NCube/papyrus huggingface dataset:
Étude-pilote portant sur une intervention de groupe auprès de femmes souffrant d’hyperphagie boulimique et l’évaluation de ses effets potentiels

This study focuses on a group intervention for binge eating disorder (BED), by measuring its potential effects on the quality of life related to weight, frequency and severity of binge episodes, depressive symptoms, body dissatisfaction and body weight, and documenting the degree of acceptance of the intervention by the participants. Thus, 11 overweight women that met the BED diagnostic criteria were recruited from spring 2012 to winter 2013, in Montreal. The program includes eight weekly sessions based on Cognitive Behavioral Therapy provided by a nutritionist and a psychotherapist. Quality of life related to weight (Impact of Weight on Quality of Life), binge eating frequency (recall of the last seven days), binge eating severity (Binge Eating Scale), depression (Beck Inventory for depression), body dissatisfaction (Body Shape Questionnaire) and body weight were measured before and after the intervention. Then, a questionnaire to assess the acceptance by the participants was submitted at the end of the program. The rate of participation was also collected. The results showed that our program has resulted in significant improvements in the overall quality of life score related to weight of 8.4 ± 13.3, and in terms of self-esteem and work. We also observed a decrease in binge eating frequency by 2.1 ± 2.1 days as well as in binge eating severity, depressive symptoms and body dissatisfaction whose scores decreased by 10.9 ± 7.7, 8.3 ± 5.7 and 32.8 ± 17.1 respectively. However, there was no significant difference in weight at the end of the intervention. Also, the program was well accepted by the participants with a participation rate of 93.8%. Satisfaction and relevance of the program scored respectively 4,6 and 4,8 out of 5. These data suggest that the group intervention seems to be a promising method to improve the symptoms and consequences of HB, except for weight.

Keyphrases: Binge eating disorder, treatment, Cognitive Behavioral Therapy, body weight, quality of life, depression, body image
Étude de la Structure-Fonction du Prosegment et du domaine CHRD de la PCSK9 humaine

Hypercholesterolemia is one of the major risk factors leading to cardiovascular disease. In this context, we focused our study on a protein that directly influences hypercholesterolemia: PCSK9. Since 2003, the coding gene for PCSK9 has been identified as the third locus responsible for familial hypercholesterolemia (FH3). PCSK9 is a protein secreted mostly from the liver by hepatocytes and has the capacity to recognize, bind and direct to degradation the LDLR receptor. The latter is responsible for the elimination the LDL particles from the plasma. The direct consequence of the LDLR degradation induced by PCSK9 is the harmful accumulation of the bad cholesterol in the blood.   Since PCSK9 activity has undesirable consequences on lipid metabolism homeostasis, we directed our research to characterize this protein to better understand its mechanism of action. Three domains compose PCSK9 structure and we focused on the ‘’structure-function study’’ of two domains, of which roles were still unknown: the prodomain located at the N-terminal extremity and the CHRD domain at the C-terminus of PCSK9.  The first manuscript presented in this thesis brings to light the importance of the acidic N-terminal sequence of the prosegment (amino acids 33-58) and its effect on the activity of PCSK9. It also presents a novel mechanism for fine-tuning the activity of PCSK9, which is enhanced at acidic pHs close to those of late endosomes. The second manuscript dissects further the PCSK9 structure, revealing that the structural requirements of the hinge and the M2 module located in the CHRD domain are not the same for the intracellular and extracellular pathways of PCSK9-induced LDLR degradation. Although the R434W natural mutation in the hinge region is absolutely deleterious for the intracellular activity of PCSK9, it reduces by ~70% the extracellular one. In contrast, the loss of M2 module of the CHRD domain is tolerated for the intracellular activity of PCSK9 but not for the extracellular one. The third manuscript demonstrates for the first time that a chimera containing the prosegment (Fcpro) directly binds PCSK9 and effectively acts as a negative regulator (inhibitor) of its ability to induce LDLR degradation.  Our work presents a new strategy to develop such inhibitors by interfering with the structure of PCSK9 and exploiting the properties of the PCSK9 prosegment and the advantage of its fusion to a humanized Fc of IgG1. In summary, the present research data sheds new light on the functional contribution of the prodomain and the CHRD domain of PCSK9.

