Mecagenius : An Innovative Learning Game for Mechanical Engineering.

International audienceThe present paper provides a description of Mecagenius, a learning game to teach mechanical engineering at an engineering faculty. Firstly, the Mecagenius game and learning content are introduced before practical ways of integrating this application in educational activities are explored in relation to the skills the teacher seeks to transmit knowledge. This is followed by a review of the literature on the educational effectiveness of serious games. Secondly, the learning game experience of Mecagenius on a course is reported, providing evaluations from both students and teachers. Interviews with teacher and students together with the collected computer records allow for an assessment of the advantages and drawbacks of teaching and learning with this kind of tool.Through a qualitative analysis of students’ game reports, the different strategies used in this educational environment are assessed

A Method to Design a Multi-Player Educational Scenario to Make Interdisciplinary Teams Experiment Risk Management Situation in a Digital Collaborative Learning Game: A Case of Study in Healthcare

In recent years, there has been an increasing interest for collaborative training in risk management. One of the critical point is to create educational and entirely controlled training environments that support industrial companies (in aviation, healthcare, nuclear…) or hospitals to train (future or not) professionals. The aim is to improve their teamwork performance making them understand the importance applying or adjusting safety recommendations. In this article, we present a method to design multi-player educational scenario for risk management in a socio-technical and dynamic context. The socio-technical situations focused in this article involve non-technical skills such as teamwork, communication, leadership, decision-making and situation awareness. The method presented here has been used to design as well regular situations as well as critical situations in which deficiencies already exist or mistakes can be freely made and fixed by the team in a controlled digital environment

Des références pour des pratiques de formation

Ce travail de recherche s’intéresse aux rapports entre le contexte professionnel et le contexte de la formation technologique supérieure lors du développement d’un simulateur de machine-outil.Le cadre conceptuel présente le contexte de la formation technologique supérieure et articule des concepts didactiques, tels que la transposition et les références dans la constitution des situations de formation. Dans cette perspective, une analyse de l’ancrage épistémologique des savoirs pratiques est présentée, à travers la spécificité disciplinaire et le rapport de ces savoirs à la pratique professionnelle. Concernant cette transposition pour la formation deux références dans la modélisation des savoirs sont explorées : les situations professionnelles et les savoirs issus de la recherche scientifique.La méthodologie est portée par le choix de contenus d’enseignement, à travers deux entretiens avec deux professeurs et deux concepteurs du simulateur et ensuite par l’analyse de l’élaboration de contenus d’enseignement (les « savoirs à enseigner »). La méthodologie utilisée mobilise certains outils développés au sein de la didactique professionnelle : l’analyse du contexte professionnel et la structure conceptuelle de la situation. Les résultats exposés permettent de comprendre les modalités de transposition effectuées à travers la simulation informatique et annoncent des possibles voies d’exploitation qui donnent continuité à ce travail.This research focuses on the relations between professional context and higher technological education context during the development of a machine tool simulator. The conceptual framework outlines the context of higher technological education and articulates the didactical concepts, such as the transposition and the references in the composition of educational situations. In this perspective, an analysis of the epistemological roots of practical knowledge is presented, through the specific disciplinary action and the relationship of such knowledge with professional practice. The methodology is driven by the choice of learning content, through two interviews with two teachers and two simulator designers and then by analysing the development of teaching content (the “knowledge to teach”) in two cases. The adopted methodology involves a number of tools developed within professional education: professional contexts analysis and the situation’s conceptual structure. The results presented provide an understanding of the transpositional process through computer simulation and introduce some possible ways of operating that give continuity to this work.Este trabajo de investigación estudia las relaciones entre le contexto profesional y el contexto de la formación tecnológica superior que se dan en le marco del desarrollo de un simulador de maquina-herramienta. El marco conceptual presenta el contexto de la formación tecnológica superior y articula conceptos didácticos como la transposición y las referencias en la constitución de situaciones de formación. En esta perspectiva, presentamos un análisis del anclaje epistemológico de los saberes prácticos, a través de la especificidad disciplinar y la relación entre esos saberes y la practica profesional. Acerca de esta transposición para la formación, se exploraron dos referencias de la modelización de los saberes : las situaciones profesionales y los saberes desde la investigación científica. La metodología esta guiada por la elección de los contenidos de la enseñanza, por medio de dos entrevistas con dos profesores y con dos diseñadores de simuladores, y luego por el análisis de la elaboración de contenidos pedagógicos (“los saberes que se enseñan”). La metodología utilizada moviliza ciertas herramientas desarrolladas en el seno de la didáctica profesional : el análisis del contexto profesional y de la estructura conceptual de la situación. Los resultados expuestos permiten comprender las modalidades de transposición efectuadas a través de la simulación informática y anuncian posibles vías de tratamiento, que serian la continuidad de este trabajo

