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Description
A synbody is a newly developed protein binding peptide which can be rapidly produced by chemical methods. The advantages of the synbody producing process make it a potential human proteome binding reagent. Most of the synbodies are designed to bind to specific proteins. The peptides incorporated in a synbody are discovered with peptide microarray technology. Nevertheless, the targets for unknown synbodies can also be discovered by searching through a protein mixture. The first part of this thesis mainly focuses on the process of target searching, which was performed with immunoprecipitation assays and mass spectrometry analysis. Proteins are pulled down from the cell lysate by certain synbodies, and then these proteins are identified using mass spectrometry. After excluding non-specific bindings, the interaction between a synbody and its real target(s) can be verified with affinity measurements. As a specific example, the binding between 1-4-KCap synbody and actin was discovered. This result proved the feasibility of the mass spectrometry based method and also suggested that a high throughput synbody discovery platform for the human proteome could be developed. Besides the application of synbody development, the peptide microarray technology can also be used for immunosignatures. The composition of all types of antibodies existing in one's blood is related to an individual's health condition. A method, called immunosignaturing, has been developed for early disease diagnosis based on this principle. CIM10K microarray slides work as a platform for blood antibody detection in immunosignaturing. During the analysis of an immunosignature, the data from these slides needs to be validated by using landing light peptides. The second part of this thesis focuses on the validation of the data. A biotinylated peptide was used as a landing light on the new CIM10K slides. The data was collected in several rounds of tests and indicated that the variation among landing lights was significantly reduced by using the newly prepared biotinylated peptide compared with old peptide mixture. Several suggestions for further landing light improvement are proposed based on the results.
ContributorsSun, Minyao (Author) / Johnston, Stephen Albert (Thesis advisor) / Diehnelt, Chris Wayne (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
Immunosignaturing is a new immunodiagnostic technology that uses random-sequence peptide microarrays to profile the humoral immune response. Though the peptides have little sequence homology to any known protein, binding of serum antibodies may be detected, and the pattern correlated to disease states. The aim of my dissertation is to analyze the factors affecting the binding patterns using monoclonal antibodies and determine how much information may be extracted from the sequences. Specifically, I examined the effects of antibody concentration, competition, peptide density, and antibody valence. Peptide binding could be detected at the low concentrations relevant to immunosignaturing, and a monoclonal's signature could even be detected in the presences of 100 fold excess naive IgG. I also found that peptide density was important, but this effect was not due to bivalent binding. Next, I examined in more detail how a polyreactive antibody binds to the random sequence peptides compared to protein sequence derived peptides, and found that it bound to many peptides from both sets, but with low apparent affinity. An in depth look at how the peptide physicochemical properties and sequence complexity revealed that there were some correlations with properties, but they were generally small and varied greatly between antibodies. However, on a limited diversity but larger peptide library, I found that sequence complexity was important for antibody binding. The redundancy on that library did enable the identification of specific sub-sequences recognized by an antibody. The current immunosignaturing platform has little repetition of sub-sequences, so I evaluated several methods to infer antibody epitopes. I found two methods that had modest prediction accuracy, and I developed a software application called GuiTope to facilitate the epitope prediction analysis. None of the methods had sufficient accuracy to identify an unknown antigen from a database. In conclusion, the characteristics of the immunosignaturing platform observed through monoclonal antibody experiments demonstrate its promise as a new diagnostic technology. However, a major limitation is the difficulty in connecting the signature back to the original antigen, though larger peptide libraries could facilitate these predictions.
ContributorsHalperin, Rebecca (Author) / Johnston, Stephen A. (Thesis advisor) / Bordner, Andrew (Committee member) / Taylor, Thomas (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
African Swine Fever (ASF), endemic in many African countries, is now spreading to other continents. Though ASF is capable of incurring serious economic losses in affected countries, no vaccine exists to provide immunity to animals. Disease control relies largely on rapid diagnosis and the implementation of movement restrictions and strict eradication programs. Developing a scalable, accurate and low cost diagnostic for ASF will be of great help for the current situation. CIM's 10K random peptide microarray is a new high-throughput platform that allows systematic investigations of immune responses associated with disease and shows promise as a diagnostic tool. In this study, this new technology was applied to characterize the immune responses of ASF virus (ASFV) infections and immunizations. Six sets of sera from ASFV antigen immunized pigs, 6 sera from infected pigs and 20 sera samples from unexposed pigs were tested and analyzed statistically. Results show that both ASFV antigen immunized pigs and ASFV viral infected pigs can be distinguished from unexposed pigs. Since it appears that immune responses to other viral infections are also distinguishable on this platform, it holds the potential of being useful in developing a new ASF diagnostic. The ability of this platform to identify specific ASFV antibody epitopes was also explored. A subtle motif was found to be shared among a set of peptides displaying the highest reactivity for an antigen specific antibody. However, this motif does not seem to match with any antibody epitopes predicted by a linear antibody epitope prediction.
ContributorsXiao, Liang (Author) / Sykes, Kathryn (Thesis advisor) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
Meteorology is an uncommon term rarely resonating through elementary classrooms. However, it is a concept found in both fourth and sixth grade Arizona science standards. As issues involving the environment are becoming more pertinent, it is important to study and understand atmospheric processes along with fulfilling the standards for each grade level. This thesis project teaches the practical skills of weather map reading and weather forecasting through the creation and execution of an after school lesson with the aide of seven teen assistants.
