QoS support in satellite and wireless networks: study under the network simulator (NS-2)

Aquest projecte es basa en l'estudi de l'oferiment de qualitat de servei en xarxes wireless i satel·litals. Per això l'estudi de les tècniques de cross-layer i del IEEE 802.11e ha sigut el punt clau per al desenvolupament teòric d’aquest estudi. Usant el simulador de xarxes network simulator, a la part de simulacions es plantegen tres situacions: l'estudi de la xarxa satel·lital, l'estudi del mètode d'accés HCCA i la interconnexió de la xarxa satel·lital amb la wireless. Encara que aquest últim punt, incomplet en aquest projecte, ha de ser la continuació per a futures investigacions.

An Archival Case Study: Revisiting The Life and Political Economy of Lauchlin Currie

This paper forms part of a wider project to show the significance of archival material on distinguished economists, in this case Lauchlin Currie (1902-93), who studied and taught at Harvard before entering government service at the US Treasury and Federal Reserve Board as the intellectual leader of Roosevelt’s New Deal, 1934-39, as FDR’s White House economic adviser in peace and war, 1939-45, and as a post-war development economist. It discusses the uses made of the written and oral material available when the author was writing his intellectual biography of Currie (Duke University Press 1990) while Currie was still alive, and the significance of the material that has come to light after Currie’s death.

Chronic beryllium disease as a re-emerging occupational disorder possibly misdiagnosed as sarcoidosis : a Swiss study project

Background: Beryllium (Be) is increasingly used worldwide for numerous industrial applications. Occupational exposure to Be may lead to Be sensitization (BeS), a CD4-mediated immune response. BeS may progress to chronic beryllium disease (CBD), a granulomatous lung disorder closely resembling sarcoidosis. The recognition of CBD requires detection of Be exposure at occupational history, and detection of BeS on blood or BAL lymphocytes. Since methods for CBD detection are not routinely available in Switzerland, we hypothesized that CBD cases are not recognized but misdiagnosis as sarcoidosis. Objective: To present an ongoing Swiss study screening patients with sarcoidosis in search of Be exposure, BeS, and CBD. Methods: Both a prospective and a retrospective cohort are being studied. In the prospective cohort, the main steps include: 1) recruitment of 100 consecutive patients with newly diagnosed pulmonary sarcoidosis at 2 centers (Lausanne, Bern). 2) screening for possible occupational Be exposure by self-administered patient questionnaire. 3) standardized detailed occupational interview and clinical visit by occupational health specialist. If step 3 is positive, then 4) blood and BAL sampling for detection of BeS by specifically developed Elispot assay and CFSE flow cytometry, with subsequent comparison to the classical Be lymphocyte proliferation test. If step 4 is positive, then 5) review of medical records and diagnostic revision from sarcoidosis to CBD. 6) appropriate measures for exposure cessation and case reporting to SUVA as occupational disease. The retrospective cohort will include 400 patients with previously diagnosed pulmonary sarcoidosis, either treated or untreated, recruited through the SIOLD Registries. Steps 2 to 5 will be peformed as above, except for a) end of study after step 2 if screening questionnaire does not reveal Be exposure, and b) step 4 done on blood sample only (BAL not needed). Current status: Self-administered screening questionnaire and tools for standardized occupational interview have been developed. BeS testing has been implemented and undergoes validation. Inclusions in the prospective phase have started at both study sites. The retrospective phase is in preparation. Conclusion: The current study status allows to conclude to technical feasibility of the project. The prospective phase if this study is funded by the SUVA. The SIOLD Registries are supported by the Swiss Pulmonary League.

