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A Multi-Tiered Approach to Improving Vaccination: Adjuvanticity, Alternate Routes of Delivery, and Science Communication
Vaccines have been used to prevent infectious disease for over 200 years. While they are an incredible way to prevent loss of life, they can be improved upon. Researchers around the globe are working to improve the immune response and ultimately the protection provided by existing and new vaccines. In this dissertation, I investigate three ways to improve vaccine immune responses: using an adjuvant, using a prime-boost intramammary delivery route in cows, and using microneedle delivery route. Cholera toxin (CT) is a bacterial toxin that has a non-toxic B subunit (CTB) used as a vaccine adjuvant. However, little is known about how CTB specifically activates the immune system differently than CT. I hypothesize that CTB can act as an adjuvant to induce local and systemic immunity and support alternate routes of vaccine delivery. The results in these studies indicate that CTB has a distinct immune response without causing the toxic damage seen in CT treatments, that CTB can act as a good vaccine adjuvant for a bovine vaccine, and that CTB can be incorporated successfully into microneedles. The CTB adjuvant was incorporated into a Staphylococcus aureus vaccine that was delivered by an intramammary prime with a subcutaneous boost to prevent bovine mastitis. Through a phase 1 USDA cow study, we showed that this vaccine delivered with this prime-boost method is safe and triggers an antigen-specific systemic humoral and cellular immune response when compared to an unvaccinated group. Another way to increase immune response is by delivering vaccines to the skin using microneedles. I developed a dissolvable sugar microneedle that can withstand application forces and deliver an antigen fused to a CTB adjuvant to the epidermis and dermis. Lastly, improvement to vaccines is only effective if people are willing to take them, so building trust and spreading awareness of the research process is critical. In this dissertation, I share several ways to communicate vaccine research to a variety of ages throughout the community, including, among others, elementary STEM, high school biology labs, health fairs, and news articles. In conclusion, this research substantiates and builds upon evidence that CTB is an effective adjuvant for vaccines delivered by alternative routes and advances the use of these routes to promote vaccine acceptance
Reproducible Infrastructure for Modeling Thermoplastic Polymer Fusion Welding
Aircraft materials must balance the demands of being light-weight and fuel efficient with being safe, durable, and strong. Carbon-fiber reinforced polymer composites are able to meet both of these requirements, and as a result, they are being utilized more and more in aircraft manufacturing. Thermoset polymers are typically used as the matrix material in these composites; however, thermoset polymers require long curing times in large autoclave ovens in order to form chemical cross-links, which once present, cannot be melted upon further heating. As a result, joining smaller thermoset composite parts together to build larger structures requires using mechanical fasteners, which act as stress risers and potential corrosion sites, or adhesives, which require intensive surface preparation. Because of these long curing times, and challenges of joining parts together, interest is growing in replacing thermosets with thermoplastic polymers as the matrix material. Unlike thermosets, thermoplastics can be heated to melt, and cooled to re-solidify. This feature of thermoplastics offers the ability to utilize fusion welding joining between parts instead of mechanical fasteners or adhesives. Before thermoplastic carbon-fiber composites can become widely adopted in critical aircraft parts, it is needed to develop a deeper understanding between material processing, properties and performance in order to meet the stringent requirements of Federal Aviation Administration (FAA) certification and regulations. Molecular dynamics (MD) offers the ability to gain atomistic insight into fusion welding of polymer materials, where polymer diffusion and entanglements can be observed and analyzed in ways inaccessible to experimental methods. However, computational limitations of MD simulations, combined with the large length scales and slow relaxation times of polymers are a significant obstacle. Furthermore, standardized methods, and the tools needed to reproducibly perform fusion welding simulation workflows are not readily available. In this work, coarse-grained models of high-performance thermoplastics poly(ether ketone ketone) (PEKK) and poly(phenylene sulfide) (PPS) are derived from atomistic models in order to reasonably access the length and time scales needed to form polymer diffusion and entanglements across a polymer-polymer interface. An open-source software package is designed in an effort to make thermoplastic fusion welding modeling more accessible while also being transparent, reproducible, usable by others, and extensible to other materials and polymer models. Fusion welds are performed using a coarse-grain model of PPS at several chain lengths, and we perform tensile test simulations to understand the mechanical properties of the welded interface
