VictorJuiz/thesis huggingface dataset:
Intention and Normative Belief

I defend the view that we act “under the guise of the good.” More specifically, I argue that an intention to do something is a belief that one ought to do it. I show how conflicts in intention and belief, as well as more complex impairments in these states, account for the central problem cases: akrasia in belief and intention, apparently unintelligible choices, and lack of motivation or accidie.

Advisor: Ginsborg, Hannah
Wallace, R. Jay
Biosynthesis and Heterologous Expression of Medicinally Active Natural Products

Natural products have long been appreciated for their potent biological activities, and their unique scaffolds and pharmacophores have served as inspiration for many pharmaceuticals. As the structural complexity of these compounds can make their production and diversification challenging for chemical synthesis, the study and engineering of natural product biosynthetic pathways can facilitate more efficient and sustainable production of natural products and their analogues. Here, we present our findings from the biosynthetic studies of several medicinally active natural products produced by Streptomyces, which reveal some unusual pathways and enzymes. In doing this work, we also demonstrate how heterologous expression can be used to expediently determine the necessity and function of individual biosynthetic enzymes, gain insight into biosynthetic mechanisms, and produce new natural product analogues./nThe compounds of focus here include the cholinesterase inhibitor physostigmine, the peptidyl epoxyketone proteasome inhibitor eponemycin, and the family of antimycin-type depsipeptides. The in vivo and in vitro characterization of physostigmine biosynthesis revealed an unexpected pathway involving an acetylation-deacetylation-dependent reaction cascade and a unique indole methyltransferase. Heterologous expression-based investigations on the biosynthesis of eponemycin then revealed an unprecedented flavin-dependent enzyme to be necessary and sufficient for the formation of the terminal epoxyketone pharmacophore in addition to indicating the involvement of a decarboxylation step. Further efforts to study the biosynthesis of antimycins likewise resulted in the in vivo reconstitution of the 3-formamidosalicylate pharmacophore, and studies on the related neoantimycins led to advances in the biosynthetic understanding and heterologous expression of this ring-expanded class of antimycin-type depsipeptides. Collectively, these biosynthetic insights not only enrich our enzymatic knowledge but can also expand our ability to perform combinatorial biosynthesis.

Advisor: Zhang, Wenjun
I. Measuring and Reducing Stress and Surface Roughness in IBAD MgO Films and II. Developing Tools to Measure Transfer in Undergraduate Chemistry Students

I. MgO may be grown with a biaxial texture onto an amorphous substrate with the use of ion beam assisted deposition (IBAD). This MgO film may then be used as a platform on which to grow epitaxial films on an amorphous membrane for characterization purposes. However, the IBAD MgO film is stressed, causing buckles in the amorphous membrane and problems with further film growth on the IBAD MgO. This dissertation work explores the source of this film stress and develops methods to relax the stress and reduce surface roughness with annealing and increased growth temperature. It is determined that annealing and increased growth temperature coupled with a higher ion-to-atom ratio (IAR) during film growth reduce stress and surface roughness sufficiently to use even thinner IBAD MgO films as an intermediate layer between an amorphous membrane and epitaxial film./nII. Much of the existing literature on knowledge transfer concludes that transfer is rare and does not occur spontaneously. However, studies supporting that transfer is rare often use methods that focus on binary success or failure to solve a problem correctly and do not analyze thought process. This dissertation work aims at developing transfer questions that allow open-ended responses, developing a method of analysis for these responses that looks for transfer in the problem-solving process, and assessing the methodology itself and its sensitivity, validity, and utility as a general transfer measurement technique for use across a broad range of expertise levels in chemistry./nDetailed analysis of responses to each transfer question show that some transfer questions are more effective at distinguishing between expertise levels while also allowing responders of all levels to show knowledge transfer. Simpler questions that are more accessible to students of introductory chemistry proved the most useful at eliciting a range of responses that correlate with expertise level while still showing some degree of transfer in all levels of responders. More challenging questions with complex systems and common misconceptions are too advanced for lower level undergraduates to show knowledge transfer, but may be useful to show transfer in advanced undergraduates and experts.

