VictorJuiz/thesis huggingface dataset:
Synthetic Routes to Well-defined Biodegradable Polymers using Organoboron Catalysts

Borinic acid catalysis is used as a tool for the synthesis of carbohydrate-derived polymers of biomedical interest. Polyols possessing 3 or 4 hydroxyl groups are subjected to site-selective polymerization without protecting group manipulations. Chapter 1 serves as an introduction describing common biomedical polymers and our approach to their synthesis. In Chapter 2, the synthesis of well-defined linear polyesters derived from glycerol is described as a proof-ofconcept for the translation of borinic acid-catalyzed polyol derivatizations to macromolecular synthesis. In Chapter 3, linear polyesters derived from anomerically protected pyranosides are described, highlighting the scope of the borinic acid-promoted polycondensation. In Chapter 4, structure–property relationships among polyesters derived from monomers with diverse anomeric side-chains are uncovered, demonstrating the versatility of this new monomer class in modulating thermal, physical and degradation behaviours. Finally, concluding remarks are made in Chapter 5, along with a summary of related research directions, including the implementation of borinic acids as a tool for methacrylate monomer synthesis as well as their use in promoting the synthesis of glycerol- and pyranoside-derived polyurethanes.

Keywords: carbohydrate
catalysis
polyester
Advisor: Taylor, Mark S
Guided Self-assembly of Human-pluripotent-Stem-cell-derived-lung-progenitors into Simplified Developmentally Relevant Architecture

Chemical and mechanical cues are known to guide the differentiation of pluripotent stem cells (PSCs) towards specific cell-types; a process known as directed differentiation. Typically, directed differentiation protocols to guide PSCs to specific cell types have focused on chemical cues. For example, lung epithelial directed differentiation protocols mimic the chemical cues observed in lung organogenesis. The products of current directed differentiation protocols are typically unorganized cellular aggregates that are often limited by their inability to generate specific cell types reliably. This suggests further improvements to these protocols are necessary for reliable cell manufacturing. Introducing developmentally relevant mechanical signals offers a potentially novel strategy to improve the predictability and reduce the heterogeneity of current directed differentiation protocols. To assess the feasibility of this concept we use polymeric substrates to guide the self-assembly of human PSC-derived lung progenitors into developmentally relevant sized tubes and assess the impact of defined architecture on differentiation. Specifically, day 17 ventralized lung progenitors, dual positive for proximal and distal lung markers SOX2 and SOX9, respectively, were cultured in polymeric tubes with diameters of 100µm and allowed to self-assemble into cellular tubes. Cells cultured in tubes were observed to become primarily SOX9+ as compared to cells in flat cultures that remained dual positive. Cells from tube cultures were retrieved and exposed to proximal or distal airway inducing conditions. Our data show that cells from flat culture are capable of expressing proximal and distal markers under proximal and distal conditions, respectively. However, cells retrieved from tubes were able to express distal markers under distal conditions but not proximal markers under proximal conditions. Our results suggest that modulation of tension in the presence of canonical WNT signaling by culturing the dual positive cells in the 100µm tubes resulted in loss of SOX2 expression. Overall, this thesis suggests that the use of a bioinspired mechanical microenvironment to organize and control the differentiation of developing lung epithelial populations during directed differentiation is a tractable strategy to control cellular differentiation in vitro.

Keywords: Biophysical forces
Lung differentiation
Stem cell differentiation
Tissue Engineering
Advisor: McGuigan, Alison P
Waddell, Thomas K
The Human Alpha Female: Social and Biological Perspectives

Today, in the popular and academic literature, women in the West who exhibit dominance-seeking behaviors to attain or maintain higher positions in social and professional networks are often referred to as “alpha females” or “alpha women”. Within this context, the term “alpha female” has become synonymous with the term leadership. Much of the research on the human alpha female takes its cues predominantly from the nonhuman primate literature on the social and biological factors that may predispose an individual to be an “alpha”, in particular, an “alpha male”. What are considered traditionally masculine traits in the West, such as aggression, leadership, and dominance, are often used to describe the alpha female. More recently, traits such as collaboration, teamwork, coalition building, and affiliative behavior, considered typical “feminine” traits in the West, have also been used to describe the alpha female. To date however, whether women socially occupy and/or biologically express this identity has not been researched.. The purpose of this thesis is to address the gaps in the literature and following what has been studied in the nonhuman primate literature, to investigate whether women who identify as alpha female are distinguishable from other women. For the present study, I examined the associations between alpha female status with the expression of specific alpha female related traits, hormone concentrations in hair, as well as differences in finger lengths, or the 2D:4D ratio, a prenatal biomarker of testosterone exposure. For the women in this study, the results suggest, that though specific masculine traits were found to be predictors of alpha female status, neither the specific hormones evaluated in the present study nor the 2D:4D ratio were associated with the expression of the alpha female identity. These results challenge present assumptions about what it means to be an alpha woman, as well as challenge what is known about the alpha female nonhuman primate as being representative of the human alpha female.

