NCube/papyrus huggingface dataset:
Description et analyse des postures épistémologiques sous-tendues par l’épreuve unique ministérielle en Histoire et éducation à la citoyenneté

This research has the objective to describe and analyze the epistemological postures underpinned by the Ministerial uniform examination in secondary IV for the History and Citizenship Education program. Two specific objectives ensue: to describe the analysis of the sources ordered by the test and to enunciate the overlap between the evaluation criteria and historical thinking. We selected uniform examinations from June 2012 to 2015 and analyzed both ministerial information and the link between questions and documents. The evaluation criteria, the role of documents, their type and nature, the possibility to criticize them as well as the evaluation and the use of historical knowledge have been described and analyzed. The examination does not assess the use of historical thinking. It suggests an epistemological posture leaning on a fixed knowledge transmitted by an authority holding the truth. Accordingly, results indicate its misalignment of history teaching purposes supported by the program and research.

Keyphrases: Historical thinking, Teaching, Learning, Epistemological posture, Uniform examination, History and Citizenship Education, Secondary IV
Coopérer pour apprendre la syntaxe écrite : recherche-action sur la phrase subordonnée relative en troisième secondaire

This research aims to document the learning of grade-nine students in writing situation following the testing of a didactic sequence based on cooperation. Given the large number of syntactic errors in the texts of secondary students as reported by the MELS (2012), our series of courses targets a syntactic structure, the relative clause. In addition to causing problems for learners of French regarding the choice of the relative pronoun in particular, the relative clause is a dense teaching object known for posing many challenges to French teachers according to the work of Groupe de recherche pour l’analyse du français enseigné (e.g. Dolz et Schneuwly, 2009a, 2009b). After describing the writing situation and the relative clause conceptually, we extricate principles from the fields of grammar didactics and writing didactics deemed relevant to foster the learning of the relative clause and the mobilization of grammatical knowledge in writing situation. An innovative principle for teaching is integrated, one based on cooperation. Developed in the field of cooperative learning, cooperation is an educational approach aimed at structuring work in small groups to establish a dynamic of positive interdependence (Johnson and Johnson, 2009) so as to induce the unfolding of verbal interactions between students shown to be more fruitful in terms of learning than those prevailing in the absence of cooperative framework (e.g. Krol et al., 2004). Following an action research approach conducted jointly with a teacher, the series of courses is designed and tested with 55 students from three grade-nine students classes of Montreal (Canada) in order to actualize the didactic principles extricated. Two instruments are used to document students’ learning. The text aims to document the evolution in the production of subordinate clauses, while metagraphic interviews are aiming at metalinguistic skills related to these relative clauses. The analysis of texts collected at pretest and post test (n = 107) shows a significant decrease of mistakes in the use of relative pronoun in the texts, and a significant increase in use of complex relative pronouns such as "dont" (whose) and "auquel" (which). Analysis of metagraphic interviews at pretest and post test (n = 34) shows that students rely more on syntactic criteria to explain their use of the relative pronoun, and they use significantly more metalanguage in their explanations. The results of this research highlight the interest of implementing in French class didactic principles used, and more specifically the innovative cooperation one in order to reduce the syntactic errors in the texts and to develop students’metalinguistic skills.

Keyphrases: Grammar instruction, Relative clause, Written syntax, Writing instruction, Cooperation, Secondary education, Action research
Nanoparticules lipidiques pH-sensibles basées sur une bascule moléculaire pour la délivrance intracytoplasmique de siRNA

Intracytoplasmic delivery of small hydrophilic molecules and genes (DNA, RNA) is a major challenge for the pharmaceutical industry, since these compounds are unable to cross biological membranes by themselves. Use of lipid nanocarriers enables overcoming the stages of blood instability of the therapeutic gene, cellular penetration, and endosomal escape. In this thesis, we report the development of new pH-sensitive lipid carriers, based on a molecular switch capable of changing its conformation upon protonation and destabilizing the nanocarrier, thus favoring endosomal escape of the therapeutic content. This pH-sensitivity mechanism has not been reported in the literature to date. Firstly, we report the elaboration of non-cationic pH-sensitive switchable lipids for liposomal delivery of hydrophilic active ingredients. This initial work introduces switchable lipids, validates the involvement of the pH-sensitive molecular switch, and provides early evidence of in vitro concept feasibility. Secondly, we present the use of pH-sensitive cationic switchable lipids for gene therapy (siRNA delivery in vitro and in vivo), again validating the involvement of the molecular switch in the effectiveness of intracytoplasmic delivery of siRNA. The two lead compounds identified during this thesis (2 and CSL3) can be included into lipid nanoparticles for drug and gene delivery, respectively. Such formulations allow intracytoplasmic delivery of therapeutic hydrophilic compounds (drugs, genes) and could be used to treat diseases such as cancer or for genome editing applications.

Keyphrases: Liposomes, Echappement endosomal, Lipids, pH-sensitive, Molecular switch, Gene therapy, Lipid nanoparticles, Endosomal escape, Drug delivery, siRNA delivery, siRNA
Effects of the mycotoxin, deoxynivalenol, and its major metabolite, de-epoxy deoxynivalenol, on bovine reproduction

Deoxynivalenol (DON) is a major mycotoxin found in animal feed and is known to reduce fertility in pigs by inhibiting progesterone secretion from granulosa cells. In cattle, it is metabolized to de-epoxy DON (DOM-1) in the rumen, and DOM-1 can reach high concentrations in blood and follicular fluid. One of the major pathways activated by DON is the ribotoxic stress response (RSR), which involves autophosphorylation of protein kinase R (PKR) and downstream activation of MAP kinases including MAPK3/1. It is not known if these mycotoxins affect bovine reproduction. The objectives of present thesis were (1) to determine how and at what doses DON affects ovarian granulosa cell function and to elucidate its mechanism of action; and (2) to determine how and at what doses major mycotoxin DON and its metabolite DOM-1 affect theca cell function in cattle. The results are separated into three articles. In the first article the effects of DON on granulosa cells were explored; treatment with DON resulted in a significant inhibition of estradiol and progesterone (P4) secretion, and an increase in the proportion of apoptotic cells after 4 days of treatment. Western blot demonstrated significant upregulation of ERK1/2 and MAPK14 phosphorylation within 15-30 minutes of adding DON. We then determined the effect of DON on ERK1/2 target genes; EGR1 and FOS mRNA levels were transiently stimulated with maximum levels at 1 h of adding DON, whereas COX2 and GADD45B mRNA levels were upregulated but not until 24 h after DON treatment. In the second article, the effects of DON and DOM-1 on theca cells were assessed. Treatment with DOM-1 resulted in a dose-dependent inhibition of P4 and testosterone secretion, and an increase in the proportion of apoptotic cells, while DON inhibited P4 but did not alter testosterone secretion or the percentage of dead cells. Both ii DON and its metabolite were maximally effective at concentrations of 1 ng/ml (in contrast, the effects of DON on occur at 100ng/ml). Western blot demonstrated rapid phosphorylation of MAPK3/1, PKR and of JUN kinase after addition of DOM-1 or DON. Interestingly, phosphorylation of MAPK14 was significantly increased by DOM-1 but decreased by DON. The addition of a PKR inhibitor abrogated the ability of DON and DOM-1 to increase phosphorylation of MAPK3/1, and partly abrogated the inhibitory effect of DON on MAPK14 phosphorylation, however, the PKR inhibitor further increased the phosphorylation of MAPK14 caused by DOM-1. Together, these results suggest that DON activates the RSR in bovine granulosa and theca cells, and that theca cells are more sensitive than granulosa cells to the effects of DON. The data also demonstrate for the first time in any cell type the ability of DOM-1 to affect cell function and health.

Keyphrases: Deoxynivalenol, Ribotoxic stress response, Mycotoxin, De-epoxy deoxynivalenol, Granulosa cells
Rôle du jeûne et de la perturbation de la cascade de signalisation de l'insuline sur le clivage du précurseur de la protéine amyloïde (APP)

Little is known about the mechanisms that trigger the onset of Alzheimer’s disease (AD), a primarily sporadic disease. Studies on the familial form of AD attributed a particular importance to Amyloid beta (Aβ), a cleavage product of the Amyloid precursor protein (APP). Many risk factors have been identified as potential triggers of the development of AD including Type 2 diabetes (T2D). Indeed, the impairment of insulin signaling by the desensitization of insulin receptors (IR) in the brain seems to be a common hallmark of both diseases. The long term effects of IR resistance on the accumulation of Aβ and Tau hyperphosphorylation have been studied, but the acute effects of IR perturbation is less characterized. Also, both diseases show metabolic defects. Our research aimed to determine whether acute perturbation of IR signaling affects APP processing and if starving (energy deprivation) could sensitize this processing to acute perturbation of IR. To assess this, we used small doses of Tyrphostin AG1024 to simulate IR perturbations rather than a complete blocakade of the receptors. To quantify APP processing, we measured the change of total full- lenght APP by Western blot. To ensure that this change reflected APP processing we developed a luciferase based readout system. This system allowed us to monitor the occurrence of APP cleavage via GAL4-UAS Firefly luciferase driven expression because we linked GAL4 transcription factor to the C-terminal region of APP. First, we showed that IR perturbation with Tyrphostin leads to APP processing and that starving increased IR susceptibility to a smaller doses of Tyrphostin. This APP processing occurs via the amyloidogenic pathway because inhibition of β- and γ-secretase inhibited APP processing. We showed that this processing absolutely requires IR perturbation, while IGF-1R perturbation alone is insufficient. Furthermore, neither autophagy, caspases nor proteasome seemed to be implicated in APP processing following starvation and small IR perturbation. The activity of mTOR is also not required. On the contrary, GSK3 activation is necessary for the processing and seems to affect γ-secretase cleavage. We then confirmed in primary cultured neurons that the combination of acute starvation and small IR perturbation causes APP cleavage and GSK3 is again strongly activated. Taken together, our results suggest that the impairment of IR signalling seen in T2D increases the processing of APP via the amyloidogenic pathway and thereby contributes to the pathology of AD.

Keyphrases: Alzheimer, APP, GSK3, Alzheimer’s disease, Diabetes, Starving, Susceptibility, Insulin receptor signaling
Analyse transcriptomique et applications en développement préclinique des médicaments

The emergence of Big Data in molecular biology, especially through the study of transcriptomics, has revolutionized the way we look at various disciplines, such as drug development and cancer research. Big data analysis is an important part of the concept of precision medicine, which primary purpose is to understand the molecular mechanisms leading to better therapeutic response in patients. This thesis is halfway between pharmaco-toxicogenomics experimental studies, and clinical and translational studies. The aim of this thesis is mainly to show the potential and limitations of these studies and their relevance, especially for the discovery of drug response biomarkers and understanding the drug mechanisms (targets, toxicities). This thesis is an original work since it proposes a global approach to analyzing the largest pharmaco-toxicogenomic datasets available to date. The key aims were: 1) Addressing the challenge of reproducibility for biomarker discovery in cancer pharmacogenomics, by comparing two large pharmacogenomics studies published in 2012; 2) Understanding drugs mechanism of action using an integrative approach to generate a superior drug-taxonomy; and 3) Evaluating the conservation of toxicogenomic responses in primary hepatocytes vs. in vivo liver samples in order to check the feasability of cell models in toxicology studies. My main contributions can be summarized as follow: - I developed a bioinformatics pipeline to study the factors that trigger (in)consistency between two major pharmacogenomic studies. I suggested that the observed differences emerged from the non-standardization of pharmacological measurements, which could limit the validation of drug response biomarker. - I implemented a bioinformatics pipeline that demonstrated the superiority of the integrative approach, since it takes into account different parameters for the drug (structure, cytotoxicity, transcriptional perturbation) to elucidate the mechanism of action (MoA). - I developed a bioinformatics pipeline to study the level of conservation of toxicity mechanisms between the in vivo and in vitro system, showing that human hepatocytes is a reliable model for hepatocarcinogens testing. Overall, our studies have provided a unique framework to leverage various types of transcriptomic data in order to understand the impact of chemicals on cell biology.

Keyphrases: Transcriptomics, bioinformatics, chemical compounds, response biomarkers, mechanism of action, toxicity, cell lines, microarrays, pharmaco-toxicogenomics, microarrays
L'utilisation des TIC à des fins de harcèlement criminel en situation de violence conjugale: la théorie des opportunités et des activités routinières de Cohen et Felson (1978) remaniée

Introduced in 1978, the lifestyle and routine activities theory of Cohen and Felson remains one of the most cited theory to explain criminal activities. The use of information and communication technologies (ICT) has transformed traditional forms of crime, such as criminal stalking and harassment. The ICT are often used in domestic violence cases to harass and stalk the victim, even when she is seeking security in shelters. This problematic was brought to our attention by shelter workers, who consider those technologies an actual threat for women and their children, but also for the shelter and the interventions. With the collaboration of police investigators, a professor from the École des sciences criminelles de Lausanne and shelter workers, data were collected through interviews then analyzed, in order to adapt the Cohen and Felson’s lifestyle and routine activities theory in cases of ICT use for stalking, in intimate partner violence relationships. The crime targeted by this study, criminal stalking and harassment committed through ICT, is developed according to the Criminal Code but also according to the police officer and the shelter workers, to understand its particularities. In this study, the motivated offender is the partner controlling his wife using various devices to track and harass her, even when she quit the violent situation to seek security in a shelter. In this case, her unstable emotional state and the fact that her partner knows her well make the present or former wife vulnerable and, therefore, a suitable target. Also, the emotional context surrounding the domestic violence situation can destabilize her when she receives text messages or e-mails from her partner, trying to convince her to come back. Finally, shelters and the police investigation are there seen as a capable guardian. In fact, women in shelters have the possibility to turn off their technology in a secure environment where they can get the support they need. Even if the ICT can, in one hand, impede the intervention, it can also be a rich source of information, on the other hand. Indeed, when a police investigation takes place, this digital information can be used as evidence in criminal court to prove the stalking. Thereby, Cohen and Felson’s theory of opportunities and routine activity is revisited in the ICT era and put forward the meeting of criminological and forensic science.

