VictorJuiz/thesis huggingface dataset:
Engineering cystine-knot peptides for molecular imaging of cancer [electronic resource]

Proteins and peptides are an incredibly versatile class of biological molecules, with a vast array of naturally occurring functions. In cancer, the natural roles of proteins become incorrectly regulated, and the presence of cancer-related proteins on tumor cells can be detected and targeted for diagnosis and treatment. This thesis decribes novel engineered peptides for molecular recognition of cell surface receptors expressed in cancers, and application of these engineered peptides as diagnostic agents to identify solid tumors in mouse models. For this work. three different cystine-knot peptides were used for development and engineering: Agatoxin (AgTx), Agouti-related protein (AgRP), and Ecballium elaterium trypsin inhibitor-II (EETI). In addition, two protein receptors were employed as model tumor targets relevant for molecular imaging of cancer: carbonic anhydrase IX (CA IX) and tumor associated integrin receptors. New methods were developed towards engineering AgTx and AgRP to bind CA IX, and work to produce these peptides for further study and their limitations are described. In a parallel line of research, to further understand the promise of using knottin peptides in cancer imaging, the influence of amino acid loops on tissue biodistribution was examined using engineered AgTx, AgRP, and EETI peptides that bind tumor target integrins in mouse xenograft models. Finally, an engineered EETI knottin peptide that binds tumor-associated integrins was shown to specifically target and illuminate brain tumors in mouse models of medulloblastoma. Importantly, the protein engineering methods and molecular imaging applications described here have promise for influencing the clinical outcome of cancer patients through image-guided surgical resection, disease staging and management, and monitoring the effectiveness of therapeutic treatments.

Keywords: Bioengineering.
Advisor: Cochran Jennifer R. primary advisor. Thesis advisor
Contag Christopher H. advisor. Thesis advisor
Graves Edward (Edward Elliot)
Lin Michael Z. advisor. Thesis advisor
Engineering of biosynthetic pathways to the type II polyketides frenolicin B and A-74528 [electronic resource]

Polyketides are a large class of structurally diverse natural products which posses a wide range of biological activities. Unfortunately, despite the potential utility of these compounds in the clinic, large scale production of many of these natural products from their native hosts remains a challenge. Additionally, due to their complexity, engineering better pharmacokinetic properties by traditional synthetic means is often challenging. A better understanding of the biosynthetic machinery which produces polyketides allows for optimization of their production and paves the way for bioactivity-based pathway reengineering. This work begins with an introduction detailing attempts to unravel the biosynthetic underpinnings of two key natural product families, the tetracyclines and the thiostreptons, with an eye toward ultimately reengineering the pathways. Then, our efforts to reconstruct and reengineer the biosynthesis and biological activity of the type II polyketides frenolicin and A-74528 are detailed. Successful reconstruction of a chimeric biosynthetic pathway to frenolicin B and subsequent reengineering of that pathway to produce novel frenolicin analogs is described. Then, the biological activity of these compounds both in vitro against the parasites Toxoplasma gondii and Plasmodium falciparum is discussed. Additional studies against Plasmodium berghi in mice show that frenolicin B is an effective antiparastic agent in vivo. Following this, engineering of a biosynthetic pathway to the novel antiviral agent A-74528 from S. sp. SANK 61196 is presented and the impact of various tailoring enzymes on metabolite production are explored.

Keywords: Chemistry
Advisor: Khosla Chaitan
Chen James
Kool Eric T. advisor. Thesis advisor
Enhancing career development agency in emerging adulthood [electronic resource] : an intervention using design thinking

Career development is an important part of emerging adulthood, the period when 18- to 30-year-olds in modern societies explore possible roles, occupations and lifestyles (Arnett, 2000). To date, most theories and interventions have focused on career decision-making (Betz, 2007); however, for emerging adults embarking on the school-to-work transition, making a single, final career decision can be a source of anxiety and depression (Rottinghaus, Jenkins & Jantzer, 2009). This study investigated the effects of a course on career development for undergraduate juniors and seniors, which used an innovative "design thinking" curriculum to help students plan creatively for life after college. The intervention was hypothesized to increase students' career development agency, a new construct based on Bandura's (1989) theory of how individuals think and act intentionally. The intervention was also hypothesized to decrease participants' psychological distress related to career concerns. The study used a quasi-experimental approach with an intervention (treatment) condition and two comparison conditions, one consisting of college students who applied for the treatment but were waitlisted, and another drawn from the general student body. An online questionnaire was administered at the beginning and after the end of the ten-week academic quarter. A multivariate analysis of variance with repeated measures showed that class participants (n = 42) increased in career development self-efficacy, and moderately decreased in career-related negative affect. The comparison conditions (n = 62) did not show these outcomes. Students in the comparison conditions also reported a rise in dysfunctional career-related beliefs, which their peers in the class did not experience. Importantly, course participants' levels of career uncertainty did not change, on average, nor did they report changes in stressful life events or situations. The effect of the intervention was not to promote career decision-making, but rather to build self-confidence through productive action, and counteract common myths about career issues in emerging adulthood. Finally, regression analyses indicated that factors of career development agency (self-efficacy and contextual stressors) were more directly predictive of career-related negative affect than career uncertainty.

