VictorJuiz/thesis huggingface dataset:
Towards Closed-Loop Stimulation To Improve Human Memory

Age-related memory decline is a major health concern. Deep brain stimulation (DBS) without any feedback (open-loop) has proven effective for neurodegenerative conditions like Parkinsonâ s disease, but its effects on human memory have shown mixed results. This projectâ s objective was to create a framework to test DBS with feedback (closed-loop) to augment human memory. A memory task was developed based on our hypothesis relating eye movements, brain electrophysiology, and hippocampal-dependent memory. The hippocampus is a key brain memory structure and a prime target for DBS. Participants completed a visual search task featuring targets embedded in realistic scenes. Results revealed above-chance corrected recognition for scenes and associated targets. Closed-loop stimulation based on the recorded response during the task was piloted in a single patient. This thesis will set the stage for further investigating DBS' functional effects on the hippocampus and DBSâ utility in improving human memory.

Keywords: Associative Memory
Deep Brain Stimulation
Electroencephalography
Epilepsy
Hippocampus
Memory
Advisor: Valiante, Taufik A
Potential for Adaptive Evolution of Brassica rapa under varying Thermal Environments

As suitable environmental conditions for species shift rapidly under anthropogenic climate change, populations that are not well adapted, or maladapted to these novel environments can face serious challenges. Evolutionary rescue of a population in decline depends on genetic variation in fitness. The adaptive potential of a population to a particular environment can be evaluated by estimating the mean and additive genetic variance in fitness itself. I used quantitative genetics coupled with ‘animal’ model MCMCglmm analysis to estimate the adaptive potential of a wild population under an expected future temperature regime. I found very low estimates of genetic variance and heritability in fitness components, however these results may correspond with the rarity of evolutionary rescue in wild populations. I did find correlations between fitness components that indicate possible selection at the germination stage of early life history stages that may be eroding genetic variance in fecundity later on.

Keywords: climate change
evolutionary rescue
genetic variance
quantitative genetics
Advisor: Weis, Arthur
Understanding Experiences and Support Needs of Families Caring for Older Adults with Depression

Background: The experiences and needs of caregivers of older adults with depression are not well understood. This study aims to explore their experiences and desired resources from the healthcare system. Methods: Eleven qualitative interviews were conducted with caregivers of older adults with a clinical depression diagnosis in Toronto, Canada. Findings were generated via thematic analysis. Findings: Caregivers perceived a transformation in the person with depression’s behaviours and personality that also changed the relationship between them. Caregivers modified their lifestyle, perceived stigma towards their love one related to depression, and experienced declines in their own well-being. Caregivers’ personal and external resources helped with caregiving role and additional resources are needed from the healthcare system. Conclusion: There is an immediate need for increased healthcare resources for older adults with depression and their family members. This study provides insight for clinicians and policy makers to implement resources to optimize the caregiving role.

Keywords: Caregiver
Depression
Family
Qualitative
Seniors
Advisor: Cameron, Jill I
Investigating the Role of LIMK1 Signaling in PKA-dependent LTP in the Hippocampus

Long-term potentiation (LTP) in the hippocampus is the most extensive form of long-lasting synaptic plasticity and is widely regarded as the cellular basis of memory formation. The canonical NMDA-receptor (NMDAR)-dependent form of LTP can be differentiated into protein kinase A (PKA)-dependent and -independent forms by the spacing between theta burst stimuli (TBS) induction. Key features of PKA-dependent LTP includes insertion of Ca2+ permeable AMPA receptors (CP-AMPARs) and initiation of de novo protein synthesis. However, the molecular mechanisms that elicit these processes remain unknown. Previous studies suggest PKA can regulate LIM-domain kinase (LIMK) 1, but this regulation has not been demonstrated in synaptic plasticity. Using a combination of electrophysiology, genetic mouse models, and pharmacology, I show that CP-AMPAR-dependent LTP requires PKA regardless of TBS spacing. Furthermore, I demonstrate that LIMK1 is required for PKA-dependent LTP. These findings provide insight into the molecular mechanisms underlying LTP and long-term memory formation.