Keyphrases: CHRD, Fc, M2 module, Structure-function, Inhibitor, LDLR degradation, Hypercholesterolemia, Prodomain
Extradition et non-refoulement : la justice fondamentale en péril? Analyse du cas Németh c. Canada (Justice)

In Németh v. Canada (Justice) (2010), the Supreme Court concludes that it is possible for the Minister of Justice to surrender a refugee facing extradition, unless it is unjust or oppressive or the discrimination clause can be applied. Cromwell J. established it isn't necessary to revoke the refugee status prior to the extradition; the Minister only has to demonstrate that the change of circumstances in the refugee's country may lead to the cessation of refugee protection. This implies that the Minister must come forward with evidence of changed circumstances and be satisfied on the balance of probabilities that the refugee no longer needs protection in Canada. Unfortunately, the extradition procedures do not properly ensure the substantive fundamental justice and protections sought by refugees. There is no discussion on a possibility to properly respond to the Minister's evidence. However, there must be an opportunity for them to disprove the evidence, especially because it is a subjective matter which challenges the refugees' credibility. Therefore, it is the Minister's responsibility to ensure there is a hearing to comply with fundamental justice. Nevertheless, the Court didn’t go on to prescribe such an obligation to the Minister. In this research, we will then ask ourselves which procedural safeguards should be given by the Minister of Justice to refugees facing extradition.

Keyphrases: Extradition Procedure, Refugees, Principles of Fundamental Justice, Evidence, Administrative Law, International Law, Constitutional Law
Apport de nouvelles techniques dans l’évaluation de patients candidats à une chirurgie d’épilepsie : résonance magnétique à haut champ, spectroscopie proche infrarouge et magnétoencéphalographie

Epilepsy is the most common chronic neurological disorder after stroke. The major form of treatment is long-term drug therapy to which approximately 30% of patients are unfortunately refractory to. Brain surgery is recommended when medication fails, especially if magnetic resonance imaging (MRI) can identify a well-defined epileptogenic lesion. Unfortunately, close to a quarter of patients have nonlesional refractory focal epilepsy. For these MRI-negative cases, identification of the epileptogenic zone rely heavily on remaining tools: clinical history, video-electroencephalography (EEG) monitoring, ictal single-photon emission computed tomography (SPECT), and a positron emission tomography (PET). Unfortunately, the limited spatial and/or temporal resolution of these localization techniques translates into poor surgical outcome rates.   In this thesis, we explore three relatively novel techniques to improve the localization of the epileptic focus for patients with drug-resistant focal epilepsy who are potential candidates for epilepsy surgery: high-field 3 Tesla (T) MRI, near-infrared spectroscopy (NIRS) and magnetoencephalography (MEG).  In the first study, we evaluated if high-field 3T MRI, providing a higher signal to noise ratio, could help detect subtle epileptogenic lesions missed by conventional 1.5T MRIs. Unfortunately, we show that the former was able to detect an epileptogenic lesion in only 5.6% of cases of 1.5T MRI-negative epileptic patients, emphasizing the need for additional techniques.   In the second and third studies, we evaluated the potential of NIRS in localizing the epileptic focus by analyzing the hemodynamic behavior of temporal and frontal lobe seizures respectively. We show that focal seizures are associated with significant increases in oxygenated haemoglobin (HbO) and total haemoglobin (HbT) over the epileptic area. While a contralateral mirror-like activation was seen in the majority of seizures, lateralization of the epileptic focus was possible most of the time. In addition, an unexpected increase in deoxygenated haemoglobin (HbR) was noted in some seizures, suggesting possible hypoxia even during relatively brief focal seizures.   In the fourth and last study, the utility of MEG in the evaluation of nonlesional drug-refractory focal epileptic patients was studied. It was found that MEG source localization of interictal epileptic spikes had an impact both on patient management for over two thirds of patients and their surgical outcome.

