Matching Items (146)
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Description
Flavivirus infections are emerging as significant threats to human health around the globe. Among them West Nile(WNV) and Dengue Virus (DV) are the most prevalent in causing human disease with WNV outbreaks occurring in all areas around the world and DV epidemics in more than 100 countries. WNV is a

Flavivirus infections are emerging as significant threats to human health around the globe. Among them West Nile(WNV) and Dengue Virus (DV) are the most prevalent in causing human disease with WNV outbreaks occurring in all areas around the world and DV epidemics in more than 100 countries. WNV is a neurotropic virus capable of causing meningitis and encephalitis in humans. Currently, there are no therapeutic treatments or vaccines available. The expanding epidemic of WNV demands studies that develop efficacious therapeutics and vaccines and produce them rapidly and inexpensively. In response, our lab developed a plant-derived monoclonal antibody (mAb) (pHu-E16) against DIII (WNV antigen) that is able to neutralize and prevent mice from lethal infection. However, this drug has a short window of efficacy due to pHu-E16's inability to cross the Blood Brain Barrier (BBB) and enter the brain. Here, we constructed a bifunctional diabody, which couples the neutralizing activity of E16 and BBB penetrating activity of 8D3 mAb. We also produced a plant-derived E16 scFv-CH1-3 variant with equivalent specific binding as the full pHu-E16 mAb, but only requiring one gene construct for production. Furthermore, a WNV vaccine based on plant-derived DIII was developed showing proper folding and potentially protective immune response in mice. DV causes severe hemorrhaging diseases especially in people exposed to secondary DV infection from a heterotypic strain. It is hypothesized that sub-neutralizing cross-reactive antibodies from the first exposure aid the second infection in a process called antibody-dependent enhancement (ADE). ADE depends on the ability of mAb to bind Fc receptors (FcγRs), and has become a major roadblock for developing mAb-based therapeutics against DV. We aim to produce an anti-Dengue mAb (E60) in different glycoengineered plant lines that exhibit reduced/differential binding to FcγRs, therefore, reducing or eliminating ADE. We have successfully cloned the molecular constructs of E60, and expressed it in two plant lines with different glycosylation patterns. We demonstrated that both plant-derived E60 mAb glycoforms retained specific recognition and neutralization activity against DV. Overall, our study demonstrates great strives to develop efficacious therapeutics and potent vaccine candidates against Flaviviruses in plant expression systems.
ContributorsHurtado, Jonathan (Author) / Chen, Qiang (Thesis advisor) / Huffman, Holly A (Committee member) / Steele, Kelly P (Committee member) / Arizona State University (Publisher)
Created2014
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Description

The Maricopa County Heat Relief Network (HRN) is an ad-hoc partially self-organized network with some attributes of hierarchical coordination that forms each year to provide heat relief and hydration to residents in need by operating as cooling centers. These HRN organizations are a collection of non-profit, governmental and religious organizations.

The Maricopa County Heat Relief Network (HRN) is an ad-hoc partially self-organized network with some attributes of hierarchical coordination that forms each year to provide heat relief and hydration to residents in need by operating as cooling centers. These HRN organizations are a collection of non-profit, governmental and religious organizations. This dissertation looks at the HRN from a complexity governance perspective and engaged different parts of the network in interviews to learn more about their perspective in delivering heat relief. Further, participatory modeling with a prototype agent based model was done with the HRN coordinating agencies to look for emergent outcomes in the HRN system and learn from their perspective. Chapter one evaluates organizational theory and complexity with climate adaptation, hazard preparedness and resilience in the HRN. Chapter two presents results from interviews with HRN facility managers and evaluates their perspective on how they function to offer heat relief. Chapter three finds that the HRN is a good example of complexity governance when engaged through a participatory agent based modeling approach. Chapter four engages the HRN coordinators in participatory agent based modeling interviews to increase their systems level awareness, learn about their perspective on heat relief delivery, and how the system can be improved. Chapter five looks across the different levels of the HRN investigated, the facility managers and coordinators, for differences and similarities in perspectives. The research conducted in this dissertation shows different levels of systems awareness of the different parts of the HRN and how participatory modeling can be used to increase systems awareness. Results indicate that there was very little horizontal network connection between HRN facility managers and most of the interaction was vertically coordinated indicating opportunities for increased network communication in the future both horizontally and vertically if communication interventions were put in place.

