Matching Items (113)
Filtering by
- Language: English
Description
A synbody is a newly developed protein binding peptide which can be rapidly produced by chemical methods. The advantages of the synbody producing process make it a potential human proteome binding reagent. Most of the synbodies are designed to bind to specific proteins. The peptides incorporated in a synbody are discovered with peptide microarray technology. Nevertheless, the targets for unknown synbodies can also be discovered by searching through a protein mixture. The first part of this thesis mainly focuses on the process of target searching, which was performed with immunoprecipitation assays and mass spectrometry analysis. Proteins are pulled down from the cell lysate by certain synbodies, and then these proteins are identified using mass spectrometry. After excluding non-specific bindings, the interaction between a synbody and its real target(s) can be verified with affinity measurements. As a specific example, the binding between 1-4-KCap synbody and actin was discovered. This result proved the feasibility of the mass spectrometry based method and also suggested that a high throughput synbody discovery platform for the human proteome could be developed. Besides the application of synbody development, the peptide microarray technology can also be used for immunosignatures. The composition of all types of antibodies existing in one's blood is related to an individual's health condition. A method, called immunosignaturing, has been developed for early disease diagnosis based on this principle. CIM10K microarray slides work as a platform for blood antibody detection in immunosignaturing. During the analysis of an immunosignature, the data from these slides needs to be validated by using landing light peptides. The second part of this thesis focuses on the validation of the data. A biotinylated peptide was used as a landing light on the new CIM10K slides. The data was collected in several rounds of tests and indicated that the variation among landing lights was significantly reduced by using the newly prepared biotinylated peptide compared with old peptide mixture. Several suggestions for further landing light improvement are proposed based on the results.
ContributorsSun, Minyao (Author) / Johnston, Stephen Albert (Thesis advisor) / Diehnelt, Chris Wayne (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
Immunosignaturing is a new immunodiagnostic technology that uses random-sequence peptide microarrays to profile the humoral immune response. Though the peptides have little sequence homology to any known protein, binding of serum antibodies may be detected, and the pattern correlated to disease states. The aim of my dissertation is to analyze the factors affecting the binding patterns using monoclonal antibodies and determine how much information may be extracted from the sequences. Specifically, I examined the effects of antibody concentration, competition, peptide density, and antibody valence. Peptide binding could be detected at the low concentrations relevant to immunosignaturing, and a monoclonal's signature could even be detected in the presences of 100 fold excess naive IgG. I also found that peptide density was important, but this effect was not due to bivalent binding. Next, I examined in more detail how a polyreactive antibody binds to the random sequence peptides compared to protein sequence derived peptides, and found that it bound to many peptides from both sets, but with low apparent affinity. An in depth look at how the peptide physicochemical properties and sequence complexity revealed that there were some correlations with properties, but they were generally small and varied greatly between antibodies. However, on a limited diversity but larger peptide library, I found that sequence complexity was important for antibody binding. The redundancy on that library did enable the identification of specific sub-sequences recognized by an antibody. The current immunosignaturing platform has little repetition of sub-sequences, so I evaluated several methods to infer antibody epitopes. I found two methods that had modest prediction accuracy, and I developed a software application called GuiTope to facilitate the epitope prediction analysis. None of the methods had sufficient accuracy to identify an unknown antigen from a database. In conclusion, the characteristics of the immunosignaturing platform observed through monoclonal antibody experiments demonstrate its promise as a new diagnostic technology. However, a major limitation is the difficulty in connecting the signature back to the original antigen, though larger peptide libraries could facilitate these predictions.
