L'ingegneria tissutale è un campo multidisciplinare in rapida crescita che si avvale delle scienze fisiche, ingegneristiche e della vita per sviluppare ed ottenere cellule funzionali, tessuti ed organi per riparare, sostituire o migliorare le funzioni biologiche perse a causa di anomalie congenite, traumi, malattie o invecchiamento. Nell’ambito della ricostruzione della cartilagine articolare sono stati fatti notevoli passi in avanti ma la soluzione per il ripristino completo del tessuto sembra ancora essere lontana. Nella prima parte di questo lavoro è stata valutata la capacità di uno scaffold a base di gelatina di indirizzare le ADSCs verso un differenziamento in senso condrogenico. Successivamente, con lo scopo di migliorare il grado differenziamento e diminuire i costi associati all’utilizzo di fattori differenziativi, l’attenzione è stata posta sullo sviluppo di un biomateriale a base di alginato e ioni cobalto in modo da mimare e sfruttare le caratteristiche fisiche della cartilagine piuttosto che il suo intorno chimico. In ultimo, è stato sviluppato un sistema low cost per la produzione di chip microfluidici sfruttabili per la realizzazione di sistemi micrometrici per incapsulazione cellulare. / Tissue engineering is an interdisciplinary and multidisciplinary field that aims at the developmentof biological substitutes that restore, mantain, or improve tissue function. Concerning the articular cartilage many improvments were made, but the complete tissue restoration approach still lacking. In the first part of this work, it was evaluated the ability of a gelatin scaffold to promote the condrogenic differentiation of ADSCs. Successively, in order to obtain a low cost sistem, a based alginate/Cobalt scaffold was designed with the aim to take advantage of the physical features of the cartilage tissue. Finally, it was developted a cost effective method to produce microfluidic chips with the aim to obtain micro-systems for cell encapsulation.

Le développement des activités humaines a engendré et engendre encore d’importants rejets d’espèces gazeuses et particulaires dans l’atmosphère. Parmi ces rejets, des gaz à effet de serre contribuent à augmenter la température moyenne du globe, on parle de forçage anthropique. Cette élévation impacte les différentes composantes du système climatique. Dans cette thèse, nous nous intéressons à l’atmosphère. La thèse, pluridisciplinaire, cherche à répondre à deux questions : le forçage anthropique peut-il influencer la circulation atmosphérique et plus précisément, sa variabilité, et peut-il avoir des conséquences sur la diffusion d’espèces polluantes ? Le travail est basé sur la comparaison de deux périodes, l’une de 1960 à 1989 représente le climat sans forçage, tandis que l’autre, de 2070 à 2099 prend en compte les différents scénarios de forçage anthropique. La première étape consiste à caractériser la variabilité de la circulation de l’atmosphère pour les mois hivernaux à partir des hauteurs du géopotentiel à 500 hPa sur une fenêtre Atlantico-Européenne. Les structures de variabilité étudiées concernent les modes de variabilité et les régimes de temps. D’après notre étude, les forçages ne modifient pas leurs structures dans l’espace mais davantage leurs fréquences d’apparition et leurs temps de persistance moyens. La deuxième étape concerne la modélisation de la qualité de l’air sur la région Nord-Pas de Calais. L’analyse des simulations actuelle et future révèle que les concentrations de particules en suspension et du dioxyde d’azote augmentent. En revanche aucune corrélation directe entre modes de variabilité sous forçage et diffusion n’est détectée. / The growth of human activities causes significant emissions of gaseous and particulate species in the atmosphere. Greenhouse gases contribute to increase the average global temperature, it’s called anthropogenic forcing. This temperature increase modifies the various components of the Earth’s climate system. In this thesis, the atmosphere is our topic of interest. The objective of this thesis is to answer two questions on a multidisciplinary basis: (1) can anthropogenic radiative forcing influences atmospheric circulation and more specifically, its variability? (2) And can it affects the spatial distribution of pollutants? This work is based on the comparison of two periods: one from 1960 to 1989 representing the climate without scenarios forcing; the other from 2070 to 2099 considering different scenarios of anthropogenic forcing. The first step is to characterize the atmospheric circulation variability, in wintertime, from the 500 hPa geopotential height at North Atlantic and European scale. The main structures of variability we studied are the so-called modes of variability and weather regimes. In our study, the scenarios do not change their structure in space but rather their frequency of occurrence and mean residence time. The second step concerns modeling of air quality over the French Northern region. Analysis of simulations reveals that actual and future concentrations of particulate matter and nitrogen dioxide increase, but no direct correlation between changes of variability modes and spatial distribution of pollutants is detected.

