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Sökning: WFRF:(Hoffmann Michael M.)

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61.
  • Abramowski, A., et al. (författare)
  • Very-high-energy gamma-ray emission from the direction of the Galactic globular cluster Terzan 5
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 531, s. L18-
  • Tidskriftsartikel (refereegranskat)abstract
    • The HESS very-high-energy (VHE, E > 0.1 TeV) gamma-ray telescope system has discovered a new source, HESS J1747-248. The measured integral flux is (1.2 +/- 0.3) x 10(-12) cm(-2) s(-1) above 440 GeV for a power-law photon spectral index of 2.5 +/- 0.3(stat) +/- 0.2(sys). The VHE gamma-ray source is located in the close vicinity of the Galactic globular cluster Terzan 5 and extends beyond the HESS point spread function (0.07 degrees). The probability of a chance coincidence with Terzan 5 and an unrelated VHE source is quite low (similar to 10(-4)). With the largest population of identified millisecond pulsars (msPSRs), a very high core stellar density and the brightest GeV range flux as measured by Fermi-LAT, Terzan 5 stands out among Galactic globular clusters. The properties of the VHE source are briefly discussed in the context of potential emission mechanisms, notably in relation to msPSRs. Interpretation of the available data accommodates several possible origins for this VHE gamma-ray source, although none of them offers a satisfying explanation of its peculiar morphology.
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62.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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63.
  • Abramowski, A., et al. (författare)
  • Search for dark matter annihilation signals from the Fornax galaxy cluster with H.E.S.S.
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 750:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Fornax galaxy cluster was observed with the High Energy Stereoscopic System for a total live time of 14.5 hr, searching for very high energy (VHE; E > 100GeV) gamma-rays from dark matter (DM) annihilation. No significant signal was found in searches for point-like and extended emissions. Using several models of the DM density distribution, upper limits on the DM velocity-weighted annihilation cross-section as a function of the DM particle mass are derived. Constraints are derived for different DM particle models, such as those arising from Kaluza-Klein and supersymmetric models. Various annihilation final states are considered. Possible enhancements of the DM annihilation gamma-ray flux, due to DM substructures of the DM host halo, or from the Sommerfeld effect, are studied. Additional gamma-ray contributions from internal bremsstrahlung and inverse Compton radiation are also discussed. For a DM particle mass of 1 TeV, the exclusion limits at 95% of confidence level reach values of (95% C.L.) similar to 10(-23) cm(3) s(-1), depending on the DM particle model and halo properties. Additional contribution from DM substructures can improve the upper limits on by more than two orders of magnitude. At masses around 4.5 TeV, the enhancement by substructures and the Sommerfeld resonance effect results in a velocity-weighted annihilation cross-section upper limit at the level of (95% C.L.) similar to 10(-26) cm(3) s(-1).
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64.
  • Abramowski, A., et al. (författare)
  • Revisiting the Westerlund 2 field with the HESS telescope array
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 525, s. A46-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. Previous observations with the HESS telescope array revealed the existence of extended very-high-energy (VHE; E > 100 GeV) gamma-ray emission, HESS J1023-575, coincident with the young stellar cluster Westerlund 2. At the time of discovery, the origin of the observed emission was not unambiguously identified, and follow-up observations have been performed to further investigate the nature of this gamma-ray source. Methods. The Carina region towards the open cluster Westerlund 2 has been re-observed, increasing the total exposure to 45.9 h. The combined dataset includes 33 h of new data and now permits a search for energy-dependent morphology and detailed spectroscopy. Results. A new, hard spectrum VHE gamma-ray source, HESS J1026-582, was discovered with a statistical significance of 7 sigma. It is positionally coincident with the Fermi LAT pulsar PSRJ1028-5819. The positional coincidence and radio/gamma-ray characteristics of the LAT pulsar favors a scenario where the TeV emission originates from a pulsar wind nebula. The nature of HESS J1023-575 is discussed in light of the deep HESS observations and recent multi-wavelength discoveries, including the Fermi LAT pulsar PSRJ1022-5746 and giant molecular clouds in the region. Despite the improved VHE dataset, a clear identification of the object responsible for the VHE emission from HESS J1023-575 is not yet possible, and contribution from the nearby high-energy pulsar and/or the open cluster remains a possibility.
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65.
  • Acero, F., et al. (författare)
  • Discovery and follow-up studies of the extended, off-plane, VHE gamma-ray source HESS J1507-622
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 525, s. A45-
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The detection of gamma-rays in the very-high-energy (VHE) range (100 GeV-100 TeV) offers the possibility of studying the parent population of ultrarelativistic particles found in astrophysical sources, so it is useful for understanding the underlying astrophysical processes in nonthermal sources. Aims. The discovery of the VHE gamma-ray source HESS J1507-622 is reported and possibilities regarding its nature are investigated. Methods. The H. E. S. S. array of imaging atmospheric Cherenkov telescopes (IACTs) has a high sensitivity compared with previous instruments (similar to 1% of the Crab flux in 25 h observation time for a 5 sigma point-source detection) and has a large field of view (similar to 5 degrees in diameter). HESS J1507-622 was discovered within the ongoing H. E. S. S. survey of the inner Galaxy, and the source was also studied by means of dedicated multiwavelength observations. Results. A Galactic gamma-ray source, HESS J1507-622, located similar to 3.5 degrees. from the Galactic plane was detected with a statistical significance >9 sigma. Its energy spectrum is well fitted by a power law with spectral index Gamma = 2.24 +/- 0.16(stat) +/- 0.20(sys) and a flux above 1 TeV of (1.5 +/- 0.4(stat) +/- 0.3(sys)) x 10(-12) cm(-2) s(-1). Possible interpretations (considering both hadronic and leptonic models) of the VHE gamma-ray emission are discussed in the absence of an obvious counterpart.
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66.
  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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67.
  • Satizabal, Claudia L., et al. (författare)
  • Genetic architecture of subcortical brain structures in 38,851 individuals
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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68.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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69.
  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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70.
  • Wessel, Jennifer, et al. (författare)
  • Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
  • 2015
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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