VictorJuiz/thesis huggingface dataset:
Tissue Mechanics Govern Tumor Quiescence and Chemosensitivity in Medulloblastoma
Keywords: Blood-tumor barrier
Gpr68
Mechanobiology
Medulloblastoma
Piezo2
Sonic Hedgehog Signaling

Medulloblastoma is the most prevalent malignant brain tumor in children (WHO grade 4) that encompasses a heterogeneous group of cerebellar or brainstem embryonal tumors. Current standard-of-care is met with therapy resistance and associated with severe neurocognitive, neuroendocrine, and psychosocial side effects. Intratumoral heterogeneity contributes to treatment resistance and poor prognosis. Loss of mechanical homeostasis is a hallmark of the tumor microenvironment. Mechanosensors, which convert mechanical stimuli into intracellular signals, are key molecules that mediate mechanotransduction mechanisms in malignant diseases. Modulating mechanosensors may offer therapeutic opportunities to reduce disease burden associated with medulloblastoma. My study reveals that Sonic Hedgehog medulloblastoma (which encompasses a third of medulloblastoma patient cases) constructs spatial tissue stiffness niches to dictate region-specific tumor properties. Mechanosensitive ion channel Piezo2 and mechanosensitive G protein-coupled receptor Gpr68 perceive stiffness cues to modulate medulloblastoma growth and chemoresistance. Piezo2 orchestrates an actomyosin-Wnt/β-catenin signaling axis to determine medulloblastoma propagating cell quiescence and blood-tumor barrier permeability. Gpr68 regulates microtubule and primary cilia to promote SHH signaling and reduce tumor quiescence. Loss of Piezo2 improves delivery of therapeutic agents and survival of chemotherapy-treated medulloblastoma-bearing mice. Loss of Gpr68 suppresses medulloblastoma tumor cell proliferation at the expense of reducing tumor chemosensitivity. Collectively, my study reveals spatial tissue mechanics in medulloblastoma, identifies specific mechanosensors that govern tumor quiescence and chemosensitivity, and demonstrates that modulating mechanosensor functions provide a viable approach to treat malignant brain tumor.
Honouring Grief Experiences in Life, Death, and the Workplace: A Critical Analysis of Bereavement Accommodation for Workers in Precarious Employment in Canada
Keywords: Bereavement
Critical
Ethics
Grief
Policy
Precarious employment

Bereavement scholarship predominantly explores psychological aspects of grief, which neglects the role of social, economic, and political factors that shape the space allotted to accommodate these experiences. The current Canadian social context offers minimal space to honour bereavement as a part of the human condition. Aiming to respond to calls for enhancing bereavement care, this dissertation explores bereavement accommodation for workers in precarious employment in Ontario, Canada. Drawing on critical qualitative research and feminist ethics, this study employs policy analysis and in-depth interviews to generate multi-scalar knowledge on the everyday experiences of bereaved workers in precarious employment. I argue that there are discrepancies between how bereavement is represented in the social context and the everyday experiences of bereaved workers. The current representation portrays bereavement as a short-term, workplace disruption, neglecting grief and many forms of practical and emotional labour in bereavement. Participants expressed they were uninformed and unprepared for grief and bereavement labour, and that navigating the current context created tension, stress, exhaustion, isolation, and stigma. I argue we need a collective, ontological reckoning with our sense of autonomy, recognizing and honouring our interdependence in life and death. I argue that bereavement is a neglected public health issue driven by socio-political forces that devalue relationality, stigmatize emotions, and render bereavement an individual responsibility. This thesis makes broad recommendations for a public health approach to bereavement care, including enhancing grief literacy, creating more responsive care pathways and strategies for addressing individual and collective grief, and establishing safeguards for precarious workers.
Understanding the Connections between Neighborhood Environments and the Burden of Infectious and Non-communicable Diseases in Ghana
Keywords: Behavior
Double burden of disease
Environmental risk
Ghana
Neighborhood environment
Non-communicable disease

