VictorJuiz/thesis huggingface dataset:
The Role of Hedgehog-Gli Pathway Regulators in Skin Development and Tumorigenesis
Keywords: Hedgehog
Gli
Basal cell carcinoma
skin

Proper control of Hedgehog (Hh) signaling is critical for hair follicle morphogenesis and ectopic Hh pathway activity is a hallmark of basal cell carcinoma (BCC), the most common type of skin cancer. Mutations in Hh pathway components such as the Hh-binding receptor PATCHED1 (PTCH1) are frequently found in BCC. However, how Hh pathway activation disrupts normal skin homeostasis to promote BCC formation remains poorly understood. Gli2, the major mediator of Hh signaling is essential for hair follicle development and its overexpression in the epidermis induces BCC formation. Despite the importance of Gli2 in the skin, how it is regulated during skin development and tumorigenesis is unclear. Using a genetic approach with loss-of-function mouse mutants and primary keratinocyte cultures, I have uncovered the distinct and overlapping functions of Sufu and Kif7, two evolutionarily conserved regulators of the Hh pathway, during skin development and tumorigenesis. Sufu and Kif7 play opposing roles in Hh signaling through the regulation of Gli2 subcellular distribution, and Kif7 performs distinct Sufu-dependent and –independent functions. In addition, deletion of both Sufu and Kif7 in embryonic skin leads to complete loss of follicular fate and compromised epidermal differentiation. In the adult skin, inactivation of Sufu does not drive BCC formation and requires additional genetic alterations such as the loss of Kif7. Using a Ptc1 mouse model for BCC, I have identified previously unrecognized molecular pathways and cellular events involved in BCC pathogenesis. This includes, aberrant cell cycle progression, loss of cell cycle checkpoint regulation, and suppression of the p53 response. Overall my work provides critical insight into the molecular control of Hh signaling and the downstream events driving BCC formation.
A Study of the Principals' and Teachers' Perceptions of the Effects of Collegial Approach to Implementing School Self-evaluation in Selected Hong Kong Schools
Keywords: School Self-Evaluation
School Cultural Changes
Professional Learning Communities
Principal Leadership
Chinese Cultural Values
School Improvement
Quality Education
Quality Assurnace
Principal's Attitude
Teacher's Attitude
Primary and Secondary Education

ABSTRACT Starting in September 1997, the Hong Kong Education Commission has adopted School Self-Evaluation as part of the framework of Quality Assurance Mechanism for promoting quality education culture in schools. Under a project initiated by the Chinese University of Hong Kong, some primary and secondary schools started to implement school self-evaluation in their school. The main purpose of this study was to investigate the effectiveness of this self-evaluation framework based on principals’ and teachers’ perception of these participating schools. The relationships among school self-evaluation, school cultural changes, teacher co-operative learning culture and principal leadership are also explored. Furthermore, this study examines whether other factors, such as school type, teacher gender, teacher ranking position, teachers’ year-of-teaching-career and Chinese cultural values, will affect the implementation of self-evaluation in schools. A mixed approach of methodology was adopted for this research work. The findings indicated that school self-evaluation can initiate teacher co-operative learning culture, which in turn effects cultural changes in these schools. Also, the above named components play specific roles in the school self-evaluation implementation – school cultural change process: teacher co-operative learning culture acts as mediator, school self-evaluation as moderator and principal leadership as change facilitator.
Ethical Complexities in the Virtual World: Teacher Perspectives of ICT Based Issues and Conflicts
Keywords: digital ethics
ICT
technology
Facebook
teacher perspectives
ethical issues
moral work of teachers
morals

