VictorJuiz/thesis huggingface dataset:
Characterization of the Zebrafish Logelei Mutant Reveals a Conserved Requirement for MED14 in the Maintenance of Stem Cell Populations
Keywords: MED14
Stem Cells
Zebrafish
Logelei

The Mediator Complex links the RNA polymerase II transcriptional machinery to enhancer bound regulatory factors that in turn establish and maintain cell fate. However, the in vivo consequences of loss of function of many Mediator subunits are largely unknown. Through positional cloning analysis we have identified med14, which encodes a tail component of the Mediator complex, as the gene affected in zebrafish logelei mutants. A slight developmental delay is noticeable by 1.5 dpf in med14 mutants and the gap in development compared to their wild-type siblings continues to widen thereafter. Ultimately, med14-/- embryos progress only as far as the long-pec stage (normally 2.0 dpf) by 3.0 dpf and expire before hallmark events of the hatching period commence (i.e. pectoral fin elongation and formation of the semi-circular canals). Interestingly, transcription is not broadly affected in mutants, with only ~2% of genes assayed by mircoarray being differential expressed relative to their wild-type siblings at 2.25 dpf (764/34858 with ≥ 2 fold difference). More striking still, there is little difference in cell death or proliferation despite the observed “arrest” in development. To gain further insight, RNAi knockdown of med14 in planarians was pursued. Homeostasis and regeneration assays implicate med14 specifically in maintenance of the planarian adult stem cell population. Further analysis of zebrafish embryonic stem cell populations suggests that this could be an evolutionarily conserved role. Finally, preliminary results of an expanded RNAi knockdown screen for multiple Mediator subunits (covering all structural Domains (Head, Middle, Tail and Kinase)), indicate that stem cell maintenance is a general property of the Mediator Complex in vivo. Taken together, these results reveal a specific function for Mediator in stem cell maintenance distinct from its role in general transcription.
Mécanismes d’impasse communicative dans le drame familial chez Michel Tremblay, Marie Laberge, Jean Marc Dalpé et Michel Marc Bouchard
Keywords: Impasse communicative
Impasse
Communication
Palo Alto
Résistance à la transformation de la relation
Conflit familial
Conflit dialogal
Recours monologal
Gestualité agonale
Family Systems Theory and Literary Study
Chronémique
Proxémique
Littérature québécoise et canadienne-française
Théâtre québécois et canadien-français
Michel Tremblay
Marie Laberge
Jean-Marc Dalpé
Michel Marc Bouchard
Dominé
Dominant
Mécanismes d’impasse communicative
Face négative
Face positive
Signes opaques
Objet scénique
Piège relationnel
Communication impossible
Incommunicabilité
Manque de communication
Monologue
Dialogue
Geste
Attitude
Posture

