Un estudio hermenéutico sobre la obra de Joan Miró. La obra mironiana contiene "una intencionalidad secreta y está inscrita no ámbito de la cabalística". Por este motivo, posibilita establecer algunas relaciones con la obra esotérica de "El Bosco" y con la mística obra de Kandisky. La parte central del estudio está dedicada a desvelar los significados: 1o) de los 20 signos de su Cortège des obsessions, siempre recurrentes en su obra y cuyo simbolismo cabalístico definiría el espíritu semita-catalán de su autor (I Parte); 2o) de "La Masia", como "metáfora mayor del habitar (existir, en sentido heideggeriano), poético- mí(s)tico del artista"(II Parte); 3o) de los "Autorretratos, cuyo discurso poético "traduce el acaecer concreto y real del devenir de su ser humano y artístico (III Parte). Así, el estudio tienta desvelar las fuentes místico-semitas,cuyas verdades dirigieron la vida y el quehacer creativo de Miró, siempre movido por una responsabilidad ética. Las conclusiones de esta lectura interpretativa son expuestas en la IV Parte del estudio. Esta lectura conjuga conocimientos sobre la teoría del arte y el poder creativo del espíritu humano y su capacidad simbólica. El estudio procesa un continuo diálogo entre el arte y la filosofía/psicología, de modo que el saber filosófico fenomenológico o existencial ayuda a entender la obra de Miró,y ésta, a su vez., ilumina la verdad del conocimiento filosófico-existencial. / An hermenéutic study about Miro's work. The mironian artistic work contains" a secret intentionality and is inscribed in a cabalistic sphere". Therefore, it allows some relations with the esoteric work of El Bosco and with the mistic work of Kandinsky. This study dedicates special attention to the meaning of those pictorial works: 1a) The Cortège des obsessions (collection of twenty signs)always recurrent in his work, whose symbolism will reveal the mironian semitic-catalanian Weltanschauung (Part I) ; 2a) "La Masia", "as the main metaphor of his poétic and mythic/mystic dwuelt"(exist, in heideggerian sense).(Part II) ; 3a) The Self-autorretrats, whose poetic oration translates "the real and concrete happening of his human and artistic becoming, (Part III) Thus, the study tries to discover the mystic- semitic sources from which truths Miro dealt his life and his artistic work, always moved by ethical responsability. The conclusions of this interpretative reading are exposed in Part IV. This reading conjugates knowledges about art's theory and creative power of the human mind and its simbolic capacity. This study processes a continuous dialogue between art and philosophy/psychogy in a way that phenomenological or existential philosophy helps to undesrtand Miró's work, which, by it's turn,enlightens the truth of philosophic-existential knowledge.

No description available.

Le rétrovirus HTLV-1 est l'agent étiologique d'une lymphoprolifération maligne, la leucémie T de l'adulte (ATL) et d'une neuromyélopathie chronique, la paraparésie spastique tropicale ou myélopathie associée à HTLV-I (TSP/HAM). Bien que la plupart des personnes infectées restent asymptomatiques tout au long de leur vie, 5% des personnes infectées développeront l'une ou l'autre de ces deux maladies pour lesquelles aucun traitement n'est connu. La pathogenèse du rétrovirus est due à l'action pléïotropique des protéines virales régulatrices Tax et HBZ. Elles organisent une dérégulation des voies de signalisation cellulaires qui permettent l'expansion clonale des cellules infectées et la réplication de l'information provirale in fine. En tant que rétrovirus complexe, HTLV-1 est capable de réguler sa propre expression via le rétrocontrôle négatif de HBZ sur les gènes contrôlés par le 5'LTR et la séquestration des facteurs se liant à Tax pour la transactivation du promoteur viral. Ce mécanisme permet l'échappement du virus à la surveillance du système immunitaire et la destruction des cellules infectées par les lymphocytes T