Matching Items (79)
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
This dissertation creates models of past potential vegetation in the Southern Levant during most of the Holocene, from the beginnings of farming through the rise of urbanized civilization (12 to 2.5 ka BP). The time scale encompasses the rise and collapse of the earliest agrarian civilizations in this region. The archaeological record suggests that increases in social complexity were linked to climatic episodes (e.g., favorable climatic conditions coincide with intervals of prosperity or marked social development such as the Neolithic Revolution ca. 11.5 ka BP, the Secondary Products Revolution ca. 6 ka BP, and the Middle Bronze Age ca. 4 ka BP). The opposite can be said about periods of climatic deterioration, when settled villages were abandoned as the inhabitants returned to nomadic or semi nomadic lifestyles (e.g., abandonment of the largest Neolithic farming towns after 8 ka BP and collapse of Bronze Age towns and cities after 3.5 ka BP during the Late Bronze Age). This study develops chronologically refined models of past vegetation from 12 to 2.5 ka BP, at 500 year intervals, using GIS, remote sensing and statistical modeling tools (MAXENT) that derive from species distribution modeling. Plants are sensitive to alterations in their environment and respond accordingly. Because of this, they are valuable indicators of landscape change. An extensive database of historical and field gathered observations was created. Using this database as well as environmental variables that include temperature and precipitation surfaces for the whole study period (also at 500 year intervals), the potential vegetation of the region was modeled. Through this means, a continuous chronology of potential vegetation of the Southern Levantwas built. The produced paleo-vegetation models generally agree with the proxy records. They indicate a gradual decline of forests and expansion of steppe and desert throughout the Holocene, interrupted briefly during the Mid Holocene (ca. 4 ka BP, Middle Bronze Age). They also suggest that during the Early Holocene, forest areas were extensive, spreading into the Northern Negev. The two remaining forested areas in the Northern and Southern Plateau Region in Jordan were also connected during this time. The models also show general agreement with the major cultural developments, with forested areas either expanding or remaining stable during prosperous periods (e.g., Pre Pottery Neolithic and Middle Bronze Age), and significantly contracting during moments of instability (e.g., Late Bronze Age).
ContributorsSoto-Berelov, Mariela (Author) / Fall, Patricia L. (Thesis advisor) / Myint, Soe (Committee member) / Turner, Billie L (Committee member) / Falconer, Steven (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
Accumulating evidence implicates exposure to adverse childhood experiences in the development of hypocortisolism in the long-term, and researchers are increasingly examining individual-level mechanisms that may underlie, exacerbate or attenuate this relation among at-risk populations. The current study takes a developmentally and theoretically informed approach to examining episodic childhood stressors, inherent and voluntary self-regulation, and physiological reactivity among a longitudinal sample of youth who experienced parental divorce. Participants were drawn from a larger randomized controlled trial of a preventive intervention for children of divorce between the ages of 9 and 12. The current sample included 159 young adults (mean age = 25.5 years; 53% male; 94% Caucasian) who participated in six waves of data collection, including a 15-year follow-up study. Participants reported on exposure to negative life events (four times over a 9-month period) during childhood, and mothers rated child temperament. Six years later, youth reported on the use of active and avoidant coping strategies, and 15 years later, they participated in a standardized psychosocial stress task and provided salivary cortisol samples prior to and following the task. Path analyses within a structural equation framework revealed that a multiple mediation model best fit the data. It was found that children with better mother-rated self-regulation (i.e. low impulsivity, low negative emotionality, and high attentional focus) exhibited lower total cortisol output 15 years later. In addition, greater self-regulation in childhood predicted greater use of active coping in adolescence, whereas a greater number of negative life events predicted increased use of avoidant coping in adolescence. Finally, a greater number of negative events in childhood predicted marginally lower total cortisol output, and higher levels of active coping in adolescence were associated with greater total cortisol output in young adulthood. Findings suggest that children of divorce who exhibit better self-regulation evidence lower cortisol output during a standardized psychosocial stress task relative to those who have higher impulsivity, lower attentional focus, and/or higher negative emotionality. The conceptual significance of the current findings, including the lack of evidence for hypothesized relations, methodological issues that arose, and issues in need of future research are discussed.
ContributorsHagan, Melissa (Author) / Luecken, Linda (Thesis advisor) / MacKinnon, David (Committee member) / Wolchik, Sharlene (Committee member) / Doane, Leah (Committee member) / Arizona State University (Publisher)
Created2013
Description
Two critical limitations for hyperspatial imagery are higher imagery variances and large data sizes. Although object-based analyses with a multi-scale framework for diverse object sizes are the solution, more data sources and large amounts of testing at high costs are required. In this study, I used tree density segmentation as the key element of a three-level hierarchical vegetation framework for reducing those costs, and a three-step procedure was used to evaluate its effects. A two-step procedure, which involved environmental stratifications and the random walker algorithm, was used for tree density segmentation. I determined whether variation in tone and texture could be reduced within environmental strata, and whether tree density segmentations could be labeled by species associations. At the final level, two tree density segmentations were partitioned into smaller subsets using eCognition in order to label individual species or tree stands in two test areas of two tree densities, and the Z values of Moran's I were used to evaluate whether imagery objects have different mean values from near segmentations as a measure of segmentation accuracy. The two-step procedure was able to delineating tree density segments and label species types robustly, compared to previous hierarchical frameworks. However, eCognition was not able to produce detailed, reasonable image objects with optimal scale parameters for species labeling. This hierarchical vegetation framework is applicable for fine-scale, time-series vegetation mapping to develop baseline data for evaluating climate change impacts on vegetation at low cost using widely available data and a personal laptop.
ContributorsLiau, Yan-ting (Author) / Franklin, Janet (Thesis advisor) / Turner, Billie (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2013
Description
Land transformation under conditions of rapid urbanization has significantly altered the structure and functioning of Earth's systems. Land fragmentation, a characteristic of land transformation, is recognized as a primary driving force in the loss of biological diversity worldwide. However, little is known about its implications in complex urban settings where interaction with social dynamics is intense. This research asks: How do patterns of land cover and land fragmentation vary over time and space, and what are the socio-ecological drivers and consequences of land transformation in a rapidly growing city? Using Metropolitan Phoenix as a case study, the research links pattern and process relationships between land cover, land fragmentation, and socio-ecological systems in the region. It examines population growth, water provision and institutions as major drivers of land transformation, and the changes in bird biodiversity that result from land transformation. How to manage socio-ecological systems is one of the biggest challenges of moving towards sustainability. This research project provides a deeper understanding of how land transformation affects socio-ecological dynamics in an urban setting. It uses a series of indices to evaluate land cover and fragmentation patterns over the past twenty years, including land patch numbers, contagion, shapes, and diversities. It then generates empirical evidence on the linkages between land cover patterns and ecosystem properties by exploring the drivers and impacts of land cover change. An interdisciplinary approach that integrates social, ecological, and spatial analysis is applied in this research. Findings of the research provide a documented dataset that can help researchers study the relationship between human activities and biotic processes in an urban setting, and contribute to sustainable urban development.
ContributorsZhang, Sainan (Author) / Boone, Christopher G. (Thesis advisor) / York, Abigail M. (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2013
Description
In order to analyze data from an instrument administered at multiple time points it is a common practice to form composites of the items at each wave and to fit a longitudinal model to the composites. The advantage of using composites of items is that smaller sample sizes are required in contrast to second order models that include the measurement and the structural relationships among the variables. However, the use of composites assumes that longitudinal measurement invariance holds; that is, it is assumed that that the relationships among the items and the latent variables remain constant over time. Previous studies conducted on latent growth models (LGM) have shown that when longitudinal metric invariance is violated, the parameter estimates are biased and that mistaken conclusions about growth can be made. The purpose of the current study was to examine the impact of non-invariant loadings and non-invariant intercepts on two longitudinal models: the LGM and the autoregressive quasi-simplex model (AR quasi-simplex). A second purpose was to determine if there are conditions in which researchers can reach adequate conclusions about stability and growth even in the presence of violations of invariance. A Monte Carlo simulation study was conducted to achieve the purposes. The method consisted of generating items under a linear curve of factors model (COFM) or under the AR quasi-simplex. Composites of the items were formed at each time point and analyzed with a linear LGM or an AR quasi-simplex model. The results showed that AR quasi-simplex model yielded biased path coefficients only in the conditions with large violations of invariance. The fit of the AR quasi-simplex was not affected by violations of invariance. In general, the growth parameter estimates of the LGM were biased under violations of invariance. Further, in the presence of non-invariant loadings the rejection rates of the hypothesis of linear growth increased as the proportion of non-invariant items and as the magnitude of violations of invariance increased. A discussion of the results and limitations of the study are provided as well as general recommendations.
