NCube/papyrus huggingface dataset:
Prédiction des impacts pharmacocinétiques des interactions médicamenteuses
impliquant des CYP3A et les glycoprotéines-P : développement de modèles physiologiques et analyse de sensibilité

Early knowledge of pharmacokinetic properties of a new drug candidate and good characterization of the impact of drug-drug interaction (DDI) on those properties is of crucial importance in the process of drug research and development. The main objective of this thesis consisted in the conception of PBPK models able to predict the drug disposition in the absence and presence of metabolic and transport activity modulation.  The first part of this work aimed to develop a PBPK model that incorporates the efflux function of P-gp expressed in various tissues, in order to predict the impact of P-gp activity modulation on drug distribution. This approach, based on in vivo-in vitro extrapolation for estimating the transport-related parameters, allowed the prediction of domperidone distribution in heart and brain of wild-type mice and P-gp deficient mice. The model pointed out the protective function of P-gp in brain whereas it showed the negligible protective effect of P-gp in heart.  The second part of the project aimed to perform the global sensitivity analysis of the previous PBPK model, in order to investigate how the uncertainly and variability of the correlated physiological parameters influence the outcome of the drug distribution process. While a moderate variability of the model predictions was observed, this analysis confirmed the importance for a better quantitative characterization of parameters related to the transport processes trough the blood-tissue membrane.  Accounting for the input correlation allowed the delineation of the true contribution of each input to the variability of the model outcome.   The last part of the project consisted in predicting the pharmacokinetics of selected CYP3A substrates administered at a single oral dose to human, alone or with an inhibitor. Successful predictions were obtained for a single administration of the CYP3A substrates. Some deviations were observed between the predictions and in vivo plasma profiles in the presence of DDI. However, the impact of inhibition on the PK parameters of the selected substrates and the impact of grapefruit juice-mediated inhibition on the extent of intestinal pre-systemic elimination were predicted within a very acceptable error range.  Overall, this thesis demonstrated the ability of PBPK models to predict DDI with promising accuracy.

Keyphrases: Physiologically based pharmacokinetic model, Drug interactions, P-glycoprotein, Cytochrome P450 3A, Sensitivity analysis
Tocqueville et Guizot: la fondation d'un libéralisme des moeurs

Alexis de Tocqueville is a canonical author of liberalism. His inscription within liberalism often commented as a unilateral emphasis of the defence of individual freedom. Certainly, Tocqueville defends individual freedom and it is a decisive part of his work where his proposed theoretical objective reveals his will to elevate the individual to the level of society and the State. But this defence is always thought of by Tocqueville in his questioning of the conditions of possibility of freedom which are inseparable of a political culture where political participation is an essential dimension. A political participation which melts collective habits, civic culture, thus insuring the permanence of its liberal democratic institutions. It appears that the liberalism of Tocqueville is determined by a broader frame than the only defence of individual freedom. For a real individual freedom that flourishes entirely, there is the absolute preference for a continuous practice of freedom, political freedom which constantly updates the conditions of possibility of individual freedom. This practice of political freedom contributes to the development of « free manners », these collective habits which organize a particular civic culture, manners necessary to the assertion of the free societies. We shall identify Tocqueville with a liberalism of manners.   To properly grasp the true range of the tocquevillian thought, we shall reveal the fundamental intellectual influences which governed the drafting of Democracy in America. Indeed, we shall restore the intertextual space between Tocqueville and François Guizot. This space reveals the certain influence of Guizot on Tocqueville, but also reveals his emphasis on a practice of political freedom.

