VictorJuiz/thesis huggingface dataset:
At the Mouth of the River: Shame, Secrecy, and Intergenerational Trauma in Newfoundland
Keywords: Cultural Studies
Folklore
Newfoundland
Psychoanalysis
Queer Theory
Trauma

In this dissertation, I engage with theories of intergenerational trauma to explore the psychic dynamics of loss and memory in Newfoundland. This inquiry works to unearth the complex historic and social conditions that contextualize ongoing legacies of social injury in Newfoundland. I explore the many ways that Newfoundlanders grapple with the messy contradictions of trauma through aesthetic expression, resilience and love. I ask: in what ways has trauma demanded a kind of suspension between spaces, both temporal and cognitive, in Newfoundland culture? How and why do historic losses define Newfoundland culture, identity, politics and industry today?This dissertation swims in the slippery waters of secrecy, shame and silence that define intergenerational trauma in Newfoundland. Working with theories of trauma, I explore how enigmatic memories move through the generations across relational, embodied, cultural and ecological passageways. By turning to the aesthetic archive of Newfoundland film, folklore and art, this dissertation traces the affective, relational, and sociopolitical legacies of trauma in Newfoundland as they move through somatic, relational, familial, cultural, and ecological passageways. Importantly, I consider how these legacies are rooted in transnational histories that have shaped the cultural landscape of this island, including the Atlantic slave trade, settler colonialism, and resource extraction. In doing so, I propose methods for attuning us to the paradoxical tensions of silence that resound through Newfoundland culture. Such methods lay the foundation for an analysis of the way in which historical contexts such as colonialism, slavery, resource extraction, poverty, rurality, and religion continue to define contemporary Newfoundland life through shame and silence. In this dissertation, I seek a range of modes for listening to transgenerational silences to working through cultural shame and to imagine radical change.
Ultrasound Jetting and Atomization of Sessile and Impacting Droplets
Keywords: Mass Spectrometer
Ultrasonic Atomization
Ultrasonic Droplet Breakup
Ultrasound Jetting

We present the results of our experimental and theoretical study of the jetting and atomization of a sessile and an impacting droplet subject to an ultrasonic surface vibration. Such high frequency vibrations result in the formation of a liquid jet shooting outwardly from the surface of the droplet, which eventually breaks up into droplets. Part of the liquid remains on the surface, which eventually goes through ultrasonic atomization. We divided this process into three categories of (i) jetting, (ii) jet breakup and liquid layer formation, and (iii) liquid layer atomization, and characterized each one separately. We have developed a model to predict the onset of jetting and jet velocity. The liquid jet may breakup into droplets, the sizes of which were measured and predicted theoretically. The liquid layer remaining on the surface may go through ultrasonic atomization resulting in bimodal droplet size and velocity distributions. Additionally, the effect of parent droplet size on the final aerosol size distribution was studied and theoretical models were proposed to characterize the ultrasonic atomization and liquid breakup (droplet size, ejection threshold, and ejection velocities). It was also shown that the ultrasonic atomization of nanoliter liquid volumes results in the formation of <10 μm mist with the large droplets being cut off.
Computational Frameworks to Interpret Genetic Abnormalities in Hematologic Malignancies
Keywords: Acute myeloid leukemia
Cancer genomics
Computational biology
Hematologic malignancies
Machine learning
Measurable residual disease

In the era of high throughput sequencing technologies, the speed of genomic data generation exceeds our abilities to store, analyze and interpret the data without high-performance computing facilities. In hematology, next-generation sequencing (NGS) is being utilized for diagnosis, prognostication, and post-treatment monitoring. Although it is undoubtedly the future of molecular testing and monitoring, computational methods to interpret results at single and longitudinal time points are highly in need. Thus, this thesis is devoted to mining clinically and scientifically meaningful information from NGS data in the context of hematologic malignancies. First, I show how incorporating allelic burdens of mutations can enhance the risk stratification of patients with acute myeloid leukemia (AML). Instead of considering mutations as binary variables, the model considers mutations as continuous variables, considering clonal architecture when predicting the prognosis. Also, I demonstrate single mutation does not determine a patient's risk alone, but the patient's risk depends on the entire mutation profile. Second, I describe computational methods to detect residual leukemia cells remaining post-treatment (termed "measurable residual disease" (MRD)). I show that NGS-based MRD detection is feasible in different subtypes of AML at various time points. In addition, estimating sequencing error rates helps reduce false positives while increasing true positives, thus maximizing clinical relevance. Throughout multiple studies, I describe different approaches to detect NGS-based MRD and to mine clinically meaningful information. Lastly, I present a computational workflow that analyzes single-cell proteogenomic sequencing data to identify relapse-fated subclones from the time of diagnosis in an FLT3-ITD+ AML case. Simultaneous proteogenomic profiles allow the refinement of clonal models relying only on mutation profiles and help identify relapse-fated AML subclones at the time of initial diagnosis. I also describe how copy-neutral loss-of-heterozygosity at chr13q can be accurately detected at the single-cell level and cell surface marker expressions help identify somatic mutations.
Adapting Manifold-Based Analyses to Describe How Personal and Task Constraints Impact Lower Extremity Movement Variability During Exercise
Keywords: Biomechanics
Movement Assessment
Movement Variability
Uncontrolled Manifold

