Matching Items (213)
Description
The majority of chronic myeloid leukemia (CML) and some of acute lymphocytic leukemia (ALL) cases are associated with possessing the BCR-Abl fusion protein from an oncogenic translocation, resulting in a constantly active form of Abl and rapid proliferation. CML and ALL cells that possess the BCR-Abl fusion protein are known as Philadelphia chromosome positive (Ph+). Currently, Imatinib (selective Abl inhibitor) is used as therapy against CML and ALL. However, some patients may have malignancies which show resistance to Imatinib. Previous work displays that the transformation of progenitor B cells with the v-Abl oncogene of Abelson murine leukemia virus results in cell cycle progression, rapid proliferation, and potentially malignant transformation while preventing any further differentiation. Progenitor B cells transformed with the temperature-sensitive form of the v-Abl oncogene have served as a model to study cellular response to Imatinib treatment. After some manipulation, very few cells were forced to progress to malignancy, forming tumor in vivo. These cells were no long sensitive to v-Abl inactivation, resembling the Imatinib resistant ALL. Autophagy is the process by which proteins and organelles are broken-down and recycled within the eukaryotic cell and has been hypothesized to play a part in cancer cell survival and drug-resistance. LC3 processing is a widely accepted marker of autophagy induction and progression. It has also been shown that Imatinib treatment of Ph+ leukemia can induce autophagy. In this study, we examined the autophagy induction in response to v-Abl inactivation in a Ph+-B-ALL cell model that shows resistance to Imatinib. In particular, we wonder whether the tumor cell line resistant to v-Abl inactivation may acquire a high level of autophagy to become resistant to apoptosis induced by v-Abl inactivation, and thus become addicted to autophagy. Indeed, this tumor cell line displays a high basal levels of LC3 I and II expression, regardless of v-Abl activity. We further demonstrated that inhibition of the autophagy pathway enhances the tumor line's sensitivity to Imatinib, resulting in cell cycle arrest and massive apoptosis. The combination of autophagy and Abl inhibitions may serve as an effective therapy for BCR-Abl positive CML.
ContributorsArkus, Nohea (Author) / Chang, Yung (Thesis advisor) / Kusumi, Kenro (Committee member) / Lake, Douglas (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2011
Description
Fluoroquinolone antibiotics have been known to cause severe, multisystem adverse side effects, termed fluoroquinolone toxicity (FQT). This toxicity syndrome can present with adverse effects that vary from individual to individual, including effects on the musculoskeletal and nervous systems, among others. The mechanism behind FQT in mammals is not known, although various possibilities have been investigated. Among the hypothesized FQT mechanisms, those that could potentially explain multisystem toxicity include off-target mammalian topoisomerase interactions, increased production of reactive oxygen species, oxidative stress, and oxidative damage, as well as metal chelating properties of FQs. This review presents relevant information on fluoroquinolone antibiotics and FQT and explores the mechanisms that have been proposed. A fluoroquinolone-induced increase in reactive oxygen species and subsequent oxidative stress and damage presents the strongest evidence to explain this multisystem toxicity syndrome. Understanding the mechanism of FQT in mammals is important to aid in the prevention and treatment of this condition.
ContributorsHall, Brooke Ashlyn (Author) / Redding, Kevin (Thesis director) / Wideman, Jeremy (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Infertility has become an increasing problem in developed countries and in many cases can be attributed to compromised sperm quality. Assessment of male fertility typically utilizes semen analysis which mainly examines sperm morphology, however many males whose sperm appear normal are sub- or infertile, suggesting that sperm from these males may be deficient in a protein or suite of proteins. To date, very little is known about the composition of sperm or the complex maturation process that confers motility and fertilization competency to sperm. Chapter 1 discusses the use of whole cell mass spectrometry to identify 1247 proteins comprising the Rhesus macaque (Macaca mulatta) sperm proteome, a commonly used model of human reproduction. This study provides a more robust proxy of human sperm composition than was previously available and facilitates studies of sperm using the rhesus macaque as a model. Chapters 2 & 3 provide a systems level overview of changes in sperm proteome composition that occurs during epididymal transit. Chapter 2 reports the proteomes of sperm collected from the caput, corpus and cauda segments of the mouse epididymis, identifying 1536, 1720 and 1234 proteins respectively. Chapter 3 reports the sperm proteome from four distinct segments of the Rhesus macaque epididymis, including the caput, proximal corpus, distal corpus and cauda, identifying 1951, 2014, 1764 and 1423 proteins respectively. These studies identify a number of proteins that are added and removed from sperm during epididymal transit which likely play an important role in the sperm maturation process. To date no comparative evolutionary studies of sperm proteomes have been undertaken. Chapter 4 compares four mammalian sperm proteomes including the human, macaque, mouse and rat. This study identified 98 proteins common to all four sperm proteomes, 82 primate and 90 rodent lineage-specific proteins and 494, 467, 566, and 193 species specific proteins in the human, macaque, mouse and rat sperm proteomes respectively and discusses how differences in sperm composition may ultimately lead to functional differences across species. Finally, chapter 5 uses sperm proteome data to inform the preliminary design of a rodent contraceptive vaccine delivered orally using recombinant attenuated Salmonella vaccine vectors.
ContributorsSkerget, Sheri Jo (Author) / Karr, Timothy L. (Thesis advisor) / Lake, Douglas (Committee member) / Petritis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
Description
Coccidioidomycosis, also known as Valley Fever, is a disease caused by the dimorphic soil-dwelling fungus, Coccidioides sp. Coccidioidomycosis is difficult to diagnose because symptoms are similar to community-acquired pneumonia. Current diagnostic tests rely on antibody responses, but immune responses can be delayed and aberrant, resulting in false negative diagnoses. Unlike serology, detection of coccidioidal proteins or other fungal components in blood could distinguish valley fever from other pulmonary infections and provide a definitive diagnosis. Using mass spectrometry (LC-MS/MS) we examined the plasma peptidome from patients with serologically confirmed coccidioidomycosis. Mass spectra were searched using the protein database from the Coccidioides species, generated and annotated by the Broad Institute. 15 of 20 patients with serologically confirmed coccidioidomycosis demonstrated the presence of a peptide in plasma, "PGLDSKSLACTFSQV" (PGLD). The peptide is derived from an open reading frame from a "conserved hypothetical protein" annotated with 2 exons, and to date, found only in the C. posadasii strain Silviera RMSCC 3488 genomic sequence. In this thesis work, cDNA sequence analysis from polyadenylated RNA confirms the peptide sequence and genomic location of the peptide, but does not indicate that the intron in the gene prediction of C. posadasii strain Silviera RMSCC 3488 is present. A monoclonal antibody generated against the peptide bound to a 16kDa protein in T27K coccidioidal lysate. Detecting components of the fungus plasma could be a useful diagnostic tool, especially when serology does not provide a definitive diagnosis.
ContributorsDuffy, Stacy Leigh (Author) / Lake, Douglas (Thesis advisor) / Magee, Dewey Mitch (Committee member) / Antwi, Kwasi (Committee member) / Arizona State University (Publisher)
Created2013
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (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