Les débuts de la communication à trois. Interactions visuelles triadiques entre père, mère et bébé

Plusieurs auteurs ont montré que les échanges visuels entre des mères dépressives ou psychotiques et leur bébé présentent de multiples perturbations : dans cet article, les auteurs proposent une étude exploratoire portant sur les échanges visuels père-mère- bébé (9-18 semaines) dans deux groupes de familles, un groupe suivi pour des difficultés du post-partum et un groupe témoin. Les observations sont réalisées dans le cadre d'un jeu à trois structuré selon diverses modalités d'interaction (un parent joue avec l'enfant en présence de l'autre parent / les deux parents jouent conjointement avec le bébé). Les variables retenues concernent d'une part le niveau d'attention visuelle conjointe des partenaires, d'autre part l'évolution de cette attention visuelle au cours du jeu. Les résultats révèlent que les échanges visuels sont plus intenses dans les familles fonctionnelles, ce qui semble indiquer que l'engagement visuel triadique établi par les partenaires peut être représentatif du fonctionnement de la triade à un moment donné de son développement. D'autre part, l'analyse de l'évolution de l'engagement visuel au travers des différents contextes de jeu amène les auteurs à proposer l'hypothèse d'une « alliance triadique » établie conjointement par les trois partenaires et formant la matrice de leurs échanges dyadiques et triadiques. De façon plus générale, les auteurs supposent que l'établissement de cette alliance joue un rôle déterminant pour le développement et l'autonomisa- tion du bébé au sein de sa famille. Disorders in the visual interaction between depressive or psychotic mothers and their baby have been widely described : in this paper, the authors propose an exploratory study of father-mother-infant visual interaction (infants are 9-18 weeks old) in two groups of families, voluntary families and families in therapy for post-par turn disorders. The observations are gathered during a three-partner play, involving different kinds of triadic interaction (one parent plays with the infant, the other parent being « only present » / both parents play together with the child). The analyses have focused on the amount of visual attention shared by the partners and on the evolution of visual interaction during the game. Results show that triadic interaction is more intense in functional triads, which means that shared visual attention may be representative of the more general functioning of the family at a definite stage of its development. Furthermore, considering the sequential organization of visual interaction throughout the game led the authors to the construct of a « triadic alliance », jointly established by the three partners and providing a matrix for their dyadic and triadic interaction. On a more general level, such an alliance could play an important role for the development and the autonomy of the baby within his j her family.

Absolute requirement for the pre-T cell receptor alpha chain during NK1.1+ TCRalphabeta cell development.

Most natural killer T (NKT) cells express a highly skewed alphabeta TCR repertoire, consisting of an invariant V alpha14-J alpha281 chain paired preferentially with a polyclonal Vbeta8.2 chain. This repertoire is positively selected by the monomorphic CD1d molecule expressed on cells of hematopoietic origin. The origin of NKT cells and their lineage relationship to conventional T cells is controversial. We show here that the development of NKT cells is absolutely dependent on expression of the pre-TCRalpha chain, in marked contrast to conventional T cells which arise in significant numbers even in the absence of a functional pre-TCR. Distinct developmental requirements for pre-TCR expression in the NKT and T cell lineages may reflect differences in the ability of the TCRalphabeta to substitute functionally for the pre-TCR in immature precursor cells.

Changing the awareness of low vitamin D status in a rheumatology population: a pre/post-study.

INTRODUCTION: In 2009 hypovitaminosis D was highly prevalent in a population of Swiss rheumatology patients (86%). We aimed to evaluate the evolution of vitamin D status in the same population two years later, after the results of the first study were disseminated to local physicians and patients, in order to determine the evolution of the problem and the impact of physician information. METHOD: Patients in our rheumatology clinic were screened for 25-OH vitamin D. Results were categorised as: deficient (<10 ng/ml or <25 nmol/l), insufficient (10 to 30 ng/ml or 25 to 75 nmol/l) or normal (>30 ng/ml or >75 nmol/l). We also used another cut-off of 20 ng/ml (50 nmol/l). We evaluated the evolution of 25-OH vitamin D dosages and vitamin D3 prescriptions between 2008 and 2011 in our institution and the number of publications on vitamin D in three important medical journals of the French speaking part of Switzerland. RESULTS: Compared with 2009, significantly more patients had normal results in 2011. Fifty-two percent of patients had levels >20 ng/ml in 2009 and 66% in 2011, difference statistically significant (p = 0.001). During the years separating the two study periods the number of 25-OH vitamin D dosages and the prescription of high doses of vitamin D3 increased in our hospital. In addition the number of publications on vitamin D increased between 2008 and 2011. CONCLUSION: We concluded that lower prevalence in hypovitaminosis D is certainly related to better adherence to daily supplements, and to better information and awareness of the physicians about hypovitaminosis D.

