Esta pesquisa aborda um momento pouco investigado pelos estudos sobre o Pacífico negro colombiano. Território de população majoritariamente negra, cujo povoamento desdobrou-se da crise da instituição escravista, o Pacífico negro organizou-se sob um padrão de relativo isolamento frente às estruturas estatais de organização social, constituindo um modelo de subsistência autônomo, baseado em mecanismos locais de parentesco, trabalho e posse da terra. A pesquisa que aqui se apresenta trata de investigar como este modelo de subsistência foi desarticulado pela ação extrativista das indústrias madeireiras, a partir dos anos 1950, as quais se disseminaram na região estimuladas pela emergência de uma nova perspectiva estatal sobre as terras baixas, que as compreendia como baldios da nação que deveriam ser explorados técnica e racionalmente. Este processo gerou focos de proletarização dos camponeses, sobretudo na porção sul da costa, mas também logrou absorver e transformar as dinâmicas locais de trabalho, produzindo uma nova forma de subordinação do trabalho, distinta do assalariamento tipicamente capitalista. Tais elementos levaram a pesquisadora a revisitar a teoria marxiana da acumulação primitiva e da subsunção formal e real do trabalho no capital, bem como as contribuições de Rosa Luxemburg sobre a acumulação do capital, para estabelecermos um patamar teórico seguro que nos permitisse compreender as transformações locais nas relações de trabalho e posse da terra dos camponeses negros, sem perder de vista que tal processo se insere em um movimento mais amplo de consolidação das relações de produção capitalistas no país. / This research address a moment not much explored by the studies about the Pacific Lowlands of Colombia. A territory where the majority of its population is black and came from the slavery crisis. The Pacific lowlands put themselves in an isolated positon according to the social organization, creating an autonomy surviving model based on the local mechanisms of kinship work and territory possession. The research presented draws upon the investigation of the existing model which was dismantled by the extractive actions from the lumber industry, starting in 1950\'s, which were disseminated in the region that urgently needed a new state perspective in the lowlands, and it was seen as a vacant state land and should be technically and rationally explored. This processes brought the proletarianization to the peasants, mostly to the South Coast, and they were also able to absorb the local work dynamics, creating a new way of subjection of labour, not as the proletariat form from the typical capitalism. These elements brought the researcher to revise the primitive accumulation and the capital\'s real and formal work subsumption from Marxist\'s theory. Also Rosa Luxemburg\'s contribution about the capital accumulation to establish theoretical level which allows us to comprehend the local transformations in the work relations and territory possession from the black peasant, keeping in mind that the process is a from a movement beyond the capitalism relations productions in the country.

Um anel noetheriano S satisfaz a propriedade ( ) se todas as extens~oes essenciais c clicas de S-m odulos simples s~ao artinianas. An eis noetherianos com esta propriedade veri cam a Conjectura de Jacobson, que e um famoso problema em aberto em teoria de an eis. Neste trabalho investigamos esta propriedade em an eis de operadores diferenciais R[ ; ], onde R e um anel comutativo noetheriano e uma deriva c~ao de R. Mais especi camente, estudamos condi c~oes necess arias e su cientes para que R[ ; ] satisfa ca ( ), quando R e um anel -simples e, tamb em, no caso em que este e um anel -primitivo. Al em disso, caracterizamos os an eis de operadores diferenciais C[x; y][ ; ] que satisfazem ( ). / A Noetherian ring S satis es the property ( ) if any cyclic essential extension of simple S-modules are Artinian. Noetherian rings with this property verify Jacobson's Conjecture, which is a famous open problem in ring theory. In this work we investigate this property in di erential operators rings R[ ; ], where R is a commutative Noetherian ring and is a derivation of R. More precisely, we study necessary and su cient conditions for R[ ; ] to satisfy property ( ) whenever R is a -simple ring and also for the case where it is a -primitive ring. Furthermore, we characterize the di erential operator rings C[x; y][ ; ] satisfying ( ).

