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.
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Induced pluripotent stem cells (iPSCs) are an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors' complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. We describe the establishment of primary dermal fibroblasts cells lines from 28 autopsy donors. These fibroblasts were used to examine the proliferative effects of establishment protocol, tissue amount, biopsy site, and donor age. As proof-of-principle, iPSCs were generated from fibroblasts from a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. To our knowledge, this is the first study describing autopsy donor-derived somatic cells being used for iPSC generation and subsequent neural differentiation. This unique approach also enables us to compare iPSC-derived cell cultures to endogenous tissues from the same donor. We utilized RNA sequencing (RNA-Seq) to evaluate the transcriptional progression of in vitro-differentiated neural cells (over a timecourse of 0, 35, 70, 105 and 140 days), and compared this with donor-identical temporal lobe tissue. We observed in vitro progression towards the reference brain tissue, supported by (i) a significant increasing monotonic correlation between the days of our timecourse and the number of actively transcribed protein-coding genes and long intergenic non-coding RNAs (lincRNAs) (P < 0.05), consistent with the transcriptional complexity of the brain, (ii) an increase in CpG methylation after neural differentiation that resembled the epigenomic signature of the endogenous tissue, and (iii) a significant decreasing monotonic correlation between the days of our timecourse and the percent of in vitro to brain-tissue differences (P < 0.05) for tissue-specific protein-coding genes and all putative lincRNAs. These studies support the utility of autopsy donors' somatic cells for iPSC-based neurological disease models, and provide evidence that in vitro neural differentiation can result in physiologically progression.
ContributorsHjelm, Brooke E (Author) / Craig, David W. (Thesis advisor) / Wilson-Rawls, Norma J. (Thesis advisor) / Huentelman, Matthew J. (Committee member) / Mason, Hugh S. (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2013
Description
Speciation is the fundamental process that has generated the vast diversity of life on earth. The hallmark of speciation is the evolution of barriers to gene flow. These barriers may reduce gene flow either by keeping incipient species from hybridizing at all (pre-zygotic), or by reducing the fitness of hybrids (post-zygotic). To understand the genetic architecture of these barriers and how they evolve, I studied a genus of wasps that exhibits barriers to gene flow that act both pre- and post-zygotically. Nasonia is a genus of four species of parasitoid wasps that can be hybridized in the laboratory. When two of these species, N. vitripennis and N. giraulti are mated, their offspring suffer, depending on the generation and cross examined, up to 80% mortality during larval development due to incompatible genic interactions between their nuclear and mitochondrial genomes. These species also exhibit pre-zygotic isolation, meaning they are more likely to mate with their own species when given the choice. I examined these two species and their hybrids to determine the genetic and physiological bases of both speciation mechanisms and to understand the evolutionary forces leading to them. I present results that indicate that the oxidative phosphorylation (OXPHOS) pathway, an essential pathway that is responsible for mitochondrial energy generation, is impaired in hybrids of these two species. These results indicate that this impairment is due to the unique evolutionary dynamics of the combined nuclear and mitochondrial origin of this pathway. I also present results showing that, as larvae, these hybrids experience retarded growth linked to the previously observed mortality and I explore possible physiological mechanisms for this. Finally, I show that the pre-mating isolation is due to a change in a single pheromone component in N. vitripennis males, that this change is under simple genetic control, and that it evolved neutrally before being co-opted as a species recognition signal. These results are an important addition to our overall understanding of the mechanisms of speciation and showcase Nasonia as an emerging model for the study of the genetics of speciation.
ContributorsGibson, Joshua D (Author) / Gadau, Jürgen (Thesis advisor) / Harrison, Jon (Committee member) / Pratt, Stephen (Committee member) / Verrelli, Brian (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013
Description
The principle of Darwinian evolution has been applied in the laboratory to nucleic acid molecules since 1990, and led to the emergence of in vitro evolution technique. The methodology of in vitro evolution surveys a large number of different molecules simultaneously for a pre-defined chemical property, and enrich for molecules with the particular property. DNA and RNA sequences with versatile functions have been identified by in vitro selection experiments, but many basic questions remain to be answered about how these molecules achieve their functions. This dissertation first focuses on addressing a fundamental question regarding the molecular recognition properties of in vitro selected DNA sequences, namely whether negatively charged DNA sequences can be evolved to bind alkaline proteins with high specificity. We showed that DNA binders could be made, through carefully designed stringent in vitro selection, to discriminate different alkaline proteins. The focus of this dissertation is then shifted to in vitro evolution of an artificial genetic polymer called threose nucleic acid (TNA). TNA has been considered a potential RNA progenitor during early evolution of life on Earth. However, further experimental evidence to support TNA as a primordial genetic material is lacking. In this dissertation we demonstrated the capacity of TNA to form stable tertiary structure with specific ligand binding property, which suggests a possible role of TNA as a pre-RNA genetic polymer. Additionally, we discussed the challenges in in vitro evolution for TNA enzymes and developed the necessary methodology for future TNA enzyme evolution.
