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

Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination

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

Untersuchung von magnetische und strukturelle Eigenschaften von Fe und MnSi Dünnfilmen mittels Streumethoden

The first aim of this study was to investigate Fe/Cu(100) thin films using an in-situ sputtering system designed for PNR. With a Selene setup, we were able to monitor the growth of Fe films almost in real time. The second aim was to clarify the magnetic structure of MnSi(111) thin films in an in-plane magnetic field. Using GISANS and off-specular reflectometry combined with PNR, we found helices with wavevectors perpendicular to the surface and the helix length changing with increasing field.Das erste Ziel dieser Arbeit war es, Fe/Cu(100) Filme während des Wachstums mit einer in-situ Sputteranlage zu untersuchen, die für PNR ausgerichtet war. Mit einem Selene Aufbau war es uns möglich, das Wachstum von Fe fast in Echtzeit zu beobachten. Das zweite Ziel war es, magnetische Strukturen in MnSi(111) Filmen zu untersuchen. Mit GISANS und PNR und einem Magnetfeld in der Filmebene, haben wir gezeigt, dass der Helixvektor senkrecht zur Filmebene ist und mit steigendem Feld springt

Verkehrssicherheit von ausländischen Arbeitnehmern und ihren Familien

Im Mittelpunkt des Forschungsprojekts stand die Erarbeitung von Kontaktmöglichkeiten, Ansprachewegen und -formen für Verkehrssicherheitsmaßnahmen, die Ausländer tatsächlich erreichen. Hierzu wurden 18 Experteninterviews mit Vertretern von vier Nationalitäten und 18 Gruppendiskussionen mit Verkehrsteilnehmern aus der Türkei, Griechenland und Portugal durchgeführt. Dabei wurde seitens der Teilnehmer durchgängig die Schilderung der Straßenverkehrssituation im Herkunftsland als (negative) Folie für die Charakterisierung der entsprechenden (positiven) Situation in Deutschland verwendet. Vor diesem Hintergrund ist die bereits erfolgte Anpassungsleistung der Migranten an die deutsche Fahrkultur nicht gering zu schätzen und der bereits erreichte Grad der Integration ausländischer Verkehrsteilnehmer in den deutschen Straßenverkehr erscheint als durchaus beachtlich. Jedoch sollten weitere mögliche innovative Zugänge zum Zielpublikum Ausländer deshalb nicht ungenutzt gelassen werden. Widersprüche zwischen der objektiven Gefährlichkeit einer Situation im Straßenverkehr und der subjektiven Einschätzung durch die Diskussionsteilnehmer (zum Beispiel hinsichtlich der Kindersicherung) sowie die generell starke Orientierung des Verhaltens im Straßenverkehr an der subjektiv wahrgenommenen Entdeckungswahrscheinlichkeit bzw. der erwarteten Sanktionsschwere im Falle einer Regelübertretung kennzeichnen die Fahrkultur der interviewten Ausländer. Aufgrund von Sprachdefiziten, anderen Mediennutzungsgewohnheiten und lebensweltlichen Besonderheiten lässt sich das Fazit ziehen, dass ausländische Familien nach wie vor in gesonderter Form und im persönlichen Umfeld bzw. im Kreis der eigenen Ethnie, zum Beispiel in Ausländervereinen, angesprochen werden müssen. Hinsichtlich Form und Inhalt der Ansprache sind zielgruppenadäquate kulturell sensible Konzepte und muttersprachige Medien zu entwickeln. Diese sollten im Rahmen eines wissenschaftlich begleiteten Modellprojektes getestet werden. Der Originalbericht enthält als Anlagen Zusammenstellungen von Verkehrssicherheitsmaterialien aus der Türkei, aus Griechenland und aus Portugal sowie eine Liste von Fragestimuli für die Gruppendiskussionen. Auf die Wiedergabe dieser Anlagen wurde in dieser Veröffentlichung verzichtet.The main emphasis of the research project lay on the discovery of ways and means of contacting and addressing foreigners with regard to road safety matters which are actually effective. To this end, 18 expert interviews were carried out with representatives of four nationalities along with 18 group discussions with road traffic users from Turkey, Greece and Portugal. In the course of these all the participants used a description of the traffic situation in their country of origin as a (negative) foil for characterisation of the corresponding (positive) situation in Germany. Against this background, the way in which the migrants have already adapted to German driving culture should not be underestimated and the degree of integration of foreign road traffic users into the German traffic situation certainly seems to be considerable. However, this dös not mean that other possible and innovative means of access to the target group should be ignored. Contradictions between the objective danger of a road traffic situation and subjective assessment by participants in the discussion (for example with regard to the safety of children) as well as the generally strong orientation of behaviour in road traffic towards the subjective estimate of the likelihood of discovery or the expected seriousness of sanctions if traffic rules are infringed, are characteristic for the driving culture of the foreigners interviewed. Because of language deficits, different habits with regard to use of the media and other cultural differences, the conclusion can be drawn that foreign families still have to be addressed separately and within their own personal environment or within their own ethnic circle, for example in foreigners' clubs and associations. With regard to the form and content of what is communicated, culturally sensitive concepts which are suited to the target group as well as mother-tongü media should be developed. These should be tested within the framework of a model project implemented on a scientific basis and with scientific support. The original report contains compilations of road safety materials from Turkey, Greece and Portugal as well as a list of qüstion stimuli for the group discussions in the form of annexes. These annexes have not been reproduced in the present publication

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