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- Creators: Nielsen, David
- Creators: Green, Matthew
- Creators: School of Historical, Philosophical and Religious Studies
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
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
Guided by the Obama administration, NASA has begun developing commercial launch capabilities. For both cargo and crew delivery to the International Space Station, NASA has selected companies to build and operate the vehicles at a fixed price. Alexander McDonald suggests that this continues a trend in space exploration established by large observatory projects, and that the Apollo-era style of funding and operation was a historical anomaly. This paper attempts to discover if historical analog can support or weaken this thesis. The analogs chosen are two episodes in the history of terrestrial exploration: the experience of the Spanish and British empires in North America. These are compared to the history of space exploration up until today, focusing on how the role of private enterprise has changed in each instance. While the analogies between historical episodes are weak in a few areas, they do possess a common narrative concerning the shifting balance between private and government interests. This narrative supports McDonald's thesis, and shows that NASA's current policy anticipates an expected transition towards a private-public hybrid model of exploration and expansion.
ContributorsRobb, Daniel Robert (Author) / Pyne, Stephen (Thesis director) / Bell, Jim (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2015-05
Description
Since Dylan Roof, a white supremacist, shot and killed nine members of a black church in Charleston on June 17, 2015, Confederate symbols have stood at the center of much controversy across the United States. Although the Confederate battle flag remains the most obvious example, the debate took a particular form in Tennessee, centering on the image of General Nathan Bedford Forrest. Born in 1822 to a poor family, he left school early to work. Although his work in the slave trade made him a millionaire, his later participation in the massacre of over 300 black soldiers at Fort Pillow in 1864 during the Civil War and association with the Ku Klux Klan cemented his reputation as a violent racist. Yet, many white Tennesseans praised him as a hero and memorialized him. This thesis examines Nathan Bedford Forrest State Park in Benton County and Forrest Park, now Health Sciences Park, in Memphis to examine what characteristics denote a controversial memorial. Specifically, I focus on the physical form, the location, and the demographics of the area, investigating how these components work together to give rise to controversy or acceptance of the memorial's image. Physical representations greatly impact the ideas associated with the memorial while racial demographics affect whether or not Forrest's representation as a hero speaks true to modern interpretations and opinions.
ContributorsFish, Caroline Rose (Author) / Longley, Rodney (Thesis director) / Suk, Mina (Committee member) / School of Historical, Philosophical and Religious Studies (Contributor) / School of Politics and Global Studies (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
This research looks at the state of Anglo-American political relations since 1980. By examining the political partnerships between Ronald Reagan and Margaret Thatcher, Margaret Thatcher and George H.W. Bush, George W. Bush and Tony Blair, Barack Obama and Gordon Brown, and Barack Obama and David Cameron, it explores if the so called ‘special relationship’ remains so special today in a world of growing political animosity and challenges. The thesis argues that the success of the ‘special relationship’ between the United States and United Kingdom has not been just due to similar political ideologies or goals, but also personal friendships which often overcame national interests or immediate personal political gain. Furthermore, it is often the periods of disagreement between these sets of leaders that helped strengthen the relationship between America and Britain, evidenced by episodes like the Falklands War, policy towards the Soviet Union, the invasion of Grenada, and the wars in Iraq and Afghanistan. Ultimately, the thesis explores how current relations have deteriorated due to problems on both sides of the Atlantic under the Obama, Brown, and Cameron administrations, but the research concludes that the special relationship is, while damaged, alive and fixable.
ContributorsGavin, Stephen Christopher (Author) / Critchlow, Donald (Thesis director) / Stermetz, Catherine (Committee member) / School of Politics and Global Studies (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Nations have a vital interest in creating a citizenry with certain attributes and beliefs and, since education contributes to the formation of children's national identity, government authorities can influence educational curricula to construct their ideal citizen. In this thesis, I study the educational systems of Pakistan and Arizona and explore the historical and conceptual origins of these entities' manipulation of curricula to construct a particular kind of citizen. I argue that an examination of the ethnic studies debate in Tucson, Arizona, in conjunction with Pakistan's history education policy, will illustrate that the educational systems in both these sites are developed to advance the interests of governing authorities. Resource material demonstrates that both educational systems endorse specific accounts of history, omitting information, perspectives, and beliefs. Eliminating or reimagining certain narratives of history alienates some students from identifying as citizens of the state, particularly when contributions of their ethnic, cultural, or religious groups are not included in the country's textbooks.
ContributorsFritcke, Emily Anne (Author) / Saikia, Yasmin (Thesis director) / Haines, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of English (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2014-12