VictorJuiz/thesis huggingface dataset:
The Role of Costimulation in the Persistence of the Immune Response in Kawasaki Disease

Superantigens (SAgs) are implicated in the initiation of many diseases, including Kawasaki disease (KD), a multi-system vasculitis that leads to persistent inflammation and damage of coronary arteries. T cells are central to the pathogenesis of SAg-mediated diseases. Lactobacillus casei cell wall extract (LCWE) induces a disease in mice that resembles human KD, and contains a novel SAg. Despite the fact that SAg-activated T cells undergo apoptosis, they persist and are necessary for coronary inflammation in this model of KD. We report rescue from apoptosis of SAg-stimulated T cells in vitro by costimulation through CD28 or 4-1BB. CD28- or 4-1BB-mediated signaling stimulated concurrently with SAg upregulated the anti-apoptotic factor Bcl-XL. In vivo, co-injection of LCWE and a 4-1BB agonist aggravated coronary disease. These findings suggest that costimulation of T cells affects extent of illness in this model of KD, and supports targeting costimulation as a therapeutic intervention in SAg-triggered diseases.

Keywords: Immunology
Kawasaki Disease
Superantigen
Costimulation
Advisor: Yeung, Rae S. M.
Family Caregivers' Experiences with Stroke Survivors' Weekend Home Passes from In-patient Rehabiltation

This qualitative study investigated the experiences of family caregivers who cared for a stroke survivor throughout weekend passes from an in-patient rehabilitation facility. Following a Husserlian phenomenological perspective, I interviewed 15 family caregivers of stroke survivors on two separate occasions: within one week after their first scheduled weekend pass, and again two weeks after their final transition home. Interviews followed a semi-structured interview guide, and were audio recorded. Interviews were transcribed verbatim, and analyzed using the principles outlined by Giorgi (1997). Analysis of the caregivers’ descriptions of their experiences led to five themes: (i) Caregivers feel overwhelmed throughout the weekend pass, (ii) Access to supportive resources influences caregiving experiences, (iii) Caregivers adjust to the weekend pass throughout its subsequent use, (iv) Caregivers feel a responsibility and a need to be included by health professionals in the care of their family stroke survivor, and (v) Caregivers describe the weekend pass as a means towards recovery. This study has implications for future health services. By appropriately training and supporting caregivers throughout the weekend pass health care professionals can increase the positive experiences of caregivers, and optimize the opportunity to prepare caregivers and stroke survivors for the eventual transition home.

Keywords: Caregivers
Transitions
Stroke
Weekend Pass
Advisor: Cameron, Jill
A Computer Controlled Endorectal Cooling Device for Laser Thermal Therapy

Interstitial laser thermal therapy is a novel local approach to treating prostate cancer. During treatment, thermal ablation may occur on the adjacent rectal wall. The aim of this thesis was therefore twofold: to study the effects of rectal cooling on lesion formation, and secondly, to engineer a computer controlled rectal cooling unit. To study the effects of the coolant temperatures and flow rate, thermal simulations were executed, followed by testing the phenomenon using agar gel phantoms which thermally mimic prostate tissue. Further simulations were run using a treatment planning software, which predicted the required coolant temperatures to protect the outer rectal wall while subsequently determining the shape and size of the resulting coagulated lesion at various laser settings. Results suggest that low coolant temperatures and low flow rates cause maximum cooling rates. Furthermore, the shape and size of the coagulated region is affected by coolant temperatures at specific laser powers and positions within the prostate.

Keywords: Prostate Cancer
Laser Thermal Therapy
Rectal Cooling
Peltier
Advisor: Weersink, Robert
Trachtenberg, John
The Effect of ILO’s Declaration on Fundamental Principles and Rights at Work on the Evolution of Legal Policy in Brazil: An Analysis of Freedom of Association

This dissertation analyzes the effects of the ILO’s 1998 Declaration on Fundamental Principles and Rights at Work, taking as a case study ILO’s promotion of freedom of association in Brazil. It suggests that the 1998 Declaration’s promotional approach offers mechanisms that have the capacity to change a country's behaviour. In the case of Brazil, this change would involve reform of a corporativist trade union law that violates the principle of freedom of association. The peculiarities of compliance with the freedom-of-association principle represent a significant challenge to the ILO, especially when a country lacks the political will to comply with the principle. This dissertation shows that the 1998 Declaration provides mechanisms − information, qualification of the bureaucracy and support of independent actors − that can be used in these situations even outside the scope of a cooperation program to reform the law and modify public policy.

