VictorJuiz/thesis huggingface dataset:
Exploring Gene-environment Interactions in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is family of complex conditions of the gastrointestinal tract. Pathogenesis of IBD remains unknown and is postulated to be multifactorial, including contributions from host genetics, environmental factors, the gut microbiome, and the immune response. This work explored environmental influences and gene-environment interactions in IBD. Vitamin D deficiency is an environmental factor involved in IBD pathogenesis. Although the mechanism remains unclear, previous studies suggest that a lack of vitamin D signaling causes a reduction in intestinal autophagy. A potential link between vitamin D deficiency and dysregulated autophagy is microRNA (miR)-142-3p, which suppresses autophagy. We found that vitamin D deficient mice had enhanced miR-142-3p expression in ileal tissues compared to control mice. Paneth cells of vitamin D deficient mice were morphologically abnormal and displayed evidence of an autophagy defect. These findings suggest that Paneth cells exhibit early markers of autophagy dysregulation within the intestinal epithelium in response to vitamin D deficiency and enhanced miR-142-3p expression. We demonstrated that treatment-naïve IBD patients with low vitamin D have increased miR-142-3p expression in colonic tissues procured from ‘involved’ areas of disease. Taken together, our findings demonstrate that insufficient vitamin D levels alter expression of autophagy-regulating miR-142-3p in intestinal tissues of mice and IBD patients, providing insight into the mechanisms by which vitamin D deficiency modulates IBD pathogenesis. We explored gene-environment interactions by evaluating the effects of vitamin D deficiency in mice that have an important IBD genetic risk variant, Nod2fs, which also disrupts autophagy. Interestingly, the combination of vitamin D deficiency and Nod2fs did not impact autophagy at baseline. However, upon microbial disturbances in the microbiome, the vitamin D deficient Nod2fs mice had pervasive autophagy defects. This is in line with the multi-hit model of IBD, which proposes that many insults converge to cause defects in the intestinal epithelium. In our gene-environment analyses, we also observed that the Nod2fs mutation led to reduced serum vitamin D, a novel interaction between an IBD genetic risk factor and environmental factor of interest. Through this work we were able to identify therapeutic targets of interest and contribute to the understanding of IBD pathogenesis.

Keywords: Autophagy
Inflammatory bowel disease
miR-142-3p
NOD2
Paneth cells
Vitamin D deficiency
Advisor: Jones, Nicola L
Higgs Boson Measurements in Leptonic Final States with the ATLAS Detector at the Large Hadron Collider

Two cross-section measurements of the Higgs boson with leptonic final states are presented in this Thesis. The measurements use proton-proton collisions measured by the ATLAS detector at a the center-of-mass√ = 13 TeV. The first analysis was performed using the of data collected between 2015 and 2017, corresponding to an integrated luminosity of 79.8 fb−1. The search specifically targeted Higgs boson production in association with a top quark pair (tt ̄H), with three electrons or muons and one hadronically decayingtau in the final state. The cross section was measured to be σˆ(tt ̄H) = 215+550 fb, where the uncertainty −425 is dominated by the statistical component. This was then combined with other similar channels that all target the tt ̄H production mode decaying to leptons. The overall cross section was measured to be σ(tt ̄H)=294+182 fb,which is consistent with the Standard Modelprediction. The second analysis was performed using the full Run-2 dataset, corresponding to an integrated luminosity of 139 fb−1. The analysis targeted the four main Higgs boson production modes at the LHC, where the Higgs decays to a pair of tau leptons. The analysis was split into 36 channels based on which production mode was targeted and the lepton multiplicity of the final state. The overall cross section was measured to be 2.89+0.21(stat.)+0.37(syst.) pb, and the cross sections for the individual production modes −0.21 −0.32 were measured to be σggF = 2.6+0.4(stat.)+0.9(syst.) pb, σV BF = 0.196+0.028(stat.)+0.032(syst.) pb, −0.4 −0.6 −0.027 −0.029 σV H = 0.11+0.06(stat.)+0.04(syst.)pb, σtt ̄H = 0.05+0.03(stat.)+0.04(syst.) pb. Differential measurements −0.06 −0.04 −0.03 −0.03 using the simplified template cross-section framework were also performed. All the results were found to be in agreement with the Standard Model predictions.

