VictorJuiz/thesis huggingface dataset:
Protein Folding and Dynamics of Calmodulin via 19F-NMR

Calmodulin (CaM) is a ubiquitous calcium sensor protein which binds and activates a variety of enzymes involved in cell signaling pathways. In its calcium loaded state, CaM is extremely resistant to heat denaturation, with a melting temperature (Tm) of around 115°C. In this study, Xenopus laevis CaM was prepared such that the eight phenylalanine residues were substituted with 3-fluorophenylalanine. 19F NMR studies then focused on properties of the hydrophobic core associated with the folding process at temperatures near the regime where the protein is completely folded. Near 70°C, near-UV circular dichroism and 1H NMR-based measurements of protein diffusion rates reveal the onset of a stable, expanded near-native folding intermediate. 19F NMR solvent isotope shifts reveal a gradual loss of water from the hydrophobic core with increasing temperature, until the point at which the near-native intermediate state is attained. At this point, water is observed to enter the hydrophobic core and destabilize the protein. Paramagnetic shifts from dissolved oxygen reveal an increase in oxygen accessibility with temperature until the near-native intermediate is reached, whereupon oxygen solubility decreases. Taken together, we conclude that hydrophobicity of the protein interior increases with temperature, until a dry near-native state is established, whereupon water cooperatively enters and destabilizes the hydrophobic core. 19F CPMG experiments provide a measure of the interconversion between the folded state and the dry near-native intermediate; at higher temperatures, folding rates are on the order of 10,000 Hz. Moreover, as temperature is lowered, folding rates increase, presumably because the effect of off-pathway misfolding events on the exchange process is diminished.

Keywords: Protein Folding
Calmodulin
19F-NMR
CPMG
Advisor: Prosser, Robert Scott
Political Ecology of Development In South Africa’s Wild Coast: Exploring Stakeholder Arguments for and Against Possible Development Strategies

Characterized by scenic beauty and biodiversity, yet impoverished peoples, the Wild Coast of South Africa lies at a development crossroads, whereby various land-use proposals offer different outcomes. This thesis sought to analyze various stakeholder arguments in support of development strategies, especially involving the local people and environment. Based on a document analysis and interviews, the predominant development strategies supported were small community development initiatives (SCDIs) and tourism, supported by NGOs, and mining, supported by the private sector yet opposed by NGOs. A major finding was that while government outlines many development “objectives”, successful results are negligible, suggesting that this sector is an overall ineffective determinant for Wild Coast development. NGO and private sectors provided valid arguments in support of their strategies, leaving the researcher to conclude that means of collaboration should be determined in order to best develop the Wild Coast (via SCDIs, tourism, and mining) and improve local livelihoods.

Keywords: Development
Wild Coast
Political ecology
South Africa
mining
natural resources
South African government
development policy
Advisor: Kepe, Thembela
Hedgehog Signalling and Tumour-initiating cells as Radioresistance Factors in Esophageal Adenocarcinoma

Clinical management of esophageal adenocarcinoma (EAC) relies on radiation therapy, yet radioresistance is a pervasive challenge in this disease. The mechanisms of EAC radioresistance remain largely unknown due to a paucity of validated preclinical models. The present studies report on the development of seven primary xenograft models established from patient tumours. These models are used to interrogate the range of radiosensitivities and mechanisms of radioresistance in EAC tumours. We found that radiation enriches the tumour-initiating cell population in two xenograft lines tested. Furthermore, three tested xenograft lines respond to irradiation by upregulating Hedgehog transcripts, a pathway involved in stem cell maintenance and proliferation. Upregulation occurs in autocrine and paracrine patterns simultaneously, suggesting that Hedgehog signalling may have a complex role in the radioresponse of EAC tumours. These findings suggest that inhibiting stem cell pathways in combination with radiotherapy may have an important role in the clinical management of EAC.

