VictorJuiz/thesis huggingface dataset:
Function and Regulation of the Cell Fate Determinant Numb in Polarized Epithelial Cells

Cell polarity is fundamental to numerous cellular processes including migration, molecular transport, and cell division. The establishment and organization of polarity is crucial to the maintenance of cellular homeostasis in mammalian systems. Deregulation of cell polarity is observed in disease states, including cancer. Numb is an adaptor protein that functions in regulating endocytic trafficking events. Numb was originally identified in Drosophila as an asymmetrically localized cell fate determinant, and was subsequently found to be conserved in vertebrates. In mammalian polarized epithelial cells, Numb is distributed asymmetrically along the basolateral membrane domain. The work herein describes phosphorylation of Numb by the Par complex protein, atypical Protein Kinase C (aPKC), as a means of regulating membrane localization and asymmetric distribution of Numb. A mutant of Numb that cannot be phosphorylated by aPKC accumulates on the plasma membrane and localizes to both apical and basolateral membranes. In aPKC-depleted cells, endogenous Numb is unable to achieve polarized distribution and localizes around the entire cell cortex. We demonstrate that this mechanism is conserved in Drosophila as mutation of the corresponding phosphorylation sites disrupts Numb asymmetric localization in dividing sensory organ precursor cells. In polarized epithelial cells, one function of Numb is to promote epithelial morphology when cells are challenged with external stimuli that disrupt cell-cell adhesion. For example, depletion of Numb results in enhanced sensitivity of cells to lose cell-cell contacts when treated with calcium chelating agents. Loss of Numb potentiates hepatocyte growth factor (HGF)-induced lamellipodia formation and cell dispersal – early steps in epithelial-mesenchymal transition (EMT). In Numb-depleted cells, Rac1-GTP loading is enhanced, which corresponds with increased rate in loss of cell-cell adhesion and increased lamellipodia formation, following depletion of extracellular calcium and HGF stimulation, respectively. Together, this work identifies a mechanism that regulates polarized distribution of Numb and provides insight into its function in polarized epithelial cells.

Keywords: Numb
phosphorylation
asymmetric localization
cell polarity
Rac activation
endocytosis
Advisor: McGlade, Jane
Practising Critical Literacy Work with English Language Learners: An Integrative Approach

Existing mainstream ESL pedagogy tends to be functionalist and assimilationist, ignoring the complex sociopolitical dimensions of language learning (Pennycook, 2001). In addition, critical inquiry is often deemed too difficult for English language learners (ELLs), hence seldom introduced in ESL classrooms. However, academic proficiency, deep understanding and critical literacy (CL) are needed for school success and world citizenship. This doctoral thesis describes a year-long participatory action research with a class of new immigrant ELLs (aged 12-14) in a city in Ontario, Canada. Informed by CL and critical pedagogy, the research aimed to find out how CL education played out in a beginning ESL classroom--the instructional choices made, negotiation of teacher and student identities, processes and challenges involved, and the extent to which students’ critical/literacy development was facilitated. Based on Cummins’ Academic Expertise Framework (2001), the sociocultural theory of learning (e.g., Lave & Wenger, 1991; Vygotsky, 1987) and Guthrie’s (1996, 2004) conception of literacy engagement, an integrative instructional approach was adopted for the design and implementation of the CL program. The program addressed ELLs’ academic language needs while affirming their cultural identities and developing their critical ability in dealing with struggles amidst their acculturation process. Following the principles of critical action research, this study was done through cycles of reflection, action and evaluation with different sets of qualitative data which were coded and analysed based on phenomenological research methods. The results showed a significant improvement in students’ level of self-confidence and critical/literacy development while the ESL teacher changed from being sceptical of doing CL work with beginning ELLs to fully embracing it and seeing herself as an advocate for ELLs. This research showed that with careful scaffolding and guided practice of functional, cultural and CL skills grounded in a collaborative learning community that set high expectations on students’ critical and creative abilities, students achieved substantial critical/literacy engagement and development. The question educators should ask is not “At which grade or language level can students be introduced to CL?”, but rather “Are we providing support and scaffolds to students’ learning that are geared towards helping them to gradually become critical language users?”

