| 1. |
- Abramowski, A., et al.
(författare)
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The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
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Tidskriftsartikel (refereegranskat)abstract
- The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
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| 2. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 3. |
- Abramowski, A., et al.
(författare)
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Discovery of VHE gamma-ray emission and multi-wavelength observations of the BL Lacertae object 1RXSJ101015.9-311909
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 542, s. A94-
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Tidskriftsartikel (refereegranskat)abstract
- 1RXS J101015.9-311909 is a galaxy located at a redshift of z = 0.14 hosting an active nucleus (called AGN) belonging to the class of bright BL Lac objects. Observations at high (HE, E > 100 MeV) and very high (VHE, E > 100 GeV) energies provide insights into the origin of very energetic particles present in such sources and the radiation processes at work. We report on results from VHE observations performed between 2006 and 2010 with the H. E. S. S. instrument, an array of four imaging atmospheric Cherenkov telescopes. H. E. S. S. data have been analysed with enhanced analysis methods, making the detection of faint sources more significant. VHE emission at a position coincident with 1RXS J101015.9-311909 is detected with H. E. S. S. for the first time. In a total good-quality livetime of about 49 h, we measure 263 excess counts, corresponding to a significance of 7.1 standard deviations. The photon spectrum above 0.2 TeV can be described by a power-law with a photon index of Gamma = 3.08 +/- 0.42(stat) +/- 0.20(sys). The integral flux above 0.2 TeV is about 0.8% of the flux of the Crab nebula and shows no significant variability over the time reported. In addition, public Fermi/LAT data are analysed to search for high energy emission from the source. The Fermi/LAT HE emission in the 100 MeV to 200 GeV energy range is significant at 8.3 standard deviations in the chosen 25-month dataset. UV and X-ray contemporaneous observations with the Swift satellite in May 2007 are also reported, together with optical observations performed with the atom telescope located at the H. E. S. S. site. Swift observations reveal an absorbed X-ray flux of F(0.3-7) keV = 1.04(-0.05)(+0.04) x 10(-11) erg cm(-2) s(-1) in the 0.3-7 keV range. Finally, all the available data are used to study the multi-wavelength properties of the source. The spectral energy distribution (SED) can be reproduced using a simple one-zone Synchrotron Self Compton (SSC) model with emission from a region with a Doppler factor of 30 and a magnetic field between 0.025 and 0.16 G. These parameters are similar to those obtained for other sources of this type.
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| 4. |
- Abramowski, A., et al.
(författare)
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A multiwavelength view of the flaring state of PKS 2155-304 in 2006
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539, s. A149-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Multiwavelength (MWL) observations of the blazar PKS 2155-304 during two weeks in July and August 2006, the period when two exceptional flares at very high energies (VHE, E greater than or similar to 100 GeV) occurred, provide a detailed picture of the evolution of its emission. The complete data set from this campaign is presented, including observations in VHE gamma-rays (H.E.S. S.), X-rays (RXTE, Chandra, Swift XRT), optical (Swift UVOT, Bronberg, Watcher, ROTSE), and in the radio band (NRT, HartRAO, ATCA). Optical and radio light curves from 2004 to 2008 are compared to the available VHE data from this period, to put the 2006 campaign into the context of the long-term evolution of the source. Aims. The data set offers a close view of the evolution of the source on different time scales and yields new insights into the properties of the emission process. The predictions of synchrotron self-Compton (SSC) scenarios are compared to the MWL data, with the aim of describing the dominant features in the data down to the hour time scale. Methods. The spectral variability in the X-ray and VHE bands is explored and correlations between the integral fluxes at different wavelengths are evaluated. SSC modelling is used to interpret the general trends of the varying spectral energy distribution. Results. The X-ray and VHE gamma-ray emission are correlated during the observed high state of the source, but show no direct connection with longer wavelengths. The long-term flux evolution in the optical and radio bands is found to be correlated and shows that the source reaches a high state at long wavelengths after the occurrence of the VHE flares. Spectral hardening is seen in the Swift XRT data. Conclusions. The nightly averaged high-energy spectra of the non-flaring nights can be reproduced by a stationary one-zone SSC model, with only small variations in the parameters. The spectral and flux evolution in the high-energy band during the night of the second VHE flare is modelled with multi-zone SSC models, which can provide relatively simple interpretations for the hour time-scale evolution of the high-energy emission, even for such a complex data set. For the first time in this type of source, a clear indication is found for a relation between high activity at high energies and a long-term increase in the low frequency fluxes.
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| 5. |
- Abramowski, A., et al.
