Matching Items (74)
Biological and immunological characterization of plant-produced HIV-1 Gag/dgp41 virus-like particles
Description
Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.
ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
Description
The concept of vaccination dates back further than Edward Jenner's first vaccine using cowpox pustules to confer immunity against smallpox in 1796. Nevertheless, it was Jenner's success that gave vaccines their name and made vaccinia virus (VACV) of particular interest. More than 200 years later there is still the need to understand vaccination from vaccine design to prediction of vaccine efficacy using mathematical models. Post-exposure vaccination with VACV has been suggested to be effective if administered within four days of smallpox exposure although this has not been definitively studied in humans. The first and second chapters analyze post-exposure prophylaxis of VACV in an animal model using v50ΔB13RMγ, a recombinant VACV expressing murine interferon gamma (IFN-γ) also known as type II IFN. While untreated animals infected with wild type VACV die by 10 days post-infection (dpi), animals treated with v50ΔB13RMγ 1 dpi had decreased morbidity and 100% survival. Despite these differences, the viral load was similar in both groups suggesting that v50ΔB13RMγ acts as an immunoregulator rather than as an antiviral. One of the main characteristics of VACV is its resistance to type I IFN, an effect primarily mediated by the E3L protein, which has a Z-DNA binding domain and a double-stranded RNA (dsRNA) binding domain. In the third chapter a VACV that independently expresses both domains of E3L was engineered and compared to wild type in cells in culture. The dual expression virus was unable to replicate in the JC murine cell line where both domains are needed together for replication. Moreover, phosphorylation of the dsRNA dependent protein kinase (PKR) was observed at late times post-infection which indicates that both domains need to be linked together in order to block the IFN response. Because smallpox has already been eradicated, the utility of mathematical modeling as a tool for predicting disease spread and vaccine efficacy was explored in the last chapter using dengue as a disease model. Current modeling approaches were reviewed and the 2000-2001 dengue outbreak in a Peruvian region was analyzed. This last section highlights the importance of interdisciplinary collaboration and how it benefits research on infectious diseases.
ContributorsHolechek, Susan A (Author) / Jacobs, Bertram L (Thesis advisor) / Castillo-Chavez, Carlos (Committee member) / Frasch, Wayne (Committee member) / Hogue, Brenda (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2011
Description
Recent changes in the energy markets structure combined with the conti-nuous load growth have caused power systems to be operated under more stressed conditions. In addition, the nature of power systems has also grown more complex and dynamic because of the increasing use of long inter-area tie-lines and the high motor loads especially those comprised mainly of residential single phase A/C motors. Therefore, delayed voltage recovery, fast voltage collapse and short term voltage stability issues in general have obtained significant importance in relia-bility studies. Shunt VAr injection has been used as a countermeasure for voltage instability. However, the dynamic and fast nature of short term voltage instability requires fast and sufficient VAr injection, and therefore dynamic VAr devices such as Static VAr Compensators (SVCs) and STATic COMpensators (STAT-COMs) are used. The location and size of such devices are optimized in order to improve their efficiency and reduce initial costs. In this work time domain dy-namic analysis was used to evaluate trajectory voltage sensitivities for each time step. Linear programming was then performed to determine the optimal amount of required VAr injection at each bus, using voltage sensitivities as weighting factors. Optimal VAr injection values from different operating conditions were weighted and averaged in order to obtain a final setting of the VAr requirement. Some buses under consideration were either assigned very small VAr injection values, or not assigned any value at all. Therefore, the approach used in this work was found to be useful in not only determining the optimal size of SVCs, but also their location.
ContributorsSalloum, Ahmed (Author) / Vittal, Vijay (Thesis advisor) / Heydt, Gerald (Committee member) / Ayyanar, Raja (Committee member) / Arizona State University (Publisher)
Created2011
Description
The electric transmission grid is conventionally treated as a fixed asset and is operated around a single topology. Though several instances of switching transmission lines for corrective mechaism, congestion management, and minimization of losses can be found in literature, the idea of co-optimizing transmission with generation dispatch has not been widely investigated. Network topology optimization exploits the redundancies that are an integral part of the network to allow for improvement in dispatch efficiency. Although, the concept of a dispatchable network initially appears counterintuitive questioning the wisdom of switching transmission lines on a more regu-lar basis, results obtained in the previous research on transmission switching with a Direct Current Optimal Power Flow (DCOPF) show significant cost reductions. This thesis on network topology optimization with ACOPF emphasizes the need for additional research in this area. It examines the performance of network topology optimization in an Alternating Current (AC) setting and its impact on various parameters like active power loss and voltages that are ignored in the DC setting. An ACOPF model, with binary variables representing the status of transmission lines incorporated into the formulation, is written in AMPL, a mathematical programming language and this optimization problem is solved using the solver KNITRO. ACOPF is a non-convex, nonlinear optimization problem, making it a very hard problem to solve. The introduction of bi-nary variables makes ACOPF a mixed integer nonlinear programming problem, further increasing the complexity of the optimization problem. An iterative method of opening each transmission line individually before choosing the best solution has been proposed as a purely investigative approach to studying the impact of transmission switching with ACOPF. Economic savings of up to 6% achieved using this approach indicate the potential of this concept. In addition, a heuristic has been proposed to improve the computational efficiency of network topology optimization. This research also makes a comparative analysis between transmission switching in a DC setting and switching in an AC setting. Results presented in this thesis indicate significant economic savings achieved by controlled topology optimization, thereby reconfirming the need for further examination of this idea.