ContributorsUebelherr, Joshua (Author) / Johnston, Erik W., 1977- (Thesis advisor) / Hondula, David M. (Committee member) / Mossberger, Karen (Committee member) / Gerber, Brian (Committee member) / Arizona State University (Publisher)
Created2017
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Description
Immunotherapy has been revitalized with the advent of immune checkpoint blockade

treatments, and neo-antigens are the targets of immune system in cancer patients who

respond to the treatments. The cancer vaccine field is focused on using neo-antigens from

unique point mutations of genomic sequence in the cancer patient for making

personalized cancer vaccines. However,

Immunotherapy has been revitalized with the advent of immune checkpoint blockade

treatments, and neo-antigens are the targets of immune system in cancer patients who

respond to the treatments. The cancer vaccine field is focused on using neo-antigens from

unique point mutations of genomic sequence in the cancer patient for making

personalized cancer vaccines. However, we choose a different path to find frameshift

neo-antigens at the mRNA level and develop broadly effective cancer vaccines based on

frameshift antigens.

In this dissertation, I have summarized and characterized all the potential frameshift

antigens from microsatellite regions in human, dog and mouse. A list of frameshift

antigens was validated by PCR in tumor samples and the mutation rate was calculated for

one candidate – SEC62. I develop a method to screen the antibody response against

frameshift antigens in human and dog cancer patients by using frameshift peptide arrays.

Frameshift antigens selected by positive antibody response in cancer patients or by MHC

predictions show protection in different mouse tumor models. A dog version of the

cancer vaccine based on frameshift antigens was developed and tested in a small safety

trial. The results demonstrate that the vaccine is safe and it can induce strong B and T cell

immune responses. Further, I built the human exon junction frameshift database which

includes all possible frameshift antigens from mis-splicing events in exon junctions, and I

develop a method to find potential frameshift antigens from large cancer

immunosignature dataset with these databases. In addition, I test the idea of ‘early cancer

diagnosis, early treatment’ in a transgenic mouse cancer model. The results show that

ii

early treatment gives significantly better protection than late treatment and the correct

time point for treatment is crucial to give the best clinical benefit. A model for early

treatment is developed with these results.

Frameshift neo-antigens from microsatellite regions and mis-splicing events are

abundant at mRNA level and they are better antigens than neo-antigens from point

mutations in the genomic sequences of cancer patients in terms of high immunogenicity,

low probability to cause autoimmune diseases and low cost to develop a broadly effective

vaccine. This dissertation demonstrates the feasibility of using frameshift antigens for

cancer vaccine development.
ContributorsZhang, Jian (Author) / Johnston, Stephen Albert (Thesis advisor) / Chang, Yung (Committee member) / Stafford, Phillip (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2018
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Description

Exertional heat stroke continues to be one of the leading causes of illness and death in sport in the United States, with an athlete’s experienced microclimate varying by venue design and location. A limited number of studies have attempted to determine the relationship between observed wet bulb globe temperature (WBGT)