(författare)
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Constraints on the gamma-ray emission from the cluster-scale AGN outburst in the Hydra A galaxy cluster
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. A103-
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Tidskriftsartikel (refereegranskat)abstract
- Context. In some galaxy clusters, powerful active galactic nuclei (AGN) have blown bubbles with cluster scale extent into the ambient medium. The main pressure support of these bubbles is not known to date, but cosmic rays are a viable possibility. For such a scenario copious gamma-ray emission is expected as a tracer of cosmic rays from these systems. Aims. Hydra A, the closest galaxy cluster hosting a cluster scale AGN outburst, located at a redshift of 0.0538, is investigated for being a gamma-ray emitter with the High Energy Stereoscopic System (H.E.S.S.) array and the Fermi Large Area Telescope (Fermi-LAT). Methods. Data obtained in 20.2 h of dedicated H. E. S. S. observations and 38 months of Fermi-LAT data, gathered by its usual all-sky scanning mode, have been analyzed to search for a gamma-ray signal. Results. No signal has been found in either data set. Upper limits on the gamma-ray flux are derived and are compared to models. These are the first limits on gamma-ray emission ever presented for galaxy clusters hosting cluster scale AGN outbursts. Conclusions. The non-detection of Hydra A in gamma-rays has important implications on the particle populations and physical conditions inside the bubbles in this system. For the case of bubbles mainly supported by hadronic cosmic rays, the most favorable scenario, which involves full mixing between cosmic rays and embedding medium, can be excluded. However, hadronic cosmic rays still remain a viable pressure support agent to sustain the bubbles against the thermal pressure of the ambient medium. The largest population of highly-energetic electrons, which are relevant for inverse-Compton gamma-ray production is found in the youngest inner lobes of Hydra A. The limit on the inverse-Compton gamma-ray flux excludes a magnetic field below half of the equipartition value of 16 mu G in the inner lobes.
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| 6. |
- Abramowski, A., et al.
(författare)
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Discovery of gamma-ray emission from the extragalactic pulsar wind nebula N 157B with HESS
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. Article ID: L2-
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Tidskriftsartikel (refereegranskat)abstract
- We present the significant detection of the first extragalactic pulsar wind nebula (PWN) detected in gamma rays, N 157B, located in the large Magellanic Cloud (LMC). Pulsars with high spin-down luminosity are found to power energised nebulae that emit gamma rays up to energies of several tens of TeV. N 157B is associated with PSR J0537-6910, which is the pulsar with the highest known spin-down luminosity. The High Energy Stereoscopic System telescope array observed this nebula on a yearly basis from 2004 to 2009 with a dead-time corrected exposure of 46 h. The gamma-ray spectrum between 600 GeV and 12 TeV is well-described by a pure power-law with a photon index of 2.8 +/- 0.2(stat) +/- 0.3(syst) and a normalisation at 1 TeV of (8.2 +/- 0.8(stat) +/- 2.5(syst)) x 10(-13) cm(-2) s(-1) TeV-1. A leptonic multi-wavelength model shows that an energy of about 4 x 10(49) erg is stored in electrons and positrons. The apparent efficiency, which is the ratio of the TeV gamma-ray luminosity to the pulsar's spin-down luminosity, 0.08% +/- 0.01%, is comparable to those of PWNe found in the Milky Way. The detection of a PWN at such a large distance is possible due to the pulsar's favourable spin-down luminosity and a bright infrared photon-field serving as an inverse-Compton-scattering target for accelerated leptons. By applying a calorimetric technique to these observations, the pulsar's birth period is estimated to be shorter than 10 ms.
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| 7. |
- Abramowski, A., et al.
(författare)
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HESS observations of the Carina nebula and its enigmatic colliding wind binary Eta Carinae
- 2012
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 424:1, s. 128-135
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Tidskriftsartikel (refereegranskat)abstract
- The massive binary system Eta Carinae and the surrounding H ii complex, the Carina nebula, are potential particle acceleration sites from which very high energy (VHE; E= 100 GeV) ?-ray emission could be expected. This paper presents data collected during VHE ?-ray observations with the HESS telescope array from 2004 to 2010, which cover a full orbit of Eta Carinae. In the 33.1-h data set no hint of significant ?-ray emission from Eta Carinae has been found and an upper limit on the ?-ray flux of (99 per cent confidence level) is derived above the energy threshold of 470 GeV. Together with the detection of high energy (HE; 0.1 =E= 100 GeV) ?-ray emission by the Fermi Large Area Telescope up to 100 GeV, and assuming a continuation of the average HE spectral index into the VHE domain, these results imply a cut-off in the ?-ray spectrum between the HE and VHE ?-ray range. This could be caused either by a cut-off in the accelerated particle distribution or by severe ?? absorption losses in the wind collision region. Furthermore, the search for extended ?-ray emission from the Carina nebula resulted in an upper limit on the ?-ray flux of (99 per cent confidence level). The derived upper limit of 23 on the cosmic ray enhancement factor is compared with results found for the old-age mixed-morphology supernova remnant W28.
