VictorJuiz/thesis huggingface dataset:
Predicting Health Outcomes from Hematopoietic Evolution

The genomic architecture of blood is complex with germline polymorphisms, somatic point mutations, and mosaic chromosomal alterations (mCAs) shaping the fitness of immune cells. Many advances have been made in understanding how the age-associated acquisition of somatic mutations in blood, termed Age-Related Clonal Hematopoiesis (ARCH), predispose individuals to blood cancer. Yet, ARCH is commonly observed in healthy individuals and our ability to predict who is at risk of progressing to disease remains limited. In this thesis, I interrogate the mutational and selective pressures within blood to understand how the full spectrum of somatic changes within an individual impact clonal fitness and cancer outcomes. I integrate deep learning and population genetics to evaluate the interplay of positive and negative selection in deeply sequenced blood samples from 92 individuals who subsequently progressed to blood cancer and 385 controls. I discriminate amongst evolutionary classes with high accuracy (86%) and capture pervasive signatures of purifying selection in blood cells. The proportion of passenger-to-driver mutations in an individual appears to be critical in determining if the selective advantage conferred by a driver mutation can overwhelm purifying selection acting on passenger mutations thus allowing disease-predisposing clones to rise to dominance. Further, I evaluate how selection shapes the prevalence of mCAs among 14,000 individuals. I find that mCA-associated ARCH is three times higher than previously estimated with up to one in eight individuals harbouring a mCA. I find that mCAs accumulate preferentially across genes implicated in blood cancer development and observe a 136% increase in the rate of cancer development for each additional autosomal mCA. To determine the functional impact of mCAs, I investigate the relationship between mCAs and gene expression and find that different types of mCAs impact gene expression distinctly. Over 30% of eQTLs are impacted by mCAs, with loss events accounting for 9.1% of allele specific expression revealing a previously overlooked somatic contribution to blood expression profiles, regulatory mechanisms, and disease development. In summary, my work explores how different evolutionary models shape clonal dynamics in healthy and pre-cancerous blood and are critical when leveraging the predictive power of somatic events for early cancer detection.

Keywords: Clonal hematopoiesis
Computational biology
Evolutionary modelling
Hematopoietic stem cells
Population genetics
Somatic mosaicism
Advisor: Awadalla, Philip
Primavera Italiana

Primavera Italiana (“Italian Spring”) is a celebration of beauty, self-regeneration and rebirth. The feelings, memories and sensations associated with the spring season in Italy are the underlying inspiration of this orchestral piece; the mild weather, warm light, clear sky, radiant colours, inebriating scents of flowers, the rebirth and regeneration of nature in all its forms are hence translated into music. The orchestra alternates between brilliant, sparkling moments and warm and intimate ones to express all the feelings and sensations associated with this season. Deeply and subtly woven within the manifold and mysterious means of the musical language are descriptivism and suggestiveness: is that trill a butterfly fluttering its wings or a daisy gently caressed by the warm breeze in a luxuriant blooming field? Is that luminous orchestral chord a sparkling ray of sun or a clear blue sky? The composer cannot answer these questions by giving precise and direct references between the music and the images it strives to depict. Instead, he will let the music speak for itself and the listener make their metaphorical and symbolic associations within their own hearts and souls. Indeed, this is the universal and inscrutable mystery of music, its eternal power and beauty: not a single word, but an infinite array of memories, images, feelings and sensations created in the mind of those who write, play, and listen to it. May the Italian spring unfold and resound and give healing, rebirth and regeneration to our souls!

Advisor: Hatzis, Christos
Interface Passivation in Perovskite Photovoltaics: Formation, Dimensionality and Photophysics

