VictorJuiz/thesis huggingface dataset:
Microplastics Affect Organisms across Multiple Levels of Biological Organization: Informing Individual and Ecological Rsk

Demonstrating the ecological consequences (or risk) of microplastics is critical to inform policies that will mitigate their presence in the environment. However, assessing the risk of microplastics is made difficult by their complexity: microplastics are a suite of contaminants varying in size, shape, polymer type, and associated chemical cocktail. In the first chapter of my thesis, I synthesize studies testing hypotheses about the effects of microplastics to measure the weight of scientific evidence regarding the effects of plastic pollution at every level of biological organization. By systematically reviewing the literature, I found that macroplastics are undoubtedly causing ecosystem-level effects, but that more research is needed to fully understand the ecological consequences of microplastics because effect mechanisms are likely driven by their diverse characteristics. By finding patterns in how particle characteristics relate to effects, I show that particle shape, size, and polymer type are all relevant to toxicity. In my second and third chapters, I conducted laboratory experiments designed to better understand the effects of environmentally relevant microplastics, comparing plastics that I purchased from a manufacturer and plastics that I collected from the environment. In my second chapter, I showed that microplastics are both a physical and a chemical stressor. Environmentally sourced microplastics were not only more harmful to developing larval fish than pristine microplastics, but they also caused impacts when the fish were exposed to the leachates alone, while the pristine microplastics did not. In my third chapter, I investigated the long-term effects of microplastics on two generations of fish. Here, I showed that both pristine and environmentally sourced microplastics caused physical stress resulting in decreased adult growth, lipid storage, and a visible dermal stress response. However, only the environmentally sourced microplastics had effects on reproduction and offspring viability. Finally, in my fourth chapter I proposed a risk and management framework to assess the harm of microplastics in the ambient environment. This framework can be used by decision-makers to inform microplastic concentration thresholds that will trigger management decisions. Throughout my thesis, I highlight the need to consider microplastics as a complex contaminant, demonstrate their complexity through laboratory studies, and suggest how their complexity can be incorporated into risk assessment.

Keywords: Ecotoxicology
Fathead minnows
Microplastic
Plastic pollution
Risk assessment
Advisor: Rochma, Chelsea M
The Behaviour and Design of Reinforced and Prestressed Concrete Members Subjected to Torsion

This thesis describes analytical and experimental investigations which were undertaken to obtain a better understanding of how reinforced and prestressed concrete members resist torsion, either in isolation, or when accompanied by shear and flexure. The results were then used to develop practical, easy-to-use tools which are suitable for analysis and design. The main analytical contribution is a new design method which addresses the shortcomings of the torsion provisions in CSA A23.3:19, namely a tendency to underestimate the strengths of very lightly reinforced members and overestimate the strengths of heavily reinforced members which fail by torsional crushing. A validation study using 451 experiments drawn from the literature demonstrates that the proposed method is more accurate than the current CSA procedures. Other analytical contributions include a nonlinear analysis tool which can determine a member’s complete torque-twist response under pure torsion, a model which can predict when a member fails by crushing before yielding of the reinforcement, and a stiffness model which can determine a member’s cracked torsional stiffness. Each model is based on an updated form of the Diagonal Compression Field Theory which incorporates more recent advancements in constitutive modelling. A spalling model which predicts the onset of torsional spalling and the resulting loss of concrete is also presented. This model forms a key component of the other design and analysis tools included in this thesis. The experimental program consisted of testing eight T-beams under combined flexure, shear, and torsion to investigate the use of open stirrups as an alternative to traditional closed torsion reinforcement. Four specimens were designed to fail by yielding of the web reinforcement, while the remaining specimens were designed to fail by yielding of the transverse reinforcement in the flange. The torsion provisions in CSA A23.3:19 consistently underestimated the strengths of the specimens by a large margin. The observed behaviour suggests that open stirrups which are “closed” with supplemental torsional reinforcement can be a safe alternative to traditional closed stirrups. A procedure for proportioning such reinforcement is included in the proposed design method.

