ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- Creators: Ahn, Gail-Joon
- Creators: Shen, Wei
- Creators: Ghirlanda, Giovanna
Description
Cyanovirin-N (CV-N) is a naturally occurring lectin originally isolated from the cyanobacteria Nostoc ellipsosporum. This 11 kDa lectin is 101 amino acids long with two binding sites, one at each end of the protein. CV-N specifically binds to terminal Manα1-2Manα motifs on the branched, high mannose Man9 and Man8 glycosylations found on enveloped viruses including Ebola, Influenza, and HIV. wt-CVN has micromolar binding to soluble Manα1-2Manα and also inhibits HIV entry at low nanomolar concentrations. CV-N's high affinity and specificity for Manα1-2Manα makes it an excellent lectin to study for its glycan-specific properties. The long-term aim of this project is to make a variety of mutant CV-Ns to specifically bind other glycan targets. Such a set of lectins may be used as screening reagents to identify biomarkers and other glycan motifs of interest. As proof of concept, a T7 phage display library was constructed using P51G-m4-CVN genes mutated at positions 41, 44, 52, 53, 56, 74, and 76 in binding Domain B. Five CV-N mutants were selected from the library and expressed in BL21(DE3) E. coli. Two of the mutants, SSDGLQQ-P51Gm4-CVN and AAGRLSK-P51Gm4-CVN, were sufficiently stable for characterization and were examined by CD, Tm, ELISA, and glycan array. Both proteins have CD minima at approximately 213 nm, indicating largely β-sheet structure, and have Tm values greater than 40°C. ELISA against gp120 and RNase B demonstrate both proteins' ability to bind high mannose glycans. To more specifically determine the binding specificity of each protein, AAGRLSK-P51Gm4-CVN, SSDGLQQ-P51Gm4-CVN, wt-CVN, and P51G-m4-CVN were sent to the Consortium for Functional Glycomics (CFG) for glycan array analysis. AAGRLSK-P51Gm4-CVN, wt-CVN, and P51G-m4-CVN, have identical specificities for high mannose glycans containing terminal Manα1-2Manα. SSDGLQQ-P51Gm4-CVN binds to terminal GlcNAcα1-4Gal motifs and a subgroup of high mannose glycans bound by P51G-m4-CVN. SSDGLQQ-wt-CVN was produced to restore anti-HIV activity and has a high nanomolar EC50 value compared to wt-CVN's low nanomolar activity. Overall, these experiments show that CV-N Domain B can be mutated and retain specificity identical to wt-CVN or acquire new glycan specificities. This first generation information can be used to produce glycan-specific lectins for a variety of applications.
ContributorsRuben, Melissa (Author) / Ghirlanda, Giovanna (Thesis advisor) / Allen, James (Committee member) / Wachter, Rebekka (Committee member) / Arizona State University (Publisher)
Created2013
Description
Answer Set Programming (ASP) is one of the most prominent and successful knowledge representation paradigms. The success of ASP is due to its expressive non-monotonic modeling language and its efficient computational methods originating from building propositional satisfiability solvers. The wide adoption of ASP has motivated several extensions to its modeling language in order to enhance expressivity, such as incorporating aggregates and interfaces with ontologies. Also, in order to overcome the grounding bottleneck of computation in ASP, there are increasing interests in integrating ASP with other computing paradigms, such as Constraint Programming (CP) and Satisfiability Modulo Theories (SMT). Due to the non-monotonic nature of the ASP semantics, such enhancements turned out to be non-trivial and the existing extensions are not fully satisfactory. We observe that one main reason for the difficulties rooted in the propositional semantics of ASP, which is limited in handling first-order constructs (such as aggregates and ontologies) and functions (such as constraint variables in CP and SMT) in natural ways. This dissertation presents a unifying view on these extensions by viewing them as instances of formulas with generalized quantifiers and intensional functions. We extend the first-order stable model semantics by by Ferraris, Lee, and Lifschitz to allow generalized quantifiers, which cover aggregate, DL-atoms, constraints and SMT theory atoms as special cases. Using this unifying framework, we study and relate different extensions of ASP. We also present a tight integration of ASP with SMT, based on which we enhance action language C+ to handle reasoning about continuous changes. Our framework yields a systematic approach to study and extend non-monotonic languages.
