Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation

International audienceObjectives: Sepsis is defined as the host's inflammatory response to a lifethreatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macrolides can exert immunomodulation of endothelial cells (ECs) in an experimental model of sepsis. Methods: Human ECs were stimulated by proinflammatory cytokines and lipopolysaccharide before exposure to macrolides. ECs phenotypes were analyzed by flow cytometry. Cocultures of ECs and peripheral blood mononuclear cells (PBMCs) were performed to study the ECs ability to alter T-cell viability and differentiation in the presence of macrolides. Soluble factor production was assessed. Results: ECs act as non-professional antigen presenting cells and expressed human leukocyte antigen (HLA) antigens, the adhesion molecules CD54, CD106, and the coinhibitory molecule CD274 after septic stimulation. Incubation with macrolides induced a significant decrease of HLA class I and HLA class II HLA-DR on septic-stimulated ECs, but did not alter either CD54, CD106, nor CD274 expression. Interleukin-6 (IL-6) and IL-8 production by stimulated ECs were unaltered by incubation with macrolides, whereas Clarithromycin exposure significantly decreased IL-6 gene expression. In cocultures of septic ECs with PBMCs, neither the proportion of CD4 + , CD8 + T nor their viability was altered by macrolides. T-helper lymphocyte subsets Th1, Th17, and Treg polarization by stimulated ECs were unaltered by macrolides. Conclusion: This study reports phenotypic and gene expression changes in septic-stimulated ECs exposed to macrolides, without resulting in altered immunogenicity of ECs in co-cultures with PBMCs. In vivo studies may help This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Enhanced quality using intensive test and analysis on simulators

Conference of 18th Euromicro Conference on Digital System Design, DSD 2015 ; Conference Date: 26 August 2015 Through 28 August 2015; Conference Code:117072International audienceEmbedded systems are becoming ubiquitous and are subject to demanding standards in both safety and reliability. Modern vehicles, which must respect ISO 26262 standards, use up to 100 Electronic Control Unit (ECUs). Advances in microelectronics enable integration of more functions in the ECU, but at the cost of greater unreliability in hostile operating environments, such as electromagnetic fields, temperature, and humidity. Their software mainly drives embedded system flexibility and smartness. However due to lack of automation, its validation and verification (V&V) takes place throughout the design process and tends to swallow up 40% to 50% of the total development cost. The 'Enhanced Quality Using Intensive Test Analysis on Simulators' (EQUITAS) project intends to limit the impact of software V&V on embedded systems cost and time-To-market while improving reliability and functional safety. Project activities include: development of a continuous tool-chain to automate the V&V process of embedded computers, improving the relevance of the test campaigns by detecting the redundant tests using equivalence classes, providing assistance for hardware failure effect analysis (FMEA), and finally assessing the tool-chain under the ISO 26262 requirements

EQUITAS: A tool-chain for functional safety and reliability improvement in automotive systems

International audienceTo support advanced features such as hybrid engine control, intelligent energy management, and advanced driver assistance systems, automotive embedded systems must use advanced technologies. As a result, systems are becoming distributed and include dozens of Electronic Control Units (ECU). On the one hand, this tendency raises the issue of robustness and reliability, due to the increase in the error ratio with the integration level and the clock frequency. On the other hand, due to a lack of automation, software Validation and Verification (V&V) tends to swallow up 40% to 50% of the total development cost. The ``Enhanced Quality Using Intensive Test Analysis on Simulators'' (EQUITAS1) project aims (1) to improve reliability and functional safety and (2) to limit the impact of software V&V on embedded systems costs and time-to-market. These two achievements are obtained by (1) developing a continuous tool-chain to automate the V&V process, (2) improving the relevance of the test campaigns by detecting redundant tests using equivalence classes, (3) providing assistance for hardware failure effect analysis (FMEA) and finally (4) assessing the tool-chain under the ISO 26262 requirements