Les adaptations florales à des pollinisateurs comme les changements de forme de la corolle entraînent souvent un isolement reproducteur et donc la spéciation. Malgré leur importance écologique, les mécanismes génétiques à l'origine de cette diversité de caractères sont encore mal compris, surtout en dehors des espèces modèles. L’objectif de mon projet de maîtrise était donc d'identifier les gènes impliqués dans la variation de la forme de la corolle entre deux espèces du genre Rhytidophyllum (famille des Gesneriaceae), qui ont des modes de pollinisation différents. La première, R. rupincola, a des fleurs tubulaires et est strictement pollinisée par les colibris, tandis que la seconde, R. auriculatum, a des fleurs plus ouvertes et est pollinisée par les colibris et les chauves-souris. Dans cette étude, nous avons fait une revue de littérature et utilisé une approche de transcriptomique comparative pour identifier des gènes candidats qui pourraient expliquer la variation de la forme florale entre R. auriculatum et R. rupincola. Nous avons ensuite testé leur association avec la variation de la forme de la corolle en utilisant la cartographie de loci de traits quantitatifs (QTLs) pour une population hybride F2. Les résultats ont montré que 7 des 29 gènes candidats étaient associés à 8 QTLs différents. La répartition et la fonction supposée de ces gènes suggèrent que la forme de la corolle est un trait complexe. Ce type d'étude est rarement entrepris chez des espèces non-modèles, mais il est important afin d'intégrer la génétique du développement floral dans une perspective évolutive. / Floral adaptations to specific pollinators like corolla shape changes often result in reproductive isolation and thus speciation. But despite their ecological importance, the genetic mechanisms behind this diversity of traits are still poorly understood, especially outside model species. Hence, our goal is to identify genes involved in corolla shape variation between two species of the Rhytidophyllum genus (Gesneriaceae family) from the West Indies, which is characterized by shifts in pollination modes during its evolution. The first one, R. rupincola, has a tubular corolla and is strictly pollinated by hummingbirds. The second one, R. auriculatum, has more open flowers and is pollinated by both hummingbirds and bats. We know from previous work that the variation in morphological floral traits between these species is explained by a few quantitative trait loci (QTLs) of moderate to small effect (Alexandre et al., 2015), but we still do not know which genes underly these loci. In this study, we surveyed the literature and used a comparative transcriptomic approach to identify candidate genes that could explain floral variation between R. auriculatum and R. rupincola. We then tested their association with corolla shape variation using QTL mapping for a F2 hybrid population. Results showed that 7 out of 29 candidate genes were included within 8 different QTL. The number, repartition and putative function of these genes suggest that corolla shape is a complex trait. This sort of investigation is rarely undertaken in non-model species, but is important to integrate developmental genetics with an evolutionary perspective.

