VictorJuiz/thesis huggingface dataset:
Examining the role of pseudouridine in RNA metabolism and differentiation of toxoplasma gondii [electronic resource]

Although more than 100 RNA modifications have been discovered the biological significance of the majority remains elusive. Pseudouridine (Ψ), the first modified RNA nucleotide discovered, is made in rRNA, tRNA, snRNA, and mRNA by a large family of pseudouridine synthases (PUSs). Despite the fact that Ψ is one of the most abundant, ubiquitous, and highly conserved modifications, it has been difficult to identify the biological function of this modification. Previously our lab identified a PUS (TgPUS1) as being necessary for the parasite Toxoplasma gondii to transition from active to chronic infection. In this work we exploit this Ψ-associated phenotype to determine the role of Ψ in a tightly regulated biological process. To this end Ψs were profiled transcriptome-wide in wild-type parasites, uncovering extensive, regulated pseudouridylation of Toxoplasma and human mRNAs, where Ψ is found unequally distributed within the codon and transcript. PUS1-disrupted parasites were used to identify TgPUS1-dependent Ψs in multiple Toxoplasma mRNAs. As mRNA pseudouridylation was only discovered recently, the biological impact of pseudouridylation on mRNAs has not been characterized. Thus we used these data to examine the abundance and stability of transcripts containing PUS1-dependent Ψs in the presence and absence of the enzyme. Our results show that PUS1-dependent Ψs are found in developmentally regulated transcripts. Loss of pseudouridylation leads to an increase in mRNA abundance, and a modest increase in RNA half-life. Taken together these results provide some of the first evidence that mRNA Ψs may affect mRNA biology.

Keywords: Microbiology and Immunology.
Advisor: Boothroyd John C. primary advisor. Thesis advisor
Bogyo Matthew
Fire Andrew Zachary advisor. Thesis advisor
Sarnow P. (Peter) advisor. Thesis advisor
Expanding the capabilities of mass cytometry data acquisition and analysis [electronic resource]

There has been an influx of novel single cell data acquisition and analysis methods promising to deepen our understanding of the variation within organ systems in healthy and diseased states. These methods are still in their infancy. Herein, I describe two respective innovations I developed for the acquisition and analysis methods. For the former, I describe an adaption of Proximity Ligation Assay to mass cytometry to add protein-protein and protein-nucleic acid interactions to this type of single cell analysis. For the latter, I describe a computational approach to make continuous comparisons between biological conditions across high-dimensional feature space. These methods provide new avenues of research available within the high-throughput high-parameter single cell analysis paradigm.

Keywords: Cancer Biology.
Advisor: Nolan Garry P. primary advisor. Thesis advisor
Crabtree Gerald R. advisor. Thesis advisor
Plevritis Sylvia advisor. Thesis advisor
Experimental investigation of the flow kinematics in model vertical axis wind turbine arrays [electronic resource]

Arrays of vertical axis wind turbines represent a potentially valuable approach to wind energy generation. To date, however, the majority of studies on the fluid mechanics of these arrays have focused on relatively small arrays or on the two-dimensional flows within the horizontal planes. The fluid mechanics of large arrays, in particular the three-dimensional interaction between the flow within the array and the flow around the array, have not previously been examined. Understanding these flows is critical to determining the fundamental scalability of the arrays and therefore in what contexts they might usefully be considered for energy generation. This dissertation reports the experimental examination of the fluid kinematics associated with aerodynamically long arrays of model vertical axis wind turbines. Ten arrays of rotating turbine models were considered, varying the spatial, rotational, and vertical configurations of the turbine models in the arrays. It was shown that there existed a developed flow region within the arrays and that within this region there could exist significant vertical flux of high streamwise momentum flow from above the array down into the array. Taken together, these results suggest that aerodynamically long arrays of vertical axis wind turbines may be physically feasible. Furthermore, the vertical fluxes of streamwise momentum were shown to be driven by complex three-dimensional patterns of both turbulent and mean flows, which in turn were strongly dependent on the spatial, rotational, and vertical configurations of the turbine models in the arrays. These results suggest the possibility for multi-objective optimization of the array, for example balancing the array power output against the turbulence intensity within the array.

