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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

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
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DescriptionBased on previous research and findings it is proven that a non-profit class to create awareness will be beneficial in the prevention of eating disorders. This analysis will provide significant research to defend the proposed class.
ContributorsAllen, Brittany (Author) / Chung, Deborah (Author) / Fey, Richard (Thesis director) / Peck, Sidnee (Committee member) / Mazurkiewicz, Milena (Committee member) / Barrett, The Honors College (Contributor) / W. P. Carey School of Business (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
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Establishing a healthcare practice in the U. S. by a Mexican national involves many different steps at federal as well as state levels. The recent implementation of the Patient Protection and Affordable Care Act overhauls some requirements which include increased Medicaid eligibility as well as mandatory health insurance coverage. With

Establishing a healthcare practice in the U. S. by a Mexican national involves many different steps at federal as well as state levels. The recent implementation of the Patient Protection and Affordable Care Act overhauls some requirements which include increased Medicaid eligibility as well as mandatory health insurance coverage. With these changes taking place over the next few years, the need for healthcare providers will expand. Consequently, I look into the requirements of establishing an urgent care practice in the state of Arizona. Given that Phoenix has a 40.8% Hispanic population and that the Affordable Care Act will increase the coverage of this demographic, it is the city of focus for my analysis. In order to make access to the Arizona healthcare market more impartial and accessible to Mexican entrepreneurs, changes need to be made to the certification process of medical physicians who graduated from Mexican universities. The general disadvantage of Mexican physicians as compared to their U. S. counterparts comes in the form of increased certification times and additional processes. An equal playing field will allow the ease in movement of medical physicians between the U. S. and Mexico which will help meet the increased demand over the next few years. From ownership to taxation and medical billing and coding, this analysis focuses on the many requirements needed to establish an urgent care in Arizona.
ContributorsIbarra, Joseph Anthony (Author) / Carlos, Velez-Ibanez (Thesis director) / Cruz-Torres, Maria (Committee member) / Barrett, The Honors College (Contributor) / W. P. Carey School of Business (Contributor)
Created2014-05
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This paper goes through a two-pronged approach in the attempt to understand E-Sports, entertainment gaming, and the creation of the E-Sports bar/Barcade. The first portion aims to explain and quantify the growth of electronic sports (or E-sports). This new craze has been growing immensely in the past 5 years, by

This paper goes through a two-pronged approach in the attempt to understand E-Sports, entertainment gaming, and the creation of the E-Sports bar/Barcade. The first portion aims to explain and quantify the growth of electronic sports (or E-sports). This new craze has been growing immensely in the past 5 years, by viewership and by monetary endorsements. With these changes and growth patterns, we then move on to explain one of the many niche markets that has been created from the growth of E-sports and entertainment gaming. Through our experience in the field, we have evaluated 8 E-sports bars and Barcades in order to confirm their viability in the marketplace. Through our worldwide research we have found that E-sports will continue to grow and that Barcades will not only be viable, but will be a competitive market in the next 10-20 years.
ContributorsNist, Nicholas (Co-author) / Hester, James (Co-author) / Brooks, Dan (Thesis director) / Forss, Brennan (Committee member) / Barrett, The Honors College (Contributor) / Department of Economics (Contributor) / Department of Supply Chain Management (Contributor) / W. P. Carey School of Business (Contributor) / Department of Psychology (Contributor)
Created2015-05
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The unprecedented rise of terrorist network ISIL has brought the revolutionary Salafi agenda to the forefront of global politics. This thesis provides an analysis of the ideology and an overview of ISIL. The research is comprised of reports on the organization from prominent think-tanks, books analyzing the tenets and thinkers

The unprecedented rise of terrorist network ISIL has brought the revolutionary Salafi agenda to the forefront of global politics. This thesis provides an analysis of the ideology and an overview of ISIL. The research is comprised of reports on the organization from prominent think-tanks, books analyzing the tenets and thinkers of Salafi radicalism and original source material confiscated from ISIL's predecessor al-Qaeda in Iraq (AQI). An international coalition is posited as a solution to the threat as well as the Middle Eastern terrorist threat more broadly. However, the likelihood of such international cooperation is minimal, and the commitment it would require may make it unfeasible.
Created2015-05
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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

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
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Description
Recombinant protein expression is essential to biotechnology and molecular medicine, but facile methods for obtaining significant quantities of folded and functional protein in mammalian cell culture have been lacking. Here I describe a novel 37-nucleotide in vitro selected sequence that promotes unusually high transgene expression in a vaccinia driven cytoplasmic

Recombinant protein expression is essential to biotechnology and molecular medicine, but facile methods for obtaining significant quantities of folded and functional protein in mammalian cell culture have been lacking. Here I describe a novel 37-nucleotide in vitro selected sequence that promotes unusually high transgene expression in a vaccinia driven cytoplasmic expression system. Vectors carrying this sequence in a monocistronic reporter plasmid produce >1,000-fold more protein than equivalent vectors with conventional vaccinia promoters. Initial mechanistic studies indicate that high protein expression results from dual activity that impacts both transcription and translation. I suggest that this motif represents a powerful new tool in vaccinia-based protein expression and vaccine development technology.
ContributorsFlores, Julia Anne (Author) / Chaput, John C (Thesis advisor) / Jacobs, Bertram (Committee member) / LaBaer, Joshua (Committee member) / Arizona State University (Publisher)
Created2012
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Description
In order to discover if Company X's current system of local trucking is the most efficient and cost-effective way to move freight between sites in the Western U.S., we will compare the current system to varying alternatives to see if there are potential avenues for Company X to create or

