VictorJuiz/thesis huggingface dataset:
Strategies for Protein Engineering
Keywords: Computational Protein Design
Protein Engineering
Structural Biology

Proteins propagate information within a cell by interacting with other proteins, DNA, RNA, and small molecules, enabling a cell to adapt to its environment and to maintain normal cellular functionality. Direct manipulation of a cell's protein interaction network can be achieved by using synthetically designed proteins to replace existing interactions or to create new interactions with other cellular components. A major challenge to engineering new synthetic proteins is the inability to search over the massive space of possible protein variants to identify candidates that bind the biological target of interest. In this thesis, I evaluate existing search strategies and propose a new search strategy for the computational design of proteins, which restricts the search space to one that is enriched for protein variants that tightly bind a protein target. I first evaluated current computational protein design strategies on two biological systems. Using the Fyn SH3 domain bound to different peptide targets, I assessed the design strategies' ability to recover the amino acid variability of the domain core as experimentally determined by phage display. Next, I evaluated the design methods by their ability to engineer the ubiquitin interface for tightly bind towards the USP21 protein. For this assessment, a new parallel validation strategy is introduced. In both biological systems, I found that ensemble protein design strategies outperformed other protein design methods. A limiting factor in current protein design strategies was found to be the accurate creation of alternative protein backbones when a single protein structure was used as a template. I present a flexible backbone design strategy, GP backbone design, that incorporates information from multiple protein structures. I show that using multiple structures to learn a space of possible protein movements increases the number of protein variants that tightly bind a protein target.
Three Essays in Financial Economics
Keywords: Corporate Finance
Human Capital
Innovations
Labour Business Cycles
Mergers and Acquisitions
Search and Match

This thesis discusses how innovations, managerial skills, and labour policies affect firms. In Chapter 1, I study how broadening innovation capacity through Mergers and Acquisitions (M) is costly for firms but beneficial for firm managers. I show that expanding a firm's innovation breadth through M leads to lower abnormal returns. I also show that despite this lower M performance, executives fare better in acquisitions that expand innovation breadth; specifically, increases in innovation breadth through acquisitions are associated with higher executive compensation and lower executive turnover. Overall, these findings suggest that expanding innovation breadth through M reduces firm value but benefits managers. In Chapter 2, I explore how well general versus specific managerial skills are allocated across firms and industries. In general, a manager with specific skills creates greater job value to the firm that requires these specific skills than does a manager with only general (i.e., transferable) skills. I provide empirical evidence that the differentiation between general and specific skills matters. I find that the match between a firm and its internally promoted executive, who brings firm-specific skills to a firm requiring more specific skills, increases firm value more than the mismatch does. My research suggests that a firm should choose to promote internally or hire externally based on its reliance on specific versus general skills. In Chapter 3, written jointly with Miquel Faig and Min Zhang, we calculate that the extension of unemployment insurance benefits during downturns has significantly increased the variability of unemployment and vacancies in the U.S. Taking this into account reduces the value of leisure necessary to match the wide labor market business cycles experienced in the U.S. using the Mortensen-Pissarides model. We analyze a version of the model where unemployment insurance benefits not only expire but they must be earned with prior employment. Our preferred calibration predicts that the standard deviation of unemployment since 1945 would have fallen by around 37 percent if there had not been programs extending unemployment benefits during recessions. We also find that the enactment of the Emergency Unemployment Compensation program in 2008 increased the unemployment rate by 0.5 percent.
Playing Rough: Racial and Gender Stereotypes, Performance and Misreading in the Fiction of Junot Díaz and Dany Laferrière
Keywords: Dany Laferrière
gender
Junot Díaz
race
reading
stereotype

Stereotyping involves the hasty, simplistic reading of a person, situation, or thing, based on a few, salient features. My dissertation examines stereotypes at four interconnected levels: (1) racial and sexual stereotypes applied to human bodies in fictional literary texts; (2) stereotypes applied to authors’ bodies, based on features of their identities; (3) stereotypical readings of texts that conform to popular and/or academic reading practices; and (4) literary genres as stereotypes that direct reading. In the works of fiction I examine, contemporary, Caribbean diasporic male writers of color write first- and second-person narratives that deploy, with irony, a similar principal stereotype. Haitian-Quebecois Dany Laferrière, in his novel Comment faire l’amour avec un Nègre sans se fatiguer, plays with the figure of the Nègre, an exotic, hypersexual, black male immigrant to Montreal who drives white female Blanches wild with desire. Dominican-American Junot Díaz deploys the stereotype of the Dominican stud in his short fiction, Drown and This Is How You Lose Her. There we witness the narrator learn, imitate and perfect the macho, womanizing role that causes female partners to leave him. These texts engage self-reflexively with the stereotypes they deploy and with the writing and reading of texts. They parody the instruction manual genre in their form while, in their content, they depict the subtle mechanisms of male-to-male instruction that form men into the racialized stud role they problematize. My dissertation examines the intersections and ironies of race, gender, sexuality and class in texts that are at once ironic and dead serious. I argue that the writers’ parodic play with a racialized stereotype of masculinity is attractive yet risky, critical yet complicit, for their ironic deployment of stereotypes necessarily reinforces them, even as it seeks to deconstruct them. Furthermore, these provocative, tongue-in-cheek narratives reproduce sexism as they critique racism.
Ammonia in Rural and Remote Environments
Keywords: Ammonia
Arctic
Atmosphere
Deposition
Dew
Soil

