Dans cette thèse on s’intéresse au problème des décompositions canoniques polyadiques de tenseurs d’ordre $N$ potentiellement grands et sous différentes contraintes (non-négativité, aspect creux lié à une possible surestimation du rang du tenseur). Pour traiter ce problème, nous proposons trois nouvelles approches itératives différentes: deux approches déterministes dont une approche proximale, et une approche stochastique. La première approche étend les travaux de thèse de J-P. Royer au cas de tenseurs de dimension $N$. Dans l’approche stochastique, nous considérons pour la première fois dans le domaine des décompositions tensorielles, des algorithmes génétiques (mimétiques) dont principe général repose sur l’évolution d’une population de candidats. Dans le dernier type d’approche, nous avons considéré un algorithme proximal pré-conditionné (le Block-Coordinate Variable Metric Forward-Backward), algorithme fonctionnant par blocs de données avec une matrice de pré-conditionnement liée à chaque bloc et fondé sur deux étapes successives principales : une étape de gradient et une étape proximale. Finalement, les différentes méthodes suggérées sont comparées entre elles et avec d’autres algorithmes classiques de la littérature sur des données synthétiques (à la fois aléatoires ou proches des données observées en spectroscopie de fluorescence) et sur des données expérimentales réelles correspondant à une campagne de surveillance des eaux d’une rivière et visant à la détection d’apparition de polluants. / In this PhD thesis, we consider the problem of the Canonical Polyadic Decomposition (CPD) of potentially large $N$-th order tensors under different constraints (non-negativity, sparsity due to a possible overestimation of the tensor rank, etc.). To tackle such a problem, we propose three new iterative methods: a standard gradient based deterministic approach, a stochastic approach (memetic) and finally a proximal approach (Block-Coordinate Variable Metric Forward-Backward). The first approach extends J-P. Royer's works to the case of non-negative N-th order tensors. In the stochastic approach, genetic (memetic) methods are considered for the first time to solve the CPD problem. Their general principle is based on the evolution of a family of candidates. In the third type of approaches, a proximal algorithm namely the Block-Coordinate Variable Metric Forward-Backward is presented. The algorithm relies on two main steps: a gradient step and a proximal step. The blocks of coordinates naturally correspond to latent matrices. We propose a majorant function as well as a preconditioner with regard to each block. All methods are compared with other popular algorithms of the literature on synthetic (fluorescence spectroscopy like or random) data and on real experimental data corresponding to a water monitoring campaign aiming at detecting the appearance of pollutants.

In this work we will try to quantize midisuperspace model of spherically sym- metric spacetime with massless scalar field. On this type of spacetimes we apply Dirac method of canonical quantization, leading to Wheeler-DeWitt equations. We will attempt to solve those equation generally for aforementioned type of spa- cetimes. Our initial midisuperspace model is Roberts dynamical spacetime. As we will see later, Roberts metric behaves badly in the asymptotic region. Due to this problematic behaviour of Roberts spacetime at the boundary, we will choose to quantize its static version, the special Janis-Newman-Winicour spacetime. This midisuperspace model is static, asymptotically flat spacetime with scalar field and it contains a naked time-like singularity. For special Janis-Newman-Winicour spacetime we will then solve Wheeler-DeWitt equations.