Achieving net zero carbon emissions requires a 30-fold increase in solar power within 30 years. To reduce costs, cheaper alternatives to Si photovoltaics are being explored. Metal halide perovskites are defect-tolerant semiconductors, meaning low-cost manufacturing methods can produce thin films with outstanding optoelectronic properties. However, perovskite cells suffer from relatively poor stability due to their soft crystal structure and high mobile ion densities. As interfaces have the highest defect densities, successful methods to improve stability and efficiency focus on perovskite film surfaces. In this thesis I present methods to passivate perovskite interfaces for improved performance and operating lifetime.I begin by exploring the formation of 2D/3D perovskite heterostructures. Converting the top surface of a perovskite film into 2D perovskite creates a barrier to ion movement and passivates surface defects. Despite their use in high efficiency devices, the formation mechanism of the 2D layer was unknown. I found three formation routes that depend on solvent and perovskite composition. By using non-polar solvents, I was able to slow down the 2D conversion reaction to produce more uniform 2D layers improving power conversion efficiency (PCE) from 20% to 21.9%. Next, I demonstrate that modifying the dimensionality of the 2D layer alters its energetic alignment. I present two methods to tune dimensionality and use drift-diffusion modeling to explain resulting photovoltaic performance. Previous studies have shown that 2D/3D heterostructures have the correct band alignment to improve only the hole contact in n-i-p configured cells. Herein I demonstrate dimensional tuning to produce p-i-n perovskite solar cells with 23.9% PCE (certified quasi-steady state, NREL). When subjected to ISOS-L3 accelerated ageing, these devices retain 92% of initial PCE after 500 h. Finally, I describe a method to alter the surface energetics of a wider bandgap perovskite absorber (1.8 eV). In this case, no 2D layer is formed. Instead, the 1,3–propanediammonium surface treatment removes structural heterogeneity and improves band alignment with a C60 (fullerene) electron transporting layer. When built into a monolithic tandem, PCE is 27.4%, higher than the best single junction Si cell. These tandems retained more than 86% of their initial PCE after 500 h of operation.

Advisor: Sargent, Edward H
Capturing Residential Preference Changes through Perception Detections of Rationally Inattentive Decision Makers

This dissertation focuses on the changes in aggregate residential trends and disaggregate perturbations in residential location choice behaviour. The empirical investigation uses the contexts of the COVID-19 pandemic in the Greater Toronto Area (GTA). Two conceptual models are presented in the study, each providing a unique perspective on analyzing residential preferences and forming the foundation of the research. The study delves into both the short- and long-term effects of the pandemic on residential location choice behaviour and aims to understand how preferences differ across various demographic groups. The research is based on Stated Preference (SP) surveys collected in July 2020 and July 2021 and housing price data for different dwelling attributes from January 2019 to August 2021. The dissertation proposes a new Efficient Adaptive Stated Preference (EASP) survey design that detects respondents’ tastes while doing the survey and integrates present information in choice experiment designs to improve the quality of SP data collection. The effectiveness of the EASP design is evaluated using a data-driven Neural Network model. The thesis also introduces an empirical model of rational inattention discrete location choice based on latent preferences and attention span. This model contributes to explaining the heteroskedasticity of different demographics in decision-making. The proposed methodology is validated by comparing its performance with comparable classical discrete choice models. Overall, the dissertation highlights the importance of high-quality data collection in the context of residential location choice and how the proposed survey design and empirical models can help improve data collection accuracy and inform policy decisions. The research has theoretical and practical implications for the planning of residential neighbourhoods, especially in the context of pandemics and other unexpected demand shocks.

Keywords: Adaptive Survey
Conjoint Analysis
Discrete Choice Modelling
Rational Inattention
Residential Location Choice
Stated Preference
Advisor: Habib, Khandker M. N.
The Evolution of NF-κB Mediated Transcriptional Regulation in Mammalian Endothelial Cells