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| 8. |
- Abramowski, A., et al.
(författare)
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Identification of HESS J1303-631 as a pulsar wind nebula through gamma-ray, X-ray, and radio observations
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 548, s. A46-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The previously unidentified very high-energy (VHE; E > 100 GeV) gamma-ray source HESS J1303-631, discovered in 2004, is re-examined including new data from the H. E. S. S. Cherenkov telescope array in order to identify this object. Archival data from the XMM-Newton X-ray satellite and from the PMN radio survey are also examined. Methods. Detailed morphological and spectral studies of VHE gamma-ray emission as well as of the XMM-Newton X-ray data are performed. Radio data from the PMN survey are used as well to construct a leptonic model of the source. The gamma-ray and X-ray spectra and radio upper limit are used to construct a one zone leptonic model of the spectral energy distribution (SED). Results. Significant energy-dependent morphology of the gamma-ray source is detected with high-energy emission (E > 10 TeV) positionally coincident with the pulsar PSR J1301-6305 and lower energy emission (E < 2 TeV) extending similar to 0.4 degrees to the southeast of the pulsar. The spectrum of the VHE source can be described with a power-law with an exponential cut-off N-0 = (5.6 +/- 0.5) x 10(-12) TeV-1 cm(-2) s(-1), Gamma = 1.5 +/- 0.2) and E-cut = (7.7 +/- 2.2) TeV. The pulsar wind nebula (PWN) is also detected in X-rays, extending similar to 2-3' from the pulsar position towards the center of the gamma-ray emission region. A potential radio counterpart from the PMN survey is also discussed, showing a hint for a counterpart at the edge of the X-ray PWN trail and is taken as an upper limit in the SED. The extended X-ray PWN has an unabsorbed flux of F2-10 (keV) similar to 1.6(-0.4)(+0.2) x 10(-13) erg cm(-2)s(-1) and is detected at a significance of 6.5 sigma. The SED is well described by a one zone leptonic scenario which, with its associated caveats, predicts a very low average magnetic field for this source. Conclusions. Significant energy-dependent morphology of this source, as well as the identification of an associated X-ray PWN from XMM-Newton observations enable identification of the VHE source as an evolved PWN associated to the pulsar PSR J1301-6305. This identification is supported by the one zone leptonic model, which suggests that the energetics of the gamma-ray and X-ray radiation are such that they may have a similar origin in the pulsar nebula. However, the large discrepancy in emission region sizes and the low level of synchrotron radiation suggest a multi-population leptonic nature. The low implied magnetic field suggests that the PWN has undergone significant expansion. This would explain the low level of synchrotron radiation and the difficulty in detecting counterparts at lower energies, the reason this source was originally classified as a "dark" VHE gamma-ray source.
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| 9. |
- Abramowski, A., et al.
(författare)
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Spectral Analysis and Interpretation of the γ-ray Emission from the Starburst Galaxy NGC 253
- 2012
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 757:2, s. 158-
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Tidskriftsartikel (refereegranskat)abstract
- Very high energy (VHE; E >= 100 GeV) and high-energy (HE; 100 MeV <= E <= 100 GeV) data from gamma-ray observations performed with the H. E. S. S. telescope array and the Fermi-LAT instrument, respectively, are analyzed in order to investigate the non-thermal processes in the starburst galaxy NGC 253. The VHE gamma-ray data can be described by a power law in energy with differential photon index Gamma = 2.14 +/- 0.18(stat) +/- 0.30(sys) and differential flux normalization at 1 TeV of F-0 = (9.6 +/- 1.5(stat)(+5.7, -2.9)(sys)) x 10(-14) TeV-1 cm(-2) s(-1). A power-law fit to the differential HE gamma-ray spectrum reveals a photon index of Gamma = 2.24 +/- 0.14(stat) +/- 0.03(sys) and an integral flux between 200 MeV and 200 GeV of F(0.2-200 GeV) = (4.9 +/- 1.0(stat) +/- 0.3(sys)) x 10(-9) cm(-2) s(-1). No evidence for a spectral break or turnover is found over the dynamic range of both the LAT instrument and the H.E.S.S. experiment: a combined fit of a power law to the HE and VHE gamma-ray data results in a differential photon index Gamma = 2.34 +/- 0.03 with a p-value of 30%. The gamma-ray observations indicate that at least about 20% of the energy of the cosmic rays (CRs) capable of producing hadronic interactions is channeled into pion production. The smooth alignment between the spectra in the HE and VHE gamma-ray domain suggests that the same transport processes dominate in the entire energy range. Advection is most likely responsible for charged particle removal from the starburst nucleus from GeV to multiple TeV energies. In a hadronic scenario for the gamma-ray production, the single overall power-law spectrum observed would therefore correspond to the mean energy spectrum produced by the ensemble of CR sources in the starburst region.
