O Processo de Raciocínio na Teoria dos Constrangimentos Aplicado numa Instituição de Ensino Superior

A Teoria dos Constrangimentos (TOC) ou das Restrições tem-se mostrado uma valiosa ferramenta de gestão, auxiliando na identificação dos constrangimentos que limitem a capacidade das empresas na prossecução da sua meta. Assim, para as restrições não físicas, a TOC desenvolveu o Processo de Raciocínio que é composto por ferramentas de análise lógica que dão subsídios para o diagnóstico de problemas bem como a formulação de soluções e planos de acção para implementá-las. Neste contexto, este trabalho se propõe a determinar a adequação do Processo de Raciocínio da Teoria dos Constrangimentos numa Instituição de Ensino Superior (IES) como forma de diagnosticar os problemas e propor soluções capazes de permitir a empresa uma melhoria contínua do seu desempenho. Serão avaliadas as ferramentas que compõem o Processo de Raciocínio, que são: Árvore de Realidade Actual, Diagrama de Dispersão de nuvens, Árvore de Realidade Futura, Árvore de Pré-Requisitos e Árvore de Transição. O trabalho inicia-se com uma pesquisa bibliográfica seguida de uma pesquisa de campo e finalizando com uma aplicação do PR numa IES localizada na ilha de São Vicente. A colecta de informações para a análise processou-se mediante a aplicação de um questionário fechado aos discentes e funcionários, questionário aberto aos docentes e entrevista estruturada aos dirigentes, elaborados em coerência com os objectivos que este estudo pretende atingir. Os resultados da aplicação do método aqui apresentado permitiram chegar as conclusões apontadas no capítulo final deste trabalho The Theory of Constraints (TOC) or Restriction Theory has proved to be a valuable management tool, assisting in the identification of constraints that restrict the ability of companies in the pursuit of its goals. Therefore, for the nonphysical constraints, TOC developed the Thinking Process (TP) that consists of logical analysis tools that provide a basis for diagnosing problems and formulating solutions and action plans to implement them. This study aims, thus, to determine the suitability of the use of the Thinking Process of the Theory of Constraints in a Higher Education Institution (HEI) as a way to diagnose problems and propose solutions that enable the firm to continually improve their performance. We will evaluate the tools that make up the TP, which are: Current Reality Tree, Evaporating Cloud Diagram, Future Reality Tree, Prerequisites Tree and Transition Tree. The work starts with a literature review, followed by a field search, and finishes with an application of the reasoning process in a higher education institution, located in São Vicente. The collection of the data for the analysis was processed through the application of a closed questionnaire to students and staff, opened questionnaire to teachers and interviews to management, drafted in line with the objectives that this study aims to reach. The results of the application of the method presented here, allowed us to reach the conclusions drawn in the final chapter of this work.

A Problemática dos Impostos Diferidos na revalorização dos activos fixos tangíveis

