Dissertations / Theses on the topic 'Gambia migration'

Crossing the Sahara to reach Libya for the purpose of onward migration across the Mediterranean to Italy is what in Gambia is called “The Back Way”. The aim of this study is to examine the ambitions and reasons behind a migratory project from The Gambia to Europe. By identifying the key constituents of a migration culture, I can get a broader insight into why the celebration of migration is evident, and how the ‘story of Europe’ is shaped. I have interviewed Gambians who are geographically in different places and who all find themselves in different life trajectories, most of them connected to migration. My conversations about migration, “The Back Way” and Europe stretches from interviews with repatriates, aspiring migrants and non-migrants. I have also interviewed Gambians in the Diaspora. In this study, I found a strong societal expectation and hope towards both migration and the diaspora which in return caused certain diasporic behavior that painted a misleading picture of Europe. I also found a strong hope and resilient aspirations in terms of social status and recognition believed to be attained easier as a migrant coming back from Europe.

Irregular migration is one of our times challenge and the news about migrants dying in the Mediterranean Sea seems to be more and more common these days. African migrants are risking their lives migrating by routes through the desert on trucks packed with migrants to get to Libya; this route is called the back way. From Libya they are crossing the Mediterranean Sea in small over loaded boats with the hope to reach Italy. This study focus on young Gambian men who say that they are prepared to risk their life by going the back way in order to reach Europe. Gambia is a small country in West Africa, a country that has been free from violence and war, a peaceful country. Yet the back way is something that is on everybody’s lips in Gambia today and a lot of people, especially young men, are trying to get to Europe through that way. This research is looking into why these young men are prepared to risk their lives to reach Europe; it is showing what it is that make people take their decisions to go. In order to find answers to this, interviews with young men in Gambia has been done and the material have then been analyzed with the help of the push and pull model, the rational choice theory and Charles Tilly’s ideas about durable inequality. What can be understood from the findings in this research is that people migrate in order to improve their lives. They consider the back way only because that is what is available to them since the legal ways of getting to Europe are few and hard to get for somebody from the developing world. The research also shows that your position in the family and in the society plays a crucial part in the decision of going or not going.

Urbanisation and the associated nutrition transition have been linked with the recent rise in osteoporotic fragility fracture incidence in many countries. Predictions indicate that hip fracture incidence will increase 6-fold in Africa and Asia by 2050, partially attributed to demographic transition and population ageing. Differences in areal bone mineral density (aBMD) between rural and urban locations indicate that urban regions of high-income countries (HIC) have lower aBMD and a higher incidence of hip fracture. The few studies conducted in low and middle-income countries (LMIC) provide inconsistent results; in contrast to HIC, most have found higher aBMD in urban populations. To investigate the impact of migrating to an urban environment, detailed studies of bone phenotype and factors affecting bone health have been conducted in two groups of pre-menopausal Gambian women: urban migrant (n=58) and rural (n=81). Both groups spent their formative years in the same rural setting of Kiang West, urban women were known to have migrated to coastal districts, concentrated in Brikama and Kanifing, when aged ≥16 years. Bone phenotype (bone mineral content (BMC); bone area (BA); aBMD, and size-adjusted BMC (adjusted for height, weight and BA) of the whole-body, lumbar spine and hip) was measured by dual energy x-ray absorptiometry (DXA), with further characterisation by peripheral quantitative computed tomography (pQCT). Data were also collected on anthropometry, body composition, food and nutrient intakes, physical activity, socio-demographic characteristics, vitamin D status, and 24hr urinary mineral outputs (Na, K, P, and Ca). Mean age and height of rural and urban migrant groups were not significantly different (p > 0.05). Urban migrant women were significantly heavier (p < 0.01). Significant differences in BMC and aBMD were found between groups at all skeletal sites, with urban women having higher BMC and aBMD; BA was not significantly different. The greatest difference in BMC was found at the lumbar spine (8.5% ± SE 3.0, p < 0.01), a meaningful difference, equivalent to 0.76 of rural SD. T- Scores were also calculated using a young adult (white, female) reference population, mean T- scores were -1.03 and -0.22, for rural and urban groups respectively. After adjusting for size, differences in whole-body and hip BMC were mostly attenuated (p > 0.05), but difference in spine BMC remained significant (6.2% ± SE 2.1, p < 0.01). These results indicate that rural-to-urban migration is associated with higher BMC; BA and height were similar, and difference in body weight could not fully account for higher BMC at the lumbar spine. Calcium intakes were low in both groups, urban migrant 294mg/d (IQR: 235 to 385) and rural 305mg/d (IQR: 222 to 420). Urban women had significantly lower intakes of potassium, magnesium and dietary fibre (p < 0.01), related to lower consumption of fruit, green leafy vegetables and groundnuts. 25-hydroxy vitamin D status was good in both groups, urban migrant 64.0 ± 14.2nmol/L and rural 68.3 ± 15.7nmol/L (M ± SD, p > 0.05). Implications for bone health of the nutrition and demographic transition, principally future fracture risk and other non-communicable diseases require further research in LMICs. ORIGINAL CONTRIBUTION TO KNOWLEDGE To my knowledge, this is the first study investigating the impact of rural-to-urban migration on bone health to be conducted in sub Saharan Africa. It is the first study of bone health and determinants of bone health in an urban population in The Gambia.

