VictorJuiz/thesis huggingface dataset:
Communication and the Construction of the Ideal in the West

This dissertation examines the conceptualization of the ideal society in Western culture in relation to changes in communication modes. The utopian discourse is defined by a concern with the relationship between language and reality. I explore this concern as a reflection of the theoretical disposition invited by changes in communication modes, which are perceived as crises of representation. Plato and Thomas More’s enlightened communities in the Republic and Utopia reflect comparable idealistic perspectives on education. In my view, this optimism stems from the social reality of growing literacies with the advent of the alphabet and printing, respectively. I contend that these writers are animated by an ethical impulse to teach their readers that language is representation. From the vantage point of this knowledge, each individual may employ language symbolically in order to create and perpetuate a moral and spiritual mode of thought. I argue that the discourse of the ideal is the symbolic expression of humanity’s engagement with death, the ultimate existential concern made acute by the aspect of historical discontinuity in the crisis of representation. Plato and More exhibit comparable efforts to open to their readers the superior space of critical reflexivity which they themselves inhabit. From this conceptual, pre-representational space of conscious choice, language is subjected to achieving spiritual progress. I introduce the concept of post-utopia, which describes a pragmatic moment when the relationship between author and the ideal society is brought into the foreground and reinforced as a way of addressing concerns with textual authority. I examine these developments in Augustine’s De Civitate Dei, François Rabelais’s episode of the Abbaye de Thélème in Gargantua, and Francis Bacon’s New Atlantis. These authors draw on the ideologies of representation inherent in utopian discourse, and position the authorial figure as link between scriptural teleology and history, ensuring spiritual and societal betterment in the textual cultures of late antiquity and early modernity. The figure of the author emerges as a symbol of history and of man’s ability to assume the limits of the mind and of language.

Keywords: utopian literature
utopian thought
communication change
ideal society
symbolic thought
literacy
Plato
Thomas More
St.Augustine
Francois Rabelais
Francis Bacon
Advisor: LeBlanc, Julie
Facilitating Clinical Trials of Parenteral Lipid Strategies for the Prevention of Intestinal Failure Associated Liver Disease (IFALD) in Infants

Objective: The objective of this thesis was to facilitate clinical trials of the optimal lipid based approach (e.g.: omega-3 containing lipid emulsions or minimization of conventional lipid) for the prevention of Intestinal Failure Associated Liver Disease (IFALD). This was achieved through 3 related projects. Project 1: The first project examined the risk of advanced IFALD associated with exposure to conventional intravenous lipid in a logistic regression model. The study demonstrated that each day of conventional lipid (> 2.5 g/kg/day) was associated with a significant increase in the risk of advanced IFALD [Odds Ratio: 1.04 95% CI: 1.003 – 1.06]. Project 2: The second project surveyed experts in Intestinal Failure regarding their beliefs of the efficacy of lipid minimization and lipid emulsions containing omega-3 fatty acids relative to conventional emulsions. The goal of the project was to develop prior distributions of the treatment response for these therapies that can be used in Bayesian analyses of clinical trials. Our results demonstrated consistent expert opinion that the novel lipid based approaches are superior to conventional therapy. Estimates of the treatment effect were similar for the two approaches (median elicited treatment response, relative to conventional lipid, was a relative risk of 0.53 for omega-3 lipid and 0.45 for lipid minimization). Project 3: The final project was a pilot randomized controlled trial of an omega-3 emulsion. The study demonstrated that the randomized design is a feasible strategy for evaluating lipid based approaches for the prevention of IFALD. A Bayesian preliminary assessment of the results of the trial, suggests a high likelihood that the trial will demonstrate a difference between the conventional and omega-3 emulsion evaluated in the trial. However, since the analysis was blinded, the direction of the difference is not known. Conclusion: This thesis will contribute to the design and analysis of high quality and feasible randomized trials that will allow investigators to address the optimal lipid based approach to the management of IFALD.

Keywords: Intestinal Failure
Clinical Trials
Parenteral Nutrition
Intestinal Failure Associated Liver Disease
Omega-3 fatty acids
Bayesian Statistics
Advisor: Feldman, Brian M.
Wales, Paul W.
Promyelocytic Leukemia Nuclear Bodies: A Meeting Place For Genomic Loci

The nucleus is a highly compartmentalized organelle where specific cellular activities are confined to discrete domains. One such domain is the promyelocytic leukemia nuclear body (PML NB). PML NBs are protein-based structures that make numerous contacts with neighboring chromatin domains. To elucidate the function of PML NBs, research has been focused on identifying the protein complement of PML NBs. More than 60 proteins have been shown to localize to PML NBs, implicating the bodies in numerous cellular activities such as transcription regulation, apoptosis, tumor suppression, and the antiviral response. This approach has not yielded a general model for PML NB function. Instead I have chosen to focus on the chromatin contacts made with PML NBs. Using live-cell microscopy, my observations support the hypothesis that changes in chromatin topology affect the structural integrity of PML NBs. Moreover, I have developed a technique, called immunoTRAP, which allows for the extraction of chromatin specifically associated with PML NBs. Analysis of these chromatin associations reveal that specific genes associate with PML NBs and these associations are cell type specific. Therefore, PML NBs make specific contacts with neighboring chromatin domains and these contacts are integral to PML NB morphology. Thus making PML NBs a meeting place for a specific set of genomic loci.

