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- Creators: Barrett, The Honors College
- Creators: Sierks, Michael
Description
Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering highly specific targets is the application of phage display utilizing single chain variable fragment antibodies (scFv). The aim of this research was to employ phage display to identify pathologies related to traumatic brain injury (TBI), particularly astrogliosis. A unique biopanning method against viable astrocyte cultures activated with TGF-β achieved this aim. Four scFv clones of interest showed varying relative affinities toward astrocytes. One of those four showed the ability to identify reactive astroctyes over basal astrocytes through max signal readings, while another showed a statistical significance in max signal reading toward basal astrocytes. Future studies will include further affinity characterization assays. This work contributes to the development of targeting therapeutics and diagnostics for TBI.
ContributorsMarsh, William (Author) / Stabenfeldt, Sarah (Thesis advisor) / Caplan, Michael (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
The goal of this thesis is to test whether Alzheimer's disease (AD) is associated with distinctive humoral immune changes that can be detected in plasma and tracked across time. This is relevant because AD is the principal cause of dementia, and yet, no specific diagnostic tests are universally employed in clinical practice to predict, diagnose or monitor disease progression. In particular, I describe herein a proteomic platform developed at the Center for Innovations in Medicine (CIM) consisting of a slide with 10.000 random-sequence peptides printed on its surface, which is used as the solid phase of an immunoassay where antibodies of interest are allowed to react and subsequently detected with a labeled secondary antibody. The pattern of antibody binding to the microarray is unique for each individual animal or person. This thesis will evaluate the versatility of the microarray platform and how it can be used to detect and characterize the binding patterns of antibodies relevant to the pathophysiology of AD as well as the plasma samples of animal models of AD and elderly humans with or without dementia. My specific aims were to evaluate the emergence and stability of immunosignature in mice with cerebral amyloidosis, and characterize the immunosignature of humans with AD. Plasma samples from APPswe/PSEN1-dE9 transgenic mice were evaluated longitudinally from 2 to 15 months of age to compare the evolving immunosignature with non-transgenic control mice. Immunological variation across different time-points was assessed, with particular emphasis on time of emergence of a characteristic pattern. In addition, plasma samples from AD patients and age-matched individuals without dementia were assayed on the peptide microarray and binding patterns were compared. It is hoped that these experiments will be the basis for a larger study of the diagnostic merits of the microarray-based immunoassay in dementia clinics.
ContributorsRestrepo Jimenez, Lucas (Author) / Johnston, Stephen A. (Thesis advisor) / Chang, Yung (Committee member) / Reiman, Eric (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2011
Description
This project aims to address the current protocol regarding the diagnosis and treatment of traumatic brain injury (TBI) in medical industries around the world. Although there are various methods used to qualitatively determine if TBI has occurred to a patient, this study attempts to aid in the creation of a system for quantitative measurement of TBI and its relative magnitude. Through a method of artificial evolution/selection called phage display, an antibody that binds highly specifically to a post-TBI upregulated brain chondroitin sulfate proteoglycan called neurocan has been identified. As TG1 Escheria Coli bacteria were infected with KM13 helper phage and M13 filamentous phage in conjunction, monovalent display of antibody fragments (ScFv) was performed. The ScFv bind directly to the neurocan and from screening, phage that produced ScFv's with higher affinity and specificity to neurocan were separated and purified. Future research aims to improve the ScFv characteristics through increased screening toward neurocan. The identification of a highly specific antibody could lead to improved targeting of neurocan post-TBI in-vivo, aiding researchers in quantitatively defining TBI by visualizing its magnitude.