Keywords: CSA
Design
Detailing
Reinforced Concrete
Shear
Torsion
Advisor: Bentz, Evan C
Collins, Michael P
Myocardial Structure and Function in Heart Failure with Preserved Ejection Fraction: Molecular Insights and Therapeutic Strategies Targeting Transforming Growth Factor Beta Signaling

Myocardial fibrosis has long been implicated in the pathophysiology of heart failure with preserved ejection fraction (HFPEF)—increasing myocardial stiffness and contributing to diastolic dysfunction. However, despite multiple therapeutic strategies to reduce myocardial fibrosis, clinically effective anti-fibrotic therapies remain sparse. At issue is that current HFPEF therapeutic strategies often target pro-fibrotic pathways indirectly or rely on associative evidence derived from animal models that do not faithfully recapitulate human HFPEF. In this thesis, the canonical signaling pathway of transforming growth factor beta (TGF-β), a master regulator of fibrosis, is directly targeted in three clinically relevant animal models of HFPEF—streptozotocin-diabetic (mRen-2)27 rats, 5/6 subtotal nephrectomy rats, and transverse aortic constriction-induced pressure overload mice. Blockade of the acetylation of Smad2/3—key intracellular signal transducers of TGF-β signaling—in cell culture and the three animal models of HFPEF reduced the expression of several pro-inflammatory and pro-fibrotic markers and also abrogated the reactivation of the fetal gene program. In the animal models, echocardiographic and invasive hemodynamic measurements revealed a reduction in interstitial cardiac fibrosis and an improvement in diastolic filling and relaxation with the inhibition of Smad2/3 acetylation. The approach of targeting fibrosis—a central pathology in HFPEF irrespective of the inciting stimuli—by selectively inhibiting a single post translational modification critical in the TGF-β signaling pathway, is a promising therapeutic approach that could be further developed to slow, or perhaps reverse, cardiac fibrosis in HFPEF.

Keywords: Fibrosis
Heart failure
Heart failure with preserved ejection fraction (HFPEF)
Smad2/3
Transforming growth factor-beta (TGF-β)
Advisor: Connelly, Kim A.
Leong-Poi, Howard
Characterizing Human Fetal Neural Stem Cell Populations and Investigating their Roles in the Initiation of Glioblastoma

Glioblastoma (GBM) is an aggressive and incurable neoplasm. The subpopulations of cells within the tumor recapitulate a developmental hierarchy such that neoplastic stem-like cells, known as cancer stem cells (CSCs), reside at the apex and are resistant to conventional therapies. Notably, the source of these CSCs, referred to as the cell-of-origin, may have a distinct identity or a more differentiated phenotype. There is evidence demonstrating that the two stem cell populations in the human fetal cortex, namely ventricular radial glia (vRG) and outer radial glia (oRG), have different propensities for GBM initiation, whereby the latter shares a similar transcriptional signature with primary GBM cells. I investigated the properties and behaviors of vRG and oRG, in the context of both normal development and cancer initiation. Sorting approaches allow for the isolation of these cells, which I identified to exhibit several functional differences. vRG are more proliferative but less potent at self-renewal compared to oRG. Furthermore, vRG are more gliogenic whereas oRG are more neurogenic. vRG and oRG also respond differently to various growth factors, such as leukemia inhibitory factor (LIF), when grown both adherently and in suspension. These differences are maintained in culture over passaging, which suggests that vRG and oRG can be captured, propagated, and studied in vitro. Through modeling GBM molecular events in these cells via deletion of the tumor suppressor gene TP53, I discovered that oRG become more proliferative/self-renewing compared to vRG. The driving force of this difference is likely attributable to mechanisms of DNA damage repair, at which oRG seem to be weaker. Finally, I performed single-cell RNA-sequencing (scRNA-seq) of normal and differentiated populations of vRG and oRG, as well as subsequent comparisons to GBM cell line/primary tumor profiles. These analyses provide insights into how normal developmental cell types and pathways influence GBM progression and suggest that oRG glial lineages may more significantly contribute to the glial signature of GBM tumors. Overall, these findings lay the groundwork for further exploration of mechanisms of neoplastic transformation in the human context, particularly within cortical precursor populations.