A nível da contabilidade tem-se assistido, nos últimos tempos, esforços no sentido de uma “ Harmonização Global” como forma de acompanhar o fenómeno da globalização, não obstante, existem temas, como o dos Impostos diferidos, que não reúnem consenso entre autores. Os impostos diferidos aparecem como o elo de ligação entre a contabilidade e a fiscalidade, no que se refere as divergências de tratamento destas duas áreas em relação a certas operações, sendo uma delas a revalorização de activos. A revalorização dos activos, na medida em que aumenta a base contabilística dos activos, dá origem a impostos diferidos caso a base fiscal não for ajustada. Assim sendo, há que contabilizar o efeito fiscal decorrente dessa revalorização, em consonância com contabilização do excedente de revalorização. A questão dos impostos diferidos aparece na medida em que o imposto sobre o rendimento passa a ser contabilizado através do método dos efeitos fiscais, em detrimento do método tradicional, o método do imposto a pagar. O método dos efeitos fiscais, assim como o tradicional, apresenta desvantagem, mas é o que melhor permite a apresentação de uma imagem mais verdadeira e apropriada sobre as operações das empresas. A revalorização dos activos fixos tangíveis é uma das operações que tem um tratamento mais adequado utilizado o método dos efeitos fiscais. Em Cabo verde, a revalorização de activos fixos tangíveis é aceite para finalidade de tributação, se for pedida a devida autorização para a sua realização às Finanças. Partindo de um estudo de caso onde não foi efectuado a autorização pelas finanças para efectuar a revalorização dos activos fixos tangíveis, demonstramos que existem impactos significativos nas demonstrações financeiras da empresa em estudo, na sua posição financeira e no seu desempenho, por via da contabilização do imposto diferidoIn level of accounting we have witnessed, in recent times, efforts in the sense of "Global Harmonization" as a means of keep up with the phenomenon of globalization, nevertheless there are themes such as the deferred taxes, which do not congregate consensus among authors. Deferred taxes appear as the link between accounting and taxation, in respect a differences of treatment of these two areas to certain transactions, one of this is the revaluation tangible fixed assets. The revaluation of the tangible fixed assets increases the accounting base of assets and originates a deferred tax if the tax base is not adjusted. Therefore, we must account for the tax effect arising from this revaluation, in line with the accounting revaluation surplus. The issue of deferred taxes appears in consequences of accounting for income tax is accounted by the method of tax effects, over the traditional method, the method of tax payable. The method of tax effects, as well as the traditional method presents disadvantage, but it is the better in allows the presentation of true and fair view of the company's operations. The revaluation of tangible fixed assets is one of the operations that utilized the tax effects, have appropriate treatment. In Cape Verde, the revaluation of tangible fixed assets is accepted for tax purposes, if requested permission for its accomplishment to Finance. Based on a case study which has not been authorized by the finance to effect the revaluation of tangible fixed assets, we demonstrate that there are significant impacts on the financial statements of the company under study in its financial position and performance, through accounting deferred tax.

Does foreign direct investment crowd out domestic entrepreneurship?

In analyzing firm entry and exit across Belgian manufacturing industries,this paper presents evidence that import competition and foreign directinvestment discourage entry and stimulate exit of domestic entrepreneurs.These results are in line with theoretical occupational choice modelsthat predict foreign direct investment would crowd out domesticentrepreneurs through their selections in product and labor markets.However, the empirical results also suggest that this crowding out effectmay be moderated or even reversed in the long-run due to the long termpositive effects of FDI on domestic entrpreneurship as a result oflearning, demonstration, networking and linkage effects between foreignand domestic firms.

Front-Crawl propulsive phase detection using inertial sensors

Front crawl is an alternating swimming stroke technique in which different phases of arm movement induce changes in acceleration of limbs and body. This study proposes a new approach to use inertial body worn sensors to estimate main temporal phases of front crawl. Distinctive features in kinematic signals are used to detect the temporal phases. These temporal phases are key information sources of qualitative and quantitative evaluation of swimming coordination, which have been assessed previously by video analysis. The present method has been evaluated upon a wide range of coordination and showed a difference of 4.9% with video based system. The results are in line with video analysis inter-operator variability yet offering an easy-to-use system for trainers.

Probabilistic maximal covering location-allocation models with constrained waiting time or queue length for congested systems

When dealing with the design of service networks, such as healthand EMS services, banking or distributed ticket selling services, thelocation of service centers has a strong influence on the congestion ateach of them, and consequently, on the quality of service. In this paper,several models are presented to consider service congestion. The firstmodel addresses the issue of the location of the least number of single--servercenters such that all the population is served within a standard distance,and nobody stands in line for a time longer than a given time--limit, or withmore than a predetermined number of other clients. We then formulateseveral maximal coverage models, with one or more servers per service center.A new heuristic is developed to solve the models and tested in a 30--nodesnetwork.