Exertional heat stroke continues to be one of the leading causes of illness and death in sport in the United States, with an athlete’s experienced microclimate varying by venue design and location. A limited number of studies have attempted to determine the relationship between observed wet bulb globe temperature (WBGT) and WBGT derived from regional weather station data. Moreover, only one study has quantified the relationship between regionally modeled and on-site measured WBGT over different athletic surfaces (natural grass, rubber track, and concrete tennis court). The current research expands on previous studies to examine how different athletic surfaces influence the thermal environment in the Phoenix Metropolitan Area using a combination of fieldwork, modeling, and statistical analysis. Meteorological data were collected from 0700–1900hr across 6 days in June and 5 days in August 2019 in Tempe, Arizona at various Sun Devil Athletics facilities. This research also explored the influence of surface temperatures on WBGT and the changes projected under a future warmer climate. Results indicate that based on American College of Sports Medicine guidelines practice would not be cancelled in June (WBGT≥32.3°C); however, in August, ~33% of practice time was lost across multiple surfaces. The second-tier recommendations (WBGT≥30.1°C) to limit intense exercise were reached an average of 7 hours each day for all surfaces in August. Further, WBGT was calculated using data from four Arizona Meteorological Network (AZMET) weather stations to provide regional WBGT values for comparison. The on-site (field/court) WBGT values were consistently higher than regional values and significantly different (p<0.05). Thus, using regionally-modeled WBGT data to guide activity or clothing modification for heat safety may lead to misclassification and unsafe conditions. Surface temperature measurements indicate a maximum temperature (170°F) occurring around solar noon, yet WBGT reached its highest level mid-afternoon and on the artificial turf surface (2–5PM). Climate projections show that WBGT values are expected to rise, further restricting the amount of practice and games than can take place outdoors during the afternoon. The findings from this study can be used to inform athletic trainers and coaches about the thermal environment through WBGT values on-field.

ContributorsGuyer, Haven Elizabeth (Author) / Vanos, Jennifer K. (Thesis advisor) / Georgescu, Matei (Thesis advisor) / Hondula, David M. (Committee member) / Arizona State University (Publisher)
Created2020
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Description

Interdisciplinary research has highlighted how social-ecological dynamics drive the structure and function of the urban landscape across multiple scales. Land management decisions operate across various levels, from individuals in their backyard to local municipalities and broader political-economic forces. These decisions then scale up and down across the landscape to influence

Interdisciplinary research has highlighted how social-ecological dynamics drive the structure and function of the urban landscape across multiple scales. Land management decisions operate across various levels, from individuals in their backyard to local municipalities and broader political-economic forces. These decisions then scale up and down across the landscape to influence ecological functioning, such as the provisioning of biodiversity. Likewise, people are influenced by, and respond to, their environment. However, there is a lack of integrated research, especially research that considers the spatial and temporal complexities of social-ecological dynamics, to fully understand how people influence ecosystems or how the resulting landscape in turn influences human decision making, attitudes, and well-being.

My dissertation connects these interdisciplinary themes to examine three questions linked by their investigation of the interactions between people and biodiversity: (1) How do the social and spatial patterns within an arid city affect people’s attitudes about their regional desert environment? (2) How are novel communities in cities assembled given the social-ecological dynamics that influence the processes that structure ecological communities? (3) How can we reposition bird species traits into a conservation framework that explains the complexity of the interactions between people and urban bird communities? I found that social-ecological dynamics between people, the environment, and biodiversity are tightly interwoven in urban ecosystems. The regional desert environment shapes people’s attitudes along spatial and social configurations, which holds implications for yard management decisions. Multi-scalar management decisions then influence biodiversity throughout cities, which shifts public perceptions of urban nature. Overall, my research acts as a bridge between social and ecological sciences to theoretically and empirically integrate research focused on biodiversity conservation in complex, social-ecological systems. My goal as a scholar is to understand the balance between social and ecological implications of landscape change to support human well-being and promote biodiversity conservation.

ContributorsAndrade, Riley (Author) / Franklin, Janet (Thesis advisor) / Larson, Kelli L (Thesis advisor) / Hondula, David M. (Committee member) / Lerman, Susannah B (Committee member) / Arizona State University (Publisher)
Created2020
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Description

This study aimed to investigate the effects of specific macronutrient feedings on competitive golf performance and perceived levels of fatigue and alertness. Participants played three, nine hole rounds of golf, consuming an isocaloric beverage as a control (CON), with the addition of carbohydrate (CHO), or combination of protein and carbohydrate