Keyphrases: Alexis de Tocqueville, François Guizot, Democracy, Equality, Freedom, Liberalism, Civic culture, Social state, Political state
Modulation du cytochrome P450 par l’insuffisance rénale chronique dans un modèle murin transgénique

Chronic renal failure (CRF) is associated with a decrease in the metabolic clearance of drugs, which is partly due to a reduced expression of cytochrome P450 (CYP450) and phase II enzymes, namely N-acetyltransferase 2 (NAT2). This phenomenon has been shown in the rat. We have previously demonstrated the role of parathyroid hormone (PTH) in CYP450 down-regulation in rats with CRF. However, the study of mechanisms underlying the down-regulation of CYP450 by PTH should be confirmed with the use of knockout mice. The aim of this study was, therefore, to confirm these results in a murine model. Firstly, to validate this experimental model, CRF was produced in C57BL/6 mice using the 3/4 subtotal nephrectomy. Protein and mRNA levels of hepatic CYP450 and Nat2 were then analyzed. The results showed that CRF down-regulates these enzymes, as previously observed in the rat.    Finally, PTH-null mice (PTH-/-) and their corresponding wild type (PTH+/+) were nephrectomized in order to analyze protein and mRNA expression of hepatic CYP450. If PTH is responsible for the decrease of CYP450 in the presence of CRF, then PTH-/- mice with CRF should not show any reduction in CYP450 expression compared to controls. The results concerning the PTH-/- mice could not be interpreted because PTH+/+ mice with CRF did not show any significant difference of CYP450 expression when compared to PTH+/+ controls. Thus, additional experiments must be conducted in order to determine the role of PTH in CYP450 down-regulation in CRF mice.

Keyphrases: Cytochrome P450, Chronic renal failure, Cytochrome P450, Knockout mice, N-acetyltransferase, Parathyroid hormone
Étude qualitative de la force mentale menée auprès d’athlètes québécois francophones de niveau universitaire

The objective of the study was to obtain a clearer understanding of the concept of mental toughness as applied to a sport context. To do so, interviews were conducted with ten university-level Francophone Quebec athletes. The data analysis was conducted by following the principles of the abridged grounded theory. The results are in general agreement with the scientific literature as mental toughness was made up of interrelated basic characteristics such as internalized motivation, self-confidence, maturity and determination. Mental toughness was solicited when the athlete faced difficult situations such as adversity, but also when the context the athletes faced was free from complications (e.g. during training or victory). In the two classes of situations, adversity and freedom from adversity, mentally tough athletes exhibited a tridimensional reaction mode (cognitive, affective and behavioural dimensions) characterized by a management and control of attention, optimistic interpretation, activation control and body language control, consciousness, management of emotions and resilience. Contrary to the existing literature, the results suggest that mental toughness would not necessarily be linked to athletes performing at the top of their game; it would instead be connected to the capacity of athletes to produce good performances relative to their individual potential. This study can be viewed as a first step in the development of an instrument that would permit the evaluation of the level of mental toughness in Francophone athletes.

Keyphrases: Performance, Mental toughness, Francophone Quebecker athlete, University-level athlete, Resilience, Grounded theory
Étude du dysfonctionnement du compartiment des cellules B chez des patients à différents stades d’infection par le virus d’immunodéficience humaine (VIH)

B lymphocyte abnormalities are an important consequence of HIV infection, where both polyclonal activation and loss of B cell memory and humoral immunity have been described, and often evolve towards rheumatic-like autoimmunity and lymphoma. Although these abnormalities are prevalent in chronically infected patients, polyclonal B cell activation is also reported in patients with primary HIV-infection (PHI), who already present signs of defective humoral immunity. Although controversial, elements of B cell dysregulation have been reported in long term non progressor (LTNP) patients, even though they bear low viral loads and present a relatively "normal" CD4+ T cell compartment, suggesting that other factors are involved. Therefore, the main objectives of this study are to 1) establish a timeline for specific B cell abnormalities in HIV-infected patients with different rates of disease progression (PHI normal and fast progressors, LTNP), and controls 2) to correlate serum levels of the B lymphocyte stimulator (BLyS) a B cell growth factor, among these patients and controls. Thus we have longitudinally assessed hyperglobulinemia, auto-antibody and soluble BLyS levels in the serum of subjects undergoing primary HIV infection (PHI) with different rates of disease progression; rapid and normal progressors, long term non-progressors (LTNPs), and healthy donors. Here, we report that B cell polyclonal activation occurs independently of the rate of disease progression, with hypergammaglobulinemia persisting beyond successful therapy in rapid progressors and despite non-progressing clinical disease in LTNPs. High levels of BLyS in the serum of PHI rapid progressors correlate with altered blood monocyte and dendritic cell frequencies suggesting their contribution in triggering B cell dysregulations.

