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- Genre: Masters Thesis
- Creators: Arizona State University
- Creators: Chakraborty, Bijeta
- Member of: ASU Electronic Theses and Dissertations
Description
Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
Description
ABSTRACT In terms of prevalence, human suffering and costs dengue infections are the most important arthropod-borne viral disease worldwide. Dengue virus (DENV) is a mosquito-borne flavivirus and the etiological agent of dengue fever and dengue hemorrhagic fever. Thus, development of a safe and efficient vaccine constitutes an urgent necessity. Besides the traditional strategies aim at generating immunization options, the usage of viral vectors to deliver antigenic stimulus in order to elicit protection are particularly attractive for the endeavor of a dengue vaccine. The viral vector (MVvac2) is genetically equivalent to the currently used measles vaccine strain Moraten, which adds practicality to my approach. The goal of the present study was to generate a recombinant measles virus expressing structural antigens from two strains of DENV (DENV2 and DENV4) The recombinant vectors replication profile was comparable to that of the parental strain and expresses either membrane bound or soluble forms of DENV2 and DENV4 E glycoproteins. I discuss future experiments in order to demonstrate its immunogenicity in our measles-susceptible mouse model.
ContributorsAbdelgalel, Rowida (Author) / Reyes del Valle, Jorge (Thesis advisor) / Hogue, Brenda (Committee member) / Frasch, Wayne D (Committee member) / Arizona State University (Publisher)
Created2013
Description
Efficiency of components is an ever increasing area of importance to portable applications, where a finite battery means finite operating time. Higher efficiency devices need to be designed that don't compromise on the performance that the consumer has come to expect. Class D amplifiers deliver on the goal of increased efficiency, but at the cost of distortion. Class AB amplifiers have low efficiency, but high linearity. By modulating the supply voltage of a Class AB amplifier to make a Class H amplifier, the efficiency can increase while still maintaining the Class AB level of linearity. A 92dB Power Supply Rejection Ratio (PSRR) Class AB amplifier and a Class H amplifier were designed in a 0.24um process for portable audio applications. Using a multiphase buck converter increased the efficiency of the Class H amplifier while still maintaining a fast response time to respond to audio frequencies. The Class H amplifier had an efficiency above the Class AB amplifier by 5-7% from 5-30mW of output power without affecting the total harmonic distortion (THD) at the design specifications. The Class H amplifier design met all design specifications and showed performance comparable to the designed Class AB amplifier across 1kHz-20kHz and 0.01mW-30mW. The Class H design was able to output 30mW into 16Ohms without any increase in THD. This design shows that Class H amplifiers merit more research into their potential for increasing efficiency of audio amplifiers and that even simple designs can give significant increases in efficiency without compromising linearity.
ContributorsPeterson, Cory (Author) / Bakkaloglu, Bertan (Thesis advisor) / Barnaby, Hugh (Committee member) / Kiaei, Sayfe (Committee member) / Arizona State University (Publisher)
Created2013
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
Class D Amplifiers are widely used in portable systems such as mobile phones to achieve high efficiency. The demands of portable electronics for low power consumption to extend battery life and reduce heat dissipation mandate efficient, high-performance audio amplifiers. The high efficiency of Class D amplifiers (CDAs) makes them particularly attractive for portable applications. The Digital class D amplifier is an interesting solution to increase the efficiency of embedded systems. However, this solution is not good enough in terms of PWM stage linearity and power supply rejection. An efficient control is needed to correct the error sources in order to get a high fidelity sound quality in the whole audio range of frequencies. A fundamental analysis on various error sources due to non idealities in the power stage have been discussed here with key focus on Power supply perturbations driving the Power stage of a Class D Audio Amplifier. Two types of closed loop Digital Class D architecture for PSRR improvement have been proposed and modeled. Double sided uniform sampling modulation has been used. One of the architecture uses feedback around the power stage and the second architecture uses feedback into digital domain. Simulation & experimental results confirm that the closed loop PSRR & PS-IMD improve by around 30-40 dB and 25 dB respectively.
