Interface tactile pour la saisie de règles dans un système expert flou

International audienceDans de nombreux logiciels d'intelligence artificielle, comme par exemple les systèmes experts, il est nécessaire qu'un utilisateur saisisse des connaissances sous différentes formes. En particulier, dans les systèmes experts flous, il s'agit de règles de la forme SI...ALORS... manipulant des concepts linguistiques plutôt que des opérateurs mathématiques. Nous présentons dans cet article une interface graphique moderne permettant la saisie des règles dans un système expert flou s'appuyant sur l'usage naturel du glisser-déposer sur des surfaces tactiles comme des tablettes

A configuration space of homologous proteins conserving mutual information and allowing a phylogeny inference based on pair-wise Z-score probabilities

BACKGROUND: Popular methods to reconstruct molecular phylogenies are based on multiple sequence alignments, in which addition or removal of data may change the resulting tree topology. We have sought a representation of homologous proteins that would conserve the information of pair-wise sequence alignments, respect probabilistic properties of Z-scores (Monte Carlo methods applied to pair-wise comparisons) and be the basis for a novel method of consistent and stable phylogenetic reconstruction. RESULTS: We have built up a spatial representation of protein sequences using concepts from particle physics (configuration space) and respecting a frame of constraints deduced from pair-wise alignment score properties in information theory. The obtained configuration space of homologous proteins (CSHP) allows the representation of real and shuffled sequences, and thereupon an expression of the TULIP theorem for Z-score probabilities. Based on the CSHP, we propose a phylogeny reconstruction using Z-scores. Deduced trees, called TULIP trees, are consistent with multiple-alignment based trees. Furthermore, the TULIP tree reconstruction method provides a solution for some previously reported incongruent results, such as the apicomplexan enolase phylogeny. CONCLUSION: The CSHP is a unified model that conserves mutual information between proteins in the way physical models conserve energy. Applications include the reconstruction of evolutionary consistent and robust trees, the topology of which is based on a spatial representation that is not reordered after addition or removal of sequences. The CSHP and its assigned phylogenetic topology, provide a powerful and easily updated representation for massive pair-wise genome comparisons based on Z-score computations

Régression linéaire généralisée PLS

Presentation of the PLS regressionPLS regression; general linear modeling; Cox model

Traitement de la maladie du greffon contre l’hôte chronique par la photophérèse extra corporelle au TH9402 : m écanisme de régulation de la maladie du greffon contre l’hôte chronique par les cellules T régulatrices

