NCube/papyrus huggingface dataset:
Le rôle du gène de la polarité apico-basale SCRIBBLE1 dans les anomalies de tube neural

Scribble (Scrib) is a key regulator of apicobasal polarity (ABP) of epithelial cells, presynaptic architecture, and short-term synaptic plasticity in Drosophila. In mammals, its homolog Scrib1 has been implicated in AB polarity and has long been studied as a tumor suppressor gene. However, Scrib1 was also implicated in another form of polarity called planar cell polarity (PCP) where epithelial cells become polarized along the plane of the epithelium. In vertebrates, PCP, also called the non-canonical Frizzled/Dishevelled (Fz/Dvl) pathway, mediates a morphogenetic process called convergent extension (CE) during gastrulation and neural tube formation. In mouse models, mutations in Scrib1 cause a severe form of neural tube defects (NTDs) as a result of a defective planar cell polarity (PCP) signaling. In this study, we dissected the role of Scrib1 in the pathogenesis of NTDs in its mouse mutant Circletail (Crc), in cell lines and in a human NTD cohort. While there were no obvious defects in ABP in the Scrib1Crc/Crc neuroepihelial cells, we identified an abnormal localization of the apical protein Par-3 and of the PCP protein Vangl2. These results were concordant with those obtained following a partial knockdown of Scrib1 in MDCK II cells. Par-3 was able to rescue the localization defect of Vangl1 (paralog of Vangl2) caused by partial knockdown of Scrib1 suggesting that Scrib1 exerts its effect on Vangl1 localization indirectly through Par-3. This conclusion is supported by our findings of an apical enrichment of Vangl1 following a partial knockdown of Par-3. Re-sequencing analysis of SCRIB1 in 473 NTD patients led to the identification of 5 rare heterozygous missense mutations that were predicted to be pathogenic. Two of these mutations, p.Gly263Ser and p.Gln808His, and 2 mouse NTD mutations, p.Ile285Lys and p.Glu814Gly, affected Scrib1 membrane localization and its modulating role of Par-3 and Vangl1 localization. Our study demonstrates an important role of Scrib1 in the pathogenesis of NTDs through its mediating effect of Par-3 and Vangl1/2 localization and most likely independently of ABP.

Keyphrases: Scribble1, Neural tube defects, Planar cell polarity, Apicobasal polarity
L'indifférence à l'avenir : réification et aliénation

Philosophy, according to Theodor Adorno, should be the knowledge of the reasons “why the world—which could be paradise here and now—can become hell itself tomorrow” (“Why Still Philosophy”). It is in this perspective that this master’s thesis explores how the phenomenon of indifference, understood as a posture that ensues from a mediated detachment from the world and which manifests itself notably through apathy, powerlessness and the coldness of individuals toward others and the social order, can help to explain why possibilities for a better future appear blocked. To this end, we limit our analysis to two concepts that have greatly influenced Adorno and that provide precious indications with respect to the causes of this indifferent detachment: reification (Verdinglichung) and alienation (Entfremdung). We start from the hypothesis that this indifference is essential to the reproduction of the logic of capitalism. In the first chapter, we begin by studying Georg Lukács’ 1923 essay “Reification and Class Consciousness” in order to learn what his ideas of “contemplative attitude” and of “indifference of form towards content” may teach us about this indifferent detachment. We complete this first chapter by examining what the figure of Odysseus, as analyzed in Theodor W. Adorno’s and Max Horkheimer’s Dialectic of Enlightenment (1947), tells us about the fundamental ambiguity of indifferent detachment which, as constitutive of thought itself, is capable of engendering the worst, while also holding a promise of justice. The second chapter is dedicated to Marx’s Economic and Philosophic Manuscripts of 1844 and to his notion of alienated labor. We show how alienated labor contributes to the reproduction of this detachment from the world which, in turn, tends to block the possibility of real collective action. This analysis of labor nevertheless hints toward ways to fight back against this indifférence à l’avenir.

Keyphrases: Indifférence, Lukács, Adorno, Marx, Philosophy, Indifference, Detachment, Reification, Alienation
Le stress protéotoxique : le prix à payer pour la tolérance au soi immunitaire

