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    Teacher Identity and Ethical Responsibility: An Exploration Through Literary Representations

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    This dissertation investigates the meaning of ethical responsibility as a fundamental feature of teacher identity. While there is a tendency to construct both responsibility and teacher identity in terms of instructional practice, agency, and competency, this research foregrounds understudied complexes of dependency, uncertainty, and failure. Drawing on continental philosophy and psychoanalysis, I frame teacher identity from the vantage of concepts of natality, hospitality, and relationality to illuminate a central conflict of responsibility that places the teacher in a tension between an idealized conception of egoless passivity and the emotional situation of an ego-based affect of self-preservation and ego interests. Conflict and anxieties result, constituting the teacher’s emotional world. Through my investigation of this tension, I offer critique of the all-loving teacher figure by exposing how this idealization conceals the implication of education in discourses of aggression, exclusion, and social control. Literary portrayals of child/adult and student/teacher relationships in novels provide novel data to examine these tensions

    Elucidating Cell Fate Regulation of the Bone Marrow Vascular Niche Through Development of Engineered Extracellular Matrices

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    Haematopoietic stem and progenitor cells (HSPCs) are crucial to the curative treatment of a variety of leukaemias and autoimmune diseases. However, their rapid differentiation and exhaustion within 72 hours ex vivo poses a barrier to efficient treatment. Here, we have developed a culture method that mimics that of the in vivo haematopoietic vascular niche in order to extend viability and maintain multipotency of HSPCs. The two-factor approach combined the paracrine support of endothelial cells as well as the structural and chemical support of an engineered two-dimensional scaffold comprised of several extracellular matrix (ECM) components. HSPCs that were co-cultured on ECM-mimicking scaffolds maintained higher viability in culture for up to seven days in comparison to solo-culture counterparts, and functional tests revealed an improvement in colony formation potential. Continued development of the culture system and understanding of the molecular pathways at play can lead to improved patient outcomes after transplantation

    The Role of TFEB and TFE3 in Mediating Mitochondrial and Lysosomal Adaptations in Skeletal Muscle

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    Skeletal muscle adapts to external stimuli to meet metabolic and energetic needs imposed on it. As a highly metabolic tissue, mitochondria are the energetic cores of the cell and are central to the adaptive nature of muscle. Essential to the maintenance of mitochondria is the process of mitophagy, a selective form of autophagy through which damaged mitochondria are removed and degraded via the lysosome. Lysosomes and autophagy machinery are regulated by transcription factors, TFEB and TFE3, that are responsive to cellular stresses including exercise, disuse and starvation. Our work aimed to address the role of TFEB and TFE3 in mediating the adaptability of mitochondria in response to exercise and disuse. To understand the role of TFEB and TFE3 in mediating the effects of exercise, we employed an in vitro model and silenced the expression of TFEB and TFE3. While the absence of TFEB or TFE3 alone impacted the mitophagic response to a single bout of contractile activity, mitochondrial and lysosomal function improved with repeated bouts. These data support the notion that exercise stimulates multifaceted and often redundant signaling pathways to promote adaptations. However, the absence of TFEB and TFE3 together abolished functional mitochondrial and lysosomal adaptations to contractile activity, indicating that both TFEB and TFE3 together are required for adaptations. We also sought to evaluate the role of TFE3 in atrophic conditions using denervation of the sciatic nerve as a model of disuse in both males and females. Basally, females exhibited increased lysosomal content, higher mitophagy flux and improved mitochondrial function. In response to denervation however, females appeared to preferentially preserve mitochondrial content at the expense of function by reducing mitophagy flux. Curiously, the absence of TFE3 in vivo preserved muscle mass in males and mitochondrial content in both sexes following denervation but this in turn increased mitochondrial dysfunction similar to wildtype females. The significance of this work is that we provide further evidence of how lysosomes and mitochondrial turnover mediate mitochondrial adaptations to both positive and negative stimuli. Our data also highlight the importance of investigating the effect of biological sex, revealing distinct mitochondrial and lysosomal phenotypes in males and females

