VictorJuiz/thesis huggingface dataset:
Beyond antibodies : high-throughput technologies for the development of synthetic affinity reagents with novel functions

The accurate measurement of molecules is of crucial importance for a wide range of both basic and applied research applications. In particular, we need to measure the abundances and activities of biomolecules (proteins, carbohydrates, lipids, and nucleic acids) to understand their biological function which form the basis of life and diseases. To this end, we rely on affinity reagents, which are molecules that specifically bind to their target molecule. While antibodies are the current 'gold standard' of affinity reagents, there is a growing need for alternative reagents. Aptamers, often referred to as chemical antibodies, are short oligonucleotides that can bind to their targets with high specificity and affinity and can be engineered to perform novel functions that cannot be achieved with conventional antibodies. In this dissertation, I will discuss the development of three high-throughput technologies that enable the creation of synthetic DNA aptamers with novel functions. The first project describes a method to generate base-modified aptamers that can recognize protein glycoforms with exquisite specificity, which is challenging for antibodies. The second project describes the creation of a massively-parallel screen which enables the multiplexed selection of aptamers with extraordinary specificity that can distinguish metabolites with minimal difference in their chemical structure. Finally, I describe a screening technology for rapidly generating optically-responsive molecular switches from an existing aptamer which can be used directly as biosensors. As a whole, these studies provide valuable new tools that help address many of the challenges associated with the development of aptamers that are suitable for real-world applications

Keywords: Chemical Engineering.
Advisor: Dunn Alexander
Soh H. Tom
Pitteri Sharon
Beyond Big Cities: A Contextual Analysis of Human Trafficking in Salinas

For her capstone project, Lina Karamali focused on issues of human and labor trafficking in California, specifically within the city of Salinas. Driven by a deep concern for the rise of human trafficking cases and statistics, Lina’s project examines legislative measures that have historically aimed to address this issue but with varying outcomes. Using Salinas as a critical case study, Lina demonstrates how anti-trafficking policies and laws can often overlook rural cities, like Salinas, that while not very populous, remain a hub of human trafficking activity. Through her research, Lina hopes to offer policy recommendations that may apply to places like Salinas, which share some commonalities with larger urban centers but also present challenges unique to smaller, rural communities that are agricultural and more isolated.

Keywords: Human trafficking
Exploitation
Legislative Policies
Text
Thesis
Beyond enhancer-promoter contact : leveraging deep learning to connect super-resolution DNA traces to transcription

Chromatin architecture plays an important role in gene regulation. Recent advances in super-resolution microscopy have made it possible to measure chromatin 3D structure and transcription in thousands of single cells. However, leveraging these complex datasets with a computationally unbiased method has not been achieved. In this dissertation, I present a deep learning-based approach to better understand to what degree chromatin structure relates to the transcriptional state of individual cells. Furthermore, I explore methods to "unpack the black box" to determine in an unbiased manner which structural features of chromatin regulation are most important for gene expression state. I apply this approach to the Optical Reconstruction of Chromatin Architecture dataset of the Bithorax gene cluster in Drosophila and show it significantly outperforms previous contact-focused methods. This work finds the structural information is distributed across the domain, overlapping and extending beyond domains identified by prior genetic analyses. Individual enhancer-promoter interactions are a minor contributor to predictions of activity

Keywords: Genetics.
Advisor: Boettiger Alistair 
Bhatt Ami (Ami Siddharth)
Kundaje Anshul
Winslow Monte
Beyond the Great Commission: Exploring the Diversity of Churches as Public Service Organizations

