Teses / dissertações sobre o tema "Pasis"
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Aljoumaa, Kadan. "Modélisation intentionnelle et annotation sémantique pour la réutilisation de services métiers PASiS: Publishing And Searching of Intentional Services". Phd thesis, Université Panthéon-Sorbonne - Paris I, 2011. http://tel.archives-ouvertes.fr/tel-00708168.
Texto completo da fonteFournier, Éric. "Paris en ruines : du Paris haussmannien au Paris communard /". Paris : Imago, 2007. http://catalogue.bnf.fr/ark:/12148/cb41196886v.
Texto completo da fonteFinski, Siarhei. "On some problems of holomorphic analytic torsion". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/FINSKI_Siarhei_va.pdf.
Texto completo da fonteIn the first context, we study the asymptotics of the analytic torsion, when a Hermitian holomorphic vector bundle is twisted by an increasing power of a positive line bundle. In the second context, we generalize the theory of analytic torsion for surfaces with hyperbolic cusps. Motivated by singularities appearing in complete metrics of constant scalar curvature -1 on stable Riemann surfaces, we suppose that the metric on the surface is smooth outside a finite number points in the neighborhood of which it can to have singularities like Poincaré metric has on a punctured disc. We fix a Hermitian holomorphic vector bundle which has at worst logarithmic singularities in the neighborhood of the marked points. For these data, by renormalizing the trace of the heat operator, we construct the analytic torsion and study its properties. Then we study the properties of the analytic torsion in family setting: we prove the curvature theorem, we study the behavior of the analytic torsion when the cusps are created by degeneration and we give some applications to the moduli spaces of pointed curves
Leyrolle, Quentin. "Rôle des acides gras polyinsaturés n-3 dans le développement cérébral normal et pathologique". Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/LEYROLLE_Quentin_va.pdf.
Texto completo da fonteThe perinatal dietary intake in n-3 and n-6 polyunsaturated fatty acids (PUFAs n-3 and n-6), also known as ‘omega-3’ and ‘omega-6’, is essential for brain development. As these lipids cannot be de novo synthesized by the body, they must be provided by the diet according to a ratio of one n-3 PUFA for four n-6 PUFAs. Western diet has dramatically evolved over the past 70 years, towards excessive omega-6 consumption and reduction in omega-3 intake. This correlated with an increasing number of children with neurodevelopmental pathologies. However, the link between perinatal nutrition and neurodevelopment remains poorly understood. The main objective of my thesis was to study the cellular and molecular mechanisms by which a reduction in perinatal n-3 PUFA dietary intake alters neural networks shaping, focusing on the interactions between glial cells (namely microglia and oligodendrocytes) and neurons. Our results show that perinatal n-3 PUFA deficiency leads to 1) an alteration of microglial and oligodendrocytes functions during brain development; 2) an increase in microglia-mediated dendritic spines pruning and deficits in myelination process; 3) the establishment of dysfunctional neural networks in the hippocampus and prefrontal cortex; 4) deficits in learning, sociability and occurrence of anxiety behaviors. Moreover, n-3 PUFA deficiency during the perinatal period exacerbates the deleterious effects of a prenatal maternal immune activation (MIA). Low n-3 PUFA intake 1) increases the maternal and fetal inflammatory response to MIA; 2) increases the duration and extent of MIA effects on neuronal morphology and microglia-neuron interactions; 3) alters the inflammatory reactivity of intestinal lymphocytes, that persists at adulthood 4) induces memory deficits and hyperactivity in offspring in adulthood. Overall, the present work specified some of the mechanisms by which n-3 PUFA deficiency affects the developing brain by highlighting its detrimental effect on microglia and oligodendrocytes function and showing how its sensitizes the brain to other developmental insults
Latis, Eleonora M. T. "Exploring immunological mechanisms of human graft-versus-host disease after hematopoietic stem cell transplantation". Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/LATIS_Eleonora_va.pdf.
Texto completo da fonteAllogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematologic malignancies. However, its success is hindered by graft-versus-host disease (GVHD), a potentially fatal complication deriving from alloreactive donor T cells attacking recipient tissues. Acute GVHD (aGVHD) prevalence lies between 40 and 80% depending on transplant characteristics. GVHD is the main cause of non-relapse morbidity and mortality after HSCT and despite the advances in the field, disease processes in humans remain poorly understood.In this study we investigated the phenotypic and molecular characteristics of immune cells in patients after HSCT and in their HLA-identical sibling donors, with the goal of defining immune parameters associated with the recovery of donor-derived immunity and with the development of acute GVHD. We analysed 101 donor-recipient pairs in three independent cohorts for which blood was collected from the donors before transplantation and for the recipients either at aGVHD onset, before any treatment, or at day 30 or 90 post-HSCT for recipients that did not develop GVHD. On the donors’ and recipients’ samples we performed cellular profiling using spectral flow cytometry as well as gene expression analysis.Immunophenotyping reveals an incomplete reconstitution of the T cell compartment in the recipients, with an inversion of the CD4/CD8 ratio, both at one and three months after HSCT. Moreover, the reconstituting T cell compartment is characterized by a shift in the effector/memory phenotype of these cells, with a parallel depletion of the naïve T cell pool. NK cell reconstitution is characterized by an expansion of the CD56bright subset, while monocytes undergo an expansion of CD16+ cells. At aGVHD onset recipients have an increase of cells with a T stem cell memory-like (TSCM-like) phenotype compared to recipients without aGVHD. These cells may represent a cellular reservoir for GVHD, maintaining the production of alloreactive T cells in the presence of host persistent antigens. Molecular profiling shows that donor T cells react to the environment of the host by acquiring an activated phenotype, with upregulation of genes associated with T cell activation, adhesion, migration and effector functions. T cell transcriptome profiling at aGVHD onset shows upregulation of inflammatory mediators as well as genes involved in cytokine signal transduction, cell migration and cell trafficking.Our data demonstrate that comprehensive analysis of the distribution of different immune cell subsets with flow cytometry together with gene expression profiling can contribute to elucidate the processes involved in immune reconstitution and acute GVHD development in humans. In the future, studies with new technologies will hopefully bring insights into the mechanisms underlying GVHD development that will help design new preventive and therapeutic strategies to be applied in the clinics
Alsina, Francisco. "L'ouverture chez Lacan et ses conséquences cliniques". Thesis, Université de Paris (2019-....), 2020. https://theses.md.univ-paris-diderot.fr/ALSINA_Francisco_va.pdf.
Texto completo da fonteFor Lacan, the notion of “the opening” is not a psychoanalytic concept. This term encompasses several different expressions and ideas, which, in Lacan’s thought, relate to holes, gaps, and unsurpassable distances. In the early nineteen-fifties, Lacan uses the word béance—a gaping hole—when he articulates his first hypothesis regarding symbolic absence. Thus, béance is the first word that contributes to Lacan’s lexicon concerning openings. In following seminars, other forms of openings appear. First, the space of the tomb, a concept Lacan addresses in his reading of the death of Oedipus, in his analysis of Antigone, and in his treatment of Hamlet. In these two tragedies by Sophocles, and in Shakespeare’s play, Lacan discoversan opening that allows him to envision modifications to the theories of subject and object in psychoanalysis. After this analysis of the grave, empty space occupies a central place in Lacan’s thought. In his discussion of Antigone, where Lacan broaches the subject of Freud’s “Thing”, and in his first treatment of the objet petit a, the question of openings is approached through art history. This project explores the intersections of psychoanalysis, literature, and art history and examines the space between the subject and the object of its desire. In doing so, the study furthers the work Lacan began in the late nineteen-fifties on the birth of linear perspective and the vanitas in painting. These preliminary explorations of the theme of the opening in psychoanalysis led Lacan, in his later work, to approach the idea of the opening through topology. The present study can be understood as a regrouping of the preliminary instances where openings and their mathematical formalizations appear in Lacan’s work
Ramirez, de Arellano José. "Politique linguistique et enseignement de langues étrangères au "Cono Sur"". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/RAMIREZ_DE_ARELLANO_Jose_va.pdf.
Texto completo da fonteThis thesis focuses on changes that took place in the teaching of Spanish and Portuguese as foreign languages in the education systems of Brazil, Argentina and Uruguay during the so-called Golden Decade spanning approximately from 2003 to 2012. Measures like the Law 11.161/2005 in Brazil, which compelled high schools to offer Spanish as an optional subject; the Law 26.468/2009 in Argentina, which established the same requirement for Portuguese; and the Law 18.437/2008 in Uruguay, which recognises Portuguese-based dialects spoken in the north of the country, imply a historical transformation of the relationship between these two Iberian languages, which had thus far been characterised by mutual marginality in school systems. However, the projects embodied in these laws clash with several budgetary, logistic, ideological and geopolitical realities which compromise their final achievement. Throughout this work we will try to identify which actors, forces and obstacles align around these languages in these three countries. Based on standard theoretical schemes integrating the notion of Language Planning, we propose a three-plane model where corpus, status and gravitation will allow us to apprehend the specificities of this case study: No other pair of languages in the world presents this level of both intelligibility and sociolinguistic importance, and never before had a generalised reciprocal teaching of them been so seriously attempted. Therefore this inquiry will focus on : (1) How does the fact that they are closely related languages determine determine their glottopolitical relationship and their insertion into education systems; (2) Which discourses accompany these and other foreign languages taught in schools and which political projects do they represent; (3) What are their internal gravitational characteristics, their projection and for which languages do they show preference in their translation flows. We thus hope to draw valid conclusions on gravitational vicissitudes of Spanish and Portuguese, as well as to shed some light on the challenges faced and resources found by supercentral languages in their quest for international spaces.This analysis shoud allow a better characterisation of the dichotomy between two models of linguistic globalisation: hypercentralist and supercentralist. One is unipolar, with English as the hegemonic language and supercentral languages relegated to local levels; the other is pluripolar, with these languages sharing their international presence under a prevailing glottopolitical horizontality
Nabuco, Leva Ferreira de Freitas Jose Americo. "Applying Systems Biology and Multi-layered Profiling Towards a Comprehensive Understanding of Cell Aging". Thesis, Université de Paris (2019-....), 2020. https://theses.md.univ-paris-diderot.fr/FREITAS_JoseAmerico_va.pdf.
