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Spaceflight and spaceflight analogue culture enhance the virulence and pathogenesis-related stress resistance of the foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). This is an alarming finding as it suggests that astronauts may have an increased risk of infection during spaceflight. This risk is further exacerbated as multiple studies indicate that spaceflight negatively impacts aspects of the immune system. In order to ensure astronaut safety during long term missions, it is important to study the phenotypic effects of the microgravity environment on a range of medically important microbial pathogens that might be encountered by the crew. This ground-based study uses the NASA-engineered Rotating Wall Vessel (RWV) bioreactor as a spaceflight analogue culture system to grow bacteria under low fluid shear forces relative to those encountered in microgravity, and interestingly, in the intestinal tract during infection. The culture environment in the RWV is commonly referred to as low shear modeled microgravity (LSMMG). In this study, we characterized the stationary phase stress response of the enteric pathogen, Salmonella enterica serovar Enteritidis (S. Enteritidis), to LSMMG culture. We showed that LSMMG enhanced the resistance of stationary phase cultures of S. Enteritidis to acid and thermal stressors, which differed from the LSSMG stationary phase response of the closely related pathovar, S. Typhimurium. Interestingly, LSMMG increased the ability of both S. Enteritidis and S. Typhimurium to adhere to, invade into, and survive within an in vitro 3-D intestinal co-culture model containing immune cells. Our results indicate that LSMMG regulates pathogenesis-related characteristics of S. Enteritidis in ways that may present an increased health risk to astronauts during spaceflight missions.
ContributorsKoroli, Sara (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, C. Mark (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
In this study, we demonstrate the effectiveness of a cancer type specific FrAmeShifT (FAST) vaccine. A murine breast cancer (mBC) FAST vaccine and a murine pancreatic cancer (mPC) FAST vaccine were tested in the 4T1 breast cancer syngeneic mouse model. The mBC FAST vaccine, both with and without check point inhibitors (CPI), significantly slowed tumor growth, reduced pulmonary metastasis and increased the cell-mediated immune response. In terms of tumor volumes, the mPC FAST vaccine was comparable to the untreated controls. However, a significant difference in tumor volume did emerge when the mPC vaccine was used with CPI. The collective data indicated that the immune checkpoint blockade therapy was only beneficial with suboptimal neoantigens. More importantly, the FAST vaccine, though requiring notably less resources, performed similarly to the personalized version of the frameshift breast cancer vaccine in the same mouse model. Furthermore, because the frameshift peptide (FSP) array provided a strong rationale for a focused vaccine, the FAST vaccine can theoretically be expanded and translated to any human cancer type. Overall, the FAST vaccine is a promising treatment that would provide the most benefit to patients while eliminating most of the challenges associated with current personal cancer vaccines.
ContributorsMurphy, Sierra Nicole (Author) / Johnston, Stephen (Thesis director) / Peterson, Milene (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Menstruation - a stigmatized topic and a social taboo- has led to a lack of menstrual hygiene awareness and improper practices impacting women’s health adversely over generations in India. Akshara aims to increase menstrual hygiene education and reduce stigma in India. A creative children’s illustrated book, and interactive workshop curriculum about menstruation were designed and published in Hindi and English. Menstrual hygiene workshops, utilizing the designed tools, were conducted in Delhi and Ghaziabad, India to over 230 students through NGO partnerships in December 2018. The response to the menstrual hygiene and stigma workshops was overwhelmingly positive, and a significant increase in the knowledge and awareness survey scores was observed after the curriculum teachings and classroom discussions. This evaluation highlights and provides a potential solution path to eradicate the root cause of the menstruation stigma in underprivileged women through education and open conversations on the topic starting at a pivotal young age. The main aim of the workshop was to help eradicate the stigma associated with menstruation and menstrual health in India through education.
ContributorsBhalla, Jahnavi (Co-author) / Dani, Advika (Co-author) / Schuster, Roseanne (Thesis director) / Hruschka, Daniel (Thesis director) / School of Molecular Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
More than 40% of all U.S. opioid overdose deaths in 2016 involved a prescription opioid, with more than 46 people dying every day from overdoses involving prescription opioids, (CDC, 2017). Over the years, lawmakers have implemented policies and laws to address the opioid epidemic, and many of these vary from state to state. This study will lay out the basic guidelines of common pieces of legislation. It also examines relationships between 6 state-specific prescribing or preventative laws and associated changes in opioid-related deaths using a longitudinal cross-state study design (2007-2015). Specifically, it uses a linear regression to examine changes in state-specific rates of opioid-related deaths after implementation of specific policies, and whether states implementing these policies saw smaller increases than states without these policies. Initial key findings of this study show that three policies have a statistically significant association with opioid related overdose deaths are—Good Samaritan Laws, Standing Order Laws, and Naloxone Liability Laws. Paradoxically, all three policies correlated with an increase in opioid overdose deaths between 2007 and 2016. However, after correcting for the potential spurious relationship between state-specific timing of policy implementation and death rates, two policies have a statistically significant association (alpha <0.05) with opioid overdose death rates. First, the Naloxone Liability Laws were significantly associated with changes in opioid-related deaths and was correlated with a 0.33 log increase in opioid overdose death rates, or a 29% increase. This equates to about 1.39 more deaths per year per 100,000 people. Second, the legislation that allows for 3rd Party Naloxone prescriptions correlated with a 0.33 log decrease in opioid overdose death rates, or a 29% decrease. This equates to 1.39 fewer deaths per year per 100,000 people.
