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    Amelia Conway Oral History

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    Characterization of molecular regulators of Connexin43 oscillations during joint morphogenesis in Danio rerio

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    Skeletal patterning is governed by a complex network of molecular and genetic regulators. These networks have been shown to be partially conserved between vertebrate species and facilitate the use of model species in understanding human disease. In particular, the gap junction protein Connexin43 (Cx43) is suggested to play a vital role in craniofacial development and formation of the long bones. Mutations in cx43 can lead to the developmental disorder oculodentodigital dysplasia which has conserved phenotypes between humans and mice. We utilize zebrafish as a model organism to answer questions about the full molecular pathways of skeletal patterning.Prior work in our lab and others has shown that Cx43-gap junctional intercellular communication (GJIC) acts to suppress joint forming pathways and promote growth. However, the exact mechanisms and molecular regulators of Cx43 itself remain poorly understood. Here, we investigate the role of several pathways in regulating Cx43-GJIC. First, we present findings that suggest that retinoic acid (RA) signaling is needed for normal expression of cx43. Second, we present the generation of two RA response element (RARE) deletions to assist in elucidating the direct role of RA signaling on skeletal patterning genes. Third, we present a bioelectric signaling pathway thought to act through Cx43-GJIC in non-excitable cells and its effect on skeletal patterning phenotypes. Finally, we present preliminary data on other genetic regulators and techniques that present promising avenues toward a more complete understanding of the full scope of these pathways. This work can grant new understandings to human disease models and hopefully provide new options for therapeutics for mitigation or treatment.</p

    Computational Study and Optimization of Nanoparticle Focusing in Microfluidic Devices

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    This study investigates nanoparticle focusing through two distinct methodologies. Thermophoresis is applied within a microfluidic platform featuring slanted grooves, which induce transverse flow, achieving a substantial temperature gradient of 10K/50 um. This configuration successfully concentrates nanoparticles, achieving up to a four-fold increase for 100nm particles and a three-fold increase for pseudo HIV particles, with findings corroborated by numerical simulations conducted in OpenFOAM. Computational analysis suggests that circulation can be utilized as a metric to represent transverse flow strength and reveals that reducing groove spacing enhances flow uniformity, thereby increasing nanoparticle concentration efficiency. To address challenges associated with viscoelastic flow, particularly at high Weissenberg numbers, a simplified log-conformation reformulation algorithm was developed to mitigate numerical discrepancies. Numerical simulations of viscoelastic flow in a two-dimensional contraction-expansion microchannel confirm the effectiveness of the OpenFOAM viscoelastic solver and the adaptability of a structured-polyhedral hybrid mesh. Barriers in two-dimensional multichannel setups reveal distinct flow regimes and limitations in achieving strong stress while maintaining stability. Qualitative analyses of shear flow in microchannels exhibit complex dynamics, with the FENE-CR model predicting first normal stress differences across various flow rates. A consistent nanoparticle focusing effect is anticipated at higher Weissenberg numbers, specifically above 50. The elastic lift coefficient was evaluated through parametric studies aligned with experimental results. Finally, a hyperbolic microchannel design with sheath flow is proposed, demonstrating an effective reduction in 200nm nanoparticle accumulation.</p

    Traces and their Combinatorial Interpretations: A Comparative Study of the Symmetric Group Algebra, Hecke Algebra, and Immanants of Totally nonnegative Matrices

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    {"value":"n this dissertation, we study how separate fields of algebraic combinatorics can be viewedthrough the lens of Young tableaux. Young tableaux were invented by Alfred Young to study representations of the symmetric group algebra, the algebra generated by the permutations on n-elements. The trace space of the symmetric group algebra is the module of linear maps from the symmetric group algebra to the integers, and bases of this space can be formed in connection with bases of the space of homogeneous symmetric polynomials. There are six well known bases of the latter space: the elementary basis, the homogeneous basis, the Schur basis, the power sum basis, the monomial basis, and the forgotten basis. These bases, as well as their analogue trace space bases, have been extensively studied by algebraic combinato- rialists, including Richard P. Stanley in his book Enumerative Combinatorics: Volume 2. A deformation of the symmetric group algebra is the Hecke algebra. A common object of study in the Hecke algebra is the Kazhdan-Lusztig basis. Hecke algebra traces are defined similarly to symmetric group traces, and their actions on these elements will be studied in this paper. Symmetric group traces can be used to define immanants, which generalize the concepts of the determinant and permanent of a matrix. Calculating immanants is computationally complex, but the process can be simplified in the context of totally nonnegative matrices, matrices whose minors are all non-negative. These three branches, the representation theory of the symmetric group algebra, the representation theory of the Hecke algebra, and immanants of totally nonnegative matrices, can all be connected through combinatorially interpreting different varieties of tableaux. In Section 2, we introduce new combinatorial proofs of symmetric group traces acting on elements associated with the chromatic polynomial in terms of Young tableaux. In Section 3, we then translate some of the results from section 2 into the context of q-analogue traces through the use of P -tableaux. In Section 4, we propose a conjecture which, if true, will allow us to generalize these results to the context of LLT-analogue traces. In Section 5, we introduce the concept of G-tableaux in the context of planar networks and then translate the results from Section 2 into this new context.","attr0":"abstract"

