1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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2. |
- Aharonian, F., et al.
(författare)
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SIMULTANEOUS OBSERVATIONS OF PKS 2155-304 WITH HESS, FERMI, RXTE, AND ATOM : SPECTRAL ENERGY DISTRIBUTIONS AND VARIABILITY IN A LOW STATE
- 2009
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 0004-637X .- 1538-4357. ; 696:2, s. L150-L155
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first simultaneous observations that cover the optical, X-ray, and high-energy gamma-ray bands of the BL Lac object PKS 2155-304. The gamma-ray bands were observed for 11 days, between 2008 August 25 and 2008 September 6 (MJD 54704-54715), jointly with the Fermi Gamma-ray Space Telescope and the HESS atmospheric Cherenkov array, providing the first simultaneous MeV-TeV spectral energy distribution (SED) with the new generation of gamma-ray telescopes. The ATOM telescope and the RXTE and Swift observatories provided optical and X-ray coverage of the low-energy component over the same time period. The object was close to the lowest archival X-ray and very high energy (VHE; > 100 GeV) state, whereas the optical flux was much higher. The light curves show relatively little (similar to 30%) variability overall when compared to past flaring episodes, but we find a clear optical/VHE correlation and evidence for a correlation of the X-rays with the high-energy spectral index. Contrary to previous observations in the flaring state, we do not find any correlation between the X-ray and VHE components. Although synchrotron self-Compton models are often invoked to explain the SEDs of BL Lac objects, the most common versions of these models are at odds with the correlated variability we find in the various bands for PKS 2155-304.
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3. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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4. |
- Aharonian, F., et al.
(författare)
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Constraints on the multi-TeV particle population in the Coma galaxy cluster with HESS observations
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 502:2, s. 437-443
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Galaxy clusters are key targets in the search for ultra high energy particle accelerators. The Coma cluster represents one of the best candidates for such a search owing to its high mass, proximity, and the established non-thermal radio emission centred on the cluster core. Methods. The HESS (High Energy Stereoscopic System) telescopes observed Coma for similar to 8 h in a search for gamma-ray emission at energies > 1 TeV. The large 3.5 degrees FWHM field of view of HESS is ideal for viewing a range of targets at various sizes including the Coma cluster core, the radio-relic (1253+275) and merger/infall (NGC 4839) regions to the southwest, and features greater than 1 degrees away. Results. No evidence for point-like nor extended TeV gamma-ray emission was found and upper limits to the TeV flux F(E) for E > 1, > 5, and > 10 TeV were set for the Coma core and other regions. Converting these limits to an energy flux E(2)F(E) the lowest or most constraining is the E > 5 TeV upper limit for the Coma core (0.2 degrees radius) at similar to 8% Crab flux units or similar to 10(-13) ph cm(-2) s(-1). Conclusions. The upper limits for the Coma core were compared with a prediction for the gamma-ray emission from proton-proton interactions, the level of which ultimately scales with the mass of the Coma cluster. A direct constraint using our most stringent limit for E > 5 TeV, on the total energy content in non-thermal protons with injection energy spectrum alpha E(-2.1) and spatial distribution following the thermal gas in the cluster, is found to be similar to 0.2 times the thermal energy, or similar to 10(62) erg. The E > 5 TeV gamma-ray threshold in this case corresponds to cosmic-ray proton energies greater than or similar to 50 TeV. Our upper limits rule out the most optimistic theoretical models for gamma ray emission from clusters and complement radio observations which constrain the cosmic ray content in clusters at significantly lower proton energies, subject to assumptions on the magnetic field strength.
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5. |
- Aharonian, F., et al.
(författare)
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Discovery of very high energy γ-ray emission from centaurus a with H.E.S.S.
