Matching Items (1,005)
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). 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
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 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
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 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
Description
This research compares shifts in a SuperSpec titanium nitride (TiN) kinetic inductance detector's (KID's) resonant frequency with accepted models for other KIDs. SuperSpec, which is being developed at the University of Colorado Boulder, is an on-chip spectrometer designed with a multiplexed readout with multiple KIDs that is set up for a broadband transmission of these measurements. It is useful for detecting radiation in the mm and sub mm wavelengths which is significant since absorption and reemission of photons by dust causes radiation from distant objects to reach us in infrared and far-infrared bands. In preparation for testing, our team installed stages designed previously by Paul Abers and his group into our cryostat and designed and installed other parts necessary for the cryostat to be able to test devices on the 250 mK stage. This work included the design and construction of additional parts, a new setup for the wiring in the cryostat, the assembly, testing, and installation of several stainless steel coaxial cables for the measurements through the devices, and other cryogenic and low pressure considerations. The SuperSpec KID was successfully tested on this 250 mK stage thus confirming that the new setup is functional. Our results are in agreement with existing models which suggest that the breaking of cooper pairs in the detector's superconductor which occurs in response to temperature, optical load, and readout power will decrease the resonant frequencies. A negative linear relationship in our results appears, as expected, since the parameters are varied only slightly so that a linear approximation is appropriate. We compared the rate at which the resonant frequency responded to temperature and found it to be close to the expected value.
ContributorsDiaz, Heriberto Chacon (Author) / Mauskopf, Philip (Thesis director) / McCartney, Martha (Committee member) / Department of Physics (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This paper considers what factors influence student interest, motivation, and continued engagement. Studies show anticipated extrinsic rewards for activity participation have been shown to reduce intrinsic value for that activity. This might suggest that grade point average (GPA) has a similar effect on academic interests. Further, when incentives such as scholarships, internships, and careers are GPA-oriented, students must adopt performance goals in courses to guarantee success. However, performance goals have not been shown to correlated with continued interest in a topic. Current literature proposes that student involvement in extracurricular activities, focused study groups, and mentored research are crucial to student success. Further, students may express either a fixed or growth mindset, which influences their approach to challenges and opportunities for growth. The purpose of this study was to collect individual cases of students' experiences in college. The interview method was chosen to collect complex information that could not be gathered from standard surveys. To accomplish this, questions were developed based on content areas related to education and motivation theory. The content areas included activities and meaning, motivation, vision, and personal development. The developed interview method relied on broad questions that would be followed by specific "probing" questions. We hypothesize that this would result in participant-led discussions and unique narratives from the participant. Initial findings suggest that some of the questions were effective in eliciting detailed responses, though results were dependent on the interviewer. From the interviews we find that students value their group involvements, leadership opportunities, and relationships with mentors, which parallels results found in other studies.
ContributorsAbrams, Sara (Author) / Hartwell, Lee (Thesis director) / Correa, Kevin (Committee member) / Department of Psychology (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This study estimates the capitalization effect of golf courses in Maricopa County using the hedonic pricing method. It draws upon a dataset of 574,989 residential transactions from 2000 to 2006 to examine how the aesthetic, non-golf benefits of golf courses capitalize across a gradient of proximity measures. The measures for amenity value extend beyond home adjacency and include considerations for homes within a range of discrete walkability buffers of golf courses. The models also distinguish between public and private golf courses as a proxy for the level of golf course access perceived by non-golfers. Unobserved spatial characteristics of the neighborhoods around golf courses are controlled for by increasing the extent of spatial fixed effects from city, to census tract, and finally to 2000 meter golf course ‘neighborhoods.’ The estimation results support two primary conclusions. First, golf course proximity is found to be highly valued for adjacent homes and homes up to 50 meters way from a course, still evident but minimal between 50 and 150 meters, and insignificant at all other distance ranges. Second, private golf courses do not command a higher proximity premia compared to public courses with the exception of homes within 25 to 50 meters of a course, indicating that the non-golf benefits of courses capitalize similarly, regardless of course type. The results of this study motivate further investigation into golf course features that signal access or add value to homes in the range of capitalization, particularly for near-adjacent homes between 50 and 150 meters thought previously not to capitalize.
