Leveraging Rehabilitation and Implantable Strain Sensors to Improve Bone Healing After Traumatic Femur Fractures

The primary objective of this thesis was to quantify patient-specific loading and rehabilitation parameters to elucidate how specific rehabilitation conditions impact bone healing after traumatic bone injuries. Our overall hypothesis was that parameters of mechanical loading and exercise will impact bone healing. To test this hypothesis, we utilized three rehabilitation platforms that enabled investigation of distinct rehabilitation parameters. These platforms including (1) a rodent running wheel with engineered resistance brakes or on/off brakes to enable running of different intensities or durations, respectively, (2) a treadwheel with an adapted on/off brake as a scalable platform, and (3) altered treadmill with speeds conducive to rodent needs. These platforms allowed for the investigate of distinct rehabilitation platforms and their relationship to bone healing. We also used implantable wireless strain sensors that enabled real-time non-invasive monitoring of mechanical cues as a function of time, rehabilitation conditions, and healing status. In collaboration with University of Utah, we used these sensors and in vivo microCT scans to develop subject-specific finite element models to quantify niche mechanical cues during different rehabilitation conditions. We discovered that higher intensity rehabilitation, relative to rehabilitation of lower intensity, increased early-stage strain magnitudes and significantly improved bone healing, with explant femurs matching intact strength. Beyond loading magnitude, we also discovered the importance of both long term and short term on bone healing. Nonlinear multivariate analyses revealed that rehabilitation must balance activity and rest to improve bone healing, where rehabilitation with longer running distance and shorter daily rest periods resulted in 100% union after 3 mm bone injuries. These results further found that the necessary balance of rehabilitation and rest depends on subject-specific factors such as injury size since the same rehabilitation conditions resulted in only 20% union after a 2 mm bone injury but 100% nonunion after a 3 mm bone injury. Using previous studies to inform a rehabilitation regimen predicted to improve bone healing, we also found the importance of short-term rest between exercise loading bouts. Rehabilitation that involved steady-state running for 12 minutes significantly hindered bridging and bone formation compared to rehabilitation that involved intermittent rest periods between one minute running bouts. Systemic myeloid-derived cell types, previously predicted to impair bone healing, were also downregulated for rehabilitation with short-term rest periods. These results highlight rehabilitation with data-informed levels of intensity, activity, and both short and long term rest as a therapeutic to modulate early mechanical loading and the immune response to enhance bone repair.This work facilitated a deeper understanding of how specific rehabilitation parameters regulate mechanical cues and bone repair and validated an implantable sensor platform to further investigate mechanobiology. This thesis aids in the development of subject-specific rehabilitation with the novel insight into the importance of rest on bone healing. Our results challenge the fields focus on optimizing the loading magnitude to improve bone repair. In addition, this thesis provides foundational support for the commercialization of implantable sensor technologies to track implant mechanics as a noninvasive feedback of healing status and to inform personalized clinical decisions. This dissertation includes content from several published articles including Nash* et al. (2022) Connective Tissue Research; Nash* et al. (2022) Physiology in Health and Disease, Springer; Williams and Harrer et al. (2024) NPJ Regenerative Medicine; and Williams et al. (submitted 2024) Science Advances. *Publication under maiden name: Kylie Nas

Disruption of Ribosome Biogenesis and Induction of Nucleolar Stress by Platinum(II)-based Chemotherapeutics

