Matching Items (12,978)
Filtering by
- Creators: Barrett, The Honors College
- Creators: Hindemith, Paul, 1895-1963
Description
Glioblastoma (GBM) is the most aggressive adult brain tumor with a devastating median survival time of about fourteen months post-surgery and standard of care therapy with radiation and temozolomide. The low incidence of GBM, cost of developing novel therapeutics, and time cost of clinical trials are dis-incentives to develop novel therapies. To overcome that obstacle, we investigated the efficacy of repurposing four FDA approved drugs known to cross the blood brain barrier (BBB), minocycline, propranolol, chlorpromazine, and metformin, to inhibit signaling and metabolism in GBM cells.
Minocycline is a tetracycline class broad spectrum antibiotic commonly used to treat severe acne and other skin infections. Propranolol is a beta blocker type heart medication primarily used to treat high blood pressure and irregular heartbeat. Chlorpromazine is a phenothiazine antipsychotic usually used for schizophrenia. Metformin is the most widely used first-line oral treatment for type-2 diabetes. Based on a literature survey, minocycline is expected to prevent the phosphorylation of STAT3, a transcription factor downstream of EGFR; propranolol is expected to disrupt EGFR trafficking; chlorpromazine is expected to target the PI3K/mTOR/Akt signaling pathway; metformin is believed to exploit vulnerabilities in cancer cell metabolism, as well as upregulate AMPK against the PI3K/mTOR/Akt pathway.
Efficacy of minocycline in inhibiting EGFR-driven STAT3 activation was investigated using western blot analysis. Our results demonstrate that Minocycline effectively inhibits activation of EGFR-driven STAT3 in U373 glioma cells at 100μM. The ability of chlorpromazine to inhibit the PI3K/mTOR/Akt pathway was similarly tested via western blot, which showed inhibition of phosphorylated Akt and S6 at 10μM. Efficacy of propranolol in perturbing EGFR trafficking was evaluated using flow cytometry and immunofluorescence, which failed to depict altered membrane-associated EGFR abundance. Finally, concentration-dependent inhibition of colony formation was tested for all four drugs. Propranolol and minocycline showed potential biphasic stimulatory effects at 10μM, but all drugs inhibited cell growth at 50μM and higher. Efficacy of these drugs in the treatment of GBM is being further evaluated using in vitro neurosphere cultures from patients identified as having the cellular vulnerabilities potentially targeted by these drugs. Successful completion of this project will lead to in vivo efficacy testing of these four drugs in orthotopic GBM PDX models.
Minocycline is a tetracycline class broad spectrum antibiotic commonly used to treat severe acne and other skin infections. Propranolol is a beta blocker type heart medication primarily used to treat high blood pressure and irregular heartbeat. Chlorpromazine is a phenothiazine antipsychotic usually used for schizophrenia. Metformin is the most widely used first-line oral treatment for type-2 diabetes. Based on a literature survey, minocycline is expected to prevent the phosphorylation of STAT3, a transcription factor downstream of EGFR; propranolol is expected to disrupt EGFR trafficking; chlorpromazine is expected to target the PI3K/mTOR/Akt signaling pathway; metformin is believed to exploit vulnerabilities in cancer cell metabolism, as well as upregulate AMPK against the PI3K/mTOR/Akt pathway.
Efficacy of minocycline in inhibiting EGFR-driven STAT3 activation was investigated using western blot analysis. Our results demonstrate that Minocycline effectively inhibits activation of EGFR-driven STAT3 in U373 glioma cells at 100μM. The ability of chlorpromazine to inhibit the PI3K/mTOR/Akt pathway was similarly tested via western blot, which showed inhibition of phosphorylated Akt and S6 at 10μM. Efficacy of propranolol in perturbing EGFR trafficking was evaluated using flow cytometry and immunofluorescence, which failed to depict altered membrane-associated EGFR abundance. Finally, concentration-dependent inhibition of colony formation was tested for all four drugs. Propranolol and minocycline showed potential biphasic stimulatory effects at 10μM, but all drugs inhibited cell growth at 50μM and higher. Efficacy of these drugs in the treatment of GBM is being further evaluated using in vitro neurosphere cultures from patients identified as having the cellular vulnerabilities potentially targeted by these drugs. Successful completion of this project will lead to in vivo efficacy testing of these four drugs in orthotopic GBM PDX models.
