ADCY5 gene expression in adipose tissue is related to obesity in men and mice

Genome wide association studies revealed an association of the single nucleotide polymorphism rs11708067 within the ADCY5 gene—encoding adenylate cyclase 5—with increased type 2 diabetes (T2D) risk and higher fasting glucose. However, it remains unclear whether the association between ADCY5 variants and glycemic traits may involve adipose tissue (AT) related mechanisms. We therefore tested the hypothesis that ADCY5 mRNA expression in human and mouse AT is related to obesity, fat distribution, T2D in humans and high fat diet (HFD) in mice. We measured ADCY5 mRNA expression in paired samples of visceral and subcutaneous adipose tissue from 244 individuals with a wide range of body weight and parameters of hyperglycemia, which have been genotyped for rs11708067. In addition, AT ADCY5 mRNA was assessed in C57BL/6NTac which underwent a 10 weeks standard chow (n = 6) or high fat diet (HFD, n = 6). In humans, visceral ADCY5 expression is significantly higher in obese compared to lean individuals. ADCY5 expression correlates with BMI, body fat mass, circulating leptin, fat distribution, waist and hip circumference, but not with fasting plasma glucose and HbA1c. Adcy5 expression in mouse AT is significantly higher after a HFD compared to chow (p<0.05). Importantly, rs11708067 is not associated with ADCY5 mRNA expression levels in either fat depot in any of the genetic models tested. Our results suggest that changes in AT ADCY5 expression are related to obesity and fat distribution, but not with impaired glucose metabolism and T2D. However, altered ADCY5 expression in AT does not seem to be the mechanism underlying the association between rs11708067 and increased T2D risk

Model reduction of nonlinear problems in structural mechanics

This contribution presents a model reduction method for nonlinear problems in structural mechanics. Emanating from a Finite Element model of the structure, a subspace and a lookup table are generated which do not require a linearisation of the equations. The method is applied to a model created with commercial FEM software. In this case, the terms describing geometrical and material nonlinearities are not explicitly known

Customer loads correlation in truck engineering

Safety and reliability requirements on the one side and short development cycles, low costs and lightweight design on the other side are two competing aspects of truck engineering. For safety critical components essentially no failures can be tolerated within the target mileage of a truck. For other components the goals are to stay below certain predefined failure rates. Reducing weight or cost of structures often also reduces strength and reliability. The requirements on the strength, however, strongly depend on the loads in actual customer usage. Without sufficient knowledge of these loads one needs large safety factors, limiting possible weight or cost reduction potentials. There are a lot of different quantities influencing the loads acting on the vehicle in actual usage. These ‘influencing quantities’ are, for example, the road quality, the driver, traffic conditions, the mission (long haulage, distribution or construction site), and the geographic region. Thus there is a need for statistical methods to model the load distribution with all its variability, which in turn can be used for the derivation of testing specifications

Nature and enactment of tasks for early English as a foreign language teaching (EFLT): a collaborative research project with teachers in Germany

Theoretical thesis.This thesis resulted from a co-tutelle arrangement with Justus Liebig-Universität Giessen.Bibliography: pages 293-325.1. Introduction -- 2. The research context and its influence on the overall research methodology -- 3. Task-as-workplan : focus on task concepts present in the literature -- 4. Task-as-workplan : focus on task concepts present in project members' teaching practice -- 5. Task-in-action : focus on task formats in grades 1-4 -- 6. Task-in-action : focus on the project teachers' enactments of tasks -- 7. The nature and enactment of EEFL tasks within the project setting -- 8. Task-in-reflection -- 9. Broadening the perspective on EEFL tasks.The ethnographic PhD case study is set within a collaborative research project in which teachers and researchers investigate early English as a foreign language (eEFL) tasks. Seven eEFL teachers from five project primary schools (PS) with students aged 6-10 years, in central urban Germany have been followed over a period of five years teaching eEFL in Grades 1-4 with a majority of Grade 4 classes. The research foci lie on: (i) the nature of eEFL tasks based on the academic conceptualisations of tasks and on the teachers' concepts of tasks to meaningfully integrate the theoretical and practical perspective; (ii) and on the teachers' task enactments that have been analysed with a multimodal and Mediated Discourse Analysis approach. The conceptualisation of the research focus poses the investigation of eEFL tasks at the centre of texts, accounts and discursive practices. This draws on the idea that social realities are constructed, insight is context-bound and views discourse as social action in which meaning is produced in interaction. Such an interdiscursive conceptualisation asks for an interdiscursive approach drawing on different data types (e.g., interviews, video recordings, observation protocols) being analysed with different methods. Results show that for eEFL tasks a strong emphasis on the students' personal interests may be beneficial to allow the young learners to experience English as a means of communication. It was found that the teachers used basic and elaborate task formats with a focus on role-plays, interviews, poster presentations or story reconstructions.Moreover, the results suggest that the often described difference between a task-as-workplan and task-as-action is also true for the eEFL classroom. Further, it can be assumed that eEFL tasks can emerge within a certain interplay of four key teaching practices of teachers:'doing school', 'providing space for learners to communicate', 'building a vocabulary' and 'teaching the spoken language'.Mode of access: World wide web1 online resource (xvi, 326 pages) illustrations (some colour