Keyphrases: Sida, Ltnps, Phi, lymphocyte B, CD4+, Blys, Hiv, Aids, dendritic cell, B lymphocyte, hyperglobulinemia
The adoption and use of SMS among Chinese teenagers

This thesis examined the adoption of mobile phones and use of SMS among Chinese teenagers based on the uses and gratification theory and computer-mediated communication research. Specific areas of Chinese teenagers’ SMS use, such as parental control, the circulation of chain messages, the popularity of greeting messages and the wide use of emoticons were studied. The social functions of SMS, especially in Chinese teenagers’ social-emotional practice, were explored as well. This study is based on a field survey conducted among one hundred Chinese teenagers. It reveals that, for Chinese teenagers, the two main reasons for the adoption of mobile phones are parental influence and the need for social communication; the use of SMS corresponds to seven uses and gratifications: flexibility, low cost, privacy, embarrassment avoidance, entertainment, fad and escape. SMS is also used by Chinese teenagers to build and maintain their social relationships.

Keyphrases: SMS (short message system), Mobile phone, Chinese teenagers, Uses and gratifications theory (U&G), Computer-mediated communication (CMC), Parental control, Chain message, Emoticon
Modèles de dysfonction érectile chez le rat

Rat is a most rodent used for erectile function studies, and many erectile dysfunction (ED) rat models have been developed and studied. However, according to our knowledge, erectile function has never been studied in high-glucose fed rat model, intrauterine growth restriction rat model (IUGR) and continuous angiotensin (Ang) II infusion rat model. In this context, we set up this study. We mesured simultaneously mean arterial pression (MAP), intracavernosal pression (ICP), aire under the curve (AUC); and erectile function was obtained by variations of the ratio ICP/MAP and AUC/MAP in response to electrical stimulation of cavernosal nerve (0.89 – 6.50 Volts) in male Sprague-Dawley rats in different protocols as follow: 1) young (12 week old), procreator adult (~30 week old) and adult (27 and 29 week old) rats randomized and fed with high-glucose diet in water (10%) or simple water for a short (1 week), middle (6 weeks) and long (12 and 13 weeks) terms; 2) adult (36 week old) IUGR rats; 3) young (12 week old)  rats randomized and  received a chronic  infusion of AngII (200 ng/kg/min) or saline by osmotic minipumps for 1 and 2 weeks. At the end of procedures, blood for measuring serum glucose and insulin in rats with chronic high-glucose diet was obtained, the heart was excised and left ventricle was weighed. Aorta and penis were excised, cleaned and a section of each was formalin fixed for histological studies and the rest snap frozen for protein studies. The short term high-glucose diet impacted negatively in young rats but positively in procreator adult rats; also, the erectile function was improved or reversed by chronic high-glucose diet in adult rats. We also observed a diminished erectile function in RCIU. The improvement or deterioration of erectile function was associated with changes in Akt expression, besides an increased insulin serum in rats with high-glucose diet. A diminished erectile function was observed after 1 week continuous Ang II infusion and was maintained after 2 week infusion without detectable structural changes on heart and aorta. In conclusion:  this study suggests that erectile system is a precoce cible of cardiovascular complications of renin-angiotensin system. High-glucose diet deteriores erectile function but maskes the ageing induced-ED, RCIU is associated with ED in later life. Akt involvement in erectile function modulation depends on aging type and the diet.

