Matching Items (674)
Description
Cancer is one of the most serious global diseases. We have focused on cancer immunoprevention. My thesis projects include developing a prophylactic primary and metastatic cancer vaccines, early cancer detection and investigation of genes involved in tumor development. These studies were focused on frame-shift (FS) antigens. The FS antigens are generated by genomic mutations or abnormal RNA processing, which cause a portion of a normal protein to be translated out of frame. The concept of the prophylactic cancer vaccine is to develop a general cancer vaccine that could prevent healthy people from developing different types of cancer. We have discovered a set of cancer specific FS antigens. One of the FS candidates, structural maintenance of chromosomes protein 1A (SMC1A) FS, could start to accumulate at early stages of tumor and be specifically exposed to the immune system by tumor cells. Prophylactic immunization with SMC1A-FS could significantly inhibit primary tumor development in different murine tumor models and also has the potential to inhibit tumor metastasis. The SMC1A-FS transcript was detected in the plasma of the 4T1/BALB/c mouse tumor model. The tumor size was correlated with the transcript ratio of the SMC1A-FS verses the WT in plasma, which could be measured by regular RT-PCR. This unique cancer biomarker has a practical potential for a large population cancer screen, as well as clinical tumor monitoring. With a set of mimotope peptides, antibodies against SMC1A-FS peptide were detected in different cancer patients, including breast cancer, pancreas cancer and lung cancer with a 53.8%, 56.5% and 12.5% positive rate respectively. This suggested that the FS antibody could be a biomarker for early cancer detection. The characterization of SMC1A suggested that: First, the deficiency of the SMC1A is common in different tumors and able to promote tumor initiation and development; second, the FS truncated protein may have nucleolus function in normal cells. Mis-control of this protein may promote tumor development. In summary, we developed a systematic general cancer prevention strategy through the variety immunological and molecular methods. The results gathered suggest the SMC1A-FS may be useful for the detection and prevention of cancer.
ContributorsShen, Luhui (Author) / Johnston, Stephen Albert (Thesis advisor) / Chang, Yung (Committee member) / Miller, Laurence (Committee member) / Sykes, Kathryn (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2012
Description
The advent of new high throughput technology allows for increasingly detailed characterization of the immune system in healthy, disease, and age states. The immune system is composed of two main branches: the innate and adaptive immune system, though the border between these two states is appearing less distinct. The adaptive immune system is further split into two main categories: humoral and cellular immunity. The humoral immune response produces antibodies against specific targets, and these antibodies can be used to learn about disease and normal states. In this document, I use antibodies to characterize the immune system in two ways: 1. I determine the Antibody Status (AbStat) from the data collected from applying sera to an array of non-natural sequence peptides, and demonstrate that this AbStat measure can distinguish between disease, normal, and aged samples as well as produce a single AbStat number for each sample; 2. I search for antigens for use in a cancer vaccine, and this search results in several candidates as well as a new hypothesis. Antibodies provide us with a powerful tool for characterizing the immune system, and this natural tool combined with emerging technologies allows us to learn more about healthy and disease states.
ContributorsWhittemore, Kurt (Author) / Sykes, Kathryn (Thesis advisor) / Johnston, Stephen A. (Committee member) / Jacobs, Bertram (Committee member) / Stafford, Phillip (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2014
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
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
This project uses Kenneth Burke’s theory of dramatism and the pentad to analyze popular narrative films about human sex trafficking. It seeks to understand the relationship between a film’s dominant philosophy (as highlighted by utilizing Burke’s pentad), its inherently suggested solutions to trafficking, and the effect that the film has on viewers’ perception of trafficking. 20 narrative feature films about sex trafficking such as the 2008 film Taken were analyzed for this study. Three out of five of Burke’s philosophies were uncovered after analysis: idealism, mysticism, and materialism. Films that aligned with idealism were found to implicitly blame women for their own trafficking. Films that aligned with mysticism were found to rally audiences around violence and racism as opposed to women’s freedom. Films that aligned with materialism were found to be the most empathetic towards trafficked women. The conclusion of this paper is that films about sex trafficking have a high potential to be harmful to women who have exited trafficking. This paper asserts that the most valuable films about trafficking are those that are not simply based on a true story but are created by trafficking survivors themselves, such as the 2016 film Apartment 407.
ContributorsHamby, Hannah Mary (Co-author) / Raum, Brionna (Co-author) / Edson, Belle (Thesis director) / Zanin, Alaina (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Hugh Downs School of Human Communication (Contributor) / School of Film, Dance and Theatre (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
This document is a proposal for a research project, submitted as an Honors Thesis to Barrett, The Honors College at Arizona State University. The proposal summarizes previous findings and literature about women survivors of domestic violence who are suffering from post-traumatic stress disorder as well as outlining the design and measures of the study. At this time, the study has not been completed. However, it may be completed at a future time.