Ein neuer Ansatz zur Ermittlung von Erprobungslasten für sicherheitsrelevante Bauteile

Bei der Erprobung sicherheitsrelevanter Bauteile von Nutzfahrzeugen steht man vor der Aufgabe, die sehr vielfältige Belastung durch die Kunden abschätzen zu müssen und daraus ein Prüfprogramm für die Bauteile abzuleiten, das mehreren gegenläufigen Anforderungen gerecht werden muss: Das Programm muss scharf genug sein, damit bei erfolgreicher Prüfung ein Ausfall im Feld im Rahmen eines bestimmungsgemäßen Gebrauchs ausgeschlossen werden kann, es soll aber nicht zu einer Überdimensionierung der Bauteile führen, und es soll mit relativ wenigen Bauteilversuchen eine ausreichende Aussagesicherheit erreicht werden. Wegen der hohen Anforderungen bzgl. Sicherheit müssen bei der klassischen statistischen Vorgehensweise – Schätzen der Verteilung der Kundenbeanspruchung aus Messdaten, Schätzen der Verteilung der Bauteilfestigkeit aus Versuchsergebnissen und Ableiten einer Ausfallwahrscheinlichkeit – die Verteilungen in den extremen Rändern bekannt sein. Dazu reicht aber das Datenmaterial in der Regel bei weitem nicht aus. Bei der klassischen „empirischen“ Vorgehensweise werden Kennwerte der Beanspruchung und der Festigkeit verglichen und ein ausreichender Sicherheitsabstand gefordert. Das hier vorgeschlagene Verfahren kombiniert beide Methoden, setzt dabei die Möglichkeiten der statistischen Modellierung soweit aufgrund der Datenlage vertretbar ein und ergänzt die Ergebnisse durch empirisch begründete Sicherheitsfaktoren. Dabei werden bei der Lastfestlegung die im Versuch vorhandenen Möglichkeiten berücksichtigt. Hauptvorteile dieses Verfahrens sind a) die Transparenz bzgl. der mit statistischen Mitteln erreichbaren Aussagen und des Zusammenspiels zwischen Lastermittlung und Versuch und b) die Möglichkeit durch entsprechenden Aufwand bei Messungen und Erprobung die empirischen zugunsten der statistischen Anteile zu reduzieren

Model reduction of nonlinear problems in structural mechanics

This contribution presents a model reduction method for nonlinear problems in structural mechanics. Emanating from a Finite Element model of the structure, a subspace and a lookup table are generated which do not require a linearisation of the equations. The method is applied to a model created with commercial FEM software. In this case, the terms describing geometrical and material nonlinearities are not explicitly known

Effects of individual reactions to driving simulators on emergency braking reaction times

Driving simulators offer advantages in the study of braking reaction times (BRT). However, individuals react markedly different to simulators, be it in their vulnerability to Simulator Sickness (SS) or in their propensity to place themselves in the virtual environment (Spatial Presence; SP). This study investigated possible relationships between BRT and both SS and SP, obtained by using repeated online measures during four consecutive drives in a moving base driving simulator. Through mixed models analyses, it was established that SS was directly associated with BRT and that this effect was more pronounced during later drives, as well as during later BRT events within the same drive. No effect of SP on BRT could be shown