Ce mémoire de thèse présente une étude fondamentale enrichie par des contributions qui sont articulées autour de la modélisation de processus ainsi qu'un diagnostic de défauts en utilisant l'analyse en composantes principales (ACP). Dans l'objectif d'un choix optimal du modèle ACP, une étude comparative de quelques critères connus dans la littérature nous a permis de conclure que le problème rencontré est souvent lié à une ignorance des variables indépendantes et quasi-indépendantes. Dans ce cadre, nous avons réalisé deux démonstrations mettant en évidence les limitations de deux critères en particulier la variance non reconstruite (VNR). En s'appuyant sur le principe d'une telle variance, nous avons proposé trois nouveaux critères. Parmi eux, deux ont été considérés comme étant empiriques car seule l'expérience permettra de prouver leur efficacité. Le troisième critère noté VNRVI représente un remède à la limitation du critère VNR. Une étude de sa consistance théorique a permis d'établir les conditions garantissant l'optimalité de son choix. Les résultats de simulation ont validé une telle théorie en prouvant ainsi que le critère VNRVI étant plus efficace que ceux étudiés dans cette thèse. Dans le cadre d'un diagnostic de défauts par ACP, l'approche de reconstruction des indices de détection ainsi que celle des contributions ont été utilisées. A travers une étude de généralisation, nous avons étendu le concept d'isolabilité de défauts par reconstruction à tout indice quadratique. / This thesis presents a fundamental study enhanced by some contributions that are focused on process modelling and fault diagnosis using principal components analysis (PCA). In order to find an optimal PCA model, we have concluded through a comparative study of some popular criteria that the problem is often related to an ignorance of the independent and quasi-independent variables. In this framework, we have performed two demonstrations highlighting the limitations of two selection criteria in particular the unreconstructed variance (VNR). Based on the principle of VNR approach, we have proposed three new criteria, among them two methods were considered as empirical criteria because only the experience will prove their effectiveness. However the third one which is noted VNRVI represents a cure for the limitation of the classical VNR criterion. Thus, the conditions that ensure an optimal selection were derived according to a theoretical consistency study of the VNRVI approach. The simulation results have successfully validated the VNRVI criterion by proving that is more effective than the other studied criteria in the present thesis. The reconstruction and contributions approaches were used for fault diagnosis using PCA. According to a unified study, we have extended the fault isolability concept based on the reconstruction method to any detection index which has a quadratic form. Such generalization has allowed us to develop a theoretical fault isolability analysis based on the reconstruction of the combined index versus those of SPE and T2 indices. This analysis has highlighted the advantage of using the combined index for fault isolation.

L'huile d'olive est un élément important de l'alimentation méditerranéenne. Cependant lorsqu'une huile vieillit, elle se dégrade et perd ses propriétés. Il est donc important de connaitre l'évolution de la composition de l'huile en fonction de ses conditions de stockage et de fabrication. Ce suivi a été effectué sur deux huiles de fabrication différente, une huile fruité vert et une huile fruité noir, obtenue à partir d'olive à maturité que l'on a laissé fermenter quelques jours. De manière à obtenir rapidement des vieillissements poussés, ces deux huiles ont été vieillies artificiellement, par procédé thermique , et par procédé photochimique. Ces vieillissements ont été réalisés sur des volumes différents de manière à déterminer l'impact du rapport surface/masse. En parallèle, des échantillons de chacune des deux huiles ont été conservés durant 24 mois dans des conditions de stockage différentes déterminées à l'aide d'un plan d'expériences. Les paramètres influençant le plus la conservation de l'huile d'olive sont l'apport en oxygène, la luminosité et la température. Ces influences ont été déterminées à partir du suivi des principaux paramètres de qualité La réponse des plans a permis de mettre en évidence des interactions entre ces différents paramètres. L'analyse de la composition de l'huile ainsi que de tous les critères de qualité demande beaucoup de temps et consomme une grande quantité de solvant. Afin de pallier à ces désagréments, les résultats ont également été utilisés pour construire des modèles chimiométriques permettant de déterminer ces grandeurs à partir des spectres proche et moyen infrarouge des échantillons. / Olive oil is an important component of the Mediterranean diet. When oil ages, it deteriorates and loses its properties. It is therefore important to know the evolution of the oil composition according to the conditions of storage and manufacturing. This monitoring was carried out on two different oils manufacturing, green fruity oil obtained from olives harvested before maturity, and black fruit oil obtained from olives harvest at maturity and fermented for few days under controlled conditions. To obtain quickly pushed aging, these two oils were artificially aged by heat process (heated to 180 °C under supply of O2), and photochemical process (under an UV lamp and under supply of O2). These aging were performed on different volumes to determine the impact of surface/weight ratio. In parallel, samples of both oils were stored for 24 months under different storage conditions determined using an experimental design. The parameters affecting the most the conservation of olive oil are oxygen, light and temperature. These influences were determined from the monitoring of key quality criteria. Response of experimental design helped to highlight the interactions between these different parameters. The analysis of the oil composition as well as all the quality criteria requires a large amount of solvents and a lot of time consumer. To overcome these inconveniences, chemometric models has been built to determine these criteria from the near and mid-infrared spectra of samples. Natural aging is very little advanced in comparison to accelerated aging, so predictive models were established from the results of natural aging and accelerated separately.

