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A synbody is a newly developed protein binding peptide which can be rapidly produced by chemical methods. The advantages of the synbody producing process make it a potential human proteome binding reagent. Most of the synbodies are designed to bind to specific proteins. The peptides incorporated in a synbody are discovered with peptide microarray technology. Nevertheless, the targets for unknown synbodies can also be discovered by searching through a protein mixture. The first part of this thesis mainly focuses on the process of target searching, which was performed with immunoprecipitation assays and mass spectrometry analysis. Proteins are pulled down from the cell lysate by certain synbodies, and then these proteins are identified using mass spectrometry. After excluding non-specific bindings, the interaction between a synbody and its real target(s) can be verified with affinity measurements. As a specific example, the binding between 1-4-KCap synbody and actin was discovered. This result proved the feasibility of the mass spectrometry based method and also suggested that a high throughput synbody discovery platform for the human proteome could be developed. Besides the application of synbody development, the peptide microarray technology can also be used for immunosignatures. The composition of all types of antibodies existing in one's blood is related to an individual's health condition. A method, called immunosignaturing, has been developed for early disease diagnosis based on this principle. CIM10K microarray slides work as a platform for blood antibody detection in immunosignaturing. During the analysis of an immunosignature, the data from these slides needs to be validated by using landing light peptides. The second part of this thesis focuses on the validation of the data. A biotinylated peptide was used as a landing light on the new CIM10K slides. The data was collected in several rounds of tests and indicated that the variation among landing lights was significantly reduced by using the newly prepared biotinylated peptide compared with old peptide mixture. Several suggestions for further landing light improvement are proposed based on the results.
ContributorsSun, Minyao (Author) / Johnston, Stephen Albert (Thesis advisor) / Diehnelt, Chris Wayne (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
Background: The purpose of this study was to assess the efficacy of a lifestyle intervention on cardiorespiratory fitness in Latino youth with obesity and prediabetes. <br/>Methods: Participants (n=50) in this study were taken from a larger randomized controlled trial (n=180, BMI ≥ 95th percentile). Youth participated in a 6-month lifestyle intervention that included physical activity (60 minutes, 3x/week) and nutrition and wellness classes (60 minutes, 1x/week) delivered to families at the Lincoln Family YMCA in Downtown Phoenix. The primary outcome was cardiorespiratory fitness measured at baseline and post-intervention.<br/>Results: The mean BMI for the sample was 33.17 ± 4.54 kg/m2, which put the participants in the 98.4th percentile. At baseline, the mean VO2max was 2737.02 ± 488.89 mL/min. The mean relative VO2max was 30.65 ± 3.87 mL/kg/min. VO2max values significantly increased from baseline to post-intervention (2737.022 ± 483.977 mL/min vs 2932.654 ± 96.062 mL/min, p<0.001). <br/>Conclusion: Culturally-grounded, family-focused lifestyle interventions are a promising approach for improving cardiorespiratory fitness in high-risk youth at risk for diabetes.
ContributorsEstrada, Lourdes Alexa (Author) / Shaibi, Gabriel (Thesis director) / Peña, Armando (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Immunosignaturing is a new immunodiagnostic technology that uses random-sequence peptide microarrays to profile the humoral immune response. Though the peptides have little sequence homology to any known protein, binding of serum antibodies may be detected, and the pattern correlated to disease states. The aim of my dissertation is to analyze the factors affecting the binding patterns using monoclonal antibodies and determine how much information may be extracted from the sequences. Specifically, I examined the effects of antibody concentration, competition, peptide density, and antibody valence. Peptide binding could be detected at the low concentrations relevant to immunosignaturing, and a monoclonal's signature could even be detected in the presences of 100 fold excess naive IgG. I also found that peptide density was important, but this effect was not due to bivalent binding. Next, I examined in more detail how a polyreactive antibody binds to the random sequence peptides compared to protein sequence derived peptides, and found that it bound to many peptides from both sets, but with low apparent affinity. An in depth look at how the peptide physicochemical properties and sequence complexity revealed that there were some correlations with properties, but they were generally small and varied greatly between antibodies. However, on a limited diversity but larger peptide library, I found that sequence complexity was important for antibody binding. The redundancy on that library did enable the identification of specific sub-sequences recognized by an antibody. The current immunosignaturing platform has little repetition of sub-sequences, so I evaluated several methods to infer antibody epitopes. I found two methods that had modest prediction accuracy, and I developed a software application called GuiTope to facilitate the epitope prediction analysis. None of the methods had sufficient accuracy to identify an unknown antigen from a database. In conclusion, the characteristics of the immunosignaturing platform observed through monoclonal antibody experiments demonstrate its promise as a new diagnostic technology. However, a major limitation is the difficulty in connecting the signature back to the original antigen, though larger peptide libraries could facilitate these predictions.
