VictorJuiz/thesis huggingface dataset:
Characterizing Brain Metabolites with Chemical Exchange Saturation Transfer MRI

Chemical exchange saturation transfer (CEST) MRI is sensitive to small molecule protons that exchange with water protons. When these protons reside on molecules that are altered by disease, such as brain metabolites, proper in vitro characterization of the physical properties of the molecules is vital to the accurate interpretation of in vivo data. In this thesis, three brain metabolites were characterized: γ-aminobutyric acid, glutamate, and glutamine. Analysis was performed by fitting experimental data to the Bloch–McConnell equations to obtain parameter estimates (T2 relaxation, exchange rate, metabolite concentration, and resonance frequency of the CEST protons) and examine any correlations between them. Results demonstrated that simultaneous fitting to multiple sample concentrations provided more consistent results and smaller uncertainty in estimated parameters when compared to individually fitting concentrations. The obtained physical parameters and correlations provide a basis for future data interpretation and indicate that certain correlated parameters must be interpreted with caution.

Keywords: Bloch-McConnell equation
chemical exchange saturation transfer
GABA
glutamate
glutamine
MRI
Advisor: Stanisz, Greg
Neurostructural Correlates of IL-1β rs16944 Polymorphism in Adolescents with and without Bipolar Disorder

Increased inflammation among youth with bipolar disorder (BD) is associated with increased illness severity. Functional inflammatory polymorphisms are associated with neurostructural changes in BD. This was examined for the first time in youth. T1-weighted images of 38 BD and 32 healthy controls (HCs) were processed through FreeSurfer to obtain cortical region of interest (ROI) volumes/surface area/thickness for dorsolateral prefrontal cortex and caudal anterior cingulate cortex, along with subcortical ROI volumes for hippocampus and amygdala. Our results show a main effect of interleukin (IL)-1β rs16944 in the lateral occipital cortex (LOC), along with a IL-1β rs16944-by-diagnosis interaction effect for a pars triangularis surface area cluster along with a LOC volume cluster. Our results suggest that the IL-1β rs16944 polymorphism is associated with neurostructural differences in youth with BD and HCs. Future studies including other imaging phenotypes and neurocognitive tasks are warranted to evaluate the relationship between IL-1β rs16944 and brain function.

Keywords: Adolescents
Bipolar disorder
Brain
Inflammation
Interleukin-1β
MRI
Advisor: Goldstein, Benjamin
Enhancing the Efficiency of CRISPR/Cas9 Precise Gene Editing for Cystic Fibrosis Gene Therapy

Cystic fibrosis (CF) is the most common cause of chronic obstructive lung disease in children and young adults, yet there is no cure for this disease. Intimations of curative strategies have emerged from gene therapy, but these approaches have failed in clinical trials due to insufficient safety and efficacy profiles. The molecular technology necessary to overcome preeminent challenges in gene therapy may reside in programmable nucleases – namely CRISPR/Cas9 – which allow for site-specific genomic integration of therapeutic transgenes. However, the clinical utility of these technologies is limited by inherently low efficiencies. Here, we use flow cytometry and PCR assays to demonstrate the efficacy of perturbing DNA repair to overcome such limitations. We demonstrate that overexpressing CtIP and EXO1-4D can enhance the efficiency of CRISPR/Cas9-directed transgene integration by ~3- and ~6-fold, respectively. These discoveries may provide necessary impetus for translating gene therapies into clinical realities for genetic diseases such as CF.

Keywords: CRISPR/Cas9
CtIP
Cystic fibrosis
EXO1
Gene targeting
Gene therapy
Advisor: Hu, Jim
Best Practice MedsCheck Annual Service: A Multi-Case Study

Purpose: To identify and describe factors that contribute to best practice adherence-focused medication reviews (MRs) in the community pharmacy. Methods: A multi-case study, following Yin’s approach, was conducted in two community pharmacies in Ontario referred for their exemplary MR services. Data sources included interviews, pharmacy observations, and service-relevant documents. Data were coded and analyzed thematically. A work systems model, the Systems Engineering Initiative for Patient Safety, served as the conceptual framework. Results: In both pharmacy cases, MR processes were systematic and normalized. Common work system features included the use of appointments, overlapping pharmacists, task delegation, and e-technologies. Both pharmacies had service leaders/champions and a clinically oriented culture focused on relationship-building with patients and healthcare providers. Conclusion: Based on common cross-case features, a conceptual definition and recommendations for best practice adherence-focused MRs were provided. Study findings will inform the development of quality improvement initiatives for medication review services in community pharmacies.