Texto completo da fonteCellular senescence (CS) is a cell fate characterized by a stable cell cyclearrest of dysfunctional cells. CS has an intricate role in physiology and patho-physiology. Senescent cells play a vital role in tumor suppression, embryonicdevelopment, and wound healing, but also in many age-related pathologies,including paradoxically, tumor development. My thesis work represents acomprehensive time-resolved analysis of the epigenome, transcriptome, andmetabolome layers of cells undergoing CS and is divided into three subprojects.First, I investigated the dynamics of transcription factor (TF) binding toenhancers in oncogene-induced senescence (OIS). TFs organize in a hierar-chical network, with pioneers shaping the enhancer landscape by recruitingsettlers and migrants to fine-tune gene expression. Specifically, I discoveredthat the AP1 family members precede the majority of other TFs, primingchromatin to initiate and coordinate the CS transcriptional response.Second, I performed an extensive analysis of the metabolic changes asso-ciated with CS, integrating results from fibroblasts undergoing replicative,oncogene-induced, and DNA damage-induced senescence, in addition to acharacterization of OIS in primary myoblasts. I identified several metabolitesthat accumulate or diminish in senescent cells, and those are associated withpost-translational modifications, protein synthesis, lipid biosynthesis and oxi-dation, and energy production. In particular, alpha-ketoglutarate (aKG) anduridine diphosphate N-acetylglucosamine (UDP-GlcNAc) act as substratesfor chromatin modifiers, suggesting roles in gene regulation.Third, I defined a mathematical model describing the transcriptionalevolution of cells undergoing OIS. I generated this model using the SparseIdentification of Nonlinear Dynamics (SINDy) algorithm in a high-performancecomputing environment. I validated the model with transcriptome dataderived from JUN and RELA depletion experiments. On inhibition of JUN, amember of the AP1 family, the model simulation behaved closer to senescentcells than on RELA, suggesting that TF rank in the chromatin bindinghierarchy may determine the predictability of its transcriptional response.Together, my integrative analysis provides a deeper understanding of CSand has the potential to reveal previously unknown vulnerabilities of senescentcells that may be exploited to treat cancer and age-related diseases, promotinga longer healthspan
Ibn, Saied Wafa. "Pneumopathie nosocomiale acquise en réanimation : caractérisation en fonction de l’existence et de la durée de ventilation mécanique". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/IBN_SAIED_Wafa_va.pdf.
Texto completo da fonteHealthcare-associated infections are the leading cause of death and the first prescription of antibiotics. Healthcare-associated pneumonia represents the first cause of morbidity mortality in ICU. In the context of limited antibiotic resources and an increase in the incidence of resistant germs, we studied:1) Risk factors for ventilator acquired pneumonia (VAP) taking into account the duration of mechanical ventilation (MV).2) If there is a difference between nonventilated and mechanically ventilated pneumonia in terms of etiology and prognostic?3) What is the impact of the adequacy of the initial antibiotic treatment, and what are the risk factors for inadequate treatment in gram-negative resistant VAP?Our results show that: Pneumonia acquired by no ventilated patient in the ICU (ICU-HAP) and VAP are due to the same germs with a higher risk of death in ICU-HAP. Early and late VAP are associated with different risk factors that may need different prevention policies. Previous-antibiotic therapy and prior-colonization with multiresistant bacteria explain the occurrence of resistant Gram Negative VAP. Duration of MV before the onset of pneumonia is no longer an independent risk factor for the occurrence of resistant gram-negative VAP. A percentage of infection or colonization with resistant BGN upper to 10% in the centre is associated with the occurrence of a gram-negative, resistant PAVM, regardless of individual risk factors. S. maltophilia VAP occurs belatedly and are very widely associated with high antibiotic consumption, especially penems. They are more often associated with inadequate initial antibiotic therapy.Our work confirms the need for further research to optimize the diagnosis and early adequacy of antibiotics, in particular in ICU-HAP and VAP caused by potentially antibiotic-resistant BGN
Sadr, Mohammad. "Les particularités liées à la sexualité : conception du médecin Rāzī (IXe-Xe)". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/SADR_Mohammad_va.pdf.
Texto completo da fonteAmong ancient Greek and Islamic period physicians there are several theories regarding the determinants of sex of the fetus. Hippocrates, Aristotle and Galen each proposed different theories for the sex determination of male or female embryos.In these theories, various factors such as strength and dominancy of male or female semen to each other, external factors like heat and cold, the location of the fetus in the uterus, the kind of winds blowing in that area and have been mentioned.In the current research, views of ancient Greek physicians on this subject will be discussed based on the transmission of their writings to the current time or translations or citations of their works in medical texts of the Islamic period such as Firdaws al-hikma fi Ṭibb and al-Ḥāwī fi Ṭibb. Afterwards Razi’s (IXe-Xe) view will be analyzed according to his independent treatise titled al-ubnah, the theories mentioned in al-Ḥāwī fi Ṭibb, and then it will be compared with the opinions of ancient Greek physicians. Rāzī, based on his point of view on the sex determination of the fetus, has explained sexual disorders like attraction between men. In this research, such attraction and his treatments proposed will be discussed
Gorsky, Mikhail. "Algèbres de Hall et localisation des catégories". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/GORSKY_Mikhail_va.pdf.
Texto completo da fonteThis thesis concerns Hall algebras. We define twisted extended Hall algebras of triangulated categories and show that in some cases they are well-defined even when their non-extended counterparts are not. We show that each exact category with weak equivalences with an appropriate extra structure naturally gives rise to a twisted extended Hall algebra of its homotopy category.We prove that this construction recovers Bridgeland's categorification of quantum groups via Hall algebras of complexes and its generalization due to Lu and Peng. We prove that the algebras thus defined are functorial under exact functors respecting weak equivalences. This allows us to prove the tilting invariance of Bridgeland's algebras and to categorify Lusztig's symmetries of quantum groups. Under suitable finiteness conditions, for two different exact structures on the same additive category with one having strictly less conflations than the other, we define a filtration on the Hall algebra of the latter whose associate graded is the Hall algebra of the former. This construction generalizes quantum PBW-type filtrations
Allibert, Laëtitia. "Érosion collisionnelle au cours de l’accrétion et origine des compositions non chondritiques de la Terre". Thesis, Université de Paris (2019-....), 2020. https://theses.md.univ-paris-diderot.fr/ALLIBERT_Laetitia_va.pdf.
Texto completo da fonteThe thesis aim is the study of the last stage of planetary formation (between 1-3 Myr and 200 Myr after the condensation of the first solids in the proto-planetary disk). This thesis is multi-disciplinary, at the interface between geosciences and planetary sciences. It must bring constrains on the dynamical processes involved in the planets formation by studying their effects on the final chemical composition of the terrestrial bodies. There are several processes that may induce chemical fractionation (i.e. processes able to change the chemical composition) during the planets growth history. Notably, the differentiation and the devolatilization are two processes that are often invoked and studied. However, successive impacts suffered by the growing embryos may also affect the global chemical composition of terrestrial planets. This chemical fractionation is the direct result of the different properties and affinities of the different chemical elements. This thesis is built on two distinct axes. Indeed, the Earth is made of three main layers of distinct chemical compositions; from the center to the surface they are: the metallic core, the mantle and the crust. The preferential erosion of one of these layers relatively to an other might thus induce a change in the global composition of Earth. A preferential erosion of crust or a preferential erosion of mantle cannot be tracked with the same tools and clues. During this thesis, we developed an erosion model named EROD that allows to track the evolution of the Bulk Silicate Earth (BSE) chemical composition during Earth assembling. It involves (1) semi-analytical laws of craterization, (2) chemical mass balance calculations and (3) a post-treatment of N-body numerical simulations of accretion. The evolution of the chemical compositions is tested for a large set a chemical elements. The second aspect of the thesis include SPH hydrodynamical numerical simulations of impacts that are run to provide a quantification of the mass transfer during a given impact. A coupling with N-body numerical simulations is also made. We show that collisional erosion may be responsible for a non chondritic Earth final composition, notably in refractory and lithophile elements. The most incompatible elements (i.e. these that have affinities with liquid phases) are the most depleted in the BSE compared to the chondrites. This highest amount of depletion reaches 40% for the heat producing elements such as U and Th. In that case, the models for the BSE composition may need to be revised. Finaly, we show that the superchondritic Fe/Mg ratio of the bulk Earth may be explained by a preferential collisional erosion of the Earth mantle relatively to its core during successive giant impacts occuring while Earth is growing
Sankara, Narayana Gautham Hari Narayana. "Role of non-muscle myosin-II isoforms in adherens junction biogenesis and collective migration". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/SANKARA_NARAYANA_Gautham_Hari_Naryana_va.pdf.
