VictorJuiz/thesis huggingface dataset:
Le discours proverbial chez Ahmadou Kourouma
Keywords: Kourouma
Proverbes

Ce travail examine le discours proverbial dans les romans d’Ahmadou Kourouma. Il fait valoir que le discours proverbial de Kourouma traduit la vision cosmologique des personnages romanesques dans cinq domaines, à savoir la religion, la culture matérielle, les animaux, le temps et la femme. Contrairement aux études publiées au cours des quarante dernières années qui traitent de certains de ces domaines sans véritablement privilégier le proverbe comme objet d’analyse, ou qui l’analysent trop rapidement chez Kourouma en utilisant de très minces corpus ou une approche peu efficace et non contextuelle, ce travail, lui, déconstruit le proverbe et fait ressortir ses dimensions esthétiques, discursives et idéologiques les plus variées et les plus significatives. La thèse se sert des approches syncrétique, fonctionnelle et intertextuelle pour examiner les proverbes comme discours religieux. Dans le but d’explorer les proverbes portant sur la culture matérielle, l’étude adopte les concepts du symbolisme, de filiation, de territorialité ainsi que les notions de la hiérarchie des métaux et d’extra-textualité. Le travail aborde les proverbes animaliers en ayant recours aux concepts de métaphore, du symbolisme et du contractualisme. Quant à l’expression temporelle des proverbes, elle est approchée dans une perspective culturelle et spatio-temporelle alors que le rapport du proverbe au genre féminin est déterminé à partir d’une analyse culturelle et sociale de son statut. Cette approche d’une étude multidimensionnelle du proverbe permet ici de déterminer le caractère biculturel, bispirituel, pragmatique, opportuniste et utilitariste de la foi religieuse des personnages kouroumiens. Elle montre en outre que les objets de la culture matérielle sont porteurs de significations sociales, culturelles, littéraires et environnementales. Grâce à son cadre conceptuel élargi et diversifié, ce travail permet également de constater que les animaux possèdent des identités distinctives et remplissent des fonctions romanesque, spirituelle, sanitaire et alimentaire. La thèse met enfin en évidence le caractère pluraliste du temps existentiel, et établit que la condition de la femme est fortement influencée par des facteurs naturels et socioculturels. De ses résultats, l’étude tire la conclusion que le proverbe permet à Kourouma de proposer sa lecture du monde et sa théorie de l’écriture romanesque.
Exploring Quinoline and Pyridine Functionalized Binucleating Ligands: Syntheses, Complexation and Reactivity
Keywords: inorganic chemistry
organometallic chemistry

The objective of this thesis is to explore quinoline and pyridine functionalized multidentate ligand systems that are capable of accommodating two metal species and to study the reactivity of the resulting bimetallic complexes, in the aim of investigating potential synergistic effects between the metal centres. A series of functionalized 1,2,4,5-tetrakis(quinolin-8-yl)benzene ligands were synthesized. The dinuclear platinum complexes of these ligands could activate C-Cl bonds of chlorinated solvents and dearomatize the central benzene ring of the ligand concurrently. A series of extended ligands where the central benzene ring was replaced by trans-stilbene, diphenylacetylene and pyrene groups were synthesized in order to explore more ligand-based reactivity. Two dinuclear diphenylplatinum complexes were synthesized. A series of mono- and bis-quinolinyl functionalized thiophene ligands have also been synthesized. Dinuclear platinum complexes of the bisquinolinyl thiophenes were isolated, which represented the first group 10 metal complexes of η2-thiophene, a long sought-after intermediate relevant to the hydrodesulfurization (HDS) process. Oxidation of these diplatinum complexes by MeOTf led to the isolation of mononuclear chiral five-coordinate platinum(IV) complexes, and a ligand twisting mechanism of these complexes was proposed on the basis of dynamic NMR studies and DFT calculations to elucidate the interconversion of two enantiomers. The reactions of monoquinolinyl functionalized thiophenes and [Pt(CH3)2(SMe2)]2/[PtH(dippe)]2 led to selective C-H/C-S bonds activation of the thiophene moieties respectively. A luminescent U-shaped bis-dipyridylamine functionalized anthracene ligand was designed and synthesized. This compound was fabricated into OLED devices and shown to be a promising emissive material. As a ligand, it adopted different coordination modes, acting as either binucleating double bidentate ligand, or mononucleating tetradentate ligand. Three dirhodium, dizinc and monozinc complexes were synthesized. Pyridine and phosphine functionalized 4,5-diazafluorene ligands were synthesized and the former ligand served as a mononucleating ligand via the two nitrogen donor atoms of the diazafluorenyl moiety while the latter ligand could act as a binucleating ligand via the phosphorus donor atom, two nitrogen donor atoms and the carbon donor atom. Several Ru, Rh, Pt, Cu and Au complexes were synthesized, and two Pt-Pt, Pt-Cu bimetallic complexes were isolated and characterized based on the phosphine functionalized ligand.
Spectrum Sensing in Cognitive Radio Networks
Keywords: Cognitive Radio
Spectrum Sensing