La maladie du greffon contre l’hôte (GVHD) est la principale cause de mortalité et de morbidité suite aux greffes de cellules souches hématopoïétiques. Plusieurs patients demeurent réfractaires aux traitements actuels ce qui rend nécessaire le développement de nouvelles stratégies afin de combattre cette maladie. Dans l’étude qui suit, nous avons utilisé un nouvel agent thérapeutique, le TH9402, une molécule photosensible et démontré qu’elle permet, lorsqu’exposée à la lumière visible (514 nm), d’éliminer sélectivement les cellules T activées in vivo tout en préservant les cellules T au repos et les cellules T régulatrices (Tregs). Les Tregs ainsi préservés peuvent abroger la réponse alloréactive par la sécrétion d’IL-10 ou par contact cellule-cellule via un mécanisme impliquant le CTLA-4. Nous avons découvert que la signalisation du CTLA-4 était associée à une hausse de la population Treg in vitro. Cette hausse est due à la conversion de cellules T CD4+CD25- en Tregs et non à une prolifération sélective des Tregs. Dans la deuxième partie de cette étude, nous avons démontré que la signalisation de CTLA-4 était associée à une augmentation de l’expression de la protéine Indoleamine 2,3 dioxygenase (IDO). Ces effets nécessitent la déplétion du tryptophane ainsi que de la protéine de phase aigue GCN2. Finalement, nous avons observé que l’infusion de cellules traitées au TH9402 chez des patients souffrant de GVHD chronique est associée à une augmentation de la population Treg chez ces patients sans causer de lymphopénie ni de diminution de la réponse immunitaire dirigée contre les antigènes viraux. Ces résultats suggèrent que le traitement au TH9402 pourrait représenter une approche particulièrement intéressante pour le traitement de la GVHD chronique réfractaire aux traitements actuels. De plus, l’augmentation de l’expression d’IDO pourrait être utilisée comme valeur prédictive de la réponse du patient au traitement. Ceci pourrait permettre d’améliorer la qualité de soins ainsi que de la qualité de vie des patients souffrant de GVHD chronique.Graft versus host disease (GVHD) is the primary cause of mortality and morbidity following hematopoietic stem cell transplantation. Many patients remain refractory to current treatments, emphasizing the need to develop new therapeutic strategies. In the present study, we have used a novel therapeutic agent, TH9402, and shown that once activated by visible light (514 nm), this photosensitizer becomes specifically cytotoxic toward activated T cells while preserving resting T cells and regulatory T cells (Tregs). Preserved Tregs can display anti GVHD activity through IL-10 and CTLA-4 dependent mechanisms. Furthermore, CTLA-4 signaling was associated with an increased Treg population. This increase resulted from FOXP3 induction in CD4+CD25- cells and not selective proliferation of Tregs. In the second part of this study, we showed that CTLA-4 signaling was associated with enhanced expression of indoleamine 2,3 dioxygenase (IDO). The expression of IDO results in the generation of anti GVHD activity and an increase in the Treg population following TH9402 treatment. This increased Treg population was mediated by tryptophan degradation and implied acute phase protein GCN2 activity. Finally, we show that the infusion of TH9402 treated cells in patients suffering from chronic GVHD resulted in an increase of the Treg population as early as 8 weeks after treatment initiation without causing lymphopenia or hyporesponsiveness toward viral antigens. Furthermore, the increase of IDO corresponded to patient response to treatment. These results suggest that TH9402 represents a most interesting therapeutic approach for patients with refractory chronic GVHD. IDO expression could also be used to predict patient responsiveness to the treatment. This could increase the quality of the treatment as well as the quality of life of patients suffering from refractory chronic GVHD

L'état de nature dans le Léviathan de Thomas Hobbes et la controverse entourant son utilisation dans les analyses des relations internationales

L'état de nature de Thomas Hobbes repose sur une étude des limites de la connaissance de l'être humain. Ces limites sont considérables, si bien qu'il est selon Hobbes impossible pour le genre humain de naturellement instaurer un système de vérité commun à l'espèce. L'homme est à l'état de nature dans une situation que nous qualifions « d'anarchie épistémologique » ce qui se traduit dans le Léviathan de Hobbes comme étant une situation de guerre de chacun contre chacun. Ce n'est que par l'institution d'un souverain tout puissant que l'homme peut espérer dépasser la condition de misère qui caractérise sa situation à l'état de nature. Le projet philosophique et politique de Hobbes concerne donc essentiellement l'être humain dans sa situation politique domestique. Hobbes ne consacre effectivement rien de substantiel à l'analyse des relations internationales. Pourtant, le nom de Thomas Hobbes revient souvent à ce niveau d'analyse, particulièrement lorsqu'il s'agit de conceptualiser les rapports interétatiques comme étant analogues à ceux des hommes à l'état de nature. Cette transposition est à notre avis problématique plutôt que constructive puisqu'elle ne reflète en rien les analyses du philosophe. Nous proposons de démontrer ce point par le biais d'une étude exégétique de la pensée de Hobbes.Hobbes's state of nature rests upon an epistemological study of human nature. It reflects important limits on the human capacity for establishing objective truths. In the state of nature then, mankind will never be able to naturally and collectively institute an epistemological system. Mankind is in the state of nature in a situation that we qualify as an '' epistemological anarchy '', which in Hobbes's Leviathan is a situation of war of all against all. It is only through the institution of a all-powerful sovereign that man can hope to free himself from the dire situation of the state of nature. Hobbes's philosophical and political project then, concerns only human activity on a domestic scale. Indeed, the english philosopher does not provide substantial analytical material concerning international relations. However, the name of Thomas Hobbes is a common one in discussions of international relations, specially when the conceptualisation of interstate relations is understood as being analogous to that of man in the state of nature. We consider that this analogy is not constructive, but problematic since it does not reflect Hobbes's analyses at all. We will show that this is the case through an exegetic study of Hobbes's arguments concerning human nature

