VictorJuiz/thesis huggingface dataset:
Constituent Characters: Representing the Electorate in the Early United States

In the early United States, literary culture was inextricably enmeshed with electoral politics. This dissertation explores the influence of the character sketch on that politicized literary culture, in which literary magazines held strong partisan affiliations, novelists moonlit as campaign biographers, and elected officials aspired to literary fame. The character sketch was a popular eighteenth-century genre whose depictions of individuals and social types generated aesthetic debates about how, exactly, written “strokes” and “outlines” could most clearly distill a character’s essence, as well as how a set of characters could collectively represent the polity as a whole. Constituent Characters traces how the character sketch was adopted by and adapted within early American campaign materials and shows that the aesthetic discourse surrounding the character sketch permeated how Americans discussed and imagined electoral representation from the Constitutional Debates through the 1840s. In doing so, the project reveals the surprisingly literary history of how Americans thought through questions like, What size legislature best represents the people? and What distinguished legitimate from illegitimate electoral district boundaries? It also points to the need for both scholars and writers to attend to how political and literary representation evolved together in the United States through an iterative process in which writers and readers continually renegotiated which character types the polity would collectively recognize, as well as the aesthetic terms on which it would do so.

Advisor: Otter, Samuel
A Proposed Method for the Computer-aided Discovery and Design of High-strength, Ductile Metals

Gum Metal, a class of Ti-Nb alloys, has generated a great deal of interest in the metallurgical community since its development in 2003. These alloys display numerous novel and anomalous properties, many of which only occur after severe plastic deformation has been incurred on the material. Such properties include: super-elasticity, super-coldworkability, Invar and Elinvar behavior, high ductility, as well as high strength. The high strength of gum metal has generated particular enthusiasm as it is on the order of the predicted ideal strength of the material. Many of the properties of gum metal appear to be a direct result of tuning the composition to be near an elastic instability resulting in a high degree of elastic anisotropy. This presents an opportunity for the computer-aided discovery and design of structural materials as the ideal strength and elastic anisotropy can be approximated from the elastic constants. Two approaches are described for searching for this high ansitropy. In the first, The possibility of forming gum metal in Mg is explored by tuning the material to be near the BCC-HCP transition either by pressure or alloying with Li. The second makes use of the Materials Project's elastic constants database, which contains thousands of ordered compounds, in order to screen for gum metal candidates. By defining an elastic anisotropy parameter consistent with the behavior of gum metal and calculating it for all cubic materials in the elastic constants database several gum metal candidates are found. In order to better assess their candidacy information on the intrinsic ductility of these materials is necessary. A method is proposed for calculating the ideal strength and deformation mode of a solid solution from first-principles. In order to validate this method the intrinsic ductile-to-brittle transition composition of Ti-V systems is calculated. It is further shown that this method can be applied to the calculation of an ideal tensile yield surface.

Advisor: Chrzan, Daryl C
Development of protein organelles for tunable metabolite diffusion and sequestration of multi-enzyme pathways

The use of bacterial production could improve commercial feasibility for biochemicals such as pharmaceuticals and natural products. However, many non-native reactions in bacterial hosts have unacceptably low yields due to pathway toxicity or competition with other cellular processes. Compartmentalization is a potential solution to these problems, but compartmentalized organelles were long thought to be found only in eukaryotic cells. Remarkably, bacterial microcompartments (MCPs) are protein-based organelles that perform this sequestration function. We aim to apply these MCPs for metabolic engineering and the enhancement of biosynthesis pathways that do not function optimally in the cytosol. MCPs may also serve as a scaffold for application outside of the cell./nTo achieve this goal, we characterized the stability of MCPs when exposed to a range of pH and temperature to define the limitations of this complex structure. We next demonstrated that it is possible to form chimeric MCPs by combining shell proteins from different systems in nature. Importantly, we found that these changes to shell protein structure can enhance the function of the encapsulated pathway. We discovered that pathway performance can also be improved by a single point mutation to the pore of a shell protein, likely altering small molecule diffusion across the shell. We are investigating the role of shell protein pore chemistry in tuning small molecule diffusion. Finally, we test signal sequence peptides at the C-terminus of proteins and find that variation of signal peptide sequence results in altered expression level and loading within MCPs. In total, these tools improve our ability to design custom bacterial organelles to control the partitioning of chemical reactions within cells.