    Heterogeneity Exhibited in Cells that Escape from Drug-Induced Senescence

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    Maintaining genomic integrity is key in the prevention of cancer. To limit the accumulation of mutations over time and stop damaged cells from continuing to proliferate and further gain subsequent mutations, intrinsic terminal cellular programs are activated. Senescence, an evolutionarily conserved stress state that traditionally has been viewed as an irreversible state of cell cycle arrest, acts as a tumour suppressive barrier. However, senescence acts as a double-edged sword, as senescent cells accumulate and contribute to age-associated diseases by altering tissue microenvironments and disrupting tissue homeostasis. Atrophied telomeres, mitotic errors, diminished DNA damage response and loss of nuclear envelope integrity all contribute to the increased rate of the formation of senescent cells during aging. In this study, I observed an age-associated accumulation of cytoplasmic DNA, in the form of micronuclei and chromatin bridges. I extended these finding to rare segmental accelerated aging diseases such as classical and non-classical Hutchinson-Gilford progeria syndrome, and Dyskeratosis Congentia. I further reveal that age-associated micronuclei and chromatin bridges undergo DNA damage and are recognized by cGAS that likely initiates an innate immune inflammatory response. My findings, along with recent reports showing chromosomal instability in senescent cells, led me to hypothesize that senescence may be reversible. To address this question, I utilized a drug-induced senescence model in BJ fibroblast and leukemia cells. Performing cloning experiments and monitoring single cells, I show that escape from a drug-induced senescent-like state occurs in a rare sub-population of cells for both transformed and normal cells. The escaped population displayed phenotypic heterogeneity, with respect to drug-response, gene expression, rate of proliferation and duration of arrest. RNA-sequencing highlighted the extensive transcriptional and metabolic reprogramming senescent cells undergo. Inhibition of lysosome function with FDA approved drug, chloroquine, specifically kills some senescent leukemia cells. By stratifying acute myeloid leukemia patients based on expression of senescent-associated gene signatures, I show that senescent gene signatures are associated with poorer overall survival. My findings provide evidence challenging the previous notion that senescence is a permanent state of cell cycle arrest and may be a mechanism which cancer cells exploit to survive therapy

    Extreme In-Plane Thermal Conductivity Anisotropy in Rhenium-Based Dichalcogenides

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    Anisotropies in thermal conductivity are important for thermal management in a variety of applications, but also provide insight on the physics of nanoscale heat transfer. As materials are discovered with more extreme transport properties, it is interesting to ask what the limits are for how dissimilar the thermal conductivity can be along different directions in a crystal. In this thesis the thermal properties of Rhenium-based transition metal dichalcogenides (TMDs), specifically Rhenium Disulfide (ReS2) and Rhenium Diselenide (ReSe2) are reported, highlighting their extraordinary thermal conductivity anisotropy. Along the basal crystal plane of ReS2, a maximum of 169 ± 11 W/mK is detected along the b-axis and a minimum of 53 ± 4 W/mK perpendicular to it. For ReSe2, the maximum and minimum values of 116 ± 3 W/mK and 27 ± 1 W/mK are found to lie 60◦ and 150◦ away from the b-axis, along the polarization direction of some of the principal Raman modes. These measurements demonstrate a remarkable anisotropy of 3.2× and 4.3× in the conductivity within the crystal basal planes, respectively. The through-plane thermal conductivities, recorded at 0.66 ± 0.01 W/mK for ReS2 and 2.31 ± 0.01 W/mK for ReSe2, highlight the impact of their layered structures, contributing to notably high in-plane to through-plane thermal conductivity ratios of 256× for ReS2 and 50× for ReSe2. This research demonstrates the unique thermal properties that these comparatively underexplored TMDs have, shedding light on the need for further exploration into the intricate thermal behavior of such materials, while underscoring their potential significance for future applications in the fields of semiconductor devices and nanotechnology

    Robust MircroRNA detection by Capillary Electrophoresis

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    MicroRNA (miRNA) are short single-stranded RNA molecules that function as post-transcriptional regulators in gene expression, The abnormal expression of small subsets of miRNAs, termed “miRNA fingerprints”, have been found as potential biomarkers in diagnosis of various diseases including cancers. However, none of miRNA-based biomarkers has been approved yet for clinical use due to the lack of a robust quantitative method for miRNA analysis. To address this issue, there have been significant efforts towards developing robust quantitative miRNA detection methods. Among a variety of initiatives, DQAMmiR is a promising approach developed by our lab which is capable of direct, quantitative analysis of multiple miRNAs in capillary electrophoresis (CE). In my PhD project, I have been focusing on investigating and improving the robustness of DQAMmiR to increase its applicability for practical use. Firstly, I demonstrated that DQAMmiR is capable of directly quantitating miRNA in crude cell lysates, indicating its robustness to the change of sample matrices, revealing its great potential to be used to analyzing miRNAs in biological samples directly without the need for complex sample processing. Secondly, I developed a second-generation DQAMmiR by replacing the ssDNA probes with the electrically neutral peptide nucleic acid (PNA) probes, which further improves the robustness of the assay by removing the need for single-stranded DNA binding protein (SSB) in the assay. Thirdly, to increase the applicability of the assay, I introduced a new sample preconcentration technique based on the integration of field-amplified sample stacking (FASS) and isotachophoresis (ITP) prior to CE separation in DQAMmiR, which successfully decreases its limit of quantification (LOQ) by 140 times. Lastly, I investigated the applicability of DQAMmiR for analyzing urinary miRNAs. I demonstrated that the concentration ratio of two miRNAs, miR-16 and miR-21, could be relative stable from different urine samples collected from the same person, although the individual concentrations of these miRNAs varied significantly in these samples. These findings suggests that the ratiometric measurements between multiple miRNAs in urine would serve as better biomarkers than individual miRNA concentrations for clinical diagnostic tests. And DQAMmiR would be an ideal analytical methodology for the development and use of such tests

