VictorJuiz/thesis huggingface dataset:
Surviving Success, Reconciling Resilience: A Critical Analysis of the Appearance of Student ‘Mental Life’ at one Canadian University
Keywords: sociology of higher education
critical disability studies
phenomenology
social theory
women and gender studies
university student mental life

This dissertation addresses the university student as a figure of mental health and illness. Drawing on the methods and theories of disability studies, interpretive sociology, critical, feminist and queer theory, as well as hermeneutically oriented phenomenology, my work explores the social production of this student figure or type – variously depicted as ‘ invisible’, ‘maladjusted’, ‘stressed’, ‘difficult’, sensitive’, ‘resilient’, ‘narcissistic’, and extraordinarily ‘ordinary’. This figure is addressed as a means of revealing contradictory understandings of the relationship between success and survival, as this relationship appears in the ordinary daily life of the University of Toronto, Ontario, Canada. The social and historical significance of the contemporary University’s Student Life Programs and Services is analyzed with a view to reveal the Western cultural values and practices which organize consciousness of success as a necessary condition of contemporary existence. Special attention is paid to the cultural production of knowledge concerning university student ‘mental life’, the appearance of which is located at the interstices of colonialism, global health policy, institutional ‘best practices’, cultural mores and folkways, and embodied experiences. I dwell with this appearance as an occasion to engage the materiality of Western mythologies of resilience, and with them the meaning of human agency under neoliberal governance. This engagement examines the productive power of the disciplinary and institutionalized ‘language of mental illness’ through a genealogy of the University of Toronto, a textual analyses of the University’s Student Life Programs and Services literature, and a discursive analysis of open-ended interviews with student services representatives which seeks both to understand and transgress conventional interpretations of the structure of Student Life. I demonstrate how University presentations of student bodies, minds and senses perceived to be lacking in ‘ordinary order’, can be reconceived as sites to reflect on the paramount presence of psychiatric knowledge in interpretations and responses to embodied difference within the university setting. Overall, this dissertation seeks to disrupt unexamined relations to the meaning of student types; and in the process, display how normative relations to the student as a figure of mental health and illness needs is currently and historically organized and socially achieved.
Reactivity of Aziridine Aldehyde Dimers and their Utility in the Synthesis of Peptidomimetics
Keywords: peptide
ligation
amino aldehyde

Amino aldehydes are important building blocks in organic synthesis. However, due to the innate propensity for condensation to occur upon combination of aldehydes and amines, uprotected amino aldehydes are unstable. One exception to this is the existence of dimeric aziridine aldehydes. We have shown that the enhanced stability observed with these unprotected aziridine aldehydes is due to their dimeric nature. In addition, we have shown that reversible dimer dissociation plays a key role in the kinetics and stereoselectivity of subsequent reactions. Reductive amination with the unprotected amino aldehyde dimers occurs without double addition or epimerization. The resulting aziridine conjugates were used towards a convergent synthesis of aminomethylene peptidomimetics, by aziridine ring opening with C-terminal peptide thioacids. We have shown that we can also utilize the aziridine aldehydes towards the assembly of branched peptides.
Retroflex Consonant Harmony in South Asia
Keywords: Phonology
Retroflex
Consonant Harmony
Assimilation
South Asia
Indo-Aryan
Dravidian
Munda

