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 85
Description
Synechocystis sp PCC 6803 is a photosynthetic cyanobacterium that can be easily transformed to produce molecules of interest; this has increased Synechocystis’ popularity as a clean energy platform. Synechocystis has been shown to produce and excrete molecules such as fatty acids, isoprene, etc. after appropriate genetic modification. Challenges faced for large–scale growth of modified Synechocystis include abiotic stress, microbial contamination and high processing costs of product and cell material. Research reported in this dissertation contributes to solutions to these challenges. First, abiotic stress was addressed by overexpression of the heat shock protein ClpB1. In contrast to the wild type, the ClpB1 overexpression mutant (Slr1641+) tolerated rapid temperature changes, but no difference was found between the strains when temperature shifts were slower. Combination of ClpB1 overexpression with DnaK2 overexpression (Slr1641+/Sll0170+) further increased thermotolerance. Next, we used a Synechocystis strain that carries an introduced isoprene synthase gene (IspS+) and that therefore produces isoprene. We attempted to increase isoprene yields by overexpression of key enzymes in the methyl erythritol phosphate (MEP) pathway that leads to synthesis of the isoprene precursor. Isoprene production was not increased greatly by MEP pathway induction, likely because of limitations in the affinity of the isoprene synthase for the substrate. Finally, two extraction principles, two–phase liquid extraction (e.g., with an organic and aqueous phase) and solid–liquid extraction (e.g., with a resin) were tested. Two–phase liquid extraction is suitable for separating isoprene but not fatty acids from the culture medium. Fatty acid removal required acidification or surfactant addition, which affected biocompatibility. Therefore, improvements of both the organism and product–harvesting methods can contribute to enhancing the potential of cyanobacteria as solar–powered biocatalysts for the production of petroleum substitutes.
ContributorsGonzalez Esquer, Cesar Raul (Author) / Vermaas, Willem (Thesis advisor) / Chandler, Douglas (Committee member) / Bingham, Scott (Committee member) / Nielsen, David (Committee member) / Arizona State University (Publisher)
Created2013
Description
Background: Evidence about the purported hypoglycemic and hypolipidemic effects of nopales (prickly pear cactus pads) is limited. Objective: To evaluate the efficacy of nopales for improving cardiometabolic risk factors and oxidative stress, compared to control, in adults with hypercholesterolemia. Design: In a randomized crossover trial, participants were assigned to a 2-wk intervention with 2 cups/day of nopales or cucumbers (control), with a 2 to 3-wk washout period. The study included 16 adults (5 male; 46±14 y; BMI = 31.4±5.7 kg/m2) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-c] = 137±21 mg/dL), but otherwise healthy. Main outcomes measured included: dietary intake (energy, macronutrients and micronutrients), cardiometabolic risk markers (total cholesterol, LDL-c, high density lipoprotein cholesterol [HDL-c], triglycerides, cholesterol distribution in LDL and HDL subfractions, glucose, insulin, homeostasis model assessment, and C-reactive protein), and oxidative stress markers (vitamin C, total antioxidant capacity, oxidized LDL, and LDL susceptibility to oxidation). Effects of treatment, time, or interactions were assessed using repeated measures ANOVA. Results: There was no significant treatment-by-time effect for any dietary composition data, lipid profile, cardiometabolic outcomes, or oxidative stress markers. A significant time effect was observed for energy, which was decreased in both treatments (cucumber, -8.3%; nopales, -10.1%; pTime=0.026) mostly due to lower mono and polyunsaturated fatty acids intake (pTime=0.023 and pTime=0.003, respectively). Both treatments significantly increased triglyceride concentrations (cucumber, 14.8%; nopales, 15.2%; pTime=0.020). Despite the lack of significant treatment-by-time effects, great individual response variability was observed for all outcomes. After the cucumber and nopales phases, a decrease in LDL-c was observed in 44% and 63% of the participants respectively. On average LDL-c was decreased by 2.0 mg/dL (-1.4%) after the cucumber phase and 3.9 mg/dL (-2.9%) after the nopales phase (pTime=0.176). Pro-atherogenic changes in HDL subfractions were observed in both interventions over time, by decreasing the proportion of HDL-c in large HDL (cucumber, -5.1%; nopales, -5.9%; pTime=0.021) and increasing the proportion in small HDL (cucumber, 4.1%; nopales, 7.9%; pTime=0.002). Conclusions: These data do not support the purported benefits of nopales at doses of 2 cups/day for 2-wk on markers of lipoprotein profile, cardiometabolic risk, and oxidative stress in hypercholesterolemic adults.
ContributorsPereira Pignotti, Giselle Adriana (Author) / Vega-Lopez, Sonia (Thesis advisor) / Gaesser, Glenn (Committee member) / Keller, Colleen (Committee member) / Shaibi, Gabriel (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance. Of these deaths, prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal in both men and women. Developing new drugs for the treatment of cancer is both a slow and expensive process. It is estimated that it takes an average of 15 years and an expense of $800 million to bring a single new drug to the market. However, it is also estimated that nearly 40% of that cost could be avoided by finding alternative uses for drugs that have already been approved by the Food and Drug Administration (FDA). The research presented in this document describes the testing, identification, and mechanistic evaluation of novel methods for treating many human carcinomas using drugs previously approved by the FDA. A tissue culture plate-based screening of FDA approved drugs will identify compounds that can be used in combination with the protein TRAIL to induce apoptosis selectively in cancer cells. Identified leads will next be optimized using high-throughput microfluidic devices to determine the most effective treatment conditions. Finally, a rigorous mechanistic analysis will be conducted to understand how the FDA-approved drug mitoxantrone, sensitizes cancer cells to TRAIL-mediated apoptosis.
ContributorsTaylor, David (Author) / Rege, Kaushal (Thesis advisor) / Jayaraman, Arul (Committee member) / Nielsen, David (Committee member) / Kodibagkar, Vikram (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2013
Description
To further the efforts producing energy from more renewable sources, microbial electrochemical cells (MXCs) can utilize anode respiring bacteria (ARB) to couple the oxidation of an organic substrate to the delivery of electrons to the anode. Although ARB such as Geobacter and Shewanella have been well-studied in terms of their microbiology and electrochemistry, much is still unknown about the mechanism of electron transfer to the anode. To this end, this thesis seeks to elucidate the complexities of electron transfer existing in Geobacter sulfurreducens biofilms by employing Electrochemical Impedance Spectroscopy (EIS) as the tool of choice. Experiments measuring EIS resistances as a function of growth were used to uncover the potential gradients that emerge in biofilms as they grow and become thicker. While a better understanding of this model ARB is sought, electrochemical characterization of a halophile, Geoalkalibacter subterraneus (Glk. subterraneus), revealed that this organism can function as an ARB and produce seemingly high current densities while consuming different organic substrates, including acetate, butyrate, and glycerol. The importance of identifying and studying novel ARB for broader MXC applications was stressed in this thesis as a potential avenue for tackling some of human energy problems.
ContributorsAjulo, Oluyomi (Author) / Torres, Cesar (Thesis advisor) / Nielsen, David (Committee member) / Krajmalnik-Brown, Rosa (Committee member) / Popat, Sudeep (Committee member) / Arizona State University (Publisher)
Created2013
Effect of a Wii Fit® intervention on balance, muscular fitness, and bone health in middle-aged women
Description
Sustaining a fall can be hazardous for those with low bone mass. Interventions exist to reduce fall-risk, but may not retain long-term interest. "Exergaming" has become popular in older adults as a therapy, but no research has been done on its preventative ability in non-clinical populations. The purpose was to determine the impact of 12-weeks of interactive play with the Wii Fit® on balance, muscular fitness, and bone health in peri- menopausal women. METHODS: 24 peri-menopausal-women were randomized into study groups. Balance was assessed using the Berg/FICSIT-4 and a force plate. Muscular strength was measured using the isokinetic dynamometer at 60°/180°/240°/sec and endurance was assessed using 50 repetitions at 240°/sec. Bone health was tracked using dual-energy x-ray absorptiometry (DXA) for the hip/lumbar spine and qualitative ultrasound (QUS) of the heel. Serum osteocalcin was assessed by enzyme immunoassay. Physical activity was quantified using the Women's Health Initiative Physical Activity Questionnaire and dietary patterns were measured using the Nurses' Health Food Frequency Questionnaire. All measures were repeated at weeks 6 and 12, except for the DXA, which was completed pre-post. RESULTS: There were no significant differences in diet and PA between groups. Wii Fit® training did not improve scores on the Berg/FICSIT-4, but improved center of pressure on the force plate for Tandem Step, Eyes Closed (p-values: 0.001-0.051). There were no significant improvements for muscular fitness at any of the angular velocities. DXA BMD of the left femoral neck improved in the intervention group (+1.15%) and decreased in the control (-1.13%), but no other sites had significant changes. Osteocalcin indicated no differences in bone turnover between groups at baseline, but the intervention group showed increased bone turnover between weeks 6 and 12. CONCLUSIONS: Findings indicate that WiiFit® training may improve balance by preserving center of pressure. QUS, DXA and osteocalcin data confirm that those in the intervention group were experiencing more bone turnover and bone formation than the control group. In summary, twelve weeks of strength /balance training with the Wii Fit® shows promise as a preventative intervention to reduce fall and fracture risk in non-clinical middle aged women who are at risk.
ContributorsWherry, Sarah Jo (Author) / Swan, Pamela D (Thesis advisor) / Adams, Marc (Committee member) / Der Ananian, Cheryl (Committee member) / Sweazea, Karen (Committee member) / Vaughan, Linda (Committee member) / Arizona State University (Publisher)
Created2014
Description
Alzheimer's disease (AD) is the most common type of dementia, affecting one in nine people age 65 and older. One of the most important neuropathological characteristics of Alzheimer's disease is the aggregation and deposition of the protein beta-amyloid. Beta-amyloid is produced by proteolytic processing of the Amyloid Precursor Protein (APP). Production of beta-amyloid from APP is increased when cells are subject to stress since both APP and beta-secretase are upregulated by stress. An increased beta-amyloid level promotes aggregation of beta-amyloid into toxic species which cause an increase in reactive oxygen species (ROS) and a decrease in cell viability. Therefore reducing beta-amyloid generation is a promising method to control cell damage following stress. The goal of this thesis was to test the effect of inhibiting beta-amyloid production inside stressed AD cell model. Hydrogen peroxide was used as stressing agent. Two treatments were used to inhibit beta-amyloid production, including iBSec1, an scFv designed to block beta-secretase site of APP, and DIA10D, a bispecific tandem scFv engineered to cleave alpha-secretase site of APP and block beta-secretase site of APP. iBSec1 treatment was added extracellularly while DIA10D was stably expressed inside cell using PSECTAG vector. Increase in reactive oxygen species and decrease in cell viability were observed after addition of hydrogen peroxide to AD cell model. The increase in stress induced toxicity caused by addition of hydrogen peroxide was dramatically decreased by simultaneously treating the cells with iBSec1 or DIA10D to block the increase in beta-amyloid levels resulting from the upregulation of APP and beta-secretase.
ContributorsSuryadi, Vicky (Author) / Sierks, Michael (Thesis advisor) / Nielsen, David (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2014
Description
Many therapeutics administered for some of the most devastating illnesses can be toxic and result in unwanted side effects. Recent developments have been made in an alternative treatment method, called gene therapy. Gene therapy has potential to rectify the genetic defects that cause a broad range of diseases. Many diseases, such as cancer, cystic fibrosis, and acquired immunodeficiency (AIDS) already have gene therapy protocols that are currently in clinical trials. Finding a non-toxic and efficient gene transfer method has been a challenge. Viral vectors are effective at transgene delivery however potential for insertion mutagenesis and activation of immune responses raises concern. For this reason, non-viral vectors have been investigated as a safer alternative to viral-mediated gene delivery. Non-viral vectors are also easy to prepare and scalable, but are limited by low transgene delivery efficacies and high cytotoxicity at effective therapeutic dosages. Thus, there is a need for a non-toxic non-viral vector with high transgene efficacies. In addition to the hurdles in finding a material for gene delivery, large-scale production of pharmaceutical grade DNA for gene therapy is needed. Current methods can be labor intensive, time consuming, and use toxic chemicals. For this reason, an efficient and safe method to collect DNA is needed. One material that is currently being explored is the hydrogel. Hydrogels are a useful subclass of biomaterials, with a wide variety of applications. This class of biomaterials can carry up to a thousand times their weight in water, and are biocompatible. At smaller dimensions, referred to as micro- and nanogels, they are very useful for many biomedical applications because of their size and ability to swell. Based on a previously synthesized hydrogel, and due to the advantages of smaller dimension in biomedical applications, we have synthesized aminoglycoside antibiotic based nanogels and microgels. Microgels and nanogels were synthesized following a ring opening polymerization of epoxide-containing crosslinkers and polyamine-containing monomers. The nanogels were screened for their cytocompatibilities and transfection efficacies, and were compared to polyethylenimine (PEI), a current standard for polymer-mediated transgene delivery. Nanogels demonstrated minimal to no toxicity to the cell line used in the study even at high concentrations. Due to the emerging need for large-scale production of DNA, microgels were evaluated for their binding capacity to plasmid DNA. Future work with the aminoglycoside antibiotic-based nanogels and microgels developed in this study will involve optimization of nanogels and microgels to facilitate in better transgene delivery and plasmid DNA binding, respectively.
