VictorJuiz/thesis huggingface dataset:
Sensitization to Death Receptor Stimuli and Anchorage-dependent Cell Death through Induction of Endoplasmic Reticulum Stress
Keywords: ER stress
death receptor stimuli
FLIP

Activation of the unfolded protein response follows induction of endoplasmic reticulum (ER) stress, resulting in widespread inhibition of protein expression. FLIP protein is particularly sensitive to stresses that perturb protein translation; as such, a reduction in FLIP is likely an early outcome of ER stress. Due to the anti-apoptotic role of FLIP, it is anticipated that potential decreases in FLIP would bring about an increase in sensitivity to death receptor stimuli and anoikis, a form of anchorage-dependent cell death. It was hypothesized that induction of ER stress results in downregulation of FLIP expression, resulting in sensitization of resistant tumour cells to death receptor stimuli and anoikis. From this hypothesis, it was determined that induction of ER stress through treatment of cells with brefeldin sensitized tumour cells to Fas-mediated cell death and anoikis. Moreover, over-expression of FLIP appeared to protect against ER stress-induced sensitization to cell death.
An Investigation of the Suitability of Using AISI 1117 Carbon Steel in a Quench and Self-tempering Process to Satisfy ASTM A 706 Standard of Rebar
Keywords: AISI 1117
reinforcing steel
rebar
QST
microstructure
quench and self-tempering
tempered martensite

Experiments were conducted to investigate the potential of using a quench and self-tempering heat treatment process with AISI 1117 steel to satisfy the mechanical properties of ASTM A 706 rebar. A series of quenching tests were performed and the resulting microstructure and mechanical properties studied using optical microscopy, microhardness measurement, and tensile tests. The presence of martensite throughout the samples contributed to the enhanced strength and strain-hardening ratio (tensile to yield strength) of the material. The experimental results showed that AISI 1117 is capable of meeting the ASTM standard. In addition to the experiments, a computer model using the finite difference method and incorporating heat transfer and microstructure evolution was developed to assist in future optimization of the heat treatment process.
Power Grid Correction Using Sensitivity Analysis Under An RC Model
Keywords: Power Grid Correction

Verifying the power grid requires checking if the voltage drops on all the nodes do not exceed the threshold. We aim to correct an RC model of the grid when some voltage drops violate the threshold condition, by making minor changes to the original design. We first propose an accurate approach to correct the grid which turns out to be too slow. We therefore propose another approach, more suitable for large grids and which can be summarized as follows. The voltage drop is estimated as a function of the metal widths on the grid. A non-linear optimization problem is then formulated and the required metal line width changes that reduce the voltage drops by a sufficient amount are determined. There is a tradeoff between accuracy and speed of the algorithm. However the results show that the gain in speed achieved by the second method, outweighs greatly the loss in accuracy.
Low-cost Hardware Profiling of Run-time and Energy in FPGA Soft Processors
Keywords: Profiling
FPGAs
hardware/software co-design
hardware/software partitioning
soft processors

Field Programmable Gate Arrays (FPGAs) are a reconfigurable hardware platform which enable the acceleration of software code through the use of custom-hardware circuits. Complex systems combining processors with programmable logic require partitioning to decide which code segments to accelerate. This thesis provides tools to help determine which software code sections would most benefit from hardware acceleration. A low-overhead profiling architecture, called LEAP, is proposed to attain real-time profiles of an FPGA-based processor. LEAP is designed to be extensible for a variety of profiling tasks, three of which are investigated and implemented to identify candidate software for acceleration. 1) Cycle profiling determines the most time-consuming functions to maximize speedup. 2) Cache stall profiling detects memory-intensive code; large memory overheads reduce the benefits of acceleration. 3) Energy consumption profiling detects energy-inefficient code through the use of an instruction-level power database to minimize the system's energy consumption.
Extraction of Proliferation and Death Rates in Cytokine-stimulated Erythroid Progenitors Using Cell-division Tracking and Mathematical Modeling
Keywords: erythroid
mathematical modeling
stem cells
cell division
differentiation
CFSE
CFDA-SE
red blood cell