- 2009
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8205. ; 695:1, s. L40-L44
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of faint very high energy (VHE; E > 100 GeV) gamma-ray emission from the radio galaxy Centaurus A in observations performed with the High Energy Stereoscopic System (H.E.S.S.) experiment, an imaging atmospheric Cherenkov telescope array consisting of four telescopes located in Namibia. Centaurus A has been observed for more than 120 hr. A signal with a statistical significance of 5.0 sigma is detected from the region including the radio core and the inner kpc jets. The integral flux above an energy threshold of similar to 250 GeV is measured to be 0.8% of the flux of the Crab Nebula (apparent luminosity: L(> 250 GeV) approximate to 2.6 x 1039 erg s(-1), adopting a distance of 3.8 Mpc). The spectrum can be described by a power law with a photon index of 2.7 +/- 0.5(stat) +/- 0.2(sys). No significant flux variability is detected in the data set. However, the low flux only allows detection of variability on the timescale of days to flux increments above a factor of similar to 15-20 (3 sigma and 4 sigma, respectively). The discovery of VHE gamma-ray emission from Centaurus A reveals particle acceleration in the source to > TeV energies and, together with M 87, establishes radio galaxies as a class of VHE emitters.
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6. |
- Aharonian, F., et al.
(författare)
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Simultaneous multiwavelength observations of the second exceptional gamma-ray flare of PKS2155-304 in July 2006
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 502:3, s. 749-770
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Forskningsöversikt (refereegranskat)abstract
- Aims. The X-ray-TeV connection and the evolution of the emitting particle population is studied in high-energy peaked BL Lac objects, by obtaining spectral information in both bands on sub-hour timescales. Methods. Simultaneous observations with HESS, Chandra and the Bronberg optical observatory were performed on the BL Lac object PKS 2155-304 in the night of July 29-30 2006, when the source underwent a major gamma-ray outburst during its high-activity state of Summer 2006. This event took place about 44 h after the other major outburst of the night of July 27-28, which is known for its ultrafast variability. An unprecedented 6 to 8 h of simultaneous, uninterrupted coverage was achieved, with spectra and light curves measured down to 7 and 2 min timescales, respectively. Results. The source exhibited one major flare along the night, at high energies. The gamma-ray flux reached a maximum of similar to 11 times the Crab flux (>400 GeV), with rise/decay timescales of similar to 1 h, plus a few smaller-amplitude flares superimposed on the decaying phase. The emission in the X-ray and VHE gamma-ray bands is strongly correlated, with no evidence of lags. The spectra also evolve with similar patterns, and are always soft ( photon index G > 2), indicating no strong shift of the peaks in the spectral energy distribution towards higher energies. Only at the flare maximum is there evidence that the gamma-ray peak is inside the observed passband, at similar to 400-600 GeV. The VHE spectrum shows a curvature that is variable with time and stronger at higher fluxes. The huge VHE variations (similar to 22x) are only accompanied by small-amplitude X-ray and optical variations (factor 2 and 15% respectively). The source has shown for the first time in a high-energy peaked BL Lac object a large Compton dominance (L(C)/L(S) similar to 10) - rapidly evolving - and a cubic relation between VHE and X-ray flux variations, during a decaying phase. These results challenge the common scenarios for the TeV-blazar emission.
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7. |
- Aharonian, F., et al.
(författare)
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Detection of very high energy radiation from HESS J1908+063 confirms the Milagro unidentified source MGRO J1908+06
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 499:3, s. 723-728
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Detection of gamma-ray source above 300 GeV is reported, confirming the unidentified source MGRO J1908+06, discovered by the Milagro collaboration at a median energy of 20 TeV. Methods. The source was observed during 27 h as part of the extension of the HESS Galactic plane survey to longitudes > 30 degrees. Results. HESS J1908+063 is detected at a significance level of 10.9 sigma with an integral flux above 1 TeV of (3.76 +/- 0.29 (stat) +/- 0.75(sys)) x 10(-12) ph cm(-2) s(-1), and a spectral photon index Gamma = 2.10 +/- 0.07 (stat) +/- 0.2(sys). The positions and fluxes of HESS J1908+063 and MGRO J1908+06 are in good agreement. Possible counterparts at other wavelengths and the origin of the gamma-ray emission are discussed. The nearby unidentified GeV source, GRO J1908+0556 (GeV) which also remains unidentified and the new Fermi pulsar 0FGL J1907.5+0617, may be connected to the TeV source.
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8. |
- Aharonian, F., et al.
