Why are mineralocorticoid receptor antagonists cardioprotective?

Two clinical trials, the Randomized ALdosterone Evaluation Study (RALES) and the EPlerenone HEart failure and SUrvival Study (EPHESUS), have recently shown that mineralocorticoid receptor (MR) antagonists reduce mortality in patients with heart failure on top of ACE inhibition. This effect could not be attributed solely to blockade of the renal MR-mediated effects on blood pressure, and it has therefore been proposed that aldosterone, the endogenous MR agonist, also acts extrarenally, in particular in the heart. Indeed, MR are present in cardiac tissue, and possibly aldosterone synthesis occurs in the heart. This review critically addresses the following questions: (1) is aldosterone synthesized at cardiac tissue sites, (2) what agonist stimulates cardiac MR normally, and (3) what effects are mediated by aldosterone/MR in the heart that could explain the beneficial effects of MR blockade in heart failure? Conclusions are that most, if not all, of cardiac aldosterone originates in the circulation (i.e., is of adrenal origin), and that glucocorticoids, in addition to aldosterone, may serve as the endogenous agonist of cardiac MR. MR-mediated effects in the heart include effects on endothelial function, cardiac fibrosis and hypertrophy, oxidative stress, cardiac inotropy, coronary flow, and arrhythmias. Some of these effects occur via or in synergy with angiotensin II, and involve a non-MR-mediated mechanism. This raises the possibility that aldosterone synthase inhibitors might exert beneficial effects on top of MR blockade

Significant Reduction of Validation Efforts for Dynamic Light Functions with FMI for Multi-Domain Integration and Test Platform

Modern advanced driver assistance systems (ADAS) provide a significant increase in comfort and safety. In many cases, a single vehicle, today, contains more than one assistance system, while the trend to use ADAS continues to grow. At the same time, the number of systems that perform control interventions with safety-relevant functions increases as well. From an overall perspective, it must be assured that the driver assistance systems – individually as well as in the way they interact – function flawlessly in any driving situation and with any driver at the wheel anywhere in the world. This results in an increased development and testing effort for modern ADAS in general. In-development testing based on virtual test driving offers an approach to a solution that allows the validation effort to be significantly reduced while meeting the requirements for safetyrelevant functions in the vehicle associated with ISO 26262. This is particularly evident when developing and testing new light functions, which in real-world road tests can often be performed only in conditions of darkness. Dynamic Light Functions are defined as the situation-dependent headlight adjustment consisting of cornering light, headlight leveling and (glare-free) headlight assistance. This paper presents this new methodology

Langfaserverstaerkte Magnesiumwerkstoffe Abschlussbericht

The increase in efficiency of lifting piston engines and the simultaneous reduction of emission are important development targets of the car industry. One possibility for this is to reduce the weight of the moving parts. An improvement in the acoustic behaviour of the engine is connected with this. The aim of the project was to realise a magnesium piston reinforced with fibres, which has the same properties as an aluminium piston with a considerably reduced weight. The research project contains the development of matrix and reinforcement materials with favourable costs and the further development of manufacturing processes for compound materials. Basic investigations, such as heat treatment and the effects on the fibre/matrix interface were also part of the investigations. At BMW AG, apart from the investigation of the basis of infiltration mechanisms in alternative casting processes, the piston design and the testing of engine components were the main part of the investigations. With the aid of the basic investigations, the infiltration phenomena in the production of magnesium reinforced with fibres can be characterised. The results can be transferred to other infiltration processes, for example to pressure casting. The results of characterisation of the material and the component testing show that magnesium material reinforced with fibres can be used for the application as piston material for the temperatures occurring in the engine. The weight of the piston can therefore be reduced by about 30% compared with a standard aluminium pistonWesentliche Entwicklungsziele der Automobilindustrie sind die Effizienzsteigerung von Hubkolbenmotoren und die gleichzeitige Reduzierung von Emissionen. Eine Moeglichkeit hierzu ist, das Gewicht der bewegten Bauteile zu vermindern. Damit verbunden ist eine Verbesserung des akustischen Verhaltens des Motors. Ziel des Projektes war die Realisierung eines faserverstaerkten Magnesiumkolbens, der die gleichen Eigenschaften wie ein Aluminiumkolben bei deutlich reduziertem Gewicht aufweist. Das Forschungsprojekt beinhaltet die Entwicklung kostenguenstiger Matrix- und Verstaerkungswerkstoffe und die Weiterentwicklung von Herstellungsverfahren fuer Verbundwerkstoffe. Grundlagenuntersuchungen wie z.B. Waermebehandlung und die Auswirkungen auf die Faser/Matrix-Grenzflaeche waren ebenfalls Bestandteil der Untersuchungen. Bei der BMW AG waren neben der Untersuchung von Grundlagen der Infiltrationsmechanismen bei alternativen Giessverfahren, die Kolbenauslegung und die motorische Bauteilerprobung Schwerpunkt der Untersuchungen. Mit Hilfe der Grundlagenuntersuchungen konnten die Infiltrationsphaenome bei der Herstellung von faserverstaerktem Magnesium charakterisiert werden. Die Ergebnisse lassen sich auf andere Infiltrationsverfahren, wie z.B. das Pressgiessen, uebertragen. Die Ergebnisse der Werkstoffcharakterisierung und der Bauteilerprobung zeigen, dass faserverstaerkte Magnesiumwerkstoffe fuer die Anwendung als Kolbenwerkstoff auch bei den im Motor auftretenden Temperaturen einsetzbar sind. Das Gewicht des Kolbens kann dadurch um ca. 30% im Vergleich zu einem Serien-Aluminiumkolben reduziert werden. (orig.)Available from TIB Hannover: F98B1084 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Trockenbearbeitung - Realisierungsphase. Teilprojekt 1: Trockenbearbeitung beim Gewindeformen und Reiben in Alu-Gusslegierungen Schlussbericht

Available from TIB Hannover: DtF QN1(68,3) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

KORSYS. Korrekte Software fuer sicherheitskritische Systeme Abschlussbericht

SIGLEAvailable from TIB Hannover: DtF QN1(67,19) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Ball Grid Array Gehaeusetechnologie fuer Multi Chip Module (BGA-MCM). Teilprojekt: Solder-BGAs fuer den KFZ-Einsatz Abschlussbericht

Available from TIB Hannover: F00B1318 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany); DLR Deutsches Zentrum fuer Luft- und Raumfahrt e.V., Bonn (Germany)DEGerman

Wissensbasierte Unterstuetzung von Wartungs- und Reparaturtaetigkeiten in Kfz-Werkstaetten (WIBUR) Abschlussbericht

Available from TIB Hannover: F97B645+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

PEM 6 integrierte Produkt- und Prozess-Modelle. Themengebiet: Methoden und Tools zur Prozesserfassung, -analyse und -bewertung sowie Anforderungen

Available from TIB Hannover: F96B1143+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman