VictorJuiz/thesis huggingface dataset:
Glucose-6-phosphate dehydrogenase deficiency: A possible risk factor for neurodegeneration associated with aging and amphetamine use
Keywords: aging
toxicology
glucose-6-phosphate dehydrogenase
behavioural testing
amphetamines
metabolism
neurotoxicity
neuroscience

Glucose-6-phosphate dehydrogenase (G6PD) regenerates the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), which is important for reactive oxygen species (ROS) detoxification. ROS have been implicated in the development of neurodegenerative diseases in aging as well as the neurotoxic effects of amphetamine analogs. Using a mutant G6PD-deficient mouse model, we investigated the potential neuroprotective role of G6PD in aging-related and amphetamine-initiated neurotoxicity. Aging G6PD-deficient mice exhibited increased DNA damage along with neurodegenerative changes including a marked loss of Purkinje cells. Locomotor deficits linked to cerebellar function were observed in aging G6PD-deficient mice, but no cognitive deficits were detected. Electrophysiological measurements in hippocampal slices showed substantial amplifications of synaptic function in aging G6PD-deficient animals. Conversely, lifespan was increased in aging homozygous G6PD-deficient mice compared to heterozygous G6PD-deficient mice and wild-type G6PD-normal mice. The potential protective role of G6PD against ROS-initiating neurotoxins was examined using 3,4-methylenedioxyamphetamine (MDA), the major active metabolite of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). Although MDA caused deficits in motor function linked to the substantia nigra, and in cognition measured by taste aversion learning, these deficits were not exacerbated in G6PD-deficient mice, and homozygous G6PD-deficient females were actually protected from one gender-specific MDA-initiated learning deficit observed in wild-type animals. My results show a complex role for G6PD. On one hand, G6PD protected against the neurodegenerative effects of oxidative stress in aging mice at the macromolecular, cellular and behavioural levels while the substantial electrophysiological alterations in G6PD-deficient mice suggest that cognitive deficits remain to be discovered. In contrast, the enhanced lifespan of G6PD-deficient mice suggests that a reduction of products from the pentose phosphate pathway including NADPH may have benefits, which mechanisms also remain to be examined. The absence of a modulatory role for G6PD in some learning deficits caused by MDA in adult mice suggests limitations in the protective ability of G6PD, while the reduction in another MDA-initiated behavioural deficit in G6PD-deficient females reveals the same paradoxical potential seen in aging mice. While G6PD appears to exert a predominantly neuroprotective role, particularly in aging, the beneficial outcomes from G6PD deficiency may be relevant to the high prevalence of it in humans.
Analytical and Numerical Results for Some Classes of Nonlinear Schrödinger Equations
Keywords: Derivative nonlinear Schrödinger equation
Nonlinear Schrödinger equation
Numerical simulations
Blowing-up Solutions
Rate of Blow-up
Dynamic Rescaling
Solitary waves
Soliton dynamics
Orbital stability/instability
Resonant tunneling

This thesis is devoted to the study of nonlinear dispersive partial differential equations of Schrödinger type. The main questions we investigate are long-time behavior or occurrence of a finite time singularity, as well as stability properties of solitary wave solutions. The derivative nonlinear Schrödinger (DNLS) equation is a nonlinear dispersive model that appears in the description of wave propagation in plasmas. The first part of this thesis concerns a DNLS equation with a generalized nonlinearity (gDNLS). We first investigate numerically the possible occurrence of singularities. We show that, in the L2-supercritical regime, singularities can occur. We obtain a precise description of the local structure of the solution in terms of the blowup rate and asymptotic profile, in a form similar to that of the nonlinear Schrödinger equation (NLS) with supercritical power law nonlinearity. We also show that the gDNLS equation possesses a two-parameter family of solitary wave solutions and study their stability. We fully classify their orbital stability or orbital instability properties according to the strength of the nonlinearity and, in some instances, their velocity. In linear quantum mechanical scattering theory, the phenomenon of resonant tunneling refers to the situation where incoming waves are fully transmitted through potential barriers at certain energies. In the second part of this thesis, we consider the one-dimensional cubic NLS equation with two classes of external potentials, namely the ‘box’ potential and a repulsive 2-delta potential. We demonstrate numerically that resonant tunneling may occur in a nonlinear setting: Taking initial condition as a slightly perturbed, fast moving NLS soliton, we show that, under a certain resonant condition, the incoming soliton is almost fully transmitted. As the velocity of the incoming soliton increases, the transmitted mass of the soliton converges to the total mass.
Functional Analysis of Neuralized in Notch Signaling and Germline Stem Cell Maintenance
Keywords: Neuralized
Notch Signaling
Germline Stem Cell