Advisor: Orr, Robert S
Nanoscale Properties of Block Copolymers, Perovskites and Boron Nitride Obtained by Near-field Scanning Optical Microscopy in the Infrared

Several material types have been studied using coupled atomic force microscopy (AFM) and Infrared Spectroscopy techniques including scanning near-field optical microscopy (SNOM) and peak force infrared microscopy (PFIR). First, the different structures formed by block copolymer thin films were studied using SNOM. With SNOM, local subsurface morphologies in block copolymer thin films were revealed. Second, the degradation of perovskites under high humidity and light soaking was monitored by PFIR, x-ray diffraction and time-of-flight secondary ions mass spectrometry. Lastly, phonon polaritons in hexagonal boron nitride were studied using SNOM. It was found that structures in the boron nitride can self-launch phonon polaritons. In addition, the effect of the adjacent layer of material on the phonon polaritons in the boron nitride was investigated.

Keywords: Atomic force microscopy
Block copolymer
Nanoscience
Near-field microscopy
Perovskite
Phonon polariton
Advisor: Walker, Gilbert C
An Intermedial Incision: Ana Mendieta's Moving Image Media

Ana Mendieta’s body of work has received attention and praise for contributions to performance art, sculpture, and earth-body art. This dissertation takes on a different aspect of Mendieta’s oeuvre, looking at moving image media as a central concern in her artistic process. Following methods from film and media theory that look to visual form as the production of thought, the dissertation focuses on formal elements of Mendieta’s films, producing close readings that make an argument for the centrality of mediation to her work and how this media-focus can change the way we think about Mendieta’s art as a whole. The dissertation focuses on three groups of questions that arise within Mendieta’s moving image-based work, dictating each chapter. The first questions arise from the abundance of figure-based expression in not only her paintings and performances, but also her films. How does Mendieta’s relationship to film change her abstract figure work that emerged from her early years studying painting? How does Mendieta’s addition of sound to her film X-Ray (1974) enhance the conversations about figure, identity, and mediation of such? The second group of questions concerns the mediatic iterations of truth and evidence that emerge from statements concerning violence and violence against women. I argue that Mendieta grapples, artistically, with crime scenes, public encounter, and the concept of justice as related to truth through a careful articulation of visual testimony. These questions unfold in her blood-work films including Blood Writing (1974) and Moffit Building Piece (1973). Lastly, the dissertation interrogates the way that an image of the cut emerges as an aesthetic gesture in Mendieta’s Sweating Blood (1974). This gesture alludes to a series of ideas including the erasure of the labor of editing or cutting, a job largely done by women. It also provokes the question about the role of violence in Mendieta’s work. Drawing together each chapter is Mendieta’s training in intermedia, which she completed at the University of Iowa. This intermedial practice, the dissertation affirms, informs Mendieta’s work to a degree much greater than previously explored.

Keywords: Ana Mendieta
experimental film
film studies
film theory
intermedia
Advisor: Sutherland, Meghan
Towards Strong Generalization from Few Examples