In order to discover if Company X's current system of local trucking is the most efficient and cost-effective way to move freight between sites in the Western U.S., we will compare the current system to varying alternatives to see if there are potential avenues for Company X to create or implement an improved cost saving freight movement system.
ContributorsPicone, David (Co-author) / Krueger, Brandon (Co-author) / Harrison, Sarah (Co-author) / Way, Noah (Co-author) / Simonson, Mark (Thesis director) / Hertzel, Michael (Committee member) / Barrett, The Honors College (Contributor) / Department of Supply Chain Management (Contributor) / Department of Finance (Contributor) / Economics Program in CLAS (Contributor) / School of Accountancy (Contributor) / W. P. Carey School of Business (Contributor) / Sandra Day O'Connor College of Law (Contributor)
Created2015-05
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Description
Company X is one of the world's largest semiconductor companies in the world, having a current market capitalization of 177.44 Billion USD, an enterprise value of 173.6 Billion USD, and generated 52.7 billion USD in revenue in fiscal year 2013. Recently, Company X has been looking to expand its Foundry

Company X is one of the world's largest semiconductor companies in the world, having a current market capitalization of 177.44 Billion USD, an enterprise value of 173.6 Billion USD, and generated 52.7 billion USD in revenue in fiscal year 2013. Recently, Company X has been looking to expand its Foundry business. The Foundry business in the semiconductor business is the actual process of making the chips. This process can be approached in several different ways by companies who need their chips built. A company, like TSMC, can be considered a pure-play company and only makes chips for other companies. A fabless company, like Apple, creates its own chip design and then allows another company to build them. It also uses other chip designs for its products, but outsources the building to another company. Lastly, the integrated device manufacturing companies like Samsung or Company X both design and build the chip. The foundry industry is a rather novel market for Company X because it owns less than 1 percent of the market. However, the industry itself is rather large, generating a total of 40 billion dollars in revenue annually, with expectations to have increasing year over year growth into the foreseeable future. The industry is fairly concentrated with TSMC being the top competitor, owning roughly 50 percent of the market with Samsung and Global Foundries lagging behind as notable competitors. It is a young industry and there is potential opportunity for companies that want to get into the business. For Company X, it is not only another market to get into, but also an added business segment to supplant their business segments that are forecasted to do poorly in the near future. This thesis will analyze the financial opportunity for Company X in the foundry space. Our final product is a series of P&L's which illustrate our findings. The results of our analysis were presented and defended in front of a panel of Company X managers and executives.
ContributorsJones, Trevor (Author) / Matiski, Matthew (Co-author) / Green, Alex (Co-author) / Simonson, Mark (Thesis director) / Hertzel, Michael (Committee member) / Department of Finance (Contributor) / W. P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2015-05
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Description
Background: Both puberty and diets composed of high levels of saturated fats have been shown to result in central adiposity, fasting hyperinsulinemia, insulin resistance and impaired glucose tolerance. While a significantly insulinogenic phenotypic change occurs in these two incidences, glucose homeostasis does not appear to be affected. Methods: Male, Sprague-dawley

Background: Both puberty and diets composed of high levels of saturated fats have been shown to result in central adiposity, fasting hyperinsulinemia, insulin resistance and impaired glucose tolerance. While a significantly insulinogenic phenotypic change occurs in these two incidences, glucose homeostasis does not appear to be affected. Methods: Male, Sprague-dawley rats were fed diets consisting of CHOW or low fat (LF), High Fat Diet and High Fat Diet (HFD) with supplementary Canola Oil (Monounsaturated fat). These rats were given these diets at 4-5 weeks old and given intraperitoneal and oral glucose tolerance tests(IPGTT; OGTT) at 4 and 8 weeks to further understand glucose and insulin behavior under different treatments. (IPGTT: LF-n=14, HFD-n=16, HFD+CAN-n=12; OGTT: LF-n=8, HFD-n=8, HFD+CAN-n=6). Results: When comparing LF fed rats at 8 weeks with 4 week glucose challenge test, area under the curve (AUC) of glucose was 1.2 that of 4 weeks. At 8 weeks, HFD fed rats AUCg was much greater than LF fed rats under both IPGTT and OGTT. When supplemented with Canola oil, HFD fed rats AUC returned to LF data range. Despite the alleviating glucose homeostasis affects of Canola oil the AUC of insulin curve, which was elevated by HFD, remained high. Conclusion: HFD in maturing rats elevates fasting insulin levels, increases insulin resistance and lowers glucose homeostasis. When given a monounsaturated fatty acid (MUFA) supplement fasting hyperinsulinemia, and late hyperinsulinemia still occur though glucose homeostasis is regained. For OGTT HFD also induced late hyper c-peptide levels and compared to LF and HFD+CAN, a higher c-peptide level over time.
ContributorsRay, Tyler John (Author) / Caplan, Michael (Thesis director) / Herman, Richard (Committee member) / Towner, Kali (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / W. P. Carey School of Business (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2015-05