Advisor: Tullman-Ercek, Danielle
Keasling, Jay D
The Talmudic Zohar: Rabbinic Interdisciplinarity in Midrash ha-Ne'lam

This study uncovers the heretofore ignored prominence of talmudic features in Midrash ha-Ne’lam on Genesis, the earliest stratum of the zoharic corpus. It demonstrates that Midrash ha-Ne’lam, more often thought of as a mystical midrash, incorporates both rhetorical components from the Babylonian Talmud and practices of cognitive creativity from the medieval discipline of talmudic study into its esoteric midrash. By mapping these intersections of Midrash, Talmud, and Esotericism, this dissertation introduces a new framework for studying rabbinic interdisciplinarity—the ways that different rabbinic disciplines impact and transform each other./nThe first half of this dissertation examines medieval and modern attempts to connect or disconnect the disciplines of talmudic study and Jewish esotericism. Spanning from Maimonides’ reliance on Islamic models of Aristotelian dialectic to conjoin Pardes (Jewish esotericism) and talmudic logic, to Gershom Scholem’s juvenile fascination with the Babylonian Talmud, to contemporary endeavours to remedy the disciplinary schisms generated by Scholem’s founding models of Kabbalah (as a form of Judaism that is in tension with “rabbinic Judaism”), these two chapters tell a series of overlapping histories of Jewish inter/disciplinary projects. The section’s juxtaposition of medieval and contemporary models of talmudic-esoteric interdisciplinarity provides a framework for overcoming the models of disciplinarity that the field of Zohar Studies inherited from Scholem’s pioneering scholarship and clears theoretical space for rethinking the disciplinary commitments of Midrash ha-Ne’lam./nThe second half of the dissertation demonstrates that Midrash ha-Ne’lam uses talmudic reasoning and rhetoric for three purposes: (1) to formulate a model of divine cosmogenesis that is akin to talmudic creativity; (2) to advocate for applying talmudic reasoning to secrets as a way to expand esoteric knowledge; (3) and to represent a scholastic community in which rabbis search for secrets together and debate each other’s esoteric lore.

Advisor: Boyarin, Daniel
Largier, Niklaus
Engineered Biosynthesis of Terminal Alkynes and Its Applications

The terminal alkyne functionality is widely used in organic synthesis, pharmaceutical science, and materials. It is also a useful moiety in the azide-alkyne [3+2] cycloaddition reaction (often known as “click chemistry”), which has recently emerged to be one of the most powerful tools in drug discovery and chemical biology. In particular, by tagging medicinally active natural products with alkynes and coupling them with subsequent click chemistry, researchers have enriched, visualized, and studied the mode of action of natural products. Despite the importance of the alkyne functionality, its applications in natural product research are limited by the underexplored alkyne biosynthetic tools and tagging strategies./nIn this study, we first elucidated an unprecedented carrier protein–dependent terminal alkyne biosynthetic pathway in microbes that featured an acyl-acyl carrier protein (ACP) synthetase (JamA), a membrane-bound bifunctional desaturase/acetylenase (JamB), and an ACP (JamC). We further demonstrated that this enzymatic machinery can be exploited for the in situ generation and incorporation of terminal alkynes into two natural product scaffolds (a polyketide pyrone, and antimycin, respectively) in Escherichia coli. However, JamB showed stringent substrate specificities and weak catalytic activities, which restricted its broader applications in synthetic and chemical biology. We addressed these limitations in two ways. In silico analysis suggested that this carrier protein–dependent terminal alkyne biosynthetic mechanism could be widespread in bacteria. We screened additional gene cassettes that are homologous to jamABC and discovered a new terminal alkyne biosynthetic pathway comprised of TtuABC from Teredinibacter turnerae T7901. Different from JamABC, TtuABC displayed altered substrate specificities and improved catalytic activities. Using TtuABC, we further in situ generated and incorporated the alkyne functionality into another medicinally important natural product, a peptidyl epoxyketone. In a parallel effort, directed evolution was adopted to create a JamB variant with improved catalytic efficiency in E. coli. To quickly assess the protein engineering outcomes, we developed a new platform for quantifying extracellular alkyne-tagged metabolites through a fluorogenic click reaction. Overall, this study not only provides us with alkyne biosynthetic tools that are useful in synthetic and chemical biology, but it can also find applications in which enzymatic generation of terminal alkynes and in situ click chemistry is required or preferred.