O presente trabalho pretende traçar o percurso diacrônico da formação e da fixação do cânon da Bíblia Hebraica, dando especial atenção às teorias e hipóteses que, no passado, foram aventadas e, modernamente, rechaçadas e substituídas por outras. A hipótese tradicional acerca da formação do cânon da Bíblia Hebraica de acordo com a qual três estágios diferentes poderiam ser destacados ao longo do processo que culminou na formação da antologia sagrada dos judeus, de forma que cada um deles equivaleria ao momento de canonização de uma das três seções em que se divide a Bíblia Hebraica (Lei, Profetas e Escritos) será apresentada, assim como as críticas modernas que diversos pesquisadores têm dirigido contra ela, propondo novas formas de entendermos a gênese do cânon bíblico. Esta dissertação trata, pois, dos escritos que viriam a compor o corpo canônico de textos que ficaria conhecido, na tradição judaica, como Tanakh ou, na cristã, como Antigo (Primeiro) Testamento. Não faz parte de nosso escopo o estudo de outros cânones sagrados, mesmo aqueles que, de maneira evidente, tenham se originado a partir do cânon judaico. O processo através do qual certos livros, em detrimento de outros, foram incorporados à compilação de escritos sagrados será evidenciado, e a existência de variações entre os cânones de diferentes grupos religiosos não será discutida, embora a sua menção seja necessária. Dado o crescente desenvolvimento dos estudos bíblicos, faz-se necessário que, de maneira semelhante, os estudos de base adolesçam, isto é, que também se desenvolvam os metaestudos da Bíblia, cujo objetivo precípuo não é lê-la ou interpretá-la, mas se debruçar sobre a sua forma final e explicitar os processos e os mecanismos que a fizeram ter a configuração com que chegou a nós. Por fim, as consequências hermenêuticas advindas do fechamento do cânon da Bíblia Hebraica serão apresentadas. / The present work intends to trace the diachronic process of formation and fixation of the Hebrew Bibles canon, giving special attention to the theories e hypotheses that, in the past, have been proposed and, nowadays, denied and replaced by another ones. The traditional hypothesis about the formation of the Hebrew Bibles canon according to which three stages can be highlighted along the process that culminated in the formation of the Jewish sacred anthology, in such a way that each one of these stages would match the respective moment in which one of the three Hebrew Bibles section (Law, Prophets and Writings) was canonized will be presented, as well as the modern critics that several researchers have raised against it, while they propose new ways to understand the biblical canons genesis. This dissertation, therefore, deals with the writings that would be included in the canonical textual corpus, which would afterwards be called Tanakh, in the Jewish tradition, or Old (First) Testament, according to the Christian heritage. It is not the scope of this work to study another sacred canons, even those that clearly originated from the Jewish canon. The process through which certain books, in lieu of other ones, have been incorporated to the compilation of sacred writings will be demonstrated, and the variations among the canons recognized by different religious groups will not be dealt with, although it will be necessary at least to mention it. Given the growing development of the biblical studies, it is imperative, equally, that the underlying studies flourish, this is, that the biblical meta-studies also evolve, whose main goal is not to read the Bible or interpret it, but to analyse its final shape and exhibit the processes and the mechanisms that originated its configuration with which it came to us. Finally, the hermeneutical consequences due to the closing of the biblical canon will be presented.

As septinas compõem o quarto componente do citoesqueleto das células eucarióticas, atrás da actina, miosina e filamentos intermediários. São proteínas filamentosas que se arranjam em forma de fibras e anéis, desempenhando um papel estrutural na célula. Os seres humanos expressam 13 septinas, que são divididas em 4 grupos diferentes de acordo com sua estrutura primária: grupo I (SEPT3, SEPT9, SEPT12); grupo II (SEPT6, SEPT8, SEPT10, SEPT11, SEPT14); grupo III (SEPT1, SEPT2, SEPT4, SEPT5) e grupo IV (SEPT7), sendo que SEPT13 foi caracterizada como um pseudogene de SEPT7. O filamento fisiológico mais bem estudado é composto por SEPT2-SEPT6-SEPT7-SEPT9 (nesta exata sequência), e é usado como a base para a descrição da formação canônica, onde se acredita que septinas do mesmo grupo ocupam o mesmo lugar no filamento. Entretanto, ensaios de duplo-híbrido identificaram muitas interações não canônicas