Advisor: Dirks, Peter
van der Kooy, Derek
The Role of Junctional Epithelium Proteins in the Epithelial Attachment of Dentogingival Junction

Teeth are the only organs in the human body that penetrate the otherwise protective epithelial cell layer. Therefore, the tooth-gum interface, the dentogingival junction, can be considered an open wound constantly exposed to oral microorganisms. The invasion of bacterial pathogens into the subgingival tissues is the main pathogenic factor for initiating periodontal disease (PD). Chronic PD is a destructive form of gum infection that can lead to tooth and bone loss. PD treatment procedures often fail to restore the structural integrity of the junctional epithelium (JE), the epithelial attachment of the gum to the tooth, leaving the tooth-gum interface prone to bacterial colonization. This emphasizes the need for novel therapeutic strategies targeting JE regeneration. The JE is an epithelial barrier located at the uppermost part of the dentogingival attachment apparatus and is considered the first line of defense to protect the tooth-supporting tissues from the invasion of bacterial pathogens. Despite the importance of the JE, its attachment mechanism to the tooth surfaces is not fully understood. The lack of a defined in vitro model system to study cell behavior on hydroxyapatite (HA), the main component of mineralized tooth surfaces, has been a barrier to simulating the JE attachment in vitro. Such model systems should be able to study both cell attachment and migration as important events in the JE repair and regeneration. To address this need, we have developed a model system based on real-time protein adsorption analysis, microfluidics, isolation of human primary JE cells, live-cell monitoring, and a wound-healing assay to study cell attachment and detachment behavior on HA surfaces. Our model system also enables cell migration studies over surfaces coated with protein-based bioadhesives. Using our model system, we discovered that a protein complex comprised of enamel protein secretory calcium-binding phosphoprotein proline-glutamine rich 1 (SCPPPQ1) and laminin332 (LAM332) had a unique capability to enhance and accelerate the attachment and migration of oral epithelial cells. Our results suggest that this novel protein complex can be used in developing a biomimetic adhesive to enhance and accelerate the re-epithelialization of the dentogingival junction in the destructive form of gum disease.

Keywords: Bioadhesives
Cell Attachment and Migration
Junctional Epithelium
Microfluidics
Oral Health
Protein Adsorption
Advisor: Ganss, Bernhard
Characterizing Metabolomic Activity in Mutant IDH Chondrosarcomas Chondrocytes

Reprogramming of cellular metabolism has gained attention as an emerging hallmark of cancer, but metabolic studies of cartilaginous neoplasms have been limited. Chondrosarcomas are the most common malignancy of cartilage and are associated with somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes. IDH mutations have also been identified in its benign precursor lesion, enchondromas; thus, suggesting that IDH mutations are early events in malignant chondrosarcoma transformation. Despite efforts from our group and others to target D-2-hydroxyglutrate (D-2HG), the downstream metabolic by-product of mutant IDH, this therapeutic strategy did not influence tumorigenic properties. We hypothesized that metabolic processes independent of D-2HG production may facilitate the development and progression of chondrosarcomas. Our targeted metabolomics study highlighted several metabolic differences between mutant IDH and non-mutant chondrosarcomas across a spectrum of organic acids, amino acids, and acylcarnitine species. This study also revealed enhanced glycolytic metabolism in mutant IDH chondrosarcoma, suggestive of increased glucose and glycogen tumor energetics. Accordingly, electron microscopical examination of patient chondrosarcoma cells revealed glycogen deposition exclusively in mutant IDH cells. We planned to uncover why this phenomenon was present in IDH mutant cells and how mutant IDH may regulate glycogen metabolism in early cartilage development and in chondrosarcomas to drive tumor growth. Upon investigation of glycogen in early cartilage development, mutant Idh1 mouse growth plates displayed glycogen accumulation upon histological analysis, confirming glycogen accumulation upon mutation of Idh1. Cartilaginous Gys1 deletion in the mutant Idh1 background revealed specific yet mild fetal skeletal deformities and partial rescue of the mutant Idh1 skeletal phenotype, suggesting that glycogen deposition plays a role in early cartilage development. Glycogen metabolism’s role in chondrosarcoma tumorigenesis was investigated by pharmacological blockade of glycogen utilization (CP-91149), which induced changes in tumor cell behavior, energetics, and tumor burden in vitro and in vivo. Finally, we identified a novel mechanism of glycogen metabolism regulation: hypoxia-inducible factor 1a (HIF1α) and mutant IDH1 interact to regulate gene expression of key metabolism enzymes. Our observations provide insight into how IDH mutational state alters cellular metabolism and how mutant IDH1 and HIF1α regulate glycogen metabolism in cartilage development and chondrosarcoma tumorigenesis.