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| 10. |
- Abramowski, A., et al.
(författare)
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Discovery of VHE emission towards the Carina arm region with the HESS telescope array : HESSJ1018-589
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541, s. A5-
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Tidskriftsartikel (refereegranskat)abstract
- The Carina arm region, containing the supernova remnant SNRG284.3-1.8, the high-energy (HE; E > 100 MeV) binary 1FGL J1018.6-5856 and the energetic pulsar PSRJ1016-5857 and its nebula, has been observed with the H. E. S. S. telescope array. The observational coverage of the region in very-high-energy (VHE; E > 0.1TeV) gamma-rays benefits from deep exposure (40 h) of the neighboring open cluster Westerlund 2. The observations have revealed a new extended region of VHE gamma-ray emission. The new VHE source HESS J1018-589 shows a bright, point-like emission region positionally coincident with SNRG284.3-1.8 and 1FGL J1018.6-5856 and a diffuse extension towards the direction of PSRJ1016-5857. A soft (Gamma = 2.7 +/- 0.5(stat)) photon index, with a differential flux at 1 TeV of N-0 = (4.2 +/- 1.1) x 10(-13) TeV-1 cm(-2) s(-1) is found for the point-like source, whereas the total emission region including the diffuse emission region is well fit by a power-law function with spectral index Gamma = 2.9 +/- 0.4(stat) and differential flux at 1 TeV of N-0 = (6.8 +/- 1.6) x 10(-1)3 TeV-1 cm(-2) s(-1). This H. E. S. S. detection motivated follow-up X-ray observations with the XMM-Newton satellite to investigate the origin of the VHE emission. The analysis of the XMM-Newton data resulted in the discovery of a bright, non-thermal point-like source (XMMU J101855.4-58564) with a photon index of Gamma = 1.65 +/- 0.08 in the center of SNRG284.3-1.8, and a thermal, extended emission region coincident with its bright northern filament. The characteristics of this thermal emission are used to estimate the plasma density in the region as n approximate to 0.5 cm(-3) (2.9 kpc/d)(2). The position of XMMUJ101855.4-58564 is compatible with the position reported by the Fermi-LAT collaboration for the binary system 1FGL J1018.6-5856 and the variable Swift XRT source identified with it. The new X-ray data are used alongside archival multi-wavelength data to investigate the relationship between the VHE gamma-ray emission from HESS J1018-589 and the various potential counterparts in the Carina arm region.
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| 11. |
- Abramowski, A., et al.
(författare)
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Discovery of extended VHE gamma-ray emission from the vicinity of the young massive stellar cluster Westerlund 1
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537, s. A114-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Results obtained in very-high-energy (VHE; E >= 100 GeV) gamma-ray observations performed with the H.E.S.S. telescope array are used to investigate particle acceleration processes in the vicinity of the young massive stellar cluster Westerlund 1 (Wd 1). Methods. Imaging of Cherenkov light from gamma-ray induced particle cascades in the Earth's atmosphere is used to search for VHE gamma rays from the region around Wd 1. Possible catalogued counterparts are searched for and discussed in terms of morphology and energetics of the H.E.S.S. source. Results. The detection of the degree-scale extended VHE gamma-ray source HESS J1646-458 is reported based on 45 h of H.E.S.S. observations performed between 2004 and 2008. The VHE gamma-ray source is centred on the nominal position of Wd 1 and detected with a total statistical significance of similar to 20 sigma. The emission region clearly extends beyond the H.E.S.S. point-spread function (PSF). The differential energy spectrum follows a power law in energy with an index of Gamma = 2.19 +/- 0.08(stat) +/- 0.20(sys) and a flux normalisation at 1 TeV of Phi(0) = (9.0 +/- 1.4(stat) +/- 1.8(sys)) x 10(-12) TeV-1 cm(-2) s(-1). The integral flux above 0.2 TeV amounts to (5.2 +/- 0.9) x 10(-11) cm(-2) s(-1). Conclusions. Four objects coincident with HESS J1646-458 are discussed in the search of a counterpart, namely the magnetar CXOU J164710.2-455216, the X-ray binary 4U 1642-45, the pulsar PSR J1648-4611 and the massive stellar cluster Wd 1. In a single-source scenario, Wd 1 is favoured as site of VHE particle acceleration. Here, a hadronic parent population would be accelerated within the stellar cluster. Beside this, there is evidence for a multi-source origin, where a scenario involving PSR J1648-4611 could be viable to explain parts of the VHE gamma-ray emission of HESS J1646-458.