This dissertation explores the nature and extent of retroflex consonant harmony in South Asia. Using statistics calculated over lexical databases from a broad sample of languages, the study demonstrates that retroflex consonant harmony is an areal trait affecting most languages in the northern half of the South Asian subcontinent, including languages from at least three of the four major families in the region: Dravidian, Indo-Aryan and Munda (but not Tibeto-Burman). Dravidian and Indo-Aryan languages in the southern half of the subcontinent do not exhibit retroflex consonant harmony. In South Asia, retroflex consonant harmony is manifested primarily as a static co-occurrence restriction on coronal consonants in roots/words. Historical-comparative evidence reveals that this pattern is the result of retroflex assimilation that is non-local, regressive and conditioned by the similarity of interacting segments. These typological properties stand in contrast to those of other retroflex assimilation patterns, which are local, primarily progressive, and not conditioned by similarity. This is argued to support the hypothesis that local feature spreading and long-distance feature agreement constitute two independent mechanisms of assimilation, each with its own set of typological properties, and that retroflex consonant harmony is the product of agreement, not spreading. Building on this hypothesis, the study offers a formal account of retroflex consonant harmony within the Agreement by Correspondence (ABC) model of Rose & Walker (2004) and Hansson (2001; 2010). Two Indo-Aryan languages, Kalasha and Indus Kohistani, figure prominently throughout the dissertation. These languages exhibit similarity effects that have not been clearly observed in other retroflex consonant harmony systems; retroflexion is contrastive in both non-sibilant (i.e., plosive) and sibilant obstruents (i.e., affricates and fricatives), but harmony applies only within each manner class, not between them. At the same time, harmony is not sensitive to laryngeal features. Theoretical implications of these and other similarity effects are discussed.
The Implications of Developmental and Evolutionary Relationships between Pancreatic Beta-cells and Neurons
Keywords: stem cells
pancreas
neural crest

A pancreatic stem cell could provide the tissue necessary for widespread β-cell transplantation therapy for diabetes. It is disputed whether pancreatic stem cells or β-cell replication are responsible for maintenance and regeneration of endocrine cells. Evidence presented here shows that pancreatic stem cells express insulin and produce multiple endocrine, exocrine and neural cells in vitro and in vivo. The human pancreas also contains stem cells that produce functional β-cells capable of reducing blood sugar levels in a diabetic mouse. Initial studies of pancreatic stem cells grown clonally in vitro indicated that they produced large numbers of neurons, suggesting they may be derived from the neural crest. Evidence shows that there are at least two distinct developmental origins for stem cells in the pancreas; one from the pancreatic lineage that produces endocrine and exocrine cells and one from the neural crest lineage that produces neurons and Schwann cells. Furthermore, pancreatic stem cells require the developmental transcription factor, Pax6, for endocrine cell formation suggesting they are using expected differentiation pathways. There is an interesting evolutionary connection between pancreatic β-cells and neurons which was applied to the derivation of pancreatic stem cells from human embryonic stem cells by using a clonal neural stem cell assay. These pancreatic stem cells express pancreatic and neural markers, self-renew and differentiate into insulin-expressing cells. The overexpression of SOX17 in these cells increases stem cell formation and self-renewal but inhibits differentiation. Overall I will show that there is a genuine stem cell in the adult mammalian pancreas capable of producing functional β-cells, that this stem cell is derived from the pancreatic developmental lineage but the pancreas also contains stem cells from the neural crest lineage, and that the neural stem cell assays that have identified these adult stem cells can be applied to the derivation of a pancreatic stem cell from hESCs.
Why AIM? - Educator Perspectives and Implementation of an Instructional Method for Teaching Core French as a Second Language in Ontario
Keywords: second language teaching
French as a second language (FSL)
Core French
Accelerative Integrated Method (AIM)
instructional method
educational change
agency

