VictorJuiz/thesis huggingface dataset:
Fundamental Studies of the Physics of an Argon Microcavity Discharge
Keywords: Electrical discharges
Microcavity discharges
Microdischarges
Microplasmas
Silicon microcavity discharges

Simulations of DC microcavity discharges in Ne predict that they are sustained by high energy (beam) electrons, which dominate at low pressure(< 500 Torr). Additional analytical studies of beam-dominated, cold-cathode discharges have identified three primary populations of the electron energy distribution: low-, mid- and high-energy electrons, with only the latter two contributing to the external current. Simulations are conducted in this thesis using COMSOL alongside data from the LXCat plasma database to compute important parameters. It is found that fields are ~10 Vμm-1, while the mean free path lengths of various processes are ~ 10 - 1000's of μm, therefore comparable to microdischarge dimensions. This implies a large rate of loss of energetic electrons as well as a pressure-dependent preference for particular reactions (depending on the gas, ionization rather than excitation). These insights are used to investigate DC microdischarges, which are fabricated as 3×3 arrays of 20×20 μm2 microcavities in silicon using standard semiconductor processing. An effective and reproducible protocol for the residue-free etching polyimide PI 2611 using standard reactive ion etching and an O2/N2 chemistry has been developed. Experiments have been conducted in Ar/air, under varied pressure conditions. Emission from N2(C3Πu) - N2(B3Πg) (N2(C-B)) nitrogen second positive system (SPS) is used as the probe, showing a progressive diminution of the N2( C-B) signal attributed to the decrease in the Ar excitation rate due to the increased population of beam electrons. Voltage-current measurements also reveal characteristics consistent with behaviour expected from the population model of segregated mid- and high-energy electrons. A diatomic ro-vibrational model has been developed based on the Dunham expansion to simulate the N 2(C–B) (0-0) transition. Fits to the spectral data have been used to extract rotational temperature, Trot, whose behaviour under different pressure conditions has been examined. Trot ranges from room temperature to ~1100 K. Trot is found to be least (~ 300 K and flat) at the highest pressure investigated (272 Torr). Other pressures show a gradual increase with applied voltage. A puzzling instability is found at ≥ 300 Torr, unexpected from the literature. Several possible reasons are proposed, but no definitive explanation is currently known.
Chemoprevention in Kidney Cancer
Keywords: carcinoma
renal cell
drug utilization
HMG-CoA reductase inhibitor
humans
pharmacoepidemiology

Background: This thesis is a composition of three studies that explore the role of statins in kidney cancer. Furthermore, I evaluate the potential for different interpretations from the same data depending on the method of classifying medication use. Methods: The first study was a population-based case-control study evaluating the association of statin use with risk of incident kidney cancer. The second study was a systematic review and meta-analysis reviewing the current evidence relating statins with kidney cancer survival outcomes. The final study was a population-based cohort study evaluating the association of statin use with survival. In the observational studies, I used fractional polynomials for the primary analysis to allow for a non-linear relationship between cumulative exposure and the risk of the outcome. I also compared risk estimates obtained by different methods of classifying medication exposure. Results: The population-based case-control study included 10,377 incident cases of kidney cancer and 35,939 matched controls. Increasing cumulative use of statins was not associated with kidney cancer risk. I identified 12 studies for inclusion in the systematic review and meta-analysis and found that statin use was significantly associated with markedly improved cancer-specific and overall survival. However, none of these studies evaluated cumulative use. In the population-based cohort study of 9124 patients with incident kidney cancer, increasing cumulative use of statins was associated with minimal improvement in cancer-specific and overall survival. The association of statin use with kidney cancer risk or survival varied depending on the method of classifying exposure. Conclusions: This thesis does not support the use of statins for the prevention or adjunctive treatment in kidney cancer. Furthermore, risk estimates in pharmacoepidemiology may be sensitive to the method of classifying exposure.
Bimaterial Lattices With Anisotropic Thermal Expansion
Keywords: Adaptive lattices
Anisotropic thermal expansion
Bimaterial lattices
Thermal switch
Thermal valve
Thjermal tweezers

