VictorJuiz/thesis huggingface dataset:
The Role of Dopamine in Cue-induced Craving: A [11C]-(+)-PHNO PET Study in Tobacco-dependent Smokers

Environmental stimuli associated with drug use are related to drug craving and relapse. The mechanism of cue-induced craving is thought to involve the release of dopamine (DA) in brain regions associated with reward and habit formation. The aim of the study was to investigate the role of DA in cue-induced craving in tobacco-dependent smokers using Positron Emission Tomography (PET) and a picture cue paradigm. Tobacco-associated cues were capable of eliciting significantly greater subjective reports of craving relative to neutral cues in tobacco smokers (n=6) in a neuroimaging environment. Using this cue paradigm and [11C]-(+)-PHNO PET (n=6), a non-significant trend towards a greater decrease in binding potential, indicative of dopamine release, was shown in selected brain regions of interest. These findings are similar to findings in cocaine-dependent individuals and suggest the involvement of dopamine in the response to smoking-associated cues in tobacco-dependent individuals.

Keywords: dopamine
craving
[11C]-(+)-PHNO
PET
Advisor: Busto, Usoa
Foll, Bernard Le
RBF Based Responsive Stimulators To Control Epilepsy

Deep Brain Simulation (DBS) has received attention in the scientific community for its potential to suppress epileptic seizures. To date, DBS has only achieved marginal positive results. We believe that a highly complex possibly chaotic (HPC) biologically inspired stimulation is superior to periodic stimulation. Using Radial Basis Functions (RBFs), we modeled interictal and postictal time series based on electroencephalograms (EEGs) of rat hippocampus slices while under low Mg2+. We then compared the RBF based interictal and postictal stimulations to the periodic stimulation using a Cognitive Rhythm Generator (CRG) model for spontaneous Seizure-Like Events (SLEs). What resulted was a significant improvement in seizure suppression with the HPC stimulators at lower gains as opposed to the periodic signal. This suggests that the use of biologically inspired HPC stimulators will achieve better results while confining the stimulation to a narrow region of the brain.

Keywords: Epilepsy
Responsive Stimulation
Control
Cognitive Rhythm Generator
Seizure
Seizure Like-Events
Advisor: Bardakjian, Berj
High Speed Homodyne Detector for Gaussian-modulated Coherent-state Quantum Key Distribution

We developed a high speed homodyne detector in the telecommunication wavelength region for a Gaussian-modulated coherent-state quantum key distribution experiment. We are able to achieve a 100 MHz bandwidth, ultra-low electronic noise and pulse-resolved homodyne detector. The bandwidth of this homodyne detector has reached the same order of magnitude of the best homodyne detectors reported. By overcoming photodiode response functions mismatch, choosing proper laser sources, ensuring the homodyne detector linearity and stabilizing the homodyne detection system, we demonstrate that the homodyne detector has a 10 dB shot-noise-to-electronic-noise ratio in the time domain at a local oscillator of 5.4*10^8 photons/pulse at a laser repetition rate of 10 MHz. With this homodyne detector, we expect to ncrease our GMCS QKD experiment speed by 100 times, which will improve the key generation rate by 1-2 orders of magnitude.

Keywords: Quantum key distribution
Homodyne detection
Advisor: Lo, Hoi-Kwong
Qian, Li
A System for Detecting, Preventing and Exposing Atomicity Violations in Multithreaded Programs

Multi-core machines have become common and have led to an increase in multithreaded software. In turn, the number of concurrency bugs has also increased. Such bugs are elusive and remain difficult to solve, despite existing research. Thus, this thesis proposes a system which detects, prevents and optionally helps expose concurrency bugs. Specifically, we focus on bugs caused by atomicity violations, which occur when thread interleaving violates the programmer’s assumption that a code section executes atomically. At compile-time, our system performs static analysis to identify code sections where violations could occur. At run-time, we use debug registers to monitor these sections for interleaving thread accesses which would cause a violation. If detected, we undo their effects and thus prevent the violation. Optionally, we help expose atomicity violations by perturbing thread scheduling during execution. Our results demonstrate that the system is effective and imposes low overhead.