The development of an organism requires precise determination of cell fate. The Notch pathway acts as a major coordinator during development, by regulating cell fate in a wide variety of tissues in multicellular organisms. A critical step in activation of Notch signaling is endocytosis of the Notch ligands, Delta and Serrate. Ligand endocytosis is regulated by one of two E3 ubiquitin ligases, Neuralized or Mind bomb. Neuralized (Neur) is composed of a C-terminal RING domain, which is required for Delta ubiquitination, and two Neur homology repeat (NHR) domains. Here, I characterized the two NHR domains. We have previously shown that the NHR1 domain is required for Delta trafficking and I further determined that NHR1 also affects binding and internalization of Serrate. Furthermore, I showed that the NHR2 domain is required for Neur function and that a point mutation in NHR2 (Gly430) abolishes Neur ubiquitination activity, thereby affecting ligand internalization. I also provided evidence that Neur can form oligomers in cultured cells and in fly tissues, which regulates Neur activity, by extension, ligand internalization. Finally, I investigated the role of Neuralized in germline stem cell (GSC) maintenance. Specifically, I found that Neuralized is required for GSC maintenance and the NHR and RING domains are indispensable for this function. Furthermore, I showed that Neuralized is a downstream target of the Jak/Stat pathway in GSC maintenance. Interestingly, I also provided evidence that Notch may not be required for GSC maintenance, suggesting that Neur can function independent of Notch signaling in GSCs. Altogether, my studies demonstrate that Neur plays critical roles in regulating cell fate in different developmental contexts.
Computational Analysis of RNA-binding Protein Target-site Selection and Function
Keywords: RNA-binding protein
RNA cis-regulatory element
RNA secondary structure
Post-transcriptional regulation

Gene expression is extensively regulated by the binding of RNA-binding proteins (RBPs) to cis-regulatory elements encoded in mRNA. A robust literature has emerged regarding the stability and intracellular distribution of transcripts genome-wide. However, clear binding preferences have only been reported for a few RBPs, and these binding data collectively explain only a small portion of these post-transcriptional events. I developed the RNA Regulatory Element Analysis and Discovery (RNA-READ) pipeline, which takes as input positive (e.g., regulated transcripts) and negative gene lists (e.g., the co-expressed transcripts not affected by the same post-transcriptional event), and outputs the RNA cis-regulatory element that distinguishes the positive from the negative transcripts. First, RNA-READ tests for enrichment of previously reported RNA motifs, then it performs novel RNA motif discovery to identify the consensus RNA motif that best discriminates between the positive and negative transcripts. An important innovation of the RNA-READ pipeline is that it considers both sequence and structural constraints on binding of RBPs. I consider two binding classes: (1) the RBP binds to mRNAs with primary sequence-specificities; (2) the RBP binds to elements in mRNAs defined completely by structure (i.e., shape recognition). I have shown that computationally estimated target-site accessibility improves prediction of sequence-specific binding for various RBPs, with >22% average relative decrease in error versus using only sequence information. The predictive power is further increased with the introduction of structural-context constraints to the single-stranded target sites. Furthermore, I showed that computationally estimated intrinsic mRNA secondary structure is also helpful for determining RBP binding via shape recognition. I identified specific structural elements enriched in dsRBP Staufen targets versus non-targets. I applied the RNA-READ pipeline to the datasets that measured translation, stability and localization of transcripts in the Drosophila early embryo and identified numerous significant associations between the presence of motif matches and specific regulatory outcomes.
Poétique de l’image dans le roman de Georges Rodenbach « Bruges-la-Morte » et dans l’œuvre autobiographique de Suzanne Lilar
Keywords: Rodenbach
Lilar
image
photographie
ekphrasis
iconotexte
écriture de soi
identité
analogie
poétique
oeuvre d'art
philosophie

