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- All Subjects: medicine
- Creators: Branaghan, Russell
- Status: Published
Description
We propose a novel solution to prevent cancer by developing a prophylactic cancer. Several sources of antigens for cancer vaccines have been published. Among these, antigens that contain a frame-shift (FS) peptide or viral peptide are quite attractive for a variety of reasons. FS sequences, from either mistake in RNA processing or in genomic DNA, may lead to generation of neo-peptides that are foreign to the immune system. Viral peptides presumably would originate from exogenous but integrated viral nucleic acid sequences. Both are non-self, therefore lessen concerns about development of autoimmunity. I have developed a bioinformatical approach to identify these aberrant transcripts in the cancer transcriptome. Their suitability for use in a vaccine is evaluated by establishing their frequencies and predicting possible epitopes along with their population coverage according to the prevalence of major histocompatibility complex (MHC) types. Viral transcripts and transcripts with FS mutations from gene fusion, insertion/deletion at coding microsatellite DNA, and alternative splicing were identified in NCBI Expressed Sequence Tag (EST) database. 48 FS chimeric transcripts were validated in 50 breast cell lines and 68 primary breast tumor samples with their frequencies from 4% to 98% by RT-PCR and sequencing confirmation. These 48 FS peptides, if translated and presented, could be used to protect more than 90% of the population in Northern America based on the prediction of epitopes derived from them. Furthermore, we synthesized 150 peptides that correspond to FS and viral peptides that we predicted would exist in tumor patients and we tested over 200 different cancer patient sera. We found a number of serological reactive peptide sequences in cancer patients that had little to no reactivity in healthy controls; strong support for the strength of our bioinformatic approach. This study describes a process used to identify aberrant transcripts that lead to a new source of antigens that can be tested and used in a prophylactic cancer vaccine. The vast amount of transcriptome data of various cancers from the Cancer Genome Atlas (TCGA) project will enhance our ability to further select better cancer antigen candidates.
ContributorsLee, HoJoon (Author) / Johnston, Stephen A. (Thesis advisor) / Kumar, Sudhir (Committee member) / Miller, Laurence (Committee member) / Stafford, Phillip (Committee member) / Sykes, Kathryn (Committee member) / Arizona State University (Publisher)
Created2012
Description
Peptide microarrays are to proteomics as sequencing is to genomics. As microarrays become more content-rich, higher resolution proteomic studies will parallel deep sequencing of nucleic acids. Antigen-antibody interactions can be studied at a much higher resolution using microarrays than was possible only a decade ago. My dissertation focuses on testing the feasibility of using either the Immunosignature platform, based on non-natural peptide sequences, or a pathogen peptide microarray, which uses bioinformatically-selected peptides from pathogens for creating sensitive diagnostics. Both diagnostic applications use relatively little serum from infected individuals, but each approaches diagnosis of disease differently. The first project compares pathogen epitope peptide (life-space) and non-natural (random-space) peptide microarrays while using them for the early detection of Coccidioidomycosis (Valley Fever). The second project uses NIAID category A, B and C priority pathogen epitope peptides in a multiplexed microarray platform to assess the feasibility of using epitope peptides to simultaneously diagnose multiple exposures using a single assay. Cross-reactivity is a consistent feature of several antigen-antibody based immunodiagnostics. This work utilizes microarray optimization and bioinformatic approaches to distill the underlying disease specific antibody signature pattern. Circumventing inherent cross-reactivity observed in antibody binding to peptides was crucial to achieve the goal of this work to accurately distinguishing multiple exposures simultaneously.
ContributorsNavalkar, Krupa Arun (Author) / Johnston, Stephen A. (Thesis advisor) / Stafford, Phillip (Thesis advisor) / Sykes, Kathryn (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2014
Description
The medical field is constantly looking for technological solutions to reduce user-error and improve procedures. As a potential solution for healthcare environments, Augmented Reality (AR) has received increasing attention in the past few decades due to advances in computing capabilities, lower cost, and better displays (Sauer, Khamene, Bascle, Vogt, & Rubino, 2002). Augmented Reality, as defined in Ronald Azuma’s initial survey of AR, combines virtual and real-world environments in three dimensions and in real-time (Azuma, 1997). Because visualization displays used in AR are related to human physiologic and cognitive constraints, any new system must improve on previous methods and be consistently aligned with human abilities in mind (Drascic & Milgram, 1996; Kruijff, Swan, & Feiner, 2010; Ziv, Wolpe, Small, & Glick, 2006). Based on promising findings from aviation and driving (Liu & Wen, 2004; Sojourner & Antin, 1990; Ververs & Wickens, 1998), this study identifies whether the spatial proximity affordance provided by a head-mounted display or alternative heads up display might benefit to attentional performance in a simulated routine medical task. Additionally, the present study explores how tasks of varying relatedness may relate to attentional performance differences when these tasks are presented at different spatial distances.