ContributorsHalperin, Rebecca (Author) / Johnston, Stephen A. (Thesis advisor) / Bordner, Andrew (Committee member) / Taylor, Thomas (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
African Swine Fever (ASF), endemic in many African countries, is now spreading to other continents. Though ASF is capable of incurring serious economic losses in affected countries, no vaccine exists to provide immunity to animals. Disease control relies largely on rapid diagnosis and the implementation of movement restrictions and strict eradication programs. Developing a scalable, accurate and low cost diagnostic for ASF will be of great help for the current situation. CIM's 10K random peptide microarray is a new high-throughput platform that allows systematic investigations of immune responses associated with disease and shows promise as a diagnostic tool. In this study, this new technology was applied to characterize the immune responses of ASF virus (ASFV) infections and immunizations. Six sets of sera from ASFV antigen immunized pigs, 6 sera from infected pigs and 20 sera samples from unexposed pigs were tested and analyzed statistically. Results show that both ASFV antigen immunized pigs and ASFV viral infected pigs can be distinguished from unexposed pigs. Since it appears that immune responses to other viral infections are also distinguishable on this platform, it holds the potential of being useful in developing a new ASF diagnostic. The ability of this platform to identify specific ASFV antibody epitopes was also explored. A subtle motif was found to be shared among a set of peptides displaying the highest reactivity for an antigen specific antibody. However, this motif does not seem to match with any antibody epitopes predicted by a linear antibody epitope prediction.
ContributorsXiao, Liang (Author) / Sykes, Kathryn (Thesis advisor) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
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
Immunosignaturing is a technology that allows the humoral immune response to be observed through the binding of antibodies to random sequence peptides. The immunosignaturing microarray is based on complex mixtures of antibodies binding to arrays of random sequence peptides in a multiplexed fashion. There are computational and statistical challenges to the analysis of immunosignaturing data. The overall aim of my dissertation is to develop novel computational and statistical methods for immunosignaturing data to access its potential for diagnostics and drug discovery. Firstly, I discovered that a classification algorithm Naive Bayes which leverages the biological independence of the probes on our array in such a way as to gather more information outperforms other classification algorithms due to speed and accuracy. Secondly, using this classifier, I then tested the specificity and sensitivity of immunosignaturing platform for its ability to resolve four different diseases (pancreatic cancer, pancreatitis, type 2 diabetes and panIN) that target the same organ (pancreas). These diseases were separated with >90% specificity from controls and from each other. Thirdly, I observed that the immunosignature of type 2 diabetes and cardiovascular complications are unique, consistent, and reproducible and can be separated by 100% accuracy from controls. But when these two complications arise in the same person, the resultant immunosignature is quite different in that of individuals with only one disease. I developed a method to trace back from informative random peptides in disease signatures to the potential antigen(s). Hence, I built a decipher system to trace random peptides in type 1 diabetes immunosignature to known antigens. Immunosignaturing, unlike the ELISA, has the ability to not only detect the presence of response but also absence of response during a disease. I observed, not only higher but also lower peptides intensities can be mapped to antigens in type 1 diabetes. To study immunosignaturing potential for population diagnostics, I studied effect of age, gender and geographical location on immunosignaturing data. For its potential to be a health monitoring technology, I proposed a single metric Coefficient of Variation that has shown potential to change significantly when a person enters a disease state.
ContributorsKukreja, Muskan (Author) / Johnston, Stephen Albert (Thesis advisor) / Stafford, Phillip (Committee member) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2012
Description
Some of the most talented, innovative, and experimental artists are students, but they are often discouraged by the price of higher education and lack of scholarship or funding opportunities. Additionally, the art industry has become stagnant. Traditional brick-and-mortar galleries are not willing to represent young, unknown artists. Their overhead is simply too high for risky choices.
The Student Art Project is art patronage for the 21st century—a curated online gallery featuring exceptional student artists. The Student Art Project is a highly curated experience for buyers. Only five artists are featured each month. Buyers are not bombarded with thousands of different products and separate artists “shops”. They can read artists bios and find art they connect with.
Student artists apply through an online form. Once accepted to the program, artists receive a $200 materials stipend to create an exclusive collection of 5-10 pieces. Original artwork and limited edition prints are sold through our website. These collections can potentially fund an entire year of college tuition, a life-changing amount for many students.
