Masters Theses

Permanent URI for this collection

https://hdl.handle.net/10919/9291

Browse

Now showing 1 - 20 of 24068

Using Nacre-Inspired Architecture to Improve the Mechanical Performance of Binder Jetted Parts
Espinosa Borja, Juan Fernando (Virginia Tech, 2026-10-15)
Residual porosity remains a barrier for industrial adoption of additively manufactured metallic parts fabricated through Binder Jetting (BJT), due to its detriment in the mechanical performance. However, local control of the pore structure poses an opportunity to turn an apparent process defect into a design feature for creating architected composites. Nacre is a natural composite that achieves high toughness by directing crack propagation through a softer, more compliant phase, effectively preventing failure in the brittle ceramic material. This research investigates whether a nacre-inspired architecture can be introduced into BJT metal composites to improve toughness relative to conventional, homogeneous parts. Two strategies within a BJT and infiltration workflow were used to control porosity at different length scales: selective binder deposition governs mesoscale porosity by dictating where powder is bound or left loose during printing, while pre-sintering provides control of the microscale porosity by controlling neck formation and pore evolution within each region. This work leverages both controls together to architect distinct infiltration pathways within a single part, producing a Nacre-inspired brick-and-mortar pattern of bronze-lean "Brick" (unbound) and bronze-rich "Mortar" (bound) regions in SS316L and bronze composites. The progression of densification of bound and unbound SS316L powder throughout the sintering process was found to differ, with unbound powder showing an advanced densification because of its greater powder packing density. A pre-sintering temperature of 1250℃ produced the greatest contrast in pore structure while providing a viable, complete infiltration path. Nacre composites were fabricated at this temperature, achieving up to a 9% bronze-content difference between the designed Brick and Mortar sections. Conventionally printed and infiltrated composites outperformed the Nacre composites, with Modulus of Toughness recording values of 0.024 J/mm3 and 0.016 J/mm3, respectively, with stiffness showing no distinction. These results are attributed to large fabrication defects and high residual porosity in the final parts (6.6 – 8.5%), rather than to the tailored architecture itself. This thesis demonstrates a novel method for producing complex architected composites with spatial composition contrast in a BJT and infiltration process, by combining selective binder deposition and a pre-sintering step. Additionally, it develops an image-analysis method applicable to other porosity-based patterns for quantifying such contrast from optical microscopy.
Predicting Heat Accumulation and Layer Geometry Variation in Continuous DED-Arc of Thin-Walled Aluminum Structures
Rosenhein, Drew David (Virginia Tech, 2026-10-15)
Compared to other metal additive manufacturing (AM) processes, wire-arc directed energy deposition-arc (DED-Arc) offers high deposition rates. However, its throughput is limited by heat accumulation within the part during the build; continuous printing without balanced heat dissipation can lead to part slumping and distortion. Existing thermal mitigation approaches, including interlayer dwell time, active cooling, and in-process parameter control, impose costs in productivity, system complexity, and/or limited applicability to large and complex parts. Continuous deposition without arc interruption eliminates dwell time and arc start and stop defects but produces a severe heat accumulation condition. Under fixed process parameters, the thermal balance determining this accumulation is strongly influenced by the part's geometry. In a closed contour geometry, the layer contour length of the profile determines the toolpath length, setting the time available for heat to dissipate between depositions of successive layers, while also determining wall surface area. Longer layer contours have been observed to reduce heat accumulation in previous research, but the relationship has not been directly investigated as a design variable in DED-Arc, nor has it been established whether interlayer temperature reaches a plateau at sufficient contour length and/or part height. The aim of this thesis is to establish a design-stage workflow that relates continuous build geometry to its in-process thermal condition and deposited wall geometry, thus allowing layer-wise prediction of part geometry before fabrication. To close this research gap, three thin-walled ER5556 aluminum cylinders of 50, 100, and 200 mm diameter were deposited continuously under identical process parameters and instrumented with embedded thermocouples along the build height. Contour length variation produced a 212.1 °C spread in interlayer temperature across builds and dictated whether steady-state interlayer temperatures could be reached. Calibrated thermal simulation indicated that the interlayer temperature of 200mm diameter cylinder reached a plateau during processing and declined as convective loss exceeded layer-wise heat input. However, the 50mm diameter contour part's interlayer temperature climbed to 401 °C by layer 50 with no sign of stabilizing. This thermal variation increased effective wall width by 99.4% along the part height, whereas porosity and microhardness remained consistent for this alloy. The calibrated simulation was applied to a test geometry and, combined with the measured temperature-geometry correlations, predicted effective wall width and layer height to 3.28% and 2.26% mean absolute percentage error, respectively, across 10 layers sampled from a 50-layer build. The study was also extended to oscillating weave deposition for producing thicker wall widths. Interlayer temperatures in the weave builds were up to 60.4 °C lower than single-track at matched contour length, despite depositing 2.8 times the path length per layer. This longer layer time increased heat dissipation, more than offsetting the higher heat input.