    Evaluating the Performance of Existing and Novel Equivalence Tests for Structural Equation Modeling

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    It has been suggested that equivalence testing (otherwise known as negligible effect testing) be used to evaluate model fit within structural equation modeling (SEM). This dissertation is composed of two studies that propose novel equivalence tests based on the popular RMSEA, CFI and SRMR fit indices. Using Monte Carlo simulations, each study compares the performance of these novel tests to other existing equivalence testing-based fit indices in SEM, as well as to other methods commonly used to evaluate model fit. In each study, results indicate that equivalence tests in SEM have good Type I error control and display considerable power for detecting well-fitting models in medium to large sample sizes. At small sample sizes, relative to traditional fit indices, equivalence tests limit the chance of supporting a poorly fitting model. Both studies also present illustrative examples to demonstrate how equivalence tests can be incorporated in model fit reporting. We recommend that equivalence tests be utilized in conjunction with descriptive fit indices to provide more evidence when evaluating model fit

    Talking Through Water: Experts, Environmentalists, and Their Publics, 1944 to 1977

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    In response to the repeated droughts of the early twentieth century in northeastern North Dakota, the U.S. Bureau of Reclamation planned a large-scale diversion project called the Garrison Diversion Unit (GDU). The GDU, a multipurpose engineering project, received its first approval in 1944 promising to redirect water from the North Dakota segment of the Missouri River through a system of dams, reservoirs, and canals for the purpose of irrigation, hydroelectricity, industrial and municipal water supply, expansion of recreation areas, and enhancement of fish and wildlife areas. The engineers who planned the GDU failed to consider the environmental impacts or international political implications of the diversion of the project’s irrigation return flows from one watershed to another and across the border into Canada. Although the project itself remains unfinished to this day, the GDU debates that raged between 1940 and 1977 provide invaluable insights into the professionalization of environmental experts, international water diplomacy, and the role of the public in the realization of mega water projects. From the GDU’s inception, various groups and individuals have contested this project. This dissertation examines how knowledge of water, technology, and public policy was mobilized in various sites of debate during a critical period in the development of environmental policy in America. I analyzed three sites of the debate: the promotion of the project by its leading engineering figurehead, the scientific and environmental organizations and committees that debated the environmental impacts of the project, and the international commission that engaged local users for the first time to determine the project’s future. I found that economic, social, political, and cultural arguments and language, rather than scientific evidence, shaped the dialogue, allowing both experts and non-experts to engage in the debate using various types of knowledge. This dissertation argues that the GDU, the reports it generated, and the talk surrounding it did not only describe the physical engineering edifices being proposed; they also and perhaps more importantly, revealed the GDU as an envirotechnical system that provided experts and non-experts alike with opportunities to communicate, translate, and challenge one another’s ideas about technology and the environment

    Gender in Autistic Late-Diagnosis Narratives

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    Major Research Paper (Master's), Critical Disability Studies, School of Health Policy and Management,Faculty of Health, York UniversityIn recent years, the discussion of how gender impacts autism diagnosis has been popular in both academic and lay contexts, such as social media. In psychology, the idea of the Female Autism Phenotype has particularly caught the attention of researchers as a possible explanation for why autistic women and girls are diagnosed later. However, studies related to gender and late autism diagnosis often do not consider how autistic adults personally perceive this link. Using thematic analysis, this study analyzes the blogs of late-diagnosed autistic adults to understand whether and how these individuals perceive a link between their gender and their timing of diagnosis. Critical discourse analysis is also used to understand how understandings of autism, group affiliations, and other factors may influence these perceptions. The study found that while the Female Autism Phenotype and similar theories have been favoured by bloggers in years past, they have not been regularly discussed by late-diagnosed bloggers in recent years. This indicates that autism researchers who focus on gender’s role in late-diagnosis may not be in line with autistic community priorities regarding autism research

    The Construct of Freedom: Comparing Baldwin and Jacobs

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    This essay won the Department of English's 2000-level Essay Prize in 2023. The Department of English awards prizes for the best essay written in courses at each of the four year levels. Faculty members may nominate students for this award.America is often colloquially referred to as the “land of the free”. However, what said freedom actually looks like differs depending on one’s perspective. In “Incidents in the Life of a Slave Girl” by Harriet Jacobs, because the events take place before the American civil war, there was a very basic standard of “freedom” for Black Americans, which was not to be enslaved or owned by another person. In “Going to Meet the Man” by James Baldwin, however, the main character desires the freedom to oppress Black Americans and enact racism upon them. Not only is freedom a social construct, the idea of “absolute freedom” is neither realistic nor achievable, because one idea of freedom may infringe on another’s idea of freedom, as occurs in these texts. In comparing the two, it is made clear that the freedom of Black Americans directly clashes with the freedom of White American oppressors

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