NCube/papyrus huggingface dataset:
Social identities and isotopic analyses of the burials from the archaeological site of Ucanal, Petén, Guatemala

With the advances in isotopic analyses over the last two decades, scholars working in the Maya area have come to realize that Pre-Columbian people were much more mobile than previously considered, even though many were sedentary agriculturalists with large urban centers. Isotopic analysis of strontium and oxygen of human teeth enables us to identify the presence of migrants since they reflect geochemical and climatic variability of where a person lived as a child. Twelve burials from the archaeological site of Ucanal, in the Petén region of Guatemala, were analyzed for strontium and oxygen isotopes. In addition, a strontium baseline study of faunal remains was undertaken to identify typical values for the Ucanal region. Out of the twelve burials, three individuals were identified as likely foreign-born. Interestingly, they underscore two different ways in which foreigners were implicated in their newly founded homelands. Together with analyses of the human remains and burial contexts, the isotopic results highlight potentially hostile treatment in the form of human sacrifice or potentially reverential treatments in the form of a cult of the ancestors in which foreign peoples were remembered as important founding ancestors.

Keyphrases: Maya, isotopes, migration, archaeology, burials, social identities, bioarchaeology
La experiencia de mujeres jóvenes en el espacio público en Zapopan (México) : análisis de género y perspectivas urbanísticas

Starting from the premise of the right to the city, of spatial (in)justice and the context of gender inequality, the problem of access to the city’s resources by young women has become evident. In particular, it translates into limited mobility and restrictions on youths’ ability to occupy and participate in the public space, which is essential for their socialization, well-being and development.  Faced with an unfavorable urban context to the fulfillment of their right to the city, this research questions the experience in public spaces of young women from disadvantaged environments, particularly through their mobilities. The research focuses on the experience of young women living in the peripheral and marginalized Miramar neighborhood, situated in Zapopan, a municipality in the Metropolitan Area of Guadalajara in Jalisco, Mexico.  The research was carried out from a feminist methodological framework, with a qualitative and participatory approach, including data collection methods based on action-research and popular education processes with 10 young women 15 and 19 years old. In addition, complementary information was collected through documentation and semi-directed interviews with 12 key actors in the local urban environment in order to deepen understanding of the situation of young women and the possibilities for intervention.  Two results should be highlighted. Firstly, we observed that young women live a double exclusion in the public space and consequently see their right to the city unfulfilled. The first exclusion is related to gender inequality and the violence they experience as young women. The second is associated with the adult-centric paradigm and the social perception that young women are vulnerable beings. Secondly, we show that participatory processes in urban planning are useful both for the production of knowledge and for the fulfillment of the right to the city.

Keyphrases: Right to the city, public space, mobility, young women, gender equality, action-research
Vers une musique hantologique instrumentale : réflexions sur l’écriture technomorphe dans le contexte de la musique instrumentale contemporaine

This research explores the notion of technomorphic writing in contemporary music. This process, consisting of transposing electronic models into instrumental music, appeared shortly after the creation of the Westdeutscher Rundfunk (WDR) and Groupe de Recherche Musicale (GRM) studios. This dissertation addresses the origin and evolution of this approach, its possible forms and examples of its dissemination in contemporary music. Four new pieces, created during this master's degree, further explore the idea of hauntological instrumental music, inspired by audio artifacts from the defective analog and digital recording media.

Keyphrases: Mark Fisher, Technomorphism, Electroacoustic music, Instrumental music, Aesthetics of failure
L’oxymétrie du nerf optique, un biomarqueur potentiel pour le glaucome

Glaucoma is a progressive optic neuropathy characterized by loss of the retinal nerve fibers layer. This disease causes a decrease in the visual field that can lead to blindness. The main risk factor for glaucoma is the increase of intraocular pressure. However, not all glaucoma patients have an elevated intraocular pressure and many patients continue to progress despite good intraocular pressure control with current therapies. Several authors have focused on the hemodynamic components of the eye. They obtained significant differences in these factors between normal and glaucoma patients. Ocular oximetry is technology that can non-invasively measure oxygen saturation of eye tissues. Several studies have verified the association between ocular oximetry and glaucoma. The Zilia device uses diffuse spectroscopic reflectance to measure oxygen saturation at a specific point. The objective of this study was to verify the repeatability of the oximetry measurements on the head of the optic nerve obtained with the Zilia device and to study the acquisition in order to determine the characteristics necessary to obtain it optimally. Also, we measured the oxygen saturation (SaO2) on the optic nerve of normal subjects and compared it with patients with glaucoma. Additionally, the SaO2 was correlated with different variables affected by glaucoma. This is a prospective repeated-measures and case-cohort study. Participants were recruited at the Laurentian Eye Institute (IOL). They completed a complete eye exam under pupil dilation including a blood pressure measurement with an automated device and the pulse oximetry was obtained by a pulse oximeter (SpO2). The ocular oximetry measures was acquired by the Zilia imaging system on the temporal side of the optic nerve. No statistically significant differences were observed between the average of three SaO2 measurements at the optic nerve. For the duration of the acquisition, the data analysis showed a statistically significant difference between the 5 seconds acquisition compared to the other acquisition duration. There was no statistically significant difference between the average of the first measurement obtained before and after the use of the data optimization technique. The result showed a significant difference in the SaO2 values between glaucomatous participants and normal. We also see a correlation statistically significantly between the SaO2 values and the global RNFL. This study is one of the first one done with the Zilia device. The average value of SaO2 obtained at a specific point of the optic nerve acquired by the Zilia device are repeatable and a 10-second acquisition could provide a precise value. Also, the SaO2 measured with the Zilia imaging system on the optic nerve is significantly lower in glaucoma patients compared to normal patients. More studies are needed to really establish the role of that device in the diagnostic and fully up of patients with glaucoma.

