VictorJuiz/thesis huggingface dataset:
NLRX1 is a Mitochondrial Matrix Protein that Links Cell Death with Tumorigenesis

NLRX1 is a recently characterized member of the intracellular family of Nod-like receptors (NLRs), and this NLR protein localizes to the mitochondrion. The function of NLRX1 in innate immunity remains debated as initial studies proposed that NLRX1 may function as negative regulator of antiviral signaling, through localization at the mitochondrial outer membrane and direct interaction with the mitochondrial antiviral signaling protein (MAVS), thus preventing MAVS-dependent antiviral signaling. In contrast, our group had demonstrated that overexpression of NLRX1 resulted in the induction of reactive oxygen species (ROS), which up-regulated NF-B and JNK pathways, most likely as a result of ROS-dependent up-regulation of pro-inflammatory pathways. Altogether, the exact function of NLRX1 remained poorly characterized.In Chapter 2, I report the precise intra-mitochondrial subcellular localization of NLRX1 and provide a possible mechanism for NLRX1-dependent ROS production. I report that NLRX1 contains a classical N-terminal mitochondrial targeting sequence (MTS), which undergoes proteolytic cleavage upon entry into the mitochondrial matrix. Furthermore, I identify an interaction between NLRX1 and UQCRC2, a protein member of the complex III of the electron transport chain. This interaction provides a plausible molecular mechanism for NLRX1-dependent ROS production, as complex III has been identified as a major source in the generation of ROS. Given the physiological localization of NLRX1 to the mitochondrial matrix, I re-assessed the role of NLRX1 in MAVS-dependent signalling. In Chapter 3 and Chapter 4 I demonstrate both in vitro an in vivo that NLRX1 does not play a significant role in MAVS-dependent antiviral signalling. Compared to scramble or WT controls, NLRX1 silencing or NLRX1-deficient mice exhibited similar levels of antiviral gene expression following viral infections. Finally, in Chapter 5 I identify the role of NLRX1 in the control of apoptotic cell death sensitivity in transformed but not primary cells, suggesting a link between NLRX1 and tumorigenesis. Altogether, in this thesis I clarify the role of this poorly characterized NLR in innate immunity and provide evidence that NLRX1 may serve as a potential therapeutic target in cancer.

Keywords: cell death
colorectal cancer
innate immunity
mitochondria
NLRX1
Nod-like receptors
Advisor: Stephen, E Girardin
Development of Ultrasound Phased Array System for Weld Inspections at Elevated Temperatures

Interruption of plant operation can be avoided if non destructive testing inspections are performed on-line at operating temperatures, which may be up to several hundred degrees Celsius in a petrochemical or electric power generating plant. However, there are operational temperature limits of the phased array transducers and associated plastic wedges used for ultrasonic inspections. In addition, there is a major gap in terms of professionally-approved high-temperature inspection techniques. In this project, the design and operation of an ultrasonic phased array system are described for inspections of engineering components such as pipe welds at elevated temperatures of up to 350oC. Wedges are built from plastics resistant to high temperature degradation, and equipped with a cooling jacket around the array. A model of the ultrasonic beam skew pattern due to thermal gradients inside a wedge is developed. The model is used in a separate algorithm to calculate transmission and reception time delays on individual array elements for generation of plane waves or focused beams in a hot test piece, while compensating for thermal gradient effects inside the wedge. The algorithm is also used to investigate the magnitude of thermal gradient effect on the calculated time delays of the phased array elements. The algorithm results for inspections of test pieces at 150oC demonstrate that application of conventional element time delays can lead to serious phase errors. This results in major distortion of the desired beam profile, and very poor imaging resolution. However, experimental trials indicate that plane waves and focused beams can be generated in a hot test piece using the new focal law algorithm with appropriate timing delays applied to all active array elements.

Keywords: beam skew
focal law
high temperatures
phased arrays
Advisor: Tony, Sinclair
Warrior Women: Indigenous Women's Anti-violence Engagement with the Canadian State

This study examines indigenous women's involvement in state-sponsored anti-violence responses since the 1980s. It focuses on three fields of political engagement: (1) the Canadian state politics of family violence; (2) the Native Women's Association of Canada's(NWAC) "Sisters in Spirit" (SIS) initiative and the politics of missing and murdered Aboriginal women and girls; and (3) the politics of prostitution and the Missing Women Commission of Inquiry. Overall, I argue that despite navigating a complex and colonizing political terrain largely out of their control, indigenous women have been "warrior women," advancing strong anti-colonial anti-violence responses that support the end goal of ending violence against indigenous women and girls in Canada. I also explore how indigenous women have sometimes employed political discourses and strategies that while appearing to offer a valid pathway of resistance, replicate dominant discourses and strategies and, thus, serve to undermine these efforts by securing the colonial Canadian state's authority over indigenous peoples and territories and, therefore, the persistence of violence against indigenous women and girls in Canada. To reinforce both of these claims, this study addresses reception: that is, I argue that the Canadian state's responses to violence against indigenous women and girls have been driven by self-interest and state political agendas which, because of the adversarial nature of colonial domination, rarely coincide with the interests or needs of indigenous women and their communities. Furthermore, I show that the state's response to indigenous women's anti-violence resistance can be favorable when it can be reconciled with its self-interest and political agendas, but quickly moves to appropriation and suppression if these anti-violence politics threaten Canadian state dominance.