O presente trabalho tem como objetivo avaliar a influência das variáveis ambientais na mortalidade de idosos (acima de 65 anos) por doenças cardiovasculares (DCV) e respiratórias (RES), nos condados de Los Angeles, Orange e Santa Bárbara na Califórnia, através de análises estatísticas, em particular de componentes principais (ACP). Para isso foram utilizados dados diários das estações meteorológicas dos condados (temperatura, pressão, umidade e velocidade do vento), de poluição do ar (NO2, CO, SO2 e O3) e da mortalidade por DCV e RES, durante o período 1975-2005. Além disso, foram calculados 7 índices de conforto térmico e estabelecidas as zonas de conforto para diferentes graus de percepção térmica a partir do índice de Temperatura Efetiva (TE). Os resultados verificaram tendências diferentes na variação temporal das DCV e RES. Enquanto as doenças RES tiveram um aumento bastante leve em todos os condados, as DCV apresentaram uma ligeira diminuição nos condados de Orange e Santa Bárbara, e uma diminuição constante e acentuada no condado de Los Angeles. Também se verificou uma variação sazonal significativa, com evidente aumento do número de óbitos de ambas as doenças durante o inverno e queda durante o verão. Em relação aos poluentes, foram observadas muitas ultrapassagens dos padrões nacionais de qualidade do ar principalmente para o O3, com 1443 vezes para o condado de Los Angeles, 771 para o Orange e 114 para Santa Bárbara. A partir dos índices de conforto térmico notou-se que o mês mais estressante devido ao calor foi setembro principalmente para os condados de Los Angeles e Santa Bárbara, e julho e agosto para o condado de Orange. Analisando a média de óbitos por sensação térmica observou-se um aumento das doenças nos extremos, principalmente quando a sensação é Muito Frio, com médias por doenças RES de 16,42, 3,31 e 0,81 e por DCV de 77,32, 15,37 e 2,92 nos condados de Los Angeles, Orange e Santa Bárbara, respectivamente. Com base na análise de correlação entre as variáveis e as doenças, observaram-se as melhores correlações no condado de Los Angeles, tanto para as doenças RES quanto DCV, e as correlações mais baixas foram observadas no condado de Santa Bárbara. Os resultados da ACP nos condados de Los Angeles e Orange verificaram o aumento da mortalidade por DCV no inverno, associadas a correlações positivas com os níveis de poluição principalmente em Los Angeles e ao estresse por frio, umidade e vento (via índice de conforto térmico) em Orange. Por outro lado, a mortalidade por doenças RES esteve mais associada às variações meteorológicas do que às concentrações de poluentes, observando-se associações positivas com o índice de calor (IC). Neste sentido, o condado de Orange apresentou maiores correlações com IC do que o condado de Los Angeles, além de uma variância maior (11,36 % contra 9,89 %). Por último, no condado de Santa Bárbara os resultados foram muito diferentes, já que tanto episódios de frio quanto de calor não mostraram impactos claros na população idosa, com respeito a ambos os grupos de doenças. O distintivo foi que os níveis de SO2 tiveram a maior associação positiva à mortalidade principalmente por DCV (0,53), embora tiver o condado as concentrações mais baixas das estudadas (média de 0,29 ppb). Em suma, os condados possuem estruturas sociais diferentes, apesar da semelhança do clima, fazendo com que os resultados sejam bastante dispares entre os mesmos. As perspectivas destes estudos pretendem colocar estes resultados para climas futuros, pois diversos episódios de ondas de calor ocorreram após o ano de 2005. / The objective of this study was to evaluate the influence of environmental variables on the mortality of elderly patients (over 65 years) due to cardiovascular diseases (CD) and respiratory diseases (RD) in the counties of Los Angeles, Orange and Santa Bárbara, California; through statistical analyzes, in particular, principal components (PCA). For this purpose, daily data of the meteorological stations of the counties (temperature, pressure, humidity and wind speed), air pollution (NO2, CO, SO2 and O3) and mortality by CD and RD were used during the period 1975-2005. In addition, seven thermal comfort indexes were calculated and comfort zones were established for different degrees of thermal perception according to the Effective Temperature index (TE). The results showed different trends in the temporal variation of CD and RD. While RD diseases had a fairly mild increase in all counties, CD showed a slight decrease in Orange and Santa Barbara counties and a steady decline in Los Angeles county. There was also a significant seasonal variation, with an evident increase in the number of deaths from both diseases during the winter and fall during the summer. In relation to the pollutants, many national standards for air quality were exceeded, mainly for the O3, with 1443 times for Los Angeles, 771 for Orange and 114 for Santa Barbara. From the thermal comfort indexes it was noted that the most stressful month due to the heat was September, mainly for the counties of Los Angeles and Santa Barbara, and July and August for the county of Orange. Analyzing the average number of deaths due to thermal sensation, there was an increase of the illnesses in extreme, especially when the sensation is Very Cold, with RD averages of 16.42, 3.31 and 0.81 and CD average of 77.32, 15.37 and 2.92 in the counties of Los Angeles, Orange and Santa Barbara, respectively. Based on correlation analysis between variables and diseases, the best correlations were found in Los Angeles for both RD and CD, and the lowest correlations were observed in Santa Barbara. The results of PAC in the counties of Los Angeles and Orange showed the increase in CD mortality in winter associated to positive correlations with the levels of pollution mainly in Los Angeles and stress due to cold, humidity and wind (via thermal comfort index) in Orange. On the other hand, mortality due to RD diseases was more associated with meteorological variations than with pollutant concentrations, with positive associations with heat index (HI). In this sense, Orange County presented higher correlations with HI than the county of Los Angeles, in addition to a greater variance (11.36% vs. 9.89%). Finally, in Santa Barbara the results were very different, since both episodes of cold and heat did not show clear impacts in the elderly population, regarding both groups of diseases. The difference was that SO2 levels had the highest positive association with CD mortality (0.53), although this county had the lowest concentrations studied (mean 0.29 ppb). In sum, counties have different social structures, despite the similarity of the climate, making the results quite different between them. The perspectives of these studies intend to place these results for future climates, since several episodes of heat waves occurred after 2005.

