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Evaluation of Cardiac and Skeletal Muscle Progenitor Cell Dynamics in Growth Restricted Fetuses
Full text linkFetal growth restriction (FGR) increases the risk of cardiometabolic disease due in part to deficits in cardiac and skeletal muscle growth that are not fully compensated for after birth. Deficits in fetal cardiomyocyte number and maturity are thought to mediate lifelong cardiac dysfunction in FGR offspring. Similarly, the total number of skeletal muscle myofibers is set in utero. Thus, reductions in fetal myofiber number and hypertrophic enlargement limit skeletal muscle growth and metabolic function throughout the lifespan. Previous studies identify decreased cell cycle activity in cardiac and skeletal muscle of FGR fetuses. Additionally, reductions in myogenic regulator factor (MRF) expression and in the frequency of binucleated cardiomyocytes imply impairments in terminal differentiation and maturation in FGR muscle. Due to limitations in current techniques, whether cardiac and skeletal muscle progenitor cells of FGR fetuses exhibit decreased proliferation and/or myogenic capacity in vivo remains a critical gap in knowledge.
Using an ovine model of placental insufficiency and FGR, this dissertation aimed to identify the cellular origins of dysregulated cardiac and skeletal muscle development in FGR fetuses. We hypothesized that intrauterine stress exposure disrupts proliferation and differentiation programs in muscle progenitor cells of FGR fetuses, thereby limiting cardiac and skeletal muscle growth and function both in utero and throughout postnatal life. To test this hypothesis, we developed a novel flow cytometry approach to evaluate cardiomyocyte and skeletal myoblast development in late-gestation FGR and CON fetuses.
We identified impairments in cardiomyocyte development in FGR hearts, with distinct phenotypes specific to the left and right ventricles (LV, RV). Cardiomyocyte endocycling was upregulated in both ventricles of FGR fetuses. However, this increase appeared to compromise LV cardiomyocyte differentiation and maturity, while RV cardiomyocyte proliferation was notably reduced in FGR hearts. In the skeletal muscle of FGR fetuses, we observed decreased rates of myoblast proliferation and fewer myoblasts in the early stages of myogenesis. The proportion of unfused, late-differentiation myoblasts was increased in FGR, but this is likely due to impairments in myoblast fusion, as indicated by decreased Myomaker abundance in FGR skeletal muscle. Both cardiomyocyte and skeletal myoblast dynamics correlated with fetal IGF-1 concentrations. Our findings suggest that exogenous growth factor stimulation may be necessary or sufficient to restore fetal cardiac and skeletal muscle growth, potentially reducing the risk of cardiometabolic disease in offspring with prior FGR
Characterization of Electro-Optic Phase Modulations for Arbitrary Unitary Transformations
Full text linkTemporal modes are a viable framework for quantum information science and technology, being well suited for use in integrated photonics and single-mode fiber
networks. Techniques for temporal mode transformations have been developed that
allow for control over the mode structure, as well as beam-splitter like transforma
tions between temporal modes. However, no scheme to perform targeted multi
mode unitary transformations on temporal modes has yet been achieved. In this
dissertation we present a pathway toward implementing programmable arbitrary
unitary transformations on temporal modes using phase-only operations. We present
techniques to measure and characterize phase modulations via electro-optic phase
modulation. We demonstrate the ability to generate and measure arbitrary phase
modulations in the time and frequency domains using photonic arbitrary waveform
generation.
This dissertation includes previously published co-authored material
Understanding Spatiotemporal Variation in Plant Form-Function Relationships
Full text linkLeaf traits represent the wide variety of leaf forms plants have evolved to maximize carbon gains over their lifetimes. Although extensive research supports the use of these physiological metrics, much variation in leaf traits remains unexplained. In this thesis, I address three influences on leaf trait variation: leaf ontogeny, environmental stress, and cross-kingdom interactions.In the first study, I use two evergreen dwarf shrubs as case studies to demonstrate that leaf traits vary depending on cohort (current year’s growth or previous year’s growth) in Vaccinium vitis-idaea and Empetrum nigrum. Despite this difference, researchers often do not specify which cohort they measured or differentiate between the cohorts.
In the second study, I test how plant form and function hold in herbaceous prairie species under experimental drought conditions in a U.S. Pacific Northwest grassland. I found that plant form-function relationships were robust against drought, and leaf traits remained unchanged.
In the third study, I used stable isotope tracers to determine if common mycorrhizal networks favor fungal resource acquisition at the expense of plant resource demands, or if they are passive channels through which plants regulate resource fluxes. I found that plant functional type and tissue stoichiometry were the most important predictors of interspecific resource transfer.
