VictorJuiz/thesis huggingface dataset:
High Frequency Shear Wave Imaging: A Feasibility Study In Tissue Mimicking Gelatin Phantoms

Shear wave (SW) imaging is an ultrasound elastogrpahy technique for estimating the elastic properties of biological tissues. Increasing the frequency would improve both the confinement of the radiation force generating the shear wave, and the imaging spatial resolution. The objectives of the study were to realize a simple high frequency (HF) system for the generation and detection of SW propagation and to implement this system to develop and characterize tissue-mimicking gelatin phantoms (TMGP) for HF SWI with elastic properties in the range of those encountered in biological tissue. A 5 MHz and 10 MHz focused transducer were used to induced SW’s in TMGP ranging from 4% to 12% gelatin with 3% silica for scattering and a 25 MHz single-element focused transducer recorded pulse-echo signals in order to capture the SW. The shear wave speeds in the TMGP were found to range linearly from 1.59-4.59 m/s in the 4% to 12% gelatin samples.

Keywords: Shear Waves
Elastography
Ultrasound
Elasticity
Tissue Mimicking Phantoms
Advisor: Foster, Stuart
Targeted Deletion of Fgl2 Enhances Anti-viral T Cell Responses and Mediates Viral Clearance in a Murine Model of Chronic Viral Infection

Chronic viral infection is a significant burden on healthcare systems worldwide. Robust anti-viral immune responses are essential for viral clearance. Persistent viruses use a variety of mechanisms to evade immune surveillance including the upregulation of host immunesuppressive factors. Secreted fibrinogen-like protein 2 (FGL2) has been identified as an inhibitory effector molecule in suppressing immune responses in patients with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) disease. In a murine model of chronic infection caused by Lymphocytic choriomeningitis virus (LCMV) clone 13, we demonstrate that mice deficient in Fgl2 have increased numbers of mature antigen-presenting cells (APC), improved virus-specific cytotoxic T cell immunity and enhanced viral clearance when compared to wild-type mice. These results highlight the importance of the FGL2 inhibitory pathway in immune evasion and provide a rationale to investigate the effects of blocking FGL2 as a novel immune therapeutic in patients suffering from persistent infections.

Keywords: Chronic viral infection
FGL2
LCMV clone 13
viral clearance
Advisor: Levy, Gary
The Imprinting Effects of Mechanical Environment on the Fibrogenesis of Mesenchymal Stem Cells

When routine repair mechanisms fail to regenerate severe burn wounds, mesenchymal stem cell therapy is considered. However, engrafted mesenchymal stem cells are prone to become myofibroblasts when exposed to high mechanical tension and pro-fibrotic cytokines in the wound microenvironment. Myofibroblast activity increases wound stiffness and activates healthy precursor cells into destructive phenotype, resulting in pathological remodelling and hypertrophic scarring. Using soft silicone substrates with near-physiological stiffness, I tested the hypothesis that myofibroblast characteristics acquired by mesenchymal stem cells in cell culture are preserved by microRNA modifications typical for fibrosis and demonstrated that priming mesenchymal stem cells on soft substrates protect them from subsequent activation and that the mechanically propagated myofibroblast memory is mediated by miR-21. This study aims to demonstrate that suppressing myofibroblast activation will maximize and prolong the beneficial regenerative effects of mesenchymal stem cells while terminating harmful and excessive tissue remodelling characteristic for fibrosis upon engraftment.

Keywords: Biomaterials
Regeneration
Advisor: Hinz, Boris
The Mechanism of a BMP-Driven Mesenchymal-to-Epithelial Transition in the Reprogramming of Induced Pluripotent Stem Cells

Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by the ectopic expression of defined factors. iPSCs hold great promise for pharmaceutical screening and regenerative medicine but the mechanism of reprogramming is not well understood. This work examines a component process of reprogramming that is the mesenchymal-to-epithelial transition (MET), an important step in the generation of iPS cells. In this thesis I demonstrate a connection between BMP signaling and the reprogramming factor Klf4 in the activation of the MET expression program. Using ChIP-Seq I mapped the binding of Klf4 and BMP Smads across the genome and linked their co-binding to a MET expression program determined by RNA-Seq. My work uncovers a thus-far unreported interaction between Klf4 and BMP signaling in cellular epithelialization that can directly improve the technical methods of reprogramming and have important implications for the induction of epithelial tissues in general.