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| 12. |
- Abramowski, A., et al.
(författare)
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Discovery of hard-spectrum gamma- ray emission from the BL Lacertae object 1ES 0414+009
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 538, s. A103-
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Tidskriftsartikel (refereegranskat)abstract
- Context. 1ES 0414+009 (z = 0.287) is a distant high-frequency- peaked BL Lac object, and has long been considered a likely emitter of very-highenergy (VHE, E > 100 GeV) gamma-rays due to its high X-ray and radio flux. Aims. Observations in the VHE gamma-ray band and across the electromagnetic spectrum can provide insights into the origin of highly energetic particles present in the source and the radiation processes at work. Because of the distance of the source, the gamma-ray spectrum might provide further limits on the level of the extragalactic background light (EBL). Methods. We report observations made between October 2005 and December 2009 with H. E. S. S., an array of four imaging atmospheric Cherenkov telescopes. Observations at high energies (HE, 100 MeV-100 GeV) with the Fermi-LAT instrument in the first 20 months of its operation are also reported. To complete the multi-wavelength picture, archival UV and X-ray observations with the Swift satellite and optical observations with the ATOM telescope are also used. Results. Based on the observations with H.E.S.S., 1ES 0414+009 is detected for the first time in the VHE band. An excess of 224 events is measured, corresponding to a significance of 7.8 sigma. The photon spectrum of the source is well described by a power law, with photon index of Gamma(VHE) = 3.45 +/- 0.25(stat) +/- 0.20(syst). The integral flux above 200 GeV is (1.88 +/- 0.20(stat) +/- 0.38(syst)) x10(-12) cm(-2) s(-1). Observations with the Fermi-LAT in the first 20 months of operation show a flux between 200 MeV and 100 GeV of (2.3 +/- 0.2(stat)) x 10(-9) erg cm(-2) s(-1), and a spectrum well described by a power-law function with a photon index Gamma(HE) = 1.85 +/- 0.18. Swift/XRT observations show an X-ray flux between 2 and 10 keV of (0.8-1) x 10(-11) erg cm(-2) s(-1), and a steep spectrum Gamma(X) = (2.2-2.3). Combining X-ray with optical-UV data, a fit with a log-parabolic function locates the synchrotron peak around 0.1 keV. Conclusions. Although the GeV-TeV observations do not provide better constraints on the EBL than previously obtained, they confirm a low density of the EBL, close to the lower limits from galaxy counts. The absorption-corrected HE and VHE gamma-ray spectra are both hard and have similar spectral indices (approximate to 1.86), indicating no significant change of slope between the HE and VHE gamma-ray bands, and locating the gamma-ray peak in the SED above 1-2 TeV. As for other TeV BL Lac objects with the gamma-ray peak at such high energies and a large separation between the two SED humps, this average broad-band SED represents a challenge for simple one-zone synchrotron self-Compton models, requiring a high Doppler factor and very low B-field.
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| 13. |
- Abramowski, A., et al.
(författare)
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Search for dark matter annihilation signals from the Fornax galaxy cluster with H.E.S.S.
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 750:2
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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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| 14. |
- Abramowski, A., et al.
(författare)
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A new SNR with TeV shell-type morphology : HESS J1731-347
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 531, s. A81-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The recent discovery of the radio shell-type supernova remnant (SNR), G353.6-0.7, in spatial coincidence with the unidentified TeV source HESS J1731-347 has motivated further observations of the source with the High Energy Stereoscopic System (HESS) Cherenkov telescope array to test a possible association of the gamma-ray emission with the SNR. Methods. With a total of 59 h of observation, representing about four times the initial exposure available in the discovery paper of HESS J1731-347, the gamma-ray morphology is investigated and compared with the radio morphology. An estimate of the distance is derived by comparing the interstellar absorption derived from X-rays and the one obtained from (12)CO and HI observations. Results. The deeper gamma-ray observation of the source has revealed a large shell-type structure with similar position and extension (r similar to 0.25 degrees) as the radio SNR, thus confirming their association. By accounting for the HESS angular resolution and projection effects within a simple shell model, the radial profile is compatible with a thin, spatially unresolved, rim. Together with RX J1713.7-3946, RX J0852.0-4622 and SN 1006, HESS J1731-347 is now the fourth SNR with a significant shell morphology at TeV energies. The derived lower limit on the distance of the SNR of 3.2 kpc is used together with radio and X-ray data to discuss the possible origin of the gamma-ray emission, either via inverse Compton scattering of electrons or the decay of neutral pions resulting from proton-proton interaction.
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| 15. |
- Abramowski, A., et al.