Keywords: Education.
Advisor: Schwartz Daniel L. primary advisor. Thesis advisor
Krumboltz John D. advisor. Thesis advisor
Roth Bernard advisor. Thesis advisor
Epigenetic regulation of olfactory receptor gene expression by the Drosophila Myb-MuvB/dREAM complex [electronic resource]

In both mammals and insects an olfactory neuron will usually select a single olfactory receptor and repress remaining members of large receptor families. Here we show that a conserved multiprotein complex Myb-MuvB(MMB)/dREAM plays an important role in mediating neuron-specific expression of the CO2 receptor genes (Gr63a/Gr21a) in Drosophila. Activity of Myb in the complex is required for expression of Gr63a/Gr21a and it acts in opposition to the histone methyltransferase Su(var)3-9. Consistent with this, we observe repressive di-methylated H3K9 modifications at the receptor gene loci suggesting a mechanism for silencing receptor gene expression. Conversely, other complex members, Mip120 and E2F2, are required for repression of Gr63a in inappropriate neurons. Misexpression in mutants is accompanied by an increase in the H3K4me3 mark of active chromatin at the receptor gene locus. Nuclei of CO2 receptor-expressing neurons contain reduced levels of the repressive subunit Mip120 compared to surrounding neurons and increased levels of Myb, suggesting that activity of the complex can be regulated in a cell-specific manner. Our evidence suggests a model in which olfactory receptors are regulated epigenetically and the MMB/dREAM complex plays a critical role in specifying, maintaining and modulating the receptor-to-neuron map.

Keywords: Genetics
Advisor: Lipsick Joseph Steven
Fuller Margaret
Luo Liqun
Sidow Arend advisor. Thesis advisor
Equality and Redress in Education: Educator Allocation in Post-Apartheid South Africa

After the democratic South African government came into power in 1994, the education system
faced the challenge to redress socioeconomic disadvantages inherited from apartheid. My
research examines one component of the new education system: the distribution of educators. I
use government data not publicly available to document educator distribution trends among
schools of different levels of poverty in two provinces, Gauteng and the Western Cape. The
quantity and level of qualifications of educators are measured, and the trends are linked to
student outcomes. The results are consistent across both provinces: Descriptive statistics and
regression analysis finds that, on average, schools with relatively less poverty experience a lower
pupil-educator ratio and have educators of higher qualifications. A contributor to this inequality
is the practice of local school governing bodies in relatively wealthier schools hiring additional
educators beyond what the state provides. State provision is itself a contributor to inequality in
some cases. The impact of the quantity of educators and of the level of qualifications on student
outcomes is unclear. Ultimately, my research suggests that the current distribution of educators
in South Africa falls short of the principles of equality and redress at the foundation of the post-
apartheid education system.

Keywords: Education
South Africa
Gauteng
Educators
Teachers
Equality
Redress
Western Cape
Teacher Characteristics
Class Size
Text
Thesis
Advisor: Hanushek Eric
Equivariant algebraic k-theory of products of motivic circles [electronic resource]

Fix an algebraically closed field k of characteristic zero. We describe a method which produces deloopings of K'(k) in the Gm(k)-direction via a homotopy limit over pth power maps, and examine the outcome of analogous constructions in an equivariant setting. These constructions provide a technique for studying actions of finite groups on motivic spheres which cannot be described by a usual smash product of Gm's with group action.

Keywords: Mathematics
Advisor: Carlsson Gunnar
Galatius Søren
Vakil Ravi advisor. Thesis advisor
Essays in applied economics [electronic resource] : evidence from natural experiments

I present 3 chapters that utilize natural and laboratory experiments to explain economic phenomena. In the first chapter, I use a natural experiment on the Yahoo! front page to identify the effectiveness of targeted advertising. The experiment randomizes users into seeing a test or a control ad and I can therefore estimate the search and clicks for the targeted and untargeted populations on both the test and control ad and can cleanly identify the effectiveness of targeting. In the second chapter, I look at a quasi natural experiment from the history of the territory of Utah. An economic crisis spawned some communities to form what was known as a United Order, or a communal type living situation. I analyze how this societal experiment influenced equality, production, and migration. Finally, in the third chapter, I investigate sequential versus simultaneous presentation of choices through a series of laboratory and field experiments.