Keywords: chromatin organization
nuclear structure and function
Advisor: Bazett-Jones, David
Development of Microfluidic Devices for Drug Delivery and Cellular Biophysics

Recent advances in micro technologies have equipped researches with novel tools for interacting with biological molecules and cells. This thesis focuses on the design, fabrication and application of microfluidic platforms for stimuli-responsive drug delivery and the electromechanical characterization of single cells. Stimuli-responsive hydrogels are promising materials for controlled drug delivery due to their ability to respond to changes in local environmental conditions. In particular, nanohydrogel particles have been a topic of considerable interest due to their rapid response times compared to micro and macro-scale counterparts. Owing to their small size and thus low drug-loading capacity, these materials are unsuitable for prolonged drug delivery. To address this issue, stimuli-responsive implantable drug delivery micro devices by integrating microfabricated drug reservoirs with smart nano-hydrogel particles embedded composite membranes have been proposed. In one proposed glucose-responsive micro device, crosslinked glucose oxidase enables the oxidation of glucose into gluconic acid, producing a microenvironment with lower pH values to modulate the pH-responsive nanoparticles. In vitro glucose-responsive drug release profiles were characterized and normoglycemic glucose levels in diabetic rats with device implantation were also recorded. The biophysical properties of single cells have recently been demonstrated as an important indicator of disease diagnosis. Existing technologies are capable of characterizing single parameter either electrical or mechanical rapidly, but not both, which could only collect limited information for cell status evaluation. To address this issue, two microfluidic platforms capable of simultaneously characterizing both the electrical and mechanical properties of single cells based on electrodeformation and integrated impedance spectroscopy with micropipette aspiration have been proposed. In one proposed microfluidic device, a negative pressure was used to suck cells continuously through the aspiration channel with impedance profiles measured. By interpreting impedance profiles, transit time and impedance amplitude ratio can be quantified as cellular mechanical and electrical property indicators. Neural network based cell classification was conducted, demonstrating that two biophysical parameters could provide a higher cell classification success rate than using electrical or mechanical parameter alone.

Keywords: Microfluidics
Controlled Drug Delivery
Cellular Biophysics
Single-Cell Analysis
Diabetes
Cancer
Advisor: Sun, Yu
Novel Molecular Mechanisms Controlling Pancreatic β-cell Function and Hepatic Glucose Homeostasis

The key defects characteristic of hyperglycemia in T2D include increased hepatic glucose production, a diminution of insulin secretion, and an absolute impairment in peripheral insulin action. The objective of my thesis was to investigate the molecular mechanisms leading to fatty acid induced β-cell dysfunction and determine the role of a novel transcriptional coregulator in the regulation of hepatic glucose homeostasis. The first part of my work focused on the chronic effects of fatty acids on human pancreatic β-cell function. Using microarray technology I established an important role for fatty acids in the pathogenesis of β-cell dysfunction. Accordingly chronic exposure of islets to oleate resulted in a significant reduction in glucose-stimulated insulin secretion and to an increase in the rate of reactive oxygen species generation. Additionally, pre-treatment of human islets with oleate led to a significant increase in the rate of oxidation of this fatty acid and to a significant decrease in glucose oxidation. My data indicate that chronic exposure of human islets to fatty acids activates inflammatory and metabolic pathways that lead to oxidative stress. In addition, the first part of my work demonstrated that fatty acids induce oxidative stress in vitro an effect that is preventable to a large extent by the use of antioxidants. In this setting and recapitulating the human islet data, fatty acids are causally linked to impaired insulin secretion, and the induction of oxidative stress. Our report demonstrated that oxidative stress plays a key role in the decrease in β-cell function induced by chronic lipotoxicity. My work also demonstrated that fatty acids are causally linked to the induction of endoplasmic reticulum stress in human islets. Finally, in the second part of my work I provide novel evidence for the role of PHIP in the regulation of hepatic gluconeogenesis. My work is the first to demonstrate that PHIP suppresses hepatic gluconeogenesis in vitro and in vivo. PHIP is amongst the few proteins that have ever been reported to suppress gluconeogenesis to date. PHIP thus represents a novel target for pharmaceutical intervention of diabetes and the suppression of hepatic glucose production.

