VictorJuiz/thesis huggingface dataset:
Sleep-wake Behaviour in Rats: The Link between Ultradian Rhythms and Sleep Homeostasis

The underlying mechanism for the origin of ultradian rhythms is not clearly understood at present. Based on a recent study from our laboratory, we have conceptualized a model for the origin of quasiperiodic ultradian rhythms in sleep-wake state. This model hypothesizes that the ultradian rhythms of sleep-wake state may be generated by a mechanism that includes the sleep-wake homeostat. The main purpose of the present study was to test the hypothesis that sleep homeostasis and sleep-wake ultradian rhythms share a common underlying mechanism. The present study has refuted that hypothesis. I conclude that: (1) the proposed model for the generation of quasiperiodic ultradian rhythms in sleep-wake state in mammals is overly simplistic in its present form, (2) the generation of ultradian rhythms in sleep-wake state probably arise from a more complex systemic interactions between the sleep-wake oscillatory network and other internal/external inputs, rather than the simple expression of sleep homeostat.

Keywords: Ultradian Rhythms
Sleep
Rats
Sleep Homeostasis
Advisor: Stephenson, Richard
Creation of a Retroviral RNAi Knockdown System to Investigate Gene Variants in SLE

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies against self-antigens. SLE has a complex multifactorial genetic basis. Genome wide association studies (GWAS) have implicated polymorphisms causing decreased expression in many genes in SLE etiology and will likely continue to implicate new genes. Therefore, the aim of my project was to create a modular system where the effect of knocking down a gene of interest can be studied in cell culture in a timely manner. This was accomplished by inserting shRNAmirs targeting our validation gene, A20, into a retroviral vector, creating viral particles using a packaging cell line, and infecting cultured cells. Two shRNAmirs were determined to be effective by qRT-PCR and Western blots on infected cells. Vectors carrying these shRNAmirs were used to infect ex vivo B cells and BMDCs, and results suggested that A20 knockdown may mediate functional changes in both cell types.

Keywords: Immunology
Systemic Lupus Erythematosus
Advisor: Wither, Joan
Experimental Realization of Decoy State Polarization Encoding Measurement-device-independent Quantum Key Distribution

Quantum key distribution (QKD) allows two remote parties to generate secret keys for cryptographic purposes. Its security has been proven with some assumptions. However, practical realizations may not comply with all the assumptions, leading to various attacks. Founded on the observation that almost all attacks are on the detection part, measurement-device-independent QKD (MDI-QKD) was proposed to remove all such attacks. This thesis presents an implementation of the protocol. In our implementation, key bit information was encoded in the polarization states of weak coherent pulses at 1542 nm wavelength in optical fibers, and decoy state techniques were employed. We ensured stable polarization preparation and alignment and developed a QKD system over 10 km of standard Telecom fibers at 500 KHz repetition rate. Our work demonstrates the practicality of MDI-QKD protocol of removing all attacks, existing and yet to be discovered, on the detection part of a QKD system.

Keywords: Decoy State
Polarization
Measurement Device Independent
Quantum Key Distribution
Advisor: Lo, Hoi-Kwong
Whether China’s State-Owned Commercial Banks Constitute “Public Bodies” within the Meaning of Article 1.1 (a) (1)

US – Definitive Anti-dumping and Countervailing Duties on Certain Products from China is the initial WTO dispute in which China claims that US-countervailing duties on certain products from China are inconsistent with the obligations of the United States under the SCM Agreement. The meaning of “public bodies” within Article 1.1 (a) (1) of the SCM Agreement and the question of whether China’s “SOCB” constitute “public bodies” are the heart of the matter. The thesis argues that the theory of the governmental function is more persuasive than that of governmental control in terms of defining “public bodies”. Although the majority ownership of China’s SOCBs has remained in the Chinese government, their policy-oriented nature has been largely marginalized. The conclusion is that the WTO system needs to give developing countries more policy flexibility, and developing countries should also make the best use of their latent comparative advantage and the effects of globalization.