Learning at a distance : Student guide, Express 2020

Ressources éducatives libresOpen educational resourcesAbstract : As a result of the exceptional situation brought about by the coronavirus pandemic, universities wishing to continue to fulfil their educational mission have had to act quickly. Distance education has emerged as the main alternative to face-to-face instruction, allowing students to continue studying in their program under better conditions than would have been the case under other potential alternatives.Everyone on the virtual starting line! -- Key terms in distance learning -- 1. Technological tools and DL -- 2. What a DL course looks like? -- 3. Conditions for successful DL

Spatiotemporal and cross-scale interactions in hydroclimate variability:a case-study in France

International audienceUnderstanding how water resources vary in response to climate at different temporal and spatial scales is crucial to inform long-term management. Climate change impacts and induced trends may indeed be substantially modulated by low-frequency (multi-year) variations, whose strength varies in time and space, with large consequences for risk forecasting systems. In this study, we present a spatial classification of precipitation, temperature, and discharge variability in France, based on a fuzzy clustering and wavelet spectra of 152 near-natural watersheds between 1958 and 2008. We also explore phase–phase and phase–amplitude causal interactions between timescales of each homogeneous region. A total of three significant timescales of variability are found in precipitation, temperature, and discharge, i.e., 1, 2–4, and 5–8 years. The magnitude of these timescales of variability is, however, not constant over the different regions. For instance, southern regions are markedly different from other regions, with much lower (5–8 years) variability and much larger (2–4 years) variability. Several temporal changes in precipitation, temperature, and discharge variability are identified during the 1980s and 1990s. Notably, in the southern regions of France, we note a decrease in annual temperature variability in the mid 1990s. Investigating cross-scale interactions, our study reveals causal and bi-directional relationships between higher- and lower-frequency variability, which may feature interactions within the coupled land–ocean–atmosphere systems. Interestingly, however, even though time frequency patterns (occurrence and timing of timescales of variability) were similar between regions, cross-scale interactions are far much complex, differ between regions, and are not systematically transferred from climate (precipitation and temperature) to hydrological variability (discharge). Phase–amplitude interactions are indeed absent in discharge variability, although significant phase–amplitude interactions are found in precipitation and temperature. This suggests that watershed characteristics cancel the negative feedback systems found in precipitation and temperature. This study allows for a multi-timescale representation of hydroclimate variability in France and provides unique insight into the complex nonlinear dynamics of this variability and its predictability

Development of a one-step embryonic stem cell-based assay for the screening of sprouting angiogenesis

BACKGROUND: Angiogenesis assays are important tools for the identification of regulatory molecules and the potential development of therapeutic strategies to modulate neovascularization. Although numerous in vitro angiogenesis models have been developed in the past, they exhibit limitations since they do not recapitulate the entire angiogenic process or correspond to multi-step procedures that are not easy to use. Convenient, reliable, easily quantifiable and physiologically relevant assays are still needed for pharmacological screenings of angiogenesis. RESULTS: Here, we have optimized an angiogenesis model based on ES cell differentiation for screening experiments. We have established conditions leading to angiogenic sprouting of embryoid bodies during ES cell differentiation in type I three-dimensional collagen gels. Immunostaining experiments carried out during these cultures showed the formation of numerous buds comprising CD31 positive cells, after 11 days of culture of ES cells. Moreover, this one-step model has been validated in response to activators and inhibitors of angiogenesis. Sprouting was specifically stimulated in the presence of VEGF and FGF2. Alternatively, endothelial sprouting induced by angiogenic activators was inhibited by angiogenesis inhibitors such as angiostatin, TGFβ and PF4. Sprouting angiogenesis can be easily quantified by image analysis after immunostaining of endothelial cells with CD31 pan-endothelial marker. CONCLUSION: Taken together, these data clearly validate that this one-step ES differentiation model constitutes a simple and versatile angiogenesis system that should facilitate, in future investigations, the screening of both activators and inhibitors of angiogenesis