inesperadas entre septinas como SEPT9-SEPT6 e SEPT9-SEPT8, sugerindo estes também possam existir in vivo. Além destes, estudos mostraram a existência de interações entre septinas do grupo I e grupo II, e especialmente no caso SEPT11-SEPT12, a interação deixa de existir ao inserir uma mutação sítio-dirigida na interface G destas proteínas. O presente trabalho investiga a interação entre SEPT3, uma septina do grupo I, com todas aquelas do grupo II. Esta interação foi estudada por análises de coexpressão e copurificação em resina de afinidade ao cobalto, onde apenas a SEPT3 possuía uma extensão de seis histidinas em seu N-terminal. Esta primeira análise mostrou que SEPT3 não foi copurificada com todos os membros do grupo II dando uma clara evidência de variação de afinidade dentro do grupo. Usando esta abordagem, SEPT6, SEPT10 e SEPT14 não mostraram interação com SEPT3, enquanto SEPT8 e SEPT11 copurificaram com SEPT3, mas não em concentrações estequiométricas. Para os complexos SEPT3-SEPT8 e SEPT3-SEPT11, uma segunda etapa de purificação foi realizada por meio de cromatografia de exclusão molecular, onde um pico de grande variância em relação à média indicou um valor de massa molecular entre monômeros e dímeros. Os mesmos, quando avaliados por espalhamento de luz a múltiplos ângulos mostraram variação na massa molecular ao longo do pico de eluição conforme ele era eluído. Tal variação era compatível com a eluição de dímeros no início até monômeros no final. Os estudos da interação entre SEPT3-SEPT8 por ultracentrifugação analítica indicou uma tendência de associação em altas concentrações das proteínas, compatível com a constante de dissociação determinada por termoforese em microescala, na ordem de dezenas de micromolar. Tais resultados levantaram questões acerca da relevância fisiológica destes complexos e reforçam a importância de um estudo mais aprofundado na formação dos complexos não canônicos de septinas para o desenvolvimento celular. / The septins are accepted to be the fourth cytoskeleton component of the eukaryotic cells, after actin, myosin and intermediate filaments. They are filament forming proteins that are organized in fibers and rings, having a structural role in the cell. Humans express 13 septins, which are divided into 4 different groups according to their primary structure: group I (SEPT3, SEPT9, SEPT12); group II (SEPT6, SEPT8, SEPT10, SEPT11, SEPT14); group III (SEPT1, SEPT2, SEPT4, SEPT5) e group IV (SEPT7). SEPT13 was later characterized as a SEPT7 pseudogene. The best characterized filament is built up from SEPT2-SEPT6-SEPT7-SEPT9 (in this exact sequence), and is used as a basis for the description of the so-called canonical arrangement, which accepts that septins from the same group can occupy the same position within the filament. However yeast two-hybrid assays identified several unexpected interactions such as SEPT9-SEPT6 and SEPT9-SEPT8, raising the possibility that these could also exist in vivo. Furthermore, studies have shown the existence of interactions between group I and group II, and especially in the SEPT11-SEPT12, the interaction dissolves when a mutation in the G interface is inserted. The present work investigates the interaction between SEPT3, a group I septin, with all of those from group II. This interaction was studied through co-expression and co-purification methods using metal affinity chromatography, where only the SEPT3 contained the six histidines extention. This initial analysis showed that SEPT3 did not co-purify with all group II members, clearly pointing to variability in the affinity within group. Using this approach SEPT6, SEPT10 e SEPT14 showed no interaction with SEPT3, whilst SEPT8 and SEPT11 co-purified with SEPT3, but not in stoichiometric concentrations. For the SEPT3-SEPT8 and SEPT3-SEPT11 complexes, a second purification stage was performed using size exclusion chromatography, where a broad peak was observed corresponding to a molecular mass value which was intermediate between a dimer and a monomer. The same complexes, when evaluated by multiple angle light scattering revealed a variation in the molecular mass across the peak as it eluted. Such variation was compatible with elution of dimers at the beginning and monomers at the end. Studies for the SEPT3-SEPT8 interaction via analytical ultracentrifugation suggested a trend to associate in high protein concentration, consistent with the dissociation constant found by microscale thermophoresis, which was of the order of ten micromolar. The results raise questions concerning the physiological relevance of these complexes and reinforce the importance of further studies on the non-canonical assembly of septin complexes for cellular development.

