NCube/papyrus huggingface dataset:
Vitamine D et prévention du cancer colorectal associé à la colite ulcéreuse : modèles murins

Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer due to continuing epithelial cell injury from the chronic inflammatory process. Vitamin D (vD) regulates NOD2, a gene involved in the inflammatory response and in IBD susceptibility, and induces its expression in monocytes and intestinal epithelial cells. In this project, we first established an azoxymethane (AOM)/dextran sodium sulfate (DSS) murine model of colitis-associated colorectal cancer (CAC) using C57Bl/6J. We then investigated the effect of vD3 deficiency on CAC development, and evaluated the ability of vD3 supplementation to prevent tumorigenesis. Lastly, we assessed whether the preventive benefits of vD3 on colon carcinogenesis are mediated via NOD2 using Nod2 knockout mice (Nod2-/-). vD3 deficient C57Bl/6J and Nod2-/- mice displayed increased severity of AOM/DSS-induced CAC compared to mice given vD3 supplemented diets. In vD3 deficient mice, body weight loss, Disease Activity Index (DAI), mortality rate and the colon weight/length ratio were higher compared to vD3-supplemented mice. An increased inflammation score was observed in the mucosa of vD3 deficient mice along with augmentation in the expression level of IL-6. Higher tumour multiplicity was also observed in vD3 deficient groups compared to vD3-supplemented groups. In both C57Bl/6J and Nod2-/- mice, vD3 regulated Cyp24, Vdr and pro-inflammatory genes. In conclusion, vD3 supplementation can prevent CAC independently of NOD2.

Keyphrases: 25-hydroxyvitamine D3, NOD2, murin, AOM/DSS, 25-hydroxyvitamin D3, Vitamin D, inflammatory bowel disease, ulcerative colitis, colorectal cancer, NOD2, murine, AOM/DSS
Studies of MHC class I antigen presentation & the origins of the immunopeptidome

Antigen presentation by major histocompatibility complex class I (MHCI) molecules allows the adaptive immune system to detect and eliminate intracellular pathogens or abnormal cells. Immune surveillance is executed by CD8 T cells that monitor the repertoire of MHCI-associated peptides (MAPs) presented at the surface of all nucleated cells.  The primary human MHCI genes, HLA-A and HLA-B, are highly polymorphic and consequentially demonstrate differences in antigen presentation. We investigated qualitative and quantitative differences in expression and peptide binding. Using quantitative flow cytometry we establish clear hierarchy of expression for the four HLA-A,B allotypes investigated. Our results are consistent with an inverse correlation between expression and peptide diversity although further work is necessary to solidify this hypothesis.  The global origins of the MAP repertoire remains a central question both fundamentally and in the search for immunotherapeutic targets. Using proteogenomics, we identified and analyzed 25,172 MAPs isolated from B lymphocytes of 18 individuals who collectively expressed 27 HLA-A,B allotypes. While 58% of genes were the source of 1-64 MAPs per gene, 42% of genes were not represented in the immunopeptidome. Overall, we estimate the immunopeptidome presented by 27 HLA-A,B allotypes covered only 17% of exomic sequences expressed in subjects’ cells. We identified several features of transcripts and proteins that enhance MAP production. From these data we built a logistic regression model that predicts with high accuracy whether a gene from our dataset or from independent datasets would generate MAPs. Our results show preferential selection of MAPs from a limited repertoire of gene products with distinct features. The notion that the immune system can monitor MAPs covering only a fraction of the protein coding genome has profound implications in autoimmunity and cancer immunology.