Keywords: Economics
Advisor: Bernheim B. Douglas primary advisor. Thesis advisor
Abramitzky Ran advisor. Thesis advisor
Bresnahan Timothy F. advisor. Thesis advisor
Essays in behavioral economics [electronic resource]

The first chapter of the dissertation, entitled "Revisiting Regret Theory", suggests a more generalized version of the regret theories proposed by economists so far. Outcome regret is experienced when one compares a realized outcome to the outcome one could have received, if one had chosen a different action. In this paper I argue that the existing theories are flawed in that they make very restrictive assumptions about how people think with respect to foregone opportunities in the face of uncertainty. In light of some evidence as to how people actually think about past choice and realized outcomes, I propose to extend and generalize the existent theories of regret. I then apply my theory to existing experimental data, hitherto unexplained by the current theories. I find that my theory is capable of accounting for these data. The second chapter, entitled "Do Responses to Hypothetical and Subjective Questions Reveal Preferences?" and co-authored with Doug Bernheim, Daniel Bjorkegren, Jeffrey Naecker and Antonio Rangel, investigates the feasibility of inferring the choices people would make (if given the opportunity) based on their responses to hypothetical and subjective questions when they are not engaged in actual decision making. The ability to make such inferences is of potential value when choice data are unavailable or limited in ways that potentially impair standard methods of estimating choice mappings. We formulate prediction models relating choice distributions to these "non-choice" reactions, estimate them with data for a given set of items, and use them to predict out-of-sample choice distributions for new items at various prices. Our analysis shows that this method performs well relative to the conventional approaches that require more extensive choice data. The third chapter, entitled "Social and Economic Networks with Unknown Utilities", deals with social and economic networks in an historical perspective. The theoretical part of the paper is concerned with situations in which a utility from forming a certain link might be unknown to the agent prior to forming the link. This is in contrast with the standard networks literature that assumes that agents are fully aware of the utilities they will have from forming any possible link to any other agent. When this is not the case, agents might benefit from a "social planner", who will either force them to form certain links they wouldn't otherwise form, or change the benefits structure of the network in a way that will result in a voluntary formation of a more efficient network. Later, the paper looks at some situations in history where networks might have been formed with agents either underestimating or overestimating the benefits resulting from those networks.

Keywords: Economics
Advisor: Bernheim B. Douglas primary advisor. Thesis advisor
Jackson Matthew O. advisor. Thesis advisor
Sprenger Charles advisor. Thesis advisor
Essays in credit portfolio management [electronic resource]

Banks often seek to reduce the default risk exposure associated with their corporate loan portfolios by entering into credit derivative positions. Asset managers seek additional yield through single and multi-name credit derivatives, and must also manage their credit exposures according to disciplined and systematic risk-return analysis. This thesis explores the portfolio selection and risk measurement problem for credit sensitive financial instruments. In comparison to its equity counterpart, the fixed-income portfolio problem presents unique challenges: the risk of issuer default induces skewed return distributions, the correlation of defaults influences the tail of the portfolio return distribution, and credit derivative positions have complex risk-return implications. The first part of this dissertation addresses the static selection problem for a fixed-income portfolio of credit sensitive securities. We optimize the total mark-to-market value of the portfolio at the investment horizon. This value incorporates the intermediate premium and default cash flows of long and short cash and derivative positions, and the survival-contingent market value of these positions at the horizon. The selection problem is cast as a polynomial goal program that involves a two-stage constrained optimization of preference weighted moments of the portfolio mark-to-market. The decision variable is the vector of contract notionals. A capital constraint guarantees the solvency of the investor. The multi-moment formulation addresses the non-Gaussian distribution of the portfolio mark-to-market. It is also computationally tractable, because we obtain analytical expressions for the moments of the portfolio mark-to-market, which are given in terms of nested expectations under risk-neutral and actual probability measures. The expressions are valid for a broad class of intensity-based, doubly-stochastic models of correlated default timing that are widely used in portfolio credit risk and derivatives pricing. Numerical results illustrate the implications for portfolio selection of idiosyncratic default risk and default correlation. They also indicate the robustness of the optimal policies with respect to estimation errors. Although higher moments provide important characterizations of the portfolio risk profile, investment managers often need to compute specific tail percentiles of the profit and loss distribution. In the second part of the thesis we develop an analytical approximation for this distribution. The approximation is based on a small-time expansion of a transform of the portfolio value. The analytical characterization permits tractable computations of Value-at-Risk, and Value-at-risk constrained optimal portfolio selections.