Amidst the persistent burden of infectious diseases (i.e., malaria, HIV) across many developing country settings, there is now the added burgeoning burden of non-communicable diseases [NCDs (i.e., cancer, and diabetes)]. This concurrence, described as the double burden of disease (DBD), presents a fundamental public health challenge to governments and relevant stakeholders situated in the global south. The DBD phenomenon has triggered a wave of research interests and policy debates with a focus on behavioral change interventions to the neglect of population-level determinants like the environment. The DBD further appears to have emerged at a time when the healthcare system is not well positioned to effectively respond to population health needs. This dissertation contributes to these gaps by examining the relationship between neighborhood environments and the burden of NCDs and infectious diseases across three cities (Accra, Tamale, and Wa) in Ghana using a sample of 1386 surveys that were collected between September – December 2021. I further examined whether NCD health outcomes differed by gender spatially using multilevel analytic techniques in Stata 14.2 software. Results show that about 1 in 4 people reported at least one NCD health condition and nearly 1 in 5 reported suffering the DBD. The findings further revealed spatial variations of NCD and infectious disease outcomes as respondents from relatively deprived neighborhoods were significantly more likely to report poor health outcomes. Men who spend time outside their residential neighborhood in a typical week were more likely to report being diagnosed with NCDs compared with their counterparts who spend the entire week in their residential neighborhoods. The results demonstrate the need to move beyond individualistic risk factors to discussing important population-level determinants of NCDs like the environment in the fight against NCDs in the developing world. Moreover, the static view of the role of place on health is too reductionist and there is the need to account for other spaces people frequent through a gendered lens. Finally, the emerging epidemiologic transition in Ghana and other developing countries calls for a retooling of the healthcare system to effectively respond to the changing health needs of the population.
Information-Theoretic Measures of Generalization in Machine Learning
Keywords: Generalization Theory
Information Theory
Machine Learning

Machine learning (ML) technologies are rapidly being adopted across various industries, scientific fields, and governments. However, despite the widespread use of ML, the research community still lacks a thorough understanding of the principles that explain when and why these technologies work in real-world applications. One of the primary challenges to deploying ML methods is ensuring generalization, or the ability of the model to perform well on unseen data as well as on training data. In this thesis, we explore generalization from an information-theoretic perspective. This perspective allows us to examine the impact of learning algorithms and data distribution on generalization error, a crucial feature that offers an opportunity to address an essential open challenge in generalization theory. Our main goals in this thesis are twofold: (I) to explain the performance of existing learning algorithms used to train modern deep neural networks and (II) to unify and simplify the landscape of generalization frameworks using the language of information theory. For goal (I), we propose a novel approach based on data-dependent estimation to estimate the mutual information terms that appear in generalization bounds. We demonstrate the applicability of this technique in studying the generalization error of Stochastic Gradient Langevin Dynamics (SGLD). Our numerical analyses show that the obtained bounds are the first non-vacuous generalization guarantees for SGLD and its full-batch counterpart for modern deep-learning datasets and architectures. Regarding goal (II), we explore the connections between information-theoretic frameworks for generalization and classical min-max frameworks for generalization. Our results indicate that information-theoretic frameworks are highly expressive in the context of binary classification. However, we also uncover some limitations of information-theoretic techniques when analyzing stochastic gradient descent in the context of stochastic convex optimization.
Social Environment Influences Interaction Dynamics and Group Structure in Drosophila melanogaster
Keywords: Behaviour
Genetics
Network

