Matching Items (30)
Description
Biological systems are complex in many dimensions as endless transportation and communication networks all function simultaneously. Our ability to intervene within both healthy and diseased systems is tied directly to our ability to understand and model core functionality. The progress in increasingly accurate and thorough high-throughput measurement technologies has provided a deluge of data from which we may attempt to infer a representation of the true genetic regulatory system. A gene regulatory network model, if accurate enough, may allow us to perform hypothesis testing in the form of computational experiments. Of great importance to modeling accuracy is the acknowledgment of biological contexts within the models -- i.e. recognizing the heterogeneous nature of the true biological system and the data it generates. This marriage of engineering, mathematics and computer science with systems biology creates a cycle of progress between computer simulation and lab experimentation, rapidly translating interventions and treatments for patients from the bench to the bedside. This dissertation will first discuss the landscape for modeling the biological system, explore the identification of targets for intervention in Boolean network models of biological interactions, and explore context specificity both in new graphical depictions of models embodying context-specific genomic regulation and in novel analysis approaches designed to reveal embedded contextual information. Overall, the dissertation will explore a spectrum of biological modeling with a goal towards therapeutic intervention, with both formal and informal notions of biological context, in such a way that will enable future work to have an even greater impact in terms of direct patient benefit on an individualized level.
ContributorsVerdicchio, Michael (Author) / Kim, Seungchan (Thesis advisor) / Baral, Chitta (Committee member) / Stolovitzky, Gustavo (Committee member) / Collofello, James (Committee member) / Arizona State University (Publisher)
Created2013
Description
Well-established model systems exist in four out of the seven major classes of vertebrates. These include the mouse, chicken, frog and zebrafish. Noticeably missing from this list is a reptilian model organism for comparative studies between the vertebrates and for studies of biological processes unique to reptiles. To help fill in this gap the green anole lizard, Anolis carolinensis, is being adapted as a model organism. Despite the recent release of the complete genomic sequence of the A. carolinensis, the lizard lacks some resources to aid researchers in their studies. Particularly, the lack of transcriptomic resources for lizard has made it difficult to identify genes complete with alternative splice forms and untranslated regions (UTRs). As part of this work the genome annotation for A. carolinensis was improved through next generation sequencing and assembly of the transcriptomes from 14 different adult and embryonic tissues. This revised annotation of the lizard will improve comparative studies between vertebrates, as well as studies within A. carolinensis itself, by providing more accurate gene models, which provide the bases for molecular studies. To demonstrate the utility of the improved annotations and reptilian model organism, the developmental process of somitogenesis in the lizard was analyzed and compared with other vertebrates. This study identified several key features both divergent and convergent between the vertebrates, which was not previously known before analysis of a reptilian model organism. The improved genome annotations have also allowed for molecular studies of tail regeneration in the lizard. With the annotation of 3' UTR sequences and next generation sequencing, it is now possible to do expressional studies of miRNA and predict their mRNA target transcripts at genomic scale. Through next generation small RNA sequencing and subsequent analysis, several differentially expressed miRNAs were identified in the regenerating tail, suggesting miRNA may play a key role in regulating this process in lizards. Through miRNA target prediction several key biological pathways were identified as potentially under the regulation of miRNAs during tail regeneration. In total, this work has both helped advance A. carolinensis as model system and displayed the utility of a reptilian model system.
ContributorsEckalbar, Walter L (Author) / Kusumi, Kenro (Thesis advisor) / Huentelman, Matthew (Committee member) / Rawls, Jeffery (Committee member) / Wilson-Rawls, Norma (Committee member) / Arizona State University (Publisher)
Created2012
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
Urbanization and infrastructure development often brings dramatic changes in the surface and groundwater regimes. These changes in moisture content may be particularly problematic when subsurface soils are moisture sensitive such as expansive soils. Residential foundations such as slab-on ground may be built on unsaturated expansive soils and therefore have to resist the deformations associated with change in moisture content (matric suction) in the soil. The problem is more pronounced in arid and semi arid regions with drying periods followed by wet season resulting in large changes in soil suction. Moisture content change causes volume change in expansive soil which causes serious damage to the structures. In order to mitigate these ill effects various mitigation are adopted. The most commonly adopted method in the US is the removal and replacement of upper soils in the profile. The remove and replace method, although heavily used, is not well understood with regard to its impact on the depth of soil wetting or near-surface differential soil movements. In this study the effectiveness of the remove and replace method is studied. A parametric study is done with various removal and replacement materials used and analyzed to obtain the optimal replacement depths and best material. The depth of wetting and heave caused in expansive soil profile under climatic conditions and common irrigation scenarios are studied for arid regions. Soil suction changes and associated soil deformations are analyzed using finite element codes for unsaturated flow and stress/deformation, SVFlux and SVSolid, respectively. The effectiveness and fundamental mechanisms at play in mitigation of expansive soils for remove and replace methods are studied, and include (1) its role in reducing the depth and degree of wetting, and (2) its effect in reducing the overall heave potential, and (3) the effectiveness of this method in pushing the seat of movement deeper within the soil profile to reduce differential soil surface movements. Various non-expansive replacement layers and different surface flux boundary conditions are analyzed, and the concept of optimal depth and soil is introduced. General observations are made concerning the efficacy of remove and replace as a mitigation method.
