Matching Items (80)
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
Mostly, manufacturing tolerance charts are used these days for manufacturing tolerance transfer but these have the limitation of being one dimensional only. Some research has been undertaken for the three dimensional geometric tolerances but it is too theoretical and yet to be ready for operator level usage. In this research, a new three dimensional model for tolerance transfer in manufacturing process planning is presented that is user friendly in the sense that it is built upon the Coordinate Measuring Machine (CMM) readings that are readily available in any decent manufacturing facility. This model can take care of datum reference change between non orthogonal datums (squeezed datums), non-linearly oriented datums (twisted datums) etc. Graph theoretic approach based upon ACIS, C++ and MFC is laid out to facilitate its implementation for automation of the model. A totally new approach to determining dimensions and tolerances for the manufacturing process plan is also presented. Secondly, a new statistical model for the statistical tolerance analysis based upon joint probability distribution of the trivariate normal distributed variables is presented. 4-D probability Maps have been developed in which the probability value of a point in space is represented by the size of the marker and the associated color. Points inside the part map represent the pass percentage for parts manufactured. The effect of refinement with form and orientation tolerance is highlighted by calculating the change in pass percentage with the pass percentage for size tolerance only. Delaunay triangulation and ray tracing algorithms have been used to automate the process of identifying the points inside and outside the part map. Proof of concept software has been implemented to demonstrate this model and to determine pass percentages for various cases. The model is further extended to assemblies by employing convolution algorithms on two trivariate statistical distributions to arrive at the statistical distribution of the assembly. Map generated by using Minkowski Sum techniques on the individual part maps is superimposed on the probability point cloud resulting from convolution. Delaunay triangulation and ray tracing algorithms are employed to determine the assembleability percentages for the assembly.
ContributorsKhan, M Nadeem Shafi (Author) / Phelan, Patrick E (Thesis advisor) / Montgomery, Douglas C. (Committee member) / Farin, Gerald (Committee member) / Roberts, Chell (Committee member) / Henderson, Mark (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
It is common in the analysis of data to provide a goodness-of-fit test to assess the performance of a model. In the analysis of contingency tables, goodness-of-fit statistics are frequently employed when modeling social science, educational or psychological data where the interest is often directed at investigating the association among multi-categorical variables. Pearson's chi-squared statistic is well-known in goodness-of-fit testing, but it is sometimes considered to produce an omnibus test as it gives little guidance to the source of poor fit once the null hypothesis is rejected. However, its components can provide powerful directional tests. In this dissertation, orthogonal components are used to develop goodness-of-fit tests for models fit to the counts obtained from the cross-classification of multi-category dependent variables. Ordinal categories are assumed. Orthogonal components defined on marginals are obtained when analyzing multi-dimensional contingency tables through the use of the QR decomposition. A subset of these orthogonal components can be used to construct limited-information tests that allow one to identify the source of lack-of-fit and provide an increase in power compared to Pearson's test. These tests can address the adverse effects presented when data are sparse. The tests rely on the set of first- and second-order marginals jointly, the set of second-order marginals only, and the random forest method, a popular algorithm for modeling large complex data sets. The performance of these tests is compared to the likelihood ratio test as well as to tests based on orthogonal polynomial components. The derived goodness-of-fit tests are evaluated with studies for detecting two- and three-way associations that are not accounted for by a categorical variable factor model with a single latent variable. In addition the tests are used to investigate the case when the model misspecification involves parameter constraints for large and sparse contingency tables. The methodology proposed here is applied to data from the 38th round of the State Survey conducted by the Institute for Public Policy and Michigan State University Social Research (2005) . The results illustrate the use of the proposed techniques in the context of a sparse data set.
ContributorsMilovanovic, Jelena (Author) / Young, Dennis (Thesis advisor) / Reiser, Mark R. (Thesis advisor) / Wilson, Jeffrey (Committee member) / Eubank, Randall (Committee member) / Yang, Yan (Committee member) / Arizona State University (Publisher)
Created2011
Description
Nowadays product reliability becomes the top concern of the manufacturers and customers always prefer the products with good performances under long period. In order to estimate the lifetime of the product, accelerated life testing (ALT) is introduced because most of the products can last years even decades. Much research has been done in the ALT area and optimal design for ALT is a major topic. This dissertation consists of three main studies. First, a methodology of finding optimal design for ALT with right censoring and interval censoring have been developed and it employs the proportional hazard (PH) model and generalized linear model (GLM) to simplify the computational process. A sensitivity study is also given to show the effects brought by parameters to the designs. Second, an extended version of I-optimal design for ALT is discussed and then a dual-objective design criterion is defined and showed with several examples. Also in order to evaluate different candidate designs, several graphical tools are developed. Finally, when there are more than one models available, different model checking designs are discussed.