Cette thèse vise à contribuer à une meilleure compréhension des facteurs qui agissent sur la décision de migrer des individus. Dans le chapitre 1, nous montrons qu’au Portugal, les immigrés occupent souvent des postes pour lesquels ils sont surqualifiés, et que cette non-adéquation entre profils et emplois occupés influence la sélection dans la migration. Les phénomènes de surqualification, plus marqués chez les individus les plus qualifiés, entrainent une sélection négative des migrants, tandis qu’une bonne adéquation entre profils et emplois conduit à une sélection positive.Dans le chapitre 2, nous tirons profit d’une expérimentation sur le terrain pour comprendre comment les décisions de migrer illégalement vers l’Europe des jeunes gambiens sont influencées par l’information qu’ils ont sur les risques associés à cette mobilité. Nous montrons d’abord que les participants au jeu surestiment à la fois le risque de périr en route et la probabilité d’obtenir un statut légal en Europe. Nos résultats suggèrent par ailleurs que la décision de migrer illégalement est influencée par l’une et l’autre probabilité. Informer les candidats au départ sur les risques réels encourus pourrait ainsi les aider à prendre des décisions en connaissance de cause et contribuerait peut-être à sauver des vies. Dans le chapitre 3, nous examinons les liens entre structure familiale et migration, en étudiant l’influence du type d’union des mères sur le comportement migratoire de leurs enfants. Nous trouvons que les enfants nés de mères en union polygame sont plus enclins à migrer vers l’étranger. Nous expliquons ce résultat par la rivalité fraternelle qui en découle
The purpose of this thesis is to contribute to a better understanding of the drivers of international migration. In Chapter 1, we document that immigrants in Portugal face a high incidence of occupational-skill mismatch, and show how it affects the selection into migration. We find that the incidence of over-education leads to negative selection while correct occupational-skill matches lead to positive selection. In Chapter 2, we rely on a lab-in-the-field experiment to understand the willingness to migrate illegally of young males aged 15 to 25 in The Gambia. We first show that potential migrants overestimate both the risk of dying en route to Europe, and the probability of obtaining legal residency status. The experimental results suggestthat the willingness to migrate illegally is affected by information on the chances of dying en route and of obtaining a legal residence permit. Providing providing potential migrants with official numbers on both probabilities thus affect their likelihood of migrating. This has the potential to help migrants make informed decisions and perhaps save lives. In Chapter 3, we investigate the impact of family structure on international migration decisions. We find that children of mothers in polygynous unions are more likely to migrate internationally. We provide further evidence suggesting that this result is due to sibling rivalry: having full- or half-siblings in migration increases the likelihood of migrating. Our evidence suggests that co-wives’ rivalry as documented elsewhere trickles down to children’s rivalry in migration, suggesting that while neglected in the literature, family structure is crucial to understanding migration

Satellite cells are adult stem cells that contribute to hypertrophy and repair in muscles. It is hypothesized that in muscular dystrophy, the satellite cells population is depleted at a very early age, due to repeated muscle damage and repair. Satellite cell transplantation is a potentially useful therapy for muscle diseases, but the lack of an efficient delivery system has hindered its application. The presented work focuses on two specific aims that address the need for more effective cell delivery methods for cell-based therapy. In Specific Aim 1 enhanced tissue culture techniques, such as heat stress, are used to increase cell survival in satellite cell transplantation studies. Also addressed within this specific aim are methods to label and evaluate performance using real-time PCR techniques.Although much work remains to enhancing the viability of in vitro expanded myoblasts derived from satellite cells, a second important hurdle is the systemic delivery of satellite cells to multiple sites (all muscles, in the case of muscular dystrophies). In vitro and in vivo experiments are being undertaken to explore the physiological role of cell signaling systems involved in directed migration and to determine if these chemokine and growth factors can be manipulated to enhance efficacy of cell-based therapies involving skeletal muscle satellite cells. Specific Aim 2 addresses migration of satellite cells to sites of injury and methods to track transplanted cells within the host. Presented here is the use of FAST SPECT II imaging of 111-Indium oxine radiolabeled satellite cells. The long lifetime of 111-indium oxine and the ability to quantify label using FAST SPECT imaging techniques make this technique ideal for in-vivo tracking of transplanted satellite cells for week long studies. Without in-vivo imaging techniques cell fate studies require sequential animal sacrifice with histological sectioning. This not only increases the number of animals used but also adds a significant inter-animal variability to their assessment. The determination of cell fate after transplantation will have a major impact on cell therapy for treatment of muscle disease as well as other stem cell therapies.

Cette thèse aborde la question de la différenciation culturelle dans les situations de contact créées par les processus migratoires. Comment les évaluent-ils la différenciation culturelle entre la société de départ et celle d'accueil ? Notre hypothèse est que plus la différenciation culturelle est évaluée comme grande par les migrants plus ils auront tendance à faire apparaître dans leurs dynamiques associatives une visibilité de l'ethnicité. Nous avons choisi de faire notre étude de cas sur les migrants originaires des îles du Saloum au Sénégal et dispersés en forme de diaspora. Les itinéraires migratoires que nous avons choisi d'analyser sont ceux qui les conduisent dans les villes sénégalaises, en Gambie et en Gironde (France). Nous avons pu tout à tour analyser, les migrations de proximiyé, des aspects de l'intégration nationale au Sénégal, la transnationalité de la migration, le traitement accorfdé aux flus migratoires par l'État sénégalais et celui français et les enjeux identitaires liés à ces migrations, etc. Nous avons pu vérifier notre hypothèse centrale sur la différenciation culturelle en montrant la variabilité des contenus de l'ethnicité suivant les espaces d'accueil. En effet, suivant que le migrant est en France ou dans une ville sénégalaise ou en Gambie, le contenu du discours sur les appartenances change. Une autre conclusion à laquelle nous sommes parvenus est que les collectivités territoriales françaises tentent de plus en plus de s'appuyer sur l'espaces associatifs immigré pour conduire des projets dans le cadre de la coopération décentralisée. A travers ce travail aussi cest la notion d'altérité qui est revisitée afin de privilégier une approche dynamique dans son analyse. Nous avons essayé de montrer les limites du primordialisme dans l'analyse des cultures en situation de contact. Enfin l'étude des itinéraires migratoires depuis leurs points de départ et dans la longue durée nous a permis de montrer comment les habitus liés à une longue pratique sociale dans ce domaine et les migrations de proximité, préparent les acteurs à investir l'espace international

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Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energéticas e Nucleares - IPEN/CNEN-SP

