Las nuevas tecnologías en enseñanza superior son un recurso potencial, un conjunto de herramientas, que se va introduciendo dentro del sistema educativo de un modo progresivo, ofreciendo tanto al docente como al discente vías alternativas abiertas a su interacción y formación. La Web como recurso educativo presenta múltiples ventajas y también nuevos retos, su estructura hipertextual posibilita la navegación del usuario por redes repletas de información que amplían su capacidad de acceder a múltiples recursos y facilitan su trabajo individual y cooperativo. La utilización de estas tecnologías como instrumentos de apoyo a la docencia y la investigación, como vías adaptadas o adaptables a las características específicas de sus usuarios, ha hecho de ellas en muchas ocasiones, una herramienta imprescindible, al tiempo que se han ido perfilando como una vía alternativa o complementaria de formación; constituyéndose en una parte importante del sistema dentro de los programas de formación e intervención psicoeducativa. Los planteamientos teóricos que justifican la inclusión de estas nuevas formas de presentación en programas de instrucción, la importancia del diseño de su interfaz con fines de favorecer el proceso de enseñanza / aprendizaje y la navegación por páginas web con fines educativos, exige conocer las potencialidades del hipertextoy los recursos multimedia como soporte del entorno mediador del aprendizaje y la formación. En este estudio se recogen la descripción y el análisis de una experiencia de estudio en web, a partir de un diseño previo de los contenidos de estudio en cinco formas de presentación distintas, cuatro en formato hipertextual y una en texto tradicional, se realiza una primera fase de implementación, en situaciones de estudio controladas en laboratorio. Con los resultados y la información obtenida en esta primera experiencia se plantea una segunda fase de estudio, en la cual se introducen modificaciones en el diseño y en las sesiones de estudio. La segmentación del grupo de estudiantes atendiendo a los resultados obtenidos, permite observar como los estudiantes de bajo rendimiento son los más beneficiados por su participación en esta experiencia de estudio, en entornos mediadores de enseñanza/aprendizaje diseñados con fines instruccionales, que utilizan como soporte las Tecnologías de la Información y la Comunicación. / The new technologies are a potential resource in superior education, a series of tools which is progressively entering the educative system, offering both the teaching staff and learners alternative ways to interact and acquire training. The World Wide Web as an educative resource shows many advantages and also new challenges: its hypertextual structure gives the user the opportunity of navigating through information- full webs, which offer many different resources and facilitates individual and cooperative work. Usage of these technologies as support means for teaching and research, and as tools that are adapted or adaptable to the specific needs of its users, has often turned them into essential instruments, and has also showed them as an alternative or complementary approach to education. Thus, it has become an important part of the system employed in many psychic-educative training and intervention programs. The theoric foundations that justify the inclusion of this new ways of presentation in instruction programs, the significance of interface design in education- related web pages, requires a greater knowledge of hypertext´s potential as a format for the mediating environment in learning and teaching. This study gathers the description and analysis of a web- based study experience, from its preliminary design and a first implementation phase in laboratory- controlled study situations, with a prototype that is progressively adapted to the potential users through successive approaches, in order to improve interface design and the final learning results.

