VictorJuiz/thesis huggingface dataset:
Spatial Organization and visual preference of high-level visual brain regions
Keywords: faces
fMRI
hippocampus
perception
population receptive fields
scenes

The human visual system represents visual features in a retinotopic pattern that is quite robust across the visual system hierarchy, from the early visual cortex to the high-level cortical areas. Though high-level areas are functionally distinct, the relationship of pRFs in the high-level visual cortex is consistently organized with a contralateral hemifield bias, corresponding to the topographical organization of the viewing plane. Though the contralateral hemifield bias is a clear sign of retinotopy, the relationship of the size of pRFs to the feature representations in high-level visual areas and memory-related areas is not well understood. In my dissertation, I explore the pRF organization in high-level vision areas, along with memory regions using a large retinotopy dataset. I also explore the relationship of feature specialization to pRF size within memory processing areas, the spatial frequency correspondence with pRF in scene-specialized areas, and finally an analysis of an in silico model of human vision. The organizational pattern extends throughout the human visual system and memory processing areas, which suggests that functional distinctions are organized similarly. Within the hippocampus and scene-specialized regions, the anterior-posterior gradient aligns with functional differences found in these areas. Additionally, the functional distinctions are supported by the decrease in correspondence with the viewing plane via the types of representations indicated by the pRF size within anterior PPA.
Successful Aging in Canada: Findings from the Canadian Longitudinal Study on Aging (CLSA)
Keywords: Canadian Longitudinal Study on Aging (CLSA)
Immigrant status
Marital trajectories
Older adults
Social participation
Successful aging

Background: Successful aging is the desire of older adults and those who have devoted their lives to the care of older adults. Few studies in Canada have focused on the associations between (1) immigrant status; (2) marital trajectories; (3) social participation, and successful aging. This three-paper dissertation introduced an expanded definition of successful aging included the ability to accomplish both activities of daily living (ADLs) and instrumental activities of daily living (IADLs), freedom from mental illness, memory problems and disabling chronic pain, adequate social support and older adults’ self-reported happiness and subjective perception of their physical health, mental health and aging process as good (Ho et al., 2022; Ho et al., 2023). Methods: The first two waves of data from the comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA) were analyzed. The final samples included 7,600+ respondents defined as “aging successfully” at baseline and were 60 years or older at time 2. Bivariate and multivariable binary logistic regression analyses were conducted. Results: The study found that (1) older immigrants, (2) older adults who were never married or had experienced widowhood, separation and divorce in later life; and (3) older adults who did not engage in volunteer or charity work, and recreational activities had a significantly lower odds of achieving successful aging than their peers. Other significant baseline factors associated with successful aging included being younger, female sex, having higher income, being married, not being obese, not smoking, engaging in moderate or strenuous physical activities, not having sleeping problems and being free of heart disease or arthritis. Conclusions: The study contributed to the body of literature on successful aging by providing an expanded definition of successful aging and studying older immigrants, older adults with different trajectories of marital status, and older adults who have participated in social activities. The findings provided a strong argument that some older adults might achieve successful aging through engaging in activities that promote physical, psychological, mental, social, and self-rated wellness. Practical implications and future research directions were discussed.
Mark of the Non-Conviction Record: Managing Stigma and Confronting the Consequences of Recorded Police Contact in Canada
Keywords: Collateral consequences
Non-conviction records
Stigma
Stigma avoidance tactics
Stigma management strategies

This dissertation investigates the experiences of people with non-conviction records (NCR) in Canada and how they contend with the stigma of this police record type. Minimal sociological and criminological research focuses on NCR holder experiences despite tens of thousands of NCRs being generated in Canada annually, and NGOs and legal scholars reporting that NCR exposure has similar stigma-induced repercussions to disclosing a conviction record (CR). I address this literature gap by investigating whether, why, and how recorded police contact leads to challenges for NCR holders, and how NCR holders address record-related repercussions. I draw on interviews with twenty-two NCR holders and twelve key informants across Ontario to understand NCR holder perceptions of NCR consequences, NCR holder strategies for contending with record stigma, and how NCR holder experiences compare to those of CR holders in other studies. I argue that the mark of an NCR can affect NCR holders in similar ways to CR holders, as indicated by the NCR-induced collateral consequences they experience, the record-induced discrimination they anticipate, and their use of strategies to prevent stigmatization. Interviews revealed diverse NCR exposure experiences and repercussions, including social, professional, and economic marginalization. All NCR holder participants anticipated, and most experienced, consequences in at least one area of their lives, including employment, financial security, volunteering, career training, U.S. travel, personal relationships, and sense of well-being. Collateral consequences resulted from NCRs appearing on security checks as well as NCR holders holding back from opportunities due to their perceived risk of record exposure and stigma-induced rejection. NCR holders used stigma avoidance tactics to retreat from opportunities with exposure and rejection potential; alternatively, they used stigma management strategies to resist consequences through impression management and information control. Strategy choice was primarily related to perceptions of when and where NCR consequences may occur. The findings suggest Canadians are not guaranteed the right to be considered “innocent until proven guilty” since the mere mark of police contact can have long-term detrimental effects on people who were never convicted of a crime. Overall, this dissertation contributes to broader discussions about criminal record stigma and record disclosure reform.
Adaptive Biology, Driven by Metabolic Reprogramming, in Soft Tissue Sarcoma
Keywords: Adaptive Biology
Hypoxia
Metabolic Reprogramming
Metastatic Model
Soft Tissue Sarcoma
Statins

