Staphylococcus aureus, est un pathogène humain majeur responsable d’infections nosocomiales et communautaires. Avec l’utilisation excessive des antibactériens, l’incidence et l’émergence de souches de S. aureus multi-résistantes aux antibiotiques ont augmenté rapidement depuis plusieurs années et constituent un véritable problème de santé publique. Le succès de S. aureus en tant que pathogène est lié à sa capacité à s’adapter rapidement à un nouvel environnement et à produire un arsenal de facteurs de virulence dont l’expression fait intervenir des protéines mais également des ARN régulateurs (ARNrég). Au cours de cette thèse, nous avons montré que les ARNrég sprG1 et SprF1 constitue un système toxine-antitoxine (STA) de type I fonctionnel où sprG1 code pour deux peptides toxiques. En condition normale de croissance, l’expression de la toxine est régulée par l’antitoxine SprF1 au niveau transcriptionnel et/ou post-transcriptionnel et traductionnel, permettant au pathogène S. aureus de croître normalement. En revanche, lorsque la bactérie est confrontée à une carence nutritive globale, l’expression de l’antitoxine est réprimée, laissant ainsi la toxine sprG1 s’accumuler dans la cellule et traduire les peptides toxiques PepG144 et PepG131, responsables de la stase bactérienne. Les deux peptides sécrétés sont capables de lyser les bactéries compétitrices présentes dans le milieu et les érythrocytes humains. Nous avons également montré, qu’en condition de stress hyperosmotique, SprF1 fixe directement les ribosomes, probablement par l’intermédiaire d’un ou de deux sites de fixation aux ribosomes, afin de réguler la synthèse protéique globale et de favoriser la persistance de S. aureus. Ces résultats montrent que SprF1 appartient à une nouvelle classe émergente d’ARNrég régulant la traduction par fixation directe sur le ribosome. Le STA sprG1/SprF1 est le premier exemple de STA de type I où l’antitoxine est le principal acteur de la fonction biologique. / Staphylococcus aureus is a major human pathogen responsible for nosocomial and community-acquired diseases. With the excessive use of antibiotics, incidence and emergence of multidrug-resistant strains of S. aureus have rapidly increased over the last decade and constitute a serious public health concern. The success of S. aureus as a pathogen is due to its ability to adapt quickly to new environment and to produce an arsenal of virulence factors whose expressions are regulated by proteins and regulatory RNA (regRNA). During my PhD thesis, we showed that RNAs sprG1 and SprF1 constitute a functional type I toxin-antitoxin system (TAS) where sprG1 encodes two toxic peptides. During normal growth conditions, toxin expression is regulated by the antitoxin SprF1 at transcriptional and/or post-transcriptional and translational level, allowing the pathogen to grow. Conversaly, when bacteria are confronted to global nutritive starvation, the antitoxin expression is repressed. This allows accumulation of the sprG1 toxin in cell and translation of both toxic peptides, PepG144 and PepG131, responsible for bacterial stasis. Interestingly, both secreted peptides are able to lyse competitor bacteria in the medium and human erythrocytes. We also showed that upon hyperosmotic stress, SprF1 directly binds ribosomes, probably though one or two ribosome-binding sites, to regulate overall protein synthesis and promote S. aureus persistence. These results suggest that SprF1 belongs to the new emerging class of regRNA regulating translation by direct ribosome-binding. The sprG1/SprF1 TAS is the first example of type I TAS where antitoxin is the leading player of the biological function.

