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- Genre: Academic theses
Description
Investigating effective elements of the interior environment in which are proactive strategies related to active shooting prevention are explored through passive and active measures. The research analyzes changes to the interior environment at Virginia Tech after the 2007 shooting based on the strategic implementation of certain actions, features, and experts involved in the decision-making process. This study aims to investigate effective proactive interior design strategies for higher education campuses (or classrooms) that engage both passive and active tactics, and to identify the process in which the decisions are made and implemented. The reviewed literature identifies important aspects of the policies, procedures, psychological/behavioral contingencies of space, and the convergence of design and the built environment. Utilizing a mixed-methods approach, the study will use interviews, photo-ethnography, and forced connections to identify changes made in policies and design which have impacted the higher education environment and safety. The findings are expected to suggest an intersecting approach between decisions made by outside experts and their effect on the interior environment. The potential impact of this research will guide and encourage collaborative, standards, and best practices relative to evidence-based decisions on protection and proactive actions against active shooter situations at Institutions of Higher Education.
ContributorsBurnett, Brooklyn Kate (Author) / Hejduk, Renata (Thesis advisor) / Barton, Scott (Committee member) / Mejía, Mauricio (Committee member) / Arizona State University (Publisher)
Created2022
Description
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of Coronavirus Disease 2019 (COVID-19). Successful vaccination aims to elicit neutralizing antibodies (NAbs) which inhibit viral infection. Traditional NAb quantification methods (neutralization assays) are labor-intensive and expensive, with limited practicality for routine use (e.g. monitoring vaccination response). Thus, a rapid (10-minute) lateral flow assay (LFA) for quantification of SARS-CoV-2 NAbs was developed. Using the NAb LFA, an 18-month longitudinal study assessing monthly NAb titers was conducted in a cohort of over 500 COVID-19 mRNA vaccine recipients. Three NAb response groups were identified: vaccine strong responders (VSRs), moderate responders (VMRs), and poor responders (VPRs). VSRs generated high and durable NAb titers. VMRs initially generated high NAb titers but showed more rapid waning with time post-vaccination. Finally, VPRs rarely generated NAb titers ≥1:160, even after 3rd dose. Although strong humoral responses correlate with vaccine effectiveness, viral-specific CD4+ and CD8+ T cells are critical for long-term protection. Discordant phenotypes of viral-specific CD8+ and CD4+CXCR5+ T follicular helper (cTfh) cells have recently been associated with differential NAb responses. The second portion of this dissertation was to investigate whether/how SARS-CoV-2 T cell responses differ in individuals with impaired NAb titers following mRNA vaccination. Thus, phenotypic and functional characterization of T cell activation across NAb response groups was conducted. It was hypothesized that VPRs would exhibit discordant SARS-CoV-2 T cell activation and altered cTfh phenotypes. Peripheral blood mononuclear cells were isolated from VPRs, VMRs, VSRs, naturally infected, and normal donors. SARS-CoV-2 responsive T cells were characterized using in vitro activation induced marker assays, multicolor flow cytometry, and multiplex cytokine analysis. Further, CXCR5+ cTfh were examined for chemokine receptor expression (CCR6 and CXCR3). Results demonstrated that despite differential NAb responses, activation of SARS-CoV-2 responsive CD4+ and CD8+ T cells was comparable across NAb groups. However, double-positive CD4+CD8+, CD8low, and activated CD4+CXCR5+CCR6-CXCR3+ (Tfh1-like) T cells were expanded in VPRs compared to VMR and VSRs. Interestingly, a unique population of CD8+CXCR5+ T cells was also expanded in VPRs. These novel findings may aid in identification of individuals with impaired or altered immune responses to COVID-19 mRNA vaccination.
