VictorJuiz/thesis huggingface dataset:
Scalable Systems and Algorithms for Genomic Variant Analysis

With the cost of sequencing a human genome dropping below $1,000, population-scale sequencing has become feasible. With projects that sequence more than 10,000 genomes becoming commonplace, there is a strong need for genome analysis tools that can scale across distributed computing resources while providing reduced analysis cost. Simultaneously, these tools must provide programming interfaces and deployment models that are easily usable by biologists./nIn this dissertation, we describe the ADAM system for processing large genomic datasets using distributed computing. ADAM provides a decoupled stack-based architecture that can accommodate many data formats, deployment models, and data access patterns. Additionally, ADAM defines schemas that describe common genomic datatypes. ADAM’s schemas and programming models enable the easy integration of disparate genomic datatypes and datasets into a single analysis./nTo validate the ADAM architecture, we implemented an end-to-end variant calling pipeline using ADAM’s APIs. To perform parallel alignment, we developed the Cannoli tool, which uses ADAM’s APIs to automatically parallelize single node aligners. We then implemented GATK-style alignment refinement as part of ADAM. Finally, we implemented a biallelic genotyping model, and novel reassembly algorithms in the Avocado variant caller. This pipeline provides state-of-the-art SNV calling accuracy, along with high (97%) INDEL calling accuracy. To further validate this pipeline, we reanalyzed 270 samples from the Simons Genome Diversity Dataset.

Advisor: Joseph, Anthony D
Patterson, David A
Emotion, emotion regulation, and sleep quality in caregivers of patients with neurodegenerative disease

Sleep is a vital biological function, necessary to physical and psychological health. Caregivers of patients with neurodegenerative disease suffer from chronically poor sleep. Research suggests that emotions can influence sleep quality, but little research has examined this relationship in caregivers of patients with neurodegenerative disease. In the present study, objective laboratory measures of emotion and emotion regulation, and a combination of prospectively-reported and objectively-measured sleep quality, were used to examine this important relationship. Caregivers’ physiological and expressive reactivity to emotion-eliciting films was measured in the laboratory. Caregivers’ physiological reactivity to two emotion regulation tasks (suppression, amplification) was also measured. During the week following laboratory testing, caregivers wore an actigraphy wristwatch, which recorded movement and ambient light in order to measure sleep quality, and completed a daily sleep diary. Data were analyzed to test the hypotheses that (a) greater physiological reactivity and (b) greater expressive reactivity would be associated with worse sleep quality during the following week, and to determine whether physiological reactivity to the emotion suppression and amplification tasks was associated with sleep quality./nSleep quality in the present study was largely similar to and for some measures, better than sleep in previously published samples of non-caregiver older adults. Results partially supported the hypothesis that greater physiological reactivity to the films would be associated with worse sleep quality. Greater physiological reactivity to a film chosen to elicit distress was associated with worse sleep quality, whereas greater physiological reactivity to a film chosen to elicit sexual arousal was associated with better sleep quality. Exploratory analyses revealed that the results were reliable across caregivers for two of the three largest neurodegenerative diagnostic groups in the sample, and across caregiver sex. Neither expressive reactivity to the films, nor physiological reactivity to the emotion suppression or amplification tasks, was associated with sleep quality. These findings indicate that caregivers’ physiological reactivity to distressing and sexually arousal stimuli are associated with sleep quality. Interventions that reduce physiological reactivity to distressing stimuli, or that increase caregivers’ physiological reactivity to sexually-arousing stimuli, may improve caregiver sleep and its downstream effects.

Advisor: Levenson, Robert W
Tool Use in Measuring: Second and Fourth Graders' Mediation of Their Linear Estimates Using Rulers and Paper Strips on Number Lines

This dissertation investigates the interplay between second and fourth graders’ use of rulers and paper strips to solve number line measurement problems. Drawing upon and extending Vygotsky’s (1978, 1986) approach to mediation in problem solving, and Saxe’s (2012) treatment of microgenesis of representational activity, I analyzed 36 second and 39 fourth graders’ measurement activity as they participated in videotaped semi-structured interviews. At each grade, students were randomly assigned to ruler, short paper strip, or long paper strip conditions, and solved five number line problems first without the tool available and then five similar problems with the tool available. For each problem, two numbers were labeled (e.g., 4 and 6) and students were asked to place a third number appropriately (e.g., 9). Problems and tools were designed to elicit unitizing strategies (splitting, iterating, counting) as students coordinated tool with target to produce a linear measure. I report findings related to the precision of students’ estimates contrasting tool absent and present conditions, and findings related to students’ adaptation of tools to serve measurement functions. Analyses of students’ precision revealed that with or without the support of tools, fourth graders were more precise than second graders, though the utility of tool varied with tool and problem type. The long paper strip was particularly difficult for second graders, and at both grades, many students rejected using the long paper strip. Students generally became precise with tools when a solving a problem type that displayed a linear unit of 1 instead of a larger unit, though this varied with tool type. On other problem types, tools interfered with precision, and on still other problem types, tools interfered with the precision of second, but supported the precision of fourth graders. Analyses of strategies revealed three levels in students’ ability to coordinate a unitization of tool and target as they tried to adapt tools to serve measurement functions. I argue that these findings can productively inform our understanding of the interplay between tool use in students’ developing measurement activity as well as the design of instructional problem environments to support students’ tool using in linear measurement.