Since 2003, the Canadian government has repeatedly called for research into innovative ways to teach Core French (CF) – a non-immersion program, where French as a Second Language (FSL) is taught on a daily basis, or a few times per week. This exploratory study investigates the driving forces behind the widespread popularity of a CF method called the Accelerative Integrated Method (AIM), which combines target language use with gestures, high-frequency vocabulary, and drama to accelerate the development of fluency from the onset of classroom instruction. In order to learn more about the “meaningfulness” of this growing trend (Fullan, 2007), this mixed-method inquiry attempts to shift the focus from product to process, comparing educator perspectives and AIM implementation within two Ontario contexts: (a) where AIM was mandated for elementary (Grades 4-6) FSL instruction, and (b) where AIM was an optional method for FSL teachers to use (or not). Survey and interview data were collected from and triangulated across a variety of educators from both contexts, including FSL consultants (n = 18), principals (n = 8), CF teachers (n = 9), and one Ontario Ministry of Education representative. Four semi-structured interviews and multiple observations were also conducted with those CF teachers who were using AIM (n = 8). An additional CF teacher who had attempted to use AIM, and had subsequently rejected it, was also interviewed. Findings showed that AIM implementation and educator perspectives did not vary significantly based on whether AIM was mandated or optional for CF instruction. A clear preference emerged towards using AIM and the accompanying resources during the beginning stages of CF instruction. Discussion about the growing popularity of AIM was positive; however, it also exposed a range of emotions about when and how AIM should be used. In terms of implementation, while some AIM routines, activities, and strategies were used by all, each AIM teacher exercised their agency while using the method, supplementing and adapting for different reasons. Implications include the need to reexamine the objectives of micro-level AIM policies, recognize the adaptability of AIM, and consider including detailed observations in future research linking AIM to student achievement.
The Principle of Coordinate Invariance and the Modelling of Curved Material Interfaces in Finite-difference Discretisations of Maxwell's Equations
Keywords: numerical techniques
finite-difference methods
material boundaries
material interfaces
artificial materials
metamaterials
FDTD
high-order methods

The principle of coordinate invariance states that all physical laws must be formulated in a mathematical form that is independent of the geometrical properties of any particular coordinate system. Embracing this principle is the key to understand how to systematically incorporate curved material interfaces into a numerical solution of Maxwell’s equations. This dissertation describes how to generate a coordinate invariant representation of Maxwell’s equations in differential form, and it demonstrates why employing such representation is crucial to the development of robust finite-difference discretisations with consistent global error properties. As part of this process, two original contributions are presented that address the issue of constructing finite-difference approximations at the locations of material interfaces. The first contribution is a domain-decomposition procedure to enforce the tangential field continuity conditions with a second-order local truncation error that can be applied in 2-D or 3-D. The second contribution is a similar domain-decomposition procedure that enforces the tangential field continuity conditions with a local truncation of order 2L—where L is an integer greater or equal to one—but that can only be applied in 1-D. To conclude, the dissertation also describes the interesting connection that exists between the use of a coordinate invariant representation of Maxwell’s equations to design artificial materials and the use of the same representation to model curved material interfaces in a finite-difference discretisation.
Health Services Utilization among Persons Living with Human Immunodeficiency Virus Infection in Ontario
Keywords: clinical epidemiology
health services research

The goals of this dissertation were to investigate aspects of the health services utilization of marginalized persons living with HIV (PLWH), including women, recent immigrants, heterosexual men and individuals living in low income neighborhoods. In the first study, an algorithm of three physician claims for HIV-infection within a three-year period was validated for case-ascertainment of PLWH in administrative databases. The sensitivity and specificity of the algorithm were 96.2% [95% confidence intervals (CI) 95.2% to 97.9%] and 99.6% (95% CI 99.1% to 99.8%), respectively. The algorithm was used to conduct a population-based study examining rates of hospitalization among all PLWH receiving care in Ontario. The introduction of combination antiretroviral therapy was associated with more pronounced reductions in rates of total (-89.9 vs. -60.5 per 1000 PLWH; p = 0.003) and HIV-related hospitalizations (- 56.9 vs. -36.3 per 1000 PLWH; p < 0.001) among men relative to women. Between 2002 and 2008, higher rates of total hospitalization were associated with female sex [adjusted relative rate (aRR) 1.15; 95% CI: 1.05 to 1.27] and low socioeconomic status (aRR 1.21; 95% CI: 1.14 to 1.29). Higher rates of HIV-related hospitalizations were associated with low socioeconomic status (aRR 1.30; 95% CI: 1.17 to 1.45). Recent immigrants had lower rates of both total (aRR 0.70; 95% CI 0.61 to 0.80) and HIV-related hospitalizations (aRR 0.77; 95% CI 0.61 to 0.96). Finally, a theoretically-informed qualitative study was conducted to characterize the help-seeking experiences of heterosexual men living with HIV. The results indicate that without the symbolic appeal of women and the social connections of gay men, heterosexual men lack the composition of capital required to benefit fully from or improve their positions within the existing HIV health and social service fields. The findings of this dissertation illustrate important disparities in health services utilization among PLWH in Ontario.
Optimizing the Tailored Treatment of Breast Cancer
Keywords: Breast Cancer
Optimized therapy

