NCube/papyrus huggingface dataset:
La perception des conséquences du décrochage scolaire du point de vue des jeunes

In Quebec, between 2002-2003 and 2012-2013, the rate of teenagers leaving high school without the full completion of the general program has dropped by 6.9 points. Presenting itself to be 22.2% a decade ago, it stood at 15.3% in 2012-2013 (MÉLS, 2014). Despite a considerable decrease in the annual dropout rate, this phenomenon remains an important preoccupation in education because of its numerous consequences for the teenager and society (MÉES, 2015). Studies on this matter have identified consequences on several levels, being economical (less active in society’s production), sanitary (more frequent development of physical and mental health problems) and social (poor social adaptation and deviance) (Blaya, 2010; Janosz, 2000). The phenomenon of early school leaving is also studied as a transgression of social norms. Wether it’s studies on the typological description of at risk youth, the risk factors of dropping out or the institutionalized speech on the matter, from this point of view, dropping out is analysed as an inacceptable response to social conventions (Bernard, 2011). Therefore, the teenager who quits school prematurely is automatically considered a deviant since his actions have disobeyed social norms. Many studies on the consequences of this phenomenon as well as it’s statistical data are present in the literature, but unfortunately, the point of view of teenagers labeled as dropouts is not brought forward. In light of this observation, this thesis solicited the participation of teenagers who left high school prematurely to offer them the space to describe their experience. Based on symbolic interactionism, this thesis tries to understand the experience of dropping out according to the teenager’s point of view. In an individual interview using a life narrative method, eight teenagers were invited to deliver their perception on the dropout label which they were attributed and the consequences that resulted. The analysis of the participant’s narratives highlight the numerous adversities they went through during their school years and the individualized needs that resulted. Their narratives show the severe inadequate response by the school institution to their individual needs as a trigger to their premature leave. Living through frequent unbearable situations due to this inadequate response pushed them to be excluded from the school system and to reject school. Unfortunately, the participant's needs were not part of the school’s fixed objectives leaving them to lose hope in finding a sense to their schooling. The participants of this study now realise the consequences they have lived and live to this day since they quit school. They present shortcomings in their knowledge, an accumulated lack of motivation, poor self-esteem, situations of stigmatisation and marginalisation, difficulties integrating socially and professionally and finally, they have developed a lack of confidence in what their future holds.

Keyphrases: education, deviance, youth in difficulty, school drop-out, symbolic interactionism, life narrative
Étude de la signature dynamique de transcrits primaires impliquée dans la maturation des microARN

MicroRNAs (miRNAs) are small non-coding RNAs, which can inhibit target messenger RNAs translation. In order to obtain a miRNA, two enzymes, Drosha and Dicer cut the gene of miRNA. The RNA interacts with the proteins by its general hairpin structure. However, the details of the structure are still missing. The objective of this project is to establish if there is a relation between the efficiency of maturation and the RNA’s structural dynamics. In order to do this, the maturation efficiency of miRNA variants is measured by Northern Blot. The structural dynamics is measured by a program assessing the information of the sequence. The correlation between the dynamics and the maturation efficiency of the miRNA is 0.74 with a p-value of 0.02206. This correlation is superior to those based on free energy, which does not reach 0.6. The tested mutants of miR128-1 and miR188 have inhibited maturation; also, those of miR125a, miR188 and miR330 have modified the cleavage site of Drosha. A better knowledge of the dynamic structure involved in maturation would help define the impact of miRNA mutation or to predict sequences that are able to generate miRNAs.