Rational reasoning or adaptive behavior? Evidence from two-person beauty contest games

Many experiments have shown that human subjects do not necessarily behave in line with game theoretic assumptions and solution concepts. The reasons for this non-conformity are multiple. In this paper we study the argument whether a deviation from game theory is because subjects are rational, but doubt that others are rational as well, compared to the argument that subjects, in general, are boundedly rational themselves. To distinguish these two hypotheses, we study behavior in repeated 2-person and many-person Beauty-Contest-Games which are strategically different from one another. We analyze four different treatments and observe that convergence toward equilibrium is driven by learning through the information about the other player s choice and adaptation rather than self-initiated rational reasoning.

Le cycle de la conjoncture chez Schumpeter : éternel retour du même ?

Cet article s'inscrit dans la lignée de précédents travaux visant à rapprocher l'entrepreneur schumpétérien et le surhumain nietzschéen. Les deux partagent une créativité pouvant s'interpréter comme l'extériorisation d'un surcroît de force qui, dans l'optique nietzschéenne, s'assimile à la source extra-morale de l'accrois- sement de la vie. Reste à savoir si le cadre dans lequel ils évoluent est le même. Au-delà d'une approche historique du cycle de la conjoncture, notre hypothèse est que l'approche philosophique d'un cycle du devenir s'avère être féconde pour une interprétation enrichie du cycle de la conjoncture, complétant et prolongeant ainsi notre interprétation du surhumain et de l'entrepreneur. Abstract: This article is in line with previous works aiming to analyse together Schumpeter's entrepreneur and Nietzsche's superhuman. Both share a creativity that can be interpreted as the externalization of an extra force. The latter, through Nietzsche's perspective, is very close to the extra-moral source of the increase of life. But what we have not analysed yet, is the context in which each of

Optimal bail out policy, conditionality and constructive ambiguity

This paper addresses the issue of the optimal behaviour of the Lender of Last Resort (LOLR) in its microeconomic role regarding individual financial institutions in distress. It has been argued that the LOLR should not intervene at the microeconomic level and let any defaulting institution face the market discipline, as it will be confronted with the consequences of the risks it has taken. By considering a simple costbenefit analysis we show that this position may lack a sufficient foundation. We establish that, instead, uder reasonable assumptions, the optimal policy has to be conditional on the amount of uninsured debt issued by the defaulting bank. Yet in equilibrium, because the rescue policy is costly, the LOLR will not rescue all the banks that fulfill the uninsured debt requirement condition, but will follow a mixed strategy. This we interpret as the confirmation of the "creative ambiguity" principle, perfectly in line with the central bankers claim that it is efficient for them to have discretion in lending to individual institutions. Alternatively, in other cases, when the social cost of a bank's bankruptcy is too high, it is optimal for the LOLR to bail out the insititution, and this gives support to the "too big to fail" policy.

Relationships of Scincid Lizards (Mabuya spp; Reptilia: Scincidae) from the Cape Verde Islands Based on Mitochondrial and Nuclear DNA Sequences

Partial DNA sequences from two mitochondrial (mt) and one nuclear gene (cytochrome b, 12S rRNA, and C-mos) were used to estimate the phylogenetic relationships among the six extant species of skinks endemic to the Cape Verde Archipelago. The species form a monophyletic unit, indicating a single colonization of the islands, probably from West Africa. Mabuya vaillanti and M. delalandii are sister taxa, as indicated by morphological characters. Mabuya fogoensis and M. stangeri are closely related, but the former is probably paraphyletic. Mabuya spinalis and M. salensis are also probably paraphyletic. Within species, samples from separate islands always form monophyletic groups. Some colonization events can be hypothesized, which are in line with the age of the islands. C-mos variation is concordant with the topology derived from mtDNA.