O presente trabalho tem como objetivo avaliar a influência das variáveis ambientais na mortalidade de idosos (acima de 65 anos) por doenças cardiovasculares (DCV) e respiratórias (RES), nos condados de Los Angeles, Orange e Santa Bárbara na Califórnia, através de análises estatísticas, em particular de componentes principais (ACP). Para isso foram utilizados dados diários das estações meteorológicas dos condados (temperatura, pressão, umidade e velocidade do vento), de poluição do ar (NO2, CO, SO2 e O3) e da mortalidade por DCV e RES, durante o período 1975-2005. Além disso, foram calculados 7 índices de conforto térmico e estabelecidas as zonas de conforto para diferentes graus de percepção térmica a partir do índice de Temperatura Efetiva (TE). Os resultados verificaram tendências diferentes na variação temporal das DCV e RES. Enquanto as doenças RES tiveram um aumento bastante leve em todos os condados, as DCV apresentaram uma ligeira diminuição nos condados de Orange e Santa Bárbara, e uma diminuição constante e acentuada no condado de Los Angeles. Também se verificou uma variação sazonal significativa, com evidente aumento do número de óbitos de ambas as doenças durante o inverno e queda durante o verão. Em relação aos poluentes, foram observadas muitas ultrapassagens dos padrões nacionais de qualidade do ar principalmente para o O3, com 1443 vezes para o condado de Los Angeles, 771 para o Orange e 114 para Santa Bárbara. A partir dos índices de conforto térmico notou-se que o mês mais estressante devido ao calor foi setembro principalmente para os condados de Los Angeles e Santa Bárbara, e julho e agosto para o condado de Orange. Analisando a média de óbitos por sensação térmica observou-se um aumento das doenças nos extremos, principalmente quando a sensação é Muito Frio, com médias por doenças RES de 16,42, 3,31 e 0,81 e por DCV de 77,32, 15,37 e 2,92 nos condados de Los Angeles, Orange e Santa Bárbara, respectivamente. Com base na análise de correlação entre as variáveis e as doenças, observaram-se as melhores correlações no condado de Los Angeles, tanto para as doenças RES quanto DCV, e as correlações mais baixas foram observadas no condado de Santa Bárbara. Os resultados da ACP nos condados de Los Angeles e Orange verificaram o aumento da mortalidade por DCV no inverno, associadas a correlações positivas com os níveis de poluição principalmente em Los Angeles e ao estresse por frio, umidade e vento (via índice de conforto térmico) em Orange. Por outro lado, a mortalidade por doenças RES esteve mais associada às variações meteorológicas do que às concentrações de poluentes, observando-se associações positivas com o índice de calor (IC). Neste sentido, o condado de Orange apresentou maiores correlações com IC do que o condado de Los Angeles, além de uma variância maior (11,36 % contra 9,89 %). Por último, no condado de Santa Bárbara os resultados foram muito diferentes, já que tanto episódios de frio quanto de calor não mostraram impactos claros na população idosa, com respeito a ambos os grupos de doenças. O distintivo foi que os níveis de SO2 tiveram a maior associação positiva à mortalidade principalmente por DCV (0,53), embora tiver o condado as concentrações mais baixas das estudadas (média de 0,29 ppb). Em suma, os condados possuem estruturas sociais diferentes, apesar da semelhança do clima, fazendo com que os resultados sejam bastante dispares entre os mesmos. As perspectivas destes estudos pretendem colocar estes resultados para climas futuros, pois diversos episódios de ondas de calor ocorreram após o ano de 2005. / The objective of this study was to evaluate the influence of environmental variables on the mortality of elderly patients (over 65 years) due to cardiovascular diseases (CD) and respiratory diseases (RD) in the counties of Los Angeles, Orange and Santa Bárbara, California; through statistical analyzes, in particular, principal components (PCA). For this purpose, daily data of the meteorological stations of the counties (temperature, pressure, humidity and wind speed), air pollution (NO2, CO, SO2 and O3) and mortality by CD and RD were used during the period 1975-2005. In addition, seven thermal comfort indexes were calculated and comfort zones were established for different degrees of thermal perception according to the Effective Temperature index (TE). The results showed different trends in the temporal variation of CD and RD. While RD diseases had a fairly mild increase in all counties, CD showed a slight decrease in Orange and Santa Barbara counties and a steady