Keywords: English Language Learners
critical literacy
middle school
participatory action research
critical pedagogy
Advisor: Cummins, James
A Study of Information and Communication Technology Integration by Faculty Teaching in a Ubiquitous Laptop Bachelor of Education Program

The fast pace of technological change within education has made it challenging for Faculty of Education professors to keep current with the integration of Information and Communication Technology (ICT) into teaching. This study focuses on an Ontario university Faculty of Education’s ubiquitous laptop program. Diffusion of innovation theory was used as a conceptual framework to examine how Faculty of Education professors perceive they are learning and integrating ICT into the preservice program despite a lack of formal ICT standards in the education system of Ontario. In 2007, data were gathered through interviews with faculty, administration, technical assistants and recent B.Ed. graduates. The faculty participated in an online survey to determine what ICT was being used and integrated within the B.Ed. program. In the analyses, data were organized into five themes based on Rogers (2003) diffusion of innovations theory: innovations used by faculty, adoption of innovations, organizational support of the adoption, unexpected consequences of the innovation, and increasing the rate of adoption. The findings from the faculty survey and interviews indicate that while many professors often integrated technology in their teaching, there existed a wide range of skills, confidence levels, and amount of ICT integrated into teaching among faculty. Issues influencing the adoption of effective technology integration that arose from the study include: lack of faculty development, off task behavior of preservice teachers, lack of time to learn ICT, technical difficulties, technical support concerns, wide range of ICT skills of preservice teachers, and the high cost of the laptops themselves. The lack of provincial ICT standards may have further contributed to the varied degrees of ICT integration at the university as well as that within schools in the practicum setting. Recommendations were made that have the potential to improve the effectiveness of ICT integration into the Bachelor of Education program and also provide direction for future faculty development initiatives, including faculty development. Findings from this study may be beneficial to researchers who are studying the faculty experience in ubiquitous laptop Faculty of Educations or other educational institutions considering ICT integration.

Keywords: Teacher Training
Technology
Advisor: Brett, Clare
Multi-parametric Magnetic Resonance Imaging (MRI) in Prostate Cancer

Prostate cancer is extremely prevalent, with shifting patient demographics leading to an increasing number of men balancing treatment efficacy with associated side-effects. Non-invasive characterization of disease – useful for guiding biopsy, to monitor disease progression during active surveillance, or for treatment planning of focal therapies – could have a significant impact on patient management. Through its excellent anatomic imaging capabilities and its ability to characterize physiologic properties, magnetic resonance imaging (MRI) has the potential to fulfill clinical goals; however, further improvements are necessary to maximize accuracy and impact. Thus, this thesis presents: 1) the development of a multi-parametric model to combine parameters derived from measurement of T2 relaxation, diffusion weighted imaging, and dynamic contrast-enhanced MRI to improve the discrimination between normal and malignant peripheral zone tissue; 2) determination of the impact that the presence of normal tissue within regions of tumour has on the measurement of apparent diffusion coefficient (ADC) and T2 relaxation in the peripheral zone; and 3) relationships between MRI measurement and underlying prostate tissue composition. A common patient cohort was used for all studies, with prostate cancer patients having in vivo MRI prior to prostatectomy followed by whole-mount histologic sectioning of the surgical specimens, facilitating the use of pathology as a gold-standard for all analyses. In the first study, the optimal multi-parametric model combines ADC, T2, and volume transfer constant (Ktrans) to yield the probability of malignancy for each voxel. Performance of the model is better than each single parameter, but not significantly so compared to ADC. The second study demonstrates that there is no difference in ADC and T2 between tumours containing significant portions of normal tissue and the surrounding normal tissue itself, indicating that full characterization of prostate cancer with MRI may be limited. Finally, by determining relationships between MRI parameters and tissue characteristics, the third study suggests mechanisms driving MR image appearance in the prostate, including the visualization of cancer. Taken together, this thesis presents potential improvements to prostate cancer imaging, and provides further insight into the interplay between the underlying histology and MRI.

Keywords: magnetic resonance imaging
prostate cancer
Advisor: Trachtenberg, John
Haider, Masoom
Principal Component Analysis of Gramicidin

Computational research making use of molecular dynamics (MD) simulations has begun to expand the paradigm of structural biology to include dynamics as the mediator between structure and function. This work aims to expand the utility of MD simulations by developing Principal Component Analysis (PCA) techniques to extract the biologically relevant information in these increasingly complex data sets. Gramicidin is a simple protein with a very clear functional role and a long history of experimental, theoretical and computational study, making it an ideal candidate for detailed quantitative study and the development of new analysis techniques. First we quantify the convergence of our PCA results to underwrite the scope and validity of three 64 ns simulations of gA and two covalently linked analogs (SS and RR) solvated in a glycerol mono-oleate (GMO) membrane. Next we introduce a number of statistical measures for identifying regions of anharmonicity on the free energy landscape and highlight the utility of PCA in identifying functional modes of motion at both long and short wavelengths. We then introduce a simple ansatz for extracting physically meaningful modes of collective dynamics from the results of PCA, through a weighted superposition of eigenvectors. Applied to the gA, SS and RR backbone, this analysis results in a small number of collective modes which relate structural differences among the three analogs to dynamic properties with functional interpretations. Finally, we apply elements of our analysis to the GMO membrane, yielding two simple modes of motion from a large number of noisy and complex eigenvectors. Our results demonstrate that PCA can be used to isolate covariant motions on a number of different length and time scales, and highlight the need for an adequate structural and dynamical account of many more PCs than have been conventionally examined in the analysis of protein motion.

