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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.
Hyperspectral REE (Rare Earth Element) Mapping of Outcrops-Applications for Neodymium Detection
(2015)
In this study, an in situ application for identifying neodymium (Nd) enriched surface materials that uses multitemporal hyperspectral images is presented (HySpex sensor). Because of the narrow shape and shallow absorption depth of the neodymium absorption feature, a method was developed for enhancing and extracting the necessary information for neodymium from image spectra, even under illumination conditions that are not optimal. For this purpose, the two following approaches were developed: (1) reducing noise and analyzing changing illumination conditions by averaging multitemporal image scenes and (2) enhancing the depth of the desired absorption band by deconvolving every image spectrum with a Gaussian curve while the rest of the spectrum remains unchanged (Richardson-Lucy deconvolution). To evaluate these findings, nine field samples from the Fen complex in Norway were analyzed using handheld X-ray fluorescence devices and by conducting detailed laboratory-based geochemical rare earth element determinations. The result is a qualitative outcrop map that highlights zones that are enriched in neodymium. To reduce the influences of non-optimal illumination, particularly at the studied site, a minimum of seven single acquisitions is required. Sharpening the neodymium absorption band allows for robust mapping, even at the outer zones of enrichment. From the geochemical investigations, we found that iron oxides decrease the applicability of the method. However, iron-related absorption bands can be used as secondary indicators for sulfidic ore zones that are mainly enriched with rare earth elements. In summary, we found that hyperspectral spectroscopy is a noninvasive, fast and cost-saving method for determining neodymium at outcrop surfaces.
Remote sensing analysis is a crucial tool for monitoring the extent of mine waste surfaces and their mineralogy in countries with a long mining history, such as South Africa, where gold and platinum have been produced for over 90 years. These mine waste sites have the potential to contain problematic trace element species (e. g., U, Pb, Cr). In our research, we aim to combine the mapping and monitoring capacities of multispectral and hyperspectral spaceborne sensors. This is done to assess the potential of existing multispectral and hyperspectral spaceborne sensors (OLI and Hyperion) and future missions, such as Sentinel-2 and EnMAP (Environmental Mapping and Analysis Program), for mapping the spatial extent of these mine waste surfaces. For this task we propose a new index, termed the iron feature depth (IFD), derived from Landsat-8 OLI data to map the 900-nm absorption feature as a potential proxy for monitoring the spatial extent of mine waste. OLI was chosen, because it represents the most suitable sensor to map the IFD over large areas in a multi-temporal manner due to its spectral band layout; its (183 km x 170 km) scene size and its revisiting time of 16 days. The IFD is in good agreement with primary and secondary iron-bearing minerals mapped by the Material Identification and Characterization Algorithm (MICA) from EO-1 Hyperion data and illustrates that a combination of hyperspectral data (EnMAP) for mineral identification with multispectral data (Sentinel-2) for repetitive area-wide mapping and monitoring of the IFD as mine waste proxy is a promising application for future spaceborne sensors. A maximum, absolute model error is used to assess the ability of existing and future multispectral sensors to characterize mine waste via its 900-nm iron absorption feature. The following sensor-signal similarity ranking can be established for spectra from gold mining material: EnMAP 100% similarity to the reference, ALI 97.5%, Sentinel-2 97%, OLI and ASTER 95% and ETM+ 91% similarity.
Modern imaging spectrometers produce an ever-growing amount of data, which increases the need for automated analysis techniques. The algorithms employed, such as the United States Geological Survey (USGS) Tetracorder and the Mineral Identification and Characterization Algorithm (MICA), use a standardized spectral library and expert knowledge for the detection of surface cover types. Correct absorption feature definition and isolation are key to successful material identification using these algorithms. Here, a new continuum removal and feature isolation technique is presented, named the 'Geometric Hull Technique'. It is compared to the well-established, knowledge-based Tetracorder feature database together with the adapted state of the art techniques scale-space filtering, alpha shapes and convex hull.
The results show that the geometric hull technique yields the smallest deviations from the feature definitions of the MICA Group 2 library with a median difference of only 8nm for the position of the features and a median difference of only 15% for the feature shapes. The modified scale-space filtering hull technique performs second best with a median feature position difference of 16nm and a median difference of 25% for the feature shapes. The scale-space alpha hull technique shows a 23nm median position difference and a median deviation of 77% for the feature shapes. The geometric hull technique proposed here performs best amongst the four feature isolation techniques and may be an important building block for next generation automatic mapping algorithms.