This thesis investigates different aspects of spectrum sensing in cognitive radio (CR) technology. First a probabilistic inference approach is presented which models the decision fusion in cooperative sensing as a probabilistic inference problem on a factor graph. This approach allows for modeling and accommodating the uncertainties and correlations in the cooperative sensing system. A constraint in the cognitive radios is the lack of knowledge about the primary signal and channel gain statistics at the secondary users. Therefore, a practical composite hypothesis approach is proposed which does not require any prior knowledge or estimates of these unknown parameters. Detection delay is an important performance measure in spectrum sensing. Quickest detection aiming to minimize detection delay has been studied in other contexts, and we apply it here to spectrum sensing. To combat the destructive channel conditions such as fading, various cooperative schemes based on the cumulative sum (CUSUM) algorithm are considered in this thesis. Furthermore, cooperative quickest sensing with imperfectly known parameters is investigated and a new solution is derived, which does not require any parameter estimation or iterative algorithm. In cognitive radios, there is a fundamental trade-off between the achievable throughput by the CRs and the level of protection for the primary user. In this thesis, this trade-off is formulated for the quickest sensing-based CRs. By throughput analysis, it is shown that for the same protection level to the primary user, the quickest sensing approach results in significantly higher average throughput compared to that of the conventional block sensing approach.
The Impact of Folic Acid Fortification on the Folate Intake of Canadians, Factors Associated with Sub-optimal Blood Folate Status among Women, and the Effect of Vitamin/Mineral Supplemental Use
Keywords: food fortification
folic acid
folate
nutrient supplementation
dietary assessment

Food fortification and nutrient supplementation are important strategies to address micronutrient deficiencies. Mandatory folic acid fortification was implemented in Canada and the U.S. in 1998 to reduce the incidence of neural tube defects (NTD). However, the actual amount of folic acid added to foods has not been reported in Canada. We analyzed 95 fortified foods and found that there is 50% more folate in foods than that reported in food composition tables, which are primarily based on minimum mandated fortification levels. We then determined if these observed folate overages impacted the prevalence of dietary folate inadequacy or intakes above the Tolerable Upper Intake Level (UL). Using data from the 2004 nationally-representative Canadian Community Health Survey (CCHS) 2.2 (n = 35,107), adjusted for folate overages, we found a low prevalence of folate inadequacy in Canada post-fortification. However, few women 14-50y consumed 400µg/d of synthetic folic acid, an amount associated with maximal protection against an NTD. Conversely, we also showed that use of folic acid-containing supplements led to intakes >UL in the general population. To develop a tool that would help clinicians identify women with red blood cell (RBC) folate concentrations that were not maximally protective against an NTD (<906nmol/L), we used data from the nationally-representative U.S. National Health and Nutrition Examination Survey 2003-2006 to define risk factors of RBC folate <906nmol/L. We found that 35% of American women 19-45y had RBC folate <906nmol/L. Younger age, low dietary folate intake, not consuming supplemental folic acid, smoking, and being African-American were associated with increased risk of RBC folate <906nmol/L. Given our observations of a low prevalence of folate inadequacy and folic acid supplement use leading to intakes >UL, we used CCHS 2.2 data to compare the diets of supplement users and non-users in terms of inadequacy and intakes >UL for other nutrients. We showed that the prevalence of inadequacy was low for most nutrients, and from diet alone, supplement users were not at increased risk of inadequacy compared to non-users. Furthermore, inclusion of supplements led to intakes >UL above 10% for vitamins A, C, niacin, folic acid, and iron, zinc and magnesium.
SPARC is Required for Larval Development and Regulation of Fat Body Dynamics in Drosophila melanogaster
Keywords: SPARC
Drosophila
Fat body
MMP