Keywords: Principal Component Analysis
Molecular Dynamics
Gramicidin
Nonlinear Dynamics
Advisor: Pomès, Régis
Homecare of Long-term Care? The Balance of Care in Urban and Rural Northwestern Ontario

While some individuals can successfully age at home, others with similar levels of need may require facility based long-term care (LTC). The question addressed in this thesis is: “What factors determine whether or not older persons age at home?” I argue that in addition to the characteristics and care needs of individuals (the demand side); access to home and community care (H&CC) at the local level (the supply side) determines whether or not older people receive care at home relative to other settings. In emphasizing the role of the supply side, I draw on Neoinstitutional Theory and the Theory of Human Ecology to examine how institutions of the state (policies, norms, values, and organizational structures) facilitate or constrain opportunities to age at home across urban and rural areas. In conducting my analysis I draw on the Balance of Care (BoC) framework to analyze the characteristics of individuals waiting for LTC placement in Thunder Bay (urban community) and the surrounding Region (rural communities) of Northwestern Ontario. The BoC framework provides the means to estimate the extent to which their needs could potentially be met in the community if home and community care (H&CC) services were available. The results show that individuals waiting for LTC placement in Thunder Bay experienced higher levels of impairment than those in the Region. However in both areas, most individuals required assistance with instrumental activities of daily living (e.g. housekeeping, meal preparation, etc). In both areas there was limited access to informal caregivers. If a H&CC package were to be made available, 8% of those waiting for facility based LTC in Thunder Bay could potentially be supported safely and cost-effectively at home compared to 50% in the surrounding Region. The results confirm that the supply side matters. When H&CC cannot be accessed, LTC may become the default option, particularly in rural and remote areas. If given access to H&CC, a significant proportion of individuals can potentially age at home.

Keywords: long-term care
balance of care
homecare
seniors
rural
policy
older persons
Advisor: Williams, A. Paul
The Protective Role of the Angiopoetin-1 - Tie2 System in Transgenic Models of Pulmonary Arterial Hypertension

The role of the Angiopoietin-1 (Ang1)-Tie2 pathway in pulmonary arterial hypertension (PAH) is controversial, with one group suggesting that increased Ang1-Tie2 activity may even play a causal role in PAH progression. However, Ang1 has been well-characterized as a homeostatic factor, which prevents endothelial cell (EC) activation and injury through Tie2 receptor stimulation. Furthermore, we have previously demonstrated that lung Tie2 expression and activity are significantly downregulated in experimental PAH, implicating reduced Tie2 signaling in the pathogenesis of this disease. Thus, we hypothesized that manipulations to increase Ang1-Tie2 signaling will protect against lung EC injury and onset of PAH, whereas a loss-of-function of this pathway in Tie2-deficient mice (Tie2+/-) would predispose to PAH. Approximately 13% of Tie2+/- mice developed spontaneous elevation in right ventricular systolic pressure (RVSP), although no significant difference was observed between the WT and Tie2+/- groups following chronic hypoxic exposure. Serotonin (5-HT) infusion for one week or daily interleukin-6 (IL-6) injection for two weeks produced substantial RVSP elevations in Tie2+/-, but not WT mice (P<0.05). Following one week of 5-HT or IL-6 treatment, there was a significant decrease in Ang1 protein expression in both WT and Tie2+/- mice (P<0.05). Similarly, following exposure of cultured pulmonary arterial smooth muscle cells to 5-HT or IL-6, Ang1 secretion was significantly decreased (P<0.01). Moreover, 5-HT or IL-6 exposure resulted in decreased Tie2 activity and increased apoptosis only in the lungs of Tie2+/- mice (P<0.01), and treatment with a pan-caspase inhibitor, Z-VAD, prevented PAH in 5-HT-treated Tie2-deficient mice. Together with in vitro studies showing that pulmonary arterial ECs subjected to Tie2-siRNA were more susceptible to apoptosis following 5-HT treatment, this strongly implicates EC death as a primary mechanism of PAH in the presence of reduced Tie2 activity. In addition, doxycycline-conditional, endothelial-targeted Ang1 binary transgenic mice showed no evidence of elevated RVSP under basal conditions and if anything, demonstrated a blunted response to 5-HT treatment compared to non-binary littermate controls. Therefore, our findings support the importance of EC survival-signaling via the Ang1-Tie2 pathway as a protective mechanism in PAH and emphasize the pivotal role of EC apoptosis in the onset of this disease.