La myélofibrose primitive (MFP) est un néoplasme myéloprolifératif chromosome Philadelphie négatif rare, mais de pronostic sévère. Elle se caractérise par une prolifération clonale et une mobilisation des cellules souches et progéniteurs hématopoïétiques (CSH/PH) de la moelle osseuse vers la rate et le foie. Cette anomalie de l’hématopoïèse est associée à une pathologie du stroma (myélofibrose, ostéosclérose et néoangiogenèse). L’existence d’anomalies moléculaires de la CSH/PH telles que les mutations de Jak2, Mpl, TET2 ou CALR ne permet pas à elle seule d’expliquer la physiopathologie de la maladie. Les résultats obtenus dans le laboratoire suggèrent que le microenvironnement médullaire au sein des niches hématopoïétiques et en particulier les cellules stromales mésenchymateuses (CSM), participe vraisemblablement à cette dérégulation de l’hématopoïèse, favorisant le développement du clone pathologique. Cependant, aucune preuve tangible d’une altération des CSM médullaires n’a été jusqu’à présent apportée.Dans ce travail, nous avons isolé les CSM de la moelle de patients atteints de MFP et réalisé une caractérisation « complète » de ces cellules : prolifération, phénotype, soutien de l’hématopoïèse, sécrétome, transcriptome, miRNome et capacités de différenciation. Nos résultats ont permis de dégager un faisceau d’arguments en faveur d’une dérégulation de leur différenciation ostéoblastique (DOB). (i) Les cytokines BMP2, RANTES, PDGF, TGF-β1, VEGF et Il-6 sont significativement produites en plus grande quantité par ces cellules. (ii) L’étude du transcriptome a révélé une expression significativement différente d’un ensemble de gènes impliqués dans la DOB tels que RUNX2, DLX5, TWIST1 et NOGGIN. (iii) De nombreux micro-ARN, dont certains sont connus pour être impliqués dans la DOB comme miR-210 ou dans le nichage des cellules souches hématopoïétiques comme miR-34a, sont dérégulés à l’état basal et au cours de cette DOB. (iv) Enfin, l’étude de leurs capacités de différenciation ostéoblastique in vitro et in vivo chez la souris immunodéprimée est en faveur d’une augmentation de ces capacités. Nous avons étudié l’impact du TGF- β1 dans cette DOB. Nous avons mis en évidence que les CSM de malades présentent un état basal d'activation de la voie de signalisation pSmad significativement augmenté, confirmant l’expression endogène de TGF-β1. En utilisant des inhibiteurs spécifiques du récepteur de type I au TGF- β, nous avons montré l’implication de cette cytokine dans les altérations de la DOB. En conclusion, notre travail montre pour la première fois que les CSM des malades de MFP sont anormales et ce indépendamment de la stimulation par le clone hématopoïétique pathologique, suggérant la présence d'anomalies constitutives ou acquises. Ces anomalies impliquent deux acteurs majeurs de la pathologie : le TGF-β1 et l'ostéogenèse. / Primary myelofibrosis (PMF) is a Philadelphia-negative myeloproliferative neoplasm, rare but associated with a poor prognosis. Its features are a clonal proliferation and an egress of hematopoietic stem cells (HSC) from bone marrow to spleen. These abnormalities of hematopoiesis are in relation with a pathological stroma (myelofibrosis, osteosclerosis and neoangiogenesis). Molecular abnormalities present in HSC partially explain the physiopathology of the disease. Results from our lab suggest that the bone marrow micro-environnement, especially mesenchymal stromal cells (MSC), are involved in the deregulation of hematopoiesis, promoting the clonal cells. However, there is no strong evidence of bone marrow MSC alterations reported for now.In our study, we isolated MSC from bone marrow of patients suffering from PMF and performed a broad characterization: proliferation, phenotype, hematopoiesis supporting capacities, secretome, transcriptome and miRNome analysis. Our results highlight arguments in favor of a deregulation of their osteogenic capacities. (i) Cytokines NMP2, RANTES, PDGF, TGF-β1, VEGF and Il-6 were significantly overproduced by MSCs. (ii) Transcriptome analysis revealed a specific signature involving genes participating in osteogenic differentiation such as RUNX2, DLX5, TWIST1 and NOGGIN. (iii) Many micro-RNAs, some know to be involved in osteogenic differentiation regulation, as mir-34a, are deregulated in MSCs and in MSC-derived osteoblasts. (iv) Finally, study of their osteogenic potency in vitro and in vivo in nude mice showed an increasing of their osteogenic potency. We studied the impact of TGF-β1 in this process and showed that PMF MSCs showed a basal expression of Smad pathway significantly increased as compared to control. Using specific inhibitor of TGF-β1 receptor, we demonstrated the implication of this cytokine in the osteogenic impairment.To summarize, our work shows for the first time that MSCs from PMF patients are abnormal, independently from stimulation by clonal cells, suggesting intrinsic abnormalities. These abnormalities involve two main factor of the disease: TGF-β1 and osteogenesis.