Keywords: Esophageal adenocarcinoma
Cancer stem cell
Hedgehog pathway
Xenograft models
Radiation
Radioresistance
Radiosensitivity
Tumour-initiating cell
Limiting dilution assay
qRT-PCR
Advisor: Liu, Geoffrey
Ailles, Laurie
Orthogonal Codes for CDMA-based Asynchronous Medical Wireless Body Area Networks (WBANs)

The presented work considers a CDMA-based Wireless Body Area Network (WBAN) where multiple biosensors communicate simultaneously to a central node in an asynchronous fashion. The asynchronous nature of the WBAN introduces Multiple Access Interference (MAI). To combat this problem, presented is a methodology that uses a set of cyclically orthogonal spreading codes extracted from the Walsh-Hadamard matrix. When using the Cyclic Orthogonal Walsh-Hadamard Codes (COWHC) as spreading codes in the CDMA-based WBAN, the cyclic orthogonality property helps mitigate MAI amongst the on-body sensors. Presented is an ideal communication system that is most effective at mitigating MAI in proactive WBANs. The work illustrates the system optimality and effectiveness at mitigating MAI by studying the sensitivity to packet-loss through simulating the link Bit Error Rate (BER) performance. It is shown that the proposed design with COWHC, a Rayleigh flat-fading channel, BPSK modulation and a conventional receiver produce optimum MAI mitigation.

Keywords: Wireless Body Area Networks (WBANs)
Medical Networks
Code Division Multiple Access (CDMA)
Orthogonal Codes
Body Sensor Networks (BSNs)
Advisor: Plataniotis, Konstantinos N.
Comparative Effects of a D2 and Mixed D1-D2 Dopamine Receptor Antagonist on Amphetamine Reinforcement in Pathological Gamblers and Healthy Controls

This study used the D2-preferring dopamine antagonist, haloperidol (3mg) and D1-D2 antagonist, fluphenazine (3mg) to investigate the roles of D1 and D2 receptors in d-amphetamine (20-mg) reinforcement in humans with (9 M; 7 F) and without (12 M; 4 F) an addictive disorder, in a placebo-controlled, between-within counterbalanced design. To preclude neurotoxicity, pathological gamblers served to evaluate effects of addiction status. Incentive motivation (e.g., Desire to Gamble), hedonic impact (e.g., Liking) and risky decision-making were assessed. Haloperidol reduced Desire to Gamble in controls, whereas fluphenazine reduced Desire in gamblers. Both antagonists reduced hedonic impact in both groups, with fluphenazine exhibiting stronger effects in gamblers. Both antagonists decreased risky decisions in controls but increased risky decisions in gamblers. Results suggest that D1 mediates amphetamine-induced motivation to gamble; D2 mediates amphetamine’s hedonic effects; D1 function is deficient in gamblers; and D2 blockade may reverse a restorative effect of amphetamine in addicted individuals.

Keywords: dopamine
D1 receptor
D2 receptor
pathological gambling
fluphenazine
haloperidol
amphetamine
Advisor: Zack, Martin
Attitude Dependent De-orbit Lifetime Analysis of an Aerodynamic Drag Sail Demonstration Spacecraft and Detailed Thermal Subsystem Design for a Polar Orbiting Communications Nanosatellite

Contributions to two missions are presented. The first is a demonstration mission called CanX-7 that uses a 4 square metre drag sail to de-orbit a 3.5 kg satellite. In order to estimate the effectiveness of the drag sail, a novel method is developed that takes into account the time-varying nature of the projected drag area. The Space Flight Laboratory designed drag sail is shown to be sufficient to de-orbit the CanX-7 spacecraft within the 25 year requirement. The Antarctic Broadband demonstrator spacecraft is a 20 cm cubical nanosatellite that will demonstrate the feasibility of a Ka-band link between the research community in Antarctica and stakeholders in Australia. In support of this mission, a passive thermal control subsystem is designed that will keep all the components within their operational temperature limits at all times throughout the mission.

Keywords: De-orbit
Drag sail
Thermal control
Attitude determination and control
Advisor: Zee, Robert E.
Direct Connections between the Lateral Entorhinal Cortex and Hippocampus or Medial Prefrontal cortex: Their Role in the Retrieval of Associative Memories

Consolidation of associative memories may depend on communication between the lateral entorhinal cortex (LEC) and hippocampus (HPC) for recently learned memories and the LEC and medial prefrontal cortex (mPFC) for remote memories. To determine whether direct connections between these regions are necessary for the retrieval of a recently or remotely learned memory, rats acquired an associative memory through trace eyeblink conditioning and were tested for memory retention after inactivating the regions of interest with the GABAA agonist, muscimol. Inactivating the LEC-HPC connection did not impair memory retrieval. However, inactivating the LEC-mPFC connection impaired remote, but not recent, memory retrieval. Thus, the LEC and mPFC connection is necessary for the retrieval of a remotely, but not recently learned associative memory. Increased reliance on the entorhinal-prefrontal connection indicates the strengthening of functional connectivity between the two regions, which may be a biological correlate for the proposed reorganization during systems consolidation.

