NCube/papyrus huggingface dataset:
Rôle du TGF-β dans la modulation du microenvironnement tumoral leucémique

The cells and signal molecules (cytokines and chemokines) making up the tumoral microenvironnement are known to play an essential role in tumor progression. It seems to be  necessary to study the relationship between infiltrating cells, tumor cells and signal molecules. TGF-β is a potent immunosuppressive and growth suppressive cytokine whose role in the formation of the leukemia microenvironnement remains unclear. In this study, we investigated the injectable T lymphocyte leukemia EL4 model (tumor cells producing TGF-β) of C57BL/6 strain. We characterised the myeloid and lymphoid infiltration in EL4 tumors using flow cytometry and fluorescence microscopy. Our analysis of EL4 tumor infiltrating cells showed a high concentration of T lymphocytes and myeloid cells CD11b+. We have undertaken our study to better characterize these cells. We showed that these cells are present at the periphery of the tumor and are surrounding blood vessels in the tumor. These cells have phenotypes leading us to believe that they belong to the family of so-called myeloid suppressor cells. They have high levels of transcripts of VEGF and MMP9 in the tumor and the systemic level, but do not seem to have a strong inhibitory capacity in vitro. To determine whether the tumor production of TGF-β affects the recruitment of these cells, we transformed EL4 cells using a shRNA to reduce the production of TGF-β (TGF-β shRNA ) and compared the myeloid and lymphoid infiltration of tumors formed with EL4 cell controls ( shRNA-Luc ) . A 50% decrease in transcript levels of TGF-β does not affect tumor growth but appears to decrease infiltration by myeloid cells. This study allowed us to better understand the pattern of EL4 leukemia and the role of myeloid leukemia cell populations in the tumor microenvironment. The decrease of TGF-β produced by tumor cells reduces the infiltration of these myeloid populations within the EL4 tumor. The precise role of these cells still needs to be determined. These results are in agreement with the fact that anti-TGF-β therapy is not sufficient to counteract tumor progression, but may affect the post-chemotherapy and immunotherapy results by altering the composition of the microenvironment.

Keyphrases: Cancer, TGF-beta, Immunosuppression, MDSCs, Leukemia, Tumor microenvironment
Mécanismes de résistance aux inhibiteurs de CCR5

The work described in this manuscript aimed to characterize the resistance pathways to CCR5 inhibitors. We first developed a phenotypic assay to identify viral tropism and to measure the resistance to CCR5 inhibitors. This assay detects R5 tropic viruses or X4 when they represent as little as 0.4% in a mixture of viral populations, demonstrating its robustness and sensitivity. Based on its clonal approach, this assay can differentiate the truly dual-tropic viruses from mixed viral populations. We then studied the impact of mutations in the variable regions of gp120 envelope protein of HIV-1 virus on resistance to CCR5 inhibitors. To do this, resistant viruses were generated by passage of CC1/85 and BAL isolates in the presence of sub-inhibitory concentrations of maraviroc (MVC) and vicriviroc (VCV). Following some passages of the CC1/85 virus in the presence of MVC, some mutations were identified in differents regions of the gp120. We further selected three mutations in the variable domains of gp120, V169M in V2, L317W in V3 and I408T in V4 to construct viruses containing single, double and triple mutations to assess the contribution of individual or combined mutations in the resistance phenotype to MVC and VCV. We determined the sensitivity of each mutant to MVC and VCV, the tropism and the percentage of infectivity compared to wild type. Our results showed that the sequences that carry mutations in the V4 domain I408T, had the most impact on susceptibility to MVC. Finally, we aimed to evaluate the antiviral activity of a new CCR5 inhibitor, VCH-286 and its interaction with representative drugs from different classes of antiretroviral (ARVs) such as reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors and fusion inhibitors used in clinic to treat HIV/AIDS and other CCR5 inhibitors such as MVC and VVC to assess whether these drugs could be used together within the same treatment regimen. To answer this question, we first evaluated the antiviral activity of the three CCR5 inhibitors: VCH-286, MVC, and VVC. We then evaluated the interactions of VCH -286 with MVC VVC. We finally evaluated the interactions of VCH -286 with other ARV drugs These studies showed that VCH-286 is a potent inhibitor of R5 viruses with antiviral activity at the nanomolar range and favorable drug interactions with the majority of ARVs such as reverse transcriptase, protease, integrase and fusion inhibitors employed clinically to treat HIV/AIDS. The combinations of CCR5 inhibitors have interactions ranging from synergy to antagonism. Our results show that the plasticity of the viral envelope of HIV-1 affects resistance to CCR5 inhibitors, its tropism and the potential combination of these drugs.