Oscillant entre l’intelligible et le sensible, entre le réel et l’imaginaire, cette catégorie d’entre-deux par excellence qu’est l’image fascine par sa dynamique fort complexe. L’image semble être encore plus fascinante lorsqu’elle entre dans le monde de la littérature et forme avec le verbal ce qu’on appelle un iconotexte. La présente thèse exploite les modalités d’inscription de l’image et ses fonctions dans l’œuvre de Georges Rodenbach (1855-1898) et de Suzanne Lilar (1901-1992), deux écrivains belges d’origine flamande et d’expression française. Comme son objet d’étude, cette thèse se veut aussi une sorte d’entre-deux, car les recherches effectuées croisent non seulement la littérature, mais aussi les beaux-arts et la philosophie. La première partie de notre thèse tente de situer la problématique de l’image dans le contexte des tendances artistiques et littéraires traversant le XIXe siècle, et présente de nombreuses réflexions théoriques sur la notion d’image. La deuxième partie de ce travail est consacrée au roman de Rodenbach Bruges-la-Morte (avec ses images photographiques et son frontispice, dessin du célèbre peintre symboliste Fernand Khnopff). Enfin, la troisième partie porte sur quatre textes autobiographiques de Suzanne Lilar. Nous analysons deux livres illustrés d’images photographiques (le Journal de l’analogiste et À la recherche d’une enfance) et deux textes non illustrés (l’autobiographie Une enfance gantoise et le roman autobiographique La Confession anonyme). Nous menons notre étude à partir de trois axes : l’image verbale (ekphraseis, descriptions), l’image matérielle (iconique) et leur interaction. L’approche adoptée vise à étudier dans les textes privilégiés les rapports entre le lisible et le visible en termes de dialogues mutuellement enrichissants plutôt qu’en terme d’oppositions. Cette thèse met en évidence les différents rôles complémentaires, ainsi que contradictoires, que joue l’image dans les textes de Rodenbach et de Lilar. Notre étude s’efforce de démontrer que l’iconotexte se prête toujours à différentes interprétations et ne fonctionne que par de constants va-et-vient entre deux systèmes sémiologiques à la fois distincts et interdépendants. Une telle dynamique se résume en cet inachèvement fécond qu’est l’entre-deux, nourri de non résolu, de non vu, de non dit, de mystères.
Literary Branding in the Romantic Period
Keywords: Literary branding
Literary labelling

This thesis argues that, unlike the study of commodity branding, the study of literary branding should not focus solely upon book advertising, but rather investigate all of the processes of attribution that connect conceptual domains with literary labels, enabling their common use in the perception and navigation of the cultural world. Such processes should not be understood exclusively by analogy with the forms of commodity branding that originated in the consumer revolutions of the eighteenth or nineteenth centuries, but rather as the inherent consequences of more ancient and fundamental practices of naming and poetry. Rather than interpret the reactions of historical readers to Byron, for instance, largely in terms of the author as subject – as has been the tendency with earlier approaches to the question – this thesis seeks to explore historical readers’ reactions to the author’s name as label. The readers of Don Juan in 1819 knew Byron, not as we do after two centuries of biographical research, scholarly inquiry, and literary criticism, but as a literary label with relatively few associations. Arguing that the recent vogue for celebrity studies risks reifying elements of what Jerome McGann has called the Romantic Ideology, this thesis attempts to begin to redress this critical imbalance by examining the deployment of a number of interconnected literary labels in a series of case studies. If we wish to know more about what “A Vindication of the Rights of Woman,” “Byron,” or “Wordsworthian” might have meant to readers in the Romantic period, we must examine the uses of those labels in situ.
Regulation of Graded Intracellular Gli Activities in Hedgehog Dependent Ventral Spinal Cord Ppatterning
Keywords: Hedgehog signaling
Morphogen
Spinal cord patterning
Cell fate specification
Suppressor of fused
Kif7
Spop E3 ubiquitin ligase adaptor protein
Gli transcription factors