Keywords: lateral entorhinal cortex
medial prefrontal cortex
hippocampus
memory
consolidation
trace eyeblink conditioning
muscimol
Advisor: Takehara-Nishiuchi, Kaori
Development of a Microfluidic Device for Single Cell Specific Membrane Capacitance Quantification

The specific membrane capacitance (SMC) of biological cell membranes correlates with cells’ electrical activity and morphology, which are physiological markers for cellular phenotype and health. Conventionally, SMC measurements are conducted using electro-rotation and Patch-clamping, which entail long time training and stringent operation skills. Both techniques also suffer from limited throughput and lengthy measurement time. In this study, a microfluidic device, which enables impedance spectroscopy measurements, was developed to quantify the SMC of single biological cells. The device has a testing speed of approximately one cell per minute and is relatively easy to operate. Three-dimensional finite element simulations of the microfluidic device confirm the feasibility of this approach. SMC measurement of two AML (Acute Myeloid Leukemia) subtypes and two UCC (Urothelium Cell Carcinoma) subtypes were conducted. Measured SMC results were found to lie in the comparable range with previously reported publications.

Keywords: Microfluidic
Cancer cell
Advisor: Sun, Yu
On Delay-sensitive Lossy Source Broadcast

In this thesis, we study the problem of sending a memoryless source over a memoryless broadcast channel, to two users that need to reconstruct the source subject to some distortion and delay constraints. Our motivation is to study the use of rateless codes for single-server broadcasting to diverse users, in an information theoretical way. We consider both analog and digital versions of this problem. When it is a binary source being sent over an erasure broadcast channel and the distortion is measured with the erasure distortion, we derive an inner bound for the achievable distortion region. If the distortion measure was instead the Hamming distortion, we derive an outer bound for the latency region. Finally, when it is a Gaussian source being sent over the Gaussian broadcast channel and the distortion is a quadratic measure, we provide an analogous inner bound for the distortion region.

Advisor: Khisti, Ashish
Cholinergic Neuromodulation of Activity-dependent Disinhibition-mediated Plasticity

Activation of muscarinic acetylcholine receptors (mAChRs) has pronounced effects on GABAergic interneurons, including depolarization of their resting membrane potential, and increasing their action potential and vesicular release frequency. Moreover, postsynaptic mAChR activation in hippocampal pyramidal neurons reduces the expression of the K+-Cl- cotransporter (KCC2). However, whether mAChR activation modulates the expression of disinhibition-mediated synaptic plasticity has not been examined. I induced inhibitory long-term potentiation (LTP) by applying coincident pre/postsynaptic stimulation in the hippocampus. This plasticity was characterized by an increase in the postsynaptic potential (PSP) amplitude and a depolarization in the inhibitory postsynaptic potential (IPSP) reversal potential; characteristics of disinhibition-mediated LTP (dmLTP). Activation of mAChRs during this plasticity induction protocol prevented the expression of dmLTP via a presynaptic downregulation of transmitter release. This was concluded from evidence that the PSP amplitude and IPSP reversal potential were unaltered, and paired-pulse depression occurred following plasticity induction in the presence of mAChR activation.

Keywords: dmLTP
cholinergic
mAChR
neuromodulation
plasticity
GABA
Advisor: Woodin, Melanie A.
Corporate Social Responsibility in the Canadian Extractive Sector. Bill C-300: What Went Wrong?

While the mining industry provides numerous benefits to the society, it also has negative impacts on communities. This thesis will discuss various voluntary policies employed by mining companies and the developmental attempts at legislative changes to enforce mandatory regulations. The primary focus will be on Corporate Social Responsibility (CSR), in particular Bill C-300, which required “Corporate Accountability for the Activities of Mining, Oil or Gas Corporations in Developing Countries”. The Bill had effective key points to ensure that Canadian extractive companies followed human rights and environmental practices while operating overseas. Although the Bill was defeated, it is believed to be critical with respect to CSR. Moreover, Dodd-Frank, the 2010 United States legislation with similar provisions of CSR, will be discussed. The differences in the two will be elaborated to determine why Bill C-300 was rejected and answer whether it would have succeeded had the provisions been drafted similarly to Dodd-Frank.

