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Description
Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies).

Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
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Description
The majority of non-small cell lung cancer (NSCLC) patients (70%) are diagnosed with adenocarcinoma versus other histological subtypes. These patients often present with advanced, metastatic disease and frequently relapse after treatment. The tumor suppressor, Liver Kinase B1, is frequently inactivated in adenocarcinomas and loss of function is associated with

The majority of non-small cell lung cancer (NSCLC) patients (70%) are diagnosed with adenocarcinoma versus other histological subtypes. These patients often present with advanced, metastatic disease and frequently relapse after treatment. The tumor suppressor, Liver Kinase B1, is frequently inactivated in adenocarcinomas and loss of function is associated with a highly aggressive, metastatic tumor (1). Identification of the mechanisms deregulated with LKB1 inactivation could yield targeted therapeutic options for adenocarcinoma patients. Re-purposing the immune system to support tumor growth and aid in metastasis has been shown to be a feature in cancer progression (2). Tumor associated macrophages (TAMs) differentiate from monocytes, which are recruited to the tumor microenvironment via secretion of chemotaxic factors by cancer cells. We find that NSCLC cells deficient in LKB1 display increased secretion of C-C motif ligand 2 (CCL2), a chemokine involved in monocyte recruitment. To elucidate the molecular pathway regulating CCL2 up-regulation, we investigated inhibitors of substrates downstream of LKB1 signaling in A549, H23, H2030 and H838 cell lines. Noticeably, BAY-11-7082 (NF-κB inhibitor) reduced CCL2 secretion by an average 92%. We further demonstrate that a CCR2 antagonist and neutralizing CCL2 antibody substantially reduce monocyte migration to NSCLC (H23) cell line conditioned media. Using an in vivo model of NSCLC, we find that LKB1 deleted tumors demonstrate a discernible increase in CCL2 levels compared to normal lung. Moreover, tumors display an increase in the M2:M1 macrophage ratio and increase in tumor associated neutrophil (TAN) infiltrate compared to normal lung. This M2 shift was significantly reduced in mice treated with anti-CCL2 or a CCR2 antagonist and the TAN infiltrate was significantly reduced with the CCR2 antagonist. These data suggest that deregulation of the CCL2/CCR2 signaling axis could play a role in cancer progression in LKB1 deficient tumors.
ContributorsFriel, Jacqueline (Author) / Inge, Landon (Thesis advisor) / Lake, Douglas (Thesis advisor) / Blattman, Joseph (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Environmental changes are occurring at an unprecedented rate, and these changes will undoubtedly lead to alterations in resource availability for many organisms. To effectively predict the implications of such changes, it is critical to better understand how organisms have adapted to coping with seasonally limited resources. The vast majority of

Environmental changes are occurring at an unprecedented rate, and these changes will undoubtedly lead to alterations in resource availability for many organisms. To effectively predict the implications of such changes, it is critical to better understand how organisms have adapted to coping with seasonally limited resources. The vast majority of previous work has focused on energy balance as the driver of changes in organismal physiology. While energy is clearly a vital currency, other resources can also be limited and impact physiological functions. Water is essential for life as it is the main constituent of cells, tissues, and organs. Yet, water has received little consideration for its role as a currency that impacts physiological functions. Given the importance of water to most major physiological systems, I investigated how water limitations interact with immune function, metabolism, and reproductive investment, an almost entirely unexplored area. Using multiple species and life stages, I demonstrated that dehydrated animals typically have enhanced innate immunity, regardless of whether the dehydration is a result of seasonal water constraints, water deprivation in the lab, or high physiological demand for water. My work contributed greatly to the understanding of immune function dynamics and lays a foundation for the study of hydration immunology as a component of the burgeoning field of ecoimmunology. While a large portion of my dissertation focused on the interaction between water balance and immune function, there are many other physiological processes that may be impacted by water restrictions. Accordingly, I recently expanded the understanding of how reproductive females can alter metabolic substrates to reallocate internal water during times of water scarcity, an important development in our knowledge of reproductive investments. Overall, by thoroughly evaluating implications and responses to water limitations, my dissertation, when combined previous acquired knowledge on food limitation, will enable scientists to better predict the impacts of future climate change, where, in many regions, rainfall events are forecasted to be less reliable, resulting in more frequent drought.
ContributorsBrusch, George, IV (Author) / DeNardo, Dale F (Thesis advisor) / Blattman, Joseph (Committee member) / French, Susannah (Committee member) / Sabo, John (Committee member) / Taylor, Emily (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Many developing countries do not have health care systems that can afford technological biomedical devices or supplies to make such devices operational. To fill this void, nonprofit organizations, like Project C.U.R.E., recondition retired biomedical instrumentation so they can send medical supplies to help these developing countries. One of the issues

