Matching Items (507)
Description
Fluoroquinolone antibiotics have been known to cause severe, multisystem adverse side effects, termed fluoroquinolone toxicity (FQT). This toxicity syndrome can present with adverse effects that vary from individual to individual, including effects on the musculoskeletal and nervous systems, among others. The mechanism behind FQT in mammals is not known, although various possibilities have been investigated. Among the hypothesized FQT mechanisms, those that could potentially explain multisystem toxicity include off-target mammalian topoisomerase interactions, increased production of reactive oxygen species, oxidative stress, and oxidative damage, as well as metal chelating properties of FQs. This review presents relevant information on fluoroquinolone antibiotics and FQT and explores the mechanisms that have been proposed. A fluoroquinolone-induced increase in reactive oxygen species and subsequent oxidative stress and damage presents the strongest evidence to explain this multisystem toxicity syndrome. Understanding the mechanism of FQT in mammals is important to aid in the prevention and treatment of this condition.
ContributorsHall, Brooke Ashlyn (Author) / Redding, Kevin (Thesis director) / Wideman, Jeremy (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Finding the optimal solution to a problem with an enormous search space can be challenging. Unless a combinatorial construction technique is found that also guarantees the optimality of the resulting solution, this could be an infeasible task. If such a technique is unavailable, different heuristic methods are generally used to improve the upper bound on the size of the optimal solution. This dissertation presents an alternative method which can be used to improve a solution to a problem rather than construct a solution from scratch. Necessity analysis, which is the key to this approach, is the process of analyzing the necessity of each element in a solution. The post-optimization algorithm presented here utilizes the result of the necessity analysis to improve the quality of the solution by eliminating unnecessary objects from the solution. While this technique could potentially be applied to different domains, this dissertation focuses on k-restriction problems, where a solution to the problem can be presented as an array. A scalable post-optimization algorithm for covering arrays is described, which starts from a valid solution and performs necessity analysis to iteratively improve the quality of the solution. It is shown that not only can this technique improve upon the previously best known results, it can also be added as a refinement step to any construction technique and in most cases further improvements are expected. The post-optimization algorithm is then modified to accommodate every k-restriction problem; and this generic algorithm can be used as a starting point to create a reasonable sized solution for any such problem. This generic algorithm is then further refined for hash family problems, by adding a conflict graph analysis to the necessity analysis phase. By recoloring the conflict graphs a new degree of flexibility is explored, which can further improve the quality of the solution.
ContributorsNayeri, Peyman (Author) / Colbourn, Charles (Thesis advisor) / Konjevod, Goran (Thesis advisor) / Sen, Arunabha (Committee member) / Stanzione Jr, Daniel (Committee member) / Arizona State University (Publisher)
Created2011
Description
Reverse engineering gene regulatory networks (GRNs) is an important problem in the domain of Systems Biology. Learning GRNs is challenging due to the inherent complexity of the real regulatory networks and the heterogeneity of samples in available biomedical data. Real world biological data are commonly collected from broad surveys (profiling studies) and aggregate highly heterogeneous biological samples. Popular methods to learn GRNs simplistically assume a single universal regulatory network corresponding to available data. They neglect regulatory network adaptation due to change in underlying conditions and cellular phenotype or both. This dissertation presents a novel computational framework to learn common regulatory interactions and networks underlying the different sets of relatively homogeneous samples from real world biological data. The characteristic set of samples/conditions and corresponding regulatory interactions defines the cellular context (context). Context, in this dissertation, represents the deterministic transcriptional activity within the specific cellular regulatory mechanism. The major contributions of this framework include - modeling and learning context specific GRNs; associating enriched samples with contexts to interpret contextual interactions using biological knowledge; pruning extraneous edges from the context-specific GRN to improve the precision of the final GRNs; integrating multisource data to learn inter and intra domain interactions and increase confidence in obtained GRNs; and finally, learning combinatorial conditioning factors from the data to identify regulatory cofactors. The framework, Expattern, was applied to both real world and synthetic data. Interesting insights were obtained into mechanism of action of drugs on analysis of NCI60 drug activity and gene expression data. Application to refractory cancer data and Glioblastoma multiforme yield GRNs that were readily annotated with context-specific phenotypic information. Refractory cancer GRNs also displayed associations between distinct cancers, not observed through only clustering. Performance comparisons on multi-context synthetic data show the framework Expattern performs better than other comparable methods.
