VictorJuiz/thesis huggingface dataset:
Uncovering virus-host interactions using haploid and CRISPR-Cas knockout screens [electronic resource]

As humans we are under constant threat from viruses. They have evolved to infect our cells, hijack cellular components and machineries, and interfere with our innate immune system in order to propagate and spread. For example, they bind to cell surface molecules to enter our cells, utilize intracellular factors to make genome copies and assemble new virus particles as well as disable viral nucleic acid sensing. The identification of host factors, which facilitate infection, can provide important insights in the molecular interactions of the virus with its host, and may ultimately lead to the discovery of new antiviral targets. However, the diploid nature of the human genome has been a challenge for high-throughput interrogation using knockout genetics. The work in this thesis describes two genetic screening approaches, haploid and CRISPR-Cas screens, which have overcome this obstacle and yielded important insights into the biology of important human viruses. We describe how these techniques resulted in the identification of host components used by dengue virus and other mosquito-borne flaviviruses (including Zika, yellow fever and West Nile virus) for infection. We further show how these insights can be translated in the development of a novel, specific antiviral compound. Furthermore, we reveal a comprehensive set of host factors for hepatitis C virus, a more distantly related member in the Flaviviridae family, and show remarkable divergence in the molecular interactions with its host compared to the mosquito-borne flaviviruses. Next, we demonstrate how haploid screening led to the discovery of cell components important for Monkeypox virus, a DNA virus related to the etiological agent of smallpox. Lastly, we utilize our screening approach to study entry of the adeno-associated virus, a virus with gene therapy application, which resulted in the discovery of its universal entry receptor. Overall, this thesis demonstrates the robustness and versatility of knockout screens in the study of virus-host interactions. Genetic screens are powerful tools for the identification of critical cell components in viral infections, enabling development of therapeutic applications for current and future epidemics.

Keywords: Microbiology and Immunology.
Advisor: Carette Jan
Boothroyd John C. advisor. Thesis advisor
Davis Ronald W. (Ronald Wayne)
Sarnow P. (Peter) advisor. Thesis advisor
The underclass and the American class structure [electronic resource]

This study is about the growth within the American class structure of an "underclass, " or a class of people outside of the social division of labor. The underclass has come to be a common feature of advanced capitalist economies, and while this study examines the phenomenon in a particular time and place, it is also intended to highlight more general principles about the relationship between an underclass and the society to which it belongs. The analysis draws on both survey data and qualitative material. In Chapter 1, I use survey data to measure the size and growth of the underclass in the U.S. between 1968 and 2015, and I identify four distinct subgroups within the underclass that represent niches in the class structure where people have tended to cluster. In Chapter 2, I use survey data to examine the social integration of members of the underclass, and I assess whether this varies over time or across demographic groups. In Chapter 3, I draw on over four decades of ethnographic fieldwork and interviews to present a more qualitative description of the underclass and its relationship to the rest of society. The first two chapters create a broad sketch of the underclass, showing its location in time and place and rough indicators of its social integration across different contexts. The third chapter then brings that sketch to life with rich descriptions of underclass members.

Keywords: Sociology.
Advisor: Grusky David B. primary advisor. Thesis advisor
Rosenfeld Michael J.
Young Cristobal advisor. Thesis advisor
Understanding environmental occurrence of soil-transmitted helminths in rural Kenyan households [electronic resource]

Globally, about 1.5 billion people are infected with at least one species of soil-transmitted helminth, with most infections occurring in South and Southeast Asia and Sub-Saharan Africa. Soil-transmitted helminths (STH) are a type of intestinal worm that require incubation in soil as part of their lifecycle. STH infection can cause malnutrition, anemia, stunting, and in severe cases, blocked intestines and perforated organs. Children are particularly impacted by the symptoms of infection. Although soil is crucial to the lifecycle of STH, few studies have examined the role of soil in STH transmission and control. Major knowledge gaps exist about the extent of STH contamination in the environment, how it drives infection, and how it can be prevented. There are also no standard laboratory methods for detection of STH in environmental samples. This dissertation focuses on the discovery of STH eggs in potential transmission routes—soil, hands, and produce—in rural Kenyan households, creation of improved methods for detection of STH in soil, and evaluation of the impact of a sanitation intervention on STH contamination in household soil. By elucidating the role of soil in STH transmission, we can further inform soil-transmitted helminth elimination efforts.