Soft tissue sarcomas (STS) are mesenchymal tumors. Undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), and leiomyosarcoma (LMS) are common types of adult STS, while rhabdomyosarcoma (RMS) is a common pediatric STS. Treatment is multimodal, yet survival rates have remained largely unchanged in the last decade. Metabolic reprogramming is the ability of cancer cells to alter their metabolism to provide energy and building blocks to support aberrant growth. Adaptation to the tumor microenvironment, such as that created by hypoxia or during metastasis, can influence growth kinetics. Therefore, metabolic pathways, such as the PI3K/mTOR pathway, are attractive targets. An understanding of how metabolic reprogramming drives adaptive STS biology may improve outcomes for these patients. To find novel therapeutic agents, we performed a drug screen on UPS cell lines. Simvastatin, which inhibits the mevalonate pathway, was a top hit at reducing the viability of UPS and LMS through a reduction in proliferation and increase in cell death. In UPS and possibly LMS cell lines, the mechanism of action occurs through a reduction in PI3K/mTOR signaling. In vivo toxicity precluded determining if simvastatin + doxorubicin, a current standard of care for patients with advanced STS, was efficacious. To model metastatic disease, we endeavored to drive STS metastasis in mice through surgical (resection or amputation) or systemic (tail vein or jugular injection) methods. While both amputations and tail veins led to metastases, we focused on amputation as this most accurately represents human disease. We established metastatic models of LMS and RMS (alveolar and embryonal), which can be used to better understand the metastatic cascade of STS and test novel therapeutics. To comprehend what drives aggressive biology in extremity UPS and MFS, we quantified hypoxia and associated epigenetic changes. Hypoxia, detected by FAZA-PET/MRI, was correlated to a worse disease-free survival. Methylation did not appear to be changed by hypoxia. In summary, we targeted metabolic pathways in UPS and LMS with simvastatin. Metabolic reprogramming may be driven by hypoxia, which we were able to quantify in UPS and MFS with two exogenous markers. With our metastatic models we can investigate the mechanism of metastasis and evaluate novel therapeutics.
Therapeutic Potential of Protein Kinases and Their Downstream Targets Following Traumatic Cervical Spinal Cord Injury
Keywords: Cross-Species Comparison
KCC2
Kinome
Spinal Cord Injury

Despite recent advances in the management and characterization of traumatic spinal cord injury (SCI), the current therapeutic options for patients remain limited. The SCI-induced cellular response is mediated through series of protein kinases, which are a group of globular proteins that reversibly phosphorylate downstream substrates to alter the transcriptional patterns of local and surrounding cells. While these altered kinase activities at the cellular level represent compelling targets for therapeutic intervention, the specific function of different kinase pathways is yet to be investigated. The objective of this doctoral thesis is to elucidate the role of protein kinases in injury progression and explore their therapeutic potential following traumatic cervical SCI. First, a comparative cross-species transcriptional and genomic analysis identified molecular pathways with great therapeutic potential and translational relevance. As these molecular targets were predominantly kinase-related, the subsequent experiments were aimed to assess the efficacy of a clinically approved protein kinase inhibitor—midostaurin—to alleviate secondary pathogenesis. While the results showed great promise, more targeted strategies would be necessary to minimize off-target effects and enhance effectiveness. Hence, gene therapy was used to modulate a downstream target of protein kinases, which demonstrated that restoring KCC2 activity can enhance functional recovery. This work demonstrates the importance of targeted kinome-based therapeutics to alter the secondary response following traumatic SCI.
Insulin Recepto Loss Impairs Mammary Tumourigenesis in Mice
Keywords: bioenergetic fitness
breast cancer
insulin receptor
mouse models
obesity