Les protéoglycanes (PGs) jouent un rôle important dans de multiples processus cellulaires tels que la prolifération, la différenciation et la migration cellulaires. Les PGs sont constitués d’une protéine porteuse sur laquelle sont fixées de façon covalente des chaînes hétéropolyssacharidiques de glycosaminoglycanes (GAGs). L’initiation de la biosynthèse des GAGs sur les PGs implique une glycosyltransférase, la ß1,3-galactosyltransférase 6 (ß3GalT6) qui catalyse l’addition d’un résidu galactose sur un disaccharide accepteur (Gal-Xyl) fixé au niveau de motifs d’ancrage des GAGs sur la protéine porteuse du PG. Des mutations de la ß3GalT6 ont été récemment associées à une forme pléiotropique du syndrome d’Ehlers-Danlos (SED), un groupe hétérogène de maladies génétiques rares touchant les constituants matriciels des tissus conjonctifs. L’implication de la ß3GalT6 dans la pathogénie du SED n’est cependant pas encore connue à ce jour, point qui sera exploré au cours de ce travail de thèse. Nous avons montré que la mutation du gène B3GALT6 conduit à une diminution de la biosynthèse des GAGs matriciels et membranaires, associée à une réduction de la capacité migratoire des fibroblastes de derme humain issus de patients atteints de SED par rapport aux fibroblastes contrôle, non porteurs de l’altération génétique. Une étude “gain et perte de fonction” a montré que l’extinction du gène B3GALT6 dans des fibroblastes contrôle impacte la biosynthèse des GAGs. De façon complémentaire, la restauration de l’expression de la ß3GalT6 dans les fibroblastes des patients a eu pour conséquences une augmentation du taux de synthèse des GAGs matriciels et membranaires, associée à une augmentation significative de la capacité de migration des cellules équivalente à celle des cellules non déficientes. Les résultats obtenus nous permettent de mieux comprendre le rôle de la ß3GalT6 dans la pathogénie du SED. Ces travaux ciblant la ß3GalT6 peuvent ouvrir la perspective de proposer des stratégies thérapeutiques visant à s’opposer à la perte d’anabolisme des GAGs et au défaut de migration observés dans le SED
Proteoglycans (PGs) play important roles in many physiological processes, including cell proliferation, differentiation and migration. PGs are composed of linear heteropolysaccharide chains, called glycosaminoglycans (GAGs), which are covalently attached to a core protein through a tetrasaccharide linkage. The addition of the third residue (galactose) of the linkage is catalyzed by ß1,3-galactosyltransferase 6 (ß3GalT6), a key glycosyltransferase in GAG initiation. Recently, mutations of ß3GalT6 have been associated to Ehlers-Danlos Syndrome (EDS), a group of rare and severe genetic connective tissue disorders. However, the role of ß3GalT6 defects in EDS pathogeny remains unknown. In my thesis, we showed that ß3GalT6 defective dermal fibroblasts of affected patients exhibited a marked reduction in GAG anabolism associated to a significant delay in wound closure compared to control cells. The ß3GalT6 gain- and loss-of-function studies demonstrated that B3GALT6 gene deletion in control fibroblasts affects the synthesis of GAGs chains. Interestingly, GAG anabolism and cell migration were restored when ß3GalT6 is overexpressed in patient fibroblasts, which could be the starting point to the development of therapeutic strategies against the loss of GAG synthesis and defect of cell migration observed in EDS. This work provides a better understanding of the crucial role of ß3GalT6 in EDS pathogeny

Le rôle de l'inflammation dans le développement des maladies cardiovasculaires reste un domaine majeur d'investigation dans la recherche de nouvelles thérapies. En effet, l'inflammation constitue un élément essentiel de la pathologie de l'athérosclérose mais également de la resténose, complication majeure du traitement par angioplastie de l'athérosclérose. Les cellules inflammatoires ainsi que les médiateurs immuns sont impliqués dans toutes les étapes du développement de l'athérosclérose. Elles participent également à la modulation phénotypique des cellules musculaires lisses (CML) qui vont acquérir un phénotype migratoire et prolifératif aboutissant à l'hyperplasie intimale, celle-ci constituant le mécanisme majeure de la resténose. L'isoforme gamma des phosphoinositide 3-kinases (PI3Kgamma) a fait l'objet d'un intérêt croissant ces dernières années dans les pathologies inflammatoires. Ces kinases appartiennent à la classe I des PI3K capables de générer du phosphatidylinositol 3,4,5-trisphosphate (PIP3) impliqués dans la régulation d'un grand nombre de processus biologiques. La classe I des PI3K est divisée en deux sous-classes, la classe IA (p110alpha, beta et delta) classiquement activée par les tyrosine kinases, et la classe IB (p110gamma) activée par les récepteurs couplés aux protéines G hétérotrimériques. La génération de souris invalidées pour la PI3Kgamma a permis de montrer que les voies de signalisation impliquant cette kinase modulaient des fonctions immunitaires plaçant la PI3Kgamma comme un bon candidat dans la recherche de cibles thérapeutiques pour le traitement de pathologies auto-immunes. De plus, des études récentes ont montré un profil d'expression complexe de la PI3Kgamma incluant de faibles taux d'expression de cette kinase dans différents types cellulaires du système cardiovasculaire notamment dans les CML. L'ensemble de ces données a permis de poser l'hypothèse d'un rôle possible de la PI3Kgamma dans l'athérogénèse et ses complications. Ainsi dans une première partie, nous nous sommes intéressés au rôle de la PI3Kgamma dans le développement de l'athérosclérose. L'administration intrapéritonéale d'un inhibiteur pharmacologique spécifique de la PI3Kgamma conduit à une diminution du développement de lésions athéromateuses précoces mais aussi de plaques plus avancées dans deux modèles murins d'athérosclérose. De plus, à l'aide de souris chimères dépourvues de la PI3Kgamma dans le système immunitaire, nous avons démontré le rôle central de la PI3Kgamma dans les processus inflammatoires de la paroi artérielle conduisant au développement de la plaque d'athérome et participant à sa déstabilisation. La deuxième partie de ce travail s'est intéressée aux fonctions de la PI3Kgamma dans les cellules composant la paroi artérielle et plus particulièrement les CML. Ce travail réalisé in vitro a permis de mettre en évidence l'implication de la PI3Kgamma dans la migration des CML stimulées par la chimiokine MCP-1 (monocyte chemotactic protein-1). De plus, nous avons montré que la PI3Kgamma pouvait servir d'amplificateur de la réponse au PDGF par un mécanisme autocrine/paracrine faisant intervenir le complexe MCP-1/CCR2 (MCP-1 receptor). L'ensemble des propriétés de la PI3Kgamma dans la paroi artérielle que nous avons démontré placent cette kinase comme une cible thérapeutique de choix dans le traitement de l'athérosclérose et de ses complications
The role of inflammation in cardiovascular diseases has become an active area of investigation for the development of novel and innovative drugs targeting inflammatory proteins. Inflammation is a crucial event in atherosclerosis and restenosis, a major complication of atherosclerosis treatment by angioplasty. Inflammatory cells and immune factors are involved in all stages of the atherosclerotic process. Moreover, these cells are in part responsible for smooth muscle cell (SMC) migration and proliferation leading to intimal hyperplasia. The gamma isoform of phosphoinositide 3-kinase (PI3Kgamma) belongs to class I PI3K family producing 3-phosphoinositides and especially phosphatidylinositol-3,4,5-trisphosphate (PIP3) involved in many biological effects. The class I of PI3K is divided in two subclasses: class IA (p110alpha, beta and delta) classically activated through tyrosine kinase receptors and class IB (p110gamma), mainly activated by G protein-coupled receptors. Mice lacking catalytic subunits p110gamma have demonstrated a role of this isoform in several inflammatory and immune functions marking PI3Kgamma as a good candidate for drug development in autoimmune diseases. In addition to its functions in the immune system recent studies have demonstrated a more complex expression pattern in other cell types, particularly in SMC. These properties suggest that PI3Kgamma could play a role in atherosclerosis and its complications. In this work, we have first focused on the role of PI3Kgamma in atherosclerosis development. Our results demonstrate that a specific PI3Kgamma inhibitor is effective in murine models of established atherosclerosis. Intraperitoneal administration of PI3Kγ inhibitor significantly decreased early atherosclerotic lesions and attenuated more advanced atherosclerosis in two mouse models of atherosclerosis. Moreover chimeric mice lacking PI3Kgamma exclusively in immune cells showed that PI3Kγ plays an essential role in inflammatory processes of the vascular wall leading to the development of atherosclerosis and to plaque stability. In a second part, we investigate the specific involvement of PI3Kgamma in arterial wall and especially in SMC functions. Our results show that this kinase is essential to SMC migration induced by MCP-1 (monocyte chemotactic protein-1) in vitro. Moreover we demonstrate that PI3Kγ could amplify PDGF (platelet-derived growth factor)-stimulated SMC migration by an autocrine/paracrine pathway involving MCP-1 secretion and its receptor CCR2 activation. Altogether our results indicate that PI3Kgamma could be a potential new therapeutic target in atherosclerosis treatment and its complications