Keyphrases: Antigen presentation, Immunopeptidome, Human leukocyte antigen (HLA), Major histocompatibility complex class I (MHC I), Mass spectrometry, Next-generation sequencing, Predictive modeling
Generation and screening of natural product-like compounds for antibiotic discovery

With the appearance of more and more antibiotic resistant strains of bacteria, the development of new antibiotics becomes an issue of utmost importance for society. It is for that reason that new platforms and methodologies to accelerate the discovery of novel antibiotics are urgently needed. For the last decades, research was mainly oriented on modifying existing antibiotics, mining natural producers or screening for synthetic molecules from giant chemical libraries but these approaches did not manage to keep the pipelines filled with a sufficient number of novel antibiotics. Therefore, our goal was to develop a way to create and screen new molecules more efficiently at a fraction of the cost when compared to traditional approaches and within a short time frame. As chemical scaffolds we use natural product-like compounds that modulate the function of individual proteins or of protein-protein interactions. To generate these compounds, I focused first on the terpene scaffold class, a class containing molecules with a wide range of biological activities and includes compounds with antibacterial activities. We developed a yeast artificial chromosome (YAC) platform that allows both directional and combinatorial assembly of biosynthetic genes that can be used to create artificial biosynthetic pathways. As a proof of principle, YACs were successfully assembled containing genes coding for enzymes involved in the biosynthesis of both B-carotene and albaflavenone, and that allowed high yield production of these compounds. Finally, YACs encoding terpene gene libraries were also created and which produced a diversity of terpenoid molecules.

Keyphrases: Drug discovery, Natural product, Synthetic biology, Yeast artificial chromosome, Gene synthesis, Terpene
L'acide valproïque inhibe la progression dans le cycle cellulaire chez Saccharomyces cerevisiae

Acetylation is an essential post-translational modification involved in many important cellular processes such as regulation of chromatin structure and proteins interactions. Two enzyme families, lysine acetyltransferases and lysine deacetylases, allow proper regulation of this modification both on histones and non-histones proteins. In recent years, the discovery of small deacetylase inhibitors has led to promising novel therapy in the treatment against various diseases such as cancer. Valproic acid, a class I and II deacetylase inhibitor, has been shown to have antiproliferative effects in various models. However, the cellular mechanisms underlying this effect remain unknown. This thesis highlights the pH-dependent effects of VPA on numerous important cellular pathways in the yeast Saccharomyces cerevisiae. Our results demonstrate that VPA inhibits the transition from G1 to S phase of the cell cycle by its action on the expression of G1 cyclins. Moreover, VPA inhibits the activation of the main kinase involved in the cell wall integrity pathway. Furthermore, VPA exposure also leads to DNA replication arrest in a DNA damage-independent manner. This is a unique effect that, to our knowledge, is not observable with other agents that inhibit S phase progression.

Keyphrases: Micafungin, Transition G1/S, Acetylation, Cyclins, DNA damage checkpoint, DNA replication, Histone deacetylase inhibitors, Homologous recombination, Lysine deacetylases, Valproic acid
Création de mutants cdc5 en vue de l’identification des substrats de PLK/Cdc5 lors de la réponse d’adaptation aux dommages à l’ADN

Polo-like kinases (PLK) play a crucial role during the cell cycle, especially in promoting essential processes such as M phase entry and mitotic exit. They are also involved in many cancers and are highly tumorigenic. Recently, our laboratory showed that Cdc5 (i.e., the Polo-kinase of Saccharomyces cerevisiae) was required for the adaptation response to DNA damage, and that the target of Cdc5 during this process would localize to the yeast centrosomes and might be a less conventional substrate. In order to identify it, an in vivo analysis of the whole phosphoproteome of PLK/Cdc5 by mass spectrometry has to be to done. Accordingly, a thermosensitive allele of CDC5, i.e. a mutant version that can be inactivated at high temperature, has to be used. This allele has to be thermosensitive at 30°C, in order to make sure that only cdc5 will be inactivated and that only its substrates will be identified. For this purpose, we created two cdc5 alleles that were thermosensitive at 30°C: cdc5-17 and cdc5-18, and then we analyzed their cell cycle at 32°C. The results of this analysis showed that cells exposure to 32°C resulted in their arrest at the end of the cell cycle as large-budded cells, which points towards a defect in the promotion of mitosis exit. This defect is due to the mutation of CDC5 whose protein allows the exit from mitosis via two pathways: the MEN pathway (Mitotic Exit Network) and the FEAR pathway (Cdc Fourteen Early Anaphase Release). cdc5-17 and cdc5-18 represent precious biological tools that will allow us to analyze PLK/Cdc5 phosphoproteome and to identify Cdc5 targets during the adaptation response to DNA damage. Since the adaptation to DNA damage caused by chemotherapeutic agents is considered one of the factors promoting cancer tumors proliferation, this discovery will be a huge step in the fight against cancer.

