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Description
In somatic cells, the mitotic spindle apparatus is centrosomal and several isoforms of Protein Kinase C (PKC) have been associated with the mitotic spindle, but their role in stabilizing the mitotic spindle is unclear. Other protein kinases such as, Glycogen Synthase Kinase 3â (GSK3â) also have been shown to be associated with the mitotic spindle. In the study in chapter 2, we show the enrichment of active (phosphorylated) PKCæ at the centrosomal region of the spindle apparatus in metaphase stage of 3T3 cells. In order to understand whether the two kinases, PKC and GSK3â are associated with the mitotic spindle, first, the co-localization and close molecular proximity of PKC isoforms with GSK3â was studied in metaphase cells. Second, the involvement of inactive GSK3â in maintaining an intact mitotic spindle was shown. Third, this study showed that addition of a phospho-PKCæ specific inhibitor to cells can disrupt the mitotic spindle microtubules. The mitotic spindle at metaphase in mouse fibroblasts appears to be maintained by PKCæ acting through GSK3â. The MAPK pathway has been implicated in various functions related to cell cycle regulation. MAPKK (MEK) is part of this pathway and the extracellular regulated kinase (ERK) is its known downstream target. GSK3â and PKCæ also have been implicated in cell cycle regulation. In the study in chapter 3, we tested the effects of inhibiting MEK on the activities of ERK, GSK3â, PKCæ, and á-tubulin. Results from this study indicate that inhibition of MEK did not inhibit GSK3â and PKCæ enrichment at the centrosomes. However, the mitotic spindle showed a reduction in the pixel intensity of microtubules and also a reduction in the number of cells in each of the M-phase stages. A peptide activation inhibitor of ERK was also used. Our results indicated a decrease in mitotic spindle microtubules and an absence of cells in most of the M-phase stages. GSK3â and PKCæ enrichment were however not inhibited at the centrosomes. Taken together, the kinases GSK3â and PKCæ may not function as a part of the MAPK pathway to regulate the mitotic spindle.
ContributorsChakravadhanula, Madhavi (Author) / Capco, David G. (Thesis advisor) / Chandler, Douglas (Committee member) / Clark-Curtiss, Josephine (Committee member) / Newfeld, Stuart (Committee member) / Arizona State University (Publisher)
Created2012
Description
Image understanding has been playing an increasingly crucial role in vision applications. Sparse models form an important component in image understanding, since the statistics of natural images reveal the presence of sparse structure. Sparse methods lead to parsimonious models, in addition to being efficient for large scale learning. In sparse modeling, data is represented as a sparse linear combination of atoms from a "dictionary" matrix. This dissertation focuses on understanding different aspects of sparse learning, thereby enhancing the use of sparse methods by incorporating tools from machine learning. With the growing need to adapt models for large scale data, it is important to design dictionaries that can model the entire data space and not just the samples considered. By exploiting the relation of dictionary learning to 1-D subspace clustering, a multilevel dictionary learning algorithm is developed, and it is shown to outperform conventional sparse models in compressed recovery, and image denoising. Theoretical aspects of learning such as algorithmic stability and generalization are considered, and ensemble learning is incorporated for effective large scale learning. In addition to building strategies for efficiently implementing 1-D subspace clustering, a discriminative clustering approach is designed to estimate the unknown mixing process in blind source separation. By exploiting the non-linear relation between the image descriptors, and allowing the use of multiple features, sparse methods can be made more effective in recognition problems. The idea of multiple kernel sparse representations is developed, and algorithms for learning dictionaries in the feature space are presented. Using object recognition experiments on standard datasets it is shown that the proposed approaches outperform other sparse coding-based recognition frameworks. Furthermore, a segmentation technique based on multiple kernel sparse representations is developed, and successfully applied for automated brain tumor identification. Using sparse codes to define the relation between data samples can lead to a more robust graph embedding for unsupervised clustering. By performing discriminative embedding using sparse coding-based graphs, an algorithm for measuring the glomerular number in kidney MRI images is developed. Finally, approaches to build dictionaries for local sparse coding of image descriptors are presented, and applied to object recognition and image retrieval.