Keywords: Mechanical Engineering.
Advisor: Dabiri John O. (John Oluseun)
Koseff Jeffrey Russell primary advisor. Thesis advisor
Eaton John K. advisor. Thesis advisor
Experimental investigation of the surface expression of a canopy-induced shear instability [electronic resource]

Submerged vegetation is a critical component of the nearshore environment, having significant effects on coastal protection and estuarine channel evolution, and providing habitat for many economically and ecologically important species including endangered marine mammals. Field studies of submerged vegetated canopies are often expensive and difficult due to reliance on point sensors that directly access the water column. Remote sensing using whole field imaging offers the potential to overcome the limitations of in situ point sensors. However, in environments strongly impacted by human interaction, remote imaging is typically limited to the free surface. To take advantage of the opportunities presented by remote imaging, we must develop a more robust understanding of the mechanisms governing the surface expression of interactions between flow and vegetation. The body of this dissertation is presented in three main chapters. Each chapter presents the results of a series of experimental investigations into the free surface dynamics of channel flows interacting with a submerged array of rigid cylinders which act as a laboratory analog for submerged vegetated canopies. In Chapter II, the instability of the canopy-induced shear layer is proposed as a potential mechanism by which submerged canopies can be detected, and some of their properties inferred, from observations of the turbulence in the near-surface velocity. The properties of this instability signal as manifest on the free surface are explored, and the limitations on detection quantified. Chapter III presents of the results of experiments using laser refractometry and free surface synthetic Schlieren imaging to demonstrate that the dynamics uncovered in the near-surface turbulent velocity field are correspondingly present in the surface slope field, indicating that the instability signal is actually manifest in free surface dynamics. The spectral differences between the instability signal and some other sources of surface distortion, including wave-like ripples and wind chop, are also discussed. Finally, Chapter IV explores the spatially varying behavior of the instability signal along the length of a submerged canopy patch. It is hoped that this work will provide a fruitful foundation on which a remote sensing platform for the detection and monitoring of sensitive submerged vegetative canopies can be built.

Advisor: Koseff Jeffrey Russell primary advisor. Thesis advisor
Fong Derek advisor. Thesis advisor
Fringer Oliver B. (Oliver Bartlett) advisor. Thesis advisor
Expert crowdsourcing with flash teams and organizations [electronic resource]

Online crowdsourcing marketplaces provide access to millions of individuals with a range of expertise and experiences. To date, however, most research has focused on microtask platforms, such as Amazon Mechanical Turk. While microtask platforms have enabled non-expert workers to complete goals like text shortening and image labeling, highly complex and interdependent goals, such as web development and design, remain out of reach. Goals of this nature require deep knowledge of the subject matter and cannot be decomposed into independent microtasks for anyone to complete. This thesis shifts away from paid microtask work and introduces diverse expert crowds as a core component of crowdsourcing systems. Specifically, this thesis introduces and evaluates two generalizable approaches for crowdsourcing complex work with experts. The first approach, flash teams, is a framework for dynamically assembling and computationally managing crowdsourced expert teams. The second approach, flash organizations, is a framework for creating rapidly assembled and reconfigurable organizations composed of large groups of expert crowd workers. Both of these approaches for interdependent expert crowd work are manifested in Foundry, which is a computational platform we have built for authoring and managing teams of expert crowd workers. Taken together, this thesis envisions a future of work in which digitally networked teams and organizations dynamically assemble from a globally distributed online workforce and computationally orchestrate their efforts to accomplish complex work.

