VictorJuiz/thesis huggingface dataset:
Understanding the response of gene networks to environmental perturbation [electronic resource]
Keywords: Genetics.

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.
Understanding white shark (Carcharodon carcharias) coastal behavior and energy expenditure using biologging tags
Keywords:  Department of Biology
biology
white shark
carcharodon carcharias
animal behavior
biologging
biotelemetry
energy expenditure
Thesis

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.
Underwater robotic terrain-relative navigation using acoustic shadows in sonar imagery [electronic resource]
Keywords: Aeronautics and Astronautics.

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.
Unraveling hedgehog signaling by single-molecule tracking [electronic resource]
Keywords: Chemistry.

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.
The unspoken heard [electronic resource] : a critical analysis of race and language in digital learning platforms
Keywords: Education.

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.
U.S. House prices [electronic resource]
Keywords: Management Science and Engineering.

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.
Using Viral Tools to Dissect Neural Circuits: Exploring the Nigrostriatal and Claustrocingulate Pathways in Mice
Keywords:  Department of Biology
Biology
Neurobiology
Claustrum
Anterior Cingulate Cortex
Substantia Nigra Pars Compacta
Striatum
Optogenetics
Light Sheet Microscopy
Thesis

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.
Using X-ray scattering and transient absorption to probe global and local structural dynamics of the bimetallic photocatalyst [Ir2(dimen)4]+2 [electronic resource]
Keywords: Chemistry.

Mechanistic pathways of inorganic homogeneous catalyts are determined not only by the reactive electronic structure but also the precise arrangement of the atoms within the catalyst. Furthermore, without knowing precisely how nuclear structure and electronic structure affect each other, computational methods may not be able to accurately portray the behavior of certain inorganic complexes. Ir2(dimen)4{+2} (dimen = 1,8-diisocyano-p-menthane) is such a system. X-ray crystallography has long supposed that this particular d8-d8 dimer has two thermally accessible minima on the same ground state and more recent temperature dependent solution spectra support this but, so far, computational efforts have not been able to recreate a double minimum potential energy surface. However, a simple quasi-empirical mechanical spring model has been proposed in the literature which features two minima with a shallow barrier. Herein, a combination of transient absorption (TA) and time-resolved X-ray diffuse scattering (XDS) is used to determine that the potential energy surfaces of ground and excited state follow this model. When exciting extremes of the HOMO-LUMO band which have been inferred to correspond to each ground state minima, we are able to use vibrational wavepacket analysis to qualitatively confirm that the ground state possesses two minima while the excited state has only one, as predicted in the literature model. Furthermore, we are able to observe ground state interconversion in real-time, occuring the in ~10ps regime, confirming that interconversion is thermally accessible but with a barrier height over five times larger than predicted. Furthermore, a combination of XDS and Born-Oppenheimer Molecular Dynamics is used to produce a global picture of Ir2(dimen)4{+2} in solution in which a detailed molecular solvent response is characterized for the excited state. Using this approach, it was found, both computationally and experimentally, that he methyl groups prefer to coordinate to the ground state and recoordinate via the nitrile group in the excited state which is quite unexpected and could not be predicted by continuum models or electrostatic arguments.
Utilizing C. elegans as Environmental Metal Biosensors to Determine the Effect of Weak Metal-Chelators in the Presence of Heavy Metals
Keywords:  Department of Biology
Biology
Transgenic C. elegans
GFP reporter
metal stress response
weak chelators
CKDu glyphosate
Thesis

Glyphosate, originally patented as a metal chelator, is a primary active ingredient in many herbicides used worldwide. While glyphosate alone is thought to be non-toxic, the possibility that its metal-chelating properties could contribute to its toxicity in vivo has not been tested. Normally, strong chelators cause bound metals to be inert, and therefore easy to dispel. However, a weaker chelator such as glyphosate could allow metal ions to pass into the body until the complex reaches a region with low pH, which can lower the stability of the metal-chelator complex in vitro. With a weaker metal-chelator bond, the complex may dissociate, leaving the heavy metal ions in the tissue, potentially causing toxicity. However, there is a lack of in vivo systems to test this hypothesis. Because of their responsiveness to metal stress, C. elegans have proven useful as environmental biosensors. For this work, a collection of transgenic GFP (green fluorescent protein) reporter strains was generated utilizing CRISPR/Cas9 to study the hypothesis. Each strain bears GFP (green fluorescent protein) under the regulation of genes involved in the metal stress response pathway and exhibit dynamic metal- and dose-dependent GFP induction. The strains were then exposed to varying conditions of both metal and chelating agents at low and high pH. The results show an ability to quantify modest and dose-dependent changes in metal response in living animals, and hence to evaluate conditions under which the weak chelator might potentiate effects seen with metal-only conditions. This work establishes a technical foundation for further study of chelation-dependent effects of metal deposition and toxicity. Future research may provide valuable insight into the potentially toxic interactions of the widely-used herbicide ingredient, glyphosate, and demonstrates the need for further investigation.
Utilizing consumer technologies to design accessible medical training and imaging tools [electronic resource]
Keywords: Mechanical Engineering.

