Universiẗat, Diss., 2003--München.

Thesis (Ph. D.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains ix, 226 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 204-212).

Thesis (Ph. D)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 115-142).

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 154-192).

Thesis (Ph. D.)--Case Western Reserve University, 2006. / [School of Medicine] Department of Epidemiology and Biostatistics. Includes bibliographical references. Available online via OhioLINK's ETD Center.

München, Techn. Univ., Diss., 2004.

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 38-51).

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De études récentes suggèrent une forte relation entre susceptibilité au paludisme et réponse allergique. Des niveaux élevés d’histamine plasmatique et tissulaire ont été associés à la sévérité de la maladie chez l’homme infecté par P. falciparum et dans de nombreux modèles animaux. Histamine releasing factor (HRF), une protéine pro-inflammatoire libérant l'histamine au cours des processus allergiques, est produite par le parasite au cours des infections palustres modérées et sévères, suggérant l’implication du HRF dans l’altération des réponses immunitaires et dans la pathogenèse. Les objectifs de ce travail consistaient à évaluer le rôle de la protéine parasitaire HRF dans le développement de la réponse immunitaire et à déterminer si son expression est associée à la sévérité de la maladie en étudiant deux parasites murins, PbANKA et PbNK65, déficients pour la protéine HRF (hrfΔ). Les souris infectées avec des sporozoïtes PbANKA-hrfΔ ont montré une diminution de la fréquence du neuropaludisme associée à un déficit du développement des parasites mutants au cours du stade hépatique et à une augmentation précoce systémique d’IL-6. En outre, l'infection par les parasites PbNK65-hrfΔ est caractérisée par l’élimination du parasite conduisant à une protection durable et au développement d’une mémoire immunitaire caractérisée par une augmentation d’IL-6, une diminution de l’expression de PD-1 sur les cellules T et une amélioration de la phagocytose dépendante des anticorps, confirmant l'importance de la protéine HRF dans la virulence du parasite. HRF est le premier gène de parasite Plasmodium dont l’effet direct sur la réponse immunitaire de l’hôte est démontré. / Recent findings have raised the hypothesis that clinical susceptibility to malaria may be related to allergy-type response. In human infection with P. falciparum, as well as in murine models of malaria, increased levels of histamine have been shown to be associated with disease severity. Histamine releasing factor (HRF), shown to be implicated in the release of pro-inflammatory histamine during late-phase allergy, was demonstrated to be produced by the parasite during mild and severe malaria infections suggesting that Plasmodium HRF may affect host immune responses and contributes to the pathogenesis. The objectives of this work were to evaluate the role of Plasmodium HRF in the development of the immune response and to determine whether its expression is associated with the severity of malaria disease by studying two HRF-deficient (hrfΔ) murine parasites (PbANKA and PbNK65). Infection with PbANKA-hrfΔ sporozoites showed a decrease in the frequency of ECM due to the impairment of the development of the mutant parasites in liver stages as a consequence of the up-regulation of IL-6. Infection with PbNK65-hrfΔ parasites confirmed the importance of HRF in enhancing the virulence of the parasite. Indeed, PbNK65-hrfΔ infection results in parasite clearance leading to a long-lasting protection and immune memory as reflected by an up-regulation of IL-6, a down-regulation of PD-1 expression on T cells and in the enhancement of Ab-mediated phagocytosis. HRF is the first parasite gene which directly modulates the host immune response.

The first empirical chapter examines the existence of a 'net equity issuance' (NEI) effect in the UK stock market. Net Equity Issuance (NEI) refers to the change in a firm's shares outstanding due to events such as SEOs, acquisitions financed by share issues, issues to staff and share repurchases. The NEI effect is the ability of share issuance by firms to predict their subsequent stock returns. My results mainly suggest that there is an NEI effect in the UK. However, a discrepancy exists between the UK results and those found in the US. In the UK market, negative-NEI stocks tend to show negative subsequent returns while zero-NEI stocks have the highest subsequent returns. I also find that the abnormal returns from the NEI effect disappear when transaction costs are taken into account. Furthermore, the asset pricing test results suggest that the new factor models partially explain the NEI effect in the UK. The second empirical chapter evaluates the information content of new asset pricing factors in the UK. I find that two new risk factors, the investment factor and the profitability factor, improve the factor model's performance in the UK while both the size factor 'small minus big' (SMB) and the value factor 'high minus low' (HML) are redundant. There is also evidence that factor construction methods matter to the information content of the profitability factor. The most informative profitability factor in the UK among the possible candidates is constructed using income before extraordinary items scaled by book equity. The third empirical chapter explores the information content of the two new factors by linking them to the state variables which predict future investment opportunities. By doing this, I find confirmative evidence that the two new risk factors may proxy for state variables that capture time variations in the investment opportunity set. I find empirical evidence which confirms that the investment factor predicts future economic growth, proxied by GDP growth, investment growth and consumption growth. In addition, the investment factor is found to be related to dividend yield shocks, whereas the profitability factor is related to inflation shocks. In addition, the pricing significance of macroeconomic variable shocks disappears when loadings on the two new factors are presented in the model. The evidence therefore provides economic interpretation to the information content of the new asset pricing factors in the UK market.