(författare)
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Discovery of the source HESS J1356-645 associated with the young and energetic PSR J1357-6429
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533, s. A103-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Several newly discovered very-high-energy (VHE; E > 100 GeV) gamma-ray sources in the Galaxy are thought to be associated with energetic pulsars. Among them, middle-aged (greater than or similar to 10(4) yr) systems exhibit large centre-filled VHE nebulae, offset from the pulsar position, which result from the complex relationship between the pulsar wind and the surrounding medium, and reflect the past evolution of the pulsar. Aims. Imaging Atmospheric Cherenkov Telescopes (IACTs) have been successful in revealing extended emission from these sources in the VHE regime. Together with radio and X-ray observations, this observational window allows one to probe the energetics and magnetic field inside these large-scale nebulae. Methods. H.E.S.S., with its large field of view, angular resolution of less than or similar to 0.1 degrees and unprecedented sensitivity, has been used to discover a large population of such VHE sources. In this paper, the H. E. S. S. data from the continuation of the Galactic Plane Survey (-80 degrees < l < 60 degrees, vertical bar b vertical bar < 3 degrees), together with the existing multi-wavelength observations, are used. Results. A new VHE gamma-ray source was discovered at RA (J2000) = 13(h)56(m)00(s), Dec (J2000) = -64 degrees 30'00 '' with a 2' statistical error in each coordinate, namely HESS J1356-645. The source is extended, with an intrinsic Gaussian width of (0.20 +/- 0.02)degrees. Its integrated energy flux between 1 and 10 TeV of 8 x 10(-12) erg cm(-2) s(-1) represents similar to 11% of the Crab Nebula flux in the same energy band. The energy spectrum between 1 and 20 TeV is well described by a power law dN/dE proportional to E-Gamma with photon index Gamma = 2.2 +/- 0.2(stat) +/- 0.2(sys). The inspection of archival radio images at three frequencies and the analysis of X-ray data from ROSAT/PSPC and XMM-Newton/MOS reveal the presence of faint non-thermal diffuse emission coincident with HESS J1356-645. Conclusions. HESS J1356-645 is most likely associated with the young and energetic pulsar PSR J1357-6429 (d = 2.4 kpc, tau(c) = 7.3 kyr and (E) over dot = 3.1 x 10(36) erg s(-1)), located at a projected distance of similar to 5 pc from the centroid of the VHE emission. HESS J1356-645 and its radio and X-ray counterparts would thus represent the nebula resulting from the past history of the PSR J1357-6429 wind. In a simple one-zone model, constraints on the magnetic field strength in the nebula are obtained from the flux of the faint and extended X-ray emission detected with ROSAT and XMM-Newton. Fermi-LAT upper limits in the high-energy ( HE; 0.1-100 GeV) domain are also used to constrain the parent electron spectrum. From the low magnetic field value inferred from this approach (similar to 3-4 mu G), HESS J1356-645 is thought to share many similarities with other known gamma-ray emitting nebulae, such as Vela X, as it exhibits a large-scale nebula seen in radio, X-rays and VHE gamma-rays.
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| 16. |
- Abramowski, A., et al.
(författare)
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Very-high-energy gamma-ray emission from the direction of the Galactic globular cluster Terzan 5
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 531, s. L18-
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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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| 17. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 18. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 19. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 20. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 21. |
- Loth, Daan W, et al.
(författare)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 22. |
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| 23. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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| 24. |
- Yang, Jian, et al.
(författare)
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FTO genotype is associated with phenotypic variability of body mass index
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
-
Tidskriftsartikel (refereegranskat)abstract
- There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
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| 25. |
- Bentley, Michael J., et al.
(författare)
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A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse la. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community.
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| 26. |
- Alonso-Mori, Roberto, et al.
(författare)
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Energy-dispersive X-ray emission spectroscopy using an X-ray free-electron laser in a shot-by-shot mode
- 2012
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:47, s. 19103-19107
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Tidskriftsartikel (refereegranskat)abstract
- The ultrabright femtosecond X-ray pulses provided by X-ray free-electron lasers open capabilities for studying the structure and dynamics of a wide variety of systems beyond what is possible with synchrotron sources. Recently, this probe-before-destroy approach has been demonstrated for atomic structure determination by serial X-ray diffraction of microcrystals. There has been the question whether a similar approach can be extended to probe the local electronic structure by X-ray spectroscopy. To address this, we have carried out femtosecond X-ray emission spectroscopy (XES) at the Linac Coherent Light Source using redox-active Mn complexes. XES probes the charge and spin states as well as the ligand environment, critical for understanding the functional role of redox-active metal sites. K beta(1,3) XES spectra of Mn-II and Mn-2(III,IV) complexes at room temperature were collected using a wavelength dispersive spectrometer and femtosecond X-ray pulses with an individual dose of up to > 100 MGy. The spectra were found in agreement with undamaged spectra collected at low dose using synchrotron radiation. Our results demonstrate that the intact electronic structure of redox active transition metal compounds in different oxidation states can be characterized with this shot-by-shot method. This opens the door for studying the chemical dynamics of metal catalytic sites by following reactions under functional conditions. The technique can be combined with X-ray diffraction to simultaneously obtain the geometric structure of the overall protein and the local chemistry of active metal sites and is expected to prove valuable for understanding the mechanism of important metalloproteins, such as photosystem II.