Advisor: Saxe, Geoffrey
Connectivity on the Edge of Empire: Movement, Liminality, and Ritual in the Southern Levantine Drylands

In the ancient Near East, the Sinai, the Negev, southern Jordan and northwestern Arabia/nconstituted a marginal and peripheral landscape, a liminal land considered both lifeless/nand teeming with fantastic creatures and divine powers. However, the position of this/nregion between the more populated areas of Egypt, the Levant, Mesopotamia, and the/nArabian Peninsula marked this landscape as a crossroads for materials and people, a/nmovement of phenomena perpetuated mainly by local mobile pastoral communities. As/nsuch, roadside ritual comprised a major expression and practice of multiple ideologies/nabout the land from earliest times. Sites of ritual along roadsides harnessed multiple,/noverlapping, and intersecting senses of liminality, the potency and danger of being/ninbetween, to lay claim to the land and offer protection against human and suprahuman/ndangers. In this context, roadside ritual sites operated as confluences of interaction for/nmultiple communities and religious traditions in this region. The ways in which these/ncommunities understood and experienced this landscape often drastically differed, and/nthe interaction of these communities generated new and distinct ways of seeing./nThis dissertation utilizes textual, ethnographic, and archaeological materials to explore/nthese phenomena in the sixth through the first millennium BCE, with a focus on the early/nfirst millennium BCE. This period sees the rise of the Neo-Assyrian Empire in ancient/nIraq, which came to dominate much of the ancient Near East in the ninth, eighth, and seventh/ncenturies BCE. Imperial domination inscribed the land with new settlement patterns,/nmonumental architecture, and fortifications that recursively interacted with the ancient/nmeshworks of pilgrimage, subsistence, memory, and liminality already engraved within/nthe landscape. Two ritual sites, Kuntillet ʾAjrûd in the northeastern Sinai (eighth century/nBCE) and Ḥorvat Qitmit in the northern Negev (seventh century BCE) act as case studies that/nboth manifest these ancient traditions of movement and interaction and presage their/nacute intensification in later Hellenistic, Roman, Byzantine, Early Islamic, and Ottoman/ncontexts.

Advisor: Feldman, Marian H.
Porter, Benjamin W.
Understanding Leadership within Comprehensive Early Childhood English Learner Reform

This is an examination of leadership within the implementation of an early learning reform model that centralizes the needs of young English Learners. The English Learner student population continues to grow in California, yet schools and districts have persistently been unable to support their learning needs. The current policy context is driven by a new set of 21st century standards in which language is situated in a more prominent and cross cutting manner. The longstanding failures of our educational systems, along with this policy setting, make this an ideal context to study reform leadership within implementation of a model that is specifically designed to support young English Learners./nThis study is situated in literature focused on systemic reform, English Learner policy and reform, and a review of scholarship about the actors that operate within reforms. The concepts that frame this inquiry are rooted in the socio-political context, shared ownership and partnership, and the crafting of coherence within reform implementation. This is a critical case study of one district, Sequoia Grove School District, in its fourth year of implementation of the Sobrato Early Academic Language model. This design is most appropriate because it enables a deep and thorough examination of the leadership dimensions of reform implementation, a context-driven aspect of school change./nThere are two overarching findings from this study. First, leaders are able to build a coalition embodying shared ownership and collaboration for the reform across actors, though crafting coherence appears to be particularly context specific and complex. Secondly, there are three key socio-political factors that leaders are navigating: 1) the socio-economic context related to declining enrollment; 2) the policy context of transitioning to new 21st century standards; and 3) the unrelenting influence of the accountability framework established within the No Child Left Behind era. This study is written in a time when public education’s legitimacy is being undermined at the federal level in new and extreme ways. Practitioners, policy makers, and researchers committed to understanding and improving education for English Learners should consider the deeply political nature of school improvement efforts that centralize English Learners’ needs.

