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Description
In this thesis I introduce a new direction to computing using nonlinear chaotic dynamics. The main idea is rich dynamics of a chaotic system enables us to (1) build better computers that have a flexible instruction set, and (2) carry out computation that conventional computers are not good at it. Here I start from the theory, explaining how one can build a computing logic block using a chaotic system, and then I introduce a new theoretical analysis for chaos computing. Specifically, I demonstrate how unstable periodic orbits and a model based on them explains and predicts how and how well a chaotic system can do computation. Furthermore, since unstable periodic orbits and their stability measures in terms of eigenvalues are extractable from experimental times series, I develop a time series technique for modeling and predicting chaos computing from a given time series of a chaotic system. After building a theoretical framework for chaos computing I proceed to architecture of these chaos-computing blocks to build a sophisticated computing system out of them. I describe how one can arrange and organize these chaos-based blocks to build a computer. I propose a brand new computer architecture using chaos computing, which shifts the limits of conventional computers by introducing flexible instruction set. Our new chaos based computer has a flexible instruction set, meaning that the user can load its desired instruction set to the computer to reconfigure the computer to be an implementation for the desired instruction set. Apart from direct application of chaos theory in generic computation, the application of chaos theory to speech processing is explained and a novel application for chaos theory in speech coding and synthesizing is introduced. More specifically it is demonstrated how a chaotic system can model the natural turbulent flow of the air in the human speech production system and how chaotic orbits can be used to excite a vocal tract model. Also as another approach to build computing system based on nonlinear system, the idea of Logical Stochastic Resonance is studied and adapted to an autoregulatory gene network in the bacteriophage λ.
ContributorsKia, Behnam (Author) / Ditto, William (Thesis advisor) / Huang, Liang (Committee member) / Lai, Ying-Cheng (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2011
Description
In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human samples. As this takes place, a serendipitous opportunity has become evident. By the virtue that as one narrows the focus towards "single" protein targets (instead of entire proteomes) using pan-antibody-based enrichment techniques, a discovery science has emerged, so to speak. This is due to the largely unknown context in which "single" proteins exist in blood (i.e. polymorphisms, transcript variants, and posttranslational modifications) and hence, targeted proteomics has applications for established biomarkers. Furthermore, besides protein heterogeneity accounting for interferences with conventional immunometric platforms, it is becoming evident that this formerly hidden dimension of structural information also contains rich-pathobiological information. Consequently, targeted proteomics studies that aim to ascertain a protein's genuine presentation within disease- stratified populations and serve as a stepping-stone within a biomarker translational pipeline are of clinical interest. Roughly 128 million Americans are pre-diabetic, diabetic, and/or have kidney disease and public and private spending for treating these diseases is in the hundreds of billions of dollars. In an effort to create new solutions for the early detection and management of these conditions, described herein is the design, development, and translation of mass spectrometric immunoassays targeted towards diabetes and kidney disease. Population proteomics experiments were performed for the following clinically relevant proteins: insulin, C-peptide, RANTES, and parathyroid hormone. At least thirty-eight protein isoforms were detected. Besides the numerous disease correlations confronted within the disease-stratified cohorts, certain isoforms also appeared to be causally related to the underlying pathophysiology and/or have therapeutic implications. Technical advancements include multiplexed isoform quantification as well a "dual- extraction" methodology for eliminating non-specific proteins while simultaneously validating isoforms. Industrial efforts towards widespread clinical adoption are also described. Consequently, this work lays a foundation for the translation of mass spectrometric immunoassays into the clinical arena and simultaneously presents the most recent advancements concerning the mass spectrometric immunoassay approach.
ContributorsOran, Paul (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Ros, Alexandra (Committee member) / Williams, Peter (Committee member) / Arizona State University (Publisher)
Created2011
Description
Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay (MSIA) which has been one of the primary methods of biomarker discovery techniques. MSIA analyzes protein molecules as potential biomarkers using time of flight mass spectrometry (TOF-MS). Peak detection in TOF-MS is important for biomarker analysis and many other MS related application. Though many peak detection algorithms exist, most of them are based on heuristics models. One of the ways of detecting signal peaks is by deploying stochastic models of the signal and noise observations. Likelihood ratio test (LRT) detector, based on the Neyman-Pearson (NP) lemma, is an uniformly most powerful test to decision making in the form of a hypothesis test. The primary goal of this dissertation is to develop signal and noise models for the electrospray ionization (ESI) TOF-MS data. A new method is proposed for developing the signal model by employing first principles calculations based on device physics and molecular properties. The noise model is developed by analyzing MS data from careful experiments in the ESI mass spectrometer. A non-flat baseline in MS data is common. The reasons behind the formation of this baseline has not been fully comprehended. A new signal model explaining the presence of baseline is proposed, though detailed experiments are needed to further substantiate the model assumptions. Signal detection schemes based on these signal and noise models are proposed. A maximum likelihood (ML) method is introduced for estimating the signal peak amplitudes. The performance of the detection methods and ML estimation are evaluated with Monte Carlo simulation which shows promising results. An application of these methods is proposed for fractional abundance calculation for biomarker analysis, which is mathematically robust and fundamentally different than the current algorithms. Biomarker panels for type 2 diabetes and cardiovascular disease are analyzed using existing MS analysis algorithms. Finally, a support vector machine based multi-classification algorithm is developed for evaluating the biomarkers' effectiveness in discriminating type 2 diabetes and cardiovascular diseases and is shown to perform better than a linear discriminant analysis based classifier.
