VictorJuiz/thesis huggingface dataset:
Optimization of Dose Schedules in Radiotherapy

Purpose: Fractionation in radiotherapy is the scheduled break up of a total treatment dose into individual doses. The goal of this thesis is to seek a mathematically optimal dose schedule, in the context of a biological tissue dose-response model, the linear-quadratic function. Methods: We examined the mathematical properties of the fractionation problem in the context of an arbitrary number of sensitive-structure constraints and determined the properties of the optima. We also implemented a numerical search technique to solve the problem. Results: On the theoretical side, we confirmed and extended the results in the literature. We showed the optima always occur at the intersection of two or more constraints or at the equal dose per fraction point (or at any arbitrary feasible point on the boundary, which includes the two points just mentioned). On the numerical side, we successfully implemented a simulated annealing algorithm to our problem.

Keywords: Fractionation
Radiotherapy
Advisor: Aleman, Dionne
Structure-based Development of Vitamin B5 Analogs and Evaluation of their Antimicrobial Efficiency against S. aureus and E. coli

The objective of this study is to evaluate pseudo-substrates of pantothenate kinase (PanK) for the therapeutic treatment of multidrug resistant bacterial infections of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Pantothenate (Pan) analogs, including N- pentylpantothenamide (N5-Pan) and N-heptylpantothenamide (N7-Pan), hamper bacterial growth by utilizing the PanK enzymes, which normally catalyze the rate determining step of the Coenzyme A biosynthetic pathway. Here we report the structures of SaPanK, Human PanK3 and EcPanK complexed with N7-Pan or N5-Pan, all of which have provided the opportunity to investigate the structural differences of bacterial and human Pan binding sites. The MTT assay showed these analogs to exhibit no apparent cytotoxicity against Human A549 lung adenocarcinoma cells, human HepG2 hepatoma cells and human umbilical vein endothelial cells (HUVEC). The presented structural differences have the potential for aiding the development of species-specific antimicrobial compounds with minimal effects on human cells.

Keywords: Structural biology
N-substituted Pan analogs
Structure-based development
Antimicrobial compounds
Pantothenate
Advisor: Park, Hee-Won
Grant, Denis M.
Interaction of Hsp104 with Hsp70: Insight into the Mechanism of Protein Disaggregation

Hsp104 and ClpB are hexameric ATPases that resolubilize aggregated proteins in collaboration with the Hsp70 chaperone system. Hsp104/ClpB functionally interact only with their respective Hsp70 system and this specificity is mapped to the Hsp104/ClpB coiled-coil domain (CCD). We hypothesize that the interaction between Hsp70 and Hsp104/ClpB CCD stimulates nucleotide exchange and release of substrate from Hsp70. In the current study, the CCDs of E. coli ClpB and S. cerevisiae Hsp104 have been purified. Isolated domains are monomeric and well folded. They inhibit refolding of aggregated firefly luciferase in a species-specific manner. We found that the ATPase activity of E. coli DnaK is stimulated at low concentrations of the E. coli ClpB CCD but not by yeast Hsp104 CCD. However, in another bacterial system (Thermus thermophilus) we found that the ClpB CCD inhibits The ATPase activity of DnaK suggesting that the interaction may have different consequences in distinct chaperone networks.

Keywords: Hsp104
Molecular Chaperones
Heat Shock Protein
Hsp70
Advisor: Glover, John R.
Examination of the Association between Voluntary Accreditation and Resident Safety in Ontario Long Term Care Homes

Objective: determine whether accreditation through Accreditation Canada is associated with more favorable resident safety in Ontario LTC homes and which facility characteristics are predictive of accreditation. Methods: logistic regression was used to determine predictors of accreditation. To examine the association between accreditation and safety, safety was operationalized as five MDS-RAI quality indicators: prevalence of falls, restraints, catheters, pressure ulcers, and infections. Separate multivariable models were developed for each indicator. Results: the odds of accreditation were approximately six times smaller for municipal (p < 0.001) and non-profit facilities (p < 0.001) relative to for-profits; three times greater for chains relative to non-chains (p < 0.001); and twice as large for urban relative to rural facilities (p = 0.04). Of the five quality indicators examined, only one (falls) was associated with accreditation. After adjusting for confounders, accredited homes were estimated to have 8% lower fall rates than non-accredited homes (p = 0.01).

Keywords: accreditation
long term care
patient safety
rurality
chain membership
ownership
falls
quality of care
quality improvement
Advisor: Wagner, Laura
Platelet Activating Factors and Depressive Symptoms in Coronary Artery Disease Patients

Depression is highly prevalent in coronary artery disease (CAD) and confers an increased risk of morbidity and mortality, yet mechanisms are unknown. Platelet activating factor (PAF) lipids are associated not only with CAD but also with inflammation, oxidative/nitrosative stress, vascular endothelial dysfunction and platelet reactivity which are proposed etiopathological mechanisms for depression. This study investigated the relationship between PAF species and depressive symptoms in 20 CAD patients. Plasma analyses were performed using electrospray ionization mass spectrometry (precursor ion scan). Primary analysis revealed no association between the potent pro-inflammatory PAF PC(O-16:0/2:0) and depressive symptoms measured by the Hamilton Depression Rating Scale [HAM-D] (F=0.405, p=0.533) or Beck Depression Inventory [BDI]-II (F=0.120, p=0.733) in a linear regression. Exploratory analyses revealed potential associations between greater PC(O-18:1/0:0) and greater HAM-D score and greater PC(O-22:6/2:0) concentrations with a greater BDI-II score. This study suggests that specific PAFs might be biomarkers for depressive symptoms in CAD patients.

Keywords: depression
coronary artery disease
platelet activating factors
lipidomics
Advisor: Lanctôt, Krista
Performance-based Design of RC Coupled Wall High-rise Buildings with Viscoelastic Coupling Dampers

A new damping technology, the Viscoelastic Coupling Damper (VCD), has been developed at the University of Toronto for reinforced concrete (RC) coupled wall high-rise buildings. These dampers are introduced in place of coupling beams to provide distributed supplemental damping in all lateral modes of vibration. This thesis presents an analytical investigation of the application of VCDs in a high-rise case study building located in a region of high seismicity. A parametric study has been conducted to determine the optimal number and placement of the dampers to achieve enhanced seismic performance without compromising the wind response of the structure. Nonlinear time history analyses have been carried out in order to compare the seismic performance of a conventional coupled wall building to alternative designs incorporating VCDs. Results highlight the improved performance of VCDs over RC coupling beams at all levels of seismic hazard. A design procedure for seismic-critical buildings is proposed.

Keywords: Seismic Engineering
Supplemental Damping
High-Rise Design
Viscoelastic Coupling Damper
Advisor: Christopoulos, Constantin
An In silico Investigation of the Metabolic Capabilities of Anaeromyxobacter Dehalogenans and Field-scale Applications

In recent years, uranium pollution in the environment has been recognized as a serious threat, and novel in situ microbial bioremediation strategies have been incorporated into field-scale contaminated sites. The Oak Ridge Integrated Field-scale Subsurface Research Challenge (IFC) site is one of the largest uranium contaminated areas in the United States, and a literature review has revealed the potential of uranium reduction by dominant Anaeromyxobacter dehalogenans species that respire during bioremediation. A genome-scale model of A. dehalogenans, a unique microbe with diverse metabolic capabilities that thrives in the natural environment, has been developed, and applied to an in silico field-scale computational setting for evaluation of the biotic uranium reduction in the Oak Ridge IFC site. The metabolic model of A. dehalogenans was integrated into an expanded microbial community framework for the prediction of chemical profiles, and subsequent scenario evaluation of in situ measured data.

Keywords: Environmental Engineering
Microbial Models
Optimization
Genome Sequences
Metabolism
Parameter Fitting
Advisor: Mahadevan, Radhakrishnan
Automated Debugging Framework for High-level Synthesis

This thesis proposes a automated test case generation technique for the aim of verifying/debugging High-level synthesis (HLS) tools. The work in this thesis builds a framework that automatically generates random programs with user specified features. These programs are used to verify the correctness of the compiled hardware by comparing the hardware simulation results with the software execution results. This way, users can have a large number of benchmarks to test their algorithms for HLS without having to manually develop test programs. The tool also provides additional ways of analyzing performance of HLS tools. Rather than being a replacement, this technique should serve as a useful complement to existing manually constructed test suites. Together, they can provide more comprehensive verification and analysis for HLS tools.

Keywords: Debug
High-level Synthesis
Advisor: Stephen, Brown
Effects of Biophysical Parameters in Radiosensitizing Prostate Tumours with Ultrasound-stimulated Microbubbles

We demonstrate here that ultrasound-stimulated microbubbles can lead to enhanced cell death within tumors when combined with radiation. The aim of this study was to investigate different ultrasound parameters in conjunction with different concentrations of microbubbles with regards to this effect. Prostate xenograft tumors in Severe Combined Immunodeficient mice were subjected to ultrasound treatment that involved various peak negative pressures (250 kPa, 570 kPa, and 750 kPa), microbubble concentrations (8 µL/kg, 80 µL/kg, and 1000 µL/kg), and different radiation doses (0 Gy, 2 Gy, and 8 Gy). Twenty-four hours after treatment, tumors were excised and assessed for cell death. Histological analyses demonstrated that increases in radiation dose, microbubble concentration, and ultrasound pressure promoted apoptotic cell death and cellular disruption within tumors. Comparable increases in ceramide, a cell death mediator, were identified using immunohistochemistry. We also demonstrate that clinically-utilized microbubble concentrations combined with ultrasound can induce an enhancement in cell death.

Keywords: Ultrasound
Microbubbles
Radiosensitization
Prostate Cancer
Advisor: Czarnota, Gregory J.
Expanding the Role of Electron Cryomicroscopy in Structural Analysis of Asymmetrical Protein Complexes

Single particle electron cryomicroscopy (cryo-EM) is a rapidly developing structural biology technique for the study of macromolecular protein complexes. Presently, cryo-EM fills an important niche by facilitating acquisition of 3-D structures of protein complexes not amenable to structure determination by other techniques. Expansion of cryo-EM beyond this niche requires continued improvement in the types of specimens that can be studied as well as the final resolutions achieved. Two studies were undertaken to address these issues. The first examined resolution limitations by quantifying the effect of beam-induced motion in images of beam-sensitive paraffin crystals. The second explored the possibility of using cryo-EM to study the interaction of small effector proteins with a large multi-protein complex, V-ATPase. The results of these studies exposed the fact that fundamental aspects of the imaging and specimen preparation processes remain poorly understood and must be addressed to facilitate future improvements in cryo-EM structure determination.

Keywords: Structural Biology
V-ATPase
Cryo-EM
Protein Purification
Advisor: Rubinstein, John
Mechanisms Underlying Exercise-induced Atrial Fibrillation

Atrial fibrillation (AF) is the most common supraventricular tachyarrhythmia that can present without cardiovascular disease (lone AF). Frequent high-intensity endurance exercise is a risk factor for lone AF, and the pathophysiology of AF induced by intense endurance exercise is unknown. We found that after 6 weeks of intense swimming and running, mice were far more susceptible to AF, but not ventricular arrhythmias. Exercise induced atrial fibrosis, inflammation and slowed conduction without detectible changes in ventricles. Since AF is associated with stretch and since a tumor necrosis factor-α (TNFα) is a mechanosensitive inflammatory factor, mice were treated with the TNFα inhibitor etanercept. Etanercept treatment blocked inflammation, fibrosis, and AF vulnerability in the exercised mice. Consistent with these findings, we found that exercise caused large elevations in atrial pressures. Our findings support the conclusion that mechanical loading of atria during exercise induces TNFα release, leading to structural remodeling and enhanced AF vulnerability.

