Optimizing a Point-of-Care Lateral Flow Assay for Measuring Eosinophil Peroxidase in the Esophageal String Test

Description
Background: Eosinophilic esophagitis (EoE) is an increasingly prevalent allergic disease characterized by eosinophilic inflammation and symptoms of esophageal dysfunction. Diagnosis and monitoring require repeated, invasive endoscopic esophageal biopsies to assess levels of eosinophilic inflammation. Recently, the minimally invasive esophageal string

Background: Eosinophilic esophagitis (EoE) is an increasingly prevalent allergic disease characterized by eosinophilic inflammation and symptoms of esophageal dysfunction. Diagnosis and monitoring require repeated, invasive endoscopic esophageal biopsies to assess levels of eosinophilic inflammation. Recently, the minimally invasive esophageal string test (EST) has been used collect protein in mucosal secretions as a surrogate for tissue biopsies in monitoring disease activity. From the string, assessment of the eosinophil-associated proteins major basic protein-1 (MBP-1) and eotaxin-3 (Eot3) is used to assess disease activity; however, this requires measurement in a reference laboratory, for which the turnaround time for results exceeds the time required for histopathologic assessment of endoscopic biopsies. In addition, MBP-1 and Eot3 are not markers unique to eosinophils. These obstacles can be overcome by targeting eosinophil peroxidase (EPX), an eosinophil-specific protein, using a rapid point-of-care test. Currently, EPX is measured by a labor-intensive enzyme-linked immunosorbent assay (ELISA), but we sought to optimize a rapid point-of-care test to measure EPX in EST segments. Methods: We extracted protein from residual EST segments and measured EPX levels by ELISA and a lateral flow assay (LFA). Results: EPX levels measured by LFA strongly correlated with those quantified by ELISA (rs = 0.90 {95% CI: 0.8283, 0.9466}). The EPX LFA is comparable to ELISA for measuring EPX levels in ESTs. Conclusions: The EPX LFA can provide a way to rapidly test EPX levels in ESTs in clinical settings and may serve as a valuable tool to facilitate diagnosis and monitoring of EoE.
Date Created
2024-05
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A Desert of Mind-Dust: An Argument for Panpsychism

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Description

Panpsychism is the view that consciousness is an intrinsic state of the world. While early forms were advanced by Spinoza and Russell, only recently has panpsychism gained widespread academic consideration. In this paper, I will argue for panpsychism, based on

Panpsychism is the view that consciousness is an intrinsic state of the world. While early forms were advanced by Spinoza and Russell, only recently has panpsychism gained widespread academic consideration. In this paper, I will argue for panpsychism, based on a similarity of the nature of our consciousness with the nature of the parts of our consciousness. This argument will be motivated by an anti-strong emergentist viewpoint, while allowing for complex consciousness to arise from a form of weak emergence between fundamental parts. Ultimately, this argument demonstrates that an identity theorist would collapse to panpsychism or strong emergentism, the former being preferred. From this, I argue that panpsychists can gain some intuitive benefits of dualism and materialism, without inheriting their issues. This positions the panpsychist well to respond to issues like Jackson’s (1982) Mary-argument. I will then discuss possible objections to panpsychism, focusing primarily on the combination problem. I conclude that the co-consciousness strategy is the optimal solution to this problem and can account for the inverse issue of the decombination problem that cosmopsychism faces. Overall, panpsychism’s explanatory power and compatibility with other disciplines makes it a favorable theory within the philosophy of mind.

Date Created
2024-05
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luca_spring_2024-fully-sized-figures.pdf

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Date Created
2024-05
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luca_spring_2024.pdf

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Date Created
2024-05
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Exploring DNA nanotechnology: Enhancing the NK cell immune response against tumors.

