Matching Items (153)
Description
The highly predictable structural and thermodynamic behavior of deoxynucleic acid (DNA) and ribonucleic acid (RNA) have made them versatile tools for creating artificial nanostructures over broad range. Moreover, DNA and RNA are able to interact with biological ligand as either synthetic aptamers or natural components, conferring direct biological functions to the nucleic acid devices. The applications of nucleic acids greatly relies on the bio-reactivity and specificity when applied to highly complexed biological systems.
This dissertation aims to 1) develop new strategy to identify high affinity nucleic acid aptamers against biological ligand; and 2) explore highly orthogonal RNA riboregulators in vivo for constructing multi-input gene circuits with NOT logic. With the aid of a DNA nanoscaffold, pairs of hetero-bivalent aptamers for human alpha thrombin were identified with ultra-high binding affinity in femtomolar range with displaying potent biological modulations for the enzyme activity. The newly identified bivalent aptamers enriched the aptamer tool box for future therapeutic applications in hemostasis, and also the strategy can be potentially developed for other target molecules. Secondly, by employing a three-way junction structure in the riboregulator structure through de-novo design, we identified a family of high-performance RNA-sensing translational repressors that down-regulates gene translation in response to cognate RNAs with remarkable dynamic range and orthogonality. Harnessing the 3WJ repressors as modular parts, we integrate them into biological circuits that execute universal NAND and NOR logic with up to four independent RNA inputs in Escherichia coli.
This dissertation aims to 1) develop new strategy to identify high affinity nucleic acid aptamers against biological ligand; and 2) explore highly orthogonal RNA riboregulators in vivo for constructing multi-input gene circuits with NOT logic. With the aid of a DNA nanoscaffold, pairs of hetero-bivalent aptamers for human alpha thrombin were identified with ultra-high binding affinity in femtomolar range with displaying potent biological modulations for the enzyme activity. The newly identified bivalent aptamers enriched the aptamer tool box for future therapeutic applications in hemostasis, and also the strategy can be potentially developed for other target molecules. Secondly, by employing a three-way junction structure in the riboregulator structure through de-novo design, we identified a family of high-performance RNA-sensing translational repressors that down-regulates gene translation in response to cognate RNAs with remarkable dynamic range and orthogonality. Harnessing the 3WJ repressors as modular parts, we integrate them into biological circuits that execute universal NAND and NOR logic with up to four independent RNA inputs in Escherichia coli.
ContributorsZhou, Yu (Ph.D.) (Author) / Yan, Hao (Thesis advisor) / Green, Alexander (Thesis advisor) / Woodbury, Neal (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2019
Description
Anthropogenic land use has irrevocably transformed the natural systems on which humankind relies. Understanding where, why, and how social and economic processes drive globally-important land-use changes, from deforestation to urbanization, has advanced substantially. Illicit and clandestine activities--behavior that is intentionally secret because it breaks formal laws or violates informal norms--are poorly understood, however, despite the recognition of their significant role in land change. This dissertation fills this lacuna by studying illicit and clandestine activity and quantifying its influence on land-use patterns through examining informal urbanization in Mexico City and deforestation Central America. The first chapter introduces the topic, presenting a framework to examine illicit transactions in land systems. The second chapter uses data from interviews with actors involved with land development in Mexico City, demonstrating how economic and political payoffs explain the persistence of four types of informal urban expansion. The third chapter examines how electoral politics influence informal urban expansion and land titling in Mexico City using panel regression. Results show land title distribution increases just before elections, and more titles are extended to loyal voters of the dominant party in power. Urban expansion increases with electoral competition in local elections for borough chiefs and legislators. The fourth chapter tests and confirms the hypothesis that narcotrafficking has a causal effect on forest loss in Central America from 2001-2016 using two proxies of narcoactivity: drug seizures and events from media reports. The fifth chapter explores the spatial signature and pattern of informal urban development. It uses a typology of urban informality identified in chapter two to hypothesize and demonstrate distinct urban expansion patterns from satellite imagery. The sixth and final chapter summarizes the role of illicit and clandestine activity in shaping deforestation and urban expansion through illegal economies, electoral politics, and other informal transactions. Measures of illicit and clandestine activity should--and could--be incorporated into land change models to account for a wider range of relevant causes. This dissertation shines a new light on the previously hidden processes behind ever-easier to detect land-use patterns as earth observing satellites increase spatial and temporal resolution.