Keyphrases: maturation, Dicer, Drosha, structure, Northern Blot, RNA, miRNA, dynamic
The genetics of red blood cell density, a biomarker of clinical severity in sickle cell disease

Sickle cell disease is one of most common blood disorder amongst human. The complications associated with the disease are systemic. They damage virtually all the organs of the body, causing severe, unpredictable pain episodes, which repercussions can eventually lead to death. The process through which a biconcave, healthy red blood cell assumes a crescent-shape is well described in the literature; under deoxygenation, as water and solutes leave erythrocytes the concentration of hemoglobin S increases thus giving us dense dehydrated cells and subsequently sickled cells. Today’s current therapies are for the most part experimental, costly, and vary widely in their long-term effectiveness from patient to patient. There is, therefore, a pressing need, to identify a biomarker that is cost-effective and provides positive health outcomes to patients. The density of red blood cell is a biological indicator largely ignored by the medical community in sickle cell disease. Exploring erythrocytes density can facilitate the development of new therapies by targeting channels to rehydrate cells back to their normal shape. Clinical and physiological characterizations of this phenotype exist in many studies, but the genetic characterization is absent. We attempted to elucidate the genetic underpinning of this phenotype, by conducting a genome-wide scan, and examining the whole-exome sequences of individuals with extreme red blood cell density. Our genome-wide association study did not highlight any new loci due to our limited statistical power reflected by the cohort’s small sample size. However, our prioritization approach highlighted an intronic variant that controls the expression of ATP2B4, the main calcium pump in erythrocytes. Our whole-exome sequencing experiment pointed out two rare missense mutations in the same patient; one in ATP1B2, a Na+/K+ transporter, and the other in SPTB, the β-spectrin gene. These variants could explain why he has the highest measured density of red blood cells amongst all of our sequenced patients, and why this person experiences several of the disease-related complications. Another rare missense mutation in two patients with elevated levels of dense cells was discovered in PIEZO1, the mechanosensitive ion channel. The mutation is predicted to be deleterious by both protein function prediction algorithms.

Keyphrases: Genome wide association, Whole-exome sequencing, Sickle cell disease, Erythrocyte density, Red blood cell hydration
Études structurales d’interactions protéine/protéine impliquées dans la leucopoïèse

Hematopoietic development is regulated through a combinatorial interplay between lineage-specific activators and the general transcription factors that enables cell-specific patterns of gene expression. In this study, the transcription factors KLF2 and KLF4 play crucial roles in lymphocytes B and T development by activating transcription of specific genes through interactions with the co-activator (CBP). These interactions involve the transactivation domains (TAD) localized in the N-terminal region of KLF2 and KLF4 factors. Previous studies have shown that TADs are also found in the tumor suppressor protein p53 and these TADs are responsible for the interactions between the p53 protein and the coactivator CBP. Recently, several structures of p53TADs in complex with the TAZ2 and KIX domains of CBP have shown that these TADs are acidic and possess a ΦΧΧΦΦ motif crucial for the formation of the interaction. Interestingly, these TADs are similar to the ones found on KLF2 and KLF4. This thesis provides a structural and functional characterization of the interactions formed by the transcription factors KLF2 and KLF4, which have opposing roles, and competes for the same interacting partner CBP to activate transcription. The analysis is done using isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) spectroscopy and a yeast activation assay. This study brings a greater understanding on the opposing roles yet complementary of KLF2 and KLF4 proteins involved in B and T lymphocytes specific lineages selection and also provides information for potential therapeutic research regarding disease such as leukemia.

Keyphrases: Kruppel-like factor (KLF), Kruppel-like factor (KLF), CREB-binding protein (CBP), Protein-protein interaction, Isothermal titration calorimetry (ITC), Nuclear magnetic resonance (NMR)
Hétérogénéité des neutrophiles dans l’asthme équin