Este trabajo pretende contribuir a disminuir las dificultades derivadas de barreras físicas y sociales de las personas con parálisis cerebral y de sus familias, mejorando su integración en la sociedad y su calidad de vida.En su parte teórica trata de situar la realidad de estas personas desde un nivel global, como sería su contexto social, hasta el nivel más concreto de las familias con personas con parálisis cerebral, pasando también por recoger algunas características de la familia en general y aspectos comunes de las familias de personas con discapacidad.Así, desde la Teoría de la Actividad, encontramos que la influencia del entorno es decisiva en el comportamiento humano y tiene lugar a través de diversos factores de dicho entorno. La familia, también, desempeñará una serie de funciones y socializará en una serie de valores, en función de su estilo educativo y del modo en que se desarrolle la vida cotidiana.Ante el nacimiento en la familia de una hija o un hijo con discapacidad podrán surgir diversos sentimientos y reacciones e implicará para los padres nuevos roles en relación a su hijo o hija, enfrentándoles también con otros problemas. La parálisis cerebral, por sus características específicas, conllevará para los padres una serie de inquietudes, que será importante tener en cuenta a la hora de realizar algún tipo de intervención con estas familias.Tal intervención la concebimos desde la Perspectiva del ciclo vital y consideramos tanto la evaluación previa a ella, como el plan de intervención propiamente dicho. Analizamos también algunos modelos de intervención desarrollados en la práctica.Los objetivos del trabajo experimental son analizar los sucesos vitales más influyentes en las personas estudiadas (adultos jóvenes con Parálisis Cerebral y sus padres) y las estrategias empleadas por ellas para afrontarlos, lo cual puede contribuir a elaborar las bases para un programa de intervención con las familias. La metodología utilizada fue, en primer lugar, la entrevista a varias personas con esta discapacidad, a las que se les preguntaba por los sucesos vitales más influyentes en sus vidas. Sus respuestas dieron pie a situarnos en la Teoría de los constructos personales y a la elaboración de una rejilla consensuada con el fin de recoger la forma en que las personas con Parálisis Cerebral de nuestro estudio, sus madres y padres construyen su estructuración cognitiva personal.La anamnesis de cada una de las personas con Parálisis Cerebral nos ayudó a reconstruir los datos más significativos de sus historias personales. Las respuestas dadas por cada una de ellas, sus madres y padres, fueron analizadas estadísticamente con el Programa Winsigrid.Con todos los datos obtenidos en el trabajo de campo hicimos un doble estudio comparativo, por un lado analizamos las convergencias y divergencias dentro de cada núcleo familiar y por otro consideramos tres grupos diferentes, personas con Parálisis Cerebral, madres y padres, estudiando los aspectos más importantes de cada uno de estos grupos específicos.Este trabajo nos permitió llegar a una serie de conclusiones acerca de las percepciones, actitudes, preocupaciones, recursos y angustias de estas personas ante sus sucesos vitales y de la influencia de determinados aspectos del entorno y de sus propias experiencias personales en todo ello.Por último recopilamos una serie de características que consideramos debería tener un programa de intervención con estas familias, así como una serie de estrategias de intervención que pensamos deberían tener en cuenta los profesionales que realizaran tal intervención. / The present research work intends to contribute to lessening difficulties coming from physical and social barriers encountered by people with cerebral palsy and their families, while at the same time improving both their integration into society and their quality of life.Its theoretical part focuses on the people's reality of life from a global level, that is, their social context, to the most particular stage, that is, the families with people suffering from cerebral palsy. As well as this, some characteristics of families in general and points in common of families with disabled people are also discussed.Some features of the intervention programmes carried out in these families are analysed as well from the life-span perspective.The aims of the experimental work are to analyse the most influential events in the lives of the people who are the subject of this study (young adults with cerebral palsy and their parents) and the strategies they used to face them, which may contribute to lay the foundations for an intervention programme in families.The methodology used in the first stages was an interview with several people with this disability, which enabled us to draw up a grid so as to compile the way people with cerebral palsy, their mothers and fathers build their personal cognitive structure. The background report of each of the people with cerebral palsy also helped us gather together the most significant data in their personal histories.With all the data obtained in the field study, we carried out a double comparative study: on the one hand, inside each family unit, on the other hand, in three different groups: people with cerebral palsy, their mothers and their fathers.This work enabled us to reach a series of conclusions about these people's perceptions, attitudes and concerns regarding their life events, and at the same time to realise the influence of certain aspects of the environment and their own personal experiences.Finally we compiled a series of characteristics we thought an intervention programme in these families ought to have and listed the strategies that professionals should make use of.