Christian churches in America have a strong commitment to serving the needy in their local communities; with the array of humanitarian services that churches offer today, the programming of these religious institutions increasingly resembles that of secular social service organizations. This is why churches as a homogenous organization type are consistently acknowledged in the literature on public service sectors for their collective impact on the public service fabric of the country. However, existing research has failed to acknowledge the circumstantial, organizational and theoretical distinctions between churches in the public service sector, nor how those distinctions are related to the diversity of ways in which churches engage with their communities. This study has two parts: the first is the analysis of interviews and census data to answer the questions, “What differences exist in how churches engage in public service? What factors correspond to these differences?” Findings show that the diversity of churches’ public service involvement comes primarily from ecological factors as well as church-level features and resource differences. Clergy visions for public service also play a role, except among three churches with similar intensities and modes of service but in which the theoretical views of service held by their clergy differ substantially. The second portion of this study further explores this finding among these three churches with the question, “What motivates clergy to do public service?” These motivations are understood through this study’s literary-historical analysis, as well as with observations of religious services and public service offerings. This array of research methods, despite its shortcomings, offers a promising direction for future research to evaluate churches and their leaders with more precise consideration for their variation as public service providers within their communities.

Keywords:  Urban Studies
church
service
public service
religious
Thesis
Advisor: Kahan Michael Bruce
Luhrmann Tanya Marie
Beyond the toolkit : lessons on implementation from a comparative study of a hybrid professional development for teachers of English learners

Students classified as English learners (ELs) typically exhibit low academic achievement, relative to their peers who only speak English. One possible reason why ELs continue to underperform is because their teachers often receive meager training in strategies to support ELs' concurrent linguistic development and content acquisition. Scholars have addressed this concern by studying how specific professional development (PD) programs impact ELs' test scores and other numeric indicators of academic achievement. This dissertation diverges from current approaches to the study of PD for teachers of ELs by taking an systems-oriented approach. It considers PD context rather than content, with the goal of identifying factors relevant to the implementation of a hybrid PD for teachers of ELs. To that end, I conducted two rounds of semi-structured interviews (n=41) with 24 stakeholders (5 administrators, 5 coaches, and 14 teachers) from four schools, who all participated in the same hybrid PD. Interviews revealed that myriad factors interacted to influence PD implementation. At the organization level, coupling between the hybrid PD and routines of alignment and teacher supports impacted implementation. How stakeholders perceived the coach role—and the degree to which those perceptions were aligned—was also important. Finally, implementation was impacted by teacher motivation and, to an even greater extent, self-efficacy. Ultimately, this dissertation seeks to support educators to develop systems of PD for teachers of ELs that are sensitive to sources of organizational variation, and that take into account coach and teacher-level variables. Attention to these contextual factors may increase PD effectiveness and, accordingly, improve outcomes for students classified as ELs

Keywords: Education.
Advisor: Solano Flores Guillermo 
Bromley Patricia (Assistant professor of education)
Silverman Rebecca D.
Biocompatible materials for fluorescence imaging in the second near-infrared window

Fluorescence imaging in the second near-infrared window (1,000-1,700 nm, NIR-II window) benefits from reduced tissue scattering, absorption and autofluorescence compared to imaging in shorter wavelength windows, allowing deep tissue imaging with high spatial resolution. In particular, imaging in the long wavelength end of the NIR-II window (1,500-1,700 nm, NIR-IIb window) minimizes scattering and completely eliminates autofluorescence, affording tissue penetration up to sub-centimeter level. However, most NIR-II/NIR-IIb fluorophores rely on nanoparticles with long retention in the body, which limits their potential for clinical translation. This work aims to develop biocompatible nanomaterials for fluorescence imaging and cancer therapy in the NIR-II window. Firstly, a biocompatible theranostic nanoparticle was prepared based on polymeric micelles encapsulating an organic NIR-II dye FE and an anti-cancer drug paclitaxel. The theranostic agent demonstrated high tumor uptake in vivo as well as good therapeutic efficacy. Secondly, a hydrophilic cross-linked surface coating strategy (denote P3 coating) was devised, allowing rapid excretion of a wide range of nanomaterials, including erbium-based rare-earth nanoparticles (ErNPs), lead sulfide quantum dots (QDs), superparamagnetic iron oxide nanoparticles and carbon nanotubes. Two-plex NIR-IIb in vivo molecular imaging of PD-L1 and CD8 with P3-coated ErNPs and QDs revealed infiltration of cytotoxic T lymphocytes in the tumor microenvironment after immune checkpoint blockade therapy. Lastly, a deep learning-based approach was applied to transform fluorescence images in the shorter wavelength near-infrared window (900-1,300 nm) to images which resembled the ground-truth NIR-IIb images. With deep learning image translation, in vivo imaging with FDA-approved fluorophores such as indocyanine green (ICG) achieved an unprecedented signal-to-background ratio, which facilitated cancer imaging and imaging-guided tumor resection surgery