Keyphrases: DE, ED, Ang II, Ang II, Glucose, Glucose, RCIU, IUGR, Aging
L’influence de la coopération patronale-syndicale sur le fonctionnement et le degré d’autonomie des équipes de travail

The main focus of the research is the analysis of the phenomena and the link between the union-management Cooperation and the work team. We are pursuing by submitting a main hypothesis: the degree of union-management Cooperation has a positive influence on the functioning and collective self-reliance of work teams. Methodology used relies on a point of multiple case study of the independent variable (the intensity of the employer-Union cooperation) in neutralizing the greatest possible number of control variables that can influence the dependent variable (operation and autonomy of the teams work). Semi-structured interviews were conducted with representative’s employer and Union. The results show that two selected plants have confirmed that the union-Cooperation was high in a factory and low in the other. Our dependent variable data analysis is based primarily on the results of a questionnaire and the resulting data indicate that Alma plant respondents have the highest ratings of dimensions related to their degree of autonomy and the functioning of their team work. Our assumption is essentially confirmed and demonstrates a positive relationship between a high degree of union-management Cooperation and assessment by the members of their team’s operations and collective self-reliance of work teams. However, this positive relationship is mixed, because it does not apply for certain dimensions that concerns more trivial aspects of the collective autonomy of work teams.

Keyphrases: Union-management Cooperation, Team work, Paper workers' union, Autonomous, Work organization
Multi-Prover and parallel repetition in non-classical interactive games

Since the introduction of quantum mechanics, many mysteries of nature have found explanations. Many quantum-mechanical concepts have merged with the field of computational complexity theory. New ideas and solutions have been put forward to solve computational problems. In particular, quantum mechanics has struck down many security proofs of classical protocols. In this thesis, we survey recent results regarding the implication of quantum mechanics to computational complexity and more precisely to classes with interaction. We present the work done in the framework of cooperative games with imperfect information. We give some differences between classical, quantum and no-signaling theories and apply them to the specific example of Odd Cycle Games. We center our attention on two different themes: the effect on a game of adding more players and of parallel repetition. We observe that depending of the physical theory considered, the consequences of these changes is very different.

Keyphrases: Multi-prover interactive proofs, Odd Cycle Games, Nonlocality, Quantum computational complexity, Intrication
In The Circle : jazz Griots and the Mapping of African American Cultural Memory in Poetry

My doctoral dissertation, In the Circle: Jazz Griots and the Mapping of African American Cultural History in Poetry studies the ways in which African American poets of the 1960s and 1970s, Langston Hughes, David Henderson, Sonia Sanchez, and Amiri Baraka employ jazz in order to ground their poetry in the tradition of performance. In so doing, each poet illustrates how black expressive culture, by conceptualizing through performance modes of resistance, has historically been used by people of African descent to challenge institutionalized racism and discriminatory discourses. Therefore, for the purpose of this dissertation, I focus on four poets who engage in dialogues with and about black musicology, aesthetics, and politics of the 1960s and 1970s; they assert the centrality of literary rendition for the survival and continuance of the collective cultural memory of Black Americans. In turn, I suggest that their theorization of artistry as political engagement becomes a central element in the construction of a Black Aesthetic based on performance. In the Circle: Jazz Griots and the Mapping of African American Cultural History in Poetry thus proposes an original analysis of how the four poets infused jazz and political references in their poetics in order to re-educate later generations about a collective black memory.

Keyphrases: Poetry, African American, Jazz, Politics, Langston Hughes, David Henderson, Sonia Sanchez, Amiri Baraka, Black Aesthetic, Cultural memory
Le rap comme lieu : ethnographie d’artistes de Montréal

The research proposition that guides my thesis is that rap in Montreal is more than a musical genre, it can best be understood as a place. The (re)definition of rap-as-place is the product of intersecting lines of force and social relations which Doreen Massey (1993, 2005) calls trajectories. According to the feminist geographer, place is constantly constructed, both in time and in space, by the simultnaeous interactions, at different levels, of «stories-so-far» (Massey, 2005). In this thesis, I identify and discuss three of the most prominent and pertinent «trajectories» that constitute rap in Montreal. I have conducted ethnographic work that consisted mainly in the shadowing of three rap groups/artists in Montreal. For a period of four months I have accompanied and followed these artists through a wide range of professional activities (media interviews, live performances, studio recording sessions, rehearsals).  Through this process, I have met and dealt with the human (journalists, festival programmers, agents, fans) and non-human (venues, recording and practice studios, shop restaurants,  métro stations) actors that inform both their practice and the music they make. It is their interactions that shape and (re)compose rap as a place.

