The global water resources and use model WaterGAP v2.2e: description and evaluation of modifications and new features

Water – Global Assessment and Prognosis (WaterGAP) is a modelling approach for quantifying water resources and water use for all land areas of the Earth that has served science and society since 1996. In this paper, the refinements, new algorithms and new data of the most recent model version v2.2e are described, together with a thorough evaluation of simulated water use, streamflow and total water storage anomaly against observation data. WaterGAP v2.2e improves the handling of inland sinks and now excludes not only large but also small man-made reservoirs when simulating naturalized conditions. The reservoir and non-irrigation water use data were updated. In addition, the model was calibrated against an updated and extended dataset of streamflow observations at 1509 gauging stations. The model can now be started using pre-scribed water storages and other conditions, which facilitates data assimilation as well as near real-time monitoring and forecast simulations. For specific applications, the model can consider the output of a glacier model, approximate the effect of rising CO2 concentrations on evapotranspiration or calculate the water temperature in rivers. In the paper, the publicly available standard model output is described and caveats of the model version are provided alongside the description of the model setup in the ISIMIP3 framework

α-Synuclein in human cerebrospinal fluid is principally derived from neurons of the central nervous system

The source of Parkinson disease-linked α-synuclein (aSyn) in human cerebrospinal fluid (CSF) remains unknown. We decided to measure the concentration of aSyn and its gradient in human CSF specimens and compared it with serum to explore its origin. We correlated aSyn concentrations in CSF versus serum (QaSyn) to the albumin quotient (Qalbumin) to evaluate its relation to blood–CSF barrier function. We also compared aSyn with several other CSF constituents of either central or peripheral sources (or both) including albumin, neuron-specific enolase, β-trace protein and total protein content. Finally, we examined whether aSyn is present within the structures of the choroid plexus (CP). We observed that QaSyn did not rise or fall with Qalbumin values, a relative measure of blood–CSF barrier integrity. In our CSF gradient analyses, aSyn levels decreased slightly from rostral to caudal fractions, in parallel to the recorded changes for neuron-specific enolase; the opposite trend was recorded for total protein, albumin and β-trace protein. The latter showed higher concentrations in caudal CSF fractions due to the diffusion-mediated transfer of proteins from blood and leptomeninges into CSF in the lower regions of the spine. In postmortem sections of human brain, we detected highly variable aSyn reactivity within the epithelial cell layer of CP in patients diagnosed with a range of neurological diseases; however, in sections of mice that express only human SNCA alleles (and in those without any Snca gene expression), we detected no aSyn signal in the epithelial cells of the CP. We conclude from these complementary results that despite its higher levels in peripheral blood products, neurons of the brain and spinal cord represent the principal source of aSyn in human CSF

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

A meta-analysis of psychological treatments and the efficacy of an internet-based self-help training.

Bei der Behandlung häufig auftretender Kopfschmerzen im Kindes- und Jugendalter finden zunehmend psychologische Therapieverfahren Anwendung, um so zum einen eine Linderung der Beschwerden und zum anderen langfristig eine Minderung des möglichen Chronifizierungsrisikos zu erreichen. Das Ziel der hier vorgelegten Arbeiten ist die Wirksamkeitsüberprüfung dieser psychologischen Interventionen sowie die Evaluierung eines ersten deutschsprachigen internet-basierten Selbsthilfetrainings zu Reduzierung häufiger Kopfschmerzen. Im ersten Kapitel wird eine kurze Einführung in epidemiologische Befunde bei Kopfschmerzen im Kindes- und Jugendalter gegeben sowie das Ziel der vorliegenden Arbeiten formuliert. Das zweite Kapitel gibt einen Überblick über bisherige Meta-Analysen zur Behandlung von Kopfschmerzen im Kindes- und Jugendalter und unterstreicht durch die Erläuterung inhaltlicher und methodischer Schwächen dieser Arbeiten die Notwendigkeit der hier vorgelegten, neuen Meta-Analyse (1.Manuskript), welche anschließend vorgestellt wird. Das dritte Kapitel gibt eine inhaltliche Einführung in eine neue, kosteneffektive Möglichkeit psychologischer Selbsthilfe via Internet. Es folgen die zwei Manuskripte (Manuskript 2 und 3) zur Evaluierung des internet-basierten Selbsthilfetrainings zur Reduzierung häufiger Kopfschmerzen bei Kindern und Jugendlichen. Die Arbeit schließt mit einer allgemeinen Diskussion in Kapitel 4 ab, in welcher die Befunde der vorgelegten Manuskripte kritisch besprochen und Empfehlungen für zukünftige Untersuchungen gegeben werden

