NCube/papyrus huggingface dataset:
Organisation anatomique et rôle du couplage astrocytaire dans l’activité rythmique du noyau sensoriel du trijumeau

Several cerebral functions depend on the capacity of neuronal circuit to generate rhythmic activity. The most intuitive example is neuronal circuits referred to as central pattern generators (CPGs), which encode the repetitive movement patterns for locomotion, respiration and mastication. Our work was performed in the trigeminal main sensory nucleus where rhythmic activity observed only in the dorsal part is thought to reflect the rhythmogenic core of the masticatory CPG. Previous studies have shown the key role that astrocytes-neurons interactions play in neuronal rhythmic firing. In these neurons, rhythmogenic activity relies on a sodium persistent current (INaP) which activation is promoted by a decrease of extracellular calcium. Astrocytes activated by afferences to the nucleus take part in this process by releasing S100β, a protein that chelates calcium and promotes INaP activation by decreasing extracellular calcium. Generally, astrocytes are coupled by gap junctions and in many cases where neurons are organized topographically, the shape of astrocytic networks overlap perfectly the underlying neuronal organization. However, the organization of astrocytic networks in CPGs has not been described so far. Our first hypothesis is that the organization of astrocytic coupling supports the rhythmogenic function in the dorsal part of the NVsnpr. We developed a vectorial analysis method to address the preferential orientation of astrocytic networks in the nucleus. Secondly, astrocytic coupling could be implicated in rhythmogenesis.  The results presented in this thesis show that rhythmogenic stimuli increase astrocytic coupling and S100β is implicated in this modulation. Astrocytic networks show a limited spread and a spatial organization which follow the boundaries of the dorsal part of NVsnpr. Finally, astrocytic coupling is required for rhythmogenesis.  Our results indicate that astrocytic networks define functional boundaries and suggest that they could play an important role in the coordination and/or synchronization of firing of neuronal populations. Astrocytic coupling may also play  a similar role in other neural circuits such as locomotion and respiration CPG.

Keyphrases: Mastication, S100β, Central pattern generator, Trigeminal main sensory nucleus, Astrocyte networks, Connexin, Vectorial analysis
Regulation of Interleukin-1 governs acute intrauterine inflammation to improve gestational and neonatal outcome

Preterm birth (PTB; birth before 37 weeks' gestation) is the leading cause of neonatal mortality and morbidity worldwide, and surviving infants are at risk of long-lasting functional impairments. The pathophysiology of spontaneous preterm labor has been largely attributed to intrauterine inflammatory processes independent of aetiology, gestation age at delivery, and presence of infection. Importantly, intrauterine inflammation can propagate to the fetus whereupon the initial trigger is amplified to cause fetal organ injury, thereby compromising neonatal outcome. Of all pro-inflammatory mediators, interleukin-1 (IL-1) stands out as a major player in PTB and fetal inflammation. Therefore, modulating its action antenatally may be key to achieve better gestational and neonatal outcomes. Herein, we show that antenatal regulation of IL-1 by lactate (or 3,5-dihydroxybenzoic acid [3,5-DHBA]) via activation of anti-inflammatory GPR81 in myometrium, or by an heptapeptide noncompetitive antagonist of IL-1 receptor developed in our laboratory and termed 101.10, prevents PTB and improves neonatal survival in intrauterine-inflammatory and systemic-infectious murine models of PTB. Specifically, we show that antenatal maternal administration of 101.10 prevents premature triggering of uterine, choriodecidual, placental, amniotic, and fetal inflammation, thereby decreasing organ injury and functional impairment in progeny. In this setting, 101.10 has shown superior efficacy as compared to anakinra (Kineret), a competitive IL-1 receptor antagonist, especially to prevent PTB and neonatal mortality. Further, we demonstrate that 101.10 exhibits functional selectivity by inhibiting IL-1-induced signals transducers p38, c-Jun N-terminal kinase (JNK), c-jun, and Rho GTPase/ Rho-associated coiled-coil-containing protein kinase (ROCK), while desirably preserving IL-1-induced activation of IκBα and nuclear factor-kappa B (NF-κB). In a second set of experiments, we uncover a novel uterine negative feedback mechanism whereby the anaerobic metabolism solicitated during active labor produces large levels of lactate, which in turn activates GPR81 in myometrium to decrease IL-1-induced acute inflammatory cascade. Correspondingly, GPR81-/- mice display increased uterine inflammation during labor and increased rates of labor dystocia, whereas inversely administration of the GPR81 agonist 3,5-DHBA decreases the uterine inflammatory response to IL-1 and prevents lipopolysaccharide (LPS, gram(-) bacteria endotoxin)-induced PTB. Altogether, this data points to a major role of antenatal IL-1 in eliciting PTB and long-lasting fetal organ injury, and describes a novel therapeutic approach to inhibit IL-1 receptor antenatally while preserving important physiological inflammatory signaling pathways.

