Matching Items (694)
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
Like individual organisms, complex social groups are able to maintain predictable trajectories of growth, from initial colony foundation to mature reproductively capable units. They do so while simultaneously responding flexibly to variation in nutrient availability and intake. Leafcutter ant colonies function as tri-trophic systems, in which the ants harvest vegetation to grow a fungus that, in turn, serves as food for the colony. Fungal growth rates and colony worker production are interdependent, regulated by nutritional and behavioral feedbacks. Fungal growth and quality are directly affected by worker foraging decisions, while worker production is, in turn, dependent on the amount and condition of the fungus. In this dissertation, I first characterized the growth relationship between the workers and the fungus of the desert leafcutter ant Acromyrmex versicolor during early stages of colony development, from colony foundation by groups of queens through the beginnings of exponential growth. I found that this relationship undergoes a period of slow growth and instability when workers first emerge, and then becomes allometrically positive. I then evaluated how mass and element ratios of resources collected by the ants are translated into fungus and worker population growth, and refuse, finding that colony digestive efficiency is comparable to digestive efficiencies of other herbivorous insects and ruminants. To test how colonies behaviorally respond to perturbations of the fungus garden, I quantified activity levels and task performance of workers in colonies with either supplemented or diminished fungus gardens, and found that colonies adjusted activity and task allocation in response to the fungus garden size. Finally, to identify possible forms of nutrient limitation, I measured how colony performance was affected by changes in the relative amounts of carbohydrates, protein, and phosphorus available in the resources used to grow the fungus garden. From this experiment, I concluded that colony growth is primarily carbohydrate-limited.
ContributorsClark, Rebecca, 1981- (Author) / Fewell, Jennifer H (Thesis advisor) / Mueller, Ulrich (Committee member) / Liebig, Juergen (Committee member) / Elser, James (Committee member) / Harrison, Jon (Committee member) / Arizona State University (Publisher)
Created2011
Description
The repression of reproductive competition and the enforcement of altruism are key components to the success of animal societies. Eusocial insects are defined by having a reproductive division of labor, in which reproduction is relegated to one or few individuals while the rest of the group members maintain the colony and help raise offspring. However, workers have retained the ability to reproduce in most insect societies. In the social Hymenoptera, due to haplodiploidy, workers can lay unfertilized male destined eggs without mating. Potential conflict between workers and queens can arise over male production, and policing behaviors performed by nestmate workers and queens are a means of repressing worker reproduction. This work describes the means and results of the regulation of worker reproduction in the ant species Aphaenogaster cockerelli. Through manipulative laboratory studies on mature colonies, the lack of egg policing and the presence of physical policing by both workers and queens of this species are described. Through chemical analysis and artificial chemical treatments, the role of cuticular hydrocarbons as indicators of fertility status and the informational basis of policing in this species is demonstrated. An additional queen-specific chemical signal in the Dufour's gland is discovered to be used to direct nestmate aggression towards reproductive competitors. Finally, the level of actual worker-derived males in field colonies is measured. Together, these studies demonstrate the effectiveness of policing behaviors on the suppression of worker reproduction in a social insect species, and provide an example of how punishment and the threat of punishment is a powerful force in maintaining cooperative societies.
ContributorsSmith, Adrian A. (Author) / Liebig, Juergen (Thesis advisor) / Hoelldobler, Bert (Thesis advisor) / Gadau, Juergen (Committee member) / Johnson, Robert A. (Committee member) / Pratt, Stephen (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
Of all the signals and cues that orchestrate the activities of a social insect colony, the reproductives' fertility pheromones are perhaps the most fundamental. These pheromones regulate reproductive division of labor, a defining characteristic of eusociality. Despite their critical role, reproductive fertility pheromones are not evenly expressed across the development of a social insect colony and may even be absent in the earliest colony stages. In the ant Camponotus floridanus, queens of incipient colonies do not produce the cuticular hydrocarbons that serve as fertility and egg-marking signals in this species. My dissertation investigates the consequences of the dramatic change in the quantity of these pheromones that occurs as the colony grows. C. floridanus workers from large, established colonies use egg surface hydrocarbons to discriminate among eggs. Eggs with surface hydrocarbons typical of eggs laid by established queens are nurtured, whereas eggs lacking these signals (i.e., eggs laid by workers and incipient queens) are destroyed. I characterized how workers from incipient colonies responded to eggs lacking queen fertility hydrocarbons. I found that established-queen-laid eggs, incipient-queen-laid eggs, and worker-laid eggs were not destroyed by workers at this colony stage. Destruction of worker-laid eggs is a form of policing, and theoretical models predict that policing should be strongest in incipient colonies. Since there was no evidence of policing by egg-eating in incipient C. floridanus colonies, I searched for evidence of another policing mechanism at this colony stage. Finding none, I discuss reasons why policing behavior may not be expressed in incipient colonies. I then considered the mechanism that accounts for the change in workers' response to eggs. By manipulating ants' egg experience and testing their egg-policing decisions, I found that ants use a combination of learned and innate criteria to discriminate between targets of care and destruction. Finally, I investigated how the increasing strength of queen-fertility hydrocarbons affects nestmate recognition, which also relies on cuticular hydrocarbons. I found that queens with strong fertility hydrocarbons can be transferred between established colonies without aggression, but they cannot be introduced into incipient colonies. Queens from incipient colonies cannot be transferred into incipient or established colonies.
ContributorsMoore, Dani (Author) / Liebig, Juergen (Thesis advisor) / Gadau, Juergen (Committee member) / Pratt, Stephen (Committee member) / Smith, Brian (Committee member) / Rutowski, Ronald (Committee member) / Arizona State University (Publisher)
Created2012
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
A notable feature of advanced eusocial insect groups is a division of labor within the sterile worker caste. However, the physiological aspects underlying the differentiation of behavioral phenotypes are poorly understood in one of the most successful social taxa, the ants. By starting to understand the foundations on which social behaviors are built, it also becomes possible to better evaluate hypothetical explanations regarding the mechanisms behind the evolution of insect eusociality, such as the argument that the reproductive regulatory infrastructure of solitary ancestors was co-opted and modified to produce distinct castes. This dissertation provides new information regarding the internal factors that could underlie the division of labor observed in both founding queens and workers of Pogonomyrmex californicus ants, and shows that changes in task performance are correlated with differences in reproductive physiology in both castes. In queens and workers, foraging behavior is linked to elevated levels of the reproductively-associated juvenile hormone (JH), and, in workers, this behavioral change is accompanied by depressed levels of ecdysteroid hormones. In both castes, the transition to foraging is also associated with reduced ovarian activity. Further investigation shows that queens remain behaviorally plastic, even after worker emergence, but the association between JH and behavioral bias remains the same, suggesting that this hormone is an important component of behavioral development in these ants. In addition to these reproductive factors, treatment with an inhibitor of the nutrient-sensing pathway Target of Rapamycin (TOR) also causes queens to become biased towards foraging, suggesting an additional sensory component that could play an important role in division of labor. Overall, this work provides novel identification of the possible regulators behind ant division of labor, and suggests how reproductive physiology could play an important role in the evolution and regulation of non-reproductive social behaviors.
ContributorsDolezal, Adam G (Author) / Amdam, Gro V (Thesis advisor) / Brent, Colin S. (Committee member) / Gadau, Juergen (Committee member) / Hoelldobler, Bert (Committee member) / Liebig, Juergen (Committee member) / Arizona State University (Publisher)
Created2012