Texto completo da fonteAdherens junction formation and remodeling is essential for many biological processes like embryo compaction, tissue morphogenesis and wound healing. It is now well described that non-muscle myosin II (NMII) acts as a mechanical support and force-generator for E-cadherin junctions during collective migration and morphogenesis. However, the contribution of NMII during early steps of junction formation remains obscure, probably because of the technical difficulty to catch such a transient event. In this work, we investigate the role of non-muscle myosin II isoforms (NMIIA and NMIIB) during adherens junction biogenesis in MDCK cells, using an in vitro reductionist approach. This system, based on chemically switchable micropatterns allows a spatio-temporal control of adherens junction formation. Our observations on MDCK cells show that the cells form irreversible E-cadherin based contacts, junction elongation is accompanied by the repolarization of actin cytoskeleton and nucleus-centrosome axis. Using isoform-specific ShRNA for NMIIA and IIB, we show that they have distinct contributions to junction formation and dynamics. NMIIA and NMIIB differentially regulate biogenesis of AJ through association with distinct actin networks. Analysis of junction dynamics, actin organization, and mechanical forces of control and knockdown cells for myosins revealed that NMIIA provides the mechanical tugging force necessary for cell-cell junction reinforcement and maintenance. NMIIB is involved in E-cadherin clustering, maintenance of a branched actin layer connecting E-cadherin complexes and perijunctional actin fibres leading to the building-up of anisotropic stress. These data reveal unanticipated complementary functions of NMIIA and NMIIB in the biogenesis and integrity of AJ
Duprilot, Marion. "Étude comparative du clade émergent de Escherichia coli ST131 O25b H4 de son clade progéniteur : fitness in vitro et in vivo et formation de biofilm". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/DUPRILOT_Marion_va.pdf.
Texto completo da fonteThe clade C of Escherichia coli ST131, an extra-intestinal pathogen (ExPEC) multidrug-resistant, emerged worldwide in the early 2000s. Understanding its expansion is one of the major public health challenges. To contribute to this understanding, we took into consideration the phylogenesis of ST131 and focused our research on comparing the clade C with its progenitor, the clade B, which is composed of strains globally sensitive to antibiotics.The phylogenesis of the clone ST131 describes the diversification of the ancestral clade B into different B subclades (from B1 to B5), B5 giving rise to clade C, which itself has diversified into two subclades, C1 and C2. We wanted to learn about the evolution of these different subclades in terms of relative frequency within all ExPECs. For this purpose, we analyzed the ST131 genomes identified within bacteriemic E. coli systematically collected in England between 2001 and 2012. This analysis showed that, during the studied period, (i) ST131 was one of the few dominant clones, with a dominance of clade C strains, particularly those of subclade C2 and (ii) clade B strains persisted in a stable manner, particularly those of subclades B4 and B5, despite an overall relative frequency lower than that of clade C. Besides, we have compiled a collection of 39 ST131 strains that have been found to be representative of the diversity of B and C clades and subclades, with the exception of one B4 strain (called Hybrid), which carries the fimH30 allele, normally specific to the clade C. Through this collection, we have explored the growth and formation of early biofilm (after 2, 3 and 5 hours of incubation) of clade B and C strains. All strains had equal growth capacities, while they differed in biofilm formation: biofilm was more frequently observed in 2 h in clade B strains than in clade C strains. Then, two representative strains of clades B and C, called Ancestor and Emergent, respectively, as well as Hybrid, were subjected to competitions two by two in vitro and in vivo (in various mouse models). Despite the absence of in vitro fitness differences between these three strains, Emergent was found to be less effective in colonizing the intestinal and/or urinary tract in mice and less virulent in the sepsis model than Ancestor and Hybrid. Referring to the non-functional fimB gene in all strains of clade C, a gene encoding one of the regulators of type 1 fimbriae synthesis involved in biofilm formation and bacterial adhesion, we have deleted it in Ancestor and Hybrid. Although the deletion of the fimB gene abolished in vitro the formation of early biofilm observed in parental strains, no effect was observed when mutants were put in competition with their parental strains, in vitro and in vivo; mutant and parental strain also behaved equally with regard to intestinal colonization and virulence in mice. In total, this work suggests that a global loss of virulence, a process known to improve the level of bacterial transmission, has occurred in ST131 clade C in addition to its acquisition of a multidrug resistance, two evolutions likely to ensure better fitness, especially in environments under antibiotic pressure
Rapone, Roberta. "Essential cytoplasmic role(s) of the histone lysine methyltransferase Setdb1 in post-transcriptional regulation of gene expression". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/RAPONE_Roberta_va.pdf.
Texto completo da fonteSetdb1 is a “histone” lysine methyltransferase (KMT) belonging to the SUV39 family that methylates lysine 9 of histone H3 (H3K9), one of the major epigenetic machineries mainly involved in gene repression. Notably, Setdb1 establishes mono-, di- and tri-methylation of H3K9. Setdb1, or Eset in mice, is essential for the survival, the pluripotency and the self-renewal of mouse embryonic stem cells (mESCs); Eset knockout is lethal at the peri-implantation stage at 3.5 dpc in mice. Setdb1 is also required for the differentiation of many progenitor cell types: spermatogenesis, neurogenesis, chondrocyte differentiation and skeletal muscle differentiation. Moreover, Setdb1 has been associated with several diseases: it is amplified in melanoma and lung cancer and it is dysregulated in liver, prostate, colorectal and breast cancers, Huntington disease and schizophrenia.Remarkably, beyond histones, Setdb1 methylates many non-histone substrates, such as UBF, p53, AKT, Tat and ING2 proteins. Although Setdb1 has been always associated with its nuclear role, it turns out that Setdb1 is the only H3K9 KMT to have also a cytoplasmic localization, in several cell types, including mESCs, mouse embryonic fibroblasts (MEFs) and HeLa cells. However, the function of Setdb1 in the cytoplasm remains totally unknown. To investigate Setdb1 cytoplasmic role, we have used mouse embryonic stem cells (mESCs), in which Setdb1 is essential. Our results show that cytoplasmic Setdb1 is crucial for the survival of mESCs: indeed, the number of apoptotic cells increases after the loss of cytoplasmic Setdb1. We found that cytoplasmic Setdb1 affects newly protein synthesis in mESCs. We further show that cytoplasmic Setdb1 interacts with mESCs-specific protein Trim71 (also called Lin41) and with the initiation translation factor eIF3c in mESCs. Finally, we reported that Setdb1 and Trim71 together co-regulate mRNA stability and translation. Our current data unravel the essential cytoplasmic function of Setdb1, for long time considered exclusively an “histone” lysine methyltransferase, and provide new insights into the post-transcriptional regulation of gene expression mediated by a fundamental epigenetic regulator
Robinot, Alexandre. "Etude physiologique du syndrome d’apnées à composante centrale de l’adulte, hors insuffisance cardiaque à fraction d’éjection systolique altérée". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/ROBINOT_Alexandre_va.pdf.
Texto completo da fontePathophysiology of obstructive and central sleep apnea is often dichotomized between obstructive sleep and central apnea, the first is associated with obstruction of upper airways, whereas central sleep apnea is the result of abnormalities of ventilatory control. We hypothesize that, in the central sleep apnea, there are phenotypic features common to obstructive apnea, both in terms of sympathovagal balance and abnormalities in the control of the upper airways, suggesting a pathophysiological continuum between these two types of apnea. In addition, we hypothesize that the respiratory neural network involved in central sleep apnea is different from control subjects but possibly shared with the one of obstructive apnea. To date, only healthy subjects have been studied within the time allotted for this PhD work with regard to this last component.Our results suggestedIn terms of respiratory neural network, in the healthy subject, the insula is the region of interest that has the most gamma 2 oscillations during respiration and communicates at a high frequency level with other regions of interests. The thalamus has a strong coherence with the sensory cortex. Further developments of this work will allow comparison between apneic patients and control, and between central and obstructive apneic patients. Noteworthy we already have a comparison groups of chronic obstructive pneumopathy disease, that will allow comparison between two respiratory pathologies of completely different mechanisms.An increase in the sympathovagal balance in REM sleep compared to slow wave sleep in controls and obstructive SAS, not observed in central SAS, together with a tendency to its decrease during REM in central SAS compared to controls, suggesting a different activation of the autonomic nervous systemPcrit measurements have not been conducted yet, but complete experimental bench is now designed, recruitment of first patients is planed for last trimester 2019. between the slow wave sleep and rapid eyes movements of patients with central and obstructives apneas and the control group.To date our data are too scarce to allow conclusions regarding common pathophysiological pathways between central and obstructive apnea, but our work during this PhD have permitted to get all technical requirement to further address tis question. In addition we propose an innovative approach, using the neural network mapping to describe specificities, if any, of the integrated neural respiratory network in apneic patients, both obstructive and central, vs controls
Denoeud, Cyprien. "Contribution à la compréhension et à la prévention de la mort massive des cellules souches mésenchymateuses post-implantation : application à l'ingénierie tissulaire". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/DENOEUD_Cyprien_va.pdf.
Texto completo da fonteMesenchymal stem cells (MSCs) are appealing candidates for regenerative medicine applications. Today, MSCs are more and more using to clinical trials for repairing injured tissues or organs. Upon implantation, however, cells encounter an avascular microenvironment depleted of oxygen and nutrients that is responsible for their massive death post-transplantation, a major roadblock to successful clinical therapies. This issue can be overcome by in situ supplying glucose that acts as the main metabolic fuel for MSCs in hypoxia and enhances their survival and functionality. However, energy-providing pathways used by MSCs upon transplantation and their plausible metabolic switches in response to this ischemic environment are not well understood. Moreover, any strategy, based on continuous glucose delivery to fuel cells, have not been designed for improving MSC survival and functionality post-implantation. The first aim of this PhD project is to better understand the energetic metabolism used by MSCs upon transplantation. We establish for the first time that the in vivo environment experienced by hMSCs is best reflected by near-anoxia (0.1% pO2) in vitro associated with glucose and serum depletion. Under this « ischemic » in vitro model, hMSCs rely almost exclusively on glucose through anaerobic glycolysis to produce ATP. Moreover, hMSCs are unable to adapt their energetic metabolism to the lack of exogenous glucose, possess a very limited stock of glucose and no ATP reserves. This lack of downregulation of energy turnover results in a rapid depletion of hMSCs energy reserves, explaining their poor survival rate. The next (and main) aim of this PhD project is to develop and test an enzyme-controlled, nutritive hydrogel with an inbuilt system of glucose delivery to improve MSC survival and functionality. This novel hydrogel, previously based on a patent (EP14306700), is made of both fibrin, starch (a polymer of glucose), and amyloglucosidase (AMG, an enzyme that releases glucose from starch), and provides physiological levels of glucose to fuel MSCs via glycolysis. hMSCS loaded in the novel starch/AMG hydrogel exhibit improved cell viability and paracrine functions for up to 14 days under the “ischemic” in vitro model. Most importantly, in addition to enhanced MSC viability, this nutritive hydrogel promoted paracrine functions when implanted in an ectopic model.Looking forward, and given the current wide interest in the use of stem cells for regenerative medicine applications, the novel inbuilt system of glucose delivery has the potential of improved tissue engineering and regenerative methodologies, which enhance cell survival and functionality after implantation
Gallo, Alessandra. "Role of non-vesicular secretion in neuronal development". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/GALLO_Alessandra_va.pdf.
