MOHICAN: human-machine performance monitoring through trust and collaboration analysis. – Towards smarter design of a virtual assistant and real time optimization of machine behavior

Evaluation of the performance of Human-Machine Teaming brings two substantial values to military effectiveness: (1) enhancing the design quality of cognitive aircraft systems, (2) synchronizing the behavior of the virtual assistant with the cockpit needs during fights. This paper presents “MOHICAN”, a system-of-systems approach for monitoring the performance of Human-Machine Teaming in combat aircraft cockpits. MOHICAN will include a method, its tools, and a model addressing a multirole aircraft. Those principles developed for the cockpit may be extended to more complex systems of systems by expanding measure criteria, and by integrating collective teaming contribution to global performance of the system as a whole (e.g., military air operations)

Nouvelles modalités d'interaction pour des opérateurs de maintenance en milieu contraint : Contribution d'une approche conjointe FH et IHM dans le contexte d'un projet multipartenaire

RESUME Dans un monde où la continuité de service est impérative, la qualité et la rapidité des interventions en maintenance deviennent des éléments clés. Pour conserver leur compétitivité, les industriels recherchent activement des solutions pour améliorer l'efficacité et la productivité des opérations de maintenance tout en préservant un très haut niveau de sécurité. L'objectif du projet est de permettre à un opérateur de maintenance, sur des terminaux mobiles de type smartphone, tablette, casque ou lunette, de disposer d'une information parfaitement contextualisée à la situation opérationnelle dans laquelle il se trouve (visualiser sur des documents, notices ou des schémas techniques, interagir avec un expert distant, se connecter à un système d'information…). Cette étude à orientation prospective propose, à partir d'une approche ergonomique centrée sur les usages (observations in situ, entretiens semi-dirigés, analyse cognitivo-discursive-ACD-, caractérisation des besoins), d'identifier un panel de nouvelles technologies d'interaction répondant aux besoins des opérateurs, aux exigences industrielles et pouvant s'adapter à des environnements opérationnels contraints.As service continuity is compelling for companies in order to satisfy their customers, maintenance quality and efficiency has become key points in the industry. To maintain their competitiveness, industrial companies strive to improve the efficiency and productivity of maintenance operations while keeping a very high level of safety. By equipping maintenance operators with a smartphone or tablet and smartglasses, the project aims at giving the right contextualized information. So that operators can better comprehend the context in which they work (e.g. for visualizing documents, notices or technical diagrams, interacting with a remote expert, connecting to an information system...) The prospective study presented is based on an ergonomic approach and user-centered approach (observations, interviews, cognitive-discursive analysis-CDA-and need characterization). It identifies a panel of new interaction technologies that best respond to operators' expectations and industrial requirements and still being able to adapt to complex and diverse environments

Une exposition à de faibles doses d'alkylphénols entraine des altérations de épithélium mammaires et des défauts transgénérationnels mais n'augmente pas le potentiel tumorigénique des cellules cancéreuses mammaires

International audienceFetal and neonatal exposure to long chain alkylphenols has been suspected to promote breast developmental disorders and consequently to increase breast cancer risk. However, disease predisposition from developmental exposures remains unclear. In this work, human MCF-10A mammary epithelial cells were exposed in vitro to a low dose of a realistic [4-nonylphenol+4-tert-octylphenol] mixture. Transcriptome and cell phenotype analyses combined to functional and signaling network modeling indicated that long chain alkylphenols triggered enhanced proliferation, migration ability and apoptosis resistance and shed light on the underlying molecular mechanisms which involved the human estrogen receptor variant ERα36. A male mouse inherited transgenerational model of exposure to 3 environmentally relevant doses of the alkylphenol mix was set up in order to determine whether and how it would impact on mammary gland architecture. Mammary glands from F3 progeny obtained after intrabuccal chronic exposure of C57BL/6J P0 pregnant mice followed by F1 to F3 male inheritance displayed an altered histology which correlated with the phenotypes observed in vitro in human mammary epithelial cells. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant, such consequences of alkylphenol exposure could be extrapolated from mouse model to human. However, transient alkylphenol treatment combined to ERα36 overexpression in mammary epithelial cells were not sufficient to trigger tumorigenesis in xenografted Nude mice. Therefore, it remains to be determined if low dose alkylphenol transgenerational exposure and subsequent abnormal mammary gland development could account for an increased breast cancer susceptibility

Transgenerational effects of ERalpha36 over-expression on mammary gland development and molecular phenotype: clinical perspective for breast cancer risk and therapy.