Market institutions and judicial rulemaking

Assuming that the degree of discretion granted to judges was the main distinguishing feature between common and civil law until the 19th century, we argue that constraining judicial discretion was instrumental in protecting freedom of contract and developing the market order in civil law. We test this hypothesis by analyzing the history of Western law. In England, a unique institutional balance between the Crown and the Parliament guaranteed private property and prompted the gradual evolution towards a legal framework that facilitated market relationships, a process that was supported by the English judiciary. On the Continent, however, legal constraints on the market were suppressed in a top-down fashion by the founders of the liberal state, often against the will of the incumbent judiciary. Constraining judicial discretion there was essential for enforcing freedom of contract and establishing the legal order of the market economy. In line with this evidence, our selection hypothesis casts doubts on the normative interpretation of empirical results that proclaim the superiority of one legal system over another, disregarding the local conditions and institutional interdependencies on which each legal system was grounded.

L'impact de l'accès à la parentalité sur l'évolution de l'identité conjugale

Cette recherche investigue l'impact de la transition à la parentalité sur l'identité conjugale. Afin de mettre en évidence les bouleversements induits par l'arrivée du premier enfant sur le système-couple, deux groupes de sujets ont constitué notre échantillon : des couples parents d'un premier enfant âgé de 9 à 12 mois et des couples sans enfant mais avec une durée de vie commune équivalente au premier groupe. Chaque couple a été rencontré dans le cadre d'un unique entretien. Leur première tâche a été de décrire leurs vies de couple passée et actuelle au travers de valeurs et devises. Un questionnaire créé pour cette recherche a ensuite permis d'évaluer la représentation des conjoints quant à l'évolution de leur couple, et ce sur la base de cinq dimensions à même de caractériser la manière d'être ensemble des conjoints. Finalement, les jeunes parents ont participé à un entretien semi-directif afin de témoigner des changements personnels et de couple vécus dans le cadre de la transition à la parentalité. Des analyses qualitatives et quantitatives basées sur les données récoltées au travers de nos trois outils révèlent plusieurs résultats. Les conjoints sans enfant décrivent avant tout leur couple comme un cocon au sein duquel deux individus autonomes trouvent refuge et réconfort. Les jeunes parents se démarquent quant à eux par une diminution de leur sentiment d'indépendance, reflet de la nécessaire collaboration propre au co-parentage. Une analyse des entretiens semi-structurés croisée avec l'évaluation du degré de satisfaction conjugale permet le constat suivant : la diminution avérée de la satisfaction conjugale lors de la transition à la parentalité n'est pas strictement associée aux bouleversements conjugaux. Ce déclin lors de l'arrivée et de l'accueil du premier enfant semble en effet être également en lien avec une difficile articulation, chez chaque partenaire, de leurs identités personnelle, conjugale, parentale et socio-professionnelle. - This research investigates the impact of the transition to parenthood on marital identity. To highlight the changes brought about by the arrival of the first child on the couple, two groups of subjects constituted our sample: couples with a first child of 9 to 12 months and childless couples but with a period of cohabitation equivalent to that of the first group. Each couple was interviewed once only. Their first task was to describe their lives as a couple past and present through values and principles. A questionnaire devised for this research was then used to evaluate partners' responses regarding the evolution of their relationship, this based on five criteria to characterise the couples' way of being together. Finally, young parents participated in a semi- structured interview to describe personal changes and those as a couple experienced in the transition to parenthood. Qualitative and quantitative analyses based on data collected through our three tools reveal several results. Spouses without children describe their relationship primarily as a cocoon in which two autonomous individuals find refuge and comfort. Young parents differ in reducing their feelings of independence, reflecting the collaborative needs specific to co-parenting. An analysis of the semi- structured interviews crossed with the assessment of marital satisfaction gives rise to the following observation: the pronounced reduction in marital satisfaction during the transition to parenthood is not strictly associated with marital disruption. This decline upon the arrival of the first child seems to be in line with a difficult balance for each partner between their personal, marital, parental and socio- professional identities.

International Union of Pharmacology. XXXV. The glucagon receptor family.