Through The Keyhole: A Nature Retreat
Perry, Mason Thomas (Virginia Tech, 2026-10-15)
Looking Through the Keyhole: A Nature Retreat explores how architecture can encourage meaningful social connection while providing opportunities for privacy, reflection, and reconnection with nature. The project responds to the growing separation between people, community, and nature by proposing a retreat organized around spatial transitions rather than isolated buildings. The design consists of three primary architectural moments: the threshold gate, firepit, and elevated cabins. The threshold transitions from everyday life to the retreat, the firepit creates a communal center, and the elevated cabins offer increasingly private spaces. A recurring keyhole motif symbolizes transitions between public and private, exterior and interior, and movement and reflection. These elements create a progression from crossing, gathering, to ascending, demonstrating how spatial sequence, material expression, and nature connection shape social interaction, solitude, and restoration.
Communication Strategies for Cognitive Radar Networks
Esser, Joseph Max (Virginia Tech, 2026-10-14)
Distributed radar networks provide the ability to monitor large and dynamic scenes by uti- lizing multiple spatially separated sensors. However, the effectiveness of such networks are constrained by limited communication resources if a central fusion center needs to collect raw data from all the radar nodes. This thesis investigates adaptive radar resource manage- ment for multi-radar multi-target tracking through the application of multi-armed bandit based scheduling methods. A simulated radar network is developed where multiple radars observe maneuvering targets while providing track updates to a centralized fusion center. Several radar selection strategies based on ϵ-Greedy and Upper Confidence Bound (UCB) multi-armed bandits are investigated and compared against a baseline communication strat- egy. Radar selection is performed by utilizing contextual information at the fusion center derived from the current tracking state and spatial distribution of targets, which allows communication resources to be dedicated to radars of interest. The performance of the re- sulting developed tracking system is evaluated using the Generalized Optimal Sub-Pattern Assignment (GOSPA) metric. Simulation results demonstrate that the adaptive scheduling methods improve tracking performance by concentrating resources on regions of high target density, while the relative results between communication methods depends highly on target conditions and communication constraints.
Influence-Guided Agent Adaptation for Dynamic Human–AI Collaboration
Dubey, Sara (Virginia Tech, 2026-10-12)
To facilitate effective human–agent collaboration, agents must not only understand the intent of their human partners and adapt to it reactively, but also account for how their own behavior influences their partners. Rather than treating this influence as a passive consequence of interaction, we propose actively predicting and optimizing it as part of the agent's decision-making process. In doing so, the agent explicitly models how its actions are likely to shape the subsequent behavior of its human partner. To this end, we introduce i-STAR, a novel framework that not only optimizes an agent's own actions but also reasons over and jointly optimizes the anticipated response of the human partner to those actions. Our framework employs a multi-layer architecture comprising three core components: (1) a team response model, which predicts how the human partner will respond to candidate agent actions; (2) a joint utility model, which estimates the overall utility of the agent's selected action together with the anticipated partner response; and (3) an action policy whose advantage function is shaped by the maximum-utility joint action. We find that, using this framework, our agent outperforms current state-of-the-art agents across all layouts of the challenging Overcooked benchmark. Furthermore, in a human-subject study, i-STAR is perceived as significantly more fluent than the strongest agent–agent baseline.