Des altérations de la signalisation en aval du récepteur à l’antigène (BCR) jouent un rôle clé dans la physiopathologie de la Leucémie Lymphoïde Chronique (LLC). Notre laboratoire a montré qu’une stimulation antigénique ex-vivo des cellules B-LLC conduit à une survie et une migration cellulaires différentielles qui distingue deux groupes de patients. Sur la base de ces résultats, nous avons montré que l’avantage de survie cellulaire en réponse à une stimulation antigénique observé dans un groupe est dépendant 1) d’un seuil imposé par les niveaux d’expression des effecteurs précoces (BCR, Syk et Zap70), de la capacité des cellules leucémiques à répondre en termes de phosphorylation de Syk, d’activation de la PLCƳ2, de mobilisation calcique et d’activation du facteur de transcription NFAT2 ; l’activation de la voie BCR/NFAT mesurée par la survie des cellules B-LLC ex-vivo étant corrélée à la survie globale des patients ; 2) de l’augmentation des niveaux de phosphorylation globale et spécifique de Syk, de la distribution subcellulaire de phospho-Syk, de la capacité de Syk à interagir avec des effecteurs positifs et négatifs et à les activer. De plus, notre étude sur la diminution de la migration des cellules B de LLC en réponse à une stimulation du BCR montre qu’elle dépend du taux d’internalisation du CXCR4 qui est régulé par l’activation des PI3Ks situées en amont des PKDs ; ces dernières activées phosphorylent le CXCR4 qui est alors internalisé. L’ensemble de ces données nous a permis de mieux définir les mécanismes moléculaires sous-jacents à une survie accrue et à une migration diminuée des cellules BLLC en réponse à une stimulation antigénique, de mettre en évidence d’éventuels biomarqueurs fonctionnels de stratification (pSyk et pPLCƳ2), de pointer de potentielles cibles thérapeutiques (NFATs et PKDs) et d’expliquer en partie l’action de drogues, comme le Fostamatinib et l’Idelalisib, utilisées en thérapie dans la LLC
Altered B-cell antigen receptor (BCR) signaling pathways play a key role in chronic lymphocytic leukemia(CLL) pathophysiology. Our lab has previously shown that ex-vivo antigenic stimulation of CLL-B cells led todifferential cell survival and cell migration, which allowed the distinction between two groups of patients. Basedon these results, we evidenced that the cell survival advantage in response to BCR engagement from one groupdepends on 1) a critical threshold mediated by the early effector expression levels (BCR, Syk et Zap70), a BCR competency of the leukemic cells translated by Syk phosphorylation, PLCƳ2 activation, intracellular Ca2+mobilization and the transcription factor NFAT2 activation; this activated BCR/NFAT signaling cascade, which is reflected by the ex-vivo measurement of CLL cell survival, was correlated to the overall survival from CLLpatients; 2) increased levels of global and specific Syk phosphorylation, phospho-Syk subcellular distribution, Sykability to interact with positive and negative effectors and to activate them. Moreover, study of BCR stimulation mediated decreased migration in CLL B cells showed that it relied on CXCR4 internalization levels that were regulated by activated PI3Ks acting upstream of the PKDs; activation of the latters allowed CXCR4 phosphorylation and then its endocytosis. Altogether, these data allowed us to better understand the molecular mechanisms underlying the survival advantage and the decreased migration of CLL B cells in response to antigenic stimulation, to evidence eventual functional biomarkers of stratification (pSyk and pPLCƳ2), to point out potential therapeutic targets (NFATs and PKDs), and to partially explain how Fostamatinib and Idelalisib function as therapeutic drugs in CLL