ContributorsYang, Tao (Author) / Pan, Rong (Thesis advisor) / Montgomery, Douglas C. (Committee member) / Borror, Connie (Committee member) / Rigdon, Steve (Committee member) / Arizona State University (Publisher)
Created2013
Description
During the initial stages of experimentation, there are usually a large number of factors to be investigated. Fractional factorial (2^(k-p)) designs are particularly useful during this initial phase of experimental work. These experiments often referred to as screening experiments help reduce the large number of factors to a smaller set. The 16 run regular fractional factorial designs for six, seven and eight factors are in common usage. These designs allow clear estimation of all main effects when the three-factor and higher order interactions are negligible, but all two-factor interactions are aliased with each other making estimation of these effects problematic without additional runs. Alternatively, certain nonregular designs called no-confounding (NC) designs by Jones and Montgomery (Jones & Montgomery, Alternatives to resolution IV screening designs in 16 runs, 2010) partially confound the main effects with the two-factor interactions but do not completely confound any two-factor interactions with each other. The NC designs are useful for independently estimating main effects and two-factor interactions without additional runs. While several methods have been suggested for the analysis of data from nonregular designs, stepwise regression is familiar to practitioners, available in commercial software, and is widely used in practice. Given that an NC design has been run, the performance of stepwise regression for model selection is unknown. In this dissertation I present a comprehensive simulation study evaluating stepwise regression for analyzing both regular fractional factorial and NC designs. Next, the projection properties of the six, seven and eight factor NC designs are studied. Studying the projection properties of these designs allows the development of analysis methods to analyze these designs. Lastly the designs and projection properties of 9 to 14 factor NC designs onto three and four factors are presented. Certain recommendations are made on analysis methods for these designs as well.
ContributorsShinde, Shilpa (Author) / Montgomery, Douglas C. (Thesis advisor) / Borror, Connie (Committee member) / Fowler, John (Committee member) / Jones, Bradley (Committee member) / Arizona State University (Publisher)
Created2012
Description
This dissertation explores different methodologies for combining two popular design paradigms in the field of computer experiments. Space-filling designs are commonly used in order to ensure that there is good coverage of the design space, but they may not result in good properties when it comes to model fitting. Optimal designs traditionally perform very well in terms of model fitting, particularly when a polynomial is intended, but can result in problematic replication in the case of insignificant factors. By bringing these two design types together, positive properties of each can be retained while mitigating potential weaknesses. Hybrid space-filling designs, generated as Latin hypercubes augmented with I-optimal points, are compared to designs of each contributing component. A second design type called a bridge design is also evaluated, which further integrates the disparate design types. Bridge designs are the result of a Latin hypercube undergoing coordinate exchange to reach constrained D-optimality, ensuring that there is zero replication of factors in any one-dimensional projection. Lastly, bridge designs were augmented with I-optimal points with two goals in mind. Augmentation with candidate points generated assuming the same underlying analysis model serves to reduce the prediction variance without greatly compromising the space-filling property of the design, while augmentation with candidate points generated assuming a different underlying analysis model can greatly reduce the impact of model misspecification during the design phase. Each of these composite designs are compared to pure space-filling and optimal designs. They typically out-perform pure space-filling designs in terms of prediction variance and alphabetic efficiency, while maintaining comparability with pure optimal designs at small sample size. This justifies them as excellent candidates for initial experimentation.
ContributorsKennedy, Kathryn (Author) / Montgomery, Douglas C. (Thesis advisor) / Johnson, Rachel T. (Thesis advisor) / Fowler, John W (Committee member) / Borror, Connie M. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Nonregular screening designs can be an economical alternative to traditional resolution IV 2^(k-p) fractional factorials. Recently 16-run nonregular designs, referred to as no-confounding designs, were introduced in the literature. These designs have the property that no pair of main effect (ME) and two-factor interaction (2FI) estimates are completely confounded. In this dissertation, orthogonal arrays were evaluated with many popular design-ranking criteria in order to identify optimal 20-run and 24-run no-confounding designs. Monte Carlo simulation was used to empirically assess the model fitting effectiveness of the recommended no-confounding designs. The results of the simulation demonstrated that these new designs, particularly the 24-run designs, are successful at detecting active effects over 95% of the time given sufficient model effect sparsity. The final chapter presents a screening design selection methodology, based on decision trees, to aid in the selection of a screening design from a list of published options. The methodology determines which of a candidate set of screening designs has the lowest expected experimental cost.
ContributorsStone, Brian (Author) / Montgomery, Douglas C. (Thesis advisor) / Silvestrini, Rachel T. (Committee member) / Fowler, John W (Committee member) / Borror, Connie M. (Committee member) / Arizona State University (Publisher)
Created2013
Description
A P-value based method is proposed for statistical monitoring of various types of profiles in phase II. The performance of the proposed method is evaluated by the average run length criterion under various shifts in the intercept, slope and error standard deviation of the model. In our proposed approach, P-values are computed at each level within a sample. If at least one of the P-values is less than a pre-specified significance level, the chart signals out-of-control. The primary advantage of our approach is that only one control chart is required to monitor several parameters simultaneously: the intercept, slope(s), and the error standard deviation. A comprehensive comparison of the proposed method and the existing KMW-Shewhart method for monitoring linear profiles is conducted. In addition, the effect that the number of observations within a sample has on the performance of the proposed method is investigated. The proposed method was also compared to the T^2 method discussed in Kang and Albin (2000) for multivariate, polynomial, and nonlinear profiles. A simulation study shows that overall the proposed P-value method performs satisfactorily for different profile types.
ContributorsAdibi, Azadeh (Author) / Montgomery, Douglas C. (Thesis advisor) / Borror, Connie (Thesis advisor) / Li, Jing (Committee member) / Zhang, Muhong (Committee member) / Arizona State University (Publisher)
Created2013