Matching Items (198)
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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

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 worked towards the development of a parameterized 3D model off a cover that could go over any specific prosthesis depending on the parameters that had been entered. It also focused on gathering user inputs, which was done with the aid of the Amputee Coalition, that could be used

This thesis worked towards the development of a parameterized 3D model off a cover that could go over any specific prosthesis depending on the parameters that had been entered. It also focused on gathering user inputs, which was done with the aid of the Amputee Coalition, that could be used to create an aesthetic design on this cover. The Amputee Coalition helped to recruit participants through its website and social media platforms. Finally, multiple methods of creating a design were developed to increase the amount of customization that a user could have for their cover.

ContributorsRiley, Nicholas (Co-author) / Fusaro, Gerard (Co-author) / Sugar, Thomas (Thesis director) / Redkar, Sangram (Committee member) / Engineering Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

This thesis worked towards the development of a parameterized 3D model off a cover that could go over any specific prosthesis depending on the parameters that had been entered. It also focused on gathering user inputs, which was done with the aid of the Amputee Coalition, that could be used

This thesis worked towards the development of a parameterized 3D model off a cover that could go over any specific prosthesis depending on the parameters that had been entered. It also focused on gathering user inputs, which was done with the aid of the Amputee Coalition, that could be used to create an aesthetic design on this cover. The Amputee Coalition helped to recruit participants through its website and social media platforms. Finally, multiple methods of creating a design were developed to increase the amount of customization that a user could have for their cover.

ContributorsFusaro, Gerard Anthony (Co-author) / Riley, Nicholas (Co-author) / Sugar, Thomas (Thesis director) / Redkar, Sangram (Committee member) / College of Integrative Sciences and Arts (Contributor) / Engineering Programs (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The purpose of this creative project was to create a stereo sound system in a unique medium. As a team, we decided to integrate a Tesla Coil with a bluetooth audio source. These high frequency, high voltage systems can be configured to emit their electrical discharge in a manner that

The purpose of this creative project was to create a stereo sound system in a unique medium. As a team, we decided to integrate a Tesla Coil with a bluetooth audio source. These high frequency, high voltage systems can be configured to emit their electrical discharge in a manner that resembles playing tunes. Originally the idea was to split the audio into left and right, then to further segregate the signals to have a treble, mid, and base emitter for each side. Due to time, budget, and scope constraints, we decided to complete the project with only two coils.<br/><br/>For this project, the team decided to use a solid-state coil kit. This kit was purchased from OneTelsa and would help ensure everyone’s safety and the project’s success. The team developed our own interrupting or driving circuit through reverse-engineering the interrupter provided by oneTesla and discussing with other engineers. The custom interpreter was controlled by the PSoC5 LP and communicated with an audio source through the DFRobot Bluetooth module. Utilizing the left and right audio signals it can drive the two Tesla Coils in stereo to play the music.

ContributorsPinkowski, Olivia N (Co-author) / Hutcherson, Cree (Co-author) / Jordan, Shawn (Thesis director) / Sugar, Thomas (Committee member) / Engineering Programs (Contributor, Contributor) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The purpose of this creative project was to create a stereo sound system in a unique medium. As a team, we decided to integrate a Tesla Coil with a bluetooth audio source. These high frequency, high voltage systems can be configured to emit their electrical discharge in a manner that

The purpose of this creative project was to create a stereo sound system in a unique medium. As a team, we decided to integrate a Tesla Coil with a bluetooth audio source. These high frequency, high voltage systems can be configured to emit their electrical discharge in a manner that resembles playing tunes. Originally the idea was to split the audio into left and right, then to further segregate the signals to have a treble, mid, and base emitter for each side. Due to time, budget, and scope constraints, we decided to complete the project with only two coils.<br/><br/>For this project, the team decided to use a solid-state coil kit. This kit was purchased from OneTelsa and would help ensure everyone’s safety and the project’s success. The team developed our own interrupting or driving circuit through reverse-engineering the interrupter provided by oneTesla and discussing with other engineers. The custom interpreter was controlled by the PSoC5 LP and communicated with an audio source through the DFRobot Bluetooth module. Utilizing the left and right audio signals it can drive the two Tesla Coils in stereo to play the music.

ContributorsHutcherson, Cree (Co-author) / Pinkowski, Olivia (Co-author) / Jordan, Shawn (Thesis director) / Sugar, Thomas (Committee member) / Engineering Programs (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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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

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
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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,

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
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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

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
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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

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
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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

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