Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
Displaying 1 - 10 of 80
Description
Creative design lies at the intersection of novelty and technical feasibility. These objectives can be achieved through cycles of divergence (idea generation) and convergence (idea evaluation) in conceptual design. The focus of this thesis is on the latter aspect. The evaluation may involve any aspect of technical feasibility and may be desired at component, sub-system or full system level. Two issues that are considered in this work are: 1. Information about design ideas is incomplete, informal and sketchy 2. Designers often work at multiple levels; different aspects or subsystems may be at different levels of abstraction Thus, high fidelity analysis and simulation tools are not appropriate for this purpose. This thesis looks at the requirements for a simulation tool and how it could facilitate concept evaluation. The specific tasks reported in this thesis are: 1. The typical types of information available after an ideation session 2. The typical types of technical evaluations done in early stages 3. How to conduct low fidelity design evaluation given a well-defined feasibility question A computational tool for supporting idea evaluation was designed and implemented. It was assumed that the results of the ideation session are represented as a morphological chart and each entry is expressed as some combination of a sketch, text and references to physical effects and machine components. Approximately 110 physical effects were identified and represented in terms of algebraic equations, physical variables and a textual description. A common ontology of physical variables was created so that physical effects could be networked together when variables are shared. This allows users to synthesize complex behaviors from simple ones, without assuming any solution sequence. A library of 16 machine elements was also created and users were given instructions about incorporating them. To support quick analysis, differential equations are transformed to algebraic equations by replacing differential terms with steady state differences), only steady state behavior is considered and interval arithmetic was used for modeling. The tool implementation is done by MATLAB; and a number of case studies are also done to show how the tool works. textual description. A common ontology of physical variables was created so that physical effects could be networked together when variables are shared. This allows users to synthesize complex behaviors from simple ones, without assuming any solution sequence. A library of 15 machine elements was also created and users were given instructions about incorporating them. To support quick analysis, differential equations are transformed to algebraic equations by replacing differential terms with steady state differences), only steady state behavior is considered and interval arithmetic was used for modeling. The tool implementation is done by MATLAB; and a number of case studies are also done to show how the tool works.
ContributorsKhorshidi, Maryam (Author) / Shah, Jami J. (Thesis advisor) / Wu, Teresa (Committee member) / Gel, Esma (Committee member) / Arizona State University (Publisher)
Created2014
Description
Vehicles powered by electricity and alternative-fuels are becoming a more popular form of transportation since they have less of an environmental impact than standard gasoline vehicles. Unfortunately, their success is currently inhibited by the sparseness of locations where the vehicles can refuel as well as the fact that many of the vehicles have a range that is less than those powered by gasoline. These factors together create a "range anxiety" in drivers, which causes the drivers to worry about the utility of alternative-fuel and electric vehicles and makes them less likely to purchase these vehicles. For the new vehicle technologies to thrive it is critical that range anxiety is minimized and performance is increased as much as possible through proper routing and scheduling. In the case of long distance trips taken by individual vehicles, the routes must be chosen such that the vehicles take the shortest routes while not running out of fuel on the trip. When many vehicles are to be routed during the day, if the refueling stations have limited capacity then care must be taken to avoid having too many vehicles arrive at the stations at any time. If the vehicles that will need to be routed in the future are unknown then this problem is stochastic. For fleets of vehicles serving scheduled operations, switching to alternative-fuels requires ensuring the schedules do not cause the vehicles to run out of fuel. This is especially problematic since the locations where the vehicles may refuel are limited due to the technology being new. This dissertation covers three related optimization problems: routing a single electric or alternative-fuel vehicle on a long distance trip, routing many electric vehicles in a network where the stations have limited capacity and the arrivals into the system are stochastic, and scheduling fleets of electric or alternative-fuel vehicles with limited locations to refuel. Different algorithms are proposed to solve each of the three problems, of which some are exact and some are heuristic. The algorithms are tested on both random data and data relating to the State of Arizona.