ContributorsTellman, Elizabeth (Author) / Turner II, Billie L (Thesis advisor) / Eakin, Hallie (Thesis advisor) / Janssen, Marco (Committee member) / Alba, Felipe de (Committee member) / Jain, Meha (Committee member) / Arizona State University (Publisher)
Created2019
Description
Humanity’s demand for energy is increasing exponentially and the dependence on fossil fuels is both unsustainable and detrimental to the environment. To provide a solution to the impending energy crisis, it is reasonable to look toward utilizing solar energy, which is abundant and renewable. One approach to harvesting solar irradiation for fuel purposes is through mimicking the processes of natural photosynthesis in an artificial design to use sunlight and water to store energy in chemical bonds for later use. Thus, in order to design an efficient energy conversion device, the underlying processes of the natural system must be understood. An artificial photosynthetic device has many components and each can be optimized separately. This work deals with the design, construction and study of some of those components. The first chapter provides an introduction to this work. The second chapter shows a proof of concept for a water splitting dye sensitized photoelectrochemical cell followed by the presentation of a new p-type semiconductor, the design of a modular cluster binding protein that can be used for incorporating catalysts, and a new anchoring group for semiconducting oxides with high electron injection efficiency. The third chapter investigates the role of electronic coupling and thermodynamics for photoprotection in artificial systems by triplet-triplet energy transfer from tetrapyrroles to carotenoids. The fourth chapter describes a mimic of the proton-coupled electron transfer in photosystem II and confirms that in the artificial system a concerted mechanism operates. In the fifth chapter, a microbial system is designed to work in tandem with a photovoltaic device to produce high energy fuels. A variety of quinone redox mediators have been synthesized to shuttle electrons from an electron donor to the microbial system. Lastly, the synthesis of a variety of photosensitizers is detailed for possible future use in artificial systems. The results of this work helps with the understanding of the processes of natural photosynthesis and suggests ways to design artificial photosynthetic devices that can contribute to solving the renewable energy challenge.
ContributorsBrown, Chelsea L (Author) / Moore, Ana L (Thesis advisor) / Gust, Devens (Committee member) / Woodbury, Neal (Committee member) / Arizona State University (Publisher)
Created2015
Description
The manipulation of biological targets using synthetic compounds has been the focal point of medicinal chemistry. The work described herein centers on the synthesis of organic small molecules that act either as probes for studying protein conformational changes or DNA–protein interaction, or as multifunctional radical quenchers.
Fluorescent labeling is of paramount importance to biological studies of proteins. For the development of new extrinsic small fluorophores, a series of tryptophan analogues has been designed and synthesized. Their pdCpA derivatives have been synthesized for tRNA activation and in vitro protein synthesis. The photophysical properties of the tryptophan (Trp) analogues have been examined, some of which can be selectively monitored even in the presence of multiple native tryptophan residues. Further, some of the Trp analogues form efficient FRET pairs with acceptors such as acridon-2-ylalanine (Acd) or L-(7-hydroxycoumarin-4-yl)ethylglycine (HCO) for the selective study of conformational changes in proteins.
Molecules which can bind with high sequence selectivity to a chosen target in a gene sequence are of interest for the development of gene therapy, diagnostic devices for genetic analysis, and as molecular tools for nucleic acid manipulations. Stereoselective synthesis of different alanyl nucleobase amino acids is described. Their pdCpA derivatives have been synthesized for tRNA activation and site-specific incorporation into the DNA-binding protein RRM1 of hnRNP LL. It is proposed that the nucleobase moieties in the protein may specifically recognize base sequence in the i-motif DNA through H-bonding and base-stacking interactions.
The mitochondrial respiratory chain accumulates more oxidative damage than any other organelle within the cell. Dysfunction of this organelle is believed to drive the progression of many diseases, thus mitochondria are an important potential drug target. Reactive oxygen species (ROS) are generated when electrons from the respiratory chain escape and interact with oxygen. ROS can react with proteins, lipids or DNA causing cell death. For the development of effective neuroprotective drugs, a series of N-hydroxy-4-pyridones have been designed and synthesized as CoQ10 analogues. All the analogues synthesized were evaluated for their ability to quench lipid peroxidation and reactive oxygen species (ROS).
