| 1. |
- 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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| 2. |
- Acciari, V. A., et al.
(författare)
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Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
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Tidskriftsartikel (refereegranskat)abstract
- The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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| 3. |
- Acero, F., et al.
(författare)
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Detection of Gamma Rays from a Starburst Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5956, s. 1080-1082
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Tidskriftsartikel (refereegranskat)abstract
- Starburst galaxies exhibit in their central regions a highly increased rate of supernovae, the remnants of which are thought to accelerate energetic cosmic rays up to energies of similar to 10(15) electron volts. We report the detection of gamma rays-tracers of such cosmic rays-from the starburst galaxy NGC 253 using the High Energy Stereoscopic System (H. E. S. S.) array of imaging atmospheric Cherenkov telescopes. The gamma-ray flux above 220 billion electron volts is F = (5.5 +/- 1.0(stat) +/- 2.8(sys)) x 10(-13) cm(-2) s(-1), implying a cosmic-ray density about three orders of magnitude larger than that in the center of the Milky Way. The fraction of cosmic-ray energy channeled into gamma rays in this starburst environment is five times as large as that in our Galaxy.
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| 4. |
- Acero, F., et al.
(författare)
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HESS upper limits on very high energy gamma-ray emission from the microquasar GRS 1915+105
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 508:3, s. 1135-1140
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Tidskriftsartikel (refereegranskat)abstract
- Context. High energy particles reside in the relativistic jets of microquasars, making them possible sources of very high energy radiation (VHE, > 100 GeV). Detecting this emission would provide a new handle on jet physics. Aims. Observations of the microquasar GRS 1915+105 with the HESS telescope array were undertaken in 2004-2008 to search for VHE emission. Methods. Stereoscopic imaging of Cherenkov radiation from extensive air showers is used to reconstruct the energy and direction of the incident gamma rays. Results. There is no evidence for a VHE gamma-ray signal either from the direction of the microquasar or its vicinity. An upper limit of 6.1 x 10(-13) ph cm(-2) s(-1) (99.9% confidence level) is set on the photon flux above 410 GeV, equivalent to a VHE luminosity of similar to 10(34) erg s(-1) at 11 kpc. Conclusions. The VHE to X-ray luminosity ratio in GRS 1915+105 is at least four orders of magnitude lower than the ratio observed in gamma-ray binaries. The VHE radiative efficiency of the compact jet is less than 0.01% based on its estimated total power of 10(38) erg s(-1). Particle acceleration in GRS 1915+105 is not efficient at high energies and/or the magnetic field is too strong. It is also possible that VHE gamma-rays are produced by GRS 1915+105, but the emission is highly time-dependent.
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| 5. |
- Aharonian, F., et al.
(författare)
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Probing the ATIC peak in the cosmic-ray electron spectrum with HESS
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 508:2, s. 561-564
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Tidskriftsartikel (refereegranskat)abstract
- The measurement of an excess in the cosmic-ray electron spectrum between 300 and 800 GeV by the ATIC experiment has - together with the PAMELA detection of a rise in the positron fraction up to approximate to 100 GeV - motivated many interpretations in terms of dark matter scenarios; alternative explanations assume a nearby electron source like a pulsar or supernova remnant. Here we present a measurement of the cosmic-ray electron spectrum with H. E. S. S. starting at 340 GeV. While the overall electron flux measured by H. E. S. S. is consistent with the ATIC data within statistical and systematic errors, the H. E. S. S. data exclude a pronounced peak in the electron spectrum as suggested for interpretation by ATIC. The H. E. S. S. data follow a power-law spectrum with spectral index of 3.0 +/- 0.1(stat.) +/- 0.3(syst.), which steepens at about 1 TeV.
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| 6. |
- Aharonian, F., et al.