Contributorsdel Rio, Richard A (Author) / Branaghan, Russell (Thesis advisor) / Gray, Rob (Committee member) / Chiou, Erin (Committee member) / Arizona State University (Publisher)
Created2017
Description
Medical errors are now estimated to be the third leading cause of death in the United States (Makary & Daniel, 2016). Look-alike, sound- alike prescription drug mix-ups contribute to this figure. The US Food and Drug Administration (FDA) and Institute for Safe Medication Practices (ISMP) have recommended the use of Tall Man lettering since 2008, in which dissimilar portions of confusable drug names pairs are capitalized in order to make them more distinguishable. Research on the efficacy of Tall Man lettering in differentiating confusable drug name pairs has been inconclusive and it is imperative to investigate potential efficacy further considering the clinical implications (Lambert, Schroeder & Galanter, 2015). The present study aimed to add to the body of research on Tall Man lettering while also investigating another possibility for the mechanism behind Tall Man’s efficacy, if it in fact exists. Studies indicate that the first letter in a word offers an advantage over other positions, resulting in more accurate and faster recognition (Adelman, Marquis & Sabatos-DeVito, 2010; Scaltritti & Balota, 2013). The present study used a 2x3 repeated measures design to analyze the effect of position on Tall Man lettering efficacy. Participants were shown a prime drug, followed by a brief mask, and then either the same drug name or its confusable pair and asked to identify whether they were the same or different. All participants completed both lowercase and Tall Man conditions. Overall performance measured by accuracy and reaction time revealed lowercase to be more effective than Tall Man. With regard to the position of Tall Man letters, a first position advantage was seen both in accuracy and reaction time. A first position advantage was seen in the lowercase condition as well, suggesting the location of the differing portion of the word matters more than the format used. These findings add to the body of inconclusive research on the efficacy of Tall Man lettering in drug name confusion. Considering its impact on patient safety, more research should be conducted to definitively answer the question as to whether or not Tall Man should be used in practice.
ContributorsKnobloch, Ashley (Author) / Branaghan, Russell (Thesis advisor) / Cooke, Nancy J. (Committee member) / Gray, Robert (Committee member) / Arizona State University (Publisher)
Created2017
Description
ABSTRACT
The cold and the flu are two of the most prevalent diseases in the world. Many over the counter (OTC) medications have been created to combat the symptoms of these illnesses. Some medications take a holistic approach by claiming to alleviate a wide range of symptoms, while others target a specific symptom. As these medications become more ubiquitous within the United State of America (USA), consumers form associations and mental models about the cold/flu field. The goal of Study 1 was to build a Pathfinder network based on the associations consumers make between cold/flu symptoms and medications. 100 participants, 18 years or older, fluent in English, and residing in the USA, completed a survey about the relatedness of cold/flu symptoms to OTC medications. They rated the relatedness on a scale of 1 (highly unrelated) to 7 (highly related) and those rankings were used to build a Pathfinder network that represented the average of those associations. Study 2 was conducted to validate the Pathfinder network. A different set of 90 participants with the same restrictions as those in Study 1 completed a matching associations test. They were prompted to match symptoms and medications they associated closely with each other. Results showered a significant negative correlation between the geodetic distance (the number of links between objects in the Pathfinder network) separating symptoms and medications and frequency of pairing symptoms with medication. This provides evidence of the validity of the Pathfinder network. It was also seen that, higher the relatedness rating between symptoms and medications in Study 1, higher the frequency of pairing symptom to medication in Study 2, and the more directly linked those symptoms and medications were in the Pathfinder network. This network can inform pharmaceutical companies about which symptoms they most closely associate with, who their competitors are, what symptoms they can dominate, and how to market their medications more effectively.
The cold and the flu are two of the most prevalent diseases in the world. Many over the counter (OTC) medications have been created to combat the symptoms of these illnesses. Some medications take a holistic approach by claiming to alleviate a wide range of symptoms, while others target a specific symptom. As these medications become more ubiquitous within the United State of America (USA), consumers form associations and mental models about the cold/flu field. The goal of Study 1 was to build a Pathfinder network based on the associations consumers make between cold/flu symptoms and medications. 100 participants, 18 years or older, fluent in English, and residing in the USA, completed a survey about the relatedness of cold/flu symptoms to OTC medications. They rated the relatedness on a scale of 1 (highly unrelated) to 7 (highly related) and those rankings were used to build a Pathfinder network that represented the average of those associations. Study 2 was conducted to validate the Pathfinder network. A different set of 90 participants with the same restrictions as those in Study 1 completed a matching associations test. They were prompted to match symptoms and medications they associated closely with each other. Results showered a significant negative correlation between the geodetic distance (the number of links between objects in the Pathfinder network) separating symptoms and medications and frequency of pairing symptoms with medication. This provides evidence of the validity of the Pathfinder network. It was also seen that, higher the relatedness rating between symptoms and medications in Study 1, higher the frequency of pairing symptom to medication in Study 2, and the more directly linked those symptoms and medications were in the Pathfinder network. This network can inform pharmaceutical companies about which symptoms they most closely associate with, who their competitors are, what symptoms they can dominate, and how to market their medications more effectively.
ContributorsTendolkar, Tanvi Gopal (Author) / Branaghan, Russell (Thesis advisor) / Chiou, Erin (Committee member) / Craig, Scotty (Committee member) / Arizona State University (Publisher)
Created2020