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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
Salmonella enterica is a gastrointestinal (GI) pathogen that can cause systemic diseases. It invades the host through the GI tract and can induce powerful immune responses in addition to disease. Thus, it is considered as a promising candidate to use as oral live vaccine vectors. Scientists have been making great efforts to get a properly attenuated Salmonella vaccine strain for a long time, but could not achieve a balance between attenuation and immunogenicity. So the regulated delayed attenuation/lysis Salmonella vaccine vectors were proposed as a design to seek this balance. The research work is progressing steadily, but more improvements need to be made. As one of the possible improvements, the cyclic adenosine monophosphate (cAMP) -independent cAMP receptor protein (Crp*) is expected to protect the Crp-dependent crucial regulator, araC PBAD, in these vaccine designs from interference by glucose, which decreases synthesis of cAMP, and enhance the colonizing ability by and immunogenicity of the vaccine strains. In this study, the cAMP-independent crp gene mutation, crp-70, with or without araC PBAD promoter cassette, was introduced into existing Salmonella vaccine strains. Then the plasmid stability, growth rate, resistance to catabolite repression, colonizing ability, immunogenicity and protection to challenge of these new strains were compared with wild-type crp or araC PBAD crp strains using western blots, enzyme-linked immunosorbent assays (ELISA) and animal studies, so as to evaluate the effects of the crp-70 mutation on the vaccine strains. The performances of the crp-70 strains in some aspects were closed to or even exceeded the crp+ strains, but generally they did not exhibit the expected advantages compared to their wild-type parents. Crp-70 rescued the expression of araC PBAD fur from catabolite repression. The strain harboring araC PBAD crp-70 was severely affected by its slow growth, and its colonizing ability and immunogenicity was much weaker than the other strains. The Pcrp crp-70 strain showed relatively good ability in colonization and immune stimulation. Both the araC PBAD crp-70 and the Pcrp crp-70 strains could provide certain levels of protection against the challenge with virulent pneumococci, which were a little lower than for the crp+ strains.
ContributorsShao, Shihuan (Author) / Curtiss, Roy (Thesis advisor) / 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
Many researchers aspire to create robotics systems that assist humans in common office tasks, especially by taking over delivery and messaging tasks. For meaningful interactions to take place, a mobile robot must be able to identify the humans it interacts with and communicate successfully with them. It must also be able to successfully navigate the office environment. While mobile robots are well suited for navigating and interacting with elements inside a deterministic office environment, attempting to interact with human beings in an office environment remains a challenge due to the limits on the amount of cost-efficient compute power onboard the robot. In this work, I propose the use of remote cloud services to offload intensive interaction tasks. I detail the interactions required in an office environment and discuss the challenges faced when implementing a human-robot interaction platform in a stochastic office environment. I also experiment with cloud services for facial recognition, speech recognition, and environment navigation and discuss my results. As part of my thesis, I have implemented a human-robot interaction system utilizing cloud APIs into a mobile robot, enabling it to navigate the office environment, identify humans within the environment, and communicate with these humans.
ContributorsDSouza, Daniel Anand (Author) / Kambhampati, Subbarao (Thesis director) / Zhang, Yu (Committee member) / Computer Science and Engineering Program (Contributor) / School of Computing, Informatics, and Decision Systems Engineering (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Traditional Reinforcement Learning (RL) assumes to learn policies with respect to reward available from the environment but sometimes learning in a complex domain requires wisdom which comes from a wide range of experience. In behavior based robotics, it is observed that a complex behavior can be described by a combination of simpler behaviors. It is tempting to apply similar idea such that simpler behaviors can be combined in a meaningful way to tailor the complex combination. Such an approach would enable faster learning and modular design of behaviors. Complex behaviors can be combined with other behaviors to create even more advanced behaviors resulting in a rich set of possibilities. Similar to RL, combined behavior can keep evolving by interacting with the environment. The requirement of this method is to specify a reasonable set of simple behaviors. In this research, I present an algorithm that aims at combining behavior such that the resulting behavior has characteristics of each individual behavior. This approach has been inspired by behavior based robotics, such as the subsumption architecture and motor schema-based design. The combination algorithm outputs n weights to combine behaviors linearly. The weights are state dependent and change dynamically at every step in an episode. This idea is tested on discrete and continuous environments like OpenAI’s “Lunar Lander” and “Biped Walker”. Results are compared with related domains like Multi-objective RL, Hierarchical RL, Transfer learning, and basic RL. It is observed that the combination of behaviors is a novel way of learning which helps the agent achieve required characteristics. A combination is learned for a given state and so the agent is able to learn faster in an efficient manner compared to other similar approaches. Agent beautifully demonstrates characteristics of multiple behaviors which helps the agent to learn and adapt to the environment. Future directions are also suggested as possible extensions to this research.
ContributorsVora, Kevin Jatin (Author) / Zhang, Yu (Thesis advisor) / Yang, Yezhou (Committee member) / Praharaj, Sarbeswar (Committee member) / Arizona State University (Publisher)
Created2021
Description
Retinotopic map, the map between visual inputs on the retina and neuronal activation in brain visual areas, is one of the central topics in visual neuroscience. For human observers, the map is typically obtained by analyzing functional magnetic resonance imaging (fMRI) signals of cortical responses to slowly moving visual stimuli on the retina. Biological evidences show the retinotopic mapping is topology-preserving/topological (i.e. keep the neighboring relationship after human brain process) within each visual region.