ContributorsJayaraman Thiagarajan, Jayaraman (Author) / Spanias, Andreas (Thesis advisor) / Frakes, David (Committee member) / Tepedelenlioğlu, Cihan (Committee member) / Turaga, Pavan (Committee member) / Arizona State University (Publisher)
Created2013
Description
A Pairwise Comparison Matrix (PCM) is used to compute for relative priorities of criteria or alternatives and are integral components of widely applied decision making tools: the Analytic Hierarchy Process (AHP) and its generalized form, the Analytic Network Process (ANP). However, a PCM suffers from several issues limiting its application to large-scale decision problems, specifically: (1) to the curse of dimensionality, that is, a large number of pairwise comparisons need to be elicited from a decision maker (DM), (2) inconsistent and (3) imprecise preferences maybe obtained due to the limited cognitive power of DMs. This dissertation proposes a PCM Framework for Large-Scale Decisions to address these limitations in three phases as follows. The first phase proposes a binary integer program (BIP) to intelligently decompose a PCM into several mutually exclusive subsets using interdependence scores. As a result, the number of pairwise comparisons is reduced and the consistency of the PCM is improved. Since the subsets are disjoint, the most independent pivot element is identified to connect all subsets. This is done to derive the global weights of the elements from the original PCM. The proposed BIP is applied to both AHP and ANP methodologies. However, it is noted that the optimal number of subsets is provided subjectively by the DM and hence is subject to biases and judgement errors. The second phase proposes a trade-off PCM decomposition methodology to decompose a PCM into a number of optimally identified subsets. A BIP is proposed to balance the: (1) time savings by reducing pairwise comparisons, the level of PCM inconsistency, and (2) the accuracy of the weights. The proposed methodology is applied to the AHP to demonstrate its advantages and is compared to established methodologies. In the third phase, a beta distribution is proposed to generalize a wide variety of imprecise pairwise comparison distributions via a method of moments methodology. A Non-Linear Programming model is then developed that calculates PCM element weights which maximizes the preferences of the DM as well as minimizes the inconsistency simultaneously. Comparison experiments are conducted using datasets collected from literature to validate the proposed methodology.
ContributorsJalao, Eugene Rex Lazaro (Author) / Shunk, Dan L. (Thesis advisor) / Wu, Teresa (Thesis advisor) / Askin, Ronald G. (Committee member) / Goul, Kenneth M (Committee member) / Arizona State University (Publisher)
Created2013
Description
In most social networking websites, users are allowed to perform interactive activities. One of the fundamental features that these sites provide is to connecting with users of their kind. On one hand, this activity makes online connections visible and tangible; on the other hand, it enables the exploration of our connections and the expansion of our social networks easier. The aggregation of people who share common interests forms social groups, which are fundamental parts of our social lives. Social behavioral analysis at a group level is an active research area and attracts many interests from the industry. Challenges of my work mainly arise from the scale and complexity of user generated behavioral data. The multiple types of interactions, highly dynamic nature of social networking and the volatile user behavior suggest that these data are complex and big in general. Effective and efficient approaches are required to analyze and interpret such data. My work provide effective channels to help connect the like-minded and, furthermore, understand user behavior at a group level. The contributions of this dissertation are in threefold: (1) proposing novel representation of collective tagging knowledge via tag networks; (2) proposing the new information spreader identification problem in egocentric soical networks; (3) defining group profiling as a systematic approach to understanding social groups. In sum, the research proposes novel concepts and approaches for connecting the like-minded, enables the understanding of user groups, and exposes interesting research opportunities.
ContributorsWang, Xufei (Author) / Liu, Huan (Thesis advisor) / Kambhampati, Subbarao (Committee member) / Sundaram, Hari (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2013
Description
DNA has recently emerged as an extremely promising material to organize molecules on nanoscale. The reliability of base recognition, self-assembling behavior, and attractive structural properties of DNA are of unparalleled value in systems of this size. DNA scaffolds have already been used to organize a variety of molecules including nanoparticles and proteins. New protein-DNA bio-conjugation chemistries make it possible to precisely position proteins and other biomolecules on underlying DNA scaffolds, generating multi-biomolecule pathways with the ability to modulate inter-molecular interactions and the local environment. This dissertation focuses on studying the application of using DNA nanostructure to direct the self-assembly of other biomolecular networks to translate biochemical pathways to non-cellular environments. Presented here are a series of studies toward this application. First, a novel strategy utilized DNA origami as a scaffold to arrange spherical virus capsids into one-dimensional arrays with precise nanoscale positioning. This hierarchical self-assembly allows us to position the virus particles with unprecedented control and allows the future construction of integrated multi-component systems from biological scaffolds using the power of rationally engineered DNA nanostructures. Next, discrete glucose oxidase (GOx)/ horseradish peroxidase (HRP) enzyme pairs were organized on DNA origami tiles with controlled interenzyme spacing and position. This study revealed two different distance-dependent kinetic processes associated with the assembled enzyme pairs. Finally, a tweezer-like DNA nanodevice was designed and constructed to actuate the activity of an enzyme/cofactor pair. Using this approach, several cycles of externally controlled enzyme inhibition and activation were successfully demonstrated. This principle of responsive enzyme nanodevices may be used to regulate other types of enzymes and to introduce feedback or feed-forward control loops.