Keyphrases: Cancer, Kinase Polo, PLK, Cell division, Mitosis, Genome stability, Polo-kinase
La responsabilité civile dans les cas de dommages causés par les robots d’assistance au Québec

The exponential development of technology and the aging of the population foster the introduction of assistive robots in our daily life. The coexistence of man with these intelligent and autonomous robots raises a fundamental question: in the event that a robot would cause an accident bringing about injury to a person or to property, who would be responsible? No law regulates the activities of assistive robotics in the world. This study aims at analysing the applicability of the Civil Code of Quebec liability regimes to cases of damages caused by assistive robots.  The analysis of the liability regimes existing in the Civil Code of Quebec shows that two systems of liability may be applied to the specific cases of damages caused by assistive robots: the regime of liability for property enunciated in Article 1465 of the C.C.Q., and the regime of liability for manufacturers and specialized sellers contained in Article 1468 of the C.C.Q. This is due to the presence of criteria and conditions of implementation of the regimes that are transferable to the different aspects of manufacture and use of assistive robots.

Keyphrases: Robot, Liability, Damage, Robot, Property, Manufacturer, Technology, Artificial Intelligence, Autonomy, Robotics
La nature juridique du contrat de réassurance en droit civil québécois

The reinsurance contract is not a new contract; its existence can be traced back to the 14th century. The reinsurance contract remains however an obscure topic in Quebec civil law and in other jurisdictions and the determination of its legal nature remains controversial.     The qualification of such legal nature requires the study of the reinsurance contract’s foundations. It is therefore essential in this process to consider the concept of reinsurance contract, its history, its purpose, the regulatory regime applicable to it and the legal relations arising therefrom.     Numerous theories have been expressed with respect to the legal nature of the reinsurance contract. The major currents now oppose essentially the thesis of the insurance contract to the thesis of innominate contract. On one hand, the reinsurance contract has several characteristic elements in common with the insurance contract. On the other hand, it also differs on several points that seem crucial in the process of qualifying the legal nature of the reinsurance contract.

Keyphrases: Qualification, Civil Law, Contract, Reinsurance, Qualification, Insurance, Nominate Contract, Innominate Contract, Privity of Contract
Les enjeux juridiques concernant les nouveaux modèles d’affaires basés sur la commercialisation des données

This essay is submitted as part of a master's thesis in Information Technology Law. This thesis discusses different business models that have the common feature of commercializing data in the context of Information Technologies. One of the goals of this thesis is to inform the reader about the workings of the studied business practices, as they are not widely known. First, in order to situate the issues, this essay will consider the theoretical concepts of Privacy and Personal Information Protection. Once the review of Data Protection and Privacy has been established, this thesis will further explore Data Brokerage, Cloud Computing and Analytic Solutions as practices. Over the course of this description, the legal issues raised by each aspect of the aforementioned practices will be studied. Finally, the last chapter of the thesis will be dedicated to two issues that are not limited to the scope of a specific business practice, but are direct consequences of the evolution of Information Technologies: the role of Consent and Data Security.