Keywords: Best Practice
Community Pharmacy
Medication Review
Multi-Case Study
Work Systems
Advisor: MacKeigan, Linda D
Dichotomy of TNF Family Ligands Expression on Classical Dendritic Cells and Monocyte-derived Antigen Presenting Cells During Viral Infection

Tumor necrosis factor receptor (TNFR) superfamily members, including 4-1BB, OX40, GITR and CD27 contribute to T cell survival during viral infection. However, the cell types that provide the ligands have not been fully investigated. Here we use multiparameter flow cytometry to follow the induction of TNF family ligands on APC subsets during lymphoytic choriomeningitis (LCMV) clone 13 infection. We found that at day 2 post infection, type I interferon induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs, whereas MHC II and B7 family ligands are highest on classical dendritic cells (cDCs) in the spleen. These findings shed light on the expression of TNF family ligands by different APC and suggest that the temporal and spatial regulation of these ligands may be important in determining immune control or pathology during viral infections.

Keywords: Antigen presenting cell
B7 family ligands
lymphoytic choriomeningitis (LCMV) clone 13 infection
Tumor necrosis factor receptor (TNFR) superfamily members
type II interferon
type I interferon
Advisor: Watts, Tania H
A CONTROL STRATEGY FOR A MICROGRID INTEGRATED WITH MULTIPLE SOLAR-PV UNITS AND A LARGE-SCALE BATTERY ENERGY STORAGE SYSTEM

This thesis presents a control strategy and its algorithms for a microgrid system that can operate in the grid-connected mode, in the islanded mode, and transfer between them. The microgrid includes three Solar-PV units and one large-scale Battery Energy Storage System (BESS). Performance evaluation of the microgrid is carried out in the time domain, using the PSCAD/EMTDC software platform, to demonstrate the effectiveness of the proposed control strategy. In the grid-connected mode, the three Solar-PV units are controlled to track their Maximum Power Points (MPPs) and the battery State of Charge (SOC) is maintained within a prespecified range. In the islanded mode, the BESS controls the voltage and frequency of the microgrid. The control system is also tested for other transient conditions such as load shedding, Solar-PV loss, temporary faults, reconnection to the utility grid and charge or discharge of the BESS in the case of low or high SOC, respectively.

Keywords: Battery Energy Storage
control strategy
microgrid
Solar-PV
Advisor: Iravani, Reza
The association of urinary vitamin D binding protein with kidney dysfunction and hypovitaminosis D in patients at risk for type 2 diabetes

One possible explanation for hypovitaminosis D in type 2 diabetes (T2DM) is that vitamin D metabolites may still be bound to the vitamin D binding protein (VDBP) as the protein is lost in urine. Given that VDBP may be linked to both kidney dysfunction and hypovitaminosis D, the objective is to investigate longitudinal associations of urinary VDBP on measures of kidney health and vitamin D status. Data from a cohort of adults at risk for T2DM was used (n=729). Albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measures of kidney function while 25-hydroxyvitamin D (25(OH)D) indicated vitamin D status. Adjusted generalized estimating equation models showed that uVDBP was associated with higher ACR over time, but was not associated with changes in eGFR or 25(OH)D. These results emphasize that although mild VDBP loss is not linked with hypovitaminosis D, urinary VDBP may be a useful biomarker for tubular damage.

