NCube/papyrus huggingface dataset:
La greffe de thymus humain lors de l'humanisation des souris NOD/SCID/IL2Rγcnull: optimisation du modèle pour l’étude de la fonction des lymphocytes T humains in vivo

Immunodeficient mice engrafted with human immune system provide an exciting in vivo model for a better understanding of its functioning and for development of new therapies.  Today, one of the most robust humanized mouse model is achieved by injecting human hematopoietic stem cells (HSC) from fetal liver along with an implantation of autologous fetal thymic tissue. This model, called BLT, was shown to be able to support an optimal T cell reconstitution, maturation and selection. BLT mice are extensively used for many studies such as understanding HIV biology or in regenerative medicine. Indeed, our work used BLT mice on one hand to study the role of plasmacytoid dendritic cells (pDC) during the HIV infection and on the other hand to better understand the formation of teratomes from iPSCs in vivo. However, one of the biggest limitations of this technique is the procurement of the fetal tissue. Here we describe a new protocol to do humanized mice engrafted with human thymus pieces by using more accessible materials: human thymus obtained during cardiac surgery and cord blood HSC. Indeed, thymus is spontaneously removed during cardiac surgery in neonates and young children, thus it is an easy and ethical way to obtain this tissue. Those thymuses pieces were implanted in the quadriceps of a immunodeficient mice, after being put in culture. CCST mice (Cord blood and Cardiac Surgery Thymus) exhibited a significant engraftment of T-cells, compared to humanized mice without thymus. T-cells from both CCST and BLT mice showed a similar function as evaluated by proliferation assays upon PHA stimulation ex vivo and rejection of allogeneic leukemic cells lines in vivo. CCST mice were susceptible to HIV-1 infection via mucosal or intraperitoneal route, as shown by detectable viral load, HIV DNA and p24+ cells, at similar levels to those of BLT mice. Importantly, CCST mice displayed more effective ex vivo HIV-1-specific T-cell responses compared to BLT. Upon antiretroviral treatment, CCST mice, like BLT, were able to diminish the viral load. Our data suggest that CCST mice represent an alternative to the regular BLT mouse model. Those easy-to-access thymuses can be used to generate a large number of mice compared to fetal thymuses.

Keyphrases: thymus, BLT, tissue fœtal, humanized mice, hematopoietic stem cell, immunodeficient mouse, fetal tissue, immune reconstitution, HIV, antiretroviral therapy
Systèmes d’intelligence artificielle et santé : les enjeux d’une innovation responsable.

The use of artificial intelligence (AI) systems in health is part of the advent of a new "high definition" medicine that is predictive, preventive and personalized, benefiting from the unprecedented amount of data that is today available. At the heart of digital health innovation, the development of AI systems promises to lead to an interconnected and self-learning healthcare system. AI systems could thus help to redefine the classification of diseases, generate new medical knowledge, or predict the health trajectories of individuals for prevention purposes. Today, various applications in healthcare are being considered, ranging from assistance to medical decision-making through expert systems to precision medicine (e.g. pharmacological targeting), as well as individualized prevention through health trajectories developed on the basis of biological markers.  However, urgent ethical concerns emerge with the increasing use of algorithms to analyze a growing number of data related to health (often personal and sensitive) as well as the reduction of human intervention in many automated processes. From the limitations of big data analysis, the need for data sharing and the algorithmic decision ‘opacity’ stems various ethical concerns relating to the protection of privacy and intimacy, free and informed consent, social justice, dehumanization of care and patients, and/or security. To address these challenges, many initiatives have focused on defining and applying principles for an ethical governance of AI. However, the operationalization of these principles faces various difficulties inherent to applied ethics, which originate either from the scope (universal or plural) of these principles or the way these principles are put into practice (inductive or deductive methods).  These issues can be addressed with context-specific or bottom-up approaches of applied ethics. However, people who embrace these approaches still face several challenges. From an analysis of citizens' fears and expectations emerging from the discussions that took place during the coconstruction of the Montreal Declaration for a Responsible Development of AI, it is possible to get a sense of what these difficulties look like. From this analysis, three main challenges emerge: the incapacitation of health professionals and patients, the many hands problem, and artificial agency. These challenges call for AI systems that empower people and that allow to maintain human agency, in order to foster the development of (pragmatic) shared responsibility among the various stakeholders involved in the development of healthcare AI systems. Meeting these challenges is essential in order to adapt existing governance mechanisms and enable the development of a responsible digital innovation in healthcare and research that allows human beings to remain at the center of its development.