SPARC is a highly conserved trimodular Ca2+- and Collagen-binding matricellular protein with diverse functions during development, wound healing and cancer metastasis. Our lab previously generated an embryonic lethal Drosophila SPARC null mutant, Df(3R)nm136, analysis of which revealed that SPARC was required for the deposition of Collagen IV into basal laminae and normal nervous system development during embryogenesis. In contrast to these previous studies, my data revealed that SPARC is not required for the deposition of Collagen IV into embryonic basal laminae or embryonic nervous system development. Further analysis showed that the Df(3R)nm136 chromosome carried a second-site mutation in the Neuralized locus which caused the nervous system defects and embryonic lethality previously associated with a loss of SPARC. Removal of this second site mutation and reanalysis of the SPARC mutant phenotype revealed that SPARC is required for larval development where it appears to play a role in the regulation fat body remodelling. SPARC mutant fat bodies showed changes in cell shape and basal lamina remodelling which resemble the fat body remodelling process that normally occurs during pre-pupal stages via up-regulation of MMP2 in response to the steroid hormone ecdysone. The effects of loss of SPARC on fat body cells were shown to be cell autonomous. Structure-function analysis of SPARC showed that secretion of SPARC is required for its function, whereas Domain1 is dispensable. Together, my studies indicate that SPARC has essential intra and extracellular roles during Drosophila larval fat body development.
High Vitamin Intakes during Pregnancy and Characteristics of Metabolic Syndrome in Wistar Rat Dams and their Offspring
Keywords: multivitamins
pregnancy
fetal programming
folic acid

High vitamin (HV), AIN-93G diet with ten-fold the regular amount of vitamins (RV), consumed by pregnant Wistar rats increases characteristics of metabolic syndrome (MetS) in their first litters. Therefore, the effects of the maternal HV-diet on tissue mechanisms regulating insulin resistance in offspring (Part 1) and on characteristics of MetS in the dams and their second litter (L2) offspring (Part 2) were examined. Part 1 (studies 1 and 2) hypothesis was that the maternal HV-diet alters tissue fatty acid (FA) concentrations, expression of peroxisome-proliferator-activated receptors (PPARs) genes, and their regulation of metabolism in the offspring, favoring insulin resistance. Part 2 (studies 3 and 4) hypothesis was that high-vitamin intakes during the first pregnancy increase weight gain, food intake and markers of MetS in both the dams and their litters. In all experiments, dams were fed the RV or HV-diet. In study 4, a high-folic-acid-diet (HFol, RV+10-fold folic acid) was added. In studies 1 and 2, the offspring were weaned to an obesogenic diet. The HV-diet affected tissue FA concentrations (study 1), increased muscle PPAR-ɑ mRNA levels and uncoupled relationships between hepatic PPAR-γ mRNA levels and insulin resistance (study 2) in male offspring. In study 3, dams fed the HV-diet during the first pregnancy were maintained on the RV-diet and then mated again after 12wk. Their litters were fed the RV-diet. The HV-diet increased weight gain and food intake of both dams and L2, and insulin resistance in their offspring. In study 4, both HV and HFol-diets increased post-weaning weight gain, but differed in their effects on biomarkers of food intake regulation. In conclusion, feeding the HV-diet during the first pregnancy increases post-weaning body weight and food intake in Wistar rat dams, uncouples tissue regulation of glucose metabolism and promotes characteristics of MetS in their litters. Folic acid is not the only vitamin involved.
Isolation and Characterization of Colon Cancer-initiating Cells
Keywords: colon cancer
initating cells