Advisor: Trujillo, Tina
Attosecond Nonlinear Spectroscopy of Atoms and Molecules

Attosecond pulses produced by high harmonic generation are excellent sources of broadband light in the extreme ultraviolet (XUV). These pulses can be used to study ultrafast electronic and nuclear motion in atoms and small molecules on their few to sub-femtosecond natural timescales by coherent excitation of numerous electronic and vibrational states. In this dissertation, nonlinear wave mixing incorporating attosecond XUV and few-femtosecond near infrared (NIR) pulses is developed on a table-top apparatus in order to probe the resultant time-dependent wavepackets. The transient spectral signatures of wave-mixing processes are recorded with exceptional temporal and spectral resolution in order to reveal electronic structure and follow ultrafast electronic dynamics./nThis dissertation details the development and application of transient wave mixing techniques from the study of electronic excitation in atomic systems to molecular systems with an additional nuclear degree of freedom. Initial experiments examining the Rydberg states of argon were performed in a collinear beam geometry with a single delayed NIR pulse. The NIR pulse was found to induce myriad processes including ionization, coupling to neighboring states, and stark shifting. The numerous overlapping pathways precluded the quantitative application of this technique to the study of more complex systems. Isolation of particular NIR-induced pathways was achieved using spectral shaping in neon and, more generally, through the implementation of a noncollinear beam geometry that produced spatially separated emission features through phase matching. In molecular nitrogen, the anharmonicity of a high-lying electronic state was observed through interferences in individual vibrational levels. The addition of a third, independently delayed NIR beam in these experiments allowed the recovery of the electronic structure of a valence state of N2 that is inaccessible with one photon excitation and was poorly characterized by existing experimental techniques as a result./nThese experiments highlight the capability of transient wave-mixing experiments to sensitively probe and manipulate bound state wavepackets. The multidimensional nature of this technique, with selective detection of signals dependent on pulse sequence and NIR-induced coupling pathway, has been fully established in this dissertation. This work represents a crucial step toward the study of ultrafast electronic dynamics in more complex systems with unprecedented time resolution and atomic level precision.

Advisor: Leone, Stephen R
Neumark, Daniel M
Zero-Dimensional and One-Dimensional Graphene Nanomaterials: Synthesis, Application, and Nanocrystal Composites Thereof

The bottom-up synthesis of graphene nanomaterials has recently emerged as an important approach for accessing carbon materials featuring desirable or exotic electronic properties. The ability to produce these materials with structural precision and synthetic flexibility makes bottom-up synthesis a powerful tool both for understanding materials at the nanoscale and for designing the next generation of high-performance nanomaterials. Although a handful of robust bottom-up synthetic techniques has been developed, investigation has been quite limited with regard to both the types of graphene nanomaterials produced and the applications for which those materials are considered. In this thesis, the extant tools of bottom-up synthesis are applied to the production of novel zero-dimensional and one-dimensional graphene nanomaterials. This includes the use of surface-assisted techniques for the synthesis of unique nanographenes featuring exotic electronic and magnetic properties, facilitated by development of a robust and general solution chemistry methodology to access challenging acene derivatives. This work also examines the unprecedented application of bottom-up synthesized one-dimensional graphene nanoribbons (GNRs) as composite materials with inorganic nanoparticles, and describes the exceptional performance these diverse composites achieve through the rational design of nanomaterial interfaces.

Advisor: Fischer, Felix R
Cognitive Biomechanics of Arboreal Locomotion

The interaction between cognitive control and biomechanics has enabled animal locomotion capabilities that far surpass state of the art mobile robot performance. But there has been little research focusing on the interaction of the cognitive processes, like learning and decision making, with the biomechanics of the animal coupled to the mechanical properties of the environment. Understanding the cognitive biomechanical strategies, specifically how cognitive processes may work synergistically with the unique mechanical properties of the organism in its environment, is likely to inspire future generations of bioinspired search-and-rescue and environmental monitoring robots. In this dissertation, two model organisms were used to study the cognitive biomechanics of arboreal locomotion. First, high speed branch locomotion was examined using the American cockroach, Periplaneta americana. This cockroach is one of the fastest runners relative to its body length. This hexapedal animal uses an alternating tripod to run up to 1.5 meters per second, becoming bipedal at the fastest speeds. Second, the Fox squirrel, Sciurus niger was studied. This arboreal specialist exhibits high performance climbing, branch navigation, and gap crossing via targeted leaping. Fox squirrels demonstrated learning to improve targeted leaping performance, a novel parkour-like wall jumping behavior, and decisions on when to leap that was dependent on the mechanical behavior of the branch and geometric properties of the gap to cross. These discoveries give new insights into the cognitive biomechanics of arboreal locomotion, and represent a promising path towards a principled understanding of canopy navigation.