Development of trypanosomatids in the phytophagous insect Dysdercus peruvianus (Hemiptera: Pyrrochoridae): a light and eletron microscopic study

Experimental infections of the phytophagous Hemiptera Dysdercus peruvianus with different trypanosomatids were studied for up to 55 days by light microscopy while the course of infection with Leptomonas seymouri and the Leptomonas isolate 49/553G.O. was analyzed by electron microscopy. Rates of infection of D. peruvianus varied according to the infecting flagellate. The lower part of the midgut was found to be the preferential site of colonization where most flagellates were found isolated or arranged in clumps or rosettes. Specialized junctional structures with host cells were never observed. Flagellates could also be seen inside midgut cells within a parasitophorous vacuole. Infection of haemocoele and salivary glands was also observed.

Chimpanzees and supporting models in the study of malaria pre-erythrocytic stages

Chimpanzees are being used in the study of immune response to Plasmodium falciparum malaria pre-erythrocytic stages (MPES). Responses induced by immunisation with recombinant/synthetic antigens and by irradiated sporozoites are being evaluated in a model system that is phylogenetically close to humans and that is amenable to limited manipulation not possible in humans. The value of chimpanzees for the in-depth study of immunological mechanisms at work in MPES-induced protection are discussed. A total number of 7 chimpanzees have been used to evaluate the immune response to recombinant antigens, and 5 have been challenged with large numbers of sporozoites, followed by surgical liver-wedge resection, in order to generate infected liver tissue for histological and immunological studies. As a complementary model, SCID mice carrying live, transplanted human and primate hepatocytes have been inoculated with sporozoites and infection of transplanted cells has been monitored by histological and immunological methods. In ongoing experiments chimpanzees are being immunised with MPES-derived lipopeptides that have been shown to overcome MHC restriction in mice, and with irradiated sporozoites.

A molecular genetic study of the variations in metabolic function during schistosome development

During their complex life cycle schistosomes alternate between the use of stored glycogen and reliance on host glucose to provide for their energy needs. In addition, there is dramatic variation between the relative contribution of aerobic versus anaerobic glucose metabolism during development. We have cloned a set of representative cDNAs that encode proteins involved in glucose uptake, glycolysis, Kreb's cycle and oxidative phosphorylation. The different cDNAs were used as probes to examine the expression of glucose metabolism genes during the schistosome life cycle. Steady state mRNA levels from whole cercariae, isolated cercarial tails, schistosomula and adult worms were analysed on Northern blots and dot blots which were quantified using storage phosphor technology. These studies reveal: (1) Transcripts encoding glycogen metabolic enzymes are expressed to much higher levels in cercarial tails than whole cercariae or schistosomula while the opposite pattern is found for glucose transporters and hexokinase transcripts; (2) Schistosomula contain low levels of transcripts encoding respiratory enzymes but regain the capacity for aerobic glucose metabolism as they mature to adulthood; (3) Male and female adults contain similar levels of the different transcripts involved in glucose metabolism.

Frailty and use of health and community services by community-dwelling older men: the Concord Health and Ageing in Men Project.

