Hypothèse de restitution d'un navire à dolia: la construction d'une maquette

International audiencePrésentation de l'étude d'architecture navale nécessaire à la réalisation d'une maquette de l'épave du navire à dolia de Ladispoli : collecte des informations archéologiques, réalisation du plan de forme, construction du modèle d'étude au 1/10e. L'expérimentation compare les données recueillies sur d'autres épaves et a permis de proposer une hypothèse sur le chargement de la cargaison

Explicit Substitutions for Contextual Type Theory

In this paper, we present an explicit substitution calculus which distinguishes between ordinary bound variables and meta-variables. Its typing discipline is derived from contextual modal type theory. We first present a dependently typed lambda calculus with explicit substitutions for ordinary variables and explicit meta-substitutions for meta-variables. We then present a weak head normalization procedure which performs both substitutions lazily and in a single pass thereby combining substitution walks for the two different classes of variables. Finally, we describe a bidirectional type checking algorithm which uses weak head normalization and prove soundness.Comment: In Proceedings LFMTP 2010, arXiv:1009.218

Étude sur l'expérience d'un partenariat entre des intervenants des ressources communautaires œuvrant en matière pénale et des services correctionnels du Québec

L'objectif de cette étude de type exploratoire est de mieux connaître les perceptions des intervenants du réseau correctionnel québécois face au partenariat en général. Plus spécifiquement, elle vise à mieux saisir les perceptions des intervenants du réseau communautaire oeuvrant en matière pénale ainsi que des intervenants des Services correctionnels (SC) du ministère de la Sécurité publique à l'égard des éléments favorables et des contraintes du partenariat vécu particulièrement dans le milieu correctionnel québécois. Pour les fins de l'étude, la méthode de type qualitatif est privilégiée, soit l'interrogation de onze répondants provenant du réseau communautaire et des SC et intervenant auprès de personnes contrevenantes quant à leurs perceptions sur le partenariat ainsi que sur les éléments favorables et les contraintes du partenariat vécu. Les données ont été recueillies sur une période de deux mois (juin et juillet 2005), par entrevues semi-dirigées. Il ressort de la recherche qu'il existe des éléments généraux favorables au partenariat; ainsi, la transparence, le respect et la confiance à l'égard des relations entre partenaires sont rapportés comme étant favorables au partenariat. Plus spécifiquement, des éléments individuels et organisationnels ont aussi été relevés à la fois par des répondants de l'étude et dans la littérature recensée. Il s'agit respectivement de la motivation à collaborer ensemble, du respect des interventions, de l'autonomie des partenaires, de la confiance envers les intervenants, de la complémentarité, de l'entraide, du travail d'équipe, de la prise de décisions communes et des buts communs

Analysis of the erosive effect of different dietary substances and medications

Excessive consumption of acidic drinks and foods contributes to tooth erosion. The aims of the present in vitro study were twofold: (1) to assess the erosive potential of different dietary substances and medications; (2) to determine the chemical properties with an impact on the erosive potential. We selected sixty agents: soft drinks, an energy drink, sports drinks, alcoholic drinks, juice, fruit, mineral water, yogurt, tea, coffee, salad dressing and medications. The erosive potential of the tested agents was quantified as the changes in surface hardness (ΔSH) of enamel specimens within the first 2 min (ΔSH2-0 = SH2 min - SHbaseline) and the second 2 min exposure (ΔSH4-2 = SH4 min - SH2 min). To characterise these agents, various chemical properties, e.g. pH, concentrations of Ca, Pi and F, titratable acidity to pH 7·0 and buffering capacity at the original pH value (β), as well as degree of saturation (pK - pI) with respect to hydroxyapatite (HAP) and fluorapatite (FAP), were determined. Erosive challenge caused a statistically significant reduction in SH for all agents except for coffee, some medications and alcoholic drinks, and non-flavoured mineral waters, teas and yogurts (P < 0·01). By multiple linear regression analysis, 52 % of the variation in ΔSH after 2 min and 61 % after 4 min immersion were explained by pH, β and concentrations of F and Ca (P < 0·05). pH was the variable with the highest impact in multiple regression and bivariate correlation analyses. Furthermore, a high bivariate correlation was also obtained between (pK - pI)HAP, (pK - pI)FAP and ΔSH

