VictorJuiz/thesis huggingface dataset:
Development of a Viral Toolbox to Study the Role of m6A RNA Methylation in Memory

Memory relies critically on local synthesis of proteins at synapses. How cells are able to precisely and independently coordinate memory-related translation at each of their synapses is not fully understood. Just as transcription is modulated by epigenetic modifications of DNA during memory formation, local translation may be regulated by mRNA modifications, like N6 methylation of the adenosine base (m6A). In this project, we investigate the m6A pathway and find that the demethylase Fto is highly expressed in the mouse brain, and regulated in the CA1 of the hippocampus following a contextual memory task, along with several other pathway components and overall levels of m6A in mRNA. To probe the role of m6A in memory formation, we then develop herpes simplex virus (HSV) vectors to rapidly and selectively manipulate Fto levels in cells, including the first HSV-mediated CRISPR/Cas9 knockdown vector, which will increase our ability to flexibly target multiple genes in vivo.

Keywords: Cas9
Fto
local mRNA translation
m6A
memory
RNA methylation
Advisor: Josselyn, Sheena A
What is the Patient's Experience of Pain after a Fragility Fracture

With the exception of pain after a vertebral fracture, there is little research on long-term pain after a fragility fracture. Most relevant research focuses on physiological healing within the first six months of fracture. In this secondary analysis of three qualitative studies, I explored the experience of long-term post-fracture pain in men and women. Data from 29 individuals (51–89 years old) were re-analyzed using qualitative description (Sandelowski 2000; 2010). Twenty-four (83%) participants had sustained a fragility fracture at least one year previously (range: 1–13 years). Only seven individuals had sustained vertebral fractures. I developed three themes examining patients’ description of pain and its impact, their perceived shortcomings of health care providers, and their responses to the pain. My findings enable a better understanding of long-term pain after a fracture and call for individualized treatment planning that includes effective analgesia and continued physiotherapy.

Keywords: experience
fracture
fragility fracture
osteoporosis
qualitative description
secondary analysis
Advisor: Sale, Joanna
"Next Generation" Approaches in Diet Pattern Analysis: Assessing the Impact of Different Statistical Methods and Physiological Intermediate Variables

The objective of this thesis was to compare dietary patterns (DPs) derived using principal component analysis (PCA), reduced rank regression (RRR) and partial least square (PLS) analysis as well as to evaluate how the selection of disease-related intermediary variables (DRIVs) alters the DPs produced. The association of DPs with type 2 diabetes mellitus (T2DM) was also explored across different statistical techniques and DRIVs. All analyses were conducted using the Insulin Resistance Atherosclerosis Study (IRAS), a cohort consisting of middle-aged adults initially free of T2DM. PCA, PLS and RRR and each a priori defined DRIVs (inflammatory biomarkers) each yielded distinctive sets of DPS; however, there were no significant differences in how the different methods or DRIVs predicted T2DM. This could be due to the limited number of T2DM converters, the duration of follow-up, the characteristics of the FFQ and/or the population under investigation.

Keywords: Partial Least Square Analysis
Principal Component Analysis
Reduced Rank Regression
Advisor: Hanley, Anthony
Application of Electrokinetic Principles for the Distribution and Delivery of Antibacterial Nanoparticles for Root Canal Disinfection

Endodontic disinfection is challenged by bacteria organized as biofilms in difficult to access areas including the extraradicular regions of teeth. The aim of this study was to propose and evaluate an electrokinetic delivery system capable of mobilizing charged antibacterial nanoparticles and inactivating biofilm located within the apical portions of the root canal and on the extraradicular root surface. A computational model was developed to predict electric field and current density distribution generated by the proposed intervention. Transport of CSnp was demonstrated using a polydimethylsiloxane (PDMS) microfluidic model. Antibacterial properties of electric current and CSnp were evaluated against Enterococcus faecalis in planktonic and biofilm forms. The proposed intervention demonstrated rapid CSnp transport with subsequent distribution and deposition in the periapical regions. The bacteriological study demonstrated enhanced antibacterial and antibiofilm effects. If translated clinically, this methodology may augment endodontic disinfection and offer the ability to treat extraradicular biofilms through a non-surgical approach.