Keywords: Pancreas
Liver
Transcription
Free fatty acids
Advisor: Rozakis-Adcock, Maria
Control of Adult Bone Marrow Erythroid Progenitor Cell Fate by Combinatorial Niche Factor Signals

Stem and progenitor cell fate (self-renewal, proliferation, survival, differentiation) is tightly controlled by niche factors and the interplay of these factors is particularly important to comprehend for the development of stem cell therapies. During erythropoiesis, erythroid progenitors at the colony forming unit-erythroid (CFU-E) stage are responsive to both stem cell factor (SCF) and erythropoietin (EPO); however, the joint action of SCF and EPO in these cells and the underlying mechanisms remain to be defined. In this study, quantitative data on the activation of signaling pathways and gene expression profiles provided definitive evidence for two parallel but complementary mechanisms that resulted in enhanced generation of red blood cells from mouse bone marrow-derived CFU-E culture in the presence of SCF and EPO. First, SCF and EPO signaling intersected within the extracellular signal-regulated kinase (ERK) pathway and the sustained ERK activation was required for the maximal changes in the expression levels of genes that are involved in the proliferation and survival of CFU-Es. Second, the apparent competition between SCF and EPO in regulating c-Kit expression was found to have a dramatic impact on the terminal differentiation of CFU-Es. The latter mechanism was, for the first time, reported in a primary cell system. In addition, a fetal liver-derived conditioned medium further enhanced the survival and proliferation of bone marrow CFU-Es in the presence of SCF and EPO by not only increasing the ERK signaling duration but also, the amplitude. The agents present in the conditioned media possess significant clinical potential to stimulate erythropoiesis both in vivo and in vitro. In conclusion, our study has provided novel insights into the mechanisms by which combinations of niche factors control the fate of erythroid progenitors at a unique transitional stage and highlighted the important role of the ERK signaling dynamics in adult erythropoiesis.

Keywords: stem cell fate
red blood cell differentiation
niche factor
cell signaling
single-cell analysis
flow cytometry
Advisor: Audet, Julie
The Role of TNFR Family Members GITR and CD30 on CD8 T Cell Responses

GITR and CD30 are T cell costimulatory members of the TNFR superfamily known to regulate T cell responses. Elucidating the mechanisms whereby these receptors modulate T cell responses is crucial for maximizing their potential for immunotherapy. In this thesis, I examine the role of GITR and CD30 on CD8 T cell responses to influenza virus. I show that CD8 T cell intrinsic GITR is required for both maximal primary and secondary CD8 T cell expansion to influenza, while in contrast, CD30 is dispensable for anti-influenza CD8 T cell responses. GITR does not impact on CD8 T cell proliferation or homing, however, it mediates CD8 T cell survival signaling. GITR induces TRAF2/TRAF5 dependent, but TRAF1 independent, NF-κB activation, resulting in the upregulation of the pro-survival molecule Bcl-xL. Furthermore, I show that GITR on CD8 T cells can augment viral clearance and confer protection from death upon severe influenza infection of mice. Similarly, CD30 also elicits protection from death upon severe influenza infection, although the cells responsible for this effect remain to be elucidated. In this thesis, I also show that in unimmunized mice GITR expression is upregulated to higher than basal levels on a population of CD8 memory phenotype cells in the bone marrow. In contrast, CD8 memory phenotype T cells in the spleen and LN have GITR levels similar to that on naïve T cells. The upregulation of GITR in the bone marrow is IL-15 dependent and therefore, GITR serves as a marker for cells that have recently received an IL-15 signal. Furthermore, GITR is required for the persistence, but not for the homeostatic proliferation of CD8 memory phenotype T cells in the bone marrow. Therefore, GITR plays a key role for CD8 T cell intrinsic responses to influenza, as well as for the persistence of CD8 memory phenotype T cells.

Keywords: CD8 T cell
GITR
influenza
T cell memory
CD30
costimulation
TNFR superfamily
Advisor: Watts, Tania
Medial Temporal Lobe Function and the Perceptual Richness of Memory for Complex Personal and Laboratory Events

