NCube/papyrus huggingface dataset:
Étude du système endocannabinoïde et ses implications dans la schizophrénie

Schizophrenia is a complex disease that has 1% worldwide prevalence. Dopamine etiological theory leads neurochemical paradigms although glutamate hypothesis is gaining in importance among several neurotransmission circuits involved. Schizophrenia patients are more prone to substance use disorders, particularly to cannabis dependence, than the general population. Therefore, we have aimed to explain the hypothesis of a deregulation in the endogenous cannabinoid system, a very important neurodulator.   First, this thesis proposes in the first article an exhaustive literature review on the endocannabinoid system and its implications in schizophrenia. Then, we present results from our clinical research on plasmatic endocannabinoids in three groups of subjects with schizophrenia and/or substance use disorders, during twelve weeks. We have observed a mirror effect involving two endocannabinoid ligands, anandamide and oleylethanolamide, which were elevated in patients with dual diagnosis and reduced in patients with only substance use disorders. At the end of the study, it seems that endocannabinoid elevation was maintained and we supposed a vulnerability to psychosis in a substance use disorder context.   Finally, we analyzed our results by integrating explanations from molecular biology and neuropharmacology and also from neurochemical and inflammatory theories already well-known in schizophrenia. We also considered the main comorbidities observed in clinic such as substance use and metabolic disorders. Then, we proposed an endogenous cannabinoid model of schizophrenia. Ultimately, this thesis suggested research perspectives and potential treatments.

Keyphrases: anandamide, oleylethanolamide, dopamine, glutamate, endogenous cannabinoid, schizophrenia, psychosis, substance use disorder
Le Canada et la politique étrangère de la France, 1945-1962 : stratégies d'une puissance moyenne

This study questions Canadian international influence during the "Golden Age" by providing a case study of Canada's foreign policy in its relations with France. Multilateral institutions were the cornerstone of Canadian foreign policy; they were providing the politico-economic counterweights allowing Canadians to distance themselves from the United States. These institutions were often perceived as a constraint by the French, who consequently tried to weaken or reform them. Meanwhile, they were trying to preserve their colonial empire and were demanding unanimous occidental support. France became the most disturbing of Canada's allies, almost systematically attacking its foreign policy project, which consisted in trying to balance a firm commitment to NATO and an overtly anti-imperialist policy designed to seduce non aligned countries of the Commonwealth. This dissertation studies the strategies of a "middle power" trying to defuse the crisis between its allies and to reconcile the contradictory dimensions of its own external policy.

Keyphrases: Canada, France, ONU, Commonwealth, Multilateralism, Middle power, NATO, Decolonization, UN, Atlanticism
Le locus 1q32 : susceptibilité aux maladies inflammatoires de l’intestin et rôles biologiques de C1orf106 et KIF21B

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by chronic inflammation along the gastrointestinal tract. These complex diseases appear to be the result of an immune system dysregulation. Genome-wide association studies have identified 99 loci that contribute to IBD susceptibility. Region 1q32 of chromosome 1 has been identified as a CD, UC and multiple sclerosis susceptibility locus and the region around this marker (rs11584383) contains four genes: Chromosome 1 open reading frame 106 (C1orf106), Kinesin family member 21B (KIF21B), Calcium channel, voltage-dependant, L type, alpha 1S subunit (CACNA1S) and Chromosome 1 open reading frame 81 (C1orf81). The goal of the present study is to place these genes in a biological context and to determine their possible involvement in IBD. By using quantitative PCR (qPCR), we determined the expression profile of these genes in murine tissues and human cell lines and we observed that KIF21B and C1orf106 were expressed in immune as well as gastrointestinal tissues. Next, we tested the involvement of KIF21B and C1orf106 in biological pathways previously implicated in IBD, more specifically NF-kB activity and endoplasmic reticulum (ER) stress. We found that overexpression of KIF21B in HEK293T cells decreased the activity of NF-kB whereas C1orf106 overexpression increased ER stress and Wnt activity. Taken together, these results suggest that KIF21B and C1orf106 are good candidate causal genes in the 1q32 region.

