VictorJuiz/thesis huggingface dataset:
Influence of Drug-polymer Interactions on Drug Transport of Pharmaceutical Polymer Materials

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.

Keywords: Controlled release
Drug-polymer interaction
Drug transport
Pharmaceutical material
Advisor: Wu, Xiao Yu S
Multinational Enterprises as Institutional Entrepreneurs: Directed and Diffused Institutional Strategies and Development

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.

Keywords: development
institutional entrepreneurship
institutions
multinational enterprises
Advisor: Trebilcock, Michael J
Prado, Mariana M
Dramaturging Research, Shaping Encounters: Working Methods and Dramaturgical Structures in Contemporary Canadian Documentary 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.

Keywords: Autobiography
Canadian
Documentary
Dramaturg
Dramaturgy
Theatre
Advisor: Copeland, Nancy
Transcriptional Regulation of the foraging Gene and its Associated Behaviours

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.

Keywords: behaviour
epigenetics
gene regulation
genetics
pleiotropy
Advisor: Sokolowski, Marla B
Soviet Mathematics Curriculum Reforms (1958-1985): Redefining the Purpose of Mathematics Education

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.

Keywords: history of mathematics education
Kolmogorov
Mathematics education
New Math
USSR history
USSR mathematics
Advisor: Fraser, Craig
Biomarkers of Neuroinflammation in Psychiatric Illnesses and their Relationship to Anti-inflammatory Medication

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.

Keywords: Major Depressive Disorder
Obsessive-Compulsive Disorder
Positron Emission Tomography
Translocator Portein
Treatment Resistance
Advisor: Meyer, Jeffrey H
Solid-liquid-liquid Wettability and its role on Targeted Emulsified Solvent Injection (TESI)

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.

Keywords: Bitumen extraction
Canadian Oil Sands
Emulsified Solvent Injection
Hydrophilic Lipophilic Difference Net Average Curvature
Solid-Liquid-Liquid Wettability
Surfactant Phase Inversion Point
Advisor: Acosta, Edgar J
Hydrogels Derived from Cellulose Nanocrystals

In quest for new functional materials, cellulose nanocrystals (CNCs) have attracted great interest due to their sustainability, biocompatibility, ease of surface functionalization, and mechanical strength. In this thesis different hydrogels derived from CNCs for various applications have been developed. The hydrogels derived from CNC in this thesis can be divided into isotropic and anisotropic hydrogels. High capacity, low cost and sustainable materials for waste water treatment and heavy metal removal are in high demand. An isotropic nanocolloidal hydrogel based on CNCs and graphene quantum dots (GQDs) was developed. The microstructure, permeability and mechanical properties of the hydrogel was dependent on the concentration and the ratio of the two precursors. Microfluidic microgels have been used for heavy metal scavenging and wastewater treatment applications. Higher concentration of GQDs lead to higher adsorption capacity for different heavy metal ions. To study the possibility of alignment of CNCs in shear field, studying the kinetic of alignment and relaxation of alignment, an oscillatory microfluidic device was used. Higher frequency of oscillations led to higher alignments in different regions of the microchannel. An increase in the viscosity of the CNC suspension led to higher degree of alignment. At higher viscosities the relaxation of alignment was also slower. Similar to the morphology of the native tissue which contains unidirectionally aligned collagen fibers, anisotropic hydrogels that mimic the native tissue morphology are highly desired. Nanofibrillar hydrogel derived from CNCs and gelatin have been prepared to study the role of shear in fabrication of anisotropic hydrogels. Variation of concentration and ratio of hydrogel precursors led to various gelation times, permeability and mechanical properties. Using different printheads, sheets of CNC/gelatin hydrogels have been extruded and fluidic control in achieving composition gradient in transverse and longitudinal direction was explored. Variation in the substrate temperature was used to tune the degree of alignment in the hydrogel sheets. Hydrogels derived from CNC and Chitosan were developed to form a shear-thinning photo crosslinkable hydrogel for fabrication of personalized wound dressings. The structure, mechanical properties and swelling of the hydrogels were dependent on the concentration and ratio of the precursors. The hydrogels could be loaded with various active ingredients (AI) to add different functionalities. These functional hydrogels were printed in different shapes to program the release of AI in a controlled manner.

Advisor: Kumacheva, Eugenia Kumacheva
Bio and Synthetic Derived Carbon Based Nanofillers for Fracture Enhancement of Epoxy for Structural Composite Applications

Nanocomposites are highly sought after for their potential to solve a vast array of engineering problems. One application of nanofillers is the enhancement in fracture and mechanical properties of structural composites when utilized as reinforcement for the matrix resin. This is important for epoxy matrices, which is the primary matrix for many structural composites, including those used in aircrafts. Many of the nanofillers currently utilized/suggested in research and practice to reinforce epoxies are expensive with complex production processes. The focus of this research is to develop methodologies to effectively incorporate carbon nanofibers (CNFs) and chitin nano-whiskers (CNWs) into epoxy matrices for enhancing its fracture, mechanical and thermal characteristics. CNFs are synthetically produced, high performance fillers also comprised of the same fundamental graphitic planes in carbon nanotubes, at a fraction of their cost. Chitin is a vastly available bio-resource from which can be extracted CNWs; similar in mechanical performance to cellulose nano-whiskers. The primary challenges for incorporation of these fillers are to maximize dispersion and filler-matrix adhesion. For the dispersion and adhesion of CNFs in epoxy, two approaches are adopted: 1) development of a novel method for solvent extraction and functionalization in two stages assisted by shear and 2) hybridization of CNF-epoxy nanocomposites with GNPs which are two dimensional nanoparticles. While the latter approach involved less fabrication complexity, the former resulted in significant enhancement of the fracture and dispersion characteristics of epoxy CNFs nanocomposites. Despite possessing richer surface functionality than nanocellulose, research in CNWs reinforcement of polymer matrices has been more limited, particularly in the case of epoxy CNWs nanocomposites. Through this research, optically transparent epoxy-CNWs nanocomposites are developed with enhanced fracture, mechanical and thermal characteristics. Rate dependency on the evolution of fracture behavior is characterized and intriguing characteristics of CNWs reinforcement is revealed, such as the tendency to promote localized ductility at the crack tip. This research is expected to pave way to further interest and development of composites of CNFs and CNWs for enhancement of not just epoxy, but other polymer matrices.

Advisor: Naguib, Hani E.