ContributorsHalperin, Rebecca (Author) / Johnston, Stephen A. (Thesis advisor) / Bordner, Andrew (Committee member) / Taylor, Thomas (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
Obesity in Hispanic youth has reached alarmingly high levels, increasing the risk of type 2 diabetes, hyperlipidemia, hypertension, and cardiovascular disease. In Mexican American children ages 6-11 years, 41.7% are overweight and obese, 24.7% are obese and 19.6% have a Body Mass Index (BMI) greater than the 97th percentile. While personal, behavioral, and environmental factors contribute to these high rates, emerging literature suggests acculturation, self-efficacy and social support are key influences. The one-group, pre- and post-test, quasi-experimental design used a community-based participatory research (CBPR) method to test the feasibility, acceptability, and preliminary efficacy of the 8-week intervention. Social Cognitive Theory (SCT) was used to guide the design. Measurements included an analysis of recruitment, retention, participant satisfaction, observation of intervention sessions, paired t-tests, effect sizes, and bivariate correlations between study variables (acculturation, nutrition and physical activity [PA] knowledge, attitude and behaviors, perceived confidence and social support) and outcome variables (BMI z-score, waist circumference and BP percentile) Findings showed the SSLN program was feasible and acceptable. Participants (n = 16) reported that the curriculum was fun and they learned about nutrition and PA. The retention rate was 94%. The preliminary effects on adolescent nutrition and PA behaviors showed mixed results with small-to-medium effect sizes for nutrition knowledge and attitude, PA and sedentary behavior. Correlation analysis among acculturation and study variables was not significant. Positive associations were found between perceived confidence in eating and nutrition attitude (r = .61, p < .05) and nutrition behavior (r = .62, p < .05), perceived confidence in exercise and nutrition behavior (r = .66, p < .05), social support from family for exercise and PA behavior (r = .67, p < .01) and social support from friends for exercise and PA behavior (r = .56, p < .05). These findings suggest a culturally specific healthy eating and activity program for adolescents was feasible and acceptable and warrants further investigation, since it may fill a gap in existing obesity programs designed for Hispanic youth. The positive correlations suggest further testing of the theoretical model.
ContributorsStevens, Carol (Author) / Gance-Cleveland, Bonnie (Thesis advisor) / Komnenich, Pauline (Committee member) / Shaibi, Gabriel (Committee member) / Arcoleo, Kimberly (Committee member) / Arizona State University (Publisher)
Created2011
Description
African Swine Fever (ASF), endemic in many African countries, is now spreading to other continents. Though ASF is capable of incurring serious economic losses in affected countries, no vaccine exists to provide immunity to animals. Disease control relies largely on rapid diagnosis and the implementation of movement restrictions and strict eradication programs. Developing a scalable, accurate and low cost diagnostic for ASF will be of great help for the current situation. CIM's 10K random peptide microarray is a new high-throughput platform that allows systematic investigations of immune responses associated with disease and shows promise as a diagnostic tool. In this study, this new technology was applied to characterize the immune responses of ASF virus (ASFV) infections and immunizations. Six sets of sera from ASFV antigen immunized pigs, 6 sera from infected pigs and 20 sera samples from unexposed pigs were tested and analyzed statistically. Results show that both ASFV antigen immunized pigs and ASFV viral infected pigs can be distinguished from unexposed pigs. Since it appears that immune responses to other viral infections are also distinguishable on this platform, it holds the potential of being useful in developing a new ASF diagnostic. The ability of this platform to identify specific ASFV antibody epitopes was also explored. A subtle motif was found to be shared among a set of peptides displaying the highest reactivity for an antigen specific antibody. However, this motif does not seem to match with any antibody epitopes predicted by a linear antibody epitope prediction.