    Analysis of Waste Material Feedstocks Using Laser-Induced Breakdown Spectroscopy and Machine Learning

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    Predicting properties such as heating value, ash fusion temperature, and mineral ashcomposition from Laser-Induced Breakdown Spectroscopy (LIBS) data can make gasifiers more flexible to different feedstocks. Understanding these feedstock properties in-situ improves feedstock conversion modelling methods that allow for consistent operation, higher carbon conversion, and reduced fouling and erosion rates. The purpose of this study is to demonstrate methods for model creation that take LIBS data as predictor features and estimate higher order material properties as a function of feedstock material properties. Six samples were chosen to represent a mixture of abundant and carbon rich waste materials. LIBS measurements were performed on these samples for elemental wavelengths and intensity values. Laboratory analytical results were obtained for each sample\u27s heating value, proximate and ultimate analysis, mineral ash composition, ash fusion temperatures, and viscosity temperatures. Thermal conductivity was measured using a HotDisk TPS 2500S. LIBS measurements were processed and used as predictor features for machine learning (ML) models to predict the sample\u27s material properties. Predictor feature selection algorithms, particularly minimum redundancy maximum relevance (mRMR), reduced the dimensionality of ML models. Many modelling methods such as Gaussian process regression (GPR), regression tree, neural networks (NN), and support vector machines (SVM) were demonstrated to be effective at predicting higher order properties; however, mRMR with GPR stood out as a clear winning combination.</p

    An Investigation of Robust Tooling for Microinjection Molding

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    The advancement of microinjection molding (μIM) as a mass production technology for components with nano/microscale features primarily depends on durable tooling to meet the increasing demand for such products. Traditional tooling made of materials such as steel, silicon (Si), and nickel (Ni) each presents distinct limitations. Steel, for instance, cannot integrate features smaller than its grain boundaries, whereas Si and Ni-based inserts often fail prematurely under high-throughput manufacturing demands. These challenges have led to the adoption of bulk metallic glass (BMG) as a durable and robust alternative for tooling, capable of enduring over 20,000 cycles as reported in the literature. BMG is increasingly employed to fabricate micro/nanostructured tooling for the μIM process.This research investigates the performance of tooling in the μIM process using BMG-based, Si-based, and Ni-based inserts, with a particular emphasis on the robustness evaluation of BMG-based tooling. The investigation involves the fabrication process of microfeatures on three BMG-based inserts, with different geometries, utilizing the focused Ion Beam (FIB) technique. It emphasizes the durability and performance of BMG-based tooling in comparison to traditional Si-based and Ni-based tooling, where performance limitations were addressed during this work. The project includes the enhancement of a previously developed model for the apparent elastic modulus of molded micropillars to address certain limitations that occurred during this research. Additionally, various aspects were investigated to enhance the scientific understanding of the μIM process. Key findings from Moldflow simulations and experimental trials identified key factors impacting the filling behavior and replication quality of microfeatures including molded part and microfeatures geometries, and processing parameters. The simulations indicated a significant deflection towards the ejection direction and less radial deflection, attributed to the proximity of the sprue to the micro-featured area. This resulted in lower aspect ratio features filling rapidly but cooling slowly, which may have contributed to various phenomena of micropillars failure observed during the inspection of molded micropillars. Experimental work with BMG-based inserts of low aspect ratio demonstrated excellent replication quality despite challenges such as potential crystallization and the instantaneous disintegration of titanium-based coatings, which showed no substantial damage to the structural integrity of the inserts. Durability testing exceeded 1,000 and 5,100 molding cycles for BMG-I, and BMG-II inserts, respectively. The BMG-I insert exhibited degradation of replication quality over molding cycles, occurring alongside surface morphology changes due to potential crystallization from elevated heating of the mold assembly. It showed a degradation rate of 0.428 nm/cycle. Additionally, the BMG-II insert exceeded 5,100 molding cycles regardless of dynamic conditions arising from various molding issues during the process. This insert showed a degradation rate of 0.0492 nm/cycle. It showed a better degradation rate compared to the previous insert and those reported in the literature with a value of 0.115 nm/cycle. Although dynamic conditions introduced process variability during molding trials, process parameter adjustments to adapt to these conditions introduced some degree of uncertainties in the height measurements of molded micropillars. Consequently, microcavities depth measurements were adopted for more reliable performance evaluation. Overall, both BMG-based inserts demonstrated robust performance, especially the BMG-II insert, which is projected to last over 83,000 molding cycles based on a simple linear fit using only two data points. In contrast, Si-based inserts with low aspect ratio microfeatures showed consistent failure patterns, potentially originating from nanoscale scallops created on the sidewalls by the deep reactive ion etching (DRIE) process. These scallops acted as high-stress concentration points, potentially initiation cracks. Additionally, Ni-based inserts with low thickness failed prematurely under high injection pressures but preserved microfeature geometry to some extent. Other inserts successfully withstood more than 150 molding cycles without visible structural damage. Larger replicated microfeatures exhibited better replication quality due to reduced flow resistance, which enhanced cavity filling, whereas smaller microfeatures showed reduced quality due to premature solidification. The replication of high aspect ratio micropillars using thermoplastic polyurethane (TPU) was prone to defects such as stretching and directional collapses. The processes of filling and stretching of micropillars were influenced by processing parameters such as packing pressure and cooling time. Lip-like features were commonly observed on low aspect ratio micropillars using polystyrene (PS), indicating contact between micropillars and the sidewalls of the microcavities. This observation was confirmed by numerical investigations of various ejection conditions. The presence of these features was notably more distinct when the substrate rotated counter-clockwise with minimal radial movements, and also when rotated clockwise but with increased radial movements. Numerical investigations of the demolding process demonstrated that changes in radial movement and rotational values drastically affect micropillar integrity and stress distribution. This dissertation advances the understanding of BMG-based tooling as robust solutions that could enhance the manufacturing process for high-volume production settings. It provides valuable insights into the interactions between polymer melts and tooling under dynamic conditions, contributing to manufacturing practices and tool design. Additionally, the research explores the impact of process variability on tooling performance throughout molding cycles to provide insights into key challenges and opportunities for improvement.</p