Advisor: Hellman, Frances
Stacy, Angelica
Outside the Institutional Box: Why Political Parties Use Pre-electoral Violence in Bangladesh

Under what conditions do political parties use pre-electoral violence as a campaign strategy in Bangladesh? Pre-electoral violence has been a consistently regular precursor to each and every election in Bangladesh, with the most recent national election on January 5, 2014, being one of the bloodiest and most undemocratic. However, not all constituencies in Bangladesh experience the same level of pre-electoral violence. There are some like Dhaka - 8 that saw approximately 150 episodes of violence prior to the 2014 elections, while others like Gopalgonj - 3 saw none. What explains this variation? In this paper, I argue and demonstrate using a negative binomial regression model as well as case study and interview data that the ways in which individuals interface with the state (either through the bureaucracy on their own or through the use of local leaders) and the level of information parties have on voter preferences impact the level of pre-electoral violence in constituencies across Bangladesh.

Advisor: Chhibber, Pradeep
The Rhetoric of Legal Crisis. Lawyers and the Politics of Juridical Expertise in Chile (1830-1990)

By the mid-1960s, different groups of Chilean law graduates pervasively began to manifest malaise about the competition of other professions in public decision-making and the unresponsiveness of legal institutions to new social needs. Socio-legal scholarship agrees, based on a preliminary reading of the historical sources and anecdotal evidence, that lawyers lost their quasi-monopoly on statecraft and were unable to resourcefully participate in the political arena during twentieth-century Latin America. However, such phenomena have not been analyzed systematically. Paying attention to Chilean elite lawyers, this dissertation tries to fill the aforesaid gap./nBuilds upon Max Weber and Pierre Bourdieu’s scholarship as theoretical scaffolding, this research examines the transformation of juridical expertise in the process of modernization and the different strategies employed by legal professionals to regain influence in public governance. Through qualitative and quantitative analysis, the first part of my dissertation studies how the legal profession lost political power along with the division of governmental labor and the bureaucratization of courts and the bar occurred in twentieth-century Chile. The second part, chapters 4 to 7, analyzes how different networks of lawyers mobilized after the erosion of their authority, employing a dual strategy of collective action to advance simultaneously their position inside the legal field and diverse political agendas during the Cold War years

Advisor: Feeley, Malcolm M
Laser sintering and ablation process for flexible transparent conducting electrodes

Recently, flexible electronics have received the attention of many researchers. Among the various fascinating and actively investigated applications of flexible electronics, flexible optoelectronics, such as touchscreen panels (TSPs), organic light-emitting diodes, and organic thin-film transistors, is one of the most aggressively developing research fields. Flexible optoelectronics are often connected by flexible transparent conducting electrodes (FTCEs). FTCEs are considered indispensable components in optoelectronic devices. Researchers are looking for novel materials and processes that enable high transparency and low resistance. Indium tin oxide is the material most widely used in creating FTCEs, as it offers good optoelectronic performance (transmittance (T): > 80%; sheet resistance (Rs): ≈ 15 Ω sq-1) for flexible electronics. However, due to its several intrinsic drawbacks, including its brittleness, high cost of materials, slow rate of deposition, and large amounts of material waste, many researchers are investigating alternative materials and processes. In this regard, the laser sintering of metals or metal oxide nanoparticles and the patterning of ultra-thin metal film by pulsed laser ablation have attracted much attention due to the characteristics of nanoparticles and ultra-thin film as well as the low-cost facile fabrication capabilities of lasers./nFirst, I synthesized a nickel oxide (NiO) nanoparticles as a cheap substitute for silver nanoparticles and demonstrated successful laser reductive sintering of this system. High-resolution nickel (Ni) patterns were generated from NiO nanoparticle thin films by continuous-wave (CW) laser irradiation. By the laser reductive sintering of NiO nanoparticles, I developed a high-transmittance (T > 87%), electrically conductive panel for TSPs that is very robust to mechanical bending and adhesion. Furthermore, the mechanisms of photo-physical reductive sintering upon the irradiation of a CW laser on NiO nanoparticle thin films were studied by modulating the power density and illumination time of the laser. Once NiO nanoparticles are reduced to Ni by laser irradiation, they begin to coalesce, forming a conductive material. In-situ optical and electrical measurements were taken during the reductive sintering process to monitor the transient evolution of the process. Finally, low-cost Cu FTCEs were fabricated using 532 nm nanosecond laser ablation under ambient conditions. The fabricated Cu FTCEs have excellent optoelectronic characteristics (T = 83%; Rs = 17.48 Ω sq-1) and mechanical durability. The potential application of Cu FTCEs in flexible optoelectronic devices was successfully demonstrated by the fabrication of TSPs using Cu FTCEs. Furthermore, we employed diffractive optics for laser beam shaping. We successfully demonstrated the opto-electrical characteristics of the percolative regime by decreasing the areal density.