Keywords: iPSC
Mesenchymal-to-Epithelial Transition
MET
BMP
RNA-Seq
ChIP-Seq
Klf4
Smad1,5,8
Advisor: Wrana, Jeffrey
Characterization and Germination of 13C Labeled Seeds by Comprehensive Multiphase NMR Spectroscopy

Seeds are complex entities, within which the intricate processes of germination and early growth occur. We describe here a novel technique of our group in 2012 which is capable of simultaneous solution-, gel-, and solid-state analysis. CMP-NMR was applied to intact seeds where all components are studied and differentiated in situ. Characterization, germination and early growth of seeds were studied by variety of 1D and 2D 1H and 13C CMP-NMR experiments. Various metabolites, lipids, carbohydrate biopolymers and structural carbohydrates were first identified and further studied in germination and early growth stages. This research demonstrates the utility of CMP- NMR as a powerful tool to better understand the composition of seeds and processes underlying early seed growth.

Keywords: multiphase
seed
NMR spectroscopy
intact sample
germination
CMP-NMR
Advisor: Simpson, Andre
QP Partitioning for Radiationless Transitions

This work presents a new implementation of the QP algorithm, a computer method to diagonalize the extremely large matrices arising in multimode vibronic problems. Benchmark calculations are included, showing the accuracy of the program. The QP algorithm is extended to treat multiple electronic surfaces for competitive control and this is demonstrated with an Hamiltonian including three electronic states, a model of the benzene radical cation. Finally, the evolution of zeroth-order states in a simple two electronic states, two dimensional model with a conical intersection is explored, towards building a time-dependent view of overlapping resonances coherent control.

Keywords: overlapping resonances
coherent control
conical intersection
pyrazine
benzene radical cation
matrix diagonalization
Wavepacket
Intramolecular
Radiationless
vibronic
Advisor: Brumer, Paul
Latitudinal Gradients in Climatic Niche Evolution

Either tropical niche divergence or tropical niche conservatism could drive the latitudinal diversity gradient. Greater niche divergence in the tropics could accelerate reproductive isolation leading to more rapid species formation. Alternatively, latitudinal asymmetry in niche conservatism, whereby tropical species are more conserved than high latitude species, could promote more dispersal in to than out of the tropics, leading to greater tropical richness. Here I test whether rates of climatic niche evolution vary across the latitudinal gradient for 164 closely related pairs of species. Using the evolutionary ages at which sister species diverge, and the niche divergence between them, I applied Brownian motion models to test whether rates of climatic niche evolution varied with latitude. My results indicate that climatic niche conservatism is strongest in the tropics. This suggests that the latitudinal diversity gradient is driven by the inability of tropical to adapt to temperate climates and colonize non-tropical latitudes.

Keywords: climatic niche
latitudinal gradients
species richness
New Wolrd birds
New World mammals
evolutionary rates
Advisor: Weir, Jason
Designing and Evaluating Technologies for Virtual Reality Therapies that Promote Neuroplasticity

Increasingly, virtual reality therapy (VRT) technologies are being used to augment pediatric rehabilitation. The mechanisms underlying success/failure of VRTs are not well understood. This thesis proposed an innovative 3-phase framework for evaluating VRT technologies with respect to neuroplasticity based on results of a scoping review of 21 studies. A case study was undertaken to demonstrate use of the framework to design and evaluate ‘Musical Steps’, a VRT technology aimed at promoting heel contact in toe-walking children. 5 therapists and 4 children were engaged in this study. The system accurately detected 88%(SD=7%) of heel contacts and was rated positively in usability testing (phase 1). Feasibility studies indicated that, while enjoyable, children did not understand the feedback provided and hence, heel contact was not increased (phase 2). These findings will direct future reiterations prior to evaluating clinical impact (phase 3). The proposed framework may enhance design and translation of therapeutically relevant VRTs.

Keywords: Pediatric rehabilitation
Motor learning
Virtual reality
Gait therapy
Rehabilitation engineering
Neuroplasticity
Technology evaluation
Evaluation methods
Augmented reality
Toe-walking
Equinus gait
Music therapy
Biofeedback
Auditory cues
Advisor: Biddiss, Elaine
Long-term Outcomes of Operatively and Non-operatively Treated Spina Bifida Scoliosis

Background The purpose of this study was to evaluate outcomes in Spina Bifida Cystica adults, treated non-operatively or operatively for scoliosis during childhood. Methods Patients with SBC scoliosis (minimum Cobb angle >50 degrees) treated at the Hospital for Sick Children or the Children’s Hospital of Eastern Ontario (1991-2007 inclusive) were recruited. In addition to clinical and radiological assessments, health related quality of life (HRQOL) outcomes included the: a) Spina Bifida Spine Questionnaire (SBSQ) and b) Medical Outcomes Study-36 Item Short Form Health Survey (SF-36). Results The operative and non-operative patients were statistically similar at baseline on the following variables: a) age, b) sex, c) living situation, d) ambulation, and e) neurological motor level. At an average follow-up of 14.1+/-4.3 years, groups were statistically similar with respect to: a) SF-36 and b) SBSQ scores. Conclusion Spinal fusion in SBC scoliosis corrected coronal deformity and stopped progression, but had no overall effect on HRQOL.

Keywords: Spina Bifida
Scoliosis
Advisor: Wright, James
Searching for Spin Crossover in Fe(bpy)3(PF6)2 using Femtosecond Electron Diffraction and Ultrafast Transient Absorption

Femtosecond electron diffraction experiments were performed on solid state iron(II) tris(2,2'-bipyridine) bis(hexafluorophosphate). The cation is known to undergo a spin crossover process when solvated in water and irradiated with 400 nm coherent light which results in a transition from a low spin to high spin state within a picosecond which is accompanied by a uniform 0.2 Å Fe-N bond elongation. A femtosecond diffraction experiment was performed on the solid sample and was unable to find evidence of a fast spin crossover transition. Suspecting this may be due to limitations of the apparatus, an ultrafast transient absorption experiment was performed. Emulating the liquid study by Gawelda et al, the pump probe experiment found evidence of spin crossover in the solid state sample. This result awaits verification by an improved transient absorption apparatus and has inspired efforts to perform an improved femtosecond electron diffraction experiment.

Keywords: spin crossover
femtosecond electron diffraction
pump probe
ultrafast transient absorption
spectroscopy
electron diffraction
Fe(bpy)3(PF6)2
iron(II) complex
diffraction
Advisor: Miller, R.J. Dwayne
Getting up to Speed: Understanding the Factors Associated with Post-stroke Gait Velocity

The factors that influence gait velocity post-stroke are not clearly understood. This thesis sought to uncover the factors associated with gait velocity, particularly those related to maximum velocity. The first of two studies investigated the associations between physical factors and preferred and maximum gait velocity. Analysis revealed that individuals with stroke were able to increase gait velocity from preferred and that this increase, along with the achieved velocity, were related to functional balance. The second study characterized the strategy individuals used to increase gait velocity, and compared between the stroke and healthy population. It also probed the relationships between cadence, step length, strategy, and post-stroke impairment. This study demonstrated that individuals with stroke rely more on cadence than step length to increase gait velocity. These results revealed the role of balance control on limiting gait velocity and the need for specific measures of impairment in research to direct clinical practice.

Keywords: Stroke
Gait
Velocity
Balance
Rehabilitation
Advisor: McIlroy, William
Mochizuki, George
Implementing a Cognitive Behavioral Skills Program for Anxious Youth: A Knowledge Translation Project

Cognitive Behavioural Therapy (CBT) is an underutilized evidence-based treatment for Anxiety Disorders. Increasing effective knowledge translation and implementation of CBT has significant public health implications. This study sought to increase the use of CBT by providing a 20-week-group-supervision program to Northern Ontario. Therapist measures of CBT knowledge competence were collected pre and post training, and treatment outcome measures were obtained by child and parent report. Clients in Northern Ontario were older (M=11.6years, Toronto M=10.0 years), were more likely on medication, and more likely to have a comorbid diagnosis than clients from an existing data-set in Toronto, Ontario. The training program was successful in increasing CBT knowledge competence and decreasing client anxiety in both locations, with greater improvements in self-reported anxiety in the Northern Ontario group. Therapist CBT knowledge competence was predictive of client symptom change as reported by parent but not child. Two therapist variables were found to be moderators.

Keywords: Cognitive Behavioral Therapy
Rural
Supervision
Knowledge Translation
Advisor: Manassis, Katharina
The History of Conscientious Objection and the Normalization of Universal Male Conscription in South Korean Society

This thesis traces the history of Conscientious Objection and draft evasion from the introduction of the Universal Male Conscription system in 1949 to the end of the authoritarian dictatorship period in 1993. I especially focus on the persecution and stigmatization of religious Conscientious Objector groups such as the South Korean Jehovah’s Witnesses and the Seventh-day Adventists. The negative labeling of these Conscientious Objectors as social deviants is part of an initiative led by the South Korean state to solidify Universal Male Conscription as a social norm. This process was supported by the implementation of a national surveillance system as well as the intensification of a nation-wide crackdown on draft evasion, which was viewed indifferently from Conscientious Objection. Thus, this project reveals the ostracization of Conscientious Objection as well as the normalization of Universal Male Conscription as an interconnected issue that came to be perpetuated throughout South Korean History.

Keywords: Conscientious Objection
Jehovah's Witnesses
Militarization
Conscription
Draft Evasion
South Korea
Advisor: Schmid, Andre
Cell Orientation Control System Using A Rotating Electric Field

The objective of this project is to design a cell orientation control system using a rotating electric field. In particular, the system utilizes two electrostatic phenomena known as electrophoresis and electro-rotation. The device used for creating the electric field was designed and fabricated using the MEMS fabrication technique. The cell orientation control system also includes a vision tracking system that senses the orientation of the cell and a PID controller. Overall, the system is able to control the orientation of the cell with zero steady state error. The objective of this project has been met.

Keywords: control
robotics
cell rotation
surgery
automation
Advisor: Mills, James
The Role of miR-605 and its Variant in Li-Fraumeni Syndrome

Li-Fraumeni Syndrome (LFS) is a rare cancer predisposition syndrome, typically involving germline mutations in the TP53 gene. Despite the high penetrance of TP53 mutations, LFS patients display striking phenotypic differences, suggesting the presence of secondary risk loci. To date, all genetic modifiers in LFS have been shown to map to either TP53 or its principal negative regulator, Mdm2. Given this strong association, we set out to interrogate the contribution of a recently-described miRNA regulator of the p53-MDM2 loop, called miR-605. We hypothesized that, if functional, the miR-605 gene and its variant (rs2043556) could impact cancer risk in TP53 mutation carriers. Consistent with this proposition, the variant allele of miR-605 was associated with a significant acceleration in tumor onset and caused a decrease in the processing efficiency of its host miRNA. We also demonstrate that miR-605 overexpression activates the MAPK pathway and leads to tumor suppression in TP53 mutant cell lines.

Keywords: MicroRNA
Li-Fraumeni Syndrome
p53
Single Nucleotide Polymorphism
Advisor: David, Malkin
Biochemical Investigation into the HNH Motif of HK97 gp74

Bacteriophages are viruses that infect bacteria. This thesis describes studies of gp74 from the bacteriophage HK97, which functions as an HNH endonuclease. HNH endonucleases are DNA digestion proteins characterized by two highly conserved His residues and an Asn residue. Like other HNH endonucleases, the activity of gp74 is dependent on binding of divalent metal ions to the HNH motif. Current work focused on confirming the identity of conserved HNH motif residues of gp74. We hypothesized the catalytic His residue is H43, the structural Asn residue is N73, and that H82 is involved in metal–binding. Additional residues in the ββα–fold, such as D42, may also bind the metal. Our bound metal analysis and the sequence of gp74 also suggest the presence of a Zn2+–finger motif. Mutations of D42 and H82 decrease the activity of gp74, without affecting the structure. These studies advance our understanding of the gp74 activity.