This dissertation includes previously published and unpublished coauthored material.2025-10-3
Microbial and Biochemical Surveys Along the Geographical Gradient of the Oregon Coast
No full textTo understand the factors shaping microbial assembly and community composition in intertidal sediments along the Oregon coast, we collected sediment samples from 10 cores at depths of 160–190 cm, spanning over 300 km. Using metagenomic and 16S rRNA data, we constructed functional and taxonomic profiles, revealing redundancy in functional groups but variability in taxonomic composition. Regression models using chemical data measured in lab, geographical distances, and environmental variables from public datasets failed to significantly predict taxonomic composition. However, permutation null model tests suggested that biological interactions play a significant role in driving taxonomic variation in subsurface sediments, namely through taxa excluding each other via different mechanisms.2026-02-1
Teacher Stress and Coping in the Early Childhood Context: A Pilot and Feasibility Study
No full textHigh quality environments include attention to the wellbeing of the teachers helping young children learn to manage emotions. Through empathetic responses and directly teaching children how to recognize and regulate physiological states. Relationships and self-regulation are interrelated and critical to establishing healthy classroom climates. Unlike older students, young children under 5 are in the process of learning critical skills that will lead to later developmental and academic success. High quality teacher–child interaction and responsive caregiving requires the teachers be adept at classroom management, stress management, and their own self-regulation. Teacher stress and wellbeing is at the crux of quality environments. Using linear regression and factor analysis respectively the purpose of this project was to pilot the use of teacher coping and stress measures to determine how coping impacts wellbeing, as well as investigate the usability and feasibility of the Professional Quality of Life (ProQOL) survey with an early childhood serving population. The data for this project were collected in the Pacific Northwest and show that emotional based coping strategies predicated burnout and secondary stress. BO, the adjusted R² =.176, F(4,113)=7.02, p<.001), specifically, escape was significant ?=.37, p< .001. Emotion-based coping also predicted STS, confirming the alternative hypothesis with an adjusted R² =.153, F (4,113) = 6.09, p<.001. Furthermore, the preliminary ProQOL results in this early childhood serving population (n=412) did not support the a 3-factor model as proposed by Stamm (2009) but evidence for a bifactor model similar to other child serving populations (Lenz et al., 2019)
Innovations in Programmable Nucleic Acid Libraries and CRISPR Enrichment for Molecular Biology Applications
Full text linkSynthetic gene libraries are pivotal in advancing protein engineering, functional genomics, and synthetic biology, yet their quality is hindered by errors in oligonucleotide synthesis. These errors pose significant challenges for large-scale gene synthesis of long genes due to excessive imperfect assemblies. This dissertation presents innovative methods that leverage CRISPR-Cas9 technologies for targeted retrieval of perfect gene assemblies, aiming to increase their length and quality.A major contribution of this work is the development of Barcode Assisted Retrieval-CRISPR Activated Targeting (BAR-CAT), a method that uses deactivated Cas9 (dCas9) to selectively enrich perfect synthetic genes from complex libraries. By tagging genes with unique DNA barcodes and targeting these barcodes with in vitro transcribed sgRNAs, we successfully enriched three targeted barcodes by up to 1,094-fold. However, BAR-CAT scalability was limited beyond 12 targeted barcodes due to challenges with excessive library diversity and competition among sgRNAs for dCas9 binding, which will require further method optimization.
Parallel to the development of BAR-CAT, I led the development of a scalable sgRNA synthesis workflow that reduces costs by over 70% by harnessing large pools of microarray-derived oligos. These oligos are assembled into dsDNA templates and in vitro transcribed to generate sgRNA libraries. Despite optimizations, RNA-seq analysis revealed biases in spacer representation driven by guanine-rich sequences near the T7 promoter. We mitigated these biases by padding sgRNA spacers with a guanine tetramer and evaluating alternative approaches, such as compartmentalization in emulsions. These strategies improved sgRNA library uniformity, with broad implications for CRISPR-Cas9 screens and sgRNA design.
