Design and realization of a sputter deposition system for the \textit{in situ-} and \textit{in operando-}use in polarized neutron reflectometry experiments

We report on the realization of a sputter deposition system for the in situ- and in operando-use in polarized neutron reflectometry experiments. Starting with the scientific requirements, which define the general design considerations, the external limitations and boundaries imposed by the available space at a neutron beamline and by the neutron and vacuum compatibility of the used materials, are assessed. The relevant aspects are then accounted for in the realization of our highly mobile deposition system, which was designed with a focus on a quick and simple installation and removability at the beamline. Apart from the general design, the in-vacuum components, the auxiliary equipment and the remote control via a computer, as well as relevant safety aspects are presented in detail.Comment: Submitted for publication in Nuclear Inst. and Methods in Physics Research, A. (1st revised version

Structural Basis of Membrane Protein Chaperoning through the Mitochondrial Intermembrane Space

International audienceThe exchange of metabolites between the mitochon- drial matrix and the cytosol depends on b-barrel channels in the outer membrane and a-helical carrier proteins in the inner membrane. The essential trans- locase of the inner membrane (TIM) chaperones escort these proteins through the intermembrane space, but the structural and mechanistic details remain elusive. We have used an integrated struc- tural biology approach to reveal the functional princi- ple of TIM chaperones. Multiple clamp-like binding sites hold the mitochondrial membrane proteins in a translocation-competent elongated form, thus mimicking characteristics of co-translational mem- brane insertion. The bound preprotein undergoes conformational dynamics within the chaperone bind- ing clefts, pointing to a multitude of dynamic local binding events. Mutations in these binding sites cause cell death or growth defects associated with impairment of carrier and b-barrel protein biogen- esis. Our work reveals how a single mitochondrial ‘‘transfer-chaperone’’ system is able to guide a-heli- cal and b-barrel membrane proteins in a ‘‘nascent chain-like’’ conformation through a ribosome-free compartment

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Schlussbericht - Energetische Querschnittserhebung deutscher Theaterspielstätten und Monitoring Scharoun Theater Wolfsburg mit Schwerpunkt Komfortuntersuchung

Die Bundesregierung hat sich verpflichtet, die Treibhausgasemissionen in den nächsten Jahren stark zu senken. Potentiale hierfür werden besonders im Gebäudesektor gesehen, da dieser einen hohen Anteil des Endenergieverbrauchs verursacht. Bisher lagen für den Gebäudetypus der „Theaterspielstätte“ im Gegensatz zu anderen Gebäudetypologien weder energetische Kennwerte noch Daten zum Raumkomfort vor. Im Rahmen einer deutschlandweiten Querschnittserhebung in 13 Theaterspielstätten über den Zeitraum von drei Wochen wurden sowohl Energieverbräuche mittels zerstörungsfrei installierter Messsensoren als auch Daten zum Raumkomfort durch den Einsatz eines Messtorsos auf Nutzerebene sowie einer parallelen Nutzerbefragung erfasst, ausgewertet und analysiert. Anhand dieser Daten wurden charakteristische Kennwerte gebildet und ein Benchmarking erstellt. Darüber hinaus konnte der Energieverbrauch mittels TEK-Tool rechnerisch auf Nutzungszonen und Gewerke verteilt werden, sodass ein Verständnis für die Struktur des Energieverbrauchs in Theaterspielstätten entwickelt wurde, auf Basis dessen die Abschätzung energetischer Einsparpotentiale möglich ist. Außerdem wurde durch ein einjähriges Intensivmonitoring im sanierten Scharoun Theater Wolfsburg exemplarisch das Einsparpotential durch Gebäudesanierungen und Anlagenoptimierungen von Theaterspielstätten messtechnisch erforscht. Die gemessenen Daten wurden dem Energieverbrauch vor der Sanierung sowie den Sanierungszielen gegenübergestellt und ebenso gegenüber den Kennwerten aus der Querschnittserhebung eingeordnet. Die Erkenntnisse über die Nutzungs- und Energieverbrauchsstruktur in Theaterspielstätten können zukünftig angewendet werden, um Energieverbräuche rechnerisch besser ermitteln zu können und um Ansatzpunkte zur Reduzierung des Energieverbrauchs zu identifizieren

Development and characterization of anti-icing surfaces: a new analytical approach

Some general Information is given about the DLR, DLR’s research topics in the field of wind turbines, an overview of the DLR’s and IAF’s research topics referring to de- and anti-icing Topic. Within the presentation it will be focused on characterization of ice-adhesion for evaluation of coatings and materials. Therefore a Motivation is given and the state of the art methods for ice-adhesion characterization is presented. The methodological approach for characterization of the DLR and IAF is presented which core part is a centrifuge test-facility. Standardized ice geometries as well as ice geometries generated within the icing wind tunnel are tested and evaluated. As result a multi-scale test methodology needed to be developed

Gene duplication and transposition of mobile elements drive evolution of the Rpv3 resistance locus in grapevine

A wild grape haplotype (Rpv3-1) confers resistance to Plasmopara viticola. We mapped the causal factor for resistance to an interval containing a TIR-NB-LRR (TNL) gene pair that originated 1.6-2.6 million years ago by a tandem segmental duplication. Transient coexpression of the TNL pair in Vitis vinifera leaves activated pathogen-induced necrosis and reduced sporulation compared to control leaves. Even though transcripts of the TNL pair from the wild haplotype appear to be partially subject to nonsense-mediated mRNA decay, mature mRNA levels in a homozygous resistant genotype were individually higher than the mRNA trace levels observed for the orthologous single-copy TNL in sensitive genotypes. Allelic expression imbalance in a resistant heterozygote confirmed that cis-acting regulatory variation promotes expression in the wild haplotype. The movement of transposable elements had a major impact on the generation of haplotype diversity, altering the DNA context around similar TNL coding sequences and the CG content in their proximal 5' intergenic regions. The wild and domesticated haplotypes also diverged in conserved single-copy intergenic DNA, but the highest divergence was observed in intraspecific and not in interspecific comparisons. In this case, introgression breeding did not transgress the genetic boundaries of the domesticated species, because haplotypes present in modern varieties sometimes predate speciation events between wild and cultivated species