VictorJuiz/thesis huggingface dataset:
Engineering non-antibody scaffolds and growth factor ligands as protein therapeutics and diagnostics [electronic resource]
Keywords: Chemical Engineering.

Protein therapeutics have emerged as an important class of pharmaceuticals, with monoclonal antibodies making up the largest group of protein drugs. While antibodies have many desirable characteristics, there are some applications in which they may be the best option. In this dissertation, we describe alternative classes of proteins that can complement the use of antibodies in the development of protein therapeutics and diagnostics. Cystine knots, or knottins, have highly desirable properties for use as molecular imaging agents due to their small size and stable structure. Previous approaches to engineering knottins have focused on a small subset of knottin scaffolds; in this work we extend those studies to engineering Agatoxin, a knottin from spider venom, for high affinity binding to tumor associated integrins. Growth factor ligand-receptor interactions modulate many cell signaling pathways and biological processes. The vascular endothelial growth factor (VEGF) and the platelet-derived growth factor (PDGF) mediate two important signaling pathways involved in angiogenesis. In this work, we used the structural similarity of PDGF and VEGF to rationally design a chimeric PDGF/VEGF ligand, creating a multi-specific antagonist of their receptors PDGFR and VEGFR. The PDGF/VEGF chimera was then engineered using combinatorial methods, including yeast surface display, for increased binding affinity to PDGFR and VEGFR. The resulting engineered protein variant strongly inhibited PDGFR and VEGFR signaling with in vitro cell models. Given the important roles of PDGFR and VEGFR in angiogenesis, the PDGF/VEGF chimera has potential application in anti-angiogenesis therapy. Collectively, the engineered proteins in this work demonstrate the promise of using non-antibody scaffolds and growth factor ligands for the development of protein therapeutics and diagnostics.
Engineering synthetic ligand-responsive RNA devices for controlling the cell cycle [electronic resource]
Keywords: Bioengineering.

Synthetic biology aims to program cells by applying engineering principles to the design of genetic circuits to control and monitor cellular behavior. Programmed cells can harness existing dynamically coordinated biologically processes to rescue cellular malfunctions, control existing cellular morphology, and introduce useful novel functionality. Recent advances in the field are leading to genetic circuits of higher-order complexity in mammalian cells, which may ultimately be used to study and reprogram phenotypes that play a key role in human health and disease, such as those linked to the cell cycle. RNA-based control devices can provide specific and modular control of gene expression in response to endogenous or exogenous inputs in living cells. Specifically, we show that for a ribozyme-based device platform, ribozyme switches previously prototyped in yeast are able to regulate gene expression in a predictable (R-squared = 0.63--0.97), ligand-responsive manner in human HEK 293, HeLa, and U2-OS cell lines without any change to device sequence nor further optimization. We also show that these simple, general-purpose components (an RNA ribozyme coupled to an RNA aptamer) are a compact (~200 nt) and effective way to control a complex phenomenon such as arresting up to 80% of a population of mammalian cells in the G2/M phase of the cell cycle. Current methods for altering cell cycle progression can present a number of limitations, including exhibiting specificity towards particular cell types, being broadly disruptive of cellular processes, and being limited in capacity to extend to different networks. A genetically encoded system supporting control over cell cycle progression has the potential to address limitations with existing chemical approaches. Further, these switches are modular and readily adapted to arrest cells in the G0/1 phase of the cell cycle and in response to at least two different small molecule inputs. This work describes the first example of the application of synthetic RNA-based gene-control devices to the regulation of cell cycle progression in human cells. We further show that siRNAs can induce the arrest of > 90% of a population of cells in the G0/1 phase of the cell cycle. This indicates the potential to build miRNA-based devices to control the cell cycle that complement the ribozyme-based approaches. Thus, ligand-responsive RNAs represent a class of synthetic biology tools that are both genetically encoded and capable of regulating intracellular protein levels in response to user-specified molecular signals, and can be adapted for sophisticated control of complex processes in human cells.
Entanglement [electronic resource] : a study in Neolithic resource exploitation in the Middle East
Keywords: Anthropology.