ContributorsLiu, Minghui (Author) / Yan, Hao (Thesis advisor) / Liu, Yan (Thesis advisor) / Chen, Julian (Committee member) / Zhang, Peiming (Committee member) / Arizona State University (Publisher)
Created2013
Description
The need for a renewable and sustainable light-driven energy source is the motivation for this work, which utilizes a challenging, yet practical and attainable bio-inspired approach to develop an artificial oxygen evolving complex, which builds upon the principles of the natural water splitting mechanism in oxygenic photosynthesis. In this work, a stable framework consisting of a three-dimensional DNA tetrahedron has been used for the design of a bio-mimic of the Oxygen-Evolving Complex (OEC) found in natural Photosystem II (PSII). PSII is a large protein complex that evolves all the oxygen in the atmosphere, but it cannot be used directly in artificial systems, as the light reactions lead to damage of one of Photosystem II's core proteins, D1, which has to be replaced every half hour in the presence of sunlight. The final goal of the project aims to build the catalytic center of the OEC, including the Mn4CaCl metal cluster and its protein environment in the stable DNA framework of a tetrahedron, which can subsequently be connected to a photo-stable artificial reaction center that performs light-induced charge separation. Regions of the peptide sequences containing Mn4CaCl ligation sites are implemented in the design of the aOEC (artificial oxygen-evolving complex) and are attached to sites within the tetrahedron to facilitate assembly. Crystals of the tetrahedron have been obtained, and X-ray crystallography has been used for characterization. As a proof of concept, metal-binding peptides have been coupled to the DNA tetrahedron which allowed metal-containing porphyrins, specifically Fe(III) meso-Tetra(4-sulfonatophenyl) porphyrin chloride, to be encapsulated inside the DNA-tetrahedron. The porphyrins were successfully assembled inside the tetrahedron through coordination of two terminal histidines from the orthogonally oriented peptides covalently attached to the DNA. The assembly has been characterized using Electron Paramagnetic Resonance (EPR), optical spectroscopy, Dynamic Light Scattering (DLS), and x-ray crystallography. The results reveal that the spin state of the metal, iron (III), switches during assembly from the high-spin state to low-spin state.
ContributorsRendek, Kimberly Nicole (Author) / Fromme, Petra (Thesis advisor) / Chen, Julian (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
A semiconductor supply chain modeling and simulation platform using Linear Program (LP) optimization and parallel Discrete Event System Specification (DEVS) process models has been developed in a joint effort by ASU and Intel Corporation. A Knowledge Interchange Broker (KIBDEVS/LP) was developed to broker information synchronously between the DEVS and LP models. Recently a single-echelon heuristic Inventory Strategy Module (ISM) was added to correct for forecast bias in customer demand data using different smoothing techniques. The optimization model could then use information provided by the forecast model to make better decisions for the process model. The composition of ISM with LP and DEVS models resulted in the first realization of what is now called the Optimization Simulation Forecast (OSF) platform. It could handle a single echelon supply chain system consisting of single hubs and single products In this thesis, this single-echelon simulation platform is extended to handle multiple echelons with multiple inventory elements handling multiple products. The main aspect for the multi-echelon OSF platform was to extend the KIBDEVS/LP such that ISM interactions with the LP and DEVS models could also be supported. To achieve this, a new, scalable XML schema for the KIB has been developed. The XML schema has also resulted in strengthening the KIB execution engine design. A sequential scheme controls the executions of the DEVS-Suite simulator, CPLEX optimizer, and ISM engine. To use the ISM for multiple echelons, it is extended to compute forecast customer demands and safety stocks over multiple hubs and products. Basic examples for semiconductor manufacturing spanning single and two echelon supply chain systems have been developed and analyzed. Experiments using perfect data were conducted to show the correctness of the OSF platform design and implementation. Simple, but realistic experiments have also been conducted. They highlight the kinds of supply chain dynamics that can be evaluated using discrete event process simulation, linear programming optimization, and heuristics forecasting models.