    Non-reproductive vocalizations, cognition, & flocking behaviors in hybridizing songbirds

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    Cognitive traits, such as learning and memory, are important for many components of fitness, including reproductive and non-reproductive behaviors. However, how hybridization could impact cognitive traits involved in nonreproductive behaviors has rarely been investigated. Avian song learning has been widely studied in songbirds, while the role of calls in speciation remains largely unknown. Avian calls, although primarily associated with non-reproductive behaviors, are learned and important for many aspects of survival, and are therefore important for fitness. Thus, like song, avian calls could influence reproductive isolation. This dissertation is aimed at examining call learning, cognition, and non-reproductive behaviors associated with the "chick-a-dee" call in hybridizing black-capped (Poecile atricapillus) and Carolina (Poecile carolinensis) chickadees. I first examined how calls and call learning might affect pre- and postzygotic reproductive isolation. I documented that parent species originating from sympatry show stronger bias towards learning their conspecific call relative to their conspecifics in allopatry. In addition, hybrids showed reduced variability in call learning. This suggests calls could contribute to pre- and postzygotic reproductive isolation, potentially through mechanisms of ecological character displacement and hybrids exhibiting constraints on plasticity in call learning, respectively. Next, I tested for differences in spatial learning and memory among the ancestry groups, as well as a relationship between call learning variability and cognitive flexibility. When raised under common garden conditions, the parental species and hybrids did not differ in their performance on spatial associative or reversal learning tests. Also, there was no relationship between call learning variability and cognitive flexibility. However, hybrids exhibited the opposite relationship between associative learning and reversal learning performance than was exhibited by both parent species. Specifically, while black-capped and Carolina chickadee performance on associative learning tests was negatively correlated with performance on reversal learning tests, hybrid performance on both tests was positively correlated. This suggests hybrids might not exhibit a trade-off between memory and cognitive flexibility. Lastly, I examined whether mobbing behavior, an anti-predator behavior initiated by flocks using the "chick-a-dee" call, differs between natural sympatric and allopatric populations. I documented a lack of chickadee flocks in sympatry, relative to the black-capped and Carolina allopatric populations. Although I cannot explain this lack of chickadee flocks, I discuss potential impacts of hybridization on flocking behaviors from an ecological perspective. In my dissertation, I present some of the first evidence of call learning as well as different ways calls and call learning could indirectly affect reproductive isolation in a hybridizing songbird system. Overall, I present new avenues of research on understanding the effects of hybridization on non-reproductive behaviors from an ecological viewpoint, and further, the potential impacts on reproductive isolation. </p

    The Effects of School-Level Achievement Goals and Student-Level Characteristics on Academic Self-Efficacy