Keyphrases: HIV, resistance, HIV inhibitors, coreceptor CCR5
Déclencher le changement institutionnel : une analyse de l’élaboration et de la mise en œuvre initiale des lignes directrices en allaitement maternel au Québec

Breastfeeding is the optimal way of feeding infants and young children. Nevertheless, breastfeeding rates in Quebec are among the lowest in Canada. Within this context, the government of Quebec included breastfeeding among its public health priorities, and in 2001 published the policy L’allaitement maternel au Québec : Lignes directrices (Breastfeeding in Quebec: Guidelines; LD). Using a qualitative single case study design, this study aimed to understand the processes of emergence, development and implementation of the LD. Institutional theory was adopted as the theoretical framework. Data were collected through individual interviews and a focus group with professionals involved in the process under examination, as well as documentary analysis. Deductive-inductive thematic analysis was performed on transcribed verbatim. The LD emerged from a professional movement which worked in close collaboration with the Ministry of Health and Social Services in the initial phases of policy development and implementation. Over time, however, the decision making was centralized, consultation mechanisms became obsolete, and the relationships between different institutional actors became less cooperative. The discomfort and dissatisfaction with the Ministry’s new way of managing the Quebec breastfeeding policy triggered the emergence of a new parallel professional movement. The study concludes, however, that even in a highly institutionalized domain such as health, those committed to breastfeeding in the province could work together as they aim to reach the same goal, i.e., higher rates of breastfeeding. The initial consensual formulation of the LD proves that, in this particular institutional field, collaboration is possible.

Keyphrases: Allaitement, Breastfeeding, Health policy, Institutional change, Institutional entrepreneur, Strategies of engagement, Institutional domain
La Cathédrale de León a-t-elle des chances de remplir les conditions
d’inscription à la Liste du patrimoine mondial de l’UNESCO?

UNESCO’s World Heritage List is widely recognized and of great importance internationally. This research outlines the steps undertaken by the State of Nicaragua to register the Cathedral of León on the List and attempts to determine the chances of success of its nomination. Firstly, we study the World Heritage List, in regards to the World Heritage Convention and the States Parties. Second, looking at the Committee’s decision concerning the Nicaragua project, we highlight the lack of coordination between the principal stakeholders, namely the national, local and diocesan levels. Data collected in León allow us to observe that coordination between the stakeholders is essential for the registration project, affecting the consolidation of the dossier as well as the protection of property. We then analyze the issues and the possible solutions. To promote the participation of all stakeholders, we apply the approach of "consensus building". However, the results of the analysis show that ”conflicts in values” prevent the creation of agreements. We therefore conclude that the Cathedral of León has a low chance of being registered on the World Heritage List. The registration process is an ambitious task, all the more as the project requires the implication of a private property under the aegis of an institution: the Catholic Church. Its fulfillment is inevitably impacted by issues of power underlying the nomination project.