Peptide hormones within the secretin-glucagon family are expressed in endocrine cells of the pancreas and gastrointestinal epithelium and in specialized neurons in the brain, and subserve multiple biological functions, including regulation of growth, nutrient intake, and transit within the gut, and digestion, energy absorption, and energy assimilation. Glucagon, glucagon-like peptide-1, glucagon-like peptide-2, glucose-dependent insulinotropic peptide, growth hormone-releasing hormone and secretin are structurally related peptides that exert their actions through unique members of a structurally related G protein-coupled receptor class 2 family. This review discusses advances in our understanding of how these peptides exert their biological activities, with a focus on the biological actions and structural features of the cognate receptors. The receptors have been named after their parent and only physiologically relevant ligand, in line with the recommendations of the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR).

Defining substance use disorders: do we really need more than heavy use?

AIMS: The aim of the study was to explore whether the concept of heavy substance use over time can be used as definition of substance use disorder. METHODS: Narrative review. RESULTS: Heavy use over time clearly underlies the neurobiological changes associated with current thinking of substance use disorders. In addition, there is evidence that heavy use over time can explain the majority of social problems and of burden of disease (morbidity and mortality). A definition of substance use disorders via heavy use over time would avoid some of the problems of current conceptualizations, for instance the cultural specificity of concepts such as loss of control. Finally, stressing the continuum of use may avoid the high level of stigmatization currently associated with substance use disorders. CONCLUSION: 'Heavy substance use over time' seems to be a definition of substance use disorders in line with results of basic research and epidemiology. Additionally, it reduces stigmatization. This approach should thus be further explored.

Development of bioreporter assays for the detection of bioavailability of long-chain alkanes based on the marine bacterium Alcanivorax borkumensis strain SK2.

Long-chain alkanes are a major component of crude oil and therefore potentially good indicators of hydrocarbon spills. Here we present a set of new bacterial bioreporters and assays that allow to detect long-chain alkanes. These reporters are based on the regulatory protein AlkS and the alkB1 promoter from Alcanivorax borkumensis SK2, a widespread alkane degrader in marine habitats. Escherichia coli cells with the reporter construct reacted strongly to octane in short-term (6 h) aqueous suspension assays but very slightly only to tetradecane, in line with what is expected from its low water solubility. In contrast, long-term assays (up to 5 days) with A. borkumensis bioreporters showed strong induction with tetradecane and crude oil. Gel-immobilized A. borkumensis reporter cells were used to demonstrate tetradecane and crude oil bioavailability at a distance from a source. Alcanivorax borkumensis bioreporters induced fivefold more rapid and more strongly when allowed physical contact with the oil phase in standing flask assays, suggesting a major contribution of adhered cells to the overall reporter signal. Using the flask assays we further demonstrated the effect of oleophilic nutrients and biosurfactants on oil availability and degradation by A. borkumensis. The fluorescence signal from flask assays could easily be captured with a normal digital camera, making such tests feasible to be carried out on, e.g. marine oil responder vessels in case of oil accidents.

