VictorJuiz/thesis huggingface dataset:
Characterization of mouse Bmp5 regulatory injury element in zebrafish wound models
Keywords: Developmental Biology.

The body plan and tissues of an organism are built during development through a series of repeatable and ordered events. Restoring the body plan or the integrity of a tissue following injury is more complex, since no two injuries are exactly alike. Zebrafish, Danio rerio, are champion tissue regenerators, and I begin this dissertation with a review of regeneration biology, specifically through the lens of zebrafish tail regeneration. One emergent theme is that key signaling molecules that specify patterning are used in both development and following injury. However, little is known about how these molecules are re-activated. I focus on understanding the re-activation of one of a classic group of signaling molecules: Bone Morphogenetic Proteins (BMPs). Previous studies have mapped a large "injury response element" (IRE) in the mouse Bmp5 gene that drives expression in bone fractures and other types of injury. Here I show that the large mouse IRE regulatory region is also activated in both zebrafish tail resection and mechanosensory hair cell injury models. Using the ability to test multiple constructs and image temporal and spatial dynamics following injury responses in fish, I have narrowed the original size of the mouse IRE region by over 100-fold and identified a small 142 bp minimal enhancer that is rapidly induced in both mesenchymal and epithelial tissues after injury. These studies identify a small mouse sequence that responds to evolutionarily conserved local signals in wounded tissues and suggest candidate pathways that contribute to BMP reactivation after injury. Mammals have lost much of their capacity to regenerate; reclaiming some of this ability would be of great significance to human health. I discuss potential therapeutic applications suggested by this work, as well as possible roles for the IRE in human diseases beyond acute injuries. I also discuss the tradeoffs that guide evolutionary modifications to the IRE and injury enhancers generally. Together, this work adds new detail to our understanding of how organisms meet the challenge of growing tissue outside the predictable events of development
Characterization of the crystallization dynamics of phase change materials via electron diffraction
Keywords: Materials Science and Engineering.

Phase change materials (PCMs) are semiconducting alloys that rapidly and reversibly switch between an amorphous, or glassy state and a crystalline, or ordered state via electrical and optical pulses. The two phases have optical and electrical properties that vary by orders of magnitude, which means that they can be used in fast, non-volatile memory devices. However, the complex nucleation and growth processes that underlie the rate-limiting step of switching from the amorphous to crystalline state remain to be understood. In the first part of this thesis I describe how the single-pulse, high temporal resolution capabilities of the MeV Ultrafast Electron Diffraction (MeV-UED) instrument at the SLAC National Accelerator Laboratory were used to explore the transient structure of laser-melt-quenched PCMs, such as pure Sb, as they crystallize. Antimony's optical properties vary as a function of its thickness, and has shown PCM-like behavior below a critical thickness of the film. Given the fact that MeV-UED gives a direct, in-situ structural observation of the transient liquid structure, we use this technique to explore the thickness dependent aspects of the crystallization process in Sb. In the second part of this thesis I demonstrate via in-situ electron diffraction that femtosecond optical excitation above a threshold fluence of the amorphous, as-deposited, PCM Ge2Sb2Te5 induces large, 100 µm-scale single crystals, more than two-orders of magnitude larger than prior reports. Transmission electron microscopy shows that these large crystals are dewetted regions with a face-centered cubic structure. Energy-dispersive X-ray spectroscopy indicates that the crystals have the same composition as the initial amorphous phase. I will present a theoretical model which shows that this arises from a crossover from a nucleation-dominated crystallization regime to a growth-dominated crystallization regime, and I show that the measured grain size is consistent with Johnson−Mehl−Avrami−Kolmogorov (JMAK) crystallization theory for temperatures near the melting temperature. The ability to grow macroscopic single crystals from an amorphous material, and on arbitrary amorphous substrates, opens up a large area of potential applications, as well as new opportunities for tuning the nucleation, growth, and switching characteristics of phase-change materials. This work provides a new understanding of the rate-limiting crystallization step in PCMs and what gives them their unique properties
Characterize change in carcinogen susceptibility in loss of RB1 mutants
Keywords: Biology.

The distribution of initial DNA damage acquisition, repair rate and distribution of mutation are strongly influenced by global and local chromatin structure of the genome. Specifically, heterochromatic regions of the genome tend to acquire more DNA damage, repair slower and accumulate more mutations. However, whether losing functions of a chromatin modifier could alter carcinogen susceptibility remains unknown. We generated a CRISPR knock out mutant of RB1 (RB1KO), a known tumor suppressor that regulates heterochromatin structure in the genome. Comparative analysis of the genome wide map of UV damage in RB1KO and wild type reveals both local and global changes of carcinogen susceptibility in RB1KO. For instance, closed domain, as well as pericentric and subtelomeric regions of the genome become more susceptible in RB1KO. More importantly, some cancer driver genes, such as telomerase reverse transcriptase(TERT), becomes more susceptible to UV. Overall, our study demonstrates for the first time that the disruption of a tumor suppressor can alter global carcinogen susceptibility, potentially influencing mutation distributions. We established that the maintenance of proper global genome architecture and regional chromatin structure can potentially regulate DNA damage acquisition upon carcinogen exposure
Characterizing cilium disassembly in the developmental program of chytrid fungi
Keywords: Biology.