Deep learning has recently driven remarkable progress in several applications, including image classification, speech recognition, autonomous driving, and creating agents that can beat human experts in challenging games. However, this success often relies on large amounts of labeled data. This is at a stark contrast with how humans learn: we are able to efficiently re-use previous knowledge or experience to expedite future learning, allowing to understand new concepts from only a handful of examples. Motivated by this discrepancy, we aim to improve upon machine learning models' ability to learn more flexibly, from fewer examples. We will discuss the early formulation of few-shot learning and argue that, despite instrumental for making initial research progress, it is overly simplistic, posing what we will refer to as `weak generalization' challenges. We argue that, to continue making progress and inspire the creation of models that can few-shot learn in the real world, we require benchmarks that examine stronger forms of generalization. To this end, we propose challenging few-shot learning tasks, including a contextual formulation, as well as a large-scale few-shot learning challenge across diverse datasets. We show that previous models suffer on these harder problems, leading us to propose novel approaches. Notably, we find that self-supervision is particularly well-suited for generalization to novel contexts. We also find that per-task model adaptation is important for generalization to diverse data distributions and propose an effective approach that achieves this. Finally, we put forth an inductive bias to learn a `template' that defines a wide array of models for strongly generalizing to previously-unseen datasets, leading to substantial performance gains over previous approaches, while also being more scalable and adaptable than previous solutions.

Keywords: few-shot learning
machine learning
Advisor: Zemel, Richard RZ
Urtasun, Raquel RU
Energy Levels and Charge Transport in Host-dopant Organic Semiconductors

The organic light-emitting diode (OLED) generates light through charge carrier recombination in the emissive organic layer which has a host-dopant structure and, thus, the OLED device performance is impacted by the electronic properties of this host-dopant organic semiconductor. In this thesis, the energy level alignment and charge transport process in the host-dopant organic semiconductor are investigated by photoelectron spectroscopy and by analysis of the current-voltage behavior, respectively.First, the energy level alignment of host-dopant organic semiconductors at electrode-organic interface is studied by photoelectron spectroscopy. The interface energy disorder is found for molecules close to an electrode surface. This energy disorder has significant impact on energy level alignment. Second, the energy level alignment of bulk host-dopant organic semiconductors is investigated. A host/dopant hetero-interface formed by a layer-by-layer method is demonstrated to correlate well the host-dopant energy level alignment in mixed form. It is found that the host-dopant energy level alignment falls into the elastic region of the universal energy level alignment rule, involving negligible charge transfer. Third, charge transport in the host-dopant organic semiconductors is studied using single carrier devices. Charge detrapping and percolation are found to be two major mechanisms for transport in the host-dopant materials. A theoretical formula is proposed and validated to describe the mobility dependence on the energy level alignment, and an empirical formula is demonstrated to describe the mobility dependence on the dopant concentration. Lastly, the impact of dopants on charge transport across an organic-organic interface is investigated. This charge injection from the transport layer into the emissive layer is critical for device efficiency. It is found that charge transport characteristics at an organic-organic junction varies depending on the energy level alignments of the dopant to that of the host and the hole transport layer. In addition, the dopant concentration is found to dictate the device electrical characteristics. Detailed numerical studies show that carrier transport across the junction is charge injection-limited at low dopant concentration (≤5 wt%), while an Ohmic junction is obtained at high dopant concentration.

Advisor: Lu, Zheng-Hong
The Impacts of Climate Change on the Potential for a Northward Expansion of Agriculture in Ontario’s Great Clay Belt Region

Climate change has widespread impacts on the agriculture sector, especially in northern latitudes where warming is amplified, and where ecosystems and traditional lifestyles are notably sensitive to the effects of warming. This may enable the northward expansion of agriculture in northern areas of Ontario, such as the Great Clay Belt (GCB) region. While the GCB region contains an abundance of productive and less expensive land, the historical trends and future agroclimatic conditions are underexplored. The first study of this thesis examined the historical trends of agroclimatic indices at seven locations within the GCB region during 1961-1990. First, how to best account for missing data in the historical record was found by imputing a daily gridded meteorological dataset. Using complete and reliable historical climate data, the trends implied a potentially more favourable climate for agriculture in the region as warming, with longer growing seasons and increases in heat accumulation, may result in the northward expansion of some crops. The second study explored the new growing conditions up to the year 2100 using climate models. Future projections indicated a warming trend using raw and bias-corrected/downscaled data for two emissions scenarios during the growing season. Bias-corrected/downscaled data was found to be more useful for impact analyses because it corrected for errors and showed better agreement with station observations compared to the raw output. The third study explored the challenges, opportunities and needs and priorities for expanding agriculture in the GCB region using climatological and socio-economic data. The results showed that the most significant barriers currently facing agricultural expansion is derived from socio-economic factors rather than from environmental factors. This thesis demonstrated that climate change presents significant opportunities for agricultural expansion in the GCB region. This suggests opportunities for economic development that may help ameliorate the disadvantages associated with rural and remote communities in northern Ontario. The challenge presented for the GCB region will be to ensure sustainable growth in the agriculture sector without compromising environmental quality, natural resources, and Indigenous autonomy. There is a need to develop adaptation strategies in response to the impacts of climate change on agriculture in the GCB region.