Keywords: gp74
HNH endonuclease
bacteriophage
HK97 gp74
lamba-like bacteriophages
Advisor: Kanelis, Voula
Craniosynostosis, Fibroblast Growth Factor Receptors and Gastrointestinal Malformations – A Possible Link

Syndromic craniosynostosis is most commonly associated with mutations in Fibroblast Growth Factor Receptor genes (FGFR)-1, 2 and 3. Clinical and animal reports suggest a link between FGFR-associated craniosynostosis and defects in the gastrointestinal tract (GIT). Objective: to determine whether GIT malformations occur more frequently in the craniosynostosis population with a known FGFR mutation when compared to the general population. Methods: A retrospective chart review of patients diagnosed with Crouzon, Pfeiffer or Apert syndromes between 1990 and 2011 was performed at the Hospital for Sick Children in Toronto. Thirty-two charts meeting inclusion criteria were analyzed for any history of GIT abnormalities. Results: Three out of 32 patients had documented intestinal/bowel malrotations while 7 had gastroesophageal reflux disease. All patients had documented FGFR2 mutations, a finding in line with previous studies and published case reports. Conclusions: Results suggest an association between FGFR-associated craniosynostosis and GIT malformations.

Keywords: Craniosynostosis
FGFR
fibroblastic growth factor receptor
Gastrointestinal tract
gastrointestinal malformation
gastrointestinal malrotation
GIT
Apert
Pfeiffer
Crouzon
GERD
Advisor: Gong, Siew-Ging
Bowdin, Sarah C
Help-seeking and use of Workplace Services for Emotional Needs among Community Residential Staff who Support Adults with Intellectual Disabilities and Aggressive Behaviour

Community workers supporting adults with intellectual disability get a lot of positive impact from their work. However, staff are also required to deal with challenges such as aggressive behaviours which can be associated with burnout. This thesis used a cross-sectional mixed methods design consisting of survey data analysis and qualitative interviews. The study aims were to examine staff report of emotional difficulties related to working with aggressive behaviours and use of available workplace resources. Staff frequently reported experiencing emotional difficulties; however use of workplace resources was low. Findings fit within existing models of general health service utilization with workplace resource use affected by: preventing and coping, severity threshold, enabling factors and cost versus benefit appraisal. Some unique factors included o-worker relationships, finding relief, lacking or inflexible rules and organizational focus on the service recipients. Multi-faceted interventions are likely to be the most successful in improving staff and related organizational outcomes.

Keywords: Developmental Services
Violence
Workplace Services
Advisor: Dewa, Carolyn S.
The Influence of Organic Coatings on Atmospheric Processes at the Air-Water Interface

The air-water interface is abundant in the environment, thus it is an important proxy for atmospheric processes such as the uptake and transfer of molecules, heterogeneous reactions, photochemistry, and cloud condensation. This thesis aims to elucidate the role of semi-soluble and insoluble organic coatings on atmospheric processes at the air-water interface. Using glancing-angle LIF it was found that monolayer coatings of 1-octanol and of octanoic acid have opposing effects on the ozonation rate of pyrene at the air-water interface. LIF was also coupled with a Profile Analysis Tensiometer (PAT-1) to measure the effect of stearic acid coating compression on the uptake of HCl to a water droplet. Due to preliminary issues with this novel technique, no significant uptake suppression was observed. The oxidation of benzene by OH radical was also explored briefly, as were the photophysics of photosensitizers and the angle dependence of Raman signal from a D2O pendent droplet.

Keywords: Atmpsheric Chemistry
Spectroscopy
Laser Induced Fluorescence
Glancing Angle
Air-Water Interface
Heterogeneous
Advisor: Donaldson, D James
The Effects of Losing Sex on Genetic Variation in Oenothera (Onagraceae)

Theory predicts that sexual reproduction confers an advantage over asexual reproduction due to the generation and maintenance of genetic variation afforded by the processes of recombination and segregation. However, this prediction has rarely been empirically tested. Oenothera is a flowering plant genus whose evolutionary history is punctuated with numerous transitions from sexual reproduction to a form of functionally asexual reproduction known as Permanent Translocation Heterozygosity (PTH). In Ch. 2, a greenhouse experiment examined patterns of phenotypic and genetic variation within and between populations across eight Oenothera species, representing four independent transitions to PTH. I found some evidence for a decrease in heritability and an increase in population differentiation in phenotypic traits associated with the loss of sex. Ch. 3 explored the possibility that rare outcrossing events represent a mechanism for the maintenance of variation in a PTH species. Analysis of microsatellite markers showed evidence for extremely low rates of outcrossing in natural populations (< 1%) of O. biennis, a PTH species.

Keywords: Evolution of sex
genetic variation
quantitative genetics
microsatellite genotyping
Advisor: Johnson, Marc