Résumé En partant de l’hypothèse qu’il existe, dans le discours dramatique, pris au sens large, un phénomène de piège relationnel qui se produit au sein du conflit familial dramatisé par Michel Tremblay, Marie Laberge, Jean Marc Dalpé et Michel Marc Bouchard, je propose un modèle d’analyse d’interaction conflictuelle qui permet de cerner les composantes de ce phénomène. Dans le premier chapitre de cette thèse, il s’agit du développement de ce modèle. Je m’appuie, en premier lieu, sur les travaux de l’école de Palo Alto, dont la théorie de la communication paradoxale (la « double contrainte » et le « jeu sans fin » et, en deuxième lieu, sur la recherche sur le discours au sens large, c'est-à-dire linguistique et pragmatique, de Austin, Searle, Grice, Ducrot, Brown et Levinson et Kerbrat-Orecchioni, pour ne nommer que ceux-ci. Menée à l’intérieur des paramètres établis par la sémiotique théâtrale, telle que développée par Elam, Ubersfeld, Pavis, Ryngaert et Rosen, entre autres, ainsi qu’à l’intérieur de ceux proposés par l’analyse sociologique et psychanalytique (Goffman, Monroy et Fournier, Jackson, Watzlawick, Leiper et Kent), mon étude de la dynamique interrelationnelle montrera la nature et la fonction de ce que j’appelle « l’impasse communicative », ses trois mécanismes de « conflit dialogal », de « recours monologal » et de « gestualité agonale », ainsi que leurs effets pathétiques sur le moteur dramatique des pièces choisies. Afin de mettre en valeur ce modèle et d’effectuer une analyse approfondie des éléments verbaux et non verbaux de l’interaction conflictuelle, dans les trois chapitres suivants, je procède à l’étude textuelle de cinq pièces à partir de chacun des mécanismes de l’impasse. Dans le chapitre cinq, j’applique mon modèle de l’impasse communicative à l’analyse de l’objet scénique dans la dernière pièce de mon corpus pour montrer le rôle fonctionnel qu’il joue dans la perpétuation du conflit qui écrase les personnages. Dans le contexte de cette étude, les interactions révèlent l’existence d’un cercle vicieux de comportements agonaux qui charpentent les interrelations de sorte que les personnages pérennisent le conflit, produisant une dynamique de piège sans issue.
Mapping Worm-Bioavailable Chemical Space for Improved Probe Discovery and Characterization with Caenorhabditis elegans
Keywords: Caenorhabditis elegans
chemical genetics

Small molecule modulators of protein activity are powerful reagents to probe the biology of living systems. Small molecules have been used repeatedly to uncover protein functions that were otherwise hidden from more conventional approaches. One way to find new small molecule probes is to screen libraries of chemicals for those that induce phenotypes in model organisms. Chemical screens in yeast, worms, fish, and plants have all resulted in the discovery of novel probes of protein function. The nematode worm Caenorhabditis elegans has great potential for the discovery and characterization of small molecule probes. Its small size, ease of culture, and genetic tractability make this animal amenable to high‐throughput chemical screens, as well as mode-of-action studies of newly identified bioactives. One drawback to using C. elegans as a screening tool for novel small molecule probes is its resistance to pharmacologically active drug‐like compounds. Given its extensive xenobiotic defenses, poor bioavailability may explain this resistance. Indeed, there are a number of bioactive compounds that are ineffective when applied to whole worms that perturb their target proteins in dissected animals. Thus, target access is likely a major limiting factor for pharmacological efficacy in C. elegans, although this idea has never been tested. In this thesis, I describe a novel HPLC‐based method for measuring the accumulation of exogenous compounds in worms, and I use this method to test the accumulation of hundreds of drug‐like molecules in C. elegans. I show for the first time that worms resist drug‐like compound accumulation, and that accumulation is generally required for bioactivity. I describe the construction of a computer‐based tool that can identify worm‐bioavailable molecules, and I highlight structural features that influence accumulation. I show that screening worm‐bioavailable molecules increases the bioactive discovery rate of C. elegans chemical screens. Next, I describe novel bioactive heterobiaryl amide compounds discovered through a C. elegans chemical screen. I apply insights gleaned from the mapping of worm‐bioavailable chemical space to facilitate their characterization, and preliminary data suggest that these compounds are agonists of the worm metabotropic glutamate receptor MGL‐1. Thus, the worm‐bioavailable chemical space I describe facilitates small‐molecule probe discovery and characterization.
The Bounds of Life: The Role of Death in Schelling's Internal Critique of German Idealism
Keywords: Kant
Schelling
Fichte
Heidegger
immortalism
mortalism
intellectual intuition
thing in itself
life
death