Low-density granulocytes (LDGs) are a subset of neutrophils first described in the bloodstream upon pathological conditions. However, several studies also reported the presence of these cells in the blood of healthy patients. Whether LDGs characteristics, especially their enhanced pro-inflammatory profile, are specific to this subset of neutrophils and not related to disease states is unknown. Thus, we sought to compare the properties of LDGs to those of autologous normal-density neutrophils (NDNs), in both health and disease. We studied 8 horses with severe equine asthma and 11 healthy animals. Neutrophil morphology was studied using optical microscopy, and content in myeloperoxidase and N-formylmethionine-leucyl-phenylalanine receptors (fMLP-R) evaluated using flow cytometry and immunofluorescence, respectively. Confocal microscopy was used to determine their functional capacity to spontaneously release neutrophil extracellular traps (NETs) stimulating with phorbol-12-myristate-13-acetate (PMA). LDGs were smaller and contained more fMLP-R than NDNs, but myeloperoxidase content was similar in both populations of neutrophils. They also had an increased capacity to produce NETs, and were more sensitive to activation stimuli. These characteristics were similar in both healthy and diseased horses, suggesting that these are intrinsic properties of LDGs. Furthermore, these results suggest that LDGs represent a population of primed and predominantly mature cells. Our study is the first to characterize LDGs in health, and to compare their characteristics with those of animals with a naturally occurring disease.

Keyphrases: Neutrophils, Low-density granulocytes (LDGs), Neutrophil extracellular traps (NETs), Asthma, Horses
Développement d'outils bio-informatique pour l'étude de la transcription cryptique

High throughout sequencing experiments have shown that transcription in not limited to coding regions and that most of the genome is transcribed into non-coding RNA (ncRNA). Among them, cryptic transcripts are aberrantly initiated from within the coding regions. Several studies in Saccharomyces cerevisiae have identified many factors that suppress cryptic transcription. One such factor is Spt6, a histone chaperone required for maintaining appropriate nucleosome levels on transcribed genes. In Spt6 mutant cells, nucleosomes are depleted, leading to activation of cryptic promoters. However, the mechanism by which these cryptic transcripts are regulated remains unclear. In this thesis, we present the development of a probabilistic method for the characterization of cryptic transcripts from RNA-Seq data. The method is used to characterize cryptic transcription in spt6-1004 cells. The method is based on a cumulative distribution function, thus taking into account variations in gene expression and gene length thanks to a data randomization step. Results show that our method is at least as good as previously published methods and provides a good compromise between false positives and false negatives. Importantly, this method allows for the prediction of genomic regions where cryptic transcripts are initiated. We have demonstrated the presence of cryptic transcripts running on the sense and antisense strands relative to genes. We also showed that, both sense and antisense cryptic promoters are enriched for TATA-like sequences and that cryptic transcripts are polyadenylated, suggesting that they may be regulated by the same mechanism that occurs on genes. While the cryptic transcripts on the sense strand terminate at the same position as the genes from which they are derived, cryptic transcripts on the antisense strand preferentially terminate at the 3’-end of upstream genes. We therefore propose that S. cerevisiae terminators have evolved to terminate transcription bidirectionally in order to prevent an aberrant transcription that could invade neighboring genes.

Keyphrases: RNA-Seq, Spt6, Cryptic transcription, Bidirectional terminators
Effet du sécrétome des cellules sénescentes sur la réponse inflammatoire orchestrée par les macrophages

Senescent cell clearance brings into play the senescence-associated secretory phenotype (SASP) and immune cells from the innate and adaptive immunity including macrophages (Mφ). In this study, we report that the SASP has a pleiotropic effect on immune cell activity including recruitment, activation and differentiation. We show that human Mφ exposed to the SASP of human fibroblasts develop a SASP-specific inflammatory profile characterized by pro- inflammatory (M1) secretion (e.g. IL-1β, GM-CSF) and anti-inflammatory (M2) surface markers (CD23 and CD206). The SASP also increases Mφ invasion but has no effect on monocyte differentiation. Co-culture models show that while NK cells are likely the direct effectors of senescent cell specific killing, their activity is modulated by other immune cells including Mφ, which reduced NK-mediated killing, suggesting a M2 profile. Alternatively, CD8+ T lymphocytes are essential for senescent cell killing by NK cells. Finally, CD4+ T cells cultured for 48h in the SASP secrete high-levels of IL-4, indicating a Th2 polarization. Overall, our data reveal that the SASP can modulate Mφ and other immune cells involved in senescent cell clearance and surprisingly promote an immunosuppressive response that could be important in tissue repair.