Keywords: 2D:4D ratio
hormones
leadership
masculine traits
social construction of female identity
the human alpha female
Advisor: Schillaci, Michael A
Environmental Policy and Discourse: An Exploration of the Toronto Green Standard

This project is a qualitative case study of the Toronto Green Standard (TGS), Toronto’s first ever green building policy, affecting all new developments in Toronto since 2010 (City of Toronto Planning and Development, 2018a). The research uses Foucault’s (1972, 1980) notions of discourse, and analyzes for various environmental policy discourses (Dryzek, 2005; Hajer, 1995; Robinson, 2004), in order to identify and question the discourses that are produced, and reproduced by the TGS. By assessing the dominant discourses, I also question what discourses are excluded, and the implications of these findings for who or what is served or excluded. Data was collected through document analysis, interviews, and the observation of TGS sites. Data was analyzed according to a six-step analytic method, which served to make discursive truths visible, and to denaturalize and destabilize the orders and hierarchies produced through discourse (Foucault, 1980; Graham, 2005; Hook, 2001). I found that the more radical, pro-environment discourses of sustainability and survivalism were present in the conception phases of the TGS. However, certain aspects of the institutional policy-making process meant the deprioritization of these discourses early on. Key moments were the Cost-benefit analysis, and stakeholder review and approvals. Through these processes, TGS discourse assumed a prioritization of development “as-is” almost from the get-go, creating a space for the production and dominance of economic development discourses. The result is that the economic-focused discourses of ecological modernization and economic rationalism are reproduced as dominant. These discourses serve Toronto’s leading, largest developer firms, such as through market transformation — the expansion of the green building sector — and through a process that I refer to as “urban environmental classism”. I argue that “urban environmental classism” is an outcome of ecological modernization, whereby being “green,” costs more, and excludes those who cannot afford it. I found that the TGS reproduces this phenomenon in the building sector. The dissertation discusses other implications of the economic-focused discourses, and concludes that in addition to economic factors, social factors should be considered during the creation of environmental policy, so that environmental policy does not exacerbate social and economic inequalities.

Keywords: discourse analysis
environmental discourse
environmental policy
Foucault
green buildings
municipal policy
Advisor: Restoule, Jean-Paul
The Evolutionary Ecology of Traits and Trait-mediated Interactions

As biologists, we seek to understand the sources of biodiversity, and the consequences of that diversity for ecological and evolutionary dynamics. But what do we mean by biodiversity? An evolutionary biologist might consider the traits of a population, while an ecologist may invoke differences among species. A key complexity of biological systems is that these facets of biodiversity occur simultaneously—all biological systems span levels of biological organization. In the first half of my thesis, I use gall-makers and dragonfly larvae to address a key facet of natural selection; species live, reproduce, and die in complex webs of interacting species, all of which can directly and indirectly shape evolutionary change. I show that subtle differences in the traits of ‘keystone’ individuals (Chapter 1), populations (Chapter 2), and indirectly interacting species (Chapter 3) all modify interactions and natural selection. These links can be further modified by environmental conditions (Chapter 4), and spatial processes that have random (Chapter 5) and deterministic (Chapter 6) effects on species composition and traits; traits, interactions, and selection are intimately linked. In the second half of my thesis, I investigate some of the ways in which a process occurring at one level of organization (e.g. evolution) can influence processes and their consequences occurring at other levels (e.g. community assembly and trophic cascades). Using dragonfly larvae, I show that ontogenetic differences (Chapter 7), individual differences (Chapter 8), and community-level differences generated by macroevolution (Chapter 9) all shape predation. In a unifying experiment, I determine that intraspecific variation may be particularly consequential for trophic dynamics and ecosystem functioning (Chapter 10). To understand classic ecological patterns (e.g. biodiversity-ecosystem functioning) requires an understanding of traits and their functions across biological scales of organization. The broad conclusions of this thesis are two-fold. First, trait variation across biological levels can reshape natural selection. Second, it will be difficult to understand patterns of diversity in ecological communities without considering trait variation at other biological levels. To understand biological systems, we require a synthesis of the causes and consequences of diversity across levels—we require a rapprochement of evolutionary biology and community ecology.