Angiogenese, die Bildung neuer Blutgefäße aus bereits bestehender Vaskulatur, ist ein Prozeß, der sowohl unter physiologischen Bedingungen abläuft, wie bei der Embryonalentwicklung und der Wundheilung, als auch unter pathologischen Bedingungen, wie der diabetischen Retinopathie und dem Wachstum und der Metastasierung solider Tumoren. Chronische Entzündungen wie die Atherosklerose und die Rheumatoide Arthritis gehen ebenfalls mit angiogenetischen Prozessen einher. Die Angiogenese ist ein stark regulierter Vorgang, der Migration, Proliferation und Differenzierung der Endothelzellen erfordert. Die Fähigkeit zur Migration ist eine wichtige biologische Funktion der Endothelzellen. Das Ziel dieser Arbeit bestand daher in der Untersuchung der Einflüsse verschiedener Zytokine auf die Endothelzellmigration und in der Charakterisierung daran beteiligter Mechanismen der Signaltransduktion. Dabei erwies sch Leptin als ein potenter Stimulus der Endothelzellmigration. Die Migration endothelialer Zellen nach Stimulation mit chemotaktischen Faktoren wie Leptin und VEGF wird durch die Aktivierung der Proteinkinasen ERK-MAPK und Akt vermittelt, deren pharmakologische Inhibition eine signifikante Hemmung der Migration bewirkte. Die antidiabetischen Thiazolidinedione Troglitazone und Ciglitazone hemmten die Leptin-induzierte Endothelzellmigration durch die Inhibition der Proteinkinase Akt, hatten aber keinen Einfluß auf die Aktivierung der ERK-MAP-Kinase. Dieses Ergebnis zeigt, dass die ERK-MAP-Kinase und die Proteinkinase Akt zwei voneinander unabängige Wege der Signaltransduktion darstellen, deren jeweilige Aktivierung für die Migration von Endothelzellen erforderlich, aber nicht ausreichend ist. Die proinflammatorischen Mediatoren TNF alpha und CD40L hemmten die VEGF-induzierte Migration humaner Endothelzellen bei Inkubation der untersuchten Zellen über 24 h signifikant. Auch bei kurzzeitiger Stimulation über 5 h steigerte TNF alpha die Rate migrierter Endothelzellen nicht. Diese Beobachtung steht im Widerspruch zur angenommen Assoziation entzündlicher und angiogenetischer Prozesse. In der vorliegenden Arbeit wird zum ersten Mal gezeigt, dass Antidiabetika aus der Gruppe der PPAR gamma-Liganden die Endothelzellmigration direkt hemmen. Dies weist auf eine mögliche Erweiterung des therapeutischen Einsatzes der Thiazilodinedione bei Patienten mit NIDDM und sekundären Symptomen wie der diabetischen Retinopathie hin.
Angiogenesis, the formation of new blood vessels from the preexisting vasculature, is a process involved in physiologic conditions, such as embryonic development and woundhealing, as well as in pathologic conditions, such as diabetic retinopathy and growth and spreading of solid tumors. Chronic inflammation such as atherosclerosis and rheumatoid arthritis is also associated with angiogenic processes. Angiogenesis is a tightly regulated process that requires migration, proliferation and differentiation of endothelial cells. Cell migration is a very important biologic function of the endothelial cell. The aim of this study was therefore to investigate the impact of various cytokines on endothelial cell migration and to characterize the chemotactic signal transduction pathways involved in this process. Leptin, the product of the ob-gene, proved to be a potent stimulus of endothelial cell migration. The actvation of the protein kinases ERK-MAPK and Akt is critical for endothelial cell migration, and their pharmacological inhibition caused a significant down-regulation of the migratory response towards migration factors such as Leptin and VEGF. The antidiabetic thiazolidinediones Troglitazone and Ciglitazone inhibited the leptin-induced endothelial cell migration by interfering with the cytosolic protein kinase Akt. They did not exert any influence on the activation of the ERK-MAPK. These findings prove the existence of two different, independent ways of signal transduction involved in endothelial cell migration: The ERK-MAPK and the protein kinase Akt. The activation of either kinase is necessary, but not sufficient to induce a migratory response in human endothelial cells. The proinflammatory mediators TNF alpha and CD40L caused a significant inhibition of endothelial cell migration in response to VEGF, when they were added to the culture medium for 24 h. TNF alpha did not stimulate the migration of endothelial cells, even when administered during a comparable short period of 5 h. This observation is in contrast with the postulated association of inflammatory and angiogenic proceses. In conclusion, the results of this study show for the first time a direct inhibition of leptin-induced endothelial cell migration by antidiabetic drugs belonging to the PPAR gamma-ligand-family through their inhibitory effect on Akt. This possibly broadens the spectrum of therapeutic applications of the antidiabetic thiazolidinediones in patients suffering from NIDDM and secondary complications such as diabetic retinopathy.

In a collaboration with limnologists at Uppsala University a planar HPGe detector has been used to find 210Pb in lake bottom sediment in hopes of getting an estimation for the sedimentation rate. Using a least squares fit to the data, the sedimentation rate was calculated to 0.08 ± 0.01 cm/year with background subtraction, and with it a timescale for the age of the sediment could be implemented. With this timescale the lake bottom sediment can be dated as far back as a century. Along with this, using 137Cs traces from the Chernobyl disaster of 1986 a consistency check can be made for our timescale. It is estimated that the Chernobyl disaster occurred at 1989 ± 7 years which is consistent with reality since 1986 is included in the interval 1982-1989. This helps us validate the determined sedimentation rates.