This thesis offers a fresh study of the sources on the history of the city of Jerusalem in the period between the reigns of the Roman emperors Theodosius the Great and Justinian I. In the Holy Land, this period roughly coincides with the arrival of St Jerome in 385 and the completion of Jerusalem's last major church building before the Persian and Muslim conquests, the Nea church, dedicated in 543. One of the main aims of this thesis is to investigate the role of imperial patronage in the city and contrast it with the growing influence of local actors, i.e. bishops, monks, and rich pilgrims who settled there. My reading of the sources makes clear that Jerusalem and the imperial court were more closely connected than previously assumed. This manifested itself not only in imperial building projects, but also in the exchange of theological concepts and ideas. One of my key findings about this traffic is that the cult of saints was introduced to Jerusalem from Constantinople, while, in contrast, the veneration of the Virgin Mary originated in the holy city and reached the capital from there. The thesis offers a new interpretation of patriarchal politics in the times of the Christological controversies following the Council of Chalcedon (451) and of the political self-perception of Jerusalem from the beginning of the sixth century onwards, when the city with its loca sancta entered into a new form of relationship with the emperor Justinian, who bestowed his favour on Jerusalem in the form of imperial donations in return for the support of his ecclesiastical policies by the clergy and monks of Jerusalem.

INTRODUÇÃO: Os tumores da família do sarcoma de Ewing (TFSE) compreendem um espectro de neoplasias de células neuroectodérmicas dos ossos e partes moles de comportamento biológico agressivo e prognóstico reservado, caracterizadas por translocações envolvendo um dos genes da família TET/FET e um dos genes da família ETS, mais comumente EWSR1 e FLI1. Com o avanço da medicina personalizada, cresce a demanda por biomarcadores em TFSE que tenham valor como fatores prognósticos e potencial para futuras terapias-alvo específicas. Este estudo propôs biomarcadores, incluindo proteínas relacionadas à supressão tumoral, proliferação celular, metabolismo energético, atividade imune, vias de reparo do DNA e células tronco. MÉTODOS: A expressão imuno-histoquímica dos biomarcadores MTAP, p16, STAG2, p53, USP22, PTEN, RKIP, Ciclina D1, MCTs (1, 2 e 4), CD147, CA IX, GLUT1, BRACHYURY, PD-L1, OCT4 e SALL4 foi analisada em uma série bem caracterizada de 113 TFSE através de amostras em tissue microarrays (TMA). Os perfis de expressão foram então associados aos parâmetros clínico-patológicos dos pacientes e à sobrevida global para uma análise do impacto no prognóstico. RESULTADOS: A hiperexpressão de p53 mostrou associação estatisticamente significativa com menor sobrevida global (p < 0,001), doença metastática no diagnóstico (p = 0,017) e idade acima de 20 anos (p = 0,04). A perda de expressão de MTAP (p = 0,039) e de Brachyury (p = 0,008) também se associaram significativamente com menor sobrevida global. Em relação às características clínicas dos pacientes, doença metastática no diagnóstico e etnia não-branca foram associados a um pior prognóstico. CONCLUSÕES: Os biomarcadores p53, MTAP e Brachyury foram identificados como fatores independentes relacionados ao prognóstico. A utilização destes biomarcadores como fator prognóstico nos TFSE pode auxiliar na estratificação de risco dos pacientes e até mesmo estimular o desenvolvimento de drogas-alvo específicas / INTRODUCTION: The Ewing sarcoma family of tumors (ESFT) comprises a spectrum of neoplasms of neuroectodermal cells of the bones and soft tissues with an aggressive biological behavior and poor outcome, characterized by translocations involving one of the genes of the TET/FET family and one of the genes of the ETS family, most commonly EWSR1 and FLI1. With the progress of personalized medicine, there is a great demand for biomarkers in ESFT that could have prognostic values and the potential for future targeted therapies. This study proposed the evaluation of protein expression of different classes of biomarkers, including proteins related to tumor suppression, cell proliferation, energy metabolism, immune activity, DNA repair pathways and stem cells. METHODS: Immunohistochemical expression of the biomarkers MTAP, p16, STAG2, p53, USP22, PTEN, RKIP, Cyclin D1, MCTs (1, 2 and 4), CD147, CA IX, GLUT1, BRACHYURY, PD-L1, OCT4 and SALL4 was analyzed in a well-characterized series of 113 ESFT in a tissue microarray (TMA) platform. Expression profiles were then associated with patients\' clinical-pathological parameters and overall survival for analysis of the prognostic impact. RESULTS: p53 hyperexpression showed a statistically significant association with lower overall survival (p <0.001), metastatic disease at diagnosis (p = 0.017) and age over 20 years (p = 0.04). Loss of MTAP (p = 0.039) and Brachyury (p = 0.008) were also significantly associated with lower overall survival. Regarding the clinical characteristics of the patients, metastatic disease at diagnosis and non-white ethnicity were associated with a worse prognosis. CONCLUSIONS: The biomarkers p53, MTAP and Brachyury were identified as independent factors related to the prognosis. The use of these biomarkers as a prognostic factor in ESFT may aid in the risk stratification of patients and even stimulate the development of specific targeted drugs