Many developing countries do not have health care systems that can afford technological biomedical devices or supplies to make such devices operational. To fill this void, nonprofit organizations, like Project C.U.R.E., recondition retired biomedical instrumentation so they can send medical supplies to help these developing countries. One of the issues with this is that sometimes the devices are unusable because components or expendable supplies are not available (Bhadelia). This issue has also been shown in the Impact Evaluations that Project C.U.R.E. receives from the clinics that explain the reasons why certain devices are no longer in use. That need underlies the idea on which this honors thesis has come into being. The purpose of this honors project was to create packing lists for biomedical instruments that Project C.U.R.E. recycles. This packing list would decrease the likelihood of important items being forgotten when sending devices. If an extra fuse, battery, light bulb, cuff or transducer is the difference between a functional or a nonfunctional medical device, such a list would be of benefit to Project C.U.R.E and these developing countries. In order to make this packing list, manuals for each device were used to determine what supplies were required, what was necessary for cleaning, and what supplies were desirable but functionally optional. This list was then added into a database that could be easily navigated and could help when packing up boxes for a shipment. The database also makes adding and editing the packing list simple and easy so that as Project C.U.R.E. gets more donated devices the packing list can grow.
ContributorsGraft, Kelsey Anne (Author) / Coursen, Jerry (Thesis director) / Walters, Danielle (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
The Hippo signaling pathway is responsible for regulating organ size through cell proliferation, stemness, and apoptosis. Through targeting proteins Yes-associated kinase 1(YAP) and transcriptional co-activator with a PDZ-binding domain(TAZ), YAP/TAZ are unable to enter the nucleus and bind with coactivators to express target genes. To understand YAP/TAZ dynamics and its

The Hippo signaling pathway is responsible for regulating organ size through cell proliferation, stemness, and apoptosis. Through targeting proteins Yes-associated kinase 1(YAP) and transcriptional co-activator with a PDZ-binding domain(TAZ), YAP/TAZ are unable to enter the nucleus and bind with coactivators to express target genes. To understand YAP/TAZ dynamics and its role in tumorigenesis, tissue regeneration, and tissue degeneration, a regulatory network was modeled by ordinary differential equations. Using MATLAB, the deterministic behavior of the network was observed to determine YAP/TAZ activity in different states. Performing the bifurcation analysis of the system through Oscill8, three states were identified: tumorigenic/regenerative, degenerative, and homeostatic states. Further analysis through parameter modification allowed a better understanding of which proteins can be targeted for cancer and degenerative disease.
ContributorsBarra Avila, Diego Rodrigo (Author) / Tian, Xiaojun (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Based on James Marcia's theory, identity development in youth is the degree to which one has explored and committed to a vocation [1], [2]. During the path to an engineering identity, students will experience a crisis, when one's values and choices are examined and reevaluated, and a commitment, when the

