Matching Items (65)
Description
Cancer diseases are among the leading cause of death in the United States. Advanced cancer diseases are characterized by genetic defects resulting in uncontrollable cell growth. Currently, chemotherapeutics are one of the mainstream treatments administered to cancer patients but are less effective if administered in the later stages of metastasis, and can result in unwanted side effects and broad toxicities. Therefore, current efforts have explored gene therapy as an alternative strategy to correct the genetic defects associated with cancer diseases, by administering genes which encode for proteins that result in cell death. While the use of viral vectors shows high level expression of the delivered transgene, the potential for insertion mutagenesis and activation of immune responses raise concern in clinical applications. Non-viral vectors, including cationic lipids and polymers, have been explored as potentially safer alternatives to viral delivery systems. These systems are advantageous for transgene delivery due to ease of synthesis, scale up, versatility, and in some cases due to their biodegradability and biocompatibility. However, low efficacies for transgene expression and high cytotoxicities limit the practical use of these polymers. In this work, a small library of twenty-one cationic polymers was synthesized following a ring opening polymerization of diglycidyl ethers (epoxides) by polyamines. The polymers were screened in parallel and transfection efficacies of individual polymers were compared to those of polyethylenimine (PEI), a current standard for polymer-mediated transgene delivery. Seven lead polymers that demonstrated higher transgene expression efficacies than PEI in pancreatic and prostate cancer cells lines were identified from the screening. A second related effort involved the generation of polymer-antibody conjugates in order to facilitate targeting of delivered plasmid DNA selectively to cancer cells. Future work with the novel lead polymers and polymer-antibody conjugates developed in this research will involve an investigation into the delivery of transgenes encoding for apoptosis-inducing proteins both in vitro and in vivo.
ContributorsVu, Lucas (Author) / Rege, Kaushal (Thesis advisor) / Nielsen, David (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2011
Description
This dissertation presents a systematic study of the sorption mechanisms of hydrophobic silica aerogel (Cabot Nanogel®) granules for oil and volatile organic compounds (VOCs) in different phases. The performance of Nanogel for removing oil from laboratory synthetic oil-in-water emulsions and real oily wastewater, and VOCs from their aqueous solution, in both packed bed (PB) and inverse fluidized bed (IFB) modes was also investigated. The sorption mechanisms of VOCs in the vapor, pure liquid, and aqueous solution phases, free oil, emulsified oil, and oil from real wastewater on Nanogel were systematically studied via batch kinetics and equilibrium experiments. The VOC results show that the adsorption of vapor is very slow due to the extremely low thermal conductivity of Nanogel. The faster adsorption rates in the liquid and solution phases are controlled by the mass transport, either by capillary flow or by vapor diffusion/adsorption. The oil results show that Nanogel has a very high capacity for adsorption of pure oils. However, the rate for adsorption of oil from an oil-water emulsion on the Nanogel is 5-10 times slower than that for adsorption of pure oils or organics from their aqueous solutions. For an oil-water emulsion, the oil adsorption capacity decreases with an increasing proportion of the surfactant added. An even lower sorption capacity and a slower sorption rate were observed for a real oily wastewater sample due to the high stability and very small droplet size of the wastewater. The performance of Nanogel granules for removing emulsified oil, oil from real oily wastewater, and toluene at low concentrations in both PB and IFB modes was systematically investigated. The hydrodynamics characteristics of the Nanogel granules in an IFB were studied by measuring the pressure drop and bed expansion with superficial water velocity. The density of the Nanogel granules was calculated from the plateau pressure drop of the IFB. The oil/toluene removal efficiency and the capacity of the Nanogel granules in the PB or IFB were also measured experimentally and predicted by two models based on equilibrium and kinetic batch measurements of the Nanogel granules.
ContributorsWang, Ding (Author) / Lin, Jerry Y.S. (Thesis advisor) / Pfeffer, Robert (Thesis advisor) / Westerhoff, Paul (Committee member) / Nielsen, David (Committee member) / Lind, Mary Laura (Committee member) / Arizona State University (Publisher)
Created2011
Description
The use of petroleum for liquid-transportation fuels has strained the environment and caused the global crude oil reserves to diminish. Therefore, there exists a need to replace petroleum as the primary fuel derivative. Butanol is a four-carbon alcohol that can be used to effectively replace gasoline without changing the current automotive infrastructure. Additionally, butanol offers the same environmentally friendly effects as ethanol, but possess a 23% higher energy density. Clostridium acetobutylicum is an anaerobic bacterium that can ferment renewable biomass-derived sugars into butanol. However, this fermentation becomes limited by relatively low butanol concentrations (1.3% w/v), making this process uneconomical. To economically produce butanol, the in-situ product removal (ISPR) strategy is employed to the butanol fermentation. ISPR entails the removal of butanol as it is produced, effectively avoiding the toxicity limit and allowing for increased overall butanol production. This thesis explores the application of ISPR through integration of expanded-bed adsorption (EBA) with the C. acetobutylicum butanol fermentations. The goal is to enhance volumetric productivity and to develop a semi-continuous biofuel production process. The hydrophobic polymer resin adsorbent Dowex Optipore L-493 was characterized in cell-free studies to determine the impact of adsorbent mass and circulation rate on butanol loading capacity and removal rate. Additionally, the EBA column was optimized to use a superficial velocity of 9.5 cm/min and a resin fraction of 50 g/L. When EBA was applied to a fed-batch butanol fermentation performed under optimal operating conditions, a total of 25.5 g butanol was produced in 120 h, corresponding to an average yield on glucose of 18.6%. At this level, integration of EBA for in situ butanol recovered enabled the production of 33% more butanol than the control fermentation. These results are very promising for the production of butanol as a biofuel. Future work will entail the optimization of the fed-batch process for higher glucose utilization and development of a reliable butanol recovery system from the resin.