La Serbie n’est certainement pas ce que l’on pourrait désigner comme étant un Etat typique de l’Europe centrale et du Sud-Est. Alliée fidèle de la Russie et de la Chine, elle a subi les plus longues sanctions internationales en Europe et des bombardements de l’OTAN en 1999. Depuis la chute du régime de Milošević en 2000, l’ « enfant terrible » du continent a vocation à adhérer à l’Union européenne, or la tendance n’est clairement pas à l’élargissement. Face aux nombreuses crises (économique, migratoire et démocratique), l’UE parait impuissante à plusieurs égards. Symbole pendant longtemps du développement, de la paix et de la démocratie, elle doit faire face à une perte d’attractivité ces dix dernières années. Toutefois, malgré les doutes de part et d’autre, Bruxelles ne peut pas se permettre de ne pas tendre la main à la Serbie qui a une place centrale dans les Balkans, de par son poids démographique et sa position géostratégique. Le 1er mars 2012, la Serbie a officiellement obtenu son statut de candidat à l’UE. En signant l’accord d’association et de stabilisation, Belgrade s’est engagé à aligner sa législation sur l’acquis communautaire et donc à effectuer de nombreuses réformes. Or, sur fond d’acculturation et de déculturation juridique, des voix s’élèvent contre les réformes en chaîne dans le seul but d’intégrer l’institution européenne. L’un des objectifs de cette thèse est d’éclairer la nature et l’avancée de ces réformes à travers les critères politiques, définis lors du Conseil européen de Copenhague en 1993. Elle étudie les difficultés que la Serbie partage avec tous les Etats du Sud-Est de l’Europe et les difficultés qui lui sont propres, tout en questionnant sur la nécessité et les conséquences de ces changements. L’étude des négociations entre Bruxelles et Belgrade est aussi l’occasion d’apporter un éclairage sur le fonctionnement de l’institution européenne et de constater les limites de l’ambigüité constructive chère à l’UE. Finalement, le comportement de l’Union européenne à l’extérieur de ses frontières est symptomatique de son comportement à l’intérieur. / Serbia is certainly not a typical state of Central and Southeastern Europe. A loyal ally of Russia and China, it suffered the longest international sanctions in Europe and NATO bombings in 1999. Since the fall of the Milošević regime in 2000, the "enfant terrible" of the continent is destined to join the European Union. However, the trend is clearly not toward a enlargement. Facing multiple crises (economic, migratory and democratic), the EU seems powerless in many ways. Although the EU has been regarded as a symbol of development, peace and democracy, it has suffered a loss of attractiveness in the last ten years. However, despite doubts on both sides, Brussels cannot afford not to reach out to Serbia, which has a central position in the Balkans, because of its demographic weight and its geostrategic position. In March 2012 Serbia was granted EU candidate status. By signing the Stabilisation Agreement, Belgrade is committed to a gradual harmonization of legislation with the acquis of the European Communities and thus implement many reforms. However, in a context of legal acculturation and deculturation, some voices are rising to denounce a chain of reforms for the sole purpose of joining the European institution. One of our aims is to clarify the nature and progress of these reforms through the political criteria, defined at the Copenhagen European Council in 1993. We will hence study the difficulties that Serbia shares with all the states from Southeast Europe and its own problems, by questioning the necessity and consequences of these changes.The study of the negotiations between Brussels and Belgrade is also an opportunity to examine the functioning of the European institution and to note the limits of constructive ambiguity cherished by the EU. Finally, the behavior of the European Union outside its borders is symptomatic of its behavior inside.

This dissertation examines elementary teacher candidates' perceptions of hip-hop culture and utilizing hip-hop pedagogy in a mathematics classroom. This study demonstrates how elements of hip-hop may be integrated into an elementary mathematics methods course to develop pedagogical knowledge that challenges teacher candidates to explore the benefits of utilizing hip-hop as a tool in the classroom. This study contributes to the growing body of research that investigates the use of hip-hop pedagogy in educator preparatory programs. Participants in this study were teacher candidates at a large university in Texas enrolled in the final year of their educator preparatory program. This research shows that as a result of integrating hip-hop pedagogy in the mathematics methods course, teacher candidates had increased knowledge and more positive perceptions of hip-hop culture, and they demonstrated a greater willingness to integrate hip-hop pedagogy in their future classrooms.

This work is aimed at the problems of finding and selecting employees through the application of the latest knowledge and approach of staff selection. From the knowledge gained it suggests a possible method of choosing employees in the company, ABC Ltd. for the position of a dealer.