Keywords: anti-violence resistance
Canada
indigenous women
state sponsored anti-violence responses
violence
Advisor: Sherene, Razack
Analysis of Sales Processes with Social Interaction

My thesis work focuses on modeling consumers' decision making under various online contexts with social externalities, and studying the optimal policies and strategies for firms in response. Recent innovations in digital economies bring both opportunity and challenges to practitioners. Firms try to leverage innovations, such as online group buying and social media, to improve their profitability. However, without a clear understanding of how the consumers participate in the process, firms are not able to utilize these innovations to their full potential. My research delves into individuals' decision making under various online contexts, investigating how consumers interact under novel sales mechanisms and how this interaction impacts on firms' profitability. Using the proposed demand models, I then study operational and marketing policies and strategies that can improve the management of various sales processes by firms.In particular, my thesis consists of two projects, namely online group buying and social-influence moderated demand process. I study the group-buying project from two perspectives. First, in Chapter 2, I investigate the information management strategy for group-buying mechanisms from an analytical perspective. Second, I study the effect of thresholds on consumers' sign-up behavior from an empirical perspective in Chapter 3. The empirical study is made possible by a real-time dataset extracted from online group-buying firms, such as Groupon and LivingSocial, using a data crawler built on a major cloud platform. Chapter 4 summarizes the results of the second project, where I study how social-influence moderated demand process, often facilitated by internal and external social media, affects the profitability of a newsvendor-type firm.

Keywords: Applied Game Theory
Operations-Marketing Inteface
Revenue Management
Social Influence
Advisor: Joseph, Milner
Optical Properties of Novel Materials

Optical Spectroscopy is a well-established experimental technique for the study of solids, gasses, and liquids. This thesis focuses on two broad topics related to optical spectroscopy; experimental instrumentation, and its application to novel materials. The first half of the thesis discusses the design and construction of a novel, multifunctional magneto-optical spectroscopy apparatus with exceptional repeatability. Included are the operating principles of FTIR reflectance and transmittance spectroscopy, and the optical ray-tracing design, physical design, and characterization of a custom built magneto-optical spectroscopy apparatus. The second half of the thesis discusses the experimental results of a comprehensive spectroscopic study of Topological Insulators and thermoelectric Pb

Advisor: Kenneth, S Burch
Metabolic Engineering for Substrate Co-utilization

Production of biofuels and bio-based chemicals is being increasingly pursued by chemical industry to reduce its dependence on petroleum. Lignocellulosic biomass (LCB) is an abundant source of sugars that can be used for producing biofuels and bio-based chemicals using fermentation. Hydrolysis of LCB results in a mixture of sugars mainly composed of glucose and xylose. Fermentation of such a sugar mixture presents multiple technical challenges at industrial scale. Most industrial microorganisms utilize sugars in a sequential manner due to the regulatory phenomenon of carbon catabolite repression (CCR). Due to sequential utilization of sugars, the LCB-based fermentation processes suffer low productivities and complicated operation. Performance of fermentation processes can be improved by metabolic engineering of microorganisms to obtain superior characteristics such as high product yield. With increased computational power and availability of complete genomes of microorganisms, use of model-based metabolic engineering is now a common practice. The problem of sequential sugar utilization, however, is a regulatory problem, and metabolic models have never been used to solve such regulatory problems. The focus of this thesis is to use model-guided metabolic engineering to construct industrial strains capable of co-utilizing sugars. First, we develop a novel bilevel optimization algorithm SimUp, that uses metabolic models to identify reaction deletion strategies to force co-utilization of two sugars. We then use SimUp to identify reaction deletion strategies to force glucose-xylose co-utilization in

Keywords: Carbon catabolite repression
Constraint-based modeling
Glucose-xylose co-utilization
Metabolic engineering
Metabolic modeling
Advisor: Radhakrishnan, Mahadevan
The Development of Judgments and Beliefs about Homosexuality