ContributorsBuddi, Sai (Author) / Taylor, Thomas (Thesis advisor) / Cochran, Douglas (Thesis advisor) / Nelson, Randall (Committee member) / Duman, Tolga (Committee member) / Arizona State University (Publisher)
Created2012
Description
Complex dynamical systems consisting interacting dynamical units are ubiquitous in nature and society. Predicting and reconstructing nonlinear dynamics of units and the complex interacting networks among them serves the base for the understanding of a variety of collective dynamical phenomena. I present a general method to address the two outstanding problems as a whole based solely on time-series measurements. The method is implemented by incorporating compressive sensing approach that enables an accurate reconstruction of complex dynamical systems in terms of both nodal equations that determines the self-dynamics of units and detailed coupling patterns among units. The representative advantages of the approach are (i) the sparse data requirement which allows for a successful reconstruction from limited measurements, and (ii) general applicability to identical and nonidentical nodal dynamics, and to networks with arbitrary interacting structure, strength and sizes. Another two challenging problem of significant interest in nonlinear dynamics: (i) predicting catastrophes in nonlinear dynamical systems in advance of their occurrences and (ii) predicting the future state for time-varying nonlinear dynamical systems, can be formulated and solved in the framework of compressive sensing using only limited measurements. Once the network structure can be inferred, the dynamics behavior on them can be investigated, for example optimize information spreading dynamics, suppress cascading dynamics and traffic congestion, enhance synchronization, game dynamics, etc. The results can yield insights to control strategies design in the real-world social and natural systems. Since 2004, there has been a tremendous amount of interest in graphene. The most amazing feature of graphene is that there exists linear energy-momentum relationship when energy is low. The quasi-particles inside the system can be treated as chiral, massless Dirac fermions obeying relativistic quantum mechanics. Therefore, the graphene provides one perfect test bed to investigate relativistic quantum phenomena, such as relativistic quantum chaotic scattering and abnormal electron paths induced by klein tunneling. This phenomenon has profound implications to the development of graphene based devices that require stable electronic properties.
ContributorsYang, Rui (Author) / Lai, Ying-Cheng (Thesis advisor) / Duman, Tolga M. (Committee member) / Akis, Richard (Committee member) / Huang, Liang (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
What can classical chaos do to quantum systems is a fundamental issue highly relevant to a number of branches in physics. The field of quantum chaos has been active for three decades, where the focus was on non-relativistic quantumsystems described by the Schr¨odinger equation. By developing an efficient method to solve the Dirac equation in the setting where relativistic particles can tunnel between two symmetric cavities through a potential barrier, chaotic cavities are found to suppress the spread in the tunneling rate. Tunneling rate for any given energy assumes a wide range that increases with the energy for integrable classical dynamics. However, for chaotic underlying dynamics, the spread is greatly reduced. A remarkable feature, which is a consequence of Klein tunneling, arise only in relativistc quantum systems that substantial tunneling exists even for particle energy approaching zero. Similar results are found in graphene tunneling devices, implying high relevance of relativistic quantum chaos to the development of such devices. Wave propagation through random media occurs in many physical systems, where interesting phenomena such as branched, fracal-like wave patterns can arise. The generic origin of these wave structures is currently a matter of active debate. It is of fundamental interest to develop a minimal, paradigmaticmodel that can generate robust branched wave structures. In so doing, a general observation in all situations where branched structures emerge is non-Gaussian statistics of wave intensity with an algebraic tail in the probability density function. Thus, a universal algebraic wave-intensity distribution becomes the criterion for the validity of any minimal model of branched wave patterns. Coexistence of competing species in spatially extended ecosystems is key to biodiversity in nature. Understanding the dynamical mechanisms of coexistence is a fundamental problem of continuous interest not only in evolutionary biology but also in nonlinear science. A continuous model is proposed for cyclically competing species and the effect of the interplay between the interaction range and mobility on coexistence is investigated. A transition from coexistence to extinction is uncovered with a non-monotonic behavior in the coexistence probability and switches between spiral and plane-wave patterns arise. Strong mobility can either promote or hamper coexistence, while absent in lattice-based models, can be explained in terms of nonlinear partial differential equations.