Failure Analysis and Re-Design of an Electromagnetic Energy Harvesting Railroad Tie
Jadhav, Advait Vishal (Virginia Tech, 2026-10-08)
Advanced Rail Technologies call for intelligent and autonomous trackside monitoring, signalling and communication equipment. This equipment must be powered where it is installed, and across much of the rail network no power supply exists. The Energy Harvesting Tie developed at the Center for Vehicle Systems and Safety at Virginia Tech captures the vertical deflection of the rail under passing wheels within the enclosure of a standard composite crosstie, converting it through a ball screw and bevel gear stage into unidirectional generator rotation by half-wave mechanical motion rectification. Following instrumented laboratory and revenue-service campaigns, the first-generation prototype was left in track to expose degradation mechanisms inaccessible to short-term testing. At nine months of continuous service, it ceased to produce voltage on any generator phase, abruptly and with no preceding decline. This thesis establishes the cause and develops a second-generation design. Teardown of the recovered unit and a failure modes and effects analysis identify degradation of the one-way clutch cage and sprags as the dominant risk driver, and reconstruct a causal chain of lost sprag positioning, lubrication loss and internally generated debris, axial migration against a compliant polymer locating member, and diversion of transmitted torque into a parasitic frictional path at the gearhead adapter joint. Eight design requirements follow, each traceable to a specific teardown observation. Design loads are derived from the revenue-service displacement record at the electrical operating point imposing the greatest mechanical duty. A nodal torque-propagation model retaining every rotating inertia gives a peak clutch torque of 23.02 N·m at zero stress ratio, an indexing rate of 0.7-1.5 Hz, and a ball-screw axial reaction reaching 11.58 kN and shows that the conventional reduction of freewheeling inertance to the generator rotor and gearhead alone understates it significantly. The redesign mitigates issues concerning race concentricity, axial location and gearhead torque reaction by consolidating the components, using a complete sealed clutch unit located by co-rotating metallic shoulders and a two-point supported eight-fastener generator mount in place of a cantilevered four-fastener arrangement. Every load-bearing member is verified analytically. Testing of the assembled unit over 131 compression events confirms half-wave rectification on consecutive events, validates the drivetrain kinematic chain, and recovers the machine constant in situ, with performance holding up to expectation. Instrumented revenue-service redeployment remains the necessary next step.
Acoustic Sensing and Asymmetry: An Improved Model for Hearing Mechanics in Ormia ochracea Or, When 'Hearing Crickets' Is a Good Thing
Mikel-Stites, Maxwell (Virginia Tech, 2026-10-08)
Ormia ochracea is a parasitoid fly known for its ability to precisely locate the origin of sounds despite its small size. It achieves this via a hearing organ composed of a pair of external tympanal membranes joined by a biomechanical bridge. The fly has inspired research projects ranging from novel micro-scale acoustic sensors to the biomechanics of hearing. However, there has been relatively little work re-examining the physical measurements of O. ochracea's sensory organs, nor the original mathematical model (a system of coupled ODEs) for ormiine hearing (first established in the mid 1990s). In the case of the former, further study provides a chance to verify the physical measurements in the literature and explore the possibility of physical asymmetry in ormiine hearing. For the latter, further work would address significant deviations between the measured and predicted sensory values relevant to ormiine hearing. To address these gaps, in our first study, we made morphometric measurements of 21 Ormia specimens and quantified the degree of tympanal asymmetry in order to determine whether the system may leverage small biologically deliberate asymmetry for a sensory advantage. In our second, we modified the prior model by adding a response to the angle of incoming sound, improving its accuracy and overall fidelity to physiological measurements when compared to the unaltered model. Together, these studies reveal the prevalence and impact of tympanal asymmetry in O. ochracea and suggest avenues of improvement for both further mathematical modeling and experimental micro-scale physical experimentation.