(författare)
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HESS upper limit on the very high energy gamma-ray emission from the globular cluster 47 Tucanae
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 499:1, s. 273-277
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Tidskriftsartikel (refereegranskat)abstract
- Observations of the globular cluster 47 Tucanae (NGC 104), which contains at least 23 ms pulsars, were performed with the HESS telescope system. The observations lead to an upper limit of F(E > 800 GeV) < 6.7 x 10(-13) cm(-2) s(-1) on the integral gamma-ray photon flux from 47 Tucanae. Considering millisecond pulsars as the unique potential source of gamma-rays in the globular cluster, constraints based on emission models are derived: on the magnetic field in the average pulsar nebula and on the conversion efficiency of spin-down power to gamma-ray photons or to relativistic leptons.
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9. |
- Aharonian, F., et al.
(författare)
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Spectrum and variability of the Galactic center VHE gamma-ray source HESS J1745-290
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 503:3, s. 817-825
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Tidskriftsartikel (refereegranskat)abstract
- Aims. A detailed study of the spectrum and variability of the source HESS J1745-290 in the Galactic Center (GC) region using new data from the H. E. S. S. array of Cherenkov telescopes is presented. Flaring activity and quasi periodic oscillations (QPO) of HESS J1745-290 are investigated. Methods. The image analysis is performed with a combination of a semi-analytical shower model and the statistical moment-based Hillas technique. The spectrum and lightcurves of HESS J1745-290 are derived with a likelihood method based on a spectral shape hypothesis. Rayleigh tests and Fourier analysis of the H. E. S. S. GC signal are used to study the periodicity of the source. Results. With a three-fold increase in statistics compared to previous work, a deviation from a simple power law spectrum is detected for the first time. The measured energy spectrum over the three years 2004, 2005 and 2006 of data taking is compatible with both a power law spectrum with an exponential cut-off and a broken power law spectrum. The curvature of the energy spectrum is likely to be intrinsic to the photon source, as opposed to effects of interstellar absorption. The power law spectrum with an exponential cut-off is characterized by a photon index of 2.10 +/- 0.04(stat) +/- 0.10(syst) and a cut-off energy at 15.7 +/- 3.4(stat) +/- 2.5(syst) TeV. The broken power law spectrum exhibits spectral indices of 2.02 +/- 0.08(stat) +/- 0.10(syst) and 2.63 +/- 0.14(stat) +/- 0.10(syst) with a break energy at 2.57 +/- 0.19(stat) +/- 0.44(syst) TeV. No significant flux variation is found. Increases in the gamma-ray flux of HESS J1745-290 by at least a factor of two would be required for a 3 sigma detection of a flare with time scales of an hour. Investigation of possible QPO activity at periods claimed to be detected in X-rays does not show any periodicities in the H. E. S. S. signal.
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10. |
- Aharonian, F., et al.
(författare)
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Very high energy gamma-ray observations of the galaxy clusters Abell 496 and Abell 85 with HESS
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 495:1, s. 27-35
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The nearby galaxy clusters Abell 496 and Abell 85 are studied in the very high-energy (VHE, E > 100 GeV) band to investigate VHE cosmic rays (CRs) in this class of objects which are the largest gravitationally bound systems in the Universe. Methods. HESS, an array of four imaging atmospheric cherenkov telescopes (IACT), was used to observe the targets in the range of VHE gamma rays. Results. No significant gamma-ray signal is found at the respective position of the two clusters with several different source size assumptions for each target. In particular, emission regions corresponding to the high-density core, to the extension of the entire X-ray emission in these clusters, and to the very extended region where the accretion shock is expected are investigated. Upper limits are derived for the gamma-ray flux at energies E > 570 GeV for Abell 496 and E > 460 GeV for Abell 85. Conclusions. From the non-detection in VHE gamma rays, upper limits on the total energy of hadronic CRs in the clusters are calculated. If the cosmic-ray energy density follows the large-scale gas density profile, the limit on the fraction of energy in these non-thermal particles with respect to the total thermal energy of the intra-cluster medium (ICM) is 51% for Abell 496 and only 8% for Abell 85 due to its higher mass and higher gas density. These upper limits are compared with theoretical estimates. They predict about similar to 10% of the thermal energy of the ICM in non-thermal particles. The observations presented here can constrain these predictions especially for the case of the Abell 85 cluster.
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11. |
- Aharonian, F., et al.