Advisor: Zhang, Wenjun
The Process and The People: Federal Recognition in California, Native American Identity, and the San Luis Rey Band of Mission Indians

The United States maintains an artificial hierarchy amongst Native American tribes by acknowledging, or recognizing, some tribes’ inherent tribal sovereignty over others. Tribes are considered federally recognized or unrecognized not because of intrinsic differences, but rather the history of their interactions with the government. Without a federally recognized sovereign status unrecognized tribes are often landless, are denied protections from federal laws designed to aid Native people and tribal nations, are unable access to federal resources for education or health services, and are limited in their ability to practice self-determination. Unrecognized tribes and tribal members are also subject to intangible difficulties from skeptics who question cultural authenticity and suggest ethnic fraud. California has the most unrecognized tribes in the country and the most that have taken steps to pursue federal recognition through the Federal Acknowledgment Process, a system using seven criteria to acknowledge tribal sovereignty that is administered by the Office of Federal Acknowledgment within the Department of the Interior./nThe Process and The People analyzes the politics and history of federal recognition in California and its connection to contemporary Native identity. This study provides critical context on the origins of federal acknowledgment and the Federal Acknowledgment Process within a broader lineage of colonial laws and policies that bear on Native American identity. Focusing explicitly on federal acknowledgment in California, it traces the settler colonial history of the state and its connection to the current crisis of federal recognition across Native California. The Process and The People also includes a case study of the San Luis Rey Band of Mission Indians, the only unrecognized tribe in San Diego County. As part of a larger movement of unrecognized tribes in California seeking recognition, the case of the San Luis Rey Band exemplifies the issues of recognition in the state while highlighting the tribe’s unique history within the broader recognition landscape. Through the experience of the San Luis Rey Band, The Process and The People contends that the tribe’s engagement with the Federal Acknowledgment Process is part of a longer history of tribal interaction with the federal government. The case illustrates to what extent tribes can use the Federal Acknowledgment Process for their own political and social purposes, how unrecognized tribes enact self-determination and tribal sovereignty, and what understandings of community identity underpin the pursuit for federal recognition.

Advisor: Huhndorf, Shari M
Broken Symmetry: Discovery, Characterization, and Structure of Hybrid Promiscuous (HyPr) GGDEF Enzymes