Keyphrases: Inflammation, Macrophages, SASP, Senescence-messaging secretome, Cancer, Lymphocytes T CD4+, Senescence, Age-associated diseases, Immune surveillance, Senescent cell clearance, Natural killer cells, CD4+ T cells, CD8+ T cells
Vers l’exploration de la créativité tactique dans les sports d’équipe

Tactical creativity (TC) has been identified as an essential component of exceptional performance in sport, more specifically in team sports where the athletes have to invade the opposition’s territory to score a goal (Altavilla et Raiola, 2015; Memmert, Baker et Bertsch, 2010). The creative athlete is one who can generate original, flexible and varying decisions in specific game situations (Greco, Memmert et Morales, 2010; Memmert et Roth, 2007). The purpose of this qualitative study was to explore in greater depth the phenomenon of tactical creativity as it is perceived and experienced by university-level athletes and coaches involved in certain invasion sports. Semi-structured interviews were conducted with head coaches of different teams and their athletes who were identified as being creative players. Transcripts were analyzed using content analysis. Results pointed to common attributes shared by creative players, the most important ones were game vision, non-conformity/novelty and quick decision-making. From a developmental perspective, TC was linked to diversification between and within sports as well as a high volume of experience. The microstructure of practice activities also contributed to the development of creative abilities, more specifically game-centered exercises that promote decision making and problem solving. Unlike previous studies, the present results revealed that autonomy-supportive coaching and a positive coach-athlete relationship facilitate the development of creativity allowing us to make links to the self-determination theory. Finally, TC was associated with social and performance related consequences. Interestingly, our results suggest a functional role for tactical creativity in the use of adaptive coping mechanisms. The practical implications of this study are twofold. First, the results of this study will provide coaches with specific guidelines in order to establish an ideal environment that enhances the development of TC. Second, the results will provide athletes with an awareness of the importance of certain developmental and environmental factors that contribute to maximizing their creative potential.

Keyphrases: tactical creativity, invasion sports, athletes, developmental experiences
A comparative study on the "Safe Country of Origin" principle between the European Union and Canadian asylum legislations

Two decades following the adoption of the 1951 Convention Relating to the Status of Refugees, the growing number of asylum seekers arriving at the Western countries’ borders convinced European States to put in place new asylum rules to prevent asylum seekers from reaching their borders and dissuade the potential refugee applicants from seeking international protection in their respective territories. One of the most recent preventive measures has been the “Safe Countries of Origin” rule (hereafter SCO) whose main purpose is to identify and reject refugee applicants who are not in real need of international protection since they originate from countries which are deemed generally safe. In this research, we conduct a comparative study between the European Union’s Directives adopted in 2005 and recasted in 2013, and the Immigration and Refugee Protection Act enacted by the Canada.  At the first step, we intend to verify the adverse impact of this deterrent rule, during the expeditious determination procedure, on the SCO asylum seekers’ fundamental human rights including the right to personal interview and the right to appeal. At the second step, our objective is to demonstrate to which extent the fundamental human rights limitations imposed on SCO asylum seekers are in contradiction with the EU’s and Canada’s constitutional obligations undertaken respectively in EU Charter of Fundamental Rights, the European Convention on Human Rights and the Canadian Charter of Rights and Freedoms. Based on this comparative research we illustrate that, while the elaboration and the application of the SCO rule in both the above-mentioned legal systems suffer from inherent flaws which infringe the basic human rights of SCO refugee applicants, Canada’s approach has had more drastic consequences on the SCO refugee applicants than those resulting from the EU’s common asylum law. Finally, we conclude that, instead of a short-term solution such as the SCO rule, the Western States must accept more responsibilities in providing international protection by supporting the countries that border the crisis zones, and establishing a workable program to accept a specific number of asylum seekers every year. Keywords: Safe Countries of Origin - Designated Countries of Origin - Human Rights -Procedural Rights - Right to Personal Interview - Right to Appeal - the European Union - Canada - Refugee Applicants - Asylum Seekers