Keyphrases: UNESCO World Heritage List, built heritage, built heritage, management, protection, protection, concertation, facilitation, consensus building, value, developing countries, Central America
Natural air conditioning, traditions and trends : high performance of sustainable indoor ventilation in a hot and dry climate

Nowadays due to the increased use of fossil fuels and electricity, the natural environment is in danger because of high levels of pollution. Hence by creating natural air conditioning, we may save a significant amount of energy. In line with the global objective of sustainable and green architecture, the use of patios to save energy and natural ventilation coupled with wind- catchers, Trombe walls and other natural air conditioning systems (both traditional and emerging architectural elements) seems pertinent. This thesis analyzes designs to produce natural air conditioning and cooler air with the minimum amount of energy, with regard to the tradition and the trends, especially in hot and dry climate regions like Iran. In this context, looking to Islamic Architecture and the Qur’anic discipline of thought are considered as a guide to the way Muslims approach the design-decision making process. We therefore look to the traditions and the trends of natural air conditioning through the most important element of the Islamic context (the Qur’an). So, within the theme of "tradition", we have introduced some thinking about the influence of Islam and particularly the respect of nature while providing for a balance between harmony and individuality, such as proposing one special kind of decision-making process to solve the main scientific problems according to the Islamic philosophy and the accompanying methods, suggesting some recommendations. Descriptions of (a) the principles of wind-catchers and (b) antecedents in nature such as the termite hills are pursued as well. Under "trends", we have introduced the use of novel materials and novel design principles. Looking at the new materials and simultaneously at the analogy of the termite mounds suggests one good sample of design of a shelter for people in earthquake-prone regions. Bam, an Iranian city, can be considered to be a specific context in which the general considerations expressed in this thesis can be most usefully applied.

Keyphrases: Islamic architecture, Qur’anic context, Wind-catcher, Trombe walls
Le port des signes religieux dans l'espace public : une réflexion à partir du droit international et d'une comparaison entre le Canada, les États-Unis, la France et la Suisse

After establishing the methodological foundations of this study, we began our reflection by examining the issue of wearing religious symbols in the public sphere within the context of the debate between differentialist and universalist perspectives in the application of equality rights. Afterwards, we conducted an overview of conceptual frameworks related to the analysis of the subject: classical liberalism and republicanism from a universalist vision, diverse types of legal feminism, the theory of intersectionality, the communitarian approach, Kymlicka's renewed liberalism and the values related to Sandra Fredman's equality of law that are aligned within differentialist philosophy.  We subsequently identified Kymlicka's renewed liberalism and the values related to Fredman's equality of law as being the most appropriate framework for the analysis of the subject under study. Our study of international law allowed us to demonstrate that while European law tends to apply the universalist perspective in the application of rights to freedom of religion, this is not the case with United Nations law that adheres to a differentialist vision, and thus of Kymlicka's renewed liberalism and  of Fredman's equality perspective. With respect to the judicial systems of the United States, Canada, France and Switzerland, we found an intermittent application of both perspectives depending upon the domain of activity. However, Canada stood out in our analysis as having an approach more focussed on the differentialist vision as a result of its inclusive neutrality that focuses on the notions of inclusion and substantive equality for its nationals.

Keyphrases: Freedom of Religion, International law, Constitutional law, Equality rights, Religious symbols, Public sphere, Neutrality, Religious accommodation
Jalons pour un cadre de référence OHADA en droit des contrats

The law of contracts is recognized as the legal crossroad of economic activities. This explains, among other things, the interest of the European, North American and Asian supranational organizations for its harmonization. OHADA is also interested in this legal phenomenon especially with the draft Uniform Act on contract law. Based on this draft, a copy of UNIDROIT Principles, the author lays the foundation of a frame of reference for African contract law. This construction starts with the identification of the key issues of an African contract law. These issues are related to theoretical and practical, economic, legal and extra-legal issues. With these issues identified, the author seeks to make fundamental guidance to OHADA’s legislator and parties to a contract. He then uses these guidelines to propose amendments to the contemporary contractual principles in accordance with the African particularities. The African contractual frame of reference thus outlined is finally confronted with the practice of existing European and North American experiences in order to assess its relevance for a better benefit of African cross-border trade.