Controlling fates of stem and progenitor cells is one of the central goals of regenerative medicine. However, conventional cell enumeration methods are unable to distinguish between the effects of cell death, proliferation, and differentiation through molecular interventions on the output of specific cell types. We have devised a strategy to simultaneously obtain proliferation and death rates in cultures of highly purified erythroid progenitors. The approach is based on combining cell-surface marker analysis, cell-division tracking and 7-amino-actinomycin-D staining to monitor cell death. A compartment model of cell proliferation was developed to evaluate cell generation-specific length of cell-division, rates of entry into division, and cell death, from the experimental cell-division tracking data obtained following stimulation with erythropoietin (EPO) and Stem cell factor (SCF). The results indicated that EPO and SCF, either as single factor or in combination, differentially affect the rates of differentiation, length of cell-division and rates of death.
Validation of an Internet-based Approach to Cognitive Screening in Multiple Sclerosis
Keywords: multiple sclerosis
cognition
neuropsychology
internet

Cognitive impairment affects approximately half of multiple sclerosis (MS) patients. The Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) has previously demonstrated validity for detecting cognitive impairment in MS, and is quick and easy to complete. The objective was to validate an internet version of the MSNQ. The following were completed at home over the internet for 82 MS patients: (a) patient self-report version of the MSNQ (P-MSNQ), (b) informant version of the MSNQ (I-MSNQ), and (c) Centre for Epidemiological Studies Depression Scale (CES-D). Thereafter, patients completed in-office neuropsychological testing using the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). Both the P-MSNQ and I-MSNQ were highly correlated with depression. The best-cut off score on the I-MSNQ was a 26, which gave a sensitivity of 72% and 60% for detecting cognitive impairment on the BRB-N. Given the modest sensitivity and specificity values, the MSNQ is not recommended for neuropsychological screening purposes over the internet.
New-generation Fully Programmable Controller for Functional Electrical Stimulation Applications
Keywords: Functional Electrical Stimulation
Neuroprostheses
Controller

Functional electrical stimulation (FES) systems have been developed to help restore various neuromuscular functions in individuals with neurological disorders leading to paralysis. Most of the current FES systems are designed for specific neuroprosthesis applications (i.e., walking, grasping, bladder voiding, coughing, etc.) and when one intends to use them in other custom made applications they are very limited due to a lack of functionality and flexibility in hardware and programmability. This prevents effective and efficient development of customized neuroprostheses. Research and development efforts at the Rehabilitation Engineering Laboratory at the University of Toronto were being carried out with an objective to produce a new, fully programmable and portable FES system. This thesis presents a novel proof-of-concept prototype controller for use in the new FES system. The controller subsystem manages and controls the overall FES system including the real-time decoding and execution of stimulation, data acquisition, external systems interfaces and user interface.
Effect of Potassium and Magnesium Doping on Sintering and Properties of Calcium Polyphosphate
Keywords: calcium polyphosphate
CPP
doping
magnesium
potassium
degradation

Porous constructs of calcium polyphosphate (CPP) are under investigation as a substrate for tissue engineering of cartilage for repair of osteochondral defects. Previous studies have shown that CPP has the required features to satisfy these requirements. However, its degradation rate is lower than desired. This study investigated the effect of doping with MgCO3, MgCl2, K2CO3 or KCl at a molar ratio of M/Ca = 0.02 on sintering and in vitro degradation behavior of CPP. Doping with magnesium or potassium improved the tensile and compressive strengths of CPP at similar porosities. After 15 days of aging in phosphate buffer saline, the rate of tensile strength loss was faster for the doped CPP groups than undoped CPP. The chemical degradation rate of Mg-doped CPP groups was the fastest among CPP groups. The chemical degradation rate of K-doped CPP groups was slower than undoped CPP.
The Appeal of Israel: Whiteness, Anti-Semitism, and the Roots of Diaspora Zionism in Canada
Keywords: Jewish
Diaspora
Israel
Zionism
Whiteness
Race