ContributorsBharadwaj, Anushree (Author) / Houston, Sandra L. (Thesis advisor) / Welfert, Bruno (Thesis advisor) / Zapata, Claudia E (Committee member) / Arizona State University (Publisher)
Created2013
Description
Obtaining high-quality experimental designs to optimize statistical efficiency and data quality is quite challenging for functional magnetic resonance imaging (fMRI). The primary fMRI design issue is on the selection of the best sequence of stimuli based on a statistically meaningful optimality criterion. Some previous studies have provided some guidance and powerful computational tools for obtaining good fMRI designs. However, these results are mainly for basic experimental settings with simple statistical models. In this work, a type of modern fMRI experiments is considered, in which the design matrix of the statistical model depends not only on the selected design, but also on the experimental subject's probabilistic behavior during the experiment. The design matrix is thus uncertain at the design stage, making it diffcult to select good designs. By taking this uncertainty into account, a very efficient approach for obtaining high-quality fMRI designs is developed in this study. The proposed approach is built upon an analytical result, and an efficient computer algorithm. It is shown through case studies that the proposed approach can outperform an existing method in terms of computing time, and the quality of the obtained designs.
ContributorsZhou, Lin (Author) / Kao, Ming-Hung (Thesis advisor) / Reiser, Mark R. (Committee member) / Stufken, John (Committee member) / Welfert, Bruno (Committee member) / Arizona State University (Publisher)
Created2014
Description
Given the process of tumorigenesis, biological signaling pathways have become of interest in the field of oncology. Many of the regulatory mechanisms that are altered in cancer are directly related to signal transduction and cellular communication. Thus, identifying signaling pathways that have become deregulated may provide useful information to better understanding altered regulatory mechanisms within cancer. Many methods that have been created to measure the distinct activity of signaling pathways have relied strictly upon transcription profiles. With advancements in comparative genomic hybridization techniques, copy number data has become extremely useful in providing valuable information pertaining to the genomic landscape of cancer. The purpose of this thesis is to develop a methodology that incorporates both gene expression and copy number data to identify signaling pathways that have become deregulated in cancer. The central idea is that copy number data may significantly assist in identifying signaling pathway deregulation by justifying the aberrant activity being measured in gene expression profiles. This method was then applied to four different subtypes of breast cancer resulting in the identification of signaling pathways associated with distinct functionalities for each of the breast cancer subtypes.
ContributorsTrevino, Robert (Author) / Kim, Seungchan (Thesis advisor) / Ringner, Markus (Committee member) / Liu, Huan (Committee member) / Arizona State University (Publisher)
Created2011
Description
In many classication problems data samples cannot be collected easily, example in drug trials, biological experiments and study on cancer patients. In many situations the data set size is small and there are many outliers. When classifying such data, example cancer vs normal patients the consequences of mis-classication are probably more important than any other data type, because the data point could be a cancer patient or the classication decision could help determine what gene might be over expressed and perhaps a cause of cancer. These mis-classications are typically higher in the presence of outlier data points. The aim of this thesis is to develop a maximum margin classier that is suited to address the lack of robustness of discriminant based classiers (like the Support Vector Machine (SVM)) to noise and outliers. The underlying notion is to adopt and develop a natural loss function that is more robust to outliers and more representative of the true loss function of the data. It is demonstrated experimentally that SVM's are indeed susceptible to outliers and that the new classier developed, here coined as Robust-SVM (RSVM), is superior to all studied classier on the synthetic datasets. It is superior to the SVM in both the synthetic and experimental data from biomedical studies and is competent to a classier derived on similar lines when real life data examples are considered.
ContributorsGupta, Sidharth (Author) / Kim, Seungchan (Thesis advisor) / Welfert, Bruno (Committee member) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2011
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
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
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