Breast cancer (BC) prognosis and outcome are adversely affected by increased body weight, obesity, and the obesity-associated type 2 diabetes. Hyperinsulinemia, common in the obese state, has been associated with higher risk of death and recurrence in BC. Up to 80% of breast cancers overexpress the insulin receptor (INSR), which correlates with worse prognosis. To directly probe the role of insulin signaling in mammary tumorigenesis, we generated the MMTV-driven polyoma middle T (PyMT) and ErbB2/Her2 BC mouse models, respectively, with coordinate mammary epithelium-restricted deletion of the INSR. In both models, deletion of either one or both copies of the INSR in the mammary gland led to a marked delay in tumor onset and burden, including in mice fed to mimic conditions of human obesity. Phenotypic characterization and longitudinal monitoring of mouse tumours, and ex vivo analysis of mammary cells from the generated mouse models revealed that tumor initiation, rather than progression and metastasis, were impacted by INSR deletion. The similarity of phenotypes elicited by the deletion of one or both copies of INSR indicates that there is a dose-dependent threshold for the contribution of INSR to mammary tumorigenesis, with major implications for primary and secondary prevention of breast cancer in the obese.
Mapping the Genesis of Malignant Gliomas at Single-Cell Resolution
Keywords: Brain injury
Cancer biology
Glioblastoma
Mouse brain development
Neural crest cells
Single-cell sequencing

Malignant gliomas and glioblastomas are genetically diverse brain malignancies of both children and adults. Despite the remarkable progress in deciphering the genomic architecture of these tumours, the cellular programmes and mechanisms that give rise to the mostly incurable late-stage tumours remain unresolved. In this thesis, I aimed to explore the roots of gliomagenesis and map the process of tumour initiation and development. First, I used the transgenic Sox2eGFP mice to explore the heterogeneity of mouse cerebral precursor cells and downstream lineages across the developmental time-course, from embryonic day 12.5 to postnatal day 365, by performing single-cell transcriptomics on >100,000 cells to generate an atlas of cerebrum development. I used this atlas as a reference to explore single-cell data from human malignant gliomas and identified the acquisition of developmentally restricted radial glial-like precursor cell states in both paediatric and adult tumours. Next, I traced the origins of tumour development from the earliest stages of initiation by combining glioma mouse modeling with serial magnetic resonance imaging (MRI) and single-cell profiling. I was able to track the process of tumour formation across four MRI-defined time points from the preneoplastic to the endpoint stage of gliomagenesis. My findings revealed entire developmental-like lineages that dominate the various stages of tumourigenesis. Importantly, I identified a malignant cell state with a strong neural crest-like gene expression signature that showed high abundance in the early stages, but was relatively diminished in the late-stage of tumourigenesis. Genomic analysis based on the presence of copy number alterations revealed that these neural crest-like cells exist as part of a heterogenous clonal hierarchy that governs tumour growth. Further, by exploring the injury response in the wounded normal mouse brain, I identified cells with a similar signature that emerge following injury and then disappear over time. Surprisingly, my experiments uncovered an injury-like microenvironment that is initiated in the brain following oncogene activation in cerebral precursor cells, suggesting that tumour initiation involves the activation of an injury-like response programme. Collectively, my results present a roadmap of glioma initiation and development, and raise exciting new possibilities for early disease diagnosis and prevention.
Investigations on soot and flow field characteristics of blended liquid and gaseous fuels in turbulent swirl-stabilized non-premixed flames
Keywords: Biofuels
Combustion
Emissions
Laser Diagnostics
Soot

Combustion of fossil/carbon-based fuels in both ground and aviation-based transportation devices produce emissions such as NOx, CO2 and soot. Among these, soot formation is a complex process and their characteristics have not been understood completely. Hence, it has been the subject of recent studies in an effort to reduce its footprint in atmospheric pollution. The current work explores the possibility of adding different fuel additives to existing carbon-based fuels in aviation-type gas turbine combustors to understand their effect on soot formation. This study involves understanding the various hydrodynamic and chemical effects on soot formation through controlled lab-scale experiments with well-defined boundary conditions in both liquid and gaseous swirl-stabilized turbulent flames. Particle image velocimetry, laser diffraction and laser induced incandescence are utilized to experimentally characterize the flow-field, spray and soot characteristics respectively within the combustor. Various biofuels and oxygenated compounds are blended in small amounts to base Jet A-1 fuel in liquid spray combustors, whereas hydrogen/helium is used as an additive to ethylene base fuel in gaseous combustor. The overall effectiveness of a certain fuel additive along with the effect of various blending ratios, flow rates and spray characteristics on soot in different combustor configurations are discussed in detail. The changes in spray characteristics was noticeable for lower alcohols, but diminished with higher alcohols as their physical properties do not deviate largely from neat Jet A-1. The measurements revealed that even though the hydrodynamic effects such as flow-field and turbulence can influence the soot formation regions, spatial soot distribution and soot intermittency, the global changes in the magnitudes of soot volume fractions were mostly affected by local fuel chemistry. Higher alcohols were found to be highly effective in reducing soot concentrations when added to neat Jet A-1, whereas addition of hydrogen in small concentrations to ethylene resulted in an increase in soot loading, opposite to that observed in atmospheric laminar flames. In addition to this, high speed planar measurements in gaseous flames revealed that apart from the effect of swirl, bulk flow unsteadiness and local flow fluctuations contributed immensely to the growth and transport of soot from formation to oxidation regions.
An Arithmetic-geometric Reciprocity between Theta Functions Attached to Real and Imaginary Quadratic Fields
Keywords: modular forms
number theory
theta correspondence
theta functions