Puisque les premières formes de vie connues à ce jour (> 3 Ga) ont été préservées grâce à la précipitation de silice sur les structures cellulaires (silicification), nous avons mené la fossilisation expérimentale de différentes souches microbiennes (les Archées Methanocaldococcus jannaschii et Pyrococcus abyssi, les Bactéries Chloroflexus aurantiacus et Geobacillus sp.), représentatives des micro-organismes thermophiles, anaérobies et autotrophes qui auraient pu exister dans les conditions environnementales de la Terre primitive ou de Mars. Il s'agit de la première fossilisation expérimentale d'Archées, et l'une des toutes premières concernant des micro-organismes thermophiles.<br />La fossilisation expérimentale a été suivie en microscopie électronique (MEB, MET, Cryo-MEB) pour l'étude morphologique, et par des analyses chimiques (GC, GC-MS, HPLC) pour l'étude de la dégradation ou de la préservation de la matière organique durant la fossilisation.<br />Cette étude a montré que tous les micro-organismes ne pouvaient pas être silicifiés. Les cellules de M. jannaschii ont ainsi lysé rapidement tandis, qu'à l'inverse, celles de P. abyssi, Geobacillus sp. et C. aurantiacus ont été préservées, avec des intensités de la fossilisation variables selon les espèces. Les micro-organismes ont souvent mis en place des mécanismes actifs pour se protéger de la silicification, comme la production d'EPS, ou la répulsion de la silice. Ces résultats suggèrent que les différences entre espèces ont une forte influence sur le potentiel des différents micro-organismes à être préservés par la fossilisation.<br />Cette étude fournit un bon aperçu des processus de silicification et de préservation des types de micro-organismes qui auraient pu exister sur la Terre primitive. La connaissance de ces mécanismes peut être utile pour la recherche et l'identification de microfossiles dans les roches terrestres et extraterrestres, tout particulièrement dans le cas de Mars.

<p>In the first part of this thesis, we contribute to the semantics of typed object calculus by giving (a) a category-theoretic denotational semantics using partial maps making use of an algebraic compactness assumption, (b) a notion of "wrappers'' by which algebraic datatypes can be represented as object types, and (c) proofs of computational soundness and adequacy of typed object calculus via Plotkin's FPC (with lazy operational semantics), thus making models of FPC suitable also for first-order typed object calculus (with recursive objects supporting method update, but not subtyping). It follows that a valid equation in the model induces operationally congruent terms in the language, so that program algebras can be studied. For (c), we also develop an extended first-order typed object calculus, and prove subject reduction. The second part of the thesis concerns recursion principles on datatypes including the untyped lambda calculus as a special case. Freyd showed that in certain domain theoretic categories, locally continuous functors have minimal invariants, which possess a structure that he termed dialgebra. This gives rise to a category of dialgebras and homomorphisms, where the minimal invariants are initial, inducing a powerful recursion scheme (direcursion) on a complete partial order. We identify a problem that appears when we translate (co)iterative functions to direcursion, and as a solution to this problem we develop a recursion scheme (primitive direcursion). This immediately gives a number of examples of direcursive functions, improving on the situation in the literature where only a few examples have appeared. By means of a case study, this line of work is connected to object calculus models.</p> / Delarbete II är även publicerad som Teknisk rapport, 2007, Oct, No2.