L’hybridation avec des ressources génétiques allochtones est largement pratiquée chez les plantes ornementales pour introduire de nouveaux caractères. Au cours du 19e siècle, âge d’or de la sélection des rosiers en France, des rosiers asiatiques ont été introduits en Europe. L’objectif ici est d’étudier l’évolution de la diversité génétique des rosiers cultivés en France au cours de cette période. La diversité a été étudiée à l’échelle du génome puis à l’échelle de gènes candidats codant pour des caractères potentiellement sélectionnés au cours du 19e siècle. Un échantillon de 1228 rosiers illustrant la diversité génétique des rosiers français cultivés à cette période a été génotypé avec 32 microsatellites. Une large diversité, structurée en seize groupes génétiques et une différenciation entre les rosiers anciens européens et les rosiers asiatiques ont été détectées. Un déplacement du fond génétique des hybrides cultivés d’un type européen vers un type asiatique a été observé au cours du 19e siècle. Les croisements fréquents et/ou la sélection pour des caractères présents chez les rosiers asiatiques ont pu induire cette évolution. Certains caractères phénotypiques, comme la remontée de floraison, deviennent prépondérants. Onze gènes candidats ont été séquencés et leur diversité a été analysée sur un sous-échantillon de 365 rosiers. Parallèlement au fond génétique, certains gènes présentent un rapprochement génétique vers des allèles asiatiques. Pour le gène KSN, une augmentation de la fréquence d’allèles portant le rétrotransposon copia, responsable de la remontée de floraison, est observée. / Innovation in ornamental plant breeding is commonly obtained by hybridization with newly introduced genetic resources. During the 19th century, golden age for rose breeding in France, Asian roses were introduced in Europe. Our objective here was to study and explain the evolution of rose genetic diversity in France during this period of time. The diversity was studied at the genome scale and at the candidate gene scale. A large sample of 1228 garden roses illustrating the French rose diversity from this period of time was genotyped with 32 microsatellites markers. A wide diversity, structured into sixteen genetic groups, was observed. A geneticdifferentiation was detected between ancient European and Asian accessions and a continuous temporal shift was observed in cultivated hybrids from a European to an Asian genetic background during the 19th century.Frequent crosses with Asian roses along the 19th century and/or selection for Asiatic traits may have induced this shift. Some phenotypic traits, like continuous flowering, became overriding traits. Eleven candidate genes, which were potentially selected during the 19th century, were sequenced and their diversity was analyzed on a subsample of 365 roses. Simultaneously to the genetic background, some genes are gettingcloser to Asian alleles. For the KSN gene, an increase in the frequency of alleles carrying the retrotransposon copia, responsible for continuous flowering, is observed.

While the molecular defect that cause sickle cell disease has well been established, the cause of vaso-occlusive crisis remains elusive and largely debated upon. Majority of studies have linked the painful episodes to polymerization of sickle hemoglobin following its deoxygenation. The variability of the disease symptoms among patients, compounds efforts for a holistic therapy. Hydroxyurea, a stimulator of Hb F induction and a widely used treatment, has ameliorated the complication of SCD but it is only effective in 50% of the patients. Expression of Hb F lowers the content of Hb S in blood and hence reduces oxidative stress caused by Hb S denaturation. Sickle cell disease severity depends on several factors. Most importantly, the ability of red cell to sickle dominates all other determinants. While deoxygenation of sickle hemoglobin may be inevitable, the duration with which the red cell remains in the deoxygenated state can be manipulated. Deoxygenation is a transient process that when compared to the time taken to develop the long filaments of deoxyhemoglobin to causes severe sickling, the red cell would have been cycled back to the lungs and re-oxygenated to restore the healthy conditions of the cell. In fact, if sickle cells would flow as fast as healthy erythrocytes, the detrimental impacts of sickling such as vaso-occlusive crisis, would not be a concern for this disease. Unfortunately, the unstable sickle hemoglobin undergoes denaturation through auto-oxidation, which imposes oxidative stress to the cells. The oxidative stress inhibits erythrocytes tyrosine phosphatases, a course which subsequently impair their constitutive action against the tyrosine kinases. In the end, a net tyrosine phosphorylation state in the red cell membrane proteins, most notably the transmembrane protein band 3, succeeds. Band 3 tyrosine phosphorylation abrogates the protein’s interaction with ankyrin and spectrin-actin cytoskeleton, hence the cytoskeleton loses its major anchorage to the membrane thus engendering membrane destabilization. A destabilized erythrocyte sheds membrane fragments in form of microvesicles/microparticles and discharges free hemoglobin into the extra cellular matrix. In consequence, the microparticles power initiation of coagulation cascade through activation of thrombin, while free Hb inflicts inflammation, scavenges nitric oxide which is necessary for vasodilation and induces further oxidative stress within the microvasculature, and activates expression of adhesion receptors on the endothelium. Taken together, these events culminate in entrapment of red cells (not naming leucocytes and platelets) in the microvasculature, blockade of blood vessels and further damage of erythrocytes through prolonged deoxygenated state thus terminating in tissue injury, strokes, and organ damage, amid vaso-occlusive episodes which always require hospitalization and extensive medical care for survival. Band 3 tyrosine phosphorylation and membrane weakening is not unique just to SCD, but also a druggable target for malaria. Malaria, a disease that is touted as the evolutionary cause of sickle cell disease, surprisingly thrives through the same mechanism. Briefly, malaria parasite consumes hemoglobin for its DNA synthesis, and in the process generate reactive oxygen species from denatured hemoglobin that feeds into the oxidative stress which triggers band 3 tyrosine phosphorylation. In this case however, a destabilized membrane offers perfect conditions for merozoites’ (malaria daughter parasites) egress/exit out of the cell to begin infecting other red cells. Ultimately, the ensuing anemia and organ dysfunction leads to patient’s death. Treatment of diseased cells with imatinib and other Syk inhibitors effectively reversed membrane weakening. A stabilized membrane not only survives longer in circulation to alleviate SCD symptoms but also traps and starves malaria parasite leading to termination of the parasitic infection. With band 3 tyrosine phosphorylation at center stage, this dissertation explores the above events in an effort to unveil a novel therapy for sickle cell and malaria diseases. First, the therapeutic strategy regarding SCD is discussed in detail beginning with non-transfused patients and ending in additional mechanistic study on inactivation of the principal erythrocyte’s protein tyrosine phosphatase 1 B, PTP1B. The dissertation then provides an initial proof of concept on efficacy of imatinib in treatment of malaria as a monotherapy and its efficacy when used in a triple combination therapy with the standard of care treatment. Finally, I outline an alternative possible mechanism of action of quinine against malaria.