Discovery of novel arenavirus receptors and entry factors

Arenaviruses are enveloped negative-strand RNA viruses that contain a bi-segmented genome. They are rodent-borne pathogens endemic to the Americas and Africa, with the exception of lymphocytic choriomeningitis virus (LCMV) that is world-wide distributed. The arenaviruses include numerous important human pathogens including the Old World arenavirus Lassa virus (LASV), the causative agent of a severe viral hemorrhagic fever in humans with several hundred thousand infections per year in Africa and thousands of deaths. Viruses are obligatory intracellular parasites, strictly depending on cellular processes and factors to complete their replication cycle. The binding of a virus to target cells is the first step of every viral infection, and is mainly mediated by viral proteins that can directly engage cellular receptors, providing a key determinant for viral tropism. This early step of infection represents a promising target to block the pathogen before it can take control over the host cell. Old World arenaviruses, such as LASV and LCMV, bind to host cells via attachment to their main receptor, dystroglycan (DG), an ubiquitous receptor for extracellular matrix proteins. The engagement of DG by LASV results in a fast internalization and transfer the virus to late endosomal compartment suggesting that the virus binding to DG causes marked changes in the dynamics of the receptor. These events could result in the clustering of the receptor and subsequent induction of signaling that could be modulated by the virus. Recently, numerous findings also suggest the presence of alternative receptor(s) for LASV in absence of the main DG receptor. In my first project, I was interested to investigate the effects of virus-receptor binding on the tyrosine phosphorylation of the cytoplasmic domain of DG and to test if this post-translational modification was crucial for the internalization of the LASV-receptor complex. We found that engagement of cellular DG by a recombinant LCMV expressing the envelope GP of LASV in human epithelial cells induced tyrosine phosphorylation of the cytoplasmic domain of DG. LASV GP binding to DG further resulted in dissociation of the adapter protein utrophin from virus-bound DG. Virus-induced dissociation of utrophin and consequent virus internalization were affected by the broadly specific tyrosine kinase inhibitor genistein. We speculate that the detachment of virus- bound DG from the actin-based cytoskeleton following DG phosphorylation may facilitate subsequent endocytosis of the virus-receptor complex. In the second project, I was interested to characterize the newly indentified LASV alternative receptor Axl in the context of productive arenavirus infection. In a first step, we demonstrated that Axl supports productive infection by rLCMV-LASVGP in a DG-independent manner. In line with previous studies, cell entry of rLCMV-LASVGP via Axl was less efficient when compared to functional DG. Interestingly, Axl-mediated infection showed rapid kinetics similar to DG-dependent entry. Using a panel of inhibitors, we found that Axl-mediated cell entry of rLCMV-LASVGP involved a clathrin-independent pathway that critically depended on actin and dynamin and was sensitive to EIPA but not to PAK inhibitors, compatible with a macropinocytosis-like mechanism of entry. In a next step, we aimed to investigate the molecular mechanism by which rLCMV-LASVGP recognizes Axl. Phosphatidylserine (PS) is the natural ligand of Axl via the adaptor protein Gas6. We detected the presence of PS in the envelope of Old World arenaviruses, suggesting that PS could mediate Axl-virus binding, in a mechanism of apoptotic mimicry already described for other viruses. Whether envelope PS and/or the GP of LASV plays any role in virus entry via Axl is still an open question. The molecular mechanisms underlying host cell-virus interaction are of particular interest to answer basic scientific questions as well as to apply key findings to translational research. Understanding pathogen induced-signaling and its link to invasion of the host cell is of great importance to develop drugs for therapeutic intervention against highly pathogenic viruses like LASV. - Les Arenavirus sont des virus enveloppés à ARN négatifs organisés sous forme de génome bisegmenté. Ils sont véhiculés par les rongeurs et se retrouvent de manière endémique aux Amériques et en Afrique avec l'exception du virus de la chorioméningite lymphocytaire (LCMV) qui lui est distribué mondialement. De nombreux pathogènes humains font parti de la famille des Arenavirus dont le virus de l'Ancien Monde Lassa (LASV), un agent responsable de fièvres hémorragiques sévères chez les humains. Le virus de Lassa cause plusieurs centaines de milliers d'infections par année en Afrique ainsi que des milliers