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Sökning: WFRF:(Gerard L)

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1.
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2.
  • Acharya, B. S., et al. (författare)
  • Introducing the CTA concept
  • 2013
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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3.
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4.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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5.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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6.
  • Abramowski, A., et al. (författare)
  • The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
  • 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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7.
  • Acciari, V. A., et al. (författare)
  • Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
  • 2009
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
  • 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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8.
  • Arndt, D. S., et al. (författare)
  • State of the Climate in 2016
  • 2017
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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9.
  • Arndt, D. S., et al. (författare)
  • STATE OF THE CLIMATE IN 2017
  • 2018
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
  • Forskningsöversikt (refereegranskat)
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10.
  • Aharonian, F., et al. (författare)
  • SIMULTANEOUS OBSERVATIONS OF PKS 2155-304 WITH HESS, FERMI, RXTE, AND ATOM : SPECTRAL ENERGY DISTRIBUTIONS AND VARIABILITY IN A LOW STATE
  • 2009
  • Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 0004-637X .- 1538-4357. ; 696:2, s. L150-L155
  • 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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11.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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12.
  • Abramowski, A., et al. (författare)
  • Simultaneous multi-wavelength campaign on PKS 2005-489 in a high state
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533, s. A110-
  • Tidskriftsartikel (refereegranskat)abstract
    • The high-frequency peaked BL Lac object PKS 2005-489 was the target of a multi-wavelength campaign with simultaneous observations in the TeV gamma-ray (H.E.S.S.), GeV gamma-ray (Fermi/LAT), X-ray (RXTE, Swift), UV (Swift) and optical (ATOM, Swift) bands. This campaign was carried out during a high flux state in the synchrotron regime. The flux in the optical and X-ray bands reached the level of the historical maxima. The hard GeV spectrum observed with Fermi/LAT connects well to the very high energy (VHE, E > 100 GeV) spectrum measured with H.E.S.S. with a peak energy between similar to 5 and 500 GeV. Compared to observations with contemporaneous coverage in the VHE and X-ray bands in 2004, the X-ray flux was similar to 50 times higher during the 2009 campaign while the TeV gamma-ray flux shows marginal variation over the years. The spectral energy distribution during this multi-wavelength campaign was fit by a one zone synchrotron self-Compton model with a well determined cutoff in X-rays. The parameters of a one zone SSC model are inconsistent with variability time scales. The variability behaviour over years with the large changes in synchrotron emission and small changes in the inverse Compton emission does not warrant an interpretation within a one-zone SSC model despite an apparently satisfying fit to the broadband data in 2009.
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13.
  • Blunden, Jessica, et al. (författare)
  • State of the Climate in 2012
  • 2013
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
  • Tidskriftsartikel (refereegranskat)abstract
    • For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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14.
  • Tinetti, Giovanna, et al. (författare)
  • The EChO science case
  • 2015
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
  • Tidskriftsartikel (refereegranskat)abstract
    • The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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15.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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16.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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17.
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18.
  • Wang, Haidong, et al. (författare)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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19.
  • Speliotes, Elizabeth K., et al. (författare)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • 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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20.
  • Abramowski, A., et al. (författare)
  • A multiwavelength view of the flaring state of PKS 2155-304 in 2006
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539, s. A149-
  • 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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21.
  • Abramowski, A., et al. (författare)
  • Discovery of hard-spectrum gamma- ray emission from the BL Lacertae object 1ES 0414+009
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 538, s. A103-
  • 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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22.