Despite the recent emphasis in the motor control literature quantifying the structure of movement variability, there is a paucity of research applying these concepts in exercise contexts. Measuring the structure of variability surrounding dynamic valgus motion, and how it is impacted by personal and task constraints, can be achieved by adapting Uncontrolled Manifold (UCM) analyses. This thesis aimed to build a foundation for a complementary approach to evaluating the execution of exercise tasks that considers both average movements and movement variability by addressing four main gaps in the literature. First, it is unclear which methods of computing dynamic valgus motion are most related to external knee abduction and external rotation moments. Second, it is unclear how many repetitions are required to monitor the variability surrounding dynamic valgus motion using adapted UCM analyses. Third, although ankle dorsiflexion range of motion (ROM) restrictions can influence the average dynamic valgus motion, it is unclear whether it also impacts the structure of movement variability. Fourth, research has demonstrated that average dynamic valgus motion is more strongly correlated between single-leg exercises. But, no studies have examined these relationships for the structure of movement variability. In Chapter 3, the data demonstrated that computing dynamic valgus motion as the orthogonal distance of the knee joint center from the hip-foot plane (OD) was a relatively better kinematic proxy of external knee abduction and external rotation moments in comparison to Cardan-Euler angles. In Chapter 4, UCM methods were adapted for use with OD. In Chapter 5, the data showed that participants should perform at least five repetitions to obtain saturated variability data for between-participant analyses and at least eight repetitions for within-participant analyses. Chapter 6 demonstrated that individuals’ ankle dorsiflexion ROM had little influence on the structure of movement variability. Chapter 7 found that the task constraints imposed during exercise strongly influence the structure of movement variability. In summary, data from this thesis provide a platform for future research and practice to expand upon a complementary approach to evaluating the execution of exercise tasks by leveraging movement variability data.
“The Right Story”: Discursive Strategies in Gender-Affirming Healthcare Access
Keywords: discourse analysis
language and healthcare
sociocultural linguistics
trans linguistics

Despite strides towards a less pathological and diagnostic-centered approach to transgender healthcare, many policies continue to present barriers in accessing gender-affirming medical support that may provide individuals with greater ease in their embodiment. Research on transgender speakers’ linguistic practices in healthcare interactions has shown that practitioners’ prerequisites for granting access to this kind of care remain largely based on criteria presented in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. This practice of evaluation has led to an impression within trans communities that accessing gender-affirming care is a test, where patients must “do” their gender or present their identity in a particular way. Meeting this expectation may feel especially imperative and dehumanizing for non-binary transgender people, as individuals who do not identify as either, or exclusively, masculine or feminine. Presenting a gender positionality outside of the binary has historically meant losing access to care, and as a result, non-binary patients often find themselves using different language to describe their experience than they would in other contexts, simply to gain access to much-needed care. As an intervention in the inequity of doctor-patient communication in this setting, this dissertation considers the metalinguistic (“talk about talk”) observations of non-binary people regarding their gender-affirming healthcare interactions in Ontario. Rather than considering non-binary patients’ practices as straightforward acts of capitulation to medical expectations, their performances in these high-risk interactions are a means to contest their marginal status within the healthcare system. Participant-collaborators express numerous strategies to simplify or obscure their non-binary identities in their pursuit of care, such as the flexible use of identity labels, vocal pitch modulation, the intensification and historicization of experiences of suffering related to gender identity, and avoiding asking questions about their care so as not to compromise doctors’ impressions of their certainty about medical transition. This dissertation thus shows how linguistic performances are a crucial part of the gender-affirming care process; in other words, whether patients get the access that they need often depends not just on what they say, but how they say it, and what they strategically omit.
Design of a Multiparameter Islet-on-a-Chip Device to Measure the Functional Variability of Individual Pancreatic Islets
Keywords: Fluorescence Anisotropy
Insulin Secretion
Islet-on-a-chip
Microfluidics
Oxygen Sensor
Pancreatic Islets