Keywords: Concurrency
Systems Design
Atomicity violation
Advisor: Lie, David
Offline Feedback Utilization for a Manual Aiming Movement Performed Under Conditions of Randomized Visual Feedback Availability

Two studies were devised to determine why the difference in manual aiming performance, between full vision and no vision, is decreased for a randomized visual feedback schedule. In study one, aiming accuracy and precision was assessed for up to four trials in the same vision condition, following a switch in visual feedback availability. In experiment one, visual feedback availability was uncertain; while in experiment two, certainty was provided. Results of both experiments revealed that the precision of the first trial immediately following the switch in visual condition was reminiscent of the trial that preceded it, even when performed under different visual conditions. For study two, the inter-trial interval was evaluated by extending the interval to five seconds. Results indicated no reminiscence effect. Overall, we suggest that when the inter-trial trial is brief, individuals rely on offline visual information from the preceding trial to plan the subsequent movement, regardless of certainty.

Keywords: manual aiming
offline visual feedback utilization
preceding trial
trial-to-trial analysis
Advisor: Tremblay, Luc
Novel MEMS Grippers for Pick-place of Micro and Nano Objects

Physical pick-and-place promises specificity, precision, and programmed motion, a feature making microrobotic manipulation amenable to automation for the construction of microsystems. Despite the significant progress made, a long-standing difficulty is the release of micro objects from the end effector due to strong adhesion forces at the micro scale. This research focuses on the development of microelectromechanical systems (MEMS) based microgrippers that integrate an active release mechanism for pick-and-release micromanipulation. The performance was experimentally quantified through the manipulation of 7.5-10.9µm glass spheres, and for the first time, achieves a 100% success rate in release (based on 700 trials) and a release accuracy of 0.45±0.24µm. Example patterns were then constructed through automated microrobotic pick-and-place of microspheres, achieving a speed of 6sec/sphere. To further miniaturize the devices for nanomanipulation, a novel fabrication process was developed. Through the manipulation of 100nm gold nano-particles inside a scanning electron microscope (SEM), preliminary demonstrations were made.

Keywords: Micromanipulation
Microgrippers
Advisor: Sun, Yu
Central Nervous System (CNS) Nutrient Sensing in Diabetes

An acute increase in hypothalamic glucose and its downstream metabolite lactate lower glucose production (GP) and plasma glucose (PG) levels in normal rodents. However, the effectiveness of this nutrient-sensing mechanism in metabolic disease is unknown. We assessed the effects of intracerebroventricular (i.c.v.) or intra-hypothalamic glucose and lactate on in vivo glucose kinetics in conscious rats. Study I revealed that i.c.v. lactate lowered PG via a suppression of GP in rodents with uncontrolled diabetes and diet-induced insulin resistance. Study II demonstrated that i.c.v. glucose was ineffective at suppressing GP in uncontrolled diabetic rodents or rodents with a prior 24 h whole-body or hypothalamic hyperglycemic insult. When PG levels per se were normalized in diabetic rodents hypothalamic glucose sensing to lower GP was rescued. As such, sustained hyperglycemia per se impairs hypothalamic glucose effectiveness in diabetes. Further studies are necessary to determine defective mechanisms upstream of lactate metabolism hindering CNS glucose sensing.

Keywords: Diabetes
Glucose Production
Hypothalamus
Rodent
Advisor: Lam, Tony K. T.
Syntaxin-1A Inhibits Cardiac ATP-Sensitive Potassium Channels by Direct Interaction with Distinct Domains within Sulphonylurea Receptor 2A Nucleotide-Binding Folds

KATP channels couple cell metabolic status to the membrane excitability by sensing the cytoplasmic ATP/ADP ratio. Present studies examined how conserved motifs (Walker A (WA), signature sequence (L), and Walker B (WB)) within each NBF of SUR2A bind to Syn-1A to affect its actions on cardiac KATP channels. In vitro binding experiments illustrated that Syn-1A binds cardiac SUR2A at WA and L of NBF-1 and WA, L, and WB of NBF-2. Electrophysiology experiments on stably expressing SUR2A/Kir6.2 cell-lines showed that only L and WB of NBF-1 and all three NBF-2 motifs could abrogate the inhibitory effect of Syn-1A on SUR2A/KATP channels. These results lead me to hypothesize that more independent motif in NBF-2 can bind and abrogate Syn-1A’s inhibition than NBF-1 on SUR2A/KATP channels. A corollary postulate is that Syn-1A acts as a scaffold to secure the NBF-1 and -2 in dimer conformation required for SUR2A to modulate Kir6.2 gating.

