VictorJuiz/thesis huggingface dataset:
Flux Balance Analysis of Plasmodium falciparum Metabolism

Plasmodium falciparum is the causative agent of malaria, one of the world‟s most prevalent infectious diseases. The emergence of strains resistant to current therapeutics creates the urgent need to identify new classes of antimalarials. Here we present and analyse a constraints-based model (iMPMP427) of P. falciparum metabolism. Consisting of 427 genes, 513 reactions, 457 metabolites, and 5 intracellular compartments, iMPMP427 is relatively streamlined and contains an abundance of transport reactions consistent with P. falciparum’s observed reliance on host nutrients. Flux Balance Analysis simulations reveal the model to be predictive in regards to nutrient transport requirements, amino acid efflux characteristics, and glycolytic flux calculation, which are validated by a wealth of experimental data. Furthermore, enzymes deemed to be essential for parasitic growth by iMPMP427 lend support to several previously computationally hypothesized metabolic drug targets, while discrepancies between essential enzymes and experimentally annotated drug targets highlight areas of malarial metabolism that could benefit from further research.

Keywords: Flux balance analysis
Plasmodium falciparum
Advisor: Parkinson, John
Videofluoroscopic and Cine-MRI Examination of Tongue Movement during Partial Glossectomees' Speech

This study evaluated the effects of a partial glossectomy on: (1) tongue velocity, movement range, and height during speech and (2) vowel production. Videofluoroscopy and cine-MRI of single German words were used to study pre- and postoperative tongue movement in seven glossectomees. Postoperative principal component analyses demonstrated reduced complexity of lingual movement. For the videofluoroscopic data, four of the five patients exhibited reduced postoperative tongue velocity, while one patient exhibited a postoperative increase. Patients produced the words with a slower speech rate after the surgery. The mean differences between pre- and postoperative average tongue height and movement range were small and variable. The cine-MRI data did not indicate a change in postoperative tongue movement range and height. The acoustic results indicated that the vowel /u/ was produced with a more neutral tongue position, postoperatively. The present study demonstrated how tongue movement can be analyzed quantitatively based on videofluorospcopy and cine-MRI.

Keywords: Glossectomy
tongue movement
Diagnostic Imaging
Tongue cancer
Advisor: Bressmann, Tim
Care Transitions from the Patient Perspective: A Focus on the Communication of Discharge Instructions

Communication of hospital discharge instructions between patient and provider is an important component of hospital discharge to ensure that patients have the information they need to manage their post-acute care. Patient perception of this interaction is a key indicator of the quality of services provided. This study examined whether there is a correlation between hospital continuity and transition scores (a measure of patient perceptions of hospital discharge instructions) and hospital readmissions in Ontario. The final regression model for the outcome of all medical readmissions within three days of hospital discharge, showed a significant positive relationship (coefficient=0.0090, p=0.011). The estimate was smaller and not significant once the data was restricted to only community hospitals located outside of Toronto (coefficient=0.0085, p=0.060), and when restricted to urban community hospitals outside of Toronto (coefficient=0.0041, p=0.384). For the outcome of specific medical readmissions within 28 days of hospital discharge, no statistically significant relationship was found.

Keywords: health services
care transition
hospital discharge
patient perspective
discharge instructions
discharge plan
patient satisfaction survey
hospital readmission
Advisor: Wodchis, Walter
Interventions to Mitigate the Effects of Interruptions During High-risk Medication Administration

Research suggests that interruptions are ubiquitous in healthcare settings and have a negative impact on patient safety. However, there is a lack of solutions to reduce harm arising from interruptions. Therefore, this research aimed to design and test the effectiveness of interventions to mitigate the effects of interruptions during medication administration. A three-phased study was conducted. First, direct observation was conducted to quantify the state of interruptions in an ambulatory unit where nurses routinely administered high-risk medications. Secondly, a user-centred approach was used to design interventions targeting errors arising from these interruptions. Finally, the effectiveness of these interventions was evaluated through a high-fidelity simulation experiment. Results showed that medication administration error rates decreased significantly on 4 of 7 measures with the use of interventions, compared to the control condition. Results of this work will help guide the implementation of interventions in nursing environments to reduce medication errors caused by interruptions.