Keywords: Public Bodies
State-Owned Commercial Banks
Advisor: Trebilcock, Michael
Design and Development of an Experimental Apparatus to Study Jet Fuel Coking in Small Gas Turbine Fuel Nozzles

An experimental apparatus was designed and built to study the thermal autoxidative carbon deposition, or coking, in the fuel injection nozzles of small gas turbine engines. The apparatus is a simplified representation of an aircraft fuel system, consisting of a preheating section and a test section, which is a passage that simulates the geometry, temperatures, pressures and flow rates seen by the fuel injection nozzles. Preliminary experiments were performed to verify the functionality of the apparatus. Pressure drop across the test section was measured throughout the experiments to monitor deposit buildup, and an effective reduction in test section diameter due to deposit blockage was calculated. The preliminary experiments showed that the pressure drop increased more significantly for higher test section temperatures, and that pressure drop measurement is an effective method of monitoring and quantifying deposit buildup.

Keywords: jet fuel
fossil fuel
thermal stability
gas turbine
coking
injector nozzle
pressure drop
engine
Advisor: Gulder, Omer L.
Role of Vesicle-associated Membrane Protein 2 in Glucagon-like Peptide-1 Secretion

Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by the enteroendocrine L-cell that potently stimulates insulin secretion. Although signaling pathways promoting GLP-1 secretion are well characterized, the mechanism by which GLP-1 containing granules fuse to the L-cell membrane remain elusive. RT-PCR and protein analysis indicate that vesicle-associated membrane protein 2 (VAMP2) is expressed and localized to secretory granules in the murine GLUTag L-cell model. VAMP2, but not VAMP1, interacted with the core SNARE complex protein, Syntaxin 1a, in GLUTag cells. Tetanus toxin (TetX) cleavage of VAMP2 in GLUTag cells prevented glucose-dependent insulinotropic peptide (GIP)- and oleic acid (OA)-stimulated GLP-1 secretion, as well as K+-stimulated exocytosis from GLUTag cells. Although components of membrane rafts were detected in GLUTag cells, their role in GLP-1 secretion remains to be determined. Together, these findings indicate an essential role for VAMP2 in GLP-1 exocytosis from the GLUTag cell.

Keywords: GLP-1
VAMP2
SNARE
Advisor: Brubaker, Patricia
Elucidating the Effects of Integrin-linked Kinase Modulation on Sarco/endoplasmic Reticulum Calcium ATPase Function in Human Induced Pluripotent Stem Cell-derived Cardiomyocytes

Integrin-linked kinase (ILK) is an important mechanoreceptor that mediates many cellular signaling pathways. Its dysregulation causes dilated cardiomyopathy and other complications in the heart. Restoration of ILK improves cardiac function and survival, but the exact mechanism is unknown. Recent studies in our lab suggest that the cardioprotective properties of ILK may be related to its regulation of sarco/endoplasmic reticulum calcium ATPase (SERCA2a). The protein expressions of ILK and SERCA2a are positively correlated based on adenoviral transduction of ILK and siRNA targeting ILK in human induced pluripotent stem cell-derived cardiomyocytes. From analysis of their calcium transients, ILK transduction resulted in increased beat rate and faster calcium clearance while siRNA knockdown produced the opposite effect. The use of SERCA-specific inhibitor thapsigargin nullified the observed effects of ILK transduction. Based on these results, we conclude that ILK’s cardioprotective properties are partly related to improving calcium handling in cardiomyocytes through the regulation of SERCA2a.

Keywords: biomedical
cardiomyocytes
integrin-linked kinase
serca2a
heart failure
dilated cardiomyopathy
Advisor: Coles, John
Radisic, Milica
Experimental Testing of Low Reynolds Number Airfoils for Unmanned Aerial Vehicles

This work is focused on the aerodynamics for a proprietary laminar flow airfoil for Unmanned Aerial Vehicle (UAV) applications. The two main focuses are (1) aerodynamic performance at Reynolds number on the order of 10,000, (2) the effect of a conventional hot-wire probe on laminar separation bubbles. For aerodynamic performance, pressure and wake velocity distributions were measured at Re = 40,000 and 60,000 for a range of angles of attack. The airfoil performed poorly for these Reynolds numbers due to laminar boundary layer separation. 2-D boundary layer trips significantly improved the lift-to-drag ratio. For probe effects, three Reynolds numbers were investigated (Re = 100,000, 150,000, and 200,000), with three angles of attack for each. Pressure and surface shear distributions were measured. Flow upstream of the probe tip was not affected. Transition was promoted downstream due to the additional disturbances in the separated shear layer.