  • Abramowski, A., et al. (författare)
  • Multi-wavelength observations of H 2356-309
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 516, s. A56-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. The properties of the broad-band emission from the high-frequency peaked BL Lac H 2356-309 (z = 0.165) are investigated. Methods. Very high energy (VHE; E > 100 GeV) observations of H 2356-309 were performed with the High Energy Stereoscopic System (HESS) from 2004 through 2007. Simultaneous optical/UV and X-ray observations were made with the XMM-Newton satellite on June 12/13 and June 14/15, 2005. NRT radio observations were also contemporaneously performed in 2005. ATOM optical monitoring observations were also made in 2007. Results. A strong VHE signal, similar to 13 sigma total, was detected by HESS after the four years HESS observations (116.8 h live time). The integral flux above 240 GeV is I(> 240 GeV) = (3.06 +/- 0.26(stat) +/- 0.61(syst)) x 10(-12) cm(-2) s(-1), corresponding to similar to 1.6% of the flux observed from the Crab Nebula. A time-averaged energy spectrum is measured from 200 GeV to 2 TeV and is characterized by a power law (photon index of Gamma = 3.06 +/- 0.15(stat) +/- 0.10(syst)). Significant small-amplitude variations in the VHE flux from H 2356-309 are seen on time scales of months and years, but not on shorter time scales. No evidence for any variations in the VHE spectral slope are found within these data. The XMM-Newton X-ray measurements show a historically low X-ray state, characterized by a hard, broken-power-law spectrum on both nights. Conclusions. The broad-band spectral energy distribution (SED) of the blazar can be adequately fit using a simple one-zone synchrotron self-Compton (SSC) model. In the SSC scenario, higher VHE fluxes could be expected in the future since the observed X-ray flux is at a historically low level.
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23.
  • Abramowski, A., et al. (författare)
  • VHE gamma-ray emission of PKS 2155-304 : spectral and temporal variability
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 520, s. A83-
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Observations of very high-energy.-rays from blazars provide information about acceleration mechanisms occurring in their innermost regions. Studies of variability in these objects lead to a better understanding of the mechanisms in play. Aims. To investigate the spectral and temporal variability of VHE (>100 GeV) gamma-rays of the well-known high-frequency-peaked BL Lac object PKS 2155-304 with the HESS imaging atmospheric Cherenkov telescopes over a wide range of flux states. Methods. Data collected from 2005 to 2007 were analyzed. Spectra were derived on time scales ranging from 3 years to 4 min. Light curve variability was studied through doubling timescales and structure functions and compared with red noise process simulations. Results. The source was found to be in a low state from 2005 to 2007, except for a set of exceptional flares that occurred in July 2006. The quiescent state of the source is characterized by an associated mean flux level of (4.32 +/- 0.09(stat) +/- 0.86(syst)) x 10(-11) cm(-2) s(-1) above 200 GeV, or approximately 15% of the Crab Nebula, and a power-law photon index of Gamma = 3.53 +/- 0.06(stat) +/- 0.10(syst). During the flares of July 2006, doubling timescales of similar to 2 min are found. The spectral index variation is examined over two orders of magnitude in flux, yielding different behavior at low and high fluxes, which is a new phenomenon in VHE gamma-ray emitting blazars. The variability amplitude characterized by the fractional rms F-var is strongly energy-dependent and is proportional to E-0.19 +/- 0.01. The light curve rms correlates with the flux. This is the signature of a multiplicative process that can be accounted for as a red noise with a Fourier index of similar to 2. Conclusions. This unique data set shows evidence of a low-level.-ray emission state from PKS 2155-304 that possibly has a different origin than the outbursts. The discovery of the light curve ognormal behavior might be an indicator of the origin of aperiodic variability in blazars.
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24.
  • Acero, F., et al. (författare)
  • PKS2005-489 at VHE : four years of monitoring with HESS and simultaneous multi-wavelength observations
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 511, s. A52-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. Our aim is to study the very high energy (VHE; E > 100 GeV) gamma-ray emission from BL Lac objects and the evolution in time of their broad-band spectral energy distribution (SED). Methods. VHE observations of the high-frequency peaked BL Lac object PKS 2005-489 were made with the High Energy Stereoscopic System (HESS) from 2004 through 2007. Three simultaneous multi-wavelength campaigns at lower energies were performed during the HESS data taking, consisting of several individual pointings with the XMM-Newton and RXTE satellites. Results. A strong VHE signal, similar to 17 sigma total, from PKS 2005-489 was detected during the four years of HESS observations (90.3 h live time). The integral flux above the average analysis threshold of 400 GeV is similar to 3% of the flux observed from the Crab Nebula and varies weakly on time scales from days to years. The average VHE spectrum measured from similar to 300 GeV to similar to 5 TeV is characterized by a power law with a photon index, Gamma = 3.20 +/- 0.16(stat) +/- 0.10(syst). At X-ray energies the flux is observed to vary by more than an order of magnitude between 2004 and 2005. Strong changes in the X-ray spectrum (Delta Gamma(X) approximate to 0.7) are also observed, which appear to be mirrored in the VHE band. Conclusions. The SED of PKS 2005-489, constructed for the first time with contemporaneous data on both humps, shows significant evolution. The large flux variations in the X-ray band, coupled with weak or no variations in the VHE band and a similar spectral behavior, suggest the emergence of a new, separate, harder emission component in September 2005.
