Matching Items (493)
Description
This dissertation is to address product design optimization including reliability-based design optimization (RBDO) and robust design with epistemic uncertainty. It is divided into four major components as outlined below. Firstly, a comprehensive study of uncertainties is performed, in which sources of uncertainty are listed, categorized and the impacts are discussed. Epistemic uncertainty is of interest, which is due to lack of knowledge and can be reduced by taking more observations. In particular, the strategies to address epistemic uncertainties due to implicit constraint function are discussed. Secondly, a sequential sampling strategy to improve RBDO under implicit constraint function is developed. In modern engineering design, an RBDO task is often performed by a computer simulation program, which can be treated as a black box, as its analytical function is implicit. An efficient sampling strategy on learning the probabilistic constraint function under the design optimization framework is presented. The method is a sequential experimentation around the approximate most probable point (MPP) at each step of optimization process. It is compared with the methods of MPP-based sampling, lifted surrogate function, and non-sequential random sampling. Thirdly, a particle splitting-based reliability analysis approach is developed in design optimization. In reliability analysis, traditional simulation methods such as Monte Carlo simulation may provide accurate results, but are often accompanied with high computational cost. To increase the efficiency, particle splitting is integrated into RBDO. It is an improvement of subset simulation with multiple particles to enhance the diversity and stability of simulation samples. This method is further extended to address problems with multiple probabilistic constraints and compared with the MPP-based methods. Finally, a reliability-based robust design optimization (RBRDO) framework is provided to integrate the consideration of design reliability and design robustness simultaneously. The quality loss objective in robust design, considered together with the production cost in RBDO, are used formulate a multi-objective optimization problem. With the epistemic uncertainty from implicit performance function, the sequential sampling strategy is extended to RBRDO, and a combined metamodel is proposed to tackle both controllable variables and uncontrollable variables. The solution is a Pareto frontier, compared with a single optimal solution in RBDO.
ContributorsZhuang, Xiaotian (Author) / Pan, Rong (Thesis advisor) / Montgomery, Douglas C. (Committee member) / Zhang, Muhong (Committee member) / Du, Xiaoping (Committee member) / Arizona State University (Publisher)
Created2012
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
In recent years, service oriented computing (SOC) has become a widely accepted paradigm for the development of distributed applications such as web services, grid computing and cloud computing systems. In service-based systems (SBS), multiple service requests with specific performance requirements make services compete for system resources. IT service providers need to allocate resources to services so the performance requirements of customers can be satisfied. Workload and performance models are required for efficient resource management and service performance assurance in SBS. This dissertation develops two methods to understand and model the cause-effect relations of service-related activities with resources workload and service performance. Part one presents an empirical method that requires the collection of system dynamics data and the application of statistical analyses. The results show that the method is capable to: 1) uncover the impacts of services on resource workload and service performance, 2) identify interaction effects of multiple services running concurrently, 3) gain insights about resource and performance tradeoffs of services, and 4) build service workload and performance models. In part two, the empirical method is used to investigate the impacts of services, security mechanisms and cyber attacks on resources workload and service performance. The information obtained is used to: 1) uncover interaction effects of services, security mechanisms and cyber attacks, 2) identify tradeoffs within limits of system resources, and 3) develop general/specific strategies for system survivability. Finally, part three presents a framework based on the usage profiles of services competing for resources and the resource-sharing schemes. The framework is used to: 1) uncover the impacts of service parameters (e.g. arrival distribution, execution time distribution, priority, workload intensity, scheduling algorithm) on workload and performance, and 2) build service workload and performance models at individual resources. The estimates obtained from service workload and performance models at individual resources can be aggregated to obtain overall estimates of services through multiple system resources. The workload and performance models of services obtained through both methods can be used for the efficient resource management and service performance assurance in SBS.
