VictorJuiz/thesis huggingface dataset:
Zebrafish Models of Idiopathic Scoliosis: Cilia, Cerebrospinal Fluid Flow and Neuroinflammatory Origins of Pathogenesis
Keywords: Cerebrospinal Fluid
Cilia
Disease modelling
Idiopathic scoliosis
Wnt signalling
Zebrafish

Adolescent idiopathic scoliosis (IS) is a spine disease characterized by three-dimensional curvatures of the vertebral column that arise in the absence of observable physiological or anatomical defects. Although there has been investigation into genetic components of IS, the cell biological and molecular mechanisms underlying disease progression remain unclear. Our lab has previously described the first genetically defined developmental model of IS in ptk7 mutant zebrafish. Zygotic ptk7 mutant zebrafish display hallmark phenotypes of the human disease, including 3-dimensional rotational spinal deformities, late onset for curve formation and sexual dimorphic bias in phenotype severity. These fish are defective in a key modulator of Wnt signalling, implicating this pathway in the onset of disease. Wnt signalling controls the biogenesis, localization and polarized architecture of motile cilia, which are essential for proper cerebrospinal fluid (CSF) flow. I found that ptk7 mutants display a late-onset ependymal cell motile cilia phenotype that was directly associated with spinal curve formation. Live imaging of CSF dynamics within the brain ventricles revealed uncoordinated flow, transgenic re-introduction of Ptk7 in motile ciliated lineages prevents scoliosis in ptk7 mutants, and mutation of multiple independent cilia motility genes also yield IS phenotypes. To identify underlying mechanisms of disease, I used lineage tracing, conditional genetic methodologies and next generation sequencing to define a spatial and biological origin of spinal curve formation in ptk7 mutant zebrafish. Strikingly, I found that ptk7 is expressed and specifically required within the brain for normal spine development and CSF homeostasis. Downstream of brain-derived CSF regulation, I uncovered an unexpected upregulation of immunogenic factors suggesting that spinal curvature may be due to a neuroinflammatory response to defective CSF homeostasis. I found that focal activation of proinflammatory signals within the spinal cord is sufficient to initiate idiopathic-like spinal curvature. Together, these data suggest that Wnt-directed motile cilia function is required for proper adolescent spine development, and that neuroinflammatory signals downstream of disrupted homeostatic CSF integrity can initiate spinal deformity.
Influence of Drug-polymer Interactions on Drug Transport of Pharmaceutical Polymer Materials
Keywords: Controlled release
Drug-polymer interaction
Drug transport
Pharmaceutical material

Interactions between drugs and polymers strongly influence the properties, functionality, and permeability of the polymers, and thereby the kinetics of drug transports. The effects of drug-polymer interactions, specifically ionic bonding between ionized drugs and polymers, were investigated in four different polymeric systems and a multifunctional terpolymeric nanoparticle was developed for three different applications: enteric coating for delayed release; microenvironmental pH (pHm) modifier for pH-independent release; and alcohol-resistant material for mitigation of alcohol-induced dose dumping. A mathematical model based on diffusion and ion exchange reaction was derived to describe drug transport of pharmaceutical polymeric films and coating in a finite volume. The model predictions strongly agreed with experimental data of drug loading into Eudragit® RS/RL films. The results demonstrated that transport of anionic drugs in Eudragit® RS/RL polymer-based dosage forms follow diffusion and ion exchange kinetics. A pH-sensitive nanoparticle (TPN) was developed as a new enteric pore former in an ethylcellulose (EC) coating system with superior properties compared to conventional pore formers. Compared to conventional water-soluble pore formers, TPNs demonstrated very low impact on viscosity of EC dispersions, minimal leaching, suitable mechanical properties, and highly pH-dependent permeability. To achieve pH-independent release of weakly basic drugs, TPN was employed as a pHm modifier by incorporating it into EC matrices loaded with verapamil HCl. The results indicated that swelling was not the primarily release mechanism and that ion exchange played a significant role, especially at higher pore former level of TPN. TPN was further developed as an alcohol-resistant material for mitigation of alcohol-induced dose dumping. TPN-EC films showed reduced drug release in alcoholic media for several ionized weakly basic drugs due to ion-dipole interactions between drugs and PMAA groups of TPN. The mathematical model and polymeric materials developed in this work presents significant contributions to the field of pharmaceutics.
Multinational Enterprises as Institutional Entrepreneurs: Directed and Diffused Institutional Strategies and Development
Keywords: development
institutional entrepreneurship
institutions
multinational enterprises