Keyphrases: Epilepsy, Epilepsy surgery, Magnetic resonance imaging 3.0 T, Electroencephalography, Near-infrared spectroscopy, Magnetoencephalography
Exploration du rôle du fragment LG3 sur les cellules souches mésenchymateuses dans le contexte du rejet vasculaire

Graft vasculopathy is diseases characterized by a progressive and obliterate narrowing of the blood vessels leading to ischemia and loss of graft function. This vascular narrowing is due to an accumulation of extracellular matrix and mononuclear cells positive for alpha smooth muscle actin (alphaSMA) including mesenchymal stem cells, thus forming an occlusive neointima. This condition is the leading cause of long term loss of kidney and heart transplants. Acute vascular rejection is a predictor of graft vasculopathy. Dr. Hébert’s team has demonstrated that endothelial apoptosis, which plays an important role in the development of vascular rejection, initiates the release of LG3, a fragment of the proteoglycan perlecan. Blood and urine levels of LG3 are increased in renal allograft recipients with vascular rejection and graft vasculopathy. The results obtained in the laboratory during my Master have helped to better characterize the impact of LG3 on an important cell type involved in neointima formation: the mesenchymal stem cells. My work has shown that the LG3 induces both the horizontal migration and the transmigration of MSC. This migration is ERK1/2-dependent, previously identified as a key molecule involved in neointima formation. In addition, our results demonstrate that Src kinase is activated by upstream activation of the MAPK pathway. Horizontal migration and transmigration induced by LG3 are also dependent on alpha2beta1 integrins, and the activation of the MAPK pathway. In a murine transplantation model, we also demonstrated that intravenous injection of recombinant LG3 promotes the accumulation of alphaSMA positive cells in the neointima. In addition, when the recipient is deficient for the alpha2 integrin but the graft is wild type, LG3 fails to induce neointima formation in the graft suggesting that recipient cells play an important role in the neointima formation. Finally, we demonstrated that intravenous injection of LG3 also increases the number of positive cells for the phosphorylated form of ERK1/2 (p-ERK1/2) in the neointima. This accumulation is dependent on the presence of alpha2beta1 integrins on recipient cells: when the recipient is wild type, there is an increase in the number of cells positive for p-ERK1/2.The investigation of these mechanisms in vascular remodeling presents new opportunities to inhibit the cellular response that leads to inadequate remodeling during chronic vascular damage and prolong graft survival.

Keyphrases: LG3, Migration, Mesenchymal stem cell, LG3, Migration, Homing, Vascular remodeling, Neointima
Warfarin-induced vitamin K deficiency is associated with cognitive and behavioral perturbations, and alterations in brain sphingolipids in rats

Vitamin K (VK) is widely known for its role in blood coagulation, however many studies suggest its involvement in brain function. VK is required for the activation of various cerebral proteins (e.g., Gas6) and menaquinone-4 (MK-4), the main K vitamer in brain, is involved in sphingolipid metabolism. Furthermore, life-long intake of a low VK diet has been associated with cognitive deficits in old rats. Warfarin (W) is a potent VK antagonist that acts by blocking the VK cycle causing a “relative VK deficiency” at the cellular level. In light of this and the emerging role of VK in brain, W could represent a risk factor for cerebral function. The finding of this study is important according to the large proportion of adults with thromboembolic diseases being treated with warfarin drugs. This study was conducted in a rat model where the impact of W was investigated with respect to cognition, behavior, and brain menaquinone-4 (MK-4) and sphingolipid status. Fourteen Wistar male rats were treated with 15 mg W/kg/d (in drinking water) and subcutaneous VK (85 mg/kg), 3X/wk, for 10 wks; 14 control rats were treated with normal water and injected with saline. At the end of the treatment period, rats were subjected to different behavioral tests, afterwhich their brains assessed for VK (phylloquinone and MK-4) and sphingolipids (gangliosides, ceramides, cerebrosides, sphingomyelin and sulfatides) and gangliosides subtypes (GT1b, GD1a, GM1, GD1b). Mean latencies to find the hidden platform were higher in the W compared to the control group (p<0.05) suggesting cognitive deficits as well as hypoactivity and lower exploratory behaviour in the open field test (p<0.05). Warfarin treatment also resulted in a dramatic decrease in MK-4 concentration in all brain regions (p<0.001), altered sphingolipid level, especially in frontal cortex and midbrain (p<0.05), and in a loss of sphingolipid regional differences, notably for gangliosides. W treatment was associated with lower GD1a in the hippocampus and higher GT1b in the striatum and prefrontal cortex. In conclusion, warfarin-induced VK deficiency alters VK and sphingolipid status in brain with potential detrimental effects on brain functions.