Although Neolithic communities in the Middle East have been the focus of much archaeological research, there has been little agreement concerning how these societies developed. This dissertation examines how Neolithic communities were shaped through acts of resource-dependency -- the constraints and limitations which emerge from relying on particular resources. It examines how certain communities came to depend on the use of specific local resources by studying how such resources were acquired and consumed. An evaluation of the long-term effects of this dependency shows that using particular resources not only promoted certain behaviors, but restricted the development of others. Ultimately, it is argued that such intimate entanglements between people and resources produced a cohesive force capable of influencing how the Neolithic developed. Understanding the processes which create these entanglements, and the resulting effects, allows us to more thoroughly address the relationship between economic practices and community development.
Enzymatic activation of dioxygen at mononuclear and binuclear copper sites [electronic resource]
Keywords: Chemistry.

The activation of dioxygen at copper sites in metalloenzymes is essential for the biosynthesis of a number of natural products including neurotransmitters and melanin. In biological systems, these reactions occur at either a mononuclear or binuclear copper site. Central to the function of these enzymes is the geometric and electronic structure of the copper dioxygen species that is formed. For a number of copper enzymes, dioxygen is activated at a single reduce copper to form a mono-nuclear copper(II) superoxo species that is activated for H-atom abstraction. Due to challenges isolating this intermediate in the enzymatic systems, these studies will focus on the characterization of synthetic copper(II) superoxo and copper(II) hydroperoxo species. Results presented here indicate that the triplet ground state of the end-on copper(II) superoxide is activated for H-atom abstraction as well as proton coupled electron transfer. In contrast, the copper(II) hydroperoxo specie is not activate for this reaction but rather decays via homolytic Cu--O bond cleavage. In contrast to these mononuclear systems, dioxygen is activated by two electrons at a binuclear copper site to form a side-on (μ-η2∶η2) copper(II) peroxide intermediate in enzyme systems including Tyrosinase (Ty). Two other Cu2O2 core isomers have been observed in synthetic systems, the binuclear end-on (μ-1,2) peroxo and the binuclear copper(III) bis-μ-oxo structure. Previous studies on these synthetic systems have shown that the side-on peroxo core can be in equilibrium with the bis-μ-oxo isomer and that both are able to perform the biomimetic hydroxylation of phenolate. The studies reported here build upon this synthetic chemistry by characterizing a new end-on peroxo/bis-μ-oxo equilibrium. The observation of this interconversion suggests that the electrophilic reactivity (phenol oxygenation and sulfoxidation) observed for complexes that form end-on peroxo species results from an accessible bis-μ-oxo isomer that is responsible for the electrophilic reactivity. In addition, the coupled binuclear copper enzyme family is extended to include a new, fourth class of enzymes, the hydroxyanilinases. These enzymes have the same side-on peroxo active site and have similar reactivity to Ty while also possessing the unique ability to convert o-aminophenols to nitrosophenols. These studies provide insight into the function of mononuclear and binuclear copper enzymes and the dioxygen intermediates that make up their catalytic cycle.
Epic and encounter [electronic resource] : form and culture in early modern narrative poetry
Keywords: English.

The prevailing reading of epic poetry is that it exists in a binary relationship with romance: epic, the argument goes, attempts to tell a linear and end-driven story, but is continually diverted by a romance impulse that acts upon it, derailing the narrative, fragmenting its structure, and prolonging its ending. In recent decades, this has taken on political dimension: European epics are seen as stories of victory attempting to marginalize or silence altogether the voices of the non-European vanquished that contradict the victors' vision of history, reflecting a real-life European colonialism. This dissertation offers an alternate model for reading the epic genre, arguing that epic tells not just the story of victory, but also of "encounter, " a register of indeterminacy and exploration that reflects Europe's greater awareness of and involvement in the world around it, rather than simply an incipient and in many cases largely imaginary colonialism. Reading epic in this way allows us to see as essential to the genre, rather than as subversive romance impulses, moments of ambiguity, conflicting perspectives, and both European and non-European visions of history as epic texts represent them. Likewise, it allows us to see different potential ways of organizing epic narrative, rather than attempting to separate out a "main" narrative from its supposedly dilatory and subversive elements. The dissertation begins by looking at the way that the Iliad and the Aeneid represent perspective and opposition, explore issues of ethnography and identity, and treat questions of cultural engagement and historical interpretation formally, by reorganizing and redistributing narrative structure and attention. The tools of ambiguity, multiplicity, and contradiction that these texts provide would have appealed to early modern writers whose rapidly changing and broadening world would have called them to engage in new forms of cultural exploration and analysis. Each of the dissertation's four chapters focuses on a European epic of the sixteenth and seventeenth centuries to see how it, diegetically and formally, deals with issues of "encounter": Luís Vaz de Camões's Os Lusíadas (1572); Torquato Tasso's Gerusalemme liberata (1581); Edmund Spenser's The Faerie Queene (1590 and 1596); and John Milton's Paradise Lost (1667 and 1674).
Equal in theory [electronic resource] : gender egalitarianism and inequality in new marriage
Keywords: Sociology.