Fluorescent labeling is of paramount importance to biological studies of proteins. For the development of new extrinsic small fluorophores, a series of tryptophan analogues has been designed and synthesized. Their pdCpA derivatives have been synthesized for tRNA activation and in vitro protein synthesis. The photophysical properties of the tryptophan (Trp) analogues have been examined, some of which can be selectively monitored even in the presence of multiple native tryptophan residues. Further, some of the Trp analogues form efficient FRET pairs with acceptors such as acridon-2-ylalanine (Acd) or L-(7-hydroxycoumarin-4-yl)ethylglycine (HCO) for the selective study of conformational changes in proteins.
Molecules which can bind with high sequence selectivity to a chosen target in a gene sequence are of interest for the development of gene therapy, diagnostic devices for genetic analysis, and as molecular tools for nucleic acid manipulations. Stereoselective synthesis of different alanyl nucleobase amino acids is described. Their pdCpA derivatives have been synthesized for tRNA activation and site-specific incorporation into the DNA-binding protein RRM1 of hnRNP LL. It is proposed that the nucleobase moieties in the protein may specifically recognize base sequence in the i-motif DNA through H-bonding and base-stacking interactions.
The mitochondrial respiratory chain accumulates more oxidative damage than any other organelle within the cell. Dysfunction of this organelle is believed to drive the progression of many diseases, thus mitochondria are an important potential drug target. Reactive oxygen species (ROS) are generated when electrons from the respiratory chain escape and interact with oxygen. ROS can react with proteins, lipids or DNA causing cell death. For the development of effective neuroprotective drugs, a series of N-hydroxy-4-pyridones have been designed and synthesized as CoQ10 analogues. All the analogues synthesized were evaluated for their ability to quench lipid peroxidation and reactive oxygen species (ROS).
ContributorsTalukder, Poulami (Author) / Hecht, Sidney M. (Thesis advisor) / Woodbury, Neal (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2016
Description
This dissertation examines the various factors and processes that have been proposed as explanations for the spread of agriculture in the west Mediterranean. The expansion of the Neolithic in the west Mediterranean (the Impresso-Cardial Neolithic) is characterized by a rapid spread of agricultural subsistence and material culture from the southern portion of the Italian peninsula to the western coast of the Iberian peninsula. To address this unique case, four conceptual models of Neolithic spread have been proposed: the Wave of Advance, the Capillary Spread Model, the Maritime Pioneer Colonization Model and the Dual Model. An agent-based model, the Cardial Spread Model, was built to simulate each conceptual spread model in a spatially explicit environment for comparison with evidence from the archaeological record. Chronological information detailing the arrival of the Neolithic was used to create a map of the initial arrival of the Neolithic (a chronosurface) throughout the study area. The results of each conceptual spread model were then compared to the chronosurface in order to evaluate the relative performance of each conceptual model of spread. These experiments suggest that both the Dual and Maritime Pioneer Colonization models best fit the available chronological and spatial distribution of the Impresso-Cardial Neolithic.
For the purpose of informing agent movement and improving the fit of the conceptual spread models, a variety of paleoenvironmental maps were tested within the Cardial Spread Model. The outcome of these experiments suggests that topographic slope was an important factor in settlement location and that rivers were important vectors of transportation for early Neolithic migration. This research demonstrates the application of techniques rare to archaeological analysis, agent-based modeling and the inclusion of paleoenvironmental information, and provides a valuable tool that future researchers can utilize to further evaluate and fabricate new models of Neolithic expansion.
For the purpose of informing agent movement and improving the fit of the conceptual spread models, a variety of paleoenvironmental maps were tested within the Cardial Spread Model. The outcome of these experiments suggests that topographic slope was an important factor in settlement location and that rivers were important vectors of transportation for early Neolithic migration. This research demonstrates the application of techniques rare to archaeological analysis, agent-based modeling and the inclusion of paleoenvironmental information, and provides a valuable tool that future researchers can utilize to further evaluate and fabricate new models of Neolithic expansion.