La thèse est constituée de deux parties. La première concerne la très amplitude du diviseur canonique relatif, tandis que la seconde traite de la positivité de la caractéristique d'Euler de surfaces.Dans la première partie, on se donne une courbe régulière propre sur un anneau de Dedekind (dont les corps résiduels aux points fermés sont parfaits), de fibre générique de genre plus grand ou égal à 2. Après contractions de certains diviseurs verticaux, on obtient son modèle canonique. On montre que toute puissance tensorielle supérieure ou égale à 3 du faisceau dualisant relatif sur le modèle canonique est très ample. Ceci améliore un résultat de Jongmin Lee.Dans la deuxième partie, pour tout nombre premier p différent de 2, nous montrons qu'il existe une constante positive k_p, telle que pour toute surface projective lisse X de type général définie sur un corps algébriquement clos de caractéristique p, on ait l'inégalité \xi(O_X) ≥ k_pc_1^2(X). / This thesis is divided into 2 parts. The first part concerns with the amplitude of relative canonical divisors, and the second part deals with the positivity of the Euler characteristics of surfaces.In the first part, given a minimal arithmetic surface over a Dedekind ring whose residue fields at closed points are perfect, suppose the general fibre has genus at least 2, after contracting some vertical divisor, we will obtain its canonical model. We prove in this part that 3 or more times the relative canonical divisor of this canonical model is very ample. This simplifies and generalizes a result of Jongmin Lee.In the second part, we prove that for all prime numbers p>2, there is a positive number k_p, such that \xi(O_X) ≥ k_p c_1^2(X) holds true for all algebraic surfaces X of general type in characteristic p. In particular, \xi(O_X)>0. This answers a question of N. Shepherd Barron when p>2.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Corn is one of the crops that produce more in the world; it has a wise geographic distribution. It happens because of the big genetic variability present, including in creole cultivates which they are normally produced in small properties. The main goals of this study were to evaluate the growing and the relation between the seeds labile, grown plants and of the Amarelão creole cultivates, Lombo Baio and Oito carreiras as well as the maternal half-brothers progenies from these cultivates. The experiment happened in Santa Maria, RS in the agricultural year of 2012/2013, in block delineations aimlessly with four repetitions and portions constituted by two lines of five meters to the creole cultivates and a lattice delineation with constituted portions one line of five meters with a space of 0,2m and between lines of 0,9m. For an analysis of the growing plants was accomplished five evaluations of the plant height and leaves numbers by plant and the growing curves were adjusted by logistic model because of the thermal sum accumulated. To analyze the canonical correlation were evaluated: mass, length, width, and seeds thickness; plant height, ear insertion height, thatch diameter and leaves number by plant for grown plants, grain weights, row numbers and grain numbers by rows to the production. The logistic model was adequate to the growing curve adjusts to progenies of maternal half-brothers and corn creole cultivates. Amarelão creole cultivates, Lombo baio and Oito carreiras present the highest plant and the biggest number of leaves by plant in comparison to concerning progenies of maternal half-brothers. The most important canonical correlations were gotten between labile groups of the grown plant and production. The labile plant height and thatch diameter were the most favorable the grain production. / O milho é uma das culturas mais produzidas no mundo, com ampla distribuição geográfica. Isso se deve a grande variabilidade genética presente, inclusive em cultivares crioulas, normalmente produzidas em pequenas propriedades. Os objetivos do estudo foram avaliar o crescimento e a relação entre variáveis de sementes, plantas adultas e de produção das cultivares: crioulas Amarelão, Lombo Baio e Oito Carreiras, bem como, de progênies de meios-irmãos maternos destas cultivares. O experimento foi conduzido em Santa Maria, RS, no ano agrícola 2012/2013, em delineamento blocos ao acaso com quatro repetições e parcelas constituídas por duas fileiras de cinco metros e espaçamento entre plantas de 0,2 m e entre fileiras de 0,9 m para as cultivares crioulas e, delineamento em látice com parcelas constituídas de uma fileira de cinco metros e espaçamento entre plantas de 0,2 m e entre fileiras de 0,9 m para as progênies. Para análise de crescimento das plantas, foram realizadas cinco avaliações de altura de planta e número de folhas por planta, com as curvas de crescimento sendo ajustadas pelo modelo logístico em função da soma térmica acumulada. Para análise das correlações canônicas foram avaliadas: massa, comprimento, largura e espessura das sementes, altura de planta, altura de inserção da espiga, diâmetro do colmo e número de folhas por planta para plantas adultas e peso de grãos, número de fileiras e grãos por fileira para a produção. O modelo logístico foi adequado para o ajuste das curvas de crescimento para progênies de meios-irmãos maternos e cultivares crioulas de milho. As cultivares crioulas: Amarelão, Lombo Baio e Oito Carreiras apresentaram maior altura de plantas e maior número de folhas por planta em comparação às respectivas progênies de meios-irmãos maternos. As correlações canônicas mais importantes foram obtidas entre os grupos de variáveis de planta adulta e de produção. As variáveis altura de planta e diâmetro do colmo as que mais favorecem a produção de grãos.