Exploring the Impact of Institutional Measures on Household Disaster Preparedness through a Recreancy Lens: A Case Study of Hurricane Beryl in Texas
Kona, Afsana (Virginia Tech, 2026-10-08)
This study uses recreancy as a theoretical and analytical hook to explore how institutional measures affect household disaster preparedness. As the concept of recreancy is broadly linked to institutional failure during a crisis, this study focuses on Hurricane Beryl (2024) in Texas as a case study. The study examines how risk perceptions, institutional trust, disaster experience, and information reliance shape household-level preparedness behaviors. The study deploys a survey research design to collect data from 540 respondents across 23 counties affected by the deadly Hurricane. For quantitative analysis, the study used Stata 18.5 version of the software and conducted descriptive analysis as well as ran hierarchical ordinary least squares regression models. Responses to open-ended questions were analyzed thematically to contextualize and interpret participants' insights. Quantitative results suggest that higher risk perception and prior disaster experience are positively associated with preparedness behaviors. However, the relationship between institutional trust and perceived institutional failure is complex and does not follow a linear pattern. While trust can facilitate preparedness, it may also reduce perceived urgency to act. In contrast, perceptions of institutional failure are associated with reduced reliance on formal information sources and, in some cases, lower preparedness. Analysis of open-ended responses further highlights challenges from inconsistent communication and dissatisfaction with prior institutional responses that adversely affect the community's preparedness actions. This study contributes to the ongoing discourse on disaster and society by emphasizing that preparedness is not solely an individual behavior but is deeply influenced by institutional credibility and performance.
Formulation and Microstructural Evaluation of Multi-Component Rare Earth Oxide Thermal Barrier Coatings via Slurry Deposition
Massignan, Connor James (Virginia Tech, 2026-10-08)
Thermal/Environmental Barrier Coatings (T/EBCs), composed of multi-component rare earth oxides (REOs), offer tunable properties for high-temperature applications due to their low thermal conductivity, high melting temperature, and low coefficient of thermal expansion. Slurry deposition of coatings is a cost-effective alternative to state-of-the-art air plasma spray methods. This study investigates a ternary REO system comprising yttria (Y2O3), erbia (Er2O3), and ytterbia (Yb2O3), to assess its suitability as a single-layer TBC material. Slip-cast samples were fabricated at varying volume percentages and sintered under controlled conditions to explore the influence of particle packing and sintering parameters on densification behavior. Then, the identified conditions were used to slurry spray a niobium-based alloy. Emphasis was placed on optimizing the slurry formulation to systematically investigate varying stabilization mechanisms to develop the suspension, influencing the rheological behavior and particle packing of components consisting of slip-cast and slurry-spray coatings. Preliminary results suggest that sintering environment and temperature significantly affect final density and coating integrity, as well as the percentage of yttria, warranting further investigation into the thermophysical interactions among REO constituents during thermal treatment.
Studies on Particle-Wall Interactions in Particle-based High Temperature Concentrating Solar Thermal Systems
Owens, Conner David (Virginia Tech, 2026-10-08)
Next-generation (Gen3) concentrating solar power (CSP) systems use solid particles as the heat capture, transfer, and storage medium to reach operating temperatures above 700 °C, but the continuous contact between flowing particles and component surfaces drives severe material degradation through the coupled action of high-temperature oxidation and abrasion. This thesis examines particle–wall interactions in particle-based high-temperature CSP through two complementary studies. First, the combined oxidation–abrasion performance of four candidate alloys, stainless steel 316 (SS316), Incoloy 800H, Haynes 230, and Inconel 718 (In718), is evaluated in a moving bed of dense sintered bauxite particles (CARBO HSP 40/70) at room temperature, 700 °C, and 800 °C. The iron-based alloys exhibit relatively stable abrasion behavior across the temperature range, whereas the Ni-based alloys undergo intermittent severe degradation at 700 °C but improved long-term wear resistance at 800 °C, where enhanced oxide regeneration and mechanically mixed layer development provide increased surface protection. Second, a nanoscale multilayered Cr/Cr2N coating deposited on In718 by reactive unbalanced DC magnetron sputtering is tested against uncoated In718 for 324 h at 700 °C and 800 °C under combined oxidation and abrasion. The coated specimens show no measurable substrate mass loss at either temperature, while uncoated In718 at 700 °C spalls at an average rate of 4.47 mg/h, identifying nanoscale Cr/Cr2N multilayers as a viable route to extending component service life. Collectively, these studies indicate that a self-replenishing mechanically mixed layer forms naturally under sustained particle contact and provides an additional protective barrier against abrasion, provided the underlying substrate or coating is capable of maintaining oxide-scale adhesion and mechanical stability under dynamic particle contact. Because the alloy is then not directly exposed to the abrasive medium, this behavior theoretically allows lower-cost materials to be used in particle-handling components, and provides a basis for the design of longer-lived, more economical receivers for Gen3 CSP.