Advisor: Boehm Alexandria primary advisor. Thesis advisor
Pickering Amy (Amy Janel) primary advisor. Thesis advisor
Luby Stephen
Understanding Sapling Recruitment and Oak Regeneration Limitation: A Meta-Analysis and Experimental Manipulations

Oak forests worldwide play a vital role in maintaining species diversity and critical ecosystem processes; yet over the last 40 years, the coverage of oak forests in California has decreased by over 50% due to a combination of extensive browsing, higher rates of desiccation due to climate change, and the rapid spread of a pathogenic disease known as sudden oak death. As a result, efforts to bolster the decreasing rates of regeneration in oaks have become increasingly important. Several scientists and conservationists have tried to remedy the situation by inhibiting browsing.
This thesis explores the effectiveness of herbivore exclosures in encouraging oak regeneration and sapling recruitment, and presents the results of a meta-analysis of 32 published studies on the subject. The meta-analysis is accompanied by data that were collected in 2016 from an ongoing exclosure experiment at Stanford’s Jasper Ridge Biological Preserve (JRBP). For three sympatric oak species, 75-pairs of seedlings were identified in 2009 and protected from or exposed to deer, a primary herbivore of oak saplings worldwide. The meta-analysis was conducted to assess the impact of this ecological factor –ungulate herbivory– worldwide, and to assess the consistency of those studies with the JRBP data. My results suggest that ungulate herbivory represents an important population regulation factor in oak populations, and that the increased abundance of these herbivores constitutes an ecological bottleneck for the natural regeneration of the populations of these emblematic trees, locally and globally.

Keywords:  Department of Biology
oak regeneration
sapling regeneration
seedling recruitment
herbivory
ungulate browsing
exclosure
meta-analysis
sudden oak death
Quercus
Thesis
Advisor: Dirzo Rodolfo
Gordon Deborah
Understanding Schwann cell mechanisms of myelin debris clearance after peripheral nerve injury [electronic resource]

Enabling axon regeneration after central nervous system (CNS) injury remains a major challenge in neurobiology. One of the major differences between the injured peripheral nervous system (PNS) and injured CNS is the pro- and antiregenerative responses of their glial cell populations. Schwann cells undergo a remarkable transformation after PNS injury into a specialized cell type that coordinates and aids peripheral nerve regeneration and repair. The work that follows is based on the hypothesis that by better understanding the Schwann cell response to injury, we might devise novel strategies for overcoming CNS regeneration failure. Specifically, we perform mechanistic studies of a key function of the post-injury Schwann cell, myelin clearance, and provide evidence that Schwann cells clear myelin debris using TAM receptor-mediated phagocytosis as well as autophagy. In collaborative studies, we also examine how the Schwann cell response to injury is altered in the aged PNS, in which regeneration and functional recovery are delayed. We demonstrate that Schwann cell plasticity is decreased in the aged PNS, resulting in delays in Schwann cell repair functions, including myelin clearance. Coupled with recent advances in our understanding of the CNS glial response to injury, these findings provide improved mechanistic insight into why the CNS does not regenerate and how the glial response to CNS insult might be manipulated to better support CNS repair.