ContributorsAdler, Jonathan D (Author) / Mirchandani, Pitu B. (Thesis advisor) / Askin, Ronald (Committee member) / Gel, Esma (Committee member) / Xue, Guoliang (Committee member) / Zhang, Muhong (Committee member) / Arizona State University (Publisher)
Created2014
Description
Membrane proteins are a vital part of cellular structure. They are directly involved in many important cellular functions, such as uptake, signaling, respiration, and photosynthesis, among others. Despite their importance, however, less than 500 unique membrane protein structures have been determined to date. This is due to several difficulties with macromolecular crystallography, primarily the difficulty of growing large, well-ordered protein crystals. Since the first proof of concept for femtosecond nanocrystallography showing that diffraction patterns can be collected on extremely small crystals, thus negating the need to grow larger crystals, there have been many exciting advancements in the field. The technique has been proven to show high spatial resolution, thus making it a viable method for structural biology. However, due to the ultrafast nature of the technique, which allows for a lack of radiation damage in imaging, even more interesting experiments are possible, and the first temporal and spatial images of an undamaged structure could be acquired. This concept was denoted as time-resolved femtosecond nanocrystallography.
This dissertation presents on the first time-resolved data set of Photosystem II where structural changes can actually be seen without radiation damage. In order to accomplish this, new crystallization techniques had to be developed so that enough crystals could be made for the liquid jet to deliver a fully hydrated stream of crystals to the high-powered X-ray source. These changes are still in the preliminary stages due to the slightly lower resolution data obtained, but they are still a promising show of the power of this new technique. With further optimization of crystal growth methods and quality, injection technique, and continued development of data analysis software, it is only a matter of time before the ability to make movies of molecules in motion from X-ray diffraction snapshots in time exists. The work presented here is the first step in that process.
This dissertation presents on the first time-resolved data set of Photosystem II where structural changes can actually be seen without radiation damage. In order to accomplish this, new crystallization techniques had to be developed so that enough crystals could be made for the liquid jet to deliver a fully hydrated stream of crystals to the high-powered X-ray source. These changes are still in the preliminary stages due to the slightly lower resolution data obtained, but they are still a promising show of the power of this new technique. With further optimization of crystal growth methods and quality, injection technique, and continued development of data analysis software, it is only a matter of time before the ability to make movies of molecules in motion from X-ray diffraction snapshots in time exists. The work presented here is the first step in that process.
ContributorsKupitz, Christopher (Author) / Fromme, Petra (Thesis advisor) / Spence, John C. (Thesis advisor) / Redding, Kevin (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2014
Description
Accelerated life testing (ALT) is the process of subjecting a product to stress conditions (temperatures, voltage, pressure etc.) in excess of its normal operating levels to accelerate failures. Product failure typically results from multiple stresses acting on it simultaneously. Multi-stress factor ALTs are challenging as they increase the number of experiments due to the stress factor-level combinations resulting from the increased number of factors. Chapter 2 provides an approach for designing ALT plans with multiple stresses utilizing Latin hypercube designs that reduces the simulation cost without loss of statistical efficiency. A comparison to full grid and large-sample approximation methods illustrates the approach computational cost gain and flexibility in determining optimal stress settings with less assumptions and more intuitive unit allocations.
Implicit in the design criteria of current ALT designs is the assumption that the form of the acceleration model is correct. This is unrealistic assumption in many real-world problems. Chapter 3 provides an approach for ALT optimum design for model discrimination. We utilize the Hellinger distance measure between predictive distributions. The optimal ALT plan at three stress levels was determined and its performance was compared to good compromise plan, best traditional plan and well-known 4:2:1 compromise test plans. In the case of linear versus quadratic ALT models, the proposed method increased the test plan's ability to distinguish among competing models and provided better guidance as to which model is appropriate for the experiment.