Effects of Changing Winter Precipitation Phase on Streamflow Magnitude in Mountainous Regions
Snowmelt-produced streamflow (Q) is the dominant water source for a large portion of the global population. This is especially true in higher elevation regions in the Western United States. Precipitation is highly variable and seasonal in this region of the world. Generally, most precipitation occurs in winter and comes as snow in higher elevations. However, due to climate change, precipitation and temperature patterns are changing. It has been observed in many areas across the Western United States that the fraction of precipitation falling as snow (Sf) is declining because of a warming climate. In addition, warmer temperatures cause snow to melt earlier in the season. These changes are causing unforeseen changes to the snowmelt-driven Q relationship. Predictions on how a warming climate will affect Q response vary and often conflict. In some studies, a reduction in Sf and earlier melt-off results in less runoff generation; in others, a decrease in Sf results in more runoff generation. The relationship between changing temperatures, precipitation patterns, and the resulting runoff magnitude is poorly understood. To better understand the relationship between precipitation, precipitation phase, and the resulting Q, this study uses meteorological data and hydrological data from multiple sub-basins within the Dry Creek Experimental Watershed (DCEW) near Boise, Idaho, to identify years in each basin where most of the precipitation fell as either snow or rain. We compared the resulting streamflows by calculating runoff ratios (Ro) for each year and sub-basin to determine if Q changes with a change in the precipitation phase. In addition to finding the trend between the precipitation phase and the resulting Ro, correlation analysis was done on various other predictor variables such as soil moisture, SWE, Sf, snow persistence (Sp), and other meteorological variables to determine why Q magnitude may be changing. We found that for years where more of the precipitation fell as snow, the resulting runoff ratios were higher, and evapotranspiration, spring precipitation, soil moisture, and snow persistence were important controlling variables. We must understand how this change will affect Q magnitude and timing to better predict water availability in snow-dominated regions, which will be primarily affected by changing precipitation patterns
Girls in God Town
Girls in God Town is a novel that weaves between childhood and young adulthood, exploring religious faith, queerness, and what we owe to our family, our friends, and ourselves. Twenty-six-year-old Summer Larson has her own life now. She shares a quaint San Antonio apartment with her girlfriend, just picked up a long-term substitute teaching job that she doesn’t hate, and avoids visiting her hometown of Chester, Texas unless she absolutely has to. In Chester, memories of Summer’s past flare up around every corner: from the river where she would secretly make out with her ex-best-friend Bethany, to the church that kept her closeted and guilty throughout her teen years. So, it’s best to stay away. But when Summer’s father Jim, a doomsday-prepping evangelical pastor, falls into ill-health, Summer is yanked back to her hometown. This includes encountering Bethany, who has settled down in Chester with a husband, two kids, and a strangely father-daughter-like relationship with Summer’s dad. As Jim’s health continues to deteriorate, Summer will find herself leaning on Bethany more than she’d like to. She’ll be forced to contend with the love and betrayal that pulled her and Bethany apart as teenagers—along with the church community that shaped her growing up and the father who loves her but cannot accept her fully as she is
Investigation in the Influence of the Device Material Layers on the Electrical Performance of the Self-Directed Channel (SDC) Memristor
The self-directed channel (SDC) memristor consists of layers of Ge40Se60 (active layer), SnSe, and Ag, which operate together to produce a memristive device that is stable at high operating temperatures, capable of cycling over 1 billion times, has a fast switching, and has low power consumption. This research explored whether altering the device materials could influence the SDC electrical performance. That was investigated by changing the chemical constituents in the individual material layers (chalcogenide atoms O, S, Se, and Te in the Ge-Ch (active layer), chalcogenide stoichiometry in the Ge-Ch (active layer), and finally, the chalcogenide in the Sn-Ch (metal chalcogenide layer), which can be measured by measuring the resulting changes in electrical performance. Also, the effect of altering the device materials on the electrical conduction in amorphous materials, including (Fowler-Nordheim Tunneling, Schottky emission, Mott-Gurney Hopping, Space Charge-Limited, and Poole Frenkel), was explored, and the differences in the electrical behavior for each material change were quantified.