ContributorsOlivera-Aguilar, Margarita (Author) / Millsap, Roger E. (Thesis advisor) / Levy, Roy (Committee member) / MacKinnon, David (Committee member) / West, Stephen G. (Committee member) / Arizona State University (Publisher)
Created2013
Description
We propose a novel solution to prevent cancer by developing a prophylactic cancer. Several sources of antigens for cancer vaccines have been published. Among these, antigens that contain a frame-shift (FS) peptide or viral peptide are quite attractive for a variety of reasons. FS sequences, from either mistake in RNA processing or in genomic DNA, may lead to generation of neo-peptides that are foreign to the immune system. Viral peptides presumably would originate from exogenous but integrated viral nucleic acid sequences. Both are non-self, therefore lessen concerns about development of autoimmunity. I have developed a bioinformatical approach to identify these aberrant transcripts in the cancer transcriptome. Their suitability for use in a vaccine is evaluated by establishing their frequencies and predicting possible epitopes along with their population coverage according to the prevalence of major histocompatibility complex (MHC) types. Viral transcripts and transcripts with FS mutations from gene fusion, insertion/deletion at coding microsatellite DNA, and alternative splicing were identified in NCBI Expressed Sequence Tag (EST) database. 48 FS chimeric transcripts were validated in 50 breast cell lines and 68 primary breast tumor samples with their frequencies from 4% to 98% by RT-PCR and sequencing confirmation. These 48 FS peptides, if translated and presented, could be used to protect more than 90% of the population in Northern America based on the prediction of epitopes derived from them. Furthermore, we synthesized 150 peptides that correspond to FS and viral peptides that we predicted would exist in tumor patients and we tested over 200 different cancer patient sera. We found a number of serological reactive peptide sequences in cancer patients that had little to no reactivity in healthy controls; strong support for the strength of our bioinformatic approach. This study describes a process used to identify aberrant transcripts that lead to a new source of antigens that can be tested and used in a prophylactic cancer vaccine. The vast amount of transcriptome data of various cancers from the Cancer Genome Atlas (TCGA) project will enhance our ability to further select better cancer antigen candidates.
ContributorsLee, HoJoon (Author) / Johnston, Stephen A. (Thesis advisor) / Kumar, Sudhir (Committee member) / Miller, Laurence (Committee member) / Stafford, Phillip (Committee member) / Sykes, Kathryn (Committee member) / Arizona State University (Publisher)
Created2012
Description
Research shows that general parenting practices (e.g., support and discipline), influence adolescent substance use. However, socialization theory suggests that parental socialization occurs not only through general parenting practices, but also through parents' attempts to influence specific behaviors and values. A growing literature supports links between substance-specific parenting and adolescent substance use. For adolescent alcohol use, there are considerable limitations and gaps within this literature. To address these limitations, the present study examined the factor structure of alcohol-specific parenting, investigated the determinants of alcohol-specific parenting, and explored its association with nondrinking adolescents' attitudes about alcohol use. Using a high-risk sample of nondrinking adolescents and their parents, the current study found three dimensions of alcohol-specific parenting using both adolescent and parent reports, but also found evidence of non-invariance across reporters. Results also revealed complex roles of parental alcohol use disorder (AUD; including recovered and current AUD), family history of AUD, and current drinking as determinants of the three dimensions of anti-alcohol parenting behaviors. Moreover, the current study showed that the effects of these determinants varied by the reporter of the parenting behavior. Finally, the current study found the dimensions of alcohol-specific parenting to be unique and significant predictors of nondrinking adolescents' attitudes about alcohol, over and above general parenting practices, parent AUD, and parent current drinking. Given its demonstrated distinctness from general parenting practices, its link with adolescent alcohol attitudes, and its potential malleability, alcohol-specific parenting may be an important complement to interventions targeting parents of adolescents.
ContributorsHandley, Elizabeth D (Author) / Chassin, Laurie (Thesis advisor) / MacKinnon, David (Committee member) / Crnic, Keith (Committee member) / Sandler, Irwin (Committee member) / Arizona State University (Publisher)
Created2012