Keywords: low Reynolds number airfoil
laminar separation bubble
oil film interferometry
Advisor: Lavoie, Philippe
Quenching H2O2 Residuals After UV/ H2O2 Drinking Water Treatment Using Granular Activated Carbon

The ability of six types of granular activated carbon (GAC) to quench H2O2 was evaluated by bench-scale H2O2 decomposition kinetics tests and pilot-scale H2O2 breakthrough tests. Bench-scale studies showed that carbon ageing significantly reduced the performance of H2O2 quenching by the GAC, but that the greatest impacts occurred within the first 25 000 bed volumes of water treated, with performance tending to stabilize afterwards. Pilot-scale studies suggested that both H2O2 exposure and exposure to natural organic matter were important factors in GAC ageing, with exposure to oxygen also suspected of being important. A continuously stirred tank reactor (CSTR)-in-series model was proposed for the prediction of H2O2 breakthrough in a GAC column.

Keywords: drinking water treatment
granular activated carbon
UV/H2O2
H2O2 quenching
Advisor: Hofmann, Ronald
Utilizing Positron Emission Tomography in Lung Cancer Treatment

We explore both robust biologically guided intensity-modulated radiation therapy (BG-IMRT) and pattern recognition to identify responders to cancer treatment for lung cancer. Heterogeneous dose prescriptions that are derived from biological images are subject to uncertainty, due to potential noise in the image. We develop a robust optimization model to design BG-IMRT plans that are de-sensitized to uncertainty. Computational results show improvements in tumor control probability and deviation from prescription dose compared to a non-robust model, while maintaining tissue dose below toxicity levels. We applied machine learning algorithms to 4D gated positron emission tomography/computed tomography (PET/CT) scans. We identified classifiers which could outperform a naive classifier. Our work shows the potential of using machine learning algorithms to predict patient response. This could hopefully lead to more adaptive treatment plans, where the clinician would adapt the treatment based on the prediction provided at certain time intervals in the treatment.

Keywords: optimization
robust
radiation therapy
IMRT
lung cancer
machine learning
Advisor: Chan, Timothy
Design of a Haptic Simulator for Pedicle Screw Insertion in Pediatric Scoliosis Surgery

The following work presents the design of a haptic training simulator for pedicle screw insertions in pediatric scoliosis surgery. In particular, the haptic simulator simulates the haptic sensations associated with probe channeling through the pedicle using the free-hand technique. The design includes 1 DOF custom haptic device, haptic model, and controller. The design is tested and evaluated for feasibility through a small pilot studying involving 5 expert surgeons. Significant agreement across expert surgeons was obtained regarding the feasibility and potential for the simulator to be a useful training tool.

Keywords: Haptics
Robotics
Training Simulator
Virtual Reality
Pedicle screw insertion
orthopedic surgery
spine surgery
Advisor: Zabjek, Karl
Wang, David
Alternatives to Decentralization of Pharmaceutical Policies in Brazil: Case Studies of HIV/AIDS and Tuberculosis

Increasing attention has been paid to decentralized health care systems in order to evaluate health outcomes. In Brazil, state-run pharmaceutical assistance falls within the scope of a decentralized health care system, also known as SUS (Brazilian Unified Health System). The research intends to shed light on pharmaceutical policy implementation in Brazil through SUS, and argues that it can be used as a guide for institutional reform. This will be accomplished by reviewing the weaknesses and strengths of the SUS decentralized structure as revealed in the pharmaceutical policy responses to HIV/AIDS and tuberculosis. Under the assumption of pharmaceutical assistance improvement conditioned to re-centralization of some functions; it can be argued that a balanced approach to decentralization is more desirable to the pharmaceutical sector than the existing decentralized system. The aim of this study is to highlight the advantages of establishing a hybrid system for pharmaceutical assistance.

Keywords: health care system
public health
pharmaceutical policy
decentralization
Advisor: Macklem, Patrick
Depoliticizing the United Nations Human Rights Council: Mixed Membership for a Brighter Future

The United Nations charter-based human rights apparatus has long been plagued by concerns of politicization. This pervasive issue first brought the demise of the United Nations Commission on Human Rights in 2006 and led to the creation of an entirely new entity, the United Nations Human Rights Council, in the hope of answering the concerns of the international community. Although major reforms were undertaken, politicization is now once again cited as one of the main issues of the new Council. In this essay, we identify the source of politicization as the intergovernmental nature of these human rights bodies, and suggest that mitigation of this issue is possible through the reform of the Council’s membership. The creation of a mixed expert-state body will allow for a more functional, depoliticized body in the protection and promotion of human rights.