ContributorsNeal, Tristan Thomas (Co-author) / Neal, Tristan (Co-author) / Byron, Sara (Co-author) / Dhruv, Harshil (Co-author, Committee member) / Berens, Michael (Co-author) / Wilson, Melissa (Thesis director) / Ferdosi, Shayesteh (Committee member) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This creative project is a children’s book designed to teach young readers about engineering through a fictional story about a group of children creating a robot for their school’s show-and-tell. The story aims to teach engineering principles to children in a lighthearted and entertaining form, narrating notions such as the design process, prototyping, specialty fields, and repurposing. Other principles such as learning patience, compromise and teamwork are also conveyed throughout the plot details. Small life lessons that transcend the realm of engineering are also embodied throughout. The plot of the story is a young girl who goes to visit her grandfather who is a garage tinkerer with a love of spare parts. He tells her about his job as a robotics engineer, and she loves it. She goes and tells her friends who decide they want to make a robot for show-and-tell at school. The grandfather agrees to help them build a robot and thus the group of kids are walked through the engineering design process, learning new things (and specialization) along the way. The story ends by revealing that the whole story was a flashback the main character was having as she is about to start her first day at an engineering firm.
ContributorsReed, Shelby Marie (Author) / Oberle, Eric (Thesis director) / Williams, Wendy (Committee member) / Engineering Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This project is a visual presentation on the value of music education in public schools. With cutbacks in funding for education, arts programs such as orchestra or band are often the first to face budget restrictions or be eliminated altogether. Many schools and administrators deem arts programs as less essential to a student’s education because they do not directly teach core subjects such as math, science or reading. This project explains why reducing or eliminating funding for arts programs is ultimately detrimental to students. A high quality musical education brings great developmental benefits in a variety of skills such as language development, memory learning and special understanding. Students trained in music also have shown higher scores on standardized tests. Additionally, music programs provide a creative outlet for students that can help relieve stress and provide an opportunity for personal expression and a sense of identity. This project is organized into three sections. Part I discusses the lack of funding for fine arts programs in schools and the affordability of playing a stringed instrument. Part II dives into the academic, cognitive and behavioral benefits of an education in music. Finally, Part III discusses potential solutions to the problem and showcases examples of out-of-school music programs. The final form of the project is displayed online through a program called Readymag, a digital tool for presenting projects, which allows for the written aspect of the project to fall seamlessly with the visual component. The visual component of the project is made of photographs captured on site at interviews, performances and practices, as well as in a studio.
ContributorsAtzenweiler, Stella Alexander (Author) / Dolin, Penny (Thesis director) / Buck, Nancy (Committee member) / Graphic Information Technology (Contributor, Contributor) / School of Art (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Axon Enterprise, Inc. is a publicly traded company founded in Scottsdale, Arizona in 1993. The company went public on June 7th, 2001. The inspiration for this topic is our interest in equity research. We believe that understanding how to fundamentally research a company is not only beneficial for our careers, but for our own personal financial learning. One thing that stood out about Axon was its dominant control of the stun gun market. Axon captures around 90%.. Because of this, we wanted to dive deeper. Surely, this has to be a good investment. What company owns almost all of the market share but isn’t a good investment? In our heads, none. But that wasn’t enough. We wanted to dive deeper and examine the fundamental business mechanisms of the firm to determine for ourselves why this is, and why we believe the company really does have tremendous growth potential. By connecting with Axon executives, developing an investment thesis, and understanding the fundamental business drivers behind Axon, we will develop a thorough understanding of Axon’s financial standing. Our goals; fundamental analysis of Axon, determine a one year price target, convince readers that Axon is a rewarding and appealing investment opportunity.