decline in Los Angeles county. There was also a significant seasonal variation, with an evident increase in the number of deaths from both diseases during the winter and fall during the summer. In relation to the pollutants, many national standards for air quality were exceeded, mainly for the O3, with 1443 times for Los Angeles, 771 for Orange and 114 for Santa Barbara. From the thermal comfort indexes it was noted that the most stressful month due to the heat was September, mainly for the counties of Los Angeles and Santa Barbara, and July and August for the county of Orange. Analyzing the average number of deaths due to thermal sensation, there was an increase of the illnesses in extreme, especially when the sensation is Very Cold, with RD averages of 16.42, 3.31 and 0.81 and CD average of 77.32, 15.37 and 2.92 in the counties of Los Angeles, Orange and Santa Barbara, respectively. Based on correlation analysis between variables and diseases, the best correlations were found in Los Angeles for both RD and CD, and the lowest correlations were observed in Santa Barbara. The results of PAC in the counties of Los Angeles and Orange showed the increase in CD mortality in winter associated to positive correlations with the levels of pollution mainly in Los Angeles and stress due to cold, humidity and wind (via thermal comfort index) in Orange. On the other hand, mortality due to RD diseases was more associated with meteorological variations than with pollutant concentrations, with positive associations with heat index (HI). In this sense, Orange County presented higher correlations with HI than the county of Los Angeles, in addition to a greater variance (11.36% vs. 9.89%). Finally, in Santa Barbara the results were very different, since both episodes of cold and heat did not show clear impacts in the elderly population, regarding both groups of diseases. The difference was that SO2 levels had the highest positive association with CD mortality (0.53), although this county had the lowest concentrations studied (mean 0.29 ppb). In sum, counties have different social structures, despite the similarity of the climate, making the results quite different between them. The perspectives of these studies intend to place these results for future climates, since several episodes of heat waves occurred after 2005.

L’Accord de Cotonou, signé en juin 2000 entre l’Union européenne et les États d’Afrique, des Caraïbes et du Pacifique (ACP), se caractérise par un respect des droits de l’homme, des normes démocratiques et de l’État de droit d’une part, et la quête d’une conformité des normes aux principes de l’Organisation mondiale du commerce (OMC), d’autre part. En effet, la politique de développement mise en place par l’Europe au profit des États ACP a vu le jour avec le Traité de Rome et la création du Fonds européen de développement au profit des ces pays. Pendant longtemps, le partenariat, essentiellement économique, a octroyé d’énormes avantages aux pays ACP en vue d’assurer leur développement. Depuis bientôt deux décennies que les normes politiques ont été insérées dans ce partenariat, force est de constater que quelques pays, dont le Togo, demeurent toujours réticents quant à l’instauration de réelles réformes démocratiques en vue d’assurer une véritable alternance politique. En dépit des sanctions infligées çà et là par l’Union européenne, ces pays trouvent un appui auprès de la Chine qui mène, avec les pays d’Afrique, un partenariat en toute exclusion de la société civile. / Cotonou agreement, signed in June 2000, between the EU and African, Caribbean and Pacific (ACP) Countries, is characterized by the respect of Human Rights, Democratic standards and Rule of Law in one side, and the quest for compliance with the standards principles of World trade Organization (WTO) in the other side. Since then the development policy implemented by Europe for ACP Countries was created with the Treaty of Rome which established European Development Funds, in favor of these countries. For many years, this partnership, mainly economic, has given huge benefits to ACP countries to ensure their development. For almost two decades that the political standards rules were introduced into this partnership, no doubt to notice that some countries, including Togo, are still reluctant to introduce real democratic reforms to ensure effective political changes. Despite sanctions here and there from the European Union, these countries find support from China who treats with African countries, a specific partnership excluding any Civil Society.

