VictorJuiz/thesis huggingface dataset:
STEM Discourses and Distinction in An Elite School: Leadership through Relationships to Knowledge
Keywords: Bourdieu
Canada
Elite Schools
Leadership
Relationship to Knowledge
STEM

STEM (Science, Technology, Engineering and Mathematics) has become an influential discourse in many educational contexts. Despite varied conceptualizations and practices of STEM and STEM education, main goals of these discourses have largely been to support skilled STEM workforce to compete in the global economies. Although there is a plethora of publication regarding STEM education, a still underexplored context for STEM education is elite private schools. The rationale for examining STEM education discourses in elite private schools stems from these schools’ roles in perpetuating the status quo and securing privilege to dominant social groups. They do so by supporting their students to cultivate recognizable forms of capital, a sense of distinction, and entitlement to their privilege. As such, they allow their students to envision leadership roles. Hence, examining how STEM education is conceptualized and practised in these schools can provide understanding of how elite identifications might be facilitated through available STEM discourses and related meanings of excellence and distinction. This is particularly significant when acknowledging that STEM fields tend to have and produce their own status hierarchy. Through critical discourse analysis, this research examines STEM discourses that are available in an elite independent, co-educational, secondary, day school in Ontario, Canada, and how educators in this school conceptualize distinction in and through STEM (education). Using semi-structured interviews with teachers/administrators and document analysis of the school’s website and viewbook, this research further theorizes how these constructs might contribute to elite identifications. This research shows that, in contrast to the narrative of skilled STEM workforce, in this elite school there is an overarching discourse of leadership that defines what distinction in STEM means and what tends to be embraced, rejected and/or recontextualized regarding dominant STEM discourses. Such a leadership discourse subsumes other discourses of impact, intellectual distinction, competitive achievements and active participation. These discourses and related conceptualizations and practices can support students to develop particular “relationship[s] to knowledge” (Bourdieu, 2004) or, more specifically, particular harmonised relationships to STEM knowledge as thinkers, experts and risk-takers, allowing students as such to envision and assume leadership roles and to validate their high status/elite positions.
The Unacknowledged Ones: An Investigation of The Resistance of LGBTQI+ Syrians
Keywords: LGBTQI+
Refugee
Resistance
Syrian

The ongoing tribulations in Syria have catapulted the number of displaced refugees to devastating levels. The trauma experienced by Syrian refugees extends onward from Syria; Syrian Canadians, regardless of their citizenship status, face a host of isolating experiences such as discrimination, racism, Islamophobia. Lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+). Syrians are particularly susceptible to these injustices. LGBTQI+ Syrians face discrimination from multiple sources, including homophobia from their cultural groups, and racism, Islamophobia, and homophobia from Western cultures. This can contribute to the development of psychological difficulties, and appreciably compromise their integration into social networks. The purpose of this study was to investigate how the lived experiences of discrimination and oppression impacted the lives of the eleven LGBTQI+ Syrians that were interviewed as participants in this research, and the types of resistance and resilience-based coping strategies that they utilized to promote successful integration of their multiple identities while settling into Canadian society. This study employed a qualitative approach and was informed by minority stress theory while operating within an intersectional framework. Additionally, the study used a community-based, narrative approach that explored the tribulations and resistance strategies of LGBTQI+ Syrians concerning their intersecting identities. The main finding of this dissertation revealed that there is ongoing discrimination which left the participants feeling inferior and led to complications in integrating their identities within a Syrian and Canadian context. Results indicated three significant themes regarding coping strategies that participants utilized in response to experiences of discrimination, humour, therapy, and social support. This dissertation added empirically supported culturally responsive practice insights, specifically tailored culturally responsive training and community resources, which are expected to improve the design and delivery of interventions that aimed to promote psychosocial wellbeing and positive experiences of immigrating to Canada for LGBTQI+ Syrians.
Peptide-based Inhibitors of Bacterial Small Multidrug Resistance Proteins
Keywords: Antibiotic Drug Resistance
Bacterial Multidrug Resistance
Efflux Pump Inhibitors
Membrane Protein-Protein Interactions
Membrane-Active Peptides