Keywords: CP-AMPAR
LIMK1
LTP
PKA
Advisor: Jia, Zhengping
Collingridge, Graham L
Hemojuvelin Maintains Blood-brain Barrier Integrity

BBB integrity is crucial in maintaining healthy brain functions. Its disruption is seen in numerous diseases, leading to neuronal damage signicantly contributing to disease progression. Therefore, understanding the mechanism in uencing BBB functional turnover is extremely important for discovering potential therapeutic targets. Here I develop a novel light-sheet imaging technique and show that a liver-secreted protein, hemojuvelin (Hfe2), is essential for maintaining BBB function during regular homoeostasis. I show that Hfe2 counteracts the function of its homologue RGMa, which severely disrupts BBB integrity. Hfe2 exerts its inhibitory eect on RGMa through competitive binding to their receptor Neogenin, which is present on cerebral endothelial cells. This Hfe2/RGMa interplay on Neogenin is potentially involved in the pathogenesis of multiple sclerosis. The present study has implications for the normal homoeostasis of BBB integrity and may shed insight on the potential pharmaceutical treatment.

Keywords: Blood brain barrier
Hfe2
Light sheet
Neogenin
Repulsive Guidance molecule
RGMa
Advisor: Carlen, Peter L
Monnier, Philippe P
“Pass me the Hookah”: An Assessment of Toronto’s Shisha Ban as Related to Muslim Placemaking, Forced Displacement, and Racializing Surveillance

Toronto’s ‘shisha ban’ came into effect on April 1st, 2016 and has since forced nearly 70 predominantly Black and brown Muslim migrant-owned businesses to close or restructure their livelihoods. Following the passing of the ban, Ali, the owner of Scarborough-based Habibiz Shisha Café, spoke to the cultural and religious significance of shisha and asked, “where else is there for us in this city?” (Hassan, 2016). Through semi-structured interviews and an analysis of the legislation enacted, I look to Ali’s question as a starting point to engage in a study of the relatively new bylaw and its impacts on Muslim placemaking in the Greater Toronto Area (GTA). Through this thesis, I put forward a non-exhaustive archive of Toronto’s shisha culture and look to traditions of Black, Indigenous, and racialized urban placemaking to consider collective futures beyond racializing surveillance and the unbelonging and displacement which often follows.

Keywords: Hookah
Muslim
Placemaking
Racializing surveillance
Surveillance
Toronto
Advisor: Gilbert, Emily
Small Molecule Probes for Photodynamic Therapy (PDT)

Photodynamic therapy is a clinically approved cancer treatment that utilizes singlet oxygen generated via a combination of photosensitizer (PS), light and molecular oxygen to kill cells. Unfortunately, the technique remains under-utilized due to the indiscriminating phototoxicity of PSs upon irradiation, causing damage to healthy cells alongside cancer cells. Pro-drug derivatives of pre-existing PSs that are activated by enzymes overexpressed in cancer cells offer a great solution. Such derivatives are inactive until acted upon by cancer biomarkers, allowing for cancer targeted cell death. This work highlights the preliminary work in the development of 2 such activatable PSs, activated by the cancer biomarkers, O6-methylguanine-DNA-methlytransferase and Nitroreductase. In addition, the development and photophysical characterization of a novel coumarin based PS is also discussed.

Keywords: Activatable Probes
Coumarin
Molecular Beacons
Nitroreductase
O6-Methylguanine DNA Methyltransferase
Photodynamic Therapy
Advisor: Beharry, Andrew A
Restoration Strategies to Improve Animal Movement in the Atlantic Forest

Habitat loss and fragmentation are leading causes of biodiversity decline worldwide. Animals sensitive to fragmentation suffer from decreased dispersal, breeding opportunities, and genetic diversity, making them vulnerable to extinction. Over the last decades the Atlantic Forest of Brazil has been extremely fragmented, with only 11-16% of forest remaining. Fortunately, ecological restoration is occurring throughout Brazil. Using computer modelling, I investigated how alternative restoration strategies improve the functional connectivity of the landscape. I used lion-tamarins of Southern Bahia, Brazil as a case study. I imposed three restoration strategies, Landowner Focused, Biodiversity Focused, and Random, on each of six sample landscapes, and five amounts of restoration (0%, 5%, 10%, 15%, 20%). I found both restoration strategy and amount had a significant effect on connectivity. Landowner and Biodiversity Focused strategies were significantly better at increasing connectivity than the Random strategy, and greater restoration amounts resulted in greater connectivity.