Chapter 4 extends the approach of Chapter 3 to ALT sequential model discrimination. An initial experiment is conducted to provide maximum possible information with respect to model discrimination. The follow-on experiment is planned by leveraging the most current information to allow for Bayesian model comparison through posterior model probability ratios. Results showed that performance of plan is adversely impacted by the amount of censoring in the data, in the case of linear vs. quadratic model form at three levels of constant stress, sequential testing can improve model recovery rate by approximately 8% when data is complete, but no apparent advantage in adopting sequential testing was found in the case of right-censored data when censoring is in excess of a certain amount.
Implicit in the design criteria of current ALT designs is the assumption that the form of the acceleration model is correct. This is unrealistic assumption in many real-world problems. Chapter 3 provides an approach for ALT optimum design for model discrimination. We utilize the Hellinger distance measure between predictive distributions. The optimal ALT plan at three stress levels was determined and its performance was compared to good compromise plan, best traditional plan and well-known 4:2:1 compromise test plans. In the case of linear versus quadratic ALT models, the proposed method increased the test plan's ability to distinguish among competing models and provided better guidance as to which model is appropriate for the experiment.
Chapter 4 extends the approach of Chapter 3 to ALT sequential model discrimination. An initial experiment is conducted to provide maximum possible information with respect to model discrimination. The follow-on experiment is planned by leveraging the most current information to allow for Bayesian model comparison through posterior model probability ratios. Results showed that performance of plan is adversely impacted by the amount of censoring in the data, in the case of linear vs. quadratic model form at three levels of constant stress, sequential testing can improve model recovery rate by approximately 8% when data is complete, but no apparent advantage in adopting sequential testing was found in the case of right-censored data when censoring is in excess of a certain amount.
ContributorsNasir, Ehab (Author) / Pan, Rong (Thesis advisor) / Runger, George C. (Committee member) / Gel, Esma (Committee member) / Kao, Ming-Hung (Committee member) / Montgomery, Douglas C. (Committee member) / Arizona State University (Publisher)
Created2014
Description
The utilization of solar energy requires an efficient means of its storage as fuel. In bio-inspired artificial photosynthesis, light energy can be used to drive water oxidation, but catalysts that produce molecular oxygen from water are required. This dissertation demonstrates a novel complex utilizing earth-abundant Ni in combination with glycine as an efficient catalyst with a modest overpotential of 0.475 ± 0.005 V for a current density of 1 mA/cm2 at pH 11. The production of molecular oxygen at a high potential was verified by measurement of the change in oxygen concentration, yielding a Faradaic efficiency of 60 ± 5%. This Ni species can achieve a current density of 4 mA/cm2 that persists for at least 10 hours. Based upon the observed pH dependence of the current amplitude and oxidation/reduction peaks, the catalysis is an electron-proton coupled process. In addition, to investigate the binding of divalent metals to proteins, four peptides were designed and synthesized with carboxylate and histidine ligands. The binding of the metals was characterized by monitoring the metal-induced changes in circular dichroism spectra. Cyclic voltammetry demonstrated that bound copper underwent a Cu(I)/Cu(II) oxidation/reduction change at a potential of approximately 0.32 V in a quasi-reversible process. The relative binding affinity of Mn(II), Fe(II), Co(II), Ni(II) and Cu(II) to the peptides is correlated with the stability constants of the Irving-Williams series for divalent metal ions. A potential application of these complexes of transition metals with amino acids or peptides is in the development of artificial photosynthetic cells.