Drosophila melanogaster engage in a variety of social behaviours and interactions including complex courtship and mating rituals, aggregation in both lab and wild environments, and aggressive fights. Using social network analysis, I explore the effects of group composition and group size on individuals’ behaviours and group network cohesion. I first show that a strain of hyperaggressive flies differs from wildtype flies in both their individual behaviors and group level network properties. When combined in different ratios, mixed groups behave differently than either all hyperaggressive or all wildtype groups, and the shift in their individual and network properties is towards and past the hyperaggressive flies regardless of the ratio. Remarkably, a single hyperaggressive fly in a group of wildtype flies is enough to define the entire groups’ structure. In my second data chapter I show that flies are capable of discerning group size changes of a single individual. As group size increases, interaction rate and Betweenness Centrality, a network parameter that captures the importance of individuals for information flow, both increase. Disrupting different sensory modalities of flies does not eliminate their ability to discern group size; however, subtle changes in variation and in trends across all group sizes suggest that vision, olfaction, hearing, and mechanosensation are all at least partially involved sensing social group size. Analyses of Coefficients of Variation suggest that flies use the Approximate Number System to assess the size of their social groups, and that there is something biologically important about group sizes 9 and 10. The size and composition of flies’ social environments affects both individual behaviours and group level phenotypes.
A Multimodal Investigation of Age Differences in Inhibitory Control
Keywords: aging
cognitive control
eye-tracking
fMRI
inhibitory control
tractography

Cognitive control – a set of mental processes that allow us to perform goal-directed actions and flexibly adapt our behavior under changing circumstances – is reduced in aging. Older age is also accompanied by changes in the structure and functioning of the frontoparietal network that supports cognitive control processes. This thesis examines the relationship between the white matter properties and functional recruitment of the frontoparietal network and their association with performance on cognitive control tasks in healthy aging. In a large, cross-sectional lifespan sample of adults, the first chapter explores the microstructural and macrostructural properties of frontoparietal white matter and its association with performance in three domains of cognitive control: working memory, inhibitory control, and updating ability. White matter microstructure (i.e., fractional anisotropy, FA) was associated with age-related reductions in response inhibition, as assessed by the go/no-go task. Based on the notion that brain function is constrained by the underlying anatomy, the second chapter investigates whether FA influences task-related activation (i.e., BOLD activity) of the frontoparietal network during inhibitory processing, as well as the joint contribution of frontoparietal FA and its functional recruitment to age-related differences in response inhibition. Frontoparietal FA was not related to BOLD activity, but it mediated age-related differences in go/no-go response times that in turn influenced age-related differences in accuracy. Thus, it appears that the microstructure of the frontoparietal network bears greater relevance than functional recruitment for explaining age-related differences in response inhibition. Lastly, the third chapter examines whether age differences in inhibitory control influence other aspects of cognition, namely, recognition memory. Inhibitory control was measured in two ways: through the ability to fixate (i.e., oculomotor control) and the ability to inhibit visual distraction (i.e., distractor suppression). Older adults were just as efficient as younger adults at inhibiting distraction, resulting in similar levels of subsequent distractor recognition between the two groups. Nonetheless, older adults still showed poor oculomotor control compared to younger adults. Altogether, this thesis demonstrates the heterogeneity in cognitive control processes as well as the neural correlates supporting one domain of control, namely, response inhibition, across the adult lifespan.
Designing for the Affective Resilience of Diasporic Population through Cultural Heritage
Keywords: cultural heritage
design
Human-Computer Interaction (HCI)
immigrant
resilience

Affective resilience refers to the ability of individuals, families, and communities to adapt, cope, and recover feelingly from adverse events, challenges, or stressors. For migrants facing diaspora, their cultural heritage can be a critical aspect of affective resilience, as it provides a sense of belonging and purpose. Previous research in Human-Computer Interaction (HCI) regarding the affective resilience of migrants explored migrants’ relations with the larger social circle and the altered family dynamics within diasporic families. However, research in this realm often overlooked the significance of cultural heritage. To address this gap, this dissertation explores different design concepts to building technologies that can support migrants in acquiring, maintaining, and transmitting their cultural heritage, with the overarching goal of fostering their affective resilience. Specifically, the dissertation presents three design concepts targeting individual, family, and community levels respectively. At the individual scale, the user-led design concept was employed, resulting in the creation of “My Home Sketcher,” an augmented paper-based tool that enables novice users to design their homes, reflect their values, and express their space, light, and privacy preferences through sketches that are then transformed into 3D models by a computer algorithm. At the family scale, the community-based gamification concept was used to develop two applications, “Bornomala” and “KnowLink Exchange,” which aim to teach migrants’ children about their heritage language. At the community scale, the reenactment concept was employed, resulting in the creation of “Be Our Guest”, an augmented reality (AR) application where a user is virtually invited to the homes of people from different cultures and is asked to help with one of their cultural rituals through simple everyday objects. This dissertation contributes to our understanding of the intricate interplay between migration, cultural heritage, and resilience. The dissertation shows the significance of cultural heritage in shaping migrants’ sense of self and presents insights and recommendations on how to design with this aspect in mind, emphasizing the critical need for intentional integration of cultural heritage in HCI research. Finally, the dissertation highlights the multifaceted challenges encompassing cultural, linguistic, social, ethical, and academic dimensions encountered when working with migrants and offers methodological approaches that could be incorporated to navigate these complexities.
Monoterpenoid Volatile Biosynthesis in Rose-Scented Geranium (Pelargonium graveolens)
Keywords: Essential oil
Glandular trichomes
Monoterpenes
Pelargonium
Terpenoids

