Thèse d'exercice : Chirurgie dentaire : Université de Nantes : 2007. / Bibliogr.

Thesis (Ph. D.)--University of Virginia, 2001. / Includes bibliographical references (leaves 142-166). Also available online through Digital Dissertations.

Esta tesis doctoral tiene por objetivo proponer una conceptualización filosófica del postfordismo y la precariedad, a partir de la metodología (post)operaista y de sus aportaciones teóricas. Nuestro trabajo de investigación consiste, fundamentalmente, en la elaboración de una cartografía de los diferentes debates que han tenido lugar en el interior de esta corriente de pensamiento. La cartografía propuesta no es un fin en sí misma. Su elaboración se justifica en tanto abre una perspectiva para el análisis de las transformaciones en la composición de la fuerza de trabajo. Por un lado, el concepto de postfordismo aporta claves fundamentales para la comprensión de las dinámicas de valorización capitalista, de las líneas de conflicto y de los procesos de constitución de subjetividades; y, por otro, el concepto de precariedad, tal y como lo delineamos, se propone como el plano de inmanencia sobre el que el capital articula sus estrategias de expropiación, subordinación y captura de la nueva composición del trabajo. / Based on a theoretical and methodological Post-Operaist approach, this Ph.D. dissertation poses a philosophical conceptualization of precarity and Post-Fordism. The fundamental focus of our research is the development of a cartography compiling the multiple debates that have taken place within this strand of thought. However, this cartography is not an end in itself; rather it aims to open a new perspective for the analysis of transformations in workforce composition. On the one hand, the concept of Post-Fordism provides not only fundamental elements for the comprehension of different dynamics of capitalist valorization, but also it is key to understand the lines of conflict as well the processes of subjectivation. On the other hand, the concept of precarity –as we outline it in this research– emerges as a plane of immanence upon which capital articulates its strategies of expropriation, subordination and capture within the new composition of labor.

Horkheimer and Adorno laid the foundations of Critical Theory from three basic disciplines: economics, psychology and studies around the culture. The second generation of Frankfurtians authors (Habermas) clearly prioritizes the philosophy of language at the expense of other disciplines, such as psychology. However, with Axel Honneth, Critical Theory gets back two elements of the first generation that had been forgotten in the second: first, the discipline of psychology in the analysis of society and, secondly, emancipatory dimension of work. In contrast to Habermas deliberative model, Honneth articulates a conception of democracy based on the ethical ideal of individual liberty. Beyond the participation of citizens in deliberative processes –so we can summarize their proposal– democracy must guarantee individual freedom that is inherent in other two areas of ethical life: personal relationships and labor relations / Horkheimer i Adorno estableixen els fonaments de la Teoria Crítica a partir de tres disciplines bàsiques: l’economia, la psicologia i els estudis envers la cultura. La segona generació d’autors francfortians (Habermas) prioritza clarament la filosofia del llenguatge en detriment d’altres disciplines com la psicologia. Tanmateix, amb Axel Honneth, la Teoria Crítica recupera dos elements de la primera generació que havien estat oblidats en la segona: d’una banda, la disciplina de la psicologia en l’anàlisi de la societat i, de l’altra, la dimensió emancipadora del treball. A diferència del model deliberatiu de Habermas, Honneth articula una concepció de la democràcia basada en l’ideal ètic de la llibertat individual. Més enllà de la participació de la ciutadania en processos de deliberació –així es pot resumir la seva proposta–, la democràcia ha de garantir la llibertat individual que és inherent a les altres dues esferes de l’eticitat: les relacions personals i les relacions laborals

This report outlines the process of creating and producing the documentary film “That Thing You Do” based on the TV series “1+1=Infinito” (1+1=Infinite). The series and the film provide a better understanding of the concept of Corporate Social Responsibility (CSR) and shows how people can incorporate CSR into their daily lives. The film production was financed by “PROhumana Foundation” (Chile) and shows how three Chilean people: Rodrigo Alonso, entrepreneur, Catalina Valdés, chef, and Javier del Río, architect, are trying to make a difference in their specific fields in terms of environmental impact, saving and using energy properly, and the importance of conscientious eating. The documentary film has taken the concept of CSR and attempted to present it to a massive audience in order to suggest the idea that all of our actions eventually come back to us. Any imbalance in the system that surrounds us and which we are a part of will affect us. In contrast, any improvement to the system will benefit us. The film thus attempts to showcase testimonials by the main characters suggesting small changes we can make in our daily lives in order to work toward this goal. / text