Une expérience d'annotation à large échelle : le projet OTIM

Nous proposons dans cette présentation de faire le point sur une opération dannotation de grande envergure conduite dans le cadre du projet OTIM. Nous avons dans le cadre de ce projet constitué un grand corpus audio-visuel de parole spontanée comprenant 8 heures de dialogues (soit 102.457 mots correspondant à 6.611 formes différentes) totalement transcrit, aligné et richement annoté pour lensemble des domaines et des modalités. Nous avons donc été confrontés aux principaux problèmes posés par lannotation de ce type de ressource. Cette présentation décrit les recommandations et les techniques que nous avons utilisées pour parvenir à nos fins

Nanobody-CD16 Catch Bond Reveals NK Cell Mechanosensitivity

International audienceAntibodies are key tools in biomedical research and medicine. Their binding properties are classically measured in solution and characterized by an affinity. However, in physiological conditions, antibodies can bridge an immune effector cell and an antigen-presenting cell, implying that mechanical forces may apply to the bonds. For example, in antibody-dependent cell cytotoxicity—a major mode of action of therapeutic monoclonal antibodies—the Fab domains bind the antigens on the target cell, whereas the Fc domain binds to the activating receptor CD16 (also known as FcgRIII) of an immune effector cell, in a quasi-bidimensional environment (2D). Therefore, there is a strong need to investigate antigen/antibody binding under force (2D) to better understand and predict antibody activity in vivo. We used two anti-CD16 nanobodies targeting two different epitopes and laminar flow chamber assay to measure the association and dissociation of single bonds formed between microsphere-bound CD16 antigens and surface-bound anti-CD16 nanobodies (or single-domain antibodies), simulating 2D encounters. The two nanobodies exhibit similar 2D association kinetics, characterized by a strong dependence on the molecular encounter duration. However, their 2D dissociation kinetics strongly differ as a function of applied force: one exhibits a slip bond behavior in which off rate increases with force, and the other exhibits a catch-bond behavior in which off rate decreases with force. This is the first time, to our knowledge, that catch-bond behavior was reported for antigen-antibody bond. Quantification of natural killer cells spreading on surfaces coated with the nanobodies provides a comparison between 2D and three-dimensional adhesion in a cellular context, supporting the hypothesis of natural killer cell mechanosensitivity. Our results may also have strong implications for the design of efficient bispecific antibodies for therapeutic applications

HE AMOT FAMILY OF PROTEINS BINDS AND ACTIVATES NEDD4 FAMILY LIGASES TO PROMOTE THE UBIQUITINATION OF LATS AND YAP

poster abstractAmot adaptor proteins bind and integrate signaling that controls cell po-larity and growth. All three Amot family members (Amot, AmotL1 and AmotL2) directly bind YAP; a transcriptional co-activator that controls the expression of genes involved in organ homeostasis and cell growth. Preven-tion of nuclear accumulation of YAP by either sequestration or degradation in the cytosol abolishes its transcriptional functions and is a major mechanism for growth arrest in response to cellular differentiation. This is mainly thought to be regulated by phosphorylation of YAP by the Hippo kinases LATS1/2. Recently, binding by the Amot proteins was also found to inhibit YAP by sequestering it in the cytosol through both LATS dependent and in-dependent mechanisms. This study identifies a novel mechanism whereby Amot proteins control YAP activation in a Hippo independent mechanism by coupling it to ubiquitination by Nedd4 family ligases. Amot proteins mediate the coupling of Nedd4 ligases with YAP by simultaneously binding both pro-teins via multiple PY motifs that are recognized by WW domains in both YAP and Nedd4. Binding of Nedd4 by Amot is also shown to relieve the auto-inhibition of its ligase activity. This may be a direct consequence of binding Amot or from being re-targeted in cells by Amot proteins to endosomes. Im-portantly, Amot induced ubiquitination of YAP by Nedd4 proteins is shown to enhance the residence of YAP in the nucleus and in YAP activated transcrip-tion. Taken together our data suggest that Amot couples Nedd4 family ubiq-uitin ligases with the transcriptional co-activator YAP to drive the ubiquitination and activation of YAP

Integrated results from the COPERNICUS and GALILEO studies.

OBJECTIVES: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. PATIENTS AND METHODS: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. RESULTS: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in CONCLUSION: This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO