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- Genre: Masters Thesis
Description
Infections caused by the Hepatitis C Virus (HCV) are very common worldwide, affecting up to 3% of the population. Chronic infection of HCV may develop into liver cirrhosis and liver cancer which is among the top five of the most common cancers. Therefore, vaccines against HCV are under intense study in order to prevent HCV from harming people's health. The envelope protein 2 (E2) of HCV is thought to be a promising vaccine candidate because it can directly bind to a human cell receptor and plays a role in viral entry. However, the E2 protein production in cells is inefficient due to its complicated matured structure. Folding of E2 in the endoplasmic reticulum (ER) is often error-prone, resulting in production of aggregates and misfolded proteins. These incorrect forms of E2 are not functional because they are not able to bind to human cells and stimulate antibody response to inhibit this binding. This study is aimed to overcome the difficulties of HCV E2 production in plant system. Protein folding in the ER requires great assistance from molecular chaperones. Thus, in this study, two molecular chaperones in the ER, calreticulin and calnexin, were transiently overexpressed in plant leaves in order to facilitate E2 folding and production. Both of them showed benefits in increasing the yield of E2 and improving the quality of E2. In addition, poorly folded E2 accumulated in the ER may cause stress in the ER and trigger transcriptional activation of ER molecular chaperones. Therefore, a transcription factor involved in this pathway, named bZIP60, was also overexpressed in plant leaves, aiming at up-regulating a major family of molecular chaperones called BiP to assist protein folding. However, our results showed that BiP mRNA levels were not up-regulated by bZIP60, but they increased in response to E2 expression. The Western blot analysis also showed that overexpression of bZIP60 had a small effect on promoting E2 folding. Overall, this study suggested that increasing the level of specific ER molecular chaperones was an effective way to promote HCV E2 protein production and maturation.
ContributorsHong, Fan (Author) / Mason, Hugh (Thesis advisor) / Gaxiola, Roberto (Committee member) / Chang, Yung (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2011
Description
Machine learning (ML) and deep learning (DL) has become an intrinsic part of multiple fields. The ability to solve complex problems makes machine learning a panacea. In the last few years, there has been an explosion of data generation, which has greatly improvised machine learning models. But this comes with a cost of high computation, which invariably increases power usage and cost of the hardware. In this thesis we explore applications of ML techniques, applied to two completely different fields - arts, media and theater and urban climate research using low-cost and low-powered edge devices. The multi-modal chatbot uses different machine learning techniques: natural language processing (NLP) and computer vision (CV) to understand inputs of the user and accordingly perform in the play and interact with the audience. This system is also equipped with other interactive hardware setups like movable LED systems, together they provide an experiential theatrical play tailored to each user. I will discuss how I used edge devices to achieve this AI system which has created a new genre in theatrical play. I will then discuss MaRTiny, which is an AI-based bio-meteorological system that calculates mean radiant temperature (MRT), which is an important parameter for urban climate research. It is also equipped with a vision system that performs different machine learning tasks like pedestrian and shade detection. The entire system costs around $200 which can potentially replace the existing setup worth $20,000. I will further discuss how I overcame the inaccuracies in MRT value caused by the system, using machine learning methods. These projects although belonging to two very different fields, are implemented using edge devices and use similar ML techniques. In this thesis I will detail out different techniques that are shared between these two projects and how they can be used in several other applications using edge devices.
ContributorsKulkarni, Karthik Kashinath (Author) / Jayasuriya, Suren (Thesis advisor) / Middel, Ariane (Thesis advisor) / Yu, Hongbin (Committee member) / Arizona State University (Publisher)
Created2021
Description
The measurement of the radiation and convection that the human body experiences are important for ensuring safety in extreme heat conditions. The radiation from the surroundings on the human body is most often measured using globe or cylindrical radiometers. The large errors stemming from differences in internal and exterior temperatures and indirect estimation of convection can be resolved by simultaneously using three cylindrical radiometers (1 cm diameter, 9 cm height) with varying surface properties and internal heating. With three surface balances, the three unknowns (heat transfer coefficient, shortwave, and longwave radiation) can be solved for directly. As compared to integral radiation measurement technique, however, the bottom mounting using a wooden-dowel of the three-cylinder radiometers resulted in underestimated the total absorbed radiation. This first part of this thesis focuses on reducing the size of the three-cylinder radiometers and an alternative mounting that resolves the prior issues. In particular, the heat transfer coefficient in laminar wind tunnel with wind speed of 0.25 to 5 m/s is measured for six polished, heated cylinders with diameter of 1 cm and height of 1.5 to 9 cm mounted using a wooden dowel. For cylinders with height of 6 cm and above, the heat transfer coefficients are independent of the height and agree with the Hilpert correlation for infinitely long cylinder. Subsequently, a side-mounting for heated 6 cm tall cylinder with top and bottom metallic caps is developed and tested within the wind tunnel. The heat transfer coefficient is shown to be independent of the flow-side mounting and in agreement with the Hilpert correlation.