Keywords: Developmental Biology.
Advisor: Barres Ben
Clandinin Thomas R. (Thomas Robert)
Fuller Margaret T.
Talbot William
Understanding the response of gene networks to environmental perturbation [electronic resource]

Large-scale screens of genetic interactions (GIs) in Saccharomyces cerevisiae have been a crucial tool for both defining overall cellular network topology and characterizing novel gene function. However, most screens have been limited to characterizing gene interaction networks in a single environment. Moving beyond this static view of the cell requires a major technological advance to increase the throughput and ease of replication in these assays. Here, I develop and apply two novel pooled screening methodologies for conditional measurements of genetic interactions. Both approaches utilize DNA double-barcoding systems, coupled with amplicon sequencing, to estimate fitness in a highly parallel fashion. These screens of up to 17,000 double-barcoded mutant strains, in up to five growth conditions, illustrate that conditional measurements can increase the number of observed interactions by 3-fold. Furthermore, statistical methods implemented on these datasets support the hypothesis that functional classification using GI screening data is improved by assaying more conditions. Finally, new links during respiratory growth between Ras-nutrient sensing pathway members are found with both the COG complex and a gene of unknown function. Together, this work provides key insights into how the gene network changes upon environmental perturbation and establishes the technology for future studies to further expand our knowledge in this domain.

Keywords: Genetics.
Advisor: Sherlock Gavin primary advisor. Thesis advisor
Bassik Michael advisor. Thesis advisor
Pringle John R.
Skotheim Jan
Understanding white shark (Carcharodon carcharias) coastal behavior and energy expenditure using biologging tags

Recent developments in the field of biologging have enabled researchers to study the fine-scale behaviors of large pelagic predators like the white shark (Carcharodon carcharias). I report on the use of a CATS camera tag to record high-definition video-image capture with a suite of biologging sensors, including a tri-axial accelerometer, to archive high frequency data on the fine-scale movements of the animal it is attached to. This study utilizes five deployments of CATS Cam tags on white sharks at two pinniped rookeries along the coast of California to analyze how the sharks budget their time and energy. My analyses indicate white sharks spend a large majority of their time (98.83% ± 0.6245) engaging in steady-state continuous swimming activity, which may be associated with a minimal cost transport. Differences in tail beat frequency (TBF) and overall dynamic body acceleration (ODBA) were observed throughout the deployments and indicate that most of the time these sharks travel at relatively consistent but low speeds and that high TBF and ODBA rates representing periods of increased activity are rare. Quantifying these fine-scale behaviors white sharks engage in while inhabiting coastal environments is essential to building a more complete understanding of their life histories and ecosystem dynamics and informing our conservation efforts.

Keywords:  Department of Biology
biology
white shark
carcharodon carcharias
animal behavior
biologging
biotelemetry
energy expenditure
Thesis
Advisor: Block Barbara
Goldbogen Jeremy
Underwater robotic terrain-relative navigation using acoustic shadows in sonar imagery [electronic resource]

This thesis presents a new underwater Terrain-Relative Navigation (TRN) method that provides a vehicle position estimate with respect to a prior seafloor topography map. This method uses imaging sonars rather than profiling sonars, and is to the knowledge of the author the first TRN work that correlates imaging sonar measurements with topography maps for localization. Imaging sonars are commonly found on operational underwater vehicles, due to their large area ensonification and low size, weight, power, and cost. However, the nature of imaging sonars makes their use with topography maps challenging. Imaging sonars measure the intensity of surface reflections versus time of flight, as opposed to directly measuring the shape of the reflecting surface as profiling sonars do. As such, comparing imaging sonar measurements to a seafloor topography map is not straightforward. An innovation of this work is the use of acoustic shadows in sonar imagery as the information source, as acoustic shadows are primarily geometric in nature, and thus predictable from a topography map. By enabling TRN with imaging sonar through the use of acoustic shadow data, this work introduces a TRN capability for typical operational underwater remotely-operated vehicles (ROVs) that has been largely unavailable to date, and can augment TRN performance for autonomous underwater vehicles (AUVs) in areas where the vehicle is operating over locally flat terrain, but where there is terrain information to the sides, and/or at low altitudes. The methods presented in this thesis are validated through field demonstrations on ROVs and AUVs operated out of the Monterey Bay Aquarium Research Insitute (MBARI). Meter-level localization accuracy is demonstrated on ROV trials using a mechanically-scanned imaging sonar, where the ROV was held motionless during sonar image formation. Further, meter-level localization accuracy is demonstrated on AUV trials using sidescan sonar, where the AUV was moving as the measurements were made. The results presented here are the first demonstrations of successful localization with respect to prior topography maps using imaging sonar measurements.