Keyphrases: Ocular oximetry, Glaucoma, Oxygen saturation, Oxyhemoglobin
L'enseignement individualisé à la formation générale des adultes

In Québec, many young adults and adults decide at some point in their lives to enroll in the adult education sector in order to obtain their high school diploma or to go further in their studies. The general objective of this research is to understand the teaching practice most used in this sector -individualized teaching and education- and to allow the people who live it on a daily basis to be able to express themselves on its dimensions. This particular pedagogy has not been the subject of attention by research in adult education. As part of this qualitative ethnographic study, twenty informants were interviewed (ten learners and ten teachers) and two questionnaires, consisting of four blocks each, were intended for them. To achieve the first specific objective of this research, namely to identify the actors (teacher-learner) of the pedagogical triangle and to describe how they live their relationship in individualized teaching, at adult education, the components of the educational triangle of Houssaye were, at first, used and this in order to know the intrinsic characteristics of the trainers and learners as well as all existing relationships between them. Then, to reach the second specific objective of this research, namely to link the "perceptions" of the actors of the pedagogical triangle, in FGA, of the individualized teaching with regard to the self-training, all the components of the theory of the self-training in Carré were included in the informant questionnaires. The results reveal that individualized teaching is a great complement to the definition of educational self-training.

Keyphrases: Individualized teaching and education, Adult education, Adults, School dropout, School drop-in, Educational triangle, Self-study, Qualitative method, Ethnography
Les effets d’une séquence d’enseignement-apprentissage de l’oral inspirée des approches de la philosophie pour enfants et des approches plurilingues sur la compétence discursive d’élèves du 3e cycle du primaire en classe d’accueil

This research presents the effects of an oral teaching-learning sequence inspired by approaches to children's philosophy and plurilingual approaches to discourse competence (the justification and reformulation) of second language learners in school. Thoses students are 3rd cycle of primary school. This is an exploratory type case study with six students cases. During the philosophical discussions, which is the oral genre set up to practice justification and reformulation, the data collected through video recordings have found that the teaching of the two discursive competence allows students to talk more in thoses discussions. The teaching-learning sequence helped the students to produce more elaborate justifications and to use reformulations to overcome communication breakdowns during the interactions. Finally, the learning of the two discursive behaviors permits to know that the interactions are more related to each other and the scaffolding is done more between the students.

Keyphrases: reformulation, justification, oral teaching, teaching-learning sequence, immigrant students in welcoming classes, discursive competence, philosophical discussion
WISP1 and EMT-associated response and resistance to immune checkpoint blockade

Immune checkpoint blockade (ICB) has revolutionized therapeutic approaches in the field of medical oncology and has largely contributed to the fact that immunotherapy is now being regarded as the fourth pillar of cancer treatment alongside surgery, radiotherapy and chemotherapy. Despite encouraging results from clinical trials using ICB, most patients ultimately relapse or succumb to their disease. Therefore, the field of immunotherapeutic resistance research is rapidly expanding. Many strategies to improve ICB responses have been undertaken, including: 1) the search for novel, actionable targets in the immune tumor microenvironment (TME) and; 2) therapeutic combination studies where an ICB backbone is combined with different, synergistic treatment modalities. Each of the studies presented in this research thesis embraces one of these strategies.  In our first study, we show that WISP1 represents a promising TME target in multiple solid tumor types by demonstrating its association with prognostic and pro-inflammatory variables, as well as to a complex epigenetic program termed Epithelial-Mesenchymal Transition (EMT). Furthermore, we show that increased WISP1 expression is associated to primary resistance to ICB, particularly when EMT-related signatures are found concomitantly. In our second study, we used in vivo mouse models of KRAS-mutant Non-Small Cell Lung Cancer (NSCLC) to test different therapeutic combinations of targeted therapies (i.e., MEK inhibitor) and ICB. We found that the addition of anti-CTLA-4 ICB to MEK inhibitor AZD6244 (selumetinib) and anti-PD-L1 ICB increases survival, and that these benefits are associated with the downregulation of EMT-related markers.  Therefore, there exists a common link between these studies, which relies on the significance of EMT as a detrimental factor within the TME and its association with ICB resistance. Moreover, we show for the first time that the benefits of ICB combination therapy can be associated to the downregulation of EMT markers in vivo. Consequently, we discuss how our results may constitute the basis for future work aiming at reducing EMT-mediated therapeutic resistance, as well as the translational relevance of our pre-clinical results through the development of a clinical trial.

