A integração produtiva com o MERCOSUL, nos últimos, anos tem recebido uma atenção especial na agenda de políticas internacionais do governo brasileiro. Esse fato pode ser explicado pelo número crescente de empresas brasileiras que procuram integrar sua produção com empresas da Argentina, Uruguai, Paraguai e Venezuela. Dentro desse contexto, o objetivo geral desta tese é analisar as relações funcionais dos fatores relacionados à natureza da firma e à formação de blocos econômicos que interferem nas estratégias de integração produtiva no MERCOSUL. Para entender o objeto de estudo desta tese, foi desenvolvida uma base teórica com foco nas abordagens epistemológicas das estratégias de integração produtiva, na teoria da firma e na formação de blocos econômicos. Logo após, foi apresentado um modelo teórico, fundamentado em hipóteses, as quais são baseadas na abordagem teórica da firma e nos estudos de formação de blocos econômicos. A pesquisa realizada utilizou uma abordagem mista, dividida em três etapas. Na primeira etapa, foram coletados 137 questionários, e serviu para a purificação do instrumento de Coleta de Dados. Na segunda etapa, com a coleta final de 516 respondentes, foi feita a análise dos dados quantitativos. Para isso, utilizou-se a Modelagem de Equações Estruturais (MEE), avaliando individualmente os construtos e discutindo as relações do modelo estrutural e suas hipóteses. Logo após a interpretação dos dados quantitativos, utilizou-se a técnica de análise de conteúdo para interpretar as relações validadas ou não na MEE. Nessa fase, foram realizadas 11 entrevistas semiestruturadas, que tiveram como objetivo analisar os achados teóricos e empíricos do trabalho. Após a validação e análise do modelo, foram feitas as considerações finais dos achados desta pesquisa. Constatou-se que a integração produtiva no MERCOSUL trata-se de um tema evidente, especialmente pelas complexas relações existentes nos fatores que antecedem (influenciam) sua prática. Como pode ser depreendida na base teórica e na análise dos resultados, a materialização dos benefícios da integração envolve um profundo processo de reorganização estratégica da estrutura produtiva das empresas e dos países-membros do MERCOSUL. Desse modo, o presente estudo pretendeu contribuir para a discussão dos estudos de internacionalização da produção em blocos econômicos, incentivando futuros debates que venham a contribuir para a evolução desse campo. / In recent years, the productive integration with Mercosur has received special attention in the international political agenda of the Brazilian government. This fact can be explained by the increasing number of Brazilian companies that seek to integrate their production with companies in Argentina, Uruguay, Paraguay and Venezuela. Within this context the overall aim of this thesis is to analyze the functional relationships of the factors related to the nature of the firm and the formation of economic blocks that interfere with productive integration strategies in MERCOSUR. To understand the subject matter of this thesis, it was developed a theoretical basis with a focus on epistemological approaches of integration strategies in production, the theory of the firm and the formation of economic blocs. Soon after, it was presented a theoretical model based on assumptions related to the theoretical approach of the firm and in studies about the formation of economic blocs. The survey used a mixed approach, divided into three steps. In the first stage 137 questionnaires were collected. This first stage was the cleansing function of the instrument Data Collection. In the second stage, with the final collection of 516 respondents, it was analyzed the quantitative data. For this matter we used the Structural Equation Modeling (MEE), evaluating the individual constructs and discussing the relationships of the structural model and its assumptions. Soon after the interpretation of quantitative data, we used the technique of content analysis to interpret the relationships validated in the MEE. This phase was conducted by eleven semi-structured interviews aimed to analyze the findings of the theoretical and empirical work. After validation and analysis of the model, it was made the final considerations of the findings of this research. It was found that the productive integration in MERCOSUR is clearly an issue, especially the complex relationships that exist in the factors leading (influencing) their practice. As can be deduced from the theoretical basis and analysis of results, the realization of the benefits of integration involves a thorough process of strategic reorganization of production structures and member countries of MERCOSUR. Thus, this study aimed to contribute to the discussion of studies about the internationalization of production blocs, encouraging future research which may contribute to the evolution of this field.