The Hedgehog (Hh) signaling pathway is essential to guide tissue patterning and cell fate specification during development. Congenital malformations arise from disruptions to Hh signaling, whereas aberrant pathway activation is implicated in cancer formation. The outcome of Hh signaling is mediated by Gli transcription factors. In the spinal cord, a balance of Gli activators and repressors orchestrates the dorsoventral spatial expression of cell fate determinants in naïve progenitors. How a gradient of Hh signaling governs Gli to generate distinct intracellular Gli activities for the specification of diverse ventral cell fates remains unclear. Proteolytic processing, proteasomal degradation, sequestration and subcellular distribution, mediated by a number of post-translational modifications including phosphorylation and ubiquitination, all play a role to regulate Gli. Using genetic and biochemical approaches, my studies have revealed that Kinesin family protein 7 (Kif7), Suppressor of fused (Sufu) and Speckle-type POZ protein (Spop) cooperatively and antagonistically regulate intracellular Gli activities. I demonstrated that the distinct and overlapping negative functions of Kif7 and Sufu restrict Hh pathway activation and prevent ectopic specification of ventral progenitor cell fates. I established a positive role for Kif7 to promote robust Hh signaling by antagonizing the formation of inhibitory Sufu-Gli complexes, a crucial step toward Gli transcriptional activation. My work also uncovered an essential, positive role for Sufu to promote maximal Hh signaling, demonstrating that sequestration of Gli by Sufu serves dual purposes. I showed that Sufu is required for Gli stabilization, to offset Spop-mediated Gli ubiquitination and proteasomal degradation. Moreover, I ascertained the biological function of mammalian Spop to down-regulate Hh pathway activity and prevent ectopic pathway activation in the ventral spinal cord. Altogether, these findings elucidate how Kif7, Sufu and Spop translate graded Shh signals into distinct intracellular Gli activities, providing significant insight to our understanding of Hh signaling.
Money, Meals, and Honour: The Economic and Honorific Organization of the Corinthian Ekklesia
Keywords: Early Christianity
social status
Corinth
Paul

In standard portrayals of Paul’s Corinthian ekklesia, the Christ-group is said to have existed without the level of economic and honorific organization we know to have been rather generalized in Greco-Roman associations: it did not collect subscription fees, failed to appoint or elect temporary officers, and neglected presentation of formal honorific prizes to its service-providers (e.g., crowns, proclamations, honorific inscriptions). In contrast to ancient associations, the ekklesia, many scholars presently maintain with very little disagreement, had no true organization (Conzelmann, 1 Corinthians, 298), and its members shared a close relationship (Meeks, First Urban, 88) that is often described as ecclesiastical egalitarianism. This dissertation offers a different perspective by setting the practices of the Corinthian Christ-group alongside practices that are much more fully known from Greco-Roman associations, and asks whether the structural features (economic and honorific) we know to have been common in Greco-Roman associations might also be evidenced in the Corinthian Christ-group. My argument is that the ekklesia was a structurally sophisticated group equipped with a common fund and a schedule for subscription fees, a hierarchy of elected temporary officers, and competition among members to perform services that would be reciprocated with crowns and other forms of formal commendation.
'The Poet and Publisher at Variance!': Comic Representations of Literary Professionals in Eighteenth-Century Fiction and Drama
Keywords: eighteenth century
fiction
drama
comedy
power
representation
book trade
authorship
Britain