ContributorsMeng, Yunsong (Author) / Lee, Joohyung (Thesis advisor) / Ahn, Gail-Joon (Committee member) / Baral, Chitta (Committee member) / Fainekos, Georgios (Committee member) / Lifschitz, Vladimir (Committee member) / Arizona State University (Publisher)
Created2013
Description
Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in the loss of lower body muscle function. SMA is the second leading genetic cause of death in infants and arises from the loss of the Survival of Motor Neuron (SMN) protein. SMN is produced by two genes, smn1 and smn2, that are identical with the exception of a C to T conversion in exon 7 of the smn2 gene. SMA patients lacking the smn1 gene, rely on smn2 for production of SMN. Due to an alternative splicing event, smn2 primarily encodes a non-functional SMN lacking exon 7 (SMN D7) as well as a low amount of functional full-length SMN (SMN WT). SMN WT is ubiquitously expressed in all cell types, and it remains unclear how low levels of SMN WT in motor neurons lead to motor neuron degradation and SMA. SMN and its associated proteins, Gemin2-8 and Unrip, make up a large dynamic complex that functions to assemble ribonucleoproteins. The aim of this project was to characterize the interactions of the core SMN-Gemin2 complex, and to identify differences between SMN WT and SMN D7. SMN and Gemin2 proteins were expressed, purified and characterized via size exclusion chromatography. A stable N-terminal deleted Gemin2 protein (N45-G2) was characterized. The SMN WT expression system was optimized resulting in a 10-fold increase of protein expression. Lastly, the oligomeric states of SMN and SMN bound to Gemin2 were determined. SMN WT formed a mixture of oligomeric states, while SMN D7 did not. Both SMN WT and D7 bound to Gemin2 with a one-to-one ratio forming a heterodimer and several higher-order oligomeric states. The SMN WT-Gemin2 complex favored high molecular weight oligomers whereas the SMN D7-Gemin2 complex formed low molecular weight oligomers. These results indicate that the SMA mutant protein, SMN D7, was still able to associate with Gemin2, but was not able to form higher-order oligomeric complexes. The observed multiple oligomerization states of SMN and SMN bound to Gemin2 may play a crucial role in regulating one or several functions of the SMN protein. The inability of SMN D7 to form higher-order oligomers may inhibit or alter those functions leading to the SMA disease phenotype.
ContributorsNiday, Tracy (Author) / Allen, James P. (Thesis advisor) / Wachter, Rebekka (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2012
Description
With the growth of IT products and sophisticated software in various operating systems, I observe that security risks in systems are skyrocketing constantly. Consequently, Security Assessment is now considered as one of primary security mechanisms to measure assurance of systems since systems that are not compliant with security requirements may lead adversaries to access critical information by circumventing security practices. In order to ensure security, considerable efforts have been spent to develop security regulations by facilitating security best-practices. Applying shared security standards to the system is critical to understand vulnerabilities and prevent well-known threats from exploiting vulnerabilities. However, many end users tend to change configurations of their systems without paying attention to the security. Hence, it is not straightforward to protect systems from being changed by unconscious users in a timely manner. Detecting the installation of harmful applications is not sufficient since attackers may exploit risky software as well as commonly used software. In addition, checking the assurance of security configurations periodically is disadvantageous in terms of time and cost due to zero-day attacks and the timing attacks that can leverage the window between each security checks. Therefore, event-driven monitoring approach is critical to continuously assess security of a target system without ignoring a particular window between security checks and lessen the burden of exhausted task to inspect the entire configurations in the system. Furthermore, the system should be able to generate a vulnerability report for any change initiated by a user if such changes refer to the requirements in the standards and turn out to be vulnerable. Assessing various systems in distributed environments also requires to consistently applying standards to each environment. Such a uniformed consistent assessment is important because the way of assessment approach for detecting security vulnerabilities may vary across applications and operating systems. In this thesis, I introduce an automated event-driven security assessment framework to overcome and accommodate the aforementioned issues. I also discuss the implementation details that are based on the commercial-off-the-self technologies and testbed being established to evaluate approach. Besides, I describe evaluation results that demonstrate the effectiveness and practicality of the approaches.