ContributorsSen, Ina (Author) / Kim, Seungchan (Thesis advisor) / Baral, Chitta (Committee member) / Bittner, Michael (Committee member) / Konjevod, Goran (Committee member) / Arizona State University (Publisher)
Created2011
Description
This dissertation studies routing in small-world networks such as grids plus long-range edges and real networks. Kleinberg showed that geography-based greedy routing in a grid-based network takes an expected number of steps polylogarithmic in the network size, thus justifying empirical efficiency observed beginning with Milgram. A counterpart for the grid-based model is provided; it creates all edges deterministically and shows an asymptotically matching upper bound on the route length. The main goal is to improve greedy routing through a decentralized machine learning process. Two considered methods are based on weighted majority and an algorithm of de Farias and Megiddo, both learning from feedback using ensembles of experts. Tests are run on both artificial and real networks, with decentralized spectral graph embedding supplying geometric information for real networks where it is not intrinsically available. An important measure analyzed in this work is overpayment, the difference between the cost of the method and that of the shortest path. Adaptive routing overtakes greedy after about a hundred or fewer searches per node, consistently across different network sizes and types. Learning stabilizes, typically at overpayment of a third to a half of that by greedy. The problem is made more difficult by eliminating the knowledge of neighbors' locations or by introducing uncooperative nodes. Even under these conditions, the learned routes are usually better than the greedy routes. The second part of the dissertation is related to the community structure of unannotated networks. A modularity-based algorithm of Newman is extended to work with overlapping communities (including considerably overlapping communities), where each node locally makes decisions to which potential communities it belongs. To measure quality of a cover of overlapping communities, a notion of a node contribution to modularity is introduced, and subsequently the notion of modularity is extended from partitions to covers. The final part considers a problem of network anonymization, mostly by the means of edge deletion. The point of interest is utility preservation. It is shown that a concentration on the preservation of routing abilities might damage the preservation of community structure, and vice versa.
ContributorsBakun, Oleg (Author) / Konjevod, Goran (Thesis advisor) / Richa, Andrea (Thesis advisor) / Syrotiuk, Violet R. (Committee member) / Czygrinow, Andrzej (Committee member) / Arizona State University (Publisher)
Created2011
Description
The primary function of the medium access control (MAC) protocol is managing access to a shared communication channel. From the viewpoint of transmitters, the MAC protocol determines each transmitter's persistence, the fraction of time it is permitted to spend transmitting. Schedule-based schemes implement stable persistences, achieving low variation in delay and throughput, and sometimes bounding maximum delay. However, they adapt slowly, if at all, to changes in the network. Contention-based schemes are agile, adapting quickly to changes in perceived contention, but suffer from short-term unfairness, large variations in packet delay, and poor performance at high load. The perfect MAC protocol, it seems, embodies the strengths of both contention- and schedule-based approaches while avoiding their weaknesses. This thesis culminates in the design of a Variable-Weight and Adaptive Topology Transparent (VWATT) MAC protocol. The design of VWATT first required answers for two questions: (1) If a node is equipped with schedules of different weights, which weight should it employ? (2) How is the node to compute the desired weight in a network lacking centralized control? The first question is answered by the Topology- and Load-Aware (TLA) allocation which defines target persistences that conform to both network topology and traffic load. Simulations show the TLA allocation to outperform IEEE 802.11, improving on the expectation and variation of delay, throughput, and drop rate. The second question is answered in the design of an Adaptive Topology- and Load-Aware Scheduled (ATLAS) MAC that computes the TLA allocation in a decentralized and adaptive manner. Simulation results show that ATLAS converges quickly on the TLA allocation, supporting highly dynamic networks. With these questions answered, a construction based on transversal designs is given for a variable-weight topology transparent schedule that allows nodes to dynamically and independently select weights to accommodate local topology and traffic load. The schedule maintains a guarantee on maximum delay when the maximum neighbourhood size is not too large. The schedule is integrated with the distributed computation of ATLAS to create VWATT. Simulations indicate that VWATT offers the stable performance characteristics of a scheduled MAC while adapting quickly to changes in topology and traffic load.