The second part of this thesis explores feasibility of employing the three-cylinder concept to measuring all air-flow parameters relevant to human convection including mean wind speed, turbulence intensity and length scale. Heated cylinders with same surface properties but varying diameters are fabricated. Uniformity of their exterior temperature, which is fundamental to the three-cylinder anemometer concept, is tested during operation using infrared camera. To provide a lab-based method to measure convection from the cylinders in turbulent flow, several designs of turbulence-generating fractal grids are laser-cut and introduced into the wind tunnel.
ContributorsGupta, Mahima (Author) / Rykaczewski, Konrad (Thesis advisor) / Pathikonda, Gokul (Thesis advisor) / Middel, Ariane (Committee member) / Arizona State University (Publisher)
Created2024
Description
During summer 2014, a study was conducted as part of the Landscape Architecture Foundation Case Study Investigation to analyze features of three sustainably designed landscapes. Each project was located in a southwest desert city: Civic Space Park in Phoenix, AZ, the Pete V. Domenici US Courthouse Sustainable Landscape Retrofit in Albuquerque, NM, and George "Doc" Cavalliere Park in Scottsdale, AZ. The principal components of each case study were performance benefits that quantified ongoing ecosystem services. Performance benefits were developed from data provided by the designers and collected by the research team. The functionality of environmental, social, and economic sustainable features was evaluated. In southwest desert cities achieving performance benefits such as microclimate cooling often come at the cost of water conservation. In each of these projects such tradeoffs were balanced by prioritizing the project goals and constraints.
During summer 2015, a study was conducted to characterize effects of tree species and shade structures on outdoor human thermal comfort under hot, arid conditions. Motivating the research was the hypothesis that tree species and shade structures will vary in their capacity to improve thermal comfort due to their respective abilities to attenuate solar radiation. Micrometeorological data was collected in full sun and under shade of six landscape tree species and park ramadas in Phoenix, AZ during pre-monsoon summer afternoons. The six landscape tree species included: Arizona ash (Fraxinus velutina Torr.), Mexican palo verde (Parkinsonia aculeata L.), Aleppo pine (Pinus halepensis Mill.), South American mesquite (Prosopis spp. L.), Texas live oak (Quercus virginiana for. fusiformis Mill.), and Chinese elm (Ulmus parvifolia Jacq.). Results showed that the tree species and ramadas were not similarly effective at improving thermal comfort, represented by physiologically equivalent temperature (PET). The difference between PET in full sun and under shade was greater under Fraxinus and Quercus than under Parkinsonia, Prosopis, and ramadas by 2.9-4.3 °C. Radiation was a significant driver of PET (p<0.0001, R2=0.69) and with the exception of ramadas, lower radiation corresponded with lower PET. Variations observed in this study suggest selecting trees or structures that attenuate the most solar radiation is a potential strategy for optimizing PET.
During summer 2015, a study was conducted to characterize effects of tree species and shade structures on outdoor human thermal comfort under hot, arid conditions. Motivating the research was the hypothesis that tree species and shade structures will vary in their capacity to improve thermal comfort due to their respective abilities to attenuate solar radiation. Micrometeorological data was collected in full sun and under shade of six landscape tree species and park ramadas in Phoenix, AZ during pre-monsoon summer afternoons. The six landscape tree species included: Arizona ash (Fraxinus velutina Torr.), Mexican palo verde (Parkinsonia aculeata L.), Aleppo pine (Pinus halepensis Mill.), South American mesquite (Prosopis spp. L.), Texas live oak (Quercus virginiana for. fusiformis Mill.), and Chinese elm (Ulmus parvifolia Jacq.). Results showed that the tree species and ramadas were not similarly effective at improving thermal comfort, represented by physiologically equivalent temperature (PET). The difference between PET in full sun and under shade was greater under Fraxinus and Quercus than under Parkinsonia, Prosopis, and ramadas by 2.9-4.3 °C. Radiation was a significant driver of PET (p<0.0001, R2=0.69) and with the exception of ramadas, lower radiation corresponded with lower PET. Variations observed in this study suggest selecting trees or structures that attenuate the most solar radiation is a potential strategy for optimizing PET.
ContributorsColter, Kaylee (Author) / Martin, Chris (Thesis advisor) / Coseo, Paul (Committee member) / Middel, Ariane (Committee member) / Arizona State University (Publisher)
Created2016
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 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
Description
The rapid rate of urbanization coupled with continued population growth and anthropogenic activities has resulted in a myriad of urban climate related impacts across different cities around the world. Hot-arid cities are more vulnerable to induced urban heat effects due to the intense solar radiation during most of the year, leading to increased ambient air temperature and outdoor/indoor discomfort in Phoenix, Arizona. With the fast growth of the capital city of Arizona, the automobile-dependent planning of the city contributed negatively to the outdoor thermal comfort and to the people's daily social lives. One of the biggest challenges for hot-arid cities is to mitigate against the induced urban heat increase and improve the outdoor thermal. The objective of this study is to propose a pragmatic and useful framework that would improve the outdoor thermal comfort, by being able to evaluate and select minimally invasive urban heat mitigation strategies that could be applied to the existing urban settings in the hot-arid area of Phoenix. The study started with an evaluation of existing microclimate conditions by means of multiple field observations cross a North-South oriented urban block of buildings within Arizona State University’s Downtown campus in Phoenix. The collected data was evaluated and analyzed for a better understanding of the different local climates within the study area, then used to evaluate and partially validate a computational fluid dynamics model, ENVI-Met. Furthermore, three mitigation strategies were analyzed to the Urban Canopy Layer (UCL) level, an increase in the fraction of permeable materials in the ground surface, adding different configurations of high/low Leaf Area Density (LAD) trees, and replacing the trees configurations with fabric shading. All the strategies were compared and analyzed to determine the most impactful and effective mitigation strategies. The evaluated strategies have shown a substantial cooling effect from the High LAD trees scenarios. Also, the fabric shading strategies have shown a higher cooling effect than the Low LAD trees. Integrating the trees scenarios with the fabric shading had close cooling effect results in the High LAD trees scenarios. Finally, how to integrate these successful strategies into practical situations was addressed.
ContributorsAldakheelallah, Abdullah (Author) / Reddy, T Agami (Thesis advisor) / Middel, Ariane (Committee member) / Coseo, Paul (Committee member) / Arizona State University (Publisher)
Created2020
Description
Influenza is a deadly disease that poses a major threat to global health. The surface proteins of influenza A, the type most often associated with epidemics and pandemics, mutate at a very high frequency from season to season, reducing the efficacy of seasonal influenza vaccines. However, certain regions of these proteins are conserved between strains of influenza A, making them attractive targets for the development of a ‘universal’ influenza vaccine. One of these highly conserved regions is the ectodomain of the influenza matrix 2 protein (M2e). Studies have shown that M2e is poorly immunogenic on its own, but when properly adjuvanted it can be used to induce protective immune responses against many strains of influenza A. In this thesis, M2e was fused to a pair experimental ‘vaccine platforms’: an antibody fusion protein designed to assemble into a recombinant immune complex (RIC) and the hepatitis B core antigen (HBc) that can assemble into virus-like particles (VLP). The two antigens were produced in Nicotiana benthamiana plants through the use of geminiviral vectors and were subsequently evaluated in mouse trials. Mice were administered three doses of either the VLP alone or a 1:1 combination of the VLP and the RIC, and recipients of both the VLP and RIC exhibited endpoint anti-M2e antibody titers that were 2 to 3 times higher than mice that received the VLP alone. While IgG2a:IgG1 ratios, which can suggest the type of immune response (TH1 vs TH2) an antigen will elicit, were higher in mice vaccinated solely with the VLP, the higher overall titers are encouraging and demonstrate a degree of interaction between the RIC and VLP vaccines. Further research is necessary to determine the optimal balance of VLP and RIC to maximize IgG2a:IGg1 ratios as well as whether such interaction would be observed through the use of a variety of diverse antigens, though the results of other studies conducted in this lab suggests that this is indeed the case. The results of this study demonstrate not only the successful development of a promising new universal influenza A vaccine, but also that co-delivering different types of recombinant vaccines could reduce the total number of vaccine doses needed to achieve a protective immune response.
ContributorsFavre, Brandon Chetan (Author) / Mason, Hugh S (Thesis advisor) / Mor, Tsafrir (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2019