This past decade has witnessed an expanded diversity in the cast of nucleotide-based second messengers. The small lineup of cyclic AMP, cyclic di-GMP and ppGpp have been joined by new co-stars, including cyclic di-AMP, cyclic oligoA, and two flavors of cyclic AMP-GMP - with one possessing a unique 2’-5’ phosphodiester linkage specific to eukaryotes. As each new signaling pathway has been uncovered, new enzymes classes have been attached to each specific second messenger, suggesting rigid evolutionary pathways in the development of new signal transduction pathways./nWe have begun to unravel this paradigm with the discovery of a subclass of GGDEF enzyme - previously associated only with cyclic di-GMP synthesis - responsible for synthesis of a different cyclic dinucleotide, cyclic AMP-GMP. Intriguingly, this enzyme behaves nothing like the other two. Our discovery of this new activity from an ancient enzyme class pinpoints a set of deltaproteobacteria that have this “hybrid promiscuous” GGDEF activity, which preliminary work suggests controls transient surface attachment in diverse bacterial lifestyles. Furthermore, we have begun to unravel how Nature has allowed this newfound activity to act separately from other GGDEF-related pathways to allow precise control over electron acceptor choice in Geobacter species. Our work suggests that there is further underappreciated potential for individual components of nucleotide second messenger signaling enzymes, and establishes a footing for engineering new bioorthogonal signaling functions into this venerable enzyme class.

Advisor: Hammond, Ming C
Phonetic Attention and Predictability: How Context Shapes Exemplars and Guides Sound Change

In this dissertation, I investigate how word predictability in context modulates the listener’s attention to phonetic details, and how this in turn affects sound change. Three sets of experiments are designed to investigate these questions: In the first set of experiments, involving discriminability tasks, I demonstrate that (1) contextual predictability affects speech perception, and that listeners attend more to the phonetic details of unpredictable speech. In the second set of experiments I use the phonetic accommodation paradigm to show that (2) the effect of contextual predictability on speech perception in turn affects speech production. This by itself suggests relevance in sound change. In the third set of experiments I apply the model to a specific example of sound change: the reduction of function words. Using an error detection task I show that (3) listeners attend to the details of content words more than function words (with all other variables controlled for) which is linked to their differences in contextual predictability. I then propose a two-step model of sound change involving the propagation of contextually-modulated variation with a perceptual (rather than production) bias followed by the acquisition of new variants./nThe results build and expand on several strands of literature which have not been fully connected previously. The findings for the effect of predictability on speech perception corroborate a number of past experiments showing that higher level linguistic information can have the effect of aiding speech recognition (Miller, Heise & Lichten 1951, Pollack & Pickett 1963), perceptually restoring missing information (Warren 1970, Marslen-Wilson, & Welsh 1978, Samuel 1981), or generally diverting attention from the raw auditory signal (Cole, Jakimik, & Cooper 1978, Ganong 1980). Additionally, this research considers dual-processing models of speech perception (Norris & Cutler 1979, Lindblom et al. 1995, Hickok and Poeppel 2004, 2007) in a broader context, considering how word predictability and expectancy modulate the type of listening used. The findings also add to the literature on exemplar theory (Johnson 1997, Pierrehumbert 2002, Goldinger 2007), particularly to hybrid models including both abstractions and exemplar clouds within the lexicon. Finally, I propose a new model of perception-based sound change driven by contextual predictability that can account for cross-linguistically common patterns of function word and morpheme reduction (Bell et al. 2001, Jurafsky et al. 2001, Beckman 1998) that does not rely on teleological production-based accounts of reduction (Lindblom 1990, Alyett & Turk 2004).

Advisor: Johnson, Keith
The Place of Atrocity: Geographical Imaginaries in Delbo, Camus, and Duras

This dissertation brings to light a poetics of space in postwar texts and films that represent the aftermath of historical trauma. I show that the spatial poetics of confinement, deportation, and diaspora in works by Charlotte Delbo, Marguerite Duras, and Albert Camus highlight the unsettling but unavoidable continuity between sites of atrocity and the everyday world. Instead of depicting the concentration camp as an enclosed and impenetrable site of extreme violence – one that must be remembered, while sealed away in both time and space – these works insist on the connections between everyday life and catastrophic violence. This focus on space enriches the critical discussion of traumatic memory, which has predominantly evaluated trauma as a temporal disruption of the psyche. By reading works of literature and film through the lens of space, I show that the ongoing political urgency of this traumatic history was envisioned as the proximity between concentration camps and the pacified, quotidian world. Across texts that range from testimony (Delbo) to fiction (Camus) and experimental film (Duras), the concentration camp comes into direct contact with urban and domestic spaces. As a result, these works radically dismantle the perceived boundaries of the camp, emphasizing its capacity – as site, system, and figure – to contaminate even the most familiar spaces of the everyday, such as the city street, the railway station, or the home.

