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Weiß, Norman. "Löffler, B., Integration in Deutschland : zwischen Assimilation und Multikulturalismus / [rezensiert von] Norman Weiß". Universität Potsdam, 2012. http://opus.kobv.de/ubp/texte_eingeschraenkt_verlag/2013/6402/.
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Monaghan, Paul. "Laying down the country : Norman B. Tindale and the linguistic construction of the North-West of South Australia". Title page, contents and abstract only, 2003. http://web4.library.adelaide.edu.au/theses/09PH/09phm734.pdf.
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"June 2003" 2 maps in pocket on back cover. Bibliography: leaves 285-308. This thesis critically examines the processes involved in the construction of the linguistic historical record for the north-west region of South Australia. Focussing on the work of Norman B. Tindale, the thesis looks at the construction of Tindale's Pitjantjatjara, Yankunytjatjara and Antikirinya representations. It argues that Tindale effectively reduced a diversity of indigenous practices to ordered categories more reflective of Western and colonial concepts than indigenous views. Tindale did not consider linguistic criteria in depth, had few informants, worked within arbitary tribal boundaries, was biased towards the category 'Pitjantjatjara' and was informed by notions of racial/linguistic purity. These factors which shaped the linguistic record must be taken into account when interpreting records for use as historical and native Title evidence.
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Mendonça, Matheus Rodrigues de. "Análise de modos normais dos movimentos conformacionais em proteínas". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/59/59135/tde-18042016-104716/.
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A caracterização das flutuações dos resíduos da proteína em torno do seu estado nativo é essencial para estudar mudanças conformacionais, interação proteína-proteína e interação proteína-ligante. Tal caracterização pode ser capturada pelo modelo de rede gaussiana (GNM). Este modelo tem sido modificado e novas propostas têm surgido nos últimos anos. Nesta Tese, apresentamos um estudo sobre como melhorar o GNM e exploramos o seu desempenho em predizer os fatores-B experimentais. Modelos de redes elásticas são construídos a partir das coordenadas experimentais dos levando em consideração pares de átomos de C? distantes entre si até um dado raio de corte Rc . Estes modelos descrevem as interações entre os atómos por molas com a mesma constante de força. Desenvolvemos um método baseado em simulações numéricas com um campo de forças simplificado para atribuir pesos a estas constantes de mola. Este método considera o tempo em que dois átomos de C? permanecem conectados na rede durante o desenovelamento parcial, estabelecendo assim uma forma de medir a intensidade de cada ligação. Examinamos dois diferentes campos de forças simplificados e exploramos o cálculo desses pesos a partir do desenovelamento das estruturas nativas. Nós comparamos o seu desempenho na predição dos fatores-B com outros modelos de rede elástica. Avaliamos tal desempenho utilizando o coeficiente de correlação entre os fatores-B preditos e experimentais. Mostramos como o nosso modelo pode descrever melhor os fatores-BThe characterization of the fluctuations in protein residues around its native state is essential to study conformational changes, protein binding interaction and protein-protein interaction. Such characterization can be captured by simple elastic network models as the Gaussian Network Model (GNM). This model has been modified and new proposals have emerged in recent years. In this Thesis we propose an extended version of GNM, namely wGNM. Elastic network models are built on the experimental C? coordinates,and they only take the pairs of C? atoms within a given cutoff distance Rc into account. These models describe the interactions by elastic springs with the same force constant to predicted the experimental B-factors, providing insights into the structure-function properties of proteins. We have developed a method based on numerical simulations with a simple coarse-grained force field, to attribute weights to these spring constants. This method considers the time that two C? atoms remain connected in the network during partial unfolding, establishing a means of measuring the strength of each link. We examined two different coarse-grained force fields and explored the computation of these weights by unfolding native structures. We compare the B-factors predicted by different elastic network models with the experimental ones employing the correlation coefficient between these two quantities. We show that wGNM performs better and consequently provides better evaluation of the B-factors
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Sampaio, de Sousa Soeiro Inês. "Proliferative signals in normal and malignant B cells". Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441947.
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Lanckman, Lies. "Norma Shearer, the happily married divorcee : marriage, modernity and movie magazines". Thesis, University of Kent, 2016. https://kar.kent.ac.uk/62963/.
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The central aim of this thesis is to examine five of Norma Shearer's pre-Code films - all made between 1930 and 1934 - and to place these films and their accompanying fan magazine rhetoric into a wider context, both within Shearer's career and within Hollywood history. It does this for two reasons. Firstly, it hopes to problematise the now commonly held view of Shearer as a noble, respectable, but ultimately rather dull star by demonstrating the ways in which these films allowed her to become an active advocate for a particular brand of often sexually transgressive modernity, in which she embraced consumer and leisure culture, female employment, companionate marriage and even the sexual single standard. Secondly, the thesis examines the fan magazine rhetoric on the star alongside these films and shows how her successful and happy marriage to MGM Head of Production Irving G. Thalberg served to strengthen, rather than soften, her position as a quintessential modern both on and off screen. After all, the marriage, in which Shearer and Thalberg were professional as well as romantic partners, allowed Shearer to promote a certain kind of companionate marriage, complete with mutual professional satisfaction, successful parenthood, and sexual compatibility. At the height of her fame, Shearer was the star who demonstrated to her female fans that a woman, in the brave new world of the early 20th century, should be able to have it all. Finally, then, the thesis examines how Shearer's ultra-modern reputation came to an end in the mid-1930s, and attributes this development primarily to two influences, one historical and one biographical. Firstly, in July 1934, the Hays Production Code was enforced; particularly targeting female sexual transgression on screen, this censorship text would make it virtually impossible for Shearer to make the types of films she had become most famous for. Secondly, then, in September 1936, Shearer's husband's premature death ensured that the star, who had previously been characterised as a modern wife, now became identified as a tragic, aristocratic, noble widow. Since her films no longer allowed her to develop an alternative persona, this is how Shearer remained known after her retirement, after her death, and to this day.
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Andersson, Åsa. "B cell repertoire development in normal physiology and autoimmune disease". Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 1993. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-101767.
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The B cell repertoire in the neonatal immune system (IS) is characterised by reactivity towards self-components, including other immunoglobulin (Ig) V-regions. These properties have been suggested to be a requirement for the development of a normal immune system. DNA sequencing of two interacting Ig idiotypes, derived from neonatal, preimmune mice, demonstrated that such idiotypic connectivity is germ- line encoded and devoid of VDJ junctional diversity. The serum levels of the same Ig idiotypes were studied in normal mice and demonstrated that the expression in serum fluctuated over time in a pattern compatible with a complex dynamic system. In contrast, similar analyses in autoimmune mice or humans demonstrated fluctuations in Ig titers that differed significantly from the healthy individuals. These findings suggested that pathological autoimmunity may be associated with fundamental alterations in the dynamics of natural antibody (ab) expression. This was further investigated in the nonobese diabetic (NOD) mouse, an animal model for human Type I diabetes. Suppression of the early B cell development in the NOD mouse prevented the development of diabetes, suggesting a role for B cells/Igs in the development of diabetes in these mice. Furthermore, neonatal injections of polyclonal Ig preparations or single, monoclonal natural abs inhibited disease induction. The prevention of diabetes development by one such natural ab was demonstrated to be dependent on both the dose injected and the timing of administration. Studies of the B cell repertoire development in NOD mice, compared to normal mice, by DNA-sequence analyses of IgVH rearrangements utilising genes from the most D-proximal Vh family, Vh7183, supported the idea of an aberrant B cell repertoire in this mouse model. Thus, the adult NOD mouse retained a neonatal pattern of Vh7183 rearrangements. This pattern could, however, be "normalised" by neonatal injection of a natural antibody, previously demonstrated to prevent the development of T cell dependent autoimmunity in the NOD mouse.Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 6 uppsatser
digitalisering@umu
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Gumina, Maria. "Growth and Survival Pathways in Normal and Malignant B-Lymphocytes". Thesis, Boston College, 2009. http://hdl.handle.net/2345/1400.
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Thesis advisor: Thomas C. ChilesNormal B lymphocytes require extrinsic factors to grow and proliferate. Surface receptors (e.g., B-cell antigen receptor, BCR) function, in part, to link growth factors to signal transduction/metabolic pathways and the cell cycle machinery. Accumulating evidence indicates that signal transduction-dependent changes in both glucose energy metabolism and de novo transcription of the D-type cyclin-cdk4/6 pathway are necessary for quiescent B-lymphocytes to enter G1-phase of the cell cycle and grow. B cell growth represents a critical checkpoint for subsequent proliferation and clonal expansion of antigen-specific lymphocytes. On the former, we have shown earlier that acquisition of extracellular glucose and metabolism via the glycolytic pathway is required for conventional splenic B-2 lymphocytes to grow (i.e., increase cell size and mass) in response to antigen challenge; however, the metabolic fate and biological significance of glucose-derived carbons are unknown. Here, we show that in response to BCR ligation, glucose carbon flow is directed into a de novo lipogenic pathway that is regulated, in part, via phosphoinositide-3 kinase (PI-3K)-dependent activation of ATP citrate lyase (ACL), a key rate-limiting enzyme in de novo lipogenesis. Inhibition of ACL results in a loss of B-cell growth and cell viability. Regarding the latter point, the B-1a lymphocyte subset expresses cyclins D2 and D3 that are transiently expressed in a non-overlapping manner, notably cyclin D3 expression immediately precedes the G1/S phase transition, suggesting distinct functions for these D-type cyclins in B-1a lymphocyte G0-to-S phase progression. We show herein that murine B-1a cells deficient in cyclin D3 proliferate normally in response to extracellular stimuli, in part, due to a compensatory sustained up-regulation of cyclin D2. In keeping with this, human diffuse large B-cell lymphoma (DLBCL) represents a malignant clonal expansion of B cells characterized by several subsets, including germinal center (GC) and activated B-cell (ABC) types. Here, we show that the GC-type LY18 human DLBCL exhibits constitutive expression of cyclin D3, but not cyclins D1 and D2. Targeting of cyclin D3-holoenzyme complexes with cell permeable chemical- and peptide-based cdk4 inhibitors results in G1-phase arrest and apoptosis via a pathway that involves inhibition of pRb phosphorylation. By contrast, endogenous knock down of cyclin D3 with siRNA did not induce growth arrest or apoptosis, in part, due to redundancy with cyclin E
Thesis (PhD) — Boston College, 2009
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology
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Christie, J. F. "Studies on the activation and differentiation of normal and leukaemic human B lymphocytes". Thesis, University of Strathclyde, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382350.
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Lu, Liwei. "B lymphopoiesis and B cell selection by apoptosis in bone marrow of normal and gene-modified mice". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ37000.pdf.
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Walton, Alexander James. "CD4+PF+ T Cells in B-CLL Patients & Normal Controls". Thesis, University of Westminster, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.502405.
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Our group has previously shown that CD4+Perforin (PFt T cells with cytotoxic potential are expanded in patients with B-CLL, accounting for up to 50% of CD4+ T cells in this disease. This study confinns the finding of increased percentages of CD4+PF+ T cells in a new cohort of B-CLL patients. However, the significance of this subset in B-CLL remains unclear. Evidence has accumulated for the potential role of CD4+ cytotoxic T cells in controlling cytomegalovirus (CMV). Therefore, a potential relationship between chronic CMV infection and CD4+PF+ T cell expansion in B-CLL was investigated. CMV seropositivity was found to be strongly associated with CD4+PF+ T cell expansion in both B-CLL patients and controls. This suggested that CD4+PF+ T cells from CMV seropositive (SP) patients and controls might contain clonally expanded populations of CMV-specific cells. To test this hypothesis, the CMV reactivity of CD4+PF+ and CD4+PF- T cells from B-CLL patients and controls was detennined using an intracellular cytokine staining flow cytometric assay. CD4+PF+ cells from untreated patients were enriched for CMV-reactive cells, as measured by . IFN-y production, compared to the CD4+PF- subset. In addition, the data indicated that CD4+ T cell immunity to CMV is dysregulated in B-CLL patients. CD4+PF+T cells from B-CLL patients are characterised by a highly differentiated CD2S-CD57+ phenotype. To further characterise the differentiation phenotype of these cells, the distribution of CD45RA and CCR7 was detennined on CD4+PF+ T cells from B-CLL patients and controls. CD4+PF+ T cells from B-CLL patients were both characterised by a highly differentiated T-effector memory TEM (CCRT) phenotype, but differed in the proportion of CD45RA expressing cells, which might reflect chronic T cell activation in the fonner group. ~inally, flowFISH analysis revealed that CD4+PF+ T cells had shorter telomeres compared CD4+PF- T cells in B-CLL patients, indicative of a more extensive replicative history. The results indicate that low, but persistent, antigenic exposure in CMVinfected individuals leads to the emergence of a CD4+PF+ T cell subset, characterised by a highly differentiated cell surface phenotype and shortened telomeres.
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McConville, Carmel M. "The effect of cytochalasin B on normal, transformed and hybrid cells". Thesis, Queen's University Belfast, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.329370.
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Verthelyi, Daniela I. "Effects of estrogen on the B cell functions of normal mice". Diss., This resource online, 1996. http://scholar.lib.vt.edu/theses/available/etd-08062007-094416/.
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Lopes, Ana Alexandra Festas. "Estudo funcional das células T de gânglio normal/reativo e com doença linfoproliferativa crónica de células B". Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/16768.
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Mestrado em Bioquímica - Bioquímica ClínicaAs doenças linfoproliferativas crónicas de células B são um grupo heterogéneo de entidades que representam cerca de 80-90% de todas as síndromes linfoproliferativas crónicas, nas quais podem ser observadas uma proliferação clonal de linfócitos B. Amostras de biópsia de gânglio linfático podem ser usadas para o diagnóstico destas doenças. Os gânglios linfáticos são o local adequado para as interações entre as células B e as células T e para ocorrer uma resposta imune. Neste sentido, é esperado que, na presença de células B malignas, com uma capacidade diferente para interagir com as células T, estas irão responder de uma forma diferente. O objetivo do presente trabalho consistiu na análise numérica e funcional das células T, nomeadamente de células T ativadas, células T reguladoras, Th/c17 e Thc/1, bem como, das células NK e quantificação de monócitos e células dendríticas. Foram analisadas dezanove amostras de biópsia de gânglio linfático, sete normais/reativas, cinco com linfoma linfocítico/LLC-B e sete com linfomas Não- Hodgkin B. Quantificou-se as subpopulações de células T CD4 e CD8; Th/c17; Th/c1; Tregs; células T ativadas através da citometria de fluxo, e após purificação das células TCD4 e TCD8, procedeu-se à quantificação da expressão de mRNA para os genes IL2 e IL10. Os nossos resultados mostraram um aumento das células Treg bem como, um decréscimo das células Th/c17 e Th/c1 no grupo com linfomas linfocíticos/LLC-B e no grupo com LNH-B. Relativamente à expressão génica, verificou-se uma diminuição de IL2 e um aumento de IL10 tanto para as células T CD4, como para as células T CD8 no grupo com linfomas linfocíticos/LLC-B e no grupo com LNH-B. Os resultados, embora preliminares, devido ao reduzido números de amostras estudadas, apontam para alterações significativas fenotípicas e funcionais nas células T e NK dos gânglios linfáticos com infiltração por células B patológicas, o que sugere diferenças ao nível da resposta imune anti-tumoral, que podem contribuir para o prognóstico destas entidades.
B cells Chronic lymphoproliferative diseases are a heterogeneous group of entities representing about 80-90% of all chronic lymphoproliferative syndromes, in which can be observed a clonal proliferation of B lymphocytes. Lymph node biopsy samples may be used to diagnosis of these diseases. Lymph nodes are suitable location for the interaction between B cells and T cells and an immune response to occur. Therefore, it is expected that in the presence of malignant B cells with a different capacity to interact with T cells, they will respond in a different way. The objective of this study was to numerical and functional analysis of T cells, particularly of activated T cells, regulatory T cells, Th/c17 and Th/c 1, as well as quantitation of NK cells and monocytes and dendritic cells. Nineteen lymph node biopsy samples were analyzed, seven normal/reactive, five with lymphocytic lymphoma/CLL-B and seven non- Hodgkin's lymphomas. Subpopulations of CD4 and CD8 T cells; Th/c17; Th/c1 Tregs; and T cells activated by flow cytometry were quantitated. After purification of CD4 and CD8 T cells, we proceeded to quantify the expression of mRNA for IL-2 and IL-10 genes. Our results showed an increase of Treg cells as well as a decrease in Th/ c17 cells and Th/c1 in the group with lymphocytic lymphoma/B-CLL and NHL-B group. For the gene expression, there was a decrease in IL2 and an increase of IL10 both CD4 T cells, as for CD8 T cells in the group with lymphocytic lymphomas/B-CLL and NHL-B group. The results, although preliminary, due to the small number of samples analyzed, indicate phenotypic and functional significant changes in the T and NK cells from lymph nodes with infiltration by pathological B-cells, suggesting differences in anti-tumor immune response, which may contribute to the prognosis of these entities.
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Murera, Uwanyirigira Diane. "Study of lymphocyte autophagy in normal and autoimmune responses". Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ068.
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L’autophagie est un processus catabolique lié aux lysosomes, essentiel à la l’homéostasie cellulaire notamment dans les lymphocytes. Elle est impliquée dans la pathogenèse de nombreuses maladies et pourrais jouer un rôle dans le développement de maladies auto-immunes. Nous avons voulu étudier son rôle in vivo dans les lymphocytes B et T. Nous avons généré des souris déficientes en autophagie spécifiquement dans ces cellules et montré que l’autophagie n’est pas essentielle au développement des LB, mais que dans un contexte auto-immun la persistance de plasmocytes et la production d’autoanticorps été diminuée. Cela démontre un rôle de l’autophagie dans les réponses à long terme. Les réponses humorales à long-terme T dépendantes sont également impactées. De plus des souris transplantées avec des LT CD4+ déficients en autophagie montrent une réponse humorale mémoire diminuée. Nous nous sommes également intéressé aux voies de signalisation conduisant à l’induction de l’autophagie en réponse à une stimulation du TCR dans des LT normaux et pathologiques. Nos résultats préliminaires montrent une implication de la voie calciqueAutophay is a catobolic lysosomal process essentail for cellular maintenance and fucntion such as lymphocyte homeosatsis. The generation of mice models with an Atg5 conditional knock-out in B and T cells respectively, have allowed us to study autophagy requirements of those immune cells in vivo. We have demonstrated that autophagy was dispensable for B cell development but that in autoimmune settings B cell autophagy was required for the maintenance of long-lived plasma cells and for the production of autoantibodies. In mice deficient for autophagy in T cells, long-term tumoral response to a T-dependent antigen is decreased. We also showed that in mice adoptively transferred with autophagy deficient CD4 T cells, the antigen specific memory humoral immune response was impaired. We also investigated the signaling pathways leading to autophagy induction upon TCR stimulation in normal and lupus T cells and showed that the calcium signaling is highly involved
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Mendonça, Matheus Rodrigues de. "Análise de modos normais em proteínas". Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/59/59135/tde-18032011-170446/.
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A abordagem de modos normais de baixa frequência na descrição das flutuações conformacionais dos estados nativos das proteínas globulares tem ajudado na caracterização das suas funções biológicas. Vários métodos teóricos e experimentais têm sido empregados para a determinação destas flutuações internas. Estes movimentos podem ser caracterizados pelo fator Debye-Waller (fator-B), correspondente à mobilidade local do resíduo em nível atômico. A análise de modos normais utilizando os modelos de rede elástica (ENM) demonstra ser uma técnica robusta. Fatores-B experimentais são reproduzidos teoricamente por meio desta técnica em tempos computacionais relativamente curtos, mostrando-se competitiva com as técnicas mais sofisticadas. O modelo de rede elástica é uma abordagem t ipo coarse-grain na qual a proteína no seu estado enovelado é representada por uma rede elástica tridimensional de carbonos conectados por molas. As molas representam as interações ligantes e não ligantes entre os carbonos . Neste trabalho, inicialmente, estudamos os modelos de rede elástica já conhecidos na literatura. Em seguida, realizamos um estudo comparativo entre eles. Neste estudo, comprovamos que os modelos pfGNM e pfANM apresentam melhor correlação com os fatores-B experimentais que os os modelos GNM e ANM tradicionais. Desenvolvemos também uma nova abordagem, a qual intitulamos número de contatos ponderados anisotrópica (AWCN). Mostramos que a abordagem AWCN apresenta um desempenho significativamente melhor que o modelo de rede elástica anisotrópica tradicional. Por fim, realizamos um estudo de caráter investigativo do comportamento do peso das interações entre resíduos. Este estudo re velou que, para os modelos WCN e AWCN, a correlação exibe o seu valor máximo para interações ponderadas $1/R^p$, entre resíduos $i$ e $j$j, para valores de $p$ em torno de 2. Nos modelos pfGNM e pfANM a correlação é maximizada para dois valores de $p$, o primeiro em torno de 2 e o segundo em torno de 4,75, indicando que a ponderação pelo recíproco do quadrado da distância, usualmente empregada na literatura, pode não ser adequada para obter a melhor correlação.Low frequency normal mode approach to describe conformational fluctuations of globular proteins has helped to characterize their biological functions. Various theoretical and experimental methods have been employed to det ermine the magnitudes of those internal motions. Those motions can be characterized by the Debye-Waller factor (B-factor), co rresponding to the local mobility of the residue at the atomic level. Normal mode analysis using elastic network models (ENM) has demonstrated to be a robust technique. Experimental B-factors has been reproduced theoretically by means of this techniq ue in a short computational time and it has been shown to be competitive with more sophisticated techniques. The ENM is a coarse-grained approach in which the protein is represented by a three-dimensional elastic network of alpha-carbon atoms connect ed by springs. Springs represent bonded and non-bonded interactions between the alpha-carbon atoms. In this work, we study th e elastic network models known in the literature. Next, we perform a comparative study between them. We show that the pfGNM a nd pfANM models present better correlation with experimental B-factors than the traditional GNM and ANM models. We also devel op a new approach, which we entitled anisotropic weighted contact number (AWCN). We show that it presents results significantly better than the traditional anisotropic elastic network model. Finally, we perform a study of investigative character of the behavior for the weight of the interactions between residues. This study revealed that, for the WCN and AWCN models, the correlation exhibits its maximum value for weighted interactions $1/R^p$, between residues $i$ and $j$, for values of $p$ around 2. In the pfGNM and pfANM models the correlation is max imized for two values of $p$, the first one around 2 and the second one around 4.75. This indicates that the weighting by the reciprocal of the square of the distance, usually employed in the literature, may not be appropriate to obtain the best correlation.
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Москаленко, Роман Андрійович, Роман Андреевич Москаленко, Roman Andriiovych Moskalenko, Анатолій Миколайович Романюк, Анатолий Николаевич Романюк, Anatolii Mykolaiovych Romaniuk e Rhim Suh Ngu'eh Shu. "Role of B-cells of the thyroid gland in normal and pathologies". Thesis, Видавництво СумДУ, 2009. http://essuir.sumdu.edu.ua/handle/123456789/6828.
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Baird, Allison Michelle. "Analysis of Low Zone Tolerance in Normal and B Cell-Deficient Mice". eScholarship@UMMS, 1996. https://escholarship.umassmed.edu/gsbs_diss/142.
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This thesis investigates the role of B cells as antigen-specific antigen-presenting cells (APC) in self tolerance to low concentrations of soluble self proteins and in acquired tolerance to low doses of soluble foreign protein antigens. Experiments were performed in normal and B cell-deficient animals, and tolerance induction was measured by T cell proliferation assays. T cell proliferation was reduced in B cell-deficient mice, indicating that B cells may be involved in efficient activation of naive T cells in response to protein antigen both in vivo and in vitro. To study acquired tolerance induced by low doses of soluble foreign protein antigen, normal and B cell-deficient adult mice were injected intravenously with repeated low doses (10 μg) of deaggregated ovalbumin (OVA), and then challenged with OVA in complete Freund's adjuvant. In animals treated with deaggregated OVA, the in vitro proliferative responses of LN T cells to OVA were significantly reduced, and production of the Th1 cytokine, IFN-γ, in response to OVA was lost. This occurred in both normal and B cell-deficient treated animals, indicating that B cell antigen presentation was not required for this phenomenon. B cells were also unnecessary for self tolerance of T cells to the transgenic self antigen, hen egg lysozyme (HEL), in a transgenic mouse strain with very low serum lysozyme concentration. Partial low zone tolerance induced by deaggregated, low-dose OVA was selective for the Th1 response, as measured by in vitro proliferation and IL-2 and IFN-γ production, because antibody responses of normal mice to this T cell-dependent antigen were largely unaffected. Both treated and untreated animals produced equivalent titers of anti-OVA antibodies, predominantly of the IgG1 and IgG2b isotypes, following challenge with OVA in complete Freund's adjuvant. Tolerance to low levels of the transgenic HEL self protein in mice expressing different MHC molecules was also addressed. Transgenic mice that were H-2b/b in the class II region were not tolerant to the transgenic self protein, whereas transgenic mice of the H-2b/k were tolerant.
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Schindler, Jay Jenson. "Immunological Effects of Amphotericin B Desoxycholate and Liposomal Amphotericin B on Splenocytes from Immune-Normal and Immune-compromised Mice". DigitalCommons@USU, 1992. https://digitalcommons.usu.edu/etd/4668.
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Because of the increasing number of serious risk factors which predispose a normally immune competent host to infection, the incidence of systemic fungal infections is steadily increasing. This epidemiological rise has especially become apparent since the onset of the AIDS epidemic. Amphotericin B is the drug of choice for these life-threatening mycotic infections. Complications due to drug toxicity, however, severely limit amphotericin B's clinical usefulness. The major complication associated with the administration of amphotericin B is renal toxicity. Research has indicated, however, that besides its antifungal activities, amphotericin B may act as an immune stimulant of both humoral and cellular responses.
A new formulation, liposomal amphotericin B, has been developed which has proven to be significantly less toxic to the kidneys. Research has suggested that liposomal amphotericin B may also act as an immune stimulant. Recent reports have also suggested that its stimulatory capabilities may possibly exceed those of the non-liposomal preparations.
The purpose of this study was to quantify the specific effects of amphotericin B and liposomal amphotericin B on the in vitro indices: cellular viability, B- and T-lymphocyte proliferation and macrophage activation as indicators of immune system functions. Spleen cells from immune normal, and immune compromised BALB/c female mice were harvested following euthanasia and incubated in the presence of the two drugs. Drug doses were chosen to correlate with those surrounding clinically relevant plasma concentrations. Cyclosporine and cyclophosphamide were used as immune suppressants to simulate organ transplant patients and patients receiving cancer chemotherapy, respectively.
Results indicated that amphotericin B consistently reduces the ability of B-cells and T-cells to proliferate and the ability of macrophages to produce interleukin-1. Though direct cytotoxicity may play a part in these assays, it is probably minor because viability studies show no more than a ten percent reduction due to amphotericin B compared with its liposomal analogue.
Liposomal amphotericin B was shown to be non-toxic in each of the immune parameters. It appeared that liposomes may be an important means of delivering more drug to a host infected with a fungal organism without further compromising the patient's already suppressed immune system.
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Abu-rish, Eman Yousuf Ali. "The role of toll-like receptor 9 on B-cell activating factor expression and function in normal human B-cells". Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/27908.
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B-cell autoreactivity is a characteristic abnormality in several autoimmune diseases. In systemic lupus erythematosus (SLE), inappropriate activation of TLR7 and TLR9, accompanied by high serum levels of BAFF, are implicated in disease pathogenesis. In murine B-cells, TLR9 activation resulted in up-regulating BAFF expression, while such a direct effect has not yet been established in normal human B-cells (nhB-cells). Therefore, the effect of CpG-2006, a synthetic TLR9 ligand, on the expression and function of BAFF and its receptors (BAFF-R, TACI and BCMA) in nhB-cells was studied. BAFF expression, in response to CpG-2006, was significantly upregulated at the level of mRNA, intracellular and membrane-bound protein in nhB-cell. In contrast, enhancement of BAFF secretion in culture supernatants of CpG-2006-stimulated nhB-cells was not detected. CpG-2006 treatment of nhB-cells significantly enhanced the expression of TACI and BCMA, but did not affect BAFF-R expression. CpG-2006-stimulated B-cells, in co-cultures with freshly isolated nhB-cells, co-stimulated B-cell receptor-induced cellular proliferation of the freshly isolated nhB-cells. This effect was completely blocked by a BAFF-specific monoclonal antibody. CpG-2006 treatment of nhB-cells sensitised them to proliferate in response to exogenous BAFF, whereas exogenous BAFF per se had no effect on the proliferation of untreated nhB-cells. This effect was inhibited by an anti-BAFF-R blocking antibody, but was not inhibited by anti-TACI or anti-BCMA antibodies. CpG-2006 mediated BAFF expression through NF-κB and ERK1/2 pathways, and partially through p38MAPK. Simultaneous treatment of nhB-cells with CpG-2006 and either of the inhibitory ODNs (ODN-TTAGGG or ODN-2088), at 1:5 ratio (CpG-2006: INH-ODN), inhibited CpG-2006-induced BAFF expression in nhB-cells. Finally, BJAB, RPMI and RAMOS B-cell tumour lines failed to represent nhB-cell’s responses to CpG-2006 treatment. Taken together, these novel findings demonstrate a functional cross-talk between TLR9 and BAFF in nhB-cells, and have possible implications for the roles of TLR9 and BAFF in the pathogenesis of SLE.
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Allen, Caroline Sarah. "Abundance analysis of normal and mercury-manganese type late -B stars from optical spectra". Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298788.
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Meier, Roger. "Phosphorylation and expression of human B-type lamins in normal and leukemic lymphoid cells /". [S.l.] : [s.n.], 1994. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Chichkov, Nikolay B. [Verfasser]. "Pulse duration and energy scaling of femtosecond all-normal dispersion fiber oscillators / Nikolay B. Chichkov". Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover (TIB), 2012. http://d-nb.info/1024816354/34.
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O'Nions, Jenny Clare. "Regulation of proliferation and cell cycle checkpoints in EBV infected and normal human B cells". Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406421.
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Srour, Nivine. "Impact de la production des immunoglobulines tronquées sur le développement lymphocytaire B normal et tumoral". Thesis, Limoges, 2016. http://www.theses.fr/2016LIMO0011/document.
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Le processus de recombinaison V(D)J des gènes d’immunoglobulines (Ig) est caractérisé par une grande imprécision des jonctions entre les segments variables (V), de diversité (D) et de jonction (J). Deux fois sur trois, un décalage du cadre de lecture apparaît, aboutissant à une jonction non productive dite « hors phase ». Plusieurs études ont démontré que les deux allèles productifs et non-productifs sont activement transcrits. Les transcrits matures issus des allèles non-productifs sont pris en charge par un mécanisme de surveillance des ARNm appelé NMD « Nonsense-Mediated mRNA Decay ». En dégradant efficacement les ARNm d’Ig contenant des codons non-sens, ce mécanisme prévient l’apparition des Ig tronquées au cours de l’ontogénie B. Néanmoins, aucune étude n’a jusqu’ici analysé l’impact de l’épissage alternatif des transcrits d’Ig non-productifs. Ce phénomène appelé NAS « Nonsense-associated Altered Splicing » peut conduire à une production d’Ig tronquées présentant des délétions internes du domaine variable (V).Les projets développés lors de cette thèse ont montré que la présence d’un codon non-sens, au niveau de l’exon variable (VJ) des transcrits Igκ, favorise le saut d’exon et la production de chaînes légères dépourvues de domaine variable (ΔV-κLCs). De façon intéressante, ces Ig tronquées provoquent un stress cellulaire et conduisent à l’apoptose des plasmocytes (Article 1). Ces observations ont permis d’identifier un nouveau point de contrôle agissant tardivement lors de la différenciation plasmocytaire : le TIE « Truncated-Ig Exclusion » checkpoint. Ce processus de contrôle provoque l’élimination des plasmocytes qui produisent des chaînes d’Ig tronquées. Nous avons également étudié l’épissage alternatif des transcrits d’Ig non-productifs en l’absence de TIE-checkpoint (Article 2). Cette étude a révélé que l’hypertranscription des gènes d’Ig dans les plasmocytes favorise l’épissage alternatif des transcrits d’Ig non-productifs. En utilisant un modèle d’expression forcée d’Ig tronquées, nous avons mis en évidence une coopération entre les mécanismes assurant la surveillance des ARNm (NMD) et la surveillance au niveau protéique (UPR : « Unfolded Protein Response », autophagie) (Article 3). Sur la base de ces résultats, nous avons mis au point une nouvelle approche thérapeutique qui consiste à forcer la production d’Ig tronquées en utilisant des oligonucléotides anti-sens (AON) capables de provoquer l’élimination de l’exon variable lors de l’épissage. Cette invention pourrait ouvrir des perspectives thérapeutiques pertinentes dans le traitement du Myélome Multiple et d’autres pathologies touchant les plasmocytesThe recombination process V(D)J of immunoglobulin (Ig) genes is characterized by random junctions between the variable (V), diversity (D) and joining (J) segments. A frameshift mutation appears in two-third of cases, generating a non-productive or « out of frame » junction. Several studies have shown that both productive and non-productive alleles are actively transcribed. The mature transcripts from nonproductive alleles are usually considered sterile and innocuous as a result of an mRNA surveillance mechanism called NMD « Nonsense-Mediated mRNA Decay ». By degrading aberrant mRNA, this mechanism prevents the appearance of truncated Ig during B cell ontogeny. However, less is known about the impact of alternative splicing on non-productive Ig transcripts. This mechanism, called NAS « Nonsense-associated Altered Splicing » can lead to the production of truncated Ig with internal deletions of variable domain (V). During my thesis, we have shown that the presence of a stop codon, within the variable exon (VJ) of Igκ transcripts, promotes exon skipping and synthesis of V domain-less κ light chains (ΔV-κLCs). Interestingly, such truncated Ig causes cellular stress and leads to plasma cells apoptosis (Article 1). These findings have identified a new checkpoint acting late during plasma cell differentiation: TIE « Truncated-Ig Exclusion » checkpoint. This process ensures counter-selection of plasma cells producing truncated-Ig. We also studied the alternative splicing of non-productive Ig transcripts in the absence of TIE-checkpoint (Article 2). We found that hypertranscription of Ig genes in plasma cells promote alternative splicing of non-productive Ig transcripts. Using a model forcing the expression of truncated Ig, we identified a cooperative action between mRNA surveillance mechanisms (NMD) and those of protein surveillance (UPR « Unfolded Protein Response », autophagy) (Article 3). Based on these results, we have developed a new therapeutic approach by increasing the production of truncated Ig using antisense oligonucleotides (AON) that leads to the elimination of the variable exon during splicing. This invention could open new avenues for the treatment of Multiple Myeloma patients and other pathologies affecting plasma cells
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Matos, Alexandre Manuel Ribeiro. "SPECTRUM : uma norma de gestão de coleções para os museus portugueses". Tese, Porto : [Edição do Autor], 2012. http://aleph.letras.up.pt/F?func=find-b&find_code=SYS&request=000222881.
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A gestão do património cultural à guarda dos museus portugueses exige a atenção dos seus responsáveis e dos organismos estatais que definem a política museológica nacional. O elevado número de museus e o aumento assinalável de bens culturais que aqueles têm vindo a incorporar, bem como as mudanças significativas que o sector museológico sofreu nas últimas décadas, obrigam estas instituições e os seus profissionais a procurar os meios mais eficientes para realizar tarefas estruturantes da sua actividade: documentar e gerir as suas coleções. O SPECTRUM - The UK Museum Collections Management Standard tem vindo a afirmar-se, na comunidade museológica internacional, como uma das mais eficientes e bem elaboradas normas de procedimentos para gestão de coleções. O sucesso do processo de internacionalização desta norma, assim o comprova. Neste sentido, com este trabalho procuramos verificar a pertinência e vantagens daquela norma para os museus portugueses e para o relevante trabalho de digitalização, documentação e gestão dos acervos que a maioria tem em curso há alguns anos. Conhecendo as dificuldades existentes, no que diz respeito aos recursos humanos e financeiros destas instituições, é nossa pretensão disponibilizar uma ferramenta que, sendo simples de utilizar, sirva a preparação e execução da gestão do património museológico. Este documento resulta de três trabalhos que empreendemos nesse sentido. A tradução e adaptação do SPECTRUM à realidade e contexto legal nacionais, a verificação da compatibilidade da norma, através do estudo de caso da sua aplicação no Museu da Ciência da Universidade de Coimbra e a adaptação e construção de um sistema de gestão de coleções compatível com aquela norma em colaboração com a empresa Sistemas do Futuro.
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Howard, Donald Raymond. "Cell surface antigens in normal and neoplastic human B lymphocyte differentiation : cellular distribution and functional implications". Thesis, University of British Columbia, 1985. http://hdl.handle.net/2429/25809.
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Differentiation within the lymphoid system produces effector cells which are involved in a variety of immune functions. For T cells these include the provision of help, suppression, cytolytic activity and the regulation of cooperative cellular interactions. The primary function of B lineage cells is the production of specific antibody. Understanding the regulation of normal lymphocyte proliferation and differentiation may lead to a better appreciation of those factors which result in the development of malignancy. The non-Hodgkin's lymphomas are neoplasms of the immune system, the majority of which are B cell in origin. Despite advances in immunology and molecular biology, little is known about the mechanisms involved in B cell activation, proliferation and differentiation or about those events leading to their malignant transformation.
The advent of monoclonal antibody technology a decade ago has revolutionized our ability to identify and characterize cell surface antigens. Because the activation and control of proliferation of B cells was already known to involve structures at the cell surface, it was logical to utilize monoclonal antibodies to identify additional cell surface molecules that might be important in the function of normal B lymphocytes and that might allow normal and various types of neoplastic B cells to be distinguished. To achieve this goal, we developed monoclonal antibodies that showed differential reactivity between large actively dividing lymphoma cells and small inactive (quiescent) lymphocytes. These were tested for their ability to inhibit various T and B lymphocyte functions (i.e. responses to anti-µ, lipopolysaccharide, phytohemagglutinin and the mixed lymphocyte response) as well as for their reactivity with cell suspensions from a variety of malignant and nonmalignant hematopoietic tissues.
From these studies emerged the following: 1) Cell surface molecules other than Immunoglobulin are involved in regulating the activation of normal B cells. This was shown by the discovery that monoclonal antibodies to both lymphocyte function associated antigen (LFA-1) and certain HLA class II determinants were able to inhibit the activation of peripheral blood mononuclear cells by the B cell mitogens anti-p and LPS. This inhibition was shown to be mediated via effects of these antibodies on T cells and/or monocytes. 2) B lymphoma cells appear to express unique cell surface antigens (defined by monoclonal antibodies LM-26 and LM-155) not detectable on cells of other lineages, and absent from normal resting or activated B lymphocytes.
Future investigations will attempt to define the mechanisms by which the indirect involvement of LFA-1 and HLA class II molecules in B cell activation in vitro suggests new regulatory interactions not previously identified. Further studies will be required to define the mechanisms underlying these interactions and their significance in vivo. Similarly, the structure and function of the antigens detected by LM-26 and LM-155 remains to be determined. Nevertheless, the expression of apparently unique molecules on B lymphoma cells holds new promise for the diagnosis, classification and treatment of this group of diseases.Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate
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Tucunduva, Maria José Albuquerque Pereira de Sousa e. "Proposta de mapeamento da vascularização normal da face por meio da ultrassonografia modo B e Doppler". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/23/23139/tde-14012013-154327/.
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O estudo do aporte sanguíneo da face é importante em função da cirurgia como para as cirurgias que fazem uso de retalhos. O bom restabelecimento da área depende da perfusão obtida. Os métodos de aquisição de imagem que investigam a vascularização da face muitas vezes são caros e acrescentam risco à condição do paciente. A ultrassonografia é um método de imagem que não oferece risco ao paciente, sendo acessível e realizado em tempo real. A intensidade do fluxo sanguíneo de uma determinada estrutura pode ser medida pelo modo Doppler e alterações do padrão de normalidade indicam uma possível deficiência na nutrição dos tecidos compreendidos, podendo mesmo levar o clínico a prever futuras afecções. O objetivo neste estudo foi captar a vascularização normal da face, por meio da ultrassonografia modo B e Doppler de modo a se propor um mapeamento dos principais vasos arteriais. Foi possível, utilizando-se transdutores linear e endocavitário proceder-se ao estudo da vascularização da face. Foram obtidos dados referentes à vascularização da face que permitissem a análise da hemodinâmica dos tecidos. Foram estudados três vasos de diâmetro reduzido (0,60mm a. angular; 0,55mm a. palatina maior; 0,45mm a. infraorbital), sendo que nestes foi possível adquirir gráficos de onda de velocidade de fluxo e, consequentemente, obter-se a velocidade de pico sistólico (VPS) e o índice de resistividade (IR).The study of the blood supply of the facial tissues is important due to oral and maxillofacial surgery as for operations that make use of flaps. The proper restoration of the perfusion is essential to the success of these procedures. The image methods that investigate the vasculature of the face are often costly and add risk to the patients condition. Ultrasound is an imaging method that offers no risk, is affordable and is performed in real time. The intensity of blood flow of a given structure can be measured by Doppler mode and changes in the normal range can indicate a deficiency in the nutrition of tissues end even influence the clinician to predict future conditions. The aim of this study was to access the normal vasculature of the face through ultrasound B-mode and Doppler in order to propose a mapping of the arterial vessels. It was possible, using the linear and endocavitary probes to study the vascularity of the face. Data was obtained allowing the analysis of the tissue hemodynamics. It was possible to access three arteries of small diameter (0,60mm angular artery; 0,55mm greater palatine artery; 0,45mm infraorbital artery) and in all cases graphics of wave flow velocity. Therefore, the resistivity index (RI) and systolic peak velocity (SPV) could also be computed.
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Saintamand, Alexis. "Etude du rôle de la région régulatrice en 3' du locus IgH au cours du développement lymphocytaire B normal et pathologique". Thesis, Limoges, 2016. http://www.theses.fr/2016LIMO0007/document.
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Durant l’ontogénie B, le locus des chaines lourdes d’immunoglobulines (IgH) subit trois processus de réarrangements géniques. Lors des phases précoces du développement B, indépendamment de la rencontre avec un antigène, les réarrangements VDJ permettent l’obtention d’un répertoire d’Ig fonctionnelles. Lors des phases tardives, l’hypermutationsomatique (SHM) permet l’augmentation de l’affinité de l’Ig pour son antigène tandis que larecombinaison isotypique (CSR) modifie ses fonctions effectrices. Ces évènements impliquent l’induction de lésions de l’ADN potentiellement oncogéniques, ce qui impose unerégulation très stricte. Cette régulation est assurée par divers éléments cis-régulateurs répartis tout au long du locus IgH, dont la région régulatrice en 3’ (3’RR). La 3’RR s’étend sur 30 kb et contient quatre activateurs transcriptionnels, les trois premiers formant une structure palindromique. Lors de ma thèse, j’ai utilisé plusieurs modèles murins porteurs de délétions de tout ou partie de la 3’RR pour étudier son rôle, ainsi que celui des différents éléments qui la compose lors des diverses étapes de l’ontogénie B. Nous avons pu déterminer comment la 3’RR régule précisément la CSR en ciblant spécifiquement la région switch acceptrice et caractériser le phénomène encore peu connu de CSR vers IgD. D’autre part, nous avons démontré l’importance de la 3’RR lors de la SHM et dans le développement des différentes sous populations lymphocytaires B. Enfin, la comparaison des résultats obtenus lors de l’analyse des différents modèles nous a permis de déterminer que la structure palindromique de la 3’RR est importante pour une SHM efficace, mais relativement dispensable lors de la CSRDuring B-cell development, the heavy chains locus (IgH) undergoes three genic rearrangement events. During the early stages, before encountering the antigen, VDJ rearrangements allow the generation of a functional Ig repertoire. During the late stages, somatic hypermutation (SHM) increases the affinity of the Ig for its antigen, while class switch recombination (CSR) modifies its effector functions. These events imply thegeneration of potentially oncogenic DNA lesions, and thus require a strict regulation. This regulation is assured by several cis-regulatory elements spread along the IgH locus, including the 3’ regulatory region (3’RR). The 3’RR extends on more than 30kb and contains four transcriptional enhancers, the first three displaying a palindromic conformation. During my PhD, I investigated several mouse models carrying deletion of part or totality of the 3’RR to investigate its role during B cell development. We demonstrated how she precisely regulates CSR by specifically targeting the acceptor switch region, and described the poorly known mechanism of CSR toward IgD. Otherwise, we have demonstrated its importance during SHM and in the correct development of the different B cell subpopulations. Finally, by comparing the results obtained during the analysis of the various mouse models, we have demonstrated that the palindromic structure of the 3’RR is required for optimal SHM, but not for CSR
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Brousseau, Jérôme. "Le vieillissement normal, le vieillissement pathologique et la question de la fonction biologique". Master's thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/33027.
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Dans un contexte où plusieurs sphères de la vie ne se rapportant pas directement aux questions de santé (la performance sportive et intellectuelle, la contraception et l’apparence physique) sont aujourd’hui médicalisées, nous croyons qu’il importe d’examiner les critères permettant de légitimer l’intervention médicale sur le vieillissement. Dans ce mémoire, nous faisons l’hypothèse que l’approche naturaliste en philosophie de la médecine réussirait à rendre compte de la distinction entre le normal et le pathologique à partir de critères naturels et objectifs, permettant ainsi de rendre unanime la prise en charge médicale et de surpasser un certain relativisme des valeurs. Pour la vérifier, nous étudions dans ce mémoire trois propositions, chacune reposant sur trois champs d’études distincts : l’épidémiologie, la physiologie et la biologie évolutive. Premièrement, nous analysons le critère de l’inévitabilité, proposé par les architectes des études longitudinales américaines sur le vieillissement et repris aujourd’hui en gériatrie, définissant le vieillissement normal comme tout changement lié à l’âge considéré comme inévitable et le plus fréquemment observé. Notamment fondée sur l’épidémiologie, nous concluons, d’une part, que cette approche ne sait faire l’impasse sur le rôle des valeurs grâce aux critiques de Canguilhem et Sedgwick, et, d’autre part, qu’elle s’éloigne de la notion de facteurs de risque caractéristique de l’épidémiologie qui tend à remettre en question le dualisme normal/pathologique. Ensuite, nous pensons que la théorie biostatistique (BST) de Christopher Boorse constitue une approche naturaliste plus prometteuse que la précédente. Cependant, le vieillissement constitue un cas limite pour la BST puisqu’il résulte davantage d’une transition épidémiologique que de l’évolution. En effet, Boorse ne veut pas faire reposer ses notions de design et de classes de référence sur des changements environnementaux soudains, voulant plutôt que le fonctionnement normal relève d’un design significatif de l’histoire évolutive d’une espèce. Plus récemment, Boorse, suivant indirectement la proposition de Caplan, tend à considérer le vieillissement comme pathologique puisqu’il ne présenterait aucune fonction sélectionnée. Finalement, nous pensons que la position d’Arthur Caplan voulant que le vieillissement soit pathologique faute de fonction sélectionnée reprend quelques erreurs de l’adaptationnisme méthodologique en confondant l’explication de l’origine évolutive d’un trait et sa fonction. Nous analysons ainsi la proposition de Caplan à l’aune des différentes théories de la fonction biologique, des débats en biologie de l’évolution sur le vieillissement et des critiques de l’adaptationnisme. En conclusion, nous pensons qu’il est difficile de soutenir une position naturaliste de la distinction entre le vieillissement normal et le vieillissement pathologique. Une telle compréhension dichotomique semble au final moins prometteuse qu’une notion continuiste fondée, par exemple, sur les facteurs de risque. Nous proposons une étude plus approfondie des perspectives continuistes et de la possibilité que le vieillissement soit une exaptation, présentant des avantages au niveau écosystémique. Si cette hypothèse s’avérait valide, alors nous pourrions objectivement limiter l’intervention biomédicale en vue de prolonger la vie au nom d’une santé écosystémique.Is aging a normal or a pathological process? To affirm the former leads to another question: how can we distinguish normal aging from its pathological deviations? This question is important since several domains in society, which are not directly concerned with matters of health and disease, are nevertheless subjected to medical intervention. Athletic and intellectual performance, or contraception and physical appearance, for instance, are all in the remit of medical interventions based on values such as productivity, youth, and fear of death. Naturalism in philosophy of medicine asserts that the distinction between health and disease can be based on natural criteria alone. With the prospect of delineating the scope of legitimate medical interventions, naturalism also hopes to avoid cultural relativism where health and disease are seen as context-dependant value judgments. This dissertation focuses on three approaches, each based on a different scientific field, namely: epidemiology, physiology and evolutionary biology. First, I consider the criterion of inevitability used in geriatrics and developed in the context of two of the most significant longitudinal studies of aging in North America. According to these studies, normal aging boils down to inevitable physiological change through time, which is based on statistical mean in an aging population. This kind of assumption has been notably criticized by the French philosopher George Canguilhem, and I conclude that it ultimately rely on value judgment. Secondly, I introduce the Biostatistical Theory (BST) of Christopher Boorse. In this naturalist theory, Boorse considers old age as a reference class of uniform functional design. According to the BST, a normal function is a statistically typical contribution of a part or process to their individual survival and reproduction. Yet, aging and old age are borderline cases for the BST because they are mostly the result of the twentieth-century epidemiological transition. For Boorse, the design and reference class need to be evolutionarily significant, and not based on sudden environmental changes. More recently, Boorse tends to consider aging as pathological, indirectly following Arthur Caplan’s assumption, because it has no selected functions. Finally I argue that Caplan’s assumption reprises methodological adaptationism which confuses the explanation of the evolutionary origin of a trait and its function. To support it, I analyze his arguments in light of the functional theories, the debates around the evolution of aging and the criticism of adaptationism. I assume from there the possibility that aging is an exaptation, having a function at other levels of biological organization namely at the ecosystem level. For example, ecosystem health could objectively delineate the premises of biomedical intervention to postpone aging and death. I generally conclude that a naturalist approach of normal and pathological aging is hard to defend. I think that digging deeper into a continuist approach could prove fruitful, while the notion of risk factor in epidemiology could open new ways to understand health and disease in aging.
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Aupperlee, Mark Douglas. "The regulation and function of progesterone receptor isoforms A and B in the normal mouse mammary gland". Diss., Connect to online resource - MSU authorized users, 2008.
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Thesis (Ph. D.)--Michigan State University. Cell and Molecular Biology Program, 2008.Title from PDF t.p. (viewed on March 30, 2009) Includes bibliographical references (p. 174-178). Also issued in print.
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Shore, Susan Louise. "The effect of a moderate aerobic training program on T, B, and natural killer cell number and function in normal adults, normal children, and children with cancer". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0028/NQ35321.pdf.
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Lindholm, Pirttilä Christopher, e Oscar Nordh. "Relativvärderingsbaserade investeringar. Hur väl fungerar de i olika branscher? : En studie över samtliga företag noterade i Norden mellan åren 2005–2014". Thesis, Linköpings universitet, Nationalekonomi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-121529.
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Bakgrund: Denna studie har genomförts för att bringa klarhet i hur väl relativvärdering fungerar som investeringsstrategi mellan åren 2005 och 2014 på de nordiska marknaderna. Huruvida det finns någon skillnad mellan hur väl strategin fungerar om marknaderna sorteras efter branschtillhörighet samt om tidigare välanvända nyckeltal kan generera olika hög avkastning i olika branscher är ett outforskat område. Tidigare studier på området har antingen undersökt hela marknader eller enskilda branscher där resultaten delvis har tolkats med hjälp av aktiemarknadspsykologi.Syfte: Syftet med studien är att analysera huruvida det finns skillnader i hur väl relativvärdering fungerar som investeringsmetod inom olika branscher för att generera överavkastning; samt huruvida det statistiskt går att säkerställa om det finns en koppling mellan bransch och nyckeltal.Genomförande: Studien använder en kvantitativ metod där aktierna sorteras i kvartilportföljer baserade på dess branschtillhörighet och sin värdering relativt branschkonkurrenter. Portföljerna omplaceras på årlig basis och avkastning räknas ut på månadsbasis samt kumulativt. Portföljerna utvärderas sedan med hjälp av välanvända riskmått samt en diversifieringsprocess och aktiemarknadspsykologi.Resultat: Relativvärdering kan användas för att generera överavkastning i samtliga branscher utom i energibranschen. En skillnad i avkastning, beroende på i vilken bransch, kvartil och nyckeltal som används för investeringen kan konstateras. Diversifiering sänker effektivt risken samtidigt som avkastningen inte sjunker i samma takt. Aktiemarknadspsykologi kan endast till viss del kopplas till skillnaderna i avkastning mellan portföljerna.Background: This thesis has been executed in order to bring clarity into the matter whether relative valuation works as an investment strategy in the Nordic region between the years 2005 and 2014. Whether the strategy performs differently if the markets are sorted by sector affiliation, as well as if previously commonly used key ratios can generate different returns in different sectors is an unexplored area. Previous studies have focused on examining entire markets or specific industries where the results partially have been interpreted with behavioral finance.Aim: The aim of the thesis is to analyze whether there are any differences in how well relative valuation works as an investment method in different sectors, in order to generate excess return; as well as if it is statistically possible to find a connection between sectors and key ratios.Completion: A quantitative approach is used where the stocks are sorted into quartile portfolios in accordance with their sector affiliation and based on their valuation relative to sector competitors. The portfolios are then rebalanced on a yearly basis and returns are calculated on monthly and cumulative basis. Furthermore the portfolios are evaluated using risk measures, a diversification process and behavioural finance.Results: Relative valuation can be used to generate excess return in all sectors except in the energy sector. A discrepancy in returns is shown, depending on which sector, quartile and key ratio that is used for the investment. Moreover, diversification effectively lowers the risk without lowering the return at the same pace. Behavioural finance can only partially explain the differences in return between the portfolios.
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BECKMANN, M. PATRICIA. "SYNTHESIS AND OLIGOSACCHARIDE PROCESSING OF NORMAL AND ALTERED IMMUNOGLOBULIN M DURING B-CELL DIFFERENTIATION (GLYCOPROTEIN, GLYCOPEPTIDE, MUTANT, CARBOHYDRATE, ASPARAGINE-LINKED)". Diss., The University of Arizona, 1985. http://hdl.handle.net/10150/187906.
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Glycoproteins play a key role in cellular growth and differentiation. In order to study glycoprotein biosynthesis and processing, we have chosen the murine Immunoglobulin M (IgM) system as a model. Our system utilizes hybridoma, lymphoma and plasmacytoma cell lines which synthesize intracellular, membrane-bound and secreted IgM. Each type of IgM is synthesized during a specific phase of B-cell differentiation. We have examined the kinetics of IgM synthesis and processing in cells at each developmental stage. The rate of synthesis of membrane-bound and soluble IgM are different. Characteristic rates for membrane versus soluble IgM may be dependent on the extent of oligosaccharide processing. The membrane-bound IgM contains more high-mannose oligosaccharide than does the secreted product. In addition, we have begun to determine how protein structural requirements can affect final glycosylation patterns on the glycoprotein. Two cell lines were studied which secreted smaller than normal IgM heavy chains in tissue culture. One cell line studied (208) contains one glycosylation site, while another (562) retains three sites on the molecule synthesized in tissue culture. Studies performed on these cell lines in tissue culture indicate greater processing of the oligosaccharides on these mutant IgM molecules when compared to the parental cell line (PC700). Studies on the 208 IgM molecules synthesized in the mouse and purified from ascites fluid confirm these results. Upon injection into the mouse, the 562 cell line reverts to produce protein and carbohydrate structures characteristic of the parental cell line. Studies on the 562 protein purified from ascites fluid illustrate the need for more precisely defined cell lines and genetic engineering for the study of altered protein structures.
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Bittencourt, Luiz Carlos Fortes. "Norma tributária antielisiva à luz da legalidade e da livre iniciativa / Luiz Carlos Fortes Bittencourt ; orientador, Roberto Catalano B. Ferraz". reponame:Biblioteca Digital de Teses e Dissertações da PUC_PR, 2006. http://www.biblioteca.pucpr.br/tede/tde_busca/arquivo.php?codArquivo=413.
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Dissertação (mestrado) - Pontifícia Universidade Católica do Paraná, Curitiba, 2006Inclui bibliografia
O presente estudo tem o objetivo de investigar a possibilidade, ou não, de inserção de norma tributária antielisiva na ordem jurídica brasileira à luz dos princípios constitucionais da legalidade e da livre iniciativa. Os referidos princípios encontram-se
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Tooze, Jennifer Anne. "Cell surface and molecular expression of immunoregulatory determinants on B-cell chronic lymphocytic leukaemia cells and their putative normal lineage counterparts". Thesis, Brunel University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359926.
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Watanabe, Norihiko. "Antigen receptor cross-linking by anti-immunoglobulin antibodies coupled to cell surface membrane induces rapid apoptosis of normal spleen B cells". Kyoto University, 1998. http://hdl.handle.net/2433/182246.
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Schmälter, Ann-Kristin [Verfasser], e Ortrud [Akademischer Betreuer] Steinlein. "Nuclear orientation patterns for mouse chromosome 11 in normal B lymphocytes and during plasmacytoma development / Ann-Kristin Schmälter ; Betreuer: Ortrud Steinlein". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1126406783/34.
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Cuevas, Sepúlveda José Ricardo. "Inconsistencias en normas de la ley sobre impuesto a la renta que regulan el cálculo de la TEF en sociedades acogidas al régimen del artículo 14 B), frente a dividendo percibido". Tesis, Universidad de Chile, 2018. http://repositorio.uchile.cl/handle/2250/167956.
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TESIS PARA OPTAR AL GRADO DE MAGÍSTER EN TRIBUTACIÓNLa Ley sobre Impuesto a la Renta está contenida en el Decreto Ley N°824, el que fue publicado en el Diario Oficial con fecha 31 de diciembre de 1974 y su última modificación se produce con las leyes 20.780 y 20.899, publicadas en el Diario Oficial con fecha 29 de septiembre de 2014 y 8 de febrero de 2016, respectivamente. Conforme a dicha ley, nuestro régimen de tributación a las rentas corresponde a un sistema perfectamente integrado, esto es, el impuesto a la renta pagado por la empresa sirve en un 100% como crédito contra los impuestos finales de los dueños, socios o accionistas, sea este, Impuesto Global Complementario en el caso de contribuyentes con residencia en Chile o Impuesto Adicional para contribuyentes sin domicilio ni residencia en Chile (Yañez, 2013, p.9 reporte tributario mayo). Es importante destacar, que, hasta el 31 de diciembre de 2016, los dueños de las empresas pagaban impuestos solo por las utilidades percibidas, lo que les permitiría postergar indefinidamente el pago del impuesto global complementario y el impuesto adicional. La postergación de los impuestos finales por utilidades no retiradas o distribuidas y algunos regímenes especiales de tributación se han desviado sustancialmente de sus objetivos iniciales y se han convertido en fuentes de elusión y evasión. En la búsqueda del mejoramiento del sistema tributario se han promulgado en los últimos años, tres leyes enfocadas a disminuir las erosiones tributarias para obtener un sistema óptimo que cumpla con los objetivos de equidad en la distribución de los ingresos, suficiencia para hacer frente a los gastos en que debe incurrir el Estado, simpleza de la ley que permita una adecuada comprensión y certeza de las normas que amparan el sistema tributario. La primera de ellas es la Ley 20.630 publicada en septiembre de 2012, que perfecciona la legislación tributaria y tiene como objetivo principal el aumentar la recaudación fiscal para financiar una reforma educacional. En abril de 2014 la presidenta de la República Michelle Bachelet envía al parlamento un proyecto de ley de reforma tributaria que establecía un sistema de tributación sobre rentas atribuidas, aplicable a los empresarios individuales, contribuyentes del articulo 58 N°1 de la LIR, comuneros, socios y accionistas de empresas que declaren renta efectiva según contabilidad completa, incorporando bajo el concepto de rentas atribuidas, aquellas establecidas en el artículo 14 de dicho proyecto. De esta manera el proyecto de ley considera un aumento de la tasa del IDPC, tributación sobre base devengada y término del Fondo de Utilidades Tributables, ajustes a la tasa máxima marginal de los impuestos a las personas y ajustes a la tributación de las ganancias de capital. Con fecha 29 de septiembre de 2014 fue publicada la Ley 20.780 sobre reforma tributaria, que constituye la mayor modificación que ha sufrido nuestro sistema tributario en las últimas tres décadas y a diferencia de la reforma del año 2012, ésta cambia el régimen de las rentas empresariales establecido en el artículo 14 de la Ley sobre Impuesto a la Renta, basado en los retiros o distribuciones de las utilidades tributarias imputadas al Fondo de Utilidades Tributables, por dos nuevos regímenes opcionales de renta efectiva con vigencia a partir del 1° de enero de 2017 y son el Régimen de renta atribuida (artículo14 letra A) y el Régimen de imputación parcial de créditos (artículo14 letra B). Cada uno de estos regímenes de tributación incorpora nuevos registros y nuevos sistemas de imputación de las utilidades para contribuyentes con contabilidad completa y balance. Una vez publicada la Ley 20.780 se observaron dificultades y problemas en su implementación, como consecuencia de su complejidad y aparición de costos asociados en su puesta en marcha y aplicación gradual1, en la pequeña y mediana empresa lo que derivó en una tercera modificación legal, dando origen a la Ley 20.899, promulgada el 1° de febrero de 2016, conocida como la ley de simplificación del sistema de tributación a la Renta y perfección de otras disposiciones legales o “la reforma de la reforma”. Esta ley considera modificaciones a la ley sobre Impuesto a la Renta, Ley sobre Impuesto a las Ventas y Servicios, Código Tributario y a normas transitorias establecidas en la Ley 20.780 con vigencia algunas a partir del 1° de enero de 2016 y 1° de enero de 2017 otras. Son estas disposiciones transitorias que norman el tratamiento tributario de los saldos existentes en el Fondo de Utilidades Tributables y sus registros anexos (FUR, FUF, FUNT) al 31 de diciembre de 2016 y su adecuación a los nuevos regímenes tributarios establecidos en el nuevo artículo 14 de la Ley sobre Impuesto a la Renta.
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Sgobbi, Alexandre Amaral. "Caracterização mecânica e microestrutural de juntas tubulares soldadas em aço API 5L Grau B com base na norma Petrobrás N-2301". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/85/85134/tde-21072015-104725/.
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Para a certificação de um procedimento de soldagem, quer seja de alta responsabilidade na soldagem de oleodutos e gasodutos em tubulações de aço carbono ou para um uso rotineiro e diário em fábricas e oficinas, deve ser realizada uma análise profunda dos fenômenos ocorridos no material de base (MB), no metal de adição (MA) e na zona afetada pelo calor (ZAC). Por meio desta análise criteriosa na qualificação de um procedimento de soldagem, o procedimento é liberado para ser utilizado, seja qual for o objetivo final da soldagem. Apenas com a Especificação do Procedimento de Soldagem (EPS) qualificada em mãos é possível iniciar os trabalhos de soldagem, e caso esta seja seguida integralmente, o sucesso do processo está a um passo de se concretizar. Para demonstração desta interação existente entre qualificação, análise dos resultados, aprovação dos ensaios e aprovação da especificação, foi desenvolvido este trabalho utilizando o material de base na forma tubular API 5L Gr. B soldado com os processos eletrodo revestido (SMAW) e arame tubular autoprotegido (FCAW-S). Foi utilizada uma junta tubular como exemplo de estudo e qualificação de um procedimento de soldagem baseado na documentação contida na norma da Petrobrás N-2301 e em outros códigos e normas, que regem a qualificação do processo de soldagem utilizado em refinarias e plantas de produção brasileiras. Foram estudados em conjunto os resultados obtidos por meio de ensaios mecânicos, ensaios não destrutivos e microestruturais. Ambas as Especificações dos Procedimentos de Soldagem preliminares (pEPS), estabelecidas antes do início da soldagem dos dois processos de soldagem, foram aprovadas e qualificadas, satisfazendo as características macro e microscópicas, metalúrgicas e mecânicas da junta soldada.A comprehensive analysis of the phenomena occurring in the base metal (MB), filler metal (FM) and the heat affected zone (HAZ) should be conducted to provide the qualification of the welding procedure, either in high-demand carbon steel oil & gas pipelines or standard factory & workshop daily, usual operation. By means of this thorough welding procedure qualification, the process will be released, whatever the ultimate goal of welding. Only after the welding procedure specification (WPS) is qualified, is possible to start any welding work, and being the norm fully observed, the process is nearly to start successfully. The present work has been elaborated to demonstrate the interaction of qualification, result analysis, tests and specification approval, by applying the following elements: tubular base metal API 5L grade B welded with Shielded Metal Arc Welding process (SMAW) and self-shielded Flux Cored Arc Welding process (FCAW-S). A tubular joint was used as sample for a welding procedure qualification studies based on technical documentation specified on Petrobras N-2301, a Brazilian standard, and any others codes and standards that rule welding qualification on refineries & production plants of this company. The results obtained through mechanical testing, non-destructive testing and microstructure were studied together. Both preliminary welding procedure specifications (pWPS) established before the welding of these two welding processes, have been approved and qualified. The support given by welding qualification record (WQR) allows the joints to be welded in production, and result in reliable weld bead that satisfy the macro & microscopic, metallurgical and mechanical characteristics.
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SGOBBI, ALEXANDRE A. "Caracterização mecanica e microestrutural de juntas tubulares soldadas em aço API 5L grau B com base na norma Petrobras N-2301". reponame:Repositório Institucional do IPEN, 2015. http://repositorio.ipen.br:8080/xmlui/handle/123456789/23823.
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Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2015-07-23T10:56:10Z
No. of bitstreams: 0Made available in DSpace on 2015-07-23T10:56:10Z (GMT). No. of bitstreams: 0
Dissertação (Mestrado em Tecnologia Nuclear)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
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Kryworuchko, Marko Andrii. "Regulation of CD44 and its adhesive interactions with the extracellular matrix component, hyaluronan, by cytokines in normal and transformed human B lymphocytes". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0015/NQ46528.pdf.
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Souza, Terezinha Batista de. "O ensino de representação descritiva nos cursos da área de Ciência da Informação no Brasil e em Portugal : estudo comparativo". Tese, Porto : [Edição do Autor], 2009. http://aleph.letras.up.pt/F?func=find-b&find_code=SYS&request=000196898.
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Krolikiewicz-Renimel, Isabelle. "Effets des rayonnements UVB sur la libération de médiateurs pro-inflammatoires impliqués dans le vieillissement cutané : activité anti-âge d’un extrait de fleurs de Butea monosperma (Lam.) Taubert". Thesis, Orléans, 2013. http://www.theses.fr/2013ORLE2015.
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Le photo-vieillissement cutané est en partie dû aux effets néfastes des rayonnements UV qui induisent un stress oxydant. Celui-ci joue un rôle promoteur dans l’installation d’un statut micro-inflammatoire lié à la production de médiateurs tels que des cytokines pro-inflammatoires, des métalloprotéinases de la matrice extracellulaire (MMPs) et des prostaglandines E2. Mes travaux ont été effectués sur le kératinocyte, cellule majeure de l’épiderme et acteur du processus de vieillissement cutané. Dans une première partie, nous décrivons différentes expériences menées pour évaluer l’association de plusieurs molécules anti-oxydantes connues afin d’en potentialiser l’activité. Cette étude a mis en évidence que dans certains cas, un effet pro-oxydant pouvait être observé. Dans une seconde partie, grâce à un système de multiplexing, nous avons pu identifier 39 cytokines et 4 MMPs sécrétées par les kératinocytes suites à une irradiation par des UVB. Nous avons également pu mettre en évidence une différence entre donneurs jeunes et âgés, avec une augmentation des cytokines pro-inflammatoires et une diminution des cytokines anti-inflammatoires pour ces derniers. Dans une dernière partie, l’activité d’un extrait de fleurs de Butea monosperma a été étudiée. L’extrait présente une activité anti-oxydante en piégeant les EORs intracellulaires, anti-inflammatoire en diminuant la sécrétion de cytokines pro-inflammatoires (IL-1; IL-6 et IL-8) et protectrice du derme en inhibant la production de MMP-1 ; 2 ; 9 et 10. Cette étude multifactorielle a permis d’expliquer les utilisations traditionnelles de cette plante comme anti-inflammatoire. En conclusion, afin de comprendre et de limiter les effets des radiations UVB sur le vieillissement cutané, il est nécessaire d’avoir une approche multifactorielle. Comme nous l’avons observé, le stress oxydant n’est pas le seul responsable du statut micro-inflammatoire cutané mais en est le promoteur. Il faut donc agir en amont en limitant la production d’EORs et en aval en contrôlant la sécrétion de cytokines pro-inflammatoires et de MMPsEarly signs of skin aging are related amongst others by UV irradiation that induces an oxidative stress. This one is associated with a skin micro-inflammatory status which is the consequence of mediator productions as pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and prostaglandin E2. Studies reported in this thesis were mainly conducted with human keratinocyte, one of the cells involved in the skin aging process. In a first part, we describe various experiments led to evaluate the association of several antioxydant molecules in the aim to increase their activities. This study has shown that in certain cases, a pro-oxidizing effect could be observed. In a second part, through a multiplexing system, we have identified 39 cytokines and 4 extracellular MMPs that are secreted upon UVB irradiation. We have also found a difference between the cytokines secreted by keratinocytes from young and old donors; the latter has an increase of pro-inflammatory cytokines and a decrease in anti-inflammatory cytokines. Finally, in a last part, an extract of flowers of Butea monosperma has been studied. The extract present an anti-oxidant activity by scavenging intracellular ROS, an anti-inflammatory effect by reducing the secretion of pro-inflammatory cytokines (IL-1 , IL-6 and IL-8) and a protective effect of the dermis by inhibiting the production of extracellular MMP-1, 2, 9 and 10. These results explain the strong protective anti-inflammatory activity of this plant which is widely used. In conclusion, in order to understand and limit the impact UVB radiations on skin aging, it is necessary to have a multifactorial approach. As we have observed, oxidative stress is not solely responsible for the micro-inflammatory status associated with photo-aging, but is the proponent. We must act upstream by limiting production of ROS and downstream by controlling the secretion of pro-inflammatory cytokines and MMPs
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Nalivaiko, Kristina [Verfasser], e Hans-Georg [Akademischer Betreuer] Rammensee. "Development of bispecific antibodies for selective stimulation of the CD95 death receptor on malignant and normal activated B-cells / Kristina Nalivaiko ; Betreuer: Hans-Georg Rammensee". Tübingen : Universitätsbibliothek Tübingen, 2017. http://d-nb.info/1165310260/34.
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Ait, Ghezali Lamia. "Expression des pompes calcique de type SERCA dans l’épithélium du plexus choroïde normal et tumoral et au cours de la différenciation précoce des lymphocytes B". Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCD015/document.