En segmentation d’images, les informations de couleur et de texture sont très utilisées. Le premier apport de cette thèse se situe au niveau de l’utilisation conjointe de ces deux sources d’informations. Nous proposons alors une méthode de combinaison couleur/texture, adaptative et non paramétrique, qui consiste à combiner un (ou plus) gradient couleur et un (ou plus) gradient texture pour ensuite générer un gradient structurel utilisé comme image de potentiel dans l’algorithme de croissance de régions par LPE. L’originalité de notre méthode réside dans l’étude de la dispersion d’un nuage de point 3D dans l’espace, en utilisant une étude comparative des valeurs propres obtenues par une analyse des composantes principales de la matrice de covariance de ce nuage de points. L’approche de combinaison couleur/texture proposée est d’abord testée sur deux bases d’images, à savoir la base générique d’images couleur de BERKELEY et la base d’images de texture VISTEX. Cette thèse s’inscrivant dans le cadre des projets ViLoc (RFC) et CAPLOC (PREDIT), le deuxième apport de celle-ci se situe au niveau de la caractérisation de l’environnement de réception des signaux GNSS pour améliorer le calcul de la position d’un mobile en milieu urbain. Dans ce cadre, nous proposons d’exclure certains satellites (NLOS dont les signaux sont reçus par réflexion voir totalement bloqués par les obstacles environnants) dans le calcul de la position d’un mobile. Deux approches de caractérisation, basées sur le traitement d’images, sont alors proposées. La première approche consiste à appliquer la méthode de combinaison couleur/texture proposée sur deux bases d’images réelles acquises en mobilité, à l’aide d’une caméra fisheye installée sur le toit du véhicule de laboratoire, suivie d’une classification binaire permettant d’obtenir les deux classes d’intérêt « ciel » (signaux LOS) et « non ciel » (signaux NLOS). Afin de satisfaire la contrainte temps réel exigée par le projet CAPLOC, nous avons proposé une deuxième approche basée sur une simplification de l’image couplée à une classification pixellaire adaptée. Le principe d’exclusion des satellites NLOS permet d’améliorer la précision de la position estimée, mais uniquement lorsque les satellites LOS (dont les signaux sont reçus de manière direct) sont géométriquement bien distribués dans l’espace. Dans le but de prendre en compte cette connaissance relative à la distribution des satellites, et par conséquent, améliorer la précision de localisation, nous avons proposé une nouvelle stratégie pour l’estimation de position, basée sur l’exclusion des satellites NLOS (identifiés par le traitement d’images), conditionnée par l’information DOP, contenue dans les trames GPS. / Color and texture are two main information used in image segmentation. The first contribution of this thesis focuses on the joint use of color and texture information by developing a robust and non parametric method combining color and texture gradients. The proposed color/texture combination allows defining a structural gradient that is used as potential image in watershed algorithm. The originality of the proposed method consists in studying a 3D points cloud generated by color and texture descriptors, followed by an eigenvalue analysis. The color/texture combination method is firstly tested and compared with well known methods in the literature, using two databases (generic BERKELEY database of color images and the VISTEX database of texture images). The applied part of the thesis is within ViLoc project (funded by RFC regional council) and CAPLOC project (funded by PREDIT). In this framework, the second contribution of the thesis concerns the characterization of the environment of GNSS signals reception. In this part, we aim to improve estimated position of a mobile in urban environment by excluding NLOS satellites (for which the signal is masked or received after reflections on obstacles surrounding the antenna environment). For that, we propose two approaches to characterize the environment of GNSS signals reception using image processing. The first one consists in applying the proposed color/texture combination on images acquired in mobility with a fisheye camera located on the roof of a vehicle and oriented toward the sky. The segmentation step is followed by a binary classification to extract two classes « sky » (LOS signals) and « not sky » (NLOS signals). The second approach is proposed in order to satisfy the real-time constraint required by the application. This approach is based on image simplification and adaptive pixel classification. The NLOS satellites exclusion principle is interesting, in terms of improving precision of position, when the LOS satellites (for which the signals are received directly) are well geometrically distributed in space. To take into account the knowledge of satellite distribution and then increase the precision of position, we propose a new strategy of position estimation, based on the exclusion of NLOS satellites (identified by the image processing step), conditioned by DOP information, which is provided by GPS data.

Des modèles dynamiques sont souvent utilisés pour simuler l'impact des pratiques agricoles et parfois pour tester des règles de décision. Ces modèles incluent de nombreux paramètres incertains et il est parfois difficile voire impossible de tous les estimer. Une pratique courante dans la littérature consiste à sélectionner les paramètres clés à l'aide d'indices de sensibilité calculés par simulation et de n'estimer que les paramètres les plus influents. Bien que cette démarche soit intuitive, son intérêt réel et ses conséquences sur la qualité prédictive des modèles ne sont pas connus. Nos travaux de recherches ont pour ambition d'évaluer cette pratique des modélisateurs en établissant une relation entre les indices de sensibilité des paramètres d'un modèle et des critères d'évaluation de modèles tels que le MSEP (Mean Square Error of Prediction) et le MSE (Mean Square Error), souvent utilisés en agronomie. L'établissement d'une telle relation nécessite le développement d'une méthode d'AS qui fournit un unique indice par facteur qui prend en compte les corrélations entre les différentes sorties du modèle obtenues à différentes dates. Nous proposons un nouvel indice de sensibilité global qui permet de synthétiser les effets des facteurs incertains sur l'ensemble des dynamiques simulées à l'aide de modèle. Plusieurs méthodes sont présentées dans ce mémoire pour calculer ces nouveaux indices. Les performances de ces méthodes sont évaluées pour deux modèles agronomiques dynamiques: Azodyn et WWDM. Nous établissons également dans ce mémoire, une relation formelle entre le MSE, le MSEP et les indices de sensibilité dans le cas d'un modèle linéaire et une relation empirique entre le MSEP et les indices dans le cas du modèle dynamique non linéaire CERES-EGC. Ces relations montrent que la sélection de paramètres à l'aide d'indices de sensibilité n'améliore les performances des modèles que sous certaines conditions.