ContributorsPotluri, Tejaswi (Author) / Hedman, Kory (Thesis advisor) / Vittal, Vijay (Committee member) / Heydt, Gerald (Committee member) / Arizona State University (Publisher)
Created2011
Description
Due to restructuring and open access to the transmission system, modern electric power systems are being operated closer to their operational limits. Additionally, the secure operational limits of modern power systems have become increasingly difficult to evaluate as the scale of the network and the number of transactions between utilities increase. To account for these challenges associated with the rapid expansion of electric power systems, dynamic equivalents have been widely applied for the purpose of reducing the computational effort of simulation-based transient security assessment. Dynamic equivalents are commonly developed using a coherency-based approach in which a retained area and an external area are first demarcated. Then the coherent generators in the external area are aggregated and replaced by equivalenced models, followed by network reduction and load aggregation. In this process, an improperly defined retained area can result in detrimental impacts on the effectiveness of the equivalents in preserving the dynamic characteristics of the original unreduced system. In this dissertation, a comprehensive approach has been proposed to determine an appropriate retained area boundary by including the critical generators in the external area that are tightly coupled with the initial retained area. Further-more, a systematic approach has also been investigated to efficiently predict the variation in generator slow coherency behavior when the system operating condition is subject to change. Based on this determination, the critical generators in the external area that are tightly coherent with the generators in the initial retained area are retained, resulting in a new retained area boundary. Finally, a novel hybrid dynamic equivalent, consisting of both a coherency-based equivalent and an artificial neural network (ANN)-based equivalent, has been proposed and analyzed. The ANN-based equivalent complements the coherency-based equivalent at all the retained area boundary buses, and it is designed to compensate for the discrepancy between the full system and the conventional coherency-based equivalent. The approaches developed have been validated on a large portion of the Western Electricity Coordinating Council (WECC) system and on a test case including a significant portion of the eastern interconnection.
ContributorsMa, Feng (Author) / Vittal, Vijay (Thesis advisor) / Tylavsky, Daniel (Committee member) / Heydt, Gerald (Committee member) / Si, Jennie (Committee member) / Ayyanar, Raja (Committee member) / Arizona State University (Publisher)
Created2011
Description
The high penetration of photovoltaic (PV) both at the utility and at the distribu-tion levels, has raised concerns about the reliability of grid-tied inverters of PV power systems. Inverters are generally considered as the weak link in PV power systems. The lack of a dedicated qualification/reliability standard for PV inverters is a main barrier in realizing higher level of confidence in reliability. Development of a well-accepted design qualification standard specifically for PV inverters will help pave the way for significant improvement in reliability and performance of inverters across the entire industry. The existing standards for PV inverters such as UL 1741 and IEC 62109-1 primarily focus on safety. IEC 62093 discusses inverter qualification but it includes all the balance of sys-tem components and therefore not specific to PV inverters. There are other general stan-dards for distributed generators including the IEEE1547 series of standards which cover major concerns like utility integration but they are not dedicated to PV inverters and are not written from a design qualification point of view. In this thesis, some of the potential requirements for a design qualification standard for PV inverters are addressed. The IEC 62093 is considered as a guideline and the possible inclusions in the framework for a dedicated design qualification standard of PV inverter are discussed. The missing links in existing PV inverter related standards are identified by performing gap analysis. Dif-ferent requirements of small residential inverters compared to large utility-scale systems, and the emerging requirements on grid support features are also considered. Electric stress test is found to be the key missing link and one of the electric stress tests, the surge withstand test is studied in detail. The use of the existing standards for surge withstand test of residential scale PV inverters is investigated and a method to suitably adopt these standards is proposed. The proposed method is studied analytically and verified using simulation. A design criterion for choosing the switch ratings of the inverter that can per-form reliably under the surge environment is derived.
