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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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Description
Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising

Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.
ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
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Description
The concept of vaccination dates back further than Edward Jenner's first vaccine using cowpox pustules to confer immunity against smallpox in 1796. Nevertheless, it was Jenner's success that gave vaccines their name and made vaccinia virus (VACV) of particular interest. More than 200 years later there is still the need

The concept of vaccination dates back further than Edward Jenner's first vaccine using cowpox pustules to confer immunity against smallpox in 1796. Nevertheless, it was Jenner's success that gave vaccines their name and made vaccinia virus (VACV) of particular interest. More than 200 years later there is still the need to understand vaccination from vaccine design to prediction of vaccine efficacy using mathematical models. Post-exposure vaccination with VACV has been suggested to be effective if administered within four days of smallpox exposure although this has not been definitively studied in humans. The first and second chapters analyze post-exposure prophylaxis of VACV in an animal model using v50ΔB13RMγ, a recombinant VACV expressing murine interferon gamma (IFN-γ) also known as type II IFN. While untreated animals infected with wild type VACV die by 10 days post-infection (dpi), animals treated with v50ΔB13RMγ 1 dpi had decreased morbidity and 100% survival. Despite these differences, the viral load was similar in both groups suggesting that v50ΔB13RMγ acts as an immunoregulator rather than as an antiviral. One of the main characteristics of VACV is its resistance to type I IFN, an effect primarily mediated by the E3L protein, which has a Z-DNA binding domain and a double-stranded RNA (dsRNA) binding domain. In the third chapter a VACV that independently expresses both domains of E3L was engineered and compared to wild type in cells in culture. The dual expression virus was unable to replicate in the JC murine cell line where both domains are needed together for replication. Moreover, phosphorylation of the dsRNA dependent protein kinase (PKR) was observed at late times post-infection which indicates that both domains need to be linked together in order to block the IFN response. Because smallpox has already been eradicated, the utility of mathematical modeling as a tool for predicting disease spread and vaccine efficacy was explored in the last chapter using dengue as a disease model. Current modeling approaches were reviewed and the 2000-2001 dengue outbreak in a Peruvian region was analyzed. This last section highlights the importance of interdisciplinary collaboration and how it benefits research on infectious diseases.
ContributorsHolechek, Susan A (Author) / Jacobs, Bertram L (Thesis advisor) / Castillo-Chavez, Carlos (Committee member) / Frasch, Wayne (Committee member) / Hogue, Brenda (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2011
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Description

This thesis identifies and explains two main problems students face during their internships. The first problem relates to feeling bored at internships due to the simplicity of projects or lack of work. From the interviews conducted, several strategies to avoid this boredom were created, including having employers design education plans

This thesis identifies and explains two main problems students face during their internships. The first problem relates to feeling bored at internships due to the simplicity of projects or lack of work. From the interviews conducted, several strategies to avoid this boredom were created, including having employers design education plans for interns to further their knowledge in programs such as excel during their downtime. The second problem with internships discovered focuses on the gap between what is taught in schools versus what is expected of interns in practice. This thesis identifies several opportunities for improvement in education and strategies on how to handle feeling overwhelmed on intern projects due to lack of knowledge.

ContributorsKomarnyckyj, Katya (Author) / Byrne, Jared (Thesis director) / Crawford, Cassidy (Committee member) / School of Molecular Sciences (Contributor) / Department of Finance (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The purpose of this study is to create and establish an efficient and cost-effective solution to decrease the effects of sedentarism in pregnant women. Our team was given a propelling question, from which we had to narrow down our scope and conduct primary and secondary research to determine our ideal

The purpose of this study is to create and establish an efficient and cost-effective solution to decrease the effects of sedentarism in pregnant women. Our team was given a propelling question, from which we had to narrow down our scope and conduct primary and secondary research to determine our ideal customers. The design of our study intends to imitate the development of a startup where ideas are created from scratch and the final deliverable is a business model plan that shows some sort of traction. Our first major finding is that a sedentary lifestyle can be treated without major challenges in low risk pregnancies. We determined that uncertainty and lack of concise and clear information is one of the main causes of an increased level of sedentary behavior in low risk pregnancies. A significant driver for women to do some sort of activity or exercise stems from feeling supported, which doesn’t necessarily come from their partner or couple, but instead from other women that are going to a similar process as them. There are apps in the market that intend to serve pregnant women; however, there is not one that incorporates a social aspect to achieve their goal. In conclusion, there is opportunity in the market for a socially integrated pregnancy fitness app. The Gleam concept has been consciously developed to decrease sedentary behavior through concise, clear, and reliable information and by encouraging women through a socialization platform.

ContributorsMosier, Jacob Ryan (Co-author) / Flores, Valeria (Co-author) / McCreary, Liam (Co-author) / Byrne, Jared (Thesis director) / Hall, Rick (Committee member) / Silverstein, Taylor (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Department of Finance (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

The digital education market has been expanding rapidly during the last few years, providing ample opportunity in the future. There are many technologies involved in this market, with the most significant being cloud client services, edge computing, and interactive flat panel displays (IFPDs). Combined, these technologies represent ninety-two percent of

The digital education market has been expanding rapidly during the last few years, providing ample opportunity in the future. There are many technologies involved in this market, with the most significant being cloud client services, edge computing, and interactive flat panel displays (IFPDs). Combined, these technologies represent ninety-two percent of the Serviceable Available Market with IFPDs as the largest opportunity with sixty-nine percent (Company X Data). Cloud computing provides anytime/anywhere services that can be accessed from any device: e-portfolios, content access, and creation. Edge computing processes data closer to its source and the point of service delivery, providing ultra-low latency to help boost efficiency, mainly used for data processing. Lastly, IFPDs are touchscreen display devices ideal for collaborative spaces and meeting rooms. They are a substitute for outdated projector technology and provide better connectivity and built-in software solutions. <br/>We decided to develop a strategy to expand the market share in the IFPD market because it is the largest, and we consider Company X has a significant advantage in this sector. Company X manufactures the processors used in IFPDs and has established good relationships with manufacturers of these devices.

