Simulating ice core 10Be on the glacial–interglacial timescale

10Be ice core measurements are an important tool for paleoclimate research, e.g., allowing for the reconstruction of past solar activity or changes in the geomagnetic dipole field. However, especially on multi-millennial timescales, the share of production and climate-induced variations of respective 10Be ice core records is still up for debate. Here we present the first quantitative climatological model of the 10Be ice concentration up to the glacial–interglacial timescale. The model approach is composed of (i) a coarse resolution global atmospheric transport model and (ii) a local 10Be air–firn transfer model. Extensive global-scale observational data of short-lived radionuclides as well as new polar 10Be snow-pit measurements are used for model calibration and validation. Being specifically configured for 10Be in polar ice, this tool thus allows for a straightforward investigation of production- and non-production-related modulation of this nuclide. We find that the polar 10Be ice concentration does not immediately record the globally mixed cosmogenic production signal. Using geomagnetic modulation and revised Greenland snow accumulation rate changes as model input, we simulate the observed Greenland Summit (GRIP and GISP2) 10Be ice core records over the last 75 kyr (on the GICC05modelext timescale). We show that our basic model is capable of reproducing the largest portion of the observed 10Be changes. However, model–measurement differences exhibit multi-millennial trends (differences up to 87% in case of normalized to the Holocene records) which call for closer investigation. Focusing on the (12–37) b2k (before the year AD 2000) period, mean model–measurement differences of 30% cannot be attributed to production changes. However, unconsidered climate-induced changes could likely explain the model–measurement mismatch. In fact, the 10Be ice concentration is very sensitive to snow accumulation changes. Here the reconstructed Greenland Summit (GRIP) snow accumulation rate record would require revision of +28% to solely account for the (12–37) b2k model–measurement differences

Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.</p

Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics

Semi solid processing of complex shaped foamable material

A hybrid process comprising aspects of casting and powder technology is used for the production of complex shaped foam precursor material. Powder mixtures of aluminium alloys and foaming agent are cold isostatically compacted to cylindrical slugs which are then heated to the semi solid state and processed in conventional cold chamber high pressure die casting machines. This approach offers a highly productive method to produce foamable precursors with almost arbitrary shapes, e.g. with holes, changing wall thicknesses, or other geometric complexities. Due to the nature of the casting process an improved pore morphology has been observed. This can be explained by the comparably isotropic microstructure of the castings and an insitu heat treatment of the foaming agen

Desorption of hydrogen from blowing agents used for foaming metals

Hydrogen desorption from TiH2, ZrH2, and MgH2 was studied by thermal desorption spectroscopy TDS , differential thermal analysis DTA and thermogravimetric analysis TGA . Loose hydride powders as well as powder compacts of zinc and various hydrides were studied. It was found that during the powder compaction process free surfaces on the hydride powder particles were created. As a consequence, the desorption temperature of the hydride in the precursor was lowered in comparison to loose powder exposed to air. Foam expansion of zinc was highest for TiH2 which also exhibits the highest desorption rate at the melting point of zinc, followed by ZrH2 and MgH2 which decompose at lower temperatures and are therefore less effective for foaming. The desorption kinetics of Al and AlSi7 compacts containing TiH2 were also studied for matters of comparison. The much lower foam expansions compared to Zn foams could be explained by higher hydrogen losses at temperatures below the melting point of Al and AlSi

Material flow in metal foams studied by neutron radioscopy

Two kinds of experiments are presented in this paper: In the first lead alloy foams were generated in a furnace by expanding a foamable precursor material containing metal and a blowing agent. Vertical columns of liquid metal foam were scanned with a beam of neutrons while recording the time-dependent local neutron transmission. The resulting transmission profiles reflect the kinetics of material redistribution in liquid metallic foams under the influence of gravity (drainage). In the second experiment pre-fabricated solid lead foams were re-melted in a furnace. Neutron transmission profiles were also obtained in these experiments. Results of each type of experiment are presented and compared with theoretical predictions for the density profile of aqueous foams

Metal foam evolution studied by synchrotron radioscopy

High-intensity synchrotron x-ray radioscopy was used to obtain real-time images of foaming metals, thus allowing the formation, growth, and decay of such systems to be studied. Bubble generation, foam coalescence and drainage of an aluminum-based alloy foam were investigated. Although the foaming process appears to be very simliar to the formation of aqueous foams, the observed rupture behavior of thin metal films suggests that the processes responsible for metal foam stabilization and destabilization must be quite different