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    Academic self-efficacy is essential to students\u27 academic success, engagement, and behavioral and emotional well-being. Higher levels of self-efficacy are associated with positive outcomes, while lower levels correlate with poor performance, disengagement, and increased behavioral and emotional risk (BER) symptoms. This issue is particularly critical for African American high school students, who often face unique challenges within the educational system. While previous research highlights the importance of academic self-efficacy, limited attention has been given to school-level contextual factors, such as mastery goal orientation. This study initially sought to examine the influence of context-level mastery goals; however, preliminary analyses revealed minimal variance in academic self-efficacy at the school level, leading to a focus on personal mastery goals as a student-level predictor. Using a quantitative design, this study analyzed data from 4,891 high school students across seven schools. Results revealed that personal mastery goals significantly predicted academic self-efficacy and were protective against the adverse effects of BER for all students. While mastery goals partially mitigated the effects of BER, this protective relationship weakened as BER levels increased. As hypothesized, African American students reported lower self-efficacy than White students. Additionally, students categorized as "Other" reported lower self-efficacy than both African American and White students. These findings provide insight into the relationships between academic self-efficacy, mastery goal orientation, BER, and race/ethnicity, contributing to a deeper understanding of student-level factors that shape academic self-efficacy outcomes.</p

    LABEL FREE IN SITU CHARACTERIZATION OF 3D TUMOR SPHEROIDS BY MICROFLUIDIC-BASED BIOIMPEDANCE SPECTROSCOPY

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    Bio-cellular analysis using electrical impedance spectroscopy (EIS) is an emerging, label free, and high throughput method to characterize cells. Measuring cell viability is essential for drug screening, point of care diagnostics, and personalized medicine. In this study, we employed microfluidic based EIS for the biophysical analysis of cells to distinguish subpopulations of each cell type. We developed a microfluidic platform with an integrated electrode capable of distinguishing human colorectal tumor (HCT-116) cells spheroid from multicellular human lung fibroblasts (nHLF) cell spheroids. Additionally, we assessed the viability and corresponding impedance of paclitaxel-treated spheroids at six different concentrations. The results showed a strong correlation between the viability and impedance of the spheroids, with a correlation coefficient of R² = 0.892. The fabricated device featuring a bi-metallic integrated electrode increased sensitivity, while the sheath flow-based microchannel ensured uniformity in the sample passing zone, thus ensuring the reproducibility of the data. The developed platform has the potential for high-throughput characterization of the drug-resistant spheroid models and viability analysis in a label-free way.</p

    The Atacames Seismic Swarm: Insights into Earthquake Migration and Fault Activation

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    The Mw 7.8 Pedernales megathrust earthquake off the central Ecuador coast in April 2016 triggered an earthquake swarm in Atacames, located on the northern coast, eight months later. This region had also previously experienced significant megathrust ruptures in 1906 (Mw 8.8) and 1958 (Mw 7.6). The Ata-cames swarm consisted of 307 seismic events (Ml <1 to 5.8; depths ~2–18 km) recorded from December 2, 2016, to January 24, 2017. Four of these events (Ml 5.1-5.8) resulted in ground shaking that damaged buildings. A dense temporary seismic network, deployed after the Pedernales earthquake, recorded the swarm. We compiled a relocated earthquake catalog by detecting phases with PhaseNet, associating them with GaMMA, and determining event locations using NonLinLoc, followed by refinement with HypoDD. The seismic activity aligned with a previously unknown northeast-dipping crustal fault system between higher-velocity (Vp ≥ 6 km/s) basement uplift and a lower velocity (Vp ≤ 5 km/s) sedimentary basin, indicating that lithological differences or mechanical weaknesses may have influenced fault activation. The swarm progressed through three distinct episodic pulses, with intervening periods of quiescence. Hypocenters migrate northeast and deeper (from 2 km to 18 km) during the sequence. The third pulse (December 19–28) accounts for over 75% of the events. Diffusion modeling suggests that transient fluid pressure changes triggered the later phases, which align with fluid-driven seismic activity in subduction zones. Waveform cross-correlation identified twenty-three event families, including seven sets of repeating events, indicating localized fault slip or pore pressure variations. Focal mechanisms of the larger magnitude events in the swarm were mostly reverse-faulting, consistent with the regional compressional stress from subduction. This study emphasizes the significance of crustal fault activation, fluid-driven processes such as pore pressure increase and episodic fluid migration, and transient stress interactions in driving swarm activity. The Atacames swarm highlights the necessity of considering moderate-magnitude earthquakes along crustal faults, in addition to megathrust ruptures, when assessing hazards and understanding earthquake sequences after large ruptures. </p

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