NCube/papyrus huggingface dataset:
Étude de la régulation des activités transcriptionnelle, réplicative et de l’instabilité de la protéine régulatrice E2 des papillomavirus

Papillomaviridae is a family of small double-stranded DNA viruses known as papillomaviruses (PV) which infect skin and mucosal epithelial cells where they cause benign lesions such as warts. A subset of these viruses is associated with the development of malignant lesions and is the causal agent of cervical cancer. Papillomavirus E2 regulatory protein is involved in several functions leading to the establishment of the viral infection. These activities include the regulation of viral genes transcription, it participation to the initiation of viral DNA replication by recruiting the viral helicase E1, and to the maintenance and segregation of the viral episome during cellular division. All these functions are associated to the ability of E2 to bind specifically the viral genome, to interact with viral and cellular proteins and to acquire post-translational modifications.  The first article of this thesis led to the identification of Brd4(L) as the major protein associated to E2 protein of different papillomavirus types. This interaction involves the amino acids associate to the transcription function of E2. The protein Brd4(L) was identified originally as a factor that maintains epigenetic memory by it interaction with acetylated histones during mitosis. This association with the chromatin, it interaction with Mediator complex and it participation to the cellular transcription by recruiting pTEFb complex allowed us to propose that the interaction between Brd4 and E2 is essential to the regulation of viral gene transcription. The second part of this work based on previous characterization of the transactivation domain dimerization interface; investigate the role of this surface in the transcriptional and replicative activities of E2. Our studies demonstrated that the integrity of the TAD dimerization interface may contribute to the DNA replication activity of E2. This discovery suggests that the dimerization interface may regulate the viral DNA replication by the redox state of the E2 protein. A fine characterization of this interface may provide new aspect of the interaction between E1 and E2 in the context of viral cycle. Finally, the third section of this thesis define a region of E2 protein associated to it degradation by the proteasome. This study also demonstrates that the stability of E2 is related to its cellular localization and suggests that the highly conserved residues found in this region may represent a PY-NLS nuclear localization signal signature.    This thesis shows the existence of different approaches to regulate the transcriptional and the replicative activities as well as the stability of the papillomavirus E2 protein to favor the establishment and the progression of viral cycle.

Keyphrases: Papillomavirus, E2, Brd4(L), transcription, replication, protein-protein interaction, dimeric interface, degradation, cellular localization, proteasome
Développement de tensioactifs à base d’acides biliaires pegylés pour des applications pharmaceutiques

Bile acids are natural compounds and may have potential for pharmaceutical applications. Their structures provide an interesting platform for polymerization to obtain well-defined architectures. The anionic polymerization of oxirane derivatives, mainly PEG derivatives, endowed new aggregation properties and improvement of biocompatibility of the new amphiphilic polymers based on bile acids.  A library of pegylated bile acids (BA(EGn)x) was prepared for the formulation of lipophilic drugs. The aqueous physicochemical behaviors of these derivatives (modulation of the length (2 < n < 19) and the number (2 < x < 4) of PEG arm) were investigated.  In order to improve the bioavailability of insoluble active compounds (itraconazole, an antifungal drug), a binary system based on the association of BA(EGn)x and oleic acid, formed self-emulsifying drug delivery systems. The in vitro evaluation of cell toxicity and solubilization capacities of the BA(EGn)x systems followed by the in vivo evaluation in rats of the pharmacokinetic parameters demonstrated the advantages of our self-assembled system for controlled drug delivery for both oral and intravenous administration. Star-shaped block copolymers of pegylated cholic acid (CA(EGn-b-AGEm)4) were prepared by the introduction of a second hydrophobic block of PAGE poly(allyl glycidyl ether). They demonstrated thermosensitivity (8 oC < LCST < 37 oC) in aqueous solution, suggesting a mechanism based on the formation of aggregates in two steps. The PAGE block with pendant groups may facilitate futher functionalization. The thiolation of allyl yields a new class of charged PEGylated star polymers (with multiple amines or carboxylic groups). CA(EGn-b-AGEm-NH2)4 and CA(EGn-b-AGEm-COOH)4  derivatives showed self-assembled structures in solution with temperature and pH responsiveness, respectively. This functionalization may lead to broader application of pegylated star derivatives in DNA transfection systems, siRNA delivery systems or as selective delivery system (pH-dependent).

Keyphrases: PEG, Bile acids, Star polymers, drug delivery system, anionic polymerization, itraconazole, thermo responsive polymers
Le Théâtre-forum : pour une délibération sous le signe de la reconnaissance?