Keyphrases: Information, Big data, Data brokerage, Personal information, Privacy, Commercialization, Cloud computing, Consent, Security
Étude sur la sécurité dynamique : le cas de Cité-des-Prairies

Intervention towards youth offenders is a difficult task as it requires both security measures and rehabilitation. This case study focuses on ways to align security practices to better match the objectives of rehabilitation. This study’s aim is to understand the practices of the two main types of interventionists who use dynamic security; a method based on interpersonal skills to maintain security at Cité-des-Prairies rehabilitation center. In order to study the contributions and perceptions of intervention agents and educators who participate in the dynamic security approach, eight semi-structured interviews were conducted. The results show that harmonization of practices between educators and intervention agents maintains the security at Cité-des-Prairies rehabilitation center. In order to adopt dynamic security practices, both types of interventionists build relationships with young offenders. These practices help the youth rehabilitate and also maintains security in the facility. The results of the study show that interventionists, educators and intervention agents, find it difficult to determine which practices contribute more to security or to rehabilitation. The interventionists in this study also recognize that maintaining the balance between security and rehabilitation appears to be a constant challenge. Although dynamic security requires that all interventionists demonstrate empathy towards youth offenders, security issues arise when those same interventionists forget that they work with youth who are dangerous and unpredictable.

Keyphrases: Dynamic Security, Private security, Rehabilitation, Youth center, Interventionists
Perspectives croisées : les déterminants sociaux de la vulnérabilité sexuelle chez les jeunes de 18 à 25 ans

Since the 1990s, public health indicators have continuously highlighted negative sexual health outcomes for youth aged 18 to 25, ranging from increases in rates of sexually transmitted infections, to major sexual health knowledge gaps. These indicators suggest that youth are increasingly sexually vulnerable. The objective of this study was to shed new light on the domain of youth sexual health from the vantage point of sociological perspectives on health. Our research interrogations are theoretically grounded in a social determinants of health perspective, in which three analytical perspectives were explored: materialist, bio-psycho-social and life course perspectives.  Our research methodology is inspired by a grounded theory approach, which was adopted to examine a youth sexual health clinic based in Montreal. In this milieu, it was possible for us to meet healthcare workers and youth aged 18 to 25 with the objective of better understanding the social determinants of youth sexual vulnerability. Our methods included semi-structured interviews and non-obtrusive observations in various locations of the clinic.   The results from this study underscore four social determinants of youth sexual vulnerability: youth sexual health knowledge, gendered sexual scripts, the period of youth during their sexual lives and characteristics of the downtown neighborhood of Montreal. An approach taking into account the perspectives of those who witness (the healthcare professionals) and those who experience (the youth) sexual vulnerabilities enabled us to better understand these determinants, their sources and effects. We analyze these determinants using the three social determinants of health perspectives. We hope that the results of this study will encourage further research in the field of youth sexual health within a sociological approach, as well as encourage and improve interventions for youth and their sexual health.

Keyphrases: social determinants of health, sexual health, youth, vulnerability, qualitative research, healthcare services
La conservation autologue de sang de cordon ombilical : une ouverture sur une forme émergente de «citoyenneté biologique»

The recent transformation of cord blood to a precious source of stem cells has given rise to a global commercial industry of conservation, which is now competing with a large network of public cord blood banks. This dissertation explores the socio-cultural context surrounding the emergence of that industry and aims at elucidating the ethical and political concerns that it generates. It begins by examining how public cord blood banks define themselves (and are defined by ethical commitees) as purveyors of values such as altruism and national solidarity -that is, values which were traditionally linked to the « redistributive » model of human blood and organs exchanges that emerged after World War II. It next argues that private banks are bringing about a radical transformation of the relationship between mothers and their biological “products”. This dissertation suggests that this innovative model of exchange is an expression of contemporary reconfigurations of the very notion of community, which is now characterized by what we call new forms of “biosociality”. Our hypothesis is that these new socialities can be understood as the consequence of a collective hope to improve familial biological conditions, which is itself the product of the growing financiarization of life sciences. By way of a foray into the « promissive » discourse employed by private banks for their promotional material, the dissertation attemps to identify how these potentialities attributed to cord blood define new maternal subjectivities characterized by specific moral duties and obligations.