Pancreatic islets are small micro-organs responsible for glucose-stimulated insulin secretion, which occurs in two phases; a rapid first phase burst followed by a sustained second phase. Islets are commonly studied ex vivo using assays that have poor temporal (>5 min) and spatial (multiple/bulk islets) resolutions. Bulk measurements are highly susceptible to uncoordinated responses, poor treatment penetration and often lack multiparametric capability. These limitations are especially exacerbated by the functional variability of pancreatic islets. The magnitude, rate, and timing of first and second-phase insulin secretion are highly variable between islets. We postulate that this variability is important to the normal function and dysfunction of islets. Hence, studying islets individually can help overcome the limitations of bulk islet studies to enhance our knowledge of functional variability. Our goal here was to measure O2 consumption rates and insulin secretion from individual pancreatic islets with a high spatiotemporal resolution. To achieve this goal, we combined microfluidics with an O2-sensitive probe and biochemical assay. We first developed O2 microsensors using SU-8 microwells to digitize the O2 measurements and a polydimethylsiloxane-based sensor to enhance oxygen diffusion. We fabricated our microfluidic platform out of polymethylmethacrylate to limit diffusion and permeation of external O2 from saturating our measurements. We combined the O2 microsensors and platform to measure islet OCR simultaneously with Ca2+-activity. Glucose-stimulated O2 consumption of individual mouse islets was found to be biphasic with the timing independent of cytoplasmic Ca2+-influx. Finally, we developed an on-chip fluorescence anisotropy immunoassay to measure c-peptide secretion as a surrogate for insulin from individual mouse islets. In this study, we designed a novel islet-on-a-chip that mixes islet effluent with the assay reagents to be imaged downstream of the islet. We showed that islets respond to glucose at varying times with different magnitudes of secretion. Future directions include combining the O2 and c-peptide sensor into the islet-on-a-chip. Overall, this thesis reveals the power of individual islet measurements, which show how current methods have been undermining islet variability. The tools engineered in this thesis provide an individual islet approach to further characterize islet metabolism and to understand the intricacies of healthy and unhealthy islets.
Targeting the MYC Oncoprotein by Disrupting the MYC-PNUTS Interaction
Keywords: Cancer Therapeutics
Dominant Negative
MYC
PNUTS-PP1 phosphatase
Protein-Protein Interaction

Despite the knowledge that the MYC protein family is a potent driver of multiple oncogenic malignancies, no targeted therapy against MYC exists for patient care. One major obstacle for conventional drug development is that MYC is an intrinsically disordered protein, that only upon binding to protein partners adapts a conformation. One of the recently identified MYC protein interactors is the Protein Phosphatase 1 (PP1)/PP1 Nuclear Targeting Subunit (PNUTS) complex. Inhibition of PP1 leads to the hyperphosphorylation and degradation of MYC, thus making this complex a potential vulnerability of MYC-driven cancers. As protein phosphatases are promiscuous enzymes with multiple substrates, we placed our focus for developing a MYC-specific inhibitor on the interaction of MYC with the regulatory protein PNUTS. To this end we took two approaches: i) characterizing the MYC-PNUTS interaction structurally; and ii) demonstrating that disruption of this interaction is detrimental to tumour growth.First, we identify the MYC-PNUTS interaction. PNUTS interacts directly through the PNUTS amino-terminal domain (PAD) with the MYC homology Box 0 (MB0) of MYC. The latter is a highly conserved region, shown to be important for MYC oncogenic activity. We also demonstrate that mutation of key residues on either protein disrupts this interaction and leads to elevated phosphorylation of MYC in human cells. Leveraging the MYC-PNUTS structural information, we designed a proof-of-principle study, in which we show that overexpression of the PAD provokes disruption of the MYC-PNUTS complex in human cells. Moreover, we find that disruption of this complex affects MYC-driven transcriptional programs, and alters breast cancer cell proliferation, transformation, and xenograft growth. Taken together, the work presented in this thesis lays the groundwork for developing novel, targeted therapeutics against the to date deemed ‘undruggable’ MYC oncoprotein. Considering the omnipresence of MYC dysregulation in human cancers, these findings hold the promise of ultimately developing a MYC-PNUTS inhibitor and benefiting many cancer patients.
Pious: Why Meta’s Business Model Drives Intolerance
Keywords: Algorithms
Anti-colonial theory
Critical Race Theory
Facebook
Social Media