We use the theta correspondence to construct classical holomorphic modular forms associated to ideal classes in quadratic number fields. These modular forms are theta functions that were originally introduced by Hecke in the 1920s andhave been investigated by several authors since. Our framework allows us to prove old and new results concerning the periods of these modular forms over certain geometric cycles defined by arithmetic data. In particular, we establish a reciprocity relationship between the periods of theta functions attached to ideal classes in real and imaginary quadratic fields. This provides an analogue of (and context for) Hecke’s discovery that certain periods of his imaginary quadratic theta functions are special values of classical Eisenstein series at CM points.
Ready for Action! When the Brain Learns, Yet Memory-Guided Behavior Does Not Follow
Keywords: Attention
Electroencephalography
Lateralized readiness potential
Long-term memory
Memory-guided attention
Response preparation

The ability to use memory for action is critical for everyday life, such as for remembering which alarm signals danger. Although research suggests that memory for past events influences how we respond to events in the present, the magnitude of behavioral benefit varies and can even be absent. How is it that the brain learns, yet the learning does not influence memory-guided action? In this thesis, I show that 1) not all learned memory representations are usable for behavior and 2) those that are usable for behavior are supported by distinct neural mechanisms during retrieval. Study 1 demonstrates that learning and behavioral expression of learning are separable and differentially affected by attention. Studies 2 and 3 provide further evidence that memory-guided behavior is supported by distinct neural substrates. Specifically, Study 1 leveraged high-density electroencephalography (EEG) and revealed a striking brain-behavior dissociation. Learning was observed neurally in two attention conditions. However, only one condition, in which attention was directed to the task-relevant object at learning, led to a memory-guided behavioral benefit at retrieval. Further, these behaviorally accessible memories were accompanied by an implicit neural memory component that correlated with the degree of response preparation, but not with response execution. In Study 2, I conducted a systematic review and a meta-analysis and demonstrated that fronto-parietal attention and control networks are critical for memory-guided behavior. Study 3 empirically validated this working model, using time-frequency source localization. Specifically, I showed that, in addition to fronto-parietal networks, memory-guided behavior is accompanied by anterior temporal lobe activity that scales with the magnitude of behavioral benefit. Together, the results of the presented studies suggest that 1) attention at learning affects memory accessibility and guided behavior at retrieval and 2) accessible memories that guide behavior are supported by distinct temporal and fronto-parietal networks and implicit neural memory that triggers response preparation.
Rejection-Free and Partial Neighbor Search MCMC Algorithms
Keywords: MCMC
Metropolis Algorithm
Partial Neighbor Search
QUBO
Rejection-Free
Unbiased PNS

The Metropolis algorithm involves producing a Markov chain to converge in distribution to a specified target density $\pi$. To improve its efficiency, we can use the Rejection-Free version of the Metropolis algorithm, which avoids the inefficiency of rejections by evaluating all neighbors. Rejection-Free can be made more efficient through parallel hardware. However, for some specialized hardware, such as Digital Annealing Unit, the number of neighbors being considered at each step is limited. Hence, we propose an enhanced version of Rejection-Free known as Partial Neighbor Search, which only considers a portion of the neighbors. Partial Neighbor Search can be applied efficiently despite the number of neighbors. Especially for continuous cases with uncountable many neighbors, Partial Neighbor Search can be applied easily and samples efficiently while Rejection-Free is not feasible, and the Metropolis algorithm is slow. Both algorithms can be used in many other circumstances as well, such as the optimization question. In combinatorial optimization, Simulated Annealing using Metropolis steps at decreasing temperatures are widely used to solve complex problems. In order to improve its efficiency, we can also use the Rejection-Free version of the Metropolis algorithm, which avoids the inefficiency of rejections by considering all the neighbors at every step. In addition, in optimization questions, Partial Neighbor Search can not only be helpful when being applied on parallel hardware, but it can also avoid the algorithm from becoming stuck in local extreme areas, and thus Partial Neighbor Search for optimization finds the optimal solution much faster than the other two algorithms. For both sampling and optimization, we demonstrate the superior performance of the Rejection-Free and Partial Neighbor Search algorithms by applying these methods to several examples, such as the Ising mode, the QUBO question, the Knapsack problem, the 3R3XOR problem, the quadratic programming, etc.