In all vertebrates, the thymus is the sole site where hematopoietic progenitors develop into functionally competent T cells. Notably, the thymus ages more rapidly than other organs because of a progressive loss of medullary thymic epithelial cells (mTECs). This so-called thymic involution increases the susceptibility to infections and autoimmune diseases and impairs response to vaccines and cancer immunosurveillance. Thus, the objective of this thesis was to elucidate the mechanisms controlling mTEC homeostasis in vivo, which would greatly facilitate the rational design of novel strategies for reversing thymic involution and ultimately, rejuvenate the immune system. The sole non-redundant role of mTECs is to induce self tolerance, a vital process that depends on a unique feature of mTECs: promiscuous gene expression (pGE). We found that, because of pGE, mature mTECs can collectively express almost the entire repertoire of known protein-coding genes and thereby induce tolerance to most antigens expressed in the organism. While pGE is the key process enabling mTECs to establish self-tolerance, our results show that the price to pay for pGE is an increased protein biogenesis and higher susceptibility to proteotoxic stress in mature mTECs, which need immunoproteasomes (IPs) to mitigate this stress. Notably, we found that IP-deficiency leads to exhaustion of postnatal mTEC progenitors and that IP-deficient mice show accelerated thymic involution and multiorgan autoimmune manifestations. Taken together, our work identifies IPs as major regulators of mTEC homeostasis and provides a potential biological target for reversing age-dependent thymic atrophy.

Keyphrases: Thymus, Thymic epithelial cells, Thymic involution, Self-tolerance, Promiscuous gene expression, Immunoproteasome, Proteotoxic stress, Autoimmunity
La subjectivation en contexte de mobilisation sociale : l’individu engagé au sein des organisations politiques chez T.W Adorno et Alain Touraine

The purpose of this master’s thesis is to understand what makes possible the change in one’s self perception and the acquisition of transformative capacities (emancipatory subjectivation) within an organisation in the context of a given social movement. As the contemporary organizations seem to give a new meaning to collective action, does the individual perceive himself as a useful object in a larger project of historical transformation, or does he sees himself as a singular individual whose particular action and inner transformation fits the goals of social emancipation? How do the internal structures of organizations in which he engages influence the very nature of the experience of himself as an individual? In order to apprehend the full tension that lies in the heart of individual subjectivation, we will compare the thoughts of Alain Touraine, a French sociologist who tries to reinstate the modern idea of the Subject, and T.W. Adorno, a German thinker who sees the acquisition of autonomy as almost impossible.

Keyphrases: Adorno, Touraine, Social epistemology, Critical theory, Subjectivity, Social movements sociology
Les fondements des droits humains : la délibération au-delà des approches naturalistes et politiques

There are two main conceptions of human rights that discuss the question of their normative foundations: natural and political conceptions. The objective of this Master’s thesis is to point out the limits of each of these approaches and to propose a way to avoid these shortcomings while preserving their respective advantages. This will be made possible through a deliberative conception of human rights. Natural conceptions illustrates that it is important to identify an independent justification to establish the full critical weight of these fundamental rights. However, they struggle to derive a practical reflection from their point of view; a complementary political approach is necessary to identify the institutional responsibilities and obligations associated with a human rights regime. In turn, political conceptions address these institutional questions directly. Nonetheless, their analysis emphasizes a difficulty about the foundations of human rights: it is both necessary to highlight an independent foundation and to inscribe them in a political discussion about their content.  The conciliation of these two requirements is possible through a deliberative conception of human rights as long as we understand deliberation as a second-order theory following the approach of Amy Gutmann and Dennis Thompson. This means that human rights are derived from a reciprocal recognition of the equal moral worth of every other person and that this recognition requires a democratic, inclusive political organisation at both the national and the international level. Consequently, one must see how normative foundational standards interact with inclusive democratic norms within a regime of human rights to ensure the protection of the equal dignity of every human person.

Keyphrases: institutions, Political philosophy, human rights, deliberation, democracy, cosmopolitism, reciprocity, dignity, civil society, non-governmental organisation
L'optimisme de Kant : les décennies 1750-1760

This Master’s thesis presents Kant’s optimism during the 1750s and 1760s. The first chapter introduces Leibniz and Malebranche, both of which are considered as the first optimists. Therefore, a brief account of their respective theory of optimism provides a reference frame, which will allow us to exhibit the originality of the Kantian optimism. The first chapter also presents a philosophical interpretation of Alexander Pope’s Essay on Man. This poem shaped considerably the first trajectory of Kant’s optimism during the 1750s. This first trajectory will be discussed in the second chapter. It analyzes three writings of this decade: 3703-3705 Über Optimismus, Allgemeine Naturgeschichte und Theorie des Himmels and Nova dilucidatio. During the 1750s, Kant holds onto a version of a posteriori optimism characterized by a physico-theological approach. The last chapter presents the second trajectory of the Kantian optimism during the 1760s. It also analyzes three writings: Versuch einiger Betrachtungen über den Optimismus, Versuch den Begriff der negativen Größen in die Weltweisheit einzuführen and Der einzig mögliche Beweisgrund zu einer Demonstration des Daseins Gottes. After these years, Kant renounces to physico-theology and his optimism becomes an a priori one.