Keyphrases: Anti-IL-1, Inflammation, Lactate, GPR81, Preterm birth, Preterm labor, Interleukin-1, Neonatal morbidity, Functional selectivity
Numerical Insights for AAA Growth Understanding and Predicting: Morphological and Hemodynamic Risk Assessment Features and Transient Coherent Structures Uncovering

Abdominal aortic aneurysms (AAA) are localized, commonly-occurring dilations of the aorta. In the event of rupture only immediate treatment can prevent morbidity and mortality. The AAA maximal diameter ($D_{max}$) and growth are the current metrics to evaluate the associated risk and plan intervention, with lower thresholds for women. However, these criteria lack patient specificity; rupture may occur at lower diameter and patients may live with large AAA. If the disease is known to be associated with altered morphology and blood flow, intra-luminal thrombus deposit and clinical symptoms, the growth mechanisms are yet to be fully understood. In this longitudinal study, morphological analysis and blood flow simulations for 32 patients with clinically diagnosed AAA and at least 3 follow-up CT-scans per patient, are performed and compared to control subjects. The aim is first to investigate which metrics stratify patients between healthy, low risk and high risk groups. Local correlations between hemodynamical metrics and AAA growth are also explored, as AAA heterogeneous growth is currently not understood. Finally, composite metrics are built from clinical, morphological, and hemodynamical data, and their ability to predict if a patient will become at risk tested. Performance of these models built from supervised learning is assessed by ROC AUCs: they are respectively, 0.73 ± 0.09, 0.93 ± 0.08 and 0.96 ± 0.10. Mixing all metrics, an AUC of 0.98 ± 0.06 is obtained. For further insights into AAA flow topology/growth interaction, a workout of patient-specific computational flow dynamics (CFD) is proposed to compute finite-time Lyapunov exponents and extract Lagrangian-coherent structures (LCS). This computational model was first compared with 4-D phase-contrast magnetic resonance imaging (MRI) on 5 patients. To better understand the impact of flow topology and transport on AAA growth, hyperbolic, repelling LCS were computed in 1 patient during 8-years follow-up, including 9 volumetric morphologic AAA measures by computed tomography-angiography (CTA). LCS defined barriers to Lagrangian jet cores entering AAA. Domains enclosed between LCS and the aortic wall were considered to be stagnation zones. Their evolution was studied during AAA growth. In addition to hyperbolic (attracting and repelling) LCS uncovered by FTLE, elliptic LCS were also considered. Those encloses rotation-dominated regions, or vortices, which are powerful tools to understand the flow transport in AAA.

Keyphrases: Abdominal aortic aneurysm, Lagrangian coherent structures, Hemodynamic, Computational fluid mechanics
Méthodes optiques d’attribution d’identifiants moléculaires à des cellules uniques pour assurer leur traçabilité

Even though they only recently appeared, single cell sequencing techniques have already highlighted huge variability among cells. Since then, numerous techniques arose that allow the characterization of each individual cell from a sample. This variability indeed holds crucial information that is lost when studies average observations across millions of cells. Outside of microscopy, most single cell protocols require the creation of a homogenized cell suspension from the sample. Because the spatial structure of the sample is broken, any information easily obtained with a microscope about shape, position, cell-cell contacts, migration direction and speed is lost. These descriptors are nevertheless key to understanding both embryo and pathology development, immune responses, nervous system functioning and cell growth and differentiation. The objective of this project is to develop a technique that allows giving an identity to cells of interest to trace them across any protocol they might later undergo. This will allow pairing microscopy generated information with that obtained with any downstream analysis. Our first goal was to tether fluorescent markers to cells that were individually chosen in a microcopy image. We developed Cell labeling via photobleaching (CLAP), in which a fluorophore is bleached using a laser to generate a free radical that allows binding a biotin to plasma membranes. This procedure is non-toxic, leaves transcriptomes untouched, and the tag can be found for several days. We show a proof of principle of the use of this technique with the Fluidigm C1TM platform to sequence individually chosen single cells. We then extended this new tool for 3-dimentional samples, for the simultaneous use of multiple color stamps, and for sorting cells by binding them to their substrate. We then considered the problem through a different angle: instead of trying to recognize data originating from single cells of interest after sequencing all cells from a sample, one can try to first isolate these few cells prior to sequencing, reinjecting or further culturing them. To this aim, we propose Single-Cell Magneto-Optical Capture (scMOCA), in which the above protocol is adapted to attach magnetic beads on cell surfaces. Viable cells can then be extracted with high efficiency and purity with a simple magnet; even from populations of very sensitive cells such as primary neurons or embryonic stem cells. Using this procedure, we generated cell lines selected for their outstanding ability to quickly repair induced DNA damage. We then purified multinucleated cells which are involved in the appearance of drug resistance and in cancer relapse and extracted cells that differentiated into adipocytes faster than the rest of the culture.