ContributorsYu, Hanyang (Author) / Chaput, John C (Thesis advisor) / Chen, Julian (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2013
Description
One of the main challenges in planetary robotics is to traverse the shortest path through a set of waypoints. The shortest distance between any two waypoints is a direct linear traversal. Often times, there are physical restrictions that prevent a rover form traversing straight to a waypoint. Thus, knowledge of the terrain is needed prior to traversal. The Digital Terrain Model (DTM) provides information about the terrain along with waypoints for the rover to traverse. However, traversing a set of waypoints linearly is burdensome, as the rovers would constantly need to modify their orientation as they successively approach waypoints. Although there are various solutions to this problem, this research paper proposes the smooth traversability of the rover using splines as a quick and easy implementation to traverse a set of waypoints. In addition, a rover was used to compare the smoothness of the linear traversal along with the spline interpolations. The data collected illustrated that spline traversals had a less rate of change in the velocity over time, indicating that the rover performed smoother than with linear paths.
ContributorsKamasamudram, Anurag (Author) / Saripalli, Srikanth (Thesis advisor) / Fainekos, Georgios (Thesis advisor) / Turaga, Pavan (Committee member) / Arizona State University (Publisher)
Created2013
Description
As the complexity of robotic systems and applications grows rapidly, development of high-performance, easy to use, and fully integrated development environments for those systems is inevitable. Model-Based Design (MBD) of dynamic systems using engineering software such as Simulink® from MathWorks®, SciCos from Metalau team and SystemModeler® from Wolfram® is quite popular nowadays. They provide tools for modeling, simulation, verification and in some cases automatic code generation for desktop applications, embedded systems and robots. For real-world implementation of models on the actual hardware, those models should be converted into compilable machine code either manually or automatically. Due to the complexity of robotic systems, manual code translation from model to code is not a feasible optimal solution so we need to move towards automated code generation for such systems. MathWorks® offers code generation facilities called Coder® products for this purpose. However in order to fully exploit the power of model-based design and code generation tools for robotic applications, we need to enhance those software systems by adding and modifying toolboxes, files and other artifacts as well as developing guidelines and procedures. In this thesis, an effort has been made to propose a guideline as well as a Simulink® library, StateFlow® interface API and a C/C++ interface API to complete this toolchain for NAO humanoid robots. Thus the model of the hierarchical control architecture can be easily and properly converted to code and built for implementation.
ContributorsRaji Kermani, Ramtin (Author) / Fainekos, Georgios (Thesis advisor) / Lee, Yann-Hang (Committee member) / Sarjoughian, Hessam S. (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 development of advanced, anthropomorphic artificial hands aims to provide upper extremity amputees with improved functionality for activities of daily living. However, many state-of-the-art hands have a large number of degrees of freedom that can be challenging to control in an intuitive manner. Automated grip responses could be built into artificial hands in order to enhance grasp stability and reduce the cognitive burden on the user. To this end, three studies were conducted to understand how human hands respond, passively and actively, to unexpected perturbations of a grasped object along and about different axes relative to the hand. The first study investigated the effect of magnitude, direction, and axis of rotation on precision grip responses to unexpected rotational perturbations of a grasped object. A robust "catch-up response" (a rapid, pulse-like increase in grip force rate previously reported only for translational perturbations) was observed whose strength scaled with the axis of rotation. Using two haptic robots, we then investigated the effects of grip surface friction, axis, and direction of perturbation on precision grip responses for unexpected translational and rotational perturbations for three different hand-centric axes. A robust catch-up response was observed for all axes and directions for both translational and rotational perturbations. Grip surface friction had no effect on the stereotypical catch-up response. Finally, we characterized the passive properties of the precision grip-object system via robot-imposed impulse perturbations. The hand-centric axis associated with the greatest translational stiffness was different than that for rotational stiffness. This work expands our understanding of the passive and active features of precision grip, a hallmark of human dexterous manipulation. Biological insights such as these could be used to enhance the functionality of artificial hands and the quality of life for upper extremity amputees.