Keywords: Human Rights Council
Politicization
International Law
human rights
Advisor: Knop, Karen C.
Structural and Biochemical Characterization of CRISPR-associated Cas4 Nucleases from a Prokaryotic Defense System

Nucleases are an essential component of the prokaryotic CRISPR-Cas immunity as well as repair mechanisms within prokaryotic organisms. To better understand the adaptation step of CRISPR-Cas immunity, I have characterized three Cas4 proteins from hyperthermophilic archaea: SSO0001 and SSO1391 from Sulfolobus solfataricus and Pcal_0546 from Pyrobaculum calidifontis. All three proteins have metal-dependent 5′ to 3′ exonuclease and endonuclease activities, while SSO1391 also demonstrates 3′ to 5′ exonuclease activity. Site-directed mutagenesis confirmed that the conserved RecB motif residues are important for the nuclease activity in all three proteins. SSO0001 and Pcal_0546 also exhibit ATP-independent unwinding and cleavage of splayed arm substrates. Structural analysis of SSO0001 showed it is a toroidal decamer with a [4Fe-4S] cluster and Mn2+ ion bound in the active site located inside the internal tunnel. Our results show that Cas4 proteins have the ability to create 3'-DNA overhangs which may contribute to the addition of novel CRISPR spacers.

Keywords: CRISPR, Cas4, nuclease, [4Fe-4S] cluster
Advisor: Yakunin, Alexander
The Role of Stretch-induced Myometrial Cytokines in Leukocyte Recruitment during Parturition

Spontaneous term labour is associated with increased inflammatory events in the myometrium including cytokine production and leukocyte infiltration. We hypothesized that mechanical stretch of the uterine wall by the growing fetus facilitates peripheral leukocyte transendothelial migration into the term pregnant myometrium through the release of various cytokines. The current study demonstrated that static mechanical stretch directly induces secretion of multiple cytokines and chemokines by human myometrial smooth muscle cells. Stretch-induced cytokines (1) increased vascular permeability; (2) enhanced leukocyte adhesion to the endothelium of the surrounding uterine microvasculature by (3) inducing the expression of endothelial cell adhesion molecules; and (4) directed the transendothelial migration of peripheral neutrophils. Our data provide a direct proof of mechanical regulation in leukocyte recruitment from the uterine blood vessels, which represents a putative mechanism for the leukocyte infiltrate seen in the myometrium during labour and postpartum involution.

Keywords: labour
stretch
cytokine
leukocyte
myometrium
Advisor: Lye, Stephen J.
Perceptions about Crime and Safety in the Region of Peel: A Qualitative Assessment of Connections between the Social and Built Environment and Crime in Three Neighbourhoods

This thesis investigated the role that local environmental factors play in influencing perceptions of crime and safety across three neighbourhoods within the Region of Peel, Ontario. Semi-structured interviews were conducted with local experts to examine their perceptions of crime and safety, and elements of the built and social environment that may influence these perceptions and identified dimensions of social capital that serve as pathways through which broader environmental determinants of crime and safety can become embedded at the local neighbourhood level. Findings of this research revealed that the perceived relationships between the social and built environment and crime are complex and that dimensions of social capital such as informal social ties serve as a mediator between the environment and perceptions about crime and how perceived and actual crime may be reduced by modifying elements of the built and social environment in order to strengthen local dimensions of social capital.