Keywords: Agriculture
Climate change
Daily temperature
Impact
Precipitation
Projections
Advisor: Gough, William A
Exploiting Diverse Chemical Collections to Uncover Compounds with Novel Activity Against Human Fungal Pathogens

Fungal pathogens are an underappreciated contributor to infectious disease related deaths, infecting billions and killing 1.6 million people annually. The rise in drug resistance amongst pathogenic fungi paired with the limited arsenal of antifungals available is an imminent threat to our medical system. To address this, I screened two distinct compound libraries to identify novel strategies to expand the antifungal armamentarium. The first collection, from Boston University, was screened to identify two types of compounds with activity against the highly drug-resistant pathogen Candida auris: those that were bioactive alone, and those that enhanced the efficacy of fluconazole, the most commonly administered systemic antifungal. Through these efforts I identified the rocaglates, a chemical class exhibiting single agent fungicidal activity. The rocaglates were found to inhibit translation initiation in C. auris but not in its close pathogenic relative Candida albicans. This species-specific activity was contingent on a single amino acid difference in the drug target, the translation initiation factor Tif1. Strikingly, rocaglate-mediated translation inhibition activated cell death in C. auris, but not in a rocaglate-sensitized C. albicans strain. From the fluconazole combination screen, I discovered a compound, subsequently termed azoffluxin, that enhanced fluconazole efficacy against C. auris through increasing its intracellular accumulation. This activity was through the inhibition of efflux pumps, indicating azoffluxin targets a key resistance mechanism. Furthermore, azoffluxin significantly reduced fungal burden alone and in combination with fluconazole in a mouse model of C. auris disseminated infection. The second chemical library screened, the RIKEN Natural Product Depository, was evaluated for antifungal activity against four major human fungal pathogens: C. auris, C. albicans, Candida glabrata, and Cryptococcus neoformans. One molecule, NPD6433, was prioritized for having broad-spectrum antifungal activity and minimal mammalian cytotoxicity. NPD6433 was determined to inhibit the enoyl reductase domain of the essential fungal enzyme fatty acid synthase 1, Fas1. Treatment with NPD6433 inhibited various virulence traits in multiple fungal species and rescued mammalian cell growth in a co-culture model with C. auris. Overall, this work identifies compounds with bioactivity against fungal pathogens, revealing important biology and paving the way for the critical development of new therapeutic strategies.

Keywords: Candida
Chemical genetics
Drug discovery
Drug resistance
Fungal biology
Advisor: Cowen, Leah E
Quantum Dynamics and Topology of the Kitaev Materials