Keywords: 1998 Declaration on Fundamental Principles and Rights at Work
International Labour Organization
Freedom of Association
Brazil
Advisor: Langille, Brian A.
Interpreting the Concept of Beneficial Ownership

The concept of “beneficial ownership” is frequently used in international tax treaties. The concept is applied in situations where taxpayers may be benefiting indirectly from the advantages a particular treaty provides by interposing a corporation in a “tax-favourable jurisdiction” for the purpose of paying less tax than the corporation might pay in other jurisdictions. This corporate behaviour is called “treaty shopping.” Recent constructions of the term “beneficial ownership” in legal literature and case law, and by national tax agencies have been contradictory. Thus, there is a need for clarification both in Canada and internationally. The author of the thesis comes to the conclusion that a new definition is not desirable and that a strict interpretation of the current concept is the lesser evil. However, he argues that, if the concept is to be effectively used to tackle the kinds of arrangements it was intended to challenge, the assistance of a substance-over-form component is inevitable. He proposes some ways this component might be developed.

Keywords: International
Taxation
Advisor: Alarie, Benjamin
A Risk-based Evaluation of the Long-term Performance of Stormwater Infiltration Facilities

Infiltration facilities are source control mechanisms that are implemented in urban developments with reduced natural permeable surfaces. Despite the development of design criteria for infiltration facilities, these systems continue to fail due to headloss development, overflow, or chemical breakthrough. The limited research on the long-term performance of these systems has emphasized the role of physical filtration mechanisms within porous media filters to address concerns surrounding system failure, namely filter clogging. A continuous macroscopic depth filtration model was developed to investigate the clogging potential of the underlying sand filter. This continuous model furthers the understanding of temporal and spatial changes in system performance for the development of more appropriate design criteria and more suitable maintenance regimes. The characterization of long-term system performance by defining three different failure modes and a probabilistic approach comprises a comprehensive methodology by considering several performance criteria rather than assuming that one criterion dictates the overall system performance.

Keywords: stormwater
filtration
trenches
infiltration
clogging
BMP
depth filtration
macroscopic model
filter performance
Advisor: Adams, Barry J.
The Role of Candidate G-protein Coupled Receptors in Mediating Remote Myocardial Ischemic Preconditioning

This study investigated the role of opioid, adenosine, bradykinin, and calcitonin-gene related peptide (CGRP) receptors, and potential ‘cross-talk’ among suspected G-protein coupled receptors in a humoral model of remote ischemic preconditioning (rIPC) cardioprotection. Compared to Control dialysate (from non-preconditioned donor rabbit blood), rIPC dialysate (from remotely preconditioned blood) reduced cell death in rabbit cardiomyocytes following simulated ischemia and reperfusion. Non-selective, δ-, or κ-opioid receptor blockade and non-selective adenosine receptor blockade abolished rIPC dialysate protection; whereas, bradykinin B2 and CGRP receptor blockade had no effect. Non-selective adenosine receptor blockade fully and partially abolished protection by κ- and δ-opioid receptors, respectively. Multiple reaction monitoring mass spectrometry detected low levels of adenosine, and other preconditioning substances, in the dialysate. An increase in extracellular adenosine was not detected during opioid-induced preconditioning to explain this cross-talk. These results suggest that δ-opioid, κ-opioid, adenosine receptors, and opioid-adenosine cross-talk are involved in rIPC of freshly isolated cardiomyocytes.

Keywords: remote ischemic preconditioning
opioid receptors
adenosine receptors
bradykinin B2 receptor
CGRP receptor
opioid-adenosine receptor cross-talk
isolated rabbit cardiomyocyte model
Advisor: Wilson, Gregory J.
Ruthenium 4,5-diazafluorene Complexes and their Reactivity

The reaction between RuCl2(PPh3)3 and 4,5-diazafluorene (LH) produced the orange, air sensitive RuCl2(LH)(PPh3)2 (1). Exposing this complex to air led to the oxidation of the CH2 group on the central ring of LH to a carbonyl group. RuCl2(LH)(dppb) (3) was synthesized but did not show the same reactivity as complex 1. The reaction between RuHCl(LH)(PPh3)2 (4) and KOtBu produced the purple complex RuH(N2)(L)(PPh3)2 (5), L = deprotonateed 4,5-diazafluorene. Complex 5 heterolytically splits H2 to form RuH2(LH)(PPh3)2 (6), quantitatively. Complex 5 shows C-D bond activation of C6D6 and is air sensitive in the solid state and in solution. Both 1 and 6 were shown to catalyze the hydrogenation of acetophenone. Bis(4,5-diazafluoren-9-yl)methane has been synthesized and fully characterized by 1H NMR, 13C NMR and X-ray crystallography.