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25.
  • Aharonian, F., et al. (författare)
  • Simultaneous multiwavelength observations of the second exceptional gamma-ray flare of PKS2155-304 in July 2006
  • 2009
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 502:3, s. 749-770
  • 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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26.
  • Fresard, Laure, et al. (författare)
  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
  • 2019
  • Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
  • Tidskriftsartikel (refereegranskat)abstract
    • It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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27.
  • Wang, Li-San, et al. (författare)
  • Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
  • 2015
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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28.
  • Abramowski, A., et al. (författare)
  • A new SNR with TeV shell-type morphology : HESS J1731-347
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 531, s. A81-
  • 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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29.
  • Abramowski, A., et al. (författare)
  • Discovery of extended VHE gamma-ray emission from the vicinity of the young massive stellar cluster Westerlund 1
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537, s. A114-
  • 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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30.
  • Abramowski, A., et al. (författare)
  • Discovery of the source HESS J1356-645 associated with the young and energetic PSR J1357-6429
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533, s. A103-
  • 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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31.
  • Abramowski, A., et al. (författare)
  • HESS constraints on dark matter annihilations towards the sculptor and carina dwarf galaxies
  • 2011
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:8, s. 608-616
  • Tidskriftsartikel (refereegranskat)abstract
    • The Sculptor and Carina dwarf spheroidal galaxies were observed with the H.E.S.S. Cherenkov telescope array between January 2008 and December 2009. The data sets consist of a total of 11.8 h and 14.811 of high quality data, respectively. No gamma-ray signal was detected at the nominal positions of these galaxies above 220 GeV and 320 GeV, respectively. Upper limits on the gamma-ray fluxes at 95% CL assuming two forms for the spectral energy distribution (a power law shape and one derived from dark matter annihilation) are obtained at the level of 10(-13)-10(-12) cm(-2) s(-1) in the TeV range. Constraints on the velocity weighted dark matter particle annihilation cross section for both Sculptor and Carina dwarf galaxies range from 10(-21) cm(3) s(-1) down to similar to 10(-2)2 cm(3) s(-1) on the dark matter halo model used. Possible enhancements of the gamma-ray flux are studied: the Sommerfeld effect, which is found to exclude some dark matter particle masses, the internal Bremsstrahlung and clumps in the dark-matter halo distributions. (C) 2010 Elsevier B.V. All rights reserved.
  •  
32.
  • Abramowski, A., et al. (författare)
  • HESS J1943+213 : a candidate extreme BL Lacertae object
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 529, s. A49-
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The H. E. S. S. Cherenkov telescope array has been surveying the Galactic plane for new VHE (>100 GeV) gamma-ray sources. Aims. We report on a newly detected point-like source, HESS J1943+213. This source coincides with an unidentified hard X-ray source IGR J19443+2117, which was proposed to have radio and infrared counterparts. Methods. We combine new H. E. S. S., Fermi/LAT and Nancay Radio Telescope observations with pre-existing non-simultaneous multi-wavelength observations of IGR J19443+2117 and discuss the likely source associations as well as the interpretation as an active galactic nucleus, a gamma-ray binary or a pulsar wind nebula. Results. HESS J1943+213 is detected at the significance level of 7.9 sigma (post-trials) at RA(J2000) = 19(h)43(m)55(s) +/- 1(stat)(s) +/- 1(sys)(s), Dec(J2000) = +21 degrees 18'8 '' +/- 17(stat)'' +/- 20(sys)''. The source has a soft spectrum with photon index Gamma = 3.1 +/- 0.3(stat) +/- 0.2(sys) and a flux above 470 GeV of (1.3 +/- 0.2(stat) +/- 0.3(sys)) x 10(-12) cm(-2) s(-1). There is no Fermi/LAT counterpart down to a flux limit of 6 x 10(-9) cm(-2) s(-1) in the 0.1-100 GeV energy range (95% confidence upper limit calculated for an assumed power-law model with a photon index Gamma = 2.0). The data from radio to VHE gamma-rays do not show any significant variability. Conclusions. The lack of a massive stellar counterpart disfavors the binary hypothesis, while the soft VHE spectrum would be very unusual in case of a pulsar wind nebula. In addition, the distance estimates for Galactic counterparts places them outside of the Milky Way. All available observations favor an interpretation as an extreme, high-frequency peaked BL Lac object with a redshift z > 0.14. This would be the first time a blazar is detected serendipitously from ground-based VHE observations, and the first VHE AGN detected in the Galactic Plane.