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L’ion calcium est un second messager qui intervient dans de nombreux processuscellulaires dont la prolifération, la différenciation et l’apoptose. Ainsi, l’homéostasiecalcique constitue un point central de régulation de la signalisation cellulaire. En effet, laconcentration calcique cytosolique de calcium subit des oscillations, qui suivant leuramplitude ou leur fréquence, vont être capables d’activer spécifiquement certains facteursde transcription. La régulation de ces oscillations implique entre autres les ATPases de typeSERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) qui accumulent le calcium dansle réticulum endoplasmique. L’objectif de ce travail de thèse a été l’étude des SERCAs aucours de la différenciation lymphocytaire B et dans l’épithélium du plexus choroïde ; ceci,afin de mieux comprendre le profil d’expression de ces pompes et les mécanismes derégulation impliqués.Au cours de la différenciation de lignées de leucémie aiguë lymphoblastique (LAL) nousavons observé que l’expression de l’isoforme SERCA2 restait stable ou augmentaitlégèrement alors que celle de l’isoforme SERCA3 était toujours fortement induite, pouvantatteindre des niveaux observés dans les cellules lymphoïdes matures. Nous avons égalementobservé que l’inhibition de l’activité des SERCAs altère la différenciation cellulaire qui estdépendante de la voie des PKC. Ces données indiquent que SERCA3 pourrait être utiliséecomme marqueur de la différenciation lymphocytaire B. Une régulation de l’expression desSERCAs a également été mise en évidence au cours de la différenciation de l’épithélium duplexus choroïde normal ou tumoral. SERCA3 est fortement exprimée dans l’épithéliumnormal, mais on retrouve une baisse ou une perte de son expression dans l’épithéliumtumoral, cette baisse est corrélée à la perte de la différenciation selon le grade des tumeurs.L’étude de l’expression des SERCAs dans les cellules primaires du plexus choroïde traitépar des agents cyto-différenciateurs (acides gras à chaîne courte), montre que ladifférenciation est associée à une surexpression de SERCA3. SERCA3 peut donc égalementêtre un marqueur de la différenciation de l’épithélium du plexus choroïde.L’ensemble de ce travail a montré que la différenciation cellulaire est associée à la régulationde protéines impliquées dans la régulation de l’homéostasie calcique : les SERCAs. On peutainsi proposer SERCA3 comme un nouveau marqueur phénotypique utile pour l’analyse dela différenciation du plexus choroïde normale et néoplasique, ainsi que pour celle de ladifférenciation lymphoïde pré-B leucémiqueCellular calcium is involved in a multitude of biological processes including thecontrol of cell proliferation, differentiation and programmed cell death, and constitutestherefore a keconcentration calcique cytosolique de calcium subit des oscillations, qui suivant leuramplitude ou leur fréquence, vont être capables d’activer spécifiquement certains facteursde transcription. La régulation de ces oscillations implique entre autres les ATPases de typeSERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) qui accumulent le calcium dansle réticulum endoplasmique. L’objectif de ce travail de thèse a été l’étude des SERCAs aucours de la différenciation lymphocytaire B et dans l’épithélium du plexus choroïde ; ceci,afin de mieux comprendre le profil d’expression de ces pompes et les mécanismes derégulation impliqués.Au cours de la différenciation de lignées de leucémie aiguë lymphoblastique (LAL) nousavons observé que l’expression de l’isoforme SERCA2 restait stable ou augmentaitlégèrement alors que celle de l’isoforme SERCA3 était toujours fortement induite, pouvantatteindre des niveaux observés dans les cellules lymphoïdes matures. Nous avons égalementobservé que l’inhibition de l’activité des SERCAs altère la différenciation cellulaire qui estdépendante de la voie des PKC. Ces données indiquent que SERCA3 pourrait être utiliséey element in cell signaling. Calcium levels vary in a dynamic mannerdepending on the state of activation of the cell, and can display oscillations the amplitudeand frequency of which can convey specific signals to various transcription factors.Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes) accumulate calciumfrom the cytosol into the endoplasmic reticulum (ER). By modulating the spatiotemporalcharacteristics of calcium signals and oscillations, SERCA pumps constitute an importantand unique point of control of calcium-dependent cell activation. In this work weinvestigated SERCA expression during early B lymphoid differentiation and in normal,tumoral and hyperplastic choroid plexus epithelial cells.We have shown that SERCA3 expression is markedly increased during thepharmacologically induced differentiation of immature B acute lymphoblastic leukemiacells, whereas the expression of the simultaneously expressed SERCA2 isoform is notmodified significantly. SERCA3 expression during this differentiation process can reachlevels observed in mature B lymphoid cells, and is dependent on the activation of proteinkinase C. Moreover, the direct pharmacological inhibition of SERCA-dependent calciumtransport interferes with the differentiation process.Our investigations on the choroid plexus show, that whereas SERCA3 is highly expressedin normal choroid plexus epithelium, expression is strongly decreased in benign choroidplexus tumors and is lost in carcinoma, whereas expression is retained in hyperplasia. Inaddition, treatment of primary normal choroid plexus epithelial cells by short chain fattyacid-type cell differentiation-inducing agents in vitro leads to the induction of SERCA3expression.Our observations when taken together indicate that ER calcium homeostasis is remodeledduring the differentiation of immature B lymphoid cells and in the choroid plexus due to theinduction of SERCA3 expression. We show that a cross-talk exists between SERCA functionand the control of differentiation in B cells, that SERCA3 constitutes a new phenotypicmarker for the study of early B cell differentiation, and that the lack of SERCA3 expressionmay be useful for the identification of choroid plexus tumors
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Kennedy, Mark Thomas. "The contribution of Dr. Sampson Paul Robins to education in the province of Québec : with special reference to the McGill Normal School". Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66200.
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Borges, Alex. "Impacto no ativo imobilizado em raz??o da converg??ncia dos padr??es internacionais de Contabilidade aplicada ao Setor P??blico: uma pesquisa-a????o na C??mara Municipal de Santa B??rbara D???Oeste". FECAP, 2015. http://tede.fecap.br:8080/jspui/handle/tede/667.
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Accounting applied to the public sector in Brazil is being elevated to a new level, through convergence to international standards. This convergence process in the public sector has as objective the adoption of IPSAS (International Public Sector Accounting). From this process was rescued in the Brazilian public sector the focus on patrimony, which made possible the introduction of new accounting procedures of the asset, such as revaluation decrease in recoverable value (impairment) and depreciation. Therefore, the present research aimed to analyze the impact on fixed assets of the city of Santa B??rbara D'oeste, due to the adoption of international standards. The methodology used was the action research, where we sought to perform procedures for the initial evaluation of the fixed assets of the city, due to the adoption of new accounting standards. The data was collected from the asset management system. To start the analysis of the fixed assets, there was the need of some items that did not meet the criteria for assets. Giving progress in the analysis were defined the life and the residual value of each of the fixed assets account group. Passing finally for the initial assessment process of fixed assets through market research, were later identified the existence of goods with nominal values very underestimated. As a result, one can consider that the situation problem and the overall objective of this work has been achieved, since through the involvement of the researcher and the commission of public employees in this research were demonstrated the impact on fixed assets of the city due to the convergence to international standards. In general it was found that the Liquid Asset was reduced and the Fixed Assets increased. In addition, could be identified several particularities involving the permanent assets of the public sector, due to the budget focus, such as the lack of registration of assets, assets that should not be registered and assets under or overvalued.
A Contabilidade Aplicada ao Setor P??blico no Brasil est?? sendo elevada a um novo n??vel por meio da converg??ncia aos padr??es internacionais. Este processo de converg??ncia tem como objetivo a ado????o das IPSAS (International Public Sector Accounting). A partir desse processo foi resgatado no setor p??blico brasileiro o foco patrimonial que possibilitou a introdu????o de novos procedimentos de contabiliza????o do ativo, tais como reavalia????o, redu????o ao valor recuper??vel (impairment) e deprecia????o. Sendo assim, a presente pesquisa tem por objetivo analisar o impacto no ativo imobilizado da C??mara Municipal de Santa B??rbara D???Oeste, em raz??o da ado????o das normas internacionais. A metodologia utilizada foi a pesquisa-a????o, onde buscou-se realizar os procedimentos para a avalia????o inicial do ativo imobilizado da C??mara Municipal, em virtude da ado????o das novas normas cont??beis. Os dados foram coletados a partir do sistema de patrim??nio. Ao iniciar a an??lise do ativo imobilizado, verificou-se a necessidade da baixa de alguns itens que n??o atendiam ao crit??rio de ativo. Durante o progresso da an??lise foram definidas a vida ??til e o valor residual de cada grupo de conta do ativo imobilizado. Posteriormente foi identificada a exist??ncia de bens com valores irris??rios, passando finalmente para o processo de avali????o inicial do ativo imobilizado, atrav??s da pesquisa de mercado. Como resultado, pode-se considerar que a situa????o problema e o objetivo geral deste trabalho foram alcan??ados uma vez que, atrav??s do envolvimento do pesquisador e da comiss??o de servidores nessa pesquisa, foram demonstrados os impactos no ativo imobilizado da C??mara Municipal em consequ??ncia da converg??ncia aos padr??es internacionais. Verificou-se que os bens m??veis sofreram uma redu????o e o bem im??vel um aumento. Al??m disso, foram identificadas v??rias particularidades que envolvem o ativo imobilizado do setor p??blico, em virtude do foco or??ament??rio, como por exemplo a falta de registro de bens que n??o deviam mais estar registrados e bens sub ou superavaliados.
48
Hamdi, Adel. "Combinatoire des opérateurs non-commutatifs et polynômes orthogonaux". Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10142.
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Cette thèse se divise en deux grandes parties, la première traite la combinatoire associée à l’ordre normal des opérateurs non-commutatifs et la seconde aborde des distributions symétriques du nombre de croisements et du nombre d’emboîtements, respectivement k-croisements et k-emboîtements, dans des structures combinatoires (partitions, permutations, permutations colorées, …). La première partie étudie l’ordre normal des opérateurs en termes de placements de tours. Nous étudions la forme de l’ordre normal en connectant deux opérateurs non-commutatifs D et U, et des polynômes orthogonaux spéciaux, et établissons des bijonctions entre les coefficients de (D+U)n et le nombre de placements de tours sur un diagramme de Ferrers. Nous donnons également des preuves combinatoires à des conjectures quantiques posées par des physiciens. Dans la seconde partie, nous définissons des statistiques, comme emboîtements et k-emboîtements, sur l’ensemble des permutations du groupe de Coxeter de type B. Nous donnons également des extensions au type B des résultats sur les croisements et les emboîtements, respectivement k-croisements et k-emboîtements dans les permutations de type A, en termes de distributions symétriques. De plus, nous étudions le lien entre les opérateurs non-commutatifs et ces statistiques. D’autres extensions de la distribution de ces statistiques sur les ensembles de partitions colorées et de permutations colorées de types A et B sont ainsi établiesThis thesis is divided into two parts, the first deals with the combinatorics associated to the normal ordering form of noncommutative operators and the second addresses the symmetric distributions of the crossing numbers and nesting numbers, respectively k-crossings and k-nestings, in combinatorial structures (partitions, permutations, colored permutations, …). The first part studies the normal order of operators in terms of rook placements. We study the normal ordering form connecting two noncommutative operators D and U, and some special orthogonal polynomials, and establish bijonctions between coefficients of (D+U)n and rook placements in Ferrers diagrams. We also give combinatorial proofs and alternatives to some quantum conjectures posed by physicists. In the second part, we define the notions of statistics, nestings and k-nestings, on the sets of permutations of the Coxeter group of type B. We also give extensions to type B of the results of the crossings and nestings, respectivelu k-crossings and K-nestings in the set of permutations of type A, in terms of symmetric distributions. Likewise, we study the link between non-commutative operators and these statistics. Other extensions of the distribution of these statistics on the sets of colored partitions and colored permutations of type A and B are established
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Padilla, Calderón Natalia Ximena. "Redacción de los manuales de organización y procedimientos para el Subdepartamento de Farmacia del Hospital El Carmen Dr. Luis Valentín Ferrada". Tesis, Universidad de Chile, 2017. http://repositorio.uchile.cl/handle/2250/159481.