Keyphrases: WISP1, anti-PD-1, anti-PD-L1, anti-CTLA-4, immunotherapy, targeted therapy, MEK inhibitor, non-small cell lung cancer (NSCLC), epithelial-mesenchymal transition (EMT)
Impacts des cannabinoïdes sur la vision: étude anatomique et fonctionnelle

The endocannabinoid (eCB) system is a great therapeutic target for the treatment of many diseases, ranging from immune system modulation to pain management. This system is implicated in developmental processes as indicated by neurofunctional afflictions following developmental exposition to cannabinoids. Since eCBs are lipophilic, they are not stored in vesicles but rather synthesized and degraded on demand by specific enzymes. Thus, the expression pattern of these enzymes could help to better understand the expression of eCBs, and their role during central nervous system maturation. The CB1 receptor is strongly distributed in the nervous system, while the CB2 receptor is traditionally associated with the immune system. The recent finding of the CB2 receptor expression and function in some neurons, especially in the retina, changes the dogma associated with cannabinoids. A study from our laboratory found that deletion of the CB2 receptor in transgenic mice (cnr2-/-) enhances the a-wave amplitude in electroretinography, this wave reflecting photoreceptor activity. This report highlighted the importance of the CB2 receptor in vision, at least in the retina. Until now, no study aimed at the impact of cannabinoids on visual acuity. We characterized the retinal distribution of diacylglycerol lipase alpha (DAGLα) and monoacylglycerol lipase (MAGL) enzymes, responsible for the synthesis and degradation of the eCB ligand 2-arachidonoyl glycerol (2-AG) during postnatal development. The enzyme DAGLα is expressed since birth and is greatly distributed across the retina such as in photoreceptors, horizontal, amacrine and ganglion cells. The enzyme MAGL is expressed later during development and is present only in amacrine and Müller cells. Our functional results show that the visual acuity of cnr2-/- mice is enhanced in adults and during postnatal development. The repeated administration of a CB2 receptor antagonist yielded a better visual acuity, and inversely a CB2 receptor agonist decreased the visual acuity. Furthermore, the administration of a MAGL inhibitor, the enzyme in charge of 2-AG degradation, induced a strong decrease in visual acuity, similar to that obtained with a CB2 receptor agonist. Inversely, a DAGL inhibitor, the enzyme responsible for 2-AG synthesis, caused an increase in visual acuity. These results suggest that 2-AG is strongly expressed early during retinal development and could be implicated in structural and functional maturation of the retina. Furthermore, we demonstrated that cannabinoids do not only affect retinal function, but also visual acuity. These results confirm that cannabinoids modulate their visual effects exclusively via the CB2 receptor. Finally, in recent years, many countries legalized cannabis for recreational and therapeutic use. The findings from this thesis increase the understanding of cannabinoids since they highlight the great impact of cannabinoids on the visual acuity.

Keyphrases: DAGL, MAGL, Cannabinoid receptors, Confocal microscopy, Electroretinography, Immunohistochemistry, Optomotor reflex, Retina, Visual acuity
Développement de modèles précliniques humanisés autologues en immuno-oncologie