Advisor: Gilbert, Benjamin
Mocking the Universe: Accurate Simulations in the Era of Large-survey Precision Cosmology

Efficient generation of accurate mock observations of the sky, tailored specifically to near-future large-scale structure and cosmic microwave background surveys, is a key technical challenge in cosmology. The increasing sensitivity and sky coverage of modern surveys probe unprecedentedly-large cosmological volumes, and when coupled with increases to angular resolution, demand simulations that are accurate to smaller scales, yet cover larger volumes, than ever before. The applications of such simulations are numerous, from performing cosmological parameter analysis, to optimizing survey designs and testing analysis pipelines, to making theoretical predictions, but to adequately perform these tasks requires state-of-the-art accuracy and computational efficiency. In this thesis we develop numerical simulations of cosmological structure formation to create synthetic observations, or mocks, of current and near-future cosmic microwave background and large-scale structure surveys. We first present our development and rigorous validation of the mass-Peak Patch method, a simulation technique to rapidly generate the large-scale structure of cosmological volumes for a fraction of the computational cost of alternative methods. Mass-Peak Patch is then used in union with a number of astrophysical sky models to produce the Websky extragalactic CMB simulations, a publicly released set of synthetic mocks of the extragalactic microwave to infrared sky. Next, we focus on the up-and-coming field of intensity mapping. We construct a suite of carbon monoxide line intensity maps, and use these to forecast the constraints on the CO luminosity function with near-future observations. Both the large data volumes and complicated statistical evaluations involved in standard cosmological analyses of survey data has recently led to the adoption of many machine learning methods throughout the field, and we finish this thesis with an investigation of machine learning methods in cosmology. We first overview machine learning in cosmology and discuss the viability and attractiveness of recently-popularized deep learning techniques, and then construct, train, and validate a convolutional neural network for the purpose of aiding cosmological simulations. Efficient simulation tools such as mass-Peak Patch, accurate mocks such as the Websky extragalactic maps, and machine learning techniques (when applied correctly), will enable precision analysis of the next generation of cosmological data sets.

Keywords: Astrophysics
Cosmology
Advisor: Bond, J. Richard R
Optimization Algorithms for Task Offloading and Scheduling in Cloud Computing

Cloud computing can augment the capabilities of resource-poor local devices with the help of resourceful servers. Computational offloading refers to the migration of application tasks from local devices for execution at the cloud. Intelligent task offloading and scheduling can help optimize parameters such as energy consumption or execution time. In this dissertation, we address such optimization problems in cloud computing environments. Several existing works that address this problem often make simplistic or impractical assumptions with respect to the system model or propose inefficient solutions. We consider more practical system models with finite-capacity and heterogeneous local devices, cloudlets, and edge-clouds. We also address offloading of applications consisting of dependent tasks, multi-user environments, and scheduling tasks that arrive over time. We consider meaningful optimization objectives and constraints. Our aim is to propose efficient algorithms with high performance to obtain these task offloading and scheduling decisions. We first consider the problem where a single user wishes to execute applications consisting of dependent tasks and a multi-tier cloud computing environment that may consist of cloudlets, peer devices, and a remote cloud. We propose the Individual Time Allocation with Greedy Scheduling (ITAGS) algorithm in order to minimize total cost subject to application deadlines. We then consider a multi-user cloud environment where each user has certain budget constraints. We propose the Single Task Unload for Budget Resolution (STUBR) algorithm to minimize sum completion time objective, and prove performance guarantees for the same. Finally, we address the online problem where tasks arrive over time, and we do not know task information in advance. We propose the Task Dispatch through Online Training (TDOT) algorithm in order to maximize prot to a cloud service provider subject to processor load constraints, and provide performance guarantees. For each of these problems, we also use trace-driven simulation results to compare against existing alternatives and analyze the performance of the proposed algorithms in various scenarios. We see that the proposed algorithms are efficient, outperform other alternatives, and exhibit near-optimal performance.

Advisor: Liang, Ben
Cross-linguistic Effects of Subjecthood, Case, and Transitivity in Syntax and Sentence Processing

The definition of a grammatical ‘subject’, and the properties an argument must have to be characterized as a subject is long debated (e.g., Comrie, 1975; Keenan, 1976). This thesis investigates the relationship between subjecthood, case marking, and transitivity, from both a typological perspective and from an in-depth study of the ergative Polynesian language Niuean. I present two original experimental studies of sentence processing in Niuean, which show that processing of long-distance dependencies and resolution of anaphoric pronouns is affected by agentivity, case marking of arguments, and predicate transitivity. Coupled with formal syntactic analysis, these findings support a view in which a subject is defined as the most agentive verbal argument present in a clause, and further reveal syntactic effects of the distribution of the case marking borne by each argument. Case distribution (known as ‘unmarkedness’ in syntactic literature) and subjecthood are argued to be two distinct factors which, together, influence how accessible an argument is in both syntactic operations and in sentence processing.

