L'ischémie/reperfusion (I/R) est un phénomène très fréquent en clinique humaine. Ce phénomène est observé lors de la désobstruction d'une artère digestive, du traitement d'un état de choc, ainsi qu'au cours d'autres pathologies. L'interruption de la perfusion tissulaire (ischémie) et le rétablissement de celle-ci (reperfusion) sont la cause de la mise en place de troubles hémodynamiques et métaboliques. L'I/R est souvent présentée comme étant la principale source de l'hyperlactatémie et le moteur de la réponse inflammatoire lors des états de choc (cardiogénique, hypovolémique, septique). Parallèlement, elle est responsable de l'induction de la production de la libération des espèces réactives de l'oxygène, des cytokines et du monoxyde d'azote. Suite à un choc hémorragique par Ischémie/reperfusion chez le rat, nous avons montré que 1) le NaHS, donneur d'H2S limite la diminution de la pression artérielle moyenne et diminue le lactate plasmatique, témoin de la souffrance tissulaire, 2) cette amélioration hémodynamique est associée à une baisse de l'expression myocardique des ARNm d'iNOS, une diminution de la concentration des dérivés NOx plasmatiques et une diminution des concentrations aortiques et myocardiques de NO et d'anion superoxyde et 3) l'inhibition d'H2S par la DL-propargylglycine aggrave le tableau hémodynamique et les conséquences tissulaires du choc. Dans un autre modèle d'ischémie/reperfusion intestinale, les résultats obtenus, montrent que l'administration de la Protéine C activée (PCa) ou de la dexaméthaosne (Dexa) : 1) améliore la PAM et la réactivité vasculaire, 2) permet d'augmenter le pH et de diminuer la lactatémie, 3) diminue la production des cytokines pro-inflammatoires et 4) inhibe les médiateurs de l'apoptose. Ces résultats sont reliés à une down régulation d'iNOS, une restauration de la voie Akt/eNOS et à une resensibilisation des adrénorécepteurs alpha. Ces résultats ouvrent de nouvelles perspectives cliniques dans les traitements de l'I/R / Ischemia/reperfusion (I/R) is a very common phenomenon, observed during intestinal artery surgery, shock treatment, as well as in several other diseases. The disruption of tissue perfusion (ischemia) and recovery (reperfusion) induce hemodynamic and metabolic dysfunction. Gut ischemia/reperfusion is often presented as the main source of lactate and the motor of the inflammatory response, such as cardiogenic, hypovolemic and septic shock. In parallel, gut reperfusion produces numerous mediators such as reactive oxygen metabolites, pro-inflammatory cytokines, and high concentrations of nitric oxide. In a model of ischemia/reperfusion induced by hemorrhagic shock, we found that 1) NaHS an injectable form of H2S, limited the decrease in arterial pressure induced by shock and decreased plasmatic lactate, a witness of tissue suffering, 2) this hemodynamic improvement was associated with a fall in myocardial iNOS mRNA expression, a reduction in the concentration of plasmatic NOx and a reduction of aortic and myocardial concentrations of NO and superoxide anion and 3) the inhibition of H2S with DL-propargylglycine worsened hemodynamics and tissue consequences of shock An experimental model of intestinal I/R has been developed, we demonstrated that the administration of APC or Dexa : 1) Improves MAP and vascular reactivity, 2) increased pH and decreased lactate, 3) decreased pro-inflammatory cytokines production and 4) inhibited apoptosis mediators expression. These results are related to a down regulation of iNOS, to a restoration of the AKT/eNOS pathway, and to alpha-adrenoreceptor resensitization. These results open new perspectives in clinical treatment of I/R

Transit agencies include buffer time in their schedules to maintain stable headways and avoid bus bunching. In this work, a real-time holding mechanism is proposed to dispatch buses on a loop-shaped route, solely based on operating conditions in real-time. Holds are applied at the terminal station to minimize the expected variance of bus headways at departure. The bus-dispatching problem is formulated as a stochastic decision process. The optimality equations are derived and structural properties of the optimal policy are inferred by backward induction. The exact optimal holding policy is then found in closed form, as a function of the expected travel time of buses currently running. A simulation assuming stochastic operating conditions and unstable headway dynamics is performed to assess the expected average waiting time of passengers at stations. The proposed control strategy is found to provide lower passenger waiting time and better resiliency than methods recommended in the literature and used in practice.