ContributorsBergin, Sean M (Author) / Barton, Michael (Thesis advisor) / Janssen, Marco (Committee member) / Coudart, Anick (Committee member) / Arizona State University (Publisher)
Created2016
Description
Sunlight, the most abundant source of energy available, is diffuse and intermittent; therefore it needs to be stored in chemicals bonds in order to be used any time. Photosynthesis converts sunlight into useful chemical energy that organisms can use for their functions. Artificial photosynthesis aims to use the essential chemistry of natural photosynthesis to harvest solar energy and convert it into fuels such as hydrogen gas. By splitting water, tandem photoelectrochemical solar cells (PESC) can produce hydrogen gas, which can be stored and used as fuel. Understanding the mechanisms of photosynthesis, such as photoinduced electron transfer, proton-coupled electron transfer (PCET) and energy transfer (singlet-singlet and triplet-triplet) can provide a detailed knowledge of those processes which can later be applied to the design of artificial photosynthetic systems. This dissertation has three main research projects. The first part focuses on design, synthesis and characterization of suitable photosensitizers for tandem cells. Different factors that can influence the performance of the photosensitizers in PESC and the attachment and use of a biomimetic electron relay to a water oxidation catalyst are explored. The second part studies PCET, using Nuclear Magnetic Resonance and computational chemistry to elucidate the structure and stability of tautomers that comprise biomimetic electron relays, focusing on the formation of intramolecular hydrogen bonds. The third part of this dissertation uses computational calculations to understand triplet-triplet energy transfer and the mechanism of quenching of the excited singlet state of phthalocyanines in antenna models by covalently attached carotenoids.
ContributorsTejeda Ferrari, Marely (Author) / Moore, Ana (Thesis advisor) / Mujica, Vladimiro (Thesis advisor) / Gust, John (Committee member) / Woodbury, Neal (Committee member) / Arizona State University (Publisher)
Created2016
Description
The closer integration of the world economy has yielded many positive benefits including the worldwide diffusion of innovative technologies and efficiency gains following the widening of international markets. However, closer integration also has negative consequences. Specifically, I focus on the ecology and economics of the spread of species and pathogens. I approach the problem using theoretical and applied models in ecology and economics. First, I use a multi-species theoretical network model to evaluate the ability of dispersal to maintain system-level biodiversity and productivity. I then extend this analysis to consider the effects of dispersal in a coupled social-ecological system where people derive benefits from species. Finally, I estimate an empirical model of the foot and mouth disease risks of trade. By combining outbreak and trade data I estimate the disease risks associated with the international trade in live animals while controlling for the biosecurity measures in place in importing countries and the presence of wild reservoirs. I find that the risks associated with the spread and dispersal of species may be positive or negative, but that this relationship depends on the ecological and economic components of the system and the interactions between them.
ContributorsShanafelt, David William (Author) / Perrings, Charles (Thesis advisor) / Fenichel, Eli (Committee member) / Richards, Timorthy (Committee member) / Janssen, Marco (Committee member) / Collins, James (Committee member) / Arizona State University (Publisher)
Created2016
Description
The coordination of group behavior in the social insects is representative of a broader phenomenon in nature, emergent biological complexity. In such systems, it is believed that large-scale patterns result from the interaction of relatively simple subunits. This dissertation involved the study of one such system: the social foraging of the ant Temnothorax rugatulus. Physically tiny with small population sizes, these cavity-dwelling ants provide a good model system to explore the mechanisms and ultimate origins of collective behavior in insect societies. My studies showed that colonies robustly exploit sugar water. Given a choice between feeders unequal in quality, colonies allocate more foragers to the better feeder. If the feeders change in quality, colonies are able to reallocate their foragers to the new location of the better feeder. These qualities of flexibility and allocation could be explained by the nature of positive feedback (tandem run recruitment) that these ants use. By observing foraging colonies with paint-marked ants, I was able to determine the `rules' that individuals follow: foragers recruit more and give up less when they find a better food source. By altering the nutritional condition of colonies, I found that these rules are flexible - attuned to the colony state. In starved colonies, individual ants are more likely to explore and recruit to food sources than in well-fed colonies. Similar to honeybees, Temmnothorax foragers appear to modulate their exploitation and recruitment behavior in response to environmental and social cues. Finally, I explored the influence of ecology (resource distribution) on the foraging success of colonies. Larger colonies showed increased consistency and a greater rate of harvest than smaller colonies, but this advantage was mediated by the distribution of resources. While patchy or rare food sources exaggerated the relative success of large colonies, regularly (or easily found) distributions leveled the playing field for smaller colonies. Social foraging in ant societies can best be understood when we view the colony as a single organism and the phenotype - group size, communication, and individual behavior - as integrated components of a homeostatic unit.