Keywords: Ruthenium
4,5-diazafluorene
Advisor: Song, Datong
A Role for ETA(253-412) in Peptide-based Delivery of Therapeutic Molecules into Cells

The delivery of biomolecules by cell penetrating peptides (CPPs) is an innovative therapeutic strategy. However delivery efficiency is hindered by the entrapment of CPPs in vesicles, degradation, or recycling out of cells, which limits their delivery into the cell cytoplasm and nucleus. To overcome these barriers, we investigated a bacterial protein domain derived from Pseudomonas aeruginosa, Exotoxin A (ETA, residues 253-412) that is able to exit vesicular compartments. A series of CPP-ETA(253-412) fusion proteins were constructed, expressed, and purified. Confocal microscopy and flow cytometry confirmed the internalization at 37oC of constructs containing CPPs (poly-arginine or TAT). In addition, constructs containing CPP-ETA(253-412)-eGFP were shown to relocate from endosomes to the cytosol. CPP-ETA(253-412) constructs were also able to act as carriers of DNA cargos facilitating their delivery to the cytosol. The ETA(253-412) translocation domain may prove useful for the intracellular delivery of drugs, protein therapeutics, siRNA delivery, and vaccine formulations.

Keywords: Drug Delivery
Endosomal Escape
Advisor: Gariepy, Jean
Scattering of High-frequency Ultrasound by Individual Bound Microbubbles

Targeted imaging with microbubbles may resolve the molecular expression within the abnormal blood vessels of tumours. Optimal imaging requires understanding the interaction between targeted microbubbles and high-frequency ultrasound. Therefore, the subharmonic signal, and backscattering cross-section of individual bound microbubbles were examined with coaligned 30 MHz pulses and optical images. The peak subharmonic signal was generated for 1.6 µm diameter microbubbles for 20% and 11% bandwidth pulses and 1.8 µm for 45% bandwidth pulses at 200 kPa, consistent with estimations of the resonant size of microbubble's at 15 MHz. In order to measure the scattering cross-section, a new method was proposed to measure the receive transfer function of a transducer. Measurements of the backscattering cross-section scaled with the square of the radius, with signi cant size-independent variability. The results of this thesis will help optimise the parameters for targeted imaging, as well as further our understanding of the behaviour of microbubbles.

Keywords: High-frequency ultrasound
Microbubbles
Molecular imaging
Subharmonic signal
Advisor: Foster, F. Stuart
Post Exercise Hypotension and Blood Pressure Circadan Rhythm in Pre-hypertensive Older Adults

Pre-hypertension (pre-HT) (Blood Pressure (BP) ≥120/80mmHg to ≤ 140/90mmHg) increases the risk of developing hypertension (HT). BP reductions following acute exercise are known as post exercise hypotension (PEH). BP and perhaps PEH shows a daily circadian rhythm. Purpose: To compare the magnitude of PEH after morning and evening aerobic exercise in adults with pre-HT. Hypothesis: The magnitude of PEH will be larger after evening versus morning exercise. Participants: Pre-HT men and women 50-65 years old. Study Design: Participants engaged in cycling exercise (60% VO2max) on two occasions: 1.5 and 11 hours following waking. Cardiovascular function was assessed for 30 minutes pre and one hour post exercise. Results: 1) Systolic PEH responses affected by TOD differed by gender. 2) Baseline Heart Rate Variability and its response to exercise differed gender but not TOD. The inconsistent significant gender and TOD differences of PEH and its mechanisms suggest that this group.