This thesis explores the appeal of Israel and Zionism for Ashkenazi Jews in Canada. The origins of Diaspora Zionism are examined using a genealogical methodology and analyzed through a bricolage of theoretical lenses including post-structuralism, psychoanalysis, and critical race theory. The active maintenance of Zionist hegemony in Canada is also explored through a discourse analysis of several Jewish-Zionist educational programs. The discursive practices of the Jewish National Fund and Taglit Birthright Israel are analyzed in light of some of the factors that have historically attracted Jews to Israel and Zionism. The desire to inhabit an alternative Jewish subject position in line with normative European ideals of whiteness is identified as a significant component of this attraction. It is nevertheless suggested that the appeal of Israel and Zionism is by no means immutable and that Jewish opposition to Zionism is likely to only increase in the coming years.
A Role for a Novel β-catenin Binding Protein in Epithelial-mesenchymal Transitions and Breast Cancer Progression
Keywords: EMT
basal phenotype breast cancer

Epithelial-mesenchymal transition (EMT) has a critical role in tumor progression and has been correlated with the basal-like subtype of human breast cancers. Here I report a novel β-catenin binding protein, which I have shown to be expressed in invasive breast cancer and hypothesized to have a role in breast tumor progression. In normal breast tissue, expression is restricted to the myoepithelium while in breast cancer the expression pattern is similar to smooth muscle actin and vimentin. I have demonstrated that silencing of this protein in breast tumor cells reduces migration by over 50 percent. Furthermore, I have identified this β-catenin binding protein as a target of the Snail EMT network and have demonstrated this protein to be a marker of basal-like carcinomas. These results define a role for this novel protein in EMT, as a marker for the basal subtype, and a promising therapeutic target for metastasis inhibition.
The Role of Mindin, a Member of the Mindin-F-spondin Family, in Immune Responses and Cardiac Remodeling Post Myocardial Infarction
Keywords: Myocardial infarction
cardiac remodeling

Mindin (Spondin 2) is a highly conserved extracellular matrix protein of the Mindin-F-spondin family and a regulator of host innate immunity. Despite its expression in the heart, its role in cardiac stress response is unknown. The objective of this study was to determine the role of mindin following myocardial infarction (MI). C57/BL6 wild-type (mindin+/+) or mindin knockout (mindin-/-) mice were randomized to permanent left anterior descending (LAD) coronary artery ligation or sham operation. Mindin expression level increased maximally on day 7 post MI, but returned to baseline by day 28. Mindin-/- mice showed reduced mortality, rupture rate, cardiac MMP-9/-2 activities, NF-kB activation, cytokines and macrophage recruitment. We concluded that mindin is a significant contributor to mortality and acute adverse remodeling post MI, partly through its unique attributes of innate immune regulator and inhibitor of angiogenesis. Mindin may function as a potential biomarker or therapeutic target post MI.
Segregation versus Self-determination: A Black and White Debate on Canada's First Africentric School
Keywords: Africentric
Afrocentric
Black-focused
Black school
Toronto District School Board
critical race theory
liberal democratic discourses
hidden transcripts
lived experiences
race
racism
education

The racialized realities faced by Black students provide an impetus to examine the controversy over Canada's first Africentric Alternative School, approved on January 29, 2008 by the Toronto District School Board. Newspaper articles, editorials and letters to the editor, as well as speeches by delegations and trustees, provide a rich snapshot of the arguments put forth in the heated political debate. Through the lens of equity and critical race theory, the diverse and divergent stances taken by both proponents and opponents of the school are analysed and understood. A conceptual framework of hidden and public transcripts (Scott, 1990) is used to distinguish arguments that reflect on the lived experiences of Black students from those that reiterate the dominant discourses of liberal democratic societies. The findings emerge as three opposing sets of themes that reveal a transcript reflective of the ongoing salience of racism within ostensibly liberal claims to racial equality.
The Role of Cell Adhesion Genes in the Pathogenesis of Medulloblastoma
Keywords: medulloblastoma
PCDH10