Keyphrases: photoblanchiment, cellule rare, cancer, single cell, labeling, sequencing, photobleaching, cell sorting, rare cells
La fabrique de l’évaluation à l’aune d’une perspective resocialisante : une négociation entre enseignants et étudiants au premier cycle universitaire

In recent decades, universities are influenced in their operation by several phenomena, including standardization and rationalization of higher education, driving respectively a new conception of the relationship between students and academic teachers (Trow, 2011), and a management of universities including evaluation as a centerpiece in their regulation (Lessard, 2014). At the same time, research on the problem of evaluations in the University context highlighted the conflictual dimension of assessment, recognized as an object of issues and multiple tensions (ADMEE, 2014). My central hypothesis argues that, on various plans, the assessment shapes the relationship between students and university teachers, including the negotiation of work activities; Hence the need to link this evaluation to the interests, projects and networks in which they participate (Morrissette, 2009). Leaning in an interactionist perspective that apprehends in its procedural dimensions and transactional evaluation among stakeholders, this thesis highlights how these crosscutting evaluations at activities negotiated continuous (Strauss, 1992) shape the relations between students and university teachers in undergraduate. For this do, 11 observations in four classes, 14 interviews with 4 teachers and 6 students, and 3 focus groups with students were taken in a Faculty of education of a Montreal University. The data collected are analyzed according to the method of reasoning from case (Becker, 2016). Taking as angle of analysis the point of view of the actors, I first show how the compromises they negotiate around these activities are built from a look focused on the anticipated consequences of an unnamed object, the assessment. This light is then used to interrogate the « making of evaluation », as it is produced by agreements negotiated and reinterpreted that support students and university teachers.

Keyphrases: Compromis, Student, University teacher, Mutual evaluations, Negotiation, University, Rationalization, New public management, Pedagogical relationship, Poles of the negotiation, Coventions, Negotiated order, Making of the evaluation, Interactionist perspective, Strategies, Issues of the evaluation, Structural context, Negotiating context, Reasoning by cases, Sociology of the assessment, Agreements, Resocialization of evaluation, Stakeholders' perspective, Academic success
Satisfaction au travail des sages femmes et qualité des soins obstétricaux : une étude au Sénégal

Despite the many interventions implemented, Senegal did not achieve the target of Millenium Development Goal target 5 in 2015, which consisted of a reduction of ¾ maternal mortality. The unavailability of motivated human resources and the poor quality of care were blamed. The general objective of this thesis is to analyze the link between the professional satisfaction of midwives and the quality of obstetric care. More specifically, it was a question of developing a tool for measuring the quality of obstetric care and secondly a tool for measuring the satisfaction of midwives. The final objective was to use these validated tools to measure the effect of midwifery satisfaction on the quality of obstetric care. This thesis was carried out within the framework of the project "Quarité", a randomized clinical trial aimed at establishing a link between a program to strengthen the clinical skills of obstetric personnel and the reduction of maternal mortality in Senegal and Mali. For the first objective, we carried out a cross-sectional study in a Dakar hospital, observing thirty consecutive deliveries. The tool used included 12 criteria including 6 for the active phase of delivery and 6 for delivery. For the second objective, using a questionnaire containing 24 items, we interviewed 937 health professionals working in 46 hospitals. Validity was assessed through exploratory and confirmatory factor analysis and discriminant analysis. Reliability was assessed by the internal consistency and the retest test. Using both tools and contextual data, we analyzed the link between midwifery satisfaction and the quality of obstetric care in Senegal through a multilevel analysis.  The linear mixed model shows that salary (ß=0.40, IC95%= 0.32:0.47), continuing education (ß=0.17; IC95%=0.07:0.27) and management style (ß=0.42, IC95%=0.34:0.49) improved the quality of care. Association between moral satisfaction and quality care was negative (ß=-0.53; IC95%=-0.39:-0.66). One of the major contributions of this thesis is the development of a valid and reliable tool for measuring satisfaction among professionals with different status. This instrument has the advantage of exploring undocumented dimensions such as workload but above all morality and stability. The fact that the effects of different dimensions of job satisfaction on quality of care have been identified is a major achievement. This is important knowledge from the perspective of an intervention aimed at improving the performance of the providers by identifying the key elements on which the authorities must act to improve the quality of obstetric care and reduce maternal mortality

Keyphrases: Motivation, Satisfaction, Sage-femme, Senegal, Quality care, Midwife, Senegal
Aller aux vues qu’ossa donne? Pour une histoire culturelle du cinéma populaire québécois (1965-1975)