Shawn Lennie, Ethical Complexities in the Virtual World: Teacher Perspectives of ICT Based Issues and Conflicts, Doctor of Philosophy, CTL, OISE, 2013. Using a qualitative research methodology, this study explores the perceptions that K-12 teachers have on the ethical issues they have experienced as a result of, or in relation to, ICT. Participants included 10 practicing teachers who had identified experience with ICT based issues in their teaching practice. Each participant engaged in two semi-structured interviews focused on the research topic. The first interview explored the perceptions and experiences that the participants had with ICT based issues in their practice, while the second involved an examination of eight vignettes involving ICT based issues that were ethical in nature. The use of this approach provides a descriptive account of the experiences and perceptions of the participants in the study. Results from the study highlight the impact that ethical issues involving technology have on the moral work of teachers and the challenges that emerge as teachers attempt to identify morally responsible ways to respond to the complex and dynamic challenges that they face. Participants demonstrate a heightened sensitivity to ethical issues involving technology that compromise the safety and well-being of children, such as cyber-bullying, as well as those that compromise professional and academic integrity, such as plagiarism. Results also reveal the predominant use of subjective moral judgment when evaluating the moral significance of ICT based issues and reluctance on the part of teachers to challenge the inappropriate use of technology by their colleagues. This contrasts with a strong belief that teachers play an important role as moral models for students who are developing an understanding of what constitutes responsible digital behaviour. These results are significant to scholarship on teacher professionalism, digital ethics and citizenship, and policy development relating to ICT based issues.
The Effects of Disc1 on Neurodevelopment in the Mouse
Keywords: Schizophrenia
DISC1

Over the past decade, a combination of genetic, biological and imaging approaches have identified Disrupted-in-Schizophrenia-1 (DISC1) as a strong susceptibility gene for psychiatric illnesses including schizophrenia, bipolar disorder and major depression. DISC1 regulates various neurodevelopmental processes including neurogenesis, neuronal migration, neurite outgrowth, spine development and neurotransmitter signaling. Human post-mortem brain studies in schizophrenia have revealed some consistent neuropathological findings such as abnormal neuron morphology, reduced spine density, aberrant cytoarchitecture and interneuron deficits in the dorsolateral prefrontal cortex and hippocampus. However, the etiology and development of these histological abnormalities remain unclear. Therefore, we investigated brain histology of two independently-derived Disc1 mutant mice with point mutations (Disc1-Q31L and -L100P). Both mutants displayed reductions in cortical neuron density, decreased neurogenesis and altered cortical neuron distribution when compared to wild-type controls. Frontal cortical pyramidal neurons had shorter dendrites and reduced dendritic surface area. Spine density was also reduced on apical dendrites of both frontal cortical and hippocampal pyramidal neurons. In addition, we observed a pronounced defect in tangential migration of interneurons in the embryonic brains of Disc1-L100P mutants when compared to wild-type mice. Adult Disc1-L100P mutants also have selective alterations of calbindin- and parvalbumin-expressing interneurons in the cortex and hippocampus, decreased glutamate decarboxylase 67/parvalbumin co-localization and mis-positioned interneurons across the neocortex. Finally, we investigated the effects of GSK3α inactivation on frontal cortical neuron morphology in Disc1-L100P mutants. Disc1-L100P, GSK3α -/- and 100P/100P;GSK3α double mutants all exhibited significant reductions in dendritic length and surface area while spine density was significantly reduced only in Disc1-L100P and 100P/100P;GSK3α +/- mutants when compared to wild-type mice. Interestingly, spine density was rescued in 100P/100P;GSK3α -/- double mutants and comparable to wild-type mice. Overall, these findings are consistent with the anomalies seen in post-mortem schizophrenia studies and other Disc1 mutant mouse models, providing further evidence that DISC1 participates in neurodevelopment. GSK3 is only one of many pathways modulated by DISC1, so more research is required to fully understand how the network of DISC1-interacting proteins is involved in the pathophysiology of psychiatric disorders. Better understanding of these mechanisms could lead to the development of new treatments.
Histone Crosstalks involving H3 Phosphorylation and their Role in Transcriptional Regulation
Keywords: histone
chromatin
transcription
phosphorylation
acetylation
crosstalk
MSK1
polycomb