ContributorsXiao, Liang (Author) / Sykes, Kathryn (Thesis advisor) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D. Recent evidence suggests high-intensity interval training (HIT) may yield similar or superior benefits in a shorter amount of time compared to traditional continuous exercise training. The purpose of this study was to compare the effects of HIT to continuous (CONT) exercise training for the improvement of endothelial function, glucose control, and visceral adipose tissue. Seventeen obese men (N=9) and women (N=8) were randomized to eight weeks of either HIT (N=9, age=34 years, BMI=37.6 kg/m2) or CONT (N=8, age=34 years, BMI=34.6 kg/m2) exercise 3 days/week for 8 weeks. Endothelial function was assessed via flow-mediated dilation (FMD), glucose control was assessed via continuous glucose monitoring (CGM), and visceral adipose tissue and body composition was measured with an iDXA. Incremental exercise testing was performed at baseline, 4 weeks, and 8 weeks. There were no changes in weight, fat mass, or visceral adipose tissue measured by the iDXA, but there was a significant reduction in body fat that did not differ by group (46±6.3 to 45.4±6.6%, P=0.025). HIT led to a significantly greater improvement in FMD compared to CONT exercise (HIT: 5.1 to 9.0%; CONT: 5.0 to 2.6%, P=0.006). Average 24-hour glucose was not improved over the whole group and there were no group x time interactions for CGM data (HIT: 103.9 to 98.2 mg/dl; CONT: 99.9 to 100.2 mg/dl, P>0.05). When statistical analysis included only the subjects who started with an average glucose at baseline > 100 mg/dl, there was a significant improvement in glucose control overall, but no group x time interaction (107.8 to 94.2 mg/dl, P=0.027). Eight weeks of HIT led to superior improvements in endothelial function and similar improvements in glucose control in obese subjects at risk for T2D and CVD. HIT was shown to have comparable or superior health benefits in this obese sample with a 36% lower total exercise time commitment.
ContributorsSawyer, Brandon J (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Lee, Chong (Committee member) / Swan, Pamela (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2013
Description
Purpose: The purpose of this study was to examine the acute effects of two novel intermittent exercise prescriptions on glucose regulation and ambulatory blood pressure. Methods: Ten subjects (5 men and 5 women, ages 31.5 ± 5.42 yr, height 170.38 ± 9.69 cm and weight 88.59 ± 18.91 kg) participated in this four-treatment crossover trial. All subjects participated in four trials, each taking place over three days. On the evening of the first day, subjects were fitted with a continuous glucose monitor (CGM). On the second day, subjects were fitted with an ambulatory blood pressure monitor (ABP) and underwent one of the following four conditions in a randomized order: 1) 30-min: 30 minutes of continuous exercise at 60 - 70% VO2peak; 2) Mod 2-min: twenty-one 2-min bouts of walking at 3 mph performed once every 20 minutes; 3) HI 2-min: eight 2-min bouts of walking at maximal incline performed once every hour; 4) Control: a no exercise control condition. On the morning of the third day, the CGM and ABP devices were removed. All meals were standardized during the study visits. Linear mixed models were used to compare mean differences in glucose and blood pressure regulation between the four trials. Results: Glucose concentrations were significantly lower following the 30-min (91.1 ± 14.9 mg/dl), Mod 2-min (93.7 ± 19.8 mg/dl) and HI 2-min (96.1 ± 16.4 mg/dl) trials as compared to the Control (101.1 ± 20 mg/dl) (P < 0.001 for all three comparisons). The 30-min trial was superior to the Mod 2-min, which was superior to the HI 2-min trial in lowering blood glucose levels (P < 0.001 and P = 0.003 respectively). Only the 30-min trial was effective in lowering systolic ABP (124 ± 12 mmHg) as compared to the Control trial (127 ± 14 mmHg; P < 0.001) for up to 11 hours post exercise. Conclusion: Performing frequent short (i.e., 2 minutes) bouts of moderate or high intensity exercise may be a viable alternative to traditional continuous exercise in improving glucose regulation. However, 2-min bouts of exercise are not effective in reducing ambulatory blood pressure in healthy adults.