ContributorsSeelig, Timothy Scott (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
The diagnosis of bacterial infections based on phage multiplication has the potential for profound clinical implications, particularly for antibiotic-resistant strains and the slow-growing Mycobacterium tuberculosis. The possibility of hastening the diagnosis of antibiotic-resistant mycobacterial infections was accomplished via the study of Mycobacterium smegmatis, a generally non-pathogenic, comparatively fast growing microorganism to M. tuberculosis. These proof-of-concept studies established that after transduction of M. smegmatis cells with bacteriophages, MALDI-TOF MS could be used to detect increased amounts of phage proteins. Recording the growth of M. smegmatis over an 8-hour period, starting with very low OD600 measurements, simulated bacterial loads in clinical settings. For the purposes of MALDI-TOF MS, the procedure for the most effective lethal exposure for M. smegmatis was determined to be a 1-hour incubation in a 95°C water bath. Successful precipitation of the lytic mycobacteriophages D29 and Giles was performed using chloroform and methanol and overlaid with 1-2 μL of α-cyano-4-hydoxycinnaminic acid, which allowed for more distinct and repeatable MALDI-TOF MS spectra. Phage D29 was found to produce an m/z peak at 18.477 kDa, which may have indicated a 2+-charged ion of the 34.8 kDa minor tail protein. The Giles proteins that were identified with MALDI-TOF MS have not been directly compared to protein values reported in the scientific literature. However, the MALDI-TOF MS spectra suggested that distinct peaks existed between M. smegmatis mc2155 and mycobacteriophages, indicating that successful infection with lytic phage and replication thereafter may have occurred. The distinct peaks between M. smegmatis and the phage can be used as indicators of the presence of mycobacteria. At this point, the limits of detection of each phage must be elucidated in order for MALDI-TOF MS spectra to be successfully implemented as a mechanism to rapidly detect antibiotic-resistant mycobacteria.
ContributorsBarrett, Rachael Lauren (Author) / Haydel, Shelley (Thesis director) / Sandrin, Todd (Committee member) / Maarsingh, Jason (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The knowledge of medical genetics is currently used with prenatal testing, and the advancements in the field of behavioral genetics may someday allow for its use with prenatal testing as well. The use of prenatal procedures for medical phenotypes has its own implications and should these techniques be used for behavioral phenotypes, such implications can also apply. The complexity of behavior in terms of the factors that may affect it, along with the way it is conceptualized and perceived, adds further implications for prenatal testing of it. In this thesis, I discuss the qualitative, quantitative, and historical facets of prenatal testing for medical and behavioral phenotypes and the undercurrent of eugenics. I do so by presenting an example of the medical phenotype (cystic fibrosis) as a case for envisioning the implications of medical phenotypes before delving into examples of behavioral phenotypes (aggression, impulsivity, extraversion, and neuroticism) in order to explore the implications shared with those for medical phenotypes as well as those unique to it. These implications then set the foundation for a discussion of eugenics, and the considerations for how behavioral genetics with prenatal testing may give way to a modern form of it.
ContributorsMinai, Mandana (Author) / Maienschein, Jane (Thesis director) / Robert, Jason (Committee member) / Magnus, David (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)
Created2014-05
Description
Epilepsy is a complex neurological disease that affects one in twenty-six people. Despite this prevalence, it is very difficult to diagnose. EpiFinder, Inc. has created an app to better diagnose epilepsy through the use of an epilepsy focused ontology and a heuristic algorithm. Throughout this project, efforts were made to improve the user interface and robustness of the EpiFinder app in order to ease usability and increase diagnostic accuracy. A general workflow of the app was created to aid new users with navigation of the app’s screens. Additionally, numerous diagnostic guidelines provided by the International League Against Epilepsy as well as de-identified case studies were annotated using the Knowtator plug-in in Protégé 3.3.1, where new terms not currently represented in the seizure and epilepsy syndrome ontology (ESSO) were identified for future integration into the ontology. This will help to increase the confidence level of the differential diagnosis reached. A basic evaluation of the user interface was done to provide feedback for the developers for future iterations of the app. Significant efforts were also made for better incorporation of the app into a physician’s typical workflow. For instance, an ontology of a basic review of systems of a medical history was built in Protégé 4.2 for later integration with the ESSO, which will help to increase efficiency and familiarity of the app for physician users. Finally, feedback regarding utility of the app was gathered from an epilepsy support group. These points will be taken into consideration for development of patient-based features in future versions of the EpiFinder app. It is the hope that these various improvements of the app will contribute to a more efficient, more accurate diagnosis of epilepsy patients, resulting in more appropriate treatments and an overall increased quality of life.
ContributorsCsernak, Lidia Maria (Author) / Crook, Sharon (Thesis director) / Greger, Bradley (Committee member) / Yao, Robert (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental disorder that is becoming increasingly common. Autism does not yet have a known etiology, nor a definitive diagnostic test, thus making diagnosis a difficult and rarely uniform task. Currently, ASD is behaviorally diagnosed based on criteria defined by the American Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders (DSM). Recently, a change was made in the criteria from more lenient criteria in DSM-IV-TR, to more narrow criteria laid out by the DSM-V, which supersedes the DSM-IV-TR. This drastic change raised many questions and debates about which set of criteria are better. The more lenient criteria offers a more inclusive diagnosis giving greater access to therapies; while the narrow diagnostic criteria excludes some individuals, creating a more uniform diagnosis that's easier to use in research. This thesis analyzes the change in diagnostic criteria from the DSM-IV-TR to the DSM-V and the effects of these changes on the practices of diagnosis. In addition, it explores the implications of this change for the families of children with autism and for those involved in autism research, examining their respective opinions and interests pertaining to narrow verses broad diagnostic criteria. Building on this analysis, the thesis offers recommendations about diagnostic criteria should be set. It argues that the wellbeing of patients takes priority over the interests of researchers, and thus diagnosis should be done in a way that offers the best prognosis for all children who suffer from autistic symptoms.