Advisor: Full, Robert J
Detection and Utilization of Small Molecule Tailoring Groups for Metabolic Engineering

The thesis presented here focuses on the discovery and applications of tailoring enzymes for metabolic engineering goals along two tracks of research. The first track is focused on enzyme discovery and presents a powerful assay called the DNA-Linked Enzyme Coupled Assay (DLEnCA). This assay is readily accessible through common molecular biology techniques, and has the potential be scaled to the level of next generation sequencing and microfluidics. The goal is that DLEnCA will enable any research laboratory to populate enzyme databases (e.g., BRENDA) or have access to a platform for the evolution of novel enzymes and pathways. These capabilities would enable the rapid application of protein engineering for biocatalysts in the tailoring space./nThe second track of research presented here is based on the in vivo application of tailoring enzymes for goals in metabolic engineering. On one level, this is focused on attempting to leverage tailoring enzymes’ role in metabolite detoxification for replacing antibiotics in industrial settings; on the other level, bioproducing valuable glucose-conjugates directly from yeast metabolism. This later focus is centered around the biosynthesis of the high value natural pigment betanin, which is found in select group of plants and utilized as a commercial food dye./nUltimately, the research conducted here seeks to provide tools and lessons that adds to the body of knowledge around the biochemistry and engineering of modified secondary metabolites.

Advisor: Dueber, John E
Place and Biological Aging: Hierarchical Analyses of Neighborhood Changes and Leukocyte Telomere Length Malleability

Background/nUnderstanding why certain population subgroups age faster than others is a pressing public health concern. Few biomarkers consistently predict morbidity and mortality, which has made it difficult to identify high-risk population subgroups earlier in the disease cascade. Telomeres are the repeat sequence at the ends of DNA that protect the cell from damage during each replicative cycle. Telomeres shorten with age, and individual-level exposures may exacerbate telomere length attrition. There is evidence that telomere length has an inverse association with psychosocial stress, poor health behaviors, and chronic diseases. However, multilevel determinants of telomere length remain understudied despite numerous connections among physical and mental health, lifestyle, and place of residence. The extant literature exhibits that better physical and social contexts have a positive association with telomere length./nMethods/nThis dissertation examines the associations among specific features of residential built, social, and socioeconomic environments and the 10-year change in telomere length using data from the Multi-Ethnic Study of Atherosclerosis (2000-2010). Chapter 2 presents cross-sectional findings on the relationship between the physical environment and leukocyte telomere length. Chapter 3 investigates the association between changes in physical environment features and the 10-year change in leukocyte telomere length. Chapter 4 explores the interplay among changes in neighborhood socioeconomic status, social context, and leukocyte telomere length. Physical environment features comprise of the physical activity and food environment. The social environment includes measures of aesthetic quality, safety, and social cohesion./nSignificance/nThis dissertation presents the first studies to examine changes in neighborhood features and change in telomere length. The findings suggest that telomere length is a biological marker that is sensitive to changes in built, social, and socioeconomic contexts. Thus, health policy interventions should target specific features of the residential environment to support healthy aging trajectories.

Advisor: Mujahid, Mahasin S
Harmonizing Technological Innovation and End-of-Life Strategy in the Lighting Industry

Today’s globalized economy largely follows a linear “take-make-dispose” model, where natural resources are extracted to manufacture products that are eventually disposed of in a landfill. Growing constraints on key resources such as energy sources, water and materials coupled with the global increased demand for goods and services render this linear model unsustainable. To address these issues, companies and governments alike are attempting to develop circular processes that preserve natural resources and reduce the global waste burden./nAs new technology products are designed and brought to market, consideration must be given to how products will be managed throughout the life-cycle as well as their end-of-life fate. This research uses light-emitting diode (LED) lighting products as a case study to assess how technological innovation can be harmonized with end-of-life strategies to create increasingly closed-loop systems, a key step to bringing the circular economy to fruition. The work will: 1) examine current end-of-life strategies, 2) analyze how various design choices and failure modes influence a product’s options at end of life, 3) assess how economic costs and environmental impacts vary among end-of-life strategies, and 4) develop a framework to determine the optimal management and end-of-life strategy for a given lighting product. Key methods employed will include product analysis, life-cycle assessment, and cost optimization. The end goal of the research is to provide a methodology for assessing the economic and environmental implications of end-of-life strategies for a given technology product.

Advisor: Horvath, Arpad