NF-κB is an essential and evolutionarily conserved transcription factor complex primarily involved in innate immunity and inflammation. In the thesis, I explore how the NF-κB-centric regulatory mechanism evolves using a comparative epigenomic/transcriptomic approach across multiple mammals. Transposable elements (TEs) have been known to innovate immune transcriptional regulatory networks; however, how TEs have contributed to the modulation of NF-κB response during mammalian evolution is not clear. In Chapter II, I characterize the contribution of TEs to NF-κB bound regions in human, mouse and cow endothelial cells following stimulation with a potent cytokine. I found that multiple transposons served as potential NF-κB recruiting enhancers, demonstrated by multiple active epigenetic features and close distribution near target genes. The majority of TE contributions to NF-κB binding were species-specific, with the most notable example being the Bov-tA1/2/3 which derived over 14,000 NF-κB binding events in cow. Meanwhile, I found several ancient transposons engaging in NF-κB binding, including MER81, which colonized the genome prior to the divergence of placental mammals with two intact NF-κB motifs. Notably, I showed that one distal MER81 element is required for the activation of IFNGR2, demonstrating TE’s functional co-option into gene regulatory networks.In order to explore NF-κB mediated gene regulation, we next performed a multi-species comparative epigenomic/transcriptomic analysis involving chromatin accessibility (ATAC-seq), TF occupancy/ histone modification profile (ChIP-seq), chromatin conformation (HiC) and transcriptional expression (RNA-seq). With the multi-species chromatin accessibility data, I found multiple transcription factors with increased (NF-κB and AP-1) and decreased (several anti-angiogenesis factors) footprint activity upon cytokine induction across species, suggesting conserved regulatory logic in gene regulation and potential functions. The cross-species comparison of gene inducibility indicates high constraints on target genes despite much relaxation on their initial response magnitudes. Importantly, conserved target genes are associated with dynamic regulatory changes around their promoters upon cytokine induction, likely indicative of specific epigenetic features for the resilience of gene inducibility. Lastly, I highlighted candidate gene loci which may exemplify how regulatory changes could lead to the evolution of gene inducibility. Altogether, my thesis reveals general principles that underlie the evolution of NF-κB mediated transcriptional regulation.

Keywords: comparative genomics
endothelial cells
mammalian evolution
NF-κB
transcriptional regulation
transposable elements
Advisor: Wilson, Michael D
Kafri, Ran
Social Norms and Ethical Entanglements: The Canadian Lawyer’s Risk of Automatic Self-Interest in Ethical Decision Making

Scholars in the area of behavioural ethics and behavioural economics have established that automatic self-interest can lead to unconscious unethical behaviour. The focus herein is on instances where automatic self-interest stems from ethical ambiguities in Canadian codes of legal ethics, opening the door to possible ethical sanctions where lawyers were not morally blameworthy for the unethical behaviour. This automatic self-interest can be mitigated by the presence of social norms. Herein, a survey of Canadian lawyers is undertaken in order to respond to two central research questions: (1) What are the ethical social norms of Canadian lawyers?; and (2) What methods can be used to alter the current social norms of Canadian lawyers to mitigate automatic self-interest? I respond to these questions while also acknowledging that social norms may differ between sub-groups of Canadian lawyers on grounds such as official language of practice and Indigeneity.

Keywords: Automatic Self-interest
Legal Ethics
Social Norms
Advisor: Yoon, Albert
Dynamical Sculpting of Compact, Multi-planet Systems

The Kepler mission discovered thousands of exoplanets and completely revolutionised planetary astronomy. Over one thousand of these exoplanets are in multi-planet systems with architectures remarkably different from that of our Solar System: compact, multi-planet systems. Many hypotheses about their evolution involve dynamical sculpting --- gravitational planet-planet interactions accumulating over billions of orbits. This can drastically alter their orbits, consequently sculpting multi-planet systems into the architectures of the observed, mature Kepler systems. In this dissertation, I explore dynamical sculpting through two different projects. First, I examine how the dynamical spacing between orbits affects the system's instability timescale. Probing a high-density distribution in dynamical spacing, I saw additional structure on top of the instability-spacing relationship which corresponded to period commensurabilities. Consequently, I hypothesise that interacting mean motion resonances of multiple pairs of planets are responsible for the dynamics of such systems, and ultimately driving the instability. Second, I re-visit the dynamical packing of the Kepler multi-planet systems. Using a machine learning method to examine the stability of over 9 million different orbital configurations, I found that most systems are strongly packed. Furthermore, dynamical packing increases with a system's observed planet multiplicity, which is consistent with dynamical sculpting throughout system evolution or with lower multiplicity systems having a higher likelihood of unseen planets. These projects advance the field's knowledge of the dynamics of compact, multi-planet systems and the role of dynamical sculpting throughout their evolution. My first project provided a foundation to further understand the dynamics and instability which are responsible for dynamical sculpting. My second project quantified a dynamical property of mature, observed systems, finding that it may be consistent with such systems being dynamically sculpted. The road ahead for research in this field is promising --- current and upcoming surveys will expand the catalogue of observed multi-planet systems and machine learning methods will continue to improve our theoretical understanding of planetary dynamics.