Advisor: Grigoropoulos, Costas
A Behavioral Approach to Contemporary Electoral Accountability

Using techniques from the experimental and computational social sciences, this dissertation identifies three central flaws in one of our most important mechanism designs – elections – and identifies institutional methods to solve these problems./nMechanism design is the “engineering” side of economic theory. Where game theory “takes the rules of the game as given, and [] makes predictions about the behavior of strategic players,” mechanism design “is about the optimal choice of the rules of the game.” For mechanism designers, identifying the optimal choice of rules typically depends on predicting how individuals will behave in certain environments. Both mechanism design and game theory, therefore, rely on identifying equilibriums – that is, joint strategic solutions where no one involved has an incentive to deviate from the strategy that they are playing./nEconomists argue that electoral accountability can be seen a special version of mechanism design. The logic is this. Electoral institutions establish processes for selecting candidates for public office, in such a way as to incentivize them to act in the public interest. To achieve this result, electoral institutions lead to a cascade of mutually-reinforcing incentives. These institutions (a) incentivize voters to retrospectively evaluate officials' performances such that (b) victorious candidates will tend to act in the public interest. Therefore, electoral accountability is a set of institutions, and the incentives that predictably flow from it. The promise of mechanism designers is that, if the institutions are created correctly, officials will be accountable to the public. And this accountability will occur as a matter of course: mechanically./nIn fact, however, this mechanism is broken. This dissertation solves its problems. Chapters 2 and 3 represent three efforts at testing rational choice-based theories of electoral accountability through randomized control trials. These studies take aim at concepts that are crucial to our understanding of a central feature driving retrospective evaluation of policy. Chapter 4 operates at a more theoretical level, but nonetheless retains its behavioral approach. It offers an approach to legal chance that highlights the strategic alternatives facing firms. Chapter 5 offers institutional fixes to the problems identified in Chapters 2, 3, and 4.

Advisor: Kutz, Christopher L
The Effects of Intermittent Drinking Water Supply in Arraiján, Panama

Over three hundred million people throughout the world receive supply from piped drinking water distribution networks that operate intermittently. This dissertation evaluates the effects of intermittent supply on water quality, pipe damage and service reliability in four study zones (one continuous and three intermittent) in a peri-urban drinking water distribution network in Arraiján, Panama. Normal water quality in all zones was good, with 97% of routine water quality grab samples from the distribution system and household taps having turbidity < 1 NTU, total coliform and E. coli bacteria concentrations < 1 MPN / 100 mL, and ≥ 0.3 mg/L free chlorine residual. However, negative pressures that represent a risk for contaminant intrusion and backflow were detected in three of the four study zones, and water quality during the first flush when supply resumed after an outage was sometimes degraded. High and transient pressures that could cause pipe damage were detected in study zones with intermittent pumping, but filling and emptying of distribution pipes due to intermittent supply was not associated with transient or extreme pressures. Operational challenges, including frequent infrastructure failures, difficulty monitoring the network, and a lack of system information, resulted in unreliable supply in the intermittent zones. Continuous pressure and flow monitoring methods used in this research could be helpful tools for operators of intermittent distribution networks to provide more reliable service and identify hydraulic conditions that could lead to contaminant intrusion or pipe breaks.