Brick-and-mortar galleries typically take 40-60% of the retail price of artwork. The Student Art Project will only take 30%, which we will use to reinvest in future artists. Other art websites, like Etsy, require the artists to ship, invoice, and communicate with customers. For students, this means less time spent in the classroom and less time developing their craft. The Student Art Project handles all business functions for our artists, allowing them to concentrate on what really matters, their education.
The Student Art Project is art patronage for the 21st century—a curated online gallery featuring exceptional student artists. The Student Art Project is a highly curated experience for buyers. Only five artists are featured each month. Buyers are not bombarded with thousands of different products and separate artists “shops”. They can read artists bios and find art they connect with.
Student artists apply through an online form. Once accepted to the program, artists receive a $200 materials stipend to create an exclusive collection of 5-10 pieces. Original artwork and limited edition prints are sold through our website. These collections can potentially fund an entire year of college tuition, a life-changing amount for many students.
Brick-and-mortar galleries typically take 40-60% of the retail price of artwork. The Student Art Project will only take 30%, which we will use to reinvest in future artists. Other art websites, like Etsy, require the artists to ship, invoice, and communicate with customers. For students, this means less time spent in the classroom and less time developing their craft. The Student Art Project handles all business functions for our artists, allowing them to concentrate on what really matters, their education.
ContributorsDangler, Rebecca Leigh (Author) / Trujillo, Rhett (Thesis director) / Coleman, Sean (Committee member) / Barrett, The Honors College (Contributor) / Herberger Institute for Design and the Arts (Contributor) / Department of Management (Contributor)
Created2015-05
Description
Drought is one of the most pressing issues affecting the future of the standard of living here in Phoenix. With the threat of water rationing and steep price hikes looming on the horizon for water customers in California, the desert southwest, and in drought-stricken communities worldwide, industrial designers are in a prime position to help improve the experience of water conservation so that consumers are willing to start taking conscious steps toward rethinking their relationship with water usage.
In a research group, several designers sought to understand the depth and complexity of this highly politicized issue by interviewing a wide variety of stakeholders, including sustainability experts, landscapers, water company executives, small business owners, reservoir forest rangers, and many more. Data synthesis led to the conclusion that residential water use is a lifestyle issue, and the only real way to conserve involves a significant shift in the collective idea of an “ideal” home—lawns, pools, and overwatered landscaping contribute to 70% of all water use by residences in the Phoenix area. The only real way to conserve involves increasing population density and creating communal green spaces.
DR. DISH is a dishwashing device that is meant to fit into the high-density living spaces that are rapidly being built in the face of the massive exodus of people into the world’s cities. To help busy apartment and condominium dwellers conserve water and time, DR. DISH converts a standard kitchen sink into a small dishwasher, which uses significantly less water than hand-washing dishes or rinsing dishes before putting them into a conventional dishwasher. Using advanced filtration technology and a powerful rinse cycle, a load dishes can be cleaned with about 2 gallons of water. Fully automating the dishwashing process also saves the user time and minimizes unpleasant contact with food residue and grease.
This device is meant to have a significant impact upon the water use of households that do not have a dishwasher, or simply do not use their dishwasher. With a low target price point and myriad convenient features, DR. DISH is a high-tech solution that promises water savings at a time when every effort toward conservation is absolutely critical. As we move toward a new era in determining water rights and imposing mandatory restrictions upon each and every person living in affected areas, creating conservation solutions that will be relevant for the lifestyles of the future is especially important, and the agility of designers in coming up with products that quickly cut consumer water consumption will be a key factor in determining whether humanity will be able to adapt to a new era in our relationship with natural resources.