<p>The EPA&rsquo / s will have an impact on regional integration in Africa, especially in the SADC region. The region has been split between the SADC and ESA EPA configuration therefore impacting on regional integration objectives set out under the SADC Trade Protocol.The EPA&rsquo / s will be concluded separately with six of the sub groupings under the ACP grouping. With the EU-SADC EPA negotiations has come a problem of overlapping of membership of the different regions which has created confusion and conflicts. Members of Southern African Development Cooperation (SADC) did not all enter into the EU-SADC EPA has one. The EU-SADC EPA configuration consists of Angola, Botswana, Lesotho, Mozambique, Namibia, South Africa, Swaziland and Tanzania. The rest of the SADC member states are negotiating with the EU-ESA configuration. With South Africa having been allowed into the negotiations, its role should be examined and what it can contribute to the negotiations. Another conflict that has been created is the fact that South Africa has its own bilateral agreement with the EU thus putting stain on the trade relationship between South African and the rest of the SADC countries.</p>

Con el ánimo de contribuir a la construcción de la nueva cooperación comercial entre la Comunidad Europea (CE) y los países de África, el Caribe y el Pacífico (ACP), esta tesis se centra en el estudio del actual régimen de acceso a productos agrícolas concedido por la CE al grupo ACP. En concreto, se realiza un análisis y una evaluación del Protocolo del Azúcar CE-ACP (o, formalmente, el Protocolo nº 3 sobre el azúcar ACP), el cual aparece, por primera vez, en el Convenio de Lomé firmado el 28 de febrero de 1975. La principal preocupación por este instrumento de cooperación en particular es que su contenido es más beneficioso que el los demás Protocolos de productos agrícolas. Así, este acuerdo comercial sobre el azúcar es el único que se basa en un compromiso de compra, por parte de la CE, y de venta, por el lado de los ACP, de unas cantidades especificadas en el marco de un elevado precio garantizado. En la práctica, estos compromisos especiales han implicado transferencias monetarias sustanciales y un nivel de estabilidad significativo de los ingresos de exportación de azúcar para algunos de los países ACP participantes, especialmente para aquellos que presentaron vínculos comerciales históricos con Gran Bretaña. El objetivo final de este estudio consiste en proponer si el Protocolo del Azúcar CE-ACP debe ser integrado en los AAE o, por lo contrario, si es mejor mantenerlo bajo la posible exclusión permitida en el artículo XXIV del Acuerdo General sobre Aranceles y Comercio (GATT). Esta investigación también presenta la opción para el Protocolo del Azúcar de ser incluido en el Sistema de Preferencias Generalizadas (SPG) de la CE, aunque las reducciones arancelarias y no arancelarias, junto a las exenciones específicas, sean menos generosas que las otorgadas a las importaciones europeas de productos ACP. Con esta finalidad, en este estudio se efectúa una evaluación de impacto del Protocolo del Azúcar CE-ACP sobre el desarrollo económico de los países ACP beneficiarios. Con ello, se demuestra que las transferencias monetarias implícitas apropiadas por las empresas azucareras de los Estados ACP participantes no han logrado, en general, una expansión del bienestar económico de sus economías. Este resultado ha sido alcanzado utilizando distintos modelos econométricos: un modelo de regresión lineal, un modelo de corrección de errores y un modelo con datos panel. En consecuencia, concluimos que el Protocolo del Azúcar CE-ACP no ha funcionado como un verdadero instrumento de cooperación al desarrollo. Para recomendar cómo mejorar las relaciones comerciales CE-ACP sobre el azúcar, el trabajo econométrico realizado se ha complementado con el análisis del funcionamiento del mercado internacional del azúcar (especialmente en relación a los precios y a los flujos comerciales). Asimismo, se ha considerado la reforma de la Política Agrícola Común ante los cambios que implicará en el mercado europeo del azúcar. Todos estos elementos nos permiten sugerir dos opciones alternativas al Protocolo, permitidas en el Acuerdo de Cotonú, con vistas a dirigir la cooperación comercial CE-ACP sobre el azúcar desde 2008, momento en el que está prevista la progresiva aplicación de los Acuerdos de Asociación Económica (AAE) CE-ACP.Ambas opciones son compatibles con las normas de la Organización Mundial del Comercio y dependen de la decisión de cada Estado ACP respecto a la celebración de un AAE con la CE. Por un lado, para aquellos Estados ACP que decidan implementar un AAE, consideramos que el azúcar debería quedar cubierto en los esquemas resultantes de integración económica entre ambas Partes, lo que significa que se debería eliminar cualquier restricción que dificulte el comercio CE-ACP de azúcar. Por otro lado, en el caso de que algunos países ACP no alcancen