Keywords: Pre-Hypertensive
Post Exercise Hypotension
Circadian Rhythm
Older Adults
Advisor: Thomas, Scott
Mortality in the Yukon: Post-harvest Effects on Structural Retention

Structural retention harvesting represents one of the most important recent silvicultural innovations and is widely practiced in the harvesting of mature boreal stands. Following structural retention harvests, mortality of retained trees is often dramatically elevated compared to pre-harvest stands. I examined tree mortality following structural retention harvests in the southeastern Yukon Territory, using dendrochronological techniques to quantify annual mortality. I estimated integrated losses in the first five years to be at least 17.3% of retained stems. Analysis of mortality type showed that windthrow was the most important post-harvest mortality mechanism. This study represents the first analysis of mortality responses following structural retention harvests in the northern extent of operational forestry in Canada. Rates of post-harvest tree mortality observed in this study are among the highest reported to date from managed Canadian boreal forests, indicating that greater attention must be given to post-harvest stand responses if sustainable forestry practices are desired.

Keywords: post-harvest mortality
sustainable forestry
structural retention
dendrochronology
Yukon
boreal
Advisor: Caspersen, John
Thomas, Sean C.
A Technical and Clinical Assessment of Stereotactic Registration Techniques to Improve MRI Guided Needle Navigation in Prostate Cancer Targeting

Prostate cancer is prevalent among men and one of the few cancer sites where local therapies currently target the entire organ instead of tumour. MRI holds promise in accurately depicting regions of cancer burden within the prostate gland and guiding tumour-targeted diagnostics and therapeutics. The clinical performance of a novel stereotactic MRI-guided needle navigation system for prostate cancer targeting was evaluated. Mean absolute in-plane stereotactic needle-targeting error for 10 patients was 2.2 mm and mean absolute depth error was 6.5 mm, highlighting a need to improve technical accuracy of the system. Consequently, alternative stereotactic registration techniques were investigated. Metrics of performance were in-plane stereotactic needle-targeting error, depth error, and registration time. A Z-shaped fiducial motif using automated registration performed best in phantom experiments with an in-plane error of 2.0 mm and depth error of 1.0 mm. These results will guide further software and hardware development to improve clinical performance.

Keywords: MRI-guided biopsy
stereotactic registration
prostate cancer
Advisor: Menard, Cynthia
The Low-dose Limits of Lung Nodule Detectability in Volumetric Computed Tomography

Purpose. Low-dose computed tomography is an important imaging modality for screening and surveillance of lung cancer. The goal of this study was to determine the extent to which dose could be minimized while maintaining diagnostic accuracy through knowledgeable selection of reconstruction techniques. Methods. An anthropomorphic phantom was imaged on a 320-slice volumetric CT scanner. Detectability of small solid lung nodules was evaluated as a function of dose, patient size, reconstruction filter and slice thickness by means of 9-alternative forced-choice observer tests. Results. Nodule detectability decreased sharply below a threshold dose level due to increased image noise. For large body habitus, optimal (smooth) filter selection reduced dose by a factor of ~3. Nodule detectability decreased for slice thicknesses larger than the nodule diameter. Conclusions. Radiation dose can be reduced well below current clinical protocols. Smooth reconstruction filters and avoidance of large slice thickness permits lower-dose techniques without tradeoff in diagnostic performance.

Keywords: Lung Nodule Surveillance
Lung Cancer Screening
Reconstruction Filter
Volumetric CT
observer performance
Advisor: Jeffrey, Siewerdsen
Use of Meconium and Hair for Detection of Prenatal Exposure to Ethanol and Other Drugs of Abuse

In-utero ethanol exposure may result in fetal alcohol spectrum disorder (FASD). Studies have suggested that women who drink ethanol are more likely to consume illicit drugs. Detection of such exposures has been done via meconium and hair testing and can serve to direct needed prevention methods and appropriate management and intervention for the neonate and the mother. This study examined maternal diabetes as a possible confounder for in-utero ethanol exposure testing and determined the trends in drug use associated with heavy in-utero ethanol exposure in a high-risk obstetric Canadian population. It was determined that maternal diabetes does not produce false-positive results in testing for in-utero ethanol exposure. Furthermore, heavy in-utero ethanol exposure was detected in 15.5% of samples and was associated with an increased exposure to amphetamines (OR=3.30) and opiates (OR=2.01), but a decreased exposure to cannabinoids (OR=0.61) when compared to neonates with no heavy in-utero ethanol exposure.