  •  
33.
  • Abramowski, A., et al. (författare)
  • HESS OBSERVATIONS OF THE GLOBULAR CLUSTERS NGC 6388 AND M15 AND SEARCH FOR A DARK MATTER SIGNAL
  • 2011
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 735:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Observations of the globular clusters (GCs) NGC 6388 and M15 were carried out by the High Energy Stereoscopic System array of Cherenkov telescopes for a live time of 27.2 and 15.2 hr, respectively. No gamma-ray signal is found at the nominal target position of NGC 6388 and M15. In the primordial formation scenario, GCs are formed in a dark matter (DM) halo and DM could still be present in the baryon-dominated environment of GCs. This opens the possibility of observing a DM self-annihilation signal. The DM content of the GCs NGC 6388 and M15 is modeled taking into account the astrophysical processes that can be expected to influence the DM distribution during the evolution of the GC: the adiabatic contraction of DM by baryons, the adiabatic growth of a black hole in the DM halo, and the kinetic heating of DM by stars. Ninety-five percent confidence level exclusion limits on the DM particle velocity-weighted annihilation cross section are derived for these DM halos. In the TeV range, the limits on the velocity-weighted annihilation cross section are derived at the 10(-25) cm(3) s(-1) level and a few 10(-24) cm(3) s(-1) for NGC 6388 and M15, respectively.
  •  
34.
  • Abramowski, A., et al. (författare)
  • Search for a Dark Matter Annihilation Signal from the Galactic Center Halo with HESS
  • 2011
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 106:16, s. 161301-
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for a very-high-energy (VHE; >= 100 GeV) gamma-ray signal from self-annihilating particle dark matter (DM) is performed towards a region of projected distance r similar to 45-150 pc from the Galactic center. The background-subtracted gamma-ray spectrum measured with the High Energy Stereoscopic System (H.E.S.S.) gamma-ray instrument in the energy range between 300 GeV and 30 TeV shows no hint of a residual gamma-ray flux. Assuming conventional Navarro-Frenk-White and Einasto density profiles, limits are derived on the velocity-weighted annihilation cross section as a function of the DM particle mass. These are among the best reported so far for this energy range and in particular differ only little between the chosen density profile parametrizations. In particular, for the DM particle mass of similar to 1 TeV, values for above 3 x 10(-25) cm(3) s(-1) are excluded for the Einasto density profile.
  •  
35.
  • Abramowski, A., et al. (författare)
  • Search for Lorentz Invariance breaking with a likelihood fit of the PKS 2155-304 flare data taken on MJD 53944
  • 2011
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:9, s. 738-747
  • Tidskriftsartikel (refereegranskat)abstract
    • Several models of Quantum Gravity predict Lorentz Symmetry breaking at energy scales approaching the Planck scale (similar to 10(19) GeV). With present photon data from the observations of distant astrophysical sources, it is possible to constrain the Lorentz Symmetry breaking linear term in the standard photon dispersion relations. Gamma Ray Bursts (GRB) and flaring Active Galactic Nuclei (AGN) are complementary to each other for this purpose, since they are observed at different distances in different energy ranges and with different levels of variability. Following a previous publication of the High Energy Stereoscopic System (H.E.S.S.) collaboration [1], a more sensitive event-by-event method consisting of a likelihood fit is applied to PKS 2155-304 flare data of MJD 53944 (July 28, 2006) as used in the previous publication. The previous limit on the linear term is improved by a factor of similar to 3 up to M(QG)(1), > 2.1 X 10(1B) GeV and is currently the best result obtained with blazars. The sensitivity to the quadratic term is lower and provides a limit of M(QG)(q) > 6.4 x 10(10) GeV, which is the best value obtained so far with an AGN and similar to the best limits obtained with GRB. (C) 2011 Elsevier B.V. All rights reserved.
