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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.
A confocal set-up is presented that improves micro-XRF and XAFS experiment with high-pressure e diamond-anvil cells (DACs) In this experiment a probing volume is defined by the focus of the incoming synchrotron radiation beam and that of a polycapillary X-ray half-lens with a very long working distance, which is placed in front of the fluorescence detector This set-up enhances the quality of the fluorescence and XAFS spectra, and thus the sensitivity for detecting elements at low concentrations. It efficiently suppresses signal from outside the sample chamber, which stems from elastic and inelastic scattering of the incoming beam by the diamond anvils as well as from excitation of fluorescence from the body of the DAC
We present an experimental approach to study the three-dimensional microstructure of gas diffusion layer (GDL) materials under realistic compression conditions. A dedicated compression device was designed that allows for synchrotron-tomographic investigation of circular samples under well-defined compression conditions. The tomographic data provide the experimental basis for stochastic modeling of nonwoven GDL materials. A plain compression tool is used to study the fiber courses in the material at different compression stages. Transport relevant geometrical parameters, such as porosity, pore size, and tortuosity distributions, are exemplarily evaluated for a GDL sample in the uncompressed state and for a compression of 30 vol.%. To mimic the geometry of the flow-field, we employed a compression punch with an integrated channel-rib-profile. It turned out that the GDL material is homogeneously compressed under the ribs, however, much less compressed underneath the channel. GDL fibers extend far into the channel volume where they might interfere with the convective gas transport and the removal of liquid water from the cell. (C) 2015 AIP Publishing LLC.
We present a new autoclave that enables in situ characterization of hydrothermal fluids at high pressures and high temperatures at synchrotron x-ray radiation sources. The autoclave has been specifically designed to enable x-ray absorption spectroscopy in fluids with applications to mineral solubility and element speciation analysis in hydrothermal fluids in complex compositions. However, other applications, such as Raman spectroscopy, in high-pressure fluids are also possible with the autoclave. First experiments were run at pressures between 100 and 600 bars and at temperatures between 25 degrees C and 550 degrees C, and preliminary results on scheelite dissolution in fluids of different compositions show that the autoclave is well suited to study the behavior of ore-forming metals at P-T conditions relevant to the Earth's crust.
We report on a new series of isoreticular frameworks based on zinc and 2-substituted imidazolate-4-amide-5-imidate (IFP-14, IFP=imidazolate framework Potsdam) that form one-dimensional, microporous hexagonal channels. Varying R in the 2-substitued linker (R=Me (IFP-1), Cl (IFP-2), Br (IFP-3), Et (IFP-4)) allowed the channel diameter (4.01.7 angstrom), the polarisability and functionality of the channel walls to be tuned. Frameworks IFP-2, IFP-3 and IFP-4 are isostructural to previously reported IFP-1. The structures of IFP-2 and IFP-3 were solved by X-ray crystallographic analyses. The structure of IFP-4 was determined by a combination of PXRD and structure modelling and was confirmed by IR spectroscopy and 1H MAS and 13C CP-MAS NMR spectroscopy. All IFPs showed high thermal stability (345400?degrees C); IFP-1 and IFP-4 were stable in boiling water for 7 d. A detailed porosity analysis was performed on the basis of adsorption measurements by using various gases. The potential of the materials to undergo specific interactions with CO2 was investigated by measuring the isosteric heats of adsorption. The capacity to adsorb CH4 (at 298 K), CO2 (at 298 K) and H2 (at 77 K) at high pressure were also investigated. In situ IR spectroscopy showed that CO2 is physisorbed on IFP-14 under dry conditions and that both CO2 and H2O are physisorbed on IFP-1 under moist conditions.
The analytical evaluation of diurnal temperature variation in riverbed sediments provides detailed information on exchange fluxes between rivers and groundwater. The underlying assumption of the stationary, one-dimensional vertical flow field is frequently violated in natural systems where subsurface water flow often has a significant horizontal component. In this paper, we present a new methodology for identifying the geometry of the subsurface flow field using vertical temperature profiles. The statistical analyses are based on model optimisation and selection and are used to evaluate the shape of vertical amplitude ratio profiles. The method was applied to multiple profiles measured around in-stream geomorphological structures in a losing reach of a gravel bed river. The predominant subsurface flow field was systematically categorised in purely vertical and horizontal (hyporheic, parafluvial) components. The results highlight that river groundwater exchange flux at the head, crest and tail of geomorphological structures significantly deviated from the one-dimensional vertical flow, due to a significant horizontal component. The geometry of the subsurface water flow depended on the position around the geomorphological structures and on the river level. The methodology presented in this paper features great potential for characterising the spatial patterns and temporal dynamics of complex subsurface flow geometries by using measured temperature time series in vertical profiles. (C) 2016 Elsevier B.V. All rights reserved.