Transcriptome profiling of the feeding-to-fasting transition in chicken liver

<p>Abstract</p> <p>Background</p> <p>Starvation triggers a complex array of adaptative metabolic responses including energy-metabolic responses, a process which must imply tissue specific alterations in gene expression and in which the liver plays a central role. The present study aimed to describe the evolution of global gene expression profiles in liver of 4-week-old male chickens during a 48 h fasting period using a chicken 20 K oligoarray.</p> <p>Results</p> <p>A large number of genes were modulated by fasting (3532 genes with a pvalue corrected by Benjamini-Hochberg < 0.01); 2062 showed an amplitude of variation higher than +/- 40% among those, 1162 presented an human ortholog, allowing to collect functional information. Notably more genes were down-regulated than up-regulated, whatever the duration of fasting (16 h or 48 h). The number of genes differentially expressed after 48 h of fasting was 3.5-fold higher than after 16 h of fasting. Four clusters of co-expressed genes were identified by a hierarchical cluster analysis. Gene Ontology, KEGG and Ingenuity databases were then used to identify the metabolic processes associated to each cluster. After 16 h of fasting, genes involved in ketogenesis, gluconeogenesis and mitochondrial or peroxisomal fatty acid beta-oxidation, were up-regulated (cluster-1) whereas genes involved in fatty acid and cholesterol synthesis were down-regulated (cluster-2). For all genes tested, the microarray data was confirmed by quantitative RT-PCR. Most genes were altered by fasting as already reported in mammals. A notable exception was the <it>HMG-CoA synthase 1 </it>gene, which was up-regulated following 16 and 48 h of fasting while the other genes involved in cholesterol metabolism were down-regulated as reported in mammalian studies. We further focused on genes not represented on the microarray and candidates for the regulation of the target genes belonging to cluster-1 and -2 and involved in lipid metabolism. Data are provided concerning PPARa, SREBP1, SREBP2, NR1H3 transcription factors and two desaturases (FADS1, FADS2).</p> <p>Conclusion</p> <p>This study evidences numerous genes altered by starvation in chickens and suggests a global repression of cellular activity in response to this stressor. The central role of lipid and acetyl-CoA metabolisms and its regulation at transcriptional level are confirmed in chicken liver in response to short-term fasting. Interesting expression modulations were observed for <it>NR1H3, FADS1 </it>and <it>FADS2 </it>genes. Further studies are needed to precise their role in the complex regulatory network controlling lipid metabolism.</p

E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells

Deletion of E4F1 inflicts mitochondrial damage and oxidative stress on murine and human myeloid leukemia cells but not healthy macrophages

Nécropoles protohistoriques de la région de Castres (Tarn)

Entre 1987 et 1995, trois nécropoles protohistoriques à incinérations de la région de Castres (Tarn) ont été fouillées dans le cadre d'opérations préventives : Gourjade et Le Martinet à Castres, Le Causse à Labruguière. Considérés comme un ensemble indissociable et inscrit sur la liste des Sites d'intérêt national en 1995, ces vastes complexes funéraires ont livré plus de 1 200 tombes de la fin de l'âge du Bronze et du premier âge du Fer. Riche de près de 5 300 vases et de quelque 1 300 objets métalliques, le mobilier archéologique a permis d'élaborer une typologie commune et simple, à l'image de celles réalisées pour les nécropoles du bas Languedoc occidental. Les caractères typologiques définis font l'objet d'un examen minutieux accompagné de cartes de distribution systématiques. Conçue de la même façon, dans la continuité de l'analyse spatiale, une étude détaillée de l'architecture funéraire et de l'organisation des dépôts est présentée dans le chapitre suivant. À partir de ces observations, une mise en séquences chronologiques des sépultures est ensuite proposée. Cet exercice a abouti à une sériation probante des ensembles en cinq groupes qui permet de préciser l'évolution de la culture matérielle et des assemblages funéraires des nécropoles du Castrais sur plus de trois siècles, du IXe à la première moitié du vie s. av. n.è, et surtout d'enregistrer les changements significatifs qui interviennent lors de la phase de transition Bronze/Fer. L'étude du développement topographique qui suit met en évidence des schémas logiques d'évolution, concentriques au Causse et à Gourjade, linéaire au Martinet. Portant sur un échantillon remarquable de plus de 1 200 lots osseux, cas unique en France pour cette période, l'analyse anthropologique permet d'apprécier le recrutement des nécropoles ainsi que l'évolution des dépôts et de leur constitution. Un chapitre est également consacré aux restes animaux, nombreux et diversifiés, notamment au Causse. L'étude met en valeur une évolution quantitative et qualitative des offrandes carnées au cours du temps et offre ainsi une vision significative de cette pratique. L'approche paléosociologique est ensuite abordée selon un schéma désormais classique où tous les paramètres sont pris en considération. Il en ressort une relative uniformité des dépôts qui semble traduire un certain nivellement social des communautés. Le dernier chapitre traite de l'identité culturelle des nécropoles et de leurs affinités régionales : un large tour d'horizon fondé sur la documentation disponible, de la Provence à l'Aquitaine, conclut à une forte parenté avec les complexes méditerranéens et principalement ceux du bas Languedoc occidental. Ces études et synthèses reposent sur une abondante documentation présentée dans son intégralité dans les volumes 2 et 3 de l'ouvrage.Between 1987 and 1995, rescue excavations were carried out on three Late Bronze Age / Early Iron Age cremation burial cemeteries in the Castres area of the Tarn region (Gourjade and Le Martinet near Castres, Le Causse at Labruguière). These vast funerary complexes, containing more than 1,200 burials, were considered to form an indivisible whole and as such were listed as sites of national importance in 1995. Study of archaeological finds from the sites, comprised of almost 5,300 vessels and some 1,300 metal objects, has led to developing a simple common typology similar to those defined for cemeteries in the western lower Languedoc region. Typological characteristics are examined in detail and presented in conjunction with distribution maps. A detailed study of funerary architecture and deposit distribution, using the same approach as the spatial analysis, is presented in the following chapter. These observations provide the basis for suggestions concerning the chronological sequencing of the burials. The resulting seriation conclusively demonstrates the presence of five groups, thus shedding light on the evolution of material culture and funerary assemblages in the Castres cemeteries over more than three centuries (from the 9th to the first half of the 6th c BCE) and indicating that significant changes took place during the Bronze Age / Iron Age transition period. The study of topographical evolution points to logical patterns of development which were concentric at Causse and Goujade and linear at Martinet. Anthropological analysis, which is based on a remarkable sample comprised of more than 1,200 bone assemblages, unique in France for this period, has provided information on selection within the cemeteries and on changes in deposits and their constituents. A chapter is also given over to animal remains which are both numerous and varied, particularly at Causse. The study demonstrates changes in both the quantity and the qua lit y of meat offerings over time and provides a pertinent view of this practice. The paleosociological analysis which follows adopts a classical approach in which ail parameters are taken into consideration. The results indicate that deposits are relatively uniform and point to a degree of social levelling within the communities. The final chapter considers the cemeteries cultural identity and their regional connections. Study of available documentation over a wide area, extending from Provence to Aquitaine, demonstrates strong links with Mediterranean groups, primarily those from the western lower Languedoc area. The studies and syntheses are based upon abundant documentary evidence which is presented in its entirety in the second and third volumes