Keyphrases: MK-4, Warfarin, Cognition, Rats, Vitamin K, Sphingolipids, Rat
Étude de protection conférée par vaccination ADN dans un modèle murin d’hépatite auto-immune

DNA immunizations were proven effective in a range of autoimmune diseases. The first goal of this master’s thesis was thus to evaluate if a protocol of 3 intramuscular plasmidic injections of pCMV-CTLA4-NP and pVR-IL-12, at 2 weeks apart, would protect TTR-NP mice, a transgenic murine model previously developed in the laboratory, against the development of an autoimmune hepatitis. The second goal was, if the protection was indeed conferred by DNA vaccination, to elucidate the mechanisms underlying this effect. The initial hypotheses were that DNA vaccination would indeed elicit a protection against autoimmune hepatitis, and that this could be attributed to a skew from the typical Th1 response to a more tolerogenic Th2 response, to the exhaustion of the immune cells and/or to the activation and the proliferation of regulatory T cells.  Results show that DNA vaccination induces a transient protection against lymphocytic infiltrates in the liver. This protection is thought to be caused by the exhaustion of the CD4+, CD8+ and CD19+ cells found in the spleen and expressing PD-1 in greater proportion at 3 months, and not to be mediated by CD4+CD25+FoxP3+ or CD8+FoxP3+ regulatory T cells. An immunomodulation from a Th1 to a Th2 response could still be a plausible explanation by the protection conferred by the DNA vaccination, but additional experimentations in a more physiological setting would be necessary to infer on its real implication. DNA vaccination had no effect on autoantibodies or on alanine aminotransferase levels, which are two biological markers of the disease.

Keyphrases: autoimmune hepatitis, DNA vaccination, autoimmunity, tolerance break, liver
Mammite bovine à Escherichia coli : identification et caractérisation de la persistance

Escherichia coli is part of the environmental mastitis pathogens. However, in some cases, persistence in the mammary gland occurs. The objectives of this study were to confirm persistent infection in Canadian dairy cows and to identify possible spread between quarters of a same cow in a cohort of 91 herds monitored over two years. Also, persistent strains were compared to transient strains. Antimicrobial susceptibility was determined by the broth microdilution method. Genetic profiles were obtained for same cow isolates by DNA fingerprinting with pulsed field gel electrophoresis. Twenty-seven virulence genes were determined by colony hybridization. Persistence was detected in 18 cows and contagion between quarters, in 2 cows. Proportions of resistance in persistent E.coli ranged from 0.0% (enrofloxacin) to 27.8% (ampicillin and tetracycline). Proportion of resistance in transient E.coli ranged from 0.0% (enrofloxacin) to 16.8% (tetracycline). For each additionnal antimicrobial resistance, odds of being classified as a persistent isolate increased by a factor of 1.6 (95% CI: 1.1, 2.4). Resistance to ampicillin and to cephalothin were both associated with higher odds of being a persistent E. coli. Isolates harboring gene iroN had 5.4 times higher odds (95% CI: 1.2, 24.0) of being classified as persistent isolates. Similarly, isolates positive to virulence gene sitA had 8.6 times higher odds (95% CI: 2.8, 27.1) of being classified as persistent isolates. In conclusion, this study confirmed that E. coli can persist in the udder of Canadian dairy cows and that these E. coli are different when compared to transient E. coli.