Des mutations du gène STK11 furent initialement décrites comme responsable du syndrome Peutz-Jeghers, dont la gravité est lliée à une incidence accrue d’apparition de tumeurs. Le produit de ce gène, la sérine/thréonine kinase LKB1, a une expression ou une activité catalytique réduite, voir perdue, consécutivement à des mutations somatiques dans plusieurs types de cancer mais principalement du poumon (30% des NSCLC). Cette kinase est considérée de ce fait comme un suppresseur de tumeur d’importance. Les mécanismes moléculaires responsables de sa propriété suppresseur de tumeur restent à identifier. En effet, alors que sa fonction dans le métabolisme cellulaire, au travers de l’activation de la kinase AMPK, fut longtemps privilégiée, elle est actuellement remise en cause au profit de sa fonction de régulatrice de la signalisation Wnt canonique. Mes travaux de thèse confortent cette éventualité dans le cas des tumeurs pulmonaires (NSCLC). En effet, parmi les deux complexes fonctionnels que forme LKB1 avec les pseudokinases STRADα ou β, mes résultats démontrent que seul celui impliquant STRADβ intervient dans la régulation de la voie Wnt. Pour cela, le complexe LKB1/STRADβ se localise au niveau du cil primaire et participe à l’activation de la kinase MARK3. Ces résultats, étayés par un modèle murin invalidé pour STRADβ ainsi que l’analyse, a posteriori, de bases de données transcriptomiques adossées aux données cliniques de patients atteints de NSCLC, suggèrent que l’activité suppresseur de tumeur de LKB1 est associée à sa localisation et à sa fonction au niveau du cil primaire en participant à l’activation de MARK3 et à la régulation de la signalisation Wnt canonique. / STK11 gene mutations were originally identified as responsible for the Peutz-Jeghers syndrome of which severity is mainly related to an increase incidence of tumor development. The product of this gene the serine/threonine kinase LKB1 gets its activity or its expression reduced, sometimes even lost, following somatic mutations in several types of cancer such as pancreas, liver but mainly from lung. Indeed, almost 30% of non-small cell lung carcinoma (NSCLC) does not express anymore or only an inactive form, has led to consider this kinase as tumor suppressor of importance. While there is no doubt of the involvement of its catalytic activity molecular mechanisms responsible for its tumor suppressor properties remain to be identified. Indeed, whereas its function as regulator of cellular metabolism through AMPK has been favor for a while, it is currently re-assess to benefit to its regulator function on canonical Wnt signaling. My thesis work, reinforce this eventuality in NSCLC. Indeed, among the two functional complexes formed by LKB1 through its association with STRADα or β pseudokinases, my results show that only the complex related to STRADβ is involved in the canonical Wnt pathway regulation. For that, LKB1/STRADβ complex localizes at primary cilia and participates to MARK3 kinase activation. These results strengthened by a STRADβ knockout mouse model and an a posteriori transcriptomic analysis of lung adenocarcinoma patient datasets related to their clinical records, suggest that LKB1 tumour suppressor activity is associated with its localization and its function at primary cilia participating in the activation of MARK3 and thus regulation of canonical Wnt signaling.