ContributorsMallik, Amrita Amy (Author) / Rege, Kaushal (Thesis advisor) / Dai, Lennore (Committee member) / Nielsen, David (Committee member) / Arizona State University (Publisher)
Created2014
Description
Life Cycle Assessment (LCA) is used in the chemical process sector to compare the environmental merits of different product or process alternatives. One of the tasks that involves much time and cost in LCA studies is the specification of the exact materials and processes modeled which has limited its widespread application. To overcome this, researchers have recently created probabilistic underspecification as an LCA streamlining method, which uses a structured data classification system to enable an LCA modeler to specify materials and processes in a less precise manner. This study presents a statistical procedure to understand when streamlined LCA methods can be used, and what their impact on overall model uncertainty is. Petrochemicals and polymer product systems were chosen to examine the impacts of underspecification and mis-specification applied to LCA modeling. Ecoinvent database, extracted using GaBi software, was used for data pertaining to generic crude oil refining and polymer manufacturing modules. By assessing the variation in LCA results arising out of streamlined materials classification, the developed statistics estimate the amount of overall error incurred by underspecifying and mis-specifying material impact data in streamlined LCA. To test the impact of underspecification and mis-specification at the level of a product footprint, case studies of HDPE containers and aerosol air fresheners were conducted. Results indicate that the variation in LCA results decreases as the specificity of materials increases. For the product systems examined, results show that most of the variability in impact assessment is due to the differences in the regions from which the environmental impact datasets were collected; the lower levels of categorization of materials have relatively smaller influence on the variance. Analyses further signify that only certain environmental impact categories viz. global warming potential, freshwater eutrophication, freshwater ecotoxicity, human toxicity and terrestrial ecotoxicity are affected by geographic variations. Outcomes for the case studies point out that the error in the estimation of global warming potential increases as the specificity of a component of the product decreases. Fossil depletion impact estimates remain relatively robust to underspecification. Further, the results of LCA are much more sensitive to underspecification of materials and processes than mis-specification.
ContributorsMurali, Ashwin Krishna (Author) / Dooley, Kevin (Thesis advisor) / Dai, Lenore (Thesis advisor) / Nielsen, David (Committee member) / Arizona State University (Publisher)
Created2014
Description
ABSTRACT
Asthma is a high-stress, chronic medical condition; 1 in 12 adults in the United States combat the bronchoconstriction from asthma. However, there are very few strong studies indicating any alternative therapy for asthmatics, particularly following a cold incidence. Vitamin C has been proven to be effective for other high-stress populations, but the asthmatic population has not yet been trialed. This study examined the effectiveness of vitamin C supplementation during the cold season on cold incidence and asthmatic symptoms. Asthmatics, otherwise-healthy, who were non-smokers and non-athletes between the ages of 18 and 55 with low plasma vitamin C concentrations were separated by anthropometrics and vitamin C status into two groups: either vitamin C (500 mg vitamin C capsule consumed twice per day) or control (placebo capsule consumed twice per day). Subjects were instructed to complete the Wisconsin Upper Respiratory Symptom Survey-21 and a short asthma symptoms questionnaire daily along with a shortened vitamin C Food Frequency Questionnaire and physical activity questionnaire weekly for eight weeks. Blood samples were drawn at Week 0 (baseline), Week 4, and Week 8. Compliance was monitored through a calendar check sheet. The vitamin C levels of both groups increased from Week 0 to Week 4, but decreased in the vitamin C group at Week 8. The vitamin C group had a 19% decrease in plasma histamine while the control group had a 53% increase in plasma histamine at the end of the trial, but this was not statistically significant (p>0.05). Total symptoms recorded from WURSS-21 were 129.3±120.7 for the vitamin C and 271.0±293.9, but the difference was not statistically significant (p=0.724). Total asthma symptoms also slightly varied between the groups, but again was not statistically significant (p=0.154). These results were hindered by the low number of subjects recruited. Continued research in this study approach is necessary to definitively reject or accept the potential role of vitamin C in asthma and cold care.