Keyphrases: Escherichia coli, Virulence, Bovine, Mastitis, Genotype, Virulence, Antimicrobial resistance
Les réseaux militaires comme acteurs des relations internationales : le cas du Multinational Interoperability Council

For more than fifty years, Western powers have created many different forms of international military networks, in order to strengthen their ties and harmonize their technics, equipment and ways of doing things. To date, these groups have remained largely ignored by the academic discipline of International Relations. And yet, globalization and the rise of information technologies have provided many new actors with an access to political processes, including in the field of security. This evolution sheds new light on the role, mission and responsibilities that states assign to these networks. This research conducts an in-depth analysis of one military network, the Multinational Interoperability Council. The aim of this analysis is threefold: to define international military networks as a category of analysis for International Relations, to document empirically their functioning, and to understand their role in the field of internal security. To do so, the analytical framework combines the conceptual apparatus of relational institutionalism, the theory of social fields, and the methodological tools of the practice turn in International Relations. This combination allows for addressing the institutional, cognitive and practical dimensions of collective action within the network. The analysis reveals that, despite a limited influence, the MIC produces its own identity, capabilities, preferences and effects. The MIC’s actors have been able to create the conditions of its institutionalization, and they have succeeded in turning the network into an intentional actor of the international security field, while it was originally created as a mere structure of exchange of information. The MIC is not able to act autonomously, without states’ control. However, the relations established by the military who belong to it have provided them with capabilities – social, political and expertise capitals – that they would not otherwise possess, and which they can mobilize in their interactions with other actors of the field.

Keyphrases: MIC, International relations, Networks, Security, Military, Practices, Institutionalism, Strategy, Interoperability
Routage adaptatif et stabilité dans les réseaux maillés sans fil

Thanks to their flexibility and their simplicity of installation, Wireless Mesh Networks (WMNs) allow a low cost deployment of network infrastructure. They can be used to extend wired networks coverage allowing connectivity anytime and anywhere. However, WMNs may suffer from drastic performance degradation (e.g., increased packet loss ratio and delay) because of interferences and congestion. In this thesis, we are interested in adaptive routing and stability in WMNs. In the first part of the thesis, we focus on defining new routing metric and gateway selection scheme to improve WMNs performance. In this context, we propose a source routing protocol based on a new metric which takes into account packet losses, intra-flow interferences, inter-flow interferences and load at gateways together to select best paths to best gateways. Simulation results show that the proposed metric improves the network performance and outperforms existing metrics in the literature. In the second part of the thesis, we focus on critical zones, in WMNs, that consist of mesh routers which are located in neighborhoods of gateways where traffic concentration may occur. This traffic concentration may increase congestion and interferences excessively on wireless channels around the gateways. Thus, we propose a proactive and adaptive routing protocol based on reinforcement learning which increasingly penalizes links with bad quality as we get closer to gateways. We use Q-learning algorithm to dynamically update path costs and to select the next hop each time a packet is forwarded toward a given gateway; learning agents in each mesh router learn the best link to forward an incoming packet and explore new alternatives in the future. Simulation results show that our distributed routing protocol is less sensitive to interferences and outperforms existing protocols in the literature. In the third part of this thesis, we focus on the problems of instability in WMNs. Instability occurs when routes flapping are frequent. Routes flapping are caused by the variations of link quality due to interferences and congestion. Thus, after analyzing factors that may cause network instability, we propose to use the number of path variations in routing tables as an indicator of network instability. Also, we use entropy function, usually used to measure uncertainty and disorder in systems, to define node stability, and thus, select the most stable routes in the WMNs. Simulation results show that our stability-based routing protocol outperforms existing routing protocols in the literature in terms of throughput, delay, loss rate, and Gini index.

Keyphrases: Wireless Mesh Networks, Routing metrics, Measures, Stability, Interferences