Matching Items (210)
Description
Telomerase is a specialized enzyme that adds telomeric DNA repeats to the chromosome ends to counterbalance the progressive telomere shortening over cell divisions. It has two essential core components, a catalytic telomerase reverse transcriptase protein (TERT), and a telomerase RNA (TR). TERT synthesizes telomeric DNA by reverse transcribing a short template sequence in TR. Unlike TERT, TR is extremely divergent in size, sequence and structure and has only been identified in three evolutionarily distant groups. The lack of knowledge on TR from important model organisms has been a roadblock for vigorous studies on telomerase regulation. To address this issue, a novel in vitro system combining deep-sequencing and bioinformatics search was developed to discover TR from new phylogenetic groups. The system has been validated by the successful identification of TR from echinoderm purple sea urchin Strongylocentrotus purpuratus. The sea urchin TR (spTR) is the first invertebrate TR that has been identified and can serve as a model for understanding how the vertebrate TR evolved with vertebrate-specific traits. By using phylogenetic comparative analysis, the secondary structure of spTR was determined. The spTR secondary structure reveals unique sea urchin specific structure elements as well as homologous structural features shared by TR from other organisms. This study enhanced the understanding of telomerase mechanism and the evolution of telomerase RNP. The system that was used to identity telomerase RNA can be employed for the discovery of other TR as well as the discovery of novel RNA from other RNP complex.
ContributorsLi, Yang (Author) / Chen, Julian Jl (Thesis advisor) / Yan, Hao (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
With the advent of technologies such as web services, service oriented architecture and cloud computing, modern organizations have to deal with policies such as Firewall policies to secure the networks, XACML (eXtensible Access Control Markup Language) policies for controlling the access to critical information as well as resources. Management of these policies is an extremely important task in order to avoid unintended security leakages via illegal accesses, while maintaining proper access to services for legitimate users. Managing and maintaining access control policies manually over long period of time is an error prone task due to their inherent complex nature. Existing tools and mechanisms for policy management use different approaches for different types of policies. This research thesis represents a generic framework to provide an unified approach for policy analysis and management of different types of policies. Generic approach captures the common semantics and structure of different access control policies with the notion of policy ontology. Policy ontology representation is then utilized for effectively analyzing and managing the policies. This thesis also discusses a proof-of-concept implementation of the proposed generic framework and demonstrates how efficiently this unified approach can be used for analysis and management of different types of access control policies.
ContributorsKulkarni, Ketan (Author) / Ahn, Gail-Joon (Thesis advisor) / Yau, Stephen S. (Committee member) / Huang, Dijiang (Committee member) / Arizona State University (Publisher)
Created2011
Description
Nucleosomes are the basic repetitive unit of eukaryotic chromatin and are responsible for packing DNA inside the nucleus of the cell. They consist of a complex of eight histone proteins (two copies of four proteins H2A, H2B, H3 and H4) around which 147 base pairs of DNA are wrapped in ~1.67 superhelical turns. Although the nucleosomes are stable protein-DNA complexes, they undergo spontaneous conformational changes that occur in an asynchronous fashion. This conformational dynamics, defined by the "site-exposure" model, involves the DNA unwrapping from the protein core and exposing itself transiently before wrapping back. Physiologically, this allows regulatory proteins to bind to their target DNA sites during cellular processes like replication, DNA repair and transcription. Traditional biochemical assays have stablished the equilibrium constants for the accessibility to various sites along the length of the nucleosomal DNA, from its end to the middle of the dyad axis. Using fluorescence correlation spectroscopy (FCS), we have established the position dependent rewrapping rates for nucleosomes. We have also used Monte Carlo simulation methods to analyze the applicability of FRET fluctuation spectroscopy towards conformational dynamics, specifically motivated by nucleosome dynamics. Another important conformational change that is involved in cellular processes is the disassembly of nucleosome into its constituent particles. The exact pathway adopted by nucleosomes is still not clear. We used dual color fluorescence correlation spectroscopy to study the intermediates during nucleosome disassembly induced by changing ionic strength. Studying the nature of nucleosome conformational change and the kinetics is very important in understanding gene expression. The results from this thesis give a quantitative description to the basic unit of the chromatin.