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Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

碩士
國立陽明大學
International Health Program
99
SECTION III. MIGRATION INTENTIONS Abstract Introduction The brain drain of health workers especially nurses from developing countries to developed countries has received international attentions (6-9) . Health professionals including nurses not only migrate from low to high income countries but also between high income countries. (7, 10) However, the financial cost and economic consequences of nurses’ migration is very high especially on resource poor countries (7, 11) .The objective of this study is to investigate the factors associated with migration intentions among nurse trainees in The Gambia. Methods This is a cross-sectional study which was conducted at the three main schools of nursing in The Gambia namely the Gambia college school of nursing which runs a program for state registered nurses (SRN), the school for community health nurses (CHNs), and the school for state enrolled nurses (SENs).The three schools had a total number of 345 registered students at the time of data collection. 179 participated but 23 dropped out remaining 156 and giving a response rate of 87 %. 4 of the students who returned the questionnaire were non Gambians and thus were dropped in the study. This gives a sample size of 152 students. The questionnaire consists of both open and closed ended questions and thus the quantitative part were analyzed using means, frequencies, chi square, ANOVA, univariate and multivariate logistic regressions .The qualitative part were thematised and analyzed using frequencies. Results Almost half (46.7 %) of the students have shown an indication to migrate. The variables most strongly associated with intention to migrate using ANOVA, chi square, and univariate logistic regression were gender, age group, school type, year in school and ranking in school. 72 .0% of the females reported likelihood to migrate as opposed to 27.9 % of the males. Females were also twice more likely to migrate in the univariate logistic regression (OR = 2.46; 95 % CI =1.11 – 5.47). With school type, the SRN students were more likely to migrate among all the students 79.5 % of the SRN students had intention to migrate while 55.0 % and 14.0 % of the CHN and SEN students respectively had intention to migrate. With the multiple logistic regression, when all the significant variables in the univariate logistic regression were entered, only age and year in school reached level of significance and when all the variables were included, only year in school was significant. The midwifery students were almost 5 times more likely to migrate compared to the other students. Although the association in the other variables did not reach significance level, the direction of the association remains the same. In the motivating factors for nurses to migrate, the recommendations on what should be done to encourage nurses to stay and the open ended questions; the most important factor that featured is opportunities for academic and career advancement. Conclusion After controlling for all other variables, the single variable most strongly associated with migration intentions is school year. Intention to migrate is highest among midwifery students. Although the other variables did not reach statistical significance after controlling for all other confounders, intention to migrate is high among SRN students, females and younger students. The high migration intentions among midwifery students and SRNs should be a cause for concern considering the high maternal mortality rate in the Gambia. Opportunities for career and academic development is the most important motivating factor for nurses to migrate and thus if nurses find these opportunities in The Gambia, most of them will stay. Key words: The Gambia, brain drain, migration, state registered nurse (SRN), state enrolled nurse (SEN), community health nurse (CHN), midwives SECTION IV. POSTING PREFERENCE Abstract Introduction The Gambia like many other low income countries not only faces the shortage of nurses, but also imbalanced distribution of nursing manpower This geographical imbalance between urban and rural areas raises issues of equity, access and quality of health care in underserved areas and poor people are more seriously affected (7, 51).The imbalanced distribution of nurses can compromise significantly effective delivery of health services. The objectives of this study are to investigate factors associated with the posting preferences of student nurses in The Gambia. Methods The research design was cross-sectional and it was conducted at the three main schools of nursing in The Gambia namely the Gambia college school of nursing which runs a program for state registered nurses (SRN), the school for community health nurses (CHNs), and the school for state enrolled nurses (SENs). The three schools had a total of 345 registered students at the time of data collection and 179 participated but 23 dropped out remaining 156 and giving a response rate of 87 %. 4 of the students who returned the questionnaire were non Gambians and thus were dropped in the study. This gives me a sample size of 152 students The questionnaire which was designed by researcher consists of both open and closed ended questions and thus the quantitative part (open ended) were analyzed using means, frequencies, chi square, ANOVA, univariate and multivariate logistic regressions .The qualitative part were thematised and analyzed using frequencies. Results 44 (28.9%) students preferred rural postings 77(50.7%) urban postings and 27(17.8%) said they had no preference and 4(2.6%) of the students did not give any response. Students’ home address is the strongest predictor of rural practice in the chi square, test, univariariate and multivariate logistic regression. Gender is also another strong predictor of rural practice. Females are less willing to work in rural areas compared to males with 71.2 % of females compared to 52.1 % males saying they prefer urban postings (x2 p value =0.032). On education and work experience characteristics, the most significant characteristics associated with posting preferences are the students’ school and their year in school. The SEN and CHN students are more willing to work in rural areas than the SRN students and the p value is significant. (x2 P value = 0.020) There is also a strong association between year in school and posting preference (p value= 0.001), with students in their first year and midwifery students more willing to work in rural areas. In the multiple logistic regressions, after controlling for all other variables, the strongest predictor of rural practice is students’ home address and year in school. Students with rural background are 3 times more willing to work in rural areas compared to those with urban background (OR = 3.03;95 % CI = 1.40 – 6.56). Students in their first year and those doing a midwifery program are also more willing to work in rural areas. On the factors motivating nurses to work in rural areas, opportunities for academic and career development for nurses are the most important factors. Availability of working tools and good communication network are also very important Conclusion The strongest predictor of rural practice is having a rural background. Midwifery students and students in the SRN School are also more willing to work in rural areas. Giving nurses the opportunities for career advancement and improving the quality of schools in rural areas for nurse’s children will retain them in rural areas. Gambian nurses don’t care much if their postings are rural or urban but are more concerned about the region they are posted to Key words: The Gambia, posting preferences, rural areas, state registered nurse (SRN), state enrolled nurse(SEN), community health nurse(CHN),midwives

This project aims to quantify natural gamma radiation in gold tailings disposal facilities (TDFs) relative to uranium concentration data in order to use natural gamma detection methods as alternative methods for uranium resource estimation modelling in gold tailings. Uranium migration within the New Machavie TDF was also investigated as migration affects both the grade of the TDF as a uranium resource and poses a threat to the environment. In order to determine the most appropriate radiometric testing procedure, various methods were employed for natural gamma detection, including surface natural gamma spectrometry, borehole natural gamma spectrometry and scintillometry, as well as incremental sampling. These measurements were then statistically compared to ICP-MS analyses to find the best method, and then modelled to apply volumetric resource estimation procedures. The oxidation reduction potential was also tested as uranium geochemistry is dependent on oxidation for mobilisation. Furthermore, leaching tests were employed to relate specific anions as a mode of transportation in solution. Results indicated that down-hole natural gamma spectrometry performed the best and that 2376.87 kg of uranium is present in the TDF. Migration modelling indicated that uranium is mobilised away from the oxidized top area of the TDF and that accumulation occurs in the saturated zone of the TDF under a reducing environment. Sulphate anions as the result of pyrite oxidation are primarily responsible for the mobilisation as radionuclides in New Machavie. The results of this project can be applied to the resource estimation of all uranium bearing tailings facilities prior to re-mining as a means to decrease exploration costs and to accurately model the distribution of uranium.
MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2014