Based on James Marcia's theory, identity development in youth is the degree to which one has explored and committed to a vocation [1], [2]. During the path to an engineering identity, students will experience a crisis, when one's values and choices are examined and reevaluated, and a commitment, when the outcome of the crisis leads the student to commit to becoming an engineer. During the crisis phase, students are offered a multitude of experiences to shape their values and choices to influence commitment to becoming an engineering student. Student's identities in engineering are fostered through mentoring from industry, alumni, and peer coaching [3], [4]; experiences that emphasize awareness of the importance of professional interactions [5]; and experiences that show creativity, collaboration, and communication as crucial components to engineering. Further strategies to increase students' persistence include support in their transition to becoming an engineering student, education about professional engineers and the workplace [6], and engagement in engineering activities beyond the classroom. Though these strategies are applied to all students, there are challenges students face in confronting their current identity and beliefs before they can understand their value to society and achieve personal satisfaction. To understand student's progression in developing their engineering identity, first year engineering students were surveyed at the beginning and end of their first semester. Students were asked to rate their level of agreement with 22 statements about their engineering experience. Data included 840 cases. Items with factor loading less than 0.6 suggesting no sufficient explanation were removed in successive factor analysis to identify the four factors. Factor analysis indicated that 60.69% of the total variance was explained by the successive factors. Survey questions were categorized into three factors: engineering identity as defined by sense of belonging and self-efficacy, doubts about becoming an engineer, and exploring engineering. Statements in exploring engineering indicated student awareness, interest and enjoyment within engineering. Students were asked to think about whether they spent time learning what engineers do and participating in engineering activities. Statements about doubts about engineering to engineering indicated whether students had formed opinions about their engineering experience and had understanding about their environment. Engineering identity required thought in belonging and self-efficacy. Belonging statements called for thought about one's opinion in the importance of being an engineer, the meaning of engineering, an attachment to engineering, and self-identification as an engineer. Statements about self-efficacy required students to contemplate their personal judgement of whether they would be able to succeed and their ability to become an engineer. Effort in engineering indicated student willingness to invest time and effort and their choices and effort in their engineering discipline.
ContributorsNguyen, Amanda (Author) / Ganesh, Tirupalavanam (Thesis director) / Robinson, Carrie (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related

Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related mutations, have provided important insights into the disease. However, these models do not display important disease-related pathologies and have been limited in their ability to model the complex genetics associated with SAD.

Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.

It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
ContributorsBounds, Lexi Rose (Author) / Brafman, David (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
The combination of immunohistochemical (IHC) stainings and optical microscopy has allowed for the visualization of specific microscopic structures within tissue; however, limitations in light and antibody penetration mitigate the scale on which these images can be taken (Alshammari et al, 2016; Marx, 2014). Tissue clearing, specifically the removal of lipids

The combination of immunohistochemical (IHC) stainings and optical microscopy has allowed for the visualization of specific microscopic structures within tissue; however, limitations in light and antibody penetration mitigate the scale on which these images can be taken (Alshammari et al, 2016; Marx, 2014). Tissue clearing, specifically the removal of lipids to improve sample transparency, solves the former weakness well, but does not improve antibody penetration significantly (Chung et al, 2013; Treweek et al, 2015). Therefore, there is a need to equalize the maximum depth that light can pass through a section with the depth at which there is recognizable fluorescence. This is particularly important when staining blood vessels as traditional size limitations exclusively allows for cross sectional visualization. Passive CLARITY Technique (PACT) has been at the forefront of tissue clearing protocols, utilizing an acrylamide hydrogel solution to maintain structure and sodium dodecyl sulfate to wash out lipids (Tomer et al, 2014). PACT is limited in its ability to clear larger sections and is not conducive to IHC antibody diffusion (Treweek et al, 2015). In order to circumvent these drawbacks, CUBIC was developed as an alternative passive protocol, aimed at being scalable to any tissue size (Richardson, 2015; Susaki et al, 2015). This study compared the effectiveness of both protocols in high and low lipid tissues in the context of blood vessel staining efficacy. Upon initial comparison, it became apparent that there was a statistically significant difference in mean DAPI intensity at all depths, up to 200 micrometers, between CUBIC and PACT \u2014 the former showcasing brighter stainings. Moreover, it was found that PACT does not remove erythrocytes from the tissue meaning that their auto-fluorescence is seen during imaging. Therefore, for blood vessel stainings, only CUBIC was optimized and quantitatively analyzed. In both tissue conditions as well as for two stainings, DAPI and fibronectin (FNCT), optimized CUBIC demonstrated a statistically significant difference from standard CUBIC with regards to mean fluorescent intensity.
ContributorsSidhu, Gurpaul Singh (Author) / VanAuker, Michael (Thesis director) / Kodibagkar, Vikram (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
This creative project created and implemented a seven-day STEM curriculum that ultimately encouraged engagement in STEM subjects in students ages 5 through 11. The activities were incorporated into Arizona State University's Kids' Camp over the summer of 2017, every Tuesday afternoon from 4 to 6 p.m. with each activity running