Keywords: Management Science and Engineering.
Advisor: Bernstein Michael S.
Valentine Melissa (Melissa A.) primary advisor. Thesis advisor
Hinds Pamela advisor. Thesis advisor
Explaining the Variation in Non-Classroom Staff in Texas Public Schools

This paper begins to address a gap in the education literature regarding nonclassroom staff. I study non-classroom staff across Texas and find substantial
variation in the staff-to-student ratio at both the school and district level. This
variation has significant ramifications for per-student spending. For instance, the
difference between the 10th and 90th percentile districts in terms of spending is
approximately $700 for support staff and $300 for educational aides. However,
much of this variation remains a puzzle. It cannot be explained by exogenous
school and district demographics, student achievement, or revenue increases.
Although I do find that non-classroom staff are correlated with policy choices like
smaller school size (controlling for population density) and more Special
Education students, these correlations capture only a small fraction of variation.
The wide variation in spending suggests that some staffing models are likely more
cost-efficient than others. If Texas can incentivize or teach local decision makers
to make cost-efficient hiring choices, it may thus be able to reduce unnecessary
costs and improve quality of education by better allocating the cost savings.

Keywords:  Department of Economics
Stanford Department of Economics
Texas
non-classroom staff
per-student spending
Thesis
Advisor: Hoxby Caroline
Exploiting molecular diversity to interrogate T cell recognition and specificities in cancer [electronic resource]

Applying protein engineering to immunological problems can provide insight into understanding the targeted nature of the T cell immune response. T cells have specificity through their T cell receptor for peptides presented by proteins called Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) in humans. This interaction is critical for the immune response to protect the host from foreign pathogens and cancer. By engineering peptide-MHC/HLA libraries for yeast-display, we can mimic the presentation of nearly 1 billion different antigens to 1) survey properties of TCR recognition and 2) identify peptide ligands. We have applied this technology in several capacities -- 1) to uncover general properties of TCR recognition at extremely low affinities by developing a novel peptide 'velcro' that raises the apparent affinity of an interaction in a peptide-dependent manner and 2) to couple the platform with novel statistical algorithms to predict the specificities of TCRs and potential off-target specificities of TCRs with known and unknown specificities, especially those derived from tumor-infiltrating lymphocytes. In application 1, we have uncovered that general principles of TCR cross-reactivity are maintained at extremely low affinities (Kd > 100 μM) as they are at normal affinities (Kd ~ 1-100 μM). The implications of conserved cross-reactivities are important for understanding recognition in positive selection, T cell tonic signaling, and the relationship between specificity and affinity of protein-protein interactions. In application 2, we are pioneering an important technology that provides an ability to directly determine the specificity of a TCR. We have validated the prediction algorithms by identifying the specificity and cross-reactivities of known TCRs and applied this to TCRs of unknown specificity isolated from tumor-infiltrating lymphocytes. We have identified a shared non-mutated target of the immune system in 2/2 colorectal adenocarcinoma patients. Approaches used here can expand the pool of knowledge in T cell biology, receptor specificity, and immune responses in cancer or other T-cell mediated diseases.

Advisor: Garcia K. Christopher
Boyd Scott
Davis Mark M. advisor. Thesis advisor
Engleman Edgar G. advisor. Thesis advisor
Quake Stephen Ronald advisor. Thesis advisor
Exploiting shared structures in large GPS trajectory datasets under uncertainty [electronic resource]

As GPS-enabled devices become ubiquitous, large collections of GPS trajectories have been used for mobility pattern mining and intelligent transportation applications, such as suggesting routes and predicting traffic jams. Compared to traditional data sources, such as traffic sensors, cameras and surveys, trajectory data from moving vehicles have the advantage of being dynamic, cheap, and highly available. Thus they allow true data-driven solutions to many problems that are traditionally solved using modeling and simulation approaches. On the other hand, the majority of available trajectory data contain a large amount of uncertainty, due to GPS noise, low sampling rates and missing data. Such uncertainty can significantly degrade the effectiveness of using large trajectory data in practice. Conventional methods for reducing uncertainty in trajectory data, such as map matching and trajectory interpolation tend to process each trajectory independently, without considering the shared structures in large trajectory data that can improve the processing of individual trajectories. In this dissertation, we present three algorithms that exploit shared structures in large trajectory collections to reduce noise and sample sparsity, and to improve trajectory-based travel time prediction under the difficult scenario of having far less GPS-tracking units than normally required in previous studies. These works make use of different kinds of shared structures, such as popular routes on a road map, trajectory clusters that represent unique traffic flows across trajectory junctions, and recurring traffic patterns over a small neighborhood. They also bring novel insights on how to extract robust knowledge from uncertain data, and how to effectively incorporate learned knowledge to individual trajectory processing tasks.