How institutions are improved is the Achilles’ heel of institutional reform. In the development agenda, institutional reform has been consigned to host states, with the help of international development agencies and international financial institutions. The multinational enterprise (MNE) is often seen as an opportunistic agent that avails itself of institutional fragilities for its own gain and rarely as an institutional change agent for development. This thesis explores when and under what circumstances it is likely for MNEs’ institutional work through the creation, maintenance, and disruption of institutions in host countries to advance the broader social welfare of the host country and not only the MNEs’ best interests. Using a multidisciplinary approach, this dissertation presents a conceptual framework and argues that MNEs engage in a range of actions of institutional work strategies. At the end point of this range are two overarching types of institutional work—directed and diffused institutional entrepreneurship. Directed institutional entrepreneurship occurs when the MNE targets one specific local institution and actively engages with it. In contrast, diffused institutional entrepreneurship is widespread, and the MNE’s institutional entrepreneurship can be seen throughout a constellation of institutions. As MNEs act using such institutional work strategies, this dissertation further proposes three conditions that increase the likelihood of positive advancement in the social welfare of the host country. The first is the robustness of the home country’s institutional quality, the second is the types of institutions that are targeted by the MNE when it engages in institutional work, and the third is the type of ally that the MNE brings on board to assist in its institutional work endeavours. To strengthen the conceptual arguments presented in this thesis, four examples of directed and diffused institutional entrepreneurship based on investments by two MNEs—Vale S.A. and Rio Tinto plc. in the Global North and the Global South—are offered.
Dramaturging Research, Shaping Encounters: Working Methods and Dramaturgical Structures in Contemporary Canadian Documentary Theatre
Keywords: Autobiography
Canadian
Documentary
Dramaturg
Dramaturgy
Theatre

This dissertation examines documentary theatre as a genre that models ways of interacting with “strangers” and interrogates what ethics of encounter are being modeled for spectators in contemporary Canadian documentary theatre. It builds on extant studies that examine documentary plays as finished products (i.e., Martin, Tomlin), extending the line of inquiry to examine the range of working methods employed in researching, writing, and rehearsing documentary theatre. Connecting process with product allows this dissertation to connect dramaturgy as a verb (the act of crafting a play) with dramaturgy as a noun (the “aesthetic architecture” of the script) (Chemers 3). It also allows me to analyse these plays as examples of “strange encounters” such as those detailed by Sara Ahmed. In Strange Encounters, Ahmed outlines how, to avoid stranger fetishism that locates strangeness in the body of the other, one must focus on the mechanisms that govern one’s encounter with this potential stranger. By turning my attention to the plays’ dramaturgy, rather than their supposed “authenticity”, this dissertation examines the rehearsal hall and the theatre as mechanisms that govern our encounters with the potentially “strange” subjects of documentary theatre. This study examines four case study companies, Rare Theatre, Human Cargo, Project: Humanity, and Porte Parole. Each company was selected for their mandates to produce documentary work, the popularity of their recent works, and their emergent commitments to mentorship, workshops, and company expansion. Personal interviews with playwrights, dramaturgs and directors illuminate these companies’ working models while dramaturgical analyses of these companies’ plays examine how the dramaturgy “casts” the audience in relation to the research subject. Analysis also explores how familiar theatrical conventions or tropes, such as the journey narrative or confessional direct address, shape what kind of encounter the spectator is encouraged to have with the documentary research subject or, at times, with the researcher/playwright.
Transcriptional Regulation of the foraging Gene and its Associated Behaviours
Keywords: behaviour
epigenetics
gene regulation
genetics
pleiotropy