Keyphrases: artificial intelligence, big data, responsible innovation, digital innovation, ethics, bioethics, digital health, agency, algorithmic governance
Rôle de HCaRG/COMMD5 dans le carcinome à cellules rénales : 
une histoire de transition.

In the 2000s, Dr. Johanne Tremblay and her team identified a gene that was negatively regulated by extracellular calcium in hypertensive rat parathyroid glands. Originally named Hypertension-related calcium regulated gene (HCaRG) and renamed COMM Domaincontaining 5 (COMMD5), this gene encoding a small protein of 24.67 kDa is part of a family of 10 proteins sharing a homologous structure in the carboxy-terminal position named COMM domain. Many roles have been associated and expressional analysis of different types of cancer shows a modulation suggesting that they have an oncogenic or tumor suppressor roles. Studies have shown that COMMD5 induces maturation of the cell junctions, decreased cell proliferation and promotes migration. The overexpression of COMMD5 in the renal proximal tubules accelerates repair by promoting cell proliferation and ultimately induces cell migration and redifferentiation after acute injury. Based on these observations, we focused on the development of renal cell carcinoma, a disease affecting 300,000 people each year worldwide. Our hypothesis is that COMMD5 plays a tumor suppressor role in kidney cancer by controlling cell proliferation and differentiation. To test our hypothesis, we investigated the role of COMMD5 in maintaining the epithelial integrity of cells through the regulation of epithelial to mesenchymal transition (EMT) and the control of epidermal growth factor receptors (EGFR). The results showed that COMMD5 is decreased in kidney carcinomas resulting of a great negative indicator of the survival prognostic. The presence of hypoxia-inducible factor 1a (HIF1α), expressed in the majority of solid tumors, leads to a decrease of COMMD5 in the proximal tubule cells (HK-2). Inhibition of COMMD5 promotes dedifferentiation and tumorigenicity of cells mediated by epithelial to mesenchymal transition. The loss of COMMD5 induces a reorganization of the actin cytoskeleton resulting in endosomal dysregulation of the EGFR receptor and promoting its activation. In renal cell carcinoma, COMMD5 overexpression decreases cell proliferation and induces their redifferentiation by two mechanisms: firstly, COMMD5 induces an inhibition of the HIF1α protein expression resulting in a mesenchymal to epithelial transition and sequesters the SNAIL transcription factor in the cytoplasm; secondly, COMMD5 negatively regulates the transcriptional expression of the ErbB receptors. Taken together, these results of this thesis show that COMMD5 is a gene showing tumor suppressor characteristics by controlling cellular differentiation and by regulating the expression of ErbB receptors.

Keyphrases: COMMD5, ErBb, traffic endosomal, Renal cell carcinoma, Epithelial to mesenchymal transition, EGFR, Endosomal trafficking
Les difficultés de financement en droit international de l’environnement : quelles perspectives pour les instruments juridiques relatifs aux produits chimiques et déchets dangereux ?

The international scene is marked by different types of interstate relationships. However, upon close consideration, this collaboration takes on a non-linear appearance from a financial point of view. In fact, funding has become the common denominator that shapes interstate relationships. International environmental law, as well as the chemical industry - particularly the hazardous waste sector - do not escape this paradigm. The exploitation of natural resources and trade constitute the foundation of this vital area of international exchanges. Since the second and third industrial revolutions, man has learned to extract and transform minerals and synthesize new molecules in order to manufacture of all sorts of products.   The overexploitation of natural resources has by the same token led to undesirable environmental impacts in the form of transboundary contamination and severe damage to human health. This state of affairs has gradually led to the adoption of international legal instruments with a view to limiting or eradicating the aforementioned effects. It was within this context that the Basel, Rotterdam, Stockholm and, most recently, the Minamata Convention on Mercury were adopted. These four legal instruments form the legal structure in the chemicals and hazardous waste sector. However, the effectiveness of this arsenal involves the implementation of these conventions. But this is not as easy in practice. The main stumbling block is often the question of financing the additional costs that their implementation entails in developing countries. Who should pay? The answer to this question lies in the explanation and interpretation of the principle of common but differentiated responsibilities and the analysis of the effectiveness of the financing mechanisms set up under each convention.  In the face of these funding concerns, the question that can be asked is whether the legal regime is not the source of the problem. Moreover, what is the impact of the restructuring attempts initiated in recent years? What improvements can be proposed? It is to this set of concerns that this thesis provides answers.