ContributorsChakraborty, Bijeta (Author) / Bakkaloglu, Bertan (Thesis advisor) / Garrity, Douglas (Committee member) / Ozev, Sule (Committee member) / Arizona State University (Publisher)
Created2012
Description
Vaccines against the arthropod-borne dengue virus (DENV) are still commercially nonexistent. A subunit immunization strategy may be of value, especially if a safe viral vector acts as a biologically active adjuvant. The DENV envelope protein (E), the main target for neutralizing immune responses, has three conformational domains. The immunoglobulin-like and independently folding domain III (DIII) contains epitopes that elicit highly specific neutralizing antibodies. The hepatitis B small surface antigen (HBsAg, S) was used as a scaffold to display DENV 2 DIII on a virus-like particle (VLP). A measles virus (MV) was engineered to vector HBsAg and the hybrid glycoprotein DIII-HBsAg in two different loci (DIII-S). Despite the relatively deleterious effect on replication caused by the insertion of two transcription cassettes, the recombinant virus MVvac2(DIII-S,S)P induced the secretion of DIII-S hybrid VLP with a similar sucrose density as HBsAg particles (1.10-1.12g/ml) and peaked at 48 h post-infection producing 1.3x106 TCID50/ml infectious MV units in vitro. A second recombinant virus, MVvac2(DIII-S)N, was engineered to vector only the hybrid DIII-S. However, it did not induce the secretion of hybrid HBsAg particles in the supernatant of infected cells. The immunogenicity of the recombinant viruses was tested in a MV-susceptible small animal model, the experimental group which received two 105 TCID50 I.P. doses of MVvac2(DIII-S,S)P in a 28 day interval developed a robust immune response against MV (1:1280), HBsAg (787 mIU/ml) and DENV2 (Log10 neutralization index of 1.2) on average. In summary, it is possible to display DENV E DIII on hybrid HBsAg particles vectored by MV that elicit an immune response. This forms the basis for a potential vaccine platform against DENV.
ContributorsHarahap, Indira (Author) / Reyes del Valle, Jorge (Thesis advisor) / Hogue, Brenda G (Thesis advisor) / Lake, Douglas (Committee member) / Mason, Hugh (Committee member) / Arizona State University (Publisher)
Created2015
Description
In this thesis, a digital input class D audio amplifier system which has the ability
to reject the power supply noise and nonlinearly of the output stage is presented. The main digital class D feed-forward path is using the fully-digital sigma-delta PWM open loop topology. Feedback loop is used to suppress the power supply noise and harmonic distortions. The design is using global foundry 0.18um technology.
Based on simulation, the power supply rejection at 200Hz is about -49dB with
81dB dynamic range and -70dB THD+N. The full scale output power can reach as high as 27mW and still keep minimum -68dB THD+N. The system efficiency at full scale is about 82%.
to reject the power supply noise and nonlinearly of the output stage is presented. The main digital class D feed-forward path is using the fully-digital sigma-delta PWM open loop topology. Feedback loop is used to suppress the power supply noise and harmonic distortions. The design is using global foundry 0.18um technology.
Based on simulation, the power supply rejection at 200Hz is about -49dB with
81dB dynamic range and -70dB THD+N. The full scale output power can reach as high as 27mW and still keep minimum -68dB THD+N. The system efficiency at full scale is about 82%.
ContributorsBai, Jing (Author) / Bakkaloglu, Bertan (Thesis advisor) / Arizona State University (Publisher)
Created2015
Description
The spread of dengue worldwide currently places half of the world’s population at risk. In the absence of a dengue vaccine, control of the disease requires control of the mosquito species that transmit the virus. The most important of these is. Advances in research detailing the responsiveness of Aedes aegypti to small changes in climate enable the production of more sophisticated remote sensing and surveillance techniques for monitoring these populations. Close monitoring of global dengue activity and outbreaks likewise enables a greater specificity when determining to which human populations the virus is most likely to spread. There have been no locally acquired cases in Arizona to date, but the high abundance of Aedes aegypti in the Phoenix Metropolitan area raises concern within the Arizona Department of Health Services over the potential transmission of dengue in the city. This study develops a model that combines mosquito abundance, micro-climatic and demographic information to delineate regions in Phoenix that are most support transmission of dengue. The first chapter focuses on the impact that daytime high and low temperatures have on Aedes aegypti’s ability to become infectious with dengue. It argues that NDVI (normal difference vegetative index) imaging of the Phoenix area can be used to plot areas where mosquitoes are most likely to become competent vectors. The second chapter focuses on the areas in the city where mosquitoes are most likely to be exposed to the virus. Based on proximity to Phoenix and the high volume of traffic across the Arizona-Mexico border, I treat the Mexican state of Sonora as the source of infection. I combine these two analyses, micro-climatic and demographic, to produce maps of Phoenix that show the locations with the highest likelihood of transmission overall.
ContributorsHughes, Tyler (Author) / Perrings, Charles (Thesis advisor) / Kinzig, Ann (Committee member) / Hall, Sharon J (Committee member) / Arizona State University (Publisher)
Created2016