, that few proteins show tissue-specific expression, that strong differences between mRNA and protein quantities within and across tissues exist and that protein expression is often more stable across tissues than that of transcripts. Only 238 of 9,848 amino acid variants found by exome sequencing could be confidently detected at the protein level showing that proteogenomics remains challenging, needs better computational methods and requires rigorous validation. Many uses of this resource can be envisaged including the study of gene/protein expression regulation and biomarker specificity evaluation.
  • Wuttke, Matthias, et al. (författare)
  • A catalog of genetic loci associated with kidney function from analyses of a million individuals
  • 2019
  • Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
  • Clement, E., et al. (författare)
  • Conceptual design of the AGATA 1 π array at GANIL
  • 2017
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 855, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • The Advanced GAmma Tracking Array (AGATA) has been installed at the GANIL facility, Caen-France. This setup exploits the stable and radioactive heavy-ions beams delivered by the cyclotron accelerator complex of GANIL. Additionally, it benefits from a large palette of ancillary detectors and spectrometers to address in-beam γ-ray spectroscopy of exotic nuclei. The set-up has been designed to couple AGATA with a magnetic spectrometer, charged-particle and neutron detectors, scintillators for the detection of high-energy γ rays and other devices such as a plunger to measure nuclear lifetimes. In this paper, the design and the mechanical characteristics of the set-up are described. Based on simulations, expected performances of the AGATA l π array are presented.
  • Felix, Janine F, et al. (författare)
  • Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
  • 2016
  • Ingår i: Human molecular genetics. - 1460-2083. ; 25:2, s. 389-403
  • Tidskriftsartikel (refereegranskat)abstract
    • A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
  • Ferreira, Pedro G., et al. (författare)
  • Sequence variation between 462 human individuals fine-tunes functional sites of RNA processing
  • 2016
  • Ingår i: Scientific Reports. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent advances in the cost-efficiency of sequencing technologies enabled the combined DNA-and RNA-sequencing of human individuals at the population-scale, making genome-wide investigations of the inter-individual genetic impact on gene expression viable. Employing mRNA-sequencing data from the Geuvadis Project and genome sequencing data from the 1000 Genomes Project we show that the computational analysis of DNA sequences around splice sites and poly-A signals is able to explain several observations in the phenotype data. In contrast to widespread assessments of statistically significant associations between DNA polymorphisms and quantitative traits, we developed a computational tool to pinpoint the molecular mechanisms by which genetic markers drive variation in RNA-processing, cataloguing and classifying alleles that change the affinity of core RNA elements to their recognizing factors. The in silico models we employ further suggest RNA editing can moonlight as a splicing-modulator, albeit less frequently than genomic sequence diversity. Beyond existing annotations, we demonstrate that the ultra-high resolution of RNA-Seq combined from 462 individuals also provides evidence for thousands of bona fide novel elements of RNA processing-alternative splice sites, introns, and cleavage sites-which are often rare and lowly expressed but in other characteristics similar to their annotated counterparts.
  • Heim, Wieland, et al. (författare)
  • Using geolocator tracking data and ringing archives to validate citizen-science based seasonal predictions of bird distribution in a data-poor region
  • 2020
  • Ingår i: Global Ecology and Conservation. - : Elsevier. - 2351-9894. ; 24
  • Tidskriftsartikel (refereegranskat)abstract
    • Unstructured citizen-science data are increasingly used for analysing the abundance and distribution of species. Here we test the usefulness of such data to predict the seasonal distribution of migratory songbirds, and to analyse patterns of migratory connectivity. We used bird occurrence data from eBird, one of the largest global citizen science databases, to predict the year-round distribution of eight songbird taxa (Agropsar philippensis, Calliope calliope, Cecropis daurica, Emberiza aureola, Hirundo rustica, Locustella certhiola, Oriolus chinensis, Saxicola torquatus stejnegeri) that migrate through East Asia, a region especially poor in data but globally important for the conservation of migratory land birds. Maximum entropy models were built to predict spring stopover, autumn stopover and wintering areas. Ring recovery and geolocator tracking data were then used to evaluate, how well the predicted occurrence at a given period of the annual cycle matched sites where the species were known to be present from ringing and tracking data. Predicted winter ranges were generally smaller than those on published extent-of-occurrence maps (the hitherto only available source of distribution information). There was little overlap in stopover regions. The overlap between areas predicted as suitable from the eBird data and areas that had records from geolocator tracking was high in winter, and lower for spring and autumn migration. Less than 50% of the ringing recoveries came from locations within the seasonal predicted areas, with the highest overlap in autumn. The seasonal range size of a species affected the matching of tracking/ringing data with the predictions. Strong migratory connectivity was evident in Siberian Rubythroats and Barn Swallows. We identified two migration corridors, one over the eastern mainland of China, and one along a chain of islands in the Pacific. We show that the combination of disparate data sources has great potential to gain a better understanding of the non-breeding distribution and migratory connectivity of Eastern Palearctic songbirds. Citizen-science observation data are useful even in remote areas to predict the seasonal distribution of migratory species, especially in periods when birds are sedentary and when supplemented with tracking data.
  • Lagou, Vasiliki, et al. (författare)
  • Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
  • 2021
  • Ingår i: Nature Communications. - : NATURE RESEARCH. - 2041-1723 .- 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
  • Lieder, R M, et al. (författare)
  • Gamma-ray tracking arrays
  • 2001
  • Konferensbidrag (refereegranskat)abstract
    • The next generation of 4 pi arrays for high-precision gamma -ray spectroscopy will involve "gamma -ray tracking front-end on digital signal processing techniques, which allows to extract energy, timing and spatial information on the interactions of a gamma -ray in the Ge detector by pulse shape analysis of its signals. Utilizing the information on the positions of the interaction points and the energies released at each point the tracks of the gamma -rays in a Ge shell can be reconstructed in three dimensions.
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  • Resultat 11-20 av 39
  • Föregående 1[2]34Nästa
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