Modularity And Associated Tools As A Mean To Master Quality Of Complex Embedded Systems

International audienceIn line with its focus on quality, RENAULT has settled a special action plan to answer the burst of complexity of engine management systems : EMS 2010. It will allow us a very high mastery of complex systems’ development with limited efforts in term of development time or development costs. This will enabled us to concentrate our forces on the benefits for our customers. Its development has been supported by our main engine management systems’ suppliers and especially the CONTINENTAL company. The basic feature of EMS 2010 is a modular architecture. This architecture is answering functional and dysfunctional requirements, and takes into accounts the constraints of embedded real time applications. The main objective is to answer all our vehicle line-up technical definitions with a limited number of versions of standardized modules. These modules have a standardized interface and adapt themselves to several parameters thanks to a particular mechanism. The second objective is to have standard modules of code that can be re-used on all our engine management electronic control units (ECU). The modules are hardware independent, thanks to specific coding rules, and are “plugged” on the basic software of ECU. The key element is our shelf that records our modules, and all the data linked to their development and their validation, allowing a high level of mastery in their development. The basis of the shelf, is a configuration management tool ; it manages the different versions of the modules but also their automatic adaptation to vehicle and engine technical definition. It supports also the development processes of our modules and is structured according to our architecture

Lieb-Robinson Bounds for Harmonic and Anharmonic Lattice Systems

We prove Lieb-Robinson bounds for the dynamics of systems with an infinite dimensional Hilbert space and generated by unbounded Hamiltonians. In particular, we consider quantum harmonic and certain anharmonic lattice systems

Lieb-Robinson Bounds for the Toda Lattice

We establish locality estimates, known as Lieb-Robinson bounds, for the Toda lattice. In contrast to harmonic models, the Lieb-Robinson velocity for these systems do depend on the initial condition. Our results also apply to the entire Toda as well as the Kac-van Moerbeke hierarchy. Under suitable assumptions, our methods also yield a finite velocity for certain perturbations of these systems

PDK4 drives metabolic alterations and muscle atrophy in cancer cachexia

Cachexia is frequently accompanied by severe metabolic derangements, although the mechanisms responsible for this debilitating condition remain unclear. Pyruvate dehydrogenase kinase (PDK)4, a critical regulator of cellular energetic metabolism, was found elevated in experimental models of cancer, starvation, diabetes, and sepsis. Here we aimed to investigate the link between PDK4 and the changes in muscle size in cancer cachexia. High PDK4 and abnormal energetic metabolism were found in the skeletal muscle of colon-26 tumor hosts, as well as in mice fed a diet enriched in Pirinixic acid, previously shown to increase PDK4 levels. Viral-mediated PDK4 overexpression in myotube cultures was sufficient to promote myofiber shrinkage, consistent with enhanced protein catabolism and mitochondrial abnormalities. On the contrary, blockade of PDK4 was sufficient to restore myotube size in C2C12 cultures exposed to tumor media. Our data support, for the first time, a direct role for PDK4 in promoting cancer-associated muscle metabolic alterations and skeletal muscle atrophy

Increased Adiposity, Dysregulated Glucose Metabolism and Systemic Inflammation in Galectin-3 KO Mice

PMCID: PMC3579848This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Who was buried with Nestor’s Cup? Macroscopic and microscopic analyses of the cremated remains from Tomb 168 (second half of the 8th century BCE, Pithekoussai, Ischia Island, Italy)

Cremation 168 from the second half of the 8th century BCE (Pithekoussai’s necropolis, Ischia Island, Italy), better known as the Tomb of Nestor’s Cup, is widely considered as one of the most intriguing discoveries in the Mediterranean Pre-Classic archaeology. A drinking cup, from which the Tomb’s name derives, bears one of the earliest surviving examples of written Greek, representing the oldest Homeric poetry ever recovered. According to previous osteological analyses, the Cup is associated with the cremated remains of a juvenile, aged approximately 10–14 years at death. Since then, a vast body of literature has attempted to explain the unique association between the exceptionality of the grave good complex, the symposiac and erotic evocation of the Nestor’s Cup inscription with the young age of the individual buried with it. This paper reconsiders previous assessments of the remains by combining gross morphology with qualitative histology and histomorphometric analyses of the burnt bone fragments. This work reveals the commingled nature of the bone assemblage, identifying for the first time, more than one human individual mixed with faunal remains. These outcomes dramatically change previous reconstructions of the cremation deposit, rewriting the answer to the question: who was buried with Nestor’s Cup

Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction

Objective: Pulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features of metabolic syndrome. The stable prostacyclin analog, treprostinil, is an effective and widely used Food and Drug Administration-approved drug for the treatment of pulmonary arterial hypertension. While the effect of treprostinil on metabolic syndrome is unknown, a recent study suggests that the prostacyclin analog beraprost can improve glucose intolerance and insulin sensitivity. We sought to evaluate the effectiveness of treprostinil in the treatment of metabolic syndrome-associated PH-HFpEF. Approach and Results: Treprostinil treatment was given to mice with mild metabolic syndrome-associated PH-HFpEF induced by high-fat diet and to SU5416/obese ZSF1 rats, a model created by the treatment of rats with a more profound metabolic syndrome due to double leptin receptor defect (obese ZSF1) with a vascular endothelial growth factor receptor blocker SU5416. In high-fat diet-exposed mice, chronic treatment with treprostinil reduced hyperglycemia and pulmonary hypertension. In SU5416/Obese ZSF1 rats, treprostinil improved hyperglycemia with similar efficacy to that of metformin (a first-line drug for type 2 diabetes mellitus); the glucose-lowering effect of treprostinil was further potentiated by the combined treatment with metformin. Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle. Conclusions: Our data suggest a potential use of treprostinil as an early treatment for mild metabolic syndrome-associated PH-HFpEF and that combined treatment with treprostinil and metformin may improve hyperglycemia and cardiac function in a more severe disease

Le gène PIG-A, nouveau marqueur de mutagenèse: Preuves de concept et exposé de la technique

International audienceGene mutations are not directly detected by current genotoxicity assays and most of them need a cell culture step. The whole blood PIG-A assay consists in the detection of the mutation frequency within the PIG-A sentinel gene by identification of glycosyl-phosphatidyl-inositol (GPI-) deficient cells. PIG-A mutated/GPI-deficient cells can be detected by flow cytometry as they no longer express surface fluorescence for GPI-linked markers. The last researches have focused on cell enrichment techniques leading to increased throughput and sensitivity. The results of this new and promising biomarker of mutagenesis, performed in humans or rodents, are now available within 2 hours after blood collection.Les tests de mutagenèse actuels ne permettent pas la détection directe des mutations géniques chez l’homme et nécessitent souvent une étape préalable de culture cellulaire. Le test PIG-A sur sang total est fondé sur la mesure de la fréquence de mutation du gène sentinelle PIG-A par la révélation par cytométrie en flux de cellules circulantes déficientes en ancre GPI (glycosyl-phosphatidyl-inositol). Il consiste à identifier les cellules mutées pour le gène PIG-A après marquage des cellules par des fluorochromes spécifiques de l’ancre GPI ou des protéines qui lui sont associées. Les dernières avancées ont permis d’améliorer la sensibilité et le débit d’analyse. Les résultats de ce biomarqueur d’effet nouveau et prometteur, réalisable chez l’homme ou le rongeur, sont désormais disponibles en moins de deux heures après le prélèvement

From Explicit to Implicit Theories of Creativity and Back: The Relevance of Naive Criteria in Defining Creativity

International audienc