Keywords: Chemistry.
Advisor: Dai Hongjie
Boxer Steven G. (Steven George)
Cui Bianxiao
Biogenesis of telomerase RNA in homeostasis and disease

Disruptions in RNA metabolism and errors in RNA processing are increasingly linked to a diverse set of human diseases. Telomerase, the ribonucleoprotein that extends telomeres to prevent replication-dependent chromosomal shortening, is composed of the reverse transcriptase TERT and the noncoding RNA (ncRNA) telomerase RNA component (hTR). Defects in hTR or in any of the protein cofactors required for hTR biogenesis precipitate telomere shortening and the stem cell disorder dyskeratosis congenita. Despite the critical importance of hTR in telomere homeostasis, the events surrounding hTR transcription, 3' end formation, and post-transcriptional regulation remain poorly understood. To interrogate the hTR biogenesis pathway in an unbiased kinetic fashion, we developed nascent 3' RNAend --Seq, which enabled us to isolate early hTR precursors and measure processing rates in vivo under different genetic conditions. We found that hTR is transcribed as an extended molecule with a short genomically encoded tail. These extended hTR precursors convert to the mature hTR species with delayed kinetics compared to related small ncRNAs. The hTR precursors can be oligoadenylated shortly after transcription by the poly(A)polymerase PAPD5 and can be deadenylated by the disease-associated enzyme Poly(A)ribonuclease (PARN). The relative activity of these two enzymes and the extent of of hTR precursors sets the maturation rate of hTR. In the absence of PARN, oligoadenylated hTR precursors stall and are degraded, causing overall hTR loss and telomere shortening. However, in the absence of both PARN and PAPD5, hTR precursor maturation is normalized and telomere lengths are maintained. We found that the H/ACA domain of hTR together with the RNA-binding protein dyskerin could direct formation of the hTR 3' end, recruit poly(A)polymerase activity, and confer sensitivity to regulation by oligoadenylation. A screen for additional enzymes involved in hTR 3' end formation revealed the DEDDh 3'-5' RNA exonuclease ISG20L2, which works together with PARN to promote maturation of the hTR 3' end and ensure accumulation of telomerase. These data reveal that mature hTR is generated through a feedforward circuit in which post-transcriptional oligoadenylation controls RNA maturation kinetics. Perturbations of hTR maturation rates read out into changes in steady-state telomerase levels and telomere length. Alterations in RNA maturation kinetics may prove to contribute to the mechanisms of other RNA based human diseases