Asthma is a high-stress, chronic medical condition; 1 in 12 adults in the United States combat the bronchoconstriction from asthma. However, there are very few strong studies indicating any alternative therapy for asthmatics, particularly following a cold incidence. Vitamin C has been proven to be effective for other high-stress populations, but the asthmatic population has not yet been trialed. This study examined the effectiveness of vitamin C supplementation during the cold season on cold incidence and asthmatic symptoms. Asthmatics, otherwise-healthy, who were non-smokers and non-athletes between the ages of 18 and 55 with low plasma vitamin C concentrations were separated by anthropometrics and vitamin C status into two groups: either vitamin C (500 mg vitamin C capsule consumed twice per day) or control (placebo capsule consumed twice per day). Subjects were instructed to complete the Wisconsin Upper Respiratory Symptom Survey-21 and a short asthma symptoms questionnaire daily along with a shortened vitamin C Food Frequency Questionnaire and physical activity questionnaire weekly for eight weeks. Blood samples were drawn at Week 0 (baseline), Week 4, and Week 8. Compliance was monitored through a calendar check sheet. The vitamin C levels of both groups increased from Week 0 to Week 4, but decreased in the vitamin C group at Week 8. The vitamin C group had a 19% decrease in plasma histamine while the control group had a 53% increase in plasma histamine at the end of the trial, but this was not statistically significant (p>0.05). Total symptoms recorded from WURSS-21 were 129.3±120.7 for the vitamin C and 271.0±293.9, but the difference was not statistically significant (p=0.724). Total asthma symptoms also slightly varied between the groups, but again was not statistically significant (p=0.154). These results were hindered by the low number of subjects recruited. Continued research in this study approach is necessary to definitively reject or accept the potential role of vitamin C in asthma and cold care.
ContributorsEarhart, Kathryn Michelle (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Lespron, Christy (Committee member) / Arizona State University (Publisher)
Created2015
Description
Post-combustion carbon capture is a viable option for reducing CO2 greenhouse gas emissions, and one potentially promising technology for this route is adsorption using chemically and physically based sorbents. A number of exceptional CO2 sorbents materials have been prepared including metal organic frameworks, zeolites, and carbon based materials. One particular group of capable materials are amine based solid sorbents that has shown to possess high adsorption capacities and favorable adsorption kinetics. A key variable in the synthesis of an amine based sorbent is the support which acts as the platform for the amine modification. Aerogels, due to their high porosities and surface areas, appear to be a promising support for an amine modified CO2 sorbent. Therefore, in order to develop a commercially viable CO2 sorbent, particulate aerogels manufactured by Cabot Corporation through an economical and proprietary ambient drying process were modified with amines using a variety of functionalization methods. Two methods of physical impregnation of the amino polymer TEPA were performed in order to observe the performance as well as understand the effects of how the TEPA distribution is affected by the method of introduction. Both samples showed excellent adsorption capacities but poor cyclic stability for lack of any covalent attachment. Furthermore the method of TEPA impregnation seems to be independent on how the polymer will be distributed in the pore space of aerogel. The last two methods utilized involved covalently attaching amino silanes to the surface silanols of the aerogel. One method was performed in the liquid phase under anhydrous and hydrous conditions. The materials developed through the hydrous method have much greater adsorption capacities relative to the anhydrous sample as a result of the greater amine content present in the hydrous sample. Water is another source of silylation where additional silanes can attach and polymerize. These samples also possessed stable cyclic stability after 100 adsorption/regeneration cycles. The other method of grafting was performed in the gas phase through ALD. These samples possessed exceptionally high amine efficiencies and levels of N content without damaging the microstructure of the aerogel in contrast to the liquid phase grafted sorbents.
ContributorsLinneen, Nick (Author) / Lin, Jerry (Thesis advisor) / Pfeffer, Robert (Thesis advisor) / Lind, Mary (Committee member) / Rege, Kaushal (Committee member) / Nielsen, David (Committee member) / Anderson, James (Committee member) / Arizona State University (Publisher)
Created2014