(författare)
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Very high energy gamma-ray observations of the binary PSR B1259-63/SS2883 around the 2007 Periastron
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 507:1, s. 389-396
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Tidskriftsartikel (refereegranskat)abstract
- Aims. This article presents very-high-energy (VHE; E > 100 GeV) data from the gamma-ray binary PSR B1259-63 as taken during the years 2005, 2006 and before as well as shortly after the 2007 periastron passage. These data extend the knowledge of the lightcurve of this object to all phases of the 3.4 year binary orbit. The lightcurve constrains physical mechanisms present in this TeV source. Methods. Observations of VHE gamma-rays with the HESS telescope array using the Imaging Atmospheric Cherenkov Technique were performed. The HESS instrument features an angular resolution of < 0.1 degrees and an energy resolution of < 20%. Gamma-ray events in an energy range of 0.5-70 TeV were recorded. From these data, energy spectra and lightcurve with a monthly time sampling were extracted. Results. VHE gamma-ray emission from PSR B1259-63 was detected with an overall significance of 9.5 standard deviations using 55 h of exposure, obtained from April to August 2007. The monthly flux of gamma-rays during the observation period was measured, yielding VHE lightcurve data for the early pre-periastron phase of the system for the first time. No spectral variability was found on timescales of months. The spectrum is described by a power law with a photon index of Gamma = 2.8 +/- 0.2(stat) +/- 0.2(sys) and flux normalisation Phi(0) = (1.1 +/- 0.1(stat) +/- 0.2(sys)) x 10(-12) TeV(-1) cm(-2) s(-1). PSR B1259-63 was also monitored in 2005 and 2006, far from periastron passage, comprising 8.9 h and 7.5 h of exposure, respectively. No significant excess of.-rays is seen in those observations. Conclusions. PSR B1259-63 has been re-confirmed as a variable TeV gamma-ray emitter. The firm detection of VHE photons emitted at a true anomaly theta approximate to -0.35 of the pulsar orbit, i.e. already similar to 50 days prior to the periastron passage, disfavors the stellar disc target scenario as a primary emission mechanism, based on current knowledge about the companion star's disc inclination, extension, and density profile.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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| 11. |
- 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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| 12. |
- 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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| 13. |
- 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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| 14. |
- 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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| 15. |
- 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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| 16. |
- 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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| 17. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 18. |
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| 19. |
- Willer, Cristen J., et al.
(författare)
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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
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| 20. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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| 21. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 22. |
- Helgadottir, Anna, et al.
(författare)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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| 23. |
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| 24. |
- Morrison, Hilary G., et al.
(författare)
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Genomic minimalism in the early diverging intestinal parasite Giardia lamblia
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 317:5846, s. 1921-1926
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Tidskriftsartikel (refereegranskat)abstract
- The genome of the eukaryotic protist Giardia lamblia, an important human intestinal parasite, is compact in structure and content, contains few introns or mitochondrial relics, and has simplified machinery for DNA replication, transcription, RNA processing, and most metabolic pathways. Protein kinases comprise the single largest protein class and reflect Giardia's requirement for a complex signal transduction network for coordinating differentiation. Lateral gene transfer from bacterial and archaeal donors has shaped Giardia's genome, and previously unknown gene families, for example, cysteine-rich structural proteins, have been discovered. Unexpectedly, the genome shows little evidence of heterozygosity, supporting recent speculations that this organism is sexual. This genome sequence will not only be valuable for investigating the evolution of eukaryotes, but will also be applied to the search for new therapeutics for this parasite.
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| 25. |
- Szatmari, Peter, et al.
(författare)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 26. |
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| 27. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 28. |
- Haller, Daniel G, et al.
(författare)
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Potential regional differences for the tolerability profiles of fluoropyrimidines.
- 2008
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 26:13, s. 2118-23
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We conducted a retrospective analysis of safety data from randomized, single-agent fluoropyrimidine clinical trials (bolus fluorouracil/leucovorin [FU/LV] and capecitabine) to test the hypothesis that there are regional differences in fluoropyrimidine tolerability. METHODS: Treatment-related safety data from three phase III clinical studies were analyzed by multivariate analysis: two comparing capecitabine with bolus FU/LV in metastatic colorectal cancer (MCRC) and one comparing capecitabine plus oxaliplatin (XELOX) with bolus FU/LV as adjuvant treatment for colon cancer. The United States (US) was compared with non-US countries (all three studies) and with the rest of the world and East Asia (adjuvant study). RESULTS: In the MCRC studies (n = 1,189), more grade 3/4 adverse events (AEs; relative risk [RR], 1.77), dose reductions (RR, 1.72), and discontinuations (RR, 1.83) were reported in US versus non-US patients. Likewise, in the adjuvant colon cancer study (n = 1,864), more grade 3/4 AEs (RR, 1.47) and discontinuations (RR, 2.09) were reported in US versus non-US patients. After further dividing non-US patients into those in East Asia and the rest of the world, differential RRs for related grade 3/4 AEs, grade 4 AEs, and serious AEs were again observed, with East Asian patients having the lowest and US patients the highest RR. CONCLUSION: Regional differences exist in the tolerability profiles of fluoropyrimidines. More treatment-related toxicity was reported in the US compared with the rest of the world for bolus FU/LV and capecitabine in first-line MCRC and adjuvant colon cancer. In the adjuvant setting, a range of fluoropyrimidine tolerability was observed, with East Asian patients having the lowest, and US patients the highest, RR.