£\1-antitrypsin¡]£\1-AT¡^is one of over 40-member family of serine protease inhibitors, regulating trypsin and elstase activities by the formation of covalently bound complex. The mechanism of which serpin and enzyme form covalent complex is not clear, but two theorise have been proposed. One is opposite pole theory (OPT) proposed by Huntington et al.¡]2000¡^, suggesting that after serpin is cleaved by serine protease, the P1-linked enzyme is over-swinging about 70

Ethylene plays a key role in square and boll abscission in cotton (Gossypium hirsutum L.). When subjected to stress, cotton plants synthesize higher rates of ethylene which can result in the loss of immature fruit. The ethylene action inhibitor 1- methylcyclopropene (1-MCP) is used in many fruit, vegetable, and floriculture crops to counter the effects of ethylene. Protecting a cotton crop from ethylene through its early reproductive stages may boost yields by increasing fruit retention. A two-year field study was conducted in 2005 and 2006 at the Texas Agricultural Experiment Station in Burleson County, Texas to evaluate the effects of 1-MCP concentration and timing on cotton growth and yield components. The study was designed as a randomized complete block with 4 replications. Three rates of 1-MCP (250, 500, and 1250 g ha-1 of actual product) were applied as a foliar spray at a delivery rate of 93.50 L -1 ha. Each rate was applied at pinhead-square and fourteen days after pinhead-square; pinhead-square, fourteen days after pinheadsquare, and early bloom; early bloom and fourteen days after early bloom; early bloom, fourteen days after early bloom, and twenty-eight days after early bloom. Plant heights, total number of nodes per plant, percent square abscission, nodes above white flower (NAWF), relative chlorophyll content, fruit number, fruit size, and fruit distribution were not affected by 1-MCP. In 2006, electrolytic leakage was significantly increased by two, 250 g ha-1, 1-MCP treatments. In 2005, yield was significantly increased by six of the 1- MCP treatments and suggests an increase in boll retention, boll size, seed number, or seed size. The analysis of yield components conducted through box-mapping, however, failed to explain the observed yield response. In 2006, 1-MCP did not significantly influence yield.

Human immunodeficiency virus type 1 (HIV-1) genome consists of two identical RNAs that appear noncovalently linked near their 5' ends. The 5' untranslated region is called leader region. The 3' part of leader, i.e. nucleotides U200 to G335 in HIV-1 genomic RNA, between the primer binding site and the gag gene, can fold into 3 stem-loops: the kissing-loop domain (KLD) or stem-loop 1 (SL1), the 5' splicing junction hairpin (SD) or SL2 and SL3. The KLD, from nucleotide (nt) 243 to 277, forms a stem-loop (kissing loop hairpin) seated on top of a small stem bulge (stem B and loop B). The kissing-loop hairpin, or dimerization initiation site (DIS) hairpin consists of stem C and loop C. Loop C contains the autocomplementary sequence (ACS) GCGCGC262 or GUGCAC262, also called DIS. / In the kissing-loop model of HIV-1 genome dimerization, HIV-1 RNA dimerization is initiated by base pairing between the ACS of one RNA monomer and that of an adjacent monomer. / To understand the role of the ACS in HIV-1 replication and HIV-1 genomic RNA dimerization, we replaced the central CGCG261 (or tetramer) of the HIV-1 Lai ACS by other tetramers. Genomic RNAs containing the UUAA tetramer (non-HIV-1 tetramer) were half dimeric, but UUAA genome packaging was unaffected. This was the first evidence that genomic RNA dimerization and packaging can be dissociated (Chapter 2). Destroying stem-loop C reduced genomic RNA dimerzation by ~50%, proviral DNA synthesis by ~85%, and reduced viral infectivity by ~3 logarithmic units. Destroying stem-loop B had similar effects on genome dimerization, reverse transcription, and viral infectivity. We also observed that mutations in stem-loop B and in the DIS hairpin were "non additive" (Chapter 2). / The existence of stem-loop C is supported by phylogenetic evidence, while that of stem-loop B is not, namely, its sequence is completely conserved. We investigated the role of stem B and loop B nucleotides in viral replication, and genomic RNA dimerization. The putative CUCG246/CGAG277 duplex was replaced by 9 alternative complementary sequences, 4 likely to base pair in long (~500 nts) RNAs, as assessed by the algorithm mfold. Among the 4 sequences, 3 preserved genome dimerzation, 1 did not significantly inhibit it, and 2 preserved viral replication. We also asked if 9 deletions or nucleotide substitutions within nucleotide 200 to 242 and/or 282 to 335 could influence genome dimerization. Delta200--226 and Delta236--242 genomic RNAs dimerized relatively poorly despite having neutral or positive influences on stem B, loop B and klh folding (Chapter 3). / Mutations within the Matrix, Capsid, p2 and nucleocapsid genes suppress several functional defects caused by KLD destruction. We tested the effect of these suppressor mutations on genome dimerization and infectiousness of viruses bearing moderate to crippling KLD mutations. Our conclusion is that these suppressor mutations can restore genomic RNA dimerization when DIS is weakened, but not when DIS is denatured or the KLD is destroyed (Chapter 4).