un AAE con la Comunidad Europea, creemos que el azúcar tendría que formar parte del SPG mejorado de la CE, que será el trato comercial más probable que la CE ofrecerá a estos países ACP, como a los demás países en desarrollo. En cualquier caso, el proceso de cambio debería acompañarse de la concesión de ayuda financiera y técnica dirigida a dichos países ACP para ayudarlos a reestructurar el sector del azúcar y, en general, apoyarlos a que se adapten a las nuevas condiciones económicas de un mercado más globalizado. NOTA: Esta tesis recibió el "Premi Maspons i Anglasell" del "Patronat Català Pro Europa" (actualmente "Patronat Catalunya-Món") de la Generalitat de Catalunya a la mejor tesis doctoral en el bienio 2004-2005 (14a edición), el día 18 de abril de 2007. / IMPACT EVALUATION OF THE ACP-EC SUGAR PROTOCOL.In order to contribute in constructing the new trade co-operation between the European Community (EC) and the African, Caribbean and Pacific States (ACP), this thesis focuses in the current European access regime for agricultural products originating from the ACP Group. To be exact, it is carried out an analysis and evaluation of the ACP-EC Sugar Protocol (or, formally, Protocol 3 on ACP sugar) appearing the first time, in the ACP-EC Convention of Lomé signed on 28th February 1975. The principal reason for this particular co-operation instrument is that its provision is more beneficial than the other agricultural products Protocols. Thus, this commercial sugar agreement is the only one based on a purchase commitment from the EC and a sale commitment from the ACP beneficiary countries, of specified quantities, in the framework of a guaranteed high price -similar to the intervention price in the European sugar market-. In practice, this special trading agreement has implied substantial income transfers and a significant stability level of sugar export earnings for some of the ACP participant countries, especially those that presented historic sugar trading links with the United Kingdom. The final goal of this study consists of proposing if the ACP-EC Sugar Protocol has to be integrated in the EPAs or, on the contrary, it is better to keep it under the possible exclusion permitted in article XXIV of the General Agreement on Tariffs and Trade (GATT). This research also presents the option for the Sugar Protocol to be included in the EC's Generalised System of Preferences (GSP), even though tariff and non-tariff reductions, together with the specific exemptions, are less generous than those granted to European imports of ACP products. Within this aim, this study deals with an impact evaluation of the ACP-EC Sugar Protocol over economic development of ACP beneficiary countries. It demonstrates that the implicit income transfers by sugar companies from the ACP Sugar Group has not implied, in general, an economic welfare expansion for their economies. This outcome has been obtained using different econometric models: a linear regression model, an error correction model and a model with panel data. In consequence, we conclude that the ACP-EC Sugar Protocol has not functioned as a true development co-operation instrument.In order to recommend how to improve the ACP-EC trade relations on sugar, that econometric study has been complemented with an analysis of the international sugar market functioning (especially, referring to prices and commercial flows). The changes the Common Agriculture Policy reform will imply on the European sugar market have been considered as well. All of these items allow us to suggest the two alternative options to the Protocol, permitted in the Cotonou Agreement, in order to lead the ACP-EC trade co-operation on sugar since 2008. Both options are compatible with the World Trade Organisation rules and depend on the ACP State decision about the celebration of an EPA with the EC. On the one hand, for those ACP States that decide to implement an EPA, we consider that sugar should be covered in the resulting economic integration schemes between both parties, which means that any restriction on ACP-EC sugar trade should be eliminated. On the other hand, in the case that some ACP countries do not achieve an EPA with the EC, we believe that sugar should take part of the improved EC's GSP, which will be the most probable trade treatment that the EC will offer to those ACP States, as well as to the rest of developing countries. In both cases, the change process should be accompanied with the granting of financial and technical assistance to these ACP countries in order to help them to restructure the sugar sector and, in general, to support them to adjust to the new economic conditions within more globalised market. N.B.: Maspons i Anglasell Prize awarded by the Patronat Català Pro Europa (presently, Patronat Catalunya-Món) of la Generalitat (government institution) of Catalonia (Spain) for the best doctoral thesis in European integration for the biennium 2004-2005 (14th edition), 18 April of 2007.