ContributorsBremer, Michelle Nichole (Author) / Hurlbut, Ben (Thesis director) / Robert, Jason (Committee member) / Brian, Jennifer (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Concussions and traumatic brain injuries are mechanical events which can derive from no specific activity or event. However, these injuries occur often during athletic and sporting events but many athletes experiencing these symptoms go undiagnosed and continue playing without proper medical attention. The current gold standard for diagnosing athletes with concussions is to have medical professionals on the sidelines of events to perform qualitative standardized assessments which may not be performed frequently enough and are not specialized for each athlete. The purpose of this report is to discuss a study sanctioned by Arizona State University's Project HoneyBee and additional affiliations to validate a third-party mouth guard device product to recognize and detect force impacts blown to an athlete's head during athletic activity. Current technology in health monitoring medical devices can allow users to apply this device as an additional safety mechanism for early concussion awareness and diagnosis. This report includes the materials and methods used for experimentation, the discussion of its results, and the complications which occurred and areas for improvement during the preliminary efforts of this project. Participants in the study were five non-varsity ASU Wrestling athletes who volunteered to wear a third-party mouth guard device during sparring contact at practice. Following a needed calibration period for the devices, results were recorded both through visual observation and with the mouth guard devices using an accelerometer and gyroscope. This study provided a sound understanding for the operation and functionality of the mouth guard devices. The mouth guard devices have the capability to provide fundamental avenues of research for future investigations.
ContributorsTielke, Austin Wyatt (Author) / Ross, Heather (Thesis director) / LaBelle, Jeffrey (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
When earning a teaching certification, there is no curriculum when it comes to the treatment of students with a diagnosis as well as how to educate their fellow classmates. Diagnoses affect the process of child development of the diagnosed as well as the friends and family. Children of all different ages have different responses and reactions to the world of health. Looking at a developmental perspective, teachers can properly educate themselves and their students about these diagnoses. To be able to successfully inform students of diagnoses, there must be an overall understanding of how well they are able to acquire the knowledge. According to Jean Piaget, a key researcher in cognitive development, the age of the child correlates with their overall understanding and comprehension. In his theory, he explained how he believed that the environment of an organism affects how it will respond and adapt to the situations at hand. There are four stages that are connected to age, from infancy to adolescence and adulthood. Therefore, this project will focus on school-age children who are in the concrete operational stage. The concrete operational stage is made up of elementary and early adolescents and focuses on intelligence that is demonstrated through logical and precise thinking of concrete ideas (Huitt, W., & Hummel, J, 2003). This type of thinking applies to all parts of the child’s life and informs their behaviors on how to “adapt” to new information. Knowing this information, we will be able to create a curriculum of lectures, informational videos, worksheets and quizzes that can properly assess the student’s and their knowledge of the diagnoses.
ContributorsGreer, Rebecca E. (Author) / Visconti, Kari (Thesis director) / Collins, Jena (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / School of Community Resources and Development (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Protein and gene circuit level synthetic bioengineering can require years to develop a single target. Phage assisted continuous evolution (PACE) is a powerful new tool for rapidly engineering new genes and proteins, but the method requires an automated cell culture system, making it inaccessible to non industrial research programs. Complex protein functions, like specific binding, require similarly dynamic PACE selection that can be alternatively induced or suppressed, with heat labile chemicals like tetracycline. Selection conditions must be controlled continuously over days, with adjustments made every few minutes. To make PACE experiments accessible to the broader community, we designed dedicated cell culture hardware and integrated optogenetically controlled plasmids. The low cost and open source platform allows a user to conduct PACE with continuous monitoring and precise control of evolution using light.
ContributorsTse, Ashley (Author) / Bartelle, Benjamin (Thesis director) / Tian, Xiaojun (Committee member) / Barrett, The Honors College (Contributor) / Materials Science and Engineering Program (Contributor) / School of International Letters and Cultures (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05