Keyphrases: Rap, Popular music, Ethnography, Rap, Montreal, Trajectories, Place
Sport moderne et spiritualité évangélique : 
une étude interdisciplinaire des concepts 
de plaisir et de motivation en lien avec l’action humaine

For a pastor in the Christian Evangelical tradition, it is difficult to explain how a believer, who once loved and served God with passion, finds that a few years later his motivation directed towards God has waned. Though using different terminology, coaches ask essentially the same question concerning some of their athletes. How can they incite those under their supervision to perform in light of their full potential? If motivation is the motor of behaviour, for the majority of people emotions are the steering wheel. People, by nature, tend to steer their behaviour in a direction that reinforces desirable emotions and avoids those that are undesirable. This is true for both athletes and believers. This thesis proposes a reflection on motivation as it relates to two fields of study: theology and psychology. More precisely it looks at the subject of pleasure, motivation, and human action in the areas of modern sport and spirituality, with the intention of shedding new light on our problem. The first few chapters seek to identify the common ground between sport and spirituality (chapter 1), and to situate our problem in its anthropological context by defining the basic concepts of emotion (chapter 2) and motivation (chapter 3) according to modern psychology. The chapters that follow examine motivation from an understanding of sport psychology (chapter 4) before moving on to its counterpart from a theological perspective (chapter 5) by consulting two protestant theologians: Jürgen Moltmann of a liberal persuasion and John Piper, a conservative evangelical. Though contemporary psychology is known as being a discipline fixed in a Darwinian or Humanist paradigm which disassociates from any theological understanding of human beings, chapter 6 presents examples of how a theological discussion, outside of empirical confirmation, may bring a complementary vision to contemporary psychology and contribute to the well being of both athlete and believer. The chapter also proposes how an understanding of psychology, acceptable to an evangelical interpretation, may shed light on the possible changes in motivation a believer may experience in his love and service for God. The last chapter projects the ideas of this study to other fields of interest such as Bible study, the counseling of believers and athletes, and the work of military chaplains.

Keyphrases: Motivation, Sport, Joie, Jürgen Moltmann, John Piper, Emotion, Motivation, Sport, Spirituality, Pleasure, Joy, Sport psychology, Jürgen Moltmann, John Piper
The Na+/H+ exchanger Nhx1 of Saccharomyces cerevisiae is essential to limit drug toxicity

Nhx1 is an intracellular Na+/H+ exchanger localized to the late endosome in Saccharomyces cerevisiae. It is believed that Nhx1 plays a major role in pH-mediated vesicle trafficking, as nhx1Δ mutant is defective in maintaining the intracellular pH in the vacuoles and cytoplasm when grown in low osmolarity media. In this work, we reported novel drug sensitivities of the nhx1Δ mutant to a range of cationic and anionic agents when cells are grown in rich media. Unlike the low osmolarity media, the nhx1Δ mutant showed no sensitivity to salt. Furthermore, we showed that the drug phenotypes of the nhx1Δ mutant, as well as the secretion of the vacuolar protein carboxypeptidase Y, were not rescued by either altering the pH or salt concentration. Although, amino acid substitution of the phylogenetically conserved residue Glu355 for Ala (E355A) in Nhx1 resulted in sensitivity to genotoxic drug bleomycin, it was not observed for the non-conserved residue Glu371Ala (E371A). Moreover, genetic analysis revealed that the nhx1Δ mutant displayed distinct drug phenotypes in comparison to mutants that are defective in retrograde trafficking from the prevacuole to the late Golgi, excluding the possibility that the drug sensitivity of the nhx1Δ mutant is related to retrograde trafficking.

Keyphrases: Bléomycine, Bleomycin, Endocytic pathway, Prevacuolar compartment, Golgi