In this work, we implemented the GHER hydrodynamic model in the Gulf of Lions (resolution 1/100°). This model is nested interactively in another model covering the North-Western basin of the Mediterranean Sea (resolution 1/20°), itself nested in a model covering the whole basin (1/4°). A data assimilation filter, called the SEEK filter, is used to test in which of those grids observations taken in the Gulf of Lions are best assimilated. Therefore, twin experiments are used: a reference run is considered as the truth, and another run, starting from different initial conditions, assimilates pseudo-observations coming from the reference run. It appeared that, in order to best constrain the coastal model, available data should be assimilated in that model. The most efficient setup, however, is to group all the state vectors from the 3 grids into a single vector, and hence coherently modify the 3 domains at once during assimilation cycles. Operational forecasting with nested models often only uses so-called passive nesting: no data feedback happens from the regional models to the global model. We propose a new idea: to use data assimilation as a substitute for the feedback. Using again twin experiments, we show that when assimilating outputs from the regional model in the global model, this has benecial impacts for the subsequent forecasts in the regional model. The data assimilation method used in those experiments corrects errors in the models using only some privileged directions in the state space. Furthermore, these directions are selected from a previous model run. This is a weakness of the method when real observations are available. We tried to build new directions of the state space using an ensemble run, this time covering only the Mediterranean basin (without grid nesting). This led to a quantitative characterization of the forecast errors we might expect when various parameters and external forcings are affected by uncertainties. Finally, using these new directions, we tried to build a statistical model supposed to simulate the hydrodynamical model using only a fraction of the computer resources needed by the latter. To achieve this goal, we tried out artifficial neural networks, nearest-neighbor and regression trees. This study constitutes only the first step toward an innovative statistical model, as in its present form, only a few degrees of freedom are considered and the primitive equation model is still required to build the AL method. We tried forecasting at 2 different time horizons: one day and one week.

In the first part of this thesis, we contribute to the semantics of typed object calculus by giving (a) a category-theoretic denotational semantics using partial maps making use of an algebraic compactness assumption, (b) a notion of "wrappers'' by which algebraic datatypes can be represented as object types, and (c) proofs of computational soundness and adequacy of typed object calculus via Plotkin's FPC (with lazy operational semantics), thus making models of FPC suitable also for first-order typed object calculus (with recursive objects supporting method update, but not subtyping). It follows that a valid equation in the model induces operationally congruent terms in the language, so that program algebras can be studied. For (c), we also develop an extended first-order typed object calculus, and prove subject reduction. The second part of the thesis concerns recursion principles on datatypes including the untyped lambda calculus as a special case. Freyd showed that in certain domain theoretic categories, locally continuous functors have minimal invariants, which possess a structure that he termed dialgebra. This gives rise to a category of dialgebras and homomorphisms, where the minimal invariants are initial, inducing a powerful recursion scheme (direcursion) on a complete partial order. We identify a problem that appears when we translate (co)iterative functions to direcursion, and as a solution to this problem we develop a recursion scheme (primitive direcursion). This immediately gives a number of examples of direcursive functions, improving on the situation in the literature where only a few examples have appeared. By means of a case study, this line of work is connected to object calculus models. / Delarbete II är även publicerad som Teknisk rapport, 2007, Oct, No2.

In this thesis, I have explored the different approaches towards proving Artin's `primitive root' conjecture unconditionally and the elliptic curve analogue of the same. This conjecture was posed by E. Artin in the year 1927, and it still remains an open problem. In 1967, C. Hooley proved the conjecture based on the assumption of the generalized Riemann hypothesis. Thereafter, the mathematicians tried to get rid of the assumption and it seemed quite a daunting task. In 1983, the pioneering attempt was made by R. Gupta and M. Ram Murty, who proved unconditionally that there exists a specific set of 13 distinct numbers such that for at least one of them, the conjecture is true. Along the same line, using sieve theory, D. R. Heath-Brown reduced this set down to 3 distinct primes in the year 1986. This is the best unconditional result we have so far. In the first part of this thesis, we will review the sieve theoretic approach taken by Gupta-Murty and Heath-Brown. The second half of the thesis will deal with the elliptic curve analogue of the Artin's conjecture, which is also known as the Lang-Trotter conjecture. Lang and Trotter proposed the elliptic curve analogue in 1977, including the higher rank version, and also proceeded to set up the mathematical formulation to prove the same. The analogue conjecture was proved by Gupta and Murty in the year 1986, assuming the generalized Riemann hypothesis, for curves with complex multiplication. They also proved the higher rank version of the same. We will discuss their proof in details, involving the sieve theoretic approach in the elliptic curve setup. Finally, I will conclude the thesis with a refinement proposed by Gupta and Murty to find out a finite set of points on the curve such that at least one satisfies the conjecture.