Inspired by the democratic virtues of public deliberation but preoccupied with its blind spots, this research explores Forum Theatre as a deliberative medium to initiate discussion about the social tensions which underscore copresence between the homeless and other dwellers of public space in downtown Montreal. Indeed, we argue that in neighborhood forums social inequalities lead to deliberative ones for the homeless who lack epistemological authority due to their status, thereby reproducing the denial of recognition they endure as pariahs of public space. Forum Theatre stems from Theatre of the Oppressed which was initiated by Augusto Boal during the Brazil dictatorial regime as a revolutionary practice for the oppressed. It is premised on active audience engagement whose members are encouraged by the Joker to become Spect-Actors by replacing the protagonist in order to overcome his oppression. As such, can stepping inside the shoes of the homeless protagonist thru character replacement facilitate a passage from indignity to recognition for the latter? In other words, can a theatrical exchange create a space of intersubjectivity between the homeless and their domiciled neighbours? After all, the virtues of deliberation, not to mention the principles defended by recognition theorists like Honneth and Renault, both rest on intersubjectivity.

Keyphrases: Espace public, Forum-Theatre, Deliberation, Public Space, Recognition, Homelessness
Études de nouvelles maladies neurogénétiques chez les Canadiens français

Since many decades we are able to identify mutations responsible for Mendelian diseases. The identification of the causative gene not only allows a better diagnostic to these families, but also allows a better understanding of the pathophysiological mechanisms of these disorders and of the normal function of a gene. Ultimately, those discoveries lead to the identification of therapeutic targets that will enable clinicians to treat these diseases. Technological progress has forever driven gene identification. Starting with traditional approaches like positional cloning passing through the first sequence of the human genome and finally the recent high-throughput sequencing technologies, more and more diseases are now linked to a genetic cause. During my PhD, I had the opportunity to use traditional approaches (leukodystrophy) as well as new sequencing technologies (painful sensory polyneuropathy) which both led to gene identification for some of our families. The efficiency of these approaches is well known, each of them has advantages and disadvantages. In these projects, we used the french-canadian population well known for its founder effect and the presence, still today, of large families. Working on these projects allowed us to establish advantages and disadvantages concerning the use of those technologies and the french-canadian population. In the presence of a homogenous and well defined phenotype, like the leukodystrophy project, the traditional approach enables us to rapidly identify the causative gene (POLR3B). On the other hand, the unbiased exome sequencing approach has had more success for diseases characterized with clinical and genetic heterogeneity. Large families are a great advantage for both methods. In the painful sensory polyneuropathy project, a large family originated from the Saguenay-Lac-St-Jean region allowed us to identify the NAGLU gene as responsible for the disease after exclusion of the candidate variants by segregation analysis. NAGLU has already been associated with a phenotype that differs in many points with the clinical features observed in our family. In this case a traditional approach would have failed to identify NAGLU as the causative gene. In the analysis of our exome sequencing results, we observed many rare variants absent from databases but shared between french-canadian individuals. This enrichment in rare variants is probably due to the particular genetic demography of Quebec. In conclusion, high-throughput sequencing technologies are advantageous in the study of clinically and genetically heterogeneous diseases. These technologies are changing the gene identification approach towards reverse genetics, meaning genetics towards clinic.

Keyphrases: Positional cloning, exome sequencing, neuropathy, pain, leukodystrophy, French-Canadian
Le cinéma des Premières Nations du Québec et des Inuit du Nunavut : réappropriation culturelle et esthétique du sacré

This Ph.D. dissertation addresses the subject of First Nations and Inuit cinema, in Quebec and Nunavut. More specifically, we examine the role of cinema as an agent of cultural re-appropriation for Indigenous and Inuit communities, who have been using a western and contemporary medium to both claim their political and economic rights, and re-write a history that, until recently, has been told by external mediators.  Therefore, choosing to borrow elements found in indigenous methodologies, will have allowed us to bring into light a particular aspect of First Nations cultures, i.e. the manifestation of an oral thought process centered on the notion of the sacred. The first part of this thesis is thus dedicated to the theorization of the sacred, a notion that is envisioned by the First Nations peoples as a way of life that can be transposed on-screen through what we chose to name the aesthetics of the sacred.   Furthermore, the viewing and analysis of short and long-length films have allowed us to identify the principal elements of an aesthetic of the sacred that reveals itself in the work ethics of the filmmakers (participation of the community in the filmmaking process, attentive listening by the filmmakers of the person speaking) as well as in the remediation, on-screen, of oral tradition. Thereby, the exploration of Abénaquis filmmaker Alanis Obomsawin’s documentary films has put forward the importance of the role played by native women in their communities, the latter remaining the principal agents of cultural change as well as the mediators of their stories and cultures. In the same way, examining the contents of the short films produced by the young Wapikoni Mobile filmmakers has allowed us to discover new facets of native youth, the majority of those short films reflecting a desire to update tradition while building relationships based on trust with the elders of their community. Finally, the last chapter addressing the subject of Inuit cinematography, demonstrates how cinema presents itself as the medium most fit to translate accurately the subtleties found in stories hailing from oral tradition.