Keywords: Atlantic Forest
Functional Connectivity
Restoration strategies
Riparian Forest
Rivers
Advisor: Raboy, Becky E
Fortin, Marie-Josee
Identification of Three Potential SPARC Isoforms Expressed by the Larval Fat Body and Wing Imaginal Discs and the Requirement for the Collagen-binding Epitopes and the Disulfide-bridged EF-hand2 for Stereotypic BM Assembly in Drosophila Melanogaster

The assembly of basement membranes (BMs) into thin sheet-like extracellular matrix networks with tissue-specific thicknesses is poorly understood. Loss of dSPARC results in 2nd instar larval lethality characterized by a fibrotic-like accumulation of Collagen IV surrounding the fat body adipocytes and retention in large vesicle-like structures during 2nd instar. Fat body-derived dSPARC and Collagen IV are co-secreted and localized on the surface of distal tissues. Stereotypic BM assembly is dependent on the conservation of the Collagen-binding epitopes and the disulfide bridge EF-hand2 of fat body-derived dSPARC. Imaginal wing disc-derived dSPARC fails to localize with Collagen IV-rich matrices, indicating that distinct isoforms of dSPARC are expressed by different tissues. Intracellular dSPARC and human SPARC yielded a novel 67 kDa isoform. The data provides the first in vivo evidence of three different isoforms of dSPARC, with potentially distinct functions in BM assembly and larval survival in Drosophila.

Keywords: basement membrane
collagen
intracellular
Isoform
SPARC
Advisor: Ringuette, Maurice
Properties of Biopolymer Films in Ionic Solutions and their Applications as 3D Printed Personalized Wound Dressings

This thesis describes the effects of ionic solutions on biopolymer films and the development of a 3D printed personalized wound dressing. Chitosan, gelatin, and composite chitosan/gelatin films were exposed to NaCl, Na2SO4, and CaCl2 solutions with varying ionic strength and their swelling and dissolution properties were measured. In addition, the release of the small ionic molecules Rhodamine B and Eosin Y from films into NaCl solutions of varying ionic strength was monitored. Next, a shear-thinning mixture of cellulose nanocrystals and chitosan-methacrylate was extruded with various patterns and polymerized by ultraviolet light irradiation or elevated temperature to form hydrogel wound dressings. Antimicrobial silver nanoparticles, a model protein (bovine serum albumin), and an antibiotic (gentamicin) were added to the hydrogel mixtures and their release from the dressings was monitored. In addition, phenol red-methacrylate was co-polymerized into the hydrogel dressing and exhibited a pH-responsive colour change suitable for the detection of infection.

Keywords: 3D Printing
Biopolymer film
Cellulose Nanocrystals
Chitosan
Advisor: Kumacheva, Eugenia
Elucidating Effects of RYR1 in a Zebrafish and a Novel Recessive Mouse Model

Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that typically present in childhood and are associated with an estimated prevalence of one in 26,000 live births. These myopathies present with significant morbidities, including wheelchair and ventilator dependence. RYR1-related myopathies are defined by mutations in Ryanodine Receptor 1 or RYR1, the gene for the protein RyR1, an intracellular Ca2+ channel required for muscle contraction. Despite the severity of this disorder, there are no treatment options available for RYR1-related myopathy patients. To address this, I screened an ryr1a-/-; ryr1b-/- zebrafish mutant against 2,000 well-characterized compounds, none of which restored mutant levels to wild type. As a secondary aim, I performed a phenotypic analysis of a recessive mouse model that recapitulates several characteristics of these myopathies that will one day serve as a useful model for therapeutic development. This work herein explores the complicated spectrum of RYR1-related myopathies and expands our current understanding.

Keywords: Ryanodine Receptor 1
Advisor: Dowling, James
Probing drug-binding to NBD1 of SUR2A, the regulatory subunit in cardiac KATP channels

The sulfonylurea receptor 2A (SUR2A) forms the regulatory subunit in ATP-sensitive potassium (KATP) channels in the heart. KATP channels open upon MgATP binding and hydrolysis at the SUR2A nucleotide-binding domains (NBDs). Channel gating by SUR2A is essential, as mutations in SUR2A NBDs cause cardiovascular disorders. Further, SUR proteins are binding sites for KATP channel openers (KCOs) drugs and pharmacological chaperones that rescue trafficking defects in mutant KATP channels. Previously we showed binding of KCO pinacidil to SUR2A NBD1 increases affinity of protein for MgATP, providing a mechanism by which pinacidil increases KATP channel gating. However, the site of drug binding is unknown. To this end, we used NMR spectroscopy to probe effects of mutations for drug binding. Our data showed drug-induced allostery with residues that bind MgATP. Structural information gained is essential for rationale design of more potent and selective drugs to treat molecular defects in the NBDs.