ContributorsBhammar, Dharini Mukeshkumar (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Buman, Matthew (Committee member) / Swan, Pamela (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2013
Description
Background: Evidence about the purported hypoglycemic and hypolipidemic effects of nopales (prickly pear cactus pads) is limited. Objective: To evaluate the efficacy of nopales for improving cardiometabolic risk factors and oxidative stress, compared to control, in adults with hypercholesterolemia. Design: In a randomized crossover trial, participants were assigned to a 2-wk intervention with 2 cups/day of nopales or cucumbers (control), with a 2 to 3-wk washout period. The study included 16 adults (5 male; 46±14 y; BMI = 31.4±5.7 kg/m2) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-c] = 137±21 mg/dL), but otherwise healthy. Main outcomes measured included: dietary intake (energy, macronutrients and micronutrients), cardiometabolic risk markers (total cholesterol, LDL-c, high density lipoprotein cholesterol [HDL-c], triglycerides, cholesterol distribution in LDL and HDL subfractions, glucose, insulin, homeostasis model assessment, and C-reactive protein), and oxidative stress markers (vitamin C, total antioxidant capacity, oxidized LDL, and LDL susceptibility to oxidation). Effects of treatment, time, or interactions were assessed using repeated measures ANOVA. Results: There was no significant treatment-by-time effect for any dietary composition data, lipid profile, cardiometabolic outcomes, or oxidative stress markers. A significant time effect was observed for energy, which was decreased in both treatments (cucumber, -8.3%; nopales, -10.1%; pTime=0.026) mostly due to lower mono and polyunsaturated fatty acids intake (pTime=0.023 and pTime=0.003, respectively). Both treatments significantly increased triglyceride concentrations (cucumber, 14.8%; nopales, 15.2%; pTime=0.020). Despite the lack of significant treatment-by-time effects, great individual response variability was observed for all outcomes. After the cucumber and nopales phases, a decrease in LDL-c was observed in 44% and 63% of the participants respectively. On average LDL-c was decreased by 2.0 mg/dL (-1.4%) after the cucumber phase and 3.9 mg/dL (-2.9%) after the nopales phase (pTime=0.176). Pro-atherogenic changes in HDL subfractions were observed in both interventions over time, by decreasing the proportion of HDL-c in large HDL (cucumber, -5.1%; nopales, -5.9%; pTime=0.021) and increasing the proportion in small HDL (cucumber, 4.1%; nopales, 7.9%; pTime=0.002). Conclusions: These data do not support the purported benefits of nopales at doses of 2 cups/day for 2-wk on markers of lipoprotein profile, cardiometabolic risk, and oxidative stress in hypercholesterolemic adults.
ContributorsPereira Pignotti, Giselle Adriana (Author) / Vega-Lopez, Sonia (Thesis advisor) / Gaesser, Glenn (Committee member) / Keller, Colleen (Committee member) / Shaibi, Gabriel (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Surgery as a profession requires significant training to improve both clinical decision making and psychomotor proficiency. In the medical knowledge domain, tools have been developed, validated, and accepted for evaluation of surgeons' competencies. However, assessment of the psychomotor skills still relies on the Halstedian model of apprenticeship, wherein surgeons are observed during residency for judgment of their skills. Although the value of this method of skills assessment cannot be ignored, novel methodologies of objective skills assessment need to be designed, developed, and evaluated that augment the traditional approach. Several sensor-based systems have been developed to measure a user's skill quantitatively, but use of sensors could interfere with skill execution and thus limit the potential for evaluating real-life surgery. However, having a method to judge skills automatically in real-life conditions should be the ultimate goal, since only with such features that a system would be widely adopted. This research proposes a novel video-based approach for observing surgeons' hand and surgical tool movements in minimally invasive surgical training exercises as well as during laparoscopic surgery. Because our system does not require surgeons to wear special sensors, it has the distinct advantage over alternatives of offering skills assessment in both learning and real-life environments. The system automatically detects major skill-measuring features from surgical task videos using a computing system composed of a series of computer vision algorithms and provides on-screen real-time performance feedback for more efficient skill learning. Finally, the machine-learning approach is used to develop an observer-independent composite scoring model through objective and quantitative measurement of surgical skills. To increase effectiveness and usability of the developed system, it is integrated with a cloud-based tool, which automatically assesses surgical videos upload to the cloud.
ContributorsIslam, Gazi (Author) / Li, Baoxin (Thesis advisor) / Liang, Jianming (Thesis advisor) / Dinu, Valentin (Committee member) / Greenes, Robert (Committee member) / Smith, Marshall (Committee member) / Kahol, Kanav (Committee member) / Patel, Vimla L. (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems biology level, I provide new targets to explore for the research community. Furthermore I present a new online web resource that unifies various bioinformatics databases to enable discovery of relevant features in 3D protein structures.
ContributorsMielke, Clinton (Author) / Mandarino, Lawrence (Committee member) / LaBaer, Joshua (Committee member) / Magee, D. Mitchell (Committee member) / Dinu, Valentin (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013