Les Entérovirus humains du groupe B (EV-B) et plus spécifiquement les virus Coxsackie B sont considérés comme une cause majeure des myocardites infectieuses aigues et chroniques dont 10% peuvent évoluer vers la cardiomyopathie dilatée (CMD). Les mécanismes moléculaires viraux impliqués dans la progression de la myocardite aiguë vers le stade de la CMD ne sont pas élucidés.L’analyse par séquençage NGS a montré chez 8 (33%) des 24 patients atteints de CMD inexpliquée l’existence de populations majoritaires tronquées de 19 à 50 nucléotides associées à des formes virales minoritaires complètes. La proportion de populations tronquées s’est révélée négativement corrélée au ratio ARN+/ARN- et à la charge virale. Des études immuno-histologiques et par hybridation in situ des tissus cardiaques ont montré que le clivage de la dystrophine était uniquement retrouvé dans les cardiomyocytes infectés par les EV-B. Pour étudier les activités de réplication des populations d’EV-B persistants, un réplicon (CVB3-emGFP) a été généré à partir d’une souche cardiotrope (CV-B3/28). La transfection d’ARN de synthèse complets et tronqués (d50) dans des cultures de cardiomyocytes humains primaires a mis en évidence des mécanismes de recombinaison et/ou de trans-complémentation entre ces 2 formes virales induisant de faibles activités de réplication.Nos résultats démontrent l’existence de mécanismes de coopération moléculaire entre des populations d’EV-B tronquées et complètes qui pourraient expliquer la mise en place du mécanisme de persistance virale observée au cours de la phase clinique de CMD. Ces résultats pourraient contribuer au développement de nouvelles stratégies thérapeutiques pour prévenir et traiter les infections cardiaques à EV-B. / Enteroviruses group B (EV-B) and more specifically Coxsackievirus B are recognized as major causes of acute and chronic infectious myocarditis, which 10% may progress towards dilated cardiomyopathy (DCM). Viral molecular mechanisms involved in the progression from acute myocarditis to the clinical stage of DCM remain unknown.Deep sequencing analysis showed in 8 (33%) of 24 unexplained DCM patients the existence of major CVB3 populations with deletions of 19 to 50 nucleotides associated with a minority of complete viral forms. The proportion of deleted viral populations was negatively correlated with RNA+/RNA- ratio and the viral load levels. Immuno-histological and in situ hybridization assays of DCM cardiac tissues demonstrated that the cleavage of dystrophin was found only in cardiomyocytes infected with EV-B. To study the replication activities of persistent EV-B populations, a replicon (CVB3-emGFP) was generated from a cardiotropic strain (CV-B3/28). Transfection of synthesized complete and truncated (d50) viral RNAs in primary human cardiomyocytes cultures revealed mechanisms of recombination and / or trans-complementation between these two viral forms inducing low replication activities.In conclusions, our original results demonstrated the existence of new molecular mechanisms of cooperation between EV-B deleted and complete viral populations that could explain the development of a viral persistence mechanism observed during the clinical phase of DCM. These findings may contribute to the development of new therapeutic strategies to prevent and treat persistent heart EV-B infections.

The paper analyses the degree of output persistence in GDP in order to empirically discriminate between the Solow growth model, the perfect competition endogenous growth model, the imperfect competition endogenous growth model, and the subcase of a multiple equilibria model of endogenous growth for the case of Austria. We find that a temporary shock in the growth rate of output induces a permanent and larger effect on the level of GDP. This leads us to refute the Solow growth model and the perfect competition model. We find strong empirical support for the imperfect competition growth model, but cannot fully rule out the possibility of multiple equilibria growth rates. / Series: Department of Economics Working Paper Series

Lactase persistence (LP) is a genetically determined trate caused by the expression of lactase in adulthood. Lactase is the intestinal enzyme responsible for digestion of milk sugar, lactose. Its production in the small intestine decreases during the childhood, this physiological condition is called lactose intolerance. However, in some individuals production of this enzyme is not stopped. The persistence of lactase activity is a recent phenomenon, which arose independently in several parts of the world over the past roughly 10,000 years, in connection with the emergence of agriculture, specifically milk production and is (likely) still under strong selection pressure. LP was first observed in Europe, where it is associated with a mutation -13 910*T. Frequency of this mutation correlates with latitude. In Africa, the presence of LP is conversely associated with herding and falls under the hypothesis of genetic and cultural co-evolution associated with cattle and the use of secondary food sources. Pastoral populations living in different areas of Africa have different LP mutations that are linked to their origin. Although many investigation on LP have already been carried out, neither analysed the Tuareg populations. This study is focused on the analysis LP mutations in 93 samples of Tuaregs from...