ContributorsSeo, Jeong-Jin (Author) / Ahn, Gail-Joon (Thesis advisor) / Yau, Stephen S. (Committee member) / Lee, Joohyung (Committee member) / Arizona State University (Publisher)
Created2014
Description
Access control is necessary for information assurance in many of today's applications such as banking and electronic health record. Access control breaches are critical security problems that can result from unintended and improper implementation of security policies. Security testing can help identify security vulnerabilities early and avoid unexpected expensive cost in handling breaches for security architects and security engineers. The process of security testing which involves creating tests that effectively examine vulnerabilities is a challenging task. Role-Based Access Control (RBAC) has been widely adopted to support fine-grained access control. However, in practice, due to its complexity including role management, role hierarchy with hundreds of roles, and their associated privileges and users, systematically testing RBAC systems is crucial to ensure the security in various domains ranging from cyber-infrastructure to mission-critical applications. In this thesis, we introduce i) a security testing technique for RBAC systems considering the principle of maximum privileges, the structure of the role hierarchy, and a new security test coverage criterion; ii) a MTBDD (Multi-Terminal Binary Decision Diagram) based representation of RBAC security policy including RHMTBDD (Role Hierarchy MTBDD) to efficiently generate effective positive and negative security test cases; and iii) a security testing framework which takes an XACML-based RBAC security policy as an input, parses it into a RHMTBDD representation and then generates positive and negative test cases. We also demonstrate the efficacy of our approach through case studies.
ContributorsGupta, Poonam (Author) / Ahn, Gail-Joon (Thesis advisor) / Collofello, James (Committee member) / Huang, Dijiang (Committee member) / Arizona State University (Publisher)
Created2014
Description
This thesis explores a wide array of topics related to the protein folding problem, ranging from the folding mechanism, ab initio structure prediction and protein design, to the mechanism of protein functional evolution, using multi-scale approaches. To investigate the role of native topology on folding mechanism, the native topology is dissected into non-local and local contacts. The number of non-local contacts and non-local contact orders are both negatively correlated with folding rates, suggesting that the non-local contacts dominate the barrier-crossing process. However, local contact orders show positive correlation with folding rates, indicating the role of a diffusive search in the denatured basin. Additionally, the folding rate distribution of E. coli and Yeast proteomes are predicted from native topology. The distribution is fitted well by a diffusion-drift population model and also directly compared with experimentally measured half life. The results indicate that proteome folding kinetics is limited by protein half life. The crucial role of local contacts in protein folding is further explored by the simulations of WW domains using Zipping and Assembly Method. The correct formation of N-terminal β-turn turns out important for the folding of WW domains. A classification model based on contact probabilities of five critical local contacts is constructed to predict the foldability of WW domains with 81% accuracy. By introducing mutations to stabilize those critical local contacts, a new protein design approach is developed to re-design the unfoldable WW domains and make them foldable. After folding, proteins exhibit inherent conformational dynamics to be functional. Using molecular dynamics simulations in conjunction with Perturbation Response Scanning, it is demonstrated that the divergence of functions can occur through the modification of conformational dynamics within existing fold for β-lactmases and GFP-like proteins: i) the modern TEM-1 lactamase shows a comparatively rigid active-site region, likely reflecting adaptation for efficient degradation of a specific substrate, while the resurrected ancient lactamases indicate enhanced active-site flexibility, which likely allows for the binding and subsequent degradation of different antibiotic molecules; ii) the chromophore and attached peptides of photocoversion-competent GFP-like protein exhibits higher flexibility than the photocoversion-incompetent one, consistent with the evolution of photocoversion capacity.