Ammonia (NH3) can harm ecosystems through deposition and react in the atmosphere to increase fine particulate (PM2.5) levels which impact climate and degrade air quality. Despite an abundance of field studies and modelling efforts there are still large uncertainties regarding the sources, sinks, and transport of NH3. These uncertainties are magnified in rural and remote regions where measurements are sparse. The Ambient Ion Monitor – Ion Chromatograph (AIM-IC) was deployed on three separate occasions to measure hourly averages of ambient NH3, SO2, and HNO3 as well as PM2.5 constituents (NH4+, SO42-, NO3-). AIM-IC measurements at a rural field in Ontario, in conjunction with soil measurements, revealed that a non-fertilized grassland exhibits bi-directional soil-atmosphere NH3 exchange. A “morning spike” of NH3 was occasionally observed around 7:00 to 9:00 local time and was investigated in a subsequent study at a remote park in Colorado. Simultaneous observations of dew composition, dew amount and NH3 suggested that the frequently observed, yet currently unexplained, morning spike is caused by NH3 released from evaporating dew. The AIM-IC was operated aboard a research icebreaker throughout the Canadian Arctic Archipelago. NH3 ranged between 30-650 ng m-3 and was usually sufficient to fully neutralize SO42-. Low values of NH4+ in the Arctic Ocean and melt ponds revealed they were always a net NH3 sink. Decomposing seabird guano and wildfires were identified as the primary NH3 sources through the use of a chemical transport model (GEOS-Chem) and particle dispersion model (FLEXPART-WRF). Lastly, AIM-IC measurements from a campaign in the Athabasca Oil Sands Region showed that air masses that had recently passed over bitumen upgrading facilities were enriched in NH3, SO2, HNO3, NH4+ SO42-, and NO3-. Comparison of observed NH3 to that predicted by the Extended – Aerosol Inorganics Model (E-AIM) implies that the aerosol system was in disequilibrium in polluted airmasses.
Form-focused Instruction in the Mainstream Classroom: Effects on the Grammatical Development of Adolescent English Language Learners
Keywords: Adolescent
English language learners
Form-focused instruction
Grammatical development
Mainstream
Secondary

Educating English language learners (ELLs) has increasingly become a challenge for schools outside major cities in Canada. ELLs in such contexts are swiftly integrated into mainstream classrooms, often without targeted language support. One way of providing support is through form-focused instruction (FFI) – an approach to language instruction in which learner attention is focused on language form during meaning-based activities. Although FFI has proved beneficial for the development of linguistic accuracy in a variety of second and foreign language contexts, its effectiveness for high school ELLs in mainstream classrooms has not been experimentally investigated. In this study, 18 participants enrolled in a secondary social studies course received FFI on two linguistic structures – passive and simple present - for 10 to 15 hours over a 15-week period. A time-series research design was used to compare the students’ performance on three pretests before the intervention with their progress at the midpoint, immediately after the intervention, and six months later. Students completed six linguistic measures at each test session: four production tasks – an oral (OPT) and written task (WPT) on each structure - and two receptive tasks – an aural (AGJ) and written (WGJ) grammaticality judgement task testing both structures. The results of the group’s overall performance immediately after instruction indicated limited improvement with significant gains observed on only two of the language measures, the passive OPT and the simple present AGJ. However, an analysis of individual and group performance based on students’ pretest knowledge of the target features (low, mid, high) indicated movement into higher levels of performance over time on the passive tasks. Learners’ performance on the simple present tasks showed less consistent patterns of change. The results are discussed in terms of the challenges of attending to language and content simultaneously.
Dynamic Tensile Failure of Rocks Subjected to Simulated In Situ Stresses
Keywords: DCA modeling
Dynamic tensile failure
In situ stress
PSO
SHPB
Underground rock