Antibiotic resistance is a global crisis that first appeared in 1940, shortly after the introduction of penicillin. With the introduction of each new antibiotic, bacteria compensated with mechanisms to avoid their lethal effects. As an alternative approach to conventional antibiotics, this thesis explores a novel, rational drug design to inhibit a resistance mechanism of antibiotic-resistant bacteria. One resistance mechanism involves membrane-embedded multidrug efflux pumps that can effectively extrude an array of substrates, including common antibiotics, dyes, and biocides. Among these pumps are the small multidrug resistance (SMR) membrane transport proteins that consist of four transmembrane (TM) helices, which homodimerize in an anti-parallel fashion through a GG7 motif in TM4. To disable this pump, we synthesized a series of TM4 peptides that contain this dimerization motif designed to disrupt the dimer interaction and reduce substrate efflux. The peptides contain two terminal tags: a C-terminal tri-lysine tag to direct the peptides toward the negatively-charged bacterial membrane, and an uncharged N-terminal sarcosine (N-methyl-glycine) tag to promote membrane insertion. A series of these TM peptides were designed to target various SMRs, and as the GG7 dimerization motif was highly conserved across bacterial species, the peptides were tested for interspecies inhibitory activity. We found that peptides designed to target the P. aeruginosa SMR (PAsmr) were shown to competitively disrupt PAsmr-mediated efflux and re-sensitize bacteria to previously sublethal doses of the commonly-used hospital disinfectant benzalkonium chloride. A range of inhibition was induced across peptides, with the inhibitor peptide for PAsmr displaying the best broad-spectrum activity. To then elucidate the biophysical details of the peptide-membrane interactions, we used circular dichroism and fluorescence spectroscopy, which confirmed that these peptides were inserted and assumed a helical conformation in membrane environments. Interestingly, differential scanning calorimetry showed that peptide insertion into liposomes caused lipid reorganization, yet dye-based in vivo and in vitro assays found that the peptides displayed minimal non-specific peptide-induced disruption of the bacterial membrane per se. As such, the efflux inhibitors designed herein show promise not only for improved treatment of bacterial infections, but more generally, may provide a successful platform to target and disrupt other membrane-embedded protein-protein interactions.
Strategies to Align DIA Proteomics Runs Across Multiple LC-MS/MS Setups
Keywords: Data Independent Acquisition
Proteomics
Retention Time Alignment

Data Independent Acquisition Mass Spectrometry (DIA-MS) is a widely used for proteomics approach given its high-throughput and reproducibility; but ensuring consistent quantification of analytes across large-scale studies of heterogeneous samples such as human plasma remains challenging. Heterogeneity in large-scale studies can be caused by several factors, such as large time intervals between data-acquisition, acquisition by multiple instruments, and normal aging or replacement of parts, such as the liquid chromatography column, all of which affect retention time (RT) reproducibility and, successively, the performance of downstream statistical analyses. Here, I present a novel algorithm, implemented in the DIAlignR package, for RT alignment of DIA-MS runs based on direct alignment of raw MS2 chromatograms using a hybrid dynamic programming approach. The algorithm provides a high alignment resolution which assists in peak-selection in crowded MS2 chromatograms. In addition, it does not impose a chronological order of elution allowing alignment of elution-order-swapped peaks. Furthermore, constraining RT mapping in a certain window around a coarse global fit makes it robust against noise. Successively, the pairwise alignment is extended to multiple runs using both reference-based Star, and reference-free minimum spanning tree (MST) and Progressive alignment approaches. On a gold standard annotated dataset, DIAlignR achieves a threefold reduction in the peak identification error-rate when compared to standard non-aligned DIA results. A similar improvement is achieved from aligning runs acquired at 11 different sites when compared against the current state-of-the-art method, TRIC. Next, on real-world clinical data, the proposed approach outperforms TRIC, mapping 98% of peaks compared with 67% cumulatively. Additionally, DIAlignR reduces alignment error up to 30-fold for extremely distant runs. Finally, when analyzing the 949 plasma runs from a prediabetic cohort, the use of DIAlignR resulted in an increase of 57% and 62% in the number of statistically significant proteins for insulin resistance and respiratory viral infection, respectively, compared to prior analysis without alignment. Hence, DIAlignR fills a gap in analyzing DIA runs acquired in-parallel using different LC-MS/MS instrumentations. The alignment algorithm is freely available at https://github.com/Roestlab/DIAlignR.
Solitude and Postbellum Literary Culture: Elizabeth Stoddard, William Dean Howells, and Henry Adams
Keywords: Liberalism
nineteenth century
Realism
Romance
Solitude