ContributorsNi, Xuan (Author) / Lai, Ying-Cheng (Thesis advisor) / Huang, Liang (Committee member) / Yu, Hongbin (Committee member) / Akis, Richard (Committee member) / Arizona State University (Publisher)
Created2012
Description
Background: National and international strategies to increase physical activity emphasize environmental and policy changes that can have widespread and long-lasting impact. Evidence from multiple countries using comparable methods is required to strengthen the evidence base for such initiatives. Because some environment and policy changes could have generalizable effects and others may depend on each country's context, only international studies using comparable methods can identify the relevant differences. Methods: Currently 12 countries are participating in the International Physical Activity and the Environment Network (IPEN) study. The IPEN Adult study design involves recruiting adult participants from neighborhoods with wide variations in environmental walkability attributes and socioeconomic status (SES). Results: Eleven of twelve countries are providing accelerometer data and 11 are providing GIS data. Current projections indicate that 14,119 participants will provide survey data on built environments and physical activity and 7145 are likely to provide objective data on both the independent and dependent variables. Though studies are highly comparable, some adaptations are required based on the local context. Conclusions: This study was designed to inform evidence-based international and country-specific physical activity policies and interventions to help prevent obesity and other chronic diseases that are high in developed countries and growing rapidly in developing countries.
ContributorsKerr, Jacqueline (Author) / Sallis, James F. (Author) / Owen, Neville (Author) / De Bourdeaudhuij, Ilse (Author) / Cerin, Ester (Author) / Sugiyama, Takemi (Author) / Reis, Rodrigo (Author) / Sarmiento, Olga (Author) / Froemel, Karel (Author) / Mitas, Josef (Author) / Troelsen, Jens (Author) / Christiansen, Lars Breum (Author) / Macfarlane, Duncan (Author) / Salvo, Deborah (Author) / Schofield, Grant (Author) / Badland, Hannah (Author) / Guillen-Grima, Francisco (Author) / Aguinaga-Ontoso, Ines (Author) / Davey, Rachel (Author) / Bauman, Adrian (Author) / Saelens, Brian (Author) / Riddoch, Chris (Author) / Ainsworth, Barbara (Author) / Pratt, Michael (Author) / Schmidt, Tom (Author) / Frank, Lawrence (Author) / Adams, Marc (Author) / Conway, Terry (Author) / Cain, Kelli (Author) / Van Dyck, Delfien (Author) / Bracy, Nicole (Author) / College of Health Solutions (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2013
Description
Background
Increasing empirical evidence supports associations between neighborhood environments and physical activity. However, since most studies were conducted in a single country, particularly western countries, the generalizability of associations in an international setting is not well understood. The current study examined whether associations between perceived attributes of neighborhood environments and physical activity differed by country.
Methods
Population representative samples from 11 countries on five continents were surveyed using comparable methodologies and measurement instruments. Neighborhood environment × country interactions were tested in logistic regression models with meeting physical activity recommendations as the outcome, adjusted for demographic characteristics. Country-specific associations were reported.
Results
Significant neighborhood environment attribute × country interactions implied some differences across countries in the association of each neighborhood attribute with meeting physical activity recommendations. Across the 11 countries, land-use mix and sidewalks had the most consistent associations with physical activity. Access to public transit, bicycle facilities, and low-cost recreation facilities had some associations with physical activity, but with less consistency across countries. There was little evidence supporting the associations of residential density and crime-related safety with physical activity in most countries.
Conclusion
There is evidence of generalizability for the associations of land use mix, and presence of sidewalks with physical activity. Associations of other neighborhood characteristics with physical activity tended to differ by country. Future studies should include objective measures of neighborhood environments, compare psychometric properties of reports across countries, and use better specified models to further understand the similarities and differences in associations across countries.
Increasing empirical evidence supports associations between neighborhood environments and physical activity. However, since most studies were conducted in a single country, particularly western countries, the generalizability of associations in an international setting is not well understood. The current study examined whether associations between perceived attributes of neighborhood environments and physical activity differed by country.