Keyphrases: OHADA, Unification, African Contractual Identity, Model Law, Unification, Uniformization, Harmonization, Common Law Contract, Bijuralism, Business Contracts, Theory of Obligations, Africa, African contracts
Inégalités sociales dans la diffusion d'une innovation en transport actif : le cas des vélos en libre-service à Montréal

Background. Public bicycle share programs (PBSP) are an active transportation innovation. No study has examined lack of awareness of PBSP as a factor limiting accessibility. Objective. Identify factors associated with lack of awareness of a PBSP across time in Montreal. Methods. Within the context of a larger study, a sample of 7,011 Montrealiers aged 18 years and over were recruited to participate in one of three telephone surveys occurring prior to implementation (n=2,000), after season 1 (n=2,502), and after season 2 (n=2,509). Multivariable logistic regression analyses were used to investigate associations between survey period, proximity to docking stations, and education with lack of PBSP awareness. Results. There was a greater likelihood of being PBSP-unaware among those with lower education after season 1 implementation in comparison to those with higher education (OR = 1.60, 95 %CI: 1.18, 2.19). There was also greater likelihood of being PBSP-unaware among those with lower education after season 2 implementation in neighbourhoods where the PBSP was available in comparison to those with higher education in neighbourhoods without PBSP docking stations (OR = 1.63, 95 %CI: 1.01, 2.64). Although lack of awareness decreased over time, greater likelihood of being PBSP-unaware was observed among those with lower education. Conclusion. Despite the physical presence of PBSP docking stations in neighbourhoods, socioeconomic inequalities persist.

Keyphrases: Awareness, Built Environment, Health Innovation, Public bicycle share programs, Population health
Le Japon en mal de reconnaissance internationale. Victoires militaires et paix ratées, 1895-1923

By the end of the 19th Century, Japan began a successful imperialistic policy against China, Russia, and Germany. From 1895 to 1923, the Japanese military forces achieved impressive and undeniable military victories. Unfortunately, Tokyo was unable to turn these triumphs into a political asset that could give Japan the power status the government wanted, as well as a solid and lasting peace through regional hegemony. Using military threats and diplomatic maneuvers, some European nations and the United States successfully prevented the realization of Japanese imperialistic ambitions, refused to recognize its power status and emphasizing European superiority by reinforcing racial inequality. Through an analysis of Japan`s first imperialist ambitions, this paper attempts to show how a third party, not involved in the war, can force the victor to reconsider how to profit from his war tributes. Ultimately, this study emphasizes the importance of the greater context, including the interests of the main international actors of the time, to making a peace treaty last.

Keyphrases: relations internationales
Description des profils des hauts consommateurs d’un département d’urgence et mise en à l’essai d’une intervention infirmière pour optimiser la trajectoire de soins

Introduction. Patients who frequently use the emergency department (ED) negatively impact ED efficiency. In order to optimize the care trajectory of these frequent users (FU), we have looked for patterns in their use of health care and implemented an intervention adapted to the patterns found. Methodology. The characteristics that describe the patterns of FU health care use, where FU are patients that have visited the ED of the ultra-specialized cardiology hospital seven times or more during a one year period from 2012 to 2013, were chosen based on the theoretical framework of Andersen (2008). The data available in the medical records was collected from the hospital’s electronic databases and analyzed. The intervention, which aims at better understanding the pattern of health care use and patient needs, was developed based on the theoretical framework of Wagner (1998). Suitable patients, who visited the ED at least five times in 2013-2014, were identified for the intervention during one of their visits to the ED. Conclusion. To determine patterns of health care use, we found 31 FU, amassing a total of 272 ED visits. We have observed that the FU of the one year period studied were no longer FU the following year, as only two of them (13%) visited the ED seven times or more during the year after. Those FU who visited outpatient clinics, visited the ED less often than those who did not. Furthermore, the frequency of use and the accessibility of ambulatory care show that multiple FU suffered from chronic illness or severe comorbidity. For the intervention, we have selected and met with five patients. Most of them said they were worried about the consequences that their medical problems could have. However, very few of these patients declared themselves to be ready to change their daily habits in favor of better health. In order to improve care for these patients, individual and organizational interventions were recommended.