This study aimed to investigate the effects of specific macronutrient feedings on competitive golf performance and perceived levels of fatigue and alertness. Participants played three, nine hole rounds of golf, consuming an isocaloric beverage as a control (CON), with the addition of carbohydrate (CHO), or combination of protein and carbohydrate (COM). Physiological and performance measurements were taken before, during, and following each nine hole round. Performance measurements include driving accuracy (DA), driving distance (DD), iron accuracy (IA), chipping accuracy (CA), and putting accuracy (PA). Pre-golf hydration status (urine specific gravity [USG]) and Sweat Rate during golf performance showed no significant differences between trials. All nine hole rounds were performed in ~2 hours. Environmental conditions were similar for all three testing days (mean WBGT=10.946). No significant differences were seen in Driving Distance, Driving Accuracy, and Iron Accuracy for all nine holes between groups receiving different macronutrient feedings. Chipping Accuracy was significantly better in CON trial compared to CHO (p=0.004) and COM (p=0.019). No significant differences were seen in putting make percentages. COM trial significantly lowered Perceived Levels of Fatigue (p=0.019) compared to CON. The CHO trial showed significant improvements in DA compared to CON (13.7 vs. 44.1, p=0.012) and COM (13.7 vs. 33.6, p=0.004) in the first four holes. In the last five holes, the COM trial showed significant improvements in DA compared to CHO (17.5 vs. 29.7, p=0.007). Low Handicap golfers (3 +/- 3) performed significantly better than High Handicap golfers (14 +/- 3.6) in DD (265 vs. 241, p<0.001), DA (15.0 vs. 29.3, p=0.004), IA (15.2 vs. 25.2, p<0.001), CA (52.0 vs. 61.5, p=0.027), and PA 5ft (64% vs. 40%, p=0.003). High Handicap players showed no significant differences between the three trials for any golf performance measurements. Low Handicap players showed significant improvements in DA for COM trial compared to CON trial (13.6 vs. 27.6, p=0.003). The results suggest that carbohydrates at the start and a combination of carbohydrate and protein is beneficial at the second part of 9 holes to improve golf performance and maintain levels of fatigue, however, it needs to be investigated how this knowledge will relate to playing more holes.

ContributorsThompsett, Daniel James (Author) / Wardenaar, Floris (Thesis advisor) / Der Ananian, Cheryl (Committee member) / Hondula, David M. (Committee member) / Arizona State University (Publisher)
Created2020
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Description

Urban heat is a growing problem that impacts public health, water and energy use, and the economy and affects population subgroups differently. Exposure and sensitivity, two key factors in determining vulnerability, have been widely researched. This dissertation focuses on the adaptive capacity component of heat vulnerability at the individual, household,

Urban heat is a growing problem that impacts public health, water and energy use, and the economy and affects population subgroups differently. Exposure and sensitivity, two key factors in determining vulnerability, have been widely researched. This dissertation focuses on the adaptive capacity component of heat vulnerability at the individual, household, and community scale. Using a mixed methods approach and metropolitan Phoenix as a test site, I explored how vulnerable communities understand and adapt to increasing extreme urban heat to uncover adaptive capacity that is not being operationalized well through current heat vulnerability frameworks. Twenty-three open-ended interviews were conducted where residents were encouraged to tell their stories about past and present extreme heat adaptive capacity behaviors. A community-based participatory research project consisting of three workshops and demonstration projects was piloted in three underserved neighborhoods to address urban heat on a local scale and collaboratively create community heat action plans. Last, a practitioner stakeholder meeting was held to discuss how the heat action plans will be integrated into other community efforts. Using data from the interviews, workshops, and stakeholder meeting, social capital was examined in the context of urban heat. Although social capital has been measured in a multitude of ways to gauge social relationships, trust, and reciprocity within a community, it is situational and reflects a position within the formal and informal aspects of any issue. Three narratives emerged from the interviews illuminating differentiated capacities to cope with urban heat: heat is an inconvenience, heat is a manageable problem, and heat is a catastrophe. For each of these narratives, generic adaptive capacity is impacted differently by specific heat adaptive capacity. The heat action plan workshops generated hyper-local heat solutions that reflected the neighborhoods’ different identities. Community-based organizations were instrumental in the success of this program. Social capital indicators were developed specific to urban heat that rely on heavily on family and personal relationships, attitudes and beliefs, perceived support, network size and community engagement. This research highlights how extreme heat vulnerability may need to be rethought to capture adaptive capacity nuances and the dynamic structure of who is vulnerable under what circumstances.

