NCube/papyrus huggingface dataset:
Étude du rôle des ARN non codants du cluster Dlk1-Dio3 dans la dystrophie myotonique de type 1

Myotonic dystrophy type 1 (DM1) is the most common adult form of muscular dystrophy. It is a complex multi-systemic disorder, characterized by progressive muscle weakness and wasting, myotonia, cataracts, cardiac and neurological defects. DM1 is caused by an expansion of CTG trinucleotide repeats in the 3’ untranslated region of the protein kinase gene DMPK. The expression of the mutant DMPK transcript leads to the sequestration and disruption of the normal functions of the members of the Muscleblind-like (MBNL) family of proteins and CELF1. These factors have primarily been implicated in the regulation of the pre-mRNA alternative splicing and multiple studies have shown that their targets are mis-spliced in DM1 patients. Despite recent advances, many mechanisms involved in DM1 pathogenesis remain largely unknown. Non-coding RNAs are emerging as key regulators of human muscle development. Recent evidence has shown that mis-regulation of specific lncRNAs and miRNAs play a role in muscular diseases. Using microarray and RT-qPCR, we found an overexpression of several mature miRNAs and lncRNAs from the Dlk1-Dio3 cluster, which play an important role in muscle development, in the muscle samples from DM1 (HSALR) mouse model and DM1 patients. Furthermore, we see a change of the splicing profile of the Dlk1-Dio3 lncRNA MEG3 in DM1 mouse model and human DM1 myoblasts. Since the transcripts containing CUG repeats sequester MBNL proteins, we explored the role of these proteins in the regulation of the Dlk1-Dio3 cluster. Therefore, the treatment of HSALR mice with furamidine, an inhibitor of CTG-expanded repeats transcription, shows a correlation between expression of the CTG-rich toxic transgene and Dlk1-Dio3 lncRNAs expression. Depletion of MBNL proteins with siRNAs leads to an up-regulation of MEG3 during myogenesis. Depletion of MEG3 by RNAi results in a delayed differentiation of myoblasts. Our results reveal a disruption of Dlk1-Dio3 cluster expression in DM1 and suggest a role for this cluster of non-coding RNAs in this disease.

Keyphrases: Myotonic dystrophy, Myogenesis, Splicing, lncRNA, miRNA
Ciblage du glioblastome multiforme par les inhibiteurs de BMI1

Glioblastoma multiforme (GBM) is the most common and most aggressive primary cancer of the central nervous system (CNS). It has a median survival of 12 to 15 months despite conventional treatment combining surgical excision, chemotherapy, temozolomide and radiotherapy. It can be secondary to the transformation of benign CNS tumors. It can also be formed immediately from neural stem cells and glial cells (astrocytes and oligodendrocytes) that has been transformed into cancer stem cells following mutations involving several genes such as EGFR, PTEN, MDM2, IDH1 / 2 and tumor suppressor genes (TP53 and Rb). These GBM cancer stem cells are mesenchymental or proneural cell type, expressing CD133 + and Sox2 markers. Previous studies have shown that GBM cancer stem cells are capable of reforming the initial tumor in vivo as well as resisting chemotherapy and radiotherapy following their enrichment in BMI1 protein, targeting this globally enriched protein in the GBM could induce tumor involution and improve the survival of people affected by this disease. The aim of this study is to test two pharmacological inhibitors of BMI1 (PTC596 and A1016) on Glioblastoma multiforme in order to improve patient survival. After treatment with PTC596 and A1016 immunodeficient mice with neurological manifestations after intracranial grafting of GBM CD133 + cancer stem cells, we obtained the result which suggests that these pharmacological inhibitors of BMI1 improve the median survival of mice (27 to 46 days) by compared to untreated mice (5 to 6.5 days) and strongly reduce tumor volume. In vitro, they reduce the growth of GBM cancer stem cells. However, they are likely to induce a phenotypic change in some relapsing glioblastomas, suggesting an epitheliomesenchyment transition.