ContributorsDavis, Joshua Alan (Author) / Hruschka, Daniel (Thesis director) / Gaughan, Monica (Committee member) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The International Space Station (ISS) utilizes recycled water for consumption, cleaning and air humidity control. The Environmental Control and Life Support Systems (ECLSS) have been rigorously tested at the NASA Johnson Space Center. Despite the advanced engineering of the water recovery system, bacterial biofilms have been recovered from this potable water source. Microbial contamination of potable water poses a potential threat to crew members onboard the ISS. Because astronauts have been found to have compromised immune systems, bacterial strains that would not typically be considered a danger must be carefully studied to better understand the mechanisms enabling their survival, including polymicrobial interactions. The need for a more thorough understanding of the effect of spaceflight environment on polymicrobial interactions and potential impact on crew health and vehicle integrity is heightened since 1) several potential pathogens have been isolated from the ISS potable water system, 2) spaceflight has been shown to induce unexpected alterations in microbial responses, and 3) emergent phenotypes are often observed when multiple bacterial species are co- cultured together, as compared to pure cultures of single species. In order to address these concerns, suitable growth media are required that will not only support the isolation of these microbes but also the ability to distinguish between them when grown as mixed cultures. In this study, selective and/or differential media were developed for bacterial isolates collected from the ISS potable water supply. In addition to facilitating discrimination between bacteria, the ideal media for each strain was intended to have a 100% recovery rate compared to traditional R2A media. Antibiotic and reagent susceptibility and resistance tests were conducted for the purpose of developing each individual medium. To study a wide range of targets, 12 antibiotics were selected from seven major classes, including penicillin, cephalosporins, fluoroquinolones, aminoglycosides, glycopeptides/lipoglycopeptides, macrolides/lincosamides/streptogramins, tetracyclines, in addition to seven unclassified antibiotics and three reagents. Once developed, medium efficacy was determined by means of growth curve experiments. The development of these media is a critical step for further research into the mechanisms utilized by these strains to survive the harsh conditions of the ISS water system. Furthermore, with an understanding of the complex nature of these polymicrobial communities, specific contamination targeting and control can be conducted to reduce the risk to crew members. Understanding these microbial species and their susceptibilities has potential application for future NASA human explorations, including those to Mars.
ContributorsKing, Olivia Grace (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Sustainability (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
The objective of this thesis was to determine whether Zika Virus (ZIKV) can be effectively inactivated by Selective Photonic Disinfection (SEPHODIS) and determine whether key proteins involved in the infection process are preserved, making SEPHODIS a possible source for vaccine development. As of January 2018, there have been 3,720 confirmed cases of Congenital Zika Syndrome in infants, making a Zika Vaccine a high priority (Mitchell, 2018). SEPHODIS is a process that involves prolonged exposure of an object to a pulsing laser which can render it ineffective. Initially, ZIKV was subjected to laser inactivation for 6 hours, then a plaque assay was performed on both laser-treated and control samples. ZIKV was inactivated two-fold? after laser treatment, when compared with control, as indicated by the plaque assay results. Additionally, both samples were submitted to ELISA to evaluate antigenicity with a panel of monoclonal and human sera. As a second control, virus inactivated by formaldehyde (2%) was used. ELISA results showed that antigenicity of some proteins were preserved while others were probably disturbed. However, ELISA results show that ZIKV envelope protein (E-protein), the protein responsible for viral entry into cells, was effectively preserved after laser-treatment, implying that if laser parameters were tweaked to obtain more complete inactivation, then SEPHODIS may be an appropriate source for the development of a vaccine.
ContributorsViafora, Ataiyo Blue (Author) / Johnston, Stephen (Thesis director) / Tsen, Kong-Thon (Committee member) / School of Life Sciences (Contributor) / School of Sustainability (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
In an increasingly interconnected world, the 17 Sustainable Development Goals are the United Nations’ framework for ensuring we continue to transform our world for the better, leaving no population behind. This study examines how the terminology of Sustainable Development Goal 17 for global partnership affects its implementation, focusing on “building capacity”—a widely referenced target in the development arena—and the involvement of the private sector. Key informant interviews with experts in the fields of conflict of interest, ethics, and development revealed a wide variety of (often conflicting) notions about partnership, frameworks for capacity development, and the interactions between public and private actors. A literature review of key policy documents examined the terminology and implementation of multistakeholder partnerships, and analysis offered considerations for risks and suggestions in policy terminology. Results indicate a need for increased attention to the use of partnership terminology as a catch-all term to encompass development work, and makes several recommendations for changes to combat misuse of the partnership label. Finally, this study acknowledges that there is a continued need for research-based evidence for effectiveness of the partnership-based development approach.