cytotoxiques.HBZ est détectée de façon systématique dans les cellules ATL et son rôle dans la pathogenèse est renforcé par de nouvelles découvertes. Une étude réalisée précédemment par l'équipe, montre que l'expression de HBZ dépend du recrutement de la protéine JunD sur le promoteur viral anti-sens. HBZ et JunD favorisent une prolifération modérée des cellules ATL et l’altération des mécanismes suppresseurs de tumeurs. La prolifération des lymphocytes T CD4+ infectés représente le dénominateur commun entre les deux maladies associées au HTLV-1. / The HTLV-1 retrovirus is the causative agent of malignant lymphoproliferation, adult T-cell leukemia (ATL) and chronic neuromyelopathy, tropical spastic paraparesis or HTLV-I associated myelopathy (TSP / HAM). Although most infected people remain asymptomatic throughout their lives, 5% of those infected will develop either of these diseases for which no treatment is known. The pathogenesis of the retrovirus is due to the pleiotropic action of the regulatory viral proteins Tax and HBZ. They organize a deregulation of the cell signaling pathways which allow the clonal expansion of the infected cells and the replication of the proviral information in fine. As a complex retrovirus, HTLV-1 is able to regulate its own expression via the negative feedback of HBZ on the 5'LTR-controlled genes and the sequestration of the Tax-binding factors for the transactivation of the viral promoter. This mechanism allows the escape of the virus to monitor the immune system and the destruction of cells infected with cytotoxic T lymphocytes.

resumen / Tesis

Since the discovery of HIV-1, the production of an effective prophylactic or therapeutic vaccine remains elusive. An effective vaccine must be able to elicit a potent humoral and cellular immune response. Neutralizing antibodies target the envelope glycoproteins on the surface of HIV-1 virions thereby preventing viral entry. Unfortunately, to date only a handful of neutralizing antibodies have been identified that are capable of neutralizing different viral strains within diverse subtypes, and none have been isolated from HIV-1 subtype C infected patients. In this study, we screened four different HIV-1 subtype C infected patient cohorts for the presence of neutralizing antibodies against a panel of 5 subtype C and 1 subtype B pseudovirus/es in a pseudovirion based neutralizing antibody assay. The CT cohort comprised 9 slow progressor plasma samples, the FV cohort consisted of 11 antiretroviral drug naïve HIV-1 subtype C infected plasma samples. Plasma samples from 10 antiretroviral treatment experienced HIV-1 subtype C infected patients failing first line therapy made up the DR cohort and the JM cohort consisted of 10 serum samples from HIV-1 seropositive or seronegative individuals with an autoimmune disorder. A pseudovirion neutralizing antibody assay was successfully established, and all plasma and serum samples were heat inactivated and screened using this assay. Analysis of the percentage neutralization and IC50 data showed no correlation between the presence of neutralizing antibodies and delayed disease progression in the SP cohort. High levels of neutralizing antibodies were observed in the DR cohort, however future studies are required to confirm if the measured neutralization is due to residual antiretroviral drugs in the plasma or neutralizing antibodies. No samples within the FV cohort showed promising neutralizing antibody activity however the JM cohort harboured 3 serum samples (TN5, TN6 and TN8) that exhibited a greater than average breadth of neutralization and are worth investigating further in future studies. Patients TN5, TN6 and TN8 were all HIV-1 positive with an additional autoimmune disease. The availability of stored bone marrow samples for TN5, TN6 and TN8 will allow for the generation of antibody phage display libraries and isolation of monoclonal antibodies, with potentially broadly cross reactive activity.

