VictorJuiz/thesis huggingface dataset:
Standardizing enteroid culture for intestinal radiotherapy modeling

Enteroids are self-organizing, three-dimensional (3D) cell clusters that mimic native intestinal tissue and offer an alternative to traditional two-dimensional (2D) and in vivo models. Enteroids contain a variety of intestinal cell types and mimic tissue architecture. While similarly expandable and affordable to traditional 2D cell culture, enteroids better recapitulate the 3D microenvironment. Enteroids can also be derived from patient-biopsies, providing a human-specific alternative to animal models. The current standard of culturing enteroids is within basement membrane extract (BME) that is derived from the matrices surrounding mouse sarcoma. Although enteroids form and grow efficiently within BME matrices, these matrices are inherently variable and cannot be easily tuned. In the second chapter of this thesis, we present a defined, engineered matrix that overcomes these limitations. Specifically, we pair Hyaluronan (HA) with Elastin-Like Protein (ELP) to form the HELP matrix. The HELP matrix supports the formation, growth, and long-term culture of primary murine and human enteroids. We demonstrate the independent tuning of the following matrix properties in HELP: 1) ligand concentration (specifically the fibronectin mimicking ligand RGD), 2) stiffness, and 3) viscoelasticity. In the third chapter of this thesis, we leverage the enteroid model to explore the effects of conventional (CONV) and ultra-high dose rate (FLASH) radiation on healthy intestinal tissue. Radiation is especially damaging to intestinal tissue due to its highly proliferative nature. Fortunately, recent work has demonstrated the potential for ultra-high dose rate delivery to effectively ablate cancerous tissue, while mitigating damage to healthy tissue. While promising, much of this work has relied on murine or 2D cell culture models. In this thesis, we demonstrate the radiation of enteroids derived from healthy primary human intestinal tissue and observe cellular and molecular level differences between CONV- and FLASH-irradiated groups. In summary, this thesis describes: an engineered matrix that was designed to standardize enteroid culture (Chapter 2) and the application of enteroids to investigate intestinal response to radiation (Chapter 3).

Keywords: Medicine.
Stem Cell Biology and Regenerative Medicine.
Advisor: Heilshorn Sarah
Desai Tushar
Rankin Erinn
State law and tribal justice in Iraq, (1914-2022)

Scholars of the British Empire lavish great attention on structural changes brought on by the imposition of the Mandate in Iraq in 1921. Exploring the Tribal Criminal and Civil Disputes Regulation (TCCDR) archives----over twenty thousand files of judicial proceedings from across Iraq covering the 1925 -- 1958 period----gave me reason to believe that many more stories remained untold. The TCCDR provided a legal framework for the prosecution of tribal disputes through a combination of state magistrates and customary authorities. It offered a full-fledged appellate system by way of petitions. In impressive displays of resiliency and agency, Iraqis manipulated often complacent authorities to set the terms of interactions, thereby tempering the overarching impact of state consolidation. The voluminous number of petitions shows the proficiency with which Iraqis appropriated legal tools available to them. More so, my dissertation breaks new ground as the first in-depth examination of the TCCDR's legacy in post-1958 Iraqi legislation. The main overarching claim of the final chapters is, contrary to the recurring paradigm that tribes are empowered by state weakness, that customary justice mechanisms are profoundly crippled by government failure. After the collapse of the Iraqi State in 2003, the withdrawal of security forces and ensuing corruption resulted in the dislocation and fragmentation of traditional power structures. This translated into the disruption of tribal justice. Ultimately, the recurrence of protracted vendetta cycles, punctuated by outbreaks of armed confrontation, is not a sign of tribal vigor. Rather, such violence should be understood as one of the ramifications of war impacting Iraqi society, and the resulting state failures

Keywords: Humanities and Sciences.
History.
Advisor: Crews Robert D.
Barakat Nora Elizabeth
Rodrigue Aron
Schmidinger Thomas
Statistical analysis of scientific machine learning

Massive data collection and computational capabilities have enabled data-driven scientific discoveries and control of engineering systems. However, there are still several questions that should be answered to understand the fundamental limits of just how much can be discovered with data and what is the value of additional information. For example, 1) How can we learn a physics law or economic principle purely from data? 2) How hard is this task, both computationally and statistically? 3) What's the impact on hardness when we add further information (e.g., adding data, model information)? I'll answer these three questions in this thesis in two learning tasks. A key insight in both two cases is that using direct plug-in estimators can result in statistically suboptimal inference. For the first learning task, the thesis focus on variational formulations for differential equation models. I discuss a prototypical Poisson equation. I provide a minimax lower bound for this problem. Based on the lower bounds, I discover that the variance in the direct plug-in estimator makes sample complexity suboptimal. I also consider the optimization dynamic for different variational forms. Finally, based on our theory, I explain an implicit acceleration of using a Sobolev norm as the objective function for training. The second learning task this thesis discuss is (linear) operator learning, which has wide applications in causal inference, time series modeling, and conditional probability learning. I build the first min-max lower bound for this problem. The min-max rate has a particular structure where the more challenging parts of the input and output spaces determine the hardness of learning a linear operator. Analysis also shows that an intuitive discretization of the infinite-dimensional operator could lead to a sub-optimal statistical learning rate. Then, I'll discuss how, by suitably trading-off bias and variance, I can construct an estimator with an optimal learning rate for learning a linear operator between infinite dimension spaces. I also illustrate how this theory can inspire a multilevel machine-learning algorithm of potential practical use.