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| 27. |
- Hattne, Johan, et al.
(författare)
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Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers
- 2014
-
Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 11:5, s. 545-548
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Tidskriftsartikel (refereegranskat)abstract
- X-ray free-electron laser (XFEL) sources enable the use of crystallography to solve three-dimensional macromolecular structures under native conditions and without radiation damage. Results to date, however, have been limited by the challenge of deriving accurate Bragg intensities from a heterogeneous population of microcrystals, while at the same time modeling the X-ray spectrum and detector geometry. Here we present a computational approach designed to extract meaningful high-resolution signals from fewer diffraction measurements.
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| 28. |
- Hattne, Johan, et al.
(författare)
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Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers
- 2014
-
Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:5, s. 545-548
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray free-electron laser (XFEL) sources enable the use of crystallography to solve three-dimensional macromolecular structures under native conditions and without radiation damage. Results to date, however, have been limited by the challenge of deriving accurate Bragg intensities from a heterogeneous population of microcrystals, while at the same time modeling the X-ray spectrum and detector geometry. Here we present a computational approach designed to extract meaningful high-resolution signals from fewer diffraction measurements.
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| 29. |
- Kern, Jan, et al.
(författare)
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Room temperature femtosecond X-ray diffraction of photosystem II microcrystals
- 2012
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:25, s. 9721-9726
-
Tidskriftsartikel (refereegranskat)abstract
- Most of the dioxygen on earth is generated by the oxidation of water by photosystem II (PS II) using light from the sun. This lightdriven, four-photon reaction is catalyzed by the Mn4CaO5 cluster located at the lumenal side of PS II. Various X-ray studies have been carried out at cryogenic temperatures to understand the intermediate steps involved in the water oxidation mechanism. However, the necessity for collecting data at room temperature, especially for studying the transient steps during the O-O bond formation, requires the development of new methodologies. In this paper we report room temperature X-ray diffraction data of PS II microcrystals obtained using ultrashort (<50 fs) 9 keV X-ray pulses from a hard X-ray free electron laser, namely the Linac Coherent Light Source. The results presented here demonstrate that the probe before destroy approach using an X-ray free electron laser works even for the highly-sensitive Mn4CaO5 cluster in PS II at room temperature. We show that these data are comparable to those obtained in synchrotron radiation studies as seen by the similarities in the overall structure of the helices, the protein subunits and the location of the various cofactors. This work is, therefore, an important step toward future studies for resolving the structure of the Mn4CaO5 cluster without any damage at room temperature, and of the reaction intermediates of PS II during O-O bond formation.
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| 30. |
- Kern, Jan, et al.
(författare)
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Simultaneous Femtosecond X-ray Spectroscopy and Diffraction of Photosystem II at Room Temperature
- 2013
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 340:6131, s. 491-495
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Tidskriftsartikel (refereegranskat)abstract
- Intense femtosecond x-ray pulses produced at the Linac Coherent Light Source (LCLS) were used for simultaneous x-ray diffraction (XRD) and x-ray emission spectroscopy (XES) of microcrystals of photosystem II (PS II) at room temperature. This method probes the overall protein structure and the electronic structure of the Mn4CaO5 cluster in the oxygen-evolving complex of PS II. XRD data are presented from both the dark state (S-1) and the first illuminated state (S-2) of PS II. Our simultaneous XRD-XES study shows that the PS II crystals are intact during our measurements at the LCLS, not only with respect to the structure of PS II, but also with regard to the electronic structure of the highly radiation-sensitive Mn4CaO5 cluster, opening new directions for future dynamics studies.
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| 31. |
- Tarning, Joel, et al.
(författare)
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Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy
- 2012
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 56:11, s. 5764-5773
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Tidskriftsartikel (refereegranskat)abstract
- Amodiaquine is effective for the treatment of Plasmodium vivax malaria, but there is little information on the pharmacokinetic and pharmacodynamic properties of amodiaquine in pregnant women with malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of amodiaquine and its biologically active metabolite, desethylamodiaquine, in pregnant women with P. vivax infection and again after delivery. Twenty-seven pregnant women infected with P. vivax malaria on the Thai-Myanmar border were treated with amodiaquine monotherapy (10 mg/kg/day) once daily for 3 days. Nineteen women, with and without P. vivax infections, returned to receive the same amodiaquine dose postpartum. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of amodiaquine and desethylamodiaquine. Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of desethylamodiaquine under the assumption of complete in vivo conversion. Body weight was implemented as an allometric function on all clearance and volume parameters. Amodiaquine clearance decreased linearly with age, and absorption lag time was reduced in pregnant patients. Recurrent malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant-hazard function with an inhibitory effect of desethylamodiaquine. Amodiaquine treatment reduced the risk of recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of amodiaquine or desethylamodiaquine. No dose adjustments are required in pregnancy.