[EN] Statistical Process Control (SPC) and the Automatic Process Control (APC) are two control philosophies have evolved independently until recently. The overall objective of both APC and SPC is to optimize the performance of processes, reducing the variability of the resulting characteristics around the desired values. The fundamentals of the two disciplines arise from the idea that the whole process has operation variations. These variations may affect, to a greater or lesser extent, the final product quality and the process productivity. The two methodologies conceptualize processes and control in different ways, they originated in different industrial sectors and have evolved independently, until the interest to integrate them in the control of industrial processes was deduced. It was warned that they could be complementary rather than conflicting methodologies as they were understood until then. The possibility of combining the advantages of both, integrating them into a new control paradigm was explored. First, the problem of identifying and estimating a process model is considered. Controlled variables in this model are the main feature of product quality and a productivity variable. The latter is innovative since the productivity variables are measured, but they are not considered as controlled variables. For this, two methods of multivariate time series are used, the Box-Jenkins multiple transfer function in the parsimonious way and the impulse response function obtained by Partial Least Squares regression (Time Series-Partial Least Squares, TS-PLS). These two methods were compared taking into account different aspects such as the simplicity of the modeling process in the stages of identification, estimation and model validation, as well as the utility of graphical tools that provide both methodologies, the goodness of fit obtained, and the simplicity of the mathematical structure of the model. The DMC (Dynamic Matrix Control) controller, an automatic control algorithm belonging to the family of MPC (Model Predictive Control) controllers, is derived from the estimated Box-Jenkins multiple transfer function that has been selected as the most suitable for this kind of processes. An optimal tuning method to maximize the controller performance, applying experimental design 2k-p, is presented. Finally, an integrated control system MESPC (Multivariate Engineering Statistical Process Control) whose monitoring component has been implemented applying latent structures based multivariate statistical process control methods (Lsb-MSPC), has been developed. The monitoring module is designed to act as both process and DMC controller supervisor. To do this, we estimate a NOC-PCA model (Normal Operation Conditions Principal Component Analysis), which has as variables both process-related and quality-related variables, all derived from the automatic control system. From this model, and DModX graphics have been derived. We assessed the performance of MESPC system, subjecting it to simulated potential failures or special causes of variability. / [ES] El Control Estadístico de Procesos (Statistical Process Control, SPC) y el Control Automático de Procesos (Automatic Process Control, APC) son dos filosofías de control se han desarrollado hasta recientemente de forma independiente. El objetivo general tanto del SPC como del APC, es optimizar el funcionamiento de los procesos, reduciendo la variabilidad de las características resultantes en torno a los valores deseados. El fundamento de ambas disciplinas, parte de la idea de que todo proceso presenta variaciones en su funcionamiento. Estas variaciones pueden afectar en mayor o en menor medida a la calidad final del producto y a la productividad del proceso. Las dos metodologías conceptualizan los procesos y su control de diferentes formas, se originaron en diferentes sectores industriales y han evolucionado de forma independiente, hasta que se dedujo el interés de integrarlas en el control de los procesos industriales, ya que se advirtió que podían ser complementarias, antes que contrapuestas, como se entendían hasta entonces y se exploró la posibilidad de aunar las ventajas de ambas, integrándolas en un nuevo paradigma de control. Esta tesis se centra en el estudio de la integración de procedimientos multivariantes para la regulación óptima y la monitorización estadística de procesos, con el propósito de contribuir a la mejora de la calidad y de la productividad de los procesos. La metodología propuesta se ha aplicado con fines ilustrativos a un proceso MIMO de producción en continuo de Polietileno de Alta Densidad (PEAD).En primer lugar, se considera el problema de la identificación y posterior estimación de un modelo del proceso. Las variables controladas en este modelo han sido la principal característica de calidad del producto y una variable de productividad, esto último es innovador puesto que las variables de productividad se miden, pero no se consideran variables controladas. Para ello, se emplean dos metodologías de series temporales multivariantes, la obtención de la función de transferencia múltiple en forma parsimoniosa de Box-Jenkins y la obtención de la función de