Keyphrases: BMI1, A1016, PTC596, Glioblastoma, Glioblastoma cancer stem cell
Impact épigénomique de mutations associées à des syndromes neurodéveloppementaux dans des régulateurs de la chromatine

Neurodevelopmental syndromes, caracterized by a global developmental delay, intellectual deficiency, or autism spectrum disorders, affect around five percent of the population. Of these, a large part of their genetic causes remains unresolved. Lately, mutations in subunits of large chromatin remodeling complexes have been associated with neurodevelopmental syndromes, affecting DNA and histone modifications, as well as nucleosome remodeling. We have identified individuals carrying mutations in TRRAP, a component of multiple histone acetyltransferase complexes; SMARCC2, a structural protein involved in the formation of the BAF (SWI/SNF) nucleosome remodeling complex; and CHD3, one of the ATP-dependent helicases of the NuRD nucleosome remodeling complex. For these three genes, we characterized gene expression patterns and chromatin structure for several individuals harboring de novo mutations by RNAseq and ATACseq in individuals’ fibroblasts or lymphoblastoïd cell lines. We observed that they showed differential expression for a number of genes, of which a large proportion is associated with neural development or neuronal function. We also showed that some differentially expressed genes in TRRAP individuals are also associated with a higher chromatin opening at their promoter.

Keyphrases: RNAseq, ATACseq, TRRAP, CHD3, SMARCC2, Neurodevelopmental syndrome, Histone acetylayion, Nucleosome remodeling
Corruption dans le milieu municipal : effets sur les élus et impacts sur les contrats

Collusion and corruption are phenomena against which society has always fought. However, they never cease to renew themselves. The elected municipal officials, due to the proximity and locality of their power are one of those most at risk to be corrupted. The Commission d’enquête sur l’octroi et la gestion des contrats publics dans l’industrie de la construction is revealing in this regard. This dissertation aims to identify the impact this commission had on municipal contracts legislation, on the individual rights of the elected municipal officials as well as on the validity of public contracts concluded in this context. Firstly, we will consider the investigations of the 20th century which led to the first legislative changes with regards to the battle against corruption at the municipal level. Secondly, we will dress a portrait of the revelations stemming from the Charbonneau Commission and the legislative changes this commission had on contractual law. Thirdly, we will study the recourse available to the municipality that has been put in place since the beginning of the investigation of the Charbonneau Commission, that being the application to declare provisionally incapable a member of a municipal council for which there are criminal accusations. In parallel, we will analyse the new interpretation that the Courts have given to the elected officials’ financial protection regime in this same context. Fourthly, we will evaluate the consequences at the penal, civil and ethical level the elected officials with reprehensible conduct are susceptible to incur. We will identify the objectives on which the Courts have put emphasis in the context of the Charbonneau Commission. Fifthly, we will study the consequences of corruption on the validity of the municipal contract. The violation of public policy rules leads to the nullity of the contract. In the context of the recent decision of the Court of appeal in Ville de Montréal c. Octane Statégie inc., 2018 QCCA 223, which of the Civil code of Québec or the common law is best adapted to the reality of municipalities? Finally, we will study the path the legislator chose, following the Charbonneau Commission, to repress businesses that participated in a fraudulent system of call for tenders. We will try to determine if the Act to ensure mainly the recovery of amounts improperly paid as a result of fraud or fraudulent tactics in connection with public contracts, RLRQ, c. R-2.2.0.0.3 provides for rules of evidence as exceptional as some argue. Throughout these different chapters, we will see that the legislator as well as the Courts are constantly searching for a balance between individual rights and public interest, balance which is, all in all, difficult to attain.

Keyphrases: Corruption, Contrat, Corruption, Municipality, Contract, Elected official, Charbonneau Commission, Nullity
L'introduction d'un régime de responsabilité civile pour le préjudice écologique dans le corpus juridique québécois

This master’s thesis aims at proposing a new model of civil liability for the ecological prejudice in Québec law. Notion that is well implemented in several jurisdictions, the ecological prejudice has not, unfortunately, to this day, been a recognized actor on the legal stage of Québec.  The ecological prejudice contains a superior degree of abstraction than his neighbors, the moral, corporal and material prejudice. It is a prejudice whose victim is not a physical person, but the environment. In light of this degree of complexity, the first part of this thesis will be dedicated to the theoretical understanding of the ecological prejudice prior to the presentation of the system used in French law to deploy the ecological prejudice.  The concept of ecological prejudice acquired, an incursion in the jurisprudence and legislation of Québec will be possible in order to determine precisely where is the ecological prejudice situated. Analyzing the jurisprudence and the legislation will permit to arrive, in the second part of this thesis, to the finding that the ecological prejudice is still wildly unknown in Québec. Considering the climate challenges that the contemporary society is confronted nowadays, an introduction of a regime of civil liability for the ecological prejudice would be more than relevant tool in the battle against climate change.  This thesis will end on a proposition of a legal model of a civil liability regime for the ecological prejudice. Its unique features make it mandatory to rethink the common regime of civil liability since it is unfit to the nature of a prejudice that doesn’t have any link attaching it to human. A new perspective of civil liability has to be discovered in order to integrate the ecological prejudice in Québec law.