Advisor: Nelson, Kara L
Engineering Adhesion Substrates as Biomaterials for Cell Fate Control

The microenvironment is known to influence cell state and behavior. In turn, cells interact with and remodel their niches. A comprehensive understanding of this bidirectional interaction is crucial to guide our design of next-generation biomaterials so as to be able to accurately control cell fate in a precise and predictable manner. In Chapter 2 of this dissertation, we present for the first time a biphasic dependence of direct neuron reprogramming, the direct conversion of adult fibroblasts into neurons without passing through a pluripotent state, on adhesion substrate stiffness. We determined that this occurred through stiffness-regulation of cell signaling pathways and additionally observed this relationship to be time-dependent and limited to the early phases of direct reprogramming. Altogether, our results provide insights into the roles of substrate stiffness in regulating direct reprogramming and the underlying mechanism, which will open a new avenue for the rational design of smart biomaterials for direct cell reprogramming. In Chapter 3, we describe the isolation of native ECM proteins from human placentas and characterize these for potential in vivo tissue regeneration applications. Finally, in Chapter 4, we discuss the rationale for and the process of generation and characterization of a novel autologous acellular ECM scaffold for application in small diameter vascular graft replacement.

Advisor: Li, Song
Restoring Human Capabilities After Punishment: Our Responsibilities Toward Incarcerated Americans

Why should non-incarcerated Americans invest in the wellbeing of incarcerated Americans? To date, our public discourse about penal reform has avoided this question, focusing on pragmatic reasons for facilitating “prisoner reentry” and “reintegration” while shelving unresolved, and deeply contested, philosophical questions about criminal justice and punishment. As a result, we as a society have engaged in much data-driven policy talk about the economic costs and benefits of reducing recidivism, but little normative reflection about the rights and responsibilities held by incarcerated adults who are at once human beings, members of society, persons convicted of crimes, victims of inhumane punishment – and, often, survivors of poverty./nThus, my first task is to clarify the individual and collective obligations that apply within our context of mass incarceration: the moral responsibilities that are held by and toward incarcerated Americans, non-incarcerated Americans, and our shared public institutions. My second task is to draw out implications for policy and discourse: to explain not only what reform measures we should prioritize, but how we should frame and assess them. In particular, I call for systemic changes that would provide all incarcerated Americans with opportunities to pursue higher education and to develop redemptive self-narratives; and I argue that we should frame and assess such measures not primarily as cost-saving devices, but as ethically significant efforts to secure capabilities that are essential to human flourishing and required by justice./nIn setting forth these arguments, my purpose is to spark deeper ethical reflection about correctional reform, and specifically to invite meaningful engagement with one key normative question: What do we, as a civilized society with a history of social and penal injustice, owe incarcerated Americans? Ultimately, I wish to underscore that the people confined in our prisons have legitimate moral claims upon us – insofar as they remain human beings and members of society and, as such, bearers of rights as well as responsibilities. Equally, I wish to establish that, in our collective efforts to repair the harms of mass incarceration, we can and should empower those Americans most directly harmed by our penal system to lead the way in transforming it.

