Matching Items (289)
Description
In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human samples. As this takes place, a serendipitous opportunity has become evident. By the virtue that as one narrows the focus towards "single" protein targets (instead of entire proteomes) using pan-antibody-based enrichment techniques, a discovery science has emerged, so to speak. This is due to the largely unknown context in which "single" proteins exist in blood (i.e. polymorphisms, transcript variants, and posttranslational modifications) and hence, targeted proteomics has applications for established biomarkers. Furthermore, besides protein heterogeneity accounting for interferences with conventional immunometric platforms, it is becoming evident that this formerly hidden dimension of structural information also contains rich-pathobiological information. Consequently, targeted proteomics studies that aim to ascertain a protein's genuine presentation within disease- stratified populations and serve as a stepping-stone within a biomarker translational pipeline are of clinical interest. Roughly 128 million Americans are pre-diabetic, diabetic, and/or have kidney disease and public and private spending for treating these diseases is in the hundreds of billions of dollars. In an effort to create new solutions for the early detection and management of these conditions, described herein is the design, development, and translation of mass spectrometric immunoassays targeted towards diabetes and kidney disease. Population proteomics experiments were performed for the following clinically relevant proteins: insulin, C-peptide, RANTES, and parathyroid hormone. At least thirty-eight protein isoforms were detected. Besides the numerous disease correlations confronted within the disease-stratified cohorts, certain isoforms also appeared to be causally related to the underlying pathophysiology and/or have therapeutic implications. Technical advancements include multiplexed isoform quantification as well a "dual- extraction" methodology for eliminating non-specific proteins while simultaneously validating isoforms. Industrial efforts towards widespread clinical adoption are also described. Consequently, this work lays a foundation for the translation of mass spectrometric immunoassays into the clinical arena and simultaneously presents the most recent advancements concerning the mass spectrometric immunoassay approach.
ContributorsOran, Paul (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Ros, Alexandra (Committee member) / Williams, Peter (Committee member) / Arizona State University (Publisher)
Created2011
Description
Rabies disease remains enzootic among raccoons, skunks, foxes and bats in the United States. It is of primary concern for public-health agencies to control spatial spread of rabies in wildlife and its potential spillover infection of domestic animals and humans. Rabies is invariably fatal in wildlife if untreated, with a non-negligible incubation period. Understanding how this latency affects spatial spread of rabies in wildlife is the concern of chapter 2 and 3. Chapter 1 deals with the background of mathematical models for rabies and lists main objectives. In chapter 2, a reaction-diffusion susceptible-exposed-infected (SEI) model and a delayed diffusive susceptible-infected (SI) model are constructed to describe the same epidemic process -- rabies spread in foxes. For the delayed diffusive model a non-local infection term with delay is resulted from modeling the dispersal during incubation stage. Comparison is made regarding minimum traveling wave speeds of the two models, which are verified using numerical experiments. In chapter 3, starting with two Kermack and McKendrick's models where infectivity, death rate and diffusion rate of infected individuals can depend on the age of infection, the asymptotic speed of spread $c^\ast$ for the cumulated force of infection can be analyzed. For the special case of fixed incubation period, the asymptotic speed of spread is governed by the same integral equation for both models. Although explicit solutions for $c^\ast$ are difficult to obtain, assuming that diffusion coefficient of incubating animals is small, $c^\ast$ can be estimated in terms of model parameter values. Chapter 4 considers the implementation of realistic landscape in simulation of rabies spread in skunks and bats in northeast Texas. The Finite Element Method (FEM) is adopted because the irregular shapes of realistic landscape naturally lead to unstructured grids in the spatial domain. This implementation leads to a more accurate description of skunk rabies cases distributions.
ContributorsLiu, Hao (Author) / Kuang, Yang (Thesis advisor) / Jackiewicz, Zdzislaw (Committee member) / Lanchier, Nicolas (Committee member) / Smith, Hal (Committee member) / Thieme, Horst (Committee member) / Arizona State University (Publisher)
Created2013
Description
Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay (MSIA) which has been one of the primary methods of biomarker discovery techniques. MSIA analyzes protein molecules as potential biomarkers using time of flight mass spectrometry (TOF-MS). Peak detection in TOF-MS is important for biomarker analysis and many other MS related application. Though many peak detection algorithms exist, most of them are based on heuristics models. One of the ways of detecting signal peaks is by deploying stochastic models of the signal and noise observations. Likelihood ratio test (LRT) detector, based on the Neyman-Pearson (NP) lemma, is an uniformly most powerful test to decision making in the form of a hypothesis test. The primary goal of this dissertation is to develop signal and noise models for the electrospray ionization (ESI) TOF-MS data. A new method is proposed for developing the signal model by employing first principles calculations based on device physics and molecular properties. The noise model is developed by analyzing MS data from careful experiments in the ESI mass spectrometer. A non-flat baseline in MS data is common. The reasons behind the formation of this baseline has not been fully comprehended. A new signal model explaining the presence of baseline is proposed, though detailed experiments are needed to further substantiate the model assumptions. Signal detection schemes based on these signal and noise models are proposed. A maximum likelihood (ML) method is introduced for estimating the signal peak amplitudes. The performance of the detection methods and ML estimation are evaluated with Monte Carlo simulation which shows promising results. An application of these methods is proposed for fractional abundance calculation for biomarker analysis, which is mathematically robust and fundamentally different than the current algorithms. Biomarker panels for type 2 diabetes and cardiovascular disease are analyzed using existing MS analysis algorithms. Finally, a support vector machine based multi-classification algorithm is developed for evaluating the biomarkers' effectiveness in discriminating type 2 diabetes and cardiovascular diseases and is shown to perform better than a linear discriminant analysis based classifier.