Numerous structures that are used in the aerospace and automobile industries, microelectronics, and civil engineering are subject to large variations of temperature. The deformations caused by temperature can be dangerous because they lead to thermal stresses and failure if materials with mismatched thermal expansion are joined. On the other hand, thermal extensions can be used to achieve desirable displacements in structures. In this work, we use bimaterial lattices made of two materials and empty space that combine low weight with high stiffness and structural robustness. The lattices can serve as adapters that eliminate or mitigate dangerous thermal stresses, as elements for fine tuning in optical systems, or as thermal actuators. To perform these functions, the lattices must be anisotropic, which can be achieved if the lattice consists of non-identical anisotropic cells. Each cell is composed of an irregular triangle made of one material surrounded by a skewed hexagon made of another material. The overall performance of the lattice is defined by six hexagon skew angles and the ratio of the two coefficients of thermal expansion (CTEs) of the lattice materials. The cells are connected to adjoining cells at three points; changes in the distances between these points as a function of temperature can be tailored. The primary goal of the research is to elaborate general principles and algorithms to design lattices, select material, and improve structural efficiency. Several adaptive lattices are designed including a polygonal ring connector to prevent distortion in cylindrical optical components, a lattice preventing shaft and collar sticking, and lattices controlling the total deflection of two substrates. Lattices providing predetermined displacements in desirable directions have been studied, and it was demonstrated that different temperature supplied to different cells of a polygonal ring connector can be used for fine tuning of optical lenses. Finally, thermal actuators - a switch, tweezers, and a valve - are designed. In terms of overall performance, the actuators are slow but do not exhibit hysteresis: their thermal expansion depends on temperature but not on preceding thermal history. The forces and deflections they achieve compare favorably with piezoelectrics and shape memory alloys.
Physiological Roles of the XB130/Tks5 Scaffold Protein Interaction for the Regulation of Cell Homeostasis
Keywords: AFAP1L2
Airway epithelial cells
Cell motility
SH3PXD2A
Signal Transduction
Tyrosine kinase signaling

XB130 is a scaffold protein that regulates cell growth, survival and migration by forming dynamic complexes with other proteins that mediate signal transduction cascades for the regulation of cell function. Yeast two-hybrid screening identified another scaffold protein, tyrosine kinase substrate 5 (Tks5), as XB130’s top putative binding partner. We hypothesized that as scaffold proteins, XB130 and Tks5 interact to facilitate the formation of distinct molecular complexes for the mediation of signal transduction, which is required for the regulation of cellular processes, like growth, survival and migration for cell homeostasis. In the present study, we characterized the structural interaction between XB130 and Tks5 by demonstrating that XB130 N-terminal polyproline rich motifs bind to a WWY ligand binding motif in the 5th SH3 domain of TKS5. Tks5 is a well studied protein in cell migration processes. This study demonstrated that Tks5 plays a role in cell proliferation and survival of airway epithelial cells. Additionally, the XB130/Tks5 interaction was shown to regulate cell proliferation, growth and survival via EGFR/Src/PI3K signaling. Surprisingly, we discovered that XB130 and TKS5 play contrasting roles in cell migration; XB130 promotes lamellipodia formation and lateral cell migration, whereas TKS5 promotes podosome formation and extracellular matrix degradation for cell invasion. Consequently, XB130 was shown to dissociate from TKS5 to interact with Rac1 for the assembly and activation of the Rac1/PAK/WAVE2 lamellipodia pathway, whereas, Tks5 mediates the Cdc42/PAK/N-WASP podosome pathway for regulation of stimulus-dependent cytoskeletal rearrangement and cell morphology changes. In conclusion, the dynamic relationship between XB130 and TKS5 facilitates distinct protein-protein interactions and complex formation for the mediation of signal transduction and regulation of cell proliferation, survival and motility. Our data suggests that these dynamic scaffold protein interactions may be a common mechanism for proteins to form unique signaling complexes that facilitate the regulation or enhancement of different physiological or pathophysiological conditions.
The Ontology, Etiology, and Moral Psychology of Action: Aristotle and Today
Keywords: Action
Ancient Philosophy
Aristotle
Causation
Responsibility