Keyphrases: Frequent users, Emergency department, Cardiology
Développement des marqueurs moléculaires spécifiques pour l'identification et la quantification de deux espèces de champignons mycorhiziens arbusculaires en utilisant la PCR en temps réel

Arbuscular Mycorrhizal Fungi (AMF) are able to form symbiosis with approximately 80% of plant species, including most important corps. This symbiosis is known as Arbuscular Mycorrhiza which has been largely used in agriculture to promote plant growth by enhancing minerals uptake and protecting plants against biotic and abiotic stresses. Despite the ecological and economical importance of this symbiosis, specific markers for spore quantification of commercial AMF strains by quantitative real-time PCR (qPCR) are extremely limited and none has been rigorously validated for quality control of manufactured products such as biofertilizers. Most of the existing AMF markers developed either for AMF identification or for AMF quantification purposes are based on either morphological characters, on Fatty Acids Methyl Esters (FAME) profiles, on specific isozymes or antibodies, or on nuclear DNA. It has been shown that mitochondrial (mt) genomes are conserved among AMF species. This allowed us to use mt genomes in order to develop efficient isolate-specfic markers. Using the alignments of 11 complete AMF mt genomes, a qPCR assay using a hydrolysis probes designed in the single copy cox3-rnl intergenic region was tested and validated to specifically and accurately quantify the spores of the model R. irregularis isolate DAOM197198 and another probe was designed in nad1-cox2 intergene specific to Glomus cerebriforme. The specificity tests performed, using standard PCR and qPCR, clearly showed that the primers specifically amplified the isolate DAOM-197198 or Glomus cerebriforme DAOM220722. Quantification assays were successfully undertaken on unknown samples in liquid suspensions, commercial solid formulations and soil samples to show the accuracy and reproducibility of the assays. This study provides a powerful molecular toolkit specifically designed to quantify spores of the model AMF isolate Glomus cerebriforme DAOM220722. The latter could be applied to other AMF taxa and will be useful to research institutions and governmental and industrial laboratories running routine quality control of AMF-based products.

Keyphrases: Identification, PCR quantitative, Sol, Glomus cerebriforme DAOM220722, Glomus irregulare DAOM197198, Mycorrhiza, Quantitative PCR, Specific TaqMan markers, Soil
La production de thiols biogéniques par les microorganismes aquatiques

Low molecular weight (LMW) thiols can affect the bioavailability of mercury and by enhancing methylmercury production by methylating microorganisms. Results of a study conducted within periphyton extracellular matrix in the littoral zone of a lake of the Laurentians have shown that LMW thiol concentrations found in this matrix are up to 1000 fold higher than those in the water column of surrounding waters. Relationships between these thiols and periphyton chlorophyll a were significant, suggesting production by algae. Mercury in the extracellular matrix, especially in the mobile colloidal fraction, was also correlated to thiols from algal sources. These results suggest thiol accumulation in the periphyton extracellular space, and that thiols likely promote mercury transfer to methylating microorganisms. A second study on preservation methods of natural water samples for LMW thiols conservation showed that a storage temperature of -80 °C was optimal and that freeze-drying led to an under-estimation of measured concentrations. Degradation rates were faster with storage at -20 °C and varied substantially depending on the chemistry of the water used as depending on thiol species observed. In regards of these results, we propose a research framework for future studies on mercury speciation processes in periphyton. We also suggest precautions on handling and storing natural samples for LMW thiol analyses.

Keyphrases: Thiols, Glutathion, Biofilms, Soufre, Thiol, Glutathione, Mercury, Methylmercury, Periphyton, Biofilm, Degradation, Preservation, Lake, Methods