This thesis concerns repeated returns of homeless people to social services. The theoretical part focuses on the description and the problem areas of homeless people, cultural-historical development of homelessness in Czech lands - defines the term of social services and discusses the model of work with the target group in Poland. At the end of the theoretical part a Center for homeless people the Bohuslav Bures social services center (BBSSC) Salvation Army is presented, in this way methods of work with the target group are demonstrated, the way of keeping documentation is described and the analysis of the shelter home relevant to the theme of the work are publicized. The research carried out in the practical part looks for factors which have caused the return of the former users of social services. For the purposes of the work the phenomenon of returning is studied in persons, who in the period of 2007 - April 2012 used a shelter home in BBSSC in Salvation Army, left for commercial housing and after their departure they come back to BBSSC within one year as candidates for a social service. In order to find this information semi- standardized interviews were held and analysis of the data was carried out (a study of documentation of personal files). This work finds out the factors which might have...

<p>  </p> <p>A multidisciplinary study that evaluated Quality Control (QC) laboratory (lab) accreditation, and a salt screen for bedaquiline. Medicines testing facilities always seek to ensure the accuracy of data from their QC labs by attaining accreditation. This research proposed that an understanding of the cross-linkages in the requirements for implementing the 2 most widely used lab standards will facilitate testing efficiencies, and reduce the risks of accreditation failures. For the salt project, the study proposed that new salts of bedaquiline will be formed from acid-base reactions following the pKa rule. Characterizing the salts will provide specifications for the new molecular entities, and form a selection-criteria for a lead candidate.</p> <p>The research reviewed 2 lab standards: the ISO/IEC17025:2017 and the WHO Good Practices for Pharmaceutical QC labs, and identified the areas of overlap in their requirements. It then developed and tested affordable models that mitigate the 3 identified areas of high risks to lab accreditation. Additionally, it mixed<em> equimolar amounts of bedaquiline base with select counterions that have ≥ 2 pKa units in organic solvents, to yield salts</em>. ICHQ6 guidance was used to characterize the new salts.</p> <p>The highest risks to laboratory accreditation were linked to 3 quality system metrics, namely: ‘Proficiency Testing’, ‘Validation’, and ‘Measurement Traceability’. Using the identified areas of overlap in the 2 laboratory standards, this research provided tutorial videos, a competency matrix, and some instrument validation data, to optimize the requirements for lab accreditation. For the salt screen, five new candidates were synthesized as alternatives to the existing fumarate salt of bedaquiline. The results of their physicochemical properties were used for selecting a lead moiety.</p> <p>The research provided evidence that the multipronged models developed will improve efficiencies in QC labs, and increase their chances of attaining international accreditations. It also discovered the best modes for synthesizing the new salts of bedaquiline, and provided critical data to help Pharma make an informed choice for a lead candidate.</p>