ContributorsGuardaro, Melissa (Author) / Redman, Charles L. (Thesis advisor) / Hondula, David M. (Committee member) / Johnston, Erik W., 1977- (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Moderate physical activity, such as walking and biking, positively affects physical and mental health. Outdoor thermal comfort is an important prerequisite for incentivizing an active lifestyle. Thus, extreme heat poses significant challenges for people who are outdoors by choice or necessity. The type and qualities of built infrastructure determine the

Moderate physical activity, such as walking and biking, positively affects physical and mental health. Outdoor thermal comfort is an important prerequisite for incentivizing an active lifestyle. Thus, extreme heat poses significant challenges for people who are outdoors by choice or necessity. The type and qualities of built infrastructure determine the intensity and duration of individual exposure to heat. As cities globally are shifting priorities towards non-motorized and public transit travel, more residents are expected to experience the city on their feet. Thus, physical conditions as well as psychological perception of the environment that affect thermal comfort will become paramount. Phoenix, Arizona, is used as a case study to examine the effectiveness of current public transit and street infrastructure to reduce heat exposure and affect the thermal comfort of walkers and public transit users.

The City of Phoenix has committed to public transit improvements in the Transportation 2050 plan and has recently adopted a Complete Streets Policy. Proposed changes include mobility improvements and creating a safe and comfortable environment for non-motorized road participants. To understand what kind of improvements would benefit thermal comfort the most, it is necessary to understand heat exposure at finer spatial scales, explore whether current bus shelter designs are adequate in mitigating heat-health effects, and comprehensively assess the impact of design on physical, psychological and behavioral aspects of thermal comfort. A study conducted at bus stops in one Phoenix neighborhood examined grey and green infrastructure types preferred for cooling and found relationships between perception of pleasantness and thermal sensation votes. Walking interviews conducted in another neighborhood event examined the applicability of a framework for walking behavior under the stress of heat, and how differences between the streets affected perceptions of the walkers. The interviews revealed that many of the structural themes from the framework of walking behavior were applicable, however, participants assessed the majority of the elements in their walk from a heat mitigation perspective. Finally, guiding questions for walkability in hot and arid climates were developed based on the literature review and results from the empirical studies. This dissertation contributes to filling the gap between walkability and outdoor thermal comfort, and presents methodology and findings that can be useful to address walkability and outdoor thermal comfort in the world’s hot cities as well as those in temperate climates that may face similar climate challenges in the future as the planet warms.
ContributorsDzyuban, Yuliya (Author) / Redman, Charles L. (Thesis advisor) / Coseo, Paul J. (Committee member) / Hondula, David M. (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Flaviviruses (FVs) are among the most medically important arboviruses of the world with the Dengue virus (DENV) accounting for a large percentage of infections observed in tropical and subtropical regions of the world. Globalization, travel, and the expanding range of mosquito vectors, such as Aedes aegypti, have increased the potential

Flaviviruses (FVs) are among the most medically important arboviruses of the world with the Dengue virus (DENV) accounting for a large percentage of infections observed in tropical and subtropical regions of the world. Globalization, travel, and the expanding range of mosquito vectors, such as Aedes aegypti, have increased the potential of infection rates and illnesses associated with FVs.

The DENV and the Zika (ZIKV) FVs frequently co-circulate and generally cause mild self-liming febrile illnesses. However, a secondary infection with a heterologous DENV serotype may lead to life threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). DHF/DSS have been linked to antibody dependent enhancement of infection (ADE), a phenomenon that occurs when antibodies (Abs) formed against an initial infection with one serotype of DENV cross-reacts but does not neutralize a heterologous DENV serotype in a secondary infection. Furthermore, Abs raised against the ZIKV have been observed to cross-react with the DENV and vice versa, which can potentially cause ADE and lead to severe DENV disease. The ZIKV can be transmitted vertically and has been linked to devastating congenital defects such as microcephaly in newborns. FDA approved treatments do not exist for DENV and ZIKV illnesses. Thus, there is a need for safe and effective treatments for these co-circulating viruses. Here, a tetravalent bispecific antibody (bsAb) targeting the ZIKV and all four serotypes of the DENV was expressed in the Nicotiana benthamiana (N. benthamiana) plant. Functional assays of the DENV/ZIKV bsAb demonstrated binding, neutralization, and a significant reduction in ADE activity against both the DENV and the ZIKV.