Suite à une infection, des lymphocytes T CD8+ naïfs (LTn CD8+) spécifiques d’un antigène du pathogène sont activés. Après, cette activation, ces lymphocytes se différencient en lymphocytes T effecteurs CD8+ (LTe CD8+) chargés d’éliminer le pathogène. Une fois que l’infection est résolue, la grande majorité des effecteurs meurent par apoptose et les survivants se différencient en lymphocytes T mémoires CD8+ (LTm CD8+). Ces derniers protègeront l’organisme à long terme contre une réinfection par le même pathogène. Il est ainsi primordial d’avoir une meilleure compréhension des mécanismes impliqués dans le développement et la maintenance des LTm CD8+. Plusieurs études ont déjà montré que certaines cytokines de la famille γC (IL-2, IL-7, IL-15 et IL-21) influençaient individuellement le développement des LTe et LTm CD8+. Cependant, nous pensons que ces cytokines ont un impact bien plus grand sur l’homéostasie des LTe et LTm CD8+ que la littérature actuelle le laisse entendre. En effet, nous émettons l’hypothèse que ces cytokines de la famille γC agissent en synergie entre elles afin de promouvoir le développement des LTe et LTm CD8+. Pour tester notre hypothèse, nous avons dans un premier temps étudié l’impact combiné des signaux IL-2 et IL-15 sur la génération des LTe et LTm CD8+ dans un modèle d’infection LCMV Armstrong. Ensuite, dans le même modèle expérimental, nous avons étudié l’effet d’une déficience en signaux IL-2, IL-15 et IL-21 sur le développement des LTe et LTm CD8+. Nos résultats montrent que ces trois cytokines collaborent afin de soutenir l’expansion et la différenciation des LTe CD8+. Plus précisément, l’IL-2, l’IL-15 et l’IL-21 sont essentielles pour l’homéostasie d’une population particulière de LTe CD8+ : les Short-Lived Effector Cells (SLECs). Nous avons également mis en évidence que ces trois cytokines sont toutes les trois requises afin de générer un nombre maximum de LTm CD8+. De plus, la différenciation et le maintien de la population effecteur mémoire (TEM) sont particulièrement réduites en l’absence des signaux combinés de l’IL-2, l’IL-15 et l’IL-21. Nos résultats mettent pour la première fois en lumière les rôles redondants et synergiques de trois cytokines dépendantes de la chaine γc dans le développement et la maintenance des LTe et LTm CD8+.
Over the course of an infection, antigenic signals trigger a specific CD8+ T cells (LTn CD8+) response. Upon antigen recognition, LTn CD8+ are activated and undergo a massive proliferation wave. This leads them to differentiate into effector cells (LTe CD8+) in charge of pathogen elimination. While most effector T cells die after the infection is resolved, a small part of this population persists and differentiates into memory T cells (LTm CD8+). These cells provide long term protection to the organism against the initial infectious agent. It is thus crucial to have a better understanding of all mechanisms governing the development and the maintenance of LTm CD8+. Several studies have already shown that some members of the "C-dependent cytokines family (IL-2, IL-7, IL-15 and IL-21) individually regulate LTe and LTm CD8+ development. However, we believe that these cytokines have a far greater impact on the homeostasis of LTe and LTm CD8+ than the current literature suggests. Indeed, we hypothesized that "C-dependant cytokines act in synergy to promote the development of LTe and LTm CD8+. To assess their effect, we first studied the combined impact of IL-2 and IL-15 signals on the generation of LTe and LTm CD8+ during an LCMV Armstrong infection in mice. In this same experimental model, we also studied the effect of a deficiency in IL-2, IL-15 and IL-21 signals on the development of LTe and LTm CD8+. Our results show that these three cytokines cooperate to support the expansion and differentiation of LTe CD8+. More accurately, IL-2, IL-15 and IL-21 are essential for the homeostasis of a particular LTe CD8+ subset : Short- Lived Effector Cells (SLECs). We also demonstrated that all three cytokines are required to generate a maximal number of LTm CD8+. In addition, differentiation and maintenance of the memory effector population (TEM) are substantially reduced in the combined absence of IL-2, IL-15 and IL-21 signals. These results are the first to our knowledge to highlight redundant and synergistic functions of three "C-dependent cytokines as promoters of the development and maintenance of LTe and LTm CD8+.