ContributorsAlampoondi Venkataramanan, Sai Balasubramanian (Author) / Ayyanar, Raja (Thesis advisor) / Vittal, Vijay (Committee member) / Heydt, Gerald (Committee member) / Arizona State University (Publisher)
Created2011
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
In modern electric power systems, energy management systems (EMSs) are responsi-ble for monitoring and controlling the generation system and transmission networks. State estimation (SE) is a critical `must run successful' component within the EMS software. This is dictated by the high reliability requirements and need to represent the closest real time model for market operations and other critical analysis functions in the EMS. Tradi-tionally, SE is run with data obtained only from supervisory control and data acquisition (SCADA) devices and systems. However, more emphasis on improving the performance of SE drives the inclusion of phasor measurement units (PMUs) into SE input data. PMU measurements are claimed to be more accurate than conventional measurements and PMUs `time stamp' measurements accurately. These widely distributed devices meas-ure the voltage phasors directly. That is, phase information for measured voltages and currents are available. PMUs provide data time stamps to synchronize measurements. Con-sidering the relatively small number of PMUs installed in contemporary power systems in North America, performing SE with only phasor measurements is not feasible. Thus a hy-brid SE, including both SCADA and PMU measurements, is the reality for contemporary power system SE. The hybrid approach is the focus of a number of research papers. There are many practical challenges in incorporating PMUs into SE input data. The higher reporting rates of PMUs as compared with SCADA measurements is one of the salient problems. The disparity of reporting rates raises a question whether buffering the phasor measurements helps to give better estimates of the states. The research presented in this thesis addresses the design of data buffers for PMU data as used in SE applications in electric power systems. The system theoretic analysis is illustrated using an operating electric power system in the southwest part of the USA. Var-ious instances of state estimation data have been used for analysis purposes. The details of the research, results obtained and conclusions drawn are presented in this document.
ContributorsMurugesan, Veerakumar (Author) / Vittal, Vijay (Committee member) / Heydt, Gerald (Committee member) / Ayyanar, Raja (Committee member) / Arizona State University (Publisher)
Created2013
Description
Vaccinia virus (VACV) is the current vaccine for the highly infectious smallpox disease. Since the eradication of smallpox, VACV has been developed extensively as a heterologous vaccine vector for several pathogens. However, due to the complications associated with this replication competent virus, the safety and efficacy of VACV vaccine vector has been reevaluated. To evaluate the safety and efficacy of VACV, we study the interactions between VACV and the host innate immune system, especially the type I interferon (IFN) signaling pathways. In this work, we evaluated the role of protein kinase R (PKR) and Adenosine Deaminase Acting on RNA 1(ADAR1), which are induced by IFN, in VACV infection. We found that PKR is necessary but is not sufficient to activate interferon regulatory factor 3 (IRF3) in the induction of type I IFN; and the activation of the stress-activated protein kinase/ c-Jun NH2-terminal kinase is required for the PKR-dependent activation of IRF3 during VACV infection. Even though PKR was found to have an antiviral effect in VACV, ADAR1 was found to have a pro-viral effect by destabilizing double stranded RNA (dsRNA), rescuing VACVΔE3L, VACV deleted of the virulence factor E3L, when provided in trans. With the lessons we learned from VACV and host cells interaction, we have developed and evaluated a safe replication-competent VACV vaccine vector for HIV. Our preliminary results indicate that our VACV vaccine vector can still induce the IFN pathway while maintaining the ability to replicate and to express the HIV antigen efficiently. This suggests that this VACV vector can be used as a safe and efficient vaccine vector for HIV.
ContributorsHuynh, Trung Phuoc (Author) / Jacobs, Bertram L (Thesis advisor) / Hogue, Brenda (Committee member) / Chang, Yung (Committee member) / Ugarova, Tatiana (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation presents a novel current source converter topology that is primarily intended for single-phase photovoltaic (PV) applications. In comparison with the existing PV inverter technology, the salient features of the proposed topology are: a) the low frequency (double of line frequency) ripple that is common to single-phase inverters is greatly reduced; b) the absence of low frequency ripple enables significantly reduced size pass components to achieve necessary DC-link stiffness and c) improved maximum power point tracking (MPPT) performance is readily achieved due to the tightened current ripple even with reduced-size passive components. The proposed topology does not utilize any electrolytic capacitors. Instead an inductor is used as the DC-link filter and reliable AC film capacitors are utilized for the filter and auxiliary capacitor. The proposed topology has a life expectancy on par with PV panels. The proposed modulation technique can be used for any current source inverter where an unbalanced three-phase operation is desires such as active filters and power controllers. The proposed topology is ready for the next phase of microgrid and power system controllers in that it accepts reactive power commands. This work presents the proposed topology and its working principle supported by with numerical verifications and hardware results. Conclusions and future work are also presented.
ContributorsBush, Craig R (Author) / Ayyanar, Raja (Thesis advisor) / Karam, Lina (Committee member) / Heydt, Gerald (Committee member) / Karady, George G. (Committee member) / Arizona State University (Publisher)
Created2013