Histone phosphorylation is often a direct outcome of activated intracellular signaling pathways, and functions to translate extracellular signals into appropriate biological outputs such as changes in gene expression. Growth factors and cellular stress trigger rapid and transient expression of immediate-early genes (such as c-fos, c-jun) in mammalian cells, and their induction strongly correlates with a transient phosphorylation of S10 and S28 on histone H3. While many signaling cascades that lead to H3 phosphorylation have been mapped out, mechanistic details of the downstream events and how H3 phosphorylation contributes to transcriptional activation are still poorly defined. To investigate the direct effects of H3 phosphorylation on transcription, we targeted the H3 kinase MSK1 to endogenous c-fos promoter, and found that this is sufficient to activate its expression. Moreover, targeting MSK1 to the tissue-specific -globin gene induces H3S28 phosphorylation and reactivates expression of this polycomb-silenced gene. Mechanistically, H3S28 phosphorylation not only disrupts binding of polycomb repressive complexes, but also induces a methyl-acetylation switch of the adjacent K27 residue. This provides the first indication that H3 phosphorylation is involved in antagonizing polycomb silencing. To further identify post-translational modifications (PTMs) that function together with MSK1-mediated H3 phosphorylation, I developed a novel nucleosome purification approach called Biotinylation-assisted Isolation of CO-modified Nucleosomes (BICON). This technique combines in vivo biotinylation by BirA and H3 phosphorylation by MSK1, allowing enrichment of phosphorylated nucleosomes using streptavidin. I found that MSK1-phosphorylated nucleosomes are hyper-acetylated on H3 and H4, and importantly, I identified a trans-tail crosstalk between H3 phosphorylation and H4 acetylation on K12. This proof-of-principle study demonstrates that BICON can be further adapted to study PTMs and crosstalks associated with other histone-modifying enzymes. Taken together, work described in this thesis shows that histone H3 phosphorylation can initiate additional PTM changes on other residues within the nucleosome, and such crosstalk plays an important role in regulating gene expression.
A Variant of Lehmer's Conjecture in the CM Case
Keywords: a variant of Lehmer's conjecture
cusp forms
Fourier coefficients

Lehmer's conjecture asserts that τ(p) ≠ 0, where τ is the Ramanujan τ-function. This is equivalent to the assertion that τ( n) ≠ 0 for any n. A related problem is to find the distribution of primes p for which τ(p) ≡ 0 (mod p). These are open problems. However, the variant of estimating the number of integers n for which n and τ( n) do not have a non-trivial common factor is more amenable to study. More generally, let f be a normalized eigenform for the Hecke operators of weight k ≥ 2 and having rational integer Fourier coefficients {a(n)}. It is interesting to study the quantity (n, a(n)). It was proved by S. Gun and V. K. Murty (2009) that for Hecke eigenforms f of weight 2 with CM and integer coefficients a(n)[special characters omitted] for some constant Uf. We extend this result to higher weight forms.
1H NMR-based Metabolomics for Elucidating the Mode of Action of Ccontaminants in the Earthworm Eisenia Fetida after Sub-lethal Exposure
Keywords: Ecotoxicology
Environmental Chemistry
Metabolic Profiling
PAHs
PFOA
PFOS
Soil contamination
Earthworms