International audienceGrowing source of evidence suggests that exposure to estrogen mimicking agents is a risk factor for breast cancer onset and progression. Long chain alkylphenols are man made compounds still present in household products, industrial and agricultural processes, leading to a global environmental and human contamination. These molecules are known to exert estrogen -like activities through binding to classical estrogen receptors. Recently, we have demonstrated that a realistic mixture of 4 tert - octylphenol and 4 - nonylphenol can stimulate proliferation and modulate epigenetic status of testicular cancer germ cells through a rapid, Estrogen Receptor alpha 36 (ERα36) -dependent non genomic pathway (Ajj et al, 2013; doi: 10.1371/journal.pone.0061758). In a retrospective study of breast tumor samples, we also validated ERα36 expression as a reliable prognostic factor for cancer progression from an estrogen dependent prolifera tive tumor toward an estrogen dispensable metastatic disease (Chamard - Jovenin et al, 2015; doi: 10.1186/s12918 - 015 - 0178 - 7). Since high ERα36 expression enhances expression of migration/invasion markers in breast tumors, we addressed the question of its involvement in response to alkylphenol exposure in vitro (MCF -10A mammary epithelial cell line and MCF -7 estrogen -sensitive cancer cells) and in vivo ( C57BL mice). A male inherited transgenerational model of exposure to environmentally relevant doses of an alkylphenol mix was set up in C57BL/6J mice to determine whether and how it impacts on mammary gland morphogenesis. Human mammary epithelial MCF -10A cells were exposed to similar doses to decipher the molecular mechanisms involved by a combination of transcriptomic study, cell phenotype analyses, functional and signaling network modeling. The relevance of mouse phenotype extrapolation to human risk is discussed. Mouse mammary gland exposed transgenerationally to the alkylphenol mix displayed a neoplastic -like histology. This phenotype was correlated with the enhanced proliferation, migration ability and apoptosis resistance observed in vitro on human mammary epithelial cells and mediated by the estrogen receptor variant ERα36. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant , such consequences of alkylphenol exposure could be extrapolated from mouse model to human. Low dose alkylphenol transgenerational exposure could promote abnormal mammary gland development and subsequently increase the risk of breast cancer at ageing

Streptococcus pyogenes Cas9 ribonucleoprotein delivery for efficient, rapid and marker-free gene editing in Trypanosoma and Leishmania

Kinetoplastids are unicellular eukaryotic flagellated parasites found in a wide range of hosts within the animal and plant kingdoms. They are known to be responsible in humans for African sleeping sickness ( Trypanosoma brucei ), Chagas disease ( Trypanosoma cruzi ), and various forms of leishmaniasis ( Leishmania spp.), as well as several animal diseases with important economic impact (African trypanosomes, including T. congolense ). Understanding the biology of these parasites necessarily implies the ability to manipulate their genomes. In this study, we demonstrate that transfection of a ribonucleoprotein complex, composed of recombinant Streptococcus pyogenes Cas9 ( Sp Cas9) and an in vitro -synthesized guide RNA, results in rapid and efficient genetic modifications of trypanosomatids, in marker-free conditions. This approach was successfully developed to inactivate, delete and mutate candidate genes in various stages of the life cycle of T. brucei and T. congolense , and Leishmania promastigotes. The functionality of Sp Cas9 in these parasites now provides, to the research community working on these parasites, a rapid and efficient method of genome editing, without requiring plasmid construction and selection by antibiotics. Importantly, this approach is adaptable to any wild-type parasite, including field isolates

Étude d’une mitofusine atypique impliquée dans la dynamique mitochondriale chez Trypanosoma brucei