Texto completo da fonteThe growth of neurites during neuronal development requires a massive increase of surface area via the insertion of new proteins and lipids. This event occurs through the fusion of secretory vesicles with the plasma membrane (PM), the final step of the secretory pathway. Recently, non-vesicular transfer of lipids at contacts between endoplasmic reticulum (ER) and PM was shown to contribute to membrane expansion. Members of the ER-integral membrane protein Extended-Synaptotagmin (E-Syt) family have been identified as Ca2+-dependent lipid transfer proteins at ER-PM contact sites, and shown to transfer glycerophospholipids via their lipid binding domains. The laboratory previously found that a novel ER-PM SNARE complex, composed of the ER-resident Sec22b and the neuronal plasmalemmal Stx1, is involved in neurite growth despite being unable to mediate membrane fusion. However, how this complex participates to neurite extension remained to be elucidated. In yeast, Sec22 interacts with lipid transfer proteins of the OSH family, enriched at the ER- PM contacts, supporting a role for Sec22b-populated ER- PM junctions in non-vesicular lipid transport between these bilayers. Based on these observations, our starting hypothesis was that E-Syts-mediated non-vesicular lipid transfer at Sec22b-populated ER-PM contacts, might contribute to neurite growth. The goal of my PhD was to explore this hypothesis with two specific questions: 1-What are the partners of Sec22b complexes which might be involved in the unconventional mechanisms of membrane expansion? 2-What is the mechanism whereby the non-fusogenic SNARE Sec22b/Stx1 complex acts in neuronal development?Here we show that Sec22b interacts with E-Syt2 and Stx1 in PC12 cells and with E-Syt2, E-Syt3 and Stx3 in HeLa cells. Overexpression of E-Syt2 stabilized Sec22b-Stx3 association, whereas silencing of E-Syt2 had the opposite effect. Overexpression of E-Syt2 full length, but not the mutant forms which are unable to transfer lipids or attach to the ER, increased the formation of filopodia particularly in the growing axon. Finally, this effect was inhibited by a clostridial neurotoxin cleaving Stx1, by the expression of Sec22b Longin domain and a by a Sec22b mutant with extended linker between SNARE and transmembrane domains.In conclusion, these results support the hypothesis that Sec22b/Stx1 junctions may contribute to membrane expansion via an interaction with phospholipid transfer proteins like E-Syts
Voegele, Alexis. "Study of the translocation mechanism of the cyaa toxin from bordetella pertussis". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/VOEGELE_Alexis_va.pdf.
Texto completo da fonteThe adenylate cyclase toxin (CyaA) is one of the major virulence factor produced by Bordetella pertussis, the causative agent of whopping cough. CyaA has the unique capacity to translocate its catalytic domain directly across the plasma membrane. Then, the catalytic domain binds to calmodulin (CaM) to produce high levels of cAMP, leading to cell intoxication. Although several models have been proposed, the molecular mechanism and the forces involved in the translocation of CyaA remain elusive. The calcium gradient, the membrane potential across the plasma membrane and post-translational acylation are required for an efficient CyaA translocation. During my PhD, I mainly investigated the translocation process. It has been previously shown that deletion of the translocation region abolishes the delivery of the catalytic domain into the cytosol of target cells. In this region, the peptide P454 (residues 454 to 484 of CyaA) was identified and exhibits membrane-active properties related to antimicrobial peptides, i.e membrane interaction, α-helical folding upon membrane insertion and membrane permeabilization. We have investigated the role of P454 on the translocation process. We observed that negatively charged and fluidic membrane favor P454 membrane insertion. The peptide contains two arginine residues that are critically involved in its membrane-active properties. We further identified that P454 exhibits the intrinsic propensity to translocate across lipid bilayers and forms a stable complex with CaM. We identified several residues from P454 involved in both membrane interaction and CaM binding. We showed in the context of the full-length CyaA toxin that these residues are essential for the efficient translocation of the catalytic domain into the cell and production of cAMP. We propose a translocation model in which the membrane-active P454 segment from the translocation region destabilizes the membrane, favoring its translocation. In the cytosol, the P454 segment is trapped by CaM and the formation of the complex may act as a driving force pulling the catalytic domain across the plasma membrane. We further showed that CaM binding to the main CaM-binding site in the catalytic domain induces local and long-range allosteric effects that stabilize the enzymatic site, allowing fast ATP catalysis to cAMP, leading to host subversion. The relevance of these results for the translocation and activation of CyaA are discussed
Laouirem, Samira. "Rôle des cellules endothéliales dans le carcinome hépatocellulaire associé au syndrome métabolique". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/LAOUIREM_Samira_va.pdf.
Texto completo da fonteMetabolic syndrome (MS) is a major risk factor for hepatocellular carcinoma (HCC). In this context, HCC display some peculiar features suggesting the involvement of specific molecular mechanisms of carcinogenesis. The aim of our study was to investigate the role of two proteins, an adipokine (FABP4, Fatty Acid Binding Protein 4) and a protein of autophagy (ATG5) in liver carcinogenesis associated with MS. We showed a FABP4 overexpression in HCC from patients with MS, mostly restricted to peritumoral sinusoidal endothelial cells. In vitro, FABP4 regulation in endothelial cells involved various mediators (insulin, glucose, TNFα, VEGF, hypoxia). We identified microvesicles as FABP4 carriers between endothelial and tumoral cells. FABP4 exerted oncogenic effects on hepatoma cell lines, increasing cell proliferation and migration, effects being reversed by a specific FABP4 inhibitor (BMS309403). In vivo, BMS309403 also significantly reduced tumour progression in heterotopic and orthotopic xenografted tumor cells in obese nude mice. In ATG5 liver endothelial deficient mice (KO ATG5), progression of liver tumour mice (induced by diethylnitrosamine injection) was greater compared to control mice. We observed an increase in senescent cells in the non-tumoral liver (NTL) of KO ATG5 mice, although not significant. In tissue specimen from patients with MS, p62 (protein of autophagy) expression was increased in HCC, and senescent cells were more frequent in NTL. This study highlighted the key role of sinusoidal endothelial cells in liver carcinogenesis related to SM through novel mediators, FABP4 and ATG5
Le, Hingrat Quentin. "Impact de la variabilité génétique dans la région Long Terminal Repeat et le gène de l'intégrase sur la réplication du VIH-2". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/LE_HINGRAT_Quentin_va.pdf.
Texto completo da fonteHIV-2 is oftenconsidered as an attenuated model of HIV-1 infection. Indeed, HIV-2 is characterized by its lower viral replication, reduced transmission rates and a slower progression towards AIDS of infected-patients. Mechanisms implied in HIV-2 reduced pathogenicity are not entirely understood. In our work, we have focused on HIV-2 diversity, especially in two genomic regions: the integrase and the Long Terminal Repeat (LTR) region.We have improved the culture method, by purifying clinical samples using anti-CD44 paramagnetic beads. This allowed us to increase the number of viral strains in our collection. Then, we used those strains to study phenotypic susceptibility to integrase strand transfer inhibitors (INSTI). During this study, we identified a new molecular mechanism of resistance to INSTI, a 5 amino-acids insertion after codon 231 of HIV-2 integrase. This insertion was responsible for a high level of resistance to raltegravir (RAL), elvitegravir (EVG), cabotegravir (CAB), and a slight increase in the resistance todolutegravir (DTG). Certain isolates harboring this insertion remained susceptible to bictegravir (BIC).A 2 amino-acids insertion was also transiently observed in one patient. We have confirmed those phenotypic data by constructing HIV-2 mutants by site-directed mutagenesis. Whether the insertion was composed of 2 or 5 amino-acids, replicative capacitywas similar to the wild-type virus, except for the mutant with a GIRGK insertion. However, the predicted structure of mutated HIV-2 integrases was modified, notably in the C-terminal domain, due to the loss of one of the two beta sheets composing the beta barrel. Phenotypic susceptibility of mutants was determined and results for HIV-2 mutants witha 5 amino-acids insertion were similar to those obtained with clinical isolates.We also determined the susceptibility of the mutant with a GK insertion. It was susceptible to BIC and DTG, but already resistant to RAL and CAB. In the last part of our work, we have characterized genetic variability within LTR region in 66 antiretroviral-naïve patients, included in the French ANRS CO5 HIV-2 cohort.Genetic variability was higher among group B sequences, due to a high number of insertions and deletions in the «regulatory» sub-region that encompasses all transcription factor binding sites. All group B viruses presented a short deletion in the region encompassing PuB1 andpets binding sites, causing the loss of the pets binding site.Furthermore, 4 group B viruses had also a deletion of the first binding site of Sp1 transcription factor. This variability impacted LTR transcriptional activity. Group A and B LTRs presented asimilar basal transcriptional activity but, in Jurkat cells, after cellular activation, transcriptional activities of group B LTR and a group A LTR in which the deletion of pets binding site has been introduced were 10-fold lower than the transcriptional activity of an intact group A LTR. The deletion of the first Sp1 binding site reduced the basal transcriptional activity in Jurkat cells and the response to transactivation by the viral protein Tat in HEK293T
Quioc-Salomon, Barbara. "Rôle de la protéine HBC du virus de l'hépatite B sur la biologie des ARN viraux". Thesis, Université de Paris (2019-....), 2019. https://theses.md.univ-paris-diderot.fr/QUIOC_SALOMON_Barbara_va.pdf.