Advisor: Guibas Leonidas J. primary advisor. Thesis advisor
Kochenderfer Mykel J.
Williams Vassilevska Virginia
Exploring the Relationship between LGBTQ+ Inclusive Education and Queer Identity Formation among Asian and Pacific Islander (API) Youth in the U.S

My research explores the relationship between inclusive education, defined as positive teachings about queer figures in classrooms, and queer identity formation of Asian and Pacific Islander (API) youth. For my study, I combined equity theory with the API Sexual Minority Acculturation Model to guide my interpretation of results. As an exploratory study, I conducted an online survey and five interviews to find the potential benefits inclusive education has on how queer API youth form their identity. The results show that inclusive education, in a boarder sense than is commonly understood, shows promise in helping queer API youth form their identity by synthesizing their racial/ethnic background with sexual/gender minority status – two traits that are oftentimes at odds with each other among APIs. These results may help devise policy that makes education more inclusive by incorporating teachings about queer API figures.

Keywords: inclusive education
LGBTQ+ Asian and Pacific Islander youth
queer identity formation
role models
safety
Stanford Graduate School of Education International Education Policy Analysis
Thesis
Exploring the temporal dynamics of host energetics and metabolism during infection [electronic resource]

Hosts that recover from infection, resilient hosts, pass through three overlapping phases during an infection cycle. In the first phase, the pathogen grows. The host subsequently mounts an immune response and presents clinical symptoms of disease. Ultimately, the resilient host resolves the infection through recovery and repair mechanisms. Scientific studies to date have focused primarily on the identification and understanding of immunological mechanisms and associated pathology, but considerably less time has been spent studying recovery and repair. By shifting our focus to these later events, we stand to learn new things about disease and may identify therapies that improve health during infection and/or speed recovery time. One approach to identifying and testing these mechanisms is to deeply characterize the temporal dynamics of an infection system. Here, we focus our efforts on the study of host energy and metabolism during infection with Plasmodium chabaudi AJ, a murine malarial parasite. As little is known about the energetics of recovery, Chapter 1 reviews literature focusing on the energy and metabolic requirements of immunity. In Chapter 2, we use respirometry cages to characterize an infection cycle with high temporal resolution. To assess the impact of energy in the system, we test glycolytic treatments that alter survival. In Chapter 3, we use a metabolomic approach to monitor changes in host metabolism throughout an infection cycle, and investigate the importance of anti-inflammatory pathways. Chapter 4 synthesizes the results from Chapters 2 and 3, offering new perspectives and opportunities for future research.

Keywords: Microbiology and Immunology.
Advisor: Schneider David (David Samuel)
Covert Markus advisor. Thesis advisor
Idoyaga Juliana
Relman David A. advisor. Thesis advisor
Exploring the αvβ3/β5 Integrin Gated Proliferation of Hippocampal Neural Progenitor Cells