Background: Breast cancer is a diverse disease. Over the past 3 decades it has been increasingly appreciated that therapy should be targeted to specific patient and tumour characteristics. In recent years the evaluation of tailored therapy has been dominated by the development of new drug therapy which when successful has been marketed at a high price. There have been few successful attempts to optimize currently available therapies. This thesis explores the optimization of currently available therapies in three domains: efficacy, toxicity and supportive care. Methods: Three independent studies were undertaken. First, a prospective cohort study was conducted to assess the impact of re-biopsy of recurrent breast cancer on physician choice of therapy and on patient satisfaction. The second study comprised a systematic review and meta-analysis of randomized trials exploring toxicities associated with different endocrine therapy options for early breast cancer with the aim of identification of patients who may be harmed by certain drugs. Finally, a randomized feasibility study was conducted to evaluate de-escalated intravenous bisphosphonates in women with low-risk metastatic breast cancer to bone. Results: All studies met their objectives in showing that the tailored use of available therapies can be optimized. The prospective study of the impact of re-biopsy showed that treatment decisions were modified in 14% of women. Patient satisfaction with the process of re-biopsy was high. The meta-analysis of toxicities of endocrine therapy identified cardiovascular disease as a statistically significant toxicity of aromatase inhibitors, thereby suggesting that those with established cardiovascular disease or risk factors thereof should reduce their exposure to these drugs. Finally, the randomized feasibility study showed that it is possible to conduct randomized trials of de-escalated bisphosphonates in women with low-risk breast cancer and there was no signal that reducing the frequency of treatment was associated with untoward outcomes. Conclusions: It is possible to optimize the tailored therapy of breast cancer using currently available treatments. This may lead to improved patient outcome while using existing resources. Further studies assessing the optimization of other treatments are warranted.
Identifying Susceptibility Genes for Familial Pancreatic Cancer Using Novel High-resolution Genome Interrogation Platforms
Keywords: familial pancreatic cancer
tumor suppressor genes
oncogenes
copy number variation
exome sequencing

Familial Pancreatic Cancer (FPC) is a cancer syndrome characterized by clustering of pancreatic cancer in families, but most FPC cases do not have a known genetic etiology. Understanding genetic predisposition to pancreatic cancer is important for improving screening as well as treatment. The central aim of this thesis is to identify candidate susceptibility genes for FPC, and I used three approaches of increasing resolution. First, based on a candidate-gene approach, I hypothesized that BRCA1 is inactivated by loss-of-heterozygosity in pancreatic adenocarcinoma of germline mutation carriers. I demonstrated that 5/7 pancreatic tumors from BRCA1-mutation carriers show LOH, compared to only 1/9 sporadic tumors, suggesting that BRCA1 inactivation is involved in tumorigenesis in germline mutation carriers. Second, I hypothesized that the germline genomes of FPC subjects differ in copy-number profile from healthy genomes, and that regions affected by rare deletions or duplications in FPC subjects overlap candidate tumor-suppressors or oncogenes. I found no significant difference in the global copy-number profile of FPC and control genomes, but I identified 93 copy-number variable genomic regions unique to FPC subjects, overlapping 88 genes of which several have functional roles in cancer development. I investigated one duplication to sequence the breakpoints, but I found that this duplication did not segregate with disease in the affected family. Third, I hypothesized that in a family with multiple pancreatic cancer patients, genes containing rare variants shared by the affected members constitute susceptibility genes. Using next-generation sequencing to capture most bases in coding regions of the genome, I interrogated the germline exome of three relatives who died of pancreatic cancer and a relative who is healthy at advanced age. I identified a short-list of nine candidate genes with unreported mutations shared by the three affected relatives and absent in the unaffected relative, of which a few had functional relevance to tumorigenesis. I performed Sanger sequencing to screen an unrelated cohort of approximately 70 FPC patients for mutations in the top two candidate genes, but I found no additional rare variants in those genes. In conclusion, I present a list of candidate FPC susceptibility genes for further validation and investigation in future studies.
Formulating Evaluation Measures for Structured Document Retrieval using Extended Structural Relevance
Keywords: information retrieval
XML
tree retrieval
relevance
redundancy
navigation