Keywords: pulmonary hypertension
angiopoietin
Advisor: Stewart, Duncan John
The Geography of Knowledge Formation: Spatial and Sectoral Aspects of Technological Change in the Canadian Economy as Indicated by Patent Citation Analysis, 1983-2007

Knowledge, learning, and innovation are vital elements in facilitating economic development and growth. Technological change, which is a synonym for generating knowledge, the diffusion thereof, and subsequent application in the marketplace in the form of novel products and processes, i.e. innovations, has a strong effect on the collective wealth of regions and nations. Knowledge spillovers, which are unintended knowledge flows that take place among spatial (geography) and sectoral (industry) units of observation, provide a rationale for diverging growth rates among spatial units, well beyond what might be explained by variations in jurisdictional factor endowments, and thus are of particular interest in this context. Measuring and quantifying the creation and diffusion of knowledge has proven to be a challenging endeavor. One way to capture technical and economically valuable knowledge is by means of patent and patent citation analysis. Following this approach, and utilizing a novel patent database that has been specifically developed for this purpose, the present dissertation investigates the spatio-sectoral patterns of knowledge spillovers in the Canadian economy over the time period 1983 to 2007. The employed research methodology addresses existing limitations in this stream of research, and contributes to the continuing debate regarding the significance of sectoral specialization versus diversity, and local versus non-local knowledge spillovers as the main driver of knowledge formation processes leading to innovation at the sub-regional scale. The findings indicate that knowledge spillovers are localized, and furthermore, that this localization effect has increased over time for both spillovers within a particular industry, as well as between industry sectors. The analysis of micro-geographic industry specific spatio-sectoral knowledge formation processes, and the inquiry into local sectoral knowledge spillover patterns, outlines how regional evolutionary technology trajectories potentially shape the rate and direction of technological change, and consequently influence economic growth, at a particular place.

Keywords: Economic Geography
Knowledge Externalities
Knowledge Spillovers
Patent Citation Analysis
Regional Technological Change
Canada
Advisor: Gertler, Meric S.
DiFrancesco, Richard J.
An Argument-based Validity Inquiry into the Empirically-derived Descriptor-based Diagnostic (EDD) Assessment in ESL Academic Writing

This study built and supported arguments for the use of diagnostic assessment in English as a second language (ESL) academic writing. In the two-phase study, a new diagnostic assessment scheme, called the Empirically-derived Descriptor-based Diagnostic (EDD) checklist, was developed and validated for use in small-scale classroom assessment. The checklist assesses ESL academic writing ability using empirically-derived evaluation criteria and estimates skill parameters in a way that overcomes the problems associated with the number of items in diagnostic models. Interpretations of and uses for the EDD checklist were validated using five assumptions: (a) that the empirically-derived diagnostic descriptors that make up the EDD checklist are relevant to the construct of ESL academic writing; (b) that the scores derived from the EDD checklist are generalizable across different teachers and essay prompts; (c) that performance on the EDD checklist is related to performance on other measures of ESL academic writing; (d) that the EDD checklist provides a useful diagnostic skill profile for ESL academic writing; and (e) that the EDD checklist helps teachers make appropriate diagnostic decisions and has the potential to positively impact teaching and learning ESL academic writing. Using a mixed-methods research design, four ESL writing experts created the EDD checklist from 35 descriptors of ESL academic writing. These descriptors had been elicited from nine ESL teachers’ think-aloud verbal protocols, in which they provided diagnostic feedback on ESL essays. Ten ESL teachers utilized the checklist to assess 480 ESL essays and were interviewed about its usefulness. Content reviews from ESL writing experts and statistical dimensionality analyses determined that the underlying structure of the EDD checklist consists of five distinct writing skills: content fulfillment, organizational effectiveness, grammatical knowledge, vocabulary use, and mechanics. The Reduced Reparameterized Unified Model (Hartz, Roussos, & Stout, 2002) then demonstrated the diagnostic quality of the checklist and produced fine-grained writing skill profiles for individual students. Overall teacher evaluation further justified the validity claims for the use of the checklist. The pedagogical implications of the use of diagnostic assessment in ESL academic writing were discussed, as were the contributions that it would make to the theory and practice of second language writing instruction and assessment.

Keywords: Language Testing
Diagnostic Assessment
ESL Writing
Writing Assessment
Advisor: Jang, Eunice