M.Sc.(Med.) (Molecular Medicine and Haematology), Faculty of Health Sciences, University of the Witwatersrand, 2011 / The Human Immunodeficiency Virus type 1 (HIV-1) integrase is an essential enzyme required for viral replication. Integrase forms part of an ensemble of proteins known as the preintegration complex and functions by a two-step process. Firstly, the cleaving of the 3’ ends of the viral cDNA genome, known as 3’-end processing. The second step is the insertion of these ends into host DNA by esterification, known as strand transfer. There is no human homologue to integrase which makes it an ideal drug target. However, the strand transfer inhibitor raltegravir is currently the only antiretroviral treatment available that inhibits integrase. The aims of this study were two-fold: firstly to characterise a cohort of South African patients so as to determine the viability of introducing raltegravir as a new treatment option, and secondly, to set up high-throughput integrase inhibitor screening assays (testing integrase enzymatic functionality). An HIV-1 subtype C specific RT-PCR and PCR assay was established for integrase genotyping using 51 integrase inhibitor-naïve patient plasma samples and 22 antiretroviral drug-naive primary viral isolates from South Africa. Seventy-one of the 73 samples were classified as HIV-1 subtype C and two samples were unique AC and CG recombinants in integrase. Amino acid sequence analysis revealed there were no primary mutations (Y143R/C/H, Q148H/R/K, and N155H/S) associated with reduced susceptibility to the integrase inhibitor raltegravir. However, one sample had the T97A mutation, three samples had the E157Q and V165I mutations, and the majority of samples contained the polymorphic mutation, V72I. The expected finding of no major integrase mutations conferring resistance to integrase inhibitors suggests that this new antiretroviral drug class will be effective in our region where HIV-1 subtype C predominates. However, the impact of E157Q and other naturally occurring polymorphisms warrants further phenotypic investigation. The integrase sequence of viral isolate, FV3, was closest to the consensus sequence, and thus chosen for preintegration complex isolation for use in strand transfer assays. Isolation of preintegration complexes following FV3 infections of several cell lines was unsuccessful as determined by western blot analysis. Subsequently, the focus was changed to isolation of HIV-1 subtype B recombinant integrase and its functional evaluation. Expression of native integrase (INwt) and soluble integrase (INsol) was induced in E. coli, and both proteins were purified by nickel chelating chromatography. The purified recombinant proteins were used to develop three assays to test for strand transfer activity, of which two were successfully established. Furthermore, only INsol showed strand transfer activity in the high-throughput microtitre plate assay and scintillation proximity assay (SPA)-bead strand transfer assay. Activity of INsol was shown to be inhibited by the control compound, chicoric acid with an IC50 of 101.5nM in the high-throughput microtitre plate assay, whereas INsol activity as well as a dose response to chicoric acid with an IC50 of 248.5nM was recorded in the SPA-bead strand transfer assay. Visualization of radiolabelled enzymatic products of strand transfer by polyacrylamide gel electrophoresis of urea sequencing gels was unsuccessful. Overall, the high-throughput microtitre plate and SPA-bead strand transfer assays have been successfully established in our laboratories, and are available to screen compound libraries for potential antiretroviral drug candidates targeting integrase strand transfer.

MSc (Med), Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, 2009 / The HIV-1 Vpu protein functions largely to target CD4 molecules for proteasomal degradation, and to enhance virion release. The subcellular localisation of Vpu is related to these functions. Previous studies showed subtype B Vpu localisation at the ER/Golgi complex, while subtype C Vpu localised to the plasma membrane (PM) at 48 hours post-transfection. To determine if subtype C Vpu can localize to the ER/Golgi, we evaluated the cellular localisation of Vpu from two South African subtype C isolates as compared to subtype B Vpu, over time. Codon optimized vpu genes from subtype C isolates FV5 and FV15 (which have a six and two amino acid insert in the N-terminal domain, respectively) and a representative subtype B vpu were TA cloned into the pcDNA6.2/C-emGFP expression vector. The three VpuemGFP recombinant plasmids were cotransfected with pDsRed-ER, pDsRed-Golgi, or pDsRed-Mem into HEK 293T cells, and observed at 24, 48, and 60 hours posttransfection under a confocal microscope to confirm the presence of Vpu at different subcellular compartments. Cotransfection and microscopy conditions were methodically optimised. At 24 hours post-transfection, the subtype C FV5 Vpu had ER/Golgi localisation, but none at the PM. The subtype C FV15 Vpu had weaker ER/Golgi localisation and no PM localisation. In contrast, the subtype B Vpu had strong PM localisation. At 48 hours, FV5 and FV15 Vpu showed PM localisation, while subtype B Vpu was clearly localised at the ER/Golgi. At 60 hours, FV5 Vpu was observed at the PM, whereas FV15 and subtype B Vpu showed ER/Golgi localisation. These findings illustrate the efficient translocation of Vpu between different cellular compartments and for the first time, the difference in timing between subtype B and C Vpu, as well as íntrasubtype differences. This difference in shuttling suggests implications for the timing of viral assembly and release. Further investigations may clarify the impact of this timing on the difference in disease pathogenesis noted between infections with the different subtypes.