The thesis deals with X-ray crystallographic analysis of two enzymes involved in the fatty acid biosynthesis pathway, known as Fatty Acid Synthase or FAS, of the malarial parasite, Plasmodium falciparum, in order to understand their functions at the atomic level and to provide structural basis for the rational design of antimalarial compounds. Targeting highly specific and well-characterized biochemical pathways to develop effective therapeutic agents has the advantage of designing new drugs or modifying the existing ones based on the details of the known features of the processes. Knowledge of the three-dimensional structures of the molecules involved in the reactions will enhance the capabilities of this procedure. The recently identified fatty acid biosynthesis pathway in Plasmodium falciparum is undoubtedly an attractive target for drug development as it differs from that in humans. In the malarial parasite, each reaction of the pathway is catalyzed by a specific enzyme whereas in humans, the synthesis is carried out by a single multidomain enzyme. Essentially each step in the FAS of P. falciparum can be a potential target to prevent the growth of the parasite as the fatty acids are essential for the formation of the cell membrane which is vital for its survival. All the reactions of this pathway have been well-characterized. Nevertheless, there is a dearth of structural information of the proteins involved in performing various functions in this pathway. When this work was initiated, crystal structures of none of these proteins were reported. The current work on the plasmodial FAS proteins has been undertaken with a view to obtain precise structural details of their reaction and inhibition mechanisms. The introductory chapter of the thesis includes a discussion on malaria, the fatty acid biosynthesis in various organisms and an overview of the structural features of the enzymes involved in the pathway that have been characterized from other organisms.The second chapter includes the tools of X-ray crystallography that were used for structural studies of the present work. It also discusses the other computational and biophysical methods used to further characterize the enzymes under study. FabI, the enoyl acyl carrier protein reductase, that regulates the third step in FAS has been crystallized as a binary complex with its cofactor NADH and as a ternary complex with NAD+and triclosan. The crystal structures of the binary and the ternary complexes have been determined at 2.5 and 2.2 ˚A, respectively. The mode of binding of the cofactor and the inhibitor triclosan to the enzyme with details of the interactions between them could be clearly obtained from these structures. Each subunit of the tetrameric FabI has the classical Rossmann fold. We carried out a thorough analysis of this structure and compared it with the FabI structures from various sources, four microbial (Escherichia coli, Mycobacterium tuberculosis and Helicobacter pylori) and one plant (Brassica napus), and arrived at a number of significant conclusions: Though the tertiary and the quaternary structures of the enzymes from different sources are similar, the substrate binding loop shows significant changes. The position and nature of the loop are strongly correlated to the affinity of triclosan to the enzyme. Small to major changes in the structure of the enzyme occur to enhance ligand binding. Water molecules play an important role in enzyme-ligand interactions. The crystal structure has also confirmed our previous prediction based on modeling studies of the enzyme that the introduction of bulkier groups at carbon 4’ of triclosan is likely to improve its efficacy as an inhibitor of FabI of P. falciparum. It has also provided the structural basis for its preference to bind to the coenzyme NADH but not to NADPH which was also predicted by our modeling studies. Chapters 3 and 4 discuss the structure solution and a comparative analysis of the crystal structures of FabIs from various sources. The crystal structure of FabZ, the β-hydroxyacyl acyl carrier protein dehydratase of P. falciparum, has been determined at a resolution of 2.4 ˚A. Each subunit of FabZ has a hotdog fold with one long central α-helix surrounded by a six-stranded antiparallel β-sheet. FabZ has been found to exist as a homodimer in the crystals of the present study in contrast to the hexameric form which is a trimer of dimers crystallized in a different condition, reported while we completed the structure of the dimeric form. In the dimeric form, the architecture of the catalytic site has been drastically altered with two catalytic histidine residues moving away from the catalytic site caused by two cis to trans peptide flips compared to the hexameric form. These alterations not only prevent the formation of a hexamer but also distort the active site geometry resulting in a dimeric form of FabZ that is incapable of substrate-binding. The dimeric state and an altered catalytic site architecture make the dimeric FabZ presented in the thesis distinctly different from the FabZ structures described so far. This is the first observation and report of the existence of an inactive form of the enzyme and its unique structural features. Further analysis using dynamic light scattering and size exclusion chromatographic studies have shown that a pH-related conformational switching occurs between the inactive dimers and active hexamers of FabZ in P. falciparum. These findings open alternate and entirely new strategies to design inhibitors to make FabZ inactive. FabZ crystals show polymorphism with varying length of its longest cell axis. We could collect X-ray diffraction data for three of these forms. An analysis of these forms revealed that three flexible loops of the structure including those containing the peptide flips compete for the space between two symmetry-related molecules. In the form with the longest cell axis, the loops have the highest stability resulting in a better diffraction from the crystal. We also performed docking studies with two previously characterized inhibitors of FabZ. The docking showed that the inhibitors bind strongly at the active site each one making a number of different interactions with the catalytic residues. Observations from our docking studies are in excellent agreement with and strongly supported by chemical modification and fluorimetric analysis of the wild type enzyme and its mutants. Chapters 5 and 6 explain in detail about the structure solution of dimeric form of PfFabZ, the pH induced conformational flipping of two cis-trans peptide flips that lead to different oligomeric states, and the structural basis for these oligomeric shifts. The mechanism of action of PfFabZ inhibitors NAS-21 and NAS-91 are also discussed in detail. Intrigued by the hot dog fold of the Fab enzyme, we have analyzed and compared proteins having this fold in their structures. It has been observed that the fold is often associated with fatty acids. However, the sequences, the quaternary structures, substrate specificities and the reactions that the proteins catalyze are quite diverse. The consensus sequence motifs lining the interface of quaternary association and at active site clearly indicated that the information for different modes of quaternary associations is embedded in the sequences itself. The diversity in function and quaternary association of hot dog fold proteins and their structure-function relationships are discussed in chapter 7. Malaria affects hundreds of millions of people worldwide causing about two million deaths every year. In spite of the commendable success of the available antimalarials, it has not been possible to contain the disease completely as the protozoan has become resistant to a majority of frontline drugs. The structural studies presented here should enhance the current biochemical knowledge to develop selective and more potent inhibitors of the pathway and contribute to the ongoing efforts to fight the disease.