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En esta investigación se presenta un trabajo exploratorio sobre el uso del verbo en pacientes afásicos motores en castellano. Se ha utilizado una muestra de 9 sujetos afásicos de predominio motor, en tres tareas diferentes: habla espontánea, repetición de frases y frases incompletas. Las conversaciones libres han sido grabadas en cinta magnetofónica con una duración aproximada de media hora por paciente. Estas grabaciones se han trascrito mediante el sistema Childes Project. Los verbos utilizados y los errores han sido registrados en tablas individuales. Posteriormente se han realizado tablas globales de datos y tablas de error. Las tareas de repetición y frases incompletas se han estudiado a partir de un protocolo de exploración, elaborado al efecto, de 96 ítems en el que el 50 % pertenecen a la tarea de frases incompletas y el 50 % a la de repetición. Los datos codificados se han analizado estadísticamente mediante el programa SPSS (11.0).Se han realizado análisis uni y multivariados sobre el total de producciones verbales y errores respecto del modo verbal, aspecto, tiempo, persona y número. Asimismo se ha analizado el carácter regular o irregular del verbo. Los resultados ponen de manifiesto efectos significativos asociados al tipo de tarea verbal ejecutada. Se observan además efectos significativos asociados al grado de severidad de la afasia en todas las medidas registradas. De otra parte, hay una tendencia al uso de estructuras cognitivamente más simples en función de la familiaridad de uso y el grado de programación cognitiva exigida por la construcción verbal. En este sentido, los pacientes tienden a sustituir el subjuntivo por el indicativo, el pasado y el futuro por presente, el plural por el singular y la segunda persona por la primera y tercera. Estos resultados contradicen los esperados a partir de la "Hipótesis del Árbol Recortado" (Friedman & Grodzinsky, 1997, 2000; Friedman, 1998, 1999, 2001, 2002, 2003) y aportan elementos de discusión importantes respecto a los modelos de producción del lenguaje. / In this research an exploratory work was presented on the use of the verb in motor aphasics patients in the Spanish language. Nine motor aphasics patients were recorded in three different tasks, spontaneous speech, sentence repetition and incomplete sentences. The conversations with each patient, of approximately half an hour, were taped. These recordings have been transcribed using the Childes Project System. The verbs used and the mistakes have been registered in individual charts. Afterwards global charts of data and error have been made up. The repetition and incomplete sentence tasks have been studied based on an exploration protocol of 96 items where, 50% was used to perform incomplete sentences and the remaining 50% for the repetition task. The data has been analysed statistically using the SPSS (11.0) programme.Univariated and multivariated analysis have been carried out on the total of oral production and errors regarding the mood verbal, aspect, tense, person and number. At the same time the regular and irregular character of the verb has been analysed. The results show significant effects associated with the type of task carried out. Significant effects associated to the degree of severity of the aphasia in all the measures taken were found too. It is observed that there is a tendency to use the simplest cognitive structures regarding the familiarity of use of words and grammatical structures and the complexity of cognitive programme necessary for the production of sentences. In this way, the patients usually substitute the subjunctive, for the indicative, the past and the future for the present, the plural for the singular and the second person for the first and third. These results don't confirm the "Tree Pruning Hypothesis" (Friedman & Grodzinsky, 1997, 2000; Friedman, 1998, 1999, 2001, 2002, 2003) and introduce important elements for discussion regarding the models for language production.

The aim of this study is to investigate on some molecular mechanisms contributing to the pathogenesis of osteoarthritis (OA) and in particular to the senescence of articular chondrocytes. It is focused on understanding molecular events downstream GSK3β inactivation or dependent on the activity of IKKα, a kinase that does not belong to the phenotype of healthy articular chondrocytes. Moreover, the potential of some nutraceuticals on scavenging ROS thus reducing oxidative stress, DNA damage, and chondrocyte senescence has been evaluated in vitro. The in vitro LiCl-mediated GSK3β inactivation resulted in increased mitochondrial ROS production, that impacted on cellular proliferation, with S-phase transient arrest, increased SA-β gal and PAS staining, cell size and granularity. ROS are also responsible for the of increased expression of two major oxidative lesions, i.e. 1) double strand breaks, tagged by γH2AX, that associates with activation of GADD45β and p21, and 2) 8-oxo-dG adducts, that associate with increased IKKα and MMP-10 expression. The pattern observed in vitro was confirmed on cartilage from OA patients. IKKa dramatically affects the intensity of the DNA damage response induced by oxidative stress (H2O2 exposure) in chondrocytes, as evidenced by silencing strategies. At early time point an higher percentage of γH2AX positive cells and more foci in IKKa-KD cells are observed, but IKKa KD cells proved to almost completely recover after 24 hours respect to their controls. Telomere attrition is also reduced in IKKaKD. Finally MSH6 and MLH1 genes are up-regulated in IKKαKD cells but not in control cells. Hydroxytyrosol and Spermidine have a great ROS scavenging capacity in vitro. Both treatments revert the H2O2 dependent increase of cell death and γH2AX-foci formation and senescence, suggesting the ability of increasing cell homeostasis. These data indicate that nutraceuticals represent a great challenge in OA management, for both therapeutical and preventive purposes.

It was the inferior black education system that kindled the uprisings that erupted in Soweto on 16 June 1976. Since then, black education has been so discredited that it now serves only to further crystallize opposition to the government. The classroom plays a far less influential role in shaping black perceptions than the informal schooling blacks get from their peers, their parents and political organizations. Simphiwe, Ben, Jabulani and Peter are students in Soweto, veterans of the 1976 uprisings.

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