Keywords: Interruptions
Medical Errors
Human Factors
Chemotherapy
Nursing
Medication Administration
Advisor: Trbovich, Patricia
Comparative Analysis of Franchising in the Russian Federation and Canada

This thesis compares franchising regulation in the Russian Federation with that of Canada. In order to be the most profitable, and function in the most efficient way, franchising must be properly regulated. Russia is currently experiencing a stagnation of franchising. This is partly because of the inefficient and outdated nature of the legislation that governs franchise relations in the country. In comparison, franchising business is flourishing in Canada. Canadian franchising legislation, reinforced by Canadian case law, represents a more developed system of regulation. The goal of this study is to reveal the strengths of Canadian franchising regulation as well as the weaknesses of Russian franchising regulation. This thesis also suggests ways to improve Russian franchising law and practice.

Keywords: franchising
Canada
Russia
comparison
regulation
analysis
franchise
Russian Federation
franchisor
franchisee
Advisor: Trebilcock, Michael
The Search for Novel Wnt Pathway Modulators

Signaling pathways are complex and function to transmit signals from the extracellular environment into the cell. Analysis of results obtained from a high throughput siRNA screen led to the identification of Membrane protein palmitoylated 3 (MPP3) and Leukocyte Tyrosine Kinase (LTK) as novel negative regulators of the Wnt pathway. MPP3 is a MAGUK family protein and domain mapping studies indicated that the Guk domain plays a role in the negative regulation of the pathway. LTK, a receptor tyrosine kinase, has several transcript variants one of which lacks the entire kinase domain (LTK∆KD). While LTK∆KD interacted with the Wnt receptor Frizzled7, the full length LTK did not, suggesting distinct modes of pathway regulation. Analysis of neuronal cells, NIE115 and Neuro2a, demonstrated LTK is expressed and that cells are Wnt3a responsive, thereby providing a neuronal model system appropriate for further studies on the mechanism and biological role of LTK as a negative regulator of the Wnt pathway

Keywords: Wnt Signaling
Receptor Tyrosine Kinase
Beta-Catenin
Frizzled
Cell Signaling
Leukocyte Tyrosine Kinase
Membrane Protein Palmitoylated 3
LTK
MPP3
MAGUK
Advisor: Attisano, Liliana
The Clinical Spectrum of Adults with Tetralogy of Fallot: Cardiac and Extra-cardiac Features and Late Outcomes

Tetralogy of Fallot (TOF) is a form of complex congenital heart disease (CHD) with clinical and genetic heterogeneity. Of the few known causes, 22q11.2 deletion syndrome is most common. We sought to define other clinical subgroups by focusing on congenital cardiac and extra-cardiac features, and cardiac outcome. Patients were prospectively categorized as “syndromic” if they had at least two of three features: dysmorphic facies, learning difficulties or voice abnormalities. We compared cardiac and extra-cardiac characteristics, and late cardiac outcomes between the syndromic group and a nonsyndromic control group. The syndromic group had a more complex cardiac disease, was at elevated risk for developing later onset conditions including neuropsychiatric disorders, endocrine disorders, and hearing deficits, and had a higher mortality rate compared to the nonsyndromic group. Increased awareness of this subgroup with a multisystem condition may be helpful for optimizing management and identifying individuals for referral to medical genetics.

Advisor: Silversides, Candice
Exploring Pretreatment Methods and Enzymatic Hydrolysis of Oat Hulls

This thesis describes a way to achieve higher conversion rates of sugars from lignocellulosic biomass that can then be used for cellulosic ethanol production. Using oat hulls as the biomass, several chemical and physical pretreatment techniques were explored to overcome the recalcitrance and allow access to cellulose and hemicellulose. Experimentation with enzyme cocktails and dosing was done to obtain the highest conversions of cellulose and xylan to produce sugars. High solids-loading of the substrate, 14-16%, enabled higher conversion rates and would amount to lower cost of production in a commercial facility; however, end-product inhibition by the accumulation of inhibitors is also realized. To remove inhibition, a solid-liquid separation step was implemented which allowed enzymes to operate at a higher efficiency. The best combination of pretreatment and enzymatic hydrolysis led to a glucose of 89% and xylose yield of 84%, for trials conducted in a 20L bioreactor.