Les métamatériaux sont des matériaux artificiels, formés par l’assemblage de nano-résonateurs, qui ont la capacité d’interagir avec les ondes qui les traversent et de conférer des propriétés inaccessibles aux matériaux homogènes. Afin de fabriquer de tels métamatériaux agissant dans le domaine du visible, un contrôle précis de l’organisation des résonateurs à l’échelle nanométrique est requis. Dans ce projet nous avons donc élaboré des voies de fabrication de type bottom-up, en organisant de façon anisotrope des nanoparticules d’or (AuNPs), qui sont des résonateurs du fait de leurs propriétés plasmoniques, dans un film de copolymères à blocs poly(styrène)-b-poly(vinylpyridine) (PS-b-PVP) nano-structuré en rangées de cylindres de PVP perpendiculaires au substrat.Au cours de ce projet, nous avons élaboré des routes de formulation permettant de produire des films de phase cylindrique hexagonale de copolymères alignés contenant des nanoparticules d’or. L’orientation des cylindres perpendiculaires au substrat a été obtenue en déposant le copolymère grâce à un solvant neutre dont la composition dépend de la fraction volumique en PVP du copolymère. La structure des films avec et sans nanoparticules a été caractérisée par microscopie et diffusion des rayons X en incidence rasante (GISAXS). Plusieurs méthodes d’incorporation des nanoparticules d’or ont été étudiées, soit en synthétisant les nanoparticules au sein du copolymère, en solution avant dépôt ou directement dans le film organisé ; soit en incorporant des nanoparticules pré-formées, en solution de copolymère ou dans le film déposé. Dans le cas de la synthèse in situ, nous avons formé les AuNPs par réduction chimique ou physique (sonication, radiolyse) d’un sel d’or dans le copolymère. L’incorporation des AuNPs pré-formées, elle, a été réalisée grâce à la fonctionnalisation des AuNPs ou par un traitement du film de copolymère afin de faciliter l’insertion des AuNPs. / Metamaterials are artificial materials, made from the assembly of nano-resonators, which can interact with incoming waves and get properties unknown for homogeneous materials. In order to fabricate metamaterials with an effect over visible light, a precise control over the organization at the nanoscale is required. The goal of this project was then the use of bottom-up approaches to achieve the anisotropic organization of gold nanoparticles (AuNPs), which are resonators due to their plasmonic properties, into a poly(styrene)-b-poly(vinylpyridine) block copolymer film, with a nanostructuration in arrays of PVP cylindrical domains perpendicular to the substrate.During this work, we investigated routes for the fabrication of copolymer films containing ordered gold nanoparticles in a hexagonal cylindrical phase. The orientation of the cylinders normal to the substrate was obtained by casting the copolymer with a neutral solvent whose composition was found dependent on the volumic fraction of PVP in the copolymer. The film structure with and without AuNPs was characterized by microscopy and Grazing-Incidence Small-Angle X-rays Scattering (GISAXS). Several incorporation methods for the insertion of AuNPs were studied, either by the in situ synthesis of the nanoparticles in solution before casting or directly into the ordered film; or by incorporating pre-formed AuNPs in the copolymer solution or in the film as-cast. In the case of the in situ synthesis, the AuNPs were formed by chemical or physical (sonication, radiolysis) reduction of a gold salt in the copolymer. The incorporation of pre-formed AuNPs was, achieved thanks to the functionalization of the AuNPs or by a treatment of the copolymer film in order to facilitate the insertion of the AuNPs.

The Ressano Garcia Border Post on the Mozambique side and the Lebombo Border post on the South African side represent the link between two of the three Maputo Corridor countries that receives the largest amount of freight traffic along the Corridor. The link has been identified as a major obstacle to the free movement of goods. As a result the process of the establishment of a One Stop Border Post was mooted by the former president Thabo Mbeki and his counter-part in Mozambique Mr. Joaquim Chissano in a bilateral agreement between these two countries. The reasons for these developments are prompted by the protracted problems that have beset intra-regional trade. For example, transport infrastructure in the region imposes significant costs on intra-regional and regional trade transactions. Long delays at border posts add to the intra-regional trade costs. The requirements by the 1996 SADC trade protocol, the basis of the FTA — that member states eliminate non-tariff barriers — poses special problems as it represents different things to different SADC member states. Addressing the SADC summit on 16 August 2006, the then South African President Thabo Mbeki said “the launch of the FTA was much more than a simple acknowledgement that the majority of traded goods in the region are duty-free. Rather we should view the achievement of this milestone as a major step towards addressing the fundamental challenges of poverty and underdevelopment through deeper integration and economic development” (Mbeki, 2006:16). Now that there will be one centre that clears all the documents for the transporters this will effectively culminate in the speedy processing of the documents. There will be no need for the transporters to stop at the other country’s customs offices to do the same job. Once the documents are complete the process is complete, because the barriers are removed between the two countries.