Chytrids are one of the only known groups of ciliated fungi and have important ecological roles in soil and aquatic environments. However, very little is known about their cell biology. In order to make chytrids more amenable to study, I have developed various tools to facilitate the use of chytrids as model organisms. Focusing on the non-amoeboid chytrid Rhizoclosmatium globosum and the amoeboid chytrid Spizellomyces punctatus, I have characterized these chytrids' life cycles, optimized imaging techniques, and made preliminary attempts at transformation. I have also identified select genes in their genomes and found that both R. globosum and S. punctatus have most of the expected centrosome and cilium associated genes. However, only S. punctatus has a full set of branched actin nucleation related genes associated with amoeboid motility. After developing these chytrid related tools and resources, I next sought to use these chytrids to study cilium disassembly. Cilia are protrusions from cells containing a tubulin-based structure called an axoneme. They can be involved in motility and sensory functions; however, due to the modified centrioles found at their bases that are used in mitosis, cilia need to be disassembled for progression through the cell cycle. Cilium disassembly is an understudied process, and most of what has been discovered has been found in Chlamydomonas reinhardtii and cultured mammalian cells, which undergo two types of cilium disassembly: gradual shortening and fast severing. However, while chytrids can sever their cilia under stressful conditions, they generally undergo a separate mechanism where their cilia are retracted into their cell body. Thus, a non-model organism is required to study a process that cannot be found in common model systems. I have found that R. globosum and S. punctatus have a common cilium disassembly mechanism of reeling in their axonemes into their cell bodies. However, amoeboid S. punctatus has additional, faster mechanisms of ciliary compartment loss and lash-around retraction, and its initiation of retraction is at least partially actin dependent. Once the axoneme is internalized, its tubulin is degraded over the course of about two hours in both species in a partially proteasome dependent manner. Axoneme disassembly also seems to be partially proteasome dependent, indicating that it is coupled with axonemal tubulin degradation. Overall, I was able to develop tools for chytrid fungi to better characterize cilium retraction and the fate of internalized axonemes
Characterizing dusty hypervelocity impact plasma plume dynamics and effects
Keywords: Aeronautics and Astronautics.

Impacts on spacecraft by dust and orbital debris are a common occurrence. These impacts are termed hypervelocity impacts and have enough energy to vaporize and ionize some of the material in the area of the impact, creating a plasma. Complicating the dynamics is the possibility of non-vaporized ejecta which can interact with the plasma altering the plume dynamics or forming a dusty plasma. An electromagnetic pulse (EMP) can result from these impacts and subsequent expansion of plasma that is potentially dangerous to spacecraft electronics. The focus of this dissertation is understanding and putting in context the results from an experimental campaign at the NASA Ames Vertical Gun Range light gas gun. Non-vaporized charged ejecta is successfully measured with a new set of plasma sensors designed specifically for this experiment. Dust is found to transport a significant amount of plasma through dust-plasma interactions and was found to be unaffected by the applied external electric fields. The neutral background affected the plume dynamics during the experiments. Plumes resulting from impacts on metal targets are separated into two expansion regions. A Rayleigh-Taylor instability is found to form on the inner expansion region at the contact surface between the plume and background gas as the plume is slowed by around 10 km/s. Two different types of FLASH hydrodynamic modeling is used for the first time to expand on analytic modeling and capture how the plume properties evolve under the influence of the gas dynamics. These simulations show that significant plume heating occurs at the contact surface where there is an increased plume density due to the plume bunching as it slows. The heating may contribute to additional ionization leading to the dust moving through a more dense plasma than would be present during an impact in a vacuum. A new EMP mechanism, rapid target charging, is observed to occur from the interaction between the outer expansion and the charged target. Additional evidence for this EMP is newly found in past experiment campaigns. This type of EMP would be explicitly dangerous to spacecraft as it involves the plume coupling to the spacecraft surface or even internal wiring
Characterizing how coronary arteries expand after embryonic development: the Postnatal Wave of Arterial Remodeling
Keywords:  Department of Biology
Biology
Developmental Biology
Coronary Artery Development
Arterial Remodeling
Thesis