respuesta a impulsos mediante los modelos de regresión por mínimos cuadrados parciales (Time Series-Partial Least Squares, TS-PLS). Estas dos metodologías se han comparado teniendo en cuenta distintos aspectos como son la simplicidad del proceso de modelado en las etapas de identificación, estimación y validación del modelo, así como la utilidad de las herramientas gráficas que proporcionan ambas metodologías, la bondad de ajuste obtenida, y la simplicidad de la estructura matemática del modelo. A partir del modelo de función de transferencia múltiple estimado, elegido como el más adecuado para este tipo de procesos, se desarrolla el controlador DMC (Dynamic Matrix Control), un algoritmo de control automático que pertenece a la familia del Control Predictivo basado en Modelos (Model Predictive Control, MPC). Se presenta un método de sintonizado óptimo del controlador que permita maximizar su rendimiento, aplicando diseño de experimentos 2k-p.Finalmente, se ha desarrollado un sistema de control integrado MESPC (Multivariate Engineering Statistical Process Control), cuya componente de monitorización se ha implementado aplicando métodos de control estadístico multivariante de procesos basados en técnicas de proyección en estructuras latentes. Este módulo de monitorización se ha diseñado para que actúe como supervisor tanto del proceso como del controlador DMC. Para ello, se ha estimado un modelo NOC-PCA (Normal Operation Conditions Principal Component Analysis), en el que han intervenido tanto variables relacionadas con el proceso como con la calidad, todas derivadas de la componente del control automático. A partir de este modelo se han derivado los gráficos y DModX. Se ha evaluado el funcionamiento del sistema MESPC, sometiéndolo a fallos potenciales o causas especiales de variabiliabilidad. / [CAT] El Control Estadístic de Processos (Statistical Process Control, SPC) i del Control Automàtic de Processos (Automatic Process Control, APC) son dues filosofies de control s'han desenvolupat fins a recentment de forma independent. L'objectiu general tant del SPC com del APC, és optimitzar el funcionament dels processos, reduint la variabilitat de les característiques resultants entorn dels valors desitjats. El fonament d'ambdues disciplines, part de la idea que tot procés presenta variacions en el seu funcionament. Aquestes variacions poden afectar en major o en menor mesura a la qualitat final del producte i a la productivitat del procés. Les dues metodologies conceptualitzen els processos i el seu control de diferents formes, es van originar en diferents sectors industrials i han evolucionat de forma independent, fins que es va deduir l'interès d'integrar-les en el control dels processos industrials, ja que es va advertir que podien ser complementàries, abans que contraposades, com s'entenien fins llavors i es va explorar la possibilitat de conjuminar els avantatges d'ambdues, integrant-les en un nou paradigma de control. Aquesta tesi se centra en l'estudi de la integració de procediments multivariants per a la regulació òptima i el monitoratge estadístic de processos amb el propòsit de contribuir a la millora de la qualitat i de la productivitat dels processos. La metodologia proposada s'ha aplicat amb finalitats il·lustratives a un procés MIMO de producció en continu de Polietilè d'Alta Densitat (PEAD). En primer lloc, es considera el problema de la identificació i posterior estimació d'un model del procés. Les variables controlades en aquest model han sigut la principal característica de qualitat del producte i una variable de productivitat, açò últim és innovador ja que les variables de productivitat es mesuren, però no es consideren variables controlades. Per a açò, s'utilitzen dues metodologies de sèries temporals multivariants, l'obtenció de la funció de transferència múltiple en forma parsimòniosa de Box-Jenkins i l'obtenció de la funció de resposta a impulsos mitjançant els models de regressió per mínims quadrats parcials (Times Series-Partial Least Squares, TS-PLS). Aquestes dues metodologies s'han comparat tenint en compte diferents aspectes com són la simplicitat del procés de modelatge en les etapes d'identificació, estimació i validació del model, així com la utilitat de les eines gràfiques que proporcionen ambdues metodologies, la bondat d'ajust obtinguda, i la simplicitat de l'estructura matemàtica del model. A partir del model de funció de transferència múltiple estimat, triat com el més adequat per a aquest tipus de processos, es desenvolupa el controlador DMC (Dynamic Matrix Control), un algorisme de control automàtic que pertany a la família del Control Predictiu basat en Models (Model Predictive Control, MPC). Es presenta un mètode de sintonitzat òptim del controlador que permeta maximitzar el seu rendiment, aplicant disseny d'experiments 2k-p. Finalment, s'ha desenvolupat un sistema de control integrat MESPC (Multivariate Engineering Statistical Process Control). Per a implementar la component de monitoratge d'aquest sistema integrat s'han usat mètodes de control estadístic multivariants de processos basats en tècniques de projecció en estructures latents (Latent structures based-Multivariate Statistical Process Control). Aquest mòdul de monitoratge s'ha dissenyat perquè actue com a supervisor tant del procés com del controlador DMC. Per a açò, s'ha estimat un model NOC-PCA (Normal Operation Conditions Principal Component Analysis), en el qual han intervingut variables relacionades tant amb el procés, com amb la qualitat, totes derivades de la component del control automàtic. A partir d'aquest model s'han derivat els gràfics i DModX. S'ha avaluat el funcionament del sistema MESPC, sotmetent-lo a fallades potencials o causes especials de / Barceló Cerdá, S. (2016). Estudio de la integración de procedimientos multivariantes para la regulación óptima y monitorización estadística de procesos [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/63442 / TESIS