ContributorsMartinez Aranda, Billibaldo (Author) / Ye, Nong (Thesis advisor) / Wu, Tong (Committee member) / Sarjoughian, Hessam S. (Committee member) / Pan, Rong (Committee member) / Arizona State University (Publisher)
Created2012
Description
This dissertation presents methods for addressing research problems that currently can only adequately be solved using Quality Reliability Engineering (QRE) approaches especially accelerated life testing (ALT) of electronic printed wiring boards with applications to avionics circuit boards. The methods presented in this research are generally applicable to circuit boards, but the data generated and their analysis is for high performance avionics. Avionics equipment typically requires 20 years expected life by aircraft equipment manufacturers and therefore ALT is the only practical way of performing life test estimates. Both thermal and vibration ALT induced failure are performed and analyzed to resolve industry questions relating to the introduction of lead-free solder product and processes into high reliability avionics. In chapter 2, thermal ALT using an industry standard failure machine implementing Interconnect Stress Test (IST) that simulates circuit board life data is compared to real production failure data by likelihood ratio tests to arrive at a mechanical theory. This mechanical theory results in a statistically equivalent energy bound such that failure distributions below a specific energy level are considered to be from the same distribution thus allowing testers to quantify parameter setting in IST prior to life testing. In chapter 3, vibration ALT comparing tin-lead and lead-free circuit board solder designs involves the use of the likelihood ratio (LR) test to assess both complete failure data and S-N curves to present methods for analyzing data. Failure data is analyzed using Regression and two-way analysis of variance (ANOVA) and reconciled with the LR test results that indicating that a costly aging pre-process may be eliminated in certain cases. In chapter 4, vibration ALT for side-by-side tin-lead and lead-free solder black box designs are life tested. Commercial models from strain data do not exist at the low levels associated with life testing and need to be developed because testing performed and presented here indicate that both tin-lead and lead-free solders are similar. In addition, earlier failures due to vibration like connector failure modes will occur before solder interconnect failures.
ContributorsJuarez, Joseph Moses (Author) / Montgomery, Douglas C. (Thesis advisor) / Borror, Connie M. (Thesis advisor) / Gel, Esma (Committee member) / Mignolet, Marc (Committee member) / Pan, Rong (Committee member) / Arizona State University (Publisher)
Created2012
Description
Immunosignaturing is a technology that allows the humoral immune response to be observed through the binding of antibodies to random sequence peptides. The immunosignaturing microarray is based on complex mixtures of antibodies binding to arrays of random sequence peptides in a multiplexed fashion. There are computational and statistical challenges to the analysis of immunosignaturing data. The overall aim of my dissertation is to develop novel computational and statistical methods for immunosignaturing data to access its potential for diagnostics and drug discovery. Firstly, I discovered that a classification algorithm Naive Bayes which leverages the biological independence of the probes on our array in such a way as to gather more information outperforms other classification algorithms due to speed and accuracy. Secondly, using this classifier, I then tested the specificity and sensitivity of immunosignaturing platform for its ability to resolve four different diseases (pancreatic cancer, pancreatitis, type 2 diabetes and panIN) that target the same organ (pancreas). These diseases were separated with >90% specificity from controls and from each other. Thirdly, I observed that the immunosignature of type 2 diabetes and cardiovascular complications are unique, consistent, and reproducible and can be separated by 100% accuracy from controls. But when these two complications arise in the same person, the resultant immunosignature is quite different in that of individuals with only one disease. I developed a method to trace back from informative random peptides in disease signatures to the potential antigen(s). Hence, I built a decipher system to trace random peptides in type 1 diabetes immunosignature to known antigens. Immunosignaturing, unlike the ELISA, has the ability to not only detect the presence of response but also absence of response during a disease. I observed, not only higher but also lower peptides intensities can be mapped to antigens in type 1 diabetes. To study immunosignaturing potential for population diagnostics, I studied effect of age, gender and geographical location on immunosignaturing data. For its potential to be a health monitoring technology, I proposed a single metric Coefficient of Variation that has shown potential to change significantly when a person enters a disease state.
