Matching Items (192)
Description
In the 1970s James Watson recognized the inability of conventional DNA replication machinery to replicate the extreme termini of chromosomes known as telomeres. This inability is due to the requirement of a building block primer and was termed the end replication problem. Telomerase is nature's answer to the end replication problem. Telomerase is a ribonucleoprotein which extends telomeres through reverse transcriptase activity by reiteratively copying a short intrinsic RNA sequence to generate 3' telomeric extensions. Telomeres protect chromosomes from erosion of coding genes during replication, as well as differentiate native chromosome ends from double stranded breaks. However, controlled erosion of telomeres functions as a naturally occurring molecular clock limiting the replicative capacity of cells. Telomerase is over activated in many cancers, while inactivation leads to multiple lifespan limiting human diseases. In order to further study the interaction between telomerase RNA (TR) and telomerase reverse transcriptase protein (TERT), vertebrate TERT fragments were screened for solubility and purity following bacterial expression. Soluble fragments of medaka TERT including the RNA binding domain (TRBD) were identified. Recombinant medaka TRBD binds specifically to telomerase RNA CR4/CR5 region. Ribonucleotide and amino acid pairs in close proximity within the medaka telomerase RNA-protein complex were identified using photo-activated cross-linking in conjunction with mass spectrometry. The identified cross-linking amino acids were mapped on known crystal structures of TERTs to reveal the RNA interaction interface of TRBD. The identification of this RNA TERT interaction interface furthers the understanding of the telomerase complex at a molecular level and could be used for the targeted interruption of the telomerase complex as a potential cancer treatment.
ContributorsBley, Christopher James (Author) / Chen, Julian (Thesis advisor) / Allen, James (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
This thesis proposed a novel approach to establish the trust model in a social network scenario based on users' emails. Email is one of the most important social connections nowadays. By analyzing email exchange activities among users, a social network trust model can be established to judge the trust rate between each two users. The whole trust checking process is divided into two steps: local checking and remote checking. Local checking directly contacts the email server to calculate the trust rate based on user's own email communication history. Remote checking is a distributed computing process to get help from user's social network friends and built the trust rate together. The email-based trust model is built upon a cloud computing framework called MobiCloud. Inside MobiCloud, each user occupies a virtual machine which can directly communicate with others. Based on this feature, the distributed trust model is implemented as a combination of local analysis and remote analysis in the cloud. Experiment results show that the trust evaluation model can give accurate trust rate even in a small scale social network which does not have lots of social connections. With this trust model, the security in both social network services and email communication could be improved.
ContributorsZhong, Yunji (Author) / Huang, Dijiang (Thesis advisor) / Dasgupta, Partha (Committee member) / Syrotiuk, Violet (Committee member) / Arizona State University (Publisher)
Created2011
Description
The use of enzyme-catalyst interfaces is underexplored in the field of biocatalysis, particularly in studies on enabling novel reactivity of enzymes. For this thesis, the HaloTag® protein tagging platform was proposed as a bioconjugation method for a pinacol coupling reaction using lipases, as a model for novel reactivities proceeding via ketyl radical intermediates and hydrogen-bonding-facilitated redox attenuation. After an initial lipase screening of 9 lipases, one lipase (Candida rugosa) was found to perform the pinacol coupling of p-anisaldehyde under standard conditions (fluorescein and 530nm light, 3% yield). Based on a retrosynthetic analysis for the photocatalyst-incorporated HaloTag® linker, the intermediates haloamine 1 and aldehyde 6 were synthesized. Further experiments are underway or planned to complete linker synthesis and conduct pinacol coupling experiments with a bioconjugated system. This project underscores the promising biocatalytic promiscuity of lipases for performing reactions proceeding through ketyl radical intermediates, as well as the underdeveloped potential of incorporating bioengineering principles like bioconjugation into biocatalysis to overcome kinetic barriers to electron transfer and optimize biocatalytic reactions.
ContributorsMcrae, Kenna Christine (Author) / Biegasiewicz, Kyle (Thesis director) / Ghirlanda, Giovanna (Committee member) / Moore, Ana (Committee member) / Department of Physics (Contributor) / School of Human Evolution & Social Change (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Telomerase ribonucleoprotein is a unique reverse transcriptase that adds telomeric DNA repeats to chromosome ends. Telomerase RNA (TER) is extremely divergent in size, sequence and has to date only been identified in vertebrate, yeast, ciliate and plant species. Herein, the identification and characterization of TERs from an evolutionarily distinct group, filamentous fungi, is presented. Based on phylogenetic analysis of 69 TER sequences and mutagenesis analysis of in vitro reconstituted Neurospora telomerase, we discovered a conserved functional core in filamentous fungal TERs sharing homologous structural features with vertebrate TERs. This core contains the template-pseudoknot and P6/P6.1 domains, essential for enzymatic activity, which retain function in trans. The in vitro reconstituted Neurospora telomerase is highly processive, synthesizing canonical TTAGGG repeats. Similar to Schizosaccharomycetes pombe, filamentous fungal TERs utilize the spliceosomal splicing machinery for 3' processing. Neurospora telomerase, while associating with the Est1 protein in vivo, does not bind homologous Ku or Sm proteins found in both budding and fission yeast telomerase holoenzyme, suggesting a unique biogenesis pathway. The development of Neurospora as a model organism to study telomeres and telomerase may shed light upon the evolution of the canonical TTAGGG telomeric repeat and telomerase processivity within fungal species.
