VictorJuiz/thesis huggingface dataset:
Sterol side-chain methylation in uncultured bacteria
Keywords: Sustainability.
Earth System Science.

Sterols are polycyclic triterpenoid lipids required by eukaryotes for many critical cellular functions. In addition, sterols are quite recalcitrant and are preserved as sterane molecular fossils, or biomarkers, in sedimentary rocks up to 1.6 billion years old. Given the persistence of these molecules in ancient rocks and their wide distribution amongst extant eukaryotes, geologists often interpret steranes broadly as biomarkers of past eukaryotic life, although diverse bacteria are also known to produce sterol lipids. Sterols with certain modifications to the side-chain, such as methylations at the C-24 position, can act as more specific biomarkers given their restriction to certain eukaryotic lineages and absence in cultured bacteria. One such side-chain methylated sterane biomarker, 24-isopropylcholestane (24-ipc), has historically been attributed to sea sponges of the Demospongiae class. 24-ipc first appears in the Cryogenian and may therefore represent the first evidence of animals on Earth. However, enzymes that produce sterols with the 24-isopropyl side-chain have not been identified in any extant organism. In this dissertation, I investigate the biochemical requirements for sterol side-chain propylation and explore the potentional for sterol side-chain methylation in yet-uncultured bacteria more broadly through a combination of laboratory experiments and bioinformatic analyses. In Chapter 1, I find that several bacterial sterol methyltransferases (SMTs) identified in metagenomes methylate the sterol side-chain in vitro and identify three bacterial SMTs that produce sterols with the 24-isopropyl side-chain of the 24-ipc biomarker. Several functional metagenomic SMTs occur in sterol biosynthesis gene clusters suggesting yet-uncultured bacteria have the genomic capacity to produce side-chain alkylated sterols de novo. In Chapter 2, I identify a necessary but not sufficient glycine residue conserved among propylating bacterial SMTs that occurs in the active site of SMT model structures. The presence of this glycine residue can therefore act as indicator of an SMT's ability to produce 24-isopropyl sterols. In Chapter 3, I find that bacterial SMTs are widely distributed in the environment but are particularly enriched in sponge metagenomes. Bacterial SMTs are actively transcribed in wastewater, soil, creeks, hot springs, and estuaries. Together, the results presented in this dissertation suggest bacteria may be an overlooked source of side-chain methylated sterols in the rock record, provide a framework for predicting SMT function directly from sequencing data, and highlight environments that can be targeted for future cultivation of bacteria that produce side-chain methylated sterols. Overall, this work demonstrates how techniques in molecular biology, biochemistry, and bioinformatics can be leveraged to improve the interpretation of molecular fossils.
Stories of Makokoba
Keywords: Zimbabwe
Southern Rhodesia
township
tourism
ethnographic
Text
Thesis

Makokoba is a formerly segregated place located in the nation of Zimbabwe, once a colony of Britain known as Southern Rhodesia. Three stories about Makokoba illuminate different perspectives and rely on various research methods. One story illuminates the lived experience of Makokoba and is told through the voices of residents, memories accessed while conducting ethnographic research in Zimbabwe. Another story is recounted through the archival record—primary source materials including maps, newspapers, and photographs--and is indicative of how white authorities used social welfare and urban planning initiatives to enforce racial segregation. A third story is based on the narrative of township tourism in Makokoba. This story highlights both the lived experience and how it is shaped around the existing colonial framework of control. Teasing out similarities and differences within these stories provides a new approach to understanding Makokoba by juxtaposing archival and ethnographic research.
A story of their own : 20th-century Jewish trans narratives in German and Yiddish
Keywords: Humanities and Sciences.
German Studies.

My dissertation sheds light on the relationship between storytelling and conceptions of gender variance in German and Yiddish trans narratives through the works of three Jewish 20th-century writers: Else Lasker-Schüler, N.O. Body, and Isaac Bashevis Singer. Scholarship on trans narratives has emphasized the role that forms of scientific assessment of transgender individuals, such as medical questionnaires and the so-called "trans biography", have played in the formation of trans narratives throughout the 20th century. Considering the centrality of narrative self-making for trans identity since the beginnings of Western sexology—particularly in the German speaking context—I foreground storytelling and theories of storytelling as an effective methodology to approach trans Jewish identities. Grounded in feminist critique, queer theory, and phenomenologies of trans embodiment, my work shows that authors turn to classic narrative forms to tell stories of gender variance in a deeply relational way, privileging personal encounters with others as sites of gendered and sexual self-understanding. Rather than rooting transness in a deviated body and mind that needs to be revealed, examined, and rendered legible to cis culture by a medical authority, these authors build on the resources of Homeric epic, Yiddish folklore, and Biblical tales to highlight the—often intimate and idiosyncratic—intersubjective process of making meaning of gender. Classic forms of storytelling place at the fore aspects of embodiment that link characters to their social surroundings, such as speech, action, physical movement, and sensual perception. In doing so, these forms enable 20th -century authors to narrate transness through social encounters rather than a medical-scientific response and open up the possibility of understanding gender variance on a foundation of collaborative worldmaking. My work embraces storytelling as an ethical challenge to efforts for complete cultural legibility of minoritized embodiment, and not only finds new perspectives on narrating transness in the 20th century but also provides a new framework for thinking about the narration of identities at large.
Strain-tuning charge density wave order in rare earth tritellurides
Keywords: Humanities and Sciences.
Applied Physics.

This work focuses on the study of one type of exotic electronic order, the charge density wave (CDW) phase, in response to strain tuning. To perform this study, the rare-earth tritelluride (RTe3, R= Y, La-Nd, Sm, Gd-Tm) crystal family are utilized as a model system. This material possesses a very simplified phase diagram, an ideal structure to explore the CDW phase, specifically unidirectional CDW states on a nearly square lattice, and lastly, these CDW states are highly tunable. Using both x-ray and transport techniques, high-precision measurements of the CDW state in RTe3 crystals under strain are conducted. These measurements demonstrate that the primary CDW order in the material can be reoriented with the application of anisotropic strain presenting one of the first direct observations of such a strain tunable CDW state. Moreover, these measurements reveal a bicritical point in the temperature-strain phase diagram where the phase transitions of the two distinct CDW states in the material are tuned to coincide. Finally, at this bicritical point, signatures in elastoresistivity measurements indicate the emergence of a tetragonal symmetry in this fundamentally orthorhombic material, demonstrating the ability of strain to modify the symmetry of a material. In the remainder of this thesis, I explore this strain-tuned phenomenology along other tuning axes and with other experimental probes. The effect of disorder is explored in this material with strain by studying palladium intercalated erbium tritelluride (PdxErTe3), providing a novel perspective on how disorder reduces the electronic orthorhombicity of the system. Additionally, a complementary strain study of a competing secondary CDW state in the material is presented. Finally, the material is also studied with inelastic x-ray scattering to explore how the phonon structure evolves with strain, providing additional information about the nature of the CDW states.
“Strangers and Pilgrims on the Earth”: Early Modern English Pilgrimage, 1536-1684
Keywords: History Department
Pilgrims and pilgrimages
Pilgrimage of Grace (1536-1537)
England
Pilgrim's progress (Bunyan, John)
Christian pilgrims and pilgrimages in literature
Pilgrims (New Plymouth Colony)
English literature > Early modern
English poetry > Early modern
Text
Thesis

After centuries of a vibrant English pilgrimage culture, in 1538, Henry VIII outlawed pilgrimage. The prohibition of the practice did not, however, reduce English religious and literary interest in the concept of pilgrimage. Almost a century and a half later, John Bunyan published The Pilgrim's Progress, an allegorical representation of the life of a Christian soul as a physical pilgrimage to heaven. How did the prohibition of pilgrimage allow for Bunyan's concept of pilgrimage to develop? This honors thesis explores how the concept of pilgrimage changed during this period through the writings of English separatists and in popular English literature; it also posits that early modern treatment of this prohibited practice allowed for the return of pilgrimage to modern Anglicanism.
Strategies for managing naturally occurring contaminants in groundwater basins of the Central Valley, California
Keywords: Sustainability.