Keyphrases: Lifestyle and routine activities theory, Cyberstalking, Intimate partner violence, Digital forensic, Information and communication technologies (ICT)
L'aveu dans les traditions occidentales accusatoire et inquisitoire : une brève histoire de l'aveu en droit pénal

This thesis analyses confession in Western legal traditions through a historical approach starting in antiquity. Through the study of English, French and Canadian law, it shows how the suspect’s statements have been apprehend by the accusatorial and inquisitorial systems of criminal justice, revealing that confession has always constituted and still constitutes to this day the cornerstone of truth and justice in criminal procedure. It also explains how confession, influenced and transformed by religion, has become an independent means of proof in both systems as a way to both identify and understand the guilty.

Keyphrases: Confession, Common law, Crime, France, Justice, Torture, Tradition, Accused, Adversary, Comparative law, Criminel, England, Evidence, History, Inquisitory, Justice, Law, Penant, Penance, Procedure, Power, Sentence, Truth, United States
L’infirmière, la pratique de soin et la négociation : ethnographie des suivis postnatals à domicile en milieu multiethnique à Montréal

This thesis is an analysis of the interactions between nurses and service users in the context of post-natal home monitoring. Based on an ethnographic study I conducted in Montreal (Bordeaux-Cartierville-Saint-Laurent), I have defined how nurses negotiate care practice with their service users. These ‘‘negotiations’’ permit them to fulfill their mandate even with the manifestation of difference that can arise between the nurse’s professional and the service users’ profane culture. The theoretical framework that I have built around the concept of negotiation is also supported by sociological literature on profession and health. In order to cater to the service users’ needs, the nurses inherently modulate their relationship to the public health norms. Five types of negotiation have resulted form this study: Cooperation, Compromise, Detachment, Typified Adaptation and Coercion. This narrative of these different forms of negotiation tells us how nurses manage to fulfil their mandate with the service users who do not subscribe to the Quebec public health prevention and promotion of healthy living values.

Keyphrases: Interaction, Soin postnatal, Negotiations, Postnatal care, Professional culture, Profane culture, Nurses
Regime crises in Africa : a study of armed forces’ behaviour

This Ph.D. dissertation analyzes the factors that influence armed forces’ decisions to tolerate or suppress opposition movements demanding political reforms which could lead to regime change. This dissertation helps to fill a large gap in the literature as only a few scholars have attempted to explain military behaviour during regime crisis. It does so through an analysis of how anti-coup policies and opposition forces’ characteristics lead to the formation of marginalized military cliques and their potential support for regime change. It theorizes that the head of state’s survival strategy, specifically coup-proofing measures, influences military factions’ willingness to preserve the status quo. Reliance on loyalists leads to armed forces with a powerful core loyal to the incumbent regime and willing to use repression, while the strategy of counterbalancing leads to armed forces largely unattached to the maintenance of the regime. Under these circumstances, opposition forces can foster regime defection when they offer a viable alternative to the incumbent government, if the opposition can unify around a moderate platform that provides realist demands vis-à-vis regime forces. The main argument, on the influence of divergent coup-proofing policies on military actions, is assessed through a comparison of Benin and Togo. In each state, authoritarian regimes responded to the challenge of opposition mobilization by initiating negotiation processes. Divergences in coup-prevention techniques and credible commitment capacity of the opposition explain why the opposition campaign in the beginning of the 1990s was successful in Benin but failed in Togo. This research is based on two methods: process-tracing and the comparative method.

Keyphrases: Afrique Sub-Saharienne, Armed forces, Authoritarian resilience, Civil-military relations, Coup-proofing, Military coups, Opposition movements, Sub-Saharan Africa, Regime crises, Togo