Additionally, the investigation included determining the device conductivity within the low resistance state operation mode and calculating the area under the hysteresis loop under the influence of a continuous-wave (CW) input signal
The Frequency, Type, and Function of Visual Displays in Upper Elementary Standardized Science Tests
Limited research has explored the use of visual displays (ViDis) in science tests, making it challenging to know how these tests align with classroom instruction and what skills students need to be successful on these tests. Therefore, the current study aims to describe the use of ViDis in upper elementary grade standardized science tests. We quantified the frequency, types, and functions of ViDis in science tests in 23 states and Washington, DC. Findings show that in the 741 test items examined, 74.5% included ViDis. Tables, diagrams, and images are the most common ViDis. Importantly, 42.1% of the ViDis in the test questions and 59.3% of the ViDis in the test answers provide essential information for correctly answering the questions. We provide implications for teachers and researchers
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Dataset for Association of Alpha-Crystallin with Human Cortical and Nuclear Lens Lipid Membrane Increases with the Grade of Cortical and Nuclear Cataract
Eye lens a-crystallin has been shown to become increasingly membrane-bound with age and cataract formation; however, to our knowledge, no studies have investigated the membrane interactions of a-crystallin throughout the development of cataracts in separated cortical membrane (CM) and nuclear membrane (NM) from single human lenses. In this study, four pairs of human lenses from age-matched male and female donors and one pair of male lenses ranging in age from 64 to 73 years old (yo) were obtained to investigate the interactions of a-crystallin with the NM and CM throughout the progression of cortical cataract (CC) and nuclear cataract (NC) using the electron paramagnetic resonance spin-labeling method. Donor health history information (diabetes, smoker, hypertension, radiation treatment), sex, and race were included in the data analysis. The right eye lenses CM and NM investigated were 64 yo male (CC: 0), 68 yo male (CC: 3, NC: 2), 73 yo male (CC: 1, NC: 2), 68 yo female (CC: 3, NC: 2), and 73 yo female (CC: 1, NC: 3). Similarly, left eye lenses CM and NM investigated were 64 yo male (CC: 0), 68 yo male (CC: 3, NC: 2), 73 yo male (CC: 2, NC: 3), 68 yo female (CC: 3, NC: 2), and 73 yo female (CC: 1, NC: 3). Analysis of a-crystallin binding to male and female eye lens CM and NM revealed that the percentage of membrane surface occupied (MSO) by a-crystallin increases with increasing grade of CC and NC. The binding of a-crystallin resulted in decreased mobility, increased order, and increased hydrophobicity on the membrane surface in male and female eye lens CM and NM. CM mobility decreased with an increase in cataracts for both males and females, whereas the male lens NM mobility showed no significant change, while female lens NM showed increased mobility with an increase in cataract grade. Our data shows that a 68 yo female donor (long-term smoker, pre-diabetic, and hypertension; grade 3 CC) showed the largest MSO by a-crystallin in CM from both the left and right lens and had the most pronounced mobility changes relative to all other analyzed samples. The variation in cholesterol (Chol) content, size and amount of cholesterol bilayer domains (CBDs), and lipid composition in the CM and NM with age and cataract might result in a variation of membrane surface mobility, membrane surface hydrophobicity, and the interactions of a-crystallin at the surface of each CM and NM. These findings provide insight into the effect of decreased Chol content and the reduced size and amount of CBDs in the cataractous CM and NM with an increased binding of a-crystallin with increased CC and NC grade, which suggests that Chol and CBDs might be a key component in maintaining lens transparency
Nutrient Density (Lecture)
Dan Kittredge has been an organic farmer for more than 30 years and is the founder and executive director of the Bionutrient Food Association (BFA), a non-profit whose mission is to “increase quality in the food supply.” Known as one of the leading proponents of “nutrient density,” Dan works to demonstrate the connections between soil health, plant health, and human health. We will cover current research on nutrient density and the vision for how this exciting work could serve to profoundly disrupt the dynamics of the food supply. Can agriculture meaningfully reverse climate imbalances, and be used to reverse chronic disease as well? We think so
Community Diversity in Closed vs. Open Habitats in the Sagebrush Steppe
The sagebrush steppe ecosystems of southern Idaho are extremely diverse and include a variety of annual, perennial, and shrub plants, as well as species well-adapted for their specific niches. This ecosystem varies in openness created by differing amounts of shrub cover, which allows for complex community interactions between predator/prey utilizing differing strategies and amounts of cover. We aim to document the species composition and richness in different cover types (open and closed understories). We hypothesize that community composition and richness differ between closed and open areas, the more complex habitat will better support greater species richness and draw more ambushing predators. Data collection included placing field cameras in habitats with dense shrubbery, high-coverage annual grasses, and sparse perennial grasslands between January 23rd and March 31st. We analyzed the images of the species present during this time and their presence in closed or open areas. If composition varies between habitats, we expect to see more ambush predators and non-burrowing species utilizing dense shrublands, and burrowing species in open habitats. Our results could prompt future studies on species habitat adaptations and interactions, as well as further studies on diversity to indicate ecosystem health