La barrière hémo-encéphalique (BHE) est formée des cellules endothéliales microvasculaires cérébrales reliées entre elles par des jonctions serrées. Grâce à sa perméabilité restreinte et sélective, la BHE entrave le passage des molécules et cellules du sang vers le système nerveux central (SNC). Chez les patients atteints de sclérose en plaques (SEP), une maladie inflammatoire du SNC, la rupture de la BHE permet aux cellules immunes actives d'infiltrer le tissu cérébral. Il s'ensuit une réaction inflammatoire excessive au cours de laquelle d'autres leucocytes sont recrutés dans le cerveau et qui culmine par la formation des plaques de démyélinisation caractéristiques de la SEP. On dénote au niveau de ces lésions une présence importante de lymphocytes T CD4⁺ activés et de cytokines pro-inflammatoires propres à une réponse de type TH1, tels l’IFN-γ et l’IL-1. Curieusement cependant, l’inhibition de la voie TH1 n’empêche pas l’apparition de la maladie dans le modèle murin de la SEP et en aggrave même les symptômes. On attribue maintenant aux lymphocytes TH17, nommées en raison de leur capacité à produire de l’IL-17, un rôle clé dans le développement de la maladie. L’objectif de ce travail de thèse visait à caractériser les lymphocytes TH17 chez l’humain et définir leur contribution exacte dans la fragilisation de la BHE, une étape décisive dans la formation des lésions de SEP. Pour ce faire, nous avons mis au point une méthode expérimentale permettant l’expansion in vitro de populations de lymphocytes TH17 à partir de cellules mononuclées du sang de donneurs sains. Nos travaux démontrent que l’IL-23 induit la production d’IL-17, d’IL-22 et de granzyme B par les lymphocytes T CD4⁺CD45RO⁺ mémoires humains et qu’une proportion des cellules exprime de manière concomitante de l’IL-17 et de l’IFN-γ. La fréquence des lymphocytes T CD4⁺ IL17⁺, IL-22⁺ et des doubles positifs IL-17⁺IFN-γ⁺ est significativement plus élevée dans les lignées de lymphocytes TH17 provenant de patientes en poussée que dans celles de contrôles. Nos analyses démontrent que les cellules endothéliales de la BHE expriment de faibles niveaux des récepteurs de l’IL-17 et de l’IL-22 à l’état basal mais que leur présence est accrue dans le cerveau de patients atteints de SEP. L’activation du récepteur de l’IL-17 entraîne une augmentation de la perméabilité de la BHE et une perturbation de l’organisation des protéines de jonction occludine et ZO-1. Finalement, nous démontrons que la migration des lymphocytes TH17 à travers la BHE est régie en grande partie par la molécule d’adhérence ICAM-1 et que les lymphocytes qui co-expriment l’IL-17 et l’IFN-γ sont plus aptes à franchir la BHE que ceux qui produisent uniquement l’une ou l’autre de ces cytokines. Nous retrouvons d’ailleurs des cellules qui expriment simultanément les facteurs de transcription T-bet et RORC, associés respectivement aux lymphocytes TH1 et aux TH17, au sein des infiltrats péri-vasculaires des lésions actives de SEP. Les travaux présentés dans cette thèse auront permis d’affiner nos connaissances sur les mécanismes d’entrée des lymphocytes TH17 dans le SNC et les propriétés délétères des cytokines qu’ils sécrètent, notamment dans l’activation et la déstabilisation de l’endothélium cérébral.
The blood-brain barrier (BBB) plays a crucial role in protecting the central nervous system (CNS) by restricting entry of cells and molecules into the brain. In the CNS disorder multiple sclerosis (MS), breakdown of the BBB allows activated leukocytes to infiltrate the brain parenchyma, leading to the formation of the characteristic demyelinated lesions. For decades, MS was viewed as a TH1-mediated disease, a notion that was largely supported by studies in its animal model and by the abundance of prototypical TH1-associated cytokines within active MS lesions. However, over the years, accumulating evidence has highlighted the involvement of another subset of CD4⁺ T cells that express IL-17, therefore named TH17 lymphocytes, in the pathology of the disease. The goal of the work presented herein was to characterize the human TH17 lymphocyte population and define their contribution to the disruption of the BBB and leukocyte infiltration into the CNS, both important early events in the formation of MS lesions. To do so, we developed and optimized a method to successfully generate human TH17 lines in vitro from peripheral blood mononuclear cells of healthy donors. We demonstrate that in response to IL-23, human memory CD4⁺CD45RO⁺ but not naïve CD4⁺CD45RA⁺ T lymphocytes produce IL-17, IL-22, and granzyme B, with a subset of cells simultaneously expressing IL-17 and IFN-γ. Interestingly, we measure a significant increase in the percentage of T CD4⁺ IL17⁺, of IL-22⁺, and of IL-17⁺IFN-γ⁺ dual producers in TH17 cell lines expanded from the peripheral blood of acutely relapsing MS women as compared to those generated from healthy controls and remitting MS patients. We show that both IL-17 and IL-22 receptors are upregulated on BBB endothelial cells in situ during inflammation and that IL-17 enhances BBB permeability by disrupting the integrity of tight junction proteins occludin and ZO-1. Finally, we provide evidence that TH17 lymphocytes transmigrate efficiently across human brain endothelial cells via the adhesion molecule ICAM-1 and show that IL-17⁺IFN-γ⁺ double producers have an increased propensity to do so. Accordingly, we detect lymphocytes that display immunoreactivity against both the TH1- and TH17-associated transcription factors T-bet and RORC within perivascular infiltrates of active MS lesions. The work presented in this thesis has refined our understanding of the mechanisms that drive TH17 lymphocyte recruitment into the CNS and shed light on the deleterious effect of TH17-secreted cytokines, specifically in the activation and breakdown of the BBB.

The present dissertation reports the findings of a study of cracking behavior of a newly developed superalloy, Allvac 718Plus during high power beam welding and post-weld heat treatment. Microstructures of the base alloy, heat affected zone (HAZ) and fusion zone (FZ) of welded and post-weld heat treated (PWHT) coupons were examined by the use of standard metallographic techniques involving optical microscopy, analytical scanning electron microscopy (SEM) and analytical transmission electron microscopy. Moreover, grain boundary segregation behavior of boron atoms during pre-weld heat treatments was evaluated using secondary ion mass spectroscopic system. In the first phase of the research, 718Plus was welded using a low and high heat input CO2 laser to assess its weld cracking response. Detailed examination of the welds by analytical electron microscopic technique revealed the occurrence of cracking in the HAZ of low heat input welds, while their FZ was crack free. However, both the FZ and HAZ of high heat input welds were crack-free. Resolidified constituents were observed along the cracked grain boundaries of the lower heat input welds, which indicated that HAZ cracking in this newly developed superalloy was associated with grain boundary liquation. However, despite a more extensive liquation of grain boundaries and grain interior in the HAZ of high heat input welds, no cracking occurred. This was attributed to the combination of lower welding stresses generated during cooling, and relaxation of these stresses by thick intergranular liquid. Although HAZ cracking was prevented by welding with a high heat input laser, it resulted in a significant damage to the parent microstructure through its extensive liquation. Thus, the use of low heat input welding is desirable. However, this resulted in HAZ cracking which needs to be minimized or eliminated. Therefore, during the second phase of this research, the effects of pre-weld thermal processing on the cracking response of 718Plus were investigated. Results from the quantification of the cracking of the alloy showed that HAZ cracking may be significantly reduced or eliminated through an adequate selection of pre-weld thermal cycle. In the third stage of this research, crack-free welds of 718Plus were post-weld heat treated using standard thermal schedules. A significant solid state cracking of the alloy occurred during the PWHT. The cracking was attributed to the presence of embrittling phases on HAZ grain boundaries, coupled with aging contraction stresses that are generated by a considerable precipitation of gamma prime phase during aging.