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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

The Electoral College, the current electoral system in the U.S., operates on a Winner-Take-All or First Past the Post (FPTP) principle, where the candidate with the most votes wins. Despite the Electoral College being the current system, it is problematic. According to Lani Guinier in Tyranny of the Majority, “the

The Electoral College, the current electoral system in the U.S., operates on a Winner-Take-All or First Past the Post (FPTP) principle, where the candidate with the most votes wins. Despite the Electoral College being the current system, it is problematic. According to Lani Guinier in Tyranny of the Majority, “the winner-take-all principle invariably wastes some votes” (121). This means that the majority group gets all of the power in an election while the votes of the minority groups are completely wasted and hold little to no significance. Additionally, FPTP systems reinforce a two-party system in which neither candidate could satisfy the majority of the electorate’s needs and issues, yet forces them to choose between the two dominant parties. Moreover, voting for a third party candidate only hurts the voter since it takes votes away from the party they might otherwise support and gives the victory to the party they prefer the least, ensuring that the two party system is inescapable. Therefore, a winner-take-all system does not provide the electorate with fair or proportional representation and creates voter disenfranchisement: it offers them very few choices that appeal to their needs and forces them to choose a candidate they dislike. There are, however, alternative voting systems that remedy these issues, such as a Ranked voting system, in which voters can rank their candidate choices in the order they prefer them, or a Proportional voting system, in which a political party acquires a number of seats based on the proportion of votes they receive from the voter base. Given these alternatives, we will implement a software simulation of one of these systems to demonstrate how they work in contrast to FPTP systems, and therefore provide evidence of how these alternative systems could work in practice and in place of the current electoral system.

ContributorsSummers, Jack Gillespie (Co-author) / Martin, Autumn (Co-author) / Burger, Kevin (Thesis director) / Voorhees, Matthew (Committee member) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

System and software verification is a vital component in the development and reliability of cyber-physical systems - especially in critical domains where the margin of error is minimal. In the case of autonomous driving systems (ADS), the vision perception subsystem is a necessity to ensure correct maneuvering of the environment

System and software verification is a vital component in the development and reliability of cyber-physical systems - especially in critical domains where the margin of error is minimal. In the case of autonomous driving systems (ADS), the vision perception subsystem is a necessity to ensure correct maneuvering of the environment and identification of objects. The challenge posed in perception systems involves verifying the accuracy and rigidity of detections. The use of Spatio-Temporal Perception Logic (STPL) enables the user to express requirements for the perception system to verify, validate, and ensure its behavior; however, a drawback to STPL involves its accessibility. It is limited to individuals with an expert or higher-level knowledge of temporal and spatial logics, and the formal-written requirements become quite verbose with more restrictions imposed. In this thesis, I propose a domain-specific language (DSL) catered to Spatio-Temporal Perception Logic to enable non-expert users the ability to capture requirements for perception subsystems while reducing the necessity to have an experienced background in said logic. The domain-specific language for the Spatio-Temporal Perception Logic is built upon the formal language with two abstractions. The main abstraction captures simple programming statements that are translated to a lower-level STPL expression accepted by the testing monitor. The STPL DSL provides a seamless interface to writing formal expressions while maintaining the power and expressiveness of STPL. These translated equivalent expressions are capable of directing a standard for perception systems to ensure the safety and reduce the risks involved in ill-formed detections.

ContributorsAnderson, Jacob (Author) / Fainekos, Georgios (Thesis director) / Yezhou, Yang (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The market for searching for food online is exploding. According to one expert at Google, “there are over 1 billion restaurant searches on Google every month” (Kelso, 2020). To capture this market and ride the general digital trend of internet personalization (as evidenced by Google search results, ads, YouTube and

The market for searching for food online is exploding. According to one expert at Google, “there are over 1 billion restaurant searches on Google every month” (Kelso, 2020). To capture this market and ride the general digital trend of internet personalization (as evidenced by Google search results, ads, YouTube and social media algorithms, etc), we created Munch to be an algorithm meant to help people find food they’ll love. <br/><br/>Munch offers the ability to search for food by restaurant or even as specific as a menu item (ex: search for the best Pad Thai). The best part? It is customized to your preferences based on a quiz you take when you open the app and from that point continuously learns from your behavior.<br/><br/>This thesis documents the journey of the team who founded Munch, what progress we made and the reasoning behind our decisions, where this idea fits in a competitive marketplace, how much it could be worth, branding, and our recommendations for a successful app in the future.

ContributorsInocencio, Phillippe Adriane (Co-author) / Rajan, Megha (Co-author) / Krug, Hayden (Co-author) / Byrne, Jared (Thesis director) / Sebold, Brent (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Animals encounter information from different resources simultaneously, integrating input from multiple sensory systems before responding behaviorally. When different cues interact with one another, they may enhance, diminish, or have no impact on their responses. In this project, we test how the presence of chemical cues affect the perception of visual