The development of modern medicine has led to an unfortunate, but popular assumption: that advanced medical technologies are exorbitantly expensive and almost exclusively relegated to big hospitals. This work aims to subvert this assumption by providing a new model for carrying over the ten-fold reductions in cost and size found in the consumer space to the medical world. It accomplishes this task by outlining three key steps to incorporating consumer technologies into medical devices: modularization, simplification, and recycling. This work is then grounded in two novel systems which utilize the proposed framework to drastically reduce their cost and size relative to current options. The first is a handheld volumetric ultrasound system that is portable and can be produced for 10% of the cost of current volumetric ultrasound systems. The second is a virtual reality surgical trainer that packs flat, runs on a phone or tablet, and can be produced for 1% of the cost of current surgical trainers. The low-cost and portability of these new devices serve to not only make the current level of care more accessible, but also to open up entirely new applications.
VCAM1 is upregulated by an aged systemic milieu and regulates hippocampal neurogenesis through brain endothelial cell-mediated interactions
Keywords:  Department of Biology
VCAM1
brain endothelial cells
hippocampal neurogenesis
systemic inflammation
neurodegeneration
aging
biology
Thesis

Brain structure and function are known to decline steadily with age, and recent models of aging implicate the circulatory environment in this process. Experiments in which young mice are exposed to aged blood demonstrate that pro-aging factors in the blood of old individuals induce hallmarks of brain aging, such as increased neuro-inflammation and a decline in neurogenesis. The inhibitory factors present in aged blood are still being identified, and whether these factors cross the highly selective blood brain barrier or act primarily through peripheral interaction with brain endothelial cells (BECs) remains unknown. In this study, we aimed to elucidate the mechanisms underlying regulation of Vascular Adhesion Molecule 1 (VCAM1), an adhesion molecule upregulated in BECs in response to aged blood and systemic inflammation, and assess whether Vcam1 deletion can rescue the decline in adult neurogenesis. We show that brain endothelial VCAM1 increases in expression in vitro and in young mice exposed to aged plasma. Additionally, while it has previously been shown that injection of aged plasma inhibits hippocampal neurogenesis in young mice, here we demonstrated that genetic deletion of Vcam1 prevents these inhibitory effects of aged plasma on hippocampal neurogenesis, suggesting that activated BECs inhibit neuronal regeneration through VCAM1-mediated peripheral interactions. Collectively, our results indicate that VCAM1 is involved in the regulation of adult neurogenesis in response to age-related systemic inflammation, making the adhesion molecule a therapeutic target for ameliorating the decline in brain function characteristic of old age.
Violence, justice, and reconciliation [electronic resource] : the politics of transitional justice in societies recovering from war
Keywords: Political Science.

Serious human rights violations committed during civil war erode the political and social fabric in decisive ways. In addition to the physical violence and tremendous emotional trauma, they also fundamentally change the way in which citizens view their state -- the very entity whose existence is premised on protecting and securing the safety of its citizens. This dissertation explores how post-conflict governments respond to such war crimes, crimes against humanity, and other serious human rights violations committed during internal armed conflict. Why do some governments aggressively punish perpetrators of human rights abuse, while others embrace a policy of truth-seeking or even forgiveness? What impact do these policies have on the relationship between the state and its citizens? Combining formal theory with econometric techniques and case studies from Sub-Saharan Africa and Latin America, this dissertation seeks to explain the diversity of government uses of transitional justice policy. Further, original experimental evidence from Guatemala casts light on the long-lasting consequences of these policy choices on the political perceptions of citizens affected by war.