Keywords: Albuminuria
Diabetes
Epidemiology
Kidney diease
Vitamin D
Vitamin D binding protein
Advisor: Hanley, Anthony JG
Prevalence and Presentation Patterns of Enamel Hypomineralisation among Paediatric Hospital Dental Patients in Toronto, Canada

Purpose: To determine the prevalence and presentation patterns of molar incisor hypomineralisation (MIH) and hypomineralised second primary molars (HSPM) in the Division of Paediatric Dentistry at The Hospital for Sick Children in Toronto, Canada. Methods: A cross-sectional study of 429 participants was performed by 9 calibrated examiners. The study used the European Academy of Paediatric Dentists criteria in diagnosing and documenting MIH/HSPM based on clinical presentation, size, and location of defects. Results: MIH prevalence was 12.4% (n=29) and 5.2% (n=19) for HSPM. Demarcated white opacities were the most common clinical finding of MIH (60%) and HSPM (67%). In both MIH and HSPM, single surface hypomineralised lesions were significantly more common than multi-surface lesions (p

Keywords: Molar incisor hypomineralisation
Advisor: Casas, Michael J
Septins in Cancer and Metastasis

Septins are GTP-binding cytoskeletal proteins that play a role in cancer cell migration. Their role in mesenchymal cell migration has been studied but not in amoeboid migration. Here, I show that in the highly invasive melanoma cell line, A375m2, loss of all isoforms of SEPT9 promotes switching from the amoeboid round to the less invasive mesenchymal elongated phenotype. It also causes the loss of RhoA-induced stress fibers while increasing the formation of Rac1-induced lamellipodia. Knocking out only the long isoforms of SEPT9 (v1-v3) brought about a similar effect on the amoeboid phenotype in 3D but in 2D caused a change in the types of stress fibers from ventral to dorsal and transverse arcs. Through immunostaining, I show that septins are localized at the back of the amoeboid migrating cell. This study thus shows the potential role of SEPT9 in amoeboid migration and thus in cancer metastasis.

Keywords: Cancer
Metastasis
Septins
Advisor: Trimble, William
Fuel Influence on Gasoline Direct Injection Particulate Matter Emissions

Particulate emissions from gasoline direct injected engines are a topic of growing research interest due to health concerns. Using engine tests of extended length and fueled with custom hydrocarbon blends, this study aimed to experimentally investigate temporal and test-to-test gasoline particulate emissions variability that has been observed in earlier work. Gasoline property changes during engine operation and engine control module adjustments were ruled out as the source of the temporal variation. Crankcase ventilation system deposits were also ruled out but they were found to increase average particle numbers. Testing of custom fuel blends demonstrated that transient cold and hot start particulate emissions are fuel independent, steady state emissions are highly influenced by fuel properties and the commonly used model to assess that influence, the PM Index, is incomplete, and that the use of fuel of consistent composition reduces test-to-test variability.

Advisor: Wallace, James S
A PILOT STUDY OF THE SIMULTANEOUS USE OF DERMAL FILLER FOR RESTORATION OF DEFICIENT PAPILLAE AND ENAMEL MATRIX DERIVATIVE FOR ROOT COVERAGE IN CONJUNCTION WITH MINIMALLY INVASIVE SURGERY: PATIENT REPORTED OUTCOMES

Gingival recession, including interdental papilla loss, is considered by most patients as aesthetically unpleasant. Yet, in most instances, no treatment is available. Our aim was to develop a minimally invasive and predictable approach to treat papilla deficiencies and gingival recession. We hypothesized that, following the formation of a subperiosteal space, dermal filler administration into deficient papillae and a coronally advanced flap with enamel matrix derivative application to exposed roots will provide significant improvements in patient satisfaction with papillary fill and root coverage. Six months following treatment there was a significant increase in patient-satisfaction regarding improvement of gingival deficiencies shown by a mean increase in visual analogue scale (VAS) measurements of 68.3% (p

Keywords: Dermal Filler
Gingival Papilla Reconstruction
Patient Related and Clinical Outcomes
Periodontal Plastics
Treatment of Recession
Advisor: Tenenbaum, Howard C
Universal Measures of Support Are Needed: A Cross-Sectional Study of Health Literacy in Patients with Dupuytren’s Disease

Health literacy represents the degree to which patients can understand and act upon health information and is highly relevant to surgical care. This cross-sectional study sought to determine the prevalence and the independent predictors of limited health literacy in patients with Dupuytren’s disease. The Newest Vital Sign, a validated and reliable tool, was selected to measure health literacy. An exploratory multivariable logistic regression model was used to identify the predictors of limited health literacy. Almost half (44%) of eligible patients (n=185) had limited health literacy. Having a lower household income or being an immigrant led to an increased in the odds of having limited health literacy by nearly 5 and 4-fold respectively. Considering the high prevalence of limited health literacy and the challenge in identifying predictors in the clinical setting, universal measures of support, such as tools aimed to facilitate communication with all patients, would be of high value.