Platinum(II) metal complexes—cisplatin, carboplatin, and oxaliplatin—represent a major class of antineoplastics agents used in a majority of cancer treatment regimens throughout the world. Despite their ubiquitous use, the precise mechanisms and targets responsible for cancer cell death are not fully understood. Overcoming these deficiencies will be necessary to address the limitation associated with current Pt-based chemotherapeutics in the clinical setting. Current literature has revealed, unlike cisplatin and carboplatin, oxaliplatin primarily kills cells through disruption of ribosome biogenesis. Ribosome biogenesis is intimately connected to the nucleolus, a phase-separated nuclear condensate, which also functions as a central hub for sensing and coordinating cellular stress response through nucleolar stress response.This work provides insight on the relationship between Pt(II) compounds and disruptions in ribosome biogenesis, and the impact on nucleolar structure. Chapter I summarizes the significance and current understanding of Pt-based chemotherapeutics in the context of ribosome biogenesis and the nucleolus. Chapter II identifies structural and chemical properties of Pt(II) compounds necessary for nucleolar stress induction through a novel immunofluorescence imaging approach for quantifying nucleolar stress. Chapter III applies this framework to a subset of monofunctional Pt(II) compounds which are also shown to induce nucleolar stress. Chapter IV examines spatiotemporal differences in nucleolar stress induced by Pt(II) compounds identified in previous studies—ruling out connections with intracellular accumulation and DNA binding. Chapter V discusses current progress on elucidating the molecular mechanisms for inhibition of rRNA synthesis by oxaliplatin by adapting a ChIP-based sequencing techniques to map the occupancy of RNA Polymerase I machinery along rDNA. Chapter VI provides a comprehensive review on the coordination metal ions with nucleic acids, highlighting recent examples of NMR and x-ray crystallography structures from the literature. This dissertation includes published and unpublished co-authored material

Timber Tectonics in the Digital Age: Multi-use Structures for Silverton

210 PagesExploring kit-of-parts construction, the Timber Tectonics team designed and prototyped an emergency shelter using modular stressed-skin panels, facilitating building expansion and sustainable reuse in alternative configurations. A kit-of-parts is a subset of building prefabrication in which building components are pre-engineered and prefabricated into standardized units from raw materials. The benefits of kit-of- parts construction are that it allows for rapid deployment as well as repeatable and reusable units that require little to no modification to be repurposed. To familiarize themselves with kit-of-parts theory and wood shelter construction, students first studied and modeled design precedents to establish a baseline of knowledge around wood shelters. The University of Oregon and Oregon State University combined diverse knowledge in the fields of architecture and engineering that was used to generate several creative design proposals. Working in groups, students from both universities met in person and on video calls throughout the project to draft, prototype, and model elements and ideas for the project. After a review from industry professionals, the student designs were consolidated into one. Students then regrouped to refine seven areas of the project: architectural design, stressed-skin panel design, connections, enclosure, structural analysis, construction, and project management. Student-led fabrication and assembly of the full-scale final prototype took place at Oregon State University’s Emmerson Lab, concluding with a final review. After the term, additional work was done to complete the components and disassemble them for future reuse. Lessons learned from this experience will be used to create a future of more sustainable, adaptable, expandable, and reusable buildings.Community partnerships are possible in part due to support from U.S. Senators Ron Wyden and Jeff Merkley, as well as former Congressman Peter DeFazio, who secured federal funding for SCYP through Congressionally Directed Spending

Enriching Euphonium Repertoire Through a Reenvisioned "Art of Phrasing"

69 pagesABSTRACT This reenvisioning of Jean-Baptiste Arban’s Art of Phrasing presents a collection of melodies by historically underrepresented composers, transcribed for brass instruments. It highlights works by women, people of color, and non-Western classical composers, whose contributions are often overlooked in brass pedagogy. Featuring music by Kassia, Hildegard von Bingen, Joseph Bologne, Florence Price, and others, the collection explores the composers' lives, the historical context of their music, and their pedagogical value. The importance of transcriptions in euphonium performance and pedagogy is examined, emphasizing their role in expanding repertoire, developing musicianship, and bridging historical gaps. Since the euphonium is a relatively recent instrument, much of its repertoire consists of transcriptions from other instruments and vocal works. This collection prioritizes vocal music, reinforcing the long-standing connection between brass playing and singing. A key objective is to increase representation in standard pedagogical materials. Selected works from historically underrepresented composers expand the scope of euphonium repertoire beyond the traditional European canon. The transcriptions maintain the integrity of the original compositions while adapting phrasing, articulation, and notation to suit brass musicians. Special attention is given to translating neumatic notation and interpreting vocal nuances for euphonium performance. Additionally, the pedagogical benefits of singing and song in brass playing are explored, drawing on the philosophies of Arnold Jacobs and other influential teachers. By integrating vocal techniques and transcriptions, euphonium players gain access to diverse, expressive, and historically rich material to develop their musicality