Spin-orbit coupled Mott insulators on trivalent lattices open up a new arena of exotic correlated quantum phases by realizing frustrating bond-directional interactions. These frustrated quantum magnets, so called the Kitaev materials, provide the platform for the long-sought quantum spin liquid with Majorana fermions and Z2 gauge fields, as well as various noncollinear magnetic orders with topological magnons. In this thesis, we study the topological properties of proximate superconducting and magnetic phases of the Kitaev materials and provide theory of a novel spectroscopic experiment for sharper characterization of quantum spin liquids. We first investigate topological nature of the emergent superconductors born out of the Kitaev spin liquid strongly Kondo coupled to conduction electrons. We discover a ferromagnetic topological superconductor carrying non-Abelian anyons and a nonmagnetic Z2 topological superconductor, whose symmetry and topology are heavily influenced by the emergent gauge structure of the parent spin liquid. Next, we discuss the nonsymmorphic symmetry protected topological nodal magnons in the three dimensional Kitaev materials. We discovered stable magnon band crossings in the field-induced canted zigzag order of the hyperhoneycomb β-Li2IrO3 and showed that the magnetic glide symmetries and the non-Hermitian nature of the bosonic magnons lead to unique topological protection that is different from the case of their fermionic counterparts. Finally, we propose a theory of two-dimensional spectroscopy, where nonlinear dynamical responses provide insight into the low-energy excitations, for quantum spin liquids. By considering the exactly solvable Kitaev honeycomb model as an archetype example, we theoretically demonstrate that the two-dimensional Fourier transform of the nonlinear dynamical response functions can reveal clear signatures of the itinerant Majorana fermions and gapped Z2 fluxes of the Kitaev spin liquid.

Keywords: frustrated magnetism
Kitaev material
Kondo lattice
quantum spin liquid
superconductivity
topological magnon
Advisor: Kim, Yong Baek
Machine Learning and Computer Vision Approaches for Phenotypic Profiling in Yeast

Functional genomics research aims to systematically discover the functions of all genes in an organism. Developing computational tools to facilitate gene function discoveries has been the overarching goal of my thesis work. I have developed computational pipelines for the automated detection of abnormal phenotypes in single cell images of the budding yeast, Saccharomyces cerevisiae. My collaborators in the Boone and Andrews labs have used methods that automate yeast genetics to produce genome-wide arrays of yeast mutants, each carrying a defined perturbation in a single gene, and expressing fluorescent markers for various subcellular compartments. The resulting large-scale image dataset consists of millions of single cells each harbouring a single gene perturbation and a single fluorescently labelled subcellular compartment for around 6000 yeast genes and 13 compartments. To develop my image analysis for discovering mutant phenotypes in single-cell images of arrayed mutants, I first focused on comparing different combinations of methods for performing outlier detection to automatically detect cells with abnormal morphologies. This analysis allowed me to quantify the percentage of cells in a mutant population with abnormal phenotypes and thus the penetrance of phenotypes associated with a specific genetic perturbation. In the second data chapter of my thesis, I combined outlier detection and a neural network-based image analysis of single cells to quantify the phenotypic variability within a population of cells. As a model system, I focused on the genes that influence the architecture of four subcellular compartments of the endocytic pathway and identified 17 distinct abnormal phenotypes that are associated with perturbation of many genes. Nearly half of these perturbed populations displayed multiple phenotypes, suggesting that morphological pleiotropy is prevalent. In the final data chapter of my thesis, I describe my work to automate the clustering of cells with abnormal morphology from a dataset of images of yeast cells expressing fluorescent markers of 13 subcellular compartments into distinct abnormal phenotypes to understand the global morphology of the yeast cell. My analyses have facilitated the identification of connections between discrete biological processes, the prediction of novel gene function, and a visual representation of basic eukaryotic cell biology.

Keywords: Computational Biology
Computer Vision
Genomics
Machine Learning
Systems Biology
Advisor: Andrews, Brenda J
Morris, Quaid
On the Geometry of the Thurston Metric on Teichmüller Spaces: Geodesics that Disobey an Analogue of Masur’s Criterion

We construct a counterexample for an analogue of Masur’s criterion in the setting of Teichmüller space with the Thurston metric. For that, we find a minimal, filling, non-uniquely ergodic lamination λ on the seven-times punctured sphere with uniformly bounded annular projection distances. Then we show that a geodesic in the corresponding Teichmüller space that converges to λ, stays in the thick part for the whole time.

Advisor: Rafi, Kasra