Keywords: enzymatic hydrolysis
cellulosic ethanol
Advisor: Saville, Bradley
Investigating the Effects of an MMP-inhibitory Biomaterial on the Host Inflammatory Response using an Air Pouch Mouse Model

An earlier approach to restore homeostatic levels of ECM degrading matrix metalloproteases (MMPs) by the Sefton Lab utilized hydroxamate-based MMP inhibitory (MI) beads. While the MI beads delayed ECM degradation in the context of skin wound healing, they caused elevated cell infiltration in a subcutaneous implant model. The primary goal of this project was to further investigate this finding using an air pouch implant model in mice and a different control group – methacrylic acid-based (MAA) beads. Exudate analysis indicated that the MI beads, implanted subcutaneously with gelatin discs, elicited a similar biological response as the MAA beads. Exudates corresponding to both biomaterials had similar cell counts and chemokine levels, which were greater than those corresponding to the control used earlier, poly-methyl methacrylate-based (PMMA) beads. Further, both MI and MAA beads activated infiltrating macrophages in the classical manner, and influenced the activity of an MMP8 catalytic domain in a similar manner.

Keywords: Bioactive drug-like biomaterials
Host response
Advisor: Sefton, Michael
China's New Documentary Movement: Alternate Realities and Changing State-society Relations in Contemporary China

Independent documentary films in contemporary China articulate a vision of Chinese politics and society that deviates from official state discourse. This thesis explores how China’s New Documentary Movement (NDM) – a spontaneous, independent phenomenon in Chinese cinema – serves as an important arena to study state and society struggles in the aftermath of the post-Mao reforms. This study first explores the politicalization of Chinese national cinema to demonstrate how the degree of control exerted over filmmaking and the documentary genre functions as a useful indicator of Chinese state-society relations. Focusing on the contentious issue of land disputes and rural rightful resistance in two documentaries – Feng Yan’s "Bing Ai" as well as Zhang Ke and Dong Yu’s "Where is the Way" – it contrasts the lived reality of displaced peasants to the official rhetoric disseminated in the state media. Also discussed is the state’s response to the NDM and its implications for greater societal autonomy in contemporary China.

Keywords: China
State-society relations
Chinese independent documentary
Post-Mao reforms
Rural rightful resistance
Land disputes
Film and cinema
Documentary
Advisor: Ong, Lynette
Testa, Bart
A Differential Polarization-time Coding Scheme for Polarization-division-multiplexed Fiber-optic Communication Systems

Polarization division multiplexing (PolDM) is a promising way to improve the spectral efficiency of fiber-optic communication systems. However, PolDM systems suffer greatly from polarization mode dispersion (PMD), especially in long-haul systems. PMD is time-varying and is intrinsically hard to compensate. Current PMD compensators are complicated and expensive to build, adding to the cost and complexity of practical PolDM systems. We propose a new differential polarization time coding scheme combined with controlled polarization rotation to increase the system tolerance to PMD. An encoding algorithm, a differential receiver design, and a decoding algorithm are described in detail. Controlled polarization rotation is achievable using conventional Mach-Zehnder interferometers that are used to modulate the signal. Simulation results show that significant improvement in PMD tolerance can be achieved with little added complexity. Given a certain transmission distance, our proposed system can also increase the achievable data rate compared to a PolDM differential quadrature phase shift keying system.