Taken together, these advances in targeted DNA enrichment and sgRNA library production are advances that will contribute to improving the scalability, affordability, and fidelity of synthetic gene libraries. BAR-CAT, in particular, offers a promising approach for multiplexed retrieval of perfect genes that could benefit applications in synthetic biology, ancient DNA analysis, diagnostics, and targeted sequencing. Future refinements to both BAR-CAT and sgRNA synthesis methods will further extend their utility, enabling high-throughput exploration of protein function and genome biology. This dissertation includes unpublished co-authored material
Probing Binary Black Hole Formation Channels with Gravitational Waves
Full text linkThis dissertation presents the work I've done with gravitational waves using data from and as part of the LIGO-Virgo-KAGRA collaboration. The work in this dissertation showcases different approaches to analyzing the data in the third gravitational wave transient catalog. Since all of the detected signals in the catalog are consistent with compact binary coalescences, most of them binary black holes, it provides a great window to peek into the black hole demographics of the universe. The parametric noise modeling algorithm was introduced to conduct joint inference on signal parameters and noise parameters, enabling probes into hidden correlations between signal and noise models. Several clustering algorithms were developed to find patterns in gravitational-wave data which have significant uncertainties, using which, a lot of the patterns found in other population analyses were recovered and a few outliers were identified. The coagulation model for hierarchical mergers was refined and constrained with the catalog, providing evidence for the massive event GW190521 being a hierarchical merger very likely produced in an active galactic nucleus disk. All the techniques established in this dissertation will prove useful in analyzing the rapidly growing gravitational-wave census, thereby improving our understanding of black holes as well as the universe at large
Towards the Quantum Regime: Ultracoherent Diamond Spin-Mechanical Resonators
Full text linkHybrid quantum systems combine the advantages of individual components and pave the road to practical quantum computing and information processing. Among varieties of candidates, spin-mechanical systems based on color centers in diamond utilize the extraordinary optical properties of nitrogen-vacancy centers or silicon vacancy centers in diamond, combined with the advantages of mechanical systems. To this date, quantum computers based on color centers in diamond have not been achieved. One central challenge is to reach the quantum regime of spin-phonon coupling where effects of single phonons become important. This dissertation will present the efforts in developing ultracoherent diamond spin-mechanical resonators as the cornerstone of reaching this regime. Through the design, fabrication and characterization of diamond nanomechanical resonators with phononic bandgap engineering, we achieved highest up-to-date quality factors of above 10^6 in diamond cantilevers at frequencies of up to 100MHz and 10^7 in Lamb wave resonators at frequencies of 1GHz. For the latter, we developed an all-optical approach that excites the fundamental compression mode with optical gradient force in a Lamb wave resonator. This thesis will then discuss the applications of our spin-mechanical system in mechanical sensing and quantum networking. Combined with superior optical properties of nitrogen vacancy and silicon vacancy centers in diamond, spin-mechanical system enables a promising platform for spin-based quantum computing and quantum networking. This dissertation contains previously published as well as unpublished co-authored materials
EXPLORING THE RELATIONSHIPS BETWEEN STAPHYLOCOCCUS AUREUS AND SKIN LIPIDS
No full text63 pagesThe human skin is a complex ecosystem where interactions between host-derived lipids and resident microbes shape the microbial community and pathogen invasion. Staphylococcus aureus is a clinically relevant skin pathogen that transiently colonizes the nares of 30% of the human population. With rising antibiotic resistance posing a significant global health challenge, it is important to investigate the role of the human skin niche in preventing infection and impacting treatment success. This thesis explores how skin lipids, both those modified by skin resident fungi Malassezia sympodialis and those produced by the host, influence S. aureus physiology, adaptation and antibiotic susceptibility. In Chapter 1, we inspect how S. aureus adapts to antagonism by Malassezia, which produces the antimicrobial fatty acid 10-hydroxy palmitic acid (10-HP). Through experimental evolution, we found that S. aureus acquires tolerance through activation of the sigma factor SigB. Further analyses of genetic regulators controlled by SigB lead to the discovery that the staphylococcal accessory regulator SarA is an important factor contributing to the survival in evolved strains. Chapter 2 examines the influence of sebum, the lipid-rich product of skin sebaceous glands, on S. aureus growth and antibiotic sensitivity. Using synthetic sebum formations and high-throughput phenotype screening of 188 known antimicrobials, we demonstrate that sebum can change the effectiveness of several clinically relevant antibiotics. Alongside this, we identified that the S. aureus fatty acid kinase is necessary for growth in sebum indicating a potential therapeutic target for S. aureus when colonizing skin. Our work presented here underscores the need to consider the unique skin environment when developing and implementing strategies to treat S. aureus infections. By elucidating how lipid contexts may modulate pathogen adaptation and antibiotic tolerance, this thesis may build our understanding of microbial physiology and skin adaptation evolution to inform future efforts to combat antibiotic resistant skin infections.2027-07-2
Holocaust Denial on Campus: The Case of Pacifica Forum (1994-2010)
Full text linkPacifica Forum began as a Eugene, Oregon pacifist group in 1994 but quickly devolved into a hotbed for Holocaust denial and other antisemitic conspiracy theories until its dissolution in the early 2010s. The Forum met on the University of Oregon campus during the final six years of its existence, sparking community debate on the limits of free speech on college campuses, especially after Pacifica Forum hosted Holocaust deniers Mark Weber and David Irving in 2007 and 2008. In 2010, the University of Oregon relocated Pacifica Forum to an off-campus but university-owned building in downtown Eugene. While this relocation eventually led to the Forum’s dissolution, it came several years after significant protest from Eugene residents, particularly the Jewish community. This thesis uses twenty-four boxes of previously unanalyzed archival material to argue that the tardiness of the university’s response was due to two interdependent phenomena. First, the relocation was a response to student and faculty protest, which came significantly later than the first Jewish protests of Pacifica Forum. Second, as Pacifica Forum became more identifiably right-wing in its latter years, Eugene residents considered the group less of a misguided amalgamation of neighbors and more of an extra-societal clan that did not share the community’s ethos and was, thus, worthy of censorship