Joan Mascaró i Fornés (1897-1987) fue filólogo, poeta, orientalista, profesor en la Universidad Cambridge y, sobretodo, traductor de la Bhagavad Gita, los Upanishads i el Dhammapada desde el sánscrito y pali al inglés. La tesis es una tesis bibliográfica centrada en la obra de Mascaró y que sistematiza en un solo documento gran variedad de obras dispersas y algunas de ellas inéditas. Pretende dar una visión de conjunto sobre su pensamiento y su relación con la filosofía oriental y sobretodo con las obras que tradujo.El interés de la tesis se centra en la actitud vital de Mascaró hacia la espiritualidad y el Yoga como herramienta para acceder a la aprehensión de la Verdad espiritual. La taxonomia que utiliza Mascaró en sus obras se basa en las palabras: Luz, Amor y Vida y la tesis pretende demostrar también su equivalencia con los términos Jñana, Bhakti y Karma Yogas.En la tesis se tratan además, desde la perspectiva de Mascaró, temas como el budismo, la unidad del fenómeno religioso, la educación, concepto de Karma, de Dharma y otros. / Joan Mascaró i Fornés (1897-1987) was philologist, poet, orientalist, professor at Cambridge University and, above all, the translator of The Bhagavad Gita, The Upanishads and The Dhammapada from Sanskrit and Pali into English. The thesis is bibliographical. It is centred in Mascaró's works, and it systematises a variety of disperses works, some of them unpublished in an only a document. It aspires to give a vision of his thoughts as a whole and their relationship with oriental philosophy and the works that he translated.The main interest of the thesis is Mascaró's vital attitude towards spirituality and Yoga as a tool to gain access to the apprehension of the spiritual Truth. Mascaró's taxonomy is based in the words: Light, Love and Life and the thesis aspires to prove their equivalence with the conceptions of Jñana, Bhakti and Karma Yogas. The Thesis also deals whith Mascaró's vision of Buddhism, the unity of religious phenomenon, education, the concepts of Karma and Dharma and others.

Esta investigación reconoce el valor pedagógico de la práctica del profesorado comprometido con un proyecto educativo en el cambio social y en la reivindicación del gusto por aprender. No intenta elaborar modelos de acción, sino compartir significados para el diálogo y el debate. Las experiencias y los juicios de nuestros profesores pueden ser consideradas tan comunes como cualquier otra; es justamente allí donde radica la relevancia de su aporte y de nuestra investigación. Creemos que mientras más profesores puedan mostrar que los derechos y libertades se pueden usufructuar a pesar de las restricciones, y realizar una enseñanza que garantice el aprendizaje y la formación ética de los educandos, habrá más posibilidades de movilizar críticamente a otros profesores, sobre todo a quienes creen que no se pueden superar las limitaciones externas o autoimpuestas. Creemos que los profesores comprometidos con un proyecto educativo pueden y deben ser referentes para otros.Dado que el proceso educativo es paradojal, simple y complejo a la vez, esperamos contribuir con aquellos elementos simples constituyentes de la identidad profesional de los profesores comprometidos con un proyecto educativo, y develar las complejidades epistemológicas de su pensamiento pedagógico.La investigación de los "buenos profesores" y sus historias de vida permitieron construir el concepto de "Profesores comprometidos con un proyecto educativo", que refiere a la implicación en un proyecto educativo y al posicionamiento político que enmarcan su quehacer cotidiano. La expresión "buenos profesores" sintetiza claramente la necesidad imperativa de impulsar un cambio radical en la cultura profesional, capaz de recuperar la importancia y trascendencia sinérgica de la profesionalidad docente, entendida desde su contexto histórico, público e institucional. El concepto "buenos" o "buenas" no tiene un significado ingenuo o falaz, sino que lo seleccionamos por sus claras implicaciones éticas y profesionales que refiere tanto al trabajo profesional bien hecho como al reconocimiento social y