Methods
Population representative samples from 11 countries on five continents were surveyed using comparable methodologies and measurement instruments. Neighborhood environment × country interactions were tested in logistic regression models with meeting physical activity recommendations as the outcome, adjusted for demographic characteristics. Country-specific associations were reported.
Results
Significant neighborhood environment attribute × country interactions implied some differences across countries in the association of each neighborhood attribute with meeting physical activity recommendations. Across the 11 countries, land-use mix and sidewalks had the most consistent associations with physical activity. Access to public transit, bicycle facilities, and low-cost recreation facilities had some associations with physical activity, but with less consistency across countries. There was little evidence supporting the associations of residential density and crime-related safety with physical activity in most countries.
Conclusion
There is evidence of generalizability for the associations of land use mix, and presence of sidewalks with physical activity. Associations of other neighborhood characteristics with physical activity tended to differ by country. Future studies should include objective measures of neighborhood environments, compare psychometric properties of reports across countries, and use better specified models to further understand the similarities and differences in associations across countries.
ContributorsDing, Ding (Author) / Adams, Marc (Author) / Sallis, James F. (Author) / Norman, Gregory J. (Author) / Hovell, Melbourn F. (Author) / Chambers, Christina D. (Author) / Hofstetter, C. Richard (Author) / Bowles, Heather R. (Author) / Hagstromer, Maria (Author) / Craig, Cora L. (Author) / Fernando Gomez, Luis (Author) / De Bourdeaudhuij, Ilse (Author) / Macfarlane, Duncan J. (Author) / Ainsworth, Barbara (Author) / Bergman, Patrick (Author) / Bull, Fiona C. (Author) / Carr, Harriette (Author) / Klasson-Heggebo, Lena (Author) / Inoue, Shigeru (Author) / Murase, Norio (Author) / Matsudo, Sandra (Author) / Matsudo, Victor (Author) / McLean, Grant (Author) / Sjostrom, Michael (Author) / Tomten, Heidi (Author) / Lefevre, Johan (Author) / Volbekiene, Vida (Author) / Bauman, Adrian E. (Author) / College of Health Solutions (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2013-05-14
Description
Background
Neighborhood environment studies of physical activity (PA) have been mainly single-country focused. The International Prevalence Study (IPS) presented a rare opportunity to examine neighborhood features across countries. The purpose of this analysis was to: 1) detect international neighborhood typologies based on participants’ response patterns to an environment survey and 2) to estimate associations between neighborhood environment patterns and PA.
Methods
A Latent Class Analysis (LCA) was conducted on pooled IPS adults (N=11,541) aged 18 to 64 years old (mean=37.5 ±12.8 yrs; 55.6% women) from 11 countries including Belgium, Brazil, Canada, Colombia, Hong Kong, Japan, Lithuania, New Zealand, Norway, Sweden, and the U.S. This subset used the Physical Activity Neighborhood Environment Survey (PANES) that briefly assessed 7 attributes within 10–15 minutes walk of participants’ residences, including residential density, access to shops/services, recreational facilities, public transit facilities, presence of sidewalks and bike paths, and personal safety. LCA derived meaningful subgroups from participants’ response patterns to PANES items, and participants were assigned to neighborhood types. The validated short-form International Physical Activity Questionnaire (IPAQ) measured likelihood of meeting the 150 minutes/week PA guideline. To validate derived classes, meeting the guideline either by walking or total PA was regressed on neighborhood types using a weighted generalized linear regression model, adjusting for gender, age and country.
Results
A 5-subgroup solution fitted the dataset and was interpretable. Neighborhood types were labeled, “Overall Activity Supportive (52% of sample)”, “High Walkable and Unsafe with Few Recreation Facilities (16%)”, “Safe with Active Transport Facilities (12%)”, “Transit and Shops Dense with Few Amenities (15%)”, and “Safe but Activity Unsupportive (5%)”. Country representation differed by type (e.g., U.S. disproportionally represented “Safe but Activity Unsupportive”). Compared to the Safe but Activity Unsupportive, two types showed greater odds of meeting PA guideline for walking outcome (High Walkable and Unsafe with Few Recreation Facilities, OR= 2.26 (95% CI 1.18-4.31); Overall Activity Supportive, OR= 1.90 (95% CI 1.13-3.21). Significant but smaller odds ratios were also found for total PA.
Conclusions
Meaningful neighborhood patterns generalized across countries and explained practical differences in PA. These observational results support WHO/UN recommendations for programs and policies targeted to improve features of the neighborhood environment for PA.