Reliving the past requires the integration of multi-modal sensory details into a coherent mental impression of the initial event. In most people, memory for life episodes, or Autobiographical Memory (AM), is rich in sensory-perceptual elements that provide the vivid impression of travelling back in time. Abundant evidence indicates that the hippocampus plays a central role in AM recollection, but much research is still needed to determine which AM attributes engage the hippocampus at retrieval. My work assessed the relationship between hippocampal function and the perceptual richness of memory episodes. I designed a paradigm that captured the complexity of AM, and that manipulated perceptual richness while controlling for other AM confounds, such as recency, rehearsal, personal relevance, and “story” content. Participants studied and recalled perceptually enriched and impoverished laboratory events (film clips and written narratives, respectively) matched for the complexity of their storyline. An AM condition was also included for comparison. I tested healthy individuals and participants with unilateral medial temporal lobe epilepsy (mTLE), a clinical population with well documented hippocampal damage, on this paradigm. Perceptual richness was greatly reduced in people with mTLE, an effect that was most salient in the perceptually enriched conditions (AM and film clips). In a functional MRI version of this paradigm conducted on healthy individuals, I identified neural regions sensitive to the perceptual richness of AM and laboratory events, which included the anterior portion of the right hippocampus and other regions known to play a role in imagery and visual processing. In patients with right-lateralized mTLE, activation in these brain regions was markedly reduced in all memory conditions, which was consistent with the reduced perceptual richness I observed behaviourally. I reveal a clear relationship between hippocampal function and the perceptual richness of episodic memory, suggesting that the hippocampus plays a central role among brain regions that support the integration of multi-modal details into enriched memory experiences. My findings also advance our knowledge of how pathology and the nature of memory representation affect the neural correlates of episodic memory.

Keywords: memory
episodic
hippocampus
epilepsy
functional magnetic resonance imaging
recollection
Advisor: Moscovitch, Morris
McAndrews, Mary Pat
The Benefit of Capacity Pooling for Repairable Spare Parts

Capacity pooling in production systems, in the form of production capacity or inventory pooling, has been extensively studied in the literature. While production capacity pooling has been proven to be beneficial, the impact of inventory pooling has been less significant. These results cannot be easily extended to repairable systems due to fundamental differences between repairable and production systems. For one thing, in repairable systems, the demand rate is a function of the number of operational machines, whereas it is exogenous and constant in production systems. In this Thesis, to serve different fleets of machines possibly at different locations, we study whether repair shop pooling is more cost effective than having dedicated on-site repair shops for each fleet. In the first model, we consider transportation delays and related costs, which have been traditionally ignored in the literature. We include on-site spare-part inventories that operate according to a continuous-review base-stock policy. Our numerical findings indicate that when transportation costs are reasonable, repair shop pooling is a better alternative. Next, we model a pooled repair shop that fixes failed components from different k-out-of-n:G systems. We permit a shared spare parts inventory serving all systems and/or reserved spare parts inventories for each system; we call this a hybrid model. The destination for a repaired component can be chosen either on a first-come-first-served basis or by following a static priority rule. Our findings show that both hybrid policies are more cost effective than having separate repair shops and inventories for each system. We propose implementing the multilevel rationing (MR) policy in systems with shared inventory. The MR policy prioritizes classes, and stops serving a class from inventory if the inventory level is below the inventory threshold identified for that class. When there is no inventory, the repaired component is sent to the highest priority class among those with down machines. To approximate the cost of the MR policy, we study an M/G/1//N queueing system serving multiple classes of customers with an unreliable server. Our numerical findings indicate that the MR policy performs as well as the epsilon-optimal policy and outperforms the hybrid policies.

Keywords: Queueing Theory
Stochastic Processes
Spare Parts Provisioning
Maintenance
Capacity Pooling
Advisor: Balcioglu, Baris
Reflecting the Other: The Thing Poetry of Marianne Moore and Francis Ponge

Across continents and independently of one another, Marianne Moore (1887-1972) and Francis Ponge (1899-1988) both made names for themselves in the twentieth century as poets who gave voice to things. Their entire oeuvres are dominated by poems that attempt to reconstruct an external thing (inanimate object, plant or animal being) through language, while emphasizing the necessary distance that exists between the writing self and the written other. Furthermore, their thing poetry establishes an “essential otherness” to the subject of representation that (ideally) rejects an objectification of that subject, thereby rendering the “thing” a subject-thing with its own being-for-itself. This dissertation argues that the thing poetry of Marianne Moore and Francis Ponge successfully challenged the hierarchy between subject and object in representation by bringing the poet’s self into a dialogue with the encountered thing. The relationship between the writing self and the written other is akin to what Maurice Merleau-Ponty refers to in Le visible et l’invisible when he describes the act of perceiving what is visible as necessitating one’s own visibility to another. The other becomes a mirror of oneself and vice versa, Merleau-Ponty explains, to the extent that together they compose a single image. The type of reflection involving self and others that Moore and Ponge employ in their thing poetry invokes the characteristically modern symbol of the crystal with its kaleidoscopic reflective properties. Self and other are distinct yet indissolubly bound, and rather than a hierarchy between subject and object there are only subjects who exist for-themselves and for-each other, reflecting the kind of reciprocal Pour soi that Merleau-Ponty’s phenomenology envisioned.

Keywords: Modernism
Poetry
Alterity
French literature
American literature
Advisor: Li, Victor
Michelucci, Pascal