Advisor: Sanyal, Debarati
Centralized and Decentralized Warehouse Logistics Collaboration

In an emerging trend in the grocery industry, multiple suppliers and retailers share a warehouse to facilitate horizontal collaboration, in order to lower transportation costs and increase outbound delivery frequencies. Typically, these systems (sometimes known as Mixing and Consolidation Centers) are operated in a decentralized manner, with little effort to coordinate shipments from multiple suppliers with shipments to multiple retailers. Indeed, implementing coordination in this setting, where potential competitors are using the same logistics resources, could be very challenging. In this thesis, we characterizes the loss due to this decentralized operation, in order to develop insight into the value of making the extra effort and investment necessary to imple- ment some form of coordinated control. To do this, we consider a setting where several suppliers ship to several retailers through a shared warehouse, so that outbound trucks from the warehouse contain the products of multiple suppliers. We extend the classic one warehouse multi-retailer analysis of Roundy (1985) to incorporate multiple suppli- ers and per truck outbound transportation cost from the warehouse, and develop a cost lower bound on centralized operation as benchmark. We then analyze decentralized versions of the system, in which each retailer and each supplier maximizes his or her own utility in a variety of settings, and we analytically bound the ratio of the cost of decentralized to centralized operation, to bound the loss due to decentralization. We find that easy-to-implement decentralized policies are efficient and effective in this set- ting, suggesting that centralization (and thus, coordination effort intended to lead to some of the benefit of centralization) does not bring significant benefits. In a compu- tational study, we explore how system parameters impact the relative performance of this system under centralized and decentralized control. Finally, we consider a stochas- tic version of this model of decentralized collaboration, where we assume independent Poisson demand occurs at each retailer for all products. To coordinate replenishment, each retailer follows an aggregate (Q,S) policy, i.e., an order is placed to raise inventory position to S whenever total demand since the last order at that retailer reaches Q./nIn this setting demand at the warehouse can be well-approximated by a compound Poisson process, and thus inventory at the warehouse is managed via an (s,S) policy. We develop optimal and heuristic algorithms to optimize parameter settings in this model.

Advisor: Kaminsky, Philip M
I.) Total Synthesis of Aryltetralin Lignans by a C-H Arylation Strategy II.) Total Synthesis of Complex Meroterpenes

Podophyllotoxin-based glycosidic derivatives have seen numerous uses in cancer chemotherapy. However, these analogs are primarily derived from semisynthetic modifications of the natural product, and the inherent restriction of semisynthesis has prevented further development of new analogs. In the first chapter of this dissertation, a concise and modular total synthesis of the prototypical aryltetralin lignan, podophyllotoxin, is disclosed. Central to the overall strategy is a palladium-catalyzed C-H arylation reaction as the point of diversification. From an advanced intermediate, a two-step sequence furnished not only the natural product but also fully synthetic podophyllotoxin analogs. Moreover, this work uncovered subtle previously overlooked conformational effects governing reductive elimination from high-valent palladium centers./nIn the second chapter, a general strategy for the synthesis of complex meroterpene natural products is reported. First, a modular 10-step synthesis of the flagship PPAP, hyperforin, is disclosed. The synthetic approach includes two key transformations 1.) a novel annulation reaction between lithium enolates and diketene, and 2.) an oxidative ring expansion reaction mediated by hypervalent iodine. Second, the substrate scope of the diketene annulation reaction is reported. Finally, a synthesis of berkeleyone A, a complex meroterpene derived from 3,5-dimethylorsellinic acid, is reported in thirteen steps.

Advisor: Maimone, Thomas J.