ContributorsGreife, Torsten Markus (Co-author) / Bailey, Eric (Co-author) / Budolfson, Arthur (Thesis director) / Licon, Lawrence (Committee member) / Department of Supply Chain Management (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The Psyche mission is based in a search for knowledge, to understand more about our Earth, our solar system, and the Universe. If scientists are right, we’ll be able to get a glimpse of the Earth’s inner workings unlike we’ve ever seen before. Educating ourselves and pursuing new knowledge is incredibly important - never stop exploring and never stop asking questions. Patagonia and Psyche share the same values. They care about people, the planet and both strive for a better world everyday. Be it through the advancement of knowledge or the efforts here on earth to better the lives of millions. Together we can excite the public about this mission, engender curiosity, and tie both stars above us to the earth below us.Our campaign is titled “Education through Exploration”, and we hope it engenders curiosity in everyone. This campaign includes a variety of different assets including huge banners for marketing ,a mini documentary about why we choose Patagonia, and a clothing line to excite the public about the Psyche mission. With the Patagonia + Psyche collaboration we wanted to release a Psyche inspired clothing line to help promote the mission. Some of Patagonia’s top selling items would be released in limited edition Psyche colors and a portion of the proceeds would help support STEM education. We hope that buying these products would help educate the importance of space and earth exploration and STEM education and research. Concern that results from outdoor recreation can lead to increased involvement in environmental issues.
ContributorsOzair, Daniella Leah (Co-author) / Peterson, Kyle (Co-author) / Sanft, Alfred (Thesis director) / Montgomery, Eric (Committee member) / The Design School (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Today, we are experiencing a world where Net Neutrality exists in most of the countries around the world except a handful. Who knows if this will be the case in 10 years? An economy shifting from net neutrality to non-net neutrality could have an effect of wiping out an entire industry of start-ups and innovation. The main stakeholders in this industry are the Internet Service Providers (ISPs), who provide services to access, use and participate in the Internet such as AT\&T, Verizon and T-Mobile. The other main stakeholders are the Content Providers (CPs), who provide information or content to the end users through websites such as Netflix, Google, Wikipedia, etc. Before diving into the effects it has on the economy, let's discuss a little about what net neutrality and non-net neutrality really means and their pricing strategies. Typically in an economy where net neutrality exists, the ISPs charge a fixed price to the CPs and the end-users. The ISPs tend to compete on price in order to attract the CPs to use their service for content due to tight competition among the ISPs to capture profits. Thus, these costs to the CPs would be minimal, encouraging individuals from all over the world to innovate and provide content to the end users. The price burden in this case would fall not on the CPs but on the end users. But, ISPs may not be able to over charge the end users either, as they would lose their demand due to competition from other ISPs. Therefore, in spite of being the bearers of heavy investment costs to improve network quality, the ISPs haven't been enjoying profits for a long time. Meanwhile, the CPs are gaining large profits with minimal investment costs thanks to their market power over the ISPs.
ContributorsKosaraju, Sreya (Author) / Bertran, Fernando Leiva (Thesis director) / Mendez, Jose (Committee member) / Department of Information Systems (Contributor) / Department of Economics (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The M&G Drive is a proposed venture project lead by Barrett seniors, Elijah Smith and Jenna Fitzgerald. This project aims to educate Arizona State University (ASU) students on the issues of food insecurity around the Phoenix valley and facilitate their involvement in helping alleviate this pressing social matter. Scientific research has shown significant inverse relationships between food insecurity and the following: mental and physical health, social skills, and academic achievement. As the largest public university in the nation, Arizona State holds a self-ascribed responsibility for the health of its communities. In order to address this issue on behalf of Arizona State and from the standpoint of college students, this proposed venture will encourage the ASU student population to reallocate their unused M&G Dollars (ASU’s on-campus currency) to go toward this cause. Rather than being absorbed back by the university system, unused M&G Dollars can instead be used to purchase non-perishables that will then be donated to the local Phoenix community in order to help fight against food insecurity.