ContributorsZou, Taisong (Author) / Ozkan, Sefika B (Thesis advisor) / Thorpe, Michael F (Committee member) / Woodbury, Neal W (Committee member) / Vaiana, Sara M (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014
Description
The digital forensics community has neglected email forensics as a process, despite the fact that email remains an important tool in the commission of crime. Current forensic practices focus mostly on that of disk forensics, while email forensics is left as an analysis task stemming from that practice. As there is no well-defined process to be used for email forensics the comprehensiveness, extensibility of tools, uniformity of evidence, usefulness in collaborative/distributed environments, and consistency of investigations are hindered. At present, there exists little support for discovering, acquiring, and representing web-based email, despite its widespread use. To remedy this, a systematic process which includes discovering, acquiring, and representing web-based email for email forensics which is integrated into the normal forensic analysis workflow, and which accommodates the distinct characteristics of email evidence will be presented. This process focuses on detecting the presence of non-obvious artifacts related to email accounts, retrieving the data from the service provider, and representing email in a well-structured format based on existing standards. As a result, developers and organizations can collaboratively create and use analysis tools that can analyze email evidence from any source in the same fashion and the examiner can access additional data relevant to their forensic cases. Following, an extensible framework implementing this novel process-driven approach has been implemented in an attempt to address the problems of comprehensiveness, extensibility, uniformity, collaboration/distribution, and consistency within forensic investigations involving email evidence.
ContributorsPaglierani, Justin W (Author) / Ahn, Gail-Joon (Thesis advisor) / Yau, Stephen S. (Committee member) / Santanam, Raghu T (Committee member) / Arizona State University (Publisher)
Created2013
Description
Attribute Based Access Control (ABAC) mechanisms have been attracting a lot of interest from the research community in recent times. This is especially because of the flexibility and extensibility it provides by using attributes assigned to subjects as the basis for access control. ABAC enables an administrator of a server to enforce access policies on the data, services and other such resources fairly easily. It also accommodates new policies and changes to existing policies gracefully, thereby making it a potentially good mechanism for implementing access control in large systems, particularly in today's age of Cloud Computing. However management of the attributes in ABAC environment is an area that has been little touched upon. Having a mechanism to allow multiple ABAC based systems to share data and resources can go a long way in making ABAC scalable. At the same time each system should be able to specify their own attribute sets independently. In the research presented in this document a new mechanism is proposed that would enable users to share resources and data in a cloud environment using ABAC techniques in a distributed manner. The focus is mainly on decentralizing the access policy specifications for the shared data so that each data owner can specify the access policy independent of others. The concept of ontologies and semantic web is introduced in the ABAC paradigm that would help in giving a scalable structure to the attributes and also allow systems having different sets of attributes to communicate and share resources.
ContributorsPrabhu Verleker, Ashwin Narayan (Author) / Huang, Dijiang (Thesis advisor) / Ahn, Gail-Joon (Committee member) / Dasgupta, Partha (Committee member) / Arizona State University (Publisher)
Created2014
Description
This thesis addresses the ever increasing threat of botnets in the smartphone domain and focuses on the Android platform and the botnets using Online Social Networks (OSNs) as Command and Control (C&C;) medium. With any botnet, C&C; is one of the components on which the survival of botnet depends. Individual bots use the C&C; channel to receive commands and send the data. This thesis develops active host based approach for identifying the presence of bot based on the anomalies in the usage patterns of the user before and after the bot is installed on the user smartphone and alerting the user to the presence of the bot. A profile is constructed for each user based on the regular web usage patterns (achieved by intercepting the http(s) traffic) and implementing machine learning techniques to continuously learn the user's behavior and changes in the behavior and all the while looking for any anomalies in the user behavior above a threshold which will cause the user to be notified of the anomalous traffic. A prototype bot which uses OSN s as C&C; channel is constructed and used for testing. Users are given smartphones(Nexus 4 and Galaxy Nexus) running Application proxy which intercepts http(s) traffic and relay it to a server which uses the traffic and constructs the model for a particular user and look for any signs of anomalies. This approach lays the groundwork for the future host-based counter measures for smartphone botnets using OSN s as C&C; channel.