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| 29. |
- Hooftman, Danny A. P., et al.
(författare)
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Introgression potential of downy mildew resistance from lettuce to Lactuca serriola and its relevance for plant fitness
- 2007
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Ingår i: Basic and Applied Ecology. - : Elsevier BV. - 1439-1791 .- 1618-0089. ; 8:2, s. 135-146
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Tidskriftsartikel (refereegranskat)abstract
- Hybridization between plant species may cause ecological changes in species, enhancing their potential to become invasive. Increasing evidence suggests that the expanding distribution of Lactuca serriola could (partly) be caused by hybridization with its closest relative, the crop plant L. sativa (lettuce). Fitness advantages in hybrids may result from heterosis and epistasis but single added traits may enhance hybrid fitness as well. Here, we study the potential for introgression of an important crop trait, downy mildew (Bremia lactucae) resistance, into L. serriola hybrids. We monitored the abundance of B. lactucae on wild L. serriola in The Netherlands to test its impact potential. We found that B. lactucae is common in The Netherlands: B. lactucae occurred in 33 of the 35 surveyed populations of L. serriola. Subsequently, under regulated conditions, using two physiotypes of B. lactucae (BL-16 and BL-18), we recorded (i) quantitative conidiophore and (ii) haustoria development in seedlings. Furthermore, we explored its effects on plant fitness. Based on the (non-) occurrence of conidiophores, genomic segments from L. sativa that include Bremia resistance are present and expressing in these hybrids for at least two hybrid generations. However, haustoria density was lower in all hybrids, irrespective of physiotype or siring cultivar. We attributed this to heterosis. Furthermore, all plants shed infected leaves, but we observed no effects of infection on reproductive fitness. We therefore suggest that when L. serriola gains resistance to B. lactucae, the fitness effects are tow. The hypothesis that the gain of B. lactucae resistance is causally related to the recent spread of L. serriola has become less Likely. If hybridization is connected to this at all, it seems through heterosis. We conclude that it is important to study fitness impacts of introgressed traits along with other ecological factors. (c) 2006 Gesellschaft fur Okologie. Published by Elsevier GmbH. All rights reserved.
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| 30. |
- Kolz, Melanie, et al.
(författare)
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Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000504-
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2×10−201), ABCG2 (p = 3.1×10−26), SLC17A1 (p = 3.0×10−14), SLC22A11 (p = 6.7×10−14), SLC22A12 (p = 2.0×10−9), SLC16A9 (p = 1.1×10−8), GCKR (p = 1.4×10−9), LRRC16A (p = 8.5×10−9), and near PDZK1 (p = 2.7×10−9). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0×10−26) and propionyl-L-carnitine (p = 5.0×10−8) concentrations, which in turn were associated with serum UA levels (p = 1.4×10−57 and p = 8.1×10−54, respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.
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| 31. |
- Larsson, Bengt, et al.
(författare)
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Molecular oxygen in the rho Ophiuchi cloud
- 2007
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 466:3, s. 5-
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Tidskriftsartikel (refereegranskat)abstract
- Context: Molecular oxygen, O2, has been expected historically to be an abundant component of the chemical species in molecular clouds and, as such, an important coolant of the dense interstellar medium. However, a number of attempts from both ground and from space have failed to detect O2 emission.Aims: The work described here uses heterodyne spectroscopy from space to search for molecular oxygen in the interstellar medium. Methods: The Odin satellite carries a 1.1 m sub-millimeter dish and a dedicated 119 GHz receiver for the ground state line of O2. Starting in 2002, the star forming molecular cloud core ρ Oph A was observed with Odin for 34 days during several observing runs.Results: We detect a spectral line at v_LSR =+3.5 km s-1 with Δ v_FWHM=1.5 km s-1, parameters which are also common to other species associated with ρ Oph A. This feature is identified as the O2 (NJ = 11 - 1_0) transition at 118 750.343 MHz.Conclusions: The abundance of molecular oxygen, relative to H{2} , is 5 × 10-8 averaged over the Odin beam. This abundance is consistently lower than previously reported upper limits.Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Étude Spatiale (CNES). The Swedish Space Corporation has been the industrial prime contractor and also is operating the satellite. Appendix A is only available in electronic form at http://www.aanda.org
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| 32. |
- Leeuw, Maaike, et al.