Casella (1996) derives theoretically the result that the gains from enlarging a trade bloc fall disproportionately on its small member states. Testing this hypothesis for the Member States of the European Community and its enlargements since 1973, we find mixed results, indicating that such a small country bonus may well exists, but that it is partly neutralized or dominated by economic forces that tend to favour large countries. / Series: EI Working Papers / Europainstitut

This dissertation uses the theory of the experimentallyorganised economy (EOE) and competence blocs to analyseeconomic development in the health care industry. The healthcare industry is both important and interesting to study fromseveral points of view. The industry is large, even larger thanthe manufacturing industry, and draws significantresources. The theory of the EOE and competence blocs is bothevolutionary and dynamic. It identifies the actors needed foran efficient selection and commercialisation of investmentprojects and the competences needed to support that process.For this, the institutional setting is important in thatinstitutions influence the incentives that guide actors in theeconomy and the nature of competitionthat forces change. Four empirical studies are carried out using severalempirical methods to study similar problems, ranging fromeconometric analyses of panel micro data to case studies. Weask if the withdrawal of a major employer (Pharmacia) from aregion (Uppsala) has had a negative effect on employmentgrowth. We then ask if the turnover of establishments has hadany effect on regional employment growth. We find no supportfor the first question. However, the regional turnover ofestablishments is found to have had a positive effect onregional employment growth, illustrating how important thisdynamic is for the economy. In addition, a case study of theintroduction of two almost identical innovations in twodifferent competence bloc environments, that of the US and thatof Sweden, captures the whole process from invention toinnovation and diffusion in the market. We find that without acomplete competence bloc the risk is high of“loosing awinner”. Finally, we study the role of the technologytransfer process from university to industry for thecommercialisation of new inventions. Among other things, thestudy illustrates how institutional changes, such as theBayh-Dole Act, have created positive effects for theeconomy. The Experimentally Organised Economy; Competence Blocs;Industrial Dynamics; Health Care Industry; IndustrialTransformation; Regional Turnover of Establishments; CaseStudies; Technology Transfer / <p>NR 20140805</p>

Cette thèse a pour but de résoudre certains problèmes de connexion et de décrire diverses propriétés asymptotiques des fonctions de Painlevé V et I. Dans le cas de l’équation de Painlevé V, nous approchons ces problèmes en développant une nouvelle approche basée sur la théorie conforme des champs bidimensionelle. Nous proposons de calculer les blocs conformes irréguliers de première et seconde espèce par confluence des blocs conformes réguliers de Virasoro. Une conséquence de cette construction est la solution du problème de connexion de l’équation de Painlevé V entre 0 et +i∞. Les formules pour les normalisations relatives (constantes de connexion) de la fonction tau de Painlevé V entre 0, +∞, et +i∞ sont également proposées. Enfin, le développement asymptotique complet de la fonction tau à courte distance pour des données de monodromie génériques est prouvé. Ce résultat est obtenu en construisant une représentation de la fonction tau en termes d’un déterminant de Fredholm. Dans le cas de l’équation de Painlevé I, nous présentons les constantes de connexion relatant les asymptotiques de la fonction tau sur les cinq raies canoniques à l’infini. Ce résultat est obtenu en construisant une extension de la forme différentielle de Jimbo-Miwa-Ueno à l’espace des données de monodromie. Ces constantes de connexion sont exprimées en termes de dilogarithmes de coordonnées de type cluster dans l’espace des données de Stokes. / The aim of this thesis is to solve several connection problems and describe asymptotic properties of Painlevé V and I functions. In the case of Painlevé V equation, we approach these problems by developing a new toolbox based on two dimensional conformal field theory. We propose to compute irregular conformal blocks of the first and second kind by confluence of regular Virasoro conformal blocks. One consequence of this construction is the solution of the connection problem for Painlevé V equation between 0 and +i∞. Formulas for the relative normalizations (connection constants) of Painlevé V tau function between 0, +∞, and +i∞ are also proposed. Finally, the full asymptotic expansion of the tau function at short distances for generic monodromy data is proved. This result is obtained by constructing a Fredholm determinant representation for the tau function. In the case of Painlevé I equation, we present connection constants relating asymptotics of the tau function on the five canonical rays at infinity. This result is obtained by extending the definition of the Jimbo-Miwa-Ueno differential to the space of monodromy data. These connection constants are expressed in terms of dilogarithms of cluster type coordinates on the space of Stokes data.