This study assessed children's (5-year-olds, 7-8-year-olds, and 10-11-year-olds), adolescents' (13-14-year-olds), and their parents' beliefs about same-sex relationships. In particular, participants' beliefs about the acceptability and legal regulation of homosexuality, their beliefs about tolerating someone with anti-gay attitudes and excluding someone on the basis of his/her sexual orientation, and finally, their essentialist beliefs about homosexuality (i.e., whether they believe sexual orientation is biologically or socially/environmentally determined) were explored. Results revealed age differences in the acceptability of same-sex relationships, with older participants holding more positive attitudes, justified by references to personal choice and moral reasoning. Adults were more tolerant of someone holding a negative belief about homosexuality than the younger participants, and both the adults and the 5-year-olds were more tolerant of someone holding a negative belief about homosexuality and expressing this belief than the other participants. The 5-year-olds were also more accepting of parents acting on this belief by restricting a child's activities. There was no association between parents' attitudes and their children's. In terms of essentialist beliefs, with age, participants were more likely to believe that homosexuality is biologically determined and this belief was generally correlated with more positive attitudes. The findings reveal that while some age differences were found in the development of attitudes about homosexuality, many scenarios revealed no age differences supporting the notion that children are not inherently more prejudiced than adults.

Keywords: Moral Development
Sexual Prejudice
Social Domain Theory
Advisor: Charles, C Helwig
Molecular Evolution of Posttranslational Regulation in Intrinsically Disordered Regions

Protein posttranslational regulation is a major facet of protein function, and efforts have been made to systematically characterize the level of control of proteins. For example, systematic determination of protein localization, phosphorylation, and interactions have allowed the examination of the regulatory network of the cell. However, the study of the evolution of this underlying regulatory network requires a higher resolution analysis of the sequences that are responsible for this level of control. The overarching goal of this thesis was to examine the role of the evolution of protein regulatory sequences as a molecular mechanism driving functional diversity. I developed computational tools and methods for the identification and characterization of these regulatory sequences, as well as experimental approaches to study the evolutionary impact of changes within these sequences.I first characterized the evolution of phosphorylation sites and used the property that they are strongly conserved relative to their flanking disordered regions as a computational means to systematically identify motifs in the budding yeast proteome. These results suggest that incorporating evolutionary conservation is sufficient for the prediction of around 30% of the known short linear motifs. Applying these computational approaches to the budding yeast proteome showed that thousands of short linear motifs exist and still remain uncharacterized.Using a relative rates test, I showed that motifs frequently change selective constraints after gene duplication and showed that these changes can alter protein regulation over evolution. Finally, I designed a high-throughput experimental pipeline to systematically, quantitatively and precisely assess the fitness consequences of rewiring a regulatory network and applied it to test whether a bi-functional protein has sub-functionalized over evolution.

Keywords: Computational Biology
Advisor: Alan, M Moses
Democratizing and Decolonizing Education: A Role for the Arts and Cultural Praxis: Lessons from Primary Schools in Maasailand, Southern Kenya

Under the impact of global neoliberal educational policies and the continuing influence of colonial-informed policies and pedagogical approaches, the arts, in schools around the world, are either being devalued or their conception is being narrowly focused towards market-based purposes. Researchers and critical theorists have argued that the arts are a vital educational tool for promoting the creative, critical and culturally responsive skills necessary for a robust democratic society. For centuries, the arts and cultural practices have been deeply embedded in the rich cultural heritage of many indigenous peoples as tools for giving voice, building community and sharing knowledge. For nation-states, like Kenya, which have struggled along a rocky road toward democracy, the arts and cultural practices could play a key role in supporting the development of critically engaged citizens for the broader purposes of democratic and transformative education. This thesis uses a two-pronged lens informed by critical-democratic theory and decolonial theory to explore teachers' understanding of their use of the arts and cultural praxis in a purposely selected case study located in Maasailand, southern Kenya. The research design followed an international case study approach and drew from comparative international education theory and methods. In order to deepen the understanding of the multi-contextual factors influencing teachers' use of the arts and cultural praxis, the study also included data gathered from policy documents and from other educational stakeholders including head-teachers, principals, supervisory officers, parents, curriculum coordinators, policy makers and community members. The analysis and discussion of the findings provides a critique of the continuing impact of colonial and neoliberal educational policies on teachers' use of the arts and cultural praxis for transformative education, and highlights the need for a broader and more equitable conception of the arts and cultural practice as

Keywords: Arts
Critical pedagogy
Cultural praxis
Decolonial pedagogy
Robust democracy
Sub-Saharan Africa
Advisor: John, P. Portelli
Control and Automation of Fluid Flow, Mass Transfer and Chemical Reactions in Microscale Segmented Flow