Keyphrases: Postcolonialisme, Indigenous methodologies, Aesthetics of the sacred, First Nations and Inuit cinema, Film analysis, Oral practices of cinema, Oral tradition, Postcolonialism, Indigenous culture
Emergencies and arbitrary coercion

This dissertation casts a skeptical eye on theories of emergency government. It argues that far from being self-evident, most accounts of emergency government assume that the notion of an “emergency” is clear, both conceptually and practically. I argue that this is not the case and that this misplaced certainty generates both practical and conceptual problems. Further, this dissertation shows that this misplaced certainty in the clarity of the concept of emergency leads authorities to act arbitrarily rather than on principle in times of emergency. Against this misplaced certainty and against many influential contemporary accounts of states of emergency I offer a more perspicuous account of the concept of “emergency.” Once the concept of emergency is defined and defended, the dissertation proceeds to show the various ways in which misunderstandings of the concept lead to arbitrary uses of state power in emergencies. By closely examining the work of competing theories of emergency, the dissertation is able to reveal where these other theories go wrong. By viewing emergencies as rare events, the dissertation avoids the temptation to view them as exceptional events that sunder the established political order. Arguing that emergency measures should be compatible with liberal democratic values more generally, the dissertation makes the case for treating emergencies from within the ambit or existing liberal democratic institutional mechanisms as opposed to jettisoning these mechanisms as some other theorist recommend. In undermining the idea that states of emergency are exceptional events, the dissertation creates a conceptual space within which more constructive proposals pertaining to emergency management can be heard. Further, by unearthing the various ways in which state authorities arbitrarily employ power in emergencies, the dissertation makes clear the need for increased institutional oversight as concerns emergency powers and their deployment in emergencies. In conclusion, the dissertation advances that liberal democracies need not fear emergencies as much as they do and argues for the view that democracies already have the required resources for dealing with emergencies in an institutional manner that is both politically liberal and institutionally democratic. Against those skeptical of these resources, the dissertation offers comprehensive philosophical reasons for abandoning said skepticism.

Keyphrases: concept, philosophy, state, emergency, democracy, liberalism, arbitrariness, power, ethics, politics, concept
Étude de la perfusion cérébrale régionale dans le trouble comportemental en sommeil paradoxal

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by intermittent loss of normal atonia during REM sleep and elaborate motor activity associated with dreams. RBD may occur in an idiopathic form (iRBD), but is frequent in neurodegenerative diseases characterized by alpha-synuclein deposition such as Parkinson’s disease (PD) and dementia with Lewy bodjes (DLB). Biomarkers of synucleinopathies, such as motor, olfaction and color discrimination dysfunctions have been found in patients with iRBD. Moreover, impaired cerebral activities with neuroimaging and cognitive perturbations have also been detected in those patients. Longitudinal studies have demonstrated that iRBD might precede PD or DLB by several years. This suggests that iRBD could represent a risk factor of synucleinopathies.  The goal of the present research was to investigate the resting regional cerebral blood flow (rCBF) in an iRBD sample using single photon emission computerized tomography (SPECT) neuroimaging. This led to two different studies. The aim of the first study was to compare the rCBF between a group of patients with iRBD and a group of healthy control subjects, and to explore correlations between rCBF of iRBD patients and markers of synucleinopathies. The results of this study showed that compared to controls, iRBD patients had decreased perfusion in frontal and parietal cortical regions and an increased perfusion in pons, putamen and hippocampus bilaterally. Moreover, a significant correlation between brain perfusion in frontal and occipital cortex and performance on a color discrimination test was found in iRBD patients. The brain perfusion anomalies observed in our iRBD patients are similar to those observed in PD in functional neuroimaging studies, suggesting similar neuroanatomic basis between these two pathologies.   The objective of the second study was to investigate brain perfusion changes associated with mild cognitive impairment (MCI) in iRBD. We compared rCBF of a sub-group of patients with iRBD and MCI, a sub-group of patients with iRBD without MCI and a group of healthy control subjects. The results showed that only iRBD with MCI showed decreased perfusion in posterior brain regions, in occipital and temporo-parietal areas. These anomalies found in iRBD with MCI are similar to those reported in other studies in PD patients with dementia (PDD) and DLB in neuroimaging studies.  To conclude, the results of this research showed brain perfusion abnormalities in iRBD patients similar to those found in synucleinopathies. One of our studies demonstrated a specific pattern of cerebral anomalies with SPECT, similar to those found in PDD and DLB, in patients with iRBD and MCI compared to iRBD without MCI. These biomarkers of synucleinopathies in iRBD  suggest that these patients  might be at higher risk to develop a neurodegenerative disease associated with alpha synuclein deposition.