African trypanosomes are unicellular parasites responsible for African sleeping sickness as well as the related cattle disease Nagana. During the trypanosome life cycle, the parasite exists in at least two replicative forms; the procyclic form, found in the tsetse fly Glossina spp., and the bloodstream form found in the vertebrate host. Unlike most other eukaryotes that contain numerous mitochondria, the pathogenic trypanosomes have a single one, which exists in at least two major forms: (i) the fully active and developed one characteristic for the procyclic stage that harbors the oxidative phosphorylation complexes (OXPHOS) for energy production and (ii) the functionally and morphologically repressed form found in the bloodstream stage with energy produced exclusively through glycolysis. The shape and functional plasticity of their single mitochondrion undergoes spectacular changes, reflecting adaptation to different environments, alternating between the proline-rich haemolymph and tissue fluids of the blood-feeding tsetse fly and the glucose-rich blood of a mammalian host. Dynamic remodelling of the organelle suggests that trypanosomes possess fusion and fission machineries.The objective of my thesis was to identify and characterize a protein that may be involved in mitochondrial dynamics. We characterized an atypical mitofusin, TbMfnL (Tb927.7.2410), involved in mitochondrial membrane remodeling. TbMfnL shows similarities with the two dynamins involved in mitochondrial membrane fusion in mammalian cells (Mfn/Opa1) and more particularly with Mfn which is involved in mitochondrial outer membrane fusion. Using fluorescence microscopy and electron microscopy techniques, we were able to show that TbMfnL is localized in mitochondrial membranes. Overexpression of the TbMfnL protein in the procyclic forms leads to an important modification of the mitochondrial structure with a strong increase of the mitochondrial branches leading to a hyperfusion phenotype. Inactivation of the protein did not reveal any structural modification, in agreement with the low level of mitochondrial fission processes observed in this parasite. We were also able to demonstrate that TbMfnL has a functional GTPase domain, characterizing it as a dynamin family protein. In-depth analysis of the protein domains has revealed the importance of an N-terminal mitochondria targeting sequence (MTS), not found in HsMfn, which is essential for the proper localization and function of the protein. In addition to the MTS domain, the two transmembrane domains identified in the protein also play an important role in the localization of TbMfnL. We have also shown that overexpression of TbMfnL stimulates lipid biogenesis resulting in a strong increase in cell, nucleus and mitochondria volumes. Finally, we searched for potential partners of the TbMfnL protein by BioID, and identified a dozen potential candidates. All these data allowed the characterization of the first protein involved in mitochondrial fusion in T. brucei: TbMfnL.Les trypanosomes africains sont des parasites unicellulaires responsables de la trypanosomiase humaine africaine ou maladie du sommeil chez l’Homme, et de la trypanosomiase animale africaine ou Nagana chez le bétail. Au cours de son cycle de vie, le trypanosome se présente sous au moins deux formes réplicatives ; la forme procyclique, retrouvée dans l’insecte vecteur (la mouche tsétsé) et la forme sanguine retrouvée dans l’hôte mammifère. Contrairement à la plupart des autres eucaryotes qui possèdent de nombreuses mitochondries, Trypanosoma brucei, n’en possède qu’une seule, qui existe sous deux formes principales : (i) une forme pleinement active et développée caractéristique de la forme procyclique qui possède les complexes de la chaîne respiratoire et utilisant la phosphorylation oxydative pour la production d’énergie et (ii) une forme fonctionnellement et morphologiquement réprimée que l’on retrouve dans la forme sanguine où l’énergie est produite exclusivement par la glycolyse. Cette unique mitochondrie subit des changements morphologiques drastiques qui reflètent l’adaptation à différents environnements, alternant entre l’hémolymphe et les fluides tissulaires riches en proline de la mouche tsétsé et le sang riche en glucose de l’hôte mammifère. Ce remodelage dynamique de la mitochondrie suggère que les trypanosomes possèdent des mécanismes permettant la fusion et la fission de la mitochondrie.L’objectif de ma thèse a été d’identifier et de caractériser une protéine pouvant être impliquée dans la dynamique mitochondriale. Nous avons ainsi caractérisé une mitofusine atypique, TbMfnL (Tb927.7.2410), impliquée dans le remodelage des membranes mitochondriales. TbMfnL présente des similitudes avec les deux dynamines impliquées dans la fusion des membranes mitochondriales chez les cellules de mammifère (Mfn/Opa1) et plus particulièrement avec Mfn qui est la protéine impliquée dans la fusion de la membrane externe de la mitochondrie. Grâce à l’utilisation de techniques de microscopie à fluorescence et de microscopie électronique, nous avons pu montrer que TbMfnL est localisée dans les membranes mitochondriales. La surexpression de la protéine TbMfnL dans les formes procycliques entraine une importante modification de la structure mitochondriale avec une forte augmentation des branchements mitochondriaux aboutissant à un phénotype d’hyperfusion. L’inactivation de la protéine n’a pas révélé de modification de structure, en accord avec le faible niveau des processus de fission mitochondriale observé chez ce parasite. Nous avons également pu démontrer que TbMfnL possède un domaine GTPase fonctionnel, la caractérisant comme une protéine de la famille des dynamines. L’analyse approfondie des domaines de la protéine a permis de mettre en évidence l’importance d’une séquence d’adressage à la mitochondrie (MTS) en N-terminal, non retrouvée chez HsMfn, qui est essentielle à la bonne localisation et à la fonction de la protéine. En plus du domaine MTS, les deux domaines transmembranaires identifiés dans la protéine jouent également un rôle important dans la localisation de TbMfnL. Nous avons également montré, lors de la surexpression de TbMfnL, une stimulation de la biogenèse lipidique qui se traduit par une forte augmentation du volume de la cellule, du noyau et de la mitochondrie. Enfin, nous avons recherché de potentiels partenaires de la protéine TbMfnL par BioID, et avons identifié une douzaine de candidats potentiels. L’ensemble de ces données a permis la caractérisation de la première protéine impliquée dans la fusion mitochondriale chez T. brucei : TbMfnL