What conditions the possibility of existentially valuable experience? Against nihilism, the threat that philosophical cognition undermines the very idea of purposiveness, German idealism posits that we are unconditionally conditioned by life, construed as the infinite purposive activity of reason. I reconstruct Schelling’s critique of this project as defending the idea that death conditions or puts into question our rational activity. Scholars tend to read the idealists as rejecting Kant’s idea of an unknowable thing in itself by grounding philosophy on a knowable first principle and tend to situate Schelling as a phase between or a late attack on Fichte and Hegel. Part I gives a systematic account missing on the former, arguing that idealism is an instance of immortalism, which holds that life is the unconditioned condition of rational activity, while death is unconditionally conditioned. Part II gives a historical account missing on the latter, arguing that Schelling is an early and continual critic of idealism on behalf of mortalism, which holds that death unconditionally conditions rational activity. My first argument modifies typical readings of German idealism, revealing a deep connection between its rejection Kant’s idea and its refusal to let death put us into question. My second complicates typical readings of Schelling, casting his mortalism as rehabilitating the idea that something radically outstrips rational activity while representing a regulative ideal. Although Schelling’s mortalism anticipates Heidegger’s, they differ: Schelling aligns death with the goal of systematic knowing, Heidegger with taking over one’s history as care. But Schelling overcomes immortalism, enabling Heidegger’s idea of death. Part III shows this idea is structurally analogous to Kant’s idea of the thing in itself. Immortalism’s failure leaves unsolved two antinomies I argue are formally identical and only solvable by thinking these ideas as boundary concepts the thought of which is necessary for the unity, respectively, of finite being and finite understanding. By reconstructing the role of death in Schelling’s internal critique of German idealism, then, my thesis also brings into closer contact Kant’s transcendental and Heidegger’s existential projects.
Advances in Quantitative Methods in Dinosaur Palaeobiology: A Case Study in Horned Dinosaur Evolution
Keywords: Palaeoecology
Palaeobiology
Evolution
Taphonomy
Dinosaur
Centrosaurinae
Ornithischia
Morphology
Allometry
Body Mass
Missing Data
Ornamentation
Paleoecology
Paleontology
Paleobiology
Palaeontology
Canada
Cretaceous
Alberta
Campanian
Preservation
Crocodylia
Geology
Stratigraphy
Fluvial
Morphometrics
Multivariate
Horn
Anagenesis
Cladogenesis
Stasis
Mesozoic

Discerning modes and rates of biological evolution and speciation are some of the primary objectives of evolutionary biology. Much palaeobiological work has focused on developing robust methods for testing and fitting evolutionary models to samples of fossils across a stratigraphic or temporal axis, with most analyses centering on marine invertebrates. Recent extensive sampling of dinosaur deposits now allows for testing of evolutionary modes in this clade, a first for large-bodied terrestrial vertebrates. Within dinosaur palaeobiology, the relative roles of anagenesis and cladogenesis in diversification, particularly for horned dinosaurs, are hotly debated. Due to their large sample sizes, well-documented stratigraphic positions, highly diagnostic ornamentation, and monodominant bonebeds (representing populations), centrosaurine dinosaurs from the Belly River Group of Alberta make an ideal model system for testing the predictions of these two divergent evolutionary modes. Despite this unparalleled fossil record, it (as well as most fossil records) is limited by missing data, small sample size, taphonomic biases, and stratigraphic error. In this thesis, I present case studies that attempt to quantify and better understand these limitations, and inform best practices for overcoming them. The first four chapters, utilizing data sets for crocodilians (extant archosaurs) and a model geological system (upper Belly River Group), allow for a better-constrained quantitative evolutionary analysis of the Belly River Group centrosaurines in chapter five. Correlations and time-series analyses of morphology and stratigraphic position of Centrosaurus apertus and Styracosaurus albertensis are used to test for directional trends and evolutionary model fitting. Evolutionary results are robust to multiple simulations of stratigraphic uncertainty, and overlap between the taxa depends on a single locality. Results find no support for anagenesis, and rather are consistent with taxonomic turnover due to punctuated evolutionary events or, more likely, ecological replacement due to habitat tracking.
The Role of Mitochondrial DNA Replication Fidelity in Toxicity Initiated by Drugs that Impair Mitochondrial Function
Keywords: Mitochondria
Toxicity
DNA