This dissertation presents the novel creation of a hybrid D-fiber electro-optic polymer electric field sensor. The sensor is made by removing a portion of the cladding from a D-shaped optical fiber, thus exposing the core to interaction with external stimulus. Then, an electro-optic polymer is deposited, partially replacing the core of the fiber. Next, the polymer is poled to endow it with electro-optic properties. This sensor is packaged in order to restore its mechanical strength. Because D-fiber is not intrinsically compatible with standard optical equipment it is fusion spliced to standard polarization maintaining fiber. Finally the sensor is tested for electro-optic sensitivity. The hybrid D-fiber electric field sensors designed and fabricated in this work meet the requirements of mechanical strength, temporal stability, minimal perturbation of the electric field by the sensor, and a small and flexible cross-sectional area so that it can be embedded into the device under test. A fully packaged hybrid electro-optic polymer D-fiber electric field sensor which is capable of detecting electric fields of 50 V/m at a frequency of 6 GHz is produced. The sensor's electro-optic response is shown to be temporally stable. Additionally, the sensor is physically robust, and physically and electrically non-intrusive. This work also adds a thorough understanding of the design and fabrication of D-fiber waveguides with a polymer material deposited in the core. Several new fabrication techniques are developed and presented. A path to greater electric field sensitivity is outlined for future research.

Tumor-induced immunosuppression can occur by multiple mechanisms, each posing a significant obstacle to immunotherapy. Evidence presented in this dissertation suggests that aberrant cytokine signaling, as a result of altered metabolism of Chronic Lymphocytic Leukemia (CLL) cells, confers a selective advantage for tumor survival and growth. Cells from CLL patients with aggressive disease (as indicated by high-risk cytogenetics) were found to exhibit prolongation in Interferon (IFN)-induced STAT3 phosphorylation, and increased levels of reactive oxygen species (ROS) in these cells reflected these signaling processes. Changes in the relative balance of phospho-STAT3 and phospho-STAT1 levels, in response to combinations of IL-2 + Toll-like receptor (TLR)-7 agonist + phorbol esters, as well as IFN, were associated with the immunosuppressive and immunogenic states of CLL cells. In addition, immunosuppressive leukemic cells were found to express high levels of proteins with O-linked N-acetylglucosamine (O-GlcNAc) modifications, due to increased metabolic activity through the Hexosamine Biosynthetic Pathway (HBP), which caused impaired intracellular signaling responses and affected disease progression. A conclusion of the studies presented here is that the intrinsic immunosuppressive properties of leukemic cells may be overcome by agents such as Resveratrol that target metabolic pathways of these cells.

Tumor-induced immunosuppression can occur by multiple mechanisms, each posing a significant obstacle to immunotherapy. Evidence presented in this dissertation suggests that aberrant cytokine signaling, as a result of altered metabolism of Chronic Lymphocytic Leukemia (CLL) cells, confers a selective advantage for tumor survival and growth. Cells from CLL patients with aggressive disease (as indicated by high-risk cytogenetics) were found to exhibit prolongation in Interferon (IFN)-induced STAT3 phosphorylation, and increased levels of reactive oxygen species (ROS) in these cells reflected these signaling processes. Changes in the relative balance of phospho-STAT3 and phospho-STAT1 levels, in response to combinations of IL-2 + Toll-like receptor (TLR)-7 agonist + phorbol esters, as well as IFN, were associated with the immunosuppressive and immunogenic states of CLL cells. In addition, immunosuppressive leukemic cells were found to express high levels of proteins with O-linked N-acetylglucosamine (O-GlcNAc) modifications, due to increased metabolic activity through the Hexosamine Biosynthetic Pathway (HBP), which caused impaired intracellular signaling responses and affected disease progression. A conclusion of the studies presented here is that the intrinsic immunosuppressive properties of leukemic cells may be overcome by agents such as Resveratrol that target metabolic pathways of these cells.