Fiscal welfare : le rôle des niches socio-fiscales dans la protection sociale en Europe

Le recours aux dispositifs fiscaux dérogatoires est un élément structurant des politiques sociales, à la fois d’un point de vue institutionnel, économique et politique. Or cet aspect, largement étudié dans le cas des États-Unis, constitue un point aveugle de l’analyse comparée de l’État social. Nous dressons un état des connaissances théoriques et empiriques sur le fiscal welfare en Europe et nous analysons les raisons spécifiques au contexte européen du recours aux dépenses fiscales de protection sociale

A Bismarckian Type of Fiscal Welfare? Insights on the Use of Social Tax Expenditures in French Social and Employment Policy

International audienceThis article argues that situated approaches are necessary to reveal institu-tion-specific or regime specific structures, forms and uses of fiscal welfare instruments. We base our analysis on the French case, for which we have previously built an exhaustive database of social tax expenditures (STEs) for the year 2014. We find that France displays a specific structure of fiscal welfare. Most STEs are concentrated in the fields of employment, family and health policy; most STEs concern social security contributions. We identify specific forms of fiscal welfare which might be common to other Bismarckian countries, principally centred around three types of use, i) the reduced taxation of family and couples, which is a core element of the fami-lialist organisation of social policy after WWII ; ii) the use of STEs as a privileged instrument of employment policy in the constrained realm of minima wages and high levels of social security contributions ; iii) the use of STEs to quietly divert resources away from the sheltered social security funds and into collective private insurance plans, fuelling their develop-ment

Fiscal welfare in Europe: a state of the art

Since the 1990s, welfare state reform has been at the core of much of the welfare state research. From an analysis of reform pressures, to an understanding of welfare state resilience, to a focus on reform trajectories, the literature has highlighted the role of politics, of institutions and of ideas in understanding processes and trajectories of reform. This paper aims to contribute to the literature on welfare state reform through a different angle, by analysing reform processes through the development of specific policy instruments, namely tax expenditures for social purposes (hereafter called social tax expenditures, or STEs), which has remained a blind spot in much of the welfare state literature

Fiscal welfare : le rôle des niches socio-fiscales dans la protection sociale en Europe

International audienc