Keywords: optical
communications
fiber
polarization mode dispersion
MIMO
unitary group
differential
coding
Advisor: Kschischang, Frank R.
Fortified Rice Premix Formulations for the Alleviation of Micronutrient Deficiencies: Stabilization of Vitamin A in the Presence of Iron

Micronutrient deficiency maintains the cycle of poverty. A steady intake of essential nutrients is not available in developing areas due to factors of socioeconomic constraints, limited variety of food sources, and single-carbohydrate based diets. Fortification of a staple food is an effective way of combating micronutrient deficiencies. The food product developed in this study is an extruded, micronutrient-fortified, rice-shaped premix. The target rice premix formulation contains iron, zinc, a B-vitamin complex, and vitamin A and is blended with market rice in a 1:100 ratio. Iron furthers the oxidation of vitamin A, thus various micronutrient encapsulation techniques and antioxidant systems are explored in this study. It is technically and economically feasible to combine the micronutrients in a single formulation by introducing efficient physical and chemical barriers. Optimal formulation designs used coated vitamin A sources and retained >85% vitamin A at 6 months storage with acceptable sensory attributes.

Advisor: Diosady, Levente L.
The Role of Glutathione Metabolism in the Neuroprotective Effect of Mood Stabilizers

Several lines of evidence implicate oxidative stress in the pathophysiology of bipolar disorder (BPD). The mood stabilizers lithium and valproate have been shown to protect against oxidative stress-induced cell death. This study examined whether an increase in cellular reductive potential due to glutathione (GSH) synthesis up-regulation underlies this neuroprotective effect. Using primary rat cortical neurons as a model, this study demonstrated that unlike lithium and valproate, carbamazepine and lamotrigine do not exert neuroprotective effects against H2O2-induced cell death. Moreover, the level of GSH and the GSH:GSSG ratio in neurons and in rat brain remained unchanged following chronic treatment with either lithium or valproate. Similarly, this study did not find a significant effect of treatment on the expression of genes encoding γ-glutamylcysteine ligase sub-units, Gclc and Gclm, in both neurons and the rat brain. These findings suggest that other molecular targets of lithium and valproate likely mediate the observed neuroprotective effects.

Keywords: Bipolar disorder
glutathione
oxidative stress
mood stabilizer
neuroprotection
Advisor: Li, Peter
Warsh, Jerry
Evolution of Chromatin Modification Machinery

This thesis explores chromatin modification (CM) as a biological system and uses known CM factors in four model organisms; yeast, worm, fly, and human to explore how CM factors have consistently evolved across a diverse spectrum of 111 organisms by using the InParanoid homology algorithm. Using InParanoid, phylogenetic profiles are constructed for each model organism to highlight evolutionary trajectories and which CM factors are lost, expanded, and are specific to some lineages. Phylogenetic tree construction demonstrates that peripheral subunits of CM complexes evolve independently. Accurate mapping of domains to CM factors and their homologs reveals that the architecture of domains is very well conserved, with only one potential case of a domain swap. Homology, domain architecture, and protein-protein interaction is then combined to illustrate an interolog example and potential interaction candidates. The techniques highlighted in this thesis represent a generic and powerful approach to analyzing any biological system of interest.

Keywords: Evolution
Chromatin modification
Advisor: Parkinson, John
A Question Of Strangeness

This paper examines leading Canadian decisions in the areas of obscenity and indecency law and freedom of religion to demonstrate that the strangeness of a practice will be a major factor in determining the harm associated with it. Since “strangeness” in sexual deviance cases turn on the perceived objectification and subjugation of women and minority religion cases turn on communal behaviours, these strands intersect in the debate over polygamy. The impact that these skewed perceptions will have on findings of harm in the polygamy context is examined, as are how the benefits of the legislation may be overstated. Finally, the effects of “othering” are addressed for the practice of polyamory, a relationship structure that lacks harm but may nevertheless be equally prohibited.

Keywords: polygamy
polyamory
harm
Advisor: Morgan, Ed
Wireless Network SNR Enhancement Using Mobile Relay Stations

With the proliferation of wireless technologies, wireless Internet access in public places will become a necessity in the near future. In outdoor areas, where the base stations are sparsely distributed, mobile users at the edge of the network communicate with the base station at a very low rate and thus waste network resources. To solve this problem, one of the previously taken approaches was the use of relay stations to improve the throughput of the network. In this work, we take this approach to the next level by updating the positions of the relays according to the particular distribution of the users at certain time instants. By comparing the proposed scheme to fixed relay placement strategies, we show that the former has 15-60% performance improvement over the latter, in terms of the average SNR of the network.