Keywords: Aeronautics and Astronautics.
Advisor: Rock Stephen
Close Sigrid
Enge Per advisor. Thesis advisor
Unraveling hedgehog signaling by single-molecule tracking [electronic resource]

Since the first optical detection of single molecules in 1989, there has been a rapid growth in applications, especially in biophysics. Single-molecule techniques are well suited for investigating the heterogeneity of populations, which is of particular interest in living systems that are defined by their complexity. Single-molecule fluorescence microscopy incorporates three main advantages of fluorescence imaging: biocompatibility, target specificity, and extreme sensitivity, and then improves upon the spatial precision by an order of magnitude relative to traditional, diffraction-limited imaging (down to tens of nanometers). This dissertation describes the application of single-molecule tracking to the investigation of the Hedgehog signaling pathway in mammalian cells. Hedgehog signaling is an essential developmental signaling pathway. Aberrant signaling leads to birth defects and has been implicated in a wide variety of cancers. Despite its oncological importance, the precise molecular mechanisms of signal transduction remain unclear. Previous work showed that pathway transduction involves the translocation of signaling proteins into and out of the primary cilium, a small organelle that protrudes from the cell surface. By tracking individual pathway proteins Patched1 and Smoothened with high spatial and temporal resolution (30 nanometers, 100 Hz), we have discovered and characterized changes in their dynamic motions within the cilium when the pathway is active or inactive at the most basic, functional level. In particular, we have found that the propensity for these proteins to bind at the base and tip of the cilium is a function of the pathway activation state. Moreover, aspects of the behavior of Smoothened are anticorrelated with the behavior of Patched1. These results have helped elucidate pathway function, and are applicable to the development of specific anti-cancer drugs that aim to disrupt particular steps of Hedgehog signaling. Chapter 1 provides an introduction to single-molecule imaging and an overview of Hedgehog signaling. Chapter 2 details the construction and operation of a fluorescence microscope with single-molecule sensitivity and outlines the various methodology utilized in later chapters. Chapters 3 and 4 describe our investigation of the Hedgehog signaling transducers Smoothened and Patched1, respectively. Chapter 5 summarizes our results and highlights several promising directions for further investigation. Finally, Chapter 6 contains the source code and manuals for the tools developed in these projects.

Keywords: Chemistry.
Advisor: Moerner W. E. (William Esco)
Boxer Steven G. (Steven George)
Dai Hongjie
The unspoken heard [electronic resource] : a critical analysis of race and language in digital learning platforms

Recent national attention on digital technology has led many to question how new technology can truly enhance students' learning as it transforms classrooms and curricula. Scholars, school leaders, and teachers who rush to integrate the 'best' technology in both formal and informal learning spaces often overlook the ways that race, language, and culture shape the digital learning platforms and tools that they give students. This research seeks to expand upon contemporary frameworks for understanding multimedia learning and racial priming, by exploring how race and language influence student learning. To explore these topics empirically, I crafted the following research questions to guide my dissertation: 1) What can we learn from students' productions when they are given options to design their own digital texts? What patterns do we find in terms of the images, voices, and cultural attributes they select when given power over design decisions? 2) How does giving students opportunities to design visual content in interactive digital science textbooks influence their sense of agency? 3) How does variance in the visual representation of racial characteristics and language delivery within interactive digital textbooks influence student's learning (as measured by digital assessments)? 4) How does matching interactive digital history textbook characters' racial identity with that of students' races influence those learners' sense of belonging and engagement with the subject matter? Specifically, this dissertation examines students' use of digital books, and analyzes quantitative data from unit assessments to track academic development— linking it back to targeted culturally responsive multimedia content that students added to digital history books. Qualitative analyses examined data from audio and video observations of the deployment of a digital e-book unit, assessment feedback from both teachers and students, and interviews discussing the impact of culturally responsive content found in the curriculum. This study seeks to further develop a theory for multimedia pedagogy to help digital content providers and educators to more effectively consider race, language, and culture in the development of digital education content that supports student learning.