Keywords: Linguistics
Niuean
Psycholinguistics
Syntax
Advisor: Heller, Daphna
Seismic Array Imaging of Teleseismic Body Waves from Finite-frequency Tomography to Full-waveform Inversions: With Applications to South-central Alaska Subduction Zone

Seismic tomography has been one of the most essential tools in mapping the images of the Earth’s interior. This thesis aims to present an introduction to various seismic tomography techniques for utilizing teleseismic body-wave data, and their applications in south-central Alaska subduction zone. Due to the continuous subduction of Pacific plate beneath the North American plate, south-central Alaska has great tectonic and geodynamic complexities that needs to be further illuminated by seismic waves. First, we invert for 3-D variations of compressional and shear wave speed as well as Vp /Vs ratio for the south-central Alaska crust and uppermost mantle based on the traditional finite-frequency tomographic methods. Approximate 5400 teleseismic events are specifically selected with magnitude ≥ Mw5.5, epicentral distance between 30 ◦ and 95 ◦ , and good signal-to-noise ratio. A large number of teleseismic P and S wave multi-channel cross-correlation (MCCC) traveltime data are collected from available records in the past two decades. Finite-frequency traveltime sensitivity kernels of P and S wavespeed are constructed by the ray-based algorithm, and the P and S velocity perturbations are directly inverted by the Newton method. Our final images provide constraints on the geometry of the subducted oceanic lithosphere as high-velocity anomalies, including its extent, thickness, and subduction angle. In addition, other lithospheric heterogeneities, such as upper crustal structures like sedimentary basins, Wrangell subduction zone, and thickened Yakutat crust, are all presented in our inversion results. Then we strive to develop a high-resolution seismic imaging technique based on full waveform inversion (FWI) of teleseismic body waveforms. We use a state-of-the-art hybrid method interfacing analytic frequency-wavenumber (FK) calculation for 1D background models with a 3-D spectral-element (SEM) solver for a 3-D regional model to accurately simulate the direct and scattered waves in short-period teleseismic body waves. The velocity models can be inverted by reducing the waveform misfit between data and synthetics through an iterative Quasi-Newton method. In particular, we explore the feasibility of teleseismic body-wave FWI based on SEM-FK hybrid method for refining the 3D velocity structures in the crust and upper mantle, with applications to south-central Alaska subduction zone.

Advisor: Liu, Qinya
Genome-wide CRISPR Screens to Uncover Novel Therapeutic Targets in Wnt-β-catenin Driven Gastrointestinal Cancers

Gastrointestinal tract cancers are some of the deadliest cancers and novel therapeutic options are needed. One hallmark of gastrointestinal cancers is the frequent mutation of tumour suppressor genes resulting in constitutive activation of the Wnt-β-catenin signalling pathway. Wnt-β-catenin signalling is a positive regulator of stem cell self-renewal in normal tissues, but cancer cells may take advantage of it to promote their proliferation and survival. Despite frequent cancer cell reliance on Wnt-β-catenin signalling, no clinical therapeutics currently exist that target it. CRISPR/Cas9 gene editing technology has recently allowed for genome-wide loss- of-function screens in vertebrate cells and may therefore be used to identify novel genetic vulnerabilities in human cancer cells. Genome-wide CRISPR screens were completed in RNF43 mutant pancreatic ductal adenocarcinoma (PDAC) cells lines, which rely on Wnt-β- catenin autocrine signaling for their proliferation. These screens revealed a single Frizzled receptor gene out of ten paralogs, FZD5, to be essential for the proliferation of each RNF43 mutant PDAC line. We generated a synthetic human monoclonal antibody specific to FZD5, and found it effective in reducing the growth of RNF43 mutant pancreatic cancers in vitro and in orthotopic xenograft models. We next identified the homeobox transcription factor CDX2 as a context-dependent fitness gene and Wnt-β-catenin transcriptional target in RNF43 mutant pancreatic cancer cells. CDX2 is uniquely overexpressed in Wnt-FZD5 dependent PDAC cells and transcriptome analysis revealed it may drive an intestinal metaplasia phenotype, and may be a suitable biomarker for Wnt-FZD5 dependency. To further identify novel therapeutic targets we completed synthetic-lethal interaction CRISPR screens in cells in which we engineered APC mutations. APC loss of function mutations cause Wnt-β-catenin pathway activation and occur in 80% of colorectal cancers. As a surrogate model for APC mutant colorectal cancer we engineered APC mutant PDAC cell lines to compare with their parental APC wild-type cell lines. Isogenic CRISPR screens comparing these cell lines identified many synthetic-lethal genes, most notably the Aryl Hydrocarbon Receptor (AHR), as a potential druggable vulnerability. Together this work demonstrates the power of genome-wide CRISPR screens for assessing signalling pathways in cancers, and may lead directly to the development of novel targeted therapeutics.

Keywords: Colorectal cancer
CRISPR
FZD5
Pancreatic cancer
RNF43
Wnt
Advisor: Angers, Stephane