BACKGROUND: frailty is a concept used to describe older people at high risk of adverse outcomes, including falls, functional decline, hospital or nursing home admission and death. The associations between frailty and use of specific health and community services have not been investigated. METHODS: the cross-sectional relationship between frailty and use of several health and community services in the last 12 months was investigated in 1,674 community-dwelling men aged 70 or older in the Concord Health and Ageing in Men study, a population-based study conducted in Sydney, Australia. Frailty was assessed using a modified version of the Cardiovascular Health Study criteria. RESULTS: overall, 158 (9.4%) subjects were frail, 679 (40.6%) were intermediate (pre-frail) and 837 (50.0%) were robust. Frailty was associated with use of health and community services in the last 12 months, including consulting a doctor, visiting or being visited by a nurse or a physiotherapist, using help with meals or household duties and spending at least one night in a hospital or nursing home. Frail men without disability in activities of daily living were twice more likely to have seen a doctor in the previous 2 weeks than robust men (adjusted odds ratio 2.04, 95% confidence interval 1.21-3.44), independent of age, comorbidity and socio-economic status. CONCLUSION: frailty is strongly associated with use of health and community services in community-dwelling older men. The high level of use of medical services suggests that doctors and nurses could play a key role in implementation of preventive interventions.

Species distribution models for conservation-oriented studies in Switzerland : filling data and tools gaps