Keyphrases: Ecological prejudice, Environmental prejudice, Ecological damage, Civil liability, Environment, Ecosystem anthropocentrism
Droit international privé et vols d’œuvres d'art, étude critique des propositions du professeur Symeonides dans la résolution des conflits mobiles relatifs aux biens culturels

Cultural objects are a big part of today's global market. But trades are not always made over good title. It can lead to a conflict of laws if a possessor and an owner claim ownership over the same piece of art. conflicts of laws regarding chattels (personal property) are usually solved by applying the law of the situs of the object, which refers to the location of the object when the conflict arised, or the location of the object when the contested transfer occured etc... This master thesis is based on the work of Pr. Symeonides who believes that cultural artefacts should be treated differently than other chattels. According to him, the law applicable to international conflicts involving cultural property should be the law of the situs of origin. This thesis compares these two rules and offers a compromise which may facilitate the application of a rule specific to the resolution of international conflicts involving cultural property.

Keyphrases: restitution, Private international law, cultural objects, comparative law, conflicts of laws, artworks
Agroécologie : pour une réconciliation de l'agriculture et du droit de l'environnement

Now that we are one-step away from the precipice and that climate change is at our doors, it is time to re-think our production methods. Indeed, agriculture is not only among the most affected sectors by climatic change, but also its activities rank it among the highest producers of greenhouse gases.  The time has come to put in place “post-productivist” methods.  A note, however, is necessary: agriculture is at the heart of life. Its importance throughout the world, and in Quebec, is undeniable. In addition to its nurturing function, it embodies an important economic pillar and a livelihood for those who chose to dedicate their life to it. Moreover, from production to transformation, agriculture represents an important sector of employment and is rooted in the identity of communities.  However, because of the pressures and anguishes that stem from the environmental footprint of its dominant model, agriculture is now at a crossroads: industrial production systems are not viable. Land deterioration, loss of biodiversity, water contamination, pesticides residue, reliance on genetically modified organisms, and its contribution to climate change are among the criticisms.  Thus, this thesis aims to initiate a discussion about the integration into law of a transdisciplinary alternative that is gaining more and more ground: agroecology.  To this end, the body of law applicable to agriculture will be presented through the lens of Quebec environmental law, following which, a diagnostic will be offered, in light of critical approaches in law, regarding the sufficiency of the existing framework. To overcome the intrinsic limitations of the existing legal system in areas of strong agricultural dominance, but also the weaknesses of the current agricultural paradigm in Quebec, the integration of agroecology will be suggested. But, what is agroecology concretely? The concept will be defined in both its scientific and legal perspective, and finally, to contribute to the discussion and inspire potential changes, the integration of agroecology among other legal jurisdictions will be addressed.

Keyphrases: agriculture, pesticides, agroecology, environmental law, climate change
Les insuffisances des grands outils juridiques protégeant le droit à l'égalité en emploi : l'exemple de la déqualification des immigrantes et migrantes au Québec

The deskilling problem of immigrant and migrant women is observed both nationally and internationally in industrial relations studies and reports from international organizations. It  is  a  situation  of  systemic  and  intersectional  discrimination,  influenced by  the international  sexual  division  of  labor.  However,  numerous  international  conventions guarantee equal protection in employment for immigrant and migrant women. In Canada, the Canadian Charter and the Quebec Charter of Rights and Freedom protect the right to equality. In light of these findings, the main legal tools protecting employment equality will  be  studied  in  order  to  determine  what  obstacles  prevent  them  from  responding adequately to the situation of deskilling of immigrant and migrant women. In  international  law,  general  conventions  protecting  the  right  to  equality  and  specific conventions protecting rights for migrant workers will be analyzed. Some obstacles will be identified, such as the lack of denunciation of the international gender division of labor in international  law  and  the  preponderance  of  political  factors  in  immigrations  issues.  A solution will be proposed to find a way to better protect immigrant and migrant women in employment, precisely by the development of soft law mechanisms.At the national level, the guarantees of the right to equality of the Canadian and Quebec charters will be studied in order to identify the obstacles of the right to equality, namely the lack of real application of the theory of intersectionality in anti-discrimination law and the challenges for the courts to develop systemic remedies. The role of judicial branch in the search for solutions is limited because of the systemic nature of the situation of deskilling of immigrant and migrant women in Quebec. However, the judiciary can be a tool to promote recognition of the existence of this discriminatory situation  and  mobilize  the  political  world  to  develop  concrete  solutions,  particularly through the application of proactive regulations.