Keywords: ABC proteins
ATP-sensitive K+ channels
drug interactions
Fluorescence spectroscopy
NMR spectroscopy
nucleotide binding domains
Advisor: Kanelis, Voula
Prosser, Scott R
Inflammation and Mitochondrial Dysfunction in Type I Bipolar Disorder

Bipolar disorder (BD) is a chronic psychiatric illness and a leading cause of disability worldwide. Several lines of evidence suggest that mitochondrial dysfunction and inflammation are present in BD. Our objective was to investigate if there was evidence for NLRP3 inflammasome activation as a link between inflammation and mitochondrial dysfunction in peripheral samples of BD. Sera, peripheral blood mononuclear cells, and DNA were obtained from 205 participants with type I BD and 205 non-psychiatric controls. We observed large differences between recruitment sites in levels of serum cytokines and L-lactate. However, controls and BD cases were not recruited from the same sites and the observed differences were largely be explained by transit time 協 the time between blood draw and when the sample arrived at the central biospecimens laboratory. The present study highlights problems inherent involving collection of biospecimens for biobanks and provides recommendations for how future studies should be conducted.

Keywords: Biobank
Bipolar Disorder
Inflammation
Mitochondria
NLRP3 Inflammasome
Advisor: Andreazza, Ana C
Biernacka, Joanna M
The Impact of Oral Health Training Taken by Personal Support Workers Caring for a Geriatric Population in a Long-term Care Facility: A Mixed Methods Study

Personal support workers (PSW) employed in long-term care (LTC) facilities provide the majority of primary resident care. Oral health care is a primary care provision that is rarely carried out to an acceptable standard. The purpose of this study was to ascertain if and how a mandatory oral health online education module impacted the PSWs’ knowledge and beliefs in their care for a geriatric population at an over 400 bed LTC facility in Ontario. The mixed methods convergent design study included a quantitative pre/post-test design and qualitative face-to-face focus groups and one-on-one interviews with 88 and 23 participants, respectively. The results indicated that the online module had limited impact on the PSWs’ oral health knowledge and beliefs in their resident oral health care. Personal support workers recognize their need for training to care for residents with complex needs and often requested dialogic hands-on training with a self-initiated dental hygienist.

Advisor: Lawrence, Herenia P
Clinical and Economic Outcomes for Gastric Cancer Patients Treated with Gastrectomy at Centres With and Without Cancer Surgery Designation in Ontario

Gastric cancer places high clinical and economic burden on healthcare systems. This study compares patient outcomes between centres with and without cancer surgery centre designation (CSCD). Gastric cancer patients diagnosed 2002-2014, and treated with gastrectomy were identified using Ontario’s linked administrative databases. Outcomes included 90-day mortality, overall survival, and healthcare costs. Institutions with CSCD (n =1,436) were associated with lower 90-day mortality (OR 0.70, 95% CI 0.52-0.94, p=0.02), and similar overall survival (HR 0.94, 95% CI 0.85-1.04, p=0.24) as institutions without CSCD (n = 1,494). The cost analysis included 1,143, and 1,256 patients treated at institutions with and without CSCD, respectively. Adjusted mean monthly costs were $3,310 (95% CI $2,384-$4,595) for the CSCD group, and $3,430 (95% CI $2,469-$4,765) for the non-CSCD group (p=0.36). Treatment at institutions with CSCD may result in lower 90-day mortality, and similar overall survival, and costs of care for gastric cancer patients.

Keywords: Clinical Outcomes
Economic Outcomes
Gastrectomy
Gastric Cancer
Specialization
Advisor: Coburn, Natalie
A Molecular Phylogeny and Review of the North American Species of Theromyzon (Hirudinea: Glossiphoniformes: Glossiphoniidae), with a New North American Species

Theromyzon (Philippi, 1867) is a genus of sanguivorous, freshwater leeches in the family Glossiphoniidae. The genus has broad distribution across the globe, in part due to their frequent feeding in the nasal and ocular cavities of migratory waterfowl (Oosthuizen and Davies, 1993). The genus has a history of taxonomic confusion resulting from mischaracterizations of type specimens that have produced a number of re-descriptions and refutations. In this thesis, I produce the first species-level phylogeny for Theromyzon and determine how many species occur in North America. I show that there are at least six species in North America, at least one more than the five species recorded by Oosthiuzen and Davies (1993) in the most recent revision of the genus. This study elucidates the number of species of Theromyzon in North America, clears up confusion around classification, and lays the groundwork for further phylogenetic studies of the genus.