Rose-scented geraniums (Pelargonium graveolens) are rich in monoterpene containing essential oil that is stored in glandular trichomes. This essential oil has substantial variation in its composition with its value directly correlated to the ratio of geraniol to p-menthane monoterpenes. Based on whole plant 13CO2 labeling experiments, at least two biosynthetic pathways contribute to the monoterpenes that are stored in glandular trichomes. Distinct chemotypic groups favor either the accumulation of cyclic p-menthanes such as isomenthone or acyclic monoterpene alcohols such as geraniol and citronellol. This metabolic split between ‘mint-like’ p-menthanes and ‘rose-like’ acyclic monoterpene alcohols reflects the relative contributions of two compartmentally separated monoterpenoid biosynthetic pathways, a scenario which departs from the classical view of plastids as the sole source of monoterpenoid backbones. In this species, p-menthane skeletons are produced in the plastid from geranyl diphosphate (GDP) derived from the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway in a pathway resembling monoterpene biosynthesis in most plant species. However, the acyclic monoterpene alcohols in P. graveolens are produced in the cytosol without the participation of a conventional monoterpene synthase. Instead, a cytosolic Nudix hydrolase acting on an atypical cytosolic pool of GDP forms geranyl monophosphate as a substrate for a phosphatase to produce geraniol directly in the cytosol. Biochemical characterization showed that a cytosolic, farnesyl diphosphate synthase-like cDNA encodes a multi-product enzyme that produces GDP which supplies substrate to this cytosolic geraniol pathway. The identification of distinct monoterpene pathways in the cytosol and plastid of these geraniums offers insight into essential oil biosynthesis in glandular trichome bearing plants.
Sensorimotor integration in Parkinson’s disease during lower limb movements
Keywords: balance
beta
lower limbs
motor blocks
Parkinson disease
sensorimotor integration

External sensory information can be applied to facilitate balance in Parkinson’s disease (PD); however, in some instances, it can also disrupt movement (e.g., doorways and fast auditory cues). We examined visual-vestibular sensory integration during gait (Study 1) and neural oscillatory activity in response to doorways (Study 2) and auditory cues (Study 3) during foot pedaling. In Study 1, we tested 13 people with PD, 13 older adults (OA), and 15 young adults (YA). While walking in a virtual environment, visual and vestibular perturbations were applied to cause deviations in gait trajectories. We found that people with PD and OA integrated perturbed sensory information and showed more gait deviations than YA. In Study 2, we tested 19 people with PD while seated with electroencephalography. They were required to bilaterally pedal their feet to navigate through a virtual series of doors. Doorway-provoked lower limb motor blocks (LLMB) correlated with freezing severity and were associated with decreased beta and theta oscillations in the left temporal pole. Dopaminergic medications increased beta and theta power in the left fusiform gyrus and reduced LLMB percent durations. In Study 3, we tested 25 people with PD undergoing deep brain stimulation surgery. We recorded in the globus pallidus internus (GPi) or subthalamic nucleus (STN) while they pedaled their feet in a supine position in synchrony with auditory cues. We found that the GPi responded to the sensory aspect of the task, showing tonic beta desynchronization with fast cue frequencies. The STN responded to motor aspects of the task with beta rebounds following motor onset. Overall, we show that i) visual-vestibular sensory integration may be preserved in PD, and ii) motor block triggers, such as doorways and fast auditory cues, are related to decreased oscillatory activity in the ventral visual pathway and increased beta modulations in the basal ganglia. Understanding the role of these neurophysiological changes can open avenues to improve treatment in PD.
Certain Cases of Hikita-Nakajima conjecture
Keywords: Algebraic geometry
Representation theory
Symplectic duality