Keyphrases: REM sleep behavior disorder, Functional neuroimaging, Mild cognitive impairment, Neurodegenerative disease, Dementia
Labour, industries and the politics of immigration

This paper-based dissertation examines the economic causes and consequences of immigration policies from the perspective of recipient countries.  I argue that immigration policies affect the industry mix, and that unskilled immigration has tempered down the development of high-technology sectors during the past decades in OECD countries.  Nonetheless, elected governments have incentives to increase immigration levels and to admit unskilled immigrants, in order to maintain the support of corporate interests, and to avoid the negative attention that would result from the depletion of traditional industries.    The first paper builds upon a model of endogenous technological change to argue that business research activities expand with the relative supply of skilled labour, and contract with relative increases in unskilled labour.  Using panel data on OECD countries between 1971 and 2003, I estimate the elasticity of R&D outlays with respect to relative factor supplies with a dynamic OLS (DOLS) model.  The empirical findings are consistent with the theory, and a key policy implication is that unskilled immigration has dampened the intensity of business investments in R&D.    The second paper examines the responsiveness of Canadian federal governments to corporate lobbying on the subject-matter of immigration, using quarterly data between 1996 and 2011.  I claim that governments have electoral incentives to increase levels of immigration despite the restrictive preferences of the public, in order to secure the support of corporate interest groups.  To test this argument, I make use of the vector autoregression methodology.  A significant finding is the positive response of temporary worker inflows to the intensity of corporate lobbying.     The third paper argues that governments have incentives to adjust the skill composition of immigration in order to maintain the existing regional industry mix.  I test this argument using panel data on Canadian provinces between 2001 and 2010, and a research design based on the two-stage least squares approach.  The empirical findings are consistent with the main argument: provinces relying intensively upon traditional industries are likely to receive higher proportions of unskilled immigration, which contribute to maintain this specialization.

Keyphrases: Immigration policies, R&D, Technological change, Lobbying, Temporary workers, Industry mix, Rybczynski theorem, Skilled labour, R&D, Lobbying
Conditions pouvant favoriser le succès global d'un projet à grand déploiement en éducation où chaque élève possède un ordinateur portable

ICT integration in education has grown considerably in the recent years, and researchers around the world have devoted it an increasing interest; the subject of ICT in education has now been prevalent within the literature for many years (Istance & Kools, 2013; Storz & Hoffman, 2013). In a world where technologies are ubiquitous in most spheres of activity, it is no longer whether technology should be integrated in education, but rather how it should be. As ICT have proven to offer many advantages, especially regarding student motivation and engagement, and also in reducing the digital divide, the various stakeholders in education are generally aware of the importance of using information and communication technologies (ICT) in education, but do not always know where to start. This thesis focuses on a particular form of integration of ICT in education, mainly referred to as “one-to-one computing projects” or “1:1 projects”. Those projects differ in that the teacher and each student have their own laptop for use in an educational context. This thesis attempts to show, through a clear and accessible language, the challenges that may be encountered in such projects, as well as what can be done to limit their negative impacts.  In order to determine the conditions that promote the overall success of one-to-one computing projects in Quebec, or even elsewhere, a comprehensive literature review has identified four main categories of factors in which the identified challenges may be classified: factors related to the project management, factors that are internal to the teacher, factors related to their work environment as well as factors related to the infrastructure and equipment. Those diverse categories of factors are discussed in detail within the theoretical framework of this thesis. In order to achieve the objectives, a questionnaire was developed and more than 300 teachers of a school board currently involved in a large-scale one-to-one computing project have responded. The mixed data (quantitative as well as qualitative) that came out of the questionnaire was analyzed using specialized software and this has allowed to verify the relevance of the challenges found in the literature review, and it allowed the finding of new additional elements. It has been found that many challenges are likely to be encountered. The most significant ones are the quality of the equipment used, the importance of teacher training in relation to ICT and the importance of developing a clear vision to ensure the full support of teachers. It was also determined that the teachers should have access to pedagogical support as well as technical support easily. Finally, it was found that the nature of large-scale one-to-one computing projects is such that it is important to take into account the local needs of teachers, which may vary depending on the context in which they work.

Keyphrases: TIC, technologie, one-to-one computing, ICT, education, technology, computer, ubiquitous computing