ContributorsWang, Dong (Author) / Allen, James P. (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Redding, Kevin (Committee member) / Arizona State University (Publisher)
Created2014
Description
Cyanovirin-N (CVN) is a cyanobacterial lectin with potent anti-HIV activity, mediated by binding to the N-linked oligosaccharide moiety of the envelope protein gp120. CVN offers a scaffold to develop multivalent carbohydrate-binding proteins with tunable specificities and affinities. I present here biophysical calculations completed on a monomeric-stabilized mutant of cyanovirin-N, P51G-m4-CVN, in which domain A binding activity is abolished by four mutations; with comparisons made to CVNmutDB, in which domain B binding activity is abolished. Using Monte Carlo calculations and docking simulations, mutations in CVNmutDB were considered singularly, and the mutations E41A/G and T57A were found to impact the affinity towards dimannose the greatest. 15N-labeled proteins were titrated with Manα(1-2)Manα, while following chemical shift perturbations in NMR spectra. The mutants, E41A/G and T57A, had a larger Kd than P51G-m4-CVN, matching the trends predicted by the calculations. We also observed that the N42A mutation affects the local fold of the binding pocket, thus removing all binding to dimannose. Characterization of the mutant N53S showed similar binding affinity to P51G-m4-CVN. Using biophysical calculations allows us to study future iterations of models to explore affinities and specificities. In order to further elucidate the role of multivalency, I report here a designed covalent dimer of CVN, Nested cyanovirin-N (Nested CVN), which has four binding sites. Nested CVN was found to have comparable binding affinity to gp120 and antiviral activity to wt CVN. These results demonstrate the ability to create a multivalent, covalent dimer that has comparable results to that of wt CVN.
WW domains are small modules consisting of 32-40 amino acids that recognize proline-rich peptides and are found in many signaling pathways. We use WW domain sequences to explore protein folding by simulations using Zipping and Assembly Method. We identified five crucial contacts that enabled us to predict the folding of WW domain sequences based on those contacts. We then designed a folded WW domain peptide from an unfolded WW domain sequence by introducing native contacts at those critical positions.
WW domains are small modules consisting of 32-40 amino acids that recognize proline-rich peptides and are found in many signaling pathways. We use WW domain sequences to explore protein folding by simulations using Zipping and Assembly Method. We identified five crucial contacts that enabled us to predict the folding of WW domain sequences based on those contacts. We then designed a folded WW domain peptide from an unfolded WW domain sequence by introducing native contacts at those critical positions.
ContributorsWoodrum, Brian William (Author) / Ghirlanda, Giovanna (Thesis advisor) / Redding, Kevin (Committee member) / Wang, Xu (Committee member) / Arizona State University (Publisher)
Created2014
Description
A vast amount of energy emanates from the sun, and at the distance of Earth, approximately 172,500 TW reaches the atmosphere. Of that, 80,600 TW reaches the surface with 15,600 TW falling on land. Photosynthesis converts 156 TW in the form of biomass, which represents all food/fuel for the biosphere with about 20 TW of the total product used by humans. Additionally, our society uses approximately 20 more TW of energy from ancient photosynthetic products i.e. fossil fuels. In order to mitigate climate problems, the carbon dioxide must be removed from the human energy usage by replacement or recycling as an energy carrier. Proposals have been made to process biomass into biofuels; this work demonstrates that current efficiencies of natural photosynthesis are inadequate for this purpose, the effects of fossil fuel replacement with biofuels is ecologically irresponsible, and new technologies are required to operate at sufficient efficiencies to utilize artificial solar-to-fuels systems. Herein a hybrid bioderived self-assembling hydrogen-evolving nanoparticle consisting of photosystem I (PSI) and platinum nanoclusters is demonstrated to operate with an overall efficiency of 6%, which exceeds that of land plants by more than an order of magnitude. The system was limited by the rate of electron donation to photooxidized PSI. Further work investigated the interactions of natural donor acceptor pairs of cytochrome c6 and PSI for the thermophilic cyanobacteria Thermosynechococcus elogantus BP1 and the red alga Galderia sulphuraria. The cyanobacterial system is typified by collisional control while the algal system demonstrates a population of prebound PSI-cytochrome c6 complexes with faster electron transfer rates. Combining the stability of cyanobacterial PSI and kinetics of the algal PSI:cytochrome would result in more efficient solar-to-fuel conversion. A second priority is the replacement of platinum with chemically abundant catalysts. In this work, protein scaffolds are employed using host-guest strategies to increase the stability of proton reduction catalysts and enhance the turnover number without the oxygen sensitivity of hydrogenases. Finally, design of unnatural electron transfer proteins are explored and may introduce a bioorthogonal method of introducing alternative electron transfer pathways in vitro or in vivo in the case of engineered photosynthetic organisms.
