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- Genre: Masters Thesis
- Language: English
Description
Infections caused by the Hepatitis C Virus (HCV) are very common worldwide, affecting up to 3% of the population. Chronic infection of HCV may develop into liver cirrhosis and liver cancer which is among the top five of the most common cancers. Therefore, vaccines against HCV are under intense study in order to prevent HCV from harming people's health. The envelope protein 2 (E2) of HCV is thought to be a promising vaccine candidate because it can directly bind to a human cell receptor and plays a role in viral entry. However, the E2 protein production in cells is inefficient due to its complicated matured structure. Folding of E2 in the endoplasmic reticulum (ER) is often error-prone, resulting in production of aggregates and misfolded proteins. These incorrect forms of E2 are not functional because they are not able to bind to human cells and stimulate antibody response to inhibit this binding. This study is aimed to overcome the difficulties of HCV E2 production in plant system. Protein folding in the ER requires great assistance from molecular chaperones. Thus, in this study, two molecular chaperones in the ER, calreticulin and calnexin, were transiently overexpressed in plant leaves in order to facilitate E2 folding and production. Both of them showed benefits in increasing the yield of E2 and improving the quality of E2. In addition, poorly folded E2 accumulated in the ER may cause stress in the ER and trigger transcriptional activation of ER molecular chaperones. Therefore, a transcription factor involved in this pathway, named bZIP60, was also overexpressed in plant leaves, aiming at up-regulating a major family of molecular chaperones called BiP to assist protein folding. However, our results showed that BiP mRNA levels were not up-regulated by bZIP60, but they increased in response to E2 expression. The Western blot analysis also showed that overexpression of bZIP60 had a small effect on promoting E2 folding. Overall, this study suggested that increasing the level of specific ER molecular chaperones was an effective way to promote HCV E2 protein production and maturation.
ContributorsHong, Fan (Author) / Mason, Hugh (Thesis advisor) / Gaxiola, Roberto (Committee member) / Chang, Yung (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2011
Description
The purpose of this pilot randomized control trial was to test the initial efficacy of a 10 week social cognitive theory (SCT)-based intervention to reduce workplace sitting time (ST). Participants were currently employed adults with predominantly sedentary occupations (n=24) working in the Greater Phoenix area in 2012-2013. Participants wore an activPAL (AP) inclinometer to assess postural allocation (i.e., sitting vs. standing) and Actigraph accelerometer (AG) to assess sedentary time for one week prior to beginning and immediately following the completion of the 10 week intervention. Self-reported measures of sedentary time were obtained via two validated questionnaires for overall (International Physical Activity Questionnaire [IPAQ]) and domain specific sedentary behaviors (Sedentary Behavior Questionnaire [SBQ]). SCT constructs were also measured pre and post via adapted physical activity questionnaires. Participants were randomly assigned to receive either (a) 10 weekly social cognitive-based e-newsletters focused on reducing workplace ST; or (b) similarly formatted 10 weekly e-newsletters focusing on health education. Baseline adjusted Analysis of Covariance statistical analyses were used to examine differences between groups in time spent sitting (AP) and sedentary (AG) during self-reported work hours from pre- to post- intervention. Both groups decreased ST and AG sedentary time; however, no significant differences were observed. SCT constructs also did not change significantly between pretest and post test in either group. These results indicate that individualized educational approaches to decreasing workplace sitting time may not be sufficient for observing long term change in behaviors. Future research should utilize a larger sample, measure main outcomes more frequently, and incorporate more environmental factors throughout the intervention.
