VictorJuiz/thesis huggingface dataset:
Normothermic Ex Vivo Kidney Perfusion - A Novel Approach for the Storage, Assessment, and Repair of Renal Grafts

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. A major problem is the worldwide severe graft shortage, which triggered interest in kidneys recovered from extended criteria donors (ECD) and donation after circulatory death (DCD). Currently utilized techniques of hypothermic preservation induce injury, especially in ECD and DCD grafts. This study investigates the feasibility and safety to preserve kidneys under normothermic, more physiologic conditions ex vivo. In a porcine model, kidneys were recovered, and preserved on ice or with â Normothermic Ex Vivo Kidney Perfusion (NEVKP)â . Kidneys preserved at normothermia providing physiologic flow, oxygen, and nutrition, demonstrated high metabolic activity and excellent graft viability during storage. Following autotransplantation, superior renal function with lower serum creatinine, higher creatinine clearance, and lower renal injury markers was demonstrated when compared to cold storage. This data suggests that NEVKP offers superior storage and provides a platform for further graft assessment and repair.

Keywords: Graft Assessment and Repair
Hypothermic Preservation
Kidney Preservation
Kidney Transplantation
Normothermic Ex Vivo Kidney Perfusion
Organ Shortage
Advisor: Robinson, Lisa A.
Selzner, Markus
Identification and Characterization of Candidate Treponema pallidum Vascular Adhesins by Heterologous Expression in the Lyme Disease Pathogen

This thesis reports novel techniques to study the candidate adhesin of unculturable syphilis pathogen Treponema pallidum in the Lyme disease pathogen Borrelia burgdorferi. The Treponema pallidum laminin-binding adhesin, Tp0751, was heterologously expressed and surface localized in a non-infectious, less-adherent B. burgdorferi strain which has the attenuated ability to interact with cultured mammalian cells in vitro and vascular endothelial cells in vivo. By using the flow chamber techniques and intravital microscopy approach, I demonstrated that Tp0751 was able to restore borrelial-endothelial interactions in vitro, and was able to confer vascular adhesion in vivo. This study has illustrated that gain-of-function B. burgdorferi strain can serve as a machinery to study the activity of treponemal outer surface proteins. The analysis of the adhesive role of Treponema pallidum will reveal its mechanisms of dissemination and tissue colonization during syphilis infection.

Advisor: Moriarty, Tara J.
Production of Bulk Metallic Glasses for Use in Airborne Gravity Gradiometry

Bulk metallic glasses (BMGs) are ideal candidates for airborne gravity gradiometer (AGG) flexures due to their unique mechanical properties. In this thesis, the role of processing variables in the production Zr-based BMGs by arc melting and suction casting was investigated and an electrochemical method for determining the degree of crystallization after electric discharge machining (EDM) was examined. Homogenization was most effectively obtained using multiple melting iterations and prolonged melting times. The difference between input and actual Zr concentration was found to be significant in arc melting and suction casting. Superior GFA was obtained using high purity argon purge gas and low purity Zr contrary to the consensus that GFA strictly increases with increasing raw material purities. The use of potentiostatic polarization in 1M NaNO3 for evaluating the degree of crystallization in Zr55Cu30Al10Ni5 samples after EDM may be feasible due to the dependence of passivation behaviour on the degree of crystallization.

Keywords: Airborne Gravity Gradiometry
Arc Melting and Suction Casting
Bulk Metallic Glass
Production
Zr-based BMGs
Advisor: Thorpe, Steven J
Singh, Chandra Veer
R740S Mutation of Tcirg1 Mutation Affects Enamel Development in Osteopetrotic Mice

Abstract Osteopetrosis is characterized by sclerotic bone due to impaired osteoclasts. Many cases are associated with defects in the TCIRG1 gene encoding the a3 subunit of vacuolar-ATPase (V-ATPase). These patients have defects in bone, tooth eruption and enamel. To elucidate the role of V-ATPases in amelogenesis, we investigated the cellular distribution of a3, expression of enamel proteins, and quality of the enamel in a mouse with a mutation (R740S) in a3. In the homozygote (R740S/R740S), micro CT and SEM demonstrated a decrease in mineralization and thickness of the enamel. Using immunohistochemistry, the expression of the secretory stage protein, amelogenin remained in the R740S/R740S ameloblasts at day 9, concurrent with lower levels of the maturation stage proteins, amelotin and ODAM, suggesting a developmental delay. Low level expression of a3 was observed in the ameloblasts during the secretory stage. Our results suggest that a3-V-ATPases may play a role in amelogenesis, possibly by affecting protein secretion.