Keyphrases: 1q32, Inflammation, Nuclear factor kappa B, KIF21B, C1orf106
Étude comparative de la morphologie du plancher pelvien des femmes âgées continentes et avec incontinence urinaire

Aims: The study’s aim was to compare: a) pelvic floor muscle (PFM), bladder neck and urethral sphincter morphologies using MRI and b) PFM function using digital palpation (PERFECT scheme) in continent women, women with stress (SUI) and mixed (MUI) urinary incontinence. Method: Women were taught how to perform PFM contractions correctly and their PFM function was assessed, then each woman completed a dynamic 3T MRI session. Results: 66 women participated in the study. Groups were similar for age, BMI, vaginal deliveries and hysterectomies. Validity and reliability of the different anatomical measures used has been confirmed at the beginning of the study. To control for the potential effect of pelvic size on study parameters, women were matched based on pelvic inlet length. MUI women seemed to have lower PFM resting position and pelvic organ support at rest, based on their M-Line, PCL/H-Line angle and urethrovesical (UV) junction height. However, SUI women seemed to have a PFM morphology similar to that of continent women, but presented a greater occurrence of bladder neck funnelling and a larger posterior UV angle. There were no differences in urethral sphincter morphology between the 3 groups. Functionally, as shown by the PERFECT scheme results, both UI groups had poorer PFM strength on MVC then continent women. The MUI group also showed poor PFM elevation on contraction. Conversely, women with SUI had a timing problem on cough. Conclusion: The deficits in women with SUI and MUI appear to be very different. Notwithstanding, they all support the rationale for PFM exercise treatment in older women with SUI and MUI. However, the findings suggest the need for rehabilitation treatments specificity for each UI type.

Keyphrases: Urinary incontinence, Women, Aging, Magnetic resonance imaging, Pelvic floor muscles, Bladder neck, Urethral striated urogenital sphincter, Pelvic organ support
Imagination et perception morale

My thesis focuses on the role of imagination for moral perception. I argue that imagination – whether accompanied by emotion or not - has an epistemic role inasmuch as it can reveal moral norms, values, and virtues that might otherwise go un-noticed. On the simulationist account, belief-like imaginings and perception-like imaginings give us access to the morally relevant but perceptually non-salient features of a situation. I identify three types of “imaginative moral perception”: 1) the perspective taking that consists of putting yourself in someone else’s shoes; 2) the imaginative framing, which refers to seeing an element of a situation as something else; 3) the imaginative comparison, which sheds light on the actual world by using counterfactuals thinking that give us access to a possible world. Each of these types of moral perception contributes to enhancing our moral knowledge hence to improving our moral deliberation. My argument appeals to recent contributions from the fields of philosophy of psychology, cognitive and social psychology, neuropsychology and, of course, moral psychology.

Keyphrases: Moral psychology, Imagination, Imagination, Moral perception, Moral epistemology, Moral knowledge, Perspective taking, Framing, Imaginative comparison, Thought experiment, Counterfactual thought
Apprentissage automatique pour la détection de relations d'affaire

Documents published by companies such as press releases, contain a wealth of information on various business activities. This is a valuable source for business intelligence analysis; but automatic tools are needed to exploit such large volume data. The work described in this thesis is part of a research project on business intelligence, namely we aim at the detection of business relationships between companies described in press releases. In this thesis, we consider business relation detection as a problem of classification. However, the existing classification methods do not allow us to obtain a satisfactory performance. This is mainly due to two problems: the representation of text using all the content words, which do not necessarily a business relationship; and the imbalance between classes. To address the first problem, we propose representations based on words that are between or close to the names of companies involved (which we call pivot words) in order to focus on words having a higher chance to describe a relation. For the second problem, we propose a two-stage classification. This method is more effective than the traditional resampling methods. We tested our approach on a collection of press releases in the automotive industry. Our experiments show that both proposed approaches can improve the classification performance. They perform much better than the traditional feature selection methods and the resampling method. This work shows the feasibility of automatic detection of business relations. The result of this detection could be used in an analysis of business intelligence.

Keyphrases: Business relation, Supervised classification, Feature selection, Unbalanced data
Implémentation de la répartition de charge et du mode TOT pour la simulation d’un détecteur Timepix à pixels

The pixelated Medipix detectors have been developed by the Medipix Collaboration to perform real-time imaging. The semiconducting chip is divided into 65536 pixels of $55\times 55\um^2$ for a total active area of nearly $2\cm^2$. Because of their sensitivity to all kinds of particles, sixteen Medipix2 detectors (ATLAS-MPX) have been placed in the ATLAS detector and its cavern to measure for the radiation produced by the head-on proton collisions produced at the LHC. At the next ATLAS upgrade, the ATLAS-MPX network will be extended to include the Timepix detectors, the latest version that allows one to measure the total energy deposited in the semiconductor.  To improve data analysis, a Geant4 simulation project of a Timepix detector was initiated by John Id\'arraga at the Université de Montréal. In the framework of the ATLAS experiment, this simulation could be used with Athena, the ATLAS analysis software, and the full ATLAS simulation.  Due to their repulsivity, the charge carriers created by an incoming particle in the pixelated detector are spread over the surrounding pixels causing a charge sharing effect. An effective model has been developed to reproduce this effect without resolving the charge drift's differential equation. This model and the \textit{time-over-threshold} mode of the Timepix have been included in the simulation to reproduce the tracks left by the striking particles. First, one had to individually calibrate each pixel of the device with $\Am$ and $\Ba$ sources. The simulation's validation has been performed with low energy protons and $\alpha$ particles delivered by the van de Graaff Tandem at the Laboratoire René-J.-A.-Lévesque of the Université de Montréal.