Keywords: Bill C-300
Corporate Social Responsibility
Mining Industry
Advisor: Lee, Ian B.
Bioavailability of Casein-bound Vitamin D3 from Fortified Cheese and its Effects on the Mental Health Status of the Institutionalized Elderly

All populations risk vitamin D inadequacy. We conducted a randomized double- blind trial of vitamin D3 fortified cheddar cheese to study bioavailability based on serum 25-hydroxyvitamin D [25(OH)D] concentrations, and its effects on mental health scores in older adults. Once a week, 28 subjects received 200 IU or 28000 IU of vitamin D3 per fortified cheese serving. The mean increases in 25(OH)D over 8 weeks were: 4.2±11.4 and 29.4±16.2 for the 200 IU/week and 28,000 IU/ week dose groups, respectively (groups differ, P<0.001). Subjects who consumed 28,000 IU/week cheese improved their Mental Component Summary (MCS) scores, based upon the SF-36v2 questionnaire conducted at baseline and at 8 weeks (P<0.05). There was also a positive correlation between the change in MCS score and the change in 25(OH)D (1 tail; P<0.05). These data demonstrate the suitability of fortified cheddar cheese, and provide evidence of neurocognitive benefits with higher 25(OH)D levels.

Keywords: Vitamin D
mental health status
Advisor: Vieth, Reinhold
Delinquent Democracy: Examining the Nature, Scope, and Effects of the Trend towards Greater Criminal Enfranchisement

Universal suffrage is a guiding principle of democracy. However, it has a long history of being selectively denied. While many of these exclusions have dissipated in twentieth century rights revolutions’, the right to vote is still widely withheld for prisoners. This paper looks at criminal disenfranchisement, its origins, development, and contemporary manifestations. Part I will discuss the history of criminal disenfranchisement to trace its development from a tool of social exclusion to a collateral consequence of criminal conviction. Part II will look at the judicial treatment of contemporary disenfranchisement laws through a selection of representative case studies. Part III will consider how the representative cases form a trend towards criminal enfranchisement, and the implications of this trend for future constitutional challenges in jurisdictions where such laws persist. This paper argues that this trend, while tangible, is tentative and its force may be strengthened through a transnational judicial dialogue.

Keywords: Criminal Disenfranchisement
Transnational Judicial Dialogue
Comparative Constitutional Law
History of Criminal Disenfranchisement
Trend Towards Criminal Enfranchisement
Advisor: Weinrib, Lorraine
Invasion of Polarized Epithelial Cells by Legionella pneumophila: an Opportunistic Strategy

Legionella pneumophila (Lp.), the causative agent of Legionnaires’ disease, has been well known for infecting and replicating inside airway macrophages. Previous results from our laboratory indicated that Lp. attaches to non-polarized lung epithelial cells by binding and activating E-cadherin and β1-integrin. However, in the polarized alveolar epithelia these receptors are segregated from the apical cell surface by tight junctions (TJs). Our results showed that Lp. behaves as an opportunistic pathogen that efficiently targets disrupted, but not integrated epithelial cell monolayer. In such conditions, Lp. can reach its host-cell receptors and consequently invade and replicate intracellularly, producing large amount of bacterial progeny. These results and clinical evidence suggest the contribution of damaged airway epithelia to Legionellosis by providing a replication reservoir for the bacteria.

Keywords: Legionella
cellular Microbiology
Advisor: Terebiznik, Mauricio
Issues related to Security Interest under Bankruptcy and Reorganization Procedures

This thesis examines issues related to security interest, especially the security that holds after acquired property as well as present property, which are caused by discharge under bankruptcy procedure. This thesis also examines security interest valuation issue under proposal under Bankruptcy and Insolvency Act. Both issues are related to the nature of security interest, which is, in my opinion, to hold the value of collateral at the time of realization. This thesis especially focuses on the security under after acquired clause, which holds interests in after acquired property as well as present property. In my view, the security on after acquired property has proprietary interest. It leads to the conclusion on the issue whether the security can attach to a property acquired after discharge.