Keywords: Dynamics
Exoplanets
Planetary systems
Advisor: Murray, Norman
p-adic Integration for Derived Equivalent Abstract Hitchin Systems

Let Mˆ denote the moduli space of SLn-Higgs bundles and let Mˇ denote the moduli space of PGLnHiggs bundles. Under the appropriate conditions and equipped with some additional data, Mˆ and Mˇ form a dual pair of abstract Hitchin systems in the sense of [GWZ20b]. The authors make the superfluous assumption in loc. cit. that the stacks defining the abstract Hitchin systems are quotient stacks. This is sufficient for their purposes as their intended application is resolving the topological mirror symmetry conjecture of Hausel-Thaddeus in [HT03]. In particular, they prove that the Hodge numbers of Mˆ , which is a smooth variety, are equal to the stringy Hodge numbers of Mˇ , which is a smooth orbifold. In this thesis, the notion of abstract Hitchin systems is extended to certain tame Deligne-Mumford stacks, subject to some conditions. This allows us to remove the assumption that the abstract Hitchin systems are Zariski-locally quotient stacks. This is achieved via passing to an ´etale cover on which the stack is a quotient stack, using an original lemma that says we can choose ´etale neighbourhoods of points such that the residue field remains unchanged. This allows us to apply the methods of p-adic integration as in [GWZ20b] and [GWZ20a]. In [HT03], it is shown that the spaces Mˆ and Mˇ are generically fibred over the Hitchin base in Lagrangian tori. Furthermore, each space is equipped with a gerbe, and are dual in the sense that the fibres are torsors over an abelian variety and are isomorphic as torsors to the equivalence classes of trivializations of the gerbe on the dual fibre. A similar algebro-geometric version of this duality is formulated for abstract Hitchin systems in [GWZ20b] and it is shown that topological mirror symmetry follows from an arithmetic version proven via p-adic integration. We reformulate this duality condition as a twisted derived equivalence of abstract Hitchin systems equipped with certain gerbes and recover arithmetic mirror symmetry via p-adic integration in this context.

Advisor: Groechenig, Michael
Aspects of Resummation in Effective and Finite Temperature Field Theory

This thesis focuses on developing resummation techniques to study collider observables and cosmological phase transitions. In the first part of the thesis, an alternative formalism of Soft-Collinear Effective Theory (SCET) is used to study next-to-leading power (NLP) corrections in deep inelastic scattering (DIS) in the endpoint limit ($x \rightarrow 1$) and Drell-Yan production of gauge boson with transverse momentum small compared to their invariant mass (small-$q_T$). In the second part of the thesis, a modified version of the Optimized Partial Dressing (OPD) scheme is developed for perturbative thermal resummation of effective potential at finite temperature. The formulation of SCET used here does not separate the infrared degrees of freedom into separate modes, which makes it calculationally simpler to study NLP corrections. This is used to obtain the inclusive cross-section for DIS in the endpoint limit. It is also demonstrated that spurious endpoint divergence which appear at NLP is cancelled by the overlap subtraction which is required to remove double counting at leading power. For Drell-Yan production at small transverse momentum this formalism is used to calculate the inclusive cross-section in terms of power-suppressed operators which are also renormalized in the rapidity space. Finally for the work related to thermal resummation, it is shown that the original formulation of OPD scheme has large scale dependence when compared to techniques like Dimensional Reduction. It is demonstrated analytically and numerically that this scale dependence is significantly reduced for a $\phi^4$ theory by the inclusion of two loop sunset graphs and its daisy descendants.