Keyphrases: Timepix, TOT, time-over-threshold, Timepix, pixelated detectors, charge sharing, TOT, time-over-threshold, Geant4 simulation
Complexité des homomorphismes de graphes avec listes

Constraint satisfaction problems, consisting in assigning values to variables while respecting a set of constraints, form a large class of natural problems. In order to study the complexity of these problems, it is convenient to see them as homomorphism problems on relational structures. One current research topic is to characterise complexity classes where the homomorphism problem belongs. The ultimate goal is to confirm conjectures that bind together algebraic properties of the relationnal structure and complexity of the homomorphism problem.   At first, the thesis characterizes digraphs which generate FO list-homomorphism problems. It is shown that in the particular case of telescopic digraphs, conjectures binding together algebra and complexity are confirmed.   Subsequently, we characterize graphs which generate arc-consistency solvable list-homomorphism problems. We introduce the notion of monochromatic polymorphism and we propose a simple algorithm which solves the list-homomorphism problem if the target graph admits a monochromatic TSI polymorphism of arity k for every k ≥ 2.

Keyphrases: complexity, digraph, list-homomorphism, polymorphism, constraint satisfaction problem
Bases génétiques de l'amusie congénitale : une étude de jumeaux

Music is an important part of every known culture, and its universality raises the question of a possible biological basis. Musical disorders, such as congenital amusia, offer compelling insight into these roots. In order to examine the genetic basis of this phenotype, we used a classical twin study paradigm. Our study had two main goals: (a) investigate if identical (monozygotic; MZ) co-twins perform more similarly on auditory and musical tasks than non-identical (dizygotic; DZ) co-twins and (b) explore the twins’ musical environments in order to better understand the contribution of environmental versus genetic factors in the differences underlying musical abilities. In addition, we sought to replicate previous investigations that demonstrated impaired pitch processing but intact rhythm perception in amusic participants. To do so, we tested eight pairs of MZ and six pairs of DZ twins in which at least one of the co-twins was potentially amusic. Participants completed an online amusia test, a pitch detection task and a singing task. We observed no performance or musical environment differences between MZ and DZ twins, suggesting that musical abilities might be more influenced by the twins’ shared environment than by genetic factors. In addition, and as reported in previous studies, amusics made pitch processing errors in both perception and production, but rhythmic perception was preserved. Future studies, particularly those with access to larger twin samples, will be able to further elucidate the roles of environmental and genetic factors in the amusic phenotype.

Keyphrases: Congenital amusia, Twins, Pitch perception, Rhythmic perception, Singing
Trois essais en économie des ressources naturelles

This thesis consists of three articles on the economics of nonrenewable natural re- sources. We consider in turn the following questions : the in-situ price of nonrenewable natural resources, the optimal extraction rate and the price of nonrenewable and durable resources. The purpose of the first article is to estimate the in-situ price of nonrenewable natural resources using average extraction cost data as proxy for marginal cost. Using the regime switching Generalized Method of Moments (GMM) estimation technique, a dynamic of the market price derived from the first-order conditions of a Hotelling model is estimated with panel data for fourteen nonrenewable resources. I find results that tend to support the model. First, it appears that the Hotelling model has a good explanatory power of the observed market prices. Second, although the fitted prices seem to be subject to structural breaks over time, this does not have a significant impact on the explanatory power of the model. Third, there is evidence that marginal extraction cost can be approximated by average extraction cost data. Fourth, when allowing for structural breaks, estimates of the in-situ price decrease or exhibit an inverted U-shape over time and appear to be positively correlated with the market price. Fifth, for nine of the fourteen minerals, the difference between the estimates of the in-situ price with and without allowing for structural breaks is a zero-mean process.