Keywords: atrial fibrillation
athletes
exercise
Advisor: Backx, Peter
The Effect of Light Emitting Diode (LED) on the Healing of Endosseous Intraoral Implants

Purpose: To assess the role of photobiomodulation on bone healing around dental implants. Materials and Methods: 72 patients requiring 76 dental implants were included. All patients received dental implant(s.) Treatment group had also to apply LED to surgical sites. ISQ of implants was measured following implant placement and at 1, 2, 4, and 8 weeks postoperatively. Radiographs were taken after insertion and at 8 weeks postoperatively. Data were analyzed using SPSS and Stata. Results: Treatment group showed an increase in ISQ values over the follow-up period compared to control (p < 0.001). Primary effect of LED on ISQ values was seen over the first 2 weeks (p < 0.05). Treatment group showed less decrease in crestal bone height at 8 weeks (p = 0.05). Conclusions: Data suggest that photobiomodulation will allow for a continuous increase in ISQ value and may reduce crestal bone resorption following implant placement.

Keywords: LED
OsseoPulse
Osstell
photobiomodulation
Implant stability
ISQ
crestal bone
RCT
Advisor: Clokie, Cameron
A Patient Opinion Survey to Identify Perceived Barriers to the Introduction of a Screening Program for Depression in a Hemodialysis Population

Patient-related barriers may reduce the effectiveness of screening for depression. This study aimed to explore perceived barriers to participation in a Screening Program for Depression by hemodialysis patients. In a cross-sectional study of hemodialysis patients, the Perceived Barriers to Psychological Treatment questionnaire was used to measure barriers to the Screening Program. Of 160 participants, 73.1% perceived at least one barrier (95% CI, 66.2% to 80.0%). The most common barriers were concerns about the side effects of antidepressant medications (40%), concerns about having more medications (32%), feeling that the problem is not severe enough (23%), and perceiving no risk of depression (23%). A high depression score was an independent predictor of barriers related to perceiving no benefit of the Screening Program and psychological, social, and practical barriers. We believe that patient-related barriers need to be addressed before implementing any case identification and treatment program for depression.

Keywords: Depression
Barriers
Screening
Hemodialysis
Advisor: Logan, Alexander
Magnetic Attitude Control of Microsatellites In Geocentric Orbits

Attitude control of spacecraft in low Earth orbits can be achieved by exploiting the torques generated by the geomagnetic field. Recent research has demonstrated that attitude stability of a spacecraft is possible using a linear combination of Euler parameters and angular velocity feedback. The research carried out in this thesis implements a hybrid scheme consisting of magnetic control using on-board dipole moments and a three-axis actuation scheme such as reaction wheels and thrusters. A stability analysis is formulated and analyzed using Floquet and Lyapunov stability theorems.

Keywords: hybrid attitude control
magnetic attitudde control
Advisor: Damaren, Christopher John
Parallel Sorting on the Heterogeneous AMD Fusion Accelerated Processing Unit

We explore efficient parallel radix sort for the AMD Fusion Accelerated Processing Unit (APU). Two challenges arise: efficiently partitioning data between the CPU and GPU and the allocation of data in memory regions. Our coarse-grained implementation utilizes both the GPU and CPU by sharing data at the begining and end of the sort. Our fine-grained implementation utilizes the APU’s integrated memory system to share data throughout the sort. Both these implementations outperform the current state of the art GPU radix sort from NVIDIA. We therefore demonstrate that the CPU can be efficiently used to speed up radix sort on the APU. Our fine-grained implementation slightly outperforms our coarse-grained implementation. This demonstrates the benefit of the APU’s integrated architecture. This performance benefit is hindered by limitations in the APU’s architecture and programming model. We believe that the performance benefits will increase once these limitations are addressed in future generations of the APU.

Keywords: Parallel sorting
Radix sort
Heterogeneous computing
GPU
GPGPU
AMD Fusion
Llano
APU
Accelerated Processing Unit
OpenCL
Fusion Sort
GPU computing
Advisor: Abdelrahman, Tarek S.
Nasometric Measurement and the Classification of Resonance Disorders: Equipment Evaluation and a Tentative Classification System

Resonance disorders due to cleft palate and other aetiologies are frequently assessed in conjunction with nasometry. The most commonly used instrument is the Nasometer by KayPentax. A new model Nasometer 6450 was compared to an older model 6200 using both synthetic and speech stimuli. There was a particular focus on test-retest variability of the instrument. The Nasometers were found to yield comparable results. The inter session test-retest variability ranged from six to eight points, depending on the stimulus. The Nasometer 6450 was then used to collect nasalance scores of simulated resonance disorders. A discriminant analysis was applied to these scores. The resultant formulas were moderately successful in predicting perceived resonance when applied to pre-existing data sets.

Keywords: Resonance Disorders
Nasometry
Nasalance
Advisor: Tim, Bressmann
Ground Segment Software Design and Development for Nanosatellite Space Missions

For spacecraft development, realizing strong supporting ground segment software is as important as designing the actual hardware component of the spacecraft. This thesis describes the author’s contributions to the ground segment software design and development for nanosatellite space missions at the UTIAS Space Flight Laboratory. Particular emphasis is given to the ground segment software for the CanX-3 and CanX-4/-5 missions. For the CanX-3 mission, several software applications are explored, specifically ground control software for the payload on-board computer and star tracker, and mission planning software. For the CanX-4/-5 mission, its mission monitor and control software, and whole orbit data parser are discussed. For each software application, design considerations and decisions made during the development are explained. Furthermore, detailed discussions on their architectural and graphical user interface design and implementation are presented.

Keywords: nanosatellite
ground segment
ground software
ground station
CanX-3
CanX-4/-5
Advisor: Zee, Robert E.
More Work, Less Play: Power, Household Work and Leisure Expereinces of Chinese Immigrant Women in Canada

This thesis focuses on Chinese immigrant women’s experiences of household work and leisure in Canada. Socialist feminist perspective is used for an analysis of in-depth conversations with ten Chinese immigrant women with children. Results show that Chinese immigrant women experienced a significant increase of household work and a dramatic decrease on leisure pursuits after immigration and/or the birth of their children, implying that gender inequalities are reproduced and reinforced. Chinese immigrant women encounter and negotiate forms of tension resulted from the striking difference of being in China and being in Canada, their change in social status and their changed gender status. This thesis may contribute background knowledge for the practitioners in recreational programs and social works specialized in immigrant settlement services. Future research could be the motives for immigration, the actual experiences of immigration; a comparative study between Chinese immigrant women and women of other ethnicities is also suggested.

Keywords: immigrant, woman
lesiure, household work
Advisor: Donnelly, Peter
Control of Time-dependent Transverse Cracking in Reinforced Concrete Bridge Decks

Transverse cracking in bridge decks has been found to be a rising problem for slab-on-girder bridges. In response to the concern, this research examined the influence of structural parameters and developed an analytical truss model, based on finite element modelling responses, for predicting the condition of long term cracking. Crack widths predicted using the truss model are very similar to that measured in a recent survey of Ontario highway overpass bridges. The approach to control cracking in deck slabs through structural design decisions enables engineers to provide high cracking resistance at locations of the bridge deck that are most likely to crack. Recommendations were made, based on the findings obtained from two sets of parametric studies, to help ensure transverse cracking in bridge decks is properly controlled for typical slab-on-girder bridges designed using the empirical design method specified in the current Canadian Highway Bridge Design Code.

Keywords: bridge
concrete
deck slab
CPCI
shrinkage
long term effect
cracking
crack width
Advisor: Gauvreau, Douglas Paul
Effect of Methylphenidate on Attention in Apathetic Alzheimer’s Disease Patients and Association with Apathy Changes in a Randomized, Placebo-controlled Trial

Emerging evidence supports the use of methylphenidate (MPH) for the treatment of apathy in Alzheimer’s disease (AD). This study aimed to investigate the additional effects of MPH on attention in an AD sample and the relationship between apathy and attention. AD patients enrolled in a randomized, double-blind placebo-controlled study to examine the safety and efficacy of MPH (10mg PO twice daily) for the treatment of apathetic symptoms were tested on attention and apathy every 2 weeks for 6 weeks. A mixed effects linear regression revealed attention change scores (endpoint - baseline) over time favouring MPH (δ=1.01, p=0.03), though there were no significant associations between apathy and attention change scores (r=-0.08, p=0.54). These results suggest that while MPH can improve both apathy and attention, the effects appear independent in this patient population. This study provides insight into the different effects MPH can produce in a heterogeneous disease such as AD.

Keywords: Alzheimer's disease
apathy
attention
methylphenidate
Advisor: Lanctôt, Krista