SUMMARYSpecies distribution models (SDMs) represent nowadays an essential tool in the research fields of ecology and conservation biology. By combining observations of species occurrence or abundance with information on the environmental characteristic of the observation sites, they can provide information on the ecology of species, predict their distributions across the landscape or extrapolate them to other spatial or time frames. The advent of SDMs, supported by geographic information systems (GIS), new developments in statistical models and constantly increasing computational capacities, has revolutionized the way ecologists can comprehend species distributions in their environment. SDMs have brought the tool that allows describing species realized niches across a multivariate environmental space and predict their spatial distribution. Predictions, in the form of probabilistic maps showing the potential distribution of the species, are an irreplaceable mean to inform every single unit of a territory about its biodiversity potential. SDMs and the corresponding spatial predictions can be used to plan conservation actions for particular species, to design field surveys, to assess the risks related to the spread of invasive species, to select reserve locations and design reserve networks, and ultimately, to forecast distributional changes according to scenarios of climate and/or land use change.By assessing the effect of several factors on model performance and on the accuracy of spatial predictions, this thesis aims at improving techniques and data available for distribution modelling and at providing the best possible information to conservation managers to support their decisions and action plans for the conservation of biodiversity in Switzerland and beyond. Several monitoring programs have been put in place from the national to the global scale, and different sources of data now exist and start to be available to researchers who want to model species distribution. However, because of the lack of means, data are often not gathered at an appropriate resolution, are sampled only over limited areas, are not spatially explicit or do not provide a sound biological information. A typical example of this is data on 'habitat' (sensu biota). Even though this is essential information for an effective conservation planning, it often has to be approximated from land use, the closest available information. Moreover, data are often not sampled according to an established sampling design, which can lead to biased samples and consequently to spurious modelling results. Understanding the sources of variability linked to the different phases of the modelling process and their importance is crucial in order to evaluate the final distribution maps that are to be used for conservation purposes.The research presented in this thesis was essentially conducted within the framework of the Landspot Project, a project supported by the Swiss National Science Foundation. The main goal of the project was to assess the possible contribution of pre-modelled 'habitat' units to model the distribution of animal species, in particular butterfly species, across Switzerland. While pursuing this goal, different aspects of data quality, sampling design and modelling process were addressed and improved, and implications for conservation discussed. The main 'habitat' units considered in this thesis are grassland and forest communities of natural and anthropogenic origin as defined in the typology of habitats for Switzerland. These communities are mainly defined at the phytosociological level of the alliance. For the time being, no comprehensive map of such communities is available at the national scale and at fine resolution. As a first step, it was therefore necessary to create distribution models and maps for these communities across Switzerland and thus to gather and collect the necessary data. In order to reach this first objective, several new developments were necessary such as the definition of expert models, the classification of the Swiss territory in environmental domains, the design of an environmentally stratified sampling of the target vegetation units across Switzerland, the development of a database integrating a decision-support system assisting in the classification of the relevés, and the downscaling of the land use/cover data from 100 m to 25 m resolution.The main contributions of this thesis to the discipline of species distribution modelling (SDM) are assembled in four main scientific papers. In the first, published in Journal of Riogeography different issues related to the modelling process itself are investigated. First is assessed the effect of five different stepwise selection methods on model performance, stability and parsimony, using data of the forest inventory of State of Vaud. In the same paper are also assessed: the effect of weighting absences to ensure a prevalence of 0.5 prior to model calibration; the effect of limiting absences beyond the environmental envelope defined by presences; four different methods for incorporating spatial autocorrelation; and finally, the effect of integrating predictor interactions. Results allowed to specifically enhance the GRASP tool (Generalized Regression Analysis and Spatial Predictions) that now incorporates new selection methods and the possibility of dealing with interactions among predictors as well as spatial autocorrelation. The contribution of different sources of remotely sensed information to species distribution models was also assessed. The second paper (to be submitted) explores the combined effects of sample size and data post-stratification on the accuracy of models using data on grassland distribution across Switzerland collected within the framework of the Landspot project and supplemented with other important vegetation databases. For the stratification of the data, different spatial frameworks were compared. In particular, environmental stratification by Swiss Environmental Domains was compared to geographical stratification either by biogeographic regions or political states (cantons). The third paper (to be submitted) assesses the contribution of pre- modelled vegetation communities to the modelling of fauna. It is a two-steps approach that combines the disciplines of community ecology and spatial ecology and integrates their corresponding concepts of habitat. First are modelled vegetation communities per se and then these 'habitat' units are used in order to model animal species habitat. A case study is presented with grassland communities and butterfly species. Different ways of integrating vegetation information in the models of butterfly distribution were also evaluated. Finally, a glimpse to climate change is given in the fourth paper, recently published in Ecological Modelling. This paper proposes a conceptual framework for analysing range shifts, namely a catalogue of the possible patterns of change in the distribution of a species along elevational or other environmental gradients and an improved quantitative methodology to identify and objectively describe these patterns. The methodology was developed using data from the Swiss national common breeding bird survey and the article presents results concerning the observed shifts in the elevational distribution of breeding birds in Switzerland.The overall objective of this thesis is to improve species distribution models as potential inputs for different conservation tools (e.g. red lists, ecological networks, risk assessment of the spread of invasive species, vulnerability assessment in the context of climate change). While no conservation issues or tools are directly tested in this thesis, the importance of the proposed improvements made in species distribution modelling is discussed in the context of the selection of reserve networks.RESUMELes modèles de distribution d'espèces (SDMs) représentent aujourd'hui un outil essentiel dans les domaines de recherche de l'écologie et de la biologie de la conservation. En combinant les observations de la présence des espèces ou de leur abondance avec des informations sur les caractéristiques environnementales des sites d'observation, ces modèles peuvent fournir des informations sur l'écologie des espèces, prédire leur distribution à travers