Advisor: Artandi Steven E.
Attardi Laura
Chua Katrin Faye
The biology of human invariant natural killer T cells and regulatory T cells in allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplant (HSCT) can be used as a curative treatment for patients with hematologic malignancies; however, acute graft-versus-host disease (aGVHD) is a highly inflammatory disease and a major complication that can occur following this therapy. Two populations capable of regulating immune responses are invariant natural killer T (iNKT) and regulatory T (Treg) cells, but their biology in the clinical aGVHD setting is not fully understood. Thus, I examined how iNKT and Treg cells regulate aGVHD in the clinical setting. To study human iNKT cells, I used a high-dimensional, data-driven approach to devise a framework for parsing human iNKT cell heterogeneity. A population of iNKT cells characterized by HLA-DR expression was found to be enriched in aGVHD patients and associated with exhaustion markers and a Th1 profile, suggesting a loss of immunoregulatory mechanisms in aGVHD. This phenotype, along with other discovered phenotypic markers, were also associated with aGVHD outcomes, suggesting that iNKT cells can potentially serve as a biomarker and therapeutic target in allogeneic HSCT. Beyond these potential clinical implications, a new framework was discovered for understanding human iNKT cell heterogeneity that advances our knowledge of human iNKT cell biology. As our understanding of fundamental human Treg cell biology is more advanced, a phase I/II study of the infusion of Treg cells with hematopoietic stem cells to prevent aGVHD in adult patients undergoing myeloablative allogeneic HSCT for hematological malignancies has been started and is ongoing. Clinically, greater than grade II aGVHD was noted in two patients in the first cohort of five patients who received cryopreserved Treg cells. In a second cohort of seven patients who received fresh Treg cells and single agent aGVHD prophylaxis, none developed aGVHD. A key finding is that patients in the second cohort showed immune reconstitution comparable to patients who underwent allogeneic HSCT on standard-of-care. Together, these studies reveal new insights into the biology of human iNKT and Treg cells in the clinical aGVHD setting

Advisor: Meyer Everett 
Negrin Robert S.
Davis Mark M.
Gentles Andrew J. 
Maecker Holden
Biomechanical optimization of cardiac valve repair operations

Valvular heart disease is a highly prevalent and increasingly clinically addressed problem worldwide, with evolving treatment guidelines supporting earlier intervention as well as valve repair over replacement when possible. Most valvular pathologies are rooted in biomechanical changes, such as the nuanced interplay between tissue degeneration, valve kinematics, and cardiac function. However, advances in repair techniques have progressed in the clinical arena primarily based upon anatomic and physiologic premises. Thus, by using biomechanical engineering tools to investigate valvular disease and analyze treatments, quantitative data can be harnessed to optimize surgical repair techniques and devices. An innovative left heart simulator was designed and produced to study the mechanics of mitral and aortic valve specimens throughout the cardiac cycle. This ex vivo analysis enables rapid and safe testing of surgical operations and offers new insight into the nuances of valvular disease and repair. This dissertation first details significant advancements to heart simulator technology: the development of low-profile chordal strain gauges, coupled image-guided robots to replicate papillary muscle motion, and two mitral annular dilation devices. Building on this heart simulator technology foundation, novel disease models were developed and analyzed: Barlow's mitral valve disease, aortic regurgitation from cusp prolapse, and bicuspid aortic valve disease. Finally, facilitated by the simulator and modeling advancements, I analyzed contemporary operative techniques and devices: valve-sparing root replacement, posterior ventricular anchoring neochordal repair, and transapical neochordal repair devices. A novel artificial papillary muscle device was also designed and tested to integrate with current minimally invasive mitral valve repair devices under trials. The research outlined herein has resulted in a significant clinical impact on aortic and mitral valve repair, and this work will continue to serve as a foundation for future investigations of clinical therapies for valve disease that can be rapidly translated to intraoperative patient care

Keywords: Mechanical Engineering.
Advisor: Levenston Marc Elliot
Woo Joseph
Ennis Daniel B.
Birthday problems and rates of convergence for Gibbs sampling