Neighborhood environment studies of physical activity (PA) have been mainly single-country focused. The International Prevalence Study (IPS) presented a rare opportunity to examine neighborhood features across countries. The purpose of this analysis was to: 1) detect international neighborhood typologies based on participants’ response patterns to an environment survey and 2) to estimate associations between neighborhood environment patterns and PA.
Methods
A Latent Class Analysis (LCA) was conducted on pooled IPS adults (N=11,541) aged 18 to 64 years old (mean=37.5 ±12.8 yrs; 55.6% women) from 11 countries including Belgium, Brazil, Canada, Colombia, Hong Kong, Japan, Lithuania, New Zealand, Norway, Sweden, and the U.S. This subset used the Physical Activity Neighborhood Environment Survey (PANES) that briefly assessed 7 attributes within 10–15 minutes walk of participants’ residences, including residential density, access to shops/services, recreational facilities, public transit facilities, presence of sidewalks and bike paths, and personal safety. LCA derived meaningful subgroups from participants’ response patterns to PANES items, and participants were assigned to neighborhood types. The validated short-form International Physical Activity Questionnaire (IPAQ) measured likelihood of meeting the 150 minutes/week PA guideline. To validate derived classes, meeting the guideline either by walking or total PA was regressed on neighborhood types using a weighted generalized linear regression model, adjusting for gender, age and country.
Results
A 5-subgroup solution fitted the dataset and was interpretable. Neighborhood types were labeled, “Overall Activity Supportive (52% of sample)”, “High Walkable and Unsafe with Few Recreation Facilities (16%)”, “Safe with Active Transport Facilities (12%)”, “Transit and Shops Dense with Few Amenities (15%)”, and “Safe but Activity Unsupportive (5%)”. Country representation differed by type (e.g., U.S. disproportionally represented “Safe but Activity Unsupportive”). Compared to the Safe but Activity Unsupportive, two types showed greater odds of meeting PA guideline for walking outcome (High Walkable and Unsafe with Few Recreation Facilities, OR= 2.26 (95% CI 1.18-4.31); Overall Activity Supportive, OR= 1.90 (95% CI 1.13-3.21). Significant but smaller odds ratios were also found for total PA.
Conclusions
Meaningful neighborhood patterns generalized across countries and explained practical differences in PA. These observational results support WHO/UN recommendations for programs and policies targeted to improve features of the neighborhood environment for PA.
ContributorsAdams, Marc (Author) / Ding, Ding (Author) / Sallis, James F. (Author) / Bowles, Heather R. (Author) / Ainsworth, Barbara (Author) / Bergman, Patrick (Author) / Bull, Fiona C. (Author) / Carr, Harriette (Author) / Craig, Cora L. (Author) / De Bourdeaudhuij, Ilse (Author) / Fernando Gomez, Luis (Author) / Hagstromer, Maria (Author) / Klasson-Heggebo, Lena (Author) / Inoue, Shigeru (Author) / Lefevre, Johan (Author) / Macfarlane, Duncan J. (Author) / Matsudo, Sandra (Author) / Matsudo, Victor (Author) / McLean, Grant (Author) / Murase, Norio (Author) / Sjostrom, Michael (Author) / Tomten, Heidi (Author) / Volbekiene, Vida (Author) / Bauman, Adrian (Author) / College of Health Solutions (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2013-03-07
Description
Massive glycerol cluster ions with many charges (~ 106 Da, ~ ±100 charges) have been generated by electrospray to bombard biomolecules and biological sample surfaces. The low impact energy per nucleon facilitates intact sputtering and ionization of biomolecules which can be subsequently imaged. Various lipids, peptides and proteins have been studied. The primary cluster ion source has been coupled with an ion-microscope imaging mass spectrometer (TRIFT-1, Physical Electronics). A lateral resolution of ~3µm has been demonstrated, which is acceptable for sub-cellular imaging of animal cells (e.g. single cancer cell imaging in early diagnosis). Since the available amount of target molecules per pixel is limited in biological samples, the measurement of useful ion yields (ratio of detected molecular ion counts to the sample molecules sputtered) is important to determine whether enough ion counts per pixel can be obtained. The useful ion yields of several lipids and peptides are in the 1-3×10-5 range. A 3×3 µm2lipid bilayer can produce ~260 counts/pixel for a meaningful 3×3 µm2 pixel ion image. This method can probably be used in cell imaging in the future, when there is a change in the lipid contents of the cell membrane (e.g. cancer cells vs. normal cells).
ContributorsZhang, Jitao (Author) / Williams, Peter (Thesis advisor) / Hayes, Mark (Committee member) / Nelson, Randall (Committee member) / Arizona State University (Publisher)
Created2015