A meta-analysis on the relationships of agency and communion with job strain
Kalmar, Sam L. (Virginia Tech, 2026-08-31)
Strain is a common phenomenon experienced in the workplace that can induce serious negative consequences for those who let it go unchecked. Individual differences are known to play distinct roles in the severity of these outcomes, but the limited exploration of personality traits has yielded inconsistent findings. The current study helps close this knowledge gap by examining the relationship that the personality traits of agency and communion exhibit with job strain outcomes. Approximately 11,496 citations were screened, resulting in 290 unique independent samples, 563 unique effect sizes, and 67,564 participants. A random-effects, individual correction meta-analysis was conducted for both the agency-strain and communion-strain relationships. Continuous moderators were analyzed with mixed-effect meta-regressions and categorial moderators were analyzed with modified asymptotic confidence intervals. Both agency and communion had negative relationships with job strain outcomes, although agency’s relationship was stronger than communion’s. Occupational orientation and sample age did not appear to moderate these relationships. In sum, both agency and communion appear to mitigate job strain, yet agency seems to be more effective overall. Further research is needed to determine if methodological moderators such as strain and personality measure types influence these relationships.
Two-Bubble Cavitation Collapse Near a Rigid Wall: Effects of Size Asymmetry and Temporal Delay
Shashidhar, Prajwal Balaji (Virginia Tech, 2026-09-03)
This study experimentally investigates the collapse dynamics of two laser-induced cavitation bubbles positioned coaxially near a rigid wall, focusing on bubble-size asymmetry and temporal generation delay. Bubble 1 is located closest to the wall, while Bubble 2 is positioned farther from the boundary. High-speed imaging, Schlieren visualization, and synchronized pressure measurements are used to characterize collapse timing, liquid-jet development, pressure-wave propagation, and wall loading. For the bubble-size study, Bubble 2 is maintained at a maximum diameter of 6.10 mm, while Bubble 1 is reduced to 5.50, 5.03, and 4.50 mm at stand-off distances of 0.52, 1.47, and 1.97. An additional highly asymmetric case with a Bubble 1 diameter of approximately 4.10 mm is also examined. The results show that bubble-size asymmetry modifies collapse order, jet direction, vapor merging, collapse topology, and wall pressure. At a stand-off distance of 0.52, the 5.50 and 5.03 mm cases exhibit torus-torus collapse, while the 4.50 mm case exhibits tip-tip collapse. At stand-off distances of 1.47 and 1.97, Bubble 1 undergoes torus collapse and Bubble 2 undergoes tip collapse. Temporal generation delay further modifies the interaction by changing the relative growth and collapse phases of the cavities. The delayed bubble grows to a larger size and restricts the growth of the bubble generated first. When Bubble 2 is delayed, the maximum jet velocity is approximately 62.55 m/s at 10 microseconds, with jet reversal between 50 and 100 microseconds. When Bubble 1 is delayed, the maximum jet velocity reaches approximately 72.23 m/s at 38 microseconds. Overall, bubble size and generation timing strongly influence collapse dynamics, liquid-jet behavior, and wall loading in interacting cavitation bubbles near a rigid boundary.