Keywords: Syntaxin-1A
ATP-sensitive potassium channel
sulfonylurea receptor
SNARE
Kir6.2
SUR2A
Advisor: Gaisano, Herbert Young
Feng, Zhong-Ping
Syntaxin-1A Inhibits the KATP Channel Through Interaction with Distinct Sites Along the Nucleotide-binding Folds of Sulfonylurea Receptor 1

The KATP channel is a key regulator of the pancreatic β-cell, effectively linking metabolic status to electrical activity. Syntaxin-1A has been previously reported by our lab to both bind and inhibit the KATP channel via the nucleotide-binding folds (NBFs). The purpose of this thesis project was to elucidate the precise regions within the NBFs responsible for the Syn-1A- KATP interaction. In vitro binding assays revealed that Syn-1A associates with the Walker domains of both NBF1 and NBF2. Furthermore, site directed mutagenesis of the conserved lysine in Walker A of both NBFs abolishes Syn-1A affinity for this region. Electrophysiological recordings indicate that channel inhibition was mediated primarily through interaction with NBF1-Walker B and both Walkers of NBF2. Based on these results, we propose a model by which Syn-1A acts as an inhibitory clamp on the KATP channel, effectively buffering minor fluctuations in ATP/ADP concentration to prevent unnecessary channel activity.

Keywords: Syntaxin-1A
KATP
nucleotide-binding folds
ATP/ADP
Advisor: Gaisano, Herbert Young
Feng, Zhong-Ping
Circuit Debugging with Error Trace Compaction and Maximum Satisfiability

Improving the performance and functionality of contemporary debugging tools is essential to alleviate the debugging task. This dissertation aims at narrowing the gap between current capabilities of debugging tools and industry requirements by improving two important debugging techniques: error trace compaction and automated debugging. Error trace compaction leverages incremental SAT and heuristics to reduce the number of clock cycles required to observe a failure in an error trace. The technique presented reduces the length of the error trace to a minimum while improving performance by 8× compared to a previous technique. The second contribution uses maximum satisfiability to enhance the functionality and performance of automated debuggers. The method proposed can identify where in the design the bug is located and when in the error trace the bug is excited. Compared to a competitive SAT-based approach, our formulation produces problems that are 80% smaller and that can be solved 4.5x faster.

Keywords: Circuit Debugging
Formal Methods
Advisor: Veneris, Andreas
Modeling of an Electrochemical Cell

This thesis explores a rigorous approach to model the behaviour of an electrochemical cell. A simple planar electrochemical cell consisting of stainless steel electrodes separated by a sulfuric acid electrolyte layer is modeled from first principles. The model is a dynamic model and is valid under constant temperature conditions. The dynamic model is based on the Poisson-Nernst-Planck electrodiffusion theory and physical attributes such as the impact of nonlinear polarization, the stoichiometric reactions of the electrolyte and changes to the transport coefficients are investigated in stages. The system of partial differential equations has been solved using a finite element software package. The simulation results are compared with experimental results and discrepancies are discussed. The results suggest that the existing theory is not adequate in explaining the physics in the immediate vicinity of the electrode/electrolyte interface even though the general experimental and simulation results are in qualitative agreement with each other.