ContributorsThomson, Azalea Mae (Author) / Gaughan, Monica (Thesis director) / Hruschka, Daniel (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The development of safe and effective vaccines has been one of the greatest public achievements of the 20th century. However, there is still considerable public debate about the relative health costs and benefits of vaccines, and the information and misinformation spread through these debates can have a direct impact on vaccination and whether or not herd immunity will continue in the United States for different diseases. To understand perceptions of vaccine risks and effectiveness among young adults in the U.S., this study describes Arizona State University students' perceptions of the harms and benefits of vaccines. A preliminary free list (n=30) identified what vaccines ASU college students were most likely to recall spontaneously. The six vaccines most commonly mentioned by ASU students were: influenza (flu), chickenpox, HPV, polio, MMR, and smallpox. Using these top six vaccines, we then developed a second survey about the knowledge and perceptions of each of these vaccines and vaccines as a whole. We found that students generally perceived vaccines as safe and important to their health, but they maintained an overall lack of understanding of how vaccines work and what they protect against. While this study is only a preliminary investigation into the perceptions of ASU college students on six commonly mentioned vaccines, this could lead to investigations on how to educate and promote the usage of vaccines to college students.
ContributorsGilson, Jacob (Co-author) / Sutton, Carly (Co-author) / Hruschka, Daniel (Thesis director) / Ruth, Alissa (Committee member) / W. P. Carey School of Business (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
PD-L1 blockade has shown recent success in cancer therapy and cancer vaccine regimens. One approach for anti-PD-L1 antibodies has been their application as adjuvants for cancer vaccines. Given the disadvantages of such antibodies, including long half-life and adverse events related to their use, a novel strategy using synbodies in place of antibodies can be tested. Synbodies offer a variety of advantages, including shorter half-life, smaller size, and cheaper cost. Peptides that could bind PD-L1 were identified via peptide arrays and used to construct synbodies. These synbodies were tested with inhibition ELISA assays, SPR, and pull down assays. Additional flow cytometry analysis was done to determine the binding specificity of the synbodies to PD-L1 and the ability of those synbodies to inhibit the PD-L1/PD-1 interaction. Although analysis of permeabilized cells expressing PD-L1 indicated that the synbodies could successfully bind PD-L1, those results were not replicated in non-permeabilized cells. Further assays suggested that the binding of the synbodies was non-specific. Other tests were done to see if the synbodies could inhibit the PD-1/PD-L1 interaction. This assay did not yield any conclusive results and further experimentation is needed to determine the efficacy of the synbodies in inhibiting this interaction.
ContributorsMujahed, Tala (Author) / Johnston, Stephen (Thesis director) / Blattman, Joseph (Committee member) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
A major recurring issue with aid-providing nonprofit organizations is the lack of accountability to recipients. In many cases, there are not clear-cut ways of measuring the efficiency or effectiveness of aid or to determine when and how the aid is failing to meet the needs of recipients. This study focused on one particular non-governmental organization, Project C.U.R.E., that provides medical aid to developing countries in the form of devices and equipment. It investigated the causes of misalignments observed in Project C.U.R.E.'s medical aid process, specifically with three loads that were shipped to the Ahwiaa, Akoti, Bassengele, Chirano, Humjibre, Ntrentrenso, Paboase, and Wenchi clinics as well as the Bibiani hospital in Ghana between June 2015 and May 2016. The medical aid donation process was observed at the each of its steps. Data was collected through interviews with Project C.U.R.E. employees and associates, and was organized and analyzed using Lean Six Sigma tools in order to find areas where the process broke down or failed. These tools included process mapping, root cause analysis through the use of Pareto charts and process failure mode and effects analysis (PFMEA). Once all of the issues from the shipment were categorized, it was found that the three most common types of issues were the preparation of the device being unclear or being unloaded incorrectly, power issues, and misalignment in terms training, needs, and infrastructure. The PFMEAs identified high-priority issues with missing fields in the Needs Assessment Booklet in the needs assessment step, misaligned products in terms of power availability in the planning step, and a lack of standardization in the warehouse operations step. 50 unique solutions were brainstormed in order to address these issues, as well as others. This means that Lean Six Sigma tools such as Pareto charts and PFMEA can be used to identify problems, identify causes and effects of problems, and help to produce solutions to the identified problems. In the future, more in-depth research into Project C.U.R.E.'s impact evaluation process could be pursued.
ContributorsFisk, Nicole Diane (Author) / Hruschka, Daniel (Thesis director) / Walters, Danielle (Committee member) / School of Human Evolution and Social Change (Contributor) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2016-12