Aristotle’s theory of action answers two central questions in Action Theory today: What causes action? What role do psychological attitudes play in action? Chapter 1 dispels misunderstandings about Aristotle’s theory of causation. Influential interpretations assume that Aristotle’s material, formal, and final causes are explanatory only as constituents of an efficient-causal event, and that all efficient causes are productive. Productive efficient causes are those for which the effect is numerically distinct from the causal activity of the cause. Aristotle makes neither assumption. Instead, he thinks that some efficient causes are not productive, and that material, formal, and final causes are explanatory in their own right rather than as constituents of efficient-causal events. Chapter 2 argues that Aristotle countenances four causes of action: Agents’ bodies are material causes of their self-movements, their occurrent psychological attitudes (such as desire and decision) are formal causes, agents themselves, as self-movers actualizing a particular potentiality, are efficient causes, and agents’ goals are final causes. This view challenges the prevailing assumption that psychological attitudes are efficient causes of actions. They are instead formal causes—paradigms for acting and parts of what defines the sort of action that the action is. Aristotle’s four-causal view makes progress in addressing problems for recent theories of action. Chapter 3 treats Davidsonian and Anscombean theories, the most prominent. Davidsonians face the problem of deviant causal chains (where psychological attitudes cause actions accidentally) and of the disappearing agent (the agent herself plays no role identifiable as agency). Anscombeans encounter the problem of deviant formal causation (a foreseen side-effect is wrongly counted by the theory as part of the intended aim) and of disappearing agency (without appeal to psychological attitudes, it is difficult to account for agential control). Aristotle's account makes headway on these problems. Chapter 4 treats constitutivist theories, which insist that agential control over action is at least partially constitutive of the action rather than a matter of antecedent efficient causes. Existing constitutivist accounts misconceive the causal role or range of psychological attitudes that are relevant for agential control. Constitutivists can advance by understanding psychological attitudes as Aristotelian formal causes of action.
Tranexamic Acid Modulation of Excitatory and Inhibitory Amino Acid Receptors: A Potential Mechanism for Postoperative Seizures
Keywords: Glycine
Ion channels
Seizures
Tonic current
Tranexamic acid

Tranexamic acid (TXA) is an antifibrinolytic drug that is used worldwide to reduce blood loss in a variety of hemorrhagic conditions. TXA causes seizures and myoclonic spasms, particularly during the postoperative period, and these seizures are associated with a higher incidence of neurological complications, longer recovery times, and higher mortality rates. The molecular mechanisms underlying TXA-associated seizures remain poorly understood and there are no effective treatment or prevention strategies. One potential mechanism by which TXA may give rise to seizures is by shifting the balance between excitatory and inhibitory neurotransmission. Specifically, TXA could promote hyperexcitability by enhancing the function of excitatory amino acid receptors (NMDA, AMPA, and kainate receptors). Alternatively, TXA could cause disinhibition by reducing the activity of inhibitory receptors (GABA and glycine receptors). The purpose of this thesis is to identify molecular targets that are sensitive to clinically relevant concentrations of TXA. TXA is a structural analogue of the amino acid glycine. Thus, we hypothesized that TXA acts as an agonist at the glycine binding site of the NMDA subtype of glutamate receptor. Alternatively, we postulated that TXA acts as a competitive antagonist of the glycine receptor. Further, we postulated that drugs that reverse TXA actions on excitatory or inhibitory receptors can be used to mitigate or prevent TXA-associated seizures. First, we determined the clinically relevant concentrations of TXA by measuring drug levels in the cerebrospinal fluid (CSF) of patients. We found that peak TXA concentration in the CSF of patients was 200 ÎźM. Next, we showed that TXA 200 ÎźM was sufficient to increase network excitability in cortical slices and reduce the resting membrane potential in mouse neurons. TXA had no effect on excitatory receptors at clinically relevant concentrations. Conversely, TXA competitively inhibited both GABAA and glycine receptors but the potency of TXA was highest for glycine receptors that generate a tonic inhibitory current. Finally, the general anesthetics isoflurane and propofol reversed TXA-mediated inhibition of glycine receptors and attenuated the effect of TXA on network excitability. Collectively, these results identify a potential mechanism for TXA-associated seizures and drugs that could be used to treat or prevent seizures.
THE PECULIAR FAMILY BUSINESS OF FAMILY CHILD CARE: POLICY AND REGULATION AFFECTING EMOTIONAL LABOUR IN CAREGIVING
Keywords: family child care
family day care
funding model in family child care
home visitors in family child care
Ontario foster care to family child care