Identification of the human’s immune system implication in cancer has guided the biotech industry towards the development of numerous and promising cancer immunotherapies. However, in the era of immuno-oncology, a distinct lack preclinical models can simulate the interactions between a patient’s tumor and immune cells.  To tackle this issue, we developed humanized mouse models combining immune reconstitution of immunodeficient mice and injection of tumor cells lines from the same human donor. The use of induced pluripotent stem cells (iPSC) allowed the generation of multiple tumorigenic cell lines from a single donor, facilitating access to autologous immune cells necessary for mouse immune humanization. The transformation of primary or iPSC-derived cell lines was done using lentiviral transduction of proto-oncogenes telomerase (hTERT), oncogenic Ras (HRASV12) and simian virus 40 early region (SV40ER) encoding large and small T antigens (LgT and SmT).  This approach allowed to generate high grade, aggressive and undifferentiated tumors from primary fibroblasts and iPSC-derived hepatic cells, neural stem cells and astrocytes. In all cases, such tumors were efficiently recognized, infiltrated and often rejected by the implanted autologous immune system. However, partial rejection of most tumors allows for preclinical evaluation of targeted immunotherapies relying on the hosts’ pre-existing immune response. For instance, we could study the impact of PD-1 checkpoint blockade inhibition on tumor growth in fibroblastic tumors where a significant increase in tumor infiltration was observed, but without an associated decrease in tumor burden. We could also produce autologous chimeric antigen receptor (CAR)-expressing T lymphocytes against GD2 ganglioside, a previously described tumor antigen detected on our neural stem cell-derived tumor cells. Cytotoxic efficiency of these autologous CAR T cells could thus be validated in vitro. Finally, we used our fibroblast-derived tumor models in autologous and allogeneic settings to determine if mesenchymal stem cells’ (MSC) immunomodulatory potential could impact tumor growth. Our results showed that MSC had no effect neither on tumor emergence and growth nor on immune infiltration, suggesting therapeutic use of these cells should be safe regarding such tumors already harboring a strongly immunodeficient microenvironment. Overall, the novel models described in this thesis aim at improving the predictive capacity of mouse pre-clinical models in immuno-oncology by recapitulating some immune interactions between a patient and its tumor. The great flexibility of this approach will allow for easy adaptation to many research problematics both preclinical and fundamental.

Keyphrases: Immunologie tumorale, Cancer, iPSC, Transformation tumorale, Tumor immunology, Immuno-oncology, Humanized mice, Cancer immunotherapy, Mesenchymal stromal cells, Tumorigenic transformation
Rôle des lymphocytes TH17 dans la fragilisation de la barrière hémo-encéphalique et la formation des lésions de sclérose en plaques

The blood-brain barrier (BBB) plays a crucial role in protecting the central nervous system (CNS) by restricting entry of cells and molecules into the brain. In the CNS disorder multiple sclerosis (MS), breakdown of the BBB allows activated leukocytes to infiltrate the brain parenchyma, leading to the formation of the characteristic demyelinated lesions. For decades, MS was viewed as a TH1-mediated disease, a notion that was largely supported by studies in its animal model and by the abundance of prototypical TH1-associated cytokines within active MS lesions. However, over the years, accumulating evidence has highlighted the involvement of another subset of CD4⁺ T cells that express IL-17, therefore named TH17 lymphocytes, in the pathology of the disease. The goal of the work presented herein was to characterize the human TH17 lymphocyte population and define their contribution to the disruption of the BBB and leukocyte infiltration into the CNS, both important early events in the formation of MS lesions. To do so, we developed and optimized a method to successfully generate human TH17 lines in vitro from peripheral blood mononuclear cells of healthy donors. We demonstrate that in response to IL-23, human memory CD4⁺CD45RO⁺ but not naïve CD4⁺CD45RA⁺ T lymphocytes produce IL-17, IL-22, and granzyme B, with a subset of cells simultaneously expressing IL-17 and IFN-γ. Interestingly, we measure a significant increase in the percentage of T CD4⁺ IL17⁺, of IL-22⁺, and of IL-17⁺IFN-γ⁺ dual producers in TH17 cell lines expanded from the peripheral blood of acutely relapsing MS women as compared to those generated from healthy controls and remitting MS patients. We show that both IL-17 and IL-22 receptors are upregulated on BBB endothelial cells in situ during inflammation and that IL-17 enhances BBB permeability by disrupting the integrity of tight junction proteins occludin and ZO-1. Finally, we provide evidence that TH17 lymphocytes transmigrate efficiently across human brain endothelial cells via the adhesion molecule ICAM-1 and show that IL-17⁺IFN-γ⁺ double producers have an increased propensity to do so. Accordingly, we detect lymphocytes that display immunoreactivity against both the TH1- and TH17-associated transcription factors T-bet and RORC within perivascular infiltrates of active MS lesions. The work presented in this thesis has refined our understanding of the mechanisms that drive TH17 lymphocyte recruitment into the CNS and shed light on the deleterious effect of TH17-secreted cytokines, specifically in the activation and breakdown of the BBB.

Keyphrases: Interleukine-17 (IL-17), Interleukine-22 (IL-22),, Blood-brain barrier (BBB), Interferon gamma (IFN-γ), Interleukin 17 (IL-17), Interleukin 22 (IL-22), Leukocyte transmigration, Multiple sclerosis (MS), TH17 lymphocytes