The rise of social media parallels a rise in distorted identity politics. The past decade has seen an increase in cases of ethnic fraud, polarizing populism, and corporate solidarity statements critiqued for capitalizing on social issues. While many critics blame these social phenomena on opportunistic individuals and businesses, this dissertation studies the role played by social media platforms: their business models, advertising datasets and ranking algorithms. I focus on Meta as a blueprint for subsequent social media platforms. I begin with my autobiography as a former QTBIPOC influencer, as a microcosm of the distorted identity politics amplified by social media infrastructures. I conduct a walkthrough of the Meta Detailed Targeting Tool (MDTT), paying close attention to how this tool fetishizes social difference: by stripping behaviors, interests and demographics down to fungible exchange value and market optimization. I argue that this process of fetishization rewards and conditions grammars of action that inherit the techniques, and problematic social dynamics, of Christian colonialism. This dissertation brings The Black Radical Tradition and anti-colonial critique to bear on social media scholarship, in order to investigate the following questions: 1) How does the MDTT shape behavior? 2) What are the motivations that compel identity politics? 3) Why have “morals” become so important to business? and 4) How can the framework of “piety” offer new theories and solutions for negative social media dynamics?
The Properties of Dirac Materials: Strain, Magnetoelectrics and Krein-Hermiticity
Keywords: cuprate
Edelstein
Krein Hermitian
magnetoelectric
magnon
strain

The study of Dirac matter offers a cross section of some of the most dynamic topics in condensed-matter physics. Interest in Dirac-like dispersions in band structures dates back to the early days of solid-state physics; however, in the past decades, emergent Dirac-like behaviour in materials has become a focal point of condensed-matter physics, in no small part because of the new, topological appreciation of these gapless phases of matter. Since then, the field has witnessed an ever-increasing understanding of the exotic properties that emerge in Dirac matter. The present thesis furthers the exploration of Dirac-like physics in condensed-matter systems and the novel properties that stem from it. After a thorough overview of the physics underpinning these states of matter, we investigate the existence of strain-induced pseudomagnetic fields in nodal superconductors like the cuprates. We provide a realistic proposal to realize strain-induced Landau levels in a cuprate sample, a unique scenario that cannot be achieved with an ordinary magnetic field. We then turn to a study of the orbital Edelstein effect resulting from spontaneous symmetry breaking within a nodal-line semimetal. In this model, the onset of charge order endows the gapless lines with a mass; they then become sources of orbital magnetic moment. Hence, we exemplify how this magnetoelectric effect can serve as a proxy for symmetry breaking in certain Dirac semimetal phases. Finally, we develop a formalism of the Schrieffer-Wolff transformation in Krein-Hermitian Hamiltonians, which arise, among other contexts, as the single-particle Hamiltonians of bosonic Bogoliubov–de Gennes systems. These Hamiltonians are Hermitian with respect to an indefinite inner product, and the Krein-unitary transformation we formulate preserves their Krein-Hermiticity. In particular, we explain why an effective Hermitian Hamiltonian can, under certain conditions, be used to describe subsets of adjacent bands of a larger Krein-Hermitian Hamiltonian, a justification of which seems to have been lacking. We then apply our findings to study the generic codimension of Dirac-like band touchings in such systems, focusing on spin-wave excitations in quantum magnets.
Causes and Consequences of Recombination Rate Variation
Keywords: Chlamydomonas
evolutionary genetics
mutation
population genetics
recombination

Recombination, the shuffling of alleles during meiosis, is a fundamental evolutionary process that is nearly ubiquitous across eukaryotes. By uncoupling linkage disequilibrium between harmful and beneficial mutations, recombination promotes more effective selection. However, recombination rate varies at multiple scales across nature, which has important implications for genome evolution at large. Here, I report four chapters that investigate recombination and genome evolution using the unicellular and facultatively sexual chlorophyte Chlamydomonas reinhardtii. I examine recombination rate variation at the level of populations, individuals, and across the genome itself. I show that recombination rates are consistent between populations and individuals, demonstrate evidence that recombination plays a role in reducing the effects of selection at linked sites, and estimate the rate of sexual reproduction in a wild population of C. reinhardtii. I also investigate recombination in a crossover-suppressed sex-determining region of the genome, and show how noncrossover recombination can still maintain effective selection, thus preventing long-term degeneration of these loci. Finally, I close off with a study pertaining to mutational biases introduced by environmental stressors in C. reinhardtii and demonstrate the effects of the former on adaptation. Altogether, my thesis addresses fundamental questions regarding recombination rate variation and adaptation in C. reinhardtii, and alongside existing detailed work on spontaneous mutation in the system, provides an empirical framework for understanding how these processes affect genome evolution over evolutionary time.