California's Central Valley provides some of the most productive agricultural land in the world. However, climate change is disrupting the hydrologic cycle and multiple stakeholders are extracting groundwater faster than it can be replenished. Such groundwater overdraft has degraded or depleted drinking water supplies, endangered groundwater dependent ecosystems, and severely damaged both crops and irrigation infrastructure. I employ qualitative, synthesis, and statistical modeling to address 1) the need for increasing California's water supply and 2) mitigating groundwater quality threats during managed aquifer recharge. In Chapter 2, I address the deleterious pathway we are on by qualitatively examining Central Valley farmer perceptions of the California water system through 30 semi-structured interviews. I describe the California farm as a coupled-infrastructure system with groundwater as a common pool resource, placing managed aquifer recharge as an economically viable option for sustainable groundwater management. I provide exploratory descriptive analysis of the economic, social-behavioral, and biophysical context of farmer decision-making with respect to groundwater quality and quantity. I explore farmers' beliefs about their roles in creating and mitigating overdraft, and I reveal farmers self-identifying as sustainable stewards of the land not solely motivated by profit. However, I also identify threats from naturally occurring contaminants such as arsenic and uranium. In Chapter 3, I propose recommendations for balancing the quantity of planned recharge with mitigation strategies that control the biogeochemical and hydrogeological mechanisms associated with naturally occurring threats. Further, on the basis of current decision support tools for siting managed aquifer recharge on farms, I propose balancing the quantity of planned recharge with mitigation strategies that control the biogeochemical and hydrogeological mechanisms associated with naturally occurring threats. Based on the need to balance quality and quantity during managed aquifer recharge, I identify the need to summarize available managed aquifer recharge siting tools and find room to augment them with naturally occurring threats. In Chapter 4, my work illustrates the benefit of augmenting managed aquifer recharge siting tools with predictive naturally occurring threat maps created with random forest modeling. I propose a scenario-based case study that emphasizes the need to balance reversing overdraft with maintaining or improving groundwater quality to ensure California has a sustainable water supply for all beneficial uses.
Striggio-Monteverdi's L'Orfeo: an excursion into its neoplatonic layers (1995)
Keywords: Monteverdi, Claudio, 1567-1643
Orfeo (Monteverdi, Claudio)
Striggio, Alessandro
Opera
Neoplatonism > Influence
Text
Thesis

The study is divided not into chapters but into areas of questions. The first area offers a structural analysis of the Prologue which supports La Musica's claims about the power of music; the second one challenges the traditional view of Orfeo as representing a consistent statement about that power; the third, is devoted to a refutation (the first as far as I know) of McClary's reading of the opera. The study concludes with a discussion of the so-called "problem" of the opera's two finales. M.Mus. (Historical Musicology) thesis, King's College London, 1995.
Structural insights into an immune checkpoint receptor reveal a novel approach to cancer immunotherapy
Keywords: Medicine.
Microbiology and Immunology.