ContributorsKilari, Vishnu Teja (Author) / Xue, Guoliang (Thesis advisor) / Ahn, Gail-Joon (Committee member) / Dasgupta, Partha (Committee member) / Arizona State University (Publisher)
Created2013
Interactions driving the collapse of islet amyloid polypeptide: implications for amyloid aggregation
Description
Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-residue intrinsically disordered hormone involved in glucose regulation and gastric emptying. The aggregation of hIAPP into amyloid fibrils is believed to play a causal role in type 2 diabetes. To date, not much is known about the monomeric state of hIAPP or how it undergoes an irreversible transformation from disordered peptide to insoluble aggregate. IAPP contains a highly conserved disulfide bond that restricts hIAPP(1-8) into a short ring-like structure: N_loop. Removal or chemical reduction of N_loop not only prevents cell response upon binding to the CGRP receptor, but also alters the mass per length distribution of hIAPP fibers and the kinetics of fibril formation. The mechanism by which N_loop affects hIAPP aggregation is not yet understood, but is important for rationalizing kinetics and developing potential inhibitors. By measuring end-to-end contact formation rates, Vaiana et al. showed that N_loop induces collapsed states in IAPP monomers, implying attractive interactions between N_loop and other regions of the disordered polypeptide chain . We show that in addition to being involved in intra-protein interactions, the N_loop is involved in inter-protein interactions, which lead to the formation of extremely long and stable β-turn fibers. These non-amyloid fibers are present in the 10 μM concentration range, under the same solution conditions in which hIAPP forms amyloid fibers. We discuss the effect of peptide cyclization on both intra- and inter-protein interactions, and its possible implications for aggregation. Our findings indicate a potential role of N_loop-N_loop interactions in hIAPP aggregation, which has not previously been explored. Though our findings suggest that N_loop plays an important role in the pathway of amyloid formation, other naturally occurring IAPP variants that contain this structural feature are incapable of forming amyloids. For example, hIAPP readily forms amyloid fibrils in vitro, whereas the rat variant (rIAPP), differing by six amino acids, does not. In addition to being highly soluble, rIAPP is an effective inhibitor of hIAPP fibril formation . Both of these properties have been attributed to rIAPP's three proline residues: A25P, S28P and S29P. Single proline mutants of hIAPP have also been shown to kinetically inhibit hIAPP fibril formation. Because of their intrinsic dihedral angle preferences, prolines are expected to affect conformational ensembles of intrinsically disordered proteins. The specific effect of proline substitutions on IAPP structure and dynamics has not yet been explored, as the detection of such properties is experimentally challenging due to the low molecular weight, fast reconfiguration times, and very low solubility of IAPP peptides. High-resolution techniques able to measure tertiary contact formations are needed to address this issue. We employ a nanosecond laser spectroscopy technique to measure end-to-end contact formation rates in IAPP mutants. We explore the proline substitutions in IAPP and quantify their effects in terms of intrinsic chain stiffness. We find that the three proline mutations found in rIAPP increase chain stiffness. Interestingly, we also find that residue R18 plays an important role in rIAPP's unique chain stiffness and, together with the proline residues, is a determinant for its non-amyloidogenic properties. We discuss the implications of our findings on the role of prolines in IDPs.
ContributorsCope, Stephanie M (Author) / Vaiana, Sara M (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Ros, Robert (Committee member) / Lindsay, Stuart M (Committee member) / Ozkan, Sefika B (Committee member) / Arizona State University (Publisher)
Created2013