In this study, an in situ application for identifying neodymium (Nd) enriched surface materials that uses multitemporal hyperspectral images is presented (HySpex sensor). Because of the narrow shape and shallow absorption depth of the neodymium absorption feature, a method was developed for enhancing and extracting the necessary information for neodymium from image spectra, even under illumination conditions that are not optimal. For this purpose, the two following approaches were developed: (1) reducing noise and analyzing changing illumination conditions by averaging multitemporal image scenes and (2) enhancing the depth of the desired absorption band by deconvolving every image spectrum with a Gaussian curve while the rest of the spectrum remains unchanged (Richardson-Lucy deconvolution). To evaluate these findings, nine field samples from the Fen complex in Norway were analyzed using handheld X-ray fluorescence devices and by conducting detailed laboratory-based geochemical rare earth element determinations. The result is a qualitative outcrop map that highlights zones that are enriched in neodymium. To reduce the influences of non-optimal illumination, particularly at the studied site, a minimum of seven single acquisitions is required. Sharpening the neodymium absorption band allows for robust mapping, even at the outer zones of enrichment. From the geochemical investigations, we found that iron oxides decrease the applicability of the method. However, iron-related absorption bands can be used as secondary indicators for sulfidic ore zones that are mainly enriched with rare earth elements. In summary, we found that hyperspectral spectroscopy is a noninvasive, fast and cost-saving method for determining neodymium at outcrop surfaces
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Advances in broad bandwidth light sources for ultrahigh resolution optical coherence tomography
(2004)
Novel ultra-broad bandwidth light sources enabling unprecedented sub-2 pm axial resolution over the 400 nm-1700 nm wavelength range have been developed and evaluated with respect to their feasibility for clinical ultrahigh resolution optical coherence tomography (UHR OCT) applications. The state-of-the-art light sources described here include a compact Kerr lens mode locked Ti:sapphire laser (lambda(c) = 785 nm, Deltalambda = 260 nm, P-out = 50 mW) and different nonlinear fibre-based light sources with spectral bandwidths (at full width at half maximum) up to 350 nm at lambda(c) = 1130 nm and 470 nm at lambda(c) = 1375 run. In vitro UHR OCT imaging is demonstrated at multiple wavelengths in human cancer cells, animal ganglion cells as well as in neuropathologic and ophthalmic biopsies in order to compare and optimize UHR OCT image contrast, resolution and penetration depth
Thematic cartography
(2001)
Climate change and its impacts already pose considerable challenges for societies that will further increase with global warming (IPCC, 2014a, b). Uncertainties of the climatic response to greenhouse gas emissions include the potential passing of large-scale tipping points (e.g. Lenton et al., 2008; Levermann et al., 2012; Schellnhuber, 2010) and changes in extreme meteorological events (Field et al., 2012) with complex impacts on societies (Hallegatte et al., 2013). Thus climate change mitigation is considered a necessary societal response for avoiding uncontrollable impacts (Conference of the Parties, 2010). On the other hand, large-scale climate change mitigation itself implies fundamental changes in, for example, the global energy system. The associated challenges come on top of others that derive from equally important ethical imperatives like the fulfilment of increasing food demand that may draw on the same resources. For example, ensuring food security for a growing population may require an expansion of cropland, thereby reducing natural carbon sinks or the area available for bio-energy production. So far, available studies addressing this problem have relied on individual impact models, ignoring uncertainty in crop model and biome model projections. Here, we propose a probabilistic decision framework that allows for an evaluation of agricultural management and mitigation options in a multi-impact-model setting. Based on simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), we outline how cross-sectorally consistent multi-model impact simulations could be used to generate the information required for robust decision making.
Using an illustrative future land use pattern, we discuss the trade-off between potential gains in crop production and associated losses in natural carbon sinks in the new multiple crop-and biome-model setting. In addition, crop and water model simulations are combined to explore irrigation increases as one possible measure of agricultural intensification that could limit the expansion of cropland required in response to climate change and growing food demand. This example shows that current impact model uncertainties pose an important challenge to long-term mitigation planning and must not be ignored in long-term strategic decision making.
Climate change and its impacts already pose considerable challenges for societies that will further increase with global warming (IPCC, 2014a, b). Uncertainties of the climatic response to greenhouse gas emissions include the potential passing of large-scale tipping points (e.g. Lenton et al., 2008; Levermann et al., 2012; Schellnhuber, 2010) and changes in extreme meteorological events (Field et al., 2012) with complex impacts on societies (Hallegatte et al., 2013). Thus climate change mitigation is considered a necessary societal response for avoiding uncontrollable impacts (Conference of the Parties, 2010). On the other hand, large-scale climate change mitigation itself implies fundamental changes in, for example, the global energy system. The associated challenges come on top of others that derive from equally important ethical imperatives like the fulfilment of increasing food demand that may draw on the same resources. For example, ensuring food security for a growing population may require an expansion of cropland, thereby reducing natural carbon sinks or the area available for bio-energy production. So far, available studies addressing this problem have relied on individual impact models, ignoring uncertainty in crop model and biome model projections. Here, we propose a probabilistic decision framework that allows for an evaluation of agricultural management and mitigation options in a multi-impact-model setting. Based on simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), we outline how cross-sectorally consistent multi-model impact simulations could be used to generate the information required for robust decision making.
Using an illustrative future land use pattern, we discuss the trade-off between potential gains in crop production and associated losses in natural carbon sinks in the new multiple crop-and biome-model setting. In addition, crop and water model simulations are combined to explore irrigation increases as one possible measure of agricultural intensification that could limit the expansion of cropland required in response to climate change and growing food demand. This example shows that current impact model uncertainties pose an important challenge to long-term mitigation planning and must not be ignored in long-term strategic decision making.
Grundlagen des Verwaltungsrechts : Bd. II Informationsordnung, Verwaltungsverfahren, Handlungsformen
(2008)
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.
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.