Medulloblastoma is the most common pediatric brain tumour, yet many of the underlying genetic and epigenetic factors have yet to be discovered. After a genome wide screen of a large cohort of primary medulloblastomas, we discovered that many of the genes within the cell adhesion family are affected by either copy number loss and/or decreased expression unexplained by copy number change. This led us to believe that both genetic and epigenetic factors were affecting this gene family. Through methylation-specific PCR, RT-PCR and high-throughput methylation status analysis, we have concluded that promoter CpG methylation plays a role in the expression of the PCDH10 protein in both medulloblastoma cell lines and primary tumours. Through functional validation with a stable cell line re-expressing PCDH10, I show that cell cycle and proliferation remain unchanged but migration is decreased in cells with PCDH10 re-expression. This suggests that PCDH10 has characteristics of a tumour suppressor in medulloblastoma.
Muscle-macrophage & Macrophage-macrophage Interactions in Diabetogenic Environment
Keywords: Obesity
Inflammation
Diabetes
Macrophage
Muscle

Diabetes and obesity are associated with inflammation and activation of the immune system with infiltration of adipose tissue by macrophages. This is mainly studied in adipose tissue, with limited information to clarify immune-skeletal muscle interactions in these conditions. We show that exposure of L6 rat skeletal muscle cells to saturated fatty acid palmitate results in insulin resistance, activation of inflammatory pathways, upregulation of pro-inflammatory cytokine and chemokine gene expression and secretion. We identified monocyte chemoattractant protein-1 [MCP-1] as the main factor responsible for macrophage attraction, as blocking it reduced macrophage migration to muscle cells. When macrophages are exposed to palmitate, a similar response ensues with production of macrophage chemoattractants and activation of inflammatory pathways and gene expression profiles, and secretion of multiple cytokines. Our work identifies MCP-1 chemokine produced in response to palmitate treatment by both muscle cells and macrophages and provides a potential link in immune-metabolic crosstalk in diabetogenic environment.
The Response of Annulus Fibrosus Cells to Fibronectin- Coated Nanofibrous Polyurethrane-Carbonate Anionic Dihydroxyoligomer Scaffolds
Keywords: annulus fibrosus
tissue engineering
nanofibrous scaffolds
polyurethane

Tissue engineering of the annulus fibrosus (AF) is challenging due to its complex lamellar structure. Polyurethane scaffolds have shown promise in AF tissue engineering. The current study examines whether matrix protein coatings (collagen type I, fibronectin, or vitronectin) would enhance cell attachment and promote cell and collagen orientation that more closely mimics native AF. The results demonstrate that the greatest cell attachment occurred with fibronectin (Fn)-coated scaffolds. Cells on Fn-coated scaffolds were also aligned parallel to scaffold fibers, a process that involved α5β1 integrin, determined by integrin-specific blocking antibodies. The inhibition of this integrin reduced AF cell spreading and alignment and the changes in cell shape were regulated by the actin cytoskeleton, demonstrated using cytochalasin D inhibitor. Cells on Fn-coated scaffolds formed fibrillar Fn, synthesized significantly more collagen, and showed alignment of type I collagen that more closely mimics native AF therefore facilitating the development of the tissue in vitro.
Role of DNedd4 Splice Isoforms in Neuromuscular Synaptogenesis in Drosophila Melanogaster
Keywords: E3 ubiquitin ligase
neuromuscular synaptogenesis
Nedd4

Drosophila Nedd4 (DNedd4), an E3 ubiquitin ligase, is known to be involved in neuromuscular (NM) synaptogenesis during embryogenesis. To further elucidate its mechanism and function in this process, two major splice isoforms, dNedd4 short (dNedd4S) and dNedd4 long (dNedd4L), were studied. My work shows that while dNedd4S positively regulates NM synaptogenesis, dNedd4L plays a negative role in this process. Unique regions in dNedd4L, including the N-terminal 66 amino acid-long sequence (but not the putative dAkt phosphorylation site) and the middle 159 amino acid-long sequence, as well as the catalytic site, are required for its negative function. I proposed one possible mechanism of dNedd4L acting as a negative regulator of dNedd4S. Results from my studies of the putative effect of dNedd4L on the catalytic activity of dNedd4S in vitro, as well as on the function of dNedd4S towards Comm in Drosophila S2 cells, did not support this mechanism.
Optimization of an Affinity Purification-mass Spectrometry Pipeline and Characterization of the Rub1p and Smt3p Interactomes
Keywords: Ubiquitin-like Proteins
Affinity Purification-Mass Spectrometry
Dcn1p
Cdc48p

