Model Driven Engineering and Dependability Analyses: The Topcased Approach

International audienceModel Driven Engineering approaches are widely promoted to overcome difficulties to design, validate and maintain large complex systems. They present interesting dependability characteristics especially in terms of prevention of design faults and validation of design correctness. However industrial needs, practices and applicable standards impose constraints on the dependability activities to perform and justify. Therefore it is necessary to analyze how a complete dependability and safety process can be integrated with model-driven approaches within a seamless global process: which dependability activities are naturally covered or facilitated by model-driven approaches, and which additional activities are needed with which support. This paper presents the results of a study aiming at the establishment of requirements to model-driven engineering methods and tools, to support dependability analyses

Integration of formal fault analysis in ASSERT: Case studies and lessons learnt

International audienceThe ASSERT European Integrated Project (Automated proof-based System and Software Engineering for Real-Time systems; EC FP6, IST-004033) has investigated, elaborated and experimented advanced methods based on the AltaRica language and support tool OCAS for architecture and fault approach propagation description analysis, and integrated in the complete ASSERT process. The paper describes lessons learnt from three case studies: safety critical spacecraft, autonomous deep exploration spacecraft, and civil aircraft

Cisplatin in combination with Phenethyl Isothiocyanate (PEITC), a potential new therapeutic strategy for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a very aggressive form of cancer with a poor diagnosis and prognosis. The first line treatment for MPM is a combination of cisplatin and Pemetrexed, which displayed limited efficacy and severe side effects. The naturally occurring compound phenethyl isothiocyanate (PEITC) previously showed interesting anti-tumor properties on several cancer cell lines. We thus aim at evaluating PEITC used alone or in combination with cisplatin in order to improve MPM treatment. Nine MPM cell lines and primary mesothelial cells (PMC), co-cultured or not with M2 macrophages present in MPM microenvironment, were used to assess PEITC and cisplatin anti-tumor properties. Compounds were used alone or in combination. Both PEITC and cisplatin were cytotoxic on MPM cells in a dose dependent manner. We herein showed that PEITC-induced cytotoxicity was due to the generation of reactive oxygen species. Moreover, we showed that cisplatin-PEITC combination allowed the potentialization of both compounds’ cytotoxic effects and prevented the emergence of resistant MPM cells. Interestingly, PMC were not sensitive to the combination. Finally, we showed that M2 macrophages did not alter the anti-tumor properties of the combination. Cisplatin-PEITC combination thus represents a promising strategy to induce a selective toxicity towards malignant cells.Iza Denis, Laurent Cellerin, Marc Gregoire and Christophe Blanquar

Characterization of proton irradiated 3D-DDTC pixel sensor prototypes fabricated at FBK

In this paper we discuss results relevant to 3D Double-Side Double Type Column (3D-DDTC) pixel sensors fabricated at FBK (Trento, Italy) and oriented to the ATLAS upgrade. Some assemblies of these sensors featuring different columnar electrode configurations (2, 3, or 4 columns per pixel) and coupled to the ATLAS FEI3 read-out chip were irradiated up to large proton fluences and tested in laboratory with radioactive sources. In spite of the non optimized columnar electrode overlap, sensors exhibit reasonably good charge collection properties up to an irradiation fluence of 2 x 10**15 neq/cm2, while requiring bias voltages in the order of 100 V. Sensor operation is further investigated by means of TCAD simulations which can effectively explain the basic mechanisms responsible for charge loss after irradiation.Comment: Preprint submitted to Nuclear Instruments and Methods A, 11 pages, 13 fig

Unresolved orthology and peculiar coding sequence properties of lamprey genes: the KCNA gene family as test case

Background:In understanding the evolutionary process of vertebrates, cyclostomes (hagfishes and lamprey) occupy crucial positions. Resolving molecular phylogenetic relationships of cyclostome genes with gnathostomes (jawed vertebrates) genes is indispensable in deciphering both the species tree and gene trees. However, molecular phylogenetic analyses, especially those including lamprey genes, have produced highly discordant results between gene families. To efficiently scrutinize this problem using partial genome assemblies of early vertebrates, we focused on the potassium voltage-gated channel, shaker-related (KCNA) family, whose members are mostly single-exon.Results:Seven sea lamprey KCNA genes as well as six elephant shark genes were identified, and their orthologies to bony vertebrate subgroups were assessed. In contrast to robustly supported orthology of the elephant shark genes to gnathostome subgroups, clear orthology of any sea lamprey gene could not be established. Notably, sea lamprey KCNA sequences displayed unique codon usage pattern and amino acid composition, probably associated with exceptionally high GC-content in their coding regions. This lamprey-specific property of coding sequences was also observed generally for genes outside this gene family.Conclusions:Our results suggest that secondary modifications of sequence properties unique to the lamprey lineage may be one of the factors preventing robust orthology assessments of lamprey genes, which deserves further genome-wide validation. The lamprey lineage-specific alteration of protein-coding sequence properties needs to be taken into consideration in tackling the key questions about early vertebrate evolution

Androgen signaling negatively controls group 2 innate lymphoid cells

Prevalence of asthma is higher in women than in men, but the mechanisms underlying this sex bias are unknown. Group 2 innate lymphoid cells (ILC2s) are key regulators of type 2 inflammatory responses. Here, we show that ILC2 development is greatly influenced by male sex hormones. Male mice have reduced numbers of ILC2 progenitors (ILC2Ps) and mature ILC2s in peripheral tissues compared with females. In consequence, males exhibit reduced susceptibility to allergic airway inflammation in response to environmental allergens and less severe IL-33-driven lung inflammation, correlating with an impaired expansion of lung ILC2s. Importantly, orchiectomy, but not ovariectomy, abolishes the sex differences in ILC2 development and restores IL-33-mediated lung inflammation. ILC2Ps express the androgen receptor (AR), and AR signaling inhibits their differentiation into mature ILC2s. Finally, we show that hematopoietic AR expression limits IL-33-driven lung inflammation through a cell-intrinsic inhibition of ILC2 expansion. Thus, androgens play a crucial protective role in type 2 airway inflammation by negatively regulating ILC2 homeostasis, thereby limiting their capacity to expand locally in response to IL-33.PMC546100