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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Protection of natural or semi-natural ecosystems is an important part of societal strategies for maintaining biodiversity, ecosystem services, and achieving overall sustainable development. The assessment of multiple emerging land use trade-offs is complicated by the fact that land use changes occur and have consequences at local, regional, and even global scale. Outcomes also depend on the underlying socio-economic trends. We apply a coupled, multi-scale modelling system to assess an increase in nature protection areas as a key policy option in the European Union (EU). The main goal of the analysis is to understand the interactions between policy-induced land use changes across different scales and sectors under two contrasting future socio-economic pathways. We demonstrate how complementary insights into land system change can be gained by coupling land use models for agriculture, forestry, and urban areas for Europe, in connection with other world regions. The simulated policy case of nature protection shows how the allocation of a certain share of total available land to newly protected areas, with specific management restrictions imposed, may have a range of impacts on different land-based sectors until the year 2040. Agricultural land in Europe is slightly reduced, which is partly compensated for by higher management intensity. As a consequence of higher costs, total calorie supply per capita is reduced within the EU. While wood harvest is projected to decrease, carbon sequestration rates increase in European forests. At the same time, imports of industrial roundwood from other world regions are expected to increase. Some of the aggregate effects of nature protection have very different implications at the local to regional scale in different parts of Europe. Due to nature protection measures, agricultural production is shifted from more productive land in Europe to on average less productive land in other parts of the world. This increases, at the global level, the allocation of land resources for agriculture, leading to a decrease in tropical forest areas, reduced carbon stocks, and higher greenhouse gas emissions outside of Europe. The integrated modelling framework provides a method to assess the land use effects of a single policy option while accounting for the trade-offs between locations, and between regional, European, and global scales.
Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
The intention of the presented study is to gain a better understanding of the mechanisms that caused the bimodal rainfall-runoff responses which occurred up to the mid-1970s regularly in the Schafertal catchment and vanished after the onset of mining activities. Understanding, this process is a first step to understanding the ongoing hydrological change in this area. It is hypothesized that either subsurface stormflow, or fast displacement of groundwater, could cause the second delayed peak. A top-down analysis of rainfall-runoff data, field observations as well as process modelling are combined within a rejectionistic framework. A statistical analysis is used to test whether different predictors. which characterize the forcing. near surface water content and deeper subsurface store, allow the prediction of the type of rainfall-runoff response. Regression analysis is used with generalized linear models Lis they can deal with non-Gaussian error distributions Lis well its a non-stationary variance. The analysis reveals that the dominant predictors are the pre-event discharge (proxy of state of the groundwater store) and the precipitation amount, In the field campaign, the subsurface at a representative hillslope was investigated by means of electrical resistivity tomography in order to identify possible strata as flow paths for subsurface stormflow. A low resistivity in approximately 4 in depth-either due to a less permeable layer or the groundwater surface-was detected. The former Could serve as a flow path for subsurface stormflow. Finally, the physical-based hydrological model CATFLOW and the groundwater model FEFLOW are compared with respect to their ability to reproduce the bimodal runoff responses. The groundwater model is able to reproduce the observations, although it uses only an abstract representation of the hillslopes. Process model analysis as well Lis statistical analysis strongly suggest that fast displacement of groundwater is the dominant process underlying the bimodal runoff reactions.
The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section <sigma nu >. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach <sigma nu > values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe <sigma nu > values expected from the thermal relic density for TeV DM particles.
A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l = -1.5 degrees, b = 0 degrees and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. results. No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.
Galactic cosmic rays reach energies of at least a few petaelectronvolts (of the order of 1015 electronvolts). This implies that our Galaxy contains petaelectronvolt accelerators (‘PeVatrons’), but all proposed models of Galactic cosmic-ray accelerators encounter difficulties at exactly these energies. Dozens of Galactic accelerators capable of accelerating particles to energies of tens of teraelectronvolts (of the order of 1013 electronvolts) were inferred from recent γ-ray observations3. However, none of the currently known accelerators—not even the handful of shell-type supernova remnants commonly believed to supply most Galactic cosmic rays—has shown the characteristic tracers of petaelectronvolt particles, namely, power-law spectra of γ-rays extending without a cut-off or a spectral break to tens of teraelectronvolts4. Here we report deep γ-ray observations with arcminute angular resolution of the region surrounding the Galactic Centre, which show the expected tracer of the presence of petaelectronvolt protons within the central 10 parsecs of the Galaxy. We propose that the supermassive black hole Sagittarius A* is linked to this PeVatron. Sagittarius A* went through active phases in the past, as demonstrated by X-ray outbursts5and an outflow from the Galactic Centre6. Although its current rate of particle acceleration is not sufficient to provide a substantial contribution to Galactic cosmic rays, Sagittarius A* could have plausibly been more active over the last 106–107 years, and therefore should be considered as a viable alternative to supernova remnants as a source of petaelectronvolt Galactic cosmic rays.
Measurement of the EBL spectral energy distribution using the VHE gamma-ray spectra of HESS blazars
(2017)
Very high-energy gamma rays (VHE, E greater than or similar to 100 GeV) propagating over cosmological distances can interact with the low-energy photons of the extragalactic background light (EBL) and produce electron-positron pairs. The transparency of the Universe to VHE gamma rays is then directly related to the spectral energy distribution (SED) of the EBL. The observation of features in the VHE energy spectra of extragalactic sources allows the EBL to be measured, which otherwise is very difficult. An EBL model-independent measurement of the EBL SED with the H.E.S.S. array of Cherenkov telescopes is presented. It was obtained by extracting the EBL absorption signal from the reanalysis of high-quality spectra of blazars. From H.E.S.S. data alone the EBL signature is detected at a significance of 9.5 sigma, and the intensity of the EBL obtained in different spectral bands is presented together with the associated gamma-ray horizon.
Re-observations with the HESS telescope array of the very high-energy (VHE) source HESS J1018-589A that is coincident with the Fermi-LAT gamma-ray binary 1FGL J1018.6-5856 have resulted in a source detection significance of more than 9 sigma and the detection of variability (chi(2)/nu of 238.3/155) in the emitted gamma-ray flux. This variability confirms the association of HESS J1018-589A with the high-energy gamma-ray binary detected Fermi-LAT and also confirms the point-like source as a new VHE binary system. The spectrum of HESS J1018-589A is best fit with a power-law function with photon index Gamma = 2.20 +/- 0.14(stat) +/- 0.2(sys). Emission is detected up to similar to 20 TeV. The mean differential flux level is (2.9 +/- 0.4) x 10(-13) TeV-1 cm(-2) s(-1) at 1 TeV, equivalent to similar to 1% of the flux from the Crab Nebula at the same energy. Variability is clearly detected the night-by-night light curve. When folded on the orbital period of 16.58 days, the rebinned light curve peaks in phase with the observed X-ray high-energy phaseograms. The fit of the HESS phaseogram to a constant flux provides evidence of periodicity at the level of N-sigma > 3 sigma. The of the VHE phaseogram and measured spectrum suggest a low-inclination, low-eccentricity system with a modest impact from VHE gamma-ray due to pair production (tau less than or similar to 1 at 300 GeV).
Introducing the CTA concept
(2013)
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.