VictorJuiz/thesis huggingface dataset:
The Evolution of NF-κB Mediated Transcriptional Regulation in Mammalian Endothelial Cells
Keywords: comparative genomics
endothelial cells
mammalian evolution
NF-κB
transcriptional regulation
transposable elements

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.
Social Norms and Ethical Entanglements: The Canadian Lawyer’s Risk of Automatic Self-Interest in Ethical Decision Making
Keywords: Automatic Self-interest
Legal Ethics
Social Norms

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.
Dynamical Sculpting of Compact, Multi-planet Systems
Keywords: Dynamics
Exoplanets
Planetary 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.
Aspects of Resummation in Effective and Finite Temperature Field Theory
Keywords: Effective Field Theory
Finite Temperature Field Theory
Quantum Chromodynamics
Resummation Methods

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.
Two Problems in Non-Linear Evolution Equations
Keywords: differential geometry
geometric analysis
hydrodynamics
partial differential 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}.
Aquinas’s Philosophy of Memory
Keywords: Aquinas
cogitative power
internal senses
medieval philosophy
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.
Politics Put to Work: Labour in the Social Economy in Italy
Keywords: Autonomist Marxism
Italy
Labour
Social Economy
Social Reproduction
Work Organizations

This dissertation uses the lived experiences of workers in Milanese social cooperatives as a vantage point to understand the ways that work extends into people’s lives, and how this extension is resisted and negotiated. Social economies require a great deal of dedicated labour. However, workers and their efforts are often overlooked by researchers. Social economy organizations bring about a particular kind of work that combines employment with activism, thus attributing new meanings and functions to work. In the social economy, work is not only an activity to sustain oneself or obtain social status. Instead, it resonates with people’s political commitment and their desires for social change. The dissertation is based on interviews and participant observation in social cooperatives in Milan, Italy. It studies how workers’ political values are put to work by social cooperatives, and how workers experience and act upon their politicized labour. To analyze the politicization of work in these organizations, the dissertation deploys a theoretical framework that merges Italian Autonomist thought with feminist economic geography. The resulting Feminist Autonomist geography is a materialist approach that troubles binary distinctions between life and work, and appreciates how work is made sense of, performed, valorized, and contested in multiple ways. Theorizing labour as a re/productive process that defies conceptual boundaries and expands across time and space makes visible the embodied, affective, interactive, and creative practices of the people who make social cooperatives work. Italian social cooperatives are a laboratory where the politicization of work is both fostered and resisted, a testing ground for transformations of the meanings and practices of work. The case studied in this dissertation is thus a window into the ever-changing geographies of labour and the active role that workers play in them.
Popular Music and Piano Pedagogy: Case Studies in Individual Instruction
Keywords: individual instruction
music education
piano pedagogy
popular music
popular music pedagogy
private lessons

In this study, I set out to examine the pedagogical backgrounds, philosophies, and practices of piano pedagogues who teach popular music in private lessons. The first goal was to understand how their formative musical experiences and education led them to teaching popular music and influenced their pedagogical practices. The second objective was to observe how and what these teachers taught when they taught popular music, and how these pedagogies and curricula departed from their classical pedagogy. In pursuit of this understanding, I developed five case studies consisting of two interviews with the teachers, two lesson observations, and document review of any curricula or lesson plans they use. The cross-case analysis unearthed two primary pathways that took the teachers to popular music: 1) for independent enjoyment, and 2) for functional purposes, such as playing for weddings or teaching students. When teaching popular music, the teachers departed from their teacher-driven classical pedagogies towards a collaborative, student-centered model. This student-centeredness impacted both the repertoire selection and how they learned the music. While the teachers were theoretically open to working with any popular music, they emphasized skills used primarily in western popular music, such as reading lead sheets, chord charts, and arranging. Because all the teachers were exclusively classically trained both musically and pedagogically, working in popular music was occasionally fraught. Teachers either worked to reconcile their classical and popular pedagogical differences, neglected popular music at times in favor of classical music, or employed strategies from both pedagogies to accommodate the student. These case studies can serve as pedagogical models or foundations for further research in how popular music is taught in individual instruction.
Lyric Diction Instruction Pedagogical Content Knowledge: A Search for Instructor Qualifications
Keywords: Diction instruction
Lyric diction
Opera pronunciation
Pedagogical Content Knowledge

