VictorJuiz/thesis huggingface dataset:
Models to inform the safe collection and transfusion of donated blood
Keywords: Management Science and Engineering.

Donated blood is a critical component of health systems around the world, but its collection and transfusion involve risk for both donors and recipients. Transfusion-transmitted diseases and non-infectious adverse events pose a risk to transfusion recipients, and repeat blood donation can cause or exacerbate iron deficiency among donors. This dissertation describes four decision-analytic modeling projects that inform blood safety policy. In Chapter 2, I integrate epidemiological, health-economic, and biovigilance data to estimate the efficacy and cost-effectiveness of a 2016 policy mandating that all blood donations are screened for Zika virus in the U.S. The analysis uses a novel microsimulation of individual transfusion recipients that captures the relationship between disease exposure risk and the number and type of blood components transfused. In Chapter 3, I develop the first health-economic assessment of whole blood pathogen inactivation. The analysis is for Ghana and improves on prior blood safety assessments for sub-Saharan Africa by considering the likelihood and timing of clinical detection for chronic viral infections. In Chapter 4, I develop an optimization-based framework for identifying the optimal portfolio of blood safety interventions that overcomes some limitations of traditional cost-effectiveness analyses for blood safety. By applying this framework retrospectively to evaluate U.S. policies for Zika and West Nile virus, I show that the optimal policy can vary by geography, season, and year. Chapter 5 focuses on how frequently donors are allowed to give blood. I develop a machine learning-based decision model that tailors the inter-donation interval to each donor's risk of iron-related adverse outcomes to balance risks to donors against risks to the sufficiency of the blood supply. Together, these model-based analyses introduce novel methods and provide guidance for efficient and effective use of resources for blood safety
Modern ethnic entrepreneurship : a pathway of economic mobility?
Keywords: Sociology.

The growth in the number of Latino-owned businesses is now outpacing the growth rate of the Latino population and the start-up growth of all other racial and ethnic groups in the United States. The sociological literature on ethnic entrepreneurship has tended to depict Latino-owned businesses as driven by necessity, operating in largely resource-constrained environments, and focuses heavily on first generation immigrants. This dissertation explores modern ethnic entrepreneurship including its potential for economic return, the interplay between business strategies and ethnic identity, and the role of institutions in advancing minority entrepreneurship. I use quantitative and qualitative methods to understand what it is like to be an ethnic entrepreneur today including 101 interviews with entrepreneurs and institutional investors. Through census data, I find entrepreneurship to be an alternative and lucrative pathway among high-skilled Latinos. This is reinforced by a subset of interviews with microbusiness and scaled business owners that examines how they make sense of their ethnoracial identity in relation to their business. I find that ethnic strategies can yield benefits as a business strategy but choosing when and how to leverage an ethnic identity is largely reserved for entrepreneurs who have obtained higher education, the later generations, and those operating in professional industries. Interviews with investment professionals shed light on the institutional logics that systematically block minority-owned investment firms' wealth-generating opportunities. Together, these findings aim to illuminate the experience of modern Latinx entrepreneurs seeking economic mobility outside of formal labor structures, with important implications for increasing diversity and capital allocation to minority-owned businesses
Modern financial markets
Keywords: Economics.

In this dissertation, I assess how well different types of financial markets function and draw implications for policy reforms in three chapters. In the first chapter, co-authored with Jason Allen (Bank of Canada), I focus on over-the-counter (OTC) markets. Traditionally, investors trade bilaterally through intermediaries, referred to as dealers, in OTC markets. An important regulatory question is whether to centralize OTC markets by shifting trades onto centralized platforms. I address this question in the context of the liquid Canadian government bond market. I document that dealers charge markups even in this market and show that there is a price gap between large investors who have access to a centralized platform and small investors who do not. I specify a model to quantify how much of this price gap is due to platform access and assess welfare effects. The model predicts that not all investors would use the platform even if platform access were universal. Nevertheless, the price gap would close by 32%-47%. Welfare would increase by 9%-30% because more trades are conducted by dealers who have high values to trade. In the second chapter, I analyze why securities are traded in isolation in most financial markets. Such a disconnected market design can be inefficient if agents trade more than one security. I assess welfare effects of connecting markets by allowing orders for one security to depend on prices of other securities. I show that everyone trades identical amounts under both market structures if and only if the clearing prices are perfectly correlated or all are price-takers. Prices in disconnected markets might allow strategic traders to extract higher rents from non-strategic traders. In expectation, connected markets generate higher welfare, but all markets become efficient as they grow large. In the third chapter, co-authored with Jason Allen (Bank of Canada), I study if and how the capitalization of dealers affects asset demand and prices. I introduce a model, in which capital-constrained dealers compete for an asset, and test its predictions with trade-level data on Canadian Treasury auctions by leveraging balance sheet movements and policy interventions during the COVID-19 pandemic. I show that both higher capitalization and weaker capital requirements flattens dealer demand. This increases the asset's price via market clearing. Based on the findings, I propose to use the slope of demand curves in Treasury auctions as a new indicator for dealer capitalization. The slope correlates with existing indicators of the literature but can be estimated easily and frequently for each dealer without balance sheet information
Modern programming models for GPU-accelerated heterogeneous supercomputers : computational fluid dynamics and in situ data compression
Keywords: Mechanical Engineering.