Advisor: Wunder, Jay S
Alman, Benjamin A
Theorizing and Addressing the Needs of Indigenous Justice-involved Populations: A Systematized Review and Qualitative Investigation of the Responsivity Principle

The dominant rehabilitation model in Western criminal justice systems, the risk-need-responsivity (RNR) framework, is criticized for disregarding the unique circumstances of Indigenous clients while at the same time under-researched on the very dimension—responsivity—that addresses this kind of tailoring. This dissertation comprises two studies investigating responsive rehabilitation for Indigenous clients from an international evidence base and local practice perspective, structured around two established and two proposed components of the responsivity principle. Study 1 is a systematized literature review of intervention with Indigenous justice-involved individuals in four countries, capturing research published between 1990 and 2022. Using narrative synthesis, I identified key themes emerging from 310 papers: that Indigenous individuals experience certain specific responsivity factors in greater numbers or to a greater degree of severity than the general justice-involved population; that services following the general responsivity principle yield positive results for Indigenous participants; that access to programs may be limited by the remoteness and poverty of Indigenous communities, representing a systemic responsivity issue; and that, at the level of ‘political responsivity,’ Indigenous scholars and communities sharply question state justice institutions and fight to implement locally owned programs under poorly resourced conditions. Study 2 presents the results of interviews with 16 service providers from northern Ontario working with Indigenous justice-involved youth in custody, probation, and community settings. I used thematic analysis to generate themes organized around the four categories of responsivity. Participants reported working in ways highly consistent with specific responsivity elements. On the topic of general responsivity, participants placed the therapeutic alliance at the core of effective treatment, noting the complexity and viability of cross-cultural relationships with Indigenous clients. With respect to systemic responsivity, participants identified remoteness and resource scarcity on reserves as significant barriers to intervention. As regards political responsivity, participants shared concerns about the “revolving door” of justice for Indigenous youth. Poverty, geography, racism, and trauma were significant cross-cutting themes. Together, these papers paint a picture of a highly vulnerable and resilient population that benefits from RNR-consistent individualized and multisystemic care but that enters the justice system with significant challenges and continues to struggle against systemic racism and inequality.

Keywords: criminal justice
Indigenous
intervention
offender
rehabilitation
risk-need-responsivity
Advisor: Peterson-Badali, Michele
Beta Capitalism: The Financialization and Minimum Viability of Food Delivery Labour

This dissertation offers an ethnography of app-based food delivery couriers and management. The app-based last-mile delivery industry is one of the most distinctive developments in capitalism in the last decade. Drawing on twenty-one months of fieldwork, I argue that Fleatz, a composite app-based food delivery company operating in Berlin, represents a new iteration of capitalism in that the role of riders is not only, or even primarily, to create profits for the company through the surplus value of their labour. Instead, they are also subject to regimes of speculative data accumulation and of beta capitalism, an organizationally, politically, and financially volatile form of high-tech accumulation that emphasizes constant optimization, speed, and market growth, underpinned by a reliance on financial capital instead of profits to be economically viable. Subjecting rider labour to multiple forms of value accumulation results in a confusing, paradoxical, yet highly quantified work experience for riders and office workers alike, but the consequences are most serious for riders.