La contamination des zones littorales par des bactéries entériques potentiellement pathogènes pour l’Homme constitue un problème majeur pour la pérennité de certains usages tel que la conchyliculture. Ces bactéries provenant de rejets agricoles ou urbains peuvent atteindre les zones conchylicoles et être impliquées dans des toxi-infections alimentaires collectives (TIAC). Actuellement, très peu de données sont disponibles sur la présence et la diversité des bactéries entériques telles que les Escherichia coli (E. coli) pathogènes de type E. coli producteurs de Shiga-toxines (STEC) et E.coli entéropathogènes (EPEC) dans les coquillages en France.La présence de ces E. coli pathogènes a été recherchée pendant deux ans, dans trois zones conchylicoles françaises et leurs bassins versants. Un total de 28 souches STEC et 89 souches EPEC différentes ont été isolées dans des coquillages, des eaux aux exutoires, le sédiment et l’eau de mer, représentant 1% de la totalité des souches E. coli isolées (n=12016). Ces souches isolées présentaient néanmoins une grande diversité. Elles étaient réparties au sein de 73 profils de virulence différents dont une souche STEC de sérotype O26 :H11 présentant 47 gènes de virulence isolée dans un lot de moule. Soixante-quinze pourcents des souches EPEC présentaient des gènes de virulence associés à des îlots de pathogénicités caractéristiques de souches pathogènes responsables d’infection grave chez l’Homme, révélant le potentiel pouvoir pathogène de certaines souches. Enfin, l’étude de la cinétique de contamination, décontamination d’huîtres au contact de souches STEC, n’a pas montré de différence comparée à un E. coli non STEC.Les travaux réalisés au cours de cette thèse sont à notre connaissance les premiers de ce genre. Ils ont permis de mettre en évidence la faible présence de STEC et de EPEC au niveau des zones conchylicoles françaises étudiées ainsi que le potentiel pouvoir pathogène de certaines souches. La faible prévalence des souches sur ces sites de catégorie B ou C (purification des coquillages avant commercialisation) reste néanmoins plutôt en faveur d’un risque faible de contamination dans les zones sélectionnées. Les résultats acquis au cours de cette thèse sont des éléments importants pour mieux appréhender le risque sanitaire potentiel lié aux STEC et aux EPEC en zone littorale. / The contamination of coastal areas by potentially pathogenic enteric bacteria is of concern for the sustainability of some uses, such as shellfish farming, recreational shellfish harvesting and bathing. The contamination of these environments may occur through the land-spreading of livestock wastes, animal feces deposited on pastures, wastewaters from slaughterhouses. The presence of these bacteria in coastal environment may present a potential risk to human health. In fact, shellfish-borne outbreaks may occur by the consumption of shellfish from contaminated areas. To date, few studies focusing on the presence and the diversity of enteric bacteria, such as pathogenic Escherichia coli (E. coli) more precisely, Shiga-toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC) in coastal environments and shellfish have been reported.For this purpose, during a 2-year study, shellfish batches, freshwater, seawater, and surface sediment samples from three French selected shellfish-harvesting areas and their upstream catchments, were analyzed to evaluate the presence of STEC and EPEC strains. Twenty-eight STEC and 89 EPEC strains were isolated representing 1% of the total E. coli(n=12 016). The isolated STEC and EPEC strains belonged to a high diversity. One STEC strain isolated from a mussel batch, belonging to the serotype O26:H11 displayed 47 additional virulence genes. Seventy-five percent of EPEC strains displayed several virulence genes associated with pathogenicity islands specific to pathogenic E. coli involved in human infections.No difference in the kinetics of the contamination and depuration of oysters by STEC and non-STEC E. coli was found.To our knowledge, this study is the first to focus on the diversity of STEC and EPEC strains isolated from coastal environments. This study highlights the weak presence of STECs and EPECs in the French shellfish-harvesting areas studied and a potential pathogenicity of some strains. The low prevalence of STEC and EPEC strains in shellfish fromB- and C-categories (depuration of shellfish before commercialization), is rather in favor of a limited risk of contamination of shellfish in the studied areas. The results obtained during this study are important to better understand the health risk associated with STEC and EPEC in coastal areas.