ContributorsJoiner, Emily (Author) / Abbott, Joshua (Thesis director) / Smith, Kerry (Committee member) / Economics Program in CLAS (Contributor) / School of Sustainability (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The objective of this paper is to provide an educational diagnostic into the technology of blockchain and its application for the supply chain. Education on the topic is important to prevent misinformation on the capabilities of blockchain. Blockchain as a new technology can be confusing to grasp given the wide possibilities it can provide. This can convolute the topic by being too broad when defined. Instead, the focus will be maintained on explaining the technical details about how and why this technology works in improving the supply chain. The scope of explanation will not be limited to the solutions, but will also detail current problems. Both public and private blockchain networks will be explained and solutions they provide in supply chains. In addition, other non-blockchain systems will be described that provide important pieces in supply chain operations that blockchain cannot provide. Blockchain when applied to the supply chain provides improved consumer transparency, management of resources, logistics, trade finance, and liquidity.
ContributorsKrukar, Joel Michael (Author) / Oke, Adegoke (Thesis director) / Duarte, Brett (Committee member) / Hahn, Richard (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Department of Economics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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 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
Description
The Super Catalan numbers are a known set of numbers which have so far eluded a combinatorial interpretation. Several weighted interpretations have appeared since their discovery, one of which was discovered by William Kuszmaul in 2017. In this paper, we connect the weighted Super Catalan structure created previously by Kuszmaul and a natural $q$-analogue of the Super Catalan numbers. We do this by creating a statistic $\sigma$ for which the $q$ Super Catalan numbers, $S_q(m,n)=\sum_X (-1)^{\mu(X)} q^{\sigma(X)}$. In doing so, we take a step towards finding a strict combinatorial interpretation for the Super Catalan numbers.
ContributorsHouse, John Douglas (Author) / Fishel, Susanna (Thesis director) / Childress, Nancy (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Construction is a defining characteristic of geometry classes. In a traditional classroom, teachers and students use physical tools (i.e. a compass and straight-edge) in their constructions. However, with modern technology, construction is possible through the use of digital applications such as GeoGebra and Geometer’s SketchPad.
Many other studies have researched the benefits of digital manipulatives and digital environments through student completion of tasks and testing. This study intends to research students’ use of the digital tools and manipulatives, along with the students’ interactions with the digital environment. To this end, I conducted exploratory teaching experiments with two calculus I students.
In the exploratory teaching experiments, students were introduced to a GeoGebra application developed by Fischer (2019), which includes instructional videos and corresponding quizzes, as well as exercises and interactive notepads, where students could use digital tools to construct line segments and circles (corresponding to the physical straight-edge and compass). The application built up the students’ foundational knowledge, culminating in the construction and verbal proof of Euclid’s Elements, Proposition 1 (Euclid, 1733).
The central findings of this thesis are the students’ interactions with the digital environment, with observed changes in their conceptions of radii and circles, and in their use of tools. The students were observed to have conceptions of radii as a process, a geometric shape, and a geometric object. I observed the students’ conceptions of a circle change from a geometric shape to a geometric object, and with that change, observed the students’ use of tools change from a measuring focus to a property focus.
I report a summary of the students’ work and classify their reasoning and actions into the above categories, and an analysis of how the digital environment impacts the students’ conceptions. I also briefly discuss the impact of the findings on pedagogy and future research.
Many other studies have researched the benefits of digital manipulatives and digital environments through student completion of tasks and testing. This study intends to research students’ use of the digital tools and manipulatives, along with the students’ interactions with the digital environment. To this end, I conducted exploratory teaching experiments with two calculus I students.
In the exploratory teaching experiments, students were introduced to a GeoGebra application developed by Fischer (2019), which includes instructional videos and corresponding quizzes, as well as exercises and interactive notepads, where students could use digital tools to construct line segments and circles (corresponding to the physical straight-edge and compass). The application built up the students’ foundational knowledge, culminating in the construction and verbal proof of Euclid’s Elements, Proposition 1 (Euclid, 1733).
The central findings of this thesis are the students’ interactions with the digital environment, with observed changes in their conceptions of radii and circles, and in their use of tools. The students were observed to have conceptions of radii as a process, a geometric shape, and a geometric object. I observed the students’ conceptions of a circle change from a geometric shape to a geometric object, and with that change, observed the students’ use of tools change from a measuring focus to a property focus.
I report a summary of the students’ work and classify their reasoning and actions into the above categories, and an analysis of how the digital environment impacts the students’ conceptions. I also briefly discuss the impact of the findings on pedagogy and future research.
ContributorsSakauye, Noelle Marie (Author) / Roh, Kyeong Hah (Thesis director) / Zandieh, Michelle (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05