This dissertation tells a new story about the role of solitude in late-nineteenth-century American culture. The figure of the solitary individual informed the consolidation of liberalism and the rise of literary romanticism in the decades leading up to the Civil War. Louis Hartz has famously argued that liberalism came to define America’s “way of life,” while F.O. Matthiessen and Richard Chase have claimed that American literature is effectively romantic. Despite solitude’s importance to American political and aesthetic thought, however, the role of isolation in American culture is under-studied outside the contexts of antebellum romanticism and the existential alienation associated with modernism. My study asks, what happens to discourses of solitude between romanticism and modernism, that is, in “the Age of Realism”? Accordingly, I examine solitude in postbellum literature, exploring how beliefs about the transformative power of solitude change under the pressures of an increasingly industrialized and mechanized society. I argue that solitude becomes an important discourse through which many late-nineteenth-century writers questioned their political assumptions and navigated the meaning of declining republican political values. The authors I consider, Elizabeth Stoddard, William Dean Howells, and Henry Adams, confronted the limitations of liberalism to grapple with a progressively unequal society, and they expressed these limits in often-contradictory celebrations and critiques of solitude. My study reveals an impasse shared by these writers regarding the value of solitude. For them, neither republican, classical liberal, nor romantic valuations of solitude fully survive America’s transition into an industrial modernity. But neither are these outlooks entirely surrendered. My readings of Stoddard, Howells, and Adams disclose an emerging American modernity still partially shaped by powerful inherited discourses of solitude reflecting romantic ideals that prove inadequate to new social and economic conditions. Postbellum realism tries but fails to escape a romantic bind in which these authors’ adherence to discourses of solitude appears to produce the very social and political problems of economic marginalization, inequality, and alienation that they sought to avoid. Complicating critical narratives in which realism develops in reaction to romanticism, this project demonstrates that romantic ideals of solitude shaped realism into the early twentieth century.
Carbonyl Functional Groups in Reaction Development: Carbonylative Cross-Coupling, α-Hydrazination, and C-C Cleavage
Keywords: BMIDA
Boron
Epoxynitrile
Iminologous
Iminology
Reaction development

The carbonyl motif (C=O) is embedded in various abundant functional groups such as carboxylic acids, ketones, aldehydes, and many more. The reactivity of the carbonyl group has contributed to several milestones in organic synthesis in the past century including the discovery of solid-phase peptide synthesis, carbonylation reactions, and most recently, in organocatalysis. Development of new synthetic methodologies is vital in advancing the field of organic synthesis and expanding our toolbox as synthetic chemists in order to create novel molecular scaffolds. This thesis describes my efforts in developing methodologies in carbonylative cross-coupling and α-hydrazination utilizing boron-containing carbonylated building blocks originating from the Yudin lab. In addition, a novel transformation that combines the concepts of C-C bond cleavage and strained ring synthesis is presented. Chapter 1 provides a brief overview on the carbonyl motif including the synthesis and various transformations that are pertinent to this thesis. Chapter 2 describes the use of carboxy-MIDA-boronate (MIDA = N-methyliminodiacetic acid) as an efficient in situ CO surrogate in the Pd-catalyzed carbonylative cross-coupling reactions to afford amides, esters, ynones, and biaryl ketones. NMR kinetic studies reveal the base catalyzed nature in the decomposition of carboxyboronate under relevant cross-coupling conditions. Chapter 3 outlines the synthesis of α-boryl-α-hydrazinoacetic acid. Subsequent transformations to boromethylated N-heterocycles, and other α-boryl-α-hydrazino scaffolds were achieved. In addition, efforts towards effecting the oxidative rearrangement of the BMIDA scaffold is described, and two rearranged molecules containing the α-aminoboron connectivity are reported. Chapter 4 contains work on the C-C cleavage-enabled ring-closure of β-hydroxy oximes to amido-epoxynitriles. Mechanistic studies suggest the stereospecific nature of the process which is in alignment with the ring-closure of halohydrins to yield epoxides.
Teachers’ Perspectives on Nutrition and Physical Education Teaching Practices
Keywords: Empowerment

This qualitative study investigates Nutrition and Physical Education and its role in student empowerment as a precondition for subsequent healthy habits and lifestyle, drawing on teachers’ perspectives in the province of Ontario, where the researcher is based. The teacher perspective is distinguished, as it is these ground level experts who are in the best position to discuss the education carried out, as well as evaluate the outcome for their students, and identify the specific challenges of the process. The critical value lens of empowerment is operationalized to investigate the lasting impact of the education upon the students. To this end, the dynamic interaction of policy, teachers and students is of interest, during the respective teacher practice process, filtering through the challenges, to produce the final outcome of student empowerment for healthy habits and lifestyle. Accordingly, the respective past and current teachers are considered, their backgrounds, workplaces and communities, their particular Health Education programs, as well as any challenges experienced by them. Specifically, a Questionnaire and several interviews explore which factors inform the teacher practice of nutrition and physical education teaching, what influences what the teachers do pedagogically when they teach nutrition and physical education, how the teachers evaluate effectiveness of the education they provide, what are the challenges encountered by the teachers during this process, and what are the teachers’ perspectives about the relationship between their teaching practices and student empowerment in the formation of healthy habits, and subsequently, a healthy lifestyle? Findings of the investigation point to a wide range of factors which directly and indirectly inform the teacher practice of nutrition and physical education teaching; numerous important direct and indirect conditions impacting the teaching practice of the participants are observed; various types of instruments employed for evaluation purposes are identified; and many challenges of direct and indirect nature encountered by the teachers during this process are uncovered. Nonetheless, the participants confirm the belief that Health Education provided leads to the formation of healthy habits and a healthy lifestyle. In conclusion, implications for policy, practice, and theory are discussed, as well as recommendations are offered for future research.
Joint Multistate Models for Correlated Disease Processes: Extending Approaches for Interval-Censoring, Mixed Observation Schemes, and Multiple Longitudinal Outcomes
Keywords: Interval censoring
Joint model
Longitudinal data
Multistate model
Multivariate longitudinal outcomes
Survival analysis