ContributorsLutz, Jonathan (Author) / Colbourn, Charles J (Thesis advisor) / Syrotiuk, Violet R. (Thesis advisor) / Konjevod, Goran (Committee member) / Lloyd, Errol L. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Laboratory automation systems have seen a lot of technological advances in recent times. As a result, the software that is written for them are becoming increasingly sophisticated. Existing software architectures and standards are targeted to a wider domain of software development and need to be customized in order to use them for developing software for laboratory automation systems. This thesis proposes an architecture that is based on existing software architectural paradigms and is specifically tailored to developing software for a laboratory automation system. The architecture is based on fairly autonomous software components that can be distributed across multiple computers. The components in the architecture make use of asynchronous communication methodologies that are facilitated by passing messages between one another. The architecture can be used to develop software that is distributed, responsive and thread-safe. The thesis also proposes a framework that has been developed to implement the ideas proposed by the architecture. The framework is used to develop software that is scalable, distributed, responsive and thread-safe. The framework currently has components to control very commonly used laboratory automation devices such as mechanical stages, cameras, and also to do common laboratory automation functionalities such as imaging.
ContributorsKuppuswamy, Venkataramanan (Author) / Meldrum, Deirdre (Thesis advisor) / Collofello, James (Thesis advisor) / Sarjoughian, Hessam S. (Committee member) / Johnson, Roger (Committee member) / Arizona State University (Publisher)
Created2012
Description
Semiconductor scaling technology has led to a sharp growth in transistor counts. This has resulted in an exponential increase on both power dissipation and heat flux (or power density) in modern microprocessors. These microprocessors are integrated as the major components in many modern embedded devices, which offer richer features and attain higher performance than ever before. Therefore, power and thermal management have become the significant design considerations for modern embedded devices. Dynamic voltage/frequency scaling (DVFS) and dynamic power management (DPM) are two well-known hardware capabilities offered by modern embedded processors. However, the power or thermal aware performance optimization is not fully explored for the mainstream embedded processors with discrete DVFS and DPM capabilities. Many key problems have not been answered yet. What is the maximum performance that an embedded processor can achieve under power or thermal constraint for a periodic application? Does there exist an efficient algorithm for the power or thermal management problems with guaranteed quality bound? These questions are hard to be answered because the discrete settings of DVFS and DPM enhance the complexity of many power and thermal management problems, which are generally NP-hard. The dissertation presents a comprehensive study on these NP-hard power and thermal management problems for embedded processors with discrete DVFS and DPM capabilities. In the domain of power management, the dissertation addresses the power minimization problem for real-time schedules, the energy-constrained make-span minimization problem on homogeneous and heterogeneous chip multiprocessors (CMP) architectures, and the battery aware energy management problem with nonlinear battery discharging model. In the domain of thermal management, the work addresses several thermal-constrained performance maximization problems for periodic embedded applications. All the addressed problems are proved to be NP-hard or strongly NP-hard in the study. Then the work focuses on the design of the off-line optimal or polynomial time approximation algorithms as solutions in the problem design space. Several addressed NP-hard problems are tackled by dynamic programming with optimal solutions and pseudo-polynomial run time complexity. Because the optimal algorithms are not efficient in worst case, the fully polynomial time approximation algorithms are provided as more efficient solutions. Some efficient heuristic algorithms are also presented as solutions to several addressed problems. The comprehensive study answers the key questions in order to fully explore the power and thermal management potentials on embedded processors with discrete DVFS and DPM capabilities. The provided solutions enable the theoretical analysis of the maximum performance for periodic embedded applications under power or thermal constraints.