Revitalizing Gresham’s Historic Downtown Hub

47 pagesDuring the fall of 2024, the School of Planning, Public Policy and Management (PPPM) offered a course at the University of Oregon titled “Urban Transportation.” Students in an Urban Transportation course worked with the City of Gresham to revitalize the city’s downtown. Students gathered information about the study area through a meeting with city staff, a site visit, and a simulated community engagement session. With this information, students began to research possibilities for downtown revitalization efforts. Student groups developed suggestions and each group focused on one of five categories: multimodal transportation, network connectivity, parking, development, and community engagement. Each group completed a needs assessment based on the existing conditions of Gresham’s current downtown. Students concluded that the downtown area sees the most activation during the lunch hour and the dinner hour, with parking occupancy peaking at 1 PM and 6 PM respectively. Otherwise, the area is relatively quiet. Students perceived few activities during the 16 hour programming window people desire, meaning there may not many opportunities for nightlife. Downtown is primarily dominated by cars and very few people choose to walk, bike, or bus downtown—despite the possibility of all three. One obstacle to revitalizing Gresham’s downtown is the busy five- lane arterial road, Powell Boulevard. It is a barrier to encouraging more pedestrians and cyclists, and it fragments the network from Main City Park, the beautiful community park adjacent to downtown. Despite these challenges, student researchers suggested ways to bring new life to the historic downtown area while keeping its small town-like charm. The most frequently suggested recommendation was to close a corridor of N Main Avenue to automobile traffic. The proposed corridor is from NE 1st to NE 5th Street, and would include a two-way bike lane, large sidewalks for pedestrians, and increased social spaces. This, along with infrastructure improvements to nearby intersections, would make walking and biking a more attractive alternative to driving downtown. Alternatively, if the city decided against a walking- and biking-only corridor, Gresham could turn N Main Street into a one-way. The unused lane could be converted into a two-way protected bike lane and would accomplish the same goal of encouraging multimodal transportation. Another common theme researchers suggested was improved and centralized signage downtown. The city could create more cohesive wayfinding signage directing visitors to special attractions like the parks and local businesses nearby. The signage could also better direct drivers to underutilized parking lots to address community members’ perceived lack of parking in the area. The use of bulletin notice boards could offer information about biking and walking as viable and safe travel options in Gresham. Other important recommendations addressing Gresham’s historic downtown district’s needs include infill underutilized parking lots with social space hubs, engage with local artists and students to create public art downtown and increase aesthetic pleasure in the area, and implement a street fair to celebrate new development downtown.Community partnerships are possible in part due to support from U.S. Senators Ron Wyden and Jeff Merkley, as well as former Congressman Peter DeFazio, who secured federal funding for SCYP through Congressionally Directed Spending

Improving Earthquake Rapid Response and Early Warning Performance with Geodesy and Machine Learning