Texto completo da fonteChronic HBV carriers (CHB) are at high risk of developing hepatocellular carcinoma. Because covalently closed circular DNA (cccDNA) persists in infected cells through RNA expression, deciphering the mechanisms involved in RNA transcription and stability is a crucial step to identify new antiviral targets. In addition to its role in capsid formation, HBV core protein (HBc) has been shown to be associated with the cccDNA and to modulate its structure, yet the impact of this modification on HBV transcription is not fully understood. To better understand the role of HBc in this context we constructed several mutants deficient for HBc expression. The first mutant has two stop codons after codon 27 in HBc followed by a substitution of the HBc sequence by a sequence encoding different epitopes. During infection, this virus shows a strong decrease in expression of viral RNA, which cannot be rescued by re-expression of HBc. The quantification of nascent RNAs shows that the defect appears to be post-transcriptional and is present as early as 2h after transcription. These results suggest that the observed defect is independent of HBc and that the deleted sequence in the HBV genome of this mutant could be involved in a post-transcriptional regulatory mechanism. With this mutant, we have been able to demonstrate that the HBc protein provided by the capsid during infection is able to re-associate onto the cccDNA in the nucleus. We then studied HBc mutants generated in the context of the the wild-type virus sequence, without the substitution. When expressed from a plasmid expressing both the genome and the HBc protein under the control of SV40 promoter, we observe a decrease of the pgRNA expression for mutants having the stop codons after the 27th or 38th codon of HBc, but not when the stop codon is located after the 67th codon. These results suggest that displacement of the HBc stop codon induces a decrease in pgRNA expression, independently of HBc protein, and that the natural stop codon of HBc could be protected from viral RNA surveillance pathways such as nonsense-mediated decay (NMD) that recognizes RNAs with a premature stop codon. During infections with these viruses, and therefore in the absence of HBc, we observed an increased in the defect for viruses having stop codons at position 27 and 38 and a defect appears for a virus having the stop codon at position 67. In this context, in the absence of HBc, we have seen that RNAs encoding surface proteins are also impacted and that RNA expression can be partially restored by HBc expression. By chromosome conformation capture techniques we were able to observe that the HBc-27* HBV virus is no longer excluded from repressed regions associated with lamins, indicating that the HBc protein could be involved in the localization of the cccDNA at active chromatin regions favorable for transcription.In order to understand the mechanisms involved in HBc regulation, we have isolated the nuclear partners of HBc and highlighted many factors involved in the RNA and DNA regulation, in the DNA damage repair and RNA processing.Overall, our results shed light on the regulatory mechanisms of HBV RNA biology
Machtou, Julie Bertrand Frédéric. "Paris : industries urbaines /". [S. l.] : [s. n.], 2000. http://catalogue.bnf.fr/ark:/12148/cb40072679b.
Texto completo da fonteTrujillo, Alexandria. "Everything is Paris". Thesis, The University of Arizona, 2010. http://hdl.handle.net/10150/146688.
Texto completo da fonteZuber, Annette-Eve. ""Bergère, Ô Tour Eiffel" : Ein Mythos in Literatur und Kunst /". Heidelberg : Neuphilologischen Fakultät der Universität Heidelberg, 2000. http://catalogue.bnf.fr/ark:/12148/cb390801921.
Texto completo da fonteTarnovski, Flávio Luiz. "Pais assumidos". Florianópolis, SC, 2002. http://repositorio.ufsc.br/xmlui/handle/123456789/82788.
Texto completo da fonteMade available in DSpace on 2012-10-19T18:20:52Z (GMT). No. of bitstreams: 1 184894.pdf: 696388 bytes, checksum: 22e1f04a55aad66b296550593afc2eb9 (MD5)
Esta pesquisa parte dos relatos de homens auto-identificados como homossexuais que adotaram filhos, para analisar os diversos modos de acesso à parentalidade disponíveis e/ou realizados por homens que se relacionam afetiva e eroticamente com outros homens. A partir do referencial oferecido pelos estudos de gênero, de sexualidade e de parentesco, propõe hipóteses para a interpretação da paternidade homossexual. Através do diálogo com a literatura francesa sobre homoparentalidade, analisa o impacto de uma conjugalidade homoerótica na formação de arranjos familiares e na atualização de relações de parentesco.
Saou-Dufrêne, Bernadette Nadia. "Art et médiatisation : le cas des grandes expositions inaugurales du Centre Georges Pompidou (Paris-New York, Paris-Berlin, Paris-Moscou)". Grenoble 3, 1998. http://www.theses.fr/1998GRE39026.
Texto completo da fonteNETO, WILSON REIS DE SOUZA. "THE PARIS-HARRINGTON THEOREM". PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2007. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=13399@1.
Texto completo da fonteSabemos pelo Teorema da Incompletude de Godel que existem afirmações verdadeiras sobre números naturais que não podem ser demonstradas na aritmética de Peano. Paris e Harrington deram um exemplo de uma variação do Teorema de Ramsey finito que não pode ser demonstrada em aritmética de Peano apesar de ser facilmente demonstrável na Teoria de Conjuntos usual. Este é geralmente considerado o primeiro exemplo matematicamente natural de uma sentença indecidível. Além da demonstração original, apresentamos nessa dissertação outra usando Teoria de Modelos.
From Godel’s Incompleteness Theorem we know that there are true sentences about natural numbers which can not be proved in Peano Arithmetic. Paris and Harrington gave an example of a variation of the finite Ramsey Theorem which can not be proved in Peano Arithmetic although it can be easily proved in usual Set Theory. This is usually considered the first example of a mathematically natural undecidable sentence. Besides the original proof, another one, using Model Theory, is presented in this dissertation.
Gammon, Sean James. "Sporting pasts – tourist futures". Thesis, University of Central Lancashire, 2011. http://clok.uclan.ac.uk/3053/.
Texto completo da fonteLotz, Sarah. "Paris on a shoestring". Master's thesis, University of Cape Town, 2007. http://hdl.handle.net/11427/8096.
Texto completo da fonteBláhová, Petra. "Imidž značky Kérastase Paris". Master's thesis, Vysoká škola ekonomická v Praze, 2014. http://www.nusl.cz/ntk/nusl-192371.
Texto completo da fonteDoulet, Jean-François Flonneau Mathieu. "Paris-Pékin, civiliser l'automobile /". Paris : Descartes & Cie, 2003. http://catalogue.bnf.fr/ark:/12148/cb39015888g.
Texto completo da fonteJean-François Doulet est l'auteur du texte sur Pékin et Mathieu Flonneau sur celui de Paris. Bibliogr. p. 75-79 et 133-136.
Guichardet, Jeannine. "Balzac, archéologue de Paris". Genève : [Paris] : Slatkine ; [diff. H. Champion], 1999. http://catalogue.bnf.fr/ark:/12148/cb37044895v.
Texto completo da fonteTurrini, Camilla <1990>. "Giovanni XXIII Defensor Pacis". Master's Degree Thesis, Università Ca' Foscari Venezia, 2015. http://hdl.handle.net/10579/6035.
Texto completo da fonteRajala, Johansson Desireé. "Paris, den trojanska prinsen : Jämförelse av Paris utifrån verket Iliaden och filmen Troy". Thesis, Linnéuniversitetet, Institutionen för kulturvetenskaper (KV), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-40154.
Texto completo da fonteVieira, Mathieu. "Régulation de l'expression du gène Nodal lors de la différenciation des cellules souches embryonnaires". Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/VIEIRA_Mathieu_2_va_20180930.pdf.
Texto completo da fonteExposure of embryonic stem cells (mESCs) to ACTIVIN/NODAL and FGF signaling initiates their differentiation into EpiSC-like cells (EpiLCs). This exposure triggers changes in the expression levels of pluripotency factors, and promotes a global shift in gene expression. Remarkably, most of the genes that maintain their expression during this differentiation also undergo a shift in their regulation from one enhancer to another. This is notably the case of the Nodal gene itself. While its expression is dependent on pluripotency factors interacting with its enhancer HBE in mESCs, it is primarily dependent on its auto-regulatory (ACTIVIN/NODAL signaling-dependent) ASE enhancer in EpiLCs. Work in the lab has however shown that mESCs where HBE has been removed are unable to express Nodal once they are differentiated into EpiLCs, revealing that, although EpiLCs do not require HBE to express Nodal, its presence is required in mESCs to ensure later Nodal expression in EpiLCs (Papanayotou et al., 2014). One question raised by this finding is whether HBE exerts its control over Nodal expression solely via its interaction with the promoter or whether it involves HBE directly influencing ASE or other Nodal regulatory regions. Another concerns the nature of the molecular means (chromatin changes) deployed to exert this control and the identity of the factors involved (chromatin remodelers and modifiers, pluripotency factors). To answer these questions I first started to generate specific deletions of HBE and ASE in mESCs using CRISPR/Cas9-mediated genome-editing. I then characterized the impact of these deletions on Nodal expression using qPCR and live imaging of a knocked-in NodalcondHBE-YFP reporter. Although HBE is essential for Nodal expression in mESCs, I found that ASE also contributes to Nodal expression in these cells. To dissect HBE functions I generated mESC lines deleted for sequence conserved subdomains of HBE. Analysis of the impact of these deletions allowed me to find that only one of these subdomains, HBE2, is essential for HBE transcriptional activity in mESC. This subdomain also contributes to Nodal expression in EpiLCs, highlighting the fact that although HBE is not essential to Nodal expression in EpiLCs it does contribute to maintaining its level. However, in contrast to the deletion of the entire HBE, none of these subdomains deletions affected the ability of ASE to drive Nodal expression in EpiLCs, indicating that the distinct functions of HBE in the regulation of Nodal expression can be experimentally dissociated and their molecular basis investigated. Furthermore, ChIP-qPCR analyses revealed that the deletion of HBE or ASE both affected histone mark profiles at the promoter and at the other regulatory element, supporting the view that the maintenance of the epigenetic landscape at the Nodal locus involves multiple interactions between its various regulatory elements. The analysis of ChIP-seq datasets and ChIP-qPCR results has allowed me to compile a list of transcription factors known to bind the Nodal locus. Interestingly, key transcription factors controlling ASE activity could be affected by the presence of HBE. This work unfolds a novel mechanism of gene regulation involving enhancer interaction. This thesis is also the first step towards revealing a new mechanism at place during the reorganization of the transcriptional landscape during mESC to EpiLC differentiation
Berland, Chloé. "Triglyceride-sensing in the mesocorticolimbic system and reward-driven behaviour control". Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/Berland_Chloe_2_va_20180911.pdf.