ContributorsKunst, Jessica (Author) / Hernandez Ruiz, Eugenia (Thesis director) / Belgrave, Melita (Committee member) / School of Music (Contributor) / Dean, W.P. Carey School of Business (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
While there are many characteristics that make up a woman, femininity is one that is difficult to define because it is a communication and expression practice defined by culture. This research explores historical accounts of femininity in the 1950s as seen through the exemplar of the white, middle-class "happy homemaker" or "happy housewife." The 1950s is important to study in light of changing gender and social dynamics due to the transition from World War II to a period of prosperity. By using primary sources from the 1950s and secondary historical analyses, this research takes the form of a sociological accounting of 1950s' femininity and the lessons that can be applied today. Four cultural forces led to homemakers having an unspoken identity crisis because they defined themselves in terms of relationship with others and struggled to uphold a certain level of femininity. The forces are: the feminine mystique, patriotism, cultural normalcy, and unnecessary choices. These forces caused women to have unhealthy home relationships in their marriages and motherhood while persistently doing acts to prove their self-worth, such as housework and consuming. It is important to not look back at the 1950s as an idyllic time without also considering the social and cultural practices that fostered a feminine conformity in women. Today, changes can be made to allow women to express femininity in modern ways by adapting to reality instead of to outdated values. For example, changes in maternity leave policies allow women to be mothers and still be in the workforce. Additionally, women should find fulfillment in themselves by establishing a strong personal identity and confidence in their womanhood before identifying through other people or through society.
ContributorsHeinauer, Richelle Diane (Author) / Brouwer, Daniel (Thesis director) / Haskin, Jennifer (Committee member) / Hugh Downs School of Human Communication (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
The Centers for Disease Control and Prevention in the United States announced that there has been roughly a 50% increase in the prevalence of food allergies among people between the years of 1997 - 2011. A food allergy can be described as a medical condition where being exposed to a certain food triggers a harmful immune response in the body, known as an allergic reaction. These reactions can range from mild to fatal, and they are caused mainly by the top 8 major food allergens: dairy, eggs, peanuts, tree nuts, wheat, soy, fish, and shellfish. Food allergies mainly plague children under the age of 3, as some of them will grow out of their allergy sensitivity over time, and most people develop their allergies at a young age, and not when they are older. The rise in prevalence is becoming a frightening problem around the world, and there are emerging theories that are attempting to ascribe a cause. There are three well-known hypotheses that will be discussed: the Hygiene Hypothesis, the Dual-Allergen Exposure Hypothesis, and the Vitamin-D Deficiency Hypothesis. Beyond that, this report proposes that a new hypothesis be studied, the Food Systems Hypothesis. This hypothesis theorizes that the cause of the rise of food allergies is actually caused by changes in the food itself and particularly the pesticides that are used to cultivate it.
ContributorsCromer, Kelly (Author) / Lee, Rebecca (Thesis director) / MacFadyen, Joshua (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Fashion is individual in its expression. It is also universal. Fashion is a cumulation of different influences and different interpretations. We currently live in a climate divided by race, culture, gender, and so much more. It is so difficult to find common ground on a global platform. Something that stands alone is fashion. Fashion is influenced by so many aspects. Of these, aspects that I am interested in are culture and sustainability. When combined with culture, fashion can anchor and have a root to the generations that came before us. When combined with sustainability, we have an anchor to the planet that we share with everyone. The result of fashion is always the same, beautiful art. I want people to see the beauty not only in the art itself, but the differences and similarities that such art provides. We all come from the same world but have different ways of expressing that world. My goal is to show people that they need to acknowledge the differences but can choose to see the similarities of each culture. Additionally, I redesign garments that capture an emotion and a story. Making each piece individual yet serving a greater purpose sustainability wise. I envision the principle of sustainable fashion to be the basis of each piece of clothing. Therefore, for my creative project I am constructing five art pieces representing five cultures that has had a significant influence on my life and personal style. These cultures are those of UAE, Germany, Nepal, Mexico, and Spain. Each of these garments are made from recycled fabric and clothing donated by family and friends. My objective is to display sustainable fashion that has deep cultural influence. Every piece has a story and an emotion attached as well to create a connection with the clothing itself.
ContributorsKreiser, Samantha Miren (Author) / Chhetri, Nalini (Thesis director) / Ellis, Naomi (Committee member) / Dean, W.P. Carey School of Business (Contributor, Contributor) / Department of Economics (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05