Motifs formels d'architectures de systèmes pour la sûreté de fonctionnement

This thesis aimed at providing methods to assist modelling and assessing qualitatively embedded complex systems safety architectures. These architectures are often based on generic systems architectures models corresponding to safety mechanisms such as redundancies, detections, etc. While taking as a starting point the principles of the design pattern approach used in the software community, we proposed a modeling of these mechanisms and attributes allowing their re-use during safety assessments. These analyses require to reason on the behavior of systems in the presence of failures which can be modelled using formal languages like AltaRica. In our case, patterns are corresponding to concrete architectures' abstractions and so require a more declarative modelling, using properties. Those properties being generally dynamic, we chose a temporal logic to model them. Safety patterns are therefore made of an AltaRica part and a property part. We believe this kind of mixed modelling to be of great interest, especially in the preliminary system architecture design phase where it is necessary to deal with detailed parts of systems as well as specifications. It should also ease the allocation of requirements and prototyping. A notation mixing operational and declarative views has been defined.Cette thèse propose des méthodes assistant la modélisation et l'évaluation qualitative de l'architecture de sûreté de fonctionnement des systèmes embarqués complexes. Ces architectures sont souvent construites à partir de motifs généraux d'architectures de systèmes correspondant à des mécanismes de sûreté récurrents comme des redondances, des détections, etc. En s'inspirant des principes des "patrons de conception" développés en génie logiciel, nous avons proposé une modélisation de ces mécanismes et des attributs permettant leur réutilisation lors des analyses de sûreté de fonctionnement. Ces analyses nécessitent de raisonner sur le comportement des systèmes en présence de pannes qui peut être modélisé à l'aide de langages formels comme AltaRica. Dans notre cas, les motifs correspondent à des abstractions d'architectures concrètes et donc requièrent une modélisation plus déclarative. Les propriétés étudiées étant en général dynamiques, nous avons choisi d'utiliser une logique temporelle pour les exprimer. Les motifs sont donc constitués d'une partie AltaRica et d'une partie propriétés. Ce type de modélisation mixte possède plusieurs intérêts, notamment lors de la conception en phase amont d'architectures de systèmes où il est possible de manipuler à la fois des parties d'un système conçues de manière détaillée et des spécifications. Elle a également pour buts de faciliter l'allocation d'exigences pour la validation d'architectures ainsi que le prototypage. Nous avons donc défini une notation mixant ces aspects opérationnels et déclaratifs

Safety Assessment with Altarica - Lessons Learnt Based on Two Aircraft System Studies

Abstract: AIRBUS and ONERA used the AltaRica formal language and associated tools to perform safety assessments. Lessons learnt during the study of an electrical and hydraulic system are presented. Key words: dependability, aircraft, formal methods AIRBUS and ONERA were recently involved in the ESACS (Enhanced Safety Assessment for Complex Systems) European project. This project aimed at developing safety assessment techniques based on the use of formal specification languages and associated tools. We used the AltaRica (Arnold et al. 2000) formal language that is supported by Cecilia OCAS workshop developed by Dassault Aviation. Two case-studies based on AIRBUS aircraft electrical and hydraulic systems were used to validate the approach (Kehren et al. 2004b). In this paper we present lessons we learnt during ESACS. Lessons are sorted in three categories: Advantages are situations where the use of AltaRica was clearly positive, Difficulties are situations where the use of AltaRica was not directly positive but we found out how to circumvent the difficulties and the remaining situations are considered to be Limitations

Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo.

The nature of dendritic cell(s) (DC[s]) that conditions efficient in vivo priming of CD8+ CTL after immunization via epithelial tissues remains largely unknown. Here, we show that myeloid DCs rapidly recruited by adjuvants into the buccal mucosa or skin are essential for CD8+ T cell crosspriming. Recruitment of circulating DC precursors, including Gr1+ monocytes, precedes the sequential accumulation of CD11c+ MHC class II+ DCs in dermis and epithelium via a CCR6/CCL20-dependent mechanism. Remarkably, a defect in CCR6, local neutralization of CCL20, or depletion of monocytes prevents in vivo priming of CD8+ CTL against an innocuous protein antigen administered with adjuvant. In addition, transfer of CCR6-sufficient Gr1+ monocytes restores CD8+ T cell priming in CCR6( degrees / degrees ) mice via a direct Ag presentation mechanism. Thus, newly recruited DCs likely derived from circulating monocytes are responsible for efficient crosspriming of CD8+ CTL after mucosal or skin immunization

Publisher Correction: LifeTime and improving European healthcare through cell-based interceptive medicine (Nature, (2020), 587, 7834, (377-386), 10.1038/s41586-020-2715-9)

10.1038/s41586-021-03287-8Nature592785

LifeTime and improving European healthcare through cell-based interceptive medicine

AUTEURS : LifeTime Community Working GroupsInternational audienceHere we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade