VictorJuiz/thesis huggingface dataset:
Psycho-socio-economic and Health Outcomes of Patients with Work-Related Asthma and Relationships to Different Models of Clinic Organization

This thesis explored the impact of clinic structure on psychological, socioeconomic, workplace and quality of life (QoL) outcomes among work-related asthma patients between two tertiary clinics (Toronto Western Hospital [TWH] and St. Michael’s Hospital [SMH]). A cross-sectional comparison was carried out between the two clinics and data was collected through administration of five questionnaires: Beck Anxiety and Depression Inventories, Marks’ Asthma QoL Questionnaire, Work Limitations Questionnaire and Survey of Work and Non-work Related Respiratory Symptoms and their Impact. Forty-seven subjects participated from TWH and 30 from SMH. This study reported a better psychological status for SMH patients compared to TWH patients. SMH patients had better QoL for the ‘mood’ domain, and less workplace limitation for the ‘mental-demands’ domain. However, SMH included a greater number of patients with reduced income compared to TWH. Future research should explore the impact of clinic structure on a more homogenous group with larger sample sizes.

Keywords: Clinic Structure
Occupational asthma
Outcomes
Work-exacerbated asthma
Work-related asthma
Advisor: Tarlo, Susan M
Silverman, Frances
Measuring Gas Composition And Temperature In Highly Particle Laden Flow Using Terahertz Spectroscopy

This work veriďŹ es that THz radiation has the potential to be used as gas sensors in industrial furnaces. Testing proved that THz signals do not attenuate due to particle scattering, of particle sizes common in furnace ducts. High-temperature (773 K) H2O vapor and room temperature CO can be measured quantitatively with terahertz (THz) spectroscopy in the frequency range of 0.5-0.9 THz. THz spectroscopy is also used with two diďŹ erent methods to perform gas temperature measurement: using the area ratio of two H2O vapor absorbance peaks, and using the relative time delay of the THz signal. The absorbance peak ratios were tested in the frequency range of 0.5 - 0.8 THz at temperatures of 523 - 773 K. The time delay was tested at a frequency of 0.5 THz and temperatures of 293 - 773 K, and is used to determine temperature by calculating the index of refraction of the gas.

Keywords: Gas Composition
Gas Temperature
Particle Laden Flow
Terahertz
Water Sensor
Advisor: Thomson, Murray J
A 4x, 3-level Blind ADC-based CDR in 65nm CMOS

This thesis presents the design, implementation, and measurement of a 4 times oversampled, 3-level blind ADC-based CDR. The goal of this work was to provide a blind ADC-based design that reduced the overall power consumption. This was achieved by reducing the ADC resolution to 3 levels, while increasing the oversampling ratio to 4. Also, by non-uniformly distributing the threshold levels of the ADC, the design incorporated a speculative DFE. The speculative DFE is implemented with comparator pairs whose symmetric offsets correspond to the first post cursor ISI. The samples from the comparator pairs are then passed to the digital CDR which uses them to recover the clock phase and data. The digital power was measured to be 18mW, while an estimate for the ADC and CLK Divider measured power was found to be 35.5mW. The estimate of the total measured power for the chip was 53.5mW.

Keywords: ADC-based
CDR
DFE
Equalizer
High-speed signalling
Receiver
Advisor: Sheikholeslami, Ali
Design and Evaluation of a Mobile Marker-based Motion Capture System Using the Kinect Sensor for Biomechanical Assessments of Caregivers in the Home

Care in the home is desirable but puts the home caregivers at high risk of injury. This problem has been ignored from a physical ergonomics perspective since lab-based motion capture (MoCap) systems to understand biomechanical challenges of providing care are too bulky and costly to be used in homes. This work describes the design and usability testing of a mobile Kinect-based MoCap system for the home environment. When compared to a lab-based system, the Kinect-based system was found to be accurate overall. RMS error in flexion angle of the spine relative to gravity was as low as 4.25째, 2.52째 flexion angle between upper back and lower back, 2.17째 for lateral bending angle and 1.51째 for twisting angle of the trunk relative to the pelvis. The percentage of data captured by the system is 82%. The Kinect-based system is also more efficient than a lab-based system. Users rated the hardware and software aspects as high as 5 on a five point scale. A second prototype was developed and tested, leading to modal usability score improvements from 2 to 5 and 3 to 5 on a five point scale for certain aspects of the system.

Keywords: Biomechanical Assessments
Confined Spaces
Home Caregivers
Kinect V2 Sensor
Motion Capture Systems
Trunk Movements
Advisor: Fernie, Geoff
Dutta, Tilak
Non-genetic Resistant Mechanism to EGFR Tyrosine Kinase Inhibitory Therapy

Despite initial high response rate to tyrosine kinase inhibitor (TKI) treatment, non-small cell lung cancer (NSCLC) patients whose tumors harbour activating mutation in their epidermal growth factor receptors (EGFR) gene invariably develop TKI resistance. Secondary mutation T790M in EGFR and MET amplification were found in over 50% tumors. However, there are up to 30% of cases, whose mechanisms underlying the acquired resistance remains unknown. In this study, we used whole-genome loss-of-function shRNA library screen and mRNA expression microarray to identify LAYN, EPDR1 and DNMT1 that could potentially confer TKI resistance in NSCLC cell lines. Unfortunately, knockdown of them using shRNA hairpins did not restore drug sensitivity in drug resistant models. Further studies are needed to investigate the resistance mechanism of TKI resistant NSCLC cell lines.

Keywords: drug resistance
lung cancer
non-small cell lung cancer
tyrosine kinase inhibitor
Advisor: Tsao, Ming-Sound
Blasutig, Ivan
The Development of Quantitative Filter Forensics for Indoor Air Quality Sampling and a Pre-retrofit Indoor Environmental Quality Assessment of Pre-war Multi-Unit Residential Buildings

Filter forensics is a promising indoor air investigation technique involving the analysis of dust which has collected on filters. In this thesis, past filter forensics research is synthesized and an approach to quantitatively link filter forensics to average indoor air concentrations is developed. A significant advantage of FF is a large increase in the limit of detection when compared to alternative sampling techniques. In the next chapter, I discuss pre-retrofit comfort and moisture results from an ongoing indoor environmental quality study of post-war multi-unit residential buildings undergoing energy retrofits. A major finding of this study was a high level of discomfort due to overheating and the lack of observed correlations between comfort, moisture and building parameters. I present an application of filter forensics to portable air cleaners deployed in the same study. Preliminary data suggests no significant relationship between particle counts and gravimetric filter results.

Keywords: Dust
Filtration
HVAC
Indoor Concentration
Literature Review
Particle Composition
Advisor: Siegel, Jeffrey A
Pre-clinical MR-based Volumetric Dosimetry: Dosimetric Characterization and the Effects of Time and Temperature

Previously developed MR-based three-dimensional Fricke-xylenol orange gel (FXG) dosimeters can provide end-to-end quality assurance and validation protocols for pre-clinical radiation platforms. Variable TR spin-echo imaging of FXG dosimeters characterize changes in spin-lattice relaxation rates (R1 = T1-1) caused by irradiation induced oxidation of Fe2+ ions to Fe3+ ions. FXG dosimeters are water and tissue equivalent over the pre-clinical energy range, 30-225 keV, and exhibit a linear dose response up to 22 Gy. However, chemical instabilities in FXG dosimeters cause time and temperature dependencies that manifest themselves as baseline R1 shifts between initiation of pre- and post-irradiation R1 mapping. By characterizing and modeling R1-temperature and R1-time dependencies, a novel correction algorithm was developed that could be applied to FXG dosimeter R1 maps. This algorithm corrected baseline R1 shift from -2.8x10-2 s-1 to 1.5x10-3 s-1, and improved the reported dose accuracy to the 1% level when compared to standardized ion chamber measurements.

Keywords: 3D Fricke dosimetry
Correction algorithm
Improved accuracy
MRI readout
Time and temperature dependencies
Advisor: Jaffray, David A.
Regulation of Gnrh mRNA Expression by the ω-3 Polyunsaturated Fatty Acid Docosahexaenoic acid and the Saturated Fatty Acid Palmitate in a GnRH-synthesizing Neuronal Cell Model

Gonadotropin-releasing hormone (GnRH) neurons coordinate reproduction. Whether GnRH neurons directly sense free fatty acids (FFAs) is unknown. We investigated the individual effects of the FFAs palmitate, palmitoleate, oleate, and docosahexaenoic acid (DHA) (100 μM each) on Gnrh mRNA expression in the mHypoA-GnRH/GFP neuronal cell model. We report that 2 h exposure to palmitate or DHA increases Gnrh transcription. Using the inhibitors AH7614, K252c, U0126, wortmannin, and LY294002, we demonstrate that the effect of DHA is mediated through G protein-coupled receptor 120 to downstream PKC/MAPK and PI3K signaling. Moreover, we propose that the effect of palmitate may depend on palmitoyl-coA synthesis and PI3K signaling. Finally, we explored the effects of FFA combinations, and we report that oleate abolishes the effect of 2 h palmitate treatment on Gnrh. Overall, these studies advance our understanding of the cellular mechanisms underlying FFA sensing in a GnRH neuronal model and may relate to reproductive function.

Keywords: DHA
Free fatty acid
Gonadotropin-releasing hormone (GnRH)
GPR120
palmitate
reproductive neuroendocrinology
Advisor: Belsham, Denise D
Development of a Population-based Pharmacokinetic-pharmacodynamic Model to Simulate Treatment Efficacy in Metastatic non-small-cell Lung Cancer Patients on Erlotinib

Erlotinib improves progression-free survival (PFS) in metastatic non-small-cell lung cancer (mNSCLC) patients, but cause toxicities leading to dose reductions. The survival impact of dose reductions is unknown. We constructed a population-based pharmacokinetic-pharmacodynamic (PK-PD) erlotinib model predicting PFS of mNSCLC patients, consisting of an erlotinib population PK component, a PD component describing the concentration-kill-constant relationship, and a tumour growth component tracking tumour size over time. This model was fit against clinical trial data to simulate population-based PFS estimates in mNSCLC patients and externally validated using other trial data. The model simulated population-based PFS estimates of placebo and erlotinib arms with 0.74-9.14% and 0.26-19.83% error, respectively. The model was externally validated with population-based PFS estimate errors of 11.3% and 16.7% in epidermal growth factor receptor (EGFR)-mutant and EGFR-wild-type mNSCLC, respectively. It predicted significant PFS decreases with dose reductions. This is the first population-based PK-PD erlotinib model that predicts PFS in mNSCLC patients.

Keywords: epidermal growth factor receptor
erlotinib
model
non-small-cell lung cancer
pharmacokinetic-pharmacodynamic
progression free survival
Advisor: De Angelis, Carlo
The Effects of Saturated Fatty Acid Palmitate on Neuropeptide Gene Expression, Signal Transduction, and Insulin Signaling in an Immortalized Hypothalamic Neuronal Cell Model, mHypoA-NPY/GFP

Recent evidence suggests a role for hypothalamic insulin resistance in obesity pathogenesis, and that obesity-associated hypothalamic inflammation underlies this resistance. However, few studies have examined the direct effects of saturated fatty acids on specific hypothalamic neurons. Therefore, an immortalized hypothalamic neuronal cell model expressing NPY and AgRP was used to determine the effects of palmitate on neuropeptide gene expression, signal transduction events and insulin signaling. In the mHypoA-NPY/GFP neuronal cell model, palmitate was found to upregulate the expression of NF-κB and IκBα within 4 hours of treatment, and upregulate expression of AgRP after 24 hours of treatment. Regulation of AgRP gene expression appeared to be palmitate metabolism-dependent. Palmitate also induced p38 MAPK phosphorylation, and prolonged palmitate pre-treatment decreased levels of phosphorylated Akt following insulin re-challenge. This is the first evidence of palmitate-mediated changes in AgRP gene expression and its signaling through p38 MAPK in a representative NPY/AgRP neuronal cell model.

Keywords: Agouti-related peptide
Hypothalamus
Inflammation
Insulin
Neuropeptide
Palmitate
Advisor: Belsham, Denise D
Investigation of PIN1 as a Genetic Modifier in Li-Fraumeni Syndrome

Li-Fraumeni syndrome (LFS) is a heterogeneous cancer predisposition syndrome caused by germline mutations in TP53. Some of this phenotypic variability can be explained by presence of oncogenic mutant p53 proteins in patients with missense TP53 mutations. Recent data suggest that the prolyl-isomerase, PIN1, serves a fundamental role in mutant TP53 oncogenic gain-of-function (GOF). We hypothesized that alterations in expression of PIN1, mediated by the promoter SNP(-)842G>C (rs2233678), modify the cancer phenotype of LFS patients. We demonstrate that the PIN1(-)842 GG genotype is associated with increased PIN1 expression at the transcript and protein level. Overexpression of PIN1 selectively enhances the clonogenicity and chemotherapy resistance of LFS fibroblasts harbouring R248Q mutant p53. Concordantly, LFS patients with the PIN1(-)842 GG genotype develop cancer earlier than those with GC/CC genotypes, with a prominent effect in pediatric patients. The GG genotype may also be associated with some predilection for the development of carcinomas.

Keywords: Li-Fraumeni Syndrome
modifier
p53
PIN1
Advisor: Malkin, David
Centralized Portfolio Optimization in the Presence of Decentralized Decision Making

We study an asset allocation problem for a multi-asset fund where multiple decentralized managers implement investment strategies in separate asset classes. To control for portfolio measures at the fund, it is a common practice to follow a traditional asset allocation methodology to obtain optimal target weights and force the investment managers to stay close to the target. However, the sophistication and high level of specialization involved in alternative investment strategies create uncertainty in investment managers achieving the target weight; hence causing misallocations. Therefore, we develop two asset allocation models that provide a range of portfolio allocations (i.e. bounds) for individual investment managers to operate in order to maintain desirable firm wise portfolio measures while accounting for potential misallocations. Also, the proposed optimization problems have potentially large number of constraints, so we suggest a procedure to reduce the number of constraints before the optimization.

Keywords: Centralized
Decentralized
Portfolio optimization
Advisor: Kwon, Roy
Lee, Chi-Guhn
Interpersonal Emotion Regulation in a High Performance Varsity Volleyball Team

An instrumental case study approach was used to investigate the use of interpersonal emotion regulation (IER) in high performance varsity female volleyball athletes. Athletes reported using a variety of emotion-improving (verbal/positive feedback, cueing teammates about emotions, humour and non-verbal strategies), and emotion-worsening IER strategies, in addition to choosing not to engage in IER in some instances. The factors that were found to influence IER included athletes’ roles, social norms, the volleyball context, athletes’ preferences for IER, and interpersonal factors (i.e., relationship quality, personality, and relatability). Athletes also discussed how they learned to regulate their teammates’ emotions, and the concept of ‘automaticity’ in which some IER behaviours become almost automatic or done out of habit. This study has theoretical implications regarding the distinction between emotion regulation versus affect regulation, athletes’ preferences and perceived effectiveness of IER, and the use of emotion worsening strategies in sport.

Keywords: Emotion Regulation
High Performance Sport
Interpersonal Emotion Regulation
Sport Psychology
Advisor: Tamminen, Katherine
Residual Micro-strain in Root Dentin after Canal Instrumentation Measured with Digital Moire Interferometry

This study evaluated the residual micro-strain and the presence of micro-defects in root dentin following nickel-titanium instrumentation of canals in teeth maintained in hydrated and non-hydrated environments. Eighteen premolars were divided into two experimental groups (ProTaper Universal, Wave-One) and one control group (hand files). Nine specimens were maintained in deionized water and nine specimens were kept in ambient conditions for 72 hours. Digital moirĂŠ interferometry (DMI) was used to qualitatively determine the residual micro-strain distribution pattern in root dentin produced by instrumentation. Subsequently, micro-computed tomography (micro-CT) and polarized light microscopy (PLM) were used to detect the micro-defects. DMI showed a dentinal strain relaxation behavior in hydrated specimens whereas, root dentin from non-hydrated specimens showed localized regions of micro-strain concentrations. Micro-CT and PLM did not reveal obvious dentinal micro-defects in all groups. These findings suggested that the biomechanical response of root dentin to instrumentation was influenced by hydration.

Keywords: Endodontics
Advisor: Kishen, Anil
Neurophysiological Signals Parametrically Track Subjective Conflict during Intertemporal Choice

When choosing between equally desirable options, how is decision conflict represented in the brain? We measured neurophysiological signals that are believed to reflect decision processes in different brain regions as participants made intertemporal decisions. Participant-specific delayed rewards (e.g., $20.30 in 10 days)â generated based on each participant's hyperbolic discount functionâ were presented to parametrically vary the amount of decision conflict in different choice pairs. We found that conflict negativity and pupil dilation track varying degrees of conflict, suggesting the anterior cingulate and locus coeruleus/norepinephrine system are implicated in value comparison and conflict monitoring processes. We show that the neuroeconomic and psychophysiological approaches can be integrated to better understand the neural systems and processes underlying decision making.