ContributorsVaughn, Michael David (Author) / Moore, Thomas (Thesis advisor) / Fromme, Petra (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Redding, Kevin (Committee member) / Arizona State University (Publisher)
Created2014
Description
The transmembrane subunit (gp41) of the envelope glycoprotein of HIV-1 associates noncovalently with the surface subunit (gp120) and together they play essential roles in viral mucosal transmission and infection of target cells. The membrane proximal region (MPR, residues 649-683) of gp41 is highly conserved and contains epitopes of broadly neutralizing antibodies. The transmembrane (TM) domain (residues 684-705) of gp41 not only anchors the envelope glycoprotein complex in the viral membrane but also dynamically affects the interactions of the MPR with the membrane. While high-resolution X-ray structures of some segments of the MPR were solved in the past, they represent the pre-fusion and post-fusion conformations, most of which could not react with the broadly neutralizing antibodies 2F5 and 4E10. Structural information on the TM domain of gp41 is scant and at low resolution.
This thesis describes the structural studies of MPR-TM (residues 649-705) of HIV-1 gp41 by X-ray crystallography. MPR-TM was fused with different fusion proteins to improve the membrane protein overexpression. The expression level of MPR-TM was improved by fusion to the C-terminus of the Mistic protein, yielding ∼1 mg of pure MPR-TM protein per liter cell culture. The fusion partner Mistic was removed for final crystallization. The isolated MPR-TM protein was biophysically characterized and is a monodisperse candidate for crystallization. However, no crystal with diffraction quality was obtained even after extensive crystallization screens. A novel construct was designed to overexpress MPR-TM as a maltose binding protein (MBP) fusion. About 60 mg of MBP/MPR-TM recombinant protein was obtained from 1 liter of cell culture. Crystals of MBP/MPR-TM recombinant protein could not be obtained when MBP and MPR-TM were separated by a 42 amino acid (aa)-long linker but were obtained after changing the linker to three alanine residues. The crystals diffracted to 2.5 Å after crystallization optimization. Further analysis of the diffraction data indicated that the crystals are twinned. The final structure demonstrated that MBP crystallized as a dimer of trimers, but the electron density did not extend beyond the linker region. We determined by SDS-PAGE and MALDI-TOF MS that the crystals contained MBP only. The MPR-TM of gp41 might be cleaved during or after the process of crystallization. Comparison of the MBP trimer reported here with published trimeric MBP fusion structures indicated that MBP might form such a trimeric conformation under the effect of MPR-TM.
This thesis describes the structural studies of MPR-TM (residues 649-705) of HIV-1 gp41 by X-ray crystallography. MPR-TM was fused with different fusion proteins to improve the membrane protein overexpression. The expression level of MPR-TM was improved by fusion to the C-terminus of the Mistic protein, yielding ∼1 mg of pure MPR-TM protein per liter cell culture. The fusion partner Mistic was removed for final crystallization. The isolated MPR-TM protein was biophysically characterized and is a monodisperse candidate for crystallization. However, no crystal with diffraction quality was obtained even after extensive crystallization screens. A novel construct was designed to overexpress MPR-TM as a maltose binding protein (MBP) fusion. About 60 mg of MBP/MPR-TM recombinant protein was obtained from 1 liter of cell culture. Crystals of MBP/MPR-TM recombinant protein could not be obtained when MBP and MPR-TM were separated by a 42 amino acid (aa)-long linker but were obtained after changing the linker to three alanine residues. The crystals diffracted to 2.5 Å after crystallization optimization. Further analysis of the diffraction data indicated that the crystals are twinned. The final structure demonstrated that MBP crystallized as a dimer of trimers, but the electron density did not extend beyond the linker region. We determined by SDS-PAGE and MALDI-TOF MS that the crystals contained MBP only. The MPR-TM of gp41 might be cleaved during or after the process of crystallization. Comparison of the MBP trimer reported here with published trimeric MBP fusion structures indicated that MBP might form such a trimeric conformation under the effect of MPR-TM.