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Berlin, Humboldt-Universiẗat, Diss., 2003.

The thermal decomposition of pentene-1 in a static system has been investigated over a temperature range of 470 to 530°C. and a pressure range of 50 to 250 mm. The decomposition was a homogeneous first-order reaction with an average overall activation energy of 52 kcal./mole. The reaction rate was retarded by propylene and by inert gases, but was unaffected by nitric oxide. Free radicals from lead tetraethyl produced an acceleration. The activation energy exhibits a slight increase with increasing initial pressure of pentene. Evidence is presented for a composite reaction mechanism involving both a free-radical chain process and a direct intramolecular rearrangement. . / Science, Faculty of / Chemistry, Department of / Graduate

YB-1 est membre de la superfamille de protéines de choc thermique. YB-1 se lie à l'ARN et l'ADN. Des corrélations entre niveau élevé de YB-1, expression élevée de la P-glycoprotéine MDR1 et un mauvais pronostic ont été faites pour plusieurs types de cancer. Le rôle de YB-1 dans la cancérogenèse peut être soutenu par plusieurs mécanismes: i) l'activation de la transcription; ii) la participation à la réparation de l'ADN; iii) la régulation de la traduction. Les deux premiers modèles supposent une localisation nucléaire de YB-1, et cela malgré le fait que YB-1 est apparaît principalement dans cytoplasme dans des conditions physiologiques et les mécanismes de son accumulation nucléaire restent obscurs. Dans ce travail, nous avons tenté d’identifier les mécanismes qui déclenchent la translocation nucléaire de YB-1. Il est apparu que cette localisation nucléaire dépend principalement du niveau d’ARNm dans le cytoplasme et ainsi d’une transcription active, plutôt que de la présence de lésion à l'ADN nucléaire. A l'inverse, le rôle de YB-1 comme régulateur de la traduction est clairement établi. YB-1 peut influencer la traduction et favoriser la progression du cancer, indépendamment de ses fonctions éventuelles dans le noyau. Nous avons démontré par microscopie à force atomique et à l’aide de méthodes biochimiques, que YB-1 se lie aux ARNm d'une manière coopérative à l’ARNm, ce qui a des conséquences directes sur sa capacité à sélectionner des ARNm spécifiques et à moduler la traduction. Au-delà de ces recherches, nous nous sommes appuyés sur notre maitrise de la biologie de YB-1 pour développer une méthode innovante pour mettre en évidence les interactions protéine-protéine dans le contexte cellulaire. Nous avons ainsi confirmé à l’aide de cette méthode la capacité de YB-1 de former des oligomères en présence d'ARNm, et également révélé son interaction potentielle avec Lin28. / YB-1 is a member of the cold-shock protein superfamily. It binds to both RNA and DNA. Correlations between high level of YB-1, elevated expression of P-glycoprotein MDR1 and poor patient prognosis were made for several types of cancer. The role of YB-1 in cancerogenesis can be accounted by several mechanisms: i) activation of transcription; ii) participation in DNA repair; iii) regulation of translation. The first two proposals imply a nuclear localization for YB-1, despite the fact that it appears mainly in the cytoplasm under physiological conditions and the mechanisms for its nuclear accumulation remain unclear. In this work we attempted to identify the mechanisms that trigger the nuclear translocation of YB-1. It appeared that this depends on the level of mRNA in the cytoplasm and thus on active transcription, rather than on the presence of nuclear DNA damages. In