This work presented in this thesis is concerned with large-scale computational fluid dynamics simulations and can be divided into two main parts. The first is an investigation into the suitability of asynchronous, task-based parallelism for computational fluid dynamics simulations targeting exascale, heterogeneous architectures. The second part is concerned with the incorporation of data compression algorithms into computational fluid dynamics simulations using interpolative decomposition methods. The first chapter is a brief introduction to computational fluid dynamics, as well as an overview of traditional parallel computing practices in the field. The second chapter details the Legion programming system, which is used in this work to develop asynchronous, task-parallel solvers. Chapter Three is a case study on the implementation of a high-order, Navier-Stokes solver using the Regent programming language and the Legion runtime; this is compared to an existing, data-parallel MPI+Fortran version of the solver. The fourth chapter provides an in-depth discussion of interpolative decomposition methods for data compression, and the fifth chapter presents results for the incorporation of a novel interpolative decomposition algorithm into the Legion flow solver described in Chapter Three. Finally, Chapter Six concludes with "lessons learned" and possible avenues for future work
Modernizing retailers in emerging markets : investigating externally-focused and internally-focused approaches
Keywords: Business.

In the retail sector globally, millions of traditional stand-alone shops — such as the Kiranas of India, Tienditas of Mexico and Xiao Mai Bu of China — co-exist alongside modern organized retail chains and compete with them to serve end-customers. In this dissertation, I study the impact of business modernization on the sales performance of these traditional retailers. I define modernization as adopting physical structures and tangible practices ubiquitous in organized retail chains(for example, exterior signage with store name and logo, or a database to record product-level information). To address this research question, I implement a randomized field experiment in Mexico City with 1148 traditional retail firms. The sample is randomized into three groups: 385 firms that are externally modernized in ways that are visible to customers; 383 firms that are internally modernized in ways that are not visible to customers; and 380 firms form a control group. I find a significant and persistent main effect of modernization on sales: firms in both treatment groups increase monthly sales by 15% to 19%, even 24 months after study recruitment. In terms of novel mechanism evidence, I find that externally-modernizing firms improve their store-level branding, while internally-modernizing firms strengthen their product management. These results have important implications for multinational managers who distribute products through traditional retail channels, and for policymakers interested in improving firm performance in the retail sector of emerging markets
Mod-p Poincaré duality in p-adic analytic geometry
Keywords: Mathematics.

We review the theory of almost coherent modules that was introduced in "Almost Ring Theory" by Gabber and Ramero. Then we globalize it by developing a new theory of almost coherent sheaves on schemes and on a class of "nice" formal schemes. We show that these sheaves satisfy many properties similar to usual coherent sheaves, i.e. the Almost Proper Mapping Theorem, the Formal GAGA, etc. We also construct an almost version of the Grothendieck twisted image functor f^! and verify its properties. We then study sheaves of p-adic nearby cycles on admissible formal models of rigid spaces and show that these sheaves provide examples of almost coherent sheaves. This gives a new proof of the finiteness result for ́etale cohomology of proper rigid spaces obtained before in the work of Peter Scholze "p-adic Hodge Theory For Rigid-Analytic Varities". Finally, we use these results to prove the Poincare Duality Theorem for F_p-etale cohomology groups of a smooth proper rigid space over a p-adic field K. It positively answers the question raised by P. Scholze. We also show versions of Poincare Duality for Z/p^nZ, Z_p, an Q_p-coefficients
Modulation of muscle stem cell function through fasting
Keywords: Stem Cell Biology and Regenerative Medicine.