ContributorsGong, Zhen (Author) / Fromme, Petra (Thesis advisor) / Mor, Tsafrir (Thesis advisor) / Ros, Alexandra (Committee member) / Redding, Kevin (Committee member) / Arizona State University (Publisher)
Created2014
Description
Rhodoferax antarcticus strain ANT.BR, a purple nonsulfur bacterium isolated from a microbial mat in Ross Island, Antarctica, is the first described anoxygenic phototrophic bacterium that is adapted to cold habitats and is the first beta-proteobacterium to undergo complete genome sequencing. R. antarcticus has unique absorption spectra and there are no obvious intracytoplasmic membranes in cells grown phototrophically, even under low light intensity. Analysis of the finished genome sequence reveals a single chromosome (3,809,266 bp) and a large plasmid (198,615 bp) that together harbor 4,262 putative genes. The genome contains two types of Rubiscos, Form IAq and Form II, which are known to exhibit quite different kinetic properties in other bacteria. The presence of multiple Rubisco forms could give R. antarcticus high metabolic flexibility in diverse environments. Annotation of the complete genome sequence along with previous experimental results predict the presence of structural genes for three types of light-harvesting (LH) complexes, LH I (B875), LH II (B800/850), and LH III (B800/820). There is evidence that expression of genes for the LH II complex might be inhibited when R. antarcticus is under low temperature and/or low light intensity. These interesting condition-dependent light-harvesting apparatuses and the control of their expression are very valuable for the further understanding of photosynthesis in cold environments. Finally, R. antarcticus exhibits a highly motile lifestyle. The genome content and organization of all putative polar flagella genes are characterized and discussed.
ContributorsZhao, Tingting, M.S (Author) / Touchman, Jeffrey (Thesis advisor) / Rosenberg, Michael (Committee member) / Redding, Kevin (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2011
Description
For more than twenty years, clinical researchers have been publishing data regarding incidence and risk of adverse events (AEs) incurred during hospitalizations. Hospitals have standard operating policies and procedures (SOPP) to protect patients from AE. The AE specifics (rates, SOPP failures, timing and risk factors) during heart failure (HF) hospitalizations are unknown. There were 1,722 patients discharged with a primary diagnosis of HF from an academic hospital between January 2005 and December 2007. Three hundred eighty-one patients experienced 566 AEs, classified into four categories: medication (43.9%), infection (18.9%), patient care (26.3%), or procedural (10.9%). Three distinct analyses were performed: 1) patient's perspective of SOPP reliability including cumulative distribution and hazard functions of time to AEs; 2) Cox proportional hazards model to determine independent patient-specific risk factors for AEs; and 3) hospital administration's perspective of SOPP reliability through three years of the study including cumulative distribution and hazard functions of time between AEs and moving range statistical process control (SPC) charts for days between failures of each type. This is the first study, to our knowledge, to consider reliability of SOPP from both the patient's and hospital administration's perspective. AE rates in hospitalized patients are similar to other recently published reports and did not improve during the study period. Operations research methodologies will be necessary to improve reliability of care delivered to hospitalized patients.
ContributorsHuddleston, Jeanne (Author) / Fowler, John (Thesis advisor) / Montgomery, Douglas C. (Thesis advisor) / Gel, Esma (Committee member) / Shunk, Dan (Committee member) / Arizona State University (Publisher)
Created2012