Keywords: Cross-sectional
Dupuytren's disease
Hand surgery
Health literacy
Measures of support
Surgery
Advisor: Urbach, David R
Automatic Reconfiguration of Untimed and Timed Discrete-Event Systems

This work introduces a general formulation of the reconfiguration problem for untimed and timed discrete-event systems treated by supervisory control theory. To model the reconfiguration requirements we introduce the concept of reconfiguration specification in which reconfiguration events are introduced to force a transition from one system configuration to another. Supervisory control theory then synthesizes a reconfiguration supervisor in which designated states serve as the target states for a particular reconfiguration event. An untimed (or timed) reconfiguration is commanded at a source state in the reconfiguration supervisor at which a change in configuration is requested. The solvability (or otherwise) of this reachability problem is checked by forcible backtracking in a recursive tree-based manner. The proposed method solves centralized and decentralized reconfiguration problems in both untimed and timed cases. To our knowledge, the solution to the timed case is the first solution to the automatic reconfiguration problem of automaton-based timed discrete-event systems.

Keywords: Automatic reconfiguration
Discrete-event systems
Timed discrete-event systems
Untimed discrete-event systems
Advisor: Wonham, Walter Murray
Novel Tripartite Motif Containing 22 Interactions in the Context of Very Early Onset Inflammatory Bowel Disease

Genetics predominate in very early onset inflammatory bowel disease (VEOIBD). With poor outcomes and therapeutic response, monogenic causes revealed by whole exome sequencing has potential for personalized therapies. Our recently published E3 ubiquitin ligase TRIM22 variants revealed novel roles in regulating NOD2. Apart from anti-viral pathways, the extent of TRIM22’s influence remains unclear. We interpreted TRIM22 BioID performed by collaborators. On the list of potential binding partners is the Nucleosome Remodeling and Deacetylase (NuRD) complex. Functional analysis shows TRIM22 binding HDAC1, the catalytic core of the NuRD complex, but may not ubiquitinate HDAC1 or alter its stability. VEOIBD variant TRIM22 R442C significantly reduces binding, and is the only variant to not form nuclear bodies. HDAC1 levels may be reduced in TRIM22 R321K patient pre-treatment colon biopsies. Given recent insights into TRIM22 mediated monocyte apoptosis, we suggest interaction with the NuRD complex plays a role in cell fate and inflammation.

Keywords: E3 Ubiquitin Ligase
HDAC1
Inflammatory Bowel Disease
Paediatric
TRIM22
Whole Exome Sequencing
Advisor: Muise, Aleixo
Characterization of Quantum State Generated on Chip

Quantum protocols, which exploit non-classical correlations produced by quantum light sources, have demonstrated their advantages over their classical counterparts. Being able to engineer and characterize on-chip quantum light sources used to implement these quantum protocols is becoming crucial, as practical quantum-enhanced applications evolve. In this thesis, we first demonstrate that the photon statistics of our on-chip quantum source can be measured using pulsed pumping and single-photon detectors. We show that non-classical correlations g (2) and noise reduction factor are degraded in a noisy and lossy environment. We also demonstrate that the bi-photon joint spectrum amplitude can be tuned by engineering the waveguide structure. The ability to engineer and characterize the on-chip quantum source paves the way to practical quantum applications, such as quantum illumination (QI) protocol. We also show that the performance of QI can be enhanced by increasing the number of frequency modes through waveguide engineering.