La mission spatiale Euclid a pour but d'apporter des réponses quant à la nature de l'accélération de l'expansion de l'Univers. Afin de déterminer les propriétés de cette accélération, la mission spatiale Euclid va effectuer un relevé de galaxies sur 15 000 deg² de champ en imagerie (instrument VIS) et en spectroscopie (instrument NISP) qui requiert un contrôle des précisions instrumentales, notamment sur le système de détection. L'étude faite pendant la thèse se résume en plusieurs étapes: la première étant d'évaluer les performances du NISP à partir de la définition du rapport signal sur bruit et d'en tirer des spécifications sur le système de détection. La seconde consiste en l'étude du besoin de la caractérisation du système de détection de l'instrument, les détecteurs H2RG. À partir de cette étude, on montrera les performances d'un détecteur sur un banc de test. La troisième étape consiste en l'étude de la détection de rayons cosmiques en vol ainsi que la réalisation d'un outil pour isoler les pixels impactés lors du traitement de données au sol. Après avoir évalué les performances de l'algorithme, on montrera les résultats de l'analyse de données. La dernière partie est l'étude de l'effet de persistance affectant les détecteurs H2RG: à partir de l'impact de ce signal sur les observations du NISP, on définira le besoin de mesures de cet effet. On décrira la campagne de prise de données, accompagnée de leur analyse et de l'interprétation physique de la persistance. Ces analyses permettant de comprendre les problématiques de l'effet de persistance et ont servi à l'élaboration d'une modélisation de cet effet pour estimer quantitativement l'impact sur la mission Euclid. / The Euclid space mission aims to provide answers about the nature of the accelerating expansion of the Universe. To determine the properties of this acceleration, the Euclid space mission will conduct a survey of galaxies on a field of 15,000 deg² field of view. Each field will be studied through imaging (VIS instrument) and spectroscopy (NISP instrument) that requires control of instrumental errors, and particularly the detection system. The study made for the thesis can be summarized in several stages: the first is to assess the performance of NISP starting from the definition of the signal to noise ratio and to derive specifications on the detection system. The second is the study of the need for characterization of the detection system of the instrument, the H2RG infrared detectors. From this study, we show the performance of a detector on a dedicated test bench. The third step is the study of the detection of cosmic rays in flight as well as the realization of a tool to isolate the pixels affected using ground data processing. After evaluating the performance of the algorithm, we will show the results of the data analysis. The last part is the study of the persistence effect affecting H2RG detectors: from the impact of the signal on the observations of NISP, we will define the necessary measures for this purpose. We will describe the data acquisition campaign, accompanied by the analysis and physical interpretation of persistence. These analyzes helped to understand the issues of the persistence effect and were used to develop a model of the effect to quantitatively estimate the impact on the Euclid mission.

Master of Science / Department of Agricultural Economics / Elizabeth Yeager / The main objective of this analysis was to examine the profitability and efficiency of Kansas farms in order to draw inferences among the profitability, efficiency, and growth of agricultural producers in Kansas. The time period analyzed was 2005 to 2015. Farms in the sample include a mix of 564 crop and/or livestock operations with 11 years of continuous data through the Kansas Farm Management Association data-bank. Efficiency scores were calculated to determine how close each farm was to the production possibilities frontier, or their cost efficiency. Profitability measures, (operating profit margin and return on assets), were obtained for each farm. The profitability dynamics in 2014 and 2015 for these farms changed compared to previous years. Crop farms generated less profits in 2014 and 2015 compared to previous years, and relative profits from average fluctuated more for sampled farms in 2014 and 2015. Farms were also categorized into risk classes. These classifications aim at distinguishing farms that are profitable or not, and their level of solvency, utilizing their net farm income from operations and their debt to asset ratio. Farms are migrating from the low risk classification, showing that Kansas farms are becoming less profitable, but are not transitioning to a higher risk solvency state. These farms will need to focus on utilizing their inputs more efficiently to keep their solvency levels in check. After analyzing persistence in profitability, the results suggest that farms with higher return on assets tend to be more solvent, but farms with higher operating profit margin tend to be less solvent. The analysis also suggests that there might have been persistence in profits in the years prior to 2015. The analysis of relative positioning of farms in terms of return on assets suggests that during 2007-2011 some farms were able to consistently differentiate themselves by generating either below or above normal profits. Some farms were able to become more profitable in 2012 and 2013, while others lagged behind supported by regression results that signaled divergence of profitability levels. The relative positioning analysis for operating profit margin indicates that farms had similar operating profit margins from 2010 through 2014, and divergence occurred in 2015 by farms that were able to differentiate themselves more through the average operating profit margin. Next the efficiencies of the farms were examined. Analysis of the efficiency scores suggests that the cost efficiencies of Kansas farms are not explained by risk classification significantly, but the crop-labor percentage ratio significantly explains the cost efficiency of the farms. The relationship between cost efficiency and profitability measures proved to be the strongest out of the three performance measures due to their correlation. The final step in the analysis was to examine farm characteristics of the top performing farms. Farms were ranked by profitability measurements and the efficiency measure. Variables of interest that were significantly different between the top 25 percent and the bottom 25 percent of farms include total farm assets, value of farm production, crop-labor percentage, crop acres, number of workers, and age of operators.