Worldwide, alcohol is the third leading risk factor for disease burden, while its harmful use leads to 2.5 million deaths every year. Alcohol dependence (AD) is a complex disease, with devastating effects on individuals, families, and society. It is estimated that 76.3 million people worldwide have suffered from alcohol use disorders (AUD), including alcohol abuse and AD. Alcohol withdrawal or alcohol withdrawal symptom (AWS) refers to a cluster of symptoms that may occur when a heavy drinker suddenly stops or significantly reduces their alcohol intake. These symptoms can start as early as 2 h after the last drink, persist for weeks, and range from mild anxiety and shakiness to severe complications, such as seizures and delirium tremens. Family, twin, and adoption studies have indicated that genetic and environmental factors and their interactions contribute to the development of AD and related phenotypes, with a heritability coefficient of more than 0.5 for AD. Whole-genome linkage and candidate gene association studies have successfully identified several chromosome regions and genes that are related to AD and AWS. Furthermore, gene expression analysis, epigenetic studies, and genome-wide association studies (GWAS) have provided regions and loci for AWS. This chapter reviews the recent findings in genetic studies of AWS.

Les travaux effectués durant cette thèse de doctorat ont pour but d’augmenter l’efficacité de codage dans 3D-HEVC. Nous proposons des approches conventionnelles orientées vers la normalisation vidéo, ainsi que des approches en rupture basées sur le flot optique. En approches conventionnelles, nous proposons une méthode qui prédit les modes Intra de profondeur avec ceux de texture. L’héritage est conditionné par un critère qui mesure le degré de similitude entre les deux modes. Ensuite, nous proposons deux méthodes pour améliorer la prédiction inter-vue du mouvement dans 3D-HEVC. La première ajoute un vecteur de disparité comme candidat inter-vue dans la liste des candidats du Merge, et la seconde modifie le processus de dérivation de ce vecteur. Finalement, un outil de codage intercomposantes est proposé, où le lien entre les arbres quaternaires de texture et de profondeur est exploité pour réduire le temps d’encodage et le débit, à travers un codage conjoint des deux arbres. Dans la catégorie des approches en rupture, nous proposons deux méthodes basées sur l’estimation de champs denses de vecteurs de mouvement en utilisant le flot optique. La première calcule un champ au niveau d’une vue de base reconstruite, puis l’extrapole au niveau d’une vue dépendante, où il est hérité par les unités de prédiction en tant que candidat dense du Merge. La deuxième méthode améliore la synthèse de vues : quatre champs sont calculés au niveau de deux vues de référence en utilisant deux références temporelles. Ils sont ensuite extrapolés au niveau d’une vue synthétisée et corrigés en utilisant une contrainte épipolaire. Les quatre prédictions correspondantes sont ensuite combinées. / This PhD. thesis deals with improving the coding efficiency in 3D-HEVC. We propose both constrained approaches aimed towards standardization, and also more innovative approaches based on optical flow. In the constrained approaches category, we first propose a method that predicts the depth Intra modes using the ones of the texture. The inheritance is driven by a criterion measuring how much the two are expected to match. Second, we propose two simple ways to improve inter-view motion prediction in 3D-HEVC. The first adds an inter-view disparity vector candidate in the Merge list and the second modifies the derivation process of this disparity vector. Third, an inter-component tool is proposed where the link between the texture and depth quadtree structures is exploited to save both runtime and bits through a joint coding of the quadtrees. In the more innovative approaches category, we propose two methods that are based on a dense motion vector field estimation using optical flow. The first computes such a field on a reconstructed base view. It is then warped at the level of a dependent view where it is inserted as a dense candidate in the Merge list of prediction units in that view. The second method improves the view synthesis process: four fields are computed at the level of the left and right reference views using a past and a future temporal reference. These are then warped at the level of the synthesized view and corrected using an epipolar constraint. The four corresponding predictions are then blended together. Both methods bring significant coding gains which confirm the potential of such innovative solutions.