Animals encounter information from different resources simultaneously, integrating input from multiple sensory systems before responding behaviorally. When different cues interact with one another, they may enhance, diminish, or have no impact on their responses. In this project, we test how the presence of chemical cues affect the perception of visual cues. Zebrafish (Danio rerio) often use both chemical cues and visual cues to communicate with shoal mates, to assess predation risk, and to locate food. For example, zebrafish rely on both olfactory cues and visual cues for kin recognition, and they frequently use both chemical and visual cues to search for and to capture prey. In zebrafish, the terminal nerve (TN) constitutes the olfacto-visual centrifugal pathway and connects the olfactory bulb with the retina, thus allowing olfactory perception also to activate visual receptors. Past studies have found that the presence of an olfactory cue can modulate visual sensitivity in zebrafish through the terminal nerve pathway. Alternatively, given that zebrafish are highly social, the presence of social chemical cues may distract individuals from responding to other visual cues, such as food and predator visual cues. Foraging and predator chemical cues, including chemical food cues and alarm cues, may also distract individuals from responding to non-essential visual cues. Here, we test whether the response to a visual cue either increases or decreases when presented in concert with alanine, an amino acid that represents the olfactory cues of zebrafish prey. We found that the presence of chemical cues did not affect whether zebrafish responded to visual cues, but that the fish took longer to respond to visual cues when chemical cues were also present. These findings suggest that different aspects of behavior could be affected by the interaction between sensory modalities. We also found that this impact of delayed response was significant only when the visual cue<br/>was weak compared to the strength of the chemical cue, suggesting that the salience of interacting cues may also have an influence on determining the outcomes of the interactions. Overall, the interactive effects of chemicals on an animal’s response to visual cues may also have wide-ranging impacts on behavior including foraging, mating, and evading predators, and the interaction of cues may affect different aspects of the same behavior.

ContributorsPuffer, Georgie Delilah (Author) / Martins, Emilia (Thesis director) / Suriyampola, Piyumika (Committee member) / Gerkin, Richard (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Humans use emotions to communicate social cues to our peers on a daily basis. Are we able to identify context from facial expressions and match them to specific scenarios? This experiment found that people can effectively distinguish negative and positive emotions from each other from a short description. However, further

Humans use emotions to communicate social cues to our peers on a daily basis. Are we able to identify context from facial expressions and match them to specific scenarios? This experiment found that people can effectively distinguish negative and positive emotions from each other from a short description. However, further research is needed to find out whether humans can learn to perceive emotions only from contextual explanations.

ContributorsCulbert, Bailie (Author) / Hartwell, Leland (Thesis director) / McAvoy, Mary (Committee member) / School of Life Sciences (Contributor) / School of Criminology and Criminal Justice (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Locusts are generalist herbivores meaning that they are able to consume a variety of plants. Because of their broad diet, and ability to respond rapidly to a favorable environment with giant swarms of voracious insects, they are dangerous pests. Their potential impacts on humans increase dramatically when individuals switch from

Locusts are generalist herbivores meaning that they are able to consume a variety of plants. Because of their broad diet, and ability to respond rapidly to a favorable environment with giant swarms of voracious insects, they are dangerous pests. Their potential impacts on humans increase dramatically when individuals switch from their solitarious phase to their gregarious phase where they congregate and begin marching and eventually swarming together. These swarms, often billions strong, can consume the vegetation of enormous swaths of land and can travel hundreds of kilometers in a single day producing a complex threat to food security. To better understand the biology of these important pests we explored the gut microbiome of the South American locust (Schistocerca cancellata). We hypothesized generally that the gut microbiome in this species would be critically important as has been shown in many other species. We extracted and homogenized entire guts from male S. cancellata, and then extracted gut microbiome genomic DNA. Genomic DNA was then confirmed on a gel. The initial extractions were of poor quality for sequencing, but subsequent extractions performed by collaborators during troubleshooting at Southern Illinois University Edwardsville proved more useful and were used for PCR. This resulted in the detections of the following bacterial genera in the gut of S. cancellata: Enterobacter, Enterococcus, Serratia, Pseudomonas, Actinobacter, and Weisella. With this data, we are able to speculate about the physiological roles that they hold within the locust gut generating hypotheses for further testing. Understanding the microbial composition of this species’ gut may help us better understand the locust in general in an effort to more sustainably manage them.

ContributorsGrief, Dustin (Author) / Overson, Rick (Thesis director) / Cease, Arianne (Committee member) / Peterson, Brittany (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

CubeSats can encounter a myriad of difficulties in space like cosmic rays, temperature<br/>issues, and loss of control. By creating better, more reliable software, these problems can be<br/>mitigated and increase the chance of success for the mission. This research sets out to answer the<br/>question: how do we create reliable flight software

CubeSats can encounter a myriad of difficulties in space like cosmic rays, temperature<br/>issues, and loss of control. By creating better, more reliable software, these problems can be<br/>mitigated and increase the chance of success for the mission. This research sets out to answer the<br/>question: how do we create reliable flight software for CubeSats? by providing a concentrated<br/>list of the best flight software development practices. The CubeSat used in this research is the<br/>Deployable Optical Receiver Aperture (DORA) CubeSat, which is a 3U CubeSat that seeks to<br/>demonstrate optical communication data rates of 1 Gbps over long distances. We present an<br/>analysis over many of the flight software development practices currently in use in the industry,<br/>from industry leads NASA, and identify three key flight software development areas of focus:<br/>memory, concurrency, and error handling. Within each of these areas, the best practices were<br/>defined for how to approach the area. These practices were also developed using experience<br/>from the creation of flight software for the DORA CubeSat in order to drive the design and<br/>testing of the system. We analyze DORA’s effectiveness in the three areas of focus, as well as<br/>discuss how following the best practices identified helped to create a more reliable flight<br/>software system for the DORA CubeSat.

ContributorsHoffmann, Zachary Christian (Author) / Chavez-Echeagaray, Maria Elena (Thesis director) / Jacobs, Daniel (Committee member) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05