Keywords: geography
social capital
social cohesion
neighbourhood
community
social disorganization theory
social environment
built environment
Advisor: Wilson, Dana
Therapeutic Peptide-functionalized Gold Nanoparticles for the Treatment of Acute Lung Injury

Acute lung injury (ALI) is a major cause of mortality after lung transplantation. Recent studies indicate protein kinase C delta (PKCδ) could be an effective target to treat ALI. We have developed a gold nanoparticle (GNP)-peptide hybrid that can inhibit PKCδ signaling. PKCδ inhibitor peptide (PKCi) and 95P2P4 stabilizing peptides were conjugated onto GNP. Physicochemical properties of the nanoformulations were examined. A lung transplant-simulated cell culture model was used to evaluate therapeutic efficacy in vitro. A pulmonary ischemia-reperfusion (IR) model was used to test therapeutic efficacy in vivo. GNP-Peptide hybrids showed good stability with high cellular uptake. GNP-PKCi formulations demonstrated anti-inflammatory and anti-apoptotic effects in vitro. When administered to rats under IR stress, GNP-PKCi formulation improved blood oxygenation, reduced pulmonary edema and histological lung injury. In conclusion, we have successfully formulated a clinically-applicable nanoparticle with therapeutic potential to ameliorate lung injury and inflammation. Our formulation strategy could be used to deliver other peptide-based drugs.

Keywords: acute lung injury
gold nanoparticle
peptide
drug delivery
protein kinase C delta
lung transplant
Advisor: Liu, Mingyao
Multidisciplinary Design Optimization of a Morphing Wingtip Concept with Multiple Morphing Stages at Cruise

Morphing an aircraft wingtip can provide substantial performance improvement. Most civil transport aircraft are optimized for range but for other flight conditions such as take-off and climb they are used as constraints. These constraints could potentially reduce the performance of an aircraft at cruise. By altering the shape of the wingtip, we can force the load distribution to adapt to the required flight condition to improve performance. Using a Variable Geometry Truss Mechanism (VGTM) concept to morph the wingtip of an aircraft with a Multidisciplinary Design Optimization (MDO) framework, the current work will attempt to find an optimal wing and wingtip shape to minimize fuel consumption for multiple morphing stages during cruise. This optimization routine was conducted with a Particle Swarm Optimization (PSO) algorithm using different fidelity tools to analyze the aerodynamic and structural disciplines.

Keywords: Optimization
Morphing Aircraft
Particle Swarm
Multidisciplinary
Advisor: Behdinan, Kamran
Validation of the Magneto-articulography for the Assessment of Speech Kinematics (MASK) System and Testing for Use in a Clinical Research Setting

A novel technology, the Magneto-articulography for the Assessment of Speech Kinematics (MASK) system, which measures brain activity and oromotor movement simultaneously, was validated for its speech tracking capabilities. MASK has not been systematically tested, so its movement tracking accuracy and practicality for research was still unknown. An error testing and mapping protocol is developed to validate MASK accuracy against established electromagnetic articulography (EMA) speech tracking systems. Data from human speech experiments are also compared. MASK exhibited higher positional error and fluctuation than EMA, and more inconsistent distribution of errors. Error mapping and potential error correction protocols were also developed. MASK spatial and temporal resolutions were found insufficient for precise tracking of small and quick articulatory movements. MASK requires much improvement to reach the capabilities of EMA. Further investigation into numerical instabilities of the position calculation algorithms is encouraged. This project provides the first assessment of MASK, which may advance speech research for future applications.

Keywords: articulography
speech
MEG
position tracking
error mapping
electromagnetic
speech kinematics
error testing
Advisor: Lieshout, Pascal van
Cheyne, Doug
Chau, Tom
Octaarginine Labelled 30 nm Gold Nanoparticles as Agents for Enhanced Radiotherapy

Traditional radiation therapy is limited by the radiotoxic effects on surrounding healthy tissues. This project investigated the use of a gold nanoparticle (AuNP) conjugated to a cell-penetrating peptide (CPP) to increase tumour cell death during radiotherapy by maximizing the cellular import of the gold nanoparticles. ~8300 octaarginine CPPs were coupled per 30 nm AuNP through poly(ethylene glycol) spacers (AuNP-PEG-CPP). The CPPs enhanced the internalization of the AuNPs into three human breast cancer cell lines by a factor &gt;2 as compared to untargeted AuNPs. Cells were treated with AuNP-PEG-CPP for 24 hours, prior to radiotherapy and their long-term proliferation was assessed in clonogenic assays. The increased internalization of AuNPs by the CPPs resulted in greater cell death following exposure to 300 kVp radiotherapy, by a dose enhancement factors between 1.3 and 2.1 depending on the cell line. These findings illustrate the potential of using AuNP-CPPs to enhance radiotherapy in patients.

Keywords: gold nanoparticle
radiotherapy
Advisor: Gariepy, Jean
Pignol, Jean-Philippe