Keyphrases: Risque, Autologous banks, Umbilical cord blood stem cells, Biopolitics, Bioeconomy, Biological enclosure, Political economy of hope, Motherhood, Risk, Biocitizenship, Neoliberalism
L’intervention en médiation familiale en présence de violence conjugale : dépistage, pratiques d’intervention, défis et préoccupations

In Quebec, family mediation cases regarding domestic violence are controversial, and the interventions used are not well documented or known. The main purpose of this thesis is to understand how family mediators deal with cases of domestic violence within their own practice. The specific research goals include the following: (1) understanding how family mediators screen for domestic violence; (2) learning how they intervene in domestic violence cases, once they have been identified; and, (3) identifying the challenges and concerns the mediators face when working with these cases. This qualitative study was conducted with eight mediators from the psychosocial and legal fields. Semi-constructed interviews were conducted with these participants. Those interviewed brought forth the importance of offering in-depth advanced training regarding domestic violence and screening tools to all mediators across Quebec and to add to the current training by addressing the issues of dangerousness, the risk of recurring or increase of domestic violence, as well as the evaluation of risk for spousal homicide. The results of this study also demonstrate the importance of distinguishing between intimate terrorism and situational couple violence, as well as the implementation of best intervention practices specific to each type of violence. Family mediation that includes the presence of domestic violence cases should be a specialized field of practice that promotes collegial collaboration in order to access pertinent and useful resources.

Keyphrases: Family mediation, Domestic violence, Screening, Intervention practices, Training
About time : life-cycle and cohort effects on support for Quebec sovereignty

Can life-cycle and cohorts effects help explain support for Quebec sovereignty? This research attempts to answer this question by drawing on theories of generational change and political socialization. It uses longitudinal survey data from 1985 to 2014 to measure the impact of age and generation on support for this constitutional option among francophone Quebeckers. Our results confirm, to a certain extent, these two hypotheses. First, as they age, Quebeckers become less likely to support sovereignty. However, the relationship between age and support for independence weakens at the beginning of the 2000s. Second, Baby boomers (born between 1945 and 1964) are more likely to support sovereignty than any other generation, regardless of their age. They are followed by the Oldest generation (born in 1944 or before), Generation X (born between 1965 and 1979) and the Millennial generation (born in 1980 and later).

Keyphrases: Quebec sovereignty, Generation, Age, Public opinion
Le processus d’élaboration des politiques publiques comme espace d’autodétermination : les cas de l’Accord de Kelowna et de la Loi sur le contrôle par les Premières Nations de leur système d’éducation

The purpose of this thesis is twofold. First, it seeks to identify factors that enable the federal government and Aboriginal peoples to agree on public policies despite the persistence of settler colonialism. It demonstrates that such an agreement is conditional upon the legitimacy, from an Aboriginal perspective, of the policy-making process. Second, this thesis uses a pragmatic approach to call for a reflection on the capacity for policy-making processes to become a space for Aboriginal self-determination. Given the flexibility of current rules that govern the policy-making process in Canada, a government – if it has the will - can shape the process in a more egalitarian fashion, thus increasing the process’s legitimacy from an Aboriginal viewpoint. In a perspective of incremental change, such policy-making process could help Aboriginal people regain some decisional autonomy and hence mitigate the unequal power relationship that actually exists between them and the Canadian state. Building on a theoretical framework that blends different approaches, notably from literatures on public policy, colonialism and legitimacy, this thesis explores two case studies : the policy-making process that led to the Kelowna Accord in 2005 and the one that led to Bill C-33, First Nations Control of First Nations Education Act, in 2014. The comparison of both cases illustrates our arguments and demonstrates its practical applicability. In brief, it shows how the policy-making process can be both a self-determination space and a tool of oppression.

Keyphrases: Participation, Aboriginal peoples, Policy-making process, Legitimacy, Colonialism, Self-determination, Kelowna Accord, Bill C-33