ContributorsKukreja, Muskan (Author) / Johnston, Stephen Albert (Thesis advisor) / Stafford, Phillip (Committee member) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2012
Description
Temporal data are increasingly prevalent and important in analytics. Time series (TS) data are chronological sequences of observations and an important class of temporal data. Fields such as medicine, finance, learning science and multimedia naturally generate TS data. Each series provide a high-dimensional data vector that challenges the learning of the relevant patterns This dissertation proposes TS representations and methods for supervised TS analysis. The approaches combine new representations that handle translations and dilations of patterns with bag-of-features strategies and tree-based ensemble learning. This provides flexibility in handling time-warped patterns in a computationally efficient way. The ensemble learners provide a classification framework that can handle high-dimensional feature spaces, multiple classes and interaction between features. The proposed representations are useful for classification and interpretation of the TS data of varying complexity. The first contribution handles the problem of time warping with a feature-based approach. An interval selection and local feature extraction strategy is proposed to learn a bag-of-features representation. This is distinctly different from common similarity-based time warping. This allows for additional features (such as pattern location) to be easily integrated into the models. The learners have the capability to account for the temporal information through the recursive partitioning method. The second contribution focuses on the comprehensibility of the models. A new representation is integrated with local feature importance measures from tree-based ensembles, to diagnose and interpret time intervals that are important to the model. Multivariate time series (MTS) are especially challenging because the input consists of a collection of TS and both features within TS and interactions between TS can be important to models. Another contribution uses a different representation to produce computationally efficient strategies that learn a symbolic representation for MTS. Relationships between the multiple TS, nominal and missing values are handled with tree-based learners. Applications such as speech recognition, medical diagnosis and gesture recognition are used to illustrate the methods. Experimental results show that the TS representations and methods provide better results than competitive methods on a comprehensive collection of benchmark datasets. Moreover, the proposed approaches naturally provide solutions to similarity analysis, predictive pattern discovery and feature selection.
ContributorsBaydogan, Mustafa Gokce (Author) / Runger, George C. (Thesis advisor) / Atkinson, Robert (Committee member) / Gel, Esma (Committee member) / Pan, Rong (Committee member) / Arizona State University (Publisher)
Created2012
Description
This dissertation presents methods for the evaluation of ocular surface protection during natural blink function. The evaluation of ocular surface protection is especially important in the diagnosis of dry eye and the evaluation of dry eye severity in clinical trials. Dry eye is a highly prevalent disease affecting vast numbers (between 11% and 22%) of an aging population. There is only one approved therapy with limited efficacy, which results in a huge unmet need. The reason so few drugs have reached approval is a lack of a recognized therapeutic pathway with reproducible endpoints. While the interplay between blink function and ocular surface protection has long been recognized, all currently used evaluation techniques have addressed blink function in isolation from tear film stability, the gold standard of which is Tear Film Break-Up Time (TFBUT). In the first part of this research a manual technique of calculating ocular surface protection during natural blink function through the use of video analysis is developed and evaluated for it's ability to differentiate between dry eye and normal subjects, the results are compared with that of TFBUT. In the second part of this research the technique is improved in precision and automated through the use of video analysis algorithms. This software, called the OPI 2.0 System, is evaluated for accuracy and precision, and comparisons are made between the OPI 2.0 System and other currently recognized dry eye diagnostic techniques (e.g. TFBUT). In the third part of this research the OPI 2.0 System is deployed for use in the evaluation of subjects before, immediately after and 30 minutes after exposure to a controlled adverse environment (CAE), once again the results are compared and contrasted against commonly used dry eye endpoints. The results demonstrate that the evaluation of ocular surface protection using the OPI 2.0 System offers superior accuracy to the current standard, TFBUT.
ContributorsAbelson, Richard (Author) / Montgomery, Douglas C. (Thesis advisor) / Borror, Connie (Committee member) / Shunk, Dan (Committee member) / Pan, Rong (Committee member) / Arizona State University (Publisher)
Created2012
Description
Lung cancer is the leading cause of cancer-related deaths in the US. Low-dose computed tomography (LDCT) scans are speculated to reduce lung cancer mortality. However LDCT scans impose multiple risks including false-negative results, false- positive results, overdiagnosis, and cancer due to repeated exposure to radiation. Immunosignaturing is a new method proposed to screen and detect lung cancer, eliminating the risks associated with LDCT scans. Known and blinded primary blood sera from participants with lung cancer and no cancer were run on peptide microarrays and analyzed. Immunosignatures for each known sample collectively indicated 120 peptides unique to lung cancer and non-cancer participants. These 120 peptides were used to determine the status of the blinded samples. Verification of the results from Vanderbilt is pending.