Keywords: Engineering.
Advisor: Blanchet Mancilla Jose
Ying Lexing
Ryzhik Leonid
Statistical analysis supports pervasive RNA subcellular localization and alternative UTR regulation

Understanding the subcellular localization of RNA molecules across different cell-types and tissues provides a window into previously unknown biology and disease. Low-plex RNA imaging technologies, where only a handful of RNA species could be observed in a single experiment, have been transformed by novel spatially resolved imaging and sequencing techniques which can simultaneously investigate thousands of genes. Named ``Method of the Year'' in 2019 by Nature Methods, the field of spatially resolved transcriptomics continues to accelerate in resolution, sensitivity, and ease of use. Large and exciting datasets have been produced from these efforts, but have been underutilized to discover subcellular RNA localization. We introduce a novel statistical framework to identify RNA subcellular localization patterns in publicly available datasets. We detect that a majority of investigated genes have non-random RNA distribution, and often differential distribution between cell-types. We've combined our analyses of spatial datasets with standard, spatially-naive, single-cell RNA sequencing to further identify genes which have subcellular localization patterning correlated with RNA isoform usage to generate testable hypotheses which we've collaborated with others to successfully validate. Spatial Transcriptomics is rapidly evolving, and we expect that our contribution of a flexible and statistically-sound algorithm will be applicable for the impending influx of spatial datasets

Keywords: Medicine.
Biochemistry.
Advisor: Salzman Julia
Harbury Pehr
Krasnow Mark
Statistical and computational problems in low-rank matrix estimation

This dissertation explores several problems in the realm of low-rank matrix estimation. A primary focus is on understanding the statistical and computational limitations. From a practical perspective, understanding such limitations not only provides practitioners with guidance on algorithm selection, but also in some cases spurs the development of cutting-edge methodologies which improve on the state of the art. Within this theme, this dissertation explores and partially answers the following two questions: (1) Given a large-scale low-rank matrix corrupted by random noise, how much information can we accurately infer from the limited observations? (2) How do restrictions on computational resources affect information retrieval? A secondary focus of this dissertation is on developing algorithms that sample from the posterior in the context of low-rank matrix estimation. A standard machinery to fulfill this task is based on Markov Chain Monte Carlo (MCMC) algorithms. However, rigorous guarantees are often difficult to obtain for MCMC algorithms of common use. This dissertation contributes to this line of work from an alternative perspective: We propose an alternative class of efficient algorithms based on diffusion processes that come with rigorous guarantee. This dissertation is organized as follows: We describe the problem in Chapter 1. Chapter 2 studies low-rank matrix estimation from an information-theoretic perspective, and Chapter 3-4 analyzes the effects of limited computational resource. In Chapter 5, we design a sampling algorithm that works well with the low-rank model. Standalone versions of each chapter can be found in [154, 50, 151]

Keywords: Humanities and Sciences.
Statistics.
Advisor: Montanari Andrea
Johnstone Iain
Schramm Tselil
Statistical explorations of deterministic functions

In this thesis, we discuss several ways that statistical approaches can be used to investigate black box functions. In the first part of the thesis, we consider the mean dimension, a statistical property of functions concerning how important the interactions between the inputs matter. We show that the mean dimension for some functions, like Gaussian radial basis functions or ridge functions, can vary widely while other functions, like multiquadric radial basis functions, converge to one under weak conditions. In the second part of the talk, we consider probing neural networks, an strategy in which we examine the intermediate outputs as a way to learn more about the mechanics of the overall network. By using tSNE and a class-specific analogue of principle components, we can visualize the progression of how the classifications are made. Further examination are made with tours, an visualization technique that animates interpolations between pairs of projections

Keywords: Engineering.
Advisor: Owen Art B.
Candès Emmanuel J. (Emmanuel Jean)
Friedman J. H. (Jerome H.)
Sterol side-chain methylation in uncultured bacteria

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.

Keywords: Sustainability.
Earth System Science.
Advisor: Welander Paula
Francis Christopher
Sperling Erik
Stories of Makokoba

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.

Keywords: Zimbabwe
Southern Rhodesia
township
tourism
ethnographic
Text
Thesis
Advisor: Campbell James
A story of their own : 20th-century Jewish trans narratives in German and Yiddish

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.

Keywords: Humanities and Sciences.
German Studies.
Advisor: Daub Adrian
Eshel Amir
Fonrobert Charlotte Elisheva
Kronfeld Chana
Strain-tuning charge density wave order in rare earth tritellurides

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.

Keywords: Humanities and Sciences.
Applied Physics.
Advisor: Fisher Ian R. (Ian Randal)
Hwang Harold Yoonsung
Kivelson Steven
“Strangers and Pilgrims on the Earth”: Early Modern English Pilgrimage, 1536-1684

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.

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
Advisor: Stokes Laura
Treharne Elaine
Como David
Strategies for managing naturally occurring contaminants in groundwater basins of the Central Valley, California

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.

Keywords: Sustainability.
Advisor: Fendorf Scott
Luthy Richard G.
Wong-Parodi Gabrielle
YingSamantha