Keyphrases: Emmanuel Kant, Leibniz, Alexander Pope, Malebranche, Philosophy, Immanuel Kant, Optimism, Theology, Precritical, Kant
Nouvelles fonctions du co-activateur transcriptionnel PGC1A dans le foie

The inability of the liver to respond to metabolic stresses such as high fat diets causes the development of non-alcoholic fatty liver disease (NAFLD). It is a liver disease that affects 25% of the population of industrialized countries. It can progress to a more severe stage: steatohepatitis, characterized by inflammation, oxidative stress and fibrosis. Non-alcoholic fatty liver disease is strongly associated with the development of insulin resistance, that is, the body's inability to respond to insulin, and with type 2 diabetes. NAFLD is difficult to diagnose early and we lack tools to understand molecular mechanisms underlying its progression. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) is a transcriptional coactivator, able to bind to transcription factors to regulate their function in response to metabolic stresses. Reduction of PGC1A expression in the liver has been associated with the development of insulin resistance and NAFLD. Moreover, genetic variants of PGC1A are also associated with the development of type diabetes and NASH. However, the causal role of PGC1A in the development of these diseases, and its role in molecular mechanisms of hepatic insulin response are unclear. We hypothesized that lack of PGC1A expression in the liver aggravates the progression of NAFLD to steatohepatitis and affects the liver's response to insulin. In this thesis, we show that PGC1A is necessary for the hepatic response to oxidative stress - especially in female mice. Indeed, PGC1A is able to bind to the estrogen receptor to induce the cellular antioxidant response. Lack of PGC1A causes liver damage and the appearance of severe steatohepatitis. We also show that PGC1A controls the hepatic response to insulin during fasting by modifying the adapter proteins Insulin Receptor Substrate 1 and Insulin Receptor Substrate 2. Finally, by proteomic methods, we have discovered potential biomarkers of NAFLD. This would allow the development of an early diagnosis method of the disease.  In conclusion, this thesis sheds new light on the activity of PGC1A in the liver in response to metabolic stress and its importance for liver health.

Keyphrases: Pgc1a, Glucagon, Ppargc1a, Biomarker, Steatosis, Liver, Steatohepatitis, Insulin, Diabetes
La lutte et la vérité : la philosophie, entre histoire des sciences et intervention politique chez Michel Foucault et Louis Althusser

This research project aims to study the encounter, in the context of the 1960s in France, between a tradition of epistemological history of sciences – represented by figures such as Gaston Bachelard and Georges Canguilhem – and a period of intensified political struggles that culminates in the series of events of May ’68. Both Louis Althusser’ and Michel Foucault’s works are a testimony of this encounter. If Althusser comes to conceive philosophy, through a theory of its history, as a battlefield or a “class struggle in theory”, Foucault engages himself in the project of a genealogy of various historical forms of truth which, attentive to the matrices of relations of power wherein they emerge and exert themselves, is inseparable from a political action aiming to have them subverted and reconfigured. Despite the differences between the two bodies of work, a common space sketches itself out for philosophy at the crossroads of history, science and politics, at a time where its traditional metaphysical and legislative ambitions begin to fade away.

Keyphrases: XXe siècle, Louis Althusser, Michel Foucault, Philosophy, Politics, Epistemology, History of sciences, French philosophy, 20th century
Financial time series analysis with competitive neural networks

The main objective of this Master’s thesis is in the modelling of non-stationary time series data. While classical statistical models attempt to correct non- stationary data through differencing and de-trending, I attempt to create localized clusters of stationary time series data through the use of the self-organizing map algorithm. While numerous techniques have been developed that model time series using the self-organizing map, I attempt to build a mathematical framework that justifies its use in the forecasting of financial times series. Additionally, I compare existing forecasting methods using the SOM with those for which a framework has been developed and which have not been applied in a forecasting context. I then compare these methods with the well known ARIMA method of time series forecasting. The second objective of this thesis is to demonstrate the self-organizing map’s ability to cluster data vectors as it was originally developed as a neural network approach to clustering. Specifically I will demonstrate its clustering abilities on limit order book data and present various visualization methods of its output.

Keyphrases: Self-organizing map, Limit order book, Classification hiérarchique, Prévisions, Neural network, Principal component analysis, Hierarchical clustering, Stationarity, Forecasting
Étude de la marche aléatoire biaisée en milieu aléatoire

The main goal of this Master thesis is to provide an introduction to the random walks in random environments (RWRE). This is a vast domain, our interest will be on models where the walk is directionnally transient in order to study asymptotical behavior. We will present severals models and associated mains results. We will see some basic techniques used in this field. One of the tools that has made the most progress is the renewal structure which allows us to answer questions about the speed of the biased random walk. This is the subject of this thesis, we deal with the following question : Is the speed of the biaised random walk on a Galton-Watson tree monotonous with respect to the environnement ? We answer in the affirmative for a high bias.