ContributorsZhang, Sushu (Author) / Chatha, Karam S (Thesis advisor) / Cao, Yu (Committee member) / Konjevod, Goran (Committee member) / Vrudhula, Sarma (Committee member) / Xue, Guoliang (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
Single cell analysis has become increasingly important in understanding disease onset, progression, treatment and prognosis, especially when applied to cancer where cellular responses are highly heterogeneous. Through the advent of single cell computerized tomography (Cell-CT), researchers and clinicians now have the ability to obtain high resolution three-dimensional (3D) reconstructions of single cells. Yet to date, no live-cell compatible version of the technology exists. In this thesis, a microfluidic chip with the ability to rotate live single cells in hydrodynamic microvortices about an axis parallel to the optical focal plane has been demonstrated. The chip utilizes a novel 3D microchamber design arranged beneath a main channel creating flow detachment into the chamber, producing recirculating flow conditions. Single cells are flowed through the main channel, held in the center of the microvortex by an optical trap, and rotated by the forces induced by the recirculating fluid flow. Computational fluid dynamics (CFD) was employed to optimize the geometry of the microchamber. Two methods for the fabrication of the 3D microchamber were devised: anisotropic etching of silicon and backside diffuser photolithography (BDPL). First, the optimization of the silicon etching conditions was demonstrated through design of experiment (DOE). In addition, a non-conventional method of soft-lithography was demonstrated which incorporates the use of two positive molds, one of the main channel and the other of the microchambers, compressed together during replication to produce a single ultra-thin (<200 µm) negative used for device assembly. Second, methods for using thick negative photoresists such as SU-8 with BDPL have been developed which include a new simple and effective method for promoting the adhesion of SU-8 to glass. An assembly method that bonds two individual ultra-thin (<100 µm) replications of the channel and the microfeatures has also been demonstrated. Finally, a pressure driven pumping system with nanoliter per minute flow rate regulation, sub-second response times, and < 3% flow variability has been designed and characterized. The fabrication and assembly of this device is inexpensive and utilizes simple variants of conventional microfluidic fabrication techniques, making it easily accessible to the single cell analysis community.
ContributorsMyers, Jakrey R (Author) / Meldrum, Deirdre (Thesis advisor) / Johnson, Roger (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2012
Description
Along with the number of technologies that have been introduced over a few years ago, gesture-based human-computer interactions are becoming the new phase in encompassing the creativity and abilities for users to communicate and interact with devices. Because of how the nature of defining free-space gestures influence user's preference and the length of usability of gesture-driven devices, defined low-stress and intuitive gestures for users to interact with gesture recognition systems are necessary to consider. To measure stress, a Galvanic Skin Response instrument was used as a primary indicator, which provided evidence of the relationship between stress and intuitive gestures, as well as user preferences towards certain tasks and gestures during performance. Fifteen participants engaged in creating and performing their own gestures for specified tasks that would be required during the use of free-space gesture-driven devices. The tasks include "activation of the display," scroll, page, selection, undo, and "return to main menu." They were also asked to repeat their gestures for around ten seconds each, which would give them time and further insight of how their gestures would be appropriate or not for them and any given task. Surveys were given at different time to the users: one after they had defined their gestures and another after they had repeated their gestures. In the surveys, they ranked their gestures based on comfort, intuition, and the ease of communication. Out of those user-ranked gestures, health-efficient gestures, given that the participants' rankings were based on comfort and intuition, were chosen in regards to the highest ranked gestures.
ContributorsLam, Christine (Author) / Walker, Erin (Thesis director) / Danielescu, Andreea (Committee member) / Barrett, The Honors College (Contributor) / Ira A. Fulton School of Engineering (Contributor) / School of Arts, Media and Engineering (Contributor) / Department of English (Contributor) / Computing and Informatics Program (Contributor)
Created2015-05