Description
Cell immunotherapies have revolutionized clinical oncology. While CAR T cell therapy has been very effective in clinical studies, off-target immune toxicity limits eligible patients. Thus, NK cells have been approached with the same therapy design since NK cells have a

Cell immunotherapies have revolutionized clinical oncology. While CAR T cell therapy has been very effective in clinical studies, off-target immune toxicity limits eligible patients. Thus, NK cells have been approached with the same therapy design since NK cells have a more favorable safety profile. Therefore, the purpose of this research project is to explore DNA nanotech-based NK cell engagers (NKCEs) that force an immunological synapse between the NK cell and the cancer cell, leading to cancer death. DNA tetrabody (TB) and DNA tetrahedron (TDN) are fabricated and armed with HER2 affibody for tight adhesion to HER2+ cancer cell lines like SKBR3. Overall, relationship between TB-NK treatment and cancer cell apoptosis is still unclear. TB-NK treatment induces an apoptotic profile similar to PMA/IO stimulation. Pilot cell assay needs to be replicated with additional controls and a shortened treatment window. For DNA TDN fabrication, HER2 affibody polishing with Ni-NTA affinity chromatography achieves high purity with 20% to 100% high-imidazole elution gradient. ssDNA-HER2 affibody conjugation is optimal when ssDNA is treated with 40-fold excess sulfo-SMCC for 4 hours. In conclusion, the manufacturing of DNA-based NKCEs is rapid and streamlined, which gives these NKCEs the potential to become a ready to use immunotherapy.
Date Created
2024-05
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Testing the Activity of Phosphoenolpyruvate carboxykinase (Pck) Variants to Improve Bioproduction

Description
Heterotrophs such as E. coli contain metabolic pathways with enzymes called carboxylases that are capable of fixing CO2 gas to form metabolites, which has implications for aiding with CO2’s role in climate change. The reductive branch of the tricarboxylic acid

Heterotrophs such as E. coli contain metabolic pathways with enzymes called carboxylases that are capable of fixing CO2 gas to form metabolites, which has implications for aiding with CO2’s role in climate change. The reductive branch of the tricarboxylic acid (TCA) cycle serves as an important pathway for NAD+ regeneration in enteric bacteria in anaerobic conditions and leads to the production of succinate, a useful industrial product. The enzyme phosphoenolpyruvate carboxykinase is responsible for fixing CO2 in the conversion of PEP to OAA within this pathway and has potential to be a significant carbon fixation module in heterotrophic organisms. This project explored pck genes from select organisms by transforming plasmids to test if these variants have improved kinetics compared to the native E. coli Pck and to investigate their ability to improve succinate bioproduction.
Date Created
2024-05
Agent

Challenges to College Nutrition: A Website to Bridge Resource Gaps

Description
This paper examines the multifaceted challenges surrounding college students' nutrition, with a specific focus on Arizona State University (ASU). Examining economic shifts, psychological influences, nutrition knowledge, and body image dynamics, it reveals the profound impact on students' food security and

This paper examines the multifaceted challenges surrounding college students' nutrition, with a specific focus on Arizona State University (ASU). Examining economic shifts, psychological influences, nutrition knowledge, and body image dynamics, it reveals the profound impact on students' food security and eating behaviors. Despite existing initiatives, persistent gaps in resources remain, necessitating comprehensive interventions to support students effectively. In response, "The Ultimate Health Resource for ASU Students," a website, was developed as an innovative solution. This platform aims to empower students by providing a centralized hub to access vital resources, connect with peers, and discover nutritious recipes. Proposed strategies encompass expanding food pantry offerings, developing mobile applications for nutritional guidance, and fostering partnerships with local organizations. By tackling these challenges head-on and fostering a culture of support, ASU can ensure that all students have equitable access to nutritious food options and the necessary resources to thrive academically and personally. The website serves as a place of empowerment, offering practical solutions and fostering a sense of community among ASU students striving for optimal health and well-being.
Date Created
2024-05
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Rethinking Societal Happiness

Description
The aim of this thesis is to explore and understand how cultural, socio-economic, and political factors intersect to influence and affect societal happiness. We examine this by exploring the discrepancies that exist between the world’s happiest country, Finland, and the