ContributorsGurunathan, Kaushik (Author) / Levitus, Marcia (Thesis advisor) / Lindsay, Stuart (Committee member) / Woodbury, Neal (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2011
Description
This dissertation is focused on building scalable Attribute Based Security Systems (ABSS), including efficient and privacy-preserving attribute based encryption schemes and applications to group communications and cloud computing. First of all, a Constant Ciphertext Policy Attribute Based Encryption (CCP-ABE) is proposed. Existing Attribute Based Encryption (ABE) schemes usually incur large, linearly increasing ciphertext. The proposed CCP-ABE dramatically reduces the ciphertext to small, constant size. This is the first existing ABE scheme that achieves constant ciphertext size. Also, the proposed CCP-ABE scheme is fully collusion-resistant such that users can not combine their attributes to elevate their decryption capacity. Next step, efficient ABE schemes are applied to construct optimal group communication schemes and broadcast encryption schemes. An attribute based Optimal Group Key (OGK) management scheme that attains communication-storage optimality without collusion vulnerability is presented. Then, a novel broadcast encryption model: Attribute Based Broadcast Encryption (ABBE) is introduced, which exploits the many-to-many nature of attributes to dramatically reduce the storage complexity from linear to logarithm and enable expressive attribute based access policies. The privacy issues are also considered and addressed in ABSS. Firstly, a hidden policy based ABE schemes is proposed to protect receivers' privacy by hiding the access policy. Secondly,a new concept: Gradual Identity Exposure (GIE) is introduced to address the restrictions of hidden policy based ABE schemes. GIE's approach is to reveal the receivers' information gradually by allowing ciphertext recipients to decrypt the message using their possessed attributes one-by-one. If the receiver does not possess one attribute in this procedure, the rest of attributes are still hidden. Compared to hidden-policy based solutions, GIE provides significant performance improvement in terms of reducing both computation and communication overhead. Last but not least, ABSS are incorporated into the mobile cloud computing scenarios. In the proposed secure mobile cloud data management framework, the light weight mobile devices can securely outsource expensive ABE operations and data storage to untrusted cloud service providers. The reported scheme includes two components: (1) a Cloud-Assisted Attribute-Based Encryption/Decryption (CA-ABE) scheme and (2) An Attribute-Based Data Storage (ABDS) scheme that achieves information theoretical optimality.
ContributorsZhou, Zhibin (Author) / Huang, Dijiang (Thesis advisor) / Yau, Sik-Sang (Committee member) / Ahn, Gail-Joon (Committee member) / Reisslein, Martin (Committee member) / Arizona State University (Publisher)
Created2011
Description
ABSTRACT The unique structural features of deoxyribonucleic acid (DNA) that are of considerable biological interest also make it a valuable engineering material. Perhaps the most useful property of DNA for molecular engineering is its ability to self-assemble into predictable, double helical secondary structures. These interactions are exploited to design a variety of DNA nanostructures, which can be organized into both discrete and periodic structures. This dissertation focuses on studying the dynamic behavior of DNA nanostructure recognition processes. The thermodynamics and kinetics of nanostructure binding are evaluated, with the intention of improving our ability to understand and control their assembly. Presented here are a series of studies toward this goal. First, multi-helical DNA nanostructures were used to investigate how the valency and arrangement of the connections between DNA nanostructures affect super-structure formation. The study revealed that both the number and the relative position of connections play a significant role in the stability of the final assembly. Next, several DNA nanostructures were designed to gain insight into how small changes to the nanostructure scaffolds, intended to vary their conformational flexibility, would affect their association equilibrium. This approach yielded quantitative information about the roles of enthalpy and entropy in the affinity of polyvalent DNA nanostructure interactions, which exhibit an intriguing compensating effect. Finally, a multi-helical DNA nanostructure was used as a model `chip' for the detection of a single stranded DNA target. The results revealed that the rate constant of hybridization is strongly dominated by a rate-limiting nucleation step.