Structured document retrieval (SDR) systems minimize the effort users spend to locate relevant information by retrieving sub-documents (i.e., parts of, as opposed to entire, documents) to focus the user's attention on the relevant parts of a retrieved document. SDR search tasks are differentiated by the multiplicity of ways that users prefer to spend effort and gain relevant information in SDR. The sub-document retrieval paradigm has required researchers to undertake costly user studies to validate whether new IR measures, based on gain and effort, accurately capture IR performance. We propose the Extended Structural Relevance (ESR) framework as a way, akin to classical set-based measures, to formulate SDR measures that share the common basis of our proposed pillars of SDR evaluation: relevance, navigation and redundancy. Our experimental results show how ESR provides a flexible way to formulate measures, and addresses the challenge of testing measures across related search tasks by replacing costly user studies with low-cost simulation.
Osteocytes: Sensors of Mechanical Forces and Regulators of Bone Remodeling
Keywords: osteocyte
bone remodeling
mechanical loading
apoptosis
microfluidics
fluid shear stress

Osteocytes make up the largest cell population in bone and are believed to be the main mechanosensory bone cells. During mechanical disuse and overuse, osteocyte viability is compromised and is found to be co-localized with increased osteoclastic bone resorption. Osteoclasts are recruited to remodel sites of apoptosis or bone microdamage; however, it is unclear whether the apoptotic or neighbouring healthy osteocytes are responsible for targeted bone remodeling. I hypothesized that apoptotic osteocytes are: (a) directly responsible for initiating bone remodeling by recruiting osteoclast precursors and directing osteoclast differentiation, and (b) indirectly responsible by signaling to nearby healthy osteocytes that, in turn, regulate osteoclastogenesis. In this in vitro study, apoptotic osteocytes were found to increase osteoclast precursor migration and osteoclast formation. Inhibition of the osteoclastogenic protein, receptor activator of nuclear factor kappa B ligand (RANKL), in conditioned medium abolished the osteoclastogenic effect of apoptotic osteocytes. Healthy osteocytes surrounded by apoptotic regions were modeled by applying apoptotic osteocyte conditioned medium to healthy osteocytes. These cells also promoted osteoclastogenesis, and had increased expression of macrophage colony stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF). Inhibition of these factors abrogated the pro-osteoclastic effect of healthy osteocytes conditioned by apoptotic osteocytes. These findings support the hypothesis that apoptotic osteocytes directly and indirectly, by signaling to nearby healthy osteocytes, initiate osteoclastogenesis. One limitation of our and other conventional in vitro models is the lack of real-time cell communication and physiologically-relevant mechanical environment. Using a microfluidics approach, a miniature fluid shear delivery system was created for in vitro osteocyte cultures. The purpose of this microsystem was to increase control of the cell microenvironment for subsequent integration into scalable screening platforms or co-culture systems for studying osteocyte mechanobiology under physiological loading conditions. Fluid shear stress was periodically applied without external pumping using a deflecting elastomer membrane, where up to 2 Pa of oscillating shear stress was possible by manipulating membrane dimensions. Osteocyte culture, viability and calcium response were demonstrated in the microdevice. Further studies should attempt to characterize calcium signaling in osteocytes which, using a conventional macro-scale system, was found to dependent on cell-cell communication.