Tensile failure of rocks is a main problem in underground engineering applications, where rocks are subjected to dynamic loadings while under in situ stresses. When disturbed by dynamic loads from blasting or seismicity, underground structures are vulnerable to tensile failure. Therefore, it is of great importance and thus the aim of this thesis to investigate the dynamic tensile failure of rocks subjected to underground in situ stresses, experimentally and theoretically. For the experimental study, the split Hopkinson pressure bar (SHPB) system is modified and developed with a hydraulic press for the dynamic tests under different in situ stress states. The Brazilian disc specimens made from Canadian Laurentian granite are first subjected to a prestress simulating in situ stress (including pre-tension, hydrostatic confinement, and triaxial stress state) and then loaded dynamically using the modified SHPB. For each stress state, several groups of tests are conducted under different levels of prestress and loading rate. The result shows that for all of the tests, the dynamic tensile strength increases with loading rate, revealing the so called rate dependency, which is common for engineering materials. The dependence of the dynamic tensile strength on different prestress conditions are also examined. For the theoretical study, the Dominant Crack Algorithm (DCA) is adopted to model the dynamic tensile failure of rock under different prestress states, with the non-linear regression method Particle Swarm Optimization (PSO). The modeling parameters are obtained using the PSO method based on the experimental results and the DCA modeling is carried out accordingly under the simulated prestress and loading rate. The results demonstrate the applicability of the model as the error is less than 5% with reasonable values of the parameters. These experimental results and the calibrated theoretical model will be of great importance in the design and safety of underground rock engineering projects.
blmp-1 is a Ras-cooperating Tumor Suppressor Gene in Caenorhabditis elegans
Keywords: Cancer
C. elegans
Genetic interactions
Ras
RNAi
Vulval development

While hypermorphic Ras mutations are found in approximately 35% of colorectal, 45% of lung and 90% of pancreatic cancers, activated Ras alone is not sufficient to transform normal cells into cancerous tumors. Additional driver mutations or epigenetic alterations are required to cooperate with the activating Ras mutations in tumorigenesis. In C. elegans, worms homozygous for activated Ras mutations have 60 - 80% penetrant visible multivulval (Muv) phenotype. Several suppressors and enhancers of this phenotype have been shown to be orthologous to Ras-cooperating proto-oncogenes and tumor-suppressor genes, respectively. Because several epigenetic regulators are now targets of cancer treatments and many cancer genomes exhibit changes in epigenetic regulation, I sought to systematically identify chromatin regulators that cooperate with activated Ras using RNAi screening in C. elegans. After screening 215 C. elegans chromatin remodeling factors and 193 C. elegans orthologs of known driver genes from Tumor Sequencing Project, I identified several attenuators of Ras signaling. By generating double mutants, I was able to confirm that loss of PRDM1/Blimp1 homolog blmp-1 served as a strong enhancer of the let-60(n1046) Muv phenotype. In addition, blmp-1(tm548) mutant worms are not Muv. I chose to investigate one of these genes, called blmp-1, in great detail because of known roles of its mammalian ortholog PRDM1/Blimp1 in cancer. PRDM1/Blimp1 is a known tumor suppressor gene in activated-B cell diffuse large B-cell lymphoma (ABC-DLBCL). Whether PRDM1/Blimp1 cooperates with activated Ras is unknown. Therefore, I further sought to understand how BLMP-1 attenuates Ras signaling in C. elegans. blmp-1 mutants have mildly elevated Ras signaling in the vulval cells. In addition, blmp-1(RNAi) and null mutant blmp-1(tm548) are strong enhancers of let-60(n1046) Muv phenotype, resulting in nearly 100% penetrance Muv. blmp-1 expression is downregulated in response to vulval induction, and this downregulation is important for correct vulval induction. However, bypassing this downregulation reduced, but did not abolish vulval induction, suggesting that blmp-1 functions late in vulval development. In addition, I also identified distinct key regions within the blmp-1 promoter which are necessary and sufficient for the regulation of blmp-1 expression in the gut, seam cells, hypodermal cells and the vulva cells. In conclusion, this is the first characterization of blmp-1 as a putative Ras-cooperating tumor suppressor gene as blmp-1 enhances the activated Ras phenotype through a novel mechanism. These results may shed light into our understanding of ABC-DCLBL as a Ras pathway-driven cancer, and PRDM1/Blimp1 as a Ras-cooperating tumor suppressor genes.
Theoretical Evolutionary Biology of Sex and Disease
Keywords: mathematical modeling
Muller's ratchet
sexual conflict
sexually transmitted diseases
theoretical evolutionary biology
virulence evolution