Keywords: Electrochemical Cell
Electrochemical Capacitor
Supercapacitor
Ultracapacitor
Modelling
Advisor: Dawson, Francis P.
Lian, Keryn
Determination of the Role of Synapse Associated Protein 97 (SAP97) in the Normal and Parkinsonian Striatum

Parkinson’s disease (PD) is a debilitating movement disorder associated with the death of dopaminergic nigrostriatal neurons. In addition to dopamine deficiency, abnormalities in glutamate and other receptors at striatal synapses have been reported. Synapse associated protein 97 (SAP97) is involved in regulation of glutamate receptor function. In the striatum of unilaterally-lesioned 6-OHDA rat model of PD, SAP97 levels are decreased in post synaptic density fraction, as well as in the whole striatum. I hypothesize that changes in striatal levels and subcellular distribution of SAP97 are responsible for abnormal neurotransmission in striatum and the motor symptoms of PD. GFP-tagged wild type SAP97 and SAP97 mutants were over-expressed in the striatum of 6-OHDA-lesioned rat model of PD. A single 6.5 mg/kg dose of L-DOPA eliminated parkinsonism in 6-OHDA-lesioned rats over-expressing SAP97-GFP, whereas, three 6.5 mg/kg doses of L-DOPA negated parkinsonism in 6-OHDA-lesioned rats over-expressing SAP97-GFP and SAP97∆1-65-GFP. The over-expression of SAP97∆1-65-GFP enhanced parkinsonism in 6-OHDA-lesioned rats and blocked the antiparkinsonian effect of L-DOPA.

Keywords: Parkinson's
SAP97
6-OHDA-lesioned
striatum
Advisor: Nash, Joanne
The Protein Interactions and Functions of Transient Receptor Potential Melastatin 7 (TRPM7) Ion Channel

Ion channels are proteins that facilitate ion diffusion across cell membrane. Nevertheless, various groups of ion channels can act as surface receptors and play important roles in signal transduction. Transient Receptor Potential Melastatin 7 (TRPM7) ion channel has been implicated in diverse cellular functions including actomyosin cytoskeletal remodeling and anoxic neuronal death. However the mechanisms behind TRPM7’s physiological roles remain undetermined. TRPM7 possesses unusually long intracellular domains and a functional C-terminal alpha kinase domain that may contribute to regulation of channel activity and signal transduction. We therefore identified proteins that interact with TRPM7 C-terminus. Pull-down assays coupled with LC-MS/MS revealed that cytoskeletal proteins (actin and tubulin) and synaptic vesicle proteins (VAMP2 and SNAP25) associate with the TRPM7. In addition, we further found that TRPM7 does not directly bind microtubules or single dimeric tubulin subunits. Thus one or more microtubule binding proteins is involved in the association between TRPM7 and microtubules.

Keywords: Protein Interactions
TRPM7
Advisor: Aarts, Michelle
Coating Collagen Modules with Fibronectin Increases in vivo HUVEC Survival and Vessel Formation through the Suppression of Apoptosis

Modular tissue engineering is a novel approach to creating scalable, self-assembling three-dimensional tissue constructs with inherent vascularisation. Under initial methods, the subcutaneous implantation of human umbilical vein endothelial cell (HUVEC)-covered collagen modules in immunocompromised mice resulted in significant host inflammation and limited HUVEC survival. Subsequently, a minimally-invasive injection technique was developed to minimize surgery-related inflammation, and cell death was attributed to extensive apoptosis within 72 hours of implantation. In confirmation of in vitro results, coating collagen modules with fibronectin (Fn) was shown in vivo to reduce short-term HUVEC apoptosis by nearly 40%, while increasing long-term HUVEC survival by 30% to 45%. Consequently, a 100% increase in the number of HUVEC-lined vessels was observed with Fn-coated modules, as compared to collagen-only modules, at 7 and 14 days post-implantation. Furthermore, vessels appeared to be perfused with host erythrocytes by day 7, and vessel maturation and stabilization was evident by day 14.

Keywords: modular tissue engineering
endothelial cells
apoptosis
extracellular matrix
fibronectin
Advisor: Sefton, Michael
Evaluating the Efficiency, Usability and Safety of Computerized Order Sets in Sunnybrook Health Sciences Centre's Computerized Provider Order Entry System

Few studies examine technical barriers, such as usability, to successful Computerized Provider Order Entry (CPOE) system implementation. This thesis explores this literature gap through the evaluation of the Sunnybrook CPOE order set system with a heuristic evaluation of the Sunnybrook CPOE system, the development of a more user friendly CPOE order set interface (Test Design), and a usability study comparing three order set formats (Sunnybrook CPOE, Test Design, and paper order sets). A randomized trial was conducted with 27 Sunnybrook physicians at the hospital. Results showed that the Sunnybrook CPOE order set system was less efficient (task times were on average 364 seconds longer than Test Design and 344 seconds longer than paper), less user-friendly (users were less confident, less satisfied, and more frustrated with Sunnybrook CPOE tasks), and less safe than paper order sets (more harmful errors). Test Design was as efficient and safe as paper order sets.