le paysage ou l'extrapoler dans l'espace et le temps. Le déploiement des SDMs, soutenu par les systèmes d'information géographique (SIG), les nouveaux développements dans les modèles statistiques, ainsi que la constante augmentation des capacités de calcul, a révolutionné la façon dont les écologistes peuvent comprendre la distribution des espèces dans leur environnement. Les SDMs ont apporté l'outil qui permet de décrire la niche réalisée des espèces dans un espace environnemental multivarié et prédire leur distribution spatiale. Les prédictions, sous forme de carte probabilistes montrant la distribution potentielle de l'espèce, sont un moyen irremplaçable d'informer chaque unité du territoire de sa biodiversité potentielle. Les SDMs et les prédictions spatiales correspondantes peuvent être utilisés pour planifier des mesures de conservation pour des espèces particulières, pour concevoir des plans d'échantillonnage, pour évaluer les risques liés à la propagation d'espèces envahissantes, pour choisir l'emplacement de réserves et les mettre en réseau, et finalement, pour prévoir les changements de répartition en fonction de scénarios de changement climatique et/ou d'utilisation du sol. En évaluant l'effet de plusieurs facteurs sur la performance des modèles et sur la précision des prédictions spatiales, cette thèse vise à améliorer les techniques et les données disponibles pour la modélisation de la distribution des espèces et à fournir la meilleure information possible aux gestionnaires pour appuyer leurs décisions et leurs plans d'action pour la conservation de la biodiversité en Suisse et au-delà. Plusieurs programmes de surveillance ont été mis en place de l'échelle nationale à l'échelle globale, et différentes sources de données sont désormais disponibles pour les chercheurs qui veulent modéliser la distribution des espèces. Toutefois, en raison du manque de moyens, les données sont souvent collectées à une résolution inappropriée, sont échantillonnées sur des zones limitées, ne sont pas spatialement explicites ou ne fournissent pas une information écologique suffisante. Un exemple typique est fourni par les données sur 'l'habitat' (sensu biota). Même s'il s'agit d'une information essentielle pour des mesures de conservation efficaces, elle est souvent approximée par l'utilisation du sol, l'information qui s'en approche le plus. En outre, les données ne sont souvent pas échantillonnées selon un plan d'échantillonnage établi, ce qui biaise les échantillons et par conséquent les résultats de la modélisation. Comprendre les sources de variabilité liées aux différentes phases du processus de modélisation s'avère crucial afin d'évaluer l'utilisation des cartes de distribution prédites à des fins de conservation.La recherche présentée dans cette thèse a été essentiellement menée dans le cadre du projet Landspot, un projet soutenu par le Fond National Suisse pour la Recherche. L'objectif principal de ce projet était d'évaluer la contribution d'unités 'd'habitat' pré-modélisées pour modéliser la répartition des espèces animales, notamment de papillons, à travers la Suisse. Tout en poursuivant cet objectif, différents aspects touchant à la qualité des données, au plan d'échantillonnage et au processus de modélisation sont abordés et améliorés, et leurs implications pour la conservation des espèces discutées. Les principaux 'habitats' considérés dans cette thèse sont des communautés de prairie et de forêt d'origine naturelle et anthropique telles que définies dans la typologie des habitats de Suisse. Ces communautés sont principalement définies au niveau phytosociologique de l'alliance. Pour l'instant aucune carte de la distribution de ces communautés n'est disponible à l'échelle nationale et à résolution fine. Dans un premier temps, il a donc été nécessaire de créer des modèles de distribution de ces communautés à travers la Suisse et par conséquent de recueillir les données nécessaires. Afin d'atteindre ce premier objectif, plusieurs nouveaux développements ont été nécessaires, tels que la définition de modèles experts, la classification du territoire suisse en domaines environnementaux, la conception d'un échantillonnage environnementalement stratifié des unités de végétation cibles dans toute la Suisse, la création d'une base de données intégrant un système d'aide à la décision pour la classification des relevés, et le « downscaling » des données de couverture du sol de 100 m à 25 m de résolution. Les principales contributions de cette thèse à la discipline de la modélisation de la distribution d'espèces (SDM) sont rassemblées dans quatre articles scientifiques. Dans le premier article, publié dans le Journal of Biogeography, différentes questions liées au processus de modélisation sont étudiées en utilisant les données de l'inventaire forestier de l'Etat de Vaud. Tout d'abord sont évalués les effets de cinq méthodes de sélection pas-à-pas sur la performance, la stabilité et la parcimonie des modèles. Dans le même article sont également évalués: l'effet de la pondération des absences afin d'assurer une prévalence de 0.5 lors de la calibration du modèle; l'effet de limiter les absences au-delà de l'enveloppe définie par les présences; quatre méthodes différentes pour l'intégration de l'autocorrélation spatiale; et enfin, l'effet de l'intégration d'interactions entre facteurs. Les résultats présentés dans cet article ont permis d'améliorer l'outil GRASP qui intègre désonnais de nouvelles méthodes de sélection et la possibilité de traiter les interactions entre variables explicatives, ainsi que l'autocorrélation spatiale. La contribution de différentes sources de données issues de la télédétection a également été évaluée. Le deuxième article (en voie de soumission) explore les effets combinés de la taille de l'échantillon et de la post-stratification sur le la précision des modèles. Les données utilisées ici sont celles concernant la répartition des prairies de Suisse recueillies dans le cadre du projet Landspot et complétées par d'autres sources. Pour la stratification des données, différents cadres spatiaux ont été comparés. En particulier, la stratification environnementale par les domaines environnementaux de Suisse a été comparée à la stratification géographique par les régions biogéographiques ou par les cantons. Le troisième article (en voie de soumission) évalue la contribution de communautés végétales pré-modélisées à la modélisation de la faune. C'est une approche en deux étapes qui combine les disciplines de l'écologie des communautés et de l'écologie spatiale en intégrant leurs concepts de 'habitat' respectifs. Les communautés végétales sont modélisées d'abord, puis ces unités de 'habitat' sont utilisées pour modéliser les espèces animales. Une étude de cas est présentée avec des communautés prairiales et des espèces de papillons. Différentes façons d'intégrer l'information sur la végétation dans les modèles de répartition des papillons sont évaluées. Enfin, un clin d'oeil aux changements climatiques dans le dernier article, publié dans Ecological Modelling. Cet article propose un cadre conceptuel pour l'analyse des changements dans la distribution des espèces qui comprend notamment un catalogue des différentes formes possibles de changement le long d'un gradient d'élévation ou autre gradient environnemental, et une méthode quantitative améliorée pour identifier et décrire ces déplacements. Cette méthodologie a été développée en utilisant des données issues du monitoring des oiseaux nicheurs répandus et l'article présente les résultats concernant les déplacements observés dans la distribution altitudinale des oiseaux nicheurs en Suisse.L'objectif général de cette thèse est d'améliorer les modèles de distribution des espèces en tant que source d'information possible pour les différents outils de conservation (par exemple, listes rouges, réseaux écologiques, évaluation des risques de propagation d'espèces envahissantes, évaluation de la vulnérabilité des espèces dans le contexte de changement climatique). Bien que ces questions de conservation ne soient pas directement testées dans cette thèse, l'importance des améliorations proposées pour la modélisation de la distribution des espèces est discutée à la fin de ce travail dans le contexte de la sélection de réseaux de réserves.