This study which is the product of library research and fieldwork seeks, on account of the persistent marginalisation of African Traditional Religion (ATR) in Sierra Leone by Islam and Christianity, to investigate the place of ATR in inter-religious encounters in the country since the advent of Islam and Christianity. As in most of sub-Saharan Africa, ATR is the indigenous religion of Sierra Leone. When the early forebears and later progenitors of Islam and Christianity arrived, they met Sierra Leone indigenes with a remarkable knowledge of God and a structured religious system. Successive Muslim clerics, traders, and missionaries were respectful of and sensitive to the culture and religion of the indigenes who accommodated them and offered them hospitality. This approach resulted in a syncretistic brand of Islam. In contrast, most Christian missionaries adopted an exclusive and insensitive approach to African culture and religiosity. Christianity, especially Protestantism, demanded a complete abandonment of African culture and religion, and a total dedication to Christianity. This attitude has continued by some indigenous clerics and religious leaders to the extent that Sierra Leone Indigenous Religion (SLIR) and it practitioners continue to be marginalised in Sierra Leone's inter-religious dialogue and cooperation. Although the indigenes of Sierra Leone were and continue to be hospitable to Islam and Christianity, and in spite of the fact that SLIR shares affinity with Islam and Christianity in many theological and practical issues, and even though there are many Muslims and Christians who still hold on to traditional spirituality and culture, Muslim and Christian leaders of these immigrant religions are reluctant to include Traditionalists in interfaith issues in the country. The formation and constitution of the Inter-Religious Council of Sierra Leone (IRCSL) which has local and international recognition did not include ATR. These considerations, then beg the questions: * Why have Muslim and Christian leaders long marginalised ATR, its practices and practitioners from interfaith dialogue and cooperation in Sierra Leone? * What is lacking in ATR that continues to prevent practitioners of Christianity and Islam from officially involving Traditionalists in the socio-religious development of the country? Muslim and Christians have given several factors that are responsible for this exclusion: * The prejudices that they inherited from their forebears * ATR lacks the hallmarks of a true religion * ATR is primitive and economically weak * The fear that the accommodation of ATR will result in syncretism and nominalism * Muslims see no need to dialogue with ATR practitioners, most of whom they considered to be already Muslims Considering the commonalities ATR shares with Islam and Christianity, and the number of Muslims and Christians who still hold on to traditional spirituality, these factors are not justifiable. Although Islam and Christianity are finding it hard to recognise and include ATR in interfaith dialogue and cooperation in Sierra Leone, ATR continues to play a vital role in Sierra Leone's national politics, in the search and maintenance of employment, and in the judicial sector. ATR played a crucial part during and after the civil war. The national government in its Truth and Reconciliation Commission (TRC) report acknowledged the importance and contribution of traditional culture and spirituality during and after the war. Outside of Sierra Leone, the progress in the place and level of the recognition of ATR continues. At varying degrees, the Sociétié Africaine de Culture (SAC) in France, the All Africa Conference of Churches (AACC), the Vatican, and the World Council of Churches, have taken positive steps to recognise and find a place for ATR in their structures. Much about the necessity for dialogue and cooperation with ATR can be learnt in the works and efforts of these secular and religious bodies. If nothing else, there are two main reasons why Islam and Christianity in Sierra Leone must be in dialogue with ATR: * Dialogue of life or in community. People living side-by-side meet and interact personally and communally on a regular basis. They share common resources and communal benefits. These factors compel people to be in dialogue * Dual religiosity. As many Muslims and Christians in Sierra Leone are still holding on to ATR practices, it is crucial for Muslims and Christians to dialogue with ATR practitioners. If Muslims and Christians are serious about meeting and starting a process of dialogue with Traditionalists, certain practical issues have to be considered: * Islam and Christianity have to validate and accept ATR as a true religion and a viable partner in the socio-religious landscape of Sierra Leone * Muslims and Christians must educate themselves about ATR, and the scriptures and teachings of their respective religious traditions in order to relate well with Traditionalists These are starting points that can produce successful results. Although at present Muslims and Christians in Sierra Leone are finding it difficult to initiate dialogue and cooperation with Traditionalists, all hope is not lost. It is now the task of the established IRCSL to ensure the inclusion of ATR. Islam and Christianity must remember that when they came as strangers, ATR, played host to them and has played and continues to play a vital role in providing hospitality, and allowing them to blossom on African soil. / Religious Studies and Arabic / D.Litt. et Phil. (Religious Studies)