ContributorsChoulet, Shayna (Author) / Walters, Debra (Thesis director) / Oliver, Jill (Committee member) / Balling, Robert (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
Plants are essential to human life. They release oxygen into the atmosphere for us to breathe. They also provide shelter, medicine, clothing, tools, and food. For many people, the food that is on their tables and in their supermarkets isn't given much thought. Where did it come from? What part of the plant is it? How does it relate to others in the plant kingdom? How do other cultures use this plant? The most many of us know about them is that they are at the supermarket when we need them for dinner (Nabhan, 2009) (Vileisis, 2008).
ContributorsBarron, Kara (Author) / Landrum, Leslie (Thesis director) / Swanson, Tod (Committee member) / Pigg, Kathleen (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
DescriptionBased on previous research and findings it is proven that a non-profit class to create awareness will be beneficial in the prevention of eating disorders. This analysis will provide significant research to defend the proposed class.
ContributorsAllen, Brittany (Author) / Chung, Deborah (Author) / Fey, Richard (Thesis director) / Peck, Sidnee (Committee member) / Mazurkiewicz, Milena (Committee member) / Barrett, The Honors College (Contributor) / W. P. Carey School of Business (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
Restraint stress is the most commonly used laboratory stressor. It is difficult to characterize as psychological or physical, because past studies show psychological features, but the nature of confinement adds a physical dimension. This was the first study to investigate how experience with restraint stress affects brain response to the next stress without a physical burden. Pair-housed adult male rats were transported to a novel context and restrained or left undisturbed (6hr). The next day, rats were returned to the same context and were either restrained or left undisturbed in the context (n=8/group). After 90min, rats were euthanized to determine functional activation in limbic structures using Fos immunohistochemistry and to measure HPA axis reactivity through blood serum corticosterone levels. Regardless of day 1 experience, context exposure on day 2 enhanced Fos expression in CA1 and CA3 of the hippocampus, basolateral amygdala, and central amygdala. Conversely, other regions and corticosterone levels demonstrated modulation from the previous day's experience. Specifically, rats that were placed back into the restraint context but not restrained on day 2 showed enhanced Fos expression in the dentate gyrus suprapyramidal blade (DGSup), and infralimbic cortex (IL). Also Fos expression was attenuated in rats that received two restraint exposures in the IL and medial amygdala (MEA), suggesting habituation. Only the DG infrapyramidal blade (DGInf) showed enhanced Fos expression to restraint on day 2 without influence of the previous day. While context predominately directed Fos activation, prior experience with restraint influenced Fos expression in the DGSup, IL, MEA and corticosterone levels to support restraint having psychological components.
ContributorsAnouti, P. Danya (Author) / Conrad, D. Cheryl (Thesis director) / Hammer, Ronald (Committee member) / Hoffman, N. Ann (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
Image resolution limits the extent to which zooming enhances clarity, restricts the size digital photographs can be printed at, and, in the context of medical images, can prevent a diagnosis. Interpolation is the supplementing of known data with estimated values based on a function or model involving some or all of the known samples. The selection of the contributing data points and the specifics of how they are used to define the interpolated values influences how effectively the interpolation algorithm is able to estimate the underlying, continuous signal. The main contributions of this dissertation are three fold: 1) Reframing edge-directed interpolation of a single image as an intensity-based registration problem. 2) Providing an analytical framework for intensity-based registration using control grid constraints. 3) Quantitative assessment of the new, single-image enlargement algorithm based on analytical intensity-based registration. In addition to single image resizing, the new methods and analytical approaches were extended to address a wide range of applications including volumetric (multi-slice) image interpolation, video deinterlacing, motion detection, and atmospheric distortion correction. Overall, the new approaches generate results that more accurately reflect the underlying signals than less computationally demanding approaches and with lower processing requirements and fewer restrictions than methods with comparable accuracy.
ContributorsZwart, Christine M. (Author) / Frakes, David H (Thesis advisor) / Karam, Lina (Committee member) / Kodibagkar, Vikram (Committee member) / Spanias, Andreas (Committee member) / Towe, Bruce (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
Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in the encoding gradient waveforms. This causes sampling discrepancies between the actual and the ideal k-space trajectory. Reconstruction assuming an ideal trajectory can result in shading and blurring artifacts in spiral images. Current methods to estimate such hardware errors require many modifications to the pulse sequence, phantom measurements or specialized hardware. This work presents a new method to estimate time-varying system delays for spiral-based trajectories. It requires a minor modification of a conventional stack-of-spirals sequence and analyzes data collected on three orthogonal cylinders. The method is fast, robust to off-resonance effects, requires no phantom measurements or specialized hardware and estimate variable system delays for the three gradient channels over the data-sampling period. The initial results are presented for acquired phantom and in-vivo data, which show a substantial reduction in the artifacts and improvement in the image quality.
ContributorsBhavsar, Payal (Author) / Pipe, James G (Thesis advisor) / Frakes, David (Committee member) / Kodibagkar, Vikram (Committee member) / Arizona State University (Publisher)
Created2013