Advisor: Kvist, Sebastian
A Changing Era in Chronic Hepatitis B: Novel Biomarkers and Therapies

Chronic Hepatitis B (CHB) infection is a severe health problem worldwide. It is challenging to achieve a complete cure for CHB as the currently available antiviral treatments cannot eradicate the covalently closed circular DNA (cccDNA) in the infected hepatocytes. Detecting cccDNA is an important goal to strive for when investigating the effectiveness of available therapies and developing novel treatments. Hepatitis B virus RNA (HBV-RNA) is a relatively new serum biomarker that correlates with cccDNA. We studied HBV-RNA kinetics and their potential role as a predictor of treatment response in HBeAg-negative CHB patients. HBV-RNA showed a greater decline in treatment responders compared to non-responders early on, at week 12 of treatment. Levels above 1700 c/mL (3.2 log10 c/mL) had a negative predictive value for treatment response of 91% at week 12 and 93% at week 24 (P=0.01). In conclusion, HBV-RNA demonstrated a rapid and significant decline associated with treatment response during long-term follow-up

Advisor: Janssen, Harry L.A
A Computational Fluid Dynamics Approach for Dissolved Oxygen Modelling with Application to Wind-powered Aeration Systems

Dissolved oxygen is one of the most critical parameters of water quality in aquaculture. Aeration systems are generally used to improve oxygen levels and yields. However, these systems have high capital and operating cost, require electricity and, thus, are out of reach for farmers in developing countries. There is a need for affordable and sustainable aeration technologies. This thesis presents the development of a computational dissolved oxygen model which evaluates the spatial and temporal distribution of dissolved oxygen to enable evaluation and optimization of new aeration approaches. The three-dimensional model was developed based on Finite Volume Method and validated by bench-scale and field experiments. Results showed that the model was capable of predicting the dissolved oxygen concentration with an average prediction error of 7.2%.

Keywords: Aeration Systems
Aquaculture
CFD
Dissolved Oxygen
Advisor: Bilton, Amy
The Synthesis and Optimization of Non-commercially Available Phthalonitriles and their Pathway to Novel Boron Subphthalocyanines

Even though they are the precursors to boron subphthalocyanines, there are many phthalonitriles that are not commercially available; furthermore their synthesis has never been approached for the purposed of scale-up and the industrial manufacturing of boron subphthalocyanines. While the synthesis of brominated and iodinated phthalonitriles is not novel, their incorporation into boron subphthalocyanines for characterization and potential use as organic photovoltaics is. This work outlines the synthesis of 4-bromophthalonitrile, 4,5-dibromophthalonitrile, 4,5-diiodophthalonitrile, and 3-methylphthalonitrile and the pathway to their subsequent boron subphthalocyanines. Discussion is also included on the failure to synthesis 3,4,5,6-tetrabromophthalonitrile and 3,6-dimethylphthalonitrile.

Keywords: Biomass Sources
Boron Subphthalocyanines
Halogenation
Methylation
Phthalonitriles
Solar Energy
Advisor: Bender, Timothy
Facilitators of, and Barriers to, Accessing Reproductive Care in Canada for Same-sex Male Couples (SSMC) and Single Men (SM)

Same-sex male couples (SSMCs) and single men (SM) are increasingly using assisted reproductive technologies (ART) to have children, yet research on their experience accessing care in Canada is limited. The objective of this preliminary study was to evaluate experiences of SSMCs and SM who have pursued ART in Canada. Data were collected from 08/2018 - 01/2019 through convenience sampling using a 58-item anonymous online survey. Seventy-two completed surveys were used for the analysis. Four of five participants (n=58, 80.5%) had a positive overall experience using ART. Resources such as high socio-economic status and social support were facilitators to accessing ART in Canada. Barriers to accessing care included: cost, time commitment, experience of stigma, and difficulties securing third parties when using ART. This research may guide practice and policy implications for reproductive healthcare services in Canada, such as provision of funding to make ART more accessible to all demographics.

Keywords: assisted reproductive technology
egg donation
health care experience
same-sex male couples
single men
surrogacy
Advisor: Librach, Clifford