Keywords: Amelogenesis
Enamel
Osteopetrosis
Tcirg1
vacuolar ATPase
Advisor: Voronov, Irina
Bradley, Grace
Investigating Simulated Driving Behaviour and Brain Activation in Mild Cognitive Impairment

There are no guidelines or tools to help physicians assess the driving safety of patients with MCI. This study combined fMRI and driving simulation to compare the driving performance, and corresponding brain activation patterns, of patients with MCI and healthy controls. Patients with MCI committed significantly more driving errors compared to controls. Patients with amnestic multiple-domain MCI patients were at a greater risk of difficulty relative to those with amnestic single-domain MCI. Patients with MCI exhibited increased recruitment of frontal brain regions compared to controls, particularly during left turns with traffic. Patients with sd-MCI exhibited increased recruitment of frontal and medial regions across turning conditions, whereas patients with md-MCI exhibited decreased recruitment of frontal and medial regions. The results suggest that patients with MCI can demonstrate driving difficulties and deviations in brain activation compared to controls and that the areas and degree of difficulty vary across the subtypes of MCI.

Keywords: driving
fMRI
mild cognitive impairment
simulation
Advisor: Schweizer, Tom A
Inhibition of Return: Underlying Mechanisms and Contributions of the Primary Motor Cortex (M1)

Inhibition of return (IOR) refers to the finding that response times (RTs) to targets are longer when targets are presented at a recently attended-to location relative to targets at new locations. The motor-based component of IOR was explored by investigating the contributions of M1 to IOR. Transcranial magnetic stimulation (TMS) was used to determine if the mechanisms associated with IOR are represented in M1. Participants completed a cue-target task with non-predictive exogenous cues. It was hypothesized that if the mechanisms underlying IOR are represented in M1, then the motor evoked potentials (MEPs) associated with the cued or uncued responses would mirror RTs. TMS of M1 altered RTs, however MEP data did not reveal an effect of cue location on M1 excitability. The data indicate a motor contribution to the IOR effect, but the question of where in the motor system the mechanisms associated with IOR is localized is unanswered.

Keywords: Neuro-Motor
Advisor: Welsh, Timothy N
Deconstructing Psychosis: Dismantling Oppression

Abstract This document deconstructs the term ‘psychosis’ through an exploration of the origins of this term, a personal narrative of this phenomenon, and the exploration of a multitude of perspectives from around the world, on experiences which fall into this category. Integrating the wisdom of five Indigenous and Alternative Health practitioners, and exploring several alternative mental health healing centre models, the limitations of the mainstream Western medical approach are presented .Also discussed, are the diversity and power of these alternatives and their possible combinations. This exploration is carried out using the Two-Eyed Seeing Framework, developed by Mi’kmaw Elders Albert and Murdena Marshall, of the Eskasoni First Nation in Cape Breton, Nova Scotia, which ensures readers appreciate each perspective on ‘psychosis’ in its own right, and invites readers to imagine and notice ways in which the healing perspectives presented, can be and are combined, in order to create new and important healing possibilities.

Keywords: anti-oppression
indigenaity
psychosis
spirituality
Advisor: Wane, Njoki
Mesenchymal Stem/Stromal Cells for Sepsis-induced Acute Respiratory Distress Syndrome: The Role of Tissue Source, Pre-activation Strategies and Measures of MSC Potency on Therapeutic Benefit in Rodent Models of ARDS

Acute Respiratory Distress Syndrome (ARDS) is a devastating illness characterized by a dysregulated inflammatory response, pulmonary edema, and compromised integrity of the endothelial and epithelial barriers of the lung. We wished to investigate the therapeutic potential of human mesenchymal stem cells (hMSCs) derived from umbilical cord perivascular tissue (hUC-MSCs) in rodent pneumonia-induced ARDS. We also aimed to examine the effects of using human platelet lysate (hPL) as a media supplement in the expansion of hUC-MSCs, and the ability of pre-activation strategies to augment the beneficial actions of hUC-MSCs. In parallel, we wished to further delineate possible mechanisms of action of MSCs using in vitro assays. Results showed that early passage hUC-MSCs cultured in serum-free media demonstrate therapeutic potential in pneumonia. Late passage hUC-MSCs abolished benefits, as did the use of hPL to expand the hMSCs. hMSCs may elicit their effects by altering the phenotype of human macrophages.