CELLOS: Capturing and Elaborating Live-coding Lectures into Organized Summaries
Zheng, Yuhang (Virginia Tech, 2026-10-05)
The Authorship Requirement in the Age of Generative AI Music: AI in Copyright Law and the Transformation of the Creative Process in Commercial Music Production
Grehawick, Coleman Daniel (Virginia Tech, 2026-10-05)
This thesis examines the collision between generative artificial intelligence and copyright law in the context of commercial music production, arguing that existing doctrine is structurally unable to address the forms of creative displacement that AI systems produce. Copyright law's human authorship requirement, which was developed over two centuries without the need for questioning an author's humanity, is applied by courts and the U.S. Copyright Office almost exclusively to finished works, leaving the framework unable to examine the creative process through which a work was produced or to distinguish human expressive judgment from AI-generated statistical output. Drawing on Supreme Court fair use precedent (Campbell v. Acuff-Rose, 1994; Andy Warhol Foundation v. Goldsmith, 2023), the Copyright Office's guidance on AI copyrightability, Thaler v. Perlmutter (2025), and the 2024 litigation between major record labels and AI music platforms Suno and Udio, this study traces how doctrine, industry rhetoric, and platform governance have each independently failed to resolve the authorship question that generative AI poses. The thesis introduces two original analytical contributions. First, it proposes creative initiation as a doctrinal standard regarding whether a human author established a work's expressive direction prior to and independently of AI involvement. Second, it identifies phantom sampling, a phenomenon in which generative systems replicate the market-relevant sonic and stylistic qualities of existing recordings through aggregate statistical patterning rather than identifiable copying, producing market displacement and loss of attribution that existing similarity doctrine has no mechanism to detect. The thesis concludes by proposing mandatory disclosure of AI involvement as a condition of distribution and licensing, and by offering practical guidance for musicians including process documentation, contractual negotiation, and collective advocacy to protect their authorship and attribution interests while formal legal reform remains slow to develop.
Agency Increased the Value of Social Signals in Adolescent Risky Decision-making
Wang, Shuhan (Virginia Tech, 2026-05-08)
Adolescence is characterized as the onset period for multiple risk-taking behaviors. The increased social susceptibility and autonomy during adolescence contribute to this elevated tendency to take risks. However, whether the autonomy to engage in social influence, i.e., the agency to acquire social signals increased their influence on the risky choices in adolescents remains unknown. In this study, we investigated the risky choices of 91 adolescents aged between 13-14 years under social influence. They acquired the social signals (i.e., the choices from two social others) either with or without agency before making risky choices. We found that participants were more likely to conform to others’ choices under agency. The Other-Conferred-Utility model revealed an increased value of social signals underlying this enhanced social influence. The functional neuroimaging analyses identified that the dorsomedial prefrontal cortex (dmPFC) encoded the social signals and the individual difference in their agency effect. Psycho-physiological interaction analyses revealed that the agency to acquire social signals increased dmPFC-vmPFC connectivity when participants conformed to others’ choices, implying agency mechanistically changed the social value integration. The agency effect on the value of signals modulated the association between participants’ risk-taking behaviors and the substance use in their peer groups, implying the possibility to predict the social sensitivity in real-life adolescent risk-taking behaviors.
Sorption of Perfluorooctanoic Acid (PFOA) in an Oligotrophic Aquifer
Vaidya, Priyashi Prashant (Virginia Tech, 2026-10-02)
Thirst
Kapoor, Karan (Virginia Tech, 2026-10-01)
Thirst is a collection of poems examining the speaker's relationship with his alcoholic father, and the paradox of writing toward a subject who resists being written about. Moving through ghazals, villanelles, prose poems, questionnaires, and fragment poems, the collection treats formal restlessness as an ethical stance — the speaker's incomplete knowledge of his father is at the heart of the book's narrative structure. Recurring motifs — whales, wolves, mirrors, birds, and the gut as a central bodily site — bind the poems into a unified imaginative world. Drawing on influences including Leonard Cohen, Bob Hicok, Alejandra Pizarnik, Franz Wright, Agha Shahid Ali, and Mohammed Rafi, Thirst argues that form must enact, rather than describe, the conditions of its making: to write toward a resistant father is to inherit his silences and to build, from refusal, a language for what cannot be said directly.