In a research group, several designers sought to understand the depth and complexity of this highly politicized issue by interviewing a wide variety of stakeholders, including sustainability experts, landscapers, water company executives, small business owners, reservoir forest rangers, and many more. Data synthesis led to the conclusion that residential water use is a lifestyle issue, and the only real way to conserve involves a significant shift in the collective idea of an “ideal” home—lawns, pools, and overwatered landscaping contribute to 70% of all water use by residences in the Phoenix area. The only real way to conserve involves increasing population density and creating communal green spaces.
DR. DISH is a dishwashing device that is meant to fit into the high-density living spaces that are rapidly being built in the face of the massive exodus of people into the world’s cities. To help busy apartment and condominium dwellers conserve water and time, DR. DISH converts a standard kitchen sink into a small dishwasher, which uses significantly less water than hand-washing dishes or rinsing dishes before putting them into a conventional dishwasher. Using advanced filtration technology and a powerful rinse cycle, a load dishes can be cleaned with about 2 gallons of water. Fully automating the dishwashing process also saves the user time and minimizes unpleasant contact with food residue and grease.
This device is meant to have a significant impact upon the water use of households that do not have a dishwasher, or simply do not use their dishwasher. With a low target price point and myriad convenient features, DR. DISH is a high-tech solution that promises water savings at a time when every effort toward conservation is absolutely critical. As we move toward a new era in determining water rights and imposing mandatory restrictions upon each and every person living in affected areas, creating conservation solutions that will be relevant for the lifestyles of the future is especially important, and the agility of designers in coming up with products that quickly cut consumer water consumption will be a key factor in determining whether humanity will be able to adapt to a new era in our relationship with natural resources.
ContributorsMarcinkowski, Margaret Nicole (Author) / Shin, Dosun (Thesis director) / McDermott, Lauren (Committee member) / Barrett, The Honors College (Contributor) / The Design School (Contributor) / Herberger Institute for Design and the Arts (Contributor)
Created2015-05
Description
Fire Shelter Foam Assist is meant as a firefighter's last effort of survival when a wildfire threatens their position. When deployed, it will cover the firefighter as the fire blows over. By reducing the time of deployment and simplifying the process, firefighters will have more time to ensure the area around them is cleared. The Fire Shelter Foam Assist has features that allow it to auto deploy around the firefighter through the use of fire foam retardant. The fire foam retardant inflates the shelter as well as provides an extra layer of protection against the wildfire.
ContributorsSmith, Tori Elizabeth (Author) / Shin, Dosun (Thesis director) / McDermott, Lauren (Committee member) / Barrett, The Honors College (Contributor) / Herberger Institute for Design and the Arts (Contributor) / The Design School (Contributor)
Created2015-05
Description
After researching pediatric cancer experiences, an opportunity emerged creating a less intimidating environment for children undergoing chemotherapy. By means of adding a creative component to their IV pole and disguising machinery, children will be a part of an Imagination Voyage adventure. Creative themes allow for a journey on a pirate ship, or being in a fantasy castle by captivating children in playtime. The design allows for a frightening experience to become a positive one.
ContributorsHerold, Brittany Ann (Author) / Shin, Dosun (Thesis director) / McDermott, Lauren (Committee member) / Barrett, The Honors College (Contributor) / Herberger Institute for Design and the Arts (Contributor) / School of Sustainability (Contributor) / The Design School (Contributor)
Created2015-05
Description
I set out to better understand the issues, perceptions & solutions surrounding drought. The question that compelled my project was "What might be all the ways that we can improve the experience of conserving, reusing & educating on the topic of water." Through the process of design research I developed a system of products that improves the user experiences surrounding water. The result is IOW, an intelligent 3-product system that aims to make your water needs & wants smarter & less wasteful.
ContributorsShappee, Christian Kyle (Author) / Shin, Dosun (Thesis director) / McDermott, Lauren (Committee member) / Barrett, The Honors College (Contributor) / Herberger Institute for Design and the Arts (Contributor) / School of Sustainability (Contributor) / The Design School (Contributor)
Created2015-05