Keywords: Effective Field Theory
Finite Temperature Field Theory
Quantum Chromodynamics
Resummation Methods
Advisor: Luke, Michael E.
Two Problems in Non-Linear Evolution Equations

Part I: The theory of coupling between internal and surface waves for stratified fluid domains is a rich source of dispersive and non-linear model equations with broad applications to ocean engineering. We study the two-dimensional water wave problem consisting of two fluid domains, the lower of which is infinitely deep, separated by a sharp interface, which is due in practice to a temperature or salinity gradient, and analyze the coupling effect of free internal and surface waves. Starting from the incompressible, irrotational Euler equations of motion for a two-layered fluid consisting of two different densities, we use its Hamiltonian formulation and the corresponding canonical variables to derive a coupled system for the evolution of two waves, where the small amplitude, internal long wave is modelled by a Benjamin-Ono equation. The surface elevation, on the other hand, has a shorter wavelength and is modelled by a modulated monochromatic wave whose envelope satisfies a time-dependent, linear Schr\"odinger equation. The coefficients of the coupled system are evaluated in terms of the physical parameters. Our results extend previous work on the coupled Korteweg-de-Vries and modulational regime for coupling between internal and surface waves in shallow water by Craig, Guyenne and Sulem (\cite{CGS10}, \cite{CGS12}) to the case of deep water.\newline \\ \noindent Part II: Bochner formulas are often the starting point for the analysis of Riemannian manifolds with bounded Ricci curvature. We generalize the classical Bochner formula for the heat flow on evolving manifolds $(M,g_{t})_{t \in [0,T]}$ to an infinite-dimensional Bochner formula for martingales on parabolic path space $P\mathcal{M}$ of space-time $\mathcal{M} = M \times [0,T]$. Our new Bochner formula and the inequalities that follow from it are strong enough to characterize solutions of the Ricci flow. Specifically, we obtain characterizations of the Ricci flow in terms of Bochner inequalities on parabolic path space. We also obtain gradient and Hessian estimates for martingales on parabolic path space, as well as condensed proofs of the prior characterizations of the Ricci flow from Haslhofer-Naber \cite{HN18a}. Our results are parabolic counterparts of the recent results in the elliptic setting from \cite{HN18b}.

Keywords: differential geometry
geometric analysis
hydrodynamics
partial differential equations
Advisor: Haslhofer, Robert
Sulem, Catherine
Aquinas’s Philosophy of Memory

This thesis is a comprehensive study of Thomas Aquinas’s philosophy of memory. It is divided into two sections. In the first part, consisting of the first three chapters, I seek to establish what memory and related concepts such as remembering, recollection, trained memory and “intellectual memory” are for Aquinas. In the second part, I explore how Aquinas conceives of memory as being operative in the cognitive and ethical life of the agent. In the first chapter, I survey the teachings of those figures who exerted the most direct influence on Aquinas on the topic of memory. In chapter two, I give an account of each of Aquinas’s other three interior senses, i.e., the common sense, imagination, and the estimative/cogitative. Given Aquinas’s famous (and prima facie puzzling) definition of memory as the “storehouse of intentions” cognized by the estimative or cogitative power (ST I.78.4), I focus especially on the estimative/cogitative, arguing that this power’s role in Aquinas’s psychology is far more pervasive than has often been surmised. In chapter three, I construct a taxonomy of memory and memory-related concepts in Aquinas’s philosophy. I argue that for Aquinas memoria is a polyvalent term, with broader and narrower meanings, referring to one or more of a number of tightly-related concepts. Uniting these three meanings, however, are three factors: the sensible phantasm, the “intention” of past time, and the “individual intention” cognized by the estimative/cogitative. In chapter four, I argue that memory plays a key (and under-appreciated) role in Aquinas’s gradualist epistemology, in which the acquisition of universals is mediated by a stratified set of sense powers, in which a sensible is progressively “prepared” for abstraction. At its highest level, i.e., the conjoint operations of memory and the cogitative power, sense generates so-called “experience” (experimentum), which Aquinas conceives of as a pre-universal form of cognition that emerges from the comparison (or collatio) of multiple cogitative intentions. In chapter five, I examine Aquinas’s claim that memory is an “integral part” of the virtue of prudence. As in chapter four, I argue that the notion of “experience” provides the key.

Keywords: Aquinas
cogitative power
internal senses
medieval philosophy
memory
Advisor: Black, Deborah