Keyphrases: Canada, Safe Countries of Origin, Designated Countries of Origin, Human Rights, Procedural Rights, Right to Personal Interview, Right to Appeal, the European Union, Canada, Refugee Applicants, Asylum Seekers
Association entre la vaccination contre le Virus du Papillome Humain (VPH) et la prévalence de l’infection à VPH dans une cohorte de femmes enceintes de 2010 à 2016 à Montréal

Background: HPV Immunization programs have been implanted in numerous countries worldwide. In Canada, in 2007-2008, many provinces including Quebec, had implemented school-based vaccination programs using 4vHPV vaccines (Gardasil®). While HPV vaccination efficacy has been demonstrated in clinical trials, it is important to verify vaccine effectiveness (VE).  Objective: To estimate VE and herd immunity of the 4vHPV vaccine using HPV prevalence data within a cohort of Canadian pregnant women.  Methods: Baseline data was gathered from a cohort of pregnant women (HERITAGE study) recruited in Montreal between 2010-2012 and 2015-2016. Cervicovaginal samples were collected in the first trimester of pregnancy and tested for HPV DNA of 36 mucosal genotypes. Vaccination status was self-reported in a questionnaire. VE and 95% confident intervals (CI) were estimated by comparing the prevalence of HPV between vaccinated and unvaccinated women using the 1 – odd ratio (OR) formula. Herd immunity was also studied by comparing HPV prevalence in unvaccinated women between the 2 recruitment periods. For both objectives, the OR (and 95% CI) adjusted for age and number of sexual partners in the last 12 months was estimated using exact logistic regression. Results: The proportion of vaccinated women was 7.06% with an average age of vaccination of 25.1 years (SD +/- 5.9).VE for HPV infections 6, 11, 16, and 18 was found to be 69.6% (95% CI: -24.4 – 96.5%). VE for HPV-31, 33, and 45 was 45.1% (95% CI: -93.5 – 99.0%). We also observed a non-statistically significant reduction in the prevalence of HPV-6, 11, 16 and 18 and HPV-31, 33 and 45 unvaccinated women who were recruited during the second recruitment period (2015-2016) compared to those recruited during the first recruitment period (2010-2012) with adjusted OR of 0.9 (95% CI: 0.4-2.0) and 0.7 (95% CI: 0.3-1.6), respectively. Conclusions: We observed a reduction of the prevalence of HPV-6, 11, 16 and 18 and HPV-31, 33 and 45 in vaccinated women. Although these reductions are not statistically significant, they are similar to those observed in other studies.

Keyphrases: Virus Papillome humain (VPH), Vaccination HPV, Gardasil, Human Papillomavirus (HPV), Prevalence, HPV vaccination, Vaccine effectiveness, Herd immunity, Cross-protection
Appropriation d’une ressource didactique permettant le développement de la pensée historienne par un enseignant au secondaire

This thesis is a case study that examines the use by a secondary school teacher of the didactic resource entitled, Reading Like a Historian (RLH). This resource offers activities that encourage the development of historical thinking skills among secondary school students, which is a goal that has become central in recent years in the teaching of history and in history programmes’ curricula. To analyze this resource’s use, we selected an instructor who adapted one of the activities suggested in RLH, and observed the classroom periods that stemmed from this application (n=3), as well as conducted an interview with the participating instructor in order to have a deeper understanding of the process of appropriation and transformation of the didactic activity. Our primary results indicate that the unfolding of the activity was strongly controlled by the teacher’s discourse, and that the time left for the students’ activity was limited. Our study also revealed that the participating instructor demonstrated difficulty in identifying the prerequisite knowledge for this sequence, and had doubts with respect to his students’ capacity to mobilize the heuristic skills related to the use of historical thinking. While the resource, the position and the objectives of our participant where clearly oriented toward fostering the development of historical thinking skills of his students, the activity observed was weakly problematized and left little room for students to practice their historical thinking skills. Thus we concluded that the lack of coaching, time, and training seem to be the avenues to explore in order to remedy this situation.

Keyphrases: ressources, historical thinking, teaching practice, resource, heuristic, secondary school, history