In diabetes and other lifelong diseases, it is not always known with certainty how chronic correlated non-fatal disease processes co-develop over time. It is also not obvious how to analyze this complex multivariate statistical problem. This thesis reviews and proposes methods that allow for the simultaneous modelling of several such processes. In a tutorial setting, it is shown that multistate and joint modelling approaches are useful for the overall research objective. Multistate models are found to be particularly applicable for questions surrounding the order and timing of disease-related processes. However, they require discretization of outcome data and possibly a very complex state space when more than two processes are modelled. In contrast, joint models can account for variations of continuous biomarkers over time and are particularly designed for modelling complex multivariate association structures. It would therefore be useful to combine elements of multistate and joint models, and the next part of the thesis develops this framework. Shared random effects can be used to link multistate and longitudinal processes, but most existing approaches assume that the multistate transition times are exactly observed. This renders them unsuitable for interval cohort studies, which are one of the most popular study designs for questions surrounding the natural history of complications. In interval cohort studies, participants are intermittently observed at regular intervals and are thus subject to mixed observation schemes where certain events are interval-censored and others are exactly observed. A novel shared random effects joint model for a longitudinal outcome and a multistate process under a mixed observation scheme is thus proposed. An appropriate likelihood function is defined and the model is fitted using a maximum likelihood framework with adaptive Gaussian quadrature. The model is assessed using simulation studies and is applied to 30-year data from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study. The model is then extended to accommodate multiple longitudinal outcomes via Bayesian estimation using Hamiltonian Monte Carlo. In the end, it is shown that the novel joint multistate model gives greater insight into the natural history of a full complications process.
Epigenetic Profiling and Therapy for Brain Cancer
Keywords: Atypical teratoid rhabdoid tumors
Brain Cancer
cfMeDIP-seq
Epigenetic Profiling
Epigenetic Therapy

Brain tumors are aggressive and lethal cancers affecting both children and adults. Genetic alterations in the regulation of epigenetic processes play a critical role in the development of brain tumors. Atypical teratoid rhabdoid tumors (ATRTs) exhibit clinical heterogeneity and a relatively stable genome, suggesting they may comprise distinct molecular subgroups driven by epigenetic mechanisms. Integrated analyses of epigenomic and transcriptional profiling on a large cohort of primary ATRTs defined three molecular subtypes that correlated with distinct clinical features, lineage-specific methylation, and transcriptional patterns. ATRT subgroups exhibited distinct epigenomic landscapes correlated with the expression of cell-lineage and signaling genes. This suggests that different subgroups of ATRTs may have distinct regulatory networks, highlighting the potential for developing treatments tailored to specific subgroups. SMARCB1 inactivating mutations in ATRTs confer an oncogenic dependency on EZH2. We found that EZH2 inhibition (EZH2i) upregulates the expression of genes enriched for intronic and 3’ UTR IR-Alu elements, leading to the formation of intramolecular stem-loop dsRNA and activation of cytosolic dsRNA sensing pathways. EZH2i induces genome instability and cytoplasmic DNA sensing pathways in a process dependent on reverse transcriptase activity. The viral mimicry state underlying the vulnerability of genetically defined, SMARCB1-deficient tumors on EZH2i is mediated via both dsRNA and DNA sensing pathways.DNA methylation patterns can be used to classify different types of brain tumors in molecular pathology, but this typically requires obtaining tissue samples through invasive surgery. To overcome this obstacle, we used a highly sensitive technology called cfMeDIP-seq to profile DNA methylation in the plasma. We found that DNA methylation patterns in the plasma can accurately identify common primary intracranial tumors that may be difficult to differentiate with standard imaging methods and have the similar cell of origins. Altogether, this thesis demonstrates epigenomic profiling as a powerful approach to classifying different brain tumor entities and reveals an important mechanism of targeting EZH2 as a potential therapeutic strategy for the treatment of ATRTs.