Advisor: Song, Sarah
The Political Economy of Global Sectoral Agreements in Information Technology, Telecommunications, and Finance

This dissertation examines variation in the institutional design of the WTO sectoral agreements in IT, telecommunications, and finance. It aims to understand why and how states negotiated sectoral agreements and traces the source of state preferences to an industry’s core business and its major user industries. Going against the conventional wisdom, my analysis leads to three surprising findings. First, sectoral negotiations were not limited to the sector under discussion. They incorporated supplier (upstream) and user (downstream) industries in the global value chain, especially the preferences of user industries. Second, an industry’s global value chains changed the politics of lobbying by shaping the preferences of the firms along the chain and the coalitions they formed. Third, global value chains and industry coalitions affected the institutional design of these international accords in IT, telecommunications, and finance. I show how the number of user industries in the global value chains affected the scope, depth, and membership of sectoral agreements. Each empirical chapter examines the trade negotiations in the IT, telecommunications, and financial services industries. By analyzing multi-country, single-issue agreements, I show a clear pathway and mechanism through which firms utilize trade policies to better serve their large corporate clients. Global value chains, which maps the linkage of goods, services, capital, people, and information, is a specific type of complex interdependence that is evolving and affects every polity within the system. This approach can help answer new theoretical puzzles in international trade such as the rise of trade in services, minilateral agreements such as the TPP and the TTIP, and the effects of these developments for developing countries. It provides a framework with which to understand trade negotiations and raises new questions for scholars.

Advisor: Aggarwal, Vinod
Dissection of the impact of tissue context on anti-cancer drug activity through the use of high dimensional combinatorial microenvironment analysis

Breast cancer alone accounts for 29 % of all new cancer diagnoses and is the second leading cause of cancer related death. Improvement in early detection and the understanding of oncogenic drivers connected to malignant transformation and cancer progression has lead to an overall decrease in breast cancer related mortality1. However, therapeutic durability remains a problem for both chemotherapies and pathway-targeted drugs. Furthermore, the poor translation from pre-clinical screening results to clinical outcomes impedes therapeutic development./nGenomic heterogeneity and other cell intrinsic mechanisms are commonly examined as a major source of therapeutic failure. Using a reductionist approach, I examined the hypothesis that the tissue microenvironment is a potent modulator of drug activity and therapeutic response. I first tested the hypothesis that matrix rigidity of microenvironments can modulate the efficacy of the targeted-therapeutic small molecule, lapatinib, in HER2-amplified breast cancer cell lines. The anti-proliferative effect of lapatinib was inversely proportional to the elastic modulus of the adhesive substrates. The modulus-dependent lapatinib responses were eliminated with treatment of mechanosensing inhibitors, Y27632 and blebbistatin. Knockdown of the hippo pathway mechanotransducer, YAP, eliminated the modulus-dependent lapatinib responses, and pharmacological inhibition of YAP phenocopied the effect of YAP knockdown. Reduction of YAP in vivo in mice also slowed the growth of implanted HER2-amplified tumors, these showing a trend of increasing sensitivity to lapatinib as YAP decreased. Thus, I addressed the role of stiffness in resistance to, and efficacy of, a HER2 pathway-targeted therapeutic via the mechanotransduction arm of the hippo pathway./nIn order to dissect and investigate the microenvironmental impact on drug responses, we developed the MicroEnvironmental microarray, (MEArray) platform. The method allows for simultaneous control of the molecular composition and the elastic modulus. Utilizing the MEArray, I further tested the hypothesis that in addition to matrix rigidity, molecular composition can modulate lapatinib responses. I systematically quantified the microenvironmental impact on cellular morphological changes and the lapatinib responses. The results were consistent with our previous report that matrix rigidity conferred lapatinib resistance. I also identified that cells adhered to fibronectin showed higher lapatinib resistance independent of stiffness. The validations showed that fibronectin conferred nuclear YAP translocation, which may explain partly the mechanism of the lapatinib resistance. Further studies for elucidation of fibronectin-induced lapatinib resistance are needed. However, simultaneous modulation of stiffness and molecular composition revealed a continuum of drug responses resulting from cell-microenvironment interactions.

Advisor: LaBarge, Mark