Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Pultrudierte Profile für Verkehr und Transport: Vortrag gehalten auf dem Interdisziplinären Fahrzeugkolloquium, 05.12.2018, Dresden

Unter dem Leitthema „Ressourceneffiziente Produktion“ beschäftigt sich das Fraunhofer-Institut für Werkzeugmaschinen und Umformtechnik IWU mit einer Vielzahl an Arbeits- und Produktionsprozessen. Dabei spielt unter anderem das Thema Leichtbau eine bedeutende Rolle, um die zukünftigen Herausforderungen zu meistern. Das langjährig aufgebaute Know-how in diesem Bereich umfasst eine Vielzahl an Leichtbauwerkstoffen und -technologien. Ein Kernthema ist dabei das wirtschaftliche Pultrusionsverfahren zur Herstellung endlosfaserverstärkter Kunststoffprofile. Mit einer Investition in eine eigene serientaugliche Pultrusionsanlage hat das Fraunhofer IWU im Jahre 2016 die Fertigungstechnologien im Faserverbundbereich stark erweitert. Das Verfahren wurde bereits vor ca. 60 Jahren entwickelt und findet heute vor allem in der Halbzeugherstellung für verschiedenste Branchen Anwendung. In einer Verfahrensweiterentwicklung ist es Thomas GmbH + Co. Technik + Innovation KG gelungen, in einem modifizierten Prozess konstant gekrümmte Profile unterschiedlicher Radius Dimensionen herzustellen und so die Anwendungsbereiche des Verfahrens zu erweitern. Gemeinsam mit weiteren Partnern aus der Industrie und Forschung zielt das Fraunhofer IWU auf eine weitere Flexibilisierung des Pultrusionsprozesses ab. Zur Umsetzung dieser Ziele und Erweiterung der Anwendungsfelder des Pultrusionsverfahrens haben sich starke Partner aus der Industrie und Forschung zu einem Netzwerk zusammengeschlossen. Das Netzwerk PulNet deckt dabei die komplette Wertschöpfungskette ab, um gemeinsame Entwicklungen im Bereich der Pultrusion voranzutreiben. Bei einem der Netzwerkpartner handelt es sich um das in Haselünne ansässige Unternehmen Techno-Composites Domine GmbH. Als Systemlieferant für GFK-basierte Bauteile kann das inhabergeführte Unternehmen auf eine knapp 25-jährige Erfolgsgeschichte zurückblicken und darf namhafte Partner wie zum Beispiel Bombardier, Siemens oder auch MAN zu seinen Kunden zählen. Auf einer Gesamtfläche von ca. 20.000 m² werden komplexe Bauteile für Schienenfahrzeuge und Busse sowohl entwickelt als auch gefertigt. Dabei beginnt der Wertschöpfungsprozess bereits mit der Idee und der konstruktiven Umsetzung der kundenspezifischen Lösungen. Für die fertigungstechnische Umsetzung greift das Unternehmen anschließend zum Großteil auf pultrudierte Strukturen aus dem Hause Exel Composites, einem der größten Pultrudeure weltweit, zurück. Die notwendige Konfektionierung dieser Profile erfolgt auf mehreren CNC Maschinen bevor die Montage der einzelnen Komponenten zum fertigen Bauteil führt. Hauptanwendungsbereiche liegen in der Außen- und Innenverkleidung für den Transportsektor sowie dem Chemieanlagenbau

Acceleration technique for Milankovitch type forcing in a coupled atmosphere-ocean circulation model: method and application for the Holocene

A method is introduced which allows the calculation of long-term climate trends within the framework of a coupled atmosphere-ocean circulation model. The change in the seasonal cycle of incident solar radiation induced by varying orbital parameters has been accelerated by factors of 10 and 100 in order to allow transient simulations over the period from the mid-Holocene until today, covering the last 7000 years. In contrast to conventional time-slice experiments, this approach is not restricted to equilibrium simulations and is capable to utilise all available data for validation. We find that opposing Holocene climate trends in tropics and extra-tropics are a robust feature in our experiments. Results from the transient simulations of the mid-Holocene climate at 6000 years before present show considerable differences to atmosphere-alone model simulations, in particular at high latitudes, attributed to atmosphere-ocean-sea ice effects. The simulations were extended for the time period 1800 to 2000 AD, where, in contrast to the Holocene climate, increased concentrations of greenhouse gases in the atmosphere provide for the strongest driving mechanism. The experiments reveal that a Northern Hemisphere cooling trend over the Holocene is completely cancelled by the warming trend during the last century, which brings the recent global warming into a long-term context

Estimating trends of Atlantic meridional overturning circulation from long-term hydrographic data and model simulations