Keywords: antibacterial
chitosan
electrokinetics
electrophoresis
endodontics
nanoparticles
Advisor: Kishen, Anil
Selvaganapathy, Ravi
The Role of the Src-like Adaptor Protein in the Regulation of GM-CSFR Signaling

GM-CSF is a cytokine that regulates proliferation and survival of myeloid progenitor cells and stimulates dendritic cell (DC) differentiation. The Src-like adaptor protein (SLAP) has been implicated in the negative regulation of the GM-CSF receptor and downstream signaling in DC, although the mechanism of SLAP action remains unknown. We hypothesized that SLAP regulates GM-CSFR by recruiting CBL to the receptor, where it can ubiquitylate and target it for degradation. In this investigation we found that SLAP interacts with both SHP2 and CBL in a GM-CSF dependent manner and that SLAP and CBL over-expression alters GM-CSFR trafficking. SLAP is also important in regulating GM-CSF-stimulated DC development. In this study we determined that the role of SLAP in regulation of GM-CSF signaling is specific to differentiation in DC and we identified differentially expressed genes in Slap knock-out DC that may be important for maturation.

Advisor: McGlade, Catherine J
Metallic Field Effect Transistors

This thesis investigates the principle of operation behind metallic-field effect transistors (METFETs) through a systematic study of atomistic simulations performed on metallic bulk, nanowire and transistor structures. In particular, density functional theory (DFT) and non-equilibrium greenâ s function (NEGF) based models were used to study the effect on the bandstructure and density of states of highly scaled metallic nanowires with varying parameters such as crystal orientation, cross-sectional area, and applied external bias. Similarly, the effect of varying similar parameters on the transfer and output characteristics of highly scaled metallic transistors was studied. Furthermore, oxide interfaces with metallic channels were investigated. The simulation results show that a gold METFET in the [100] crystal orientation has an I ON /I OFF ratio of 41, I ON of 29.5ÂľA and f T of 6.7THz, outperforming similarly sized MOSFETs as a promising alternative for use in high-frequency circuits.

Keywords: atomistic
gold
nanoscale
semiconductor
simulation
transistor
Advisor: Voinigescu, Sorin
The Regionalized Health Care System and Access for Mobile Populations in Southern Ontario

This case study of the Ontario regionalized health care system has investigated health care access in the context of an increasingly mobile population (including commuting and seasonal travel). Semi-structured interviews were conducted with staff members of Local Health Integration Networks and a Health Centre within southern Ontario alongside secondary research on federal and provincial health system structures and governance. The results of this research suggest there are mobility and geography system barriers to health care access in this region. The participants characterized obtaining transportation to health services as a current access challenge, and urban development and population growth as future concerns. Commuting and seasonal travel were not considered to present significant barriers outside logistics in arranging appointments. The health care systemâ s ability to mitigate such barriers may be limited by the structure of the health care system due to the regional-focus of planning and the necessity of inter-organizational collaboration.

Keywords: commuting
health care access
mobility
regionalization
system barriers
transportation
Advisor: Boland, Alana
Wakefield, Sarah
Palladium Complexes with Pendant Electrophilic Phosphonium Cations

Prototypical phosphorus compounds behave as Lewis bases, or electron donors, and are commonly employed as ligands for transition metal complexes. In contrast, examples and applications of phosphorus compounds with electron-accepting ability have recently emerged in the field of main group chemistry. Electrophilic P(V) cations (EPCs) exhibit strong Lewis acidity which has been exploited for a variety of catalytic transformations. In this work, the first transition metal complexes with pendant fluorophosphonium cations are reported and have been comprehensively characterized. The synthesis of a series of palladium compounds is described and the synergy between the metal and Lewis acid centres is investigated. The system demonstrates activation of a Pd-bound acyl fragment by the pendant phosphorus centre. This first example of metal-acyl derived phosphorane illustrates a new strategy for small molecule activation that has promising implications for the rational design of new and more efficient catalysts.