This dissertation investigates the fictionalization of the eighteenth-century literary marketplace, which is consistently presented through the lens of comedy in the imaginative literature of the period. Illuminating the surprising degree of variation among representations of literary professionals in conversation, my analysis of texts like Henry Fielding’s The Author’s Farce and Tobias Smollett’s The Expedition of Humphry Clinker underlines how seemingly programmatic scenes of the author-character’s oppression by the bookseller-character are complicated and subverted by comedy. I posit that readers are encouraged to construct a paradigm of Literary Professionalism against the unprofessionalism—as well as glimpses of professionalism—among the characters involved in the "literary" literary marketplace. Both the conflict and concord among characters accentuate a set of professional standards graspable to individual readers sensitive to the nuances of comedy and power in these negotiations. A lively and persuasive argument for print is ultimately made through the interactive nature of the comedy in these works. The first chapter examines the conditions of eighteenth-century literary marketplace, surveying developments in professional writing and publishing. I also present an overview of the period’s debate about commercial authorship and introduce the literary stereotypes of the author and the bookseller. In the middle chapters of the dissertation I use outcome power, the ability to affect outcomes, to group and separate the fictional dialogues between literary professionals that appear in eighteenth-century fiction and drama. The final chapter is a focused reading of The Adventures of an Author, which contains multiple representations of literary professionals in different kinds of narrative encounters.
Advances in Debug Automation for a Modern Verification Environment
Keywords: debugging
diagnosis
verification
debug

Over the past three decades, the growing list of requirements for integrated circuits has continually presented new challenges to the electronic design community. One of the biggest challenges in the design process is that of functional debugging, which aims to find the root-cause of a functional failure after it has been detected. In recent years, this key challenge has grown in size and scope as bugs commonly appear in both the design and verification environment. This increase in size and scope has made functional debugging one of the largest bottlenecks in the design cycle and points to an urgent need for more scalable and innovative debugging solutions. This dissertation presents multiple novel contributions that address the challenges of increased size and scope of modern functional debugging. In particular, these contributions address the scalability of existing automated design debugging techniques, as well as introduce novel automated tools specifically for debugging the verification environment. The first contribution introduces an unsatsifiable core-guided abstraction and refinement technique for design debugging that focuses on managing the design size aspect of debugging complexity. The second contribution introduces a path-directed abstraction and refinement technique that aims to manage the error trace length aspect of debugging complexity. The third contribution presents a novel method that utilizes unsatisfiable cores in design debugging to manage the multiple design errors aspect of debugging complexity. The fourth contribution presents an automated technique to aid debugging of errors found within formal properties themselves. The final contribution presents an automated technique to aid debugging of missing assumptions that are needed during verification methodologies that use formal methods.
Regulation of mRNA decay by Pumilio in Drosophila melanogaster
Keywords: post-transcriptional regulation
maternal mRNA decay

During early embryogenesis in all animals, development is driven by maternally loaded mRNAs synthesized in the female parent during oogenesis. These maternally synthesized mRNAs are regulated by post-transcriptional mechanisms, including mRNA localization, degradation and translational activation and repression. Many of these processes rely on RNA-binding proteins to initially recognize and bind specific mRNAs and then, subsequently, recruit the appropriate post-transcriptional machinery. Eventually the products encoded by the zygotic genome regulate embryo development. My thesis focuses on an RNA-binding protein called Pumilio and its role in regulating the degradation of maternal mRNAs in Drosophila melanogaster embryos. Pumilio protein and pumilio mRNA are both maternally loaded and deficiencies in pumilio are maternal-effect lethal. While homologs of Pumilio had been implicated in mediating mRNA degradation, the global role of Pumilio itself had been unclear, with contradictory results from embryos and whole flies with a conditional pumilio mutant genotype. I first produced transgenic flies expressing a tandem affinity tagged Pumilio transgene. Then, by pulling down tagged Pumilio followed by next-generation sequencing of co-purifying RNAs, I found that the Pumilio protein associates with ~200 mRNAs in early embryos. Using a null pumilio allele combination, I found that Pumilio regulates the decay of a set of mRNAs in a manner that, in part, appears to be dependent on zygotically encoded factors. I observed that many of the mRNAs whose stability is affected in pumilio mutant embryos are amongst those physically associated with Pumilio protein in early embryos and validated my findings using reporter transgenes. My data show that Pumilio is a regulator of maternal transcript degradation in D. melanogaster.