Keyphrases: Nonrenewable natural resources, In-situ price, Natural resource prices, Switching model, GMM analysis, Panel data, Ressources durables, Durable resources, intertemporal asset pricing model, MEDAF-C, Extraction rate
L’encadrement juridique des biobanques populationnelles et leurs obligations au Québec

The collection of human samples and related data is not a recent practice. However, in the last few decades, such practices have taken much importance mainly due to the creation of population type biobanks. Defined as research infrastructures, they are conceived to last several decades. They invite thousands and, in some cases, hundreds of thousands of participants to contribute their samples, undergo physical and biochemical tests and answer various questions regarding their health and socio-demographic environment. In this context, what are the obligations of these initiatives and the researchers involved therein towards the participants? Considering their duration, what is the legal setting surrounding such biobanks in Québec? These are the two questions addressed by this study. With respect to the legal setting, we propose an analysis based on three axes: i) laws, rules, professional deontology and norms; ii) the legal qualification of the act of banking samples and data; and iii) obligations resulting from the nature of the object of the legal relation. Our analysis reveals that the legal setting surrounding biobanks is a mosaic composed of legislative, contractual, deontological and normative obligations that, despite its complexities and challenges of accessibility for the participant, ensure a certain level of protection for the latter. Regarding the obligations of the biobank and its researchers, they are, for the majority, affected by particularities of population type biobanks. Indeed, specific challenges exist with respect to consent, the obligation to inform, the return of results and the security of samples and data. Given the evolving nature of the theses obligations, we propose to consider an approach based on the best interests of the participants when determining the nature and the intensity of the different obligations applicable to the biobank and its researchers.

Keyphrases: Biobank, Population biobank, Researcher's obligations, Obligations of medical researchers, Information access, Human samples, Research contract, Research infrastructures, Return of results, Act of banking
Validation des modèles statistiques tenant compte des variables dépendantes du temps en prévention primaire des maladies cérébrovasculaires

The main interest of this research is the validation of a statistical method in pharmacoepidemiology. Specifically, we will compare the results of a previous study performed with a nested case-control which took into account the average exposure to treatment to : – results obtained in a cohort study, using the time-dependent exposure, with no adjustment for time since exposure ; – results obtained using the cumulative exposure weighted by the recent past ; – results obtained using the Bayesian model averaging. Covariates are estimated by the classical approach and by using a nonparametric Bayesian approach. In the later, the Bayesian model averaging will be used to model the uncertainty in the choice of models. To model the cumulative effect of exposure which varies over time, in the classical approach the function assigning weights according to recency will be estimated using regression splines. In order to compare the results with previous studies, a cohort of people diagnosed with hypertension will be constructed using the databases of the RAMQ and Med-Echo. The Cox model including two variables which vary in time will be used. The time-dependent variables considered in this paper are the dependent variable (first stroke event) and one of the independent variables, namely the exposure.

Keyphrases: B-spline, Cox model, Bayesian model averaging, survival analysis
Axe et rotaxane parapluie : vers de nouveaux
transporteurs transmembranaires de chlorures et de médicaments cycliques

The cell membrane is a phospholipid bilayer barrier that controls the exchanges between the cell and its environment. Its hydrophobic core prevents the entrance of hydrophilic, charged or large polar species that are transported through the bilayer by proteins. In some dysfunctional systems e.g. channelopathies), the balance of ion concentrations between the interior and exterior of the cell is no longer insured and the cell’s health is compromised. That is why the synthesis of synthetic transmembrane transporters is needed. There have been many synthetic anion carriers (especially chloride) developed in this area using different strategies. In this thesis we present our work on a new anion transporter, an umbrella thread. First, we designed and synthesized umbrella threads that showed significant chloride transport activity. These compounds combine two concepts: - the umbrella moiety, made from facial amphiphilic bile acids. The flexibility and large surface of the cholic acids can shield disfavored interactions between hydrophilic and hydrophobic elements that should ease their insertion into the bilayer. - a secondary ammonium recognition site on the thread that can form hydrogen bonds with chloride ions. Furthermore, the thread moiety is able to complex a crown-ether like wheel to form an umbrella pseudo-rotaxane or rotaxane that showed partially inhibited properties for chloride transport. This leads us to the second goal of this thesis, i.e. the development of a new vehicle for drug delivery. Some biologically active polar macrocycles (e.g. nactins) need to reach their target inside the cell to be efficient. The cell membrane also represents an obstacle here. In our work, we imagined using an umbrella thread as the vehicle for the cyclic drug as the wheel of the umbrella rotaxane). The umbrella rotaxanes were successfully assembled by the clipping method. The behavior of both the umbrella thread and umbrella rotaxane was extensively studied by NMR and fluorimetry. The umbrella motion from a shield conformation to an exposed one depending on the environment was observed for the rotaxane. Interactions between the umbrella rotaxane and phospholipid vesicles were also noticed. Finally, its ability to cross the lipid bilayer to deliver the wheel inside the vesicle was shown with α-chymotrypsin-filled liposome assays. This enzyme was able to cleave amide bonds on the umbrella thread to release the wheel.

Keyphrases: Conformation, Rotaxane, Transport transmembranaire, Transmembrane transport, Molecular umbrella, Chloride transport, Thread, Cyclic drug, Facial amphiphilicity, Phospholipid bilayer