VictorJuiz/thesis huggingface dataset:
Engineering protein microenvironments [electronic resource] : integrin-binding ligands and neurotrophic cues for neural regeneration

Regenerative therapies for peripheral nerve injury have achieved significant success in neural regeneration by combining growth-permissive materials with anisotropic features to guide regenerating neurites across the injury gap. Despite their success in the peripheral nervous system, these strategies tend to neglect the neuron-level precision required for fully functional regeneration. Fortunately, studies of the developing peripheral nervous system have revealed a variety of innate molecular-level tools to promote outgrowth, guide axons toward targets of re-innervation, and stimulate re-myelination by glial cells. We have developed a class of customizable, protein-engineered microenvironments to study three aspects of the neural microenvironment involved in regeneration: cell-adhesive ligands in the Extracellular Matrix (ECM), soluble neurotrophic factors, and cell-cell contact. In particular, we demonstrated the ability of RGD ligand density in the ECM to enhance neurite outgrowth from Dorsal Root Ganglia. Furthermore, the strategic inclusion of Nerve Growth Factor in these microenvironments enhanced L1CAM-mediated interaction between Schwann cells and neurons, resulting in cooperative outgrowth between the two cell types. Microenvironments promoting both cell-cell and cell-matrix interactions resulted in better neural outgrowth than those that prioritized either one or the other. Finally, we incorporated a chemoattractive gradient of Nerve Growth Factor to induce directed outgrowth within 3-dimensional protein matrices. The density of cell-adhesive RGD ligands in the microenvironment impacted the ability of neurites to initiate outgrowth, progress through the matrix, and turn toward the chemoattractive source. These findings underscore the ability of orthogonal strategies to synergistically enhance neural regeneration, and the utility of protein-engineered microenvironments to apply those strategies.

Keywords: Materials Science and Engineering.
Advisor: Heilshorn Sarah primary advisor. Thesis advisor
Dunn Alexander Robert advisor. Thesis advisor
Lee Jin Hyung advisor. Thesis advisor
Engineering Saccharomyces cerevisiae for the production of plant-derived pharmaceuticals [electronic resource]

Natural products and their derivatives comprise over 60% of all drugs currently on the market, and natural product pharmaceuticals have been the subject of renewed interest to revitalize drug discovery pipelines. Plant secondary metabolites are a significant source of bioactive compounds. The discovery and screening of new natural products from plants is difficult, however, because many compounds exist only in trace amounts and the methods for isolating and purifying these compounds from the native plant hosts are generally inefficient. Microbial biosynthesis of plant metabolites is an exciting alternative production platform that provides several distinct advantages over the native plant hosts, including well-developed genetic tools for pathway expression and manipulation, fast growth rates, and established large-scale culture methods. Here we describe engineering Saccharomyces cerevisiae as a microbial production platform for the benzylisoquinoline alkaloids (BIAs), a large class of plant secondary metabolites that exhibit a wide range of pharmacological activities, including anti-HIV, anticancer, and antimicrobial activities. We engineered strains capable of producing protoberberine, protopine, benzophenanthridine and bisbenzylisoquinoline alkaloids. The number and types of chemical transformation steps achieved in this work represent one of the most complex examples in the field of metabolic engineering. In addition, we have developed strategies for the microbial expression of plant cytochrome P450s including expression methods and culture condition optimizations. Through engineering BIA biosynthetic pathways in yeast we have sought to create a reliable and scalable source of valuable drugs and drug candidates and develop generalizable optimization strategies that will broadly advance the development of microbial production platforms for plant natural products.

Keywords: Bioengineering.
Advisor: Smolke Christina D. primary advisor. Thesis advisor
Endy Andrew D. advisor. Thesis advisor
Swartz James R. advisor. Thesis advisor
An environmental and social history of the Chilean salmon farming industry, 1976-2009 [electronic resource]

Recognizing that it is difficult to ameliorate environmental problems without understanding their connections to associated social changes, I researched the complex feedback loops that connect environmental and social change in the salmon-farming industry of southern Chile. The research covers the period from its experimental beginnings during the Pinochet dictatorship through the environmental and economic crisis resulting from the salmon flu. I analyze the environmental and social transformations brought about by comparing the region before and after the advent of salmon-farming using methodologies from both the humanities and social sciences. Chapter One introduces the study; Chapter Two gives a snapshot of the island of Chiloé before the industry; Chapter Three traces the changes in working life among salmon farm workers through the industry; Chapter Four characterizes the environmental effects of the industry and analyzes the infectious salmon anemia; Chapter Five analyzes the ways in which the industry shaped society in central Chiloé by 2009; and Chapter Six concludes. Data was gathered through both quantitative and qualitative surveys, open-ended interviews, archival research, and collaborations with ongoing research in Chile.