Texto completo da fonteObesity spreading is due to an imbalance of energy homeostasis, with excessive consumption of sweet and fat food, and sedentary lifestyles. Food intake partly depends on dopamine release in the mesocorticolimbic system, and calorie-rich hedonic food, among other objects of desire, stimulate this reward circuit. Dopaminergic release in the mesocorticolimbic system is a main factor for compulsive feeding, and calorie-rich food could be responsible for abnormal feeding behaviours, where excessive food intake is assimilated to MCL malfunctions similar to drugs addiction. More particularly, postprandial triglycerides represent a major source of dietary lipids, and obesity is often associated with hypertriglyceridemia, but also with dopaminergic signalling impairments. Mesocorticolimbic system neurons express several enzymes involved in triglycerides hydrolysis, such as the lipoprotein lipase, suggesting an ability to sense triglycerides and modulate their activity accordingly. The aim of this thesis is to identify cellular and molecular mechanisms by which dietary triglycerides act onto dopaminergic structures and control food intake
Picot, Pauline. "L'heure de nous-mêmes a sonné". Mobilisations antiracistes et rapports sociaux en Ile-de-France (2005-2018)". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/PICOT_Pauline_2_complete_20190315.pdf.
Texto completo da fonteThis research is based on the ethnographic study of the day-to-day activities (observation and interviews) of several antiracist activist groups, and content analysis of their written productions. It focuses on antiracist groups from the Paris region : the Brigade anti-négrophobie, the Conseil représentatif des associations noires, the Parti des Indigènes de la République, the network Reprenons l’initiative contre les politiques de racialisation and the organization committee for the annual Journées contre l’islamophobie. Combining theoretical frames from the sociology of collective action and the sociology of race, gender and class relations, the thesis is centered on the analysis of the division of militant labour within those groups. The first aim is to explain how such mobilisations emerged, by replacing them in the particular political context of the early 2000’s and situating them within the previously established antiracist field ; but also by showing how this context interacts with the social trajectories of the activists. The second aim is to examine the effects of collective action on those who participate, or in other words, the products of antiracist action.Indeed, these collectives have been intiated in the 2000’s by French activists, « heirs » of the (post)colonial immigration. They participate in the struggle for (counter) hegemony regarding the definition of racism and antiracism in France. Thereby, antiracist mobilisation produces its own intellectuals, who themselves elaborate social theory. Moreover, the different forms of militant labour (intellectual/domestic/emotional, visible/invisible) constitute entries to study the ways in which social relations of power – mainly race, gender and class relations – manifest within the course of collective action, but also how they are being reshaped. Finally, these antiracist mobilisations also imply the use of racial categories as self-categorization. Fueled by the activists’ emotional labour, this process of identification opens the possibility for racialized minority groups to become a group or a class « for itself », or in other words, a process of communalisation
Henry, Benoît. "Splénomégalie, déformabilité des globules rouges circulants et héritabilité de la diversité phénotypique chez des sujets exposés à Plasmodium falciparum". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/HENRY_Benoit_complete_depot_2.pdf.
Texto completo da fonteIn subsaharan Africa, the Fulani people display a specific phenotypic response to the infection with Plasmodium falciparum, defined by the over-prevalence of splenomegaly and anemia, less frequent or lower parasitemia), and a stronger anti plasmodial immune response. This “protective” phenotype is reminiscent of hyper-reactive malarial splenomegaly, a rare and chronic form of malarial infection. Determinants of this specific phenotype remain elusive, but a genetic basis is suspected. We hypothesized that specificities of erythrocytes (parasitized or not) would play a role in the emergence of this phenotype.We have studied the phenotypic response to malarial infection in a 800 subjects (193 families) multi-ethnic cohort (Bariba, Gando, Otamari, Fulani) living in sympatry in Northern Benin, a malarial hyperendemic region. Eight cross-sectional studies were performed between June, 2015 and December, 2017. We confirmed, among Fulani, a greater prevalence of splenomegaly. Total plasma IgM were also higher among Fulani at 2 time points. Analysis of temporal trends of Plasmodium infection markers, fever and anemia showed inconstant inter-ethnic differences.We then evaluated erythrocyte phenotype in the same cohort, during a cross-sectional study in December, 2017. At this time, prevalence of splenomegaly was significantly higher among Fulani, but the trend towards anemia and lower parasitic load, although present, was unsignificant. We found a higher, non-significant, prevalence of malarial infection among Fulani. Deformability of circulating erythrocytes, measured through ektacytometry and microsphiltration, was higher among Fulani. Uni- then multivariate analysis of factors associated with erythrocyte deformability showed that the major determinants of this trait were ethnicity and markers of plasmodial infection (rapid diagnostic test or PCR); increase in deformability being almost exclusively observed among infected Fulani subjects. In a subgroup of 120 subjects, in vitro infection of erythrocytes with P. falciparum did not show inter-ethnic differences regarding erythrocyte deformability or parasite growth. However, a positive correlation was observed between circulating erythrocytes deformability and parasite growth. This was more pronounced in Fulani. Heritability of erythrocyte deformability (through microsphiltration) was very high in Fulani and in infected subjects. Fulani also displayed a higher proportion of circulating IgM-positive memory B cells.These data confirm the reality of a peculiar phenotypic response to malarial infection among Fulani; this phenotype is nevertheless subject to marked temporal variations. The enhanced deformability of circulating erythrocytes in Fulani, its strong heritability, and the correlation between circulating erythrocytes deformability and parasite growth after in vitro infection could be explained by three non-mutually exclusive hypotheses: and enhanced erythropoietic response to malarial infection in Fulani; an increased circulating erythrocytes deformability in a subgroup of Fulani, which would favor infection; or by an enhanced splenic filtration of erythrocytes by the spleen in reaction to infection in Fulani. These elements suggest that in malaria-exposed subjects, erythrocytes or spleen-related specificities could act upstream of antimalarial immune response. This also paves the way to the identification of genes involved in this novel trait
Quetel, Lisa. "Altérations génétiques et hétérogénéité tumorale du mésothéliome pleural malin". Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/QUETEL_Lisa_2_complete_20181127.pdf.
Texto completo da fonteMalignant pleural mesothelioma (MPM) is a rare cancer that affects 900 cases per year in France and arises in the pleura, the membrane around the lungs. To date, no curative treatment exists for this disease. The main risk factor is asbestos and accounts for about 80% of cases. Asbestos was banned in France in 1997 but its use is still effective in several developing countries. In addition, mesothelioma is characterized by a significant latency period between exposure and the development of the disease, the incidence continues to increase in France and around the world.The MPM has three histological types: the most common epithelioid and associated with better survival, sarcomatoid, less common but with poorer survival and biphasic, frequency and intermediate survival. However, this histological classification does not reflect the full complexity of the heterogeneity of the MPM. Indeed, like many cancers, MPM has a great molecular and clinical heterogeneity. To better take into account and improve patient care, we aim to characterize the molecular profile at different levels and make the link with clinical data and also the sensitivity to anti-tumor molecules. We are also conducting functional approaches to understand the mechanisms inherent in mesothelial carcinogenesis.My thesis project is part of the laboratory theme and has increased our knowledge about the genetics of this pathology. First, I characterized genetic mutations in a series of 266 tumor samples out of 20 genes of interest in the MPM. I then correlated genetic profiles with histological and clinical data and established associations between gene mutations and histological type as well as survival to better describe the heterogeneity of MPM and to establish prognostic markers.Genetic data has identified a gene named SETD2 that has recently been described as mutated between 5 and 8% in MPM in only a few studies. So I decided to study the function of this gene in the MPM. SETD2 is a methyltransferase responsible for the trimethylation of lysine 36 of histone 3 (H3K36me3). I was able to show that mutations in this gene in MPM lead to a decrease in the H3K36me3 mark. In contrast to what is found in other types of cancer, I have not established a link between the mutational status of SETD2 and the regulation of gene expression and splicing, proliferation, microsatellite instability, ability to repair DNA damage, or susceptibility to Wee1 and PI3Kβ inhibitors.Throughout these studies, I tested anti-tumor molecules in order to find a link between molecular profile and sensitivity in order to predict the response to these inhibitors. In particular, I tested an inhibitor of FAK, defactinib, because it has been suggested that sensitivity to this molecule is predicted by the loss of merlin, the protein encoded by NF2. This link has not been verified in the laboratory or in other studies but I was able to identify a potential predictor of sensitivity to this inhibitor. Indeed, the expression of LUM, which codes for lumican, an extracellular matrix protein is associated with defactinib sensitivity and could therefore be a predictor of susceptibility to FAK inhibitors. I also participated in the characterization of tumor heterogeneity by being involved in a project that led to the identification of a new subgroup of the classification C1/C2 and in a new approach that led to define this heterogeneity by molecular gradients
Dobashi, Yuriko. "L'histoire textuelle des "Dialogues" de Jean-Jacques Rousseau (de 1772 jusqu'à leur première édition)". Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/DOBASHI_Yuriko_va2_28292019.pdf.