Els factors de transcripció de la família Snail són fonamentals en la "transició epiteli-mesènquima", procés morfogènic essencial en el desenvolupament embrionari i en els fenòmens metastàsics tumorals.En els mamífers l'activitat d'Snail és modulada per dos mecanismes. (i) En el promotor humà es troben regions definides de resposta a factors repressors, predominants en les cèl·lules epitelials, i elements diferenciats de resposta a inductors de la "transició epiteli-mesènquima". (ii) L'activitat d'Snail és condicionada també per la seva localització subcel·lular, modulada per mecanismes no transcripcionals: la fosforilació d'Snail determina si és o no exclós del nucli. Al citosol no pot actuar com a repressor transcripcional però pot interaccionar amb la xarxa microtubular, que estabilitza i en condiciona el dinamisme. Això coincideix amb l'activació de la GTPasa RhoA i la reorientació dels filaments de vimentina, fets associats a l'adquisició de capacitat migratòria. L'efecte com a repressor transcripcional i la modulació del dinamisme microtubular són possiblement esdeveniments coordinats necessaris per al rol biològic d'Snail en mamífers. / Snail family of transcription factors is fundamental to the "epithelial-mesenchymal transition", morphogenic process essential to embryonic development and metastatic phenomena in tumors.Snail's activity is modulated in two ways in mammals. (i) The human promoter harbors definite regions that respond to repressor factors, which prevail in epithelial cells; and differentiated elements that respond to known inducers of the "epithelial-mesenchymal transition". (ii) Snail's activity is also conditioned by its subcellular localization, mechanism not dependent on its transcriptional control: Snail phosphorylation determines whether Snail is excluded or not from the nucleus. When in the cytosol, Snail is unable to act as a transcriptional repressor, but however binds to the microtubular meshwork, which becomes stabilized and whose dynamism is conditioned as a result. This fact coincides with the activation of the RhoA GTPase and reorientation of vimentin filaments, both phenomena being related to the acquisition of cell motility. The transcriptional repressor and the microtubule dynamics effects are probably two coordinated events necessary to Snail's biological role in mammals.

This study which is the product of library research and fieldwork seeks, on account of the persistent marginalisation of African Traditional Religion (ATR) in Sierra Leone by Islam and Christianity, to investigate the place of ATR in inter-religious encounters in the country since the advent of Islam and Christianity. As in most of sub-Saharan Africa, ATR is the indigenous religion of Sierra Leone. When the early forebears and later progenitors of Islam and Christianity arrived, they met Sierra Leone indigenes with a remarkable knowledge of God and a structured religious system. Successive Muslim clerics, traders, and missionaries were respectful of and sensitive to the culture and religion of the indigenes who accommodated them and offered them hospitality. This approach resulted in a syncretistic brand of Islam. In contrast, most Christian missionaries adopted an exclusive and insensitive approach to African culture and religiosity. Christianity, especially Protestantism, demanded a complete abandonment of African culture and religion, and a total dedication to Christianity. This attitude has continued by some indigenous clerics and religious leaders to the extent that Sierra Leone Indigenous Religion (SLIR) and it practitioners continue to be marginalised in Sierra Leone's inter-religious dialogue and cooperation. Although the indigenes of Sierra Leone were and continue to be hospitable to Islam and Christianity, and in spite of the fact that SLIR shares affinity with Islam and Christianity in many theological and practical issues, and even though there are many Muslims and Christians who still hold on to traditional spirituality and culture, Muslim and Christian leaders of these immigrant religions are reluctant to include Traditionalists in interfaith issues in the country. The formation and constitution of the Inter-Religious Council of Sierra Leone (IRCSL) which has local and international recognition did not include ATR. These considerations, then beg the questions: * Why have Muslim and Christian leaders long marginalised ATR, its practices and practitioners from interfaith dialogue and cooperation in Sierra Leone? * What is lacking in ATR that continues to prevent practitioners of Christianity and Islam from officially involving