CHEM Graduate Student Conference Papers

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    Characterization of PET tracer Flutemetamol (GE-067) binding to Aβ1-40 fibrils
    (Wichita State University, 2022-04-29) Wijegunawardena, Gayani; Duan, Pu; Kelly, J. Chen; Aurelio, J. Dregni; Harrison, K. Wang; Hong, Mei; Wu, Haifan
    Alzheimer's disease (AD) is a neurological disorder and the most common cause of dementia. One of the major pathological hallmarks of AD is the deposition of amyloid beta peptide (Aβ) into plaques. In the past decade, Positron Emission Tomography (PET) has been used to detect plaques in patients for diagnosis. Although several PET tracers including Flutemetamol (GE-067) have been developed and approved by FDA, their interaction with Aβ fibrils at molecular level is not fully understood. In this study, we aim to characterize the binding of GE-067 to Aβ1-40 fibrils in detail. We developed a binding assay based on HPLC quantification. Using Aβ1-40 fibrils prepared in vitro, we determined the binding stoichiometry of 1:4.6 (GE-067 to Aβ1-40 as a monomer). In collaboration with Prof. Hong, solid-state NMR and molecular docking were used to determine the binding sites of flutemetamol using $^{13}C$, $^{15}N$-labeled Aβ1-40. Our data support multiple binding sites for flutemetamol in Aβ1-40 fibrils. We believe our binding study will guide the effort to further optimize these amyloid PET tracers for higher affinity and selectivity.
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    STEAM education: GeoGebra in 3D printing
    (Wichita State University, 2022-04-29) Uppala, Taraka Rama; Alagic, Mara
    This research is investigating what Science, Technology, Engineering, Arts, and Mathematics (STEAM) concepts and skills can be developed through the use of GeoGebra in 3D printing for learners at all levels, starting from elementary to the university level. Special attention is given to the mathematical concepts and processes as well as to engineering design behind the GeoGebra 3D constructions and consequent 3D printing contributing to interactive ways of teaching rather than the traditional lecturing. GeoGebra (geogebra.com) is a free, dynamic mathematics software for all levels of STEAM education that brings together geometry, algebra, spreadsheets, graphing, statistics, and calculus in one engine. During the design process, students learn how to create models for 3D printing while further developing their critical and creative thinking as well as conceptual understanding of underlying mathematical concepts. So, instructional design research - from GeoGebra to 3D printing - for mathematical investigations, demonstrates how by identifying different problems around them and finding useful and creative 3D printed solutions, learners understand the significant role of STEAM education in becoming responsible citizens ready to live and work in the digital age. Furthermore, animations are designed to capture and demonstrate all the steps in the process, from the idea of an object to its 3D printed production.
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    Identification of lithic processing stages at Boxed Springs (41UR30)
    (Wichita State University, 2022-04-29) Haley, Cambria; Dozier, Crystal A.
    Boxed Springs (41UR30) is an early Caddo site (800-1200 CE) located in East Texas that has been a known site since the 1950s and excavated by archaeologists, volunteers, and looters. The site is documented to be poor in stone deposits suggesting the people had to source their stone from different regions. Stone tools as well as flakes and debitage left behind tell us about the production process and where the raw materials originated. There are two ways in which raw materials can be transported to make tools: whole pieces of raw stone and preforms, the latter of which is stone worked to a rough shape making it smaller and easier for transportation. To understand the process in which the raw materials were transported back to the site, both the size of debitage and flakes will be analyzed to determine which stages of production appear frequently. WSU Archaeology of Food Laboratory currently has a small collection of lithics from the August 2021 excavation which will be used in the analysis. With a sample size of 188 flakes the average length, width, and thickness were found to be 12.45 mm (L), 12.41 mm (W), and T 2.49 mm (T). The small size of the flakes shows stone being worked in stages 3 and 4. In these later stages, larger pieces of stone and cortex have been removed. This is consistent with the minimal amount of cortex found, making up only 9% of the sample size with even fewer having 100% cortex on one side. Evidence shows the transport of preform materials being brought into the Boxed Springs region to be worked and reshaped into tools needed for everyday life. Further excavation and research should be conducted on other lithic materials from the site to determine the extent of the creation and retouching of tools at Boxed Springs.
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    Dependence of proline isomerization on the kinetics of folding of anthrax lethal factor
    (Wichita State University, 2022-04-29) Halimeh, Wyel; Bann, James G.
    The death that can come within a few days after exposure to the anthrax toxin from $Bacillus$ $anthracis$ is due to the presence and effects of anthrax lethal factor (LF). LF is a zinc metalloproteinase whose function depends upon the translocation of LF from the endosome of a host cell into the cytosol, where it cleaves mitogen-activated protein kinase kinases and disrupting cell signaling pathways. The translocation requires LF to unfold as it transits through the narrow channel of the pore, formed by the anthrax protective antigen (PA). Unfolding of LF has been shown to be pH-dependent, but little is known regarding the kinetics of unfolding and refolding of LF. Specifically, refolding of LF must occur fairly rapidly within the cell cytosol to prevent degradation of the protein by cellular proteases. The N-terminal PA binding domain of LF, LFN, has a single cis-proline residue (Pro16, and we hypothesized that this cis proline must isomerize to trans during the unfolding and translocation process and that refolding would be slow, and perhaps dependent on cellular prolyl isomerases for refolding. To this end, we have performed a detailed kinetic refolding/unfolding study of LFN from urea solutions. Our preliminary experiments indicate that LFN refolding occurs rapidly (within 1 second), suggesting that Pro166 does not isomerize to an appreciable extent in the unfolded state, or if it does isomerize, that isomerization back to cis is a fast process. The implications of these experiments on the mechanism of anthrax toxin lethality will be discussed.
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    Hot-press manufacturing of aluminum based multi-layered wick structures for enhanced thermal performance
    (Wichita State University, 2022-04-29) Kumaran, Surendhar; Nair, Rajeev
    INTRODUCTION: Two phase passive heat transfer devices such as vapor chambers are used in modern miniaturized electronic devices and state-of-the-art CubeSat systems. These vapor chambers consist of three base components viz., substrate, wick structure and the working fluid. PURPOSE: The complexity of design and fabrication using conventional manufacturing methodologies such as furnace sintering of the three-dimensional wick structures resulting in longer manufacturing timelines. The current state-of-the-art vapor chambers are solely made using copper as the base material due to its high thermal conductivity and diffusivity, however these properties hinder the manufacturability of the wick. METHODS: In this study, aluminum is used as the base material for manufacturing of three-dimensional wick structures to address the aforementioned problems. Aluminum based multilayered wick structures are fabricated using hot-press sintering process. This novel manufacturing process depends upon temperature, pressure and time period which is then optimized based on design of experiments to determine the most efficient parameters for successful fabrication RESULTS: Successful development of wick structures was observed when the aluminum particles are hot-pressed at temperature and pressure conditions of 200 °C and 1.379 MPa (200 psi). By varying the time period of manufacturing, the structural integrity of the wick structure changes accordingly. CONCLUSION: Aluminum based multi-layered wick structures could be developed by hot-press manufacturing which is much easier to manufacture in comparison with copper based multilayered wick structures. Although, there is performance loss due to the material properties of aluminum, an overall weight of the wick structures is one-third of copper based wick structures.
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