ContributorsRoeder, Alexa Jordan (Author) / Lake, Douglas (Thesis advisor) / McFadden, Grant (Committee member) / Borges Florsheim, Esther (Committee member) / Chang, Yung (Committee member) / Rahman, Masmudur (Committee member) / Arizona State University (Publisher)
Created2023
Description
The innate immune system serves as an immediate response to pathogenic infection and an informant to the adaptive immune system. The 2′,5′-oligoadenylate (2-5A) synthetase (OAS)–RNase-L system is a component of the innate immune system induced by interferons (IFNs) and serves to eliminate viral infections. In humans, three enzymatically active OAS proteins exist, OAS1, OAS2, and OAS3. Recent evidence suggests variations in cellular localization of OAS proteins may influence the impact and influence of those proteins on viral replication. However, viral suppression mechanisms involving specific OAS proteins are still unclear for most viruses. Here, I overexpress different isoforms of OAS and determined that though viruses within the same family have similar replication strategies, the extent to which each OAS protein impacts viral replication for Flaviviruses, and Alphaviruses varies. In contrast to the innate immune system, the adaptive immune system provides specific and long-lived immune responses. In the context of cancer, T cells have been shown to play a prominent role in tumor regression. It has previously been demonstrated that administration α-CTLA-4/α-PD-L1 immune checkpoint blockade (ICB) to mice inoculated with a K7M2 metastatic osteosarcoma (mOS) cell line resulted in ~50% survival. Here, I sought to determine biological differences among murine responders and non-responders to ICB for mOS to understand better what factors could increase ICB efficacy. A prospective culprit is a variance in circulating antibodies (Abs). I have shown that sera from mice, before inoculation with mOS or ICB, display distinct differences in Ab repertoire between responders and non-responders, suggesting the presence or absence of particular Abs may influence the outcome of ICB. Recent studies have also shown that malleable environmental factors, such as differences in microbiome composition, can yield subsequent changes in circulating Abs.
Strong associations have been made between host-microbiome interactions and their effects on health. Here, I study potential associations of microbiome-mediated impacts on ICB efficacy for mOS. Additionally, I sought to determine potential changes in T-cellular response to mOS due to modulations in microbiome composition and showed that ICB efficacy can change in conjunction with microbiome composition changes in a murine model.
ContributorsDi Palma, Michelle Pina (Author) / Blattman, Joseph N (Thesis advisor) / Li, Yize (Thesis advisor) / Anderson, Karen S (Committee member) / McFadden, Grant (Committee member) / Arizona State University (Publisher)
Created2023
Description
Lung metastatic cancers represent a major challenge in both basic and clinical cancer research. The ability to treat lung metastases to date has been challenging, current treatment paradigms are a mix of classic radiotherapy, chemotherapies and tumor-targeted therapies, with no one treatment that is effective for all tumors. Oncolytic viruses (OVs) represent a new therapeutic modality for hard-to-treat tumors. However, major questions still exist in the field, especially around how to therapeutically arm and deliver OVs to sites of disseminated tumors. To address this need, oncolytic myxoma viruses (MYXV) that expresses TNF superfamily member transgenes (vMYX-hTNF or vMyx-mLIGHT) were tested in an immunocompetent syngeneic lung metastatic murine osteosarcoma model. Three versions of this model were used; 1-an early intervention model, 2-an established tumor model, defined by both average tumor burden and failure of anti-PD-L1 and vMyx-TNF monotherapies, and 3-a late-stage disease model, defined by the failure the combination of vMyx-hTNF/PBMCs and anti-PD-L1 therapy. These three models were designed to test different questions about therapeutic efficacy of armed MYXV and delivery of MYXV to lung metastases. In the early intervention model, vMyx-hTNF was found to be an effective therapy, especially when delivered by leukocyte carrier cells (either bone marrow or PBMCs). Next, the combination of immune checkpoint inhibitors, including anti-PD-L1, anti-PD-1 and anti-CTLA-4, with vMyx-TNF/PBMCs were found to increase efficacy in treated mice compared to monotherapies. The established model was used to test potential synergy of vMyx-hTNF with anti-PD-L1 therapy. This model was defined by the failure of the monotherapies, however, in combination, treated mice survived significantly longer, and had lower average tumor burden throughout. This model was also used to test tumor specific delivery using ex vivo loaded PBMCs as carrier cells. Using MYXV expressing Tdtomato, PBMCs were found to deliver MYXV to tumors more effectively than free virus. In the most stringent late-stage disease model, vMyx-mLIGHT/PBMCs and vMyx-mLIGHT/PBMCs plus anti-PD-1 were tested and found to be efficacious where combination vMyx-TNF/PBMCs plus PD-1 failed. These results taken together show that TNFSF arming of MYXV, especially when delivered by autologous PBMCs, represents a new potential treatment strategy for lung metastatic tumors.