Neurogenin 2 (Ngn2) is a basic Helix-Loop-Helix (bHLH) transcription factor regulating differentiation and cell cycle exit in the developing brain. By transcriptional upregulation of a cascade of other bHLH factors, neural progenitor cells exit the cell cycle and differentiate towards a neuronal fate. Xenopus laevis Ngn2 (xNgn2) is a short-lived protein, targeted for degradation by the 26S proteasome. I have investigated the stability of Ngn2 mediated by post-translational modifications and structural disorder. Firstly I will describe work focused on ubiquitylation of xNgn2, targeting it for proteasomal degradation. xNgn2 is ubiquitylated on lysines, the recognized site of modification. I will discuss the role of lysines in ubiquitylation and stability of xNgn2. In addition to canonical ubiquitylation on lysines, I describe ubiquitylation of xNgn2 on non-canonical sites, namely its amino-terminal amino group, and cysteine, serine and threonine residues. I show that the ubiquitylation of cysteines in particular exhibits cell cycle dependence and is also observed in mammalian cell lines, resulting in cell cycle-dependent regulation of stability. I will then discuss whether phosphorylation, a regulator of xNgn2 activity, also affects xNgn2 stability. I will provide evidence of cell cycle-dependent phosphorylation of cyclin dependent kinase (cdk) consensus sites affecting the stability of xNgn2. Finally I describe studies on the folding properties of Ngn2 to assess their role in protein stability. xNgn2 associates with DNA and its heterodimeric binding partner xE12 and may interact directly with the cyclin-dependent kinase inhibitor Xic1. I will discuss the role of these interaction partners in xNgn2 stability. xNeuroD, a downstream target of xNgn2, is a related bHLH transcription factor which is stable. Here I describe domain swapping experiments between these two proteins highlighting regions conferring instability on the chimeric protein. Finally I will provide nuclear magnetic resonance (NMR) data looking at the effect of phosphorylation on protein structure in mouse Ngn2 (mNgn2).

We sought to investigate the role of the Planar Cell Polarity (PCP) pathway in neuronal positioning along the Anterior-Posterior (AP) axis of C. elegans, and chose the worm’s DD-type motor neurons as a model. The six DD neurons (DD1-DD6) are evenly spaced in the ventral nerve cord of wild type animals. Here we showed that mutations in core PCP genes caused DD neuron spacing and positioning defects. prkl-1 double mutant combinations with vang-1 and fmi-1 showed a suppression of the more severe prkl-1 single mutant defects, which was evidence of genetic interactions between these PCP components. We also conducted a candidate screen of Frizzled, Dishevelled, Wnt, and ROCK genes, and found that dsh-1/Dishevelled, mom-2/Wnt and let-502/ROCK also played roles in DD neuronal positioning. Both vang-1 and prkl-1 were found to function within the nervous system to guide DD neuronal positioning, and prkl-1 was further identified as playing a cell autonomous role. The origins of observed DD neuron anterior positioning defects were investigated during embryogenesis, in which 1.5 fold stage prkl-1(ok3182) embryos displayed delayed intercalation of the DD neurons. This represents a novel role for the PCP pathway in mediating DD neuronal intercalation.

There were two major goals of this study - to examine validity of scores for the Boholst Life Position Scale and to examine potential associations between life positions and affective traits. Two hundred seventy-seven students enrolled in undergraduate psychology classes at a large university volunteered for the study. Concurrent validity of scores for the life position scale was supported based on two compared instruments. Pearson product-moment correlations for the comparisons were -.765 and .617, both statistically significant at the p < .001 level. Factor analysis demonstrated that the scale could accurately be conceptualized as consisting of two factors - an "I" factor and a "You" factor. MANOVA, ANOVA, multiple linear regression, and canonical correlation analysis were used to examine associations between life positions and the affective traits of angry, sad, glad, social anxiety, loneliness, and satisfaction with life. Subjects were catagorized into four groups representing their life position: "I'm OK, you're OK," "I'm OK, you're not OK," "I'm not OK, you're OK," and "I'm not OK, you're not OK." A MANOVA employing life position as the independent variable with four levels and the six affective traits as the dependent variables demonstrated statistical significance (p < .001 level) and h2 was .505. All six separate ANOVAs, with life position as the independent variable and each separate affective trait as the dependent variable, revealed statistical significance (p < .001) and h2 varied from a high of .396 for the sadness variable to a low of .116 for social anxiety. Six separate multiple linear regression equations using two independent variables, a measure of self-esteem and a measure of the perceived OK-ness of others, and each separate affective trait as the dependent variable, showed statistical significance (p < .001). The average Adjusted R2 was .475. Both canonical correlation functions were statistically significant (Rc12 = .77 and Rc22 = .21). In summary, life positions were strongly associated with specific affective traits.