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| 32. |
- Sierra, Raymond G., et al.
(författare)
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Nanoflow electrospinning serial femtosecond crystallography
- 2012
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Ingår i: Acta Crystallographica Section D. - : Wiley-Blackwell. - 0907-4449 .- 1399-0047. ; 68, s. 1584-1587
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Tidskriftsartikel (refereegranskat)abstract
- An electrospun liquid microjet has been developed that delivers protein microcrystal suspensions at flow rates of 0.14-3.1 mu l min(-1) to perform serial femtosecond crystallography (SFX) studies with X-ray lasers. Thermolysin microcrystals flowed at 0.17 mu l min(-1) and diffracted to beyond 4 angstrom resolution, producing 14 000 indexable diffraction patterns, or four per second, from 140 mu g of protein. Nanoflow electrospinning extends SFX to biological samples that necessitate minimal sample consumption.
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| 33. |
- Höglund, Richard, 1984, et al.
(författare)
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A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan.
- 2012
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Ingår i: Malaria journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Pregnancy is associated with an increased risk of developing a malaria infection and a higher risk of developing severe malaria. The pharmacokinetic properties of many anti-malarials are also altered during pregnancy, often resulting in a decreased drug exposure. Piperaquine is a promising anti-malarial partner drug used in a fixed-dose combination with dihydroartemisinin. The aim of this study was to investigate the population pharmacokinetics of piperaquine in pregnant and non-pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria. METHOD: Symptomatic patients received a standard dose regimen of the fixed dose oral piperaquine-dihydroartemisinin combination treatment. Densely sampled plasma aliquots were collected and analysed using a previously described LC-MS/MS method. Data from 12 pregnant and 12 non-pregnant women were analysed using nonlinear mixed-effects modelling. A Monte Carlo Mapped Power (MCMP) analysis was conducted based on a previously published study to evaluate the power of detecting covariates in this relatively small study. RESULTS: A three-compartment disposition model with a transit-absorption model described the observed data well. Body weight was added as an allometric function on all clearance and volume parameters. A statistically significant decrease in estimated terminal piperaquine half-life in pregnant compared with non-pregnant women was found, but there were no differences in post-hoc estimates of total piperaquine exposure. The MCMP analysis indicated a minimum of 13 pregnant and 13 non-pregnant women were required to identify pregnancy as a covariate on relevant pharmacokinetic parameters (80% power and p=0.05). Pregnancy was, therefore, evaluated as a categorical and continuous covariate (i.e. estimate gestational age) in a full covariate approach. Using this approach pregnancy was not associated with any major change in piperaquine elimination clearance. However, a trend of increasing elimination clearance with increasing gestational age could be seen. CONCLUSIONS: The population pharmacokinetic properties of piperaquine were well described by a three-compartment disposition model in pregnant and non-pregnant women with uncomplicated malaria. The modelling approach showed no major difference in piperaquine exposure between the two groups and data presented here do not warrant a dose adjustment in pregnancy in this vulnerable population.
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| 34. |
- Bergstrand, Martin, et al.
(författare)
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Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:260, s. 260ra147-
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Tidskriftsartikel (refereegranskat)abstract
- A randomized, placebo-controlled trial conducted on the northwest border of Thailand compared malaria chemoprevention with monthly or bimonthly standard 3-day treatment regimens of dihydroartemisinin-piperaquine. Healthy adult male subjects (N = 1000) were followed weekly during 9 months of treatment. Using nonlinear mixed-effects modeling, the concentration-effect relationship for the malaria-preventive effect of piperaquine was best characterized with a sigmoidal E-max relationship, where plasma concentrations of 6.7 ng/ml [relative standard error (RSE), 23%] and 20 ng/ml were found to reduce the hazard of acquiring a malaria infection by 50% [that is, median inhibitory concentration (IC50)] and 95% (IC95), respectively. Simulations of monthly dosing, based on the final model and published pharmacokinetic data, suggested that the incidence of malaria infections over 1 year could be reduced by 70% with a recently suggested dosing regimen compared to the current manufacturer's recommendations for small children (8 to 12 kg). This model provides a rational framework for piperaquine dose optimization in different patient groups.
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