Keywords: Chemistry
Inorganic Chemistry
Organometallic Chemistry
Advisor: Stephan, Douglas W
‘I Had to be Brave’: Exploring Children’s Perspectives of Paediatric Medical Trauma and Resilience

Using a phenomenological design, eight (8) children from a paediatric rehabilitation hospital, between the ages of 6 and 12, were interviewed to understand their medical experiences and issues of resilience. All children were exposed to what has been defined in the literature as paediatric medical trauma, or the overwhelming experiences that can occur in medical settings. Through an iterative hermeneutic based analysis, themes emerged about their medical trauma, understanding of resilience, and ways in which they viewed themselves and their environment. Children reported their most challenging symptoms in acute care, and experiences in rehabilitation that maintained difficulties. Though children did not understand the formal term resilience, they understood the concept in simpler terms. All children identified themselves as resilient, describing and giving examples of their resilience, which are discussed throughout the thesis. This study importantly amplifies childrenâ s voices within their own care. Implications for future practice and research are discussed.

Keywords: Children's perspectives
Medical Trauma
Paediatric
Phenomenology
Rehabilitation
Resilience
Advisor: Alaggia, Ramona
Validation of the Radiographic Union Score for Tibial Fractures (RUST) using Medical Imaging and Biomechanical Testing in an In-vivo Rat Model

Introduction. The lack of objective parameter to define bone fracture union makes it difficult for orthopedists to properly treat fractures. The Radiographic Union Score for Tibial fractures (RUST) is becoming widespread as an objective means of assessing fracture repair however its accuracy has yet to be validated. Methods. A group of 24 rats underwent standardized femoral osteotomies. At their assigned endpoint, the healing femur was radiographed, scored with RUST and modified RUST, scanned with micro-CT, and tested in torsion. Results. The RUST and modified RUST scores correlate highly with the mineralized callus volume, total callus volume, mineralized to total callus volume ratio, ultimate torque, stiffness, maximum shear strain and torsional strength. RUST showed slightly higher interobserver agreement among reviewers than modified RUST. Conclusion. RUST and modified RUST have strong relationships many with imaging and biomechanical parameters providing evidence of the accuracy of the scores as assessment tools for fracture healing.

Advisor: Schemitsch, Emil H
Comparing UV/Chlorine Advanced Oxidation Efficiency to UV/H2O2 when using Monochromatic UV light

This thesis compares the efficiency of the UV/chlorine and UV/H2O2 advanced oxidation processes for contaminant removal using monochromatic UV light. Previous work reported that UV/chlorine is more efficient than UV/H2O2 for trichloroethylene removal in pure water at approximately pH 5 and below using medium pressure (MP) lamps (Wang et al., 2012), and that it may even be more competitive in the presence of elevated total inorganic carbon (TIC) and total organic carbon (TOC). In this work, a LP kinetics model was adapted from the MP model developed by Wang et al. (2012). The modelled results of sucralose decay were then validated by bench-scale experiments with a collimated beam apparatus. The adapted LP models successfully predicted sucralose decay under most of the experimental conditions, but not at pH 10 for the UV/chlorine process. The reason for the inaccuracy of the UV/chlorine model at pH 10 is not clear, and requires more work.

Keywords: advanced oxidation processes
sucralose
UV/chlorine
UV/H2O2
Advisor: Hofmann, Ron
Andrews, Susan
Variation in Strategies for the Facilitation of Dental Treatment in Pediatric Patients

Background: Pediatric dentists (PD) use a variety of non-pharmacological and pharmacological methods to facilitate the delivery of dental care for children. Aim: To assess current treatment facilitation strategies amongst Canadian PD and to compare these strategies to facilitation strategies of dental anesthesiologists (DA) and pediatric emergency physicians (EP) who also provide care for children requiring dental interventions. Design: An online survey consisting of a series of questions based on the respondentâ s area of expertise was sent to Canadian PD, DA and EP. Results: PD utilized restraint alone to facilitate dental treatment significantly more than DA and EP. Quebec PD were significantly more likely to choose restraint as a preferred dental treatment facilitation strategy. PD graduating from Canadian training programs were significantly more likely to utilize restraint in their practices. Conclusions: PD are more likely than DA and EP to use restraint without pharmacological adjuncts in order to facilitate dental treatment.

Keywords: Pediatric dentistry
Restraint
Sedation
Advisor: Casas, Michael J
The Quality of Dying and Death of Long-term Care Residents

Objective: To determine the quality of dying and death in residents of a long-term care facility. Methods: Primary caregivers (n=79) were recruited 6.4 (+2.20) months after the resident’s death. The quality of dying was assessed using the Quality of Dying and Death (QODD) questionnaire, which yields scores from 0-100 for overall QODD and for subscales of Symptom Control, Death Preparation, Connectedness, and Transcendence. Results: The mean patient age was 87.6 (+8.11) years and 86.1% had dementia. Overall QODD was rated “neither good nor bad” by 75.9% and “good to almost perfect” by 24.1% of caregivers. In a multi-variable model, correlates of overall QODD (R2=0.429) were: palliative care receipt (p=0.015), family satisfaction with care (p=0.001), patient’s cognitive functioning (p=0.230) and presence of caregiver illness/disability (p=0.022). Conclusion: The overall QODD in a long-term care home was intermediate. A good death can be achieved in this setting, especially when palliative care is available.

Keywords: Long-term care
Palliative care
Quality of dying and death
Advisor: Rodin, Gary
Trends in Utilization of a Children's Hospital Emergency Department for Caries-related Complaints

Purpose: To determine trends in caries-related visits to a children’s hospital emergency department and associated costs. Methods: A review of health records of all children who presented to the ED at The Hospital for Sick Children, Toronto, with caries-related complaints from January 1, 2003 to December 31, 2012 was completed. Institutional costs for the episodes of care were calculated using encounter level costing. A Poisson model examined trends over time. A log-linear model examined the impact of sex, age, comorbidity, and socioeconomic status. Results: Over the study period, the numbers of visits for caries-related complaints increased by 48 percent (p=0.001). Characteristics of the children were being male, under 5 years old, low socioeconomic status and no co-morbidity. The mean cost per visit was $575.17 CDN. Conclusions: With an increasing volume and mean visit cost of almost $600 CDN, children’s hospital EDs caries-related visits to children’s hospital EDs are not insignificant.

Keywords: caries
emergency department
Advisor: Casas, Michael J
Barrett, Edward J
A Validated Peripheral Nerve Model for the Simulation of Multicontact Nerve Cuff Recordings

Accurate simulations of peripheral nerve recordings are needed to develop improved neuroprostheses. Previous models of peripheral nerves contained simplifications whose effects have not been tested. We have created an anatomically detailed finite element model of a rat sciatic nerve using MRI imaging, and used it to carry out a sensitivity analysis of relevant parameters. We simulated neural recordings from a multicontact nerve cuff electrode and validated them with in vivo experimental data. We found that varying tissue conductivities had little influence on the simulated recording selectivity of the cuff, as we found high correlations between in vivo and simulated measurements for a wide range of conductivity values. On the other hand, the increased anatomical detail did substantially alter the recording patterns observed. It can be concluded that our model is an improved simulation tool and can be used in the design of neural interfaces.

Advisor: Zariffa, Jose
Selectivity of Neural Activation During Percutaneous Tibial Nerve Stimulation for Overactive Bladder: A Computational Study

Percutaneous tibial nerve stimulation (PTNS) is a minimally-invasive neuromodulation therapy for overactive bladder (OAB) that uses an uninsulated needle electrode to electrically activate the tibial nerve (TN). Discrepancies between clinically applied stimulation amplitudes and those used in recent preclinical animal studies led us to hypothesize that the effect of PTNS involves a secondary neural pathway, the saphenous nerve (SAFN). A computational model was developed and used to investigate the relative activation of the TN and the SAFN during PTNS treatment for varying needle electrode locations, types (uninsulated vs. insulated), and stimulation amplitudes. Significant SAFN activation was found to occur in response to clinical PTNS parameters. Selective TN stimulation was found to be possible via the use of an accurately placed insulated needle electrode. The effect SAFN activation may have on clinical outcomes is not yet understood, however the work presented here along with recent preclinical trials support further investigation of the subject.