de morts. De manière générale, les virus sont des parasites intracellulaires obligatoires qui dépendent strictement de processus et facteurs cellulaires pour clore leur cycle de réplication. L'attachement d'un virus à sa cellule cible représente la première étape de chaque infection virale et est principalement dirigée par des protéines virales qui interagissent directement avec leur récepteurs cellulaires respectifs fournissant ainsi un indicateur déterminant pour le tropisme d'un virus. Cette première étape de l'infection représente aussi une cible prometteuse pour bloquer le pathogène avant qu'il ne puisse prendre le contrôle de la cellule. Les Arenavirus de l'Ancien Monde comme LASV et LCMV s'attachent à la cellule hôte en se liant à leur récepteur principal, le dystroglycan (DG), un récepteur ubiquitaire pour les protéines de la matrice extracellulaire. La liaison du DG par LASV résulte en une rapide internalisation transférant le virus aux endosomes tardifs suggérant ainsi que l'attachement du virus au DG peut provoquer des changements marqués dans la dynamique moléculaire du récepteur. Ces événements sont susceptibles d'induire un regroupement du récepteur à la surface cellulaire, ainsi qu'une induction subséquente qui pourrait être, par la suite, modulée par le virus. Récemment, plusieurs découvertes suggèrent aussi la présence d'un récepteur alternatif pour LASV en l'absence du récepteur principal, le DG. Concernant mon premier projet, j'étais intéressée à étudier les effets de la liaison virus- récepteur sur la phosphorylation des acides aminés tyrosines se trouvant dans la partie cytoplasmique du DG, le but étant de tester si cette modification post-translationnelle était cruciale pour Γ internalisation du complexe LASV-DG récepteur. Nous avons découvert que l'engagement du récepteur DG par le virus recombinant LCMV, exprimant la glycoprotéine de LASV, dans des cellules épithéliales humaines induit une phosphorylation de résidu(s) tyrosine se situant dans le domaine cytoplasmique du DG. La liaison de la glycoprotéine de LASV au DG induit par la suite la dissociation de la protéine adaptatrice utrophine du complexe virus-DG récepteur. Nous avons observé que cette dissociation de l'utrophine, induite par le virus, ainsi que son internalisation, sont affectées par l'inhibiteur à large spectre des tyrosines kinases, la génistéine. Nous avons donc supposé que le détachement du virus, lié au récepteur DG, du cytosquelette d'actine suite à la phosphorylation du DG faciliterait l'endocytose subséquente du complexe virus-récepteur. Dans le second projet, j'étais intéressée à caractériser le récepteur alternatif Axl qui a été récemment identifié dans le contexte de l'infection productive des Arenavirus. Dans un premier temps, nous avons démontré que le récepteur alternatif Axl permet l'infection des cellules par le virus LCMV recombinant LASV indépendamment du récepteur DG. Conformément aux études publiées précédemment, nous avons pu observer que l'entrée du virus recombinant LASV via Axl est moins efficace que via le récepteur principal DG. De façon intéressante, nous avons aussi remarqué que l'infection autorisée par Axl manifeste une cinétique virale d'entrée similaire à celle observée avec le récepteur DG. Utilisant un éventail de différents inhibiteurs, nous avons trouvé que l'entrée du virus recombinant rLCMV-LASVGP via Axl implique une voie d'entrée indépendante de la clathrine et dépendant de manière critique de l'actine et de la dynamine. Cette nouvelle voie d'entrée est aussi sensible à l'EIPA contrairement aux inhibiteurs PAK indiquant un mécanisme d'entrée compatible avec un mécanisme de macropinocytose. L'étape suivante du projet a été d'investiguer le mécanisme moléculaire par lequel le virus recombinant rLCMV-LASVGP reconnaît le récepteur alternatif Axl. La phosphatidylsérine (PS) se trouve être un ligand naturel pour Axl via la protéine adaptatrice Gas6. Nous avons détecté la présence de PS dans l'enveloppe des Arenavirus du Vieux Monde suggérant que la PS pourrait médier la liaison du virus à Axl dans un mécanisme de mimétisme apoptotique déjà observé et décrit pour d'autres virus. Cependant, il reste encore à déterminer qui de la PS ou de la glycoprotéine de l'enveloppe virale intervient dans le processus d'entrée de LASV via le récepteur alternatif Axl. Les mécanismes moléculaires à la base de l'interaction entre virus et cellule hôte sont d'intérêts particuliers pour répondre aux questions scientifiques de base ainsi que dans l'application de découvertes clés pour la recherche translationnelle. La compréhension de la signalisation induite par les pathogènes ainsi que son lien à l'invasion de la cellule hôte est d'une importance considérable pour le développement de drogues pour l'intervention thérapeutique contre les virus hautement pathogènes comme LASV.