There is a growing need to develop rapid and cost-effective ecotoxicological tools for risk assessment because traditional methods examine endpoints such as mortality, which do not provide any insight into the mode of action (MOA) of the chemical. Research presented within this thesis illustrates the potential of 1H NMR-based metabolomics as a rapid and routine ecotoxicological tool that can elucidate a chemical’s MOA and also aid in the identification of metabolites of exposure. Metabolomics involves measuring the fluctuations in the endogenous metabolites of an organism within a cell, tissue, bio-fluid or whole organism in response to an external stressor. We focused on the model polycyclic aromatic hydrocarbon (PAH) phenanthrene, and the perfluoroalkyl acids (PFAAs) perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), due to their recalcitrant nature and widespread prevalence in soil environments. 1H NMR-based metabolomics analysis of the exposure of Eisenia fetida earthworms to sub-lethal phenanthrene exposure via filter paper contact tests revealed a concentration-dependent two-phased MOA: a linear correlation between the metabolic response and exposure concentration at low concentrations followed by a plateau in the responses at high concentrations. Alanine, glutamate, maltose, cholesterol and phosphatidylcholine emerged as potential indicators of phenanthrene exposure. An increased energy demand and an interruption in the conversion of succinate to fumarate in the Krebs cycle were observed due to phenanthrene exposure. Sub-lethal PFOA and PFOS exposure to E. fetida via contact tests for two days revealed heightened responses with higher PFOA and PFOS concentrations. Leucine, arginine, glutamate, maltose, and ATP were identified as potential indicators of PFOA or PFOS exposure. E. fetida responses were then investigated after exposure for two, seven and fourteen days to an artificial soil that was spiked with sub-lethal PFOS concentrations. An exposure time-dependent operation of two separate MOAs were identified. Both the contact tests and artificial soil exposure studies identified an elevation in fatty acid oxidation, a disruption in energy metabolism and biological membrane structure, and also an interruption of ATP synthesis following PFOA and PFOS exposure. This thesis illustrates the promise of NMR-based metabolomics as a routine tool for ecotoxicological assessment of contaminated sites.
Eager, Lazy, and Other Executions for Predicative Programming
Keywords: software engineering
programming methodology
formal methods
predicative programming
operational semantics
evaluation strategies
lazy evaluation
bound analysis

Many programs are executed according to the conventional, eager execution order, for which verification of execution costs is well-understood. However, there are other execution orders in use. One such order in common use is lazy execution or lazy evaluation, which is mostly demand-driven. Laziness supports better decompositions of algorithms, e.g., into modular producers and consumers, which enables compositional reasoning of answer correctness, but then timing correctness is more elusive. This thesis gives a formal method for verifying lazy timing, compositional with respect to program structure; it is an extension of a predicative programming theory. Predicative programming theories are formal methods that unify both specifications and programs as predicates or boolean-typed expressions over memory state and other quantities of interest. Their strengths are mathematical simplicity and support of program development and verification by incremental refinements. Among these theories, Hehner's a Practical Theory of Programming has the further strength of leaving termination and timing open rather than a built-in, and therefore is a flexible substrate for various timing schemes corresponding to various execution strategies. We use this substrate for our method for lazy timing. This thesis also proves soundness of the eager timing scheme in Hehner's work with respect to an eager operational semantics, and our lazy timing scheme with respect to a lazy operational semantics. Thus, if refinements promise an upper time bound, then execution actually stops within that time. Lastly, this thesis outlines a space of more operational semantics. It is possible ground for more execution strategies.
Characterization of Kallikrein 6 N-glycosylation Patterns and Identification of Sialylated Glycoproteins in Ovarian Cancer
Keywords: glycosylation
ovarian cancer