Advisor: Laffey, John
Curley, Gerard
Human-robot Interactions for Single Robots and Multi-robot Teams

For robots to successfully take part in bi-directional social interactions with people, they must be capable of recognizing and responding to human affect. Such robots would promote effective and engaging interactions with users. In this thesis, a multimodal bi-directional affect architecture is proposed that determines user affect using a unique combination of user body language and vocal intonation. In addition to one-on-one human-robot interactions, multi-robot teams can provide valuable assistance in Urban Search and Rescue (USAR) missions by exploring dangerous environments, while searching for victims. One of the main challenges an operator may face in controlling a multi-robot team is the simultaneous control of multiple robots while juggling between tasks and keeping situational awareness. This thesis also proposes a multi-robot collaboration architecture using a learning-based semi-autonomous controller that provides the ability to effectively allocate sub-tasks to robots to complete USAR missions.

Keywords: Affect Recognition
Human-Robot Interaction
Multimodal Bi-directional Communication
Multi-Robot Team
Semi-Autonomous Controller
Urban Search and Rescue
Advisor: Nejat, Goldie
Benhabib, Beno
Evaluating the Sociocultural Risks for Suicide Attempt in Schizophrenia

Sociocultural factors involved in immigration and ethnicity are believed to independently influence the risk for schizophrenia and suicidal behaviour. Schizophrenia patients are known to be at an increased risk for suicide. Though many risk factors have been identified, few have any significant clinical impact on predicting suicide. Whether immigration and ethnicity are potential risk factors for suicide attempt in schizophrenia has yet to be investigated. Schizophrenia patients with clear suicide attempt history, immigration history, self-reported ethnicity, and other sociocultural and clinical variables were recruited to test whether independently, or synthesized in a classification algorithm, these variables can accurately predict a history of suicide attempt. Both immigration and ethnicity had a non-significant association with suicide attempt. Inclusion of these predictor variables also did little to improve classification accuracy in our algorithms. Taken together, we found no evidence that these sociocultural factors have a significant influence on the risk for suicide attempt in schizophrenia.

Keywords: Ethnicity
Genetics
Immigration
Psychiatry
Schizophrenia
Suicide
Advisor: De Luca, Vincenzo
Patterned Linear Systems and Control

A method to characterize the symmetries inherent within physical systems via automorphism groups has already been established. In this thesis, we elaborate on this method and define a special reduced form to which the system matrices of a linear system can be decomposed based on these inherent patterns. We employ this decomposition and the resulting block diagonal form to adapt basic control theory concepts such as controllability and stabilizability to a pattern-preserving framework. We give a pole placement algorithm that synthesizes a feedback matrix that is constrained by the patterns of the system. Moreover, we apply our patterned framework to traditional control problems such as stabilization by measurement feedback and output stabilization, and give pattern-preserving feedback synthesis procedures for these problems. Finally, we provide a set of computational tools that can be used to nd the aforementioned decomposition and generate pattern-preserving feedbacks for a given patterned system.

Keywords: Control Theory
Group Theory
Linear Systems
Pattern
Symmetry
Systems
Advisor: Broucke, Mireille E.
Impact of Irradiance Change on MPPT and Flicker Phenomenon of Solar-PV Units

This thesis investigates the effect the solar-PV array's response to a rapid change in irradiance has on the individual solar-PV unit and electric power distribution system to which it is connected. The study system is a weak, radial distribution system with 30% solar-PV penetration levels. Specifically, 3 solar PV units, each 1.5 MW capacity, are distributed downstream in the feeder. First, at the individual, solar PV unit level, an augmented incremental conductance (IC) method for maximum power point tracking (MPPT) is proposed to improve DC power control performance in response to change in irradiance, i.e., cloud movement. The augmented MPPT algorithm shows up to 2.49 % energy harvest improvement when compared to the classical IC method. Second, at the system level, the impact of rapid changes in irradiance on voltage flicker is evaluated. It is shown that flicker levels are kept well below acceptable levels (the highest Pst observed is 0.21 pu) for citable weather patterns.