Keywords: Neuromodulation
Overactive Bladder
Saphenous Nerve
Tibial Nerve
Advisor: Yoo, Paul B
Investigating the Capacity of Continuous Household Travel Surveys in Replacing Traditional Cross-sectional Surveys

In this thesis, the capacity of continuous surveys in replacing cross-sectional surveys is examined. A flexible framework for both cross-sectional and continuous household travel survey sample size determination is proposed. After that, the state of practice of continuous surveys is closely examined. It is believed that the main advantage of continuous surveys is the availability of data over a continuous spectrum of time. This claim is put to the test by estimating mixed effects models on different levels using the Montreal Continuous Survey data. The use of the mixed effects econometric framework allows for partitioning the variance of the dependent variable to a set of grouping factors, such as time periods and spatial units, enabling the understanding of the underlying causes of variation in travel behavior. The thesis concludes that the temporal variability in trip behavior is only observed when modelling on the regional or modal level.

Keywords: Continuous Surveys
Mixed Effects Models
Origin-Destination Matrices
Sample Size
Advisor: Nurul Habib, Khandker M
In Vitro Analysis of ER Maleate as a Novel Anticancer Agent for Oral Cancer

A high throughput chemical screen identified ER maleate as a potential anticancer agent for oral squamous cell carcinoma (OSCC). ER maleate treatment of OSCC cell lines and patient-derived OSCC cells led to dose-dependent decrease in cell viability, and polo-like kinase 1 (Plk1) and spleen tyrosine kinase (Syk) expression. Overexpression of Plk1 rescued cell viability in drug treated cells. The clinical significance of Plk1, Syk, and programmed-death ligand 1 (PD-L1) as biomarkers was determined in oral dysplasia and OSCC patients. Biomarker risk score was generated for oral dysplasia (n = 120, Hazard Ratio (HR) = 1.11, c-statistic = 0.633, p

Keywords: Biomarkers
Molecular-targeted therapy
Oral Cancer
Pathology
Treatment
Advisor: Ralhan, Ranju
Enhancement of Peripheral Nerve Regeneration with Controlled Release of Glial Cell Line-derived Neurotrophic Factor (GDNF)

Nerve injuries cause severe disability. The present investigational drug delivery strategies for enhancing peripheral nerve regeneration after nerve transection are not yet clinically translatable due to lack of efficiency or biocompatibility. We developed a local delivery system using drug-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) embedded in a fibrin gel. This drug delivery system (DDS) could be applied at the nerve injury site to deliver exogenous glial cell line-derived neurotrophic factor (GDNF) to the regenerating axons. We used our developed DDS to enhance nerve regeneration in clinically applicable models of severe nerve injuries, including cases with delayed nerve repair and with large nerve defects.

Keywords: acellular nerve allograft
biomaterials
drug delivery
glial cell line-derived neurotrophic factor
nerve injury
regenerative medicine
Advisor: Borschel, Gregory H.
Gordon, Tessa
InPRO: Automated Indoor Construction Progress Monitoring Using Unmanned Aerial Vehicles

In this research, an envisioned automated intelligent robotic solution for automated indoor data collection and inspection that employs a series of unmanned aerial vehicles (UAV), entitled â InPROâ , is presented. InPRO consists of four stages, namely: 1) automated path planning; 2) autonomous UAV-based indoor inspection; 3) automated computer vision-based assessment of progress; and, 4) automated updating of 4D building information models (BIM). The works presented in this thesis address the third stage of InPRO. A series of computer vision-based methods that automate the assessment of construction progress using images captured at indoor sites are introduced. The proposed methods employ computer vision and machine learning techniques to detect the components of under-construction indoor partitions. In particular, framing (studs), insulation, electrical outlets, and different states of drywall sheets (installing, plastering, and painting) are automatically detected using digital images. High accuracy rates, real-time performance, and operation without a priori information are indicators of the methodsâ promising performance.

Keywords: automated data collection
computer vision
construction progress monitoring
indoor construction
machine learning
unmanned aerial vehicles
Advisor: McCabe, Brenda