Keywords: anterior cingulate cortex
conflict negativity
corrugator activity
decision conflict
intertemporal choice
pupil dilation
Advisor: Inzlicht, Michael
Hutcherson, Cendri A
The Protein Arginine Deiminases: Inhibitors and Characteristics

The Protein Arginine Deiminases: Inhibitors and Characteristics MSc Pharmaceutical Sciences Convocation year of 2015 Elizabeth Joanne Curiel Tejeda Department of Pharmaceutical Sciences University of Toronto Protein arginine deiminases (PADs) are Ca2+ dependent enzymes involved in the post-translational modification of proteins through citrullination. Overexpression of PAD2 and PAD4 has been observed in a number of neurodegenerative diseases. In this thesis, two broad investigations were undertaken to look at the expression patterns of endogenous PADs and how they provide means to the development of disease modifying treatments. First, a BODIPY-based fluorescent probe was designed to assess the expression levels in vitro and in vivo of endogenous PAD. Secondly, medicinal chemistry approaches were adopted to design a library of novel non-covalent compounds to establish a structure activity relationship on PADs and identify a potential hit. Results indicated that a BODIPY-based biomarker was a feasible approach to monitor PAD enzymes in vivo. Through structure-activity relationship investigations, it was established that small heterocycles on an amino acid side chain were contributing to the inhibitory activities towards PADs.

Keywords: chemsitry
drug discovery
medicinal chemistry
multiple sclerosis
pharmaceutical sciences
Protein arginine deiminases
Advisor: Kotra, Lakshmi P
The Requirement of B-cell Lymphoma Maloney Murine Leukemia Virus Insertion Region-1 Homolog for the Proliferative Effects of Glucagon-like Peptide-2 in the Murine Small Intestine

Glucagon-like peptide-2 (GLP-2) stimulates growth of the intestinal epithelium upon nutrient ingestion. The goal of the present study was to determine which crypt cell population GLP-2 activates to induce its proliferative effect. It was hypothesized that GLP-2-induced proliferation requires a full complement of B-cell specific Mo-MLV insertion region-1 homolog (Bmi-1) in the small intestine, assessed using the Bmi-1enhanced Green Fluorescent Protein (eGFP)/+ mouse model. The acute (1d) and chronic (11d) proliferative response to GLP-2 in the transit-amplifying zone was impaired in Bmi-1eGFP/+ crypts compared to Bmi-1+/+ crypts. Chronic GLP-2-treated Bmi-1eGFP/+ mice had an adaptive growth response to GLP-2 in which the epithelial cell migration rate was increased. After a lethal dose of ionizing-radiation, the Bmi-1eGFP/+ intestine also had an impaired proliferative response to chronic (18-19d) GLP-2 treatment. Therefore, a full genetic complement of Bmi-1 is required for GLP-2’s proliferative effects in the physiological and pathological settings.

Keywords: bmi-1
GLP-2
intestinal stem cells
proliferation
radiation
transit-amplifying cells
Advisor: Brubaker, Patricia L
Word Representation Using A Deep Neural Network

Word representation or word embedding is an important step in understanding languages. It maps similar words to vectors that are close in space. In this thesis, we introduce a deep neural network model called the Character-Morphology-Word network (CMW) for word representation. We implemented our CMW model and trained it on the Wikipedia corpus. We compared our model against two past approaches in a number of word-embedding tasks and found that, while the average performance of our model is not as good as the past approaches, our model achieves comparable precision and, in one task, our model outperforms these approaches. We also used our model to generate random text and found that our model produces words in the vocabulary and can produce lexical-correct text. The results of our research indicate that a deeper neural network can be used to represent words and ultimately, help solve related Natural Language Processing (NLP) tasks.

Keywords: Morphology
Natural Language Processing
Recurrent Neural Networks
Recursive Neural Networks
Word Embedding
Advisor: Lyons, Kelly A
Exploring the Integrated Curriculum: A Critical Analysis of the Ontario Ministry of Education's Language Curriculum Document

Students demonstrate increased engagement and knowledge retention when they are able to make connections between the text and the outside world. Despite the real world not being formed into neat subjects, the Ontario curriculum is. Through integrated curriculum, Susan Drake and James Beane argue that students are better equipped to become life-long learners and global citizens. As leading professionals in the field of integrated curriculum, this document analysis utilizes inductive analysis to explore the Ontario Ministry of Educationâ s 2006 curriculum document for Language (Revised) to determine if Drake and Beaneâ s approaches are explicitly stated. Results found that neither approach was explicitly stated, although the Ministry utilized similar integrated approaches as presented by Drake, while desired student outcomes aligned with Beane. The Ontario Ministry of Education should consider the interdisciplinary and transdisciplinary frameworks of Drake and Beane when producing future editions of the Ontario curriculum documents.

Keywords: holistic
integrated curriculum
James Beane
Ontario Ministry of Education
pedagogy
Susan Drake
Advisor: Miller, Jack