Keywords: algorithms
Berlin
data
finance
Germany
labour process
Advisor: Barker, Joshua
Muehlebach, Andrea
On Electric Vehicle Demand, Price Competition and Environmental Policies

Chapter 1 investigates the effects of two types of policies on consumer demand for EVs, subsidy programs and driving restrictions on gasoline cars, using rich consumer-level data from a major Chinese city on all car purchases. I estimate a structural demand model for differentiated products that incorporates these policies. I find both policies show their success in stimulating consumer demand for EVs and the positive effect of driving restrictions on the demand for EVs is stronger for consumers who already own a car than for those who do not.Chapter 2 studies the contribution to the dramatic decline of the market share of BYD Company in the Electric Vehicle (EV) market: from above 95% in 2014 to close to 10% in 2020 in a changing environment characterized by growing demand, rapid technological progress, disruptive market entry, and frequent changes in government subsidies to EVs. Our results are based on the estimation of a structural model of demand and price competition, and on a large set of counterfactual experiments that identify the contribution of different factors to the observed decline. We find that most of the decline in BYD’s market share can be explained by product proliferation and product design from early competitors. A second important factor was the rapid technological improvement in the industry during this period that made BYD to lose its initial cost advantage. Despite the decline in its market share, BYD increased its average price cost margin during this period. Our counterfactuals show that the decline in BYD’s market share and the increase in its markup are both closely related to changes in product design by BYD and its competitors. Chapter 3 compares the performance of estimation methods using market level data with a maximum likelihood–control function estimator to deal with the issue of zero market shares in demand estimation. We apply these methods to study consumer behavior during the COVID-19 pandemic using data from a leading department store in China. We find very substantial biases in the methods using market level data while estimates using consumer level data show a more plausible result.

Keywords: Differentiated product
Industrial Organization
Price competition
Advisor: Aguirregabiria, Victor
High-Resolution Spectroscopy of Exoplanet Atmospheres

Over five thousand exoplanets have been discovered, but relatively little is known about their atmospheric properties and compositions. Characterizing exoplanet atmospheres is the most promising avenue through which we can learn more about exoplanets themselves, and analyzing high-resolution spectra through Doppler cross-correlation is currently one of the best methods by which this can be accomplished. In this thesis, I use state-of-the-art ground-based spectrographs in the optical and near-infrared wavelength regimes to detect, characterize, and understand the atmospheres of exoplanets. My focus is on super-Earths and hot Jupiters, for which there are no Solar System analogues and which remain poorly understood. I begin by characterizing the atmospheres of two warm, sub-Saturn mass exoplanets with high-resolution optical spectroscopy, pushing current observational techniques to lower masses and temperatures and exploring the effects of clouds on high-resolution optical spectra. I then investigate the atmospheric composition of a hot super-Earth with high-resolution near-infrared spectroscopy, providing stringent constraints on its chemical composition and presenting the first atmospheric characterization of an exoplanet from a new near-infrared spectrograph. I also investigate the efficacy of telluric removal methods across a broad, near-infrared wavelength range. Lastly, I turn my attention to the atmosphere of a highly irradiated ultra-hot Jupiter with high-resolution optical spectroscopy, resulting in a new detection of ionized calcium indicative of atmospheric outflows and/or a hotter-than-expected temperature. I then carry out a detailed search for atomic and molecular species in this planet's atmosphere, shedding light on its chemical composition and setting the stage for a multi-year optical survey of exoplanet atmospheres at high spectral resolution. These works expand our knowledge and understanding of exoplanet atmospheres, and shed light on the enigmatic populations of super-Earths and hot Jupiters. They also introduce novel techniques across a range of new instruments and surveys, paving the way for future studies in the field and opening the doors to an era of comparative exoplanetology.

Keywords: Atmospheres
Exoplanet Characterization
Exoplanets
Observational Astronomy
Advisor: Jayawardhana, Ray
Sivanandam, Suresh