(författare)
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Simultaneous HESS and Chandra observations of Sagitarius A(star) during an X-ray flare
- 2008
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 492:1, s. L25-L28
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Tidskriftsartikel (refereegranskat)abstract
- The rapidly varying (similar to 10 min timescale) non-thermal X-ray emission observed from Sgr A(star) implies that particle acceleration is occuring close to the event horizon of the supermassive black hole. The TeV gamma-ray source HESS J1745-290 is coincident with Sgr A(star) and may be closely related to its X-ray emission. Simultaneous X-ray and TeV observations are required to elucidate the relationship between these objects. We report on joint HESS/Chandra observations performed in July 2005, during which an X-ray flare was detected. Despite a factor of approximate to 9 increase in the X-ray flux of Sgr A(star), no evidence is found for an increase in the TeV gamma-ray flux from this region. We find that an increase in the gamma-ray flux of a factor of 2 or greater can be excluded at a confidence level of 99%. This finding disfavours scenarios in which the keV and TeV emission are associated with the same population of accelerated particles and in which the bulk of the gamma-ray emission is produced within similar to 1014 cm (similar to 100 RS) of the supermassive black hole.
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12. |
- Aharonian, F., et al.
(författare)
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Energy Spectrum of Cosmic-Ray Electrons at TeV Energies
- 2008
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Ingår i: Physical Review Letters. - : APS Physics. - 0031-9007 .- 1079-7114. ; 101:26
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Tidskriftsartikel (refereegranskat)abstract
- The very large collection area of ground-based gamma-ray telescopes gives them a substantial advantage over balloon or satellite based instruments in the detection of very-high-energy (> 600 GeV) cosmic-ray electrons. Here we present the electron spectrum derived from data taken with the High Energy Stereoscopic System (H.E.S.S.) of imaging atmospheric Cherenkov telescopes. In this measurement, the first of this type, we are able to extend the measurement of the electron spectrum beyond the range accessible to direct measurements. We find evidence for a substantial steepening in the energy spectrum above 600 GeV compared to lower energies.
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13. |
- Aharonian, F., et al.
(författare)
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Limits on an Energy Dependence of the Speed of Light from a Flare of the Active Galaxy PKS 2155-304
- 2008
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Ingår i: Physical Review Letters. - : APS Physics. - 0031-9007 .- 1079-7114. ; 101:17
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Tidskriftsartikel (refereegranskat)abstract
- In the past few decades, several models have predicted an energy dependence of the speed of light in the context of quantum gravity. For cosmological sources such as active galaxies, this minuscule effect can add up to measurable photon-energy dependent time lags. In this Letter a search for such time lags during the High Energy Stereoscopic System observations of the exceptional very high energy flare of the active galaxy PKS 2155-304 on 28 July 2006 is presented. Since no significant time lag is found, lower limits on the energy scale of speed of light modifications are derived.
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14. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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15. |
- Pinese, Mark, et al.
(författare)
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The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing. Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.
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16. |
- Altenburger, R., et al.
(författare)
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Future water quality monitoring - Adapting tools to deal with mixtures of pollutants in water resource management
- 2015
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 512, s. 540-551
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Tidskriftsartikel (refereegranskat)abstract
- Environmental quality monitoring of water resources is challenged with providing the basis for safeguarding the environment against adverse biological effects of anthropogenic chemical contamination from diffuse and point sources. While current regulatory efforts focus on monitoring and assessing a few legacy chemicals, many more anthropogenic chemicals can be detected simultaneously in our aquatic resources. However, exposure to chemical mixtures does not necessarily translate into adverse biological effects nor clearly shows whether mitigation measures are needed. Thus, the question which mixtures are present and which have associated combined effects becomes central for defining adequate monitoring and assessment strategies. Here we describe the vision of the international, EU-funded project SOLUTIONS, where three routes are explored to link the occurrence of chemical mixtures at specific sites to the assessment of adverse biological combination effects. First of all, multi-residue target and non-target screening techniques covering a broader range of anticipated chemicals co-occurring in the environment are being developed. By improving sensitivity and detection limits for known bioactive compounds of concern, new analytical chemistry data for multiple components can be obtained and used to characterise priority mixtures. This information on chemical occurrence will be used to predict mixture toxicity and to derive combined effect estimates suitable for advancing environmental quality standards. Secondly, bioanalytical tools will be explored to provide aggregate bioactivity measures integrating all components that produce common (adverse) outcomes even for mixtures of varying compositions. The ambition is to provide comprehensive arrays of effect-based tools and trait-based field observations that link multiple chemical exposures to various environmental protection goals more directly and to provide improved in situ observations for impact assessment of mixtures. Thirdly, effect-directed analysis (EDA) will be applied to identify major drivers of mixture toxicity. Refinements of EDA include the use of statistical approaches with monitoring information for guidance of experimental EDA studies. These three approaches will be explored using case studies at the Danube and Rhine river basins as well as rivers of the Iberian Peninsula. The synthesis of findings will be organised to provide guidance for future solution-oriented environmental monitoring and explore more systematic ways to assess mixture exposures and combination effects in future water quality monitoring. (C) 2015 Elsevier B.V. All rights reserved.