A single chain variable fragment (scFv) and a diabody based on an antibody directed against the immune checkpoint inhibitor PD-L1, were also expressed in N. benthamiana leaves. The smaller sizes of the scFv and diabody confers them with the ability to penetrate deeper tissues making them beneficial in diagnostics, imaging, and possibly cancer therapy. The past few decades has seen long strives in recombinant protein production in plants with significant improvements in production, safety, and efficacy. These characteristics make plants an attractive platform for the production of recombinant proteins, biologics, and therapeutics.
ContributorsEsqueda, Adrian (Author) / Chen, Qiang (Thesis advisor) / Arntzen, Charles (Committee member) / Lake, Douglas (Committee member) / Mason, Hugh (Committee member) / Arizona State University (Publisher)
Created2019
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Environmental hazards and disaster researchers have demonstrated strong associations between sociodemographic indicators, such as age and socio-economic status (SES), and hazard exposures and health outcomes for individuals and in certain communities. At the same time, behavioral health and risk communications research has examined how individual psychology influences adaptive strategies and

Environmental hazards and disaster researchers have demonstrated strong associations between sociodemographic indicators, such as age and socio-economic status (SES), and hazard exposures and health outcomes for individuals and in certain communities. At the same time, behavioral health and risk communications research has examined how individual psychology influences adaptive strategies and behaviors in the face of hazards. However, at present, we do not understand the explanatory mechanisms that explain relationships between larger scale social structure, individual psychology, and specific behaviors that may attenuate or amplify risk. Extreme heat presents growing risks in a rapidly warming and urbanizing world. This dissertation examines the social and behavioral mechanisms that may explain inequitable health outcomes from exposure to concurrent extreme heat and electrical power failure in Phoenix, AZ and extreme heat in Detroit, MI. Exploratory analysis of 163 surveys in Phoenix, AZ showed that age, gender, and respondent’s racialized group identity did not relate to thermal discomfort and self-reported heat illness, which were only predicted by SES (StdB = -0.52, p < 0.01). Of the explanatory mechanisms tested in the study, only relative air conditioning intensity and thermal discomfort explained self-reported heat illness. Thermal discomfort was tested as both a mechanism and outcome measure. Content analysis of 40 semi-structured interviews in Phoenix, AZ revealed that social vulnerability was associated with an increase in perceived hazard severity (StdB = 0.44, p < 0.01), a decrease in perceived adaptation efficacy (StdB = -0.38, p = 0.02), and an indirect increase (through adaptive efficacy) in maladaptive intentions (StdB = 0.18, p = 0.01). Structural equation modeling of 244 surveys in Phoenix, AZ and Detroit, MI revealed that relationships between previous heat illness experience, perceived heat risk, and adaptive intentions were significantly moderated by adaptive capacity: high adaptive capacity households were more likely to undertake adaptive behaviors, and those decisions were more heavily influenced by risk perceptions and previous experiences. However, high adaptive capacity households had lower risk perceptions and fewer heat illness experiences than low adaptive capacity households. A better understanding of the mechanisms that produce social vulnerability can facilitate more salient risk messaging and more targeted public health interventions. For example, public health risk messaging that provides information on the efficacy of specific adaptations may be more likely to motivate self-protective action, and ultimately protect populations.

ContributorsChakalian, Paul Michael (Author) / Harlan, Sharon L (Thesis advisor) / Hondula, David M. (Thesis advisor) / White, Dave D (Committee member) / Arizona State University (Publisher)
Created2019