político de sus pares y alumnos.Las reflexiones finales se refieren a los comportamientos típicos de estos profesores y no de otros profesionales, por lo que, obviamente, solo nos es posible señalar tendencias y no conclusiones definitivas y válidas para cualquier profesor. Sin embargo, dado que la cultura escolar favorece el desarrollo de un ethos específico de prácticas pedagógicas, es altamente probable, casi inevitable, encontrar a otros profesores que se ajustan con flexibilidad a estos patrones.A modo de conclusiones podemos señalar que: a) la valoración de la profesionalidad docente depende del compromiso de los profesores con un proyecto educativo, ya que sus instropecciones muestran el ejercicio de una opción ética clara: cumplir bien su trabajo docente para que sus alumnos aprendan de manera significativa; b) los profesores comprometidos con un proyecto educativo contribuyen al desarrollo de un movimiento cultural de profesionalización que parte de sus prácticas. Afectan a la escuela y a la sociedad porque construyen relaciones de solidaridad con sus compañeros, promueven la participación y el debate sobre las formas de mejorar las prácticas escolares ineficientes, para que respondan mejor a las necesidades de los alumnos y la sociedad; c) esos profesores no solo son buenos profesores que dan buenas clases, sino que contribuyen a educar ciudadanos justos y dignos en una sociedad que también se espera que lo sea. Conciben la enseñanza como la comprensión crítica y ética de los contenidos y del rol que cada uno desempeña en el mundo.Lo que ahora nos compete es dar nuevos significados a lo que ya conocemos, encontrar un nuevo lenguaje y re-leer la cultura escolar. / This research recognizes the pedagogical value of the teachers practice involved in an educational project in the social change and in the recovery of the learning delight. We do not intend to elaborate action models but to share meanings for the dialogue and the debate. We believe that the teachers involved in an educational project can and must be a reference for other teachers. Meanwhile more teachers can show that the rights and liberties can be usufructed although restrictions and that they can carry out a teaching that guarantees the learning and the ethic education of pupils, there will be more possibilities to mobilize other teachers in a critical way, principally to who believe that external or self-imposed limitations can not be overcome.The teachers that we are concerned with are the professionals prepared with the scientific strictness and the artist's emotionality that like their job and are politically placed.The "good teachers" are the ones, whose expression synthesizes the imperative necessity to impel a radical change in the professional culture able to recover the synergic importance and transcendence of the teacher's professionalism, understood from its historical context, public and institutional. The concept "good" doesn't have a naive or fallacious meaning; we selected it because of its ethic and professional implications that refer not only to a well done work but, to the social and politic recognition of their peers and pupils as well.Although the educational process is, paradoxically, simple and complex at the same time, we hope contributing to those simple elements that constitute the professional identity of the teachers involved in an educational project and, to discover and give account of the epistemological complexities of their pedagogical thinking.We can point out that, a) the valuation of the teachers professionalism depends on the teachers compromise with an educational project; b) the teachers involved with an educational project contribute to the development of a cultural movement of professionalization that begins from their practices; c) the teachers involved in an educational project are not only good teachers because they give good classes, but also because they contribute to educate fair and honorable citizens in a society that also expect that from them. What we are concern is to give new meanings to what we already know and re-read the school culture.