ContributorsNangreave, Jeanette (Author) / Yan, Hao (Thesis advisor) / Liu, Yan (Thesis advisor) / Chen, Julian J.-L. (Committee member) / Seo, Dong Kyun (Committee member) / Arizona State University (Publisher)
Created2011
Description
A major goal of synthetic biology is to recapitulate emergent properties of life. Despite a significant body of work, a longstanding question that remains to be answered is how such a complex system arose? In this dissertation, synthetic nucleic acid molecules with alternative sugar-phosphate backbones were investigated as potential ancestors of DNA and RNA. Threose nucleic acid (TNA) is capable of forming stable helical structures with complementary strands of itself and RNA. This provides a plausible mechanism for genetic information transfer between TNA and RNA. Therefore TNA has been proposed as a potential RNA progenitor. Using molecular evolution, functional sequences were isolated from a pool of random TNA molecules. This implicates a possible chemical framework capable of crosstalk between TNA and RNA. Further, this shows that heredity and evolution are not limited to the natural genetic system based on ribofuranosyl nucleic acids. Another alternative genetic system, glycerol nucleic acid (GNA) undergoes intrasystem pairing with superior thermalstability compared to that of DNA. Inspired by this property, I demonstrated a minimal nanostructure composed of both left- and right-handed mirro image GNA. This work suggested that GNA could be useful as promising orthogonal material in structural DNA nanotechnology.
ContributorsZhang, Su (Author) / Chaut, John C (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2011
Description
Natural photosynthesis features a complex biophysical/chemical process that requires sunlight to produce energy rich products. It is one of the most important processes responsible for the appearance and sustainability of life on earth. The first part of the thesis focuses on understanding the mechanisms involved in regulation of light harvesting, which is necessary to balance the absorption and utilization of light energy and in that way reduce the effect caused by photooxidative damage. In photosynthesis, carotenoids are responsible not only for collection of light, but also play a major role in protecting the photosynthetic system. To investigate the role of carotenoids in the quenching of the excited state of cyclic tetrapyrroles, two sets of dyads were studied. Both sets of dyads contain zinc phthalocyanine (Pc) covalently attached to carotenoids of varying conjugation lengths. In the first set of dyads, carotenoids were attached to the phthalocyanine via amide linkage. This set of dyads serves as a good model for understanding the molecular "gear-shift" mechanism, where the addition of one double bond can turn the carotenoid from a nonquencher to a very strong quencher of the excited state of a tetrapyrrole. In the second set of dyads, carotenoids were attached to phthalocyanine via a phenyl amino group. Two independent studies were performed on these dyads: femtosecond transient absorption and steady state fluorescence induced by two-photon excitation. In the transient absorption study it was observed that there is an instantaneous population of the carotenoid S1 state after Pc excitation, while two-photon excitation of the optically forbidden carotenoid S1 state shows 1Pc population. Both observations provide a strong indication of the existence of a shared excitonic state between carotenoid and Pc. Similar results were observed in LHC II complexes in plants, supporting the role of such interactions in photosynthetic down regulation. In the second chapter we describe the synthesis of porphyrin dyes functionalized with carboxylate and phosphonate anchoring groups to be used in the construction of photoelectrochemical cells containing a porphyrin-IrO2·nH2O complex immobilized on a TiO2 electrode. The research presented here is a step in the development of high potential porphyrin-metal oxide complexes to be used in the photooxidation of water. The last chapter focuses on developing synthetic strategies for the construction of an artificial antenna system consisting of porphyrin-silver nanoparticle conjugates, linked by DNA of varied length to study the distance dependence of the interaction between nanoparticles and the porphyrin chromophore. Preliminary studies indicate that at the distance of about 7-10 nm between porphyrin and silver nanoparticle is where the porphyrin absorption leading to fluorescence shows maximum enhancement. These new hybrid constructs will be helpful for designing efficient light harvesting systems.