Cette thèse regroupe des contributions méthodologiques à l'analyse statistique des bases de données de pharmacovigilance. Les difficultés de modélisation de ces données résident dans le fait qu'elles produisent des matrices souvent creuses et de grandes dimensions. La première partie des travaux de cette thèse porte sur la classification croisée du tableau de contingence de pharmacovigilance à l’aide du modèle des blocs latents de Poisson normalisé. L'objectif de la classification est d'une part de fournir aux pharmacologues des zones intéressantes plus réduites à explorer de manière plus précise, et d'autre part de constituer une information a priori utilisable lors de l'analyse des données individuelles de pharmacovigilance. Dans ce cadre, nous détaillons une procédure d'estimation partiellement bayésienne des paramètres du modèle et des critères de sélection de modèles afin de choisir le modèle le plus adapté aux données étudiées. Les données étant de grandes dimensions, nous proposons également une procédure pour explorer de manière non exhaustive mais pertinente, l'espace des modèles en coclustering. Enfin, pour mesurer la performance des algorithmes, nous développons un indice de classification croisée calculable en pratique pour un nombre de classes élevé. Les développements de ces outils statistiques ne sont pas spécifiques à la pharmacovigilance et peuvent être utile à toute analyse en classification croisée. La seconde partie des travaux de cette thèse porte sur l'analyse statistique des données individuelles, plus nombreuses mais également plus riches en information. L'objectif est d'établir des classes d'individus selon leur profil médicamenteux et des sous-groupes d'effets et de médicaments possiblement en interaction, palliant ainsi le phénomène de coprescription et de masquage que peuvent présenter les méthodes existantes sur le tableau de contingence. De plus, l'interaction entre plusieurs effets indésirables y est prise en compte. Nous proposons alors le modèle des blocs latents multiple qui fournit une classification croisée simultanée des lignes et des colonnes de deux tableaux de données binaires en leur imposant le même classement en ligne. Nous discutons des hypothèses inhérentes à ce nouveau modèle et nous énonçons des conditions suffisantes de son identifiabilité. Ensuite, nous présentons une procédure d'estimation de ses paramètres et développons des critères de sélection de modèles associés. De plus, un modèle de simulation numérique des données individuelles de pharmacovigilance est proposé et permet de confronter les méthodes entre elles et d'étudier leurs limites. Enfin, la méthodologie proposée pour traiter les données individuelles de pharmacovigilance est explicitée et appliquée à un échantillon de la base française de pharmacovigilance entre 2002 et 2010. / This thesis gathers methodological contributions to the statistical analysis of large datasets in pharmacovigilance. The pharmacovigilance datasets produce sparse and large matrices and these two characteritics are the main statistical challenges for modelling them. The first part of the thesis is dedicated to the coclustering of the pharmacovigilance contingency table thanks to the normalized Poisson latent block model. The objective is on the one hand, to provide pharmacologists with some interesting and reduced areas to explore more precisely. On the other hand, this coclustering remains a useful background information for dealing with individual database. Within this framework, a parameter estimation procedure for this model is detailed and objective model selection criteria are developed to choose the best fit model. Datasets are so large that we propose a procedure to explore the model space in coclustering, in a non exhaustive way but a relevant one. Additionnally, to assess the performances of the methods, a convenient coclustering index is developed to compare partitions with high numbers of clusters. The developments of these statistical tools are not specific to pharmacovigilance and can be used for any coclustering issue. The second part of the thesis is devoted to the statistical analysis of the large individual data, which are more numerous but also provides even more valuable information. The aim is to produce individual clusters according their drug profiles and subgroups of drugs and adverse effects with possible links, which overcomes the coprescription and masking phenomenons, common contingency table issues in pharmacovigilance. Moreover, the interaction between several adverse effects is taken into account. For this purpose, we propose a new model, the multiple latent block model which enables to cocluster two binary tables by imposing the same row ranking. Assertions inherent to the model are discussed and sufficient identifiability conditions for the model are presented. Then a parameter estimation algorithm is studied and objective model selection criteria are developed. Moreover, a numeric simulation model of the individual data is proposed to compare existing methods and study its limits. Finally, the proposed methodology to deal with individual pharmacovigilance data is presented and applied to a sample of the French pharmacovigilance database between 2002 and 2010.