Trash Goes To School

Series of solid waste lesson plans for grades K-12. http://cwmi.css.cornell.edu/TrashGoesToSchool/TrashIntro.htmlCornell Cooperative Extension, Cornell University's College of Agriculture and Life Sciences, New York State agencie

Moralische Verantwortung - Österreichische Experten über Vergangenheitsbewältigung

Diese Arbeit untersucht und analysiert die Meinungen von fünf österreichischen Experten zur österreichischen Vergangenheitsbewältigung. Die qualitativen Interviews wurden eingesetzt, um diese Meinungen zutage treten zu lassen. Das Ergebniskapitel zeigt, dass finanzielle Ent-schädigung, Kunst- und Vermögensrestitution und die moralische Verantwortung des öster-reichischen Staates die wichtigsten Faktoren dieser Arbeit sind. Vor allem die jungen Men-schen sollen in diesem Bereich gut ausgebildet und sensibilisiert werden, sei es im Unterricht, beim Besuch in der KZ-Gedenkstätte Mauthausen oder durch die Arbeit der Zivilgesellschaft. Die Erfahrungen werden auch in tagesaktuellen Themen benutzt, besonders in Fragen über Roma und Sinti in Österreich. Die Experten unterstreichen, dass die Ereignisse des Zweiten Weltkriegs sich nie wiederholen dürfen. Die Experten bestreiten nicht die späte Anfang der Vergangenheitsbewältigung, und weisen auf die Geschichte nach dem Zweiten Weltkrieg. Jetzt arbeiten viele Kräfte auf allen Ebenen der Gesellschaft zusammen für eine aktive Auseinandersetzung mit der eigenen Geschichte, um den Überlebenden und ihren Familien zu zeigen, dass sie nicht vergessen werden. Viele Menschen, und nicht nur Experten, haben Interesse an der eigenen Geschichte. Die österrei-chische Zivilgesellschaft zeigt, dass das Land höchstens braune Flecken hat, und, dass sie eine moralische Verantwortung trägt

WaterGAP v2.2e

<p>This version of the source code from the WaterGAP Global Hydrological Model (WGHM) is used in version v2.2e.</p&gt

Increased glucosylceramide production leads to decreased cell energy metabolism and lowered tumor marker expression in non-cancerous liver cells

Hepatocellular carcinoma (HCC) is one of the most difficult cancer types to treat. Liver cancer is often diagnosed at late stages and therapeutic treatment is frequently accompanied by development of multidrug resistance. This leads to poor outcomes for cancer patients. Understanding the fundamental molecular mechanisms leading to liver cancer development is crucial for developing new therapeutic approaches, which are more efficient in treating cancer. Mice with a liver specific UDP-glucose ceramide glucosyltransferase (UGCG) knockout (KO) show delayed diethylnitrosamine (DEN)-induced liver tumor growth. Accordingly, the rationale for our study was to determine whether UGCG overexpression is sufficient to drive cancer phenotypes in liver cells. We investigated the effect of UGCG overexpression (OE) on normal murine liver (NMuLi) cells. Increased UGCG expression results in decreased mitochondrial respiration and glycolysis, which is reversible by treatment with EtDO-P4, an UGCG inhibitor. Furthermore, tumor markers such as FGF21 and EPCAM are lowered following UGCG OE, which could be related to glucosylceramide (GlcCer) and lactosylceramide (LacCer) accumulation in glycosphingolipid-enriched microdomains (GEMs) and subsequently altered signaling protein phosphorylation. These cellular processes lead to decreased proliferation in NMuLi/UGCG OE cells. Our data show that increased UGCG expression itself does not induce pro-cancerous processes in normal liver cells, which indicates that increased GlcCer expression leads to different outcomes in different cancer types