The genetic underpinnings of animal behaviour are exceedingly complex. The behavioural effects of a gene often depend on environmental conditions, as the ability to adjust to new conditions is essential for fitness. Furthermore, genetic background can affect behaviour, introducing additional variability in behavioural responses. To complicate the study of behavioural genetics further, many genes that regulate behavioural phenotypes are themselves very complex genes, with several gene products and functions. One example of such a complex gene is the foraging gene in Drosophila melanogaster, which encodes a signaling protein that is involved in regulating many phenotypes, including feeding behaviour, metabolism, learning and memory, and sleep. foraging has four promoters, twenty-one transcripts, and nine distinct open reading frames (ORFs). The putative FOR isoforms encoded by these ORFs share the same 3’ protein kinase domain and cGMP binding domains but differ in their subcellular localization and self-regulatory domains. This complex molecular structure allows for the production of different gene products at different times in different tissues, likely using different transcriptional regulators. This thesis examines different mechanisms of transcriptional regulation of the foraging gene and the role of those mechanisms in Drosophila behaviour. Using gene expression measurements, behavioural assays and transgenic tools I investigate the regulatory underpinnings of differences in adult Drosophila feeding behaviour, and larval food-related behaviours. The results provide a complex picture of pleotropic behavioural regulation by different products generated by a single gene. I found that strain differences in adult, but not larval, feeding behaviour are regulated by the transcriptional regulator G9a, a histone methyl transferase which differentially methylates foraging’s promoters. Select larval food-related behaviours are under regulation by Pumilio, an mRNA binding protein that binds the 3’ UTR of foraging mRNA transcripts. Furthermore, I show that foraging and its transcriptional regulators play a role in the behavioural response to nutritional stress. Collectively, my thesis provides new insights into the complex molecular mechanisms (genetic, epigenetic and post-transcriptional) that underlie the regulation of behavioural pleiotropy of foraging, a complex gene.
Soviet Mathematics Curriculum Reforms (1958-1985): Redefining the Purpose of Mathematics Education
Keywords: history of mathematics education
Kolmogorov
Mathematics education
New Math
USSR history
USSR mathematics

ABSTRACT This thesis is a study of the major mathematics education reforms that took place in the period from 1958 to 1985 in the USSR, and are referred to as Kolmogorov’s reforms, after the prominent mathematician and educator Professor Andrei Kolmogorov. The thesis examines the political and intellectual factors that influenced the designers of the new curriculum. The Soviet Union was in competition with the United States in 1958, when a general education reform was launched by Nikita Khrushchev’s government. This reform was intended to bridge the gap between theoretical and practical skills, and prepare students for entering postsecondary study and the workplace. Kolmogorov was influenced by Khrushchev’s reforms, although his revision of the mathematics curriculum differed in philosophy and emphasis from those reforms. The mathematics reforms were spearheaded by accomplished researchers who were strongly influenced by the character of modern mathematics. The Kolmogorov curriculum included the introduction of set theory at a fairly stage, a deductive logical approach, and a stronger focus on the abstract and conceptual character of mathematics. In certain respects, the curriculum resembled the famous new mathematics movement in American education in the 1960s. The Soviet curriculum was fully implemented only in the 1970s. The authors of the new curriculum had experience in teaching mathematically gifted youth, and were involved in special schools established for them. Although the Kolmogorov curriculum was intended in principle for anyone wishing to learn mathematics, it turned out to be unsuitable for the broad range of students. Student grades in mathematics dropped and performance on mathematics entrance examinations to postsecondary institutions declined. In the later 1970s criticisms of the new curriculum mounted from both teachers and academic mathematicians. Kolmogorov’s reforms were replaced with counter reforms, advocated by senior professors of mathematics and educators Ivan Vinogradov and Lev Pontryagin in the late 1970s and implemented in the 1980s. However, the legacy of Kolmogorov’s reforms endures in the form of educational materials that are used for teaching mathematically gifted students and as a model for learning mathematics that remains today of substantial interest to educators.
Biomarkers of Neuroinflammation in Psychiatric Illnesses and their Relationship to Anti-inflammatory Medication
Keywords: Major Depressive Disorder
Obsessive-Compulsive Disorder
Positron Emission Tomography
Translocator Portein
Treatment Resistance