ContributorsQi, Xiaodong (Author) / Chen, Julian (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Chaput, John (Committee member) / Arizona State University (Publisher)
Created2011
Description
The theme for this work is the development of fast numerical algorithms for sparse optimization as well as their applications in medical imaging and source localization using sensor array processing. Due to the recently proposed theory of Compressive Sensing (CS), the $\ell_1$ minimization problem attracts more attention for its ability to exploit sparsity. Traditional interior point methods encounter difficulties in computation for solving the CS applications. In the first part of this work, a fast algorithm based on the augmented Lagrangian method for solving the large-scale TV-$\ell_1$ regularized inverse problem is proposed. Specifically, by taking advantage of the separable structure, the original problem can be approximated via the sum of a series of simple functions with closed form solutions. A preconditioner for solving the block Toeplitz with Toeplitz block (BTTB) linear system is proposed to accelerate the computation. An in-depth discussion on the rate of convergence and the optimal parameter selection criteria is given. Numerical experiments are used to test the performance and the robustness of the proposed algorithm to a wide range of parameter values. Applications of the algorithm in magnetic resonance (MR) imaging and a comparison with other existing methods are included. The second part of this work is the application of the TV-$\ell_1$ model in source localization using sensor arrays. The array output is reformulated into a sparse waveform via an over-complete basis and study the $\ell_p$-norm properties in detecting the sparsity. An algorithm is proposed for minimizing a non-convex problem. According to the results of numerical experiments, the proposed algorithm with the aid of the $\ell_p$-norm can resolve closely distributed sources with higher accuracy than other existing methods.
ContributorsShen, Wei (Author) / Mittlemann, Hans D (Thesis advisor) / Renaut, Rosemary A. (Committee member) / Jackiewicz, Zdzislaw (Committee member) / Gelb, Anne (Committee member) / Ringhofer, Christian (Committee member) / Arizona State University (Publisher)
Created2011
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
This research describes software based remote attestation schemes for obtaining the integrity of an executing user application and the Operating System (OS) text section of an untrusted client platform. A trusted external entity issues a challenge to the client platform. The challenge is executable code which the client must execute, and the code generates results which are sent to the external entity. These results provide the external entity an assurance as to whether the client application and the OS are in pristine condition. This work also presents a technique where it can be verified that the application which was attested, did not get replaced by a different application after completion of the attestation. The implementation of these three techniques was achieved entirely in software and is backward compatible with legacy machines on the Intel x86 architecture. This research also presents two approaches to incorporating software based "root of trust" using Virtual Machine Monitors (VMMs). The first approach determines the integrity of an executing Guest OS from the Host OS using Linux Kernel-based Virtual Machine (KVM) and qemu emulation software. The second approach implements a small VMM called MIvmm that can be utilized as a trusted codebase to build security applications such as those implemented in this research. MIvmm was conceptualized and implemented without using any existing codebase; its minimal size allows it to be trustworthy. Both the VMM approaches leverage processor support for virtualization in the Intel x86 architecture.
ContributorsSrinivasan, Raghunathan (Author) / Dasgupta, Partha (Thesis advisor) / Colbourn, Charles (Committee member) / Shrivastava, Aviral (Committee member) / Huang, Dijiang (Committee member) / Dewan, Prashant (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
Natural products that target the DNA of cancer cells have been an important source of knowledge and understanding in the development of anticancer chemotherapeutic agents. Bleomycin (BLM) exemplifies this class of DNA damaging agent. The ability of BLM to chelate metal ions and effect oxidative damage of the deoxyribose sugar moiety of DNA has been studied extensively for four decades. Here, the study of BLM A5 was conducted using a previously isolated library of hairpin DNAs found to bind strongly to metal free BLM. The ability of BLM to effect single-stranded was then extensively characterized on both the 3′ and 5′-arms of the hairpin DNAs. The strongly bound DNAs were found to be efficient substrates for Fe·BLM A5-mediated cleavage. Surprisingly, the most prevalent site of damage by BLM was found to be a 5′-AT-3′ dinucleotide sequence. This dinucleotide sequence and others generally not cleaved by BLM when examined using arbitrarily chosen DNA substrate were found in examining the library of ten hairpin DNAs. In total, 111 sites of DNA damage were found to be produced by exposure of the hairpin DNA library to Fe·BLM A5. Also, an assay was developed with which to test the propensity of the hairpin DNAs to undergo double stranded DNA damage. Adapting methods previously described by the Povirk laboratory, one hairpin was characterized using this method. The results were in accordance with those previously reported.
ContributorsSegerman, Zachary (Author) / Hecht, Sidney M. (Thesis advisor) / Levitus, Marcia (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011