ContributorsSmith, James Melkon (Author) / Sarjoughian, Hessam S. (Thesis advisor) / Davulcu, Hasan (Committee member) / Fainekos, Georgios (Committee member) / Arizona State University (Publisher)
Created2012
Description
The F1Fo ATP synthase is required for energy conversion in almost all living organisms. The F1 complex is a molecular motor that uses ATP hydrolysis to drive rotation of the γ–subunit. It has not been previously possible to resolve the speed and position of the γ–subunit of the F1–ATPase as it rotates during a power stroke. The single molecule experiments presented here measured light scattered from 45X91 nm gold nanorods attached to the γ–subunit that provide an unprecedented 5 μs resolution of rotational position as a function of time. The product of velocity and drag, which were both measured directly, resulted in an average torque of 63±8 pN nm for the Escherichia coli F1-ATPase that was determined to be independent of the load. The rotational velocity had an initial (I) acceleration phase 15° from the end of the catalytic dwell, a slow (S) acceleration phase during ATP binding/ADP release (15°–60°), and a fast (F) acceleration phase (60°–90°) containing an interim deceleration (ID) phase (75°–82°). High ADP concentrations decreased the velocity of the S phase proportional to 'ADP-release' dwells, and the F phase proportional to the free energy derived from the [ADP][Pi]/[ATP] chemical equilibrium. The decreased affinity for ITP increased ITP-binding dwells by 10%, but decreased velocity by 40% during the S phase. This is the first direct evidence that nucleotide binding contributes to F1–ATPase torque. Mutations that affect specific phases of rotation were identified, some in regions of F1 previously considered not to contribute to rotation. Mutations βD372V and γK9I increased the F phase velocity, and γK9I increased the depth of the ID phase. The conversion between S and F phases was specifically affected by γQ269L. While βT273D, βD305E, and αR283Q decreased the velocity of all phases, decreases in velocity due to βD302T, γR268L and γT82A were confined to the I and S phases. The correlations between the structural locations of these mutations and the phases of rotation they affect provide new insight into the molecular basis for F1–ATPase γ-subunit rotation.
ContributorsMartin, James (Author) / Frasch, Wayne D (Thesis advisor) / Chandler, Douglas (Committee member) / Gaxiola, Roberto (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2012
Description
In this dissertation I develop a deep theory of temporal planning well-suited to analyzing, understanding, and improving the state of the art implementations (as of 2012). At face-value the work is strictly theoretical; nonetheless its impact is entirely real and practical. The easiest portion of that impact to highlight concerns the notable improvements to the format of the temporal fragment of the International Planning Competitions (IPCs). Particularly: the theory I expound upon here is the primary cause of--and justification for--the altered (i) selection of benchmark problems, and (ii) notion of "winning temporal planner". For higher level motivation: robotics, web service composition, industrial manufacturing, business process management, cybersecurity, space exploration, deep ocean exploration, and logistics all benefit from applying domain-independent automated planning technique. Naturally, actually carrying out such case studies has much to offer. For example, we may extract the lesson that reasoning carefully about deadlines is rather crucial to planning in practice. More generally, effectively automating specifically temporal planning is well-motivated from applications. Entirely abstractly, the aim is to improve the theory of automated temporal planning by distilling from its practice. My thesis is that the key feature of computational interest is concurrency. To support, I demonstrate by way of compilation methods, worst-case counting arguments, and analysis of algorithmic properties such as completeness that the more immediately pressing computational obstacles (facing would-be temporal generalizations of classical planning systems) can be dealt with in theoretically efficient manner. So more accurately the technical contribution here is to demonstrate: The computationally significant obstacle to automated temporal planning that remains is just concurrency.
ContributorsCushing, William Albemarle (Author) / Kambhampati, Subbarao (Thesis advisor) / Weld, Daniel S. (Committee member) / Smith, David E. (Committee member) / Baral, Chitta (Committee member) / Davalcu, Hasan (Committee member) / Arizona State University (Publisher)
Created2012
Description
Communication networks, both wired and wireless, are expected to have a certain level of fault-tolerance capability.These networks are also expected to ensure a graceful degradation in performance when some of the network components fail. Traditional studies on fault tolerance in communication networks, for the most part, make no assumptions regarding the location of node/link faults, i.e., the faulty nodes and links may be close to each other or far from each other. However, in many real life scenarios, there exists a strong spatial correlation among the faulty nodes and links. Such failures are often encountered in disaster situations, e.g., natural calamities or enemy attacks. In presence of such region-based faults, many of traditional network analysis and fault-tolerant metrics, that are valid under non-spatially correlated faults, are no longer applicable. To this effect, the main thrust of this research is design and analysis of robust networks in presence of such region-based faults. One important finding of this research is that if some prior knowledge is available on the maximum size of the region that might be affected due to a region-based fault, this piece of knowledge can be effectively utilized for resource efficient design of networks. It has been shown in this dissertation that in some scenarios, effective utilization of this knowledge may result in substantial saving is transmission power in wireless networks. In this dissertation, the impact of region-based faults on the connectivity of wireless networks has been studied and a new metric, region-based connectivity, is proposed to measure the fault-tolerance capability of a network. In addition, novel metrics, such as the region-based component decomposition number(RBCDN) and region-based largest component size(RBLCS) have been proposed to capture the network state, when a region-based fault disconnects the network. Finally, this dissertation presents efficient resource allocation techniques that ensure tolerance against region-based faults, in distributed file storage networks and data center networks.
ContributorsBanerjee, Sujogya (Author) / Sen, Arunabha (Thesis advisor) / Xue, Guoliang (Committee member) / Richa, Andrea (Committee member) / Hurlbert, Glenn (Committee member) / Arizona State University (Publisher)
Created2013