Coronary artery disease (CAD) is the deadliest disease in the world. Thus, understanding the mechanisms behind coronary artery development could lead to new therapeutics to treat CAD. Although advances in cardiovascular research have broadened our understanding of cardiovascular development, most are focused on early embryonic stages. This project aims to investigate a less understood coronary arterial developmental event: postnatal coronary artery remodeling. A newly developed imaging technique called iDISCO allows for optical clearing of tissue and visualization of their integrated structures, such as neurons in brain tissue. By applying this technique to wild-type mice hearts, the coronary artery structure can be visualized in detail throughout the entire heart. This is done with light-sheet microscopy, a technology for generating image stacks that can be used to 3D render the arterial map. Six postnatal and juvenile timepoints were analyzed to address whether postnatal remodeling is an acute or gradual event. The resulting image stacks were mapped by a semi-automated method that yields 3D models of the coronary artery tree at each timepoint. With this experimental strategy, we hypothesize to get a holistic view of coronary arteries through different postnatal stages, pinpointing critical timepoints in which remodeling occurs. Additionally, to correlate arterial tree complexity to cardiac tissue growth, volumetric myocardial measurements were related to branch density. Understanding the mechanisms of normal postnatal coronary artery remodeling could inform the development of therapeutic manipulations aimed at resupplying blood to hypoxic areas of damaged hearts.
Characterizing induced earthquake sequences with machine learning
Keywords: Geophysics.

There has been increasing concern regarding induced earthquakes and their related hazard, especially since the last decade. Although many of the induced earthquake sequences have been extensively investigated by researchers, there are still unresolved questions about their mechanism, which is crucial for hazard assessment. In this thesis, I focused on two induced earthquake sequences: the Timpson induced earthquakes from 2012 to 2013 and the seismicity in the Rangely earthquake control experiment from 1972 to 1974. To better characterize them, I applied various machine learning techniques including both supervised and unsupervised methods. Our results offer new insights on the physical mechanism of the two induced earthquake sequences. Moreover, I developed an image-based, deep-learning workflow to efficiently process Develocorder film seismograms, which demonstrates the potential to conduct seismic analysis on analog data at scale. Chapter 2 focused on the Timpson induced earthquakes, aiming to explain the discrepancy between the predicted fault slip potential in local stress field and the observed seismicity. I applied a deep-learning based phase picker to build an enriched catalog and followed by waveform similarity based earthquake clustering. This revealed the fine structure of the Timpson fault and thus successfully explained the stress and seismicity discrepancy. Chapter 3 described an image-based, machine learning workflow to process Develocorder film seismograms. I demonstrated its performance on one month of the analog seismograms in the Rangely experiment and showed the feasibility of image-based processing for analog data. Chapter 4 further improved this method by training a deep-learning neural network, DevelNet, to perform image-based earthquake detection on Develocorder films. I then applied DevelNet on two years of the film recordings in the Rangely experiment and showed that our reconstructed catalog outperformed the original one by Raleigh et al. (1976). Finally, Chapter 5 built on our reconstructed catalog and performed geomechanical analysis to determine the stress state of the Rangely faults. I further conducted earthquake clustering analysis and found characteristic short-lived sub-sequences in the Rangely earthquakes. Based on the spatiotemporal distribution of the seismicity and its relation to the observed reservoir pressure, I discussed possible mechanisms that may drive the Rangely earthquakes
Characterizing the behavior of coronary endothelial cells in the mouse heart after injury and during neonatal development
Keywords:  Department of Biology
Biology
developmental biology
coronary artery disease
vascular endothelial cells
neonatal regeneration
Thesis

Coronary artery disease (CAD) compromises the heart muscle’s essential blood supply and remains the leading cause of death worldwide. Surgical interventions to restore blood flow are too invasive for many CAD patients. Studying how the coronary vasculature develops and responds to injury may inform new therapies based on stimulating artery growth and regeneration. Coronary endothelial cells (ECs) derive from multiple progenitor sources, yet it remains unknown whether their developmental lineage affects their response to injury in the adult heart. By modeling cardiac injury in adult mice and quantifying lineage-labeled proliferating ECs, we discovered that lineage did not influence response to injury with respect to proliferation. Proliferating ECs were observed in arteries, suggesting that injury can induce arteries to re-enter the cell cycle at adult stages. During neonatal development, injury induces more substantial artery proliferation which enables the neonatal mouse heart to revascularize and regenerate damaged tissue. Using single-cell RNA sequencing, this study explores transcriptional properties in artery ECs that may support neonatal regeneration. Based on the analysis of differentially expressed genes between early and late neonatal stages, we present a list of candidate genes regulating artery regeneration. Unexpectedly, we also identified a population of artery cells that retain cell fate plasticity and switch to a capillary fate during neonatal development. Our findings contribute to a more complete understanding of EC behaviors in the postnatal heart and may inform future therapies to achieve artery regeneration and mitigate CAD mortality.
Characterizing the functional effects of transcription factor mutations using a high-throughput microfluidic platform
Keywords: Bioengineering.