ContributorsShaffer, Zachary (Author) / Pratt, Stephen C (Thesis advisor) / Hölldobler, Bert (Committee member) / Janssen, Marco (Committee member) / Fewell, Jennifer (Committee member) / Liebig, Juergen (Committee member) / Arizona State University (Publisher)
Created2014
Description
In Latin America food insecurity is still prevailing in those regions where extreme poverty and political instability are common. Tseltal communities are experiencing changes due to religious conversions and the incursion of external political institutions. These changes have diminished the importance of traditional reciprocal and redistributive institutions that historically have been essential for personal and community survival. This dissertation investigated the impact that variations on governance systems and presence of reciprocal and distributional exchanges have on the food security status of communities. Qualitative data collected in four communities through 117 free lists and 117 semi-structured interviews was used to elaborate six scales that correspond to the traditional and civic authority system and to inter-community and intra-community reciprocity and redistribution. I explore the relationship that the scores of four communities on those scales have on the food security status of their inhabitants based on their results on the National Health and Nutrition Survey 2012. Findings from this study suggest that in marginalized communities that many scientists would described as experiencing market failure, participation in inter-community reciprocal, intra-community reciprocal and intra-community redistribution are better predictors of food security than enrollment in food security programs. Additionally, communities that participated the most in these non-market mechanisms have stronger traditional institutions. In contrast, communities that participated more in inter-community redistribution scored higher on the civic authority scale, are enrolled in more food aid programs, but are less food secure.
ContributorsDe La Torre Pacheco, Sindy Yaneth (Author) / Janssen, Marco (Thesis advisor) / Eakin, Hallie (Committee member) / BurnSilver, Shauna (Committee member) / Arizona State University (Publisher)
Created2015
Description
The healthcare system in this country is currently unacceptable. New technologies may contribute to reducing cost and improving outcomes. Early diagnosis and treatment represents the least risky option for addressing this issue. Such a technology needs to be inexpensive, highly sensitive, highly specific, and amenable to adoption in a clinic. This thesis explores an immunodiagnostic technology based on highly scalable, non-natural sequence peptide microarrays designed to profile the humoral immune response and address the healthcare problem. The primary aim of this thesis is to explore the ability of these arrays to map continuous (linear) epitopes. I discovered that using a technique termed subsequence analysis where epitopes could be decisively mapped to an eliciting protein with high success rate. This led to the discovery of novel linear epitopes from Plasmodium falciparum (Malaria) and Treponema palladium (Syphilis), as well as validation of previously discovered epitopes in Dengue and monoclonal antibodies. Next, I developed and tested a classification scheme based on Support Vector Machines for development of a Dengue Fever diagnostic, achieving higher sensitivity and specificity than current FDA approved techniques. The software underlying this method is available for download under the BSD license. Following this, I developed a kinetic model for immunosignatures and tested it against existing data driven by previously unexplained phenomena. This model provides a framework and informs ways to optimize the platform for maximum stability and efficiency. I also explored the role of sequence composition in explaining an immunosignature binding profile, determining a strong role for charged residues that seems to have some predictive ability for disease. Finally, I developed a database, software and indexing strategy based on Apache Lucene for searching motif patterns (regular expressions) in large biological databases. These projects as a whole have advanced knowledge of how to approach high throughput immunodiagnostics and provide an example of how technology can be fused with biology in order to affect scientific and health outcomes.
ContributorsRicher, Joshua Amos (Author) / Johnston, Stephen A. (Thesis advisor) / Woodbury, Neal (Committee member) / Stafford, Phillip (Committee member) / Papandreou-Suppappola, Antonia (Committee member) / Arizona State University (Publisher)
Created2014