Keywords: Flicker
IEC Flickermeter
Irradiance
MPPT
Solar-PV
Advisor: Iravani, Reza
Activation of a Medullary Respiratory Motor Circuit by Remote Control

Obstructive sleep apnea (OSA) can be triggered by reduced tongue muscle tone during sleep. The hypoglossal motor nucleus (HMN) is the source of motor output to the tongue, and is a logical pharmacological target for treatment. Targets in this region exist; drugs able to specifically modulate them do not. To test the feasibility of this approach, we modelled a drug-receptor interaction at the HMN by selectively activating engineered receptors inserted into the HMN. Receptor activation by a systemically administered drug increased tongue muscle activity during sleep. Importantly, tongue muscle activity was increased during both rapid eye movement (REM) and non-REM sleep to near-waking levels. The results of this thesis show that selective activation of a pharmacological target locally expressed at the HMN results in sustained tongue muscle activity throughout sleep. This establishes proof-of-principle for modulating a restricted target at the HMN as a viable strategy for pharmacologically treating OSA.

Keywords: Apnea
Chemogenetics
DREADD
Hypoglossal
Obstructive
Sleep
Advisor: Horner, Richard L
Multi-agent Learning in Coverage Control Games

Multi-agent systems have found a variety of industrial applications from economics to robotics. With the increasing complexity of multi-agent systems, multi-agent control has become a challenging problem in many areas. While studying multi-agent systems is not identical to studying game theory, there is no doubt that game theory can be a key tool to manage such complex systems. Game theoretic multi-agent learning is one of relatively new solutions to the complex problem of multi-agent control. In such learning scheme, each agent eventually discovers a solution on his own. The main focus of this thesis is on enhancement of multi-agent learning in game theory and its application in multi-robot control. Each algorithm proposed in this thesis, relaxes and imposes different assumptions to fit a class of multi-robot learning problems. Numerical experiments are also conducted to verify each algorithm's robustness and performance.

Keywords: Control
Game Theory
Machine Learning
Multi-agent
Robotics
Advisor: Pavel, Lacra
Delayed Expression of Plasticity in Neuronal Excitability Induced by Co-activation of NMDAR and mGluR at a Developing Central Synapse

The development of effective neurotransmission in central synapses requires intricate regulation of synaptic receptors and active intrinsic membrane properties. Previous studies have shown that patterned activity can concurrently activate NMDARs and mGluRs and increase the fidelity of neurotransmission at high rates by translational and post-translational modifications of glutamate receptors. It is however unknown whether or how activity drives the development and maturation in the intrinsic excitability of central neurons. Using the developing calyx of Held-MNTB synapse as a model, we examined this issue by using NMDA and DHPG to selectively co-activate postsynaptic NMDARs and Group I metabotropic glutamate receptors (mGluRs) of postsynaptic neurons in acute slices from the auditory brainstem of prehearing mice. We found that co-activation of NMDAR and mGluRs induced a delayed expression of plasticity in the action potential waveform and a multiplicative output modulation of the I/O relationship in response to injected current steps. We performed whole-cell voltage-clamp recordings to determine potential mechanisms underlying observed changes in AP waveform. The average density, kinetics and the ratio of maximal spike-generating (INa/IK) currents of isolated sodium and potassium currents were comparable in naive compared to treated cells. A systematic exploration of conductance based models showed that multiple combinations of modifications to conductance densities could underlie the observed plasticity. These results suggest that selective co-activation of NMDAR and mGluR can regulate multiple intrinsic membrane properties to play a role in shaping action potential waveform and the ability to spike at high-frequencies.