Immunotherapy has revolutionized cancer treatment, but the limited response rates to current checkpoint inhibitors necessitate the identification of additional immunotherapeutic approaches. Lymphocyte-activation gene 3 (LAG-3) has emerged as a potential orthogonal checkpoint molecule that negatively regulates T cell activation. First-generation monoclonal antibodies against LAG-3 demonstrated moderate success, despite a lack of knowledge about the mechanism by which LAG-3 functions. This thesis aims to provide key details focused on LAG3 structural characterization, including functional consequences of LAG-3 dimerization on ligand binding and activation, as well as epitope mapping of murine and clinical human LAG-3 antibodies. The first major accomplishment of this work was the elucidation of the crystal structure of the glycosylated mouse LAG-3 extracellular domain, providing valuable insights into its overall architecture and molecular features. This structural information, which was generated in collaboration with Irimpan Mathews at SLAC, served as a foundation for further investigations into the functional aspects of LAG-3. By employing sophisticated biochemical and biophysical techniques in collaborative work with the laboratories of Jun Wang and Xiang-Peng Kong at NYU, we demonstrated that disruption of D2 domain dimerization severely compromised LAG-3's ability to engage with its ligands and modulate T-cell responses. To further explore the potential therapeutic implications of disrupting LAG-3 dimerization, we performed fine epitope mapping of an antibody called C9B7W, known to bind the LAG-3 D2 domain that we identified as being key to LAG-3 dimerization. The study pinpointed the binding site of C9B7W squarely at the D2 dimerization interface, suggesting a potential mechanism by which this antibody disrupts LAG-3 function. Epitope mapping and electron microscopy showed that like C9B7W, murine antibodies which bind LAG-3 D1 and D3 can also disrupt dimerization and ligand binding. Lastly, we undertook a comprehensive epitope mapping analysis of 11 currently known human LAG-3 antibodies under clinical development. Intriguingly, unlike C9B7W, none of the LAG-3 antibodies under clinical development bound to the D2 dimerization interface, and all bound to the LAG-3 D1 domain, some with overlapping and others with disparate epitopes. Collectively, these findings significantly contribute to our understanding of LAG-3 biology and provide crucial insights into its therapeutic potential. The structural characterization, identification of the critical role of D2 dimerization, and epitope mapping of disruptive and clinical human LAG-3 antibodies pave the way for the development of novel immunotherapeutic strategies targeting LAG-3 in the fight against cancer and other immune-related diseases.
Structure and thiazide inhibition mechanism of the human sodium-chloride cotransporter
Keywords: Medicine.
Molecular and Cellular Physiology.

The sodium-chloride cotransporter (NCC) functions as the major salt reabsorption pathway in the distal convoluted tubule of the kidney nephron and is responsible for the fine-tuning of renal sodium excretion. Because of its importance in sodium homeostasis, NCC plays a critical role in blood pressure regulation. Thiazide diuretics, inhibitors of NCC, are therefore important first-line therapeutic agents for hypertension. Here, the work to determine the cryo-electron microscopy structures of the human NCC alone and in complex with a thiazide diuretic, polythiazide is described. I also detail my efforts to develop assays for the functional characterization of NCC, which is essential for studying its structure-function relationships. These structural and functional studies provide insights into NCC's major conformational states and transport mechanism. They also shed light on the molecular basis of how thiazide diuretics inhibit NCC and uncover several intriguing regulatory mechanisms. Together, these studies advance our understanding of the molecular mechanisms of NCC and lay the foundations to facilitate future development of next-generation NCC modulators
Structure formation at the juncture of simulations and perturbation theory
Keywords: Humanities and Sciences.
Physics.