contrast to its function in the nucleus, the role of YB-1 in the regulation of translation was clearly established. YB-1 may therefore orchestrate a translation bias in order to promote cancer progression independently of its putative functions in the nucleus. Here we demonstrated, using atomic force microscopy and biochemical methods, that YB-1 binds mRNA in a highly cooperative manner and this has direct consequences on mRNA selection and following translational modulation. Beyond this research, we took advantage of our knowledge of the biology of YB-1 to develop a new method to detect protein-protein interactions in cellular context, using YB-1 as model protein. Besides the fact that we confirmed ability of YB-1 to make oligomers in the presence of mRNA, we also highlighted its potential interaction with Lin28, using this method.

La sulfatation protéique est une modification post-traductionnelle qui intervient principalement sur les récepteurs cellulaires. Parmi eux, le récepteur CXCR4 est particulièrement étudié en raison de son implication dans de nombreux processus physiopathologiques (réponse immunitaire, infection au VIH). Le domaine extracellulaire de 38 acides aminés de CXCR4 (le peptide P38), contenant trois tyrosines connues pour être sulfatées, est important pour l’interaction avec son ligand spécifique, la chimiokine SDF-1α/CXCL12 (Stromal Cell-Derived Factor-1α). Le rôle de la sulfatation de CXCR4 dans cette interaction est encore méconnu.Le peptide P38 a été synthétisé et sulfaté de façon régiosélective sur toutes les tyrosines (peptides mono-, di- ou tri-sulfatés, soit 7 combinaisons). L’impact du nombre et de la position des groupements sulfate le long du peptide P38 sur son interaction avec SDF-1α a été étudié par électrophorèse capillaire d’affinité (ACE) couplée ou non à la spectrométrie de masse électrospray (ESI-MS). Une interaction entre P38 et SDF-1α a été mise en évidence par ACE. Une augmentation de l’affinité peut être associée à l’augmentation du degré de sulfatation de P38. La stœchiométrie des complexes a ensuite été déterminée en utilisant l’ACE-MS, qui a mis en évidence une majorité de complexes 1:1, quel que soit le peptide étudiéCes travaux ouvrent la voie à l'étude d'une interaction à trois partenaires avec des glycosaminoglycanes. / Sulfation is one of the most important post-translational modifications of proteins. The known sulfated proteins are mostly cell receptors and among them, CXCR4 attracts growing attention because of its involvement in numerous physio-pathological processes (immune response, HIV infection). The 38 amino-acid extracellular domain of CXCR4 (P38 peptide), containing three tyrosine residues known to be sulfated, is important for the interaction with its specific ligand, the SDF-1α/CXCL12 chemokine (Stromal cell-derived factor-1α). The role of sulfation in this interaction remains to be established.The P38 peptide was chemically synthesized and regioselectively sulfated on all the tyrosines (mono-, di- or tri-sulfated peptides, 7 combinations). The impact of both distribution and position of sulfate groups on the interaction between P38 and SDF-1α was studied by affinity capillary electrophoresis (ACE) hyphenated to electrospray mass spectrometry (ESI-MS).An interaction between P38 and SDF-1α was highlighted by ACE. It was strongly enhanced by the increase of P38 sulfation degree. The complex stoichiometry was then determined by ACE-MS, and 1:1 complexes were predominantly obtained, with all the peptides. This work opens the orad to the three-partner interaction studies involving glycosaminoglycans.