Fasting is a dietary restriction paradigm that promotes stress resistance, modulates tissue function, and extends lifespan in a variety of organisms. Some of the benefits of fasting are attributed to its ability to influence stem cell function, though the effects of fasting on muscle stem cells (MuSCs) and muscle regeneration are unknown. Here, we show that fasting increases the depth of MuSC quiescence, driving them into a state of deep quiescence (DQ) that is characterized by heightened stress resistance and delayed cell cycle entry. While DQ is not conducive to rapid muscle repair, DQ MuSCs are resistant to apoptotic stimuli, including oxidative stress, irradiation, nutrient deprivation, and proliferative stress. DQ MuSCs also exhibit improved transplantation potency, reliably outcompeting co-transplanted MuSCs from ad lib fed animals in competitive transplantation assays. Mechanistically, induction of MuSC DQ is dependent on the nutrient- and stress- responsive mTORC1 pathway. Indeed, downregulation of mTORC1 is both necessary and sufficient for induction of DQ, as revealed by pharmacological and MuSC specific genetic manipulations. Furthermore, ketosis, a physiological adaptation to fasting, contributes to the effects of fasting on MuSCs. The ketone body β hydroxybutyrate (BHB) downregulates mTORC1 and drives DQ in MuSCs from fed animals in a p53 dependent manner. Indeed, pharmacological activation of p53 phenocopies the effects of BHB on MuSCs, and BHB-induced DQ is abrogated in MuSCs that lack p53. We conclude that the effects of exogenous ketosis derive from the established role of BHB as an endogenous histone deacetylase (HDAC) inhibitor, as pharmacological HDAC inhibition mimics the effects of fasting on MuSCs. These findings are consistent with numerous reports of increased stress resistance in response to fasting, and they establish ketosis as a novel physiological regulator of stem cell quiescence and resilience
Molecular dynamics of supercritical fluids
Keywords: Physics.

Supercritical fluids have received renewed interest in the past few decades because of their industrial applications. Underlying many of these applications is the high tunability of the fluid properties in the near-critical region, which is not captured by the widely held notion of the supercritical state as a single broad continuum. In fact, recent works show that the supercritical region can be divided into liquid-like and gas-like states based on thermodynamic and transport properties with a rapid crossover at the Widom line. However, the picture is less clear when it comes to the microscopic dynamics due to a lack of experimental data and physical understanding of the molecular-scale dynamics in the supercritical state. This dissertation focuses on this problem and contains two main parts. In the first part, a combination of inelastic X-ray scattering measurements and molecular dynamics (MD) simulations is used to study supercritical water. The results show that, contrary to commonly used models, there exist two components in the intermolecular dynamics, and it is the ratio between them that changes rapidly at the Widom line and drives the liquid-like to gas-like transition. In the second part, three additional systems—silicon, tellurium, and the Lennard-Jones fluid—are investigated via MD simulations, and the two-component behavior is found to be universal among these systems. The fraction of the liquid-like component is quantified and found to correlate with the degree of intermolecular bonding. The consequences of the two-component phenomenon for modeling supercritical fluid properties will be discussed
The molecular forces shaping enzyme function and evolution : from hydrogen bonds to enzyme temperature adaptation
Keywords: Biochemistry.

For billions of years, organisms and their enzymes have been evolving and adapting in response to selection pressures and opportunities presented by their environments. The mechanisms that underly enzyme adaptation are fundamental to our understanding of how enzymes work and the process of molecular evolution. Enzyme adaptation occurs through changes in the molecular interactions that specify enzyme structure and function. In particular, hydrogen bonds are central to how enzymes have evolved and are ubiquitous in enzyme structures, where they are often found in extended networks. Given the ubiquity and importance of hydrogen bonds, this dissertation seeks to understand the physical principles that govern hydrogen bond structure and energetics and their contribution to enzyme function and adaptation. I first define the physical principles that determine hydrogen bond lengths and energies. I then investigate the extent that hydrogen bonds in networks are coupled, structurally an energetically, to one another, improving our understanding of hydrogen bonds and the local and collective structural dynamics that exist within proteins and providing quantitative benchmarks for the design of hydrogen bonds and their networks. Second, to address the interplay between hydrogen bonds and other molecular interactions and enzyme evolution, I investigated enzyme temperature adaptation, as temperature profoundly influences enzyme stabilities and activities, providing a direct link between an environmental selection pressure and enzyme function. Performing deep mechanistic and structural studies and broad phylogenetic and sequence analyses, I identify new molecular mechanisms of enzyme temperature adaptation, test and revise nearly all prior proposals for enzyme adaptation to increased temperature, provide evidence that enzymes frequently adapt to temperature at sites of low epistasis, favoring parallel adaptation. This work improves our understanding of the molecular and evolutionary mechanisms underly enzyme evolution and suggests design principles that can be applied to enzyme engineering
Molecular mechanism of pathogenic LRRK2 membrane recruitment
Keywords: Biochemistry.