CDK4 Phosphorylates AMPKα2 to Inhibit Its Activity and Repress Fatty Acid Oxidation

The roles of CDK4 in the cell cycle have been extensively studied, but less is known about the mechanisms underlying the metabolic regulation by CDK4. Here, we report that CDK4 promotes anaerobic glycolysis and represses fatty acid oxidation in mouse embryonic fibroblasts (MEFs) by targeting the AMP-activated protein kinase (AMPK). We also show that fatty acid oxidation (FAO) is specifically induced by AMPK complexes containing the α2 subunit. Moreover, we report that CDK4 represses FAO through direct phosphorylation and inhibition of AMPKα2. The expression of non-phosphorylatable AMPKα2 mutants, or the use of a CDK4 inhibitor, increased FAO rates in MEFs and myotubes. In addition, Cdk4(-/-) mice have increased oxidative metabolism and exercise capacity. Inhibition of CDK4 mimicked these alterations in normal mice, but not when skeletal muscle was AMPK deficient. This novel mechanism explains how CDK4 promotes anabolism by blocking catabolic processes (FAO) that are activated by AMPK

Protection against Mycobacterium ulcerans Lesion Development by Exposure to Aquatic Insect Saliva

BACKGROUND: Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment. The mode of transmission of this Mycobacterium species remains a matter of debate, and relevant interventions to prevent this disease lack (i) the proper understanding of the M. ulcerans life history traits in its natural aquatic ecosystem and (ii) immune signatures that could be correlates of protection. We previously set up a laboratory ecosystem with predatory aquatic insects of the family Naucoridae and laboratory mice and showed that (i) M. ulcerans-carrying aquatic insects can transmit the mycobacterium through bites and (ii) that their salivary glands are the only tissues hosting replicative M. ulcerans. Further investigation in natural settings revealed that 5%–10% of these aquatic insects captured in endemic areas have M. ulcerans–loaded salivary glands. In search of novel epidemiological features we noticed that individuals working close to aquatic environments inhabited by insect predators were less prone to developing Buruli ulcers than their relatives. Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection. METHODS AND FINDINGS: We took a two-pronged approach in this study, first investigating whether the insect bites are protective in a mouse model, and subsequently looking for possibly protective immune signatures in humans. We found that, in contrast to control BALB/c mice, BALB/c mice exposed to Naucoris aquatic insect bites or sensitized to Naucoris salivary gland homogenates (SGHs) displayed no lesion at the site of inoculation of M. ulcerans coated with Naucoris SGH components. Then using human serum samples collected in a Buruli ulcer–endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies. IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group. CONCLUSIONS: These data will help structure future investigations in Buruli ulcer–endemic areas, providing a rationale for research into human immune signatures of exposure to predatory aquatic insects, with special attention to those insect saliva molecules that bind to M. ulcerans

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p &lt; 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM &gt; 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM &gt; 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015