Este estudio nace desde tres areas de investigación: la estetica feminista, la terapia artística y la expresión plastica, partiendo de la obra de la artista Louise Bourgeois. El primer capítulo, "Influencia feminista en Louise Bourgeois", considera la estética y crítica feministas en relación al postmodernismo, el feminismo y la historia. Por una parte, el trabajo de Bourgeois se aprecia bajo la relación entre semiótica, filosofía, sociología, psicología y estética. Por otra parte, se estudia la presencia de la tejeduría y labor de aguja en la obra de Bourgeois, analizándose la representación pictorica o interpretación literaria de la costura junto con el oficio del hilado, desde la estética feminista. Además, se consideran las similitudes de su obra con el "fiber art", arte realizado principalmente con fibras y vincula culturas ancestrales. Más alla, se estudia la presencia de la moda en la obra de Bourgeois, como objeto de reflexión feminista. "Razones intimas para la creación", el segundo capitulo, muestra como Bourgeois busca una cura para un dolor generado en los traumas de su niñez y adolescencia. El análisis que varios autores han realizado sobre el aspecto terapeútico de la obra de Bourgeois expone la traición y el abandono que la artista sufre por parte de sus seres queridos. Como consecuencia de que los traumas son generados en el entorno familiar, la familia sera el nucleo desde el cual Bourgeois genera su plástica curativa. A traves de representaciones parciales del cuerpo, Bourgeois reflexiona sobre el dolor y denuncia la violencia hacia la mujer, ya sea de tipo psíquico o fisico. Esto nos permite comparar su obra con la de artistas como Magadalena Abakanowicz u Orlan, que han recurrido a la deconstrucción del cuerpo para expresar el dolor. Pero, el anhelo por la cura se ve reflejado principalmente en la figura de su madre, la cual inspira en Bourgeois, de modo ambiguo, una actitud contradictoria hacia los recuerdos de su niñez. Además, considerando las multiples y animalescas representaciones que realiza de la madre, es posible analizar su obra desde un plano en el que la mitología y las teorías feministas se solapan. "Bajo la optica surrealista" es el último capítulo de esta tesis. En el se exponen las connotaciones psicoterapéuticas del universo plastico de Bourgeois. A su vez, se analizan las influencias recibidas de artistas como Joan Miró, Salvador Dalí, Remedios Varo o Leonora Carrington, entre otros, en torno a la representación de la androginia, la símbologia, la convivencia con la naturaleza, el autoanálisis y el sueño. / This study parts from three areas of investigation: feminist aesthetic, artistic therapy and plastic expression, based on Louise Bourgeois work.In the the first chapter, "Feminist influence on Louise Bourgeois", feminist criticism and aesthetics are considered in relation to postmodernism, feminism and history. On the one hand, Bourgeois work is appreciated under the relation between semiotics, philosophy, sociology, psicology and aesthetics. On the other hand, her work is analized through pictorial representations or literary interpretations of sewing and spinning from feminist aesthetics's point of view . Besides, it is also considered the similitude of her drawings and sculptures with fiber art works, constructed with fibers and rooted in ancient cultures. And, as a way towards feminism, the presence of fashion in Bourgeois work is also analized. "Intimate reasons for creation", the second chapter, shows how Bourgeois searches for a way to heal her pain, generated in her childhood and youth traumas. The analisys that several authors have done about the therapeutic aspect of her work, shows the treason and abandonment of her loved ones, even her mother. As a consequence of her traumas being originated within the familiar environment, it is from the family unit that Bourgeois generates her healing practice.From partial representations of the body, Bourgeois reflects her pain and denounces violence against women wether phisic or psychic. This allows the comparison of her works with that of others like Magdalena Abakanowicz or Orlan. But, her wish for healing is mainly expressed by representations of her mother. This figure, inspires her ambiguous actitude towards childhood memories. Considering multiples and animallike representations of her mother is possible to analize her work from overlapped mithology and feminist aesthetics. "Under a surrealist view" is the last chapter of this thesis. Psicotherapeutical connotations of Bourgeois plastic universe are shown here. Influences concerning androginy, simbology, convivial with nature, autoanalisis and dream, of artists as Joan Miro, Salvador Dalí, Remedios Varo or Leonora Carrington, among others, are analized.