Mitochondrial DNA (mtDNA) is crucial for proper mitochondrial function in part because it encodes for 13 subunits of the electron transport chain (ETC). mtDNA is replicated exclusively by DNA polymerase gamma (Polg), which has an exonuclease proof-reading domain critical for maintaining mtDNA replication fidelity. Drug-induced mitochondrial toxicity is a common problem that can occur by many mechanisms, including ETC inhibition and mtDNA damage. Gene-environment interactions can modulate mitochondrial toxicity, and individuals with POLG mutations are at risk for toxicity from valproic acid, a drug that impairs mitochondrial function. We hypothesize that mtDNA replication fidelity protects against toxicity initiated by drugs that impair mitochondrial function. I observed that mouse embryonic fibroblasts (MEFs) with impaired polymerase gamma exonuclease activity (Polgm/m) and increased mtDNA mutation load have increased susceptibility to toxicity caused by drugs that impair mitochondrial function. The ETC complex I inhibitor rotenone caused increased apoptosis in Polgm/m MEFs relative to wild type. This sensitivity was also observed for other ETC complex inhibitors and clinical drugs with off-target ETC complex I inhibition. A mitochondria-penetrating peptide (MPP) was used to target the alkylating agent chlorambucil (Cbl) specifically to mitochondria. Mitochondria-targeted Cbl (mt-Cbl) caused bioenergetic differences between Polgm/m and wild type MEFs, but was not differentially toxic at the level of cell viability. Increasing mitochondrial autophagy with rapamycin attenuated rotenone toxicity in Polgm/m MEFs, while changes to mitochondrial fusion/fission dynamics did not alter toxicity. Overall, these data suggest that mtDNA replication fidelity maintained by polymerase gamma exonuclease activity protects against bioenergetic stress caused by ETC inhibition.
Communist Upbringing under Stalin: The Political Socialization and Militarization of Soviet Youth, 1934-1941
Keywords: Youth
Komsomol

In 1935 the Communist Youth League (Komsomol) embraced a policy called "communist upbringing" that changed the purpose of Soviet official youth culture. Founded in 1918, the Komsomol had been an organization of cultural proletarianization and economic mobilization. After the turmoil of Stalin’s revolution from above, Soviet leaders declared that the country had entered the period of socialism. Under the new conditions of socialism, including the threat of war with the capitalist world, "communist upbringing" transformed the youth league into an organization of mass socialization meant to mold youth in the shape of the regime. The key goals of "communist upbringing" were to broaden the influence of Soviet political culture and to enforce a code of "cultured" behavior among youth. Youth leaders transformed the Komsomol from a league of young male workers into an organization that included more than a quarter of Soviet youth by 1941, incorporating more adolescents, women, and non-workers. Employing recreation, reward and disciplinary practices that blurred into repression, mass socialization in the Komsomol attempted to create a cohort of "Soviet" youth - sober, orderly, physically strong and politically loyal to Stalin’s regime. The transformation of youth culture under Stalin reflected a general shift in Stalinist social policies in the mid-1930s. Historians have argued whether this turn was a conservative retreat from Bolshevik ideals or the use of apolitical modern state practices in the service of socialism. This dissertation shows that while youth leaders were intensely interested in modern state practices, they made these practices into central elements of Soviet socialism. Through the Komsomol, youth became a resource for the state to guide along the uncertain and dangerous road to the future of communism. Reacting to domestic and international crises, Stalinist leaders created a system of state socialization for youth that would last until the fall of the Soviet Union.
Doubt, Faith, and the World to Come in Peter of Cornwall's Book of Revelations
Keywords: Belief and Doubt
Visions in Literature
Soul in Literature
Christian Literature, Latin (Medieval)