Lyric Diction Instruction is a field which has no qualifying degree programs, no apprentice programs, a dearth of research, and no governing body ensuring standards and best practices to which the Lyric Diction instructors could be held accountable. Motivated by this lack of codified standards and training programs, I designed a study to investigate my own Lyric Diction instructional practice, and to identify, through the research framework of action research: (1) What comprises Lyric Diction Instruction Pedagogical Content Knowledge (PCK)? and (2) What impact does my Lyric Diction Instruction approach have on the participants’ diction development over the course of time between an initial Lyric Diction Instruction one-on-one session, and the final performance? Data were collected from two individual case study projects comprised of ten (Case 1) and eleven (Case 2) one-on-one Lyric Diction Instruction sessions. The data included: audio recordings of the one-on-one sessions, which were partially transcribed post-session; field notes; post-session instructor/researcher reflections; and post-instruction feedback given to the lyric diction students by experts in the field. The study generated a literature and data-based PCK break-away specialization entitled Lyric Diction Instruction Pedagogical Content Knowledge, or LyD-PaCK. The investigation identified the fields of research and education which comprise the pillars of Lyric Diction Instruction. It also delineated the role of accountability in Lyric Diction Instruction, on three disparate levels. This study precipitated the design of a Lyric Diction Instruction-specific data collection tool; a process for data coding and analysis; and it delineated the process by which findings were elicited and then connected back to the literature. Finally, through the one-on-one sessions detailed in this study, Lyric Diction Instruction research now has multiple empirically tested Lyric Diction Instruction-specific Methods Approaches Tools and Techniques (MATTS), with in-action examples of each. In sum, and critically, Lyric Diction Instruction can never again be thought of as a field for which no academic credentials are required.
Elucidating the Role of the Hippocampus in Pain
Keywords: Hippocampus
Neuroimaging
Pain

Multiple lines of evidence in animal and human studies have shown that the hippocampus, a brain region canonically responsible for memory, may be involved in pain. However, there is no consistent or direct evidence establishing this relationship. Hence, my primary goal is to determine whether the hippocampus is consistently associated with pain perception in humans. In two meta-analyses of acute and chronic pain neuroimaging studies, respectively, I found two major findings: 1) consistent increase in hippocampal activation in response to acute experimental pain in healthy individuals, and 2) less hippocampal activity in chronic pain patients compared to healthy individuals. In a follow-up functional connectivity study, I found that patients with chronic low-back pain had reduced hippocampal resting state connectivity with the medial prefrontal cortex, compared to healthy individuals. Then, quantitative and qualitative methods in a clinical model of hippocampal damage revealed that nociception is intact in patients with temporal lobe epilepsy (TLE). They feel blunted pain to suprathreshold stimuli in the noxious range. Finally, the extent of hippocampal damage in patients with TLE is associated with the degree of pain sensitivity. In other words, patients with more hippocampal damage were less pain sensitive. Overall, these findings establish a role of the hippocampus in pain: it is an important site for the human pain experience.
Towards Single-Cell Proteomics: Integrated Methods Relying on Digital Microfluidics and Mass Spectrometry
Keywords: Bioinformatics
Digital Microfluidics
Mass Spectrometry
Proteomics
Surfactants
Ultrasensitive

Cellular heterogeneity is a fundamental property of the trillions of cells that make up living mammals. Specialized single-cell analysis techniques are required to identify and interpret these differences, to be able to better understand the role of this heterogeneity in biological processes. Single-cell proteomics, or the attempt to evaluate all of the proteins expressed in a given single cell, has historically been limited by the complexity of the proteins, and limitations on analytical sensitivity (exacerbated by analyte loss during sample preparation). Microfluidic technologies have the potential to reduce the amount (or at least standardize the amount) of sample that is lost, through miniaturization, automation, and precise liquid handling. This dissertation describes my efforts to develop ultrasensitive digital microfluidic workflows coupled to liquid chromatography and mass spectrometry for the analysis of precious mass-limited protein samples, including single cells. The first chapter introduces methods for protein analysis and conventional mass spectrometry-based proteomics workflows. Chapter 2 presents an all-in-one digital microfluidic platform for proteomic sample preparation of a limited number of cells. A multiplexed sample preparation process was completed on the all-in-one platform with direct coupling to a nanoflow chromatography autosampler, and was applied towards the proteomic cancer sub-typing of breast cancer cell and tissue samples. Chapter 3 presents the first digital microfluidics proteomic workflow for the analysis of small tissue samples on-chip, facilitated by a photocleavable mass spectrometry compatible surfactant. This workflow combined surfactant-aided liquid extraction with on-chip sample preparation to profile proteins from microgram biopsies of murine brain tissue. Chapter 4 compares seven commonly used protein database searching algorithms against three sets of single-cell proteomics data. The differences in identification in this dataset highlight the importance of algorithm selection and continued development of new algorithms for specific applications in the future. Overall, this dissertation details important steps towards routine ultrasensitive mass spectrometry-based proteomics analysis of mass-limited samples, down to the single-cell level, using digital microfluidics technology.