Texto completo da fonteJean-Jacques Rousseau, haunted by the delusion of persecution, undertakes to write an extraordinary work : Rousseau judge of Jean-Jacques-Dialogues. In this book, the author, who considers himself disfigured and defamed by the unanimous hostility of the enemies and the public, makes "Rousseau" and "the Frenchman" dialogue in order to prove desperately the innocence of "Jean-Jacques" and reveal the injustices that are made to him. This work, which even the true friends or supporters of Rousseau have hesitated to publish because of its strangeness, has long been considered the document of Rousseau's paranoid delusion and was held at a distance by literary researchers. This was his status until the interventions of Michel Foucault and Jean-Marie Goulemot.Is it for this reason that the studies not only on their content, but also on their writing, their manuscripts and their editions do not advance at the same rate as his other works, in particular the Confessions? About Confessions, there are many studies on manuscripts and editions. In this thesis, it will be necessary to reconstitute the textual history of the Dialogues by effectively using not only his correspondence and the four manuscripts of the Dialogues, but also the Memoirs and the correspondences of the contemporaries. The ambition is threefold : to clarify the history of writing, to put the manuscripts in order and to continue the examination until the first edition of Geneva by his friends
Afsharijoo, Pooneh. "Looking for a new version of Gordon's identities : from algebraic geometry to combinatorics through partitions". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/AFSHARIJOO_Pooneh_2_complete_20190510.pdf.
Texto completo da fonteA partition of a positive integer n is a decreasing sequence of positive integers such that their sum is equal to n. The integers which appear in this sequence are called the parts of this partition. My thesis studies the partitions of integers and the identities between them. A partition identity is an equality between the number of partitions of an integer n satisfying a certain condition A and the number of partitions of n satisfying another condition B. They play an important role in many areas: number theory, combinatorics, Lie theory, particle physics and statistical mechanics. One of these identities is as follows: Theorem. (The first Rogers-Ramanujan identity) The number of partitions of a positive integer n with no equal or consecutive parts is equal to the number of partitions of n into parts 1 or 4(mod.5). In this work, we study partition identities using the relation between the combinatorics of partitions and the combinatorics of graded algebras associated to an important object of algebraic geometry: arc spaces. Given a field k of characteristic zero and polynomials f1,…,fm in k[x1,…, xn], the associated arc space is the space corresponds to the ideal I of S:=k[x1j,…, xnj|j>-1], generated by the coefficients of some developments associated to the above polynomials and the variables xij. For focussed arcs, which is when we take xi0 = 0 for i=1,…,n, the Hilbert-Poincaré series of the graded algebra S\I is closely related to partitions of integers satisfying conditions depending on I. In the case where f(x) = x^r in k[x], the ideal I of k[x1, x2,… ] is a differential ideal for the derivation D(xi) = xi+1, in the sens that DI is included in I. In fact it is generated by x1^r and all its iterated derivatives. We show that when r = 2 the computation of a Gröbner basis of I with respect to the weighted lexicographical monomial order is related with an identity involving the partitions that appear in the first Rogers-Ramanujan identity. We then prove that a Gröbner basis of this ideal is not differentially finite in contrary with the case of the weighted reverse lexicographical order. We give a prove from this point of view of Gordon’s identities which is a family of important partitions identities. Using differential ideals we state a conjecture which could add a new member to Gordon’s identities. we prove then this conjecture for a special case. At the end, we give a simple and direct proof of a theorem of Nguyen Duc Tam about the Gröbner basis of the differential ideal [x1y1]; we then obtain identities involving partitions with 2 colors
Almayrac, Etienne. "Rôle de l’organisation des chromosomes et de yH2A dans la mobilité globale de la chromatine après un dommage à l’ADN". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/ALMAYRAC_Etienne_2_complete_20190513.pdf.
Texto completo da fonteThe non-random organization and mobility of chromosomes in the nucleus of eukaryotic cells can influence DNA metabolisme and genome stability. Double-strand breaks are the most dangerous damages to the cell. Different studies of chromatin mobility after DNAdamage have been shown to increase mobility of the damaged locus, but also of undamaged genome region. During my thesis, I first participated in a study describing the mechanisms responsible for the increase of global chromatin mobility after multiple DSBs with zeocin. Results of this study made it possible to propose the hypothesis of a global chromatin stiffening, by phosphorylation of histone H2A (yH2A), as the main cause of the increase in global mobility after damage. In a second time, I was interested in global chromatin mobility after a single double-strand break, the possible causes of an increase of global mobility and its function during repair by homologous recombination (HR). For this, I designed a THRIV system (Tracking Homologous Recombination In Vivo) that allowed controling the induction of a targeted DSB and to discriminate individually the cells that repaired by HR over time. In addition, using time-lapse microscopy, I followed the mobility of a locus on an undamaged chromosome and thus measured changes in global chromatin mobility after damage. Thus, it has been demonstrated that 1) a single targeted DSB results in an increase in the mobility of a locus in trans when close to a centromere 2) the spatial position of a donor sequence, determine probably also the increase of global chromatin mobility after DSBand 3) the increase in mobility after DSB depends on the phosphorylation of histone H2A(yH2A), but not on the mediator Rad9, unlike in a context of multiple DSBs. Finally, my first results tend to invalidate the importance of the global increase of mobility on HR efficiency. This work reinforces the hypothesis of yH2A as the main and first cause of increase in global chromatin mobility after damage
Bonamy, Clément. "Signalisation cellulaire et peptides antimicrobiens : rôle de la voie EGFR dans la régulation de la B-défensine 1 humaine". Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/BONAMY_Clement_2_complete_20181005.pdf.
Texto completo da fonteThe human ß-defensin-1 (HBD1) is an antimicrobial peptide constitutively expressed by epithelial cells at mucosal surfaces. In addition to its microbicidal properties, the loss of HBD1 expression in several cancers suggests that it may also have an anti-tumor activity. Here, we investigated the link between HBD1 expression and cancer signaling pathways in human colon cancer and primary cells. Using available datasets from patient cohorts, we found that HBD1 expression is decreased in colorectal cancer. We demonstrated that inhibiting the Epidermal Growth Factor Receptor (EGFR) increased HBD1 transcription, whereas activating EGFR repressed HBD1 transcription, through the MEK1/2-ERK1/2 pathway that ultimately regulates MYC. We finally present evidence supporting the direct role of MYC, together with the MIZ1 coregulator, in HBD1 regulation. Our work uncovers the role and deciphers the function of the EGFR-ERK-MYC axis as a repressor of HBD1 transcription and contributes to the understanding of HBD1 suppression observed in colorectal cancer. This work opens also the reflection about the therapeutic interest of HBD1 regulation in cancer treatment
Fahy, Lucine. "Etude des conséquences d’un environnement hypoxique sur le développement et la chimiorésistance des leucémies aiguës lymphoblastiques T (LAL-T)". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/FAHY_Lucine_2_complete_20190627.pdf.
Texto completo da fonteBackground: T cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disorder characterized by an increased proliferation of T lymphocyte precursors that are unable to complete their maturation. Treatments are effective in 90% of children T-ALL cases. However, children with relapse have a very poor prognosis. Resistance to chemotherapy is thus a major therapeutic challenge in the treatment of T-ALL that can be driven by interactions between leukemic cells and the microenvironment. Bone marrow microenvironment, a crucial site of propagation and maintenance of leukemia, is hypoxic with oxygen levels varying from 0.1 to 5%. As hypoxic solid tumors are more resistant to radiotherapy and chemotherapy, the aims of the study were to investigate to which extent oxygen levels impact on leukemia development and chemoresistance and to characterize the implicated molecular mechanisms. Methods: Mouse models and patients derived samples of T-ALL were cultured in low (1% and 3.5%) and high (21%) oxygen levels. Growth, apoptosis, cell cycle, metabolism and chemoresistance were measured as well as in vivo leukemia propagation using immune deficient mice as ways to define the impact of oxygen levels on T-ALL.Results: Results show that hypoxia inhibits the growth of T-ALL by slowing down cell cycle progression and decreasing metabolism, making them less sensitive to anti-leukemic drugs and preserving their ability to initiate leukemia in vivo after treatment. Knocking down (KD) HIF1α counteracted the effects observed in hypoxic T-ALL and restored their chemosensitivity. Interestingly activation of mTOR was diminished in hypoxic leukemic cells and HIF-1α KD restored mTOR activation in these low O2 conditions. Moreover, inhibiting mTOR in HIF1aKD T-ALL enhanced their chemoresistance, indicating a functional relationship between these two pathways.Conclusion: This work shows that hypoxic niches can play a protective role during the treatment of T-ALL through a HIF1α/mTOR molecular loop. Inhibition of HIF1α and/or activation of the mTOR pathway may help suppress the chemoresistance of T-ALL in hypoxic niches
Abs, Elsa. "Eco-evolutionary modeling of soil microbial decomposition in a warming climate". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/ABS_Elsa_2_complete_20190108.pdf.