ContributorsNguyen, Geneva Trieu (Author) / Woodbury, Neal (Thesis director) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
Cancer remains one of the leading killers throughout the world. Death and disability due to lung cancer in particular accounts for one of the largest global economic burdens a disease presents. The burden on third-world countries is especially large due to the unusually large financial stress that comes from late tumor detection and expensive treatment options. Early detection using inexpensive techniques may relieve much of the burden throughout the world, not just in more developed countries. I examined the immune responses of lung cancer patients using immunosignatures – patterns of reactivity between host serum antibodies and random peptides. Immunosignatures reveal disease-specific patterns that are very reproducible. Immunosignaturing is a chip-based method that has the ability to display the antibody diversity from individual sera sample with low cost. Immunosignaturing is a medical diagnostic test that has many applications in current medical research and in diagnosis. From a previous clinical study, patients diagnosed for lung cancer were tested for their immunosignature vs. healthy non-cancer volunteers. The pattern of reactivity against the random peptides (the ‘immunosignature’) revealed common signals in cancer patients, absent from healthy controls. My study involved the search for common amino acid motifs in the cancer-specific peptides. My search through the hundreds of ‘hits’ revealed certain motifs that were repeated more times than expected by random chance. The amino acids that were the most conserved in each set include tryptophan, aspartic acid, glutamic acid, proline, alanine, serine, and lysine. The most overall conserved amino acid observed between each set was D - aspartic acid. The motifs were short (no more than 5-6 amino acids in a row), but the total number of motifs I identified was large enough to assure significance. I utilized Excel to organize the large peptide sequence libraries, then CLUSTALW to cluster similar-sequence peptides, then GLAM2 to find common themes in groups of peptides. In so doing, I found sequences that were also present in translated cancer expression libraries (RNA) that matched my motifs, suggesting that immunosignatures can find cancer-specific antigens that can be both diagnostic and potentially therapeutic.
ContributorsShiehzadegan, Shima (Author) / Johnston, Stephen (Thesis director) / Stafford, Phillip (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Methicillin-Resistant Staphylococcus aureus (MRSA) infections are a major challenge to healthcare professionals. Treatment of MRSA is expensive, and otherwise avoidable deaths occur every year in the United States due to MRSA infections. Additionally, such infections lengthen patients’ stays in hospitals, keeping them out of work and adversely affecting the economy. Beta lactam antibiotics used to be highly effective against S. aureus infections, but resistance mechanisms have rendered methicillin, oxacillin, and other beta lactam antibiotics ineffective against these infections. A promising avenue for MRSA treatment lies in the use of synthetic antibodies—molecules that bind with specificity to a given compound. Synbody 14 is an example of such a synbody, and has been designed with MRSA treatment in mind. Mouse model studies have even associated Syn14 treatment with reduced weight loss and morbidity in MRSA-infected mice. In this experiment, in vitro activity of Syn 14 and oxacillin was assessed. Early experiments measured Syn 14 and oxacillin’s effectiveness in inhibiting colony growth in growth media, mouse serum, and mouse blood. Syn14 and oxacillin had limited efficacy against USA300 strain MRSA, though interestingly it was noted that Syn14 outperformed oxacillin in mouse serum and whole mouse blood, indicating the benefits of its binding properties. A second experiment measured the impact that a mix of oxacillin and Syn 14 had on colony growth, as well as the effect of adding them simultaneously or one after the other. While use of either bactericidal alone did not show a major inhibitory effect on USA300 MRSA colony growth, their use in combination showed major decreases in colony growth. Moreover, it was found that unlike other combination therapies, Syn14 and oxacillin did not require simultaneous addition to MRSA cells to achieve inhibition of cell growth. They merely required that Syn14 be added first. This result suggests Syn14’s possible utility in therapeutic settings, as the time insensitivity of synergy removes a major hurdle to clinical use—the difficulty in ensuring that two drugs reach an affected area at the same time. Syn14 remains a promising antimicrobial agent, and further study should focus on its precise mechanism of action and suitability in clinical treatment of MRSA infections.
ContributorsMichael, Alexander (Author) / Diehnelt, Chris (Thesis director) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05