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17. |
- Tyrrell, Jessica, et al.
(författare)
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Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.
- 2012
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 21:24, s. 5344-5358
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Tidskriftsartikel (refereegranskat)abstract
- Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.
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20. |
- Bertorello, Alejandro M., et al.
(författare)
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Increased Arterial Blood Pressure and Vascular Remodeling in Mice Lacking Salt-Inducible Kinase 1 (SIK1)
- 2015
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Ingår i: Circulation Research. - : American Heart Association. - 0009-7330 .- 1524-4571. ; 116:4, s. 642-U190
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: In human genetic studies a single nucleotide polymorphism within the salt-inducible kinase 1 (SIK1) gene was associated with hypertension. Lower SIK1 activity in vascular smooth muscle cells (VSMCs) leads to decreased sodium-potassium ATPase activity, which associates with increased vascular tone. Also, SIK1 participates in a negative feedback mechanism on the transforming growth factor-beta 1 signaling and downregulation of SIK1 induces the expression of extracellular matrix remodeling genes. Objective: To evaluate whether reduced expression/activity of SIK1 alone or in combination with elevated salt intake could modify the structure and function of the vasculature, leading to higher blood pressure. Methods and Results: SIK1 knockout (sik1(-/-)) and wild-type (sik1(+/+)) mice were challenged to a normal-or chronic high-salt intake (1% NaCl). Under normal-salt conditions, the sik1(-/-) mice showed increased collagen deposition in the aorta but similar blood pressure compared with the sik1(+/+) mice. During high-salt intake, the sik1+/+ mice exhibited an increase in SIK1 expression in the VSMCs layer of the aorta, whereas the sik1(-/-) mice exhibited upregulated transforming growth factor-beta 1 signaling and increased expression of endothelin-1 and genes involved in VSMC contraction, higher systolic blood pressure, and signs of cardiac hypertrophy. In vitro knockdown of SIK1 induced upregulation of collagen in aortic adventitial fibroblasts and enhanced the expression of contractile markers and of endothelin-1 in VSMCs. Conclusions: Vascular SIK1 activation might represent a novel mechanism involved in the prevention of high blood pressure development triggered by high-salt intake through the modulation of the contractile phenotype of VSMCs via transforming growth factor-beta 1-signaling inhibition.
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21. |
- Brion, G, et al.
(författare)
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Probing Norwalk-like virus presence in shellfish, using artificial neural networks.
- 2004
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Ingår i: Water Science and Technology. - 0273-1223 .- 1996-9732. ; 50:1, s. 125-9
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Tidskriftsartikel (refereegranskat)abstract
- A database was examined using artificial neural network (ANN) models to investigate the efficacy of predicting PCR-identified Norwalk-like virus presence and absence in shellfish. The relative importance of variables in the model and the predictive power obtained by application of ANN modelling methods were compared with previously developed logistic regression models. In addition, two country-specific datasets were analysed separately with ANN models to determine if the relative importance of the input variables was similar for geographically diverse regions. The results of this analysis found that ANN models predicted Norwalk-like virus presence and absence in shellfish with equivalent, and better, precision than logistic regression models. For overall classification performance, ANN modelling had a rate of 93%, vs 75% for the logistic regression. ANN models were able to illuminate the site-specific relationships between indicators and pathogens.
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