Keywords: CPOE
Human Factors
Usability
Advisor: Etchells, Edward
Improving Patient Safety during Radiation Therapy through Human Factors Methods

This study aimed to apply human factors methods to identify potentially unsafe aspects of a radiation therapy delivery system at Princess Margaret Hospital, and to provide recommendations accordingly. Analyses were conducted to examine the workflow, work environment and user interfaces involved in the treatment process. Based on findings from these analyses, components of the user interface were redesigned to address some of the issues found. Sixteen radiation therapy students were then used to experimentally evaluate the redesigned interface through a usability test. Compared to the current interface, the error rates of two common errors were significantly lower, and the average task completion time was significantly shorter when the redesigned interface was used. Results from a post-test questionnaire also indicated a high degree of satisfaction with the redesigned interface. Therefore, human factors methods can be applied to evaluate and design radiation therapy systems for improved error rates, efficiency and user satisfaction.

Keywords: Radiation Therapy
Human Factors
Advisor: Cafazzo, Joseph
Islam, Mohammad
Identification of Molecular Alterations Associated with Loco-regional and Distant Breast Cancer Metastasis

Metastasis initiation is a complex process encompassing numerous steps. To identify molecular alterations associated with early and late stages of metastasis, we used high throughput screening techniques. Early events in metastasis were investigated by differential proteomic analysis of lymph node-negative and positive breast cancer samples. Two candidate biomarkers (DCN and HSP90B1) were discovered and further validated through tissue microarray analyses. To examine late events in metastasis formation, we prospectively evaluated genomic differences between disseminated tumour cells in bone marrow, and metastatic tumour cells obtained from computed tomography guided biopsies of bone metastases. Results indicate that specific subsets of genes are required for breast cancer cells to initiate bone metastases. Discovery of proteomic and genomic alterations specifically associated with metastases may yield biomarkers capable of stratifying patients into different risk categories. Proteins and genes identified in this work may form the foundation of a biomarker panel for metastatic risk assessment.

Keywords: Breast cancer
Biomarkers
Advisor: Done, Susan Jane
Human Rights and the War Against International Terrorism: A War Without Rights?

The United States has justified targeted operations against suspected terrorists as a legitimate tool in the war against terrorism. In response to international criticism that a November 2002 targeted killing operation in Yemen violated human rights standards, the US asserted that the right to life was suspended during war. While this assertion is prima facie incorrect, many legal experts, scholars and authors agree in principle that a military response to international terrorism -- along with the concomitant dilution of the right to life -- is not only appropriate, but also complies with international law. However, the modern jus ad bellum limit the circumstances in which a state may lawfully resort to armed force. A fulsome understanding of international humanitarian law and the characteristics of groups such as Al Qaeda reveals that international law does not permit states to employ their military forces to responde to the international crime of international terrorism.

Keywords: international humanitarian law
international human rights law
targeted killing
terrorism
Advisor: Morgan, Ed
Law as a Social Determinant of Unsafe Abortion in Argentina

Using Burris et al.’s model of law as a social determinant of health, this thesis postulates that the law and its application contribute to abortion-related morbidity and mortality among those women who qualify for a legal and safe abortion according to the justifications stipulated in the Criminal Code. This thesis proposes a circular model in order to show how the application of the law, through courts rulings, contributes to unsafe abortion. On the one hand, Argentine law acts as a pathway along which inequity in socioeconomic status exposes certain women to pathogenic practices, such as self-induced abortions. On the other hand, the law acts as a shaper of socioeconomic status as it perpetuates gender stereotypes, constructing a normative world where sex-role stereotypes are naturalized, and having an impact in women’s lack of access to legal and safe abortions.

Keywords: abortion
Argentina
Social Determinants of Health
Advisor: Cook, Rebecca J.