This thesis analyses a marginalized part of the history of Quebec cinema: the "popular" cinema produced in the 1960s and 1970s. Its goal is to reassess the "cultural weight" of this production by examining a specific corpus: the comedy genre. This study means to answer two main questions related to each other. First, it investigates the social and cultural reasons that led to the disqualification of comedies from the historiography of Québécois national cinema. Further, it studies the role of the corpus in building a new national consciousness among a very large public during the Quiet Revolution, an era of social, political, and cultural changes. This thesis is divided into four parts. The first allows me to take a stand on three key concepts (popular culture, popular cinema and the nation) and see how these ideas interact together. I explore the history of those concepts to define a historical position that takes into account the experience of popular cinema and its role in the development of a new national consciousness that moves away from those promoted by the Catholic and later by the modern elites. The second part describes the origins of the experience of vernacular modernity and the development of an industrial culture of entertainment in Quebec territory. The portrait shows the enthusiasm of the population, but also the reluctance and blame of the Catholic clerical elite. I then show the equally acrimonious treatment of the modern cinema intelligentsia against 1960s and 1970s comedies. In the third part, the cultural history of comedy is described. I provide a detail account of the phases of production, mediation and reception of cultural objects and practices. I portray the many networks of influences on the local film culture, while showing its important impact in the global popular culture and its strong acceptance in the community. The last part presents three case studies that provide a portrait of three major cultural trends in the decade. For each film, I examine the presence of various disengagement strategies from motherland, influencing the reception of members of a new vernacular community in Quebec.

Keyphrases: Nation, Popular culture, Popular cinema, Quebec cinema, Comedy
La nécessité d'associer la biopiraterie à la criminalité environnementale pour une meilleure protection des ressources génétiques et des savoirs traditionnels en droit international

Although biopiracy has been a well-known practice for decades, it has been reinforced by the international regimes established under the Convention on Biological Diversity (CBD), and by the intellectual property framework created under the World Trade Organization (WTO). Despite the lack of consensus surrounding its definition, biopiracy includes acts of appropriation by biotechnology firms of the genetic resources and / or traditional knowledge of Indigenous and local communities. Situated primarily in developing countries that are rich in biodiversity, these communities have played a vital role in the conservation of global biodiversity for generations. But because of threats to the survival of Indigenous and local communities, and perhaps even to the survival of the planet itself due to the rapid erosion of biodiversity that it entails, biopiracy is now considered by experts to be an environmental crime. Numerous recent studies in the field of green criminology have arrived at the same conclusion. Nevertheless, the international legal instruments currently in force do not recognize biopiracy as a criminal act. And while attempts to criminalize biopiracy through legislation in certain biodiversity-rich countries have been successful, giving rise to some hope, these actions have largely failed to provide an adequate response to the environmental concerns of Indigenous peoples. This thesis examines the extent to which the implementation of existing international environmental criminal law could provide an avenue for further exploration in this regard.

Keyphrases: Bioprospection, Brevet, Crime, Biodiversity, Biopiracy, Bioprospecting, Crime, Genetic, Criminology, Environmental, Indigenous, Patent, Knowledge
La rémunération des hauts dirigeants en droit des sociétés par actions : le rôle et les limites du droit

The corporation, its functioning, its governance structure and the relationships that take shape in it are based on premises rooted in economic orthodoxy. In particular, the separation of ownership and decision-making functions creates conflicts of interest between management and shareholders. By default, the inherently conflictual nature of relationships requires a series of governance mechanisms to discipline executives and constrain them to act in the interests of shareholders. From this perspective, the executive compensation system is the preferred benchmark for assessing the effectiveness of the governance structure since it mobilizes all of its mechanisms. Consequently, compensation is the result of a complex set of interactions between different complementary and non-exclusive mechanisms. The objective of this thesis is to critically evaluate the explanatory and normative propositions of economic theory in executive compensation practices and policies. In so doing, the issue of compensation gives concrete expression to concerns relating to the purpose of the corporate entity, the incentive, the regulation of action and contractual performance within the organization. However, the economic conception of governance is not well adapted to the otherness that sometimes animates the joint-stock company and the contractual relations that are established there. For this reason, adjustments make it possible to bring the various instruments of governance closer to an observed reality where other behavioural assumptions and other normative constraints allow a better framework for the leader's action and power. In this way, our approach views executive compensation in corporate law as a cooperative process at the crossroads of contract, law and ethics.

Keyphrases: Aléa moral, Applied ethics, Best practices, Corporate law, Directors’ fiduciary duties, Ethics of cooperation, Executive compensation, Corporate governance, Moral hazard, Norms of exemplary behaviour, Shareholders engagement, Social norms, Theories of the firm