Let $\mathfrak{M}_0$ be an affine Nakajima quiver variety, and $\mathcal{M}$ is the corresponding BFN Coulomb branch. Assume that $\mathfrak{M}_0$ can be resolved by the (smooth) Nakajima quiver variety $\mathfrak{M}$. The Hikita-Nakajima conjecture claims that there should be an isomorphism of (graded) algebras $H^*_{S}(\mathfrak{M},\mathbb{C}) \simeq \mathbb{C}[\mathcal{M}_{\mathfrak{s}}^{\mathbb{C}^\times}]$, where $S \curvearrowright \mathfrak{M}_0$ is a torus acting on $\mathfrak{M}_0$ preserving the Poisson structure, $\mathcal{M}_{\mathfrak{s}}$ is the (Poisson) deformation of $\mathcal{M}$ over $\mathfrak{s}=\on{Lie}S$, $\mathbb{C}^\times$ is a generic one-dimensional torus acting on $\mathcal{M}$, and $\mathbb{C}[\mathcal{M}_{\mathfrak{s}}^{\mathbb{C}^\times}]$ is the algebra of schematic $\mathbb{C}^\times$-fixed points of $\mathcal{M}_{\mathfrak{s}}$. In this thesis we prove the Hikita-Nakajima conjecture for $\mathfrak{M}= \widetilde{\C^2/ \Gamma}$ (Kleinian singularities) and $\mathfrak{M}=\mathfrak{M}(n,r)$ Gieseker variety ($ADHM$ space). In the latter case we produce the isomorphism explicitly on generators. We also describe the Hikita-Nakajima isomorphism above using the realization of $\mathcal{M}_{\mathfrak{s}}$ as the spectrum of the center of the rational Cherednik algebra corresponding to $S_n \ltimes (\mathbb{Z}/r\mathbb{Z})^n$ and identify all the algebras that appear in the isomorphism with the center of the degenerate cyclotomic Hecke algebra.
A Self-Determination Theory Perspective on Motivational Interviewing for Emerging Adults Who Use Cannabis
Keywords: Brief Intervention
Cannabis
Emerging Adulthood
Motivational Interviewing
Self-Determination Theory

Emerging adults (EAs) between the ages of 20-to-24-years-old have the highest prevalence of past year cannabis use in Canada. It can be challenging to engage EAs in interventions to reduce their cannabis use and brief interventions have an important function as an initial step in the continuum of care. The current study involved a pilot of a single session of motivational interviewing delivered virtually. We also tested whether changes in basic psychological needs were associated with treatment, given recent theoretical models highlighting the link between motivational interviewing (MI) and Self Determination Theory (SDT). Participants were 40 EAs (ages 19-25), who engaged in high frequency cannabis use and were randomized to either a virtual MI intervention (n=20) or a control group (n=20). At a 90-day follow up, there was a significant increase in perceived competence to change cannabis use for the total sample, along with changes in basic psychological needs (autonomy satisfaction) (p = 0.00), there were no group differences in cannabis use consequences, autonomy satisfaction/frustration, competence satisfaction/frustration or relatedness satisfaction/frustration, autonomous and controlled treatment motivation, perceived competence to change one’s cannabis use, or participants’ willingness to initiate contact with follow-up treatment resources. The findings are discussed in the context of future directions for brief interventions and some of the limitations of the study, including delivery online during COVID-19, where sense of control and autonomy may have been more limited and changes to cannabis use more challenging.