The ocean meridional overturning circulation (MOC) plays a central role for the climate in the Atlantic realm. Since scenarios for future climate change indicate a significant reduction of the MOC under global warming, an assessment of variations and trends of the real MOC is important. Using observations at ocean weather ship (OWS) stations and along oceanic sections, we examine the hydrographic information that can be used to determine MOC trends via its signature in water mass properties obtained from model simulations with the climate model ECHAM5/MPI-OM. We show that temperature trends at mid-latitudes provide useful indirect measure of large-scale changes of deep circulation: A mid-depth warming is related to MOC weakening and a cooling to MOC strengthening. Based on our model experiments, we argue that a continuation of measurements at key OWS sites may contribute to a timely detection of a possible future MOC slowdown and to separate the signal from interannual-to-multidecadal MOC variability. The simulations suggest that the subsurface hydrographic information related to MOC has a lower variability than the MOC trend measured directly. Based on our model and the available long-term hydrographic data, we estimate non-significant MOC trends for the last 80 years. For the twenty-first century, however, the model simulations predict a significant MOC decline and accompanied mid-depth warming trend

Estimating the harms and costs of cannabis-attributable collisions in the Canadian provinces

Introduction: In 2012, 10% of Canadians used cannabis and just under half of those who use cannabis were estimated to have driven under the influence of cannabis. Substantial evidence has accumulated to indicate that driving after cannabis use increases collision risk significantly; however, little is known about the extent and costs associated with cannabis-related traffic collisions. This study quantifies the costs of cannabis-related traffic collisions in the Canadian provinces. Methods: Province and age specific cannabis-attributable fractions (CAFs) were calculated for traffic collisions of varying severity. The CAFs were applied to traffic collision data in order to estimate the total number of persons involved in cannabis-attributable fatal, injury and property damage only collisions. Social cost values, based on willingness-to-pay and direct costs, were applied to estimate the costs associated with cannabis-related traffic collisions. The 95% confidence intervals were calculated using Monte Carlo methodology. Results: Cannabis-attributable traffic collisions were estimated to have caused 75 deaths (95% CI: 0–213), 4407 injuries (95% CI: 20–11,549) and 7794 people (95% CI: 3107–13,086) were involved in property damage only collisions in Canada in 2012, totalling $1,094,972,062 (95% CI: 37,069,392–2,934,108,175) with costs being highest among younger people. Discussion: The cannabis-attributable driving harms and costs are substantial. The harm and cost of cannabis-related collisions is an important factor to consider as Canada looks to legalize and regulate the sale of cannabis. This analysis provides evidence to help inform Canadian policy to reduce the human and economic costs of drug-impaired driving.Medicine, Faculty ofNon UBCEmergency Medicine, Department ofReviewedFacultyResearche

An implantable two channel drop foot stimulator: initial clinical results

This article reports preliminary results of pilot studies of a new implantable two channel drop foot stimulator. The stimulator consists of an externally worn transmitter inductively coupled to an implanted receiver unit located in the lower leg, lateral and distal to the knee. The receiver is connected to electrodes located under the epineurium of the deep and the superficial peroneal nerves. Stimulation is triggered by detection of heel lift and terminated at heel strike in a manner similar to surface mounted systems. The location of the electrodes allows for a degree of selectivity over the resultant moment about the ankle joint that is not possible with surface stimulation of the common peroneal nerve. The two subjects used the stimulator on a regular basis and showed increases in walking speed of between 10% and 44% when compared to their baseline measurements. Isometric tests have demonstrated that the stimulator allows selective and repeatable stimulation of ankle joint muscles. Keywords: Drop foot; Implant; Functional electrical stimulation; Stroke patient

Das Europäische Parlament

In einem jahrzehntelangen Prozess hat sich das Europäische Parlament von einer beratenden Einrichtung zu einem Mitgestalter europäischer Politik entwickelt. Heute besitzt es sowohl innerhalb der Union als auch als globaler Akteur politisches Gewicht. Diese Erfolgsgeschichte wird von den europäischen Bürgerinnen und Bürgern nur beschränkt wahrgenommen, wie die geringe Beteiligung an den Wahlen zum Europäischen Parlament zeigt. Das vorliegende Buch beantwortet zentrale Fragen: Wie funktioniert diese demokratisch legitimierte Institution? Was bedeutet ihr Machtzuwachs konkret? Welche weiteren Entwicklungen können erwartet werden?In May 2014 the 8th European elections take place. 751 Members of Parliament form 28 different countries are directly elected for a five-year term form an electorate of 383 Mio citizens. The European Parliament is a dynamic, truly supranational and since Lisbon a more and more powerful actor. It negotiates on eye-level with the Council of Ministers, holds the European Commission effectively accountable, represents the aggregated interests, ideas and concerns of the Union's citizens, and supervises the development of the EU together with the national parliaments. As a global player the European Parliament deals with members of parliaments of third countries, negotiates international agreements and watches over the protection of human rights and democracy. The authors - MEPs, officials, stakeholders and experts - gibe a deep practical and academic insight into all functions of the European Parliament. The different articles take into account the specific conditions of the EU's only directly legitimized institution. For academics and practitioners alike, Dialer, Neisser and Lichtenberger offer a superb "guide" for any serious understanding of the world's only elected transnational parliament