Colorectal cancer is the second leading cause of death from cancer (men and women combined) in the U.S. and Canada. The mainstay of treatment remains surgical resection and although new agents are constantly emerging to treat colorectal cancer, to date none of the agents have been successful at curing patients with advanced disease. In recent years there has been an increasing interest in the notion that cancers are organized as a hierarchy with the cancer-initiating cell (C-IC or cancer stem cell) existing at the apex. The C-ICs only represent a subset of the total tumour cells; however, research indicates that they are responsible for both the initiation and maintenance of tumour growth. In the studies presented here, we determined that human colon cancers are organized in a hierarchical manner. Furthermore, we prospectively isolated a subset of colon cancer-initiating cells (CC-ICs) based on the expression of the cell surface marker, CD133. The identification of CC-ICs has led to a number of questions concerning the molecular mechanisms driving these cells. Functionally all C-ICs are characterized by their ability to: i) generate a xenograft that histologically resembles the parent tumour from which it was derived, (ii) be serially transplanted in a xenograft assay thereby demonstrating the ability to self-renew and, (iii) generate daughter cells that possess some proliferative capacity but are unable to maintain the cancer because they lack intrinsic regenerative potential. It is becoming evident that cancer cells evolve as a result of their ability to hijack normal self-renewal pathways, a process that can drive malignant transformation. Studying self-renewal in the context of cancer and C-IC maintenance will lead to a better understanding of the mechanisms driving tumour growth. In this work we demonstrate that the inhibitors of differentiation genes (Id1 and Id3) play a central role in driving self-renewal in the CC-IC subset. Furthermore, we demonstrate that this effect is partially mediated through the cdk-inhibitor, p21cip1/waf1.
The Role of NKR-P1B:Clr-b Recognition in NK Cell Mediated Immunity To Cytomegalovirus Infection
Keywords: Immunology
Infectious Disease

NK cells are innate lymphocytes that are crucial for host immunity during infections. Discrimination between healthy and infected cells is facilitated through a sum of inhibitory and stimulatory signals. Host cells can modulate the expression of NK ligands in response to infection, transformation, and stress, while viruses can exploit these mechanisms to prevent the killing of the infected cells. This thesis focuses on the interaction between the NK receptor, NKR-P1B, and its ligand, Clr-b. First, we used a reporter cell-based protocol to establish hybridomas producing monoclonal antibodies against a putative viral immunoevasin, RCTL. We express CD3ζ-fusion proteins on the reporter cells, which we then use to immunize and screen hybridoma specificities. Our results demonstrate a rapid, efficient, and high-throughput method of monoclonal antibody screening, and provide the framework for our work on cytomegalovirus evasion of the NKR-P1B:Clr-b system. Next, we show that RCMV infection results in a notable downregulation of rClr-b at the protein and transcript levels. Conversely, RCTL is upregulated during infection, and binds to the same NK-inhibitory receptor as Clr-b, NKR-P1B. In the absence of RCTL, RCMV-mediated Clr-b loss leads to increased NK-killing of infected targets and an NK-dependent reduction of viral titers in vivo. Notably, NKR-P1B is highly polymorphic, and certain rat NKR-P1B alleles have lost binding to the viral RCTL but not to the host Clr-b molecule, suggesting co-evolution between the host and the virus. In the next chapter, we address some of the mechanisms responsible for CMV-mediated Clr-b downregulation, and show that Clr-b downregulation also occurs to mice in response to MCMV infection. Moreover, early gene expression (host or viral) appears to be required for Clr-b downregulation. Interestingly, engagement of any one conventional pattern recognition receptor is insufficient to mimic MCMV-mediated Clr-b downregulation. Similarly, fibroblasts lacking various intermediates for the interferon or inflammasome pathways still downregulate mClr-b, with the exception of the DNA sensor, Zbp-1. Lastly, a recently identified autocatalytic motif conserved in the rat and mouse Clr-b transcripts, the hammerhead ribozyme, appears to be involved in Clr-b regulation. Taken together, our results explore a novel and important role for NKR-P1B:Clr-b interactions in viral immunity.
Pre-B Cell Colony-enhancing Factor (PBEF) Promotes Neutrophil Inflammatory Function through Enzymatic and Non-enzymatic Mechanisms
Keywords: Inflammation
Neutrophil
Apoptosis
Oxidative burst
Innate immunity
Nampt
NAD
PBEF