This creative project created and implemented a seven-day STEM curriculum that ultimately encouraged engagement in STEM subjects in students ages 5 through 11. The activities were incorporated into Arizona State University's Kids' Camp over the summer of 2017, every Tuesday afternoon from 4 to 6 p.m. with each activity running for roughly 40 minutes. The lesson plans were created to cover a myriad of scientific topics to account for varied student interest. The topics covered were plant biology, aerodynamics, zoology, geology, chemistry, physics, and astronomy. Each lesson was scaffolded to match the learning needs of the three age groups (5-6 year olds, 7-8 year olds, 9-11 year olds) and to encourage engagement. "Engagement" was measured by pre- and post-activity surveys approved by IRB. The surveys were in the form of statements where the children would totally agree, agree, be undecided, disagree, or totally disagree with it. To more accurately test engagement, the smiley face Likert scale was incorporated with the answer choices. After implementation of the intervention, two-tailed paired t-tests showed that student engagement significantly increased for the two lesson plans of Aerodynamics and Chemistry.
ContributorsHunt, Allison Rene (Co-author) / Belko, Sara (Co-author) / Merritt, Eileen (Thesis director) / Ankeny, Casey (Committee member) / Division of Teacher Preparation (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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Description
This thesis will examine the recruitment process of educated millennials coming from four-year institutions to their first job out of college. When referring to millennials throughout my research, I am specifically focusing on current college graduates in order to better relate to my own experiences as a soon-to-be-graduate seeking a

This thesis will examine the recruitment process of educated millennials coming from four-year institutions to their first job out of college. When referring to millennials throughout my research, I am specifically focusing on current college graduates in order to better relate to my own experiences as a soon-to-be-graduate seeking a job. I will examine the various recruiting techniques, i.e. channels to connect with graduates, and the hiring and interview process as a whole. This thesis will also discuss the challenges and differences of recruiting millennials versus other generations. It will also discuss the latest trends in college and early talent recruiting. In order to do this, I conducted a number of in-depth interviews with recruiters and hiring managers from various companies that recruit heavily from Arizona State University (ASU), in order to determine what these companies have done to be successful among young college graduates. I aimed to identify the specific techniques that these companies use to connect with recent college graduates, what skills these firms are looking for, and what the hiring process looks like for new millennial employees. I also conducted an extensive online literature search about recruiting educated millennials in the workforce, and I used that information as a basis to form my interview questions. The interviews were meant to confirm or deny that research, but the interviewees also revealed many new trends and insights. I hope that this information will be beneficial not only to college seniors seeking first-time employment, but also to other companies who feel that they are struggling to capture young talent.
ContributorsCapra, Alexandria Luccia (Author) / Kalika, Dale (Thesis director) / Eaton, Kathryn (Committee member) / W. P. Carey School of Business (Contributor) / Department of Marketing (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05