Keywords: Nonlinear Photonics
Nonlinear Waveguide
Quantum Imaging
Quantum Optics
Advisor: Helmy, Amr S.
Effects of the Saturated Fatty Acid Palmitate on Neuroinflammation, ER Stress, and Pomc mRNA Expression in Hypothalamic mHypoA-POMC/GFP Neurons

Dietary fats can modulate brain function. How free fatty acids (FFAs) alter hypothalamic pro-opiomelanocortin (POMC) neurons remain undefined. The saturated FFA, palmitate, increased neuroinflammatory and ER stress markers, as well as Pomc mRNA levels, but did not affect insulin signalling, in mHypoA-POMC/GFP-2 neurons. This effect was mediated through the MAPK JNK and ERK. Further, the increase in Pomc was dependent on palmitoyl-coA synthesis, but not de novo ceramide synthesis, as inhibition of SPT enhanced palmitate-induced Pomc expression, while methylpalmitate had no effect. While palmitate concomitantly induces neuroinflammation and ER stress, these effects were independent of changes in Pomc expression. Palmitate thus has direct acute effects on Pomc, which appears to be important for negative feedback, but not directly related to neuroinflammation. The monounsaturated FFA oleate completely blocked the palmitate-mediated increase in neuroinflammation, ER stress, and Pomc mRNAs. This study provides insight into the complex central metabolic regulation by FFAs.

Keywords: ER stress
hypothalamus
JNK
neuroinflammation
palmitate
Pro-opiomelanocortin (POMC)
Advisor: Belsham, Denise D
Life Cycle and Techno-Economic Analysis of Fischer-Tropsch Renewable Diesel and Jet Fuel Production

Three different possible scenarios of renewable diesel and renewable jet fuel production from hybrid poplar through gasification combined with Fischer-Tropsch synthesis are studied in terms of process efficiency, life cycle greenhouse gas emissions, and techno-economic feasibility. The process modeling results indicate that it is technically possible to produce both renewable diesel and renewable jet fuel from this feedstock. The product yields are highly dependent on the process configuration in each scenario. Producing renewable diesel and jet fuel through this process results in low greenhouse gas emissions compared to conventional petroleum-based diesel and jet fuel, approximately a 95% reduction in emissions. The levered rate of return on investment associated with each scenario is highly dependent on not only the price of the fuel products and co-products but also the feedstock price.

Keywords: Fischer-Tropsch
Life cycle assessment
Renewable diesel
Renewable jet fuel
Advisor: Saville, Bradley A.
MacLean, Heather
Magnetic Resonance - Based Evaluation of Small Molecule Release from a Thermosensitive Drug Delivery System

There is an unmet need for clinically-implementable imaging toolsets to evaluate spatio-temporal drug release from thermosensitive nanocarriers in response to hyperthermia. This thesis presents a magnetic resonance (MR)-based platform for (1) evaluating hyperthermia-induced destabilization of thermosensitive drug carriers and (2) quantifying subsequent small molecule diffusion. The platform consists of a custom designed agar phantom, a temperature-controlled T1-weighted imaging workflow and a MATLAB analysis algorithm for semi-automated quantification of small molecule kinetics. Using this platform, thermosensitive liposomes (TSL) encapsulating gadoteridol were assessed at 22°C, 37°C, and 43°C and compared to free imaging agent and non-thermosensitive liposomes. In addition, the physiological relevance of the gel phantom was benchmarked against muscle and tumor tissue. Results demonstrated complete destabilization of TSL at 43°C in 1.5% agar, with a measured diffusion coefficient of (2.90 ± 0.52)×10-4 mm2/s which was not statistically different from free small molecule diffusion at 43°C, (2.72 ± 0.87)×10-4 mm2/s.

Keywords: MR
Thermosensitive drug delivery
Advisor: Zheng, Jinzi
The Ecological and Population Genetic Consequences of Invasion by the European Fire Ant, Myrmica rubra, in Ontario

When a species is introduced to a new area there are often consequences both for the population genetics of the species, and for the community it invades. In order to understand the population biology and spread of the invasive European fire ant, M. rubra, in its introduced range, we examined the existing population genetic structure of M. rubra in urban-parkland areas of Toronto. We discovered two genetic groups, and discuss the possibility that this may be the result of multiple introductions of the ant or local adaptation to variable habitats. To examine the effects that M. rubra has on a native ant seed-dispersal mutualism, we used a mesocosm experiment. We showed that M. rubra disperses seeds further from its nests than a native â keystoneâ seed-dispersing ant. This resulted in a long-term influence of ant species identity on plant survival, spatial arrangement, and community composition.

Keywords: Ants
Invasion biology
Mutualism
Seed dispersal
Advisor: Frederickson, Megan E