ContributorsChristie, John Douglas (Author) / McFadden, Grant (Thesis advisor) / Blattman, Joseph (Committee member) / Jacobs, Bertram (Committee member) / Anderson, Karen (Committee member) / Arizona State University (Publisher)
Created2021
Description
Myxoma virus (MYXV), a Leporipoxvirus, is being developed as an oncolytic agent against various types of human cancers. It successfully infects and has oncolytic effects on cancer cells while remaining nonpathogenic to normal human cells and all other non-leporid species. To develop virus constructs and maximize their effectiveness against cancer cells, the interaction between virus and host should be well characterized. DEAD-box RNA helicase DDX3 was previously identified as an intrinsic host factor that regulates MYXV replication in human cancer cell lines. Here, it is reported that transient knockdown of DDX3 in human cancer cells significantly enhances MYXV replication and progeny virus production. In uninfected cells, DDX3 localizes throughout the cytoplasm of human cells; however, in the MYXV-infected cells, DDX3 localizes to the perinuclear region of the cells and forms granule-like particles. It is further demonstrated that DDX3 is likely enhancing the type-1 interferon (IFN) production as the expression of the cytokine is decreased when DDX3 is knocked down during MYXV virus infection. Thus, the absence of DDX3 significantly enhanced myxoma virus spread by reducing the production of type-1 IFN and IFN-mediated signaling. These results suggest that DDX3 is a potential cellular target for enhancing the oncolytic activity of MYXV in human cancers.
ContributorsMunig, Saige (Author) / Rahman, Masmudur (Thesis advisor) / McFadden, Grant (Thesis advisor) / Li, Yize (Committee member) / Arizona State University (Publisher)
Created2024
Description
Children, everywhere around the world, are deprived of their basic right to play. More than half of these children are urban dwellers who have limited access to outdoor and natural play areas, whose indoor environments are injected with technological attractions that keep them occupied in a sedentary life. This play deprivation is prompting a global reaction towards what the American play historian Joe L. Frost calls a “contemporary child-saving movement” that aims to save children from a “dual crisis:” decrease of outdoor play and alienation from nature. Studies demonstrate the importance of contact with nature, either by bringing nature into the urban environment or by taking children out to nature’s wilderness. However, the question is: What are the play-space principles that allow natural environments to afford children with play opportunities of developmental value?This descriptive case study utilizes a sensory ethnographic approach to observe the interaction of children with the natural environment at The Native School, a nature school in Carlsbad, California. Data is collected in intervals for six months to consider the impact of dynamic and cyclical processes of nature on play. The collected data is coded and analyzed using multiple lenses. The “functional approach” by the environmental psychologist Harry Heft, is used to categorize the observed play affordances into a “functional taxonomy.” Secondly, the non-linear dynamic theory is used to identify dynamic play-conducive aspects of nature: transformation, organized complexity, diversity, and ecological attunement. These play-space making principles can guide a biophilic approach to designing play-conducive and developmentally beneficial environments.
ContributorsMalak, Sarah Khaled (Author) / Hejduk, Renata (Thesis advisor) / Petrucci, Darren (Thesis advisor) / Bradley, Robert (Committee member) / Brooks, Kenneth (Committee member) / Arizona State University (Publisher)
Created2021
Description
The human gut microbiome is associated with health outcomes including gastrointestinal and metabolic health, autoimmune disease and cancer. However, the role of the microbiome in many disease processes, including in the preterm gastrointestinal tract and female genital tract, has yet to be defined. Further, the diverse community of viruses within the microbiome (the virome) is understudied compared to bacteria. Here, I examine the microbiome and virome in specific disease models that are poorly understood: necrotizing enterocolitis (NEC), discordant HIV shedding in women living with HIV (WHLIV), female genital tract inflammation and gammaherpesvirus infection. Specifically, I examined the gut virome longitudinally in a cohort of preterm infants at risk for NEC; the female genital tract (FGT) microbiome and virome longitudinally in a cohort of WLHIV from Lima, Peru; the FGT virome in women from Phoenix, Arizona with differing levels of genital inflammation and different microbiome compositions; and the gut microbiome in murine gammaherpesvirus 68 (MHV68) infection. Further, I contributed to research responding to the spread of SARS-CoV-2 in Arizona. I found that 1) gut virome beta diversity decreased before NEC onset in preterm infants, suggesting a role for the virome in NEC; 2) FGT microbiome instability was associated with discordant HIV shedding, while FGT virome composition changed in association with ART duration and immune recovery; 3) FGT virome composition was associated with inflammation and microbiome composition; and 4) MHV68 infection outcomes were independent of microbiome perturbation, which may reflect environmental influences. The results of this research advance understanding of the microbiome and virome in these specific disease processes, and support further investigation of the microbiome and virome in preterm infant gastrointestinal health and FGT health, as well as environmental effects in microbiome research.