  •  
36.
  • Abramowski, A., et al. (författare)
  • Very-high-energy gamma-ray emission from the direction of the Galactic globular cluster Terzan 5
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 531, s. L18-
  • Tidskriftsartikel (refereegranskat)abstract
    • The HESS very-high-energy (VHE, E > 0.1 TeV) gamma-ray telescope system has discovered a new source, HESS J1747-248. The measured integral flux is (1.2 +/- 0.3) x 10(-12) cm(-2) s(-1) above 440 GeV for a power-law photon spectral index of 2.5 +/- 0.3(stat) +/- 0.2(sys). The VHE gamma-ray source is located in the close vicinity of the Galactic globular cluster Terzan 5 and extends beyond the HESS point spread function (0.07 degrees). The probability of a chance coincidence with Terzan 5 and an unrelated VHE source is quite low (similar to 10(-4)). With the largest population of identified millisecond pulsars (msPSRs), a very high core stellar density and the brightest GeV range flux as measured by Fermi-LAT, Terzan 5 stands out among Galactic globular clusters. The properties of the VHE source are briefly discussed in the context of potential emission mechanisms, notably in relation to msPSRs. Interpretation of the available data accommodates several possible origins for this VHE gamma-ray source, although none of them offers a satisfying explanation of its peculiar morphology.
  •  
37.
  • Acero, F., et al. (författare)
  • First detection of VHE gamma-rays from SN 1006 by HESS
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 516, s. A62-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. Recent theoretical predictions of the lowest very high energy (VHE) luminosity of SN 1006 are only a factor 5 below the previously published HESS upper limit, thus motivating further in-depth observations of this source. Methods. Deep observations at VHE energies (above 100 GeV) were carried out with the high energy stereoscopic system (HESS) of Cherenkov Telescopes from 2003 to 2008. More than 100 h of data have been collected and subjected to an improved analysis procedure. Results. Observations resulted in the detection of VHE gamma-rays from SN 1006. The measured gamma-ray spectrum is compatible with a power-law, the flux is of the order of 1% of that detected from the Crab Nebula, and is thus consistent with the previously established HESS upper limit. The source exhibits a bipolar morphology, which is strongly correlated with non-thermal X-rays. Conclusions. Because the thickness of the VHE-shell is compatible with emission from a thin rim, particle acceleration in shock waves is likely to be the origin of the gamma-ray signal. The measured flux level can be accounted for by inverse Compton emission, but a mixed scenario that includes leptonic and hadronic components and takes into account the ambient matter density inferred from observations also leads to a satisfactory description of the multi-wavelength spectrum.
  •  
38.
  • Acero, F., et al. (författare)
  • HESS upper limits on very high energy gamma-ray emission from the microquasar GRS 1915+105
  • 2009
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 508:3, s. 1135-1140
  • 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.
  •  
39.
  • Acero, F., et al. (författare)
  • Localizing the VHE gamma-ray source at the Galactic Centre
  • 2010
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 402:3, s. 1877-1882
  • Tidskriftsartikel (refereegranskat)abstract
    • The inner 10 pc of our Galaxy contains many counterpart candidates of the very high energy (VHE; > 100 GeV) gamma-ray point source HESS J1745-290. Within the point spread function of the H.E.S.S. measurement, at least three objects are capable of accelerating particles to VHE and beyond and of providing the observed gamma-ray flux. Previous attempts to address this source confusion were hampered by the fact that the projected distances between these objects were of the order of the error circle radius of the emission centroid (34 arcsec, dominated by the pointing uncertainty of the H.E.S.S. instrument). Here we present H.E.S.S. data of the Galactic Centre region, recorded with an improved control of the instrument pointing compared to H.E.S.S. standard pointing procedures. Stars observed during gamma-ray observations by optical guiding cameras mounted on each H.E.S.S. telescope are used for off-line pointing calibration, thereby decreasing the systematic pointing uncertainties from 20 to 6 arcsec per axis. The position of HESS J1745-290 is obtained by fitting a multi-Gaussian profile to the background-subtracted gamma-ray count map. A spatial comparison of the best-fitting position of HESS J1745-290 with the position and morphology of candidate counterparts is performed. The position is, within a total error circle radius of 13 arcsec, coincident with the position of the supermassive black hole Sgr A* and the recently discovered pulsar wind nebula candidate G359.95-0.04. It is significantly displaced from the centroid of the supernova remnant Sgr A East, excluding this object with high probability as the dominant source of the VHE gamma-ray emission.