ContributorsDe Gregorio, Michael (Author) / Santos, Veronica J. (Thesis advisor) / Artemiadis, Panagiotis K. (Committee member) / Santello, Marco (Committee member) / Sugar, Thomas (Committee member) / Helms Tillery, Stephen I. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Human fingertips contain thousands of specialized mechanoreceptors that enable effortless physical interactions with the environment. Haptic perception capabilities enable grasp and manipulation in the absence of visual feedback, as when reaching into one's pocket or wrapping a belt around oneself. Unfortunately, state-of-the-art artificial tactile sensors and processing algorithms are no match for their biological counterparts. Tactile sensors must not only meet stringent practical specifications for everyday use, but their signals must be processed and interpreted within hundreds of milliseconds. Control of artificial manipulators, ranging from prosthetic hands to bomb defusal robots, requires a constant reliance on visual feedback that is not entirely practical. To address this, we conducted three studies aimed at advancing artificial haptic intelligence. First, we developed a novel, robust, microfluidic tactile sensor skin capable of measuring normal forces on flat or curved surfaces, such as a fingertip. The sensor consists of microchannels in an elastomer filled with a liquid metal alloy. The fluid serves as both electrical interconnects and tunable capacitive sensing units, and enables functionality despite substantial deformation. The second study investigated the use of a commercially-available, multimodal tactile sensor (BioTac sensor, SynTouch) to characterize edge orientation with respect to a body fixed reference frame, such as a fingertip. Trained on data from a robot testbed, a support vector regression model was developed to relate haptic exploration actions to perception of edge orientation. The model performed comparably to humans for estimating edge orientation. Finally, the robot testbed was used to perceive small, finger-sized geometric features. The efficiency and accuracy of different haptic exploratory procedures and supervised learning models were assessed for estimating feature properties such as type (bump, pit), order of curvature (flat, conical, spherical), and size. This study highlights the importance of tactile sensing in situations where other modalities fail, such as when the finger itself blocks line of sight. Insights from this work could be used to advance tactile sensor technology and haptic intelligence for artificial manipulators that improve quality of life, such as prosthetic hands and wheelchair-mounted robotic hands.
ContributorsPonce Wong, Ruben Dario (Author) / Santos, Veronica J (Thesis advisor) / Artemiadis, Panagiotis K (Committee member) / Helms Tillery, Stephen I (Committee member) / Posner, Jonathan D (Committee member) / Runger, George C. (Committee member) / Arizona State University (Publisher)
Created2013
Description
The purpose of the current study was to use structural equation modeling-based quantitative genetic models to characterize latent genetic and environmental influences on proneness to three discrete negative emotions in middle childhood, according to mother-report, father-report and in-home observation. One primary aim was to test the extent to which covariance among the three emotions could be accounted for by a single, common genetically- and environmentally-influenced negative emotionality factor. A second aim was to examine the extent to which different reporters appeared to be tapping into the same genetically- and environmentally-influenced aspects of each emotion. According to mother- and father-report, moderate to high genetic influences were evident for all emotions, with mother- and father-report of fear and father-report of anger showing the highest heritability. Significant common environmental influences were also found for mother-report of anger and sadness in both univariate and multivariate models. For observed emotion, anger was moderately heritable with no evidence for common environmental variance, but sadness, object fear and social fear all showed modest to moderate common environmental influences and no significant genetic variance. In addition, cholesky decompositions examining genetic and environmental influences across reporter suggested that despite considerable overlap between mother-report and father-report, there was also reporter-specific variance on anger, sadness, and fear. Specifically, there were significant common environmental influences on mother-report of anger- and sadness that were not shared with father-report, and genetic influences on father-report of sadness and fear that were not shared with mother-report. In-home observations were not highly correlated enough with parent-report to support multivariate analysis for any emotion. Finally, according to both mother- and father-report, a single set of genetic and environmental influences was sufficient to account for covariance among all three negative emotions. However, fear was primarily explained by genetic influences not shared with other emotions, and anger also showed considerable emotion-specific genetic variance. In both cases, findings support the value of a more emotion-specific approach to temperament, and highlight the need to consider distinctions as well as commonalities across emotions, reporters and situations.
ContributorsClifford, Sierra (Author) / Lemery, Kathryn (Thesis advisor) / Shiota, Michelle (Committee member) / Eisenberg, Nancy (Committee member) / Arizona State University (Publisher)
Created2013
Description
Electromyogram (EMG)-based control interfaces are increasingly used in robot teleoperation, prosthetic devices control and also in controlling robotic exoskeletons. Over the last two decades researchers have come up with a plethora of decoding functions to map myoelectric signals to robot motions. However, this requires a lot of training and validation data sets, while the parameters of the decoding function are specific for each subject. In this thesis we propose a new methodology that doesn't require training and is not user-specific. The main idea is to supplement the decoding functional error with the human ability to learn inverse model of an arbitrary mapping function. We have shown that the subjects gradually learned the control strategy and their learning rates improved. We also worked on identifying an optimized control scheme that would be even more effective and easy to learn for the subjects. Optimization was done by taking into account that muscles act in synergies while performing a motion task. The low-dimensional representation of the neural activity was used to control a two-dimensional task. Results showed that in the case of reduced dimensionality mapping, the subjects were able to learn to control the device in a slower pace, however they were able to reach and retain the same level of controllability. To summarize, we were able to build an EMG-based controller for robot devices that would work for any subject, without any training or decoding function, suggesting human-embedded controllers for robotic devices.
ContributorsAntuvan, Chris Wilson (Author) / Artemiadis, Panagiotis (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Santos, Veronica J (Committee member) / Arizona State University (Publisher)
Created2013