Dynamics of solute export from catchments can be classified in terms of chemostatic and chemodynamic export regimes by an analysis of concentration-discharge relationships. Previous studies hypothesized that distinct export regimes emerge from the presence of solute mass stores within the catchment and their connectivity to the stream. However, so far a direct link of solute export to identifiable catchment characteristics is missing. Here we investigate long-term time series of stream water quality and quantity of nine neighboring catchments in Central Germany ranging from relatively pristine mountain catchments to agriculturally dominated lowland catchments, spanning large gradients in land use, geology, and climatic conditions. Given the strong collinearity of catchment characteristics we used partial least square regression analysis to quantify the predictive power of these characteristics for median concentrations and the metrics of export regime. We can show that median concentrations and metrics of the export regimes of major ions and nutrients can indeed be inferred from catchment characteristics. Strongest predictors for median concentrations were the share of arable land, discharge per area, runoff coefficient and available water capacity in the root zone of the catchments. The available water capacity in the root zone, the share of arable land being artificially drained and the topographic gradient were found to be the most relevant predictors for the metrics of export regime. These catchment characteristics can represent the size of solute mass store such as the fraction of arable land being a measure for the store of nitrate. On the other hand, catchment characteristics can be a measure for the connectivity of these solute stores to the stream such as the fraction of tile drained land in the catchments. This study demonstrates the potential of data-driven, top down analyses using simple metrics to classify and better understand dominant controls of solute export from catchments. (C) 2015 Elsevier Ltd. All rights reserved.
We present a study of the local atomic environment of the oxygen atoms in the aqueous solutions of NaOH and HCl under simultaneous high-temperature and high-pressure conditions. Experimental nonresonant X-ray Raman scattering core-level spectra at the oxygen K-edge show systematic changes as a function of temperature and pressure. These systematic changes are distinct for the two different solutes and are described well by calculations within the Bethe- Salpeter formalism for snapshots from ab initio molecular dynamics simulations. The agreement between experimental and simulation results allows us to use the computations for a detailed fingerprinting analysis in an effort to elucidate the local atomic structure and hydrogen-bonding topology in these relevant solutions. We observe that both electrolytes, especially NaOH, enhance hydrogen bonding and tetrahedrality in the water structure at supercritical conditions, in particular in the vicinity of the hydration shells. This effect is accompanied with the association of the HCl and NaOH molecules at elevated temperatures.
The volume provides a field-analytical methodology for researching knowledge based sociopolitical processes of transnationalization. Drawing on the seminal work by Pierre Bourdieu, we apply concepts of practice, habitus, and field to phenomena such as cross-national social trajectories, international procedures of evaluation, standardization and certification or supranational political structures. These transnational phenomena form part of general political struggles that legitimate social relationships in and beyond the nation state. Part 1 on "Methodological Foundations" discusses the consequences of Bourdieu's epistemology and methodology for theorizing and investigating transnational phenomena. The contributions show the import of field-theoretical concepts for post-national insights. Part 2 on "Investigating Political Fields" presents exemplary case studies in diverse research areas such as colonial imperialism, international academic rankings, European policy fields, and local school policy. While focusing on their research objects, the contributions also give an insight into the mechanisms involved in processes of transnationalization. The volume is an invitation for sociologists, political scientists and scholars in adjacent research areas to engage with reflexive and relational research practice and to further develop field-theoretical thought.
Computerised mirror therapy with Augmented Reflection Technology for early stroke rehabilitation
(2017)
Purpose: New rehabilitation strategies for post-stroke upper limb rehabilitation employing visual stimulation show promising results, however, cost-efficient and clinically feasible ways to provide these interventions are still lacking. An integral step is to translate recent technological advances, such as in virtual and augmented reality, into therapeutic practice to improve outcomes for patients. This requires research on the adaptation of the technology for clinical use as well as on the appropriate guidelines and protocols for sustainable integration into therapeutic routines. Here, we present and evaluate a novel and affordable augmented reality system (Augmented Reflection Technology, ART) in combination with a validated mirror therapy protocol for upper limb rehabilitation after stroke. Results: The results showed that the combination and application of the Berlin Protocol for Mirror Therapy together with ART was feasible for clinical use. This combination was integrated into the therapeutic plan of subacute stroke patients at the two clinical locations where the second part of this research was conducted. Conclusions: Our findings pave the way for using technology to provide mirror therapy in clinical settings and show potential for the more effective use of inpatient time and enhanced recoveries for patients. IMPLICATIONS FOR REHABILITATION Computerised Mirror Therapy is feasible for clinical use Augmented Reflection Technology can be integrated as an adjunctive therapeutic intervention for subacute stroke patients in an inpatient setting Virtual Rehabilitation devices such as Augmented Reflection Technology have considerable potential to enhance stroke rehabilitation