This dissertation is comprised of three distinct papers, each of which draws from in-depth interviews conducted with a sample of 31 egalitarian-minded heterosexual couples (62 individuals) and explores gender inequality in marriage. The first paper shows how childless women and men's career aspirations are differentially shaped by anticipations of parenthood, with women being more likely than men to assume the mental labor of worrying about future parenthood, and thus more likely than men to scale back on their career aspirations even before the act of having children. The second paper demonstrates how social power differentials between women and men influence the marital surnaming choices women make following marriage. I find that many women who would otherwise keep their birth-given name choose to change it to appease male partners. The third paper shows that while couples resist gendered expectations in marriage proposals privately, instead choosing more egalitarian proposal options, many still present stories to the public that conform to traditional gender expectations. Collectively the papers demonstrate the continued presence of gender inequality in heterosexual marriage, despite the rise of egalitarian attitudes among contemporary young adults.
Equal opportunity politics in post-civil rights America [electronic resource] : African Americans and Mexican Americans in Los Angeles, 1964-1980
Keywords: History.

"Equal Opportunity Politics In Post-Civil Rights America: African Americans and Mexican Americans in Los Angeles, 1964-1980" examines the relationship between African American and Mexican American communities in Los Angeles during the 1960s and 1970s. This study uses the federal War on Poverty program to argue that the mid-1960s were a critical moment for the development of African American and Mexican American relations in the city and brought these groups into contact at a level unprecedented in U.S. history. By combining the fields of African American history and Mexican American history, this story demonstrates that key historical moments, including the Black Freedom Movement, Chicano Movement, and urban uprisings were linked through the War on Poverty and set the foundation for recent debates about black/brown relations.
Essays in applied microeconomics [electronic resource]
Keywords: Economics.

This dissertation in applied microeconomics examines supply-side behavior, particularly responses to policy changes. The first chapter studies the supply response of urban private schools to public school funding changes in New York City. We find that private schools whose public school competitors received larger funding increases were more likely to close in the subsequent two years. These closures amplified student sorting and undid some of the funding reform's positive achievement effects. The second chapter investigates how stimulus-motivated federal funding directed to universities affected their revenues, expenditures, employment, tuition, student aid, endowment spending, and receipt of state government appropriations. We find that private universities spent additional funding on many categories of expenditures while public universities used federal funds as leverage to gain independence from state governments-gaining the ability to set tuition and other prices closer to market-based rates but losing state appropriations in the bargain. Overall, the stimulus apparently caused universities to increase their investments in research and human capital. The third chapter examines how online platform design interacts with consumer search and seller price-setting to affect market outcomes. We use browsing data from eBay to estimate a model of consumer search and price competition when retailers offer homogeneous goods. We find that retail margins are on the order of 10%, and use the model to analyze the design of search rankings. Our model explains most of the effects of a major re-design of eBay's product search, and allows us to identify conditions where narrowing consumer choice sets can be pro-competitive.
Essays in behavioral and experimental economics with applications to risk and social preferences [electronic resource]
Keywords: Economics.

This dissertation describes my research in several related areas of behavioral and experimental economics. In the first chapter, I use subjective and hypothetical responses to show that opt-in choice framing leads to greater organ donor designation rates than active choice framing. I use the same methodology to accurately predict behavior in settings where standard models of social preferences fail. In the second chapter, I show that machine learning models and economic models predict equally well in domains of risk, but economic models fall behind when ambiguity is introduced. In the final chapter, I present a field experiment that shows that making a commitment choice public increases demand for the device, indicating that participants believe they can reveal something positive about themselves by using the device.
Essays in corporate finance [electronic resource]
Keywords: Business.