This thesis investigates the formation of the largest-scale cosmic structures found in the Universe through time, on the scales of hundreds of millions of megaparsecs and ten billion years. Modern telescopes are currently probing this large-scale structure by observing the 3D distributions of tens of millions of galaxies, and the shapes of hundreds of millions to billions. The correlations between their spatial distribution in the sky, their shapes, and cross-correlations therein contain a vast treasure trove of hitherto untapped cosmological information. We focus on the problem of accurately modeling the correlations of galaxy properties, induced by clustering and weak lensing, in regimes where past models have failed to do so. The goal of analyzing these cross-correlations is to probe the nature of dark matter, dark energy, the sum of neutrino masses, the primordial fluctuations of the Universe, and many other pressing questions about our Universe at high precision. These high precision measurements beget high accuracy models, lest we risk being biased about our inferences of the fundamental properties of the Universe. The creation of high accuracy models is the goal of this thesis, and this is achieved by leveraging two disparate paradigms for structure formation that have their individual strengths and weaknesses -- perturbation theory-based models and supercomputer simulations of the formation of structures. The `hybrid models' discussed in this thesis combine aspects of these two paradigms, creating a description of the formation of large-scale structures that is more accurate than the sum of its parts. This model for structure formation, at the juncture of simulations and perturbation theory, is investigated in several facets in subsequent chapters
Structure-function relationships in metal oxides and carbon-based catalysts for electrochemical energy conversion reactions
Keywords: Engineering.
Chemical Engineering.

As the imperative to mitigate climate change intensifies, the shift towards sustainable energy practices has never been more crucial. At the heart of this transformation lies electrochemical energy and chemical conversion, which, through the potential-driven control over catalysts, provides a promising pathway to sustainable energy and commodity development over traditional thermochemical methods. This presentation will focus on two electrochemical systems using a combined electrochemical and theoretical approach: the upgrading of biomass to value-added chemicals and the material development and characterization of metal-organic frameworks (MOFs) for the oxygen reduction reaction (ORR) in alkaline hydrogen fuel cells. The electrochemical benzyl alcohol oxidation (BAO) reaction, a model system for studying the biomass upgrading process, can be promoted using Ni-based thin-film catalysts. We will focus on Ni3+ surfaces (lower potential region) under standard operating conditions, correlating BAO onset potentials and the Ni(II/III) redox peak positions across different microenvironments as well as unraveling the mechanisms during BAO. Through the systematic investigation of experimental reaction conditions and computational free energy thermodynamics, this work opens research avenues for the oxidation of related organic molecules from renewable feedstocks. The latter half of the presentation will pivot to the domain of hydrogen fuel cells, centered on the utilization of phthalocyanine-based MOF materials with dual active centers (M-N4 moieties, M1 = amine coordinated metal node, M2 = phthalocyanine center) that can facilitate the ORR. In a combined experimental and theoretical approach, we correlate structural properties (choice and placement of transition metals) with electrochemical performance (activity, selectivity, and material stability) during ORR. Moreover, we highlight metal and site dominance (M1 vs. M2) with insights into possible MOF degradation pathways using preferential metal dissolution profiles. This presentation aims to present a comprehensive understanding of these complex systems and pave the way for practical and scalable solutions to current and future energy challenges.
Structure-property relationships in dynamic polymer networks
Keywords: Engineering.
Chemical Engineering.

Many emerging applications including wearable electronics and e-skins, soft robotics and actuators, and biomaterials, require material platforms with precisely controlled mechanical, electrical, thermal, and optical properties. The practical realization of devices for these applications is often restricted not by the lack of novel designs, but rather by the sparsity of materials with the required properties. Dynamic polymers, which employ both permanent and reversible linkages, offer a promising platform for the design of new materials due to their highly tunable and responsive chemical structures. This dissertation explores structure-property relationships in different dynamic polymer networks with well-defined polymer design and is structured as follows. Chapter 1 introduces the concept of dynamic polymers, provides comparisons to supramolecular polymers and segmented block copolymers, and concludes with emerging applications for these systems. Chapter 2 examines the molecular design rules for spontaneous self-assembly of periodic dynamic polymers into supramolecular nanofibers. Chapter 3 discusses the phenomenon of strain-induced supramolecular structures exhibited by entangled periodic dynamic polymers. Chapter 4 highlights how the clustered nanomorphology exhibited by periodic dynamic polymers can be used to design recyclable underwater adhesives. Chapter 5 explains how immiscible dynamic polymers can be used to achieve autonomous alignment of multilayered soft electronics. Chapter 6 concludes with key observations and on the future outlook of next-generation materials