ContributorsBuddi, Sai (Author) / Taylor, Thomas (Thesis advisor) / Cochran, Douglas (Thesis advisor) / Nelson, Randall (Committee member) / Duman, Tolga (Committee member) / Arizona State University (Publisher)
Created2012
Description
Bacteriophage (phage) are viruses that infect bacteria. Typical laboratory experiments show that in a chemostat containing phage and susceptible bacteria species, a mutant bacteria species will evolve. This mutant species is usually resistant to the phage infection and less competitive compared to the susceptible bacteria species. In some experiments, both susceptible and resistant bacteria species, as well as phage, can coexist at an equilibrium for hundreds of hours. The current research is inspired by these observations, and the goal is to establish a mathematical model and explore sufficient and necessary conditions for the coexistence. In this dissertation a model with infinite distributed delay terms based on some existing work is established. A rigorous analysis of the well-posedness of this model is provided, and it is proved that the susceptible bacteria persist. To study the persistence of phage species, a "Phage Reproduction Number" (PRN) is defined. The mathematical analysis shows phage persist if PRN > 1 and vanish if PRN < 1. A sufficient condition and a necessary condition for persistence of resistant bacteria are given. The persistence of the phage is essential for the persistence of resistant bacteria. Also, the resistant bacteria persist if its fitness is the same as the susceptible bacteria and if PRN > 1. A special case of the general model leads to a system of ordinary differential equations, for which numerical simulation results are presented.
ContributorsHan, Zhun (Author) / Smith, Hal (Thesis advisor) / Armbruster, Dieter (Committee member) / Kawski, Matthias (Committee member) / Kuang, Yang (Committee member) / Thieme, Horst (Committee member) / Arizona State University (Publisher)
Created2012
Description
In vertebrate outer retina, changes in the membrane potential of horizontal cells affect the calcium influx and glutamate release of cone photoreceptors via a negative feedback. This feedback has a number of important physiological consequences. One is called background-induced flicker enhancement (BIFE) in which the onset of dim background enhances the center flicker response of horizontal cells. The underlying mechanism for the feedback is still unclear but competing hypotheses have been proposed. One is the GABA hypothesis, which states that the feedback is mediated by gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter released from horizontal cells. Another is the ephaptic hypothesis, which contends that the feedback is non-GABAergic and is achieved through the modulation of electrical potential in the intersynaptic cleft between cones and horizontal cells. In this study, a continuum spine model of the cone-horizontal cell synaptic circuitry is formulated. This model, a partial differential equation system, incorporates both the GABA and ephaptic feedback mechanisms. Simulation results, in comparison with experiments, indicate that the ephaptic mechanism is necessary in order for the model to capture the major spatial and temporal dynamics of the BIFE effect. In addition, simulations indicate that the GABA mechanism may play some minor modulation role.
ContributorsChang, Shaojie (Author) / Baer, Steven M. (Thesis advisor) / Gardner, Carl L (Thesis advisor) / Crook, Sharon M (Committee member) / Kuang, Yang (Committee member) / Ringhofer, Christian (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
I conducted a qualitative, comparative study on the nursing education systems in the United Kingdom and the United States, focusing on two universities—Arizona State University in Phoenix, Arizona and Leeds Beckett University in Leeds, England. The goals of my thesis included comparing the educational, economic, and cultural aspects of the countries and how those aspects impact nursing students on both sides of the pond. The educational and economic aspects were compared by utilizing existing literature and open data sources such as the university websites and publications from comparative education journals, while the cultural differences were evaluated by conducting short, one-on-one interviews with students enrolled in the Adult Health courses at both universities. The findings from the interviews were transcribed and coded, and findings from the sites were compared. While there is an extensive amount of research published regarding comparative education, there has not been much published comparing these developed countries. While there is a significant difference in the structure and cost of the nursing programs, there are more similarities than differences in culture between nursing students interviewed in the US and those interviewed in the UK.