Les structures protéiques sont de nature hautement dynamique contrairement à leur représentation dans les structures cristallines. Une composante majeure de la dynamique structurelle est la flexibilité des protéines inhérentes. L'objectif principal de cette thèse est de comprendre le rôle de la dynamique inhérente dans les structures protéiques et leur propagation. La flexibilité des protéines est analysée à différents niveaux de complexité structurelle, du niveau d'organisation primaire au niveau quaternaire. Chacun des cinq premiers chapitres traite un niveau différent d'organisation structurelle locale avec le premier chapitre traitant des structures secondaires classiques tandis que le second analyse la même chose en utilisant un alphabet structurel - les blocs protéiques. Le troisième chapitre se concentre sur l'impact d'événements physiologiques spéciaux comme les modifications post-traductionnelles et le désordre sur les transitions d'ordre sur la flexibilité des protéines. Ces trois chapitres indiquent une mise en œuvre dépendante du contexte de la flexibilité structurelle dans leur environnement local. Dans les chapitres suivants, des structures plus complexes sont prises en compte. Le chapitre 4 traite de l'intégrine αIIbβ3 impliquée dans des troubles génétiques rares. L'impact des mutations pathologiques sur la flexibilité locale est étudié dans deux domaines rigides de l'intégrine αIIbβ3 ectodomaine. La flexibilité inhérente dans ces domaines est montrée pour moduler l'impact des mutations vers les boucles. Le chapitre 5 traite de la modélisation structurelle et de la dynamique d'une structure protéique plus complexe du récepteur des chimiokines des antigènes du groupe Duffy incorporé dans un système de membrane mimétique érythrocytaire. Le modèle est soutenu par l'analyse phylogénétique la plus complète sur les récepteurs de chimiokines jusqu'à ce jour, comme expliqué dans le dernier chapitre de la thèse. / Protein structures are highly dynamic in nature contrary to their depiction in crystal structures. A major component of structural dynamics is the inherent protein flexibility. The prime objective of this thesis is to understand the role of the inherent dynamics in protein structures and its propagation. Protein flexibility is analyzed at various levels of structural complexity, from primary to quaternary levels of organization. Each of the first five chapters’ deal with a different level of local structural organization with first chapter dealing with classical secondary structures while the second one analysis the same using a structural alphabet - Protein Blocks. The third chapter focuses on the impact of special physiological events like post-translational modifications and disorder to order transitions on protein flexibility. These three chapters indicate towards a context dependent implementation of structural flexibility in their local environment. In subsequent chapters, more complex structures are taken under investigation. Chapter 4 deals with integrin αIIbβ3 that is involved in rare genetic disorders. Impact of the pathological mutations on the local flexibility is studied in two rigid domains of integrin αIIbβ3 ectodomain. Inherent flexibility in these domains is shown to modulate the impact of mutations towards the loops. Chapter 5 deals with the structural modelling and dynamics of a more complex protein structure of Duffy Antigen Chemokine Receptor embedded in an erythrocyte mimic membrane system. The model is supported by the most comprehensive phylogenetic analysis on chemokine receptors till date as explained in the last chapter of the thesis.