Advisor: Naylor Rosamond primary advisor. Thesis advisor
White Richard
Frank Zephyr L.
Epigenetics in mouse placental development [electronic resource]

Epigenetic pathways are differentially regulated in embryo versus placenta. This differential regulation allows co-option of genes and gene pathways, facilitating both the evolution and function of the placenta. Alterations in these pathways have severe impacts on placental growth and health. Hence, understanding epigenetics in the placenta is of great interest. In chapter 2, I describe a genome-wide screen for placental imprinting. While mammals generally express both alleles of each gene, a small number of loci show parent-of-origin bias. This bias is called "imprinting"; it is particularly common in the placenta. I used a new methodology with improved reproducibility to identify candidate imprinted genes. I discovered bias at 78 novel genes, and a preference for the maternal allele. I found a handful of genes that escape X-inactivation. Finally, I observed striking litter-specific variation. These results underline several themes of placental imprinting: it is widespread, variable, and with a likely maternal bias. In chapter 3, I used a tissue-specific mutant mouse to determine the function of DNA methyltransferases in the placenta. These proteins are responsible for adding a methyl group to cytosines, creating a repressive mark associated with the silencing of repetitive regions as well as inactive alleles of imprinted genes. Mutants lacking DNA methyltransferase function show placental phenotypes, although the placenta is in general hypomethylated. While mutant males were viable, females died early in development. This suggests two conclusions: that DNA methylation in the placenta is not required on autosomes, and that DNA methylation plays an essential role in continued silencing of the X chromosome. Thus, in the absence of this silencing female placentas are nonfunctional and female embryos die. In chapter 4 I describe general conclusions of my work: the extraordinary epigenetic flexibility of the placenta, the importance of silencing the X chromosome, and a subtle preference for the maternal allele. I also suggest several promising avenues for future study, including examining placental histone modifications and studying cell- or cell-type-specific variation.

Keywords: Genetics.
Advisor: Baker Julie (Professor of genetics) primary advisor. Thesis advisor
Lipsick Joseph Steven
Sherlock Gavin advisor. Thesis advisor
Sidow Arend advisor. Thesis advisor
The episode [electronic resource] : serial storytelling in television and the nineteenth-century novel

The idea that contemporary television programs share some affinity with the nineteenth-century serial novel is popular and yet remarkably under-explored. This dissertation is an effort to take the issue of their association seriously, with a particular emphasis on taking apart the now-familiar assumption that television is like the novel. This is achieved by exploring serialization as a fundamentally narrative feature, which allows for an appreciation of the tensions inherent in all serial fiction and establishes a frame for productive comparisons between these two disparate bodies of text. The dissertation begins with a focus on the television episode as a formal device in an effort to understand its persistence in televisual narratives and its role as a narrative constraint. Where the novel's serial parts have no regular relationship with the narratives they contain and interrupt, the television episode is a foundational feature of television storytelling with no novelistic corollary. In the second and third chapters, the dissertation shifts to a consideration of the way serial structures in both television and the novel intersect with questions of genre and perpetuation, namely, by exploring concepts of open and closed seriality. The second chapter on open seriality examines works that enact seriality's promise of continuous narrative, and includes readings of Northern Exposure, Deadwood, Elizabeth Gaskell's Wives and Daughters and works by Anthony Trollope. The third chapter, on closed seriality, investigates the serialized mystery through readings of The Moonstone, Conan Doyle's Sherlock Holmes stories, and the television series Law & Order, Bones, and Lost. As the thesis explores genre and the concept of closed versus open serial storytelling in both of these chapters, it continues to follow the thread of episodic logic in various serial contexts. Finally, the dissertation's fourth chapter deals with what episodic structure erases, and what is lost when narrative is forced into segmented serial form. This argument connects the episode's opportunity for narrative amnesia with memory's diminished potency as a tool for character development and narrative change, and considers this idea in the context of Austen's Emma, as well as television series like Law & Order: SVU and Breaking Bad.