Ovarian cancer is the leading cause of death among all gynecological disorders. Aberrant glycosylation, or more specifically, increased sialylation of proteins has been observed in this malignancy. Several sialyltransferase genes have been shown to be up-regulated at both mRNA and and protein levels in a number of cancers, including that of the ovary. In the present study, we have analyzed the glycosylation patterns of kallikrein 6 in the context of ovarian cancer. We have discovered that the carbohydrate structures found at the single N-glycosylation site of kallikrein 6 derived from ovarian cancer cells found in the ascites fluid of ovarian cancer patients is enriched in sialic acid moieties and has an increased branching pattern when compared to controls. We have also developed a reliable anion-exchange HPLC-based methodology capable of quantifying different glycoform subpopulations of kallikrein 6 in serum and other biological fluids, which was capable of differentiating between samples from ovarian cancer patients and healthy controls. A variety of classic molecular biology and mass spectrometry based techniques were utilized in these experiments. Based on the results of the analysis of kallikrein 6 glycosylation and other literature reports showing upregulated sialylation of proteins in ovarian cancer, we have also identified sialylated glycoproteins from ovarian cancer proximal fluids and conditioned media of ovarian cancer cell lines. Sialylated proteins were enriched utilizing lectin affinity or hydrazide chemistry. In total, 333 sialylated glycoproteins and 579 glycosylation sites were identified. A list of 21 potential candidate ovarian cancer biomarkers was produced from proteins that were identified solely in ovarian cancer proximal fluids, which could form the basis for any future studies.
HIV Vulnerability amongst South Asian Immigrant Women in Toronto
Keywords: HIV Risk
South Asian Women
Immigrant Women
Social Theory of Gender
Power Ideologies
Anti-racist Frameworks
Feminist Theories
Narratives
Structural Factors
Women PHAs

This thesis focuses on the structural and behavioural factors that placed South Asian immigrant women living with HIV/AIDS in the Greater Toronto Area at risk. Informed by Connell's social theory of gender (1987), this study examined the role of hegemonic masculinity in legitimizing male power and contributing to the HIV risk of these women. By conducting one-on-one interviews with 12 HIV-positive immigrant women, meaningful constructions of the women's narratives and accounts of their experiences relative to HIV were created. This study examined the intersection of power ideologies such as gender, race and class in specific contexts as they generated particular experiences that affected women's risk for HIV. Following a community-based research approach, a collaborative relationship was established with the Alliance for South Asian AIDS Prevention where qualitative methods of analysis and an inductive approach with an iterative process were followed. Factors such as isolation, economic dependence on their husbands, discrimination, racism, investment in psychologically and emotionally abusive relationships, combined with the absence of support from their family of origin exacerbated the women's risk of HIV infection. The strong ties exhibited by most of the women to their religious/ethnic communities helped sustain a gender-based social hierarchy. To facilitate dialogue and social change for South Asian women, gender and culture need to be situated in social and historical contexts. As such, programs should be understood within a larger critical understanding of the social power relations and history of Canadian immigration patterns. Using anti-racist frameworks, initiatives should address violence against women, while tackling interrelated issues (i.e., housing, poverty, etc.). This work draws attention to oppressions through the experiences of a community of women who are rarely given a voice within the context of research on HIV/AIDS. It will be also helpful for Ontario’s HIV prevention strategy and the field of women's sexual health.
Architecting the Optics, Energetics and Geometry of Colloidal Quantum Dot Photovoltaics
Keywords: Photovoltaics
Solar Cell
Quantum Dot
Semiconductor
Device Architecture

Solution processed solar cells offer the promise of a low cost solution to global energy concerns. Colloidal quantum dots are one material that can be easily synthesized in and deposited from solution. These nanoparticles also offer the unique ability to select the desired optical and electrical characteristics, all within the same materials system, through small variations in their physical dimensions. These materials, unfortunately, are not without their limitations. To date, films made from colloidal quantum dots exhibit limited mobilities and short minority diffusion lengths. These limitations imply that simple device structures may not be sufficient to make an efficient solar cell. Here we show that through clever manipulation of the geometric and energetic structures, we can utilize the size-tunability of CQDs while masking their poor electrical characteristics. We further outline the physical mechanisms present within these architectures, namely the utilization of a distributed built-in electric field to extract current through drift rather than diffusion. These architectures have consequently exceeded the performance of legacy architectures such as the Schottky cell. Finally, we discuss some of the limiting modes within these architectures and within CQD films in general including the impact of surface traps and polydispersity in CQD populations. Through the development of these novel architectures, the power conversion efficiency of CQD solar cells has increased from ~3.5% to 7.4%; the highest efficiencies yet reported for colloidal quantum dot solar cells.