  •  
40.
  • Aharonian, F., et al. (författare)
  • Energy Spectrum of Cosmic-Ray Electrons at TeV Energies
  • 2008
  • Ingår i: Physical Review Letters. - : APS Physics. - 0031-9007 .- 1079-7114. ; 101:26
  • 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.
  •  
41.
  • Aharonian, F., et al. (författare)
  • Limits on an Energy Dependence of the Speed of Light from a Flare of the Active Galaxy PKS 2155-304
  • 2008
  • Ingår i: Physical Review Letters. - : APS Physics. - 0031-9007 .- 1079-7114. ; 101:17
  • 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.
  •  
42.
  • Aharonian, F., et al. (författare)
  • Spectrum and variability of the Galactic center VHE gamma-ray source HESS J1745-290
  • 2009
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 503:3, s. 817-825
  • 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.
  •  
43.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
  •  
44.
  • Kanoni, Stavroula, et al. (författare)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
  •  
45.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
  •  
46.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
  •  
47.
  • Abramowski, A., et al. (författare)
  • Constraints on the gamma-ray emission from the cluster-scale AGN outburst in the Hydra A galaxy cluster
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. A103-
  • 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.
  •  
48.
  • Abramowski, A., et al. (författare)
  • Detection of very-high-energy gamma-ray emission from the vicinity of PSR B1706-44 and G 343.1-2.3 with HESS
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 528, s. A143-
  • Tidskriftsartikel (refereegranskat)abstract
    • The gamma-ray pulsar PSR B1706-44 and the adjacent supernova remnant (SNR) candidate G 343.1-2.3 were observed by H. E. S. S. during a dedicated observation campaign in 2007. As a result of this observation campaign, a new source of very-high-energy (VHE; E > 100 GeV) gamma-ray emission, H.E.S.S. J1708-443, was detected with a statistical significance of 7 sigma, although no significant point-like emission was detected at the position of the energetic pulsar itself. In this paper, the morphological and spectral analyses of the newly-discovered TeV source are presented. The centroid of H. E. S. S. J1708-443 is considerably offset from the pulsar and located near the apparent center of the SNR, at alpha(J2000) = 17(h)08(m)11(s) +/- 17(s) and delta(J2000) = -44 degrees 20' +/- 4'. The source is found to be significantly more extended than the H. E. S. S. point spread function (similar to 0.1 degrees), with an intrinsic Gaussian width of 0.29 degrees +/- 0.04 degrees. Its integral flux between 1 and 10 TeV is similar to 3.8 x 10(-1)2 ph cm(-2) s(-1), equivalent to 17% of the Crab Nebula flux in the same energy range. The measured energy spectrum is well-fit by a power law with a relatively hard photon index Gamma = 2.0 +/- 0.1(stat) +/-0.2(sys). Additional multi-wavelength data, including 330 MHz VLA observations, were used to investigate the VHE gamma-ray source's possible associations with the pulsar wind nebula of PSR B1706-44 and/or with the complex radio structure of the partial shell-type SNR G 343.1-2.3.
  •  
49.
  • Abramowski, A., et al. (författare)
  • Discovery of gamma-ray emission from the extragalactic pulsar wind nebula N 157B with HESS
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. Article ID: L2-
  • 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.
  •  
50.
  • Abramowski, A., et al. (författare)
  • Discovery of VHE emission towards the Carina arm region with the HESS telescope array : HESSJ1018-589
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541, s. A5-
  • 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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