Activating mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) cause Parkinson's disease and we showed previously that activated LRRK2 phosphorylates a subset of Rab GTPases. Moreover, Golgi-associated Rab29 can recruit LRRK2 to the surface of the Golgi and activate it there for both auto- and Rab substrate phosphorylation. Here we define the Rab29 binding region of the LRRK2 Armadillo domain and show that it can also bind additional LRRK2 substrates, Rab8A and 10. Moreover, we identify a distinct and higher affinity interaction interface between phosphorylated Rab8 and Rab10 within LRRK2's N-terminus that can retain LRRK2 on membranes in cells to catalyze multiple phosphorylation events. These findings reveal a feed-forward pathway that provides spatial control and apparent membrane activation of LRRK2 kinase activity
Molecular Mechanisms of Neuronal Activity Mediated NF1 Optic Glioma Initiation
Keywords:  Department of Biology
Biology
pediatric brain tumor
neurofibromatosis type 1
optic pathway glioma
glioma
NF1
cancer
Neuroligin-3
Text
Thesis

In pediatric brain tumors, a permissive tumor microenvironment is known to be central for promoting the proliferation of cancerous cells. While a great variety of cell types may occupy the tumor microenvironment, neurons have been shown to be essential components, where their activity increases growth of high-grade glioma tumors (Venkatesh et al., 2015). However, the relationship between neural activity and initiation of the tumor is not well understood. Currently, many forms of pediatric brain cancers are unamenable to many classes of therapeutics and current treatment strategies remain unsatisfactory. Neurofibromatosis Type 1 (NF1), a tumor predisposition syndrome, causes small tumors to develop which associate with nerves. Patients may also develop low-grade gliomas of the optic pathway, optic pathway gliomas (OPG), where retinal ganglion cells (RGCs) constitute the sole neuronal component. Using a mouse model of these NF1-OPGs as a platform, we can interrogate the mechanisms of initiation of these gliomas, as they relate to neural activity. By manipulating the light-induced activity of this visual pathway, this project helps characterize the relationship between neuronal activity and glioma initiation. Mice possessing mutations in Nf1 were sacrificed after tumor initiation and their optic chiasms were analyzed for tumor volume, cellular proliferation, among other molecular markers. We demonstrated that neuronal activity plays a central role in the initiation of these gliomas and that this initiation is mediated through the ADAM10/neuroligin-3 molecular pathway. This demonstrates a novel characterization of the mechanisms of glioma initiation, which could yield novel therapeutic strategies for these pediatric low-grade gliomas along with other neuroligin-3 mediated adult high-grade gliomas.
Molecular mechanisms of STING signaling
Keywords: Biochemistry.

The innate immune STING pathway exists at a unique tipping point in cell signaling: not enough STING activation leaves cells vulnerable to cancer or viral infection, while too much STING signaling causes inflammation and autoimmunity. It is therefore paramount that we understand the complete molecular mechanism of how STING is activated and regulated. Here I describe the use of structural and biochemical techniques to elucidate a more complete molecular picture of STING activation. l explain how these findings have led us toward a molecular tool for inhibiting STING activation, which may prove valuable for the future treatment of autoimmune and inflammatory syndromes. Finally, I discuss how STING is activated and regulated in the context of the cell, which gives us clues into how it delivers an effective and robust immune response without causing harmful inflammatory effects
Molecular modeling of mechanically reliable hybrid organosilicate materials
Keywords: Mechanical Engineering.

Hybrid organosilicate glass materials have unique properties and functionalities due to combining characteristics of organic and inorganic species which renders them a very appealing material choice for a wide range of current and emerging nanotechnologies in microelectronics, protective and antireflective coatings, flexible electronics, solar cell applications and many more. However, material innovations are needed to enhance the mechanical reliability of hybrid organosilicate materials which are inherently very brittle and fragile for their reliable use and integration in these device technologies. The focus of this thesis dissertation is to elucidate the fundamental structure-property relationships in hybrid organosilicate glasses through computational techniques; and ultimately establish a computational design space where the elastic and fracture properties of these materials are tuned through the proper exploitation of several of their structural features to enhance their mechanical reliability, which is evaluated in terms of elastic stiffness and fracture energy. Remarkably, it is shown that ultrastiff low density hybrid organosilicate networks with fracture energies comparable to fully dense silica can be generated with the use of hyperconnected hybrid organosilicate glass networks derived from cyclic and molecularly planar precursors. Furthermore, the structural features that lead to increased elastic and fracture properties help improve the mechanical reliability of hybrid organosilicate glasses under extreme temperature regimes, in the presence moisture and under nanoscale confinement, which is a significant step for the reliable service use and integration of hybrid organosilicate materials in next generation device technologies