ContributorsTahiliani, Shreja (Author) / Hagler, Debra (Thesis director) / Allen, Angela (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The goal of this creative project is to explain the different roles of advanced practice nursing as well as the role of a registered nurse. Advanced practice nursing roles include Certified Nurse Practitioner, Certified Registered Nurse Anesthetist, Certified Clinical Nurse Specialist, and Certified Nurse Midwife. The role of the registered nurse is included in this website because this role is the foundation for becoming an advanced practice nurse and is an equally important role. The target audience for the website is potential nursing students, current nursing students, and licensed nurses who desire to advance their career and are looking for more information about each role. This comprehensive website includes the scope of practice, salary, educational programs, and an interview with a nurse in each role. The description of each advanced practice role includes audio and visual aids to appeal to different types of learners. In depth education regarding advanced practice nursing roles will make current and future nurses more aware of the endless possibilities of a career in nursing. Nurses provide education to patients every day, but there is rarely adequate education provided to nurses regarding their profession or professional advancement opportunities. Nursing is a patient-focused career and sometimes nurses forget to focus on their own personal growth while caring for others. This one-stop website promotes nurse to nurse education by thoroughly explaining each advanced practice role. All of the information in this website is publically available through the internet and this website is meant solely for educational purposes.
ContributorsThompson, Rachel (Co-author) / Banchik, Jennifer (Co-author) / Peterson, Katherine (Thesis director) / Kriz, Lindsey (Committee member) / Spahr, Nancy (Committee member) / School of Community Resources and Development (Contributor) / School of Social Transformation (Contributor) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Colorectal cancer (CRC) is the third most prevalent form of cancer in both genders and second highest cause of cancer-related death in the United States. Despite the availability of preventative CRC screening, Latinos as a group are of particular concern for CRC as they tend to have a lower screening rate, contributing to the possibility of late-stage diagnosis or even death. However, little is known about the perceptions of CRC screening and factors which contribute to beliefs about CRC in Latinos. Most studies are quantitative and rarely include a qualitative approach focusing on cultural aspects and communication with physicians. The purpose of this study was to explore participants' perceived facilitators and barriers to CRC screening, as well as perspectives on physician recommendation and fatalism, using a qualitative approach. A convenience and snowball sampling were used to collect the data. Eight English-speaking Latino individuals (M age=56 years; 75% female) in the Phoenix, Arizona area were invited to 60-90 minute in-depth interviews on perceptions of the colorectal cancer screening process. Ten major themes emerged from the interviews: (1) lacking awareness and knowledge of CRC screening, (2) attitude toward CRC and screening, (3) availability of preventive care, (4) physician trust, (5) fear, (6) desire for increased information, (7) personal learning, (8) lifestyle factors, (9) cultural impact, and (10) willingness to change lifestyle. Results indicated varying levels of perceived knowledge of colorectal cancer, little perceived risk of diagnosis, desire for more information, and a high level of physician trust. Implications for nursing included increased need for CRC screening educational resources, as well as further investigation of the influence of fatalistic belief in CRC screening compliance for the Latino population.
ContributorsMagdaleno, Claire Rose (Author) / Kim, Sunny (Thesis director) / McNulty, Julie (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
This past summer, I met a young lady named Ashley (name has been changed) who has been diagnosed with chronic Lyme disease. Upon researching this condition in greater detail, I learned that many medical providers who base their practice on the best evidence do not support treating patients for a chronic Lyme infection, the existence of which has not been substantially supported with research. I inquired about the process that led her to seek treatment for chronic Lyme disease at Jemsek Specialty Clinic. I learned that after many inaccurate diagnoses and years of unhelpful treatments, Ashley finally rejected the help offered by traditional medical doctors because she felt they were uncaring and inattentive, and went somewhere she felt heard. What she deserved, however, was both care that was based in scientific research and care that felt compassionate, as has been promoted by the nursing field. Despite the lack of a confirmed medical diagnosis, Ashley's day to day symptoms and struggles could be addressed with nursing care. I then constructed a nursing care plan to be implemented by Ashley's family and friends to help her feel her best and live a fulfilling life despite chronic disease. Patients should not have to choose between a healthcare provider who utilizes the strongest scientific evidence and one they feel understands them, though many do. Nursing can unite these mindsets by alleviating the daily challenges patients face. Please see the website http://careplanforashley.blogspot.com
ContributorsKnochel, Amanda Marie (Author) / Panchmatia, Bella (Thesis director) / Mishark, Kenneth (Committee member) / Barrett, The Honors College (Contributor) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor)
Created2014-05