This qualitative study utilized surveys, interviews and document review to explore the transition experiences of international students at a large, public research university, specifically as it relates to their persistence and success. Within the context of challenges that they face, the study examined factors that the students perceived as jeopardizing their success and further explored both institutional and personal factors these students perceived as enhancing their success and persistence. Findings revealed that academic challenges tended to occur during the first year and included teaching styles, course-load/assignments, language issues, time management and understanding the US academic system. Social and cultural challenges included homesickness, cultural misunderstandings, culture-shock and language barriers. Daily living challenges included transportation, finances, food, visa/immigration issues, job restrictions and housing. The study results also indicated that students utilized a blend of coping strategies, support systems and personal strengths to overcome these challenges and persist. More specifically, students identified campus involvement, family support, friend support and university support services as integral to their success. The findings from this study have implications for faculty, as well as student affairs, international services and orientation practitioners as they identify international student needs and challenges as well as factors that positively impact international student persistence and success.

Les principaux processus et facteurs qui influent sur le devenir du glyphosate dans les sols et le risque de contamination de la ressource en eau ont été étudiés. Son adsorption sur les sols est très rapide (Kf compris suivant le sol entre 16,6 à 34,5) et l’effet du pH sur ce processus a été confirmé : l’adsorption diminue quand le pH des sols augmente. Par contre, le glyphosate se désorbe difficilement et sa dégradation en conditions contrôlées ou naturelles est rapide, mais sa dynamique est très variable suivant l’activité biologique des sols. La dégradation conduit à la formation d’un métabolite, l’AMPA qui tend à s’accumuler dans le sol. L’expérimentation en colonnes de sol confirme la faible mobilité du glyphosate et de l’AMPA. Les résidus exportés par les percolats sur une période de 332 jours représentent moins de 0,28 % de la dose appliquée. Les propriétés hydrodynamique du sol et la pluviométrie rencontrée ont un effet important dans le lessivage des résidus. / The main processes and factors which influence glyphosate fate in soils and the risks of water resources contamination were studied. Its adsorption in the soils was very fast and intense (Kf between 16.6 to 34.5 depending on the soil) and the effect of pH on this process was confirmed: adsorption decreases when soil pH increased. In addition, glyphosate was slightly desorbed and its degradation in controlled or natural conditions was fast, but its kinetics was very variable according to the biological activity of the soils. Degradation led to the formation of the metabolite (AMPA), which tends to accumulate in the soil. The experimentation in columns of different soils confirmed the low mobility of the glyphosate and the AMPA. The residues exported by the leachates after more than 332 days represented less than 0.28% of the amount applied. The hydrodynamic properties of the soil and the pluviometry observed had a significant effect on the leaching of the residues.

The purpose of this study was to compare response rates and resistance to extinction in single-task and multiple-task phases. Research was conducted with thirty undergraduate college students in a controlled experimental setting. Each Participant was exposed to 4 treatment phases: single-task, fixed-ratio of one (ST-FR1), multiple-task fixed-ratio of one (MT-FR1), single-task fixed-ratio of 5 (ST-FR5) and multiple-task fixed-ratio of 5 (MT-FR5) all beginning with a baseline phase and reverting back to baseline after the first two conditions were presented. Half of the Participants received the single-task phase first, and the other half received the multiple-task phase first, in order to observe the behavior in transition. A trials-to-criterion measure was used to determine how long it took each Participant’s behavior to adapt to the new contingency in the next phase, which was presented without any signal. The data reveal that regardless of the order of phase presentation it took Participants more than twice as long to reach the criterion in the single-task phases, than in the multiple-task phases.