The ubiquitin-like proteins (Ubls) are small polypeptides that function as post-translational modifications. Modification of a protein with a Ubl can alter its localization, activity and/or half-life. SUMO and Rub1p/Nedd8 are two Ubls that play important roles in a number of critical cellular processes, yet their specific cellular functions remain poorly understood. To better understand these important Ubls, we developed a robust affinity purification-mass spectrometry (AP-MS) technique to generate protein-protein interaction maps for the Ubl systems. Each bait was systematically expressed as a C-terminal HA-tagged fusion protein in S. cerevisiae. A standardized method in which affinity purification via the HA epitope, followed by mild washing and mass spectrometric analysis, was performed and the data generated were used to build interaction maps. Affinity purification of the Rub1p E3 ligase Dcn1p identified a novel interaction with the AAA ATPase Cdc48p. This interaction was further studied to determine its biological significance.
Depression, Psychological Distress and Breast and Cervical Cancer Screening: A Population-based Study in Ontario Women
Keywords: Depression
Psychological Distress
breast cancer screening
cervical cancer screening

Purpose: The objective of this study was to investigate both depression and psychological distress as determinants of breast and cervical cancer screening. Methods: Ontario female respondents to the Canadian Community Health Survey version 1.2 (2002) were assessed for both Major Depressive Disorder (World Mental Health-Composite International Diagnostic Interview for depression) and psychological distress (Kessler 6-item Distress Scale (K6)>/= 8). Respondents eligible for screening (N=4042 for cervical cancer; N=1403 for breast cancer) were linked to Ontario administrative health service data to prospectively ascertain screening outcomes. Results: Women with K6 >/= 8 had reduced breast cancer screening compliance in adjusted analyses (AOR 0.63, 95% CI 0.40-0.97). The association between K6 >/= 8 and cervical cancer screening approached significance in women over age 40 (AOR=0.65, 95%CI 0.41-1.04). Conclusion: Decreased likelihood of screening in women with clinically significant psychological distress suggests that attention to adequacy of preventive services is a potential target for intervention.
Oxygen Transport Measured by Isotope Tracing through Solid Oxides
Keywords: Isotope tracing
Solid oxides
Secondary Ion Mass Spectroscopy
SIMS
Residence Time Distributions
RTD

The following thesis demonstrates two isotope tracing experiments that measure oxygen transport through electrochemically polarized solid oxides. Cathode-symmetric ‘button’ cells with yttria stabilized zirconia(YSZ) electrolytes and either strontium doped lanthanum manganate(LSM) or composite LSM/YSZ cathodes were studied. The first experiment measured the residence time distributions(RTD) of 34O2. The measured RTDs were compared at different temperatures(700-800°C) and applied potentials(-2 to -8V). Comparisons with simulated RTDs revealed that oxygen transport was laterally heterogeneous. Delamination of the counter electrode is likely the source of the heterogeneity. The second experiment measured a wave of 18O by exposing an interior cross section and applying ToF-SIMS analysis. A depth profile was produced that spans the cathode and electrolyte interface. The depth profile was compared with a variety of limiting oxygen activation scenarios predicted by a simple 1-D model. Comparisons demonstrated that oxygen activation is likely not restricted to the cathode and electrolyte interface.
Teaching Mathematics for Social Justice and its Effects on Affluent Students
Keywords: social justice
mathematics
social agency

There is a crisis in mathematics education (National Research Council, 1989). This crisis has caused stakeholders to question the purpose of mathematics education. Teaching mathematics for social justice is a pedagogy that uses mathematics as a tool to expose students to issues concerning power, resource inequities, and disparate opportunities between different social groups to illicit social and political action (Gutstein, 2006). This study uses action research to explore the effects of incorporating social justice issues in mathematics with affluent, middle school students. Findings indicate that integrating social justice issues into mathematics affected some students’ cognitive and affective domains and in some cases led to empowerment and action. The study also found that students’ perception of responsibility, their age and personal connections along with the amount of teacher direction may have affected students’ development of social agency. These findings help to inform teachers’ practices and contribute to literature on critical mathematics.