ContributorsKaelin, Emily (Author) / Lim, Efrem (Thesis advisor) / Varsani, Arvind (Committee member) / Jacobs, Bertram (Committee member) / McFadden, Grant (Committee member) / Rahman, Masmudur (Committee member) / Arizona State University (Publisher)
Created2024
Description
Subjectivity, phenomenology, and the expression of the human/nonhuman other are critical impasses for makers to challenge, curate, or circumvent within Posthumanism. Through an Abnatural aesthetic ungrounding of the WE as self/other/avatars, identities of a maker are infinitely reconstituted into variable signatures, logics, ethics, and moralities.Avatars exist as differentiable iterations of the perceived self, but they are also independent beings that flicker between states of the real/fake as simulacrums and contradictions embedded within the WE. This unfixity of a formal silhouette provides the self, as a maker, the opportunity to move beyond Paragonical structures toward x.
Troubling in an unpredictable liminal directionality, the WE is subjected to another kind of alterity that fronts imperceivable biases. This process, rather than being extractive and intrusive, seeks expansive freedoms into the unexplored landscapes of each maker by dismantling the socio-cultural confines of practice. As an amateur, as a maker, and as an avatar, the WE is challenged to perceive otherness from within. In so doing, it becomes embedded, knowable, demystified, and embodied as a new modality for made/maker. How far can these tentacular forms reach, stray, and grasp?
Pushing toward a nonhuman space, to critique the Posthuman, an Abnatural aesthetic produces elastic, generative collaborations that simultaneously critique the WE. Through case studies on Combinatorial strategies to frame objects, subjects, and making practices, an asymptote of trouble arises where subjects are entangled within their unfixable subjectivity. Experiencing as an avatar, how can an Abnatural aesthetic generate pathways toward inclusive and expansive making practices?
ContributorsSchoenekase, Benjamin David (Author) / Hejduk, Renata (Thesis advisor) / Broglio, Ron (Committee member) / McHugh, Kevin (Committee member) / Surjan, _ (Committee member) / Arizona State University (Publisher)
Created2024
Description
Public awareness of nature and environmental issues has grown in the last decades and zoos have successfully followed suit by re-branding themselves as key representatives for conservation. However, considering the fast rate of environmental degradation, in the near future, zoos may become the only place left for wildlife. Some scholars argue that we have entered a new epoch titled the “Anthropocene” that postulates the idea that untouched pristine nature is almost nowhere to be found. Many scientists and scholars argue that it is time that we embraced this environmental situation and anticipated the change. Clearly, the impact of urbanization is reaching into the wild, so how can we design for animals in our artificializing world? Using the Manoa School method that argues that every future includes these four, generic, alternatives: growth, discipline, collapse, and transformation , this dissertation explores possible future animal archetypes by considering multiple possibilities of post zoo design.
ContributorsAlshaheen, Rua (Author) / Hejduk, Renata (Thesis advisor) / Allenby, Braden (Committee member) / Finn, Ed (Committee member) / Petrucci, Darren (Committee member) / Arizona State University (Publisher)
Created2019
Description
Immunosignature is a technology that retrieves information from the immune system. The technology is based on microarrays with peptides chosen from random sequence space. My thesis focuses on improving the Immunosignature platform and using Immunosignatures to improve diagnosis for diseases. I first contributed to the optimization of the immunosignature platform by introducing scoring metrics to select optimal parameters, considering performance as well as practicality. Next, I primarily worked on identifying a signature shared across various pathogens that can distinguish them from the healthy population. I further retrieved consensus epitopes from the disease common signature and proposed that most pathogens could share the signature by studying the enrichment of the common signature in the pathogen proteomes. Following this, I worked on studying cancer samples from different stages and correlated the immune response with whether the epitope presented by tumor is similar to the pathogen proteome. An effective immune response is defined as an antibody titer increasing followed by decrease, suggesting elimination of the epitope. I found that an effective immune response usually correlates with epitopes that are more similar to pathogens. This suggests that the immune system might occupy a limited space and can be effective against only certain epitopes that have similarity with pathogens. I then participated in the attempt to solve the antibiotic resistance problem by developing a classification algorithm that can distinguish bacterial versus viral infection. This algorithm outperforms other currently available classification methods. Finally, I worked on the concept of deriving a single number to represent all the data on the immunosignature platform. This is in resemblance to the concept of temperature, which is an approximate measurement of whether an individual is healthy. The measure of Immune Entropy was found to work best as a single measurement to describe the immune system information derived from the immunosignature. Entropy is relatively invariant in healthy population, but shows significant differences when comparing healthy donors with patients either infected with a pathogen or have cancer.
ContributorsWang, Lu (Author) / Johnston, Stephen (Thesis advisor) / Stafford, Phillip (Committee member) / Buetow, Kenneth (Committee member) / McFadden, Grant (Committee member) / Arizona State University (Publisher)
Created2018