Keyphrases: Convention de Stockholm, Convention de Rotterdam, Synergies, Chemicals, Hazardous waste, Basel Convention, Stockholm Convention, Rotterdam Convention, Minamata Convention on mercury, Environmental funding, Principle of common but differentiated responsibilities, Synergies
The art of living together : on political engagement and the ethics of companionship

This dissertation proposes that popular movements or uprisings can unite ethics and politics in a direct, practical manner and constitute an illuminating domain from which to advance normative theory that responds to the challenges of injustice in our world today. Any study of these movements ought to engage with a specific event and its context and renounce the position of ‘observer.’ Accordingly, I have chosen to examine the revolutions sparked in the Arab world over the past decade, particularly focusing on the account of Tahrir Square. In order to appreciate the novelty these revolutions offer, it is necessary to first dismantle the deeply entrenched epistemic grounds of Western political theory which consider revolutions only on the basis of their end results, particularly whether or not they effect regime change. These popular movements not only defy democratization studies and its prescription for change from above, they also fundamentally challenge the domain of politics and some of its basic tenets. This confrontation occurs the moment the people gain their agency and use their political power demonstrably and concretely. The domain of politics is further challenged when the people create, as they did in Tahrir Square, a public sphere that is receptive to individual desires and interests as well as collective solidarity and responsibility.  The conditions under which these movements organize their collective political action – horizontally, non-hierarchically, and unmediated by representative and leaders – resist the threat of their power being instrumentalized to obtain middling results pertaining to state power. This form of organization also reconfigures the crowd’s ethical interactions, unmistakeably on display in Tahrir Square, producing what I call “ethics of companionship.” These ethics can be reformulated and practiced in manner attuned to both self and other, and adapted to the specific needs and injustices of the world around us. An ethics of companionship is responsive and open for negotiation and persuasion, and above all, it makes an art out of our living together.

Keyphrases: Civic ethics, Democratization studies, Solidarity, Political engagement, Political power, Arab spring, Companionship
Analysis of 3D human gait reconstructed with a depth camera and mirrors

The problem of assessing human gaits has received a great attention in the literature since gait analysis is one of key components in healthcare. Marker-based and multi-camera systems are widely employed to deal with this problem. However, such systems usually require specific equipments with high price and/or high computational cost. In order to reduce the cost of devices, we focus on a system of gait analysis which employs only one depth sensor. The principle of our work is similar to multi-camera systems, but the collection of cameras is replaced by one depth sensor and mirrors. Each mirror in our setup plays the role of a camera which captures the scene at a different viewpoint. Since we use only one camera, the step of synchronization can thus be avoided and the cost of devices is also reduced.  Our studies can be separated into two categories: 3D reconstruction and gait analysis. The result of the former category is used as the input of the latter one. Our system for 3D reconstruction is built with a depth camera and two mirrors. Two types of depth sensor, which are distinguished based on the scheme of depth estimation, have been employed in our works. With the structured light (SL) technique integrated into the Kinect 1, we perform the 3D reconstruction based on geometrical optics. In order to increase the level of details of the 3D reconstructed model, the Kinect 2 with time-of-flight (ToF) depth measurement is used for image acquisition instead of the previous generation. However, due to multiple reflections on the mirrors, depth distortion occurs in our setup. We thus propose a simple approach for reducing such distortion before applying geometrical optics to reconstruct a point cloud of the 3D object.  For the task of gait analysis, we propose various alternative approaches focusing on the problem of gait normality/symmetry measurement. They are expected to be useful for clinical treatments such as monitoring patient's recovery after surgery. These methods consist of model-free and model-based approaches that have different cons and pros. In this dissertation, we present 3 methods that directly process point clouds reconstructed from the previous work. The first one uses cross-correlation of left and right half-bodies to assess gait symmetry while the other ones employ deep auto-encoders to measure gait normality.

Keyphrases: Geometrical Optics, Depth Distortion, Space Carving, Point Cloud, Mirror, Kinect, Gait Normality, Gait Symmetry, Adversarial, Auto-Encoder, Cylindrical Histogram, Cross-Correlation, Adverse
Accurate and efficient strategies for the appearance filtering of complex materials

Realistic computer generated images and simulations require physically-based models to properly capture and reproduce light-material interactions. The underlying mathematical formulations are complex and mandate the use of efficient numerical methods, since analytic solutions are not available. Monte Carlo integration is one such commonly used numerical method, although, alternative approaches leveraging, e.g., basis expansions, may be suitable to solve these challenging problems. In this thesis by articles, we present two works where we efficiently devise numerical integration strategies for the rendering of complex materials. First, we propose a method to compute a spatial-angular multi-dimensional integration problem present when rendering materials with high-frequency normal variation under large, angularly varying illumination. By computing and manipulating a novel spherical histogram data representation, we are able to use spherical harmonics to efficiently solve the integral, outperforming the state-of-the-art by a factor of roughly 30×. Our second work describes a high-performance Monte Carlo integration strategy for rendering layered materials. By identifying the best path sampling strategies in the micro-scale light transport context, we are able to tailor an unbiased and efficient path construction method to evaluate high throughput, low variance paths through an arbitrary number of layers.