Keywords: Education.
Advisor: Brown Bryan Anthony primary advisor. Thesis advisor
Pea Roy D. primary advisor. Thesis advisor
Antonio Anthony Lising
Barron Brigid advisor. Thesis advisor
U.S. House prices [electronic resource]

In this thesis, I develop a deep learning model for predicting house prices in the U.S. House price prediction has been increasingly important to many sectors of the economy, such as real estate, mortgage investment and risk management, and government property tax collection. Among all the factors, foreclosure is believed to have a huge impact on house prices. When the real estate bubble burst after the 2008 subprime crisis, there has been a significant portion of sales being foreclosed. This motivates researchers to investigate how foreclosure impacts house prices and by which channels it happens. Here I use an unprecedented dataset provided by the data vendor CoreLogic of over 100 million housing transactions across the U.S. from 2004 to 2014. Within my deep learning framework, I handle missing data through an efficient imputation method, address spatial and temporal effects through new features created, and finally achieve a superior out-of-sample predictive performance on datasets across the country. With the fitted model, I further explore the relationship between foreclosure discount and other variables such as the underlying house price, the age of the house and the neighborhood house price, which couldn't be fully characterized by previous linear models. I find significant regional differences as well as universal patterns across different areas.

Keywords: Management Science and Engineering.
Advisor: Giesecke Kay primary advisor. Thesis advisor
Lai T. L. advisor. Thesis advisor
Pelger Markus advisor. Thesis advisor
Using Viral Tools to Dissect Neural Circuits: Exploring the Nigrostriatal and Claustrocingulate Pathways in Mice

Viral tools are uniquely positioned to isolate and study neural circuits since their intrinsic properties bridge systems and molecular neuroscience. Here, we present two applications of viral tools that reveal novel aspects of the nigrostriatal pathway and the claustrocingulate pathway. In the first project, we examined heterogeneity in the dopaminergic neurons of the substantia nigra pars compacta (SNc) that project to the dorsal striatum. We used TRIO (tracing the relationship between inputs and outputs), a multi-virus monosynaptic tracing approach, to demonstrate that SNc neurons that project to the dorsal medial striatum and dorsal lateral striatum preferentially receive reciprocal inputs from their defined projection region in the dorsal striatum. These two nigrostriatal dopamine neuron subpopulations subsequently were described to have distinct biophysical properties and activity patterns during free behavior. In the second project, we examined the claustrum (CLA), a small brain region found between the cortex and the striatum that forms reciprocal connections with almost all cortical areas. The thin, irregular structure of the CLA has made this region difficult to study to the exclusion of the surrounding cortical structures. Using a brain-wide computational search we found that the anterior cingulate cortex (ACC) receives strong inputs from the CLA, but not from surrounding regions. By taking advantage of this connectivity, we used anterograde and retrograde viral tracing techniques to specifically express genetically encoded fluorophores in cortically-projecting claustrum neurons, and claustrum-projecting cingulate neurons. By combining anatomical tracing with the tissue clearing technique CLARITY, we produced a brain-wide visualization of the reciprocal and cross- hemispheric connectivity of the claustrocingulate pathway. Using optogenetics, we stimulated ACC-projecting CLA neurons in awake, behaving mice, revealing an anxiogenic effect. This anatomical characterization and determination of a causal, behaviorally relevant role of the claustrocingulate pathway is an important and enabling step forward in understanding the function of the claustrum.

Keywords:  Department of Biology
Biology
Neurobiology
Claustrum
Anterior Cingulate Cortex
Substantia Nigra Pars Compacta
Striatum
Optogenetics
Light Sheet Microscopy
Thesis
Advisor: Deisseroth Karl
Luo Liqun