Transcription factors (TFs) are DNA binding proteins that regulate gene expression in cells, enabling cellular processes and organismal development. Mutations in TFs and regulatory DNA sequences are also implicated in developmental disease and cancer. While various technologies have enabled high-throughput studies of mutations to regulatory DNA sequences, far less is known about how TF mutations alter DNA binding, largely due to technical hurdles associated with expressing and purifying proteins at scale. To remedy this, we developed STAMMP (Simultaneous Transcription Factor Affinity Measurements via Microfluidic Protein arrays), a microfluidic platform that enables quantitative characterization of hundreds of TF mutants simultaneously. As proof-of-concept, we applied STAMMP to measure binding affinities for ~210 mutants of Pho4, a model TF from yeast, interacting with 9 DNA sequences (> 1800 Kds). Our work reveals that Pho4 is highly sensitive to protein mutations, even at poorly conserved protein regions, and that mutations can both strengthen and weaken binding, suggesting a selective pressure for moderate affinity binding. Using biochemical double-mutant cycles, we further identify novel residues that contribute to Pho4 DNA binding specificity. More recently, we have applied STAMMP to study MAX, a TF from humans mutated in cancer, yielding biophysical functional characterizations for a wide variety of variants of unknown significance. In the future, STAMMP will enable rapid characterization of disease variants of TFs to accelerate functional characterization of clinically relevant TF mutants and assist therapeutic development. More broadly, STAMMP will enable deciphering of rules and biophysical principles governing TF function, providing a strong basis to study and engineer genetic regulation
Charles Carrick, The Victorian Everyman Who Aspired to be Extraordinary
Keywords:  School of Humanities and Sciences
Master of Liberal Arts Program
School of Humanities and Sciences
Charles Carrick
Victorian Studies
Marquetry
Calligraphy
Victorian Poetry
Fine Art
Canterbury
Victoria and Albert Museum
Beaney Museum
Legion of Honor
Victorian Eschatology
Victorian Theology
pietre dure
William Morris
Alfred Tennyson
John Keble
Pre-Raphaelites
John Ruskin
Thesis

Charles Carrick (1823-90), a Canterbury schoolteacher, has until now been known for his personal manuscript, which is filled with startling paintings. His life and work have gone largely unstudied. My research has uncovered a more complete picture of Carrick that illuminates key connections between his work and the cultural trends of the time. Despite his working-class background, Carrick was a polymath who aspired to do splendid work in fine art, marquetry, calligraphy, and poetry. Carrick’s eschatological art and poetry aligned him with Victorian theology and culture. His heavenly poetry is aligned with the heavenly section of Tennyson’s In Memoriam. His marquetry was influenced by the sixteenth-century Florentine pietre dure technique; his emulation of an ancient European craft echoed the approach of the Pre-Raphaelites and John Ruskin’s Venetian Gothic revival. Carrick’s botanical images have an affinity with similar images that are part of William Morris’s design for the Morris Room at the Victoria and Albert Museum. Carrick’s calligraphy career also paralleled that of Morris at a time when there was a popular revival of calligraphy. As an aspiring polymath from a humble background, Carrick, through his life and work, sheds new light on an era that is often understood through the works of more famous, wealthy, and privileged writers, thinkers, and artists.
Chemical looping : a platform for GHG-free hydrogen and carbon monoxide production
Keywords: Mechanical Engineering.

The world energy consumption will likely rise from 584 ExaJoules (EJ) today to more than 800 EJ by 2040. The industrial sector in non-OECD countries is predicted to account for ~20% of this energy usage due to rapid growth in GDP in these countries. As a result, the need for energy will increase because of the demand for construction materials, fertilizers plants, refineries, long-term energy storage facilities and others. If zero emissions technologies are not available when these plants are built, investors and developers will find themselves with no choice but to commit to another cycle of investment in emissions-intensive assets, which run the risking of becoming stranded in the future. The use of a "clean" fuel to target the greenhouse gas emissions produced by hard-to-abate sectors is a promising solution. Hydrogen has been proposed as the ideal candidate1, but the production of carbon-free hydrogen at scale has been a challenge. Today, hydrogen is almost entirely supplied from fossil fuels ("brown hydrogen"), thus annually consuming approximately 6% of natural gas and 2% of coal globally. Capturing and sequestering these CO2 emissions turns them into blue hydrogen but increases their costs. This dissertation focuses on material design strategies, thermodynamic driving forces and technoeconomics of chemical looping processes such as thermochemical water splitting, thermochemical CO2 splitting, methane-assisted chemical looping hydrogen production, and reverse-water gas shift chemical looping. The ultimate goal is to connect the understanding from materials level to systems level. These discoveries related to thermodynamics, new materials and new system-level insights may not only advance the field of chemical looping but could also improve other areas of chemical engineering