Keywords: English.
Advisor: Moretti Franco
Bukatman Scott
O'Sullivan Sean
Woloch Alex
Epstein-Barr Virus and latent membrane protein 1 modulate host B cell microRNA to promote cell survival [electronic resource]

Over 90% of humans are carriers for the B cell lymphotrophic [gamma]-herpes virus Epstein-Barr Virus (EBV). Though normally benign, EBV is the causative agent of infectious mononucleosis (IM) and is associated with multiple B cell malignancies, including post-transplant lymphoproliferative disease (PTLD). In immunodeficient and immune compromised individuals, proliferating EBV-infected B cells can progress to lymphoproliferative disease, transformation and malignancy due to the absence of a robust immune system to constrain the expansion of EBV-infected cells. Here we examine the expression of host cell microRNA in EBV-transformed B cells and following activation of the EBV viral oncogene latent membrane protein 1 (LMP1). We find that microRNA-194 is expressed at lower levels in EBV+ B lymphoma cell lines derived from patients with PTLD and that this microRNA is specifically suppressed by activation of tumor-derived LMP1 molecules. IL-10, required for autonomous growth of EBV-transformed B cells, is a direct target of microRNA-194. The overexpression of microRNA-194 in tumor-derived EBV-transformed B cells significantly decreased IL-10 production and significantly increased apoptosis. This phenotype was partially yet significantly rescued by the addition of exogenous IL-10. Thus, IL-10 expression, which acts as an autocrine growth factor for EBV+ B cell lymphomas, is promoted by EBV-induced suppression of microRNA-194.

Advisor: Martinez Olivia
Krams Sheri Michele advisor. Thesis advisor
Lewis David advisor. Thesis advisor
Mellins Elizabeth advisor. Thesis advisor
Essay in empirical industrial organization and public finance [electronic resource]

This dissertation comprises three chapters. The first two chapters investigate competition in the U.S. credit card market. The first looks at broad changes in the market's competitive environment over the past two decades. More specifically, it establishes how the classical facts characterizing a failure of competition in credit card lending during the 1980s are largely reversed in the decades following. Extending previous theories of limited competition in credit card lending, it illustrates how many of these changes can be explained by considering the role of costly screening in mitigating adverse selection. The second chapter studies more directly how issuers compete in today's market. To this end, it presents an equilibrium model of credit card issuers' mail out decisions and estimates it using data on direct mail credit card offers. In contrast to previous work, the model accounts for the complexity of card products, for heterogeneity in individuals' tastes for cards, and for differences in how profitable consumers are to issuers. It then explores the equilibrium supply effects of changes in the market environment. Specifically, it shows that an increase in the cost of funds (Treasury rate) unambiguously reduces consumers' propensity to receive offers and the range of rates on offers received. Conversely, reducing sending costs unambiguously increases the number and variety of offers. It also leads to an increase in the average rate on offered products. Adding a competitor on net increases the propensity to receive credit. However, it also deters existing competitors from making offers to some individuals whom they might have otherwise found profitable. The third chapter looks at the potential effects of differing methods for taxing inter-generational wealth transfers. Using wealth data on U.S. households, it forecasts changes in household wealth in the coming decade and calculates the importance of untaxed wealth in bequeathed estates. It then compares the aggregate and distributional effects of the current estate tax to those in which only the unrealized capital gains are subject to tax. It estimates that, in the coming decade, policies taxing capital gains can potentially raise more revenue than the current estate tax, but not without a substantial increase in the fraction of households facing a tax. Moreover, modest increases in capital gains allowance is likely to both sharply reduce total revenue and focus the burden of the tax on high wealth households.

Keywords: Economics.
Advisor: Bresnahan Timothy F. primary advisor. Thesis advisor
Einav Liran primary advisor. Thesis advisor
Bloom Nick
Levin Jonathan D. (Jonathan David)
Essays in corporate finance [electronic resource] : financial contracts and their implications

Chapter 1 studies the joint design of optimal incentive pay and information disclosure in a dynamic moral hazard problem. The principal is more informed about the outcomes of agent's actions and actively manages information available to the agent. Sharing information with the agent increases productivity (for example, allowing a better allocation of resources or effort), but increases the cost of providing incentives. The optimal contract features incomplete information sharing with positive information shared more than negative information and past negative information leading to less information sharing in the future. Chapter 2 explores the role of short-term debt in the financial crisis. We analyze a novel data set of repurchase agreements (repo), that is, loans between non-bank cash lenders and dealer banks collateralized with securities. Consistent with a run, repo volume backed by private asset-backed securities falls to near zero in the crisis. However, the reduction is only