Texto completo da fonteOne major source of uncertainty in global climate predictions is the extent to which global warming will increase atmospheric CO2 concentrations through enhanced microbial decomposition of soil organic matter. There is therefore a critical need for models that mechanistically link decomposition to the dynamics of microbial communities, and integration of these mechanistic models in global projection models of the Earth system. Mathematical models of soil microbial decomposition models have recently been introduced to predict soil C stocks and heterotrophic soil respiration, especially in the context of climate change. Thus far, models focused on physiological and ecological mechanisms of microbial responses, leaving the role of evolutionary adaptation poorly understood. My thesis addresses this gap and evaluates the hypothesis that microbial evolutionary adaptation to warming can have a significant impact on the global carbon cycle. After reviewing mechanistic, non- evolutionary microbial models of decomposition, I construct an eco-evolutionary spatially explicit, stochastic model, scaling up from microscopic processes acting at the level of cells and extracellular molecules. I use an approximated version of the model (spatially implicit, deterministic) to investigate the eco-evolutionary response of a soil microbe-enzyme system to warming, under three possible scenarios for the influence of temperature on microbial activity. In the absence of microbial evolution, warming results in soil carbon loss to the atmosphere (an amplification of climate change) in all scenarios. Microbial evolutionary adaptation generally aggravates soil carbon loss in cold ecosystems, and may aggravate, buffer or even reverse carbon loss in warm ecosystems. Constraining the model with observations from five contrasting biomes reveals evolutionary aggravation of soil carbon loss to be the most likely outcome. Earth-scale projections of carbon stocks that integrate my eco-evolutionary model support the prediction of a significant global aggravation of soil C loss due to microbial evolution. Dormant soils, in which microbial activity is very low, play a special role in the long-term eco-evolutionary dynamics of global soil carbon, since in these regions, the negative effect of evolution on soil carbon stocks may not kick in until the microbial community shifts from dormant to active, and may thus be delayed by decades. Overall, my work is a first step toward predictive modeling of eco- evolutionary dynamics of carbon cycling; it also lays the ground for a broad future research program that will empirically test model predictions about the role of evolutionary mechanisms in different systems across the globe, by leveraging the growing global archive of soil metagenomics data to quantify variations in microbial metabolic functions and their response to selection. Mots clés en français (10 max) : changement climatique, cycle du carbone, décomposition, projections globales, évolution microbienne, dynamiques adaptatives, rétroaction sol-climat, évolution de la coopération, modèles individu-centrés.Mots clés en anglais : climate change, carbon cycle, decomposition, global predictions, microbial evolution, adaptive dynamics, soil-climate feedbacks, evolution of cooperation, individual-based models
Wei, Xiaoli. "Control of McKean-Vlasov systems and applications". Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/WEI_Xiaoli_2_complete_20181127.pdf.
Texto completo da fonteThis thesis deals with the study of optimal control of McKean-Vlasov dynamics and its applications in mathematical finance. This thesis contains two parts. In the first part, we develop the dynamic programming (DP) method for solving McKean-Vlasov control problem. Using suitable admissible controls, we propose to reformulate the value function of the problem with the law (resp. conditional law) of the controlled state process as sole state variable and get the flow property of the law (resp. conditional law) of the process, which allow us to derive in its general form the Bellman programming principle. Then by relying on the notion of differentiability with respect to probability measures introduced by P.L. Lions [Lio12], and Itô’s formula along measure-valued processes, we obtain the corresponding Bellman equation. At last we show the viscosity property and uniqueness of the value function to the Bellman equation. In the first chapter, we summarize some useful results of differential calculus and stochastic analysis on the Wasserstein space. In the second chapter, we consider the optimal control of nonlinear stochastic dynamical systems in discrete time of McKean-Vlasov type. The third chapter focuses on the stochastic optimal control problem of McKean-Vlasov SDEs without common noise in continuous time where the coefficients may depend upon the joint law of the state and control. In the last chapter, we are interested in the optimal control of stochastic McKean-Vlasov dynamics in the presence of common noise in continuous time.In the second part, we propose a robust portfolio selection model, which takes into account ambiguity about both expected rate of return and correlation matrix of multiply assets, in a continuous-time mean-variance setting. This problem is formulated as a mean-field type differential game. Then we derive a separation principle for the associated problem. Our explicit results provide an explanation to under-diversification, as documented in empirical studies
Maltese, Giorgio. "Generation and manipulation of high-dimensional photonics states with AlGaAs chips". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/MALTESE_Giorgio_2_complete_20190915.pdf.
Texto completo da fonteThis thesis is devoted to the development of novel integrated semiconductor devices and methods for the generation and manipulation of high-dimensional states of light. We report on the study of an AlGaAs waveguide implementing type-II spontaneous parametric down conversion process in a monochromatic pump regime, with a focus on the joint spectral amplitude of the emitted biphoton state. The source works at room temperature, emits photon pairs in the telecom range and is compliant with electrical injection. The generation of broadband biphoton states is experimentally demonstrated via the reconstruction of the joint spectral intensity and via a Hong-Ou-Mandel experiment indicating that signal and idler photons are emitted over a large bandwidth (170nm) and with a high degree of indistinguishability (V=0.86). Moreover, we show that the cavity effect due to waveguide facets reflectivity leads to the production of biphoton frequency-comb states. This platform is used to demonstrate an original method to generate and control the symmetry of biphoton frequency combs exploiting cavity effects and a delay between the two photons of each pair. More specifically, we show that a fine tuning of the pump frequency enables the generation of resonant and anti-resonant comb states allowing to manipulate the wavefunction symmetry. The method can be adapted and applied to a large variety of systems, either bulk or integrated, thus increasing their flexibility and the richness of the generated states in view of implementation of new quantum information protocols.In addition, we demonstrate the realization of an AlGaAs ridge waveguide for the generation of light beams with tailored phase and polarization distributions, carrying spin angular momentum, and present the design of a device for the generation of a twisted light beam, carrying first order orbital angular momentum
Maruani, Anna. "Exploration de l'hétérogénéité phénotypique des Troubles du Spectre Autistique". Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/MARUANI_Anna_2_va_20181123.pdf.
Texto completo da fonteAutism Spectrum Disorder (ASD) are defined by persistent deficits in social communication and social interaction as well as by the restricted and repetitive nature of behaviors and interests. This entity covers very heterogeneous clinical situations, as much by the spectrum of severity of symptoms as by the variety of comorbidities and associated signs. If the genetic etiology seems preponderant, the mechanisms involved are complex and heterogeneous. One possible strategy to break down this heterogeneity is to rely on the study of phenotype-genotype relationships and more broadly on the study of phenotypic subgroups such as sensory peculiarities, co-morbidities or neuro-anatomical peculiarities, in order to to define more homogeneous categories. The aim of the thesis was to explore multi-modally the heterogeneity of these disorders.The first part of my thesis focused on the exploration of phenotype-genotype relationships. The first study focused on the exploration of Jacobsen syndrome (JS, 11q24.2-25 deletion) characterized by intellectual disability (ID) and a higher risk of ASD. In this critical region 11q24.2-25, we hypothesized that haploinsufficiency of neurotrimin (NTM) (neuronal cell adhesion molecule) may increase the risk of ASD and may affect volumes of brain structures. In the end, NTM could not be incriminated as a susceptibility gene for ASD, but the explorations provided new information on the impact of the 11q24.2-25 deletion on brain anatomy. Indeed, using automatic segmentation we explored macrocephaly in a patient with a large NTM deletion with NTM and a clinical phenotype of JS: we observed an increased volume of subcortical structures in this patient. But a decrease in the occipital gray matter. The second study focused on the CNTN5 and CNTN6 genes that encode neuronal cell adhesion molecules of the sensory-motor neural pathways. Clinical investigations of patients with deleterious variants of CNTN5 and / or CNTN6 showed that these patients were hypersensitive to sound and that their auditory evoked potentials (ABRs) showed changes in latency. These results shed new light on genes related to sensory peculiarities in ASDs. I will present the preliminary results of a third linkage study in a multiplexed family with TSA and synesthesia.In the second part of the thesis, I will expose an exploratory study in which we hypothesized that the lowered plasma concentrations of melatonin observed in our ASD patients (vs controls and related) could be related to a decrease in the volume of the pineal gland (PGV). The PGV were measured with a voxel-based volumetric measurement method from magnetic resonance imaging (MRI). To better understand the relationship between VGP and plasma melatonin levels in our population, we generated a normative model. The melatonin deficiency seemed more related to the subject's status with respect to ASD than to VGP. This study led us to hypothesize that melatonin variations in ASD may be mainly caused by deregulation of the melatonin pathway.In conclusion, all of this work shows the importance of a multimodal approach for understanding ASD to open new avenues in terms of therapeutic strategy
Aden-Antoniów, Florent. "Etude des propriétés mécaniques et de la déformation transitoire dans les zones de subduction à partir de l'analyse de l'activité sismique, le cas du Chili". Thesis, Sorbonne Paris Cité, 2019. https://theses.md.univ-paris-diderot.fr/ADEN_Florent_2_complete_20190111_2.pdf.
Texto completo da fonteThe subduction zones are the most seismically active places in the world and are also the seat of megathrust-earthquakes such as the one that stroke Chile in 1960 with a magnitude estimated at 9.5. The last major ruptures in Chile have revealed complex seismic-aseismic interactions. In order to study these interactions, we investigated on at two seismic crises: the seismic swarm of April 2017; the preparatory phase of the Iquique earthquake (M w 8.1) from April 1 st , 2014. The seismic swarm took place near the city of Valparaiso in an area known to have experienced mega-earthquakes in the past: in 1730 and in 1906. In order to study the dynamics of this swarm we have built a rich catalog of more than 2000 earthquakes composing the sequence. An intense seismic activity began on April 22 nd , two days before the main earthquake of the sequence M w 6.9 and was accompanied by a gradual slip along the interface that we observed both in the GPS data and using repeating-earthquakes. Our analysis suggest that the swarm was driven by aseismic slip. The second study concerns an earthquake of mag-nitude 8.2 which occurred on April 1 st 2014 near the city of Iquique and broke one-third of the seismic gap in northern Chile. This earthquake was preceded by a sequence of precursor seismic swarms that appeared to have been accompanied by stable slip in the subduction interface as well. By building a more complete earthquake catalog, we were able to thoroughly analyze the preparation of the Iquique earthquake. We show, following a statistical approach, the occurrence of a large-scale seismic quiescence in the region of the mainshock. We link this quiescence to a downdip transient-slip potentially related to fluid channeling along the subduction interface