Keywords: Management Science and Engineering
Advisor: Giesecke Kay primary advisor. Thesis advisor
Primbs James advisor. Thesis advisor
Weyant John P. (John Peter) advisor. Thesis advisor
Essays in energy and environmental economics [electronic resource]

This dissertation consists of three essays in energy and environmental economics that all have a bearing on various concepts from public economics. The first essay uses fiscal data on 2,468 oil extraction agreements in 38 countries to study tax contracts between resource-rich countries and independent oil companies. We analyze why expropriations occur and what determines the degree of oil price exposure of host countries. We show theoretically and verify empirically that oil price insurance provided by tax contracts is increasing in a country's cost of expropriation, and decreasing in its production expertise. The second essay reveals significant unintended consequences from recent 14-state efforts to reduce greenhouse gas emissions through emissions limits per mile from new cars. While such efforts significantly reduce emissions from new cars sold in the adopting states, they cause substantial emissions increases from new cars sold in other (non-adopting) states and from used cars. Such offsets (or "leakage") reflect interactions between the state-level and federal fuel-economy standards: the state-level efforts loosen the national standard, so that automakers can profitably increase sales of high-emissions vehicles in non-adopting states. Our simulation model estimates that leakage associated with recent legislation is 65-74%. In the third essay, I analyze speed limits. When choosing his speed, a driver faces a trade-off between private benefits (time savings) and private costs (fuel cost and own damage and injury). Driving faster also has external costs (pollution, adverse health impacts and injury to other drivers). I use large-scale speed limit increases in the western United States in 1987 and 1996 to address three related questions. First, do the social benefits of raising speed limits exceed the social (private plus external) costs? Second, do the private benefits of driving faster as a result of higher speed limits exceed the private costs? Third, could completely eliminating speed limits improve efficiency? I find that a 10 mph speed limit increase on highways leads to a 3-4 mph increase in travel speed, 9-15% more accidents, 34-60% more fatal accidents, and elevated pollutant concentrations of 14-25% (carbon monoxide), 9-16% (nitrogen oxides), 1-11% (ozone) and 9% higher fetal death rates around the affected freeways. I use these estimates to calculate private and external benefits and costs, and find that the social costs of speed limit increases are three to ten times larger than the social benefits. In contrast, many individual drivers would enjoy a net private benefit from driving faster. The substantial difference between private and social optimal speed choices provides a strong rationale for having speed limits.

Keywords: Economics
Advisor: Goulder Lawrence H. (Lawrence Herbert)
Abramitzky Ran
Harding Matthew C.
Hoxby Caroline Minter
Jacobsen Mark R.
Essays in game theory [electronic resource]

This dissertation consists of three essays on the foundation and applications of game theory. In Chapter 1 we study a refinement of correlated equilibrium in which players' actions are driven by their beliefs and higher order beliefs about the play of the game (beliefs over what other players will do, over what other players believe others will do, etc.). For any finite, complete-information game, we characterize the behavioral implications of this refinement with and without a common prior, and up to any a priori fixed depth of reasoning. In every finite game "most" correlated equilibrium distributions are consistent with this refinement; as a consequence, this refinement gives a classification of "most" correlated equilibrium distributions based on the maximum order of beliefs used by players in the equilibrium. On the other hand, in a generic two-player game any non-degenerate mixed-strategy Nash equilibrium is not consistent with this refinement. In the next two chapters we turn to the applications of game theory. In Chapter 2 we show that without flexible transfers, the timing of transactions is difficult to coordinate in large matching markets. In our model, some agents have the option of matching early before others arrive. We compare two regimes. In the first regime, transfers which divide surpluses created between the two sides of the market are exogenously fixed, perhaps due to some institutional constraints. Then even with a centralized mechanism that implements a stable matching after all agents arrive, some agents have incentives to match early. We prove that in this setting, as the market gets large, on average approximately one quarter of all agents have strict incentives to match early. Moreover, as the market gets large, with probability tending to 1 there is no early matching scheme that is dynamically stable. On the other hand, in the second regime in which agents can freely negotiate transfers, a stable matching after all agents arrive eliminates all incentives to match early and is dynamically stable. In Chapter 3 we study settlement auctions for credit default swaps (CDS). We find that the one-sided design of CDS auctions used in practice gives CDS buyers and sellers strong incentives to distort the final auction price, in order to maximize payoffs from existing CDS positions. Consequently, these auctions tend to overprice defaulted bonds conditional on an excess supply and underprice defaulted bonds conditional on an excess demand. In our model bidders have a commonly-known bond value but privately-known CDS positions. We prove that with a one-sided auction in every Bayesian-Nash equilibrium the final auction price is strictly greater than the common bond value given an excess supply of bonds, and strictly less than the common bond value given an excess demand of bonds. We propose a double auction to mitigate this price bias. Finally, we find the predictions of our model on bidding behavior to be consistent with data on CDS auctions.

Keywords: Business.
Advisor: Skrzypacz Andrzej
Wilson Robert
Ostrovsky Michael advisor. Thesis advisor