ContributorsPillai, Smitha (Author) / Moore, Ana (Thesis advisor) / Moore, Thomas (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2011
Description
Action language C+ is a formalism for describing properties of actions, which is based on nonmonotonic causal logic. The definite fragment of C+ is implemented in the Causal Calculator (CCalc), which is based on the reduction of nonmonotonic causal logic to propositional logic. This thesis describes the language of CCalc in terms of answer set programming (ASP), based on the translation of nonmonotonic causal logic to formulas under the stable model semantics. I designed a standard library which describes the constructs of the input language of CCalc in terms of ASP, allowing a simple modular method to represent CCalc input programs in the language of ASP. Using the combination of system F2LP and answer set solvers, this method achieves functionality close to that of CCalc while taking advantage of answer set solvers to yield efficient computation that is orders of magnitude faster than CCalc for many benchmark examples. In support of this, I created an automated translation system Cplus2ASP that implements the translation and encoding method and automatically invokes the necessary software to solve the translated input programs.
ContributorsCasolary, Michael (Author) / Lee, Joohyung (Thesis advisor) / Ahn, Gail-Joon (Committee member) / Baral, Chitta (Committee member) / Arizona State University (Publisher)
Created2011
Description
In order to catch the smartest criminals in the world, digital forensics examiners need a means of collaborating and sharing information with each other and outside experts that is not prohibitively difficult. However, standard operating procedures and the rules of evidence generally disallow the use of the collaboration software and techniques that are currently available because they do not fully adhere to the dictated procedures for the handling, analysis, and disclosure of items relating to cases. The aim of this work is to conceive and design a framework that provides a completely new architecture that 1) can perform fundamental functions that are common and necessary to forensic analyses, and 2) is structured such that it is possible to include collaboration-facilitating components without changing the way users interact with the system sans collaboration. This framework is called the Collaborative Forensic Framework (CUFF). CUFF is constructed from four main components: Cuff Link, Storage, Web Interface, and Analysis Block. With the Cuff Link acting as a mediator between components, CUFF is flexible in both the method of deployment and the technologies used in implementation. The details of a realization of CUFF are given, which uses a combination of Java, the Google Web Toolkit, Django with Apache for a RESTful web service, and an Ubuntu Enterprise Cloud using Eucalyptus. The functionality of CUFF's components is demonstrated by the integration of an acquisition script designed for Android OS-based mobile devices that use the YAFFS2 file system. While this work has obvious application to examination labs which work under the mandate of judicial or investigative bodies, security officers at any organization would benefit from the improved ability to cooperate in electronic discovery efforts and internal investigations.
ContributorsMabey, Michael Kent (Author) / Ahn, Gail-Joon (Thesis advisor) / Yau, Stephen S. (Committee member) / Huang, Dijiang (Committee member) / Arizona State University (Publisher)
Created2011
Description
A potential new class of cancer chemotherapeutic agents has been synthesized by varying the 2 position of a benzimidazole based extended amidine. Compounds 6-amino-2-chloromethyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1A) and 6-amino-2-hydroxypropyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1B) were assayed at the National Cancer Institute's (NCI) Developmental Therapeutic Program (DTP) and found to be cytotoxic at sub-micromolar concentrations, and have shown between a 100 and a 1000-fold increase in specificity towards lung, colon, CNS, and melanoma cell lines. These ATP mimics have been found to correlate with sequestosome 1 (SQSTM1), a protein implicated in drug resistance and cell survival in various cancer cell lines. Using the DTP COMPARE algorithm, compounds 1A and 1B were shown to correlate to each other at 77%, but failed to correlate with other benzimidazole based extended amidines previously synthesized in this laboratory suggesting they operate through a different biological mechanism.
ContributorsDarzi, Evan (Author) / Skibo, Edward (Thesis advisor) / Gould, Ian (Committee member) / Francisco, Wilson (Committee member) / Arizona State University (Publisher)
Created2011