165 page PDF and 6 MP4 data files.This dissertation focuses on the work I have undertaken to investigate how quickly and accurately we can characterize earthquakes while and immediately after they occur, and potential ways to improve the systems we use for this. I focus on how we can use the modern technology we have for Earth monitoring as well as modern data processing and analysis techniques such as machine learning to improve the capabilities of the systems we rely on for earthquake disaster response. In this dissertation I present an exploration into the question of how early earthquakes are distinguishable by magnitude using borehole strainmeters, where we found that earthquakes do not appear to be strongly deterministic (i.e., large earthquakes are not inherently different from small earthquakes in their beginning stages). This has implications for how long it takes to accurately determine the magnitude of an earthquake, particularly for large events which rupture over longer periods of time. I then discuss our development of a machine learning algorithm for improving the performance of earthquake early warning systems for large earthquakes. This algorithm allows for discrimination between noisy GNSS waveforms which do actually contain seismic waves from earthquakes and those which do not, which enables us to reduce the amount of high-noise/low quality data that enters algorithms which determine the magnitude of such earthquakes. While earthquake early warning systems tend to operate only over specific regions such as the U.S. West Coast, organizations such as the USGS’s National Earthquake Information Center also must rapidly publish information such as magnitude about worldwide earthquakes to aid in response efforts. However, magnitude estimation across a large range of earthquake sizes and tectonic settings is technically difficult. To help streamline this process, we developed another machine learning model which allows for the estimation of earthquake magnitudes uniformly for all locations and tectonic settings worldwide, which is also presented in this dissertation. Six multi-frame animations with more figures from this chapter are included as supplemental video files. This dissertation includes previously published and unpublished co-authored material

The Influence of Positive Maternal Involvement on the Relationship Between Maternal Emotion Dysregulation and Preschooler Internalizing and Externalizing Problems

Children of mothers with elevated emotion dysregulation (ED) may be at greater risk for developing internalizing (INT) and externalizing (EXT) problems and, in turn, future psychopathology. While previous studies have investigated early risk pathways that may explain this association (e.g., unsupportive maternal responding), our understanding of factors that protect against the downstream effects of maternal ED on child outcomes is limited. To explore prospective protective factors, the current study examined the moderating role of positive maternal involvement on the relationship between maternal ED and preschoolers’ INT and EXT problems. This study included 178 mother-child dyads, where maternal ED was assessed using the Difficulties in Emotion Regulation Scale, positive maternal involvement was assessed using the Alabama Parenting Questionnaire – Preschool Revision, and preschoolers’ INT and EXT problems were assessed with the Child Behavior Checklist. Maternal ED and positive maternal involvement had significant direct effects on preschoolers’ INT and EXT problems; however, the moderating effect of positive maternal involvement on the relationship between maternal ED and preschooler INT and EXT problems was nonsignificant. Further examination of factors that may mitigate risk among children of mothers with elevated ED is necessary to inform effective prevention and intervention efforts

The Roles of Processing Difficulty and Numeracy in the Use of Numeric Risk Information

One of the key challenges in risk communication is effectively conveying numeric information to the public. Research suggests that numeric information is often more complex and less likely to be used than narrative information, such as individual stories. This may be because numbers are more cognitively demanding, leading decision-makers to rely on easier-to-use narrative content. However, a study on the representativeness heuristic (judging probabilities based on resemblance) found that the use of information depends not on its type but on its difficulty and the cognitive resources available. Specifically, when cognitive resources are limited, people are more likely to use numeric information that is easier to process (shorter and presented before a long narrative) than they are to use more complex numeric information (longer and presented after a short narrative). However, when resources are ample, they are more likely to use more complex numeric information (longer and presented after a short narrative) than they are to use numeric information that is easier to process (shorter and presented before a long narrative). The present two studies extended these ideas into risk assessment, focusing on numeracy instead of cognitive resources. It was hypothesized that participants paradoxically would be more sensitive to risk levels when numeric information was harder to process, with this effect being stronger among highly numerate individuals. In Study 1, the difficulty of information was manipulated by varying its length and order of presentation; in Study 2, it was manipulated by varying numeric precision and order of presentation. Results from Study 1 supported the hypothesis that participants would be more sensitive to risk levels when numeric information was harder to process (longer and presented after a short narrative) compared to when it was easier to process (shorter and presented before a long narrative). Interestingly, number preferences, rather than numeracy, emerged as a significant moderator in Study 1. However, the manipulation in Study 2 was unsuccessful, and the anticipated effects were not observed. Implications for enhancing risk communication strategies were subsequently discussed

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Navigating EDI in Academic Libraries: A Strategic Framework for Inclusive Library Practices

Diversity, Equity, and Inclusion Academic LibrariesUniversity of Oregon University of California, Berkeley Emory Universit