Traditionalists in the socio-religious development of the country? Muslim and Christians have given several factors that are responsible for this exclusion: * The prejudices that they inherited from their forebears * ATR lacks the hallmarks of a true religion * ATR is primitive and economically weak * The fear that the accommodation of ATR will result in syncretism and nominalism * Muslims see no need to dialogue with ATR practitioners, most of whom they considered to be already Muslims Considering the commonalities ATR shares with Islam and Christianity, and the number of Muslims and Christians who still hold on to traditional spirituality, these factors are not justifiable. Although Islam and Christianity are finding it hard to recognise and include ATR in interfaith dialogue and cooperation in Sierra Leone, ATR continues to play a vital role in Sierra Leone's national politics, in the search and maintenance of employment, and in the judicial sector. ATR played a crucial part during and after the civil war. The national government in its Truth and Reconciliation Commission (TRC) report acknowledged the importance and contribution of traditional culture and spirituality during and after the war. Outside of Sierra Leone, the progress in the place and level of the recognition of ATR continues. At varying degrees, the Sociétié Africaine de Culture (SAC) in France, the All Africa Conference of Churches (AACC), the Vatican, and the World Council of Churches, have taken positive steps to recognise and find a place for ATR in their structures. Much about the necessity for dialogue and cooperation with ATR can be learnt in the works and efforts of these secular and religious bodies. If nothing else, there are two main reasons why Islam and Christianity in Sierra Leone must be in dialogue with ATR: * Dialogue of life or in community. People living side-by-side meet and interact personally and communally on a regular basis. They share common resources and communal benefits. These factors compel people to be in dialogue * Dual religiosity. As many Muslims and Christians in Sierra Leone are still holding on to ATR practices, it is crucial for Muslims and Christians to dialogue with ATR practitioners. If Muslims and Christians are serious about meeting and starting a process of dialogue with Traditionalists, certain practical issues have to be considered: * Islam and Christianity have to validate and accept ATR as a true religion and a viable partner in the socio-religious landscape of Sierra Leone * Muslims and Christians must educate themselves about ATR, and the scriptures and teachings of their respective religious traditions in order to relate well with Traditionalists These are starting points that can produce successful results. Although at present Muslims and Christians in Sierra Leone are finding it difficult to initiate dialogue and cooperation with Traditionalists, all hope is not lost. It is now the task of the established IRCSL to ensure the inclusion of ATR. Islam and Christianity must remember that when they came as strangers, ATR, played host to them and has played and continues to play a vital role in providing hospitality, and allowing them to blossom on African soil. / Religious Studies and Arabic / D.Litt. et Phil. (Religious Studies)

L'activació sostinguda de Hog1 porta a una inhibició del creixement cel·lular. En aquest treball, hem observat que el fenotip de letalitat causat per l'activació sostinguda de Hog1 és parcialment inhibida per la mutació del complexe SCFCDC4. La inhibició de la mort causada per l'activació sostinguda de Hog1 depèn de la via d'extensió de la vida. Quan Hog1 s'activa de manera sostinguda, la mutació al complexe SCFCDC4 fa que augmenti l'expressió gènica depenent de Msn2 i Msn4 que condueix a una sobreexpressió del gen PNC1 i a una hiperactivació de la deacetilassa Sir2. La hiperactivació de Sir2 és capaç d'inhibir la mort causada per l'activació sostinguda de Hog1. També hem observat que la mort cel·lular causada per l'activació sostinguda de Hog1 és deguda a una inducció d'apoptosi. L'apoptosi induïda per Hog1 és inhibida per la mutació al complexe SCFCDC4. Per tant, la via d'extensió de la vida és capaç de prevenir l'apoptosi a través d'un mecanisme desconegut. / Sustained Hog1 activation leads to an inhibition of cell growth. In this work, we have observed that the lethal phenotype caused by sustained Hog1 activation is prevented by SCFCDC4 mutants. The prevention of Hog1-induced cell death by SCFCDC4 mutation depends on the lifespan extension pathway. Upon sustained Hog1 activation, SCFCDC4 mutation increases Msn2 and Msn4 dependent gene expression that leads to a PNC1 overexpression and a Sir2 deacetylase hyperactivation. Then, hyperactivation of Sir2 is able to prevent cell death caused by sustained Hog1 activation. We have also observed that cell death upon sustained Hog1 activation is due to an induction of apoptosis. The apoptosis induced by Hog1 is decreased by SCFCDC4 mutation. Therefore, lifespan extension pathway is able to prevent apoptosis by an unknown mechanism.