Development of a method to investigate the hydrolysis of xenobiotic esters by a Mycobacterium smegmatis homogenate.

One of the main problems in combating tuberculosis is caused by a poor penetration of drugs into the mycobacterial cells. A prodrug approach via activation inside mycobacterial cells is a possible strategy to overcome this hurdle and achieve efficient drug uptake. Esters are attractive candidates for such a strategy and we and others communicated previously the activity of esters of weak organic acids against mycobacteria. However very little is known about ester hydrolysis by mycobacteria and no biological model is available to study the activation of prodrugs by these microorganisms. To begin filling this gap, we have embarked in a project to develop an in vitro method to study prodrug activation by mycobacteria using Mycobacterium smegmatis homogenates. Model ester substrates were ethyl nicotinate and ethyl benzoate whose hydrolysis was monitored and characterized kinetically. Our studies showed that in M. smegmatis most esterase activity is associated with the soluble fraction (cytosol) and is preserved by storage at 5°C or at room temperature for one hour, or by storage at -80°C up to one year. In the range of homogenate concentrations studied (5-80% in buffer), k(obs) varied linearly with homogenate concentration for both substrates. We also found that the homogenates showed Michaelis-Menten kinetics behavior with both prodrugs. Since ethyl benzoate is a good substrate for the mycobacterial esterases, this compound can be used to standardize the esterasic activity of homogenates, allowing results of incubations of prodrugs with homogenates from different batches to be readily compared.