In Ontario, Canadaâ s licensed family child care system, there is a dissonance between expectations embedded in state-licensed family child care regulation and policy, and the lived experience of regulated family child care providers. Gender, social class and more recently, race/ethnicity intersect to exacerbate complicated working conditions for the care providers leading to poor recognition and financial compensation from both parents and the state. I have combined an analysis of the historical development of the care model with my own qualitative investigation of the everyday experience of 11 regulated care providers in Toronto, their material circumstances and the emotional labour they invest in caring for young children. Detailing the historical development of the system shows that the core elements of the contemporary care model can be traced through its child welfare lineage dating from 19th century child saving, and from foster care to family child care, which remains largely unchanged since the inception of regulation in 1978. The elements I have examined are the role of the mandatory home visitor in relation to the care provider and their occupational segregation; the bureaucratic expectations of the state as implemented in a private domain; and the social construction of the care provider as someone who requires surveillance to provide quality care for children, particularly because of her vulnerable location as a low-income, self-employed worker. I have identified these elements for discussion to support a case for change in the contemporary care model. Poor recognition and compensation have been compounded by the deeply entrenched funding model dependent on child care fee subsidies to parents. This circular challenge of an outdated funding model supporting outdated gendered assumptions about a care model is at the heart of the puzzle to solve for jurisdictions that have foisted self-employment on regulated care providers working in their own homes. I conclude with policy and research recommendations for licensed family child care agencies and the Ontario government.
"It hath no bottom" and is "beyond beyond": Shakespeare on the Mystery of Love
Keywords: Early Modern
Love
Religion
Shakespeare
Subjectivity
Theatre

Abstract This thesis examines how Shakespeare represents love. Love is resistant to definition because its experience is entirely subjective, yet Shakespeare does not retreat from any attempt to represent selfless love, which contrasts to the more easily comprehended mechanisms and effects of desire. Shakespeare’s works suggest that love can be both eros and agape at the same time. The experience of being in love constitutes one’s subjectivity: these works show that to know oneself is to know what is worth dying for, and in this regard love is stronger than death. This thesis argues that Shakespeare views love as a mystery, yet also as something profoundly real and revolutionary. Shakespeare intersects Christianity’s belief in the mystery of divine love with the experience of romantic and sexual love; he uses theology and the experiences of religious faith to express the possibilities of secular love. Shakespeare makes the sacred secular: he reinvents spiritual love as a human experience, and in turn his works elevate human love and characterize it as a religious experience. Further, these texts suggest that secular love can be an access point for the experience of divine love; that is, human love participates in the divine mystery of God’s love. The transformative possibilities that accompany moments of love are communicated through the mystery of poetry and theatrical performance: it is through artifice and illusion that we are able to understand the experience and meaning of love. In his construction of subjectivity, Shakespeare’s texts suggest that radical selflessness is paradoxically the pathway to becoming most fully the self. This thesis considers both Shakespeare’s dramatic works and his poetry. This dissertation contextualizes Shakespeare’s writing within the larger Christian culture of early modern England and also considers contemporary theory and criticism. The mysteries of love, of faith, and of the possibilities of the imagination do not merely intersect in Shakespeare’s works; these ideas gain meaning and are understood precisely through their intersections.
The Quantification and Prediction of Graduate School Performance
Keywords: Performance
Personality
Psychometrics
Scientometrics