Inverse Screening of Metal-Organic Frameworks for Low-to-Mid-Pressure Carbon Dioxide Adsorption using Geometric, AP-RDF, and RAC Descriptors
Rengasamy, Padmapriya (Virginia Tech, 2026-09-24)
Metal-Organic Frameworks (MOFs) are promising materials for carbon dioxide (CO₂) capture because of their high porosity, tunable chemistry, and structural diversity. However, the enormous design space of MOFs makes exhaustive experimental and computational screening prohibitively expensive. Consequently, there is a growing need for computational approaches that can rapidly identify promising materials while reducing the cost of materials discovery. This thesis investigates the use of geometric, revised autocorrelation (RAC), and atomic property-weighted radial distribution function (AP-RDF) descriptors for predicting low-to-mid-pressure CO₂ adsorption using machine learning (ML) models. The predictive capabilities of different descriptor combinations are systematically evaluated to establish an accurate surrogate modeling framework. The best-performing model, selected based on predictive accuracy, is subsequently used for interpretability analyses to quantify the relative contribution of different descriptor groups to model predictions and to examine how descriptor importance varies across pressure conditions. These findings facilitate a deeper understanding of the factors influencing CO₂ adsorption predictions. The best-performing XGBoost model using the combined geometric, RAC, and AP-RDF descriptor set achieved R² values of 0.739 and 0.904 at 0.015 and 0.15 bar, respectively. Descriptor ablation and SHAP analyses showed that geometric descriptors provided the strongest overall predictive contribution, while AP-RDF and RAC descriptors supplied complementary information; surrogate-guided screening further demonstrated that high-performing MOFs could be efficiently recovered from a large candidate pool using limited training data. Building upon these insights, surrogate-guided inverse screening is employed to efficiently recover top-performing MOFs from a large candidate pool of 208,849 MOFs using limited training data. The descriptor-level insights obtained from the interpretability analyses are further evaluated through chemistry-aware matched-analog screening, which tests whether AP-RDF and RAC information can help identify higher working capacity candidates among MOFs with similar pore geometry compared with geometry-only selection. Across 234 matched neighborhoods, chemistry-aware guided selection achieved a median working capacity gain of 5.85 wt%, compared with 1.20 wt% for geometry-only selection and 0.15 wt% for the repeated-random benchmark. Predicted and actual guided gains showed strong agreement (Spearman correlation = 0.90), while the grouped chemistry-aware contribution was also strongly associated with actual guided gain (Spearman correlation = 0.89). These results demonstrate that the developed surrogate framework can support both large-scale inverse screening of MOF databases and the selection of higher working capacity candidates among geometrically similar MOFs, while providing descriptor-level information that helps interpret the model predictions and prioritize promising candidates for subsequent simulation or experimental evaluation.
The Impact of Tamoxifen on Cardiac Electrophysiology in the Context of the Tamoxifen-Inducible Cre-Loxp System in Mice
Albrecht, Maxwell Reid (Virginia Tech, 2026-09-22)
Sudden cardiac death is one of the leading causes of death worldwide, with lethal ventricular arrhythmias being likely responsible for most incidents. The frequency of sudden cardiac death is increasing, presenting the need for more research into the causes and treatments of these deadly arrhythmias. As arrhythmia research increases to meet the need for more effective treatments, there is a distinct need for increased scrutiny into the possible confounding variables present in current models of arrhythmogenic disease. One of the most common and effective models for arrhythmia research is mice, utilizing the tamoxifen-inducible cardiac specific Cre-loxp system. In this system, tamoxifen is used to activate the Cre recombinase protein, made to express only in the heart. This protein targets and removes two inserted artificial loxp sites and the sequence between them, resulting in a gene knockout or other manipulation. This system can be used to target specific proteins known to contribute to arrhythmia formation, while avoiding developmental complications common in constitutive knockouts of cardiac proteins. The cardiac-specific Cre-loxp system is known to have off-target effects, including inflammation, fibrosis, and reduced cardiac performance. Tamoxifen also has effects on cardiac electrophysiology, with the ability to block sodium channels, which can slow conduction and promote arrhythmias. As many studies focus on tamoxifen in the context of its use in human patients, it is unknown whether tamoxifen on its own, as used in the mouse Cre-loxp system, can create an arrhythmogenic phenotype. We conducted studies to determine how tamoxifen impacts cardiac electrophysiology and the expression of key proteins responsible for conduction in an ex vivio mouse model. We found that tamoxifen could slow conduction, and change action potential duration characteristics, particularly at shorter paced cycle lengths. This indicates that tamoxifen can interfere with cardiac electrophysiology, and that these effects need to be controlled for in arrhythmia research using models which are exposed to tamoxifen.