Neural progenitor cell (NPC) proliferation and differentiation is influenced by factors like local cell-to-cell interactions, soluble mitogens and extracellular matrix (ECM) molecules. These factors have been shown to maintain NPC pools and restrict the production of new neurons to neurogenic zones in the adult brain. Previous research has not yet addressed whether the interaction between ECM molecules localized to the subgranular zone, and the NPCs via the αvβ3/β5 integrin receptor could enable the maintenance of the stem cell pool and the production of neurons. Thus, we investigated the gating effects of various (Arg-Gly-Asp) RGD-motif ECM molecules through the αvβ3/β5 integrin receptor on growth factor mediated NPC proliferation. Using hippocampal mouse-derived NPCs that express or lack the integrin αvβ3/β5, we investigated the difference in endogenous proliferation rates, and then tested the gating effect of various ECM substrates via the integrin αvβ3/β5 on Shh, VEGF, and IGF-1 mediated NPC proliferation. Here, we show that NPCs with the αvβ3/β5 integrin have increased NPC proliferation compared to those that lack the integrin αvβ3/β5 when plated on the ECM substrates vitronectin, fibronectin, and collagen. Next, we show that IGF-1 yields a greater increase in proliferation in NPCs that express the integrin αvβ3/β5 compared to those that lack the integrin αvβ3/β5 when plated on vitronectin, fibronectin, laminin, and MFG-E8. This work improves our understanding of the interaction between NPCs and the local microenvironment of the adult brain as we seek to develop the tools to understand and artificially manipulate NPC proliferation and differentiation.

Keywords:  Department of Biology
Biology
Developmental Neurobiology
Adult Neurogenesis
Thesis
Advisor: Palmer Theo
Luo Liqun
An ex-situ study of retained structural changes and densification in oxide glasses recovered from high pressure and temperature using NMR spectroscopy [electronic resource]

This study attempts to understand the pressure effects on the structure and density of glasses recovered from 1-3 GPa pressure using 27Al, 11B, 29Si and 23Na MAS NMR spectroscopy. A quantitative spectroscopic study of the pressure-induced structural changes and densification is conducted on aluminosilicate and aluminoborosilicate glass compositions. We have demonstrated that high-pressure experiments in solid media pressure apparatus conducted at high-pressure and near the glass transition temperature retain much of the pressure-induced structural changes and densification compared to high-pressure experiments above the melting temperature. Our study of Na, Ca and Mg aluminosilicate glasses show that the role of non-bridging oxygen (NBO) in pressure-induced structural changes varies systematically upon changing modifier from Na to Ca to Mg. The network cation coordination (Al) increase are larger for the NBO-rich composition compared to NBO-poor composition in Na aluminosilicate glasses, while both NBO-rich and poor Mg aluminosilicate glasses showed no apparent difference in aluminum coordination increase. In Ca aluminoborosilicate glasses with varying B/Si ratio, we observe both aluminum and boron coordination to rise with pressure. However, the average aluminum coordination and densification increases were larger for the high boron composition compared to that of low boron. In this thesis, we propose a mechanism that describe such interaction between boron and aluminum network cations. We also look at aluminoborosilicate glasses with varying modifier from Ca2+ to La3+ to Y3+ studying the effect of modifier field strength on network cation coordination increases with pressure. Our results show that network cation coordination increases (B and Al) are dramatically larger for smaller and highly charged modifier cations (La and Y) compared to Ca.

Keywords: Geological and Environmental Sciences.
Advisor: Stebbins Jonathan Farwell primary advisor. Thesis advisor
Brown Gordon
Mao Wendy (Wendy Li-wen) advisor. Thesis advisor
The fact of fiction [electronic resource] : race, money, gender and nation in American modernism

This dissertation considers the relationship between American modernist literary forms and what I call the "fact of fiction." The "fact of fiction" refers to the sense, increasing in the modernist era, that the boundaries between real and made up things were more porous than previously supposed, meaning that facts were largely fictional, and fictions were often facts. This was particularly important for what I call "social fictions, " phenomena like race or money that are constructed, but have attained a degree of real-world facticity. As social fictions became apparent as fictions, they created artistic anxiety. I tie this to the modernist interest in self-aware experimentation as well as the complex relationship of modernism to politics. Chapters cover Langston Hughes's revolutionary use of jazz improvisation in response to the social fiction of race, Ezra Pound's reactionary use of imagism in response to Keynesian re-conceptions of money, Ernest Hemingway's refusal to accept the performative nature of gender even as his literary style reveals it, and Claude McKay's plotless revelry in the face of the breakdown of the nation.

Advisor: Moya Paula M. L. primary advisor. Thesis advisor
Jones Gavin Roger
Rasberry Vaughn advisor. Thesis advisor