In today’s competitive job market, many students graduate with a bachelor’s degree and move on to pursue higher education in hopes of standing out from the crowd. As the number of graduate students has steadily increased in the recent years, there is also growing interest in understanding how to cultivate successful graduate careers. Surprisingly, there has been little empirical work examining this topic. The current dissertation has two primary aims: 1. to quantify graduate school performance and 2. explore some of the potential predictors of success. Because publication output is believed to be the most valuable metric of success, the primary focus was on publications. Chapter 1 examines the publication trajectories of graduate students, post-doctoral fellows, and junior faculty members to establish a benchmark of success. Junior faculty members had twice the number of publications as post-doctoral fellows, who had twice the number of publications as senior graduate students. Chapter 2 and 3 aim to better accurately quantify a researcher’s scientific output beyond just the number of publications with the introduction of a new bibliometric index called the zp-index. The zp-index, compared to other bibliometric indices, better discriminated the productive output of high-functioning academics. Finally, Chapter 4 identifies potential personality predictors of graduate school performance. Industriousness was a key variable that predicted publication success. Results across the studies provide practical recommendations to apply to the current graduate school system and highlight some potential avenues for future research on this understudied topic.
Systematic Analysis of Protein-RNA Interactions in Drosophila
Keywords: Drosophila embryogenesis
Maternal-to-zygotic transition
Post-transcriptional regulation
RNA-binding protein
RNA cis-regulatory element
Synthetic antibody

Post-transcriptional regulation of gene expression, through the control of mRNA splicing, polyadenylation, nuclear export, localization, translation, and stability, is essential for achieving appropriate temporal and spatial patterns of protein expression. This regulation is mediated by trans-acting factors, such as RNA-binding proteins (RBPs) and non-coding RNAs, which associate with specific mRNA targets through the recognition of sequence- or structure-based cis-elements present in the transcripts. The genomes of most organisms encode hundreds of RBPs, each of which likely associates with hundreds of mRNAs. Thus, a genome-wide view of the regulation being mediated by all trans-factors is essential for a complete understanding of post-transcriptional control. While post-transcriptional regulation is crucial in all biological systems, it has a particularly prominent role during early embryo development, as during this time there is no transcription from the zygotic genome of the embryo, and, thus, gene expression and development is controlled entirely post-transcriptionally. In this thesis, I describe my efforts towards obtaining a global understanding of post-transcriptional regulation in early Drosophila melanogaster embryos, through the development and use of synthetic antibodies as tools to identify, genome-wide, RBP-mRNA interactions. First, I demonstrated that synthetic antibodies generated against RBPs can be used as tools to identify RBP-associated mRNAs through immunoprecipitation-based approaches, or, conversely, to disrupt RBP-mRNA interactions. I then used synthetic antibodies to identify the entire complement of mRNAs associated with 3 developmentally-important RBPs: the double-stranded RBP Staufen, the TRIM-NHL protein Brain Tumor, and the PUF protein Pumilio. Computational analyses of these mRNAs revealed: (1) novel cis-elements likely mediating the mRNA-binding activity of Staufen and Brain Tumor; (2) that, unexpectedly, Brain Tumor and Pumilio function largely independently of each other in early embryos; and, (3) a novel role for Brain Tumor in promoting mRNA decay, which was demonstrated through a transcriptome-wide analysis of mRNA levels in brain tumor mutant embryos. To facilitate a truly genome-wide analysis of RBP-mRNA interactions, we developed a high-throughput pipeline for production of synthetic antibodies, and used this pipeline to generate 279 antibodies against 61 RBPs. In future this pipeline and the antibodies generated will allow for global studies of post-transcriptional regulation.