Major depressive disorder (MDD) is a leading cause of death and disability worldwide, with inadequate response to current pharmacotherapies being present in over 50% of cases. A logical explanation for treatment resistance is that MDD and other similarly treatment resistant psychiatric illnesses such as obsessive-compulsive disorder (OCD), may have multiple pathologies which present treatments do not effectively target. Interestingly, neuroinflammatory and immunological abnormalities have been documented in some patients with psychiatric disorders, leading to a theory of inflammatory processes affecting the brain and contributing to the pathogenesis of psychiatric illnesses. Positron emission tomography (PET) imaging enables the quantification of gliosis by measuring the level of translocator protein (TSPO), which is increased during neuroinflammation. Accordingly using [18F]FEPPA PET, in study one, we examined the relationship of TSPO distribution volume (VT), in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and insula (INS) to duration of untreated MDD. In study two, we determined whether TSPO VT is elevated in the cortico-striato-thalamo-cortical circuit of OCD. In study three, we assessed a serum blood marker to predict PFC, ACC, and INS TSPO VT in unmedicated MDD and treatment resistant depressed (TRD) participants and dorsal caudate TSPO VT in OCD participants. In study four, we determined whether oral minocycline can reduce elevated PFC, ACC, and INS TSPO VT in TRD participants. In study five, we determined the relationship of PFC TSPO VT to reduction in symptom severity associated with celecoxib administration. In study one, the results suggest that there is an increasing glial response in MDD reflecting neuroprogression of this illness. In study two, the results strongly argue that neuroinflammation, in particular glial activation is a pathological abnormality of OCD. In study three, the results suggest systematic assessment of selected peripheral inflammatory markers is promising for developing low cost predictors of TSPO VT. In study four, the results suggest that oral minocycline is not effective enough to elicit a change in TSPO VT in MDD. In study 5, we demonstrate that oral celecoxib has a differential effect on depression symptom severity, depending on the level of microglial activation as indexed by the baseline TSPO VT value.
Solid-liquid-liquid Wettability and its role on Targeted Emulsified Solvent Injection (TESI)
Keywords: Bitumen extraction
Canadian Oil Sands
Emulsified Solvent Injection
Hydrophilic Lipophilic Difference Net Average Curvature
Solid-Liquid-Liquid Wettability
Surfactant Phase Inversion Point

Canada possesses the third largest world reserves of crude oil, mostly in the forms of heavy oil or bitumen in the oil sands. However, 80% are too deep to be mined, requiring in-situ extraction methods. This work involved the design of a chemical enhanced oil recovery (EOR) approach, referred to as Targeted Emulsified Solvent Injection (TESI), that uses a surfactant-oil-water (SOW) system in the form of an emulsified solvent formulation at low surfactant concentration (~0.8%) to extract bitumen from oil sands. Different from previous approaches, TESI features an unstable emulsion delivered to the porous media where it is meant to break, dilute the bitumen, reducing its viscosity, and producing an ultralow interfacial tension (IFT). According to a known theory of capillary displacement, the ultralow IFT should facilitate bitumen removal via shear forces. A gap in this theory was addressed, concerning the effect of surfactants on wettability and its potential impact on bitumen recovery. To this end, existing Surface-Liquid-Air (SLA) wettability models were evaluated for their suitability to predict Solid-Liquid-Liquid (SLL) contact angles for a wide range of interfacial tensions (IFTs) of surfactant-free systems on various materials. The Neumann’s equation of state (EQS) was found to predict well wettability changes with IFT changes. This extended-EQS was then combined with the Hydrophilic-Lipophilic-Difference (HLD) + Net-Average Curvature (NAC) framework, used to predict IFT, to estimate changes in wettability around the phase inversion point (PIP) of SOW systems. It was found that at the PIP –where IFT is ultralow– the wettability is nearly neutral, and more importantly, is nearly independent of the solid’s hydrophilicity, explaining why wettability did not seem to affect TESI performance. The most influential factor on TESI performance was the delivery of solvent. Under optimal delivery conditions, bitumen recoveries of 60-80% can be achieved.
The Impact of Robotic Guidance on the Learning of a Golf Putt
Keywords: error detection mechanisms
motor skill acquisition
robotic guidance