Keywords: security
collateral
Advisor: Fadel, Mohammad
Investigation into the Origin and Nature of Variability in Quantitative Measurements of Tumour Blood Flow with Contrast-enhanced Ultrasound

Microbubble ultrasound (US) contrast agents have been used to monitor the progression of anti-angiogenic chemotherapies. However, US backscatter measurements used in contrast imaging are inherently variable, given the presence of many microbubbles of random position and size. A model was developed to investigate the influence of US scanner and microbubble characteristics on these variable measurements. The Coefficient of Variation was used to measure variability. It was found that an optimum excitation frequency exists that minimizes this variability. In the case of DefinityTM, a 2.25 MHz centre-frequency pulse yielded a less variable measurement than at 5 MHz. Conversely, decreasing microbubbble concentration was found to significantly increase variability. Evidence suggests that microbubbles are no longer Rayleigh scatterers at sufficient low concentrations. Post-processing was found to aid in reducing measurement variability by averaging samples where microbubble positions are uncorrelated. As well, reduction can be achieved by averaging about a region-of-interest of uniform perfusion.

Keywords: microbubbles
ultrasound
population statistics
numerical modelling
anti-angiogenesis
coefficient of variation
Advisor: Burns, Peter N.
Nutrition-related Marketing in Canada: A Case Study of Whole Grains

In response to evidence of inadequate fibre and magnesium intakes across the Canadian population, the most recent edition of Canada’s Food Guide included a recommendation for increased whole grain consumption. However, whole grain labelling on food packaging remains voluntary and unregulated. The aim of this research was to examine the nature of nutrition guidance provided by whole grain labelling in the Canadian marketplace through a survey of front-of-package nutrition-related marketing in three supermarkets and a detailed examination of nutrient content, ingredients, and price of breads. Whole grain promotion occurred on relatively few products, predominantly among processed foods, and it frequently appeared in conjunction with references to other nutritional characteristics. The whole grain labelling observed was not misleading with respect to highlighting products with whole grain ingredients and higher levels of fibre and magnesium content; however, products with whole grain labelling were less likely to be lower in price.

Keywords: nutrition-related marketing
whole grains
Advisor: Tarasuk, Valerie
Mendelson, Rena
Magnetic Attitude Control For Spacecraft with Flexible Appendages

The design of an attitude control system for a flexible spacecraft using magnetic actuation is considered. The nonlinear, linear, and modal equations of motion are developed for a general flexible body. Magnetic control is shown to be instantaneously underactuated, and is only controllable in the time-varying sense. A PD-like control scheme is proposed to address the attitude control problem for the linear system. Control gain limitations are shown to exist for the purely magnetic control. A hybrid control scheme is also proposed that relaxes these restrictions by adding a minimum control effort from an alternate three-axis actuation system. Floquet and passivity theory are used to obtain gain selection criteria that ensure a stable closed-loop system, which would aid in the design of a hybrid controller for a flexible spacecraft. The ability of the linearized system to predict the stability of the corresponding nonlinear system is also investigated.

Keywords: aerospace
engineering
magnetic attitude control
attitude control
flexible spacecraft
spacecraft attitude control
control of flexible appendages
spacecraft control
magnetic control
geomagnetic field
aerospace control
aerospace engineering
spacecraft dynamics
dynamics and control
dynamics
control
Advisor: Damaren, Christopher John
Designing Products to Enable Environmentally Significant Behaviour

Resources such as energy and water are forecasted to become scarcer in the future. The traditional engineering approach for dealing with this problem can be compromised by the rebound effect. Therefore, it is important that we design products that also encourage users to engage in pro-environmental behaviours, also known as environmentally significant behaviours (ESB). Lead-user theory was first applied to the problem of ESB, resulting in the discovery that resources, when presented in discrete instead of continuous form, enable conservation. The principle was verified empirically. A method was developed to help designers develop products that implement the discretization principle without compromising user needs. Affordance theory was also applied to the problem of ESB. Two methods, one to expedite the finding of affordances and the second to change a product’s affordances to enable ESB, were developed. The application of design theory and techniques to the ESB problem shows promise.

Keywords: Product Design
Environmentally Significant Behaviour
Advisor: Shu, Lily H.