(författare)
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Measuring perceived harmfulness of physical activities in patients with chronic low back pain : The photograph series of daily activities-short electronic version
- 2007
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 8:11, s. 840-849
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive-behavioral models of chronic low back pain (CLBP) predict that dysfunctional assumptions about the harmfulness of activities may maintain pain-related fear and disability levels. The Photograph Series of Daily Activities (PHODA) is an instrument to determine the perceived harmfulness of daily activities in patients with CLBP. This study examined the psychometric properties of a short electronic version of the PHODA (PHODA-SeV). The results show that the PHODA-SeV measures a single factor and has a high internal consistency. The test-retest reliability and stability of the PHODA-SeV over a 2-week time interval are good, with discrepancies between 2 measurements over 20 points suggesting true change. The construct validity is supported by the finding that both self-reported pain severity and fear of movement/(re)injury were uniquely related to the PHODA-SeV. Validity is further corroborated by the finding that patients who have received exposure in vivo, that aimed to systematically reduce the perceived harmfulness of activities, had significantly lower PHODA-SeV scores after treatment than patients receiving graded activity that did not address these assumptions. The findings support the PHODA-SeV as a valid and reliable measure of the perceived harmfulness of activities in patients with CLBP. Preliminary normative data of the PHODA-SeV are presented. Perspective: This article describes a pictorial measurement too/(PHODA-SeV) for the assessment of the perceived harmfulness of activities in patients with chronic low back pain. The PHODA-SeV has good psychometric properties and can be used to elaborate on the contribution of beliefs about harmful consequences of activities to pain and disability. (c) 2007 by the American Pain Society.
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| 33. |
- Lindgren, Cecilia M, et al.
(författare)
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Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
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| 34. |
- Nobel, Gerard, 1964-, et al.
(författare)
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Motion sickness increases the risk of accidental hypothermia
- 2006
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 98:1, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- Motion sickness (MS) has been found to increase body-core cooling during immersion in 28 degrees C degrees C water, an effect ascribed to attenuation of the cold- induced peripheral vasoconstriction (Mekjavic et al. in J Physiol 535(2):619-623, 2001). The present study tested the hypothesis that a more profound cold stimulus would override the MS effect on peripheral vasoconstriction and hence on the core cooling rate. Eleven healthy subjects underwent two separate head-out immersions in 15 degrees C water. In the control trial (CN), subjects were immersed after baseline measurements. In the MS-trial, subjects were rendered motion sick prior to immersion, by using a rotating chair in combination with a regimen of standardized head movements. During immersion in the MS-trial, subjects were exposed to an optokinetic stimulus (rotating drum). At 5-min intervals subjects rated their temperature perception, thermal comfort and MS discomfort. During immersion mean skin temperature, rectal temperature, the difference in temperature between the non-immersed right forearm and 3rd finger of the right hand (Delta T (ff)), oxygen uptake and heart rate were recorded. In the MS-trial, rectal temperature decreased substantially faster (33%, P < 0.01). Also, the Delta T (ff) response, an index of peripheral vasomotor tone, as well as the oxygen uptake, indicative of the shivering response, were significantly attenuated (P < 0.01 and P < 0.001, respectively) by MS. Thus, MS may predispose individuals to hypothermia by enhancing heat loss and attenuating heat production. This might have significant implications for survival in maritime accidents.
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| 35. |
- Ong, Ken K., et al.
(författare)
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Genetic variation in LIN28B is associated with the timing of puberty
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:6, s. 729-733
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Tidskriftsartikel (refereegranskat)abstract
- The timing of puberty is highly variable(1). We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 x 10(-8)). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08-0.16; P = 2.8 x 10(-10); combined P = 3.6 x 10(-16)). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 x 10(-7); N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing(2), as the first genetic determinant regulating the timing of human pubertal growth and development.
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| 36. |
- Prokopenko, Inga, et al.
(författare)
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Variants in MTNR1B influence fasting glucose levels
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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