Keywords: Mobile Relays
SNR Enhancement
k-means
Clustering
Advisor: Liang, Ben
The Search for a Model System which Balances Freedom and Respect for End of Life Decisions and Strict Regulation to Protect the Vulnerable from Abuse

This thesis proposes a model for legalized Physician-Assisted Suicide [PAS] for adoption into Canadian legislation. The basis of this model is one which respects the individual freedom to make end-of-life decisions free from state interference. The research herein supports the provisions contained in Oregon legislation where PAS has been legalized on the basis that the Oregon model is consistent with the guarantees afforded under s.7 of the Charter of Rights and Freedoms. Oregon maintains strict regulatory barriers which protect against the threat of abuse which the Supreme Court reasoned in Rodriguez outweighed her s.7 rights to autonomy. This thesis will engage in the theories of Ronald Dworkin who supports the preservation of the sanctity of human life which Sopinka J. held prevailed over s. 7 violations in Rodriguez and seeks a model which respects individual freedom without compromising that sanctity or value of life.

Keywords: End of Life decisions
Physician Assisted Suicide
Euthanasia
s.7 Charter of Rights and Freedoms
Advisor: Stewart, Hamish
Reducing the Water Absorption of Thermoplastic Starch Processed by Extrusion

Novel plastics that are biodegradable and made from renewable natural resources are currently being researched as alternatives to traditional petroleum-based plastics. One such plastic, thermoplastic starch (TPS) is produced from starch processed at high temperatures in the presence of plasticizers, such as water and glycerol. However, because of its hydrophilic nature, TPS exhibits poor mechanical properties when exposed to environmental conditions, such as rain or humidity. The overall objective of this thesis was to produce a thermoplastic starch based material with low water absorption that may be used to replace petroleum-based plastics. Three different methods for reducing water absorption were investigated, including the following: extrusion of starch with hydrophobic polymers, starch modifying chemicals, and citric acid/sorbitol as plasticizers. It was found that all methods reduced the water absorption of TPS.

Keywords: thermoplastic starch
extrusion
bioplastic
Advisor: Sain, Mohini
Investigation of a Metabolic Pathway Leading to an Idiosyncratic Drug Reaction: Is the Sulfate of 12-Hydroxynevirapine Responsible for the Skin Rash in Brown Norway rats?

An animal model of nevirapine (NVP)-induced skin rash was used to test the hypothesis that sulfonation of 12-OH NVP, a metabolite of NVP proven essential for rash development, is the link between 12-OH NVP and the skin rash. Female Brown Norway (BN) rats were co-treated with NVP or 12-OH NVP and sulfation inhibitors dehydroepiandrosterone (DHEA) and salicylamide. Co-treatment with salicylamide markedly decreased formation of the sulfate conjugate but did not prevent development of the rash suggesting that the sulfate is not involved. However, it is not known whether the sulfate formation in the skin was affected. Co-treatments with DHEA decreased the sulfate formation and prevented the rash but also had other effects on NVP metabolism. This implies that the sulfate metabolite is responsible for the rash. Additional studies will be required to resolve these conflicting results.

Keywords: nevirapine
drug metabolism
adverse drug reactions
idiosyncratic drug reactions
Advisor: Uetrecht, Jack
Nonlinear FEA of the Crush Behaviour of Functionally Graded Foam-filled Columns

The use of metallic foams as a filler in thin-walled structures can enhance their crashworthiness characteristics. It is believed that, tailoring the properties of the foam filler would enhance the effectiveness of these characteristics. This view is also supported by recent works in the literature. It is the objective of this study to examine the crush behaviour of functionally graded foam-filled tubes and evaluate the effect of discretely graded density upon the specific energy absorbed. Nonlinear parametric finite element simulations of the foam-filled tube were developed to estimate the most favourable foam density gradient in the lateral and axial directions. The effect of various design parameters such as density grading, number of grading layers, and thickness of the interactive layer upon the resulting specific energy absorption was investigated. The results show that the specific energy absorption of a tube filled with functionally graded foam is better than uniform density foam.

Keywords: Functionally Graded Foam
Foam-Filled Columns
Advisor: Meguid, Shaker A.