Keywords: Alcoholism
Drugs of abuse
Ethanol
FAEE
Meconium
Neonatal hair
Glucose
Advisor: Koren, Gideon
Comparing Tyrosine Phosphorylation Changes after Erlotinib Treatment betweem Drug Sensitive and Drug Resistant Non-small Cell Lung Cancer Lines by Mass Spectrometry

Non-Small-Cell-Lung Cancer (NSCLC) patients with mutations in EGFR have greater response rates and survival when treated with the tyrosine kinase inhibitor erlotinib. To elucidate how erlotinib inhibits EGFR, this study included: 1) inhibiting an EGFR mutant cell line to reveal EGFR regulated phosphotyrosine (pY) sites; 2) comparing erlotinib sensitive and insensitive cell lines to reveal functionally important pY sites; 3) revealing novel pY sites. Observations were collected using the LTQ-Orbitrap mass spectrometer. This study identified five new EGFR regulated pY sites and five pY sites that correlated with erlotinib sensitivity; the majority of them are related to cell-cell interactions. By comparing all observed pY sites to the Phosphosite and PhosphoELM database, our results included 67 unregistered sites. This study has identified novel biomarkers and potential therapeutic targets, many of which were associated with cell migration and adhesion function. Further functional validation is necessary.

Keywords: EGFR
Non-Small Cell Lung Cancer
Erlotinib/Tarceva
Proteomics
Cell Signaling
Advisor: Tsao, Ming-Sound
Synaptic Noise-like Activity in Hippocampal Interneurons

Noise-like activity (NLA) refers to spontaneous subthreshold fluctuations in membrane potential. In this thesis, we examine the role that synaptic channel fluctuations play in contributing to NLA by comparing a detailed biophysical model to experimental data from whole-intact hippocampal interneurons. To represent the contribution from synaptic channel fluctuations, we switch the synapses in the model from traditional to Markovian formalisms and demonstrate statistically relevant increases the standard deviation; power-law scaling exponent; and power spectral density in the 5-100 Hz and 1-5 kHz ranges. However, while synaptic channel fluctuations have a definite effect, we found that they were significantly more subtle than the synaptic response to network activity. This indicates that synaptic channel fluctuations do indeed play a significant role in subthreshold noise, but, overall, synaptic NLA is dominated by the synaptic response to presynaptic network activity.

Keywords: synaptic channel fluctuations
Markov model
multi compartment
Hodgkin-Huxley
neuron
noise
interneuron
hippocampus
Advisor: Bardakjian, Berj
Scalable and Transparent Parallelization of Multiplayer Games

In this thesis, we study parallelization of multiplayer games using software Transactional Memory (STM) support. We show that STM provides not only ease of programming, but also better scalability than achievable with state-of-the-art lock-based programming for this realistic high impact application. We evaluate and compare two parallel implementations of a simplified version (named SynQuake) of the popular game Quake. While in STM SynQuake support for maintaining consistency of each potentially complex game action is automatic, conservative locking of surrounding objects within a bounding-box for the duration of the game action is inherently needed in lock-based SynQuake. This leads to higher scalability of STM SynQuake versus lock-based SynQuake due to increased false sharing in the latter. Task assignment to threads has a second-order effect on scalability of STM-SynQuake, impacting the application's true sharing patterns. We show that a locality-aware task assignment provides the best trade-off between load balancing and conflict reduction.

Keywords: multiplayer games
parallelization
transactional memory
lock-based synchronization
scalability
load balancing
performance
Advisor: Amza, Cristiana
Bidirectional Integrated Neural Interface for Adaptive Cortical Stimulation

This thesis presents the VLSI implementation and characterization of a 256-channel bidirectional integrated neural interface for adaptive cortical stimulation. The microsystem consists of 64 stimulation and 256 recording channels, implemented in a 0.35um CMOS technology with a cell pitch of 200um and total die size of 3.5mm x3.65mm. The stimulator is a current driver with an output current range of 20uA – 250uA. The current memory in every stimulator allows for simultaneous stimulation on multiple active channels. Circuit reuse in the stimulator and utilization of a single DAC yields a compact and low-power implementation. The recording channel has two stages of signal amplification and conditioning and a single-slope ADC. The measured input-referred noise is 7.99uVrms over a 5kHz bandwidth. The total power consumption is 13.3mW. A new approach to CMOS-microelectrode hybrid integration by on-chip Au multi-stud-bumping is also presented. It is validated by in vitro experimental measurements.

Keywords: neural
amplifier
stimulation circuit
array
cmos
ADC
Advisor: Genov, Roman