ContributorsFitzgerald, Jenna Mary (Co-author) / Smith, Elijah (Co-author) / Mokwa, Michael (Thesis director) / Eaton, John (Committee member) / Department of Psychology (Contributor) / Department of Marketing (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Herpes simplex virus 2 (HSV-2) is one of the most common sexually transmitted infections (STI), affecting over 267 million women worldwide. HSV-2 causes a chronic, latent infection that increases the risk for acquisition with other STI, including HIV. Currently, there is no vaccine against HSV-2 and novel anti-viral treatments are needed. IL-36γ is a newly characterized cytokine that has been shown to play a role in inflammation and be upregulated in response to microbial infection and tissue damage. We have shown that IL-36γ is expressed in the female reproductive tract (FRT) and is upregulated by HSV-2 infection in vitro and in vivo. IL-36γ in turn induces production of proinflammatory cytokines and chemokines in human vaginal epithelial cells (VEC) that can aid in immune cell recruitment. We hypothesize that IL-36γ is a key regulator of mucosal inflammation in the FRT and functions to limit HSV-2 infection. We have demonstrated that IL-36γ treatment prior to infection protects against HSV-2 replication, disease severity, and promotes survival in a lethal mouse model. Thus, the objective of this study is to understand the mechanisms whereby IL-36γ inhibits HSV-2 replication. To understand the impact of IL-36γ on the HSV-2 lifecycle, we pretreated VEC with IL-36γ and evaluated viral titer during virus attachment and entry, replication, and cell-to-cell spread by plaque assay. Pretreatment with IL-36γ 4h prior to infection did not significantly reduce viral titers in VEC monolayers relative to untreated groups. This suggesting that IL-36γ may play a more significant role in immune cell recruitment during HSV-2 infection. To test this, FRT tissue samples from HSV-2 infected IL-36γ -/- and WT mice were analyzed by histochemistry to characterize immune cell recruitment. No clear pattern was determined for tissue samples in which cell clusters were observed and cell type within recruited clusters was unable to be identified at the current magnification. As these projects continue, the data will aid in elucidating the mechanism and level to which IL-36γ impacts HSV-2 infection in human VEC and FRT models.
ContributorsAlexander, Thessaly E (Author) / Herbst-Kralovetz, Melissa (Thesis director) / Capco, David (Committee member) / Hogue, Ian (Committee member) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
As the Internet of Things continues to expand, not only must our computing power grow
alongside it, our very approach must evolve. While the recent trend has been to centralize our
computing resources in the cloud, it now looks beneficial to push more computing power
towards the “edge” with so called edge computing, reducing the immense strain on cloud
servers and the latency experienced by IoT devices. A new computing paradigm also brings
new opportunities for innovation, and one such innovation could be the use of FPGAs as edge
servers. In this research project, I learn the design flow for developing OpenCL kernels and
custom FPGA BSPs. Using these tools, I investigate the viability of using FPGAs as standalone
edge computing devices. Concluding that—although the technology is a great fit—the current
necessity of dynamically reprogrammable FPGAs to be closely coupled with a host CPU is
holding them back from this purpose. I propose a modification to the architecture of the Intel
Arria 10 GX that would allow it to be decoupled from its host CPU, allowing it to truly serve as a
viable edge computing solution.
alongside it, our very approach must evolve. While the recent trend has been to centralize our
computing resources in the cloud, it now looks beneficial to push more computing power
towards the “edge” with so called edge computing, reducing the immense strain on cloud
servers and the latency experienced by IoT devices. A new computing paradigm also brings
new opportunities for innovation, and one such innovation could be the use of FPGAs as edge
servers. In this research project, I learn the design flow for developing OpenCL kernels and
custom FPGA BSPs. Using these tools, I investigate the viability of using FPGAs as standalone
edge computing devices. Concluding that—although the technology is a great fit—the current
necessity of dynamically reprogrammable FPGAs to be closely coupled with a host CPU is
holding them back from this purpose. I propose a modification to the architecture of the Intel
Arria 10 GX that would allow it to be decoupled from its host CPU, allowing it to truly serve as a
viable edge computing solution.
ContributorsBarth, Brandon Albert (Author) / Ren, Fengbo (Thesis director) / Vrudhula, Sarma (Committee member) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This study examines the flaked-stone economy at the Epiclassic site of Los Mogotes, located north of the Basin of Mexico in central Mexico. Chert and obsidian artifacts were classified based on form and material in order to examine the nature of the regional lithic economy during this time. The findings suggest that the inhabitants of Los Mogotes were not primary producers of obsidian tools but were dependent on long-distance exchange for already manufactured goods. This pattern contrasts with evidence of primary production using more locally available chert. Despite being closer to high quality obsidian sources in Pachuca, Hidalgo, Los Mogotes relied on gray obsidian from sources located farther away (such as Ucareo, Michoacan). These findings conform to broader regional trends observed at contemporaneous sites during this time. Our interpretations focus on how the broader political economy shaped access to resources and the institutions necessary for their distribution.
ContributorsBlumenfeld, Dean Michael (Author) / Morehart, Christopher (Thesis director) / Nelson, Ben (Committee member) / School of Human Evolution & Social Change (Contributor, Contributor) / School of Geographical Sciences and Urban Planning (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05