From Biofilms to Bubbles: Dispersion of Bacteria from Biofilms Using Histotripsy
Hoffman, Carson Lee (Virginia Tech, 2026-09-21)
Orthopedic infections are difficult to treat and diagnose because bacteria often persist within biofilms, fibrin networks, host tissue, and other protective infection-associated matrices. These structures limit antimicrobial penetration, reduce bacterial susceptibility, and make viable bacteria difficult to recover for culture. This thesis investigated whether focused ultrasound technologies could mechanically disrupt these protective bacterial environments to improve both antibiotic-mediated bacterial killing and culture-based diagnostic recovery. The first objective was to evaluate histotripsy as an adjunctive strategy to improve antibiotic killing of biofilm-associated bacteria in equine synovial environments. Staphylococcus aureus ATCC™ 25923 and an agrC knockout strain were grown as biofilm-associated aggregates in either biofilm media or pooled equine synovial fluid and treated with histotripsy, proteinase K (200 µg/ml), amikacin sulfate, or combination treatments. Histotripsy consistently disrupted biofilm structure and produced greater dispersal than untreated controls and proteinase K (200 µg/ml), as measured by optical density. Amikacin alone had limited activity against protected biofilm-associated bacteria, while combination treatment with histotripsy and amikacin produced greater bacterial killing than amikacin alone. In biofilm media, combination treatment reduced viable bacterial counts by up to approximately 6 log₁₀ CFU/mL compared with untreated controls. Bacterial killing was less pronounced in synovial fluid, where viable bacteria persisted despite dispersal and antibiotic exposure. These findings suggest that mechanical disruption of biofilm-associated aggregates can improve antibiotic access and enhance bacterial killing, while also demonstrating the protective effect of synovial fluid and infection-associated matrices. The second objective was to evaluate Focused Ultrasound Extraction (FUSE), as a rapid dispersal method to improve bacterial recovery from biofilms and infected tissue. Biofilms of Staphylococcus aureus ATCC™ 25923 and Pseudomonas aeruginosa PAO1 were grown for 24 hours in RPMI containing 20% equine plasma and treated with proteinase K (200 µg/ml), sonication, or FUSE at increasing total pulse doses. For S. aureus ATCC™ 25923, FUSE at 40 cycles, 200 Hz pulse repetition frequency, and 20,000 total pulses produced the greatest mean recovery of culturable bacteria, while higher pulse doses reduced recoverability. For P. aeruginosa PAO1, lower FUSE doses did not significantly increase recovery, and higher pulse doses significantly reduced recoverability. These findings demonstrate that FUSE dose must be optimized to favor bacterial release while preserving viability, and that the effective dose window differs by organism. FUSE was then evaluated using equine-derived clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. FUSE significantly improved recovery from K. pneumoniae M26-1142 at 10,000 pulses and from S. aureus M22-2451 at 20,000 pulses, while no significant treatment effect was detected for E. coli M25-0692 under the conditions tested. These isolate-dependent differences likely reflect differences in biofilm structure, density, and matrix composition. S. aureus formed a visibly more robust and structured biofilm than K. pneumoniae or E. coli, creating a greater opportunity for dispersal-based methods to improve bacterial recovery. In contrast, relatively high bacterial recovery from untreated controls for some Gram-negative isolates suggests that these organisms may have been more readily recoverable without active dispersal in this model. Finally, FUSE was evaluated using human periprosthetic joint infection tissue samples and compared with an enzymatic dispersal agent. FUSE rapidly disrupted infected tissue and released culturable bacteria within minutes. In the majority of samples, FUSE produced greater colony recovery per gram of tissue than enzymatic dispersal, while requiring only a brief treatment period. These findings support the potential use of FUSE as a rapid culture-preparation strategy for infected tissue. Together, these studies support focused ultrasound as a versatile mechanical disruption platform for orthopedic infections. In the therapeutic setting, histotripsy improved antibiotic-mediated bacterial killing by disrupting protected bacterial aggregates. In the diagnostic setting, FUSE improved recovery of viable bacteria from biofilms and infected tissue when delivered within an organism-appropriate dose range. These findings address a shared clinical problem: bacteria embedded within protective matrices are difficult to kill and difficult to culture. Further optimization and validation using larger clinical sample sets may support future development of focused ultrasound strategies for both treatment and diagnosis of biofilm-associated orthopedic infections.

Browse

Recent Submissions