This dissertation explores the relationship between doubt and faith as it appears in a large collection of visions and revelations from the turn of the thirteenth century, entitled the Liber revelationum, or the Book of Revelations. The Liber revelationum was compiled in London by an Augustinian canon named Peter of Cornwall around the year 1200. He collected scores of visions and revelations from books, friends, and acquaintances in order to prove that angels, God, and the human soul existed. My work focuses on the first book of the collection dealing with proofs for life after death. This study explores the context of this manuscript both in Peter’s works and also in the larger twelfth-century literary genres in which it participates. I interrogate the various means by which the spiritual world is revealed to the living. I question what exactly about the spiritual world is revealed, and what specific doubts these revelations address. Finally, I explore the culture of desire for contact with the spiritual world at the turn of the thirteenth century that is glimpsed through Peter’s collection and its immediate sources. Peter’s work results from what he took as a central epistemological problem facing human beings: as a result of sin, humanity has lost the ability to directly know God. As a result, it is natural to doubt His existence as He cannot be known through experience. Peter’s revelations address this doubt. I analyze the ways in which visions and revelations in their response to these doubts run up against recurrent restrictions and frustrations due to the very epistemological limitations that inspire them. These very shortcomings played a role in the process of faith to the religious culture around visions and the desire for them around the year 1200. This faith, which also required a similar separation from the divinity, exists in the same space as visionary and revelatory experience, defined by humanity’s limited ways of knowing and desire for a seemingly infinitely deferred transcendence. I argue that experiential medieval religion and belief, as glimpsed in Peter’s collection, requires and is enriched by doubt as well as challenged by it.
The Epigenesis of Pure Reason: Systematicity in Kant's Critical Philosophy
Keywords: Kant, critique, systematicity, epigenesis

The Epigenesis of Pure Reason: Systematicity in Kant's Critical Philosophy -- Kant's critical philosophy explicitly aspires to be systematic. Whether it achieves this aspiration is another question. Comparing pure reason to an organized body, Kant requires a critique of pure reason to be entirely complete down to the least elements, and regards this completeness or systematicity as a matter of all or nothing. He even speaks of critique as a system of the epigenesis of pure reason, i.e., an organic whole or system of possible ends that pure reason generates and organizes entirely out of itself. Nonetheless, the epigenetic model of systematicity, which underlies critical philosophy, remains buried in Kant's corpus. Neither Kant nor any interpreter of critical philosophy makes clear why and how pure reason generates and organizes itself as a self-standing operating system or whole of possible ends. They also do not explicate what this epigenetic conception of systematicity entails for the functioning of theoretical reason, practical reason, and the power of judgement. This dissertation investigates the question of the systematicity of pure reason in Kant's critical philosophy, presenting an epigenetic interpretation of Critique of Pure Reason through the lens of the transcendental doctrine of method. It argues that, in its primary sense, a critique of pure reason is the methodological epigenesis, i.e., self-generation and self-organization, of pure reason as an organic system or embryonic whole of possible ends. The dissertation proceeds by discussing: 1) what motivates pure reason to generate itself as a system or whole of possible ends; 2) how pure reason generates itself as a whole of possible ends; 3) how pure reason structures this whole into organic parts; and 4) how pure reason's self-generation and self-organization make the table of judgements transcendentally systematic.
Escritura en movimiento, movimientos de escritura: narrativas de la vanguardia historica latinoamericana y el auge del cine mudo internacional
Keywords: Literature
Latin American

Escritura en movimiento, movimientos de escritura: narrativas de la vanguardia historica latinoamericana y el auge del cine mudo internacional da cuenta del grado con el que el cine mudo internacional de los anos veinte determino el trabajo original de la vanguardia historica en America Latina. Exploramos, bajo una perspectiva taxonomica deleuziana, la influencia que tuvieron las cuatro grandes industrias filmicas internacionales de principios del siglo veinte (Hollywood, montaje sovietico, Impresionismo frances y Expresionismo aleman) en la formacion de paradigmas narrativos en cuatro latitudes de la America hispanica: amautistas peruanos, Contemporáneos en Mexico, minorismo cubano y creacionismo huidobriano. Deseamos responder a la pregunta sobre la diferencia esencial de producir escritura despues de la aparicion del cine. Arguimos, en breve, que las propiedades del medio cinematografico modificaron el panorama cultural de Latinoamerica y contribuyeron al replanteamiento de la labor del artista y su obra en la reconstruccion de una identidad.