Customs services are increasing and becoming more important as global and cross-border trade increases. New trade agreements are developing which changes the prerequisites for actors concerned by the customs market. The customs industry is in many cases old-fashioned where customs service providers are making declarations by hand. The purpose of this study is to gain a deeper understanding about development of customs services based on the parameters: technology, trade blocs, climate issues and customer requirements. This study is based on a deductive approach where a qualitative method has been used for data collection. The data collection has been done by interviewing people from various companies and organizations with significant knowledge within the customs area. With support of the interviews and theoretical learnings a presumptive future of the customs industry has been developed. The results were constructed by assembling learnings from the interviews and are visualized based on the four parameters. Quality and price are important factors that reflect all the respondents’ answers regarding the customer requirements of the industry. Reputation and the opportunity to cover a larger geographical area are also parameters that the respondents mentioned. In the upcoming years there are demands regarding more data integration and digitalization between customs service providers and companies within the industry. This digitalization might help companies to evaluate and use trade agreements. Environment is a topic that is constantly being noticed in all industries, the customs industry as well. Common to the respondents was that climate issues will generate a future of more national and local nature. We see an increased degree of protectionism according to respondent seven. Block chain is a technology that has received increased attention lately, which leading to the question of whether this is something that customs companies should consider. In the future, blockchain may be worth investing in, but at the moment there are several limitations with the technology.

L'objectif principal de ce travail de thèse étant la préparation de nanovecteurs biocompatibles, nous avons mis au point des systèmes catalytiques exempts de métal pour polymériser les différents monomères préparés dérivés de l’acide diméthylmalique. En présence de ces systèmes catalytiques, la polymérisation anionique par ouverture de cycle (aROP) se déroule de manière contrôlée avec une cinétique plus rapide que celle réalisée en présence d’autres organo-catalyseurs déjà décrit dans la littérature. Nous avons ainsi synthétisé trois homopolymères hydrophobes et deux familles de copolymères di-blocs amphiphiles ayant différentes balances hydrophiles/hydrophobes. Des nanoparticules (NPs) ont été préparées par nanoprécipitation à partir des homopolymères hydrophobes et des copolymères à blocs amphiphiles. La taille des NPs varie entre 30 et 170 nm avec de faibles dispersités (PDI ≤ 0,23) et ayant une très bonne stabilité à 4°C et à 37°C. Des études de cytotoxicité in vitro sur la lignée cellulaire d'hépatome HepaRG ont mis en évidence que toutes les NPs ont une faible toxicité à des concentrations inférieures à 3 μM. En parallèle, une sonde fluorescente, le DiR, a été encapsulée dans les NPs lors de la nanoprécipitation sans affecter les caractéristiques et la stabilité des NPs correspondantes. Enfin, des études in vitro utilisant ces NPs chargées en DiR ont montré que ces dernières étaient effectivement captées par les cellules HepaRG avec différents pourcentages de captation. / The main objective of this PhD thesis being the preparation of biocompatible nanovectors, we have set up metal-free catalytic systems to polymerize various prepared monomers derived from dimethylmalic acid. Using such catalytic systems, the anionic ring opening polymerization (aROP) proceeds in a controlled manner with faster kinetics compared to the organo-catalysts already reported in the literature. Three hydrophobic homopolymers and two families of amphiphilic block copolymers with different hydrophilic/hydrophobic balances have been therefore synthesized. Nanoparticles (NPs) have been prepared by nanoprecipitation of these hydrophobic homopolymers and amphiphilic block copolymers. The size of the NPs ranges from 30 to 170 nm with low dispersity values (PDI ≤ 0.23) and high stability at 4°C and 37°C. In vitro cytotoxicity studies on HepaRG hepatoma cell line have highlighted that all the NPs have low toxicity at concentrations lower than 3μM. In parallel, NPs were loaded with the fluorescent probe DiR without altering the characteristics and the stability of the corresponding DiR loaded NPs. Finally, in vitro studies using NPs loaded with DiR have shown that HepaRG cells effectively uptake the NPs in different percentages of uptake.