Unfortunately, due to limited spatial resolution and the signal-noise ratio of fMRI, state of art retinotopic map is not topological.
The topic was to model the topology-preserving condition mathematically, fix non-topological retinotopic map with numerical methods, and improve the quality of retinotopic maps.
The impose of topological condition, benefits several applications.
With the topological retinotopic maps, one may have a better insight on human retinotopic maps, including better cortical magnification factor quantification, more precise description of retinotopic maps, and potentially better exam ways of in Ophthalmology clinic.
ContributorsTu, Yanshuai (Author) / Wang, Yalin (Thesis advisor) / Lu, Zhong-Lin (Committee member) / Crook, Sharon (Committee member) / Yang, Yezhou (Committee member) / Zhang, Yu (Committee member) / Arizona State University (Publisher)
Created2022
Description
Multiple robotic arms collaboration is to control multiple robotic arms to collaborate with each other to work on the same task. During the collaboration, theagent is required to avoid all possible collisions between each part of the robotic arms.
Thus, incentivizing collaboration and preventing collisions are the two principles which
are followed by the agent during the training process. Nowadays, more and more
applications, both in industry and daily lives, require at least two arms, instead of
requiring only a single arm. A dual-arm robot satisfies much more needs of different
types of tasks, such as folding clothes at home, making a hamburger in a grill or
picking and placing a product in a warehouse.
The applications done in this paper are all about object pushing. This thesis
focuses on how to train the agent to learn pushing an object away as far as possible.
Reinforcement Learning (RL), which is a type of Machine Learning (ML), is then
utilized in this paper to train the agent to generate optimal actions. Deep Deterministic
Policy Gradient (DDPG) and Hindsight Experience Replay (HER) are the two RL
methods used in this thesis.
ContributorsLin, Steve (Author) / Ben Amor, Hani (Thesis advisor) / Redkar, Sangram (Committee member) / Zhang, Yu (Committee member) / Arizona State University (Publisher)
Created2023
Description
Millimeter wave (mmWave) and massive multiple-input multiple-output (MIMO) systems are intrinsic components of 5G and beyond. These systems rely on using beamforming codebooks for both initial access and data transmission. Current beam codebooks, however, are not optimized for the given deployment, which can sometimes incur noticeable performance loss. To address these problems, in this dissertation, three novel machine learning (ML) based frameworks for site-specific analog beam codebook design are proposed. In the first framework, two special neural network-based architectures are designed for learning environment and hardware aware beam codebooks through supervised and self-supervised learning respectively. To avoid explicitly estimating the channels, in the second framework, a deep reinforcement learning-based architecture is developed. The proposed solution significantly relaxes the system requirements and is particularly interesting in scenarios where the channel acquisition is challenging. Building upon it, in the third framework, a sample-efficient online reinforcement learning-based beam codebook design algorithm that learns how to shape the beam patterns to null the interfering directions, without requiring any coordination with the interferers, is developed. In the last part of the dissertation, the proposed beamforming framework is further extended to tackle the beam focusing problem in near field wideband systems. %Specifically, the developed solution can achieve beam focusing without knowing the user position and can account for unknown and non-uniform array geometry. All the frameworks are numerically evaluated and the simulation results highlight their potential of learning site-specific codebooks that adapt to the deployment. Furthermore, a hardware proof-of-concept prototype based on mmWave phased arrays is built and used to evaluate the developed online beam learning solutions in realistic scenarios. The learned beam patterns, measured in an anechoic chamber, show the performance gains of the developed framework. All that highlights a promising ML-based beam/codebook optimization direction for practical and hardware-constrained mmWave and terahertz systems.
ContributorsZhang, Yu (Author) / Alkhateeb, Ahmed AA (Thesis advisor) / Tepedelenlioglu, Cihan CT (Committee member) / Bliss, Daniel DB (Committee member) / Dasarathy, Gautam GD (Committee member) / Arizona State University (Publisher)
Created2023
Description
In this thesis work, a novel learning approach to solving the problem of controllinga quadcopter (drone) swarm is explored. To deal with large sizes, swarm control is
often achieved in a distributed fashion by combining different behaviors such that
each behavior implements some desired swarm characteristics, such as avoiding ob-
stacles and staying close to neighbors. One common approach in distributed swarm
control uses potential fields. A limitation of this approach is that the potential fields
often depend statically on a set of control parameters that are manually specified a
priori. This paper introduces Dynamic Potential Fields for flexible swarm control.
These potential fields are modulated by a set of dynamic control parameters (DCPs)
that can change under different environment situations. Since the focus is only on
these DCPs, it simplifies the learning problem and makes it feasible for practical use.
This approach uses soft actor critic (SAC) where the actor only determines how to
modify DCPs in the current situation, resulting in more flexible swarm control. In
the results, this work will show that the DCP approach allows for the drones to bet-
ter traverse environments with obstacles compared to several state-of-the-art swarm
control methods with a fixed set of control parameters. This approach also obtained
a higher safety score commonly used to assess swarm behavior. A basic reinforce-
ment learning approach is compared to demonstrate faster convergence. Finally, an
ablation study is conducted to validate the design of this approach.
ContributorsFerraro, Calvin Shores (Author) / Zhang, Yu (Thesis advisor) / Ben Amor, Hani (Committee member) / Berman, Spring (Committee member) / Arizona State University (Publisher)
Created2022