The aim of this thesis is to explore and understand how cultural, socio-economic, and political factors intersect to influence and affect societal happiness. We examine this by exploring the discrepancies that exist between the world’s happiest country, Finland, and the world’s 15th happiest nation, the United States. Through our explanation, we find that the cultural differences within nations is the implicit key to success in happiness. More specifically, the differences between femininity, experienced in the Nordic region, and masculinity, experienced in the United States. Social, economic, and political factors are in large part a result of the underlying culture. We see the nuanced ways in which cultural orientations shape social structures and policies which directly impact a society’s well-being. In analysis of the World Happiness Report, we acknowledge the multifaceted nature of happiness metrics, highlighting the importance of inclusive policy-making and responsive governance. Amidst its growing popularity the topic of societal happiness is growing in attention from both the public and policymakers. A collective pursuit of happiness emerges despite the cultural diversity prevalent throughout the world. By examining these complex relationships, we look to offer insight that helps create a deeper understanding of the complex relationship that exists between culture and societal happiness and well-being.
Date Created
2024-05
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The Advantages of Treating Metastatic Melanoma with Immunotherapy Instead of Chemotherapy or Excision

Description
The treatment of melanoma is dependent on what stage the cancer has developed into. Metastatic melanoma is commonly treated with immune checkpoint inhibitors. Unfortunately, not all patients will respond to the treatment as expected. This paper develops important background knowledge

The treatment of melanoma is dependent on what stage the cancer has developed into. Metastatic melanoma is commonly treated with immune checkpoint inhibitors. Unfortunately, not all patients will respond to the treatment as expected. This paper develops important background knowledge on melanoma, how it is treated for each stage, and immune checkpoint inhibitors.
Date Created
2024-05
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Testing the Effects of Catechol and Lemon Juice Components on Differentiation in Adipocytes.

Description
Asphalt is a widely used mixture in the paving and roofing industries and its sales are expected to increase by 57% in the next eight years alone (Mandaokar, 2024). However, it is known to have highly toxic constituents such as

Asphalt is a widely used mixture in the paving and roofing industries and its sales are expected to increase by 57% in the next eight years alone (Mandaokar, 2024). However, it is known to have highly toxic constituents such as benzo[a]pyrene (BaP) and catechol, (National Institute, 1977, Hazard Review, 2000, Neghab et al., 2015, and Rozewski et al., 2023). Lemon juice, which is an inexpensive and easily accessible natural substance that is shown to have health benefits such as increasing insulin sensitivity, aiding with weight loss, and preventing heart disease (Tejpal et al., 2020), may counteract the effects of asphalt. The question of what the biological effects of asphalt, lemon juice, and the combination of the two on adipocytes was tested via computational analysis and experiments. It was predicted that catechol and lemon juice components will show biological effects in adipocytes that could be opposing, additive, or synergistic. A computational analysis involving the docking of fourteen components of asphalt and thirty-five components of lemon juice constituents to a targetome of 7,529 proteins (Ovanessians et al., 2024) suggests that asphalt and lemon juice components have many possible protein targets. Experiments were carried out with 3T3L1 mouse adipocytes to study five different lemon extracts (crude, hexane organic and aqueous, and ether organic and aqueous), and two components of asphalt (catechol and BaP): 1) Thiazolyl Blue Tetrazolium Bromide (MTT) cell viability and toxicity assay, 2) reactive oxygen species fluorescence assay, 3) Nile red staining assay, 4) red oil o staining assay, and a 5) lipidomics analysis on the hexane and ether organic extracts of lemon juice. This study has shown that asphalt components BaP and catechol and lemon juice components combined have the following biological effects on adipocytes: 1) Of the 5 lemon extracts tested, the organic layer of the hexane extract solubilized in DMSO (LE4) decreases differentiation the most. 2) Nile red staining is inhibited by 0.1 mg/mL of LE4, 1 µM BaP, and 20 µM catechol at a similar level. 3) Cell morphology differs between LE4, BaP, and catechol. Future work will include an insulin sensitivity assay to confirm the indicative inhibitory relationship found between lemon juice and asphalt. Expanding upon the lipidomic results of the lemon juices, as well as maximizing the potential of dockings by connecting results with the experiments, may also prove to be useful in future studies.
Date Created
2024-05
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