Flowing trains of uniformly sized bubbles/droplets (i.e., segmented flows) and the associated mass transfer enhancement over their single-phase counterparts have been studied extensively during the past fifty years. Although the scaling behaviour of segmented flow formation is increasingly well understood, the predictive adjustment of the desired flow characteristics that influence the mixing and residence times, remains a challenge. Currently, a time consuming, slow and often inconsistent manual manipulation of experimental conditions is required to address this task. In my thesis, I have overcome the above-mentioned challenges and developed an experimental strategy that for the first time provided predictive control over segmented flows in a hands-off manner. A computer-controlled platform that consisted of a real-time image processing module within an integral controller, a silicon-based microreactor and automated fluid delivery technique was designed, implemented and validated. In a first part of my thesis I utilized this approach for the automated screening of physical mass transfer and solubility characteristics of carbon dioxide (CO2) in a physical solvent at a well-defined temperature and pressure and a throughput of 12 conditions per hour. Second, by applying the segmented flow approach to a recently discovered CO2 chemical absorbent, frustrated Lewis pairs (FLPs), I determined the thermodynamic characteristics of the CO2-FLP reaction. Finally, the segmented flow approach was employed for characterization and investigation of CO2-governed liquid-liquid phase separation process.The second part of my thesis utilized the segmented flow platform for the preparation and shape control of high quality colloidal nanomaterials (e.g., CdSe/CdS) via the automated control of residence times up to approximately 5 minutes. By introducing a novel oscillatory segmented flow concept, I was able to further extend the residence time limitation to 24 hours. A case study of a slow candidate reaction, the etching of gold nanorods during up to five hours, served to illustrate the utility of oscillatory segmented flows in assessing the shape evolution of colloidal nanomaterials on-chip via continuous optical interrogation at only one sensing location. The developed cruise control strategy will enable plug'n play operation of segmented flows in applications that include flow chemistry, material synthesis and in-flow analysis and screening.

Keywords: Carbon Dioxide
Gas-Liquid Solubility
Microfluidics
Quantum Dots
Segmented Flow
Switchable Water
Advisor: Axel, Günther
The Role of Local Strains from Prior Cold Work on Stress Corrosion

Several studies have recently reported that cold working exacerbates stress corrosion cracking (SCC) of materials in various environments, including those in which they were previously thought to be immune. While these studies usually consider cold work as a homogeneous effect, the presence of grain boundaries results in local strain concentrations that are inhomogeneously distributed within the microstructure. In order to understand the underlying mechanisms by which the local strains generated by cold work influences SCC, α-brass and Alloy 600 were used in this study. The microscopic changes in the local strains caused by cold work and by SCC were measured using electron backscatter diffraction (EBSD) and polychromatic X-ray microdiffraction (PXM). While the plastic strains were qualitatively expressed through the local misorientation calculated from the orientation data measured by both EBSD and PXM, the elastic strains were determined from the Laue patterns measured by PXM. The interaction between the local strains, and the crack initiation and propagation during SCC was studied by comparing the strain distribution from the same area measured before cold work, after cold work, and again after SCC. In this way, apart from obtaining insights on the interaction, the relative importance of pre-existing strain concentrations and those created by crack propagation can be identified. Additionally, statistical analysis of the EBSD data from uncracked and cracked grain boundaries in Alloy 600 showed the susceptibility of the boundaries to increase when they were surrounded by high local strain concentrations and when the grains sharing the boundary had similar deformation tendency, but to be independent of the grain boundary angle. Finally, one of the contributors for the changes in the strain distribution during SCC can be the corrosion process itself which was examined by intermittently measuring the changes in local strains caused by intergranular corrosion on an unstressed sample.

Keywords: Alloy 600
Brass
Cold Work
Electron Backscatter Diffraction
Polychromatic X-ray Microdiffraction
Stress Corrosion Cracking
Advisor: Roger, C Newman
Essays in Volatility Modeling and Option Pricing

The common thread that runs through my research is the implication of volatility dynamics for option pricing. In the first chapter of this thesis, my co-authors and I study the presence of a factor structure in equity options. A principal component analysis of equity options reveals a strong factor structure. Guided by this finding, we develop an equity option valuation model that captures this factor structure. The model allows for stochastic volatility in the market return and also in the idiosyncratic component of equity returns. The model has a series of predictions relating individual firm's beta to patterns in implied volatilities. The equity option data support the cross-sectional implications of the estimated model. In the second chapter, I focus on the impact of intermediaries' risk sharing capacity on index options. I examine how inventory risk and market-maker wealth jointly determine the value of index options through their effects on the variance risk premium. My analysis shows that part of the variance risk premium compensates option market-makers for their exposure to market variance. Based on these findings, I develop a theoretical model in which market variance is stochastic and the representative market-maker accumulates inventory over time by absorbing end-users' net demand for index options. Starting from the market-maker's optimal trading strategy, I derive an explicit formula linking the variance risk premium to inventory risk and market-maker wealth. The model predicts that the variance risk premium is influenced by the ratio of inventory risk to the market-maker's wealth. Estimating the model on S 500 index returns and options, I find that it performs well.

Keywords: Factor Structure
Option pricing
Variance Risk Premium
Volatility Modeling
Advisor: Peter, Christoffersen