ContributorsWiehn, Michael (Author) / Nielsen, David (Thesis advisor) / Lin, Jerry (Committee member) / Lind, Mary Laura (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
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
The disordered nature of glass-forming melts results in two features for its dynamics i.e. non-Arrhenius and non-exponential behavior. Their macroscopic properties are studied through observing spatial heterogeneity of the molecular relaxation. Experiments performed in a low-frequency range tracks the flow of energy in time on slow degrees of freedom and transfer to the vibrational heat bath of the liquid, as is the case for microwave heating. High field measurements on supercooled liquids result in generation of fictive temperatures of the absorbing modes which eventually result in elevated true bath temperatures. The absorbed energy allows us to quantify the changes in the 'configurational', real sample, and electrode temperatures. The slow modes absorb energy on the structural relaxation time scale causing the increase of configurational temperature resulting in the rise of dielectric loss. Time-resolved high field dielectric relaxation experiments show the impact of 'configurational heating' for low frequencies of the electric field and samples that are thermally clamped to a thermostat. Relevant thermal behavior of monohydroxy alcohols is considerably different from the cases of simple non-associating liquids, due to their distinct origins of the prominent dielectric loss. Monohydroxy alcohols display very small changes due to observed nonthermal effects without increasing sample temperature. These changes have been reflected in polymers in our measurements.
ContributorsPathak, Ullas (Author) / Richert, Ranko (Thesis advisor) / Dai, Lenore (Thesis advisor) / Nielsen, David (Committee member) / Arizona State University (Publisher)
Created2012
Description
Due to the environmental problems caused by global warming, it has become necessary to reduce greenhouse gas emissions across the planet. Biofuels, such as ethanol, have proven to release cleaner emissions when combusted. However, large scale production of these alcohols is uneconomical and inefficient due to limitations in standard separation processes, the most common being distillation. Pervaporation is a novel separation technique that utilizes a specialized membrane to separate multicomponent solutions. In this research project, pervaporation utilizing ZIF-71/PDMS mixed matrix membranes are investigated to see their ability to recover ethanol from an ethanol/aqueous separation. Membranes with varying nanoparticle concentrations were created and their performances were analyzed. While the final results indicate that no correlation exists between nanoparticle weight percentage and selectivity, this technology is still a promising avenue for biofuel production. Future work will be conducted to improve this existing process and enhance membrane selectivity.
ContributorsHoward, Chelsea Elizabeth (Author) / Lind, Mary Laura (Thesis director) / Nielsen, David (Committee member) / Greenlee, Lauren (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / Materials Science and Engineering Program (Contributor)
Created2015-05
Description
Depletion of fossil fuel resources has led to the investigation of alternate feedstocks for and methods of chemical synthesis, in particular the use of E. coli biocatalysts to produce fine commodity chemicals from renewable glucose sources. Production of phenol, 2-phenylethanol, and styrene was investigated, in particular the limitation in yield and accumulation that results from high product toxicity. This paper examines two methods of product toxicity mitigation: the use of efflux pumps and the separation of pathways which produce less toxic intermediates. A library of 43 efflux pumps from various organisms were screened for their potential to confer resistance to phenol, 2-phenylethanol, and styrene on an E. coli host. A pump sourced from P. putida was found to allow for increased host growth in the presence of styrene as compared to a cell with no efflux pump. The separation of styrene producing pathway was also investigated. Cells capable of performing the first and latter halves of the synthesis were allowed to grow separately and later combined in order to capitalize on the relatively lower toxicity of the intermediate, trans-cinnamate. The styrene production and yield from this separated set of cultures was compared to that resulting from the growth of cells containing the full set of styrene synthesis genes. Results from this experiment were inconclusive.
ContributorsLallmamode, Noor Atiya Jabeen (Author) / Nielsen, David (Thesis director) / Cadillo-Quiroz, Hinsby (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
This thesis focused on the development of a system that can sense light intensity and then control a smart film to provide the optimal light intensity for cyanobacteria. The overarching goal of this project is to further the study of biofuels as an alternative energy source by increasing growth rates. If more algae or cyanobacteria can be grown per day, then the cost to produce the biofuel will decrease. To achieve this goal, PDLC (polymer dispersed liquid crystal) film was selected to be controlled due to its unique properties. It can be controlled with electricity and has variable states, in other words, not restricted to simply on or off. It also blocks 80% ultraviolet light and reduces thermal heat gain by 40% which is an important consideration for outdoor growing situations. To control the film, a simple control system was created using an Arduino Uno, SainSmart 8 channel relay board, an inverter, and a power supply. A relay board was utilized to manage the 40 volts required by the PDLC film and protected the electronics on the Arduino Uno. To sense the light intensity, the Arduino Uno was connected to a photoresistor, which changes resistance with light intensity. A 15 day test of two flasks of Cyanobacteria Synechocycstis sp. 6803, one shaded by the PDLC film, and the other unshaded, yielded 65% difference in optical densities. Overall, the experiment showed promise for controlling light intensity for photobioreactors. Ideally, this research will help to optimize light intensities when growing cyanobacteria or algae outdoors or it will help to discover what an ideal light intensity is by allowing a researcher unprecedented control.
ContributorsRoney, Kitt Alicia (Author) / Nielsen, David (Thesis director) / Middleton, James (Committee member) / Barrett, The Honors College (Contributor) / Mechanical and Aerospace Engineering Program (Contributor)
Created2015-05