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Unidad de Práctica Prolongada para optar al título de Químico FarmacéuticoUn establecimiento de salud asistencial cuenta con varios servicios clínicos y unidades de apoyo, que sustentan actividades relacionadas con la salud de los pacientes que ahí se atienden. Una de estas unidades de apoyo, es Farmacia, donde se desarrollan diferentes labores relacionadas con la promoción, protección y recuperación de la salud de los pacientes, usando los servicios farmacéuticos y los medicamentos como herramienta principal. El Hospital El Carmen Dr. Luis Valentín Ferrada, es un establecimiento asistencial de alta complejidad, concesionado y autogestionado, que se encuentra en la comuna de Maipú, Región Metropolitana. En este hospital, la Unidad de Farmacia es un subdepartamento, el cual está separado en un área de producción y otra de control y gestión; que en conjunto cumplen con los objetivos sanitarios. El Subdepartamento de Farmacia fue sometido a una auditoría ministerial en el año 2015, y los resultados de esta se dieron a conocer en diciembre del mismo año. Dentro de las falencias identificadas se encontraba la falta de manuales que dieran cuenta de la organización y procedimientos llevados a cabo en la unidad. Como parte del plan de mejoras de Farmacia 2016, y para cerrar esta brecha, se planteó como objetivo de esta práctica profesional redactar los manuales de organización y procedimientos de Farmacia. Para la redacción de estos manuales, se revisaron algunos pertenecientes a establecimientos asistenciales, con el fin de tener conocimiento respecto a la estructura y contenidos que estos debían tener. Luego, se recopiló información por vía oral y escrita, entregada por profesionales del subdepartamento. Además, se obtuvieron otros datos a través de la observación de las actividades realizadas en cada área de Farmacia. Todos los datos reunidos fueron revisados y después incluidos en los manuales respectivos. En el Manual de Organización se adjuntaron antecedentes históricos respecto al funcionamiento de Farmacia. Además, se incluyeron gráficos que evidencian el aumento en la actividad de las secciones de Dosis Unitaria, Farmacia Ambulatoria y Farmacia Hospitalizados. También, se creó un organigrama jerárquico de Farmacia, una tabla explicativa con la dotación de personal y perfiles para todos los cargos existentes. El Manual de Procedimientos incluyó por separado protocolos generales y específicos. Los generales, son aquellos que involucran actividades que afectan a todo el subdepartamento, mientras que los específicos abarcan los procedimientos propios de cada área de Farmacia. Para este manual se redactaron protocolos nuevos (generales y específicos), y apartados con información que no se encontraba presente en protocolos que ya estaban escritos. Concluida la redacción de ambos manuales, estos fueron revisados por la Jefa de Farmacia y la coordinadora del área de Calidad de Farmacia, quienes dieron su aprobación para enviarlos al Departamento de Calidad del hospital. Tanto el Manual de Organización como el de Procedimientos, conforman ahora una herramienta importante que ayudará a garantizar, mantener y/o mejorar la calidad de los servicios otorgados, de la atención asistencial y la gestión administrativa del Subdepartamento de Farmacia del Hospital El Carmen
A health care institution is formed by several clinical services and support units, holding activities related to the wellness of patients. One of these support units is Pharmacy, where different activities related to the promotion, protection and recovery of patients' health are carried out, using pharmaceutical services and drugs as their main tool. El Carmen Dr. Luis Valentín Ferrada Hospital is a high complexity, concessioned and self-managed care institution, located in Maipú, Metropolitan Region. In this hospital, the Pharmacy Unit is a sub-department, separated into a production area and a control and management area; together they achieve sanitary goals. In 2015, Pharmacy Subdepartment was submitted to a ministerial audit, and the results were announced in December of the same year. One of the biggest shortcomings, was the lack of manuals that show the organization structure and the procedures done in the unit. As part of the Pharmacy 2016 improvement plan, and to close this gap, it was proposed as an objective of this professional practice to write the manuals of the organization and procedures of Pharmacy. To write these manuals, it was necessary to review manuals belonging to other health care facilities, to have an idea of the structure and contents they should have. The information was collected orally and written, delivered by professionals from the subdepartment. Furthermore, other data were obtained by observing the activities performed in each Pharmacy area. All data was revised and then included in the respective manuals. In the Organization Manual, historical precedents related to the operation of Pharmacy were attached. In addition, graphs that show the increase in the activity of the sections of Unitary Dose, Ambulatory Pharmacy and Hospitalized Pharmacy were included. Also, it was created a hierarchical organization chart of Pharmacy, an explanatory table with staffing and profiles for all existing appointments. The Procedures Manual included general and specific protocols sepparately. The general ones are those which involve activities that affect the entire subdepartment, while the specific ones include the procedures of each Pharmacy areas. For this manual the new protocols (general and specific) have been written, and the sections with information not found in protocols, were attached. Once concluded the writing of both manuals, these were reviewed by the Chief of Pharmacy and the Pharmacy’s Quality coordinator, who gave their approval to send them to the Quality Department of the Hospital. Both, Organization and Procedures Manual are now an important tool and will help to guarantee, maintain and / or improve the quality of the services provided, the care and administrative management of the El Carmen Hospital Pharmacy Subdepartment
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Martinez, Juan David Santos. "Estudo comparativo da resistência à corrosão e permeabilidade do hidrogênio de aços API grau X65 baixo manganês em solução B da norma NACE TM-0284". Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/3/3133/tde-15012018-145847/.
Texto completo da fonteResumo:
Aços de alta resistência e baixa liga (ARBL) têm sido bastante utilizados na fabricação de tubulações para o transporte de petróleo e gás. Entretanto, o uso destes materiais em meios com elevadas concentrações de H2S, denominados sour, tem resultado em falhas frequentes, devido à suscetibilidade destes materiais ao desenvolvimento do fenômeno de trincamento induzido pelo hidrogênio (Hydrogen Induced Cracking - HIC), assim como devido a problemas de corrosão. O desenvolvimento de diferentes processos tecnológicos para a produção de tubos de aços ARBL, tais como a laminação controlada e resfriamento acelerado, a adição de microligantes, assim como a diminuição do teor de enxofre, fósforo, carbono e manganês, tem levado à elaboração de materiais com propriedades mecânicas otimizadas, permitindo também um melhor controle da microestrutura. As perdas de dureza e resistência mecânica devidas à redução do teor de manganês, são compensadas pela adição de elementos como cromo e nióbio. Neste trabalho estão sendo comparadas a resistência à corrosão e os parâmetros de permeabilidade do hidrogênio de dois tubos de aço API 5L X65 e uma chapa API 5L X65, todos do tipo ARBL e com baixo manganês (0,27%) e alto nióbio (0,083% a 0,090%), na solução B da norma NACE, TM-0284 (2011). Para isto, foram realizados ensaios de potencial de circuito aberto (Open Circuit Potential - OCP), espectroscopia de impedância eletroquímica (Electrochemical Impedance Spectroscopy - EIS) e curvas de polarização potenciodinâmicas no eletrólito naturalmente aerado, desaerado e saturado com H2S. Os testes de permeabilidade do hidrogênio foram realizados com base na norma ASTM INTERNATIONAL G148 - 97, porém usando a célula modificada de DEVANATHAN e STACHURSKY (1962) e com H2S como veneno catódico. Os materiais foram caracterizados por microscopia óptica (MO), microscopia eletrônica de varredura (MEV) e espectroscopia de energia dispersiva de Raios-X (X-Ray Energy Dispersive Spectroscopy - EDS) antes e depois de testes de imersão nos diferentes eletrólitos. Caracterização dos produtos de corrosão por difração de raios-X (DRX) também foi realizada após imersão em meio saturado com H2S (sour). As análises por MO e MEV mostraram matrizes ferríticas para os três aços, com a presença de baixos teores do microconstituinte martensita/austenita (M/A), de perlita e com baixo nível de inclusões uniformemente distribuídas e com composições químicas semelhantes. Os resultados dos ensaios de corrosão mostraram que, para todos os meios investigados, o aço denominado como B apresentou a melhor resistência à corrosão, enquanto aquele denominado como C se mostrou o mais suscetível em todas as condições estudadas. Para os três aços, a resistência à corrosão apresentou a seguinte ordem crescente de acordo com o meio de exposição: meio saturado com H2S < meio naturalmente aerado < meios desaerados. Ensaios de OCP e EIS no meio saturado com H2S em um período de 24h mostraram que a resistência à corrosão aumenta com o tempo em razão da formação de uma camada de sulfeto de ferro, que, no entanto, se apresentou pouco aderente. Os resultados dos ensaios de permeação de hidrogênio mostraram que o aço denominado B, que apresentou maior resistência à corrosão em todos os meios e que não apresenta perlita em sua microestrutura, teve o maior valor de difusividade efetiva de hidrogênio, menor concentração de hidrogênio atômico na sub-superfície e menor quantidade de traps por unidade de volume. Quanto aos outros dois materiais, os resultados dos testes de permeabilidade ficaram em desacordo com os resultados da caracterização microestrutural e dos testes de resistência à corrosão, indicando que fatores diferentes dos detectados neste estudo são importantes para governar essas propriedades.High strength low alloy (HSLA) steels have been widely used in the manufacture of pipelines for the transport of oil and gas. However, the application of these steels in media with high H2S concentrations, denominated sour, has resulted in frequent failures due to the susceptibility of these materials to the development of Hydrogen Induced Cracking (HIC) phenomena, as well as due to corrosion problems. The development of different technological processes for HSLA piping production, like controlled rolling and accelerated cooling, the addition of microalloying elements, as well as the reduction of the amounts of sulphur, phosphorus, carbon and manganese, has led to the development of materials with optimized mechanical properties, also allowing a better microstructural control. Hardness and mechanical resistance reduction due to the lowering of Mn content are compensated by niobium and chromium addition. In this work, the corrosion resistance and the hydrogen permeability parameters of two API 5L X65 steel tubes and an API 5L X65 plate, all HSLA type and with low manganese (0.27%) and high niobium (0.083% to 0.090%) contents, are compared in solution B of NACE standard TM-0284 (2011). For this, open circuit potential (OCP), electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization curves were carried out in the naturally aerated, deaerated and H2S saturated electrolyte. Hydrogen permeability tests were performed based on ASTM INTERNATIONAL G148-97, but using a modified DEVANATHAN and STACHURSKY (1962) cell and with H2S as cathodic poison. The materials were characterized by means of optical microscopy (OM), scanning electron microscopy (SEM) and X-Ray Energy Dispersive Spectroscopy (EDS) prior and after immersion tests in the different electrolytes. Characterization of the corrosion products by X-ray diffraction (XRD) was also performed after immersion in the H2S-saturated (sour) medium. The OM and SEM characterization showed ferritic matrices for the three steels, with the presence of low levels of the martensite/austenite (M/A) microconstituent, perlite and with a low level of inclusions evenly distributed and with similar chemical compositions. The results of the corrosion tests showed that, for all investigated media, the steel denominated as B presented the best resistance to corrosion, whereas the one denominated as C showed to be the most susceptible in all the conditions studied. For the three steels, the corrosion resistance showed the following ascending order according to the exposure medium: H2S saturated < naturally aerated medium < deaerated media. OCP and EIS tests in the H2S-saturated medium in a period of 24 hours showed that the corrosion resistance increases over time due to the formation of an iron sulphide layer, which, however, presented little adhesion. The results of the hydrogen permeation tests showed that the steel denominated B, that presented greater corrosion resistance in all media and that does not present perlite in its microstructure, had the highest values of effective hydrogen diffusivity, the lowest concentration of atomic hydrogen in the subsurface and the smallest amount of traps per unit volume. Concerning the other two materials, the results of the permeability tests were at variance with the results of the microstructural characterization and corrosion resistance tests, indicating that factors other than those detected in this study are important to govern such properties.