Robotic guidance has been recently shown to improve movement smoothness by providing participants with an ideal trajectory. The main purpose of the current thesis was to investigate the impact of robotic physical guidance on the execution of a golf putting task. To investigate how robotic guidance influences the consistency and performance of a golf putting task, the studies employed a pre-test, acquisition, and retention testing phases in which participants completed putts to multiple targets. Using custom-built software, participants’ kinematic data were collected and converted into robotic coordinates to be delivered by a robot arm. As demonstrated in the first experiment, the robot’s trajectories were highly accurate, consistent, and smooth, replicating human trajectories. In the second experiment, participants trained with the robot (50% or 100% of training trials) or without the robot (0%). Following the training phase, participants performed an immediate retention test, putting to a target without the help of the robot arm. Participants that trained with the robot 50% of the trials were the only group to both improve their performance (i.e., stop the ball closer to the hole as well as task consistency). In the third experiment, participants were unable to see the ball’s trajectory and were asked to estimate the ball endpoint. As anticipated, the benefits of robotic guidance were replicated while showing that robotic guidance can also help develop error detection mechanisms. This research has improved our understanding of motor skill acquisition, especially as it pertains to the implementation of robotic guidance methods. Also, this project has led to novel robotic guidance tools, first applied to golf putting performance successfully and perhaps, can be expanded to different sports and other practical areas in the future (e.g., rehabilitation).
"The Dream of Kurdistan is Buried Here": History, Violence, and Martyrdom in the Borderlands of the Modern Middle East
Keywords: Dialetical Image
Feminism
Kurdistan
Resistance
State Violence
Temporality

This dissertation attempts to answer two main questions. Firstly, how do you tell a history of national struggle that has not ended in the foundation of a nation state? Secondly, is here a way to include women in histories of national resistance without erasing their own desires for and understandings of liberation or reducing their participation in national struggle to accommodation or critique? This dissertation poses these questions from Kurdistan, what many Kurdish scholars describe as the largest nation without a state. Rather than attempting to explain why Kurds have not achieved statehood despite a long history of national resistance, the dissertation’s four chapters explore ways to narrate the nation that has not ended in a nation-state. The dissertation is about the writing of history from Kurdistan and the processing of the past in Doğubayazıt, a Kurdish town in Turkey that sits in the foothills of Mount Ararat. How do ‘ordinary’ Kurdish men and women make sense of an unfinished history of national resistance? How do they use this history to make sense of the ongoing history of state violence? There is no attempt to corroborate or verify the histories told in Doğubayazıt. Rather, the dissertation engages ethnographically with the past. Tracing and following the reanimation of the defeat of the Mount Ararat Rebellion (Ağrı Dağı İsyanı, 1926-1931) by its ‘descendants,’ this dissertation attempts to ‘rescue’ Kurdish history from the triumphal narrative of the nation-state. The reanimations of the defeat of the Mount Ararat Uprising by Kurdish resistance needs to be read as a critique rather than a celebration of the nation-state. Despite the profound transformations in the thought, practices, and goals of Kurdish nationalism over the last decades, scholars continue to confine the “dream of Kurdistan” to what Turkish Foreign Minister Tewfik Rüştü Bey described in 1927 as the two options for “smaller groups”—to “disappear” or to wait.. But if grasped as Walter Benjamin suggests as “it flashes up at a moment of danger,” Kurdish resistance is no longer the tragedy or romance of the nation-state in the Middle East but a desire for the possibility of other forms of belonging.