Keyphrases: Immigration et migration, Industrial Relations, International  Law, International  Conventions, Equal  Protection, Canadian and Quebec Charter of Rights and Freedom, Immigration and migration, Systemic Discrimination, Women, International Sexual Division of Labor
Responsabilité civile en cas de diffamation sur Internet : étude comparative entre les systèmes québécois et français

The rise of information technology in recent decades has been such that it has been called a « digital revolution ». To keep only the information aspect, the internet has given freedom of expression another dimension, allowing those who have no voice to express themselves freely on accessible platforms to all, around the world. However, this outbidding in terms of free expression on the Internet proves to be a double-edged sword, as some decisions have noted, calling this tool « a formidable means of communication ». This observation refers in particular to the defamation or damage to the reputation of natural or legal persons, giving rise to very damaging consequences, cyberspace being the ultimate place for defamation of the world scale, considering the ubiquity what the Internet implies. And this, without being able to control often this phenomenon with traditional methods of regulation. Our study is to understand this phenomenon with regard to the civil liability, in a review of the legal rules applicable in the matter, and more precisely to know if these rules are appropriate or effective. We have opted for a comparative study between the Quebec and French legal systems, both of which have a civil law tradition, one of which is influenced by the Common Law and the other by European law. Although in both systems, defamation is generator of civil liability, it is interesting to know how they take into account this issue, knowing that the offense of defamation obeys two different regimes, depending on whether one is in one or the other system. If under Quebec law, defamation falls under the general civil liability regime, it is considered in French law as a criminal offense, provided for by a special law whose complexity raises many questions. This comparative study contains many lessons that can benefit both systems. In addition, by treating in two different chapters the responsibility of the authors of damaging information and that of the technical intermediaries, our study will lead us to embrace, beyond the Quebec and French systems, the Canadian, American and European law, taking into account the interaction that exists on the subject, at the level of applicable texts and case law.

Keyphrases: Cyberdiffamation, Defamation, Cyberdefamation, Damage to reputation, Freedom of expression, Civil liability, Quebec civil law, French law, Technical intermediaries, Damages and interests
Le cadre juridique applicable à une infrastructure sous forme de service (IaaS) dans le milieu universitaire

Cloud Computing is a very broad concept that covers a multitude of online services that we all use, without necessarily being aware of it. It is subdivided into different service delivery models, one of which is the infrastructure as a service which is defined as a ready-to-use infrastructure, leased on demand from a service provider, accessible through the Internet or by the network of an organization, or both. This constantly evolving technology is coveted in all areas, especially by the academic community. Of course, the use of such technology raises many legal issues regarding information security and the obligation to ensure confidentiality, integrity, and availability of data found on these systems. The objective of this master’s thesis is therefore to define the legislative framework applicable to the infrastructure as a service model in order to better prepare institutions wishing to migration to this environment.

Keyphrases: IaaS, Cloud computing, Infrastructure as a service, Infrastructure, Security obligation, Confidentiality, Integrity, Availability, Informational security, Information technology
L’affaire Canada : certaines mesures affectant le secteur de la production d’énergie renouvelable à l’OMC : une occasion manquée de mettre en œuvre l’article XX du GATT de 1994?

Based onthe WTO’scaseCanada –Certain measures affecting the renewable energy generation sector, this research addressesthe applicability of article XX of the GATT 1994 to incentive measures for the production of renewable energy. In fact, the implementation of the FIT  program  and  incentives  for  renewable  energy  generation  in  Ontario  (Canada)  has  been objectedby the Dispute Settlement Body due to inconsistency of these support mechanisms with WTO  law. Furthermore,  it  should  be  noted  that  support  measures  for  renewable  energies constitute  ambitious  means  envisaged  by  some  WTO  members  to  achieve  the  objectives  of environmental protection and sustainable development.In this context, this research attempts to demonstrate  the  possibility  of  reconciling  the  granting  of  these  support  measures  with  WTO law.Based  on  the  provisions  of  Article  XX  (b)  and  (g)  of  the  GATT1994  relating  to  the protection  of  the  environment,  we  seek  to  determine  the  extent  to  which  this  case  could contribute to the implementation of the exception environmental law in WTO law.At the end of  this  analysis,  this  research  underlines  the  importance  of  taking  intoconsiderations  the measures to encourage the development of renewable energies in the jurisprudence of the WTO.

Keyphrases: GATT, commerce international, WTO, international trade, WTO law, FIT program, renewable energies, subsidies, sustainable development, environmental protection, free trade, domestic content requirements, national treatment, environmental exception