Pre-B Cell Colony-Enhancing Factor (PBEF) is a cytokine-like molecule that functions as a nicotinamide phosphoribosyl transferase (Nampt) in a salvage pathway of NAD biosynthesis. PBEF has well-characterized activity as an extracellular inflammatory mediator and has been proposed to signal through the insulin receptor (IR). As neutrophils are key effectors of the innate immune response to infection and injury, we hypothesized that PBEF promotes pro-inflammatory function in neutrophils and that these pro-inflammatory effects may occur through interactions with the neutrophil IR or through PBEF’s enzymatic Nampt activity. Our studies focused on two important facets of neutrophil inflammatory function: their ability to generate reactive oxygen species (ROS) and undergo constitutive apoptosis. We found that, although PBEF does not activate oxidative burst on its own, it primes for ROS generation through the NADPH oxidase. PBEF promotes membrane translocation of cytosolic NADPH oxidase subunits p40phox and p47phox, but not p67phox, induces p40phox phosphorylation and activates Rac. Priming, translocation and phosphorylation are dependent on activation of p38 and ERK mitogen activated protein kinases. PBEF priming of neutrophils occurs independent of its Nampt capacity or of interactions with IR. We next investigated the effects of PBEF on neutrophil constitutive apoptosis. Our lab previously established that extracellular PBEF delays neutrophil apoptosis. Accordingly, we next investigated the mechanism through which this delay was occurring. PBEF-induced delayed apoptosis was enhanced in the presence of Nampt substrates, and NAD alone could delay apoptosis to an extent comparable to PBEF. Delayed apoptosis was blocked by a Nampt inhibitor and was lacking when a mutated PBEF deficient in Nampt activity was utilized. The cell-surface NAD glycohydrolase, CD38, can convert NAD to cyclic ADP-ribose (cADPR). Blocking CD38 activity with a blocking antibody partially reversed the delay of apoptosis induced by PBEF in conjunction with its substrates, and delayed apoptosis could be achieved by addition of the CD38 product cADPR. Finally, we found that delayed apoptosis induced by PBEF did not involve IR. These results indicate that PBEF can prime for enhanced oxidative burst and delay apoptosis in neutrophils, and that these phenomena occur through distinct mechanisms.
Dissecting the Role of 4-1BB and its Ligand in Enhancing CD8 Effector and Memory T Cell Responses
Keywords: 4-1BB
CD8 T cells
Influenza
Tumor immunotherapy
CD8 memory T cells
Co-stimulation

The Tumor necrosis factor receptor (TNFR) family member 4-1BB and its TNF family ligand, 4-1BBL, are important in modulating multiple stages of the CD8 T cell response. Here I show that during a mild influenza infection, 4-1BBL is completely dispensable for initial T cell responses, viral clearance and mouse survival. In contrast, during severe influenza infection with prolonged viral load, 4-1BB expression is sustained on lung T cells and 4-1BBL is upregulated in the lung compared to mild influenza infection. Under these conditions, 4-1BBL-deficiency results in a decreased CD8 T cell response in the lungs, higher viral load, impaired lung function and increased mortality. These findings suggest that the sustained expression of 4-1BB and its ligand as a function of viral load fine-tunes the CD8 T cell response to a level appropriate for the severity of infection. 4-1BBL is also important for maintaining CD8 memory T cell survival following the clearance of an infection. I found that 4-1BB is selectively expressed on a subset of memory CD8 T cells in the bone marrow. I further showed that the TNFR family member GITR is intrinsically required on CD8 memory T cells for 4-1BB expression in vivo, and that 4-1BB on CD8 T cells interacting with 4-1BBL on a radio-resistant cell in the bone marrow contributes to CD8 memory T cell survival. Immunotherapy with 4-1BB agonists has shown efficacy in eradication of tumors in several mouse models. These effects have been attributed to 4-1BB on multiple cell types. I found that 4-1BB either on transferred T cells or on host T cells was necessary and sufficient for inducing regression of established tumors when anti-4-1BB is combined with adoptive T cell therapy. This thesis highlights the importance of the CD8 T cell intrinsic role of 4-1BB in the immune system.