This thesis is concerned with classical topics in probability theory: the birthday problem and mixing time for Markov chains. Some of this work is contained in \cite{Ottolini2020, Gerencsr2019}. \\ \\ The first two chapters deal with variations of the classical birthday problem: what does the maximum of $ discrete random variables with a given sum $ look like as $ and $ are large? The classical birthday problem is concerned with the maximum box count when =O(\sqrt n)$ balls are dropped into $ boxes. In the first chapter, variations of this problem are studied for a large class of allocation models when $ and $ are of the same order, using the tools of conditional limit theory. In the second chapter, this is done when the random variables follow an hyper-geometric distribution, and the result is used to give sharp estimates on the expected number of correct guesses in certain card-guessing games with feedback.\\ \\ The last two chapters are concerned with the Gibbs sampler, a Markov chain used to sample from intractable measures on product spaces. The third chapter analyzes the evolution of Hamming distance between a Gibbs sampler and its stationary distribution, in the case the latter is close to a product measure. This situation covers many statistical mechanical models at sufficiently high temperature, and we investigate this in details for the Curie-Weiss model. The fourth chapter analyses the performance of a Gibbs sampler used to sample from a class of measures introduced by de Finetti in the analysis of partially exchangeable binary data. \\ \\

Keywords: Mathematics.
Advisor: Diaconis Persi
Chatterjee Sourav
Dembo Amir
Black Women's Representation in Television: a Deep Dive into the History of Television and the 1990s Sitcom Living Single

Throughout history, Black women have been ostracized from reputable representations of themselves in the media. Over time, scholars began to notice that these representations were doing much to harm the social and emotional wellbeing of Black femme audiences (Anderson and Merritt Williams 1983, Noble and Tynes 2016). To understand the depths of these issues and to present an answer to how television may rise to the occasion of presenting socially just representations of Black women, I answered the questions: How has the scientific and technological design of television systems changed? How has this evolution affected access to “socially just" representations on television? What is “The Television?” To answer the next four questions, I focused on the first network-television show ever created by a Black woman, Living Single, as I surmise that this show provides one model for “socially just” representations which Noble and Tynes seek for Black girls. Therefore I ask: How has Living Single influenced representation in the context of non-familial centered Black experiences? How did the creator of the show use humor to normalize the “Angry Black Woman” trope, mental health, and homosexuality in the narratives of everyday Black women in the 1990s through reflection politics, instead of condemnation politics? Finally, I answer how television has evolved in “socially just” representations. I conducted exhaustive research on the history of television and technology through a host of sources to better understand the accessibility of socially just representations of Black women, followed by a multi-episodic analysis of the 1990s television show Living Single, and an analysis of the legacy of this culturally significant show.

Keywords: Living Single
Bowser, Yvette Lee
Television
Women, Black
Technology transfer
Text
Thesis
Boosting macrophage appetites for cancer immunotherapy

Recent progress in the field of cancer immunotherapy has demonstrated the potential for harnessing the innate immune system in order to effectively treat cancers. Macrophages are an especially attractive target for cancer immunotherapy, as they are abundant in the vast majority of tumors and are capable of detecting and directly clearing cancer cells through phagocytosis. However, recent work has demonstrated that cancer cells are capable of evading clearance by macrophages within tumors by overexpressing innate immune checkpoint molecules called "don't eat me" signals. The prototypical "don't eat me" signal, CD47, is a surface protein expressed highly in many cancers, and monoclonal antibodies targeting the CD47 innate immune checkpoint have demonstrated great clinical promise, and even cures, in hematologic malignancies including myelodysplastic syndromes and AML. Despite these successes, CD47 blockade does not promote complete phagocytosis in all types of cancers, which suggests the presence of additional "don't eat me" signals. Through this work we have identified two previously-unknown innate immune checkpoints that exist between macrophages and cancer cells, MHC class I:LILRB1 and CD24:Siglec- 10, and we demonstrate the therapeutic promise of blocking these novel "don't eat me" signals in order to maximize macrophage function, reduce cancer growth, and extend survival in vivo. Collectively, this work suggests a new paradigm that innate immune checkpoints are redundant and employed in a tissue-specific and even tumor-specific manner, and makes clear the need to measure the collective expression of these "don't eat me" signals in order to optimize patient responses to both innate and adaptive immunotherapies

Advisor: Weissman Irving L.
Jaiswal Siddhartha 
Majeti Ravindra