Keyphrases: BSDF, Monte Carlo, Rendering, normal maps, glints, summed-area tables, spherical harmonics, layered materials, Monte Carlo integration
L'exposition revisitée par le sonore : l'émergence de nouveaux régimes d'écoute au musée d'art

Sound art and music have appeared in art museum programming with increasing regularity since the turn of the 21st Century and have caused major shifts in the exhibitory practices. However, no exhibition model has so far been able to properly account for the multifarious issues raised by sound in the museum space. There has been a failure to adequately address both the technological and audible opportunities of sound and, concomitantly, an inability to re-evaluate the intrinsic limits of oculocentric models that have guided the discourses and practices of museum institutions. This thesis revisits the exhibition practices of the art museum—the set of discursive and physical spaces that interact within these locations. It demonstrates the limits of a logic built on codes reminiscent of the white cube and the black box, proposing instead the idea of the sound studio and the music concert as new exhibition models, which are related to the production and distribution models of the music industry. To do so, this research initially argues that the development of sound in an exhibition context depends on the recorded sounds of reproduction and distribution technologies as well as the practices—individual and collective—of listening in everyday. The study is based on a series of exhibitions that reveal variations in the relation between the museum discourse mapped out above and the organization of the exhibition spaces according to sound-specific pieces: the exhibition of sound art Soundings: A Contemporary Score (2013) at the Museum of Modern Art; Ragnar Kjartansson (2015) and Anri Sala (2011) at the Museum of Contemporary Art in Montreal; the electronic music of Sonic Process (2002) at the Center Pompidou; and finally, popular music in the David Bowie Is exhibition (2013) developed by the Victoria & Albert Museum. From here, the thesis will demonstrate—based on the theories derived from both sound studies and listening phenomenology—the ways in which the sound within the exhibition space raises specific issues, how mixing encourages regimes of listening in the art museum and how the visitor's posture is transformed by the possibilities of wandering through the museum space. Beyond the sensory dimension, sound in the art museum context brings about a shift in theoretical and disciplinary models; abolishing hierarchies and reconfiguring how we understand the idea of the museum from the concept of resonance.

Keyphrases: sound studies, exhibition, art museum, sound art, music, sound studies, space, sound technology
I : Synthèse de carbazole en débit continu. II : Transfert de proton couplé à l’électron photocatalysé au cuivre

Photochemistry and photocatalysis have had a significant impact in organic synthesis, often offering low-energy alternatives to traditional thermal chemistry, or even affording complementary reactivity. The thesis is divided into two sections describing photochemical methods for the synthesis of carbazoles and 1,2-diols. The first section described the conception of a flow chemistry apparatus and a comparison of two photochemical methods, one using visible light and another using UV-light for carbazole synthesis via flow chemistry. While UV irradiation affords better yields, it does not tolerate sensitive functionals groups that are accessible when irradiated in the visible range. The chemoselectivity of the carbazoles synthesis is also examined with both methods. The second section explores the development of copper(I) photocatalysts for promoting a reductive proton-coupled electron transfer (PCET). General guidelines and structure/activity relationships were established for the PCET process through evaluation of a 50-member library of heteroleptic copper complexes bearing one diamine and one bisphosphine. Furthermore, it was demonstrated that a copper photocatalyst could be designed a priori to incorporate a hydrogen-bond donor within its framework to promote PCET reactions. The newly designed catalyst was applied in a photochemical pinacol coupling and was capable of transforming substrates that were unreactive using existing technology, even with a hydrogen bond donor that was orders of magnitude less acidic than common additives. Mechanistic studies demonstrated that the copper catalyst functioned via reductive quenching before PCET, which could not have been easily predicted given the literature precedent. The thesis describes the preparation of molecules such as pinacols and heterocycles that are of high value. Importantly, the new photochemical methods developed lower the energy requirements for synthesis, decrease reaction times and use continuous flow technology that would facilitate and intensify scale-up. In sum, the research herein contributes to efforts to promote sustainable and greener methods of synthesis for fine chemicals.

Keyphrases: Carbazoles, PCET, Photochemistry, Flow chemistry, Carbazoles, Copper