Theoretical approaches have the potential to improve our conceptual understanding of evolutionary biology. Using mathematical modeling and computer simulations we can test verbal hypotheses about biological processes and make qualitative predictions about how biological factors interact to produce the patterns we observe in nature. My thesis is a series of theoretical chapters, each focused on a different aspect of evolutionary biology. In Chapter 2, I explore the accumulation of deleterious mutations by Muller's ratchet in asexual populations experiencing temporal fluctuations in selection. My finding that temporal autocorrelation in selection increases the rate of fitness decline contributes to our understanding of the role of environmental heterogeneity and drift in the extinction of asexual lineages. In Chapter 3, I investigate virulence evolution of parasites infecting host populations that have multiple host types differing in their contact patterns and their susceptibility and resistance to disease. I found susceptibility and resistance interact with contact pattern to change evolutionarily stable virulence, highlighting the importance of considering non-random contact patterns between different host types when modeling biologically realistic host populations. In Chapter 4, I model the coevolution of virulence of a sexually transmitted disease (STD) in a host population experiencing sexual conflict over mating rate. In my model, a coevolving STD selects for higher sexually antagonistic host trait values, escalating the conflict and demonstrating that disease could be an important factor in sexually antagonistic coevolution. Overall, my chapters make advancements in their respective fields by adding some dimension of biological realism to the general model and analyzing how this addition affects the evolutionary outcome.
Product Design Theory and Methods for Changing User Behaviour
Keywords: Affordances
Behavior Change
Creativity
Motivation
Product Design
Pro-Environmental Behavior

Design for behaviour-change is a growing field with a great deal of potential. Changing the behaviour of users through products and services can help users be happier, companies be more profitable and also help mitigate environmental problems. My research goals were to gain a good understanding of human behaviour models, models of product-user interaction and design methods for generating concepts that solve behaviour-change problems. First, I developed an ontology to formally represent and connect the varied sources of literature. Next I developed a new way of studying and working with the notion of affordances and using that to design products that change behaviour. Finally, I discuss a multi-motive framework that allows designers to change the behaviour of users with different needs, apply many different types of behaviour change strategies and be able to work on problems of many different types. This model and design tool were tested with student and professional designers who both derived benefits from it. Directions for further development of this work include testing the efficacy of the products designed using the methods presented in this dissertation to change user behaviour.
Beyond the Warring Sects: Universalism, Dissent, and Canon in Tamil Śaivism, ca. 1675-1994
Keywords: Historiography
Religious Modernity
Tamil Ĺ aivism

Scholarship on the formation of modern Hindu universalism in colonial South Asia has tended to focus on the Western-gazing and nationalist discourses of acculturated elites. Less attention, however, has been paid to comparable developments within the regionally situated vernacular religious traditions. The present dissertation addresses this issue by considering how several distinctly vernacular Śaiva traditions in Tamil-speaking Southern India transformed through the impact of the colonial encounter. At the center of this transformation, which produced “Tamil Śaivism” as a monolithic Tamil religion, was a shift in the way in which these sectarian traditions articulated and contested specific interpretations of Śaiva theology and sacred textuality. Chapter One contextualizes the thesis’ arguments by focusing on the internally diverse character of early-modern Tamil Śaiva intellectual culture, and more especially on the phenomenon of pan-sectarianism in two contemporary eclectic Tamil Vīraśaiva treatises. The next three chapters explore how such pan-sectarian claims were placed under enormous pressure in the nineteenth century. Chapter Two examines a low-caste commentary on a classic of Tamil Advaita Vedānta that attempts to critique the orthodox religious establishment and reinscribe Śaivism as a monism. In Chapter Three I look at how the fiery Śaiva Siddhāntin Cōmacuntara Nāyakar responds to the perceived threat of Brahminical religion by consolidating a monolithic account of Tamil Śaivism around the medieval poet-saint Tiruñāṉacampantar. Chapter Four situates this consolidation within a more general fracturing of the Tamil religious public sphere in the late nineteenth century, which I elucidate by examining an emergent debate over the sectarian identity of a major early-modern poet. The final substantive chapter analyzes the postcolonial afterlife of Śaiva sectarianism as it is expressed in the recorded discourses of the twentieth-century monastic Cantiracēkarēntira Carasvati Cuvāmikaḷ. By investigating these diverse attempts to claim the right to speak for Tamil Śaivism, the thesis contributes to current scholarly debates about the emergence of modern South Asian religion, while also mapping out important but neglected aspects of South Indian religion and religious historiography.