Cytochrome c oxidase (COX) is a multimeric protein complex whose enzymatic activity contributes to the generation of an electrochemical potential required to synthesize adenosine triphosphate (ATP). Synthesis of Cytochrome c Oxidase 1 (SCO1) and SCO2 are two of the many accessory factors that are required to assemble individual structural subunits of COX into a functional holoenzyme complex. Mutations in either SCO gene cause severe, early onset forms of human disease. SCO1 and SCO2 are closely related paralogues localized to the inner mitochondrial membrane. Both proteins bind copper and exhibit a thiol disulphide oxidoreductase activity. Copper is bound by a highly conserved Cysteine x x x Cysteine motif and a histidine found within a thioredoxin fold, which is contained in the C-terminal half of the protein and projects into the mitochondrial intermembrane space. Mutations in either SCO1 or SCO2 affect their ability to deliver copper to COX II and metallate its CuA site, and also result in an increased rate of copper efflux from the cell. However, the relative importance of the ability to bind and transfer copper to SCO protein function remains poorly understood. Therefore, to investigate the significance of several cysteine residues and the conserved histidine to the copper-binding properties of SCO1, I functionally characterized a series of N- and C-terminal SCO1 mutant proteins by transducing them into control and patient fibroblasts, and quantifying their phenotypic effect on COX activity. I found that the two cysteines within the soluble, N-terminal matrix domain of SCO1 are not required for protein function. Overexpression of C-terminal SCO1 mutants only affected COX activity in SCO1-2 patient fibroblasts. To further characterize the copper-binding properties of these C-terminal mutants, soluble forms of each SCO1 variant were expressed and purified from bacteria, and the amount of total bound copper and the relative abundance of Cu(I) and Cu(II) were quantified. Although these analyses suggested that one mutant, SCO1 C169H, binds significantly more Cu(I) than the wild-type protein, none of the SCO1 variants exhibited properties that furthered our understanding of the precise role of SCO1 in the biogenesis of the CuA site of COX II.

Previous studies revealed that, upon exposure to hypoxia, tumour cells acquire resistance to the cytolytic activity of IL-2-activated lymphocytes. The MHC class I chain-related (MIC) molecules – comprised of MICA and MICB – are ligands for the activating NKG2D receptor on Natural Killer (NK) and CD8+ T cells. MIC-NKG2D interactions lead to the activation of NK and CD8+ T cells and the subsequent lysis of the tumour cells. The study also showed that the mechanism of the hypoxia-mediated immune escape involves the shedding of MIC, specifically MICA, from the tumour cell surface. The objective of the present study was to determine whether the shedding of MICA requires the expression of hypoxia inducible factor-1 (HIF-1), a transcription factor that regulates cellular adaptations to hypoxia. Exposure to hypoxia (0.5% O2 vs. 20% O2) led to the shedding of MIC from the surface of MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells as determined by flow cytometry. Knockdown of HIF-1α mRNA using siRNA technology resulted in inhibition of HIF-1α accumulation under hypoxic conditions as determined by Western blot analysis. Parallel study revealed that knockdown of HIF-1α also blocked the shedding of MICA from the surface of MDA-MB-231 cells exposed to hypoxia. These results indicate that HIF-1 is required for the hypoxia-mediated shedding of MICA and, consequently, that HIF-1 may play an important role in tumour immune escape. Ongoing studies aim to determine the HIF-1 target genes involved in the shedding of MICA under hypoxia. / Thesis (Master, Anatomy & Cell Biology) -- Queen's University, 2009-08-19 21:09:13.707

No description available.

The great adaptability of the Human Immunodeficiency Virus type 1 (HIV-1) and the exclusive use of zidovudine (3$ sp prime$azido-3$ sp prime$deoxythymidine or AZT) in the treatment of AIDS has motivated our search for HIV-1 strains resistant to this drug. / Our first attempt at obtaining such strains was made by using an in vitro approach in which a lymphoid cell line, chronically infected with HIV-1, was exposed to various drug concentrations. Although this system has never generated such mutants, we found that the progeny virus population, present in the culture fluids of these chronically infected drug-treated cells lost infectivity. These results suggest a potential post-integrational role for zidovudine, possibly acting at the level of viral assembly or budding. / However, we were successful in isolating zidovudine-resistant HIV-1 strains from the blood of patients undergoing AZT treatment. Our work shows that a minimum of 27 weeks of treatment is necessary for the appearance of the resistant phenotype and that the majority (75%) of patients treated with AZT for more than one year will generate such resistant strains. No correlation between the clinical status of the patients and the occurrence of resistant variants can be drawn from our work. However, in vitro experiments have shown that the resistant isolates are more cytopathic, although less infectious, than the sensitive strains. Reverse transcriptase enzymes from both AZT-resistant and -sensitive strains were virtually identical when their respective enzymatic activities or their affinity for the substrate or the inhibitor were compared. Finally, some zidovudine-resistant isolates demonstrate cross-resistance to other nucleoside analogs with potential clinical applications.

This thesis presents a diagnosis of the problem of luck in epistemology and an analysis of the concept of knowledge. Part I gives an account of the ordinary concept of luck. Part II gives an account of the philosophical notion of epistemic luck and develops an original account of the concept of knowledge: the control theory of knowledge / Aquesta tesi presenta un diagnòstic del problema de la sort en epistemologia i una anàlisi del concepte de coneixement. La primera part ofereix una teoria del concepte ordinari de sort. La segona part ofereix una teoria de la noció filosòfica de sort epistèmica i desenvolupa una teoria original del concepte de coneixement: la teoria del control