Keywords: Business.
Advisor: Skrzypacz Andrzej
Zwiebel Jeffrey primary advisor. Thesis advisor
DeMarzo Peter M. advisor. Thesis advisor
Koudijs Peter advisor. Thesis advisor
Essays in empirical corporate finance [electronic resource]

This thesis studies how government regulation affects firms' financial and governance decisions. In the first chapter I examine how deregulation in the railroad industry affects CEO-firm matches and firms' performance. I exploit the 1980 Staggers Rail Act, which introduced competition to the highly regulated freight railroad industry. The results show that after the deregulation there was an increase in CEO turnover and in the percentage of CEOs with business education and with broader work experience. I also find that CEO turnover was less related to firm performance in the deregulated period. The next two chapters study the unintended consequences of two different types of financial regulation, which intended to protect consumers. In Chapter 2, I use the introduction of state deposit guarantee systems in the early 20th century as a quasi-natural experiment to study its effects on the banking system. I find that insured banks experienced higher growth rates than uninsured banks. However, I find no effects of deposit insurance on failure rates, or risk taking proxied by leverage and illiquid assets holdings. Finally, Chapter 3 analyzes the effects of double liability for banks' shareholders in the United States during the Great Depression. In case of a bank failure, shareholders subject to double liability could not only lose their equity, but an additional amount equal to the par value of their shares. My coauthors and I find that single-liability banks were riskier than double-liability banks in terms of their asset allocation. We also conclude that an unintended effect was the higher exit rates via merger or voluntary liquidation of double-liability banks. This is consistent with the hypothesis that in the presence of double liability, shareholders decide to liquidate their investment earlier to avoid risking their personal assets in case of failure.

Keywords: Business.
Advisor: Jenter Dirk
Koudijs Peter
Pérez González Francisco
Essays in empirical macroeconomics [electronic resource]

This dissertation contains four distinct essays in two broad areas of empirical macroeconomics. The first area analyzes two drivers of household behavior during the great recession as relates to consumption choices and job search when unemployed. The second area covers the measurement and impact of economic and policy uncertainty on economic outcomes.

Keywords: Economics.
Advisor: Bloom Nick
Abramitzky Ran advisor. Thesis advisor
Hoxby Caroline Minter advisor. Thesis advisor
Pistaferri Luigi advisor. Thesis advisor
Essays in experimental economics and matching theory

This dissertation discusses that, as market designers and experimental economists, we must be willing to accept that individuals may not play complicated equilibrium strategies. This departure from classical game theory predictions leaves us with a dilemma as market designers. One approach could be to make optimal play in matching algorithms as easy as possible by constructing strategyproof mechanisms, where individuals have dominant strategies of truthfully stating their preferences. We develop novel strategyproof algorithms in the first chapter of this dissertation that can be used in markets seeking to meet distributional goals. Many prominent markets in the field that would benefit from our mechanisms are currently inefficiently using strategyproof algorithms (presumably because they value such a strong incentive property); our contribution is to preserve strategyproofness but improve efficiency. In the second chapter of the dissertation, we show that efficiency can be improved even further if we are willing to sacrifice strategyproofness. Venturing into manipulable (non-strategyproof) algorithms can be risky, however. In manipulable mechanisms, individuals may state their preferences in ways that ultimately make themselves (and others) worse off in comparison to their outcomes in strategyproof algorithms. Whether or not we should even consider manipulable algorithms is a big question in market design. The second chapter in this dissertation finds that subjects actually fare better on average when we move away from strategyproofness. The welfare-improving algorithms we study discuss in the second chapter lead many individuals to manipulate their preferences in the same ways, suggesting that the mechanisms' specific designs stimulate non-random non-equilibrium behavior. As market designers, we can use these systematic deviations from equilibrium to develop algorithms that are best suited for the types of agents in the population. In particular, as market designers we should start thinking about creating algorithms for agents who play according to well-documented behavioral game theory models, such as the level-k model that explains many subjects' actions in the third chapter of this dissertation. Altogether, there is much additional theoretical and experimental work that needs to be done to fully understand (1) the way subjects behave in strategic settings and (2) which mechanisms will lead to the highest realized levels of agent welfare in practice. Fortunately, making progress on either of these questions will simultaneously advance our position on solving the other. It seems there is much potential for future work to make valuable contributions to what may ultimately become known as ``behavioral market design.''.

Keywords: Economics.
Advisor: Niederle Muriel 
Kojima Fuhito 
Roth Alvin E.