This thesis studies the investment and financing decisions of firms in dynamic markets with asymmetric information. In the first chapter I analyze the effects of time-varying market conditions and endogenous entry on the equilibrium dynamics of markets plagued by adverse selection. I show that variation in gains from trade, stemming from market conditions, creates an option value and distorts liquidity when gains from trade are low. An improvement in market conditions triggers a wave of high-quality deals due to the preceding illiquidity and lack of incentives to signal quality. When gains from trade are high, the market is fully liquid; high prices and no delay in trade attract low-grade assets, and the average quality deteriorates. My analysis also reveals that illiquidity can act as a remedy as well as a cause of inefficiency: partial illiquidity allows for screening of assets and restores efficient entry incentives. I demonstrate model implications using several applications: early stage financing, initial public offerings, and private equity buyouts. Chapter 2, which is a joint work with Ilya Strebulaev and Haoxiang Zhu, reexamines the classic yet static information asymmetry model of Myers and Majluf (1984) in a fully dynamic market. A firm has access to an investment project and can finance it by debt or equity. The market learns the quality of the firm over time by observing cash flows generated by the firm's assets in place. In the dynamic equilibrium, the firm optimally delays investment, but investment eventually takes place. In a ``two-threshold'' equilibrium, a high-quality firm invests only if the market's belief goes above an optimal upper threshold, while a low-quality firm invests if the market's belief goes above the upper threshold or below a lower threshold. However, a different ``four-threshold'' equilibrium can emerge if cash flows are sufficiently volatile. Relatively risky growth options are optimally financed with equity, whereas relatively safe projects are financed with debt, in line with stylized facts. Finally, Chapter 3, which is based on an ongoing work with Ilya Strebulaev and Haoxiang Zhu, extends the analysis of Chapter 2 by allowing cash accumulation within the firm. We consider a firm whose managers possess superior information about the firm's value relative to the rest of the market and analyze the optimal timing of equity issuance. We show that equilibrium features socially inefficient, but privately optimal, delay of investment and equity financing of positive NPV projects. Waiting allows high quality firms to accumulate internal cash and increase investors' beliefs, therefore, reducing the cost of adverse selection. In the dynamic equilibrium low quality firms delay investment as well in hope of being mistaken for the high quality ones. However, when market beliefs are sufficiently low and/or internally accumulated level of cash is sufficiently high the low quality firm prefers to reveal itself.
Essays in economic theory [electronic resource]
Keywords: Economics.

This dissertation consists of three self-contained essays. The first essay reconciles two seemingly competing explanations of context-dependent choice, one invoking psychological mechanisms, and the other Bayesian learning. We prove that standard context effects are features of the optimal solution to a general dynamic stochastic resource-acquisition problem. The model has two key ingredients: intertemporal substitution and learning about the environment. Interpreted as a description of animal foraging behavior, it explains why context effects might be adaptive in nature. Interpreted as a description of consumer choice problems, it suggests that context effects might result from rational inference. We ran a simple experiment to show that the latter interpretation sometimes holds. The second essay investigates the performance of rotating savings and credit associations (ROSCAs) in investment acceleration and welfare promotion for small-business entrepreneurs. In a model of privately observed investment returns, random ROSCAs improve upon autarky, while bidding ROSCAs can achieve efficiency. By relaxing the assumption of homogeneous agents calculating equilibria, it is shown that an expected-utility maximizer prefers some bidding ROSCAs to random ROSCAs regardless of her belief about others' strategies. Such analysis respects the Wilson doctrine, putting forth a novel framework for comparing mechanisms. The results highlight why more ROSCAs may embrace auction designs as economic development differentiates economic opportunities. The third essay explores the frontier between possibility and impossibility results in social choice theory by analyzing different combinations of "pro-socialness" and "consistency" conditions. This exercise delivers stronger versions of four classical impossibility theorems, and offers a thorough understanding of connections among them. We also characterize social choice functions that are "independent of irrelevant alternatives, " which makes evident that the fundamental difficulty of social choice lies in "pairwise" consistency requirements. We also introduce a concise pedagogical approach to classical impossibility theorems.
Essays in finance [electronic resource]
Keywords: Business.

This thesis studies how bank level capital structure frictions impact both banks and borrowers. In the first chapter, I use bank level capital structure frictions to explain banks' seniority in corporate debt structure. In the second chapter, I look at how bank level capital structure frictions can be passed on to borrowers and impact both bank and borrower behavior. In the third chapter, I look at how capital regulation, bailout expectation, and deposit insurance interact with bank level capital structure frictions.