Keywords: development
excitability
neurotransmission
Advisor: Wang, Lu-Yang
Characterization of Mammalian ER Quality Control Systems in the Context of Select Human Pathologies

Quality control (QC) systems in the endoplasmic reticulum (ER) are established by intricate networks of molecular chaperones and foldases, and sophisticated degradative processes such as the ER-associated degradation (ERAD) pathway that promote the proper folding of translocated nascent chains and clearance of misfolded proteins, respectively. This thesis demonstrates my efforts to expand upon the current understanding of ERQC mechanisms, first by identifying novel components of the mammalian ERAD pathway. From a genome-wide shRNA screen conducted in the context of a viral immunoevasion-based ERAD model system, several potential candidates were selected, validated, and identified as promising targets for future investigation. Secondly, the ER-resident FKBP-type peptidyl prolyl isomerase, FKBP10, was verified as a regulator of cellular prion protein (PrPC) biogenesis, and newly identified as a potential therapeutic target against prion diseases as its depletion resulted in PrPC attenuation â an effective method of impeding disease progression - via proteasomal and lysosomal degradation pathways.

Keywords: Endoplasmic reticulum
ERAD
FKBP10
Prion protein
Protein folding
Quality control
Advisor: Williams, David B
Mechanisms of Neurogenesis Mediated Forgetting

Memories allow experiences to have some permanence in our minds. Increasing adult neurogenesis in the dentate gyrus of the hippocampus has been shown to reduce this permanency, leading to forgetting. The hippocampus encodes memories through the activation of a selection of neurons and successful memory retrieval is believed to involve reactivation of these neurons. Although successful memory retrieval has been linked to reactivation, we investigate whether decreased reactivation is the mechanism that underlies forgetting. This is achieved by permanently tagging neurons activated during the acquisition of a contextual fear conditioning task and analyzing dentate gyrus neuronal reactivation levels of forgotten memories after 28 days of exercise-induced neurogenesis. The data shows less reactivation in animals that demonstrated neurogenesis-induced forgetting, and a positive correlation between retrieval success and reactivation levels. These results indicate that neurogenesis-mediated forgetting can be explained at the cellular level as a reduction of complete reactivation of encoding neurons.

Keywords: Dentate gyrus
Forgetting
Hippocampus
Advisor: Frankland, Paul
Socioeconomic Discrepancies in Children’s Accessibility to Health Promoting Resources: An Activity Space Analysis

Approximately one third of Canada’s youth are overweight or obese. Children living in low socioeconomic status (SES) households are at greater risk of this condition. Little research examines how mobility and time shape accessibility to food environments and physical activity (PA) facilities, two likely determinants of health expected to vary by SES. Using data from Project BEAT, a study investigating the built environment and Toronto schoolchildren’s active travel, this thesis examines how SES shapes children’s accessibility to food establishments and PA facilities. The activity space construct is used in order to incorporate mobility and time into measures of accessibility. Results indicate that higher SES is associated with greater accessibility and access to PA facilities and lower accessibility to fast food establishments. Furthermore, accessibility to PA facilities and retail food establishments varies over the week. This thesis contributes a more comprehensive understanding of how mobility, time, and SES shape children’s health.

Keywords: Accessibility
Activity space
Children
Food environment
Mobility
Physical activity
Advisor: Buliung, Ron
Wilson, Kathi
Drosophila Nedd4-long Reduces Amphiphysin Levels in Muscles and Leads to Impaired T-tubule Formation

Drosophila Nedd4 (dNedd4) is a HECT ubiquitin ligase with two main splice isoforms: dNedd4 short (dNedd4S) and long (dNedd4Lo). We previously showed that while dNedd4S promotes neuromuscular synaptogenesis, dNedd4Lo inhibits it. To delineate the cause of this inhibition, we searched for binding partners to the N-terminal unique region of dNedd4Lo in embryo lysates using mass-spectrometry and identified Amphiphysin (dAmph). dAmph is a postsynaptic protein containing SH3-BAR domains, which regulates muscle T-tubule formation in flies. We validated the interaction by co-immunoprecipitation and showed direct binding between dAmph-SH3 domain and dNedd4Lo-N-terminus. Accordingly, dNedd4Lo was co-expressed with dAmph postsynaptically and at muscle T-tubules. Moreover, expression of dNedd4Lo in the muscle during embryonic development led to disappearance of dAmph and to impaired T-tubules formation, phenocopying amph null mutants. This effect was not seen in muscles expressing dNedd4S or a catalytically-inactive dNedd4Lo(CA). We propose that dNedd4Lo destabilizes dAmph in muscles, leading to impaired T-tubule formation.

Keywords: Amphiphysin
muscle developemt
Nedd4
Advisor: Rotin, Daniela