ContributorsPhillips, Maya (Co-author) / Hauck, Tanner (Co-author) / Morales Rincon, Herwin (Thesis director) / Koroli, Eri (Thesis director) / Simonson, Mark (Committee member) / Department of Finance (Contributor) / Department of Management and Entrepreneurship (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

Edge computing is a new and growing market that Company X has an opportunity to expand their presence. Within this paper, we compare many external research studies to better quantify the Total Addressable Market of the Edge Computing space. Furthermore, we highlight which Segments within Edge Computing have the most

Edge computing is a new and growing market that Company X has an opportunity to expand their presence. Within this paper, we compare many external research studies to better quantify the Total Addressable Market of the Edge Computing space. Furthermore, we highlight which Segments within Edge Computing have the most opportunities for growth, along with identify a specific market strategy that Company X could do to capture market share within the most opportunistic segment.

ContributorsRaimondi, Ronald Frank (Co-author) / Hamkins, Sean (Co-author) / Gandolfi, Michael (Co-author) / Simonson, Mark (Thesis director) / Hertzel, Mike (Committee member) / Department of Information Systems (Contributor) / Department of Management and Entrepreneurship (Contributor) / Department of Finance (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Over the course of 2020, individuals and organizations were thrown various unprecedented obstacles that necessitated flexibility, empathy, and understanding. Many organizations were forced to reevaluate their financial status, their purpose, and how they could provide for their employees. The COVID-19 pandemic meant that most companies had to introduce a ‘work

Over the course of 2020, individuals and organizations were thrown various unprecedented obstacles that necessitated flexibility, empathy, and understanding. Many organizations were forced to reevaluate their financial status, their purpose, and how they could provide for their employees. The COVID-19 pandemic meant that most companies had to introduce a ‘work from home’ policy, drastically decreasing the face-to-face contact that employees had with each other and leadership. The virus, coupled with the social and political unrest in the U.S. in the wake of the Black Lives Matter movement and the 2020 presidential election, inspired many companies to reframe their organization and redefine their goals.<br/> The B2B (business-to-business) Marketing Agency, The Mx Group, is preparing for a change in leadership, with the current Chief Executive Officer and Founder stepping down, being replaced by the President of the company. The company plans to execute the transition in the spring of 2022, allowing them the rest of 2021 to plan for the change, catering to employees’ individual and the company’s collective needs. It was also prompted by factors such as the COVID-19 pandemic to reevaluate the values that it upholds as an organization, coinciding with the change in leadership. Leaders of the company are actively encouraging employees to engage with these values by recognizing when a colleague performs in alignment with a value.<br/> In reframing their organization, The Mx Group has a significant opportunity to uniquely position itself in the industry. Lee G. Bolman and Terrence E. Deal (2017) introduced four frames: human resources, symbolic, structural, and political, as a way to guide a transformative application of leadership and management in business. Analyzed from these perspectives, The Mx Group can utilize contemporary ideas to efficiently and effectively seize its opportunity of embedding new values and a change in leadership.

ContributorsLanghorn, Chloe Nicole (Author) / deLusé, Stephanie (Thesis director) / Fishburne, Kate (Committee member) / School of Politics and Global Studies (Contributor) / Department of Management and Entrepreneurship (Contributor) / Department of Finance (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Edge computing is a new and growing market that Company X has an opportunity to expand their presence. Within this paper, we compare many external research studies to better quantify the Total Addressable Market of the Edge Computing space. Furthermore, we highlight which Segments within Edge Computing have the most

Edge computing is a new and growing market that Company X has an opportunity to expand their presence. Within this paper, we compare many external research studies to better quantify the Total Addressable Market of the Edge Computing space. Furthermore, we highlight which Segments within Edge Computing have the most opportunities for growth, along with identify a specific market strategy that Company X could do to capture market share within the most opportunistic segment.

ContributorsHamkins, Sean (Co-author) / Raimondi, Ronnie (Co-author) / Gandolfi, Micheal (Co-author) / Simonson, Mark (Thesis director) / Hertzel, Mike (Committee member) / School of Accountancy (Contributor) / Department of Finance (Contributor, Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Information Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

This thesis examines the value creation potential of renovating an existing commercial real estate asset to a medical office. It begins by examining commercial real estate and the medical sector at a high level. It then discusses the various criteria used to select a subject property for renovation. This renovation

This thesis examines the value creation potential of renovating an existing commercial real estate asset to a medical office. It begins by examining commercial real estate and the medical sector at a high level. It then discusses the various criteria used to select a subject property for renovation. This renovation is then depicted through a modified pitch book that contains a financial model and pro forma.

ContributorsPeters, Matthew Scott (Co-author) / Larrea, Justin (Co-author) / Berger, Nicholas (Co-author) / Simonson, Mark (Thesis director) / Gray, William (Committee member) / Department of Finance (Contributor, Contributor) / Department of Information Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05