Keyphrases: Random walk in random environment (RWRE), Galton-Watson tree, Velocity of the biased random walk in random environment, Renewal structure
Vieillissement pour la marche aléatoire biaisée sur des conductances aléatoires dans l'hyper-grille à d dimensions

We examine the property of ageing exhibited by several models of random walk on random environments that display trapping behavior. In particular we present a proof of such a property for the biased random walk on random conductances in the d-dimensional hyper-cubic lattice, when the conductances are independant and heavy-tailed (i.e. no first moment).

Keyphrases: random walk, random environment, Levy process, Ageing, Trapping
Violette Leduc in translation : between censure, recognition and emancipation

French writer Violette Leduc’s books, published between 1946 and 1973, are some of the earliest examples of autobiographical feminist writing addressing issues such as mental health, unideal motherhood and sexuality from a female perspective. Due to the controversial nature of her work, she was repeatedly censored throughout the publication process in France – from the initial manuscript production in the form of self-censorship, through her relationship with Simone de Beauvoir, by the editors at Gallimard and, ultimately, by the press. After finding critical success despite the resistance to her work, her books were translated into many languages, including English. Although Leduc’s censorship has been documented and discussed from a range of perspectives, the translation of her writing and its circulation outside of France is barely mentioned. This study therefore addresses the question of how translation, specifically the English translation, as another gatekeeper in Leduc’s publication process, responds to the previous censorship of her writing – does it magnify or attenuate repression, does it help emancipate or repress minority representations? To explore these questions, we present the case of Leduc’s most controversial 200 pages of writing – a passage removed from its original place at the beginning of another book to become the standalone Thérèse et Isabelle. This text, which recounts the brief romantic relationship between two female boarding school students, was overtly censored in French. It was translated into English in 1967 and, unlike Leduc’s other books, was rereleased in its unexpurgated form in 2000 and was retranslated in 2012. For the purposes of this analysis, these two translations are considered within the wider production process, from initial writing to ongoing critical reception. In so doing, translational theories of censorship and queer and feminist studies provide a critical lens through which to understand contextual and historical significance, while translation-specific discussions of complexity theory are applied as an analytical framework through which to populate a nuanced understanding of inter-related sources of influence and emergence. From this complex perspective, patterns are identified that highlight the role of translation as an agent of censorship and/or emancipation, significantly influencing the contemporary understanding of Leduc’s legacy.

Keyphrases: Translation, Violette Leduc, Censorship, Queer studies, Feminism, Literary translation, Complexity theory
WikiGames : une plateforme de jeux dédiée à la validation d’une base de connaissances produite à partir de techniques d’extraction d’information ouverte

Open information extraction techniques can generate a large amount of relation triplets from unstructured corpus of texts. These large collections of triplets often contain a good portion of noisy triplets that brings little to no usable information. These collections of triplets can become too large to be manually validated by most small teams in a reasonable amount of time and hiring the number of validators required for such task would be too costly for most teams. The use of games as a crowdsourcing tool has shown great success in acquiring a large pool of volunteer for the realization of similar tasks. We have therefore looked into the extraction of a set of useful knowledge from a rather large and noisy relation triplets collection that was previously extracted using an open information extraction tool. We have then started the process of validating the resulting knowledge base with the help of a games with a purpose platform.

Keyphrases: Natural language processing, Knowledge base, Machine learning, Games with a purpose
ReLiS: un outil flexible pour réaliser des revues systématiques itératives et collaboratives

Systematic Reviews (SR) provide a rigorous method to find and analyze the literature evidence relating to a particular topic of interest. Conducting SR is known to be an effort intensive and time-consuming endeavor that requires a properly documented protocol and several iterations to setup right. It follows a systematic process to achieve repeatable, unbiased and complete outcomes.  Tools that help automate some tasks of the process are of tremendous value for researchers. However, important features related the conduction of SR in a collaborative and iterative way are still lacking in existing tools. In this thesis we present ReLiS, a tool to automatically install and configure SR projects to conduct them collaboratively and iteratively on the cloud. ReLiS is engineered following a model-driven development approach. It features a domain-specific modeling editor tailored for researchers who perform SR and an architecture that enables on-the-fly installation and (re)configuration of multiple concurrently running SR projects.

Keyphrases: Systematic literature review, Systematic mapping study, Model-driven development, Automatic installation, Software engineering