ContributorsGordon, Amanda (Author) / Buman, Matthew (Thesis advisor) / Der Ananian, Cheryl (Committee member) / Swan, Pamela (Committee member) / Arizona State University (Publisher)
Created2013
Description
INTRODUCTION: Exercise performed at moderate to vigorous intensities has been shown to generate a post exercise hypotensive response. Whether this response is observed with very low exercise intensities is unclear. PURPOSE: To compare post physical activity ambulatory blood pressure (ABP) response to a single worksite walking day and a normal sedentary work day in pre-hypertensive adults. METHODS: Participants were 7 pre-hypertensive (127 + 8 mmHg / 83 + 8 mmHg) adults (3 male, 4 female, age = 42 + 12 yr) who participated in a randomized, cross-over study that included a control and a walking treatment. Only those who indicated regularly sitting at least 8 hours/day and no structured physical activity were enrolled. Treatment days were randomly assigned and were performed one week apart. Walking treatment consisted of periodically increasing walk time up to 2.5 hours over the course of an 8 hour work day on a walking workstation (Steelcase Company, Grand Rapids, MI). Walk speed was set at 1 mph. Participants wore an ambulatory blood pressure cuff (Oscar 2, SunTech Medical, Morrisville, NC) for 24-hours on both treatment days. Participants maintained normal daily activities on the control day. ABP data collected from 9:00 am until 10:00 pm of the same day were included in statistical analyses. Linear mixed models were used to detect differences in systolic (SBP) and diastolic blood pressure (DBP) by treatment condition over the whole day and post workday for the time periods between 4 -10 pm when participants were no longer at work. RESULTS:BP was significantly lower in response to the walking treatment compared to the control day (Mean SBP 126 +7 mmHg vs.124 +7 mmHg, p=.043; DBP 80 + 3 mmHg vs. 77 + 3 mmHg, p = 0.001 respectively). Post workday (4:00 to 10:00 pm) SBP decreased 3 mmHg (p=.017) and DBP decreased 4 mmHg (p<.001) following walking. CONCLUSION: Even low intensity exercise such as walking on a walking workstation is effective for significantly reducing acute BP when compared to a normal work day.
ContributorsZeigler, Zachary (Author) / Swan, Pamela (Thesis advisor) / Buman, Matthew (Committee member) / Gaesser, Glenn (Committee member) / Arizona State University (Publisher)
Created2013
Description
This study examines cognitive and motor function in typical older adults following acute exercise. Ten older adults (Mage = 65.1) completed a single session of assisted cycling (AC) (i.e., exercise accomplished through the use of a motor), voluntary cycling (VC) (self-selected cadence), and a no cycling (NC) control group. These sessions were randomized and separated by approximately one week. Both ACT and VC groups rode a stationary bicycle for 30-minutes each session. These sessions were separated by at least two days. Participants completed cognitive testing that assessed information processing and set shifting and motor testing including gross and fine motor performance at the beginning and at the end of each session. Consistent with our hypothesis concerning manual dexterity, the results showed that manual dexterity improved following the ACT session more than the VC or NC sessions. Improvements in set shifting were also found for the ACT session but not for the VC or NC sessions. The results are interpreted with respect to improvements in neurological function in older adults following acute cycling exercise. These improvements are balance, manual dexterity, and set shifting which have a positive effects on activities of daily living; such as, decrease risk of falls, improve movements like eating and handwriting, and increase ability to multitask.
ContributorsSemken, Keith (Author) / Ringenbach, Shannon (Thesis advisor) / Der Ananian, Cheryl (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2015
Description
The purpose of this study was to examine whether a workplace environmental intervention would improve work-related outcomes including productivity, presenteeism and cognition. The secondary aim was to investigate whether work-related outcomes are correlated to observed changes in sitting time, physical activity, and sleep. The study was introduced as part of a naturalistic environmental change in which university staff and faculty were relocated into a new building (n=23). The comparison group consisted of university staff within the same college with no imminent plans to re-locate during the intervention period; there were no environmental changes to this workplace (n =10). Participants wore two behavioral monitoring devices, activPAL and GeneActiv, for 7 consecutive days at two time points (immediately prior and 16 weeks following the office relocation). Measures of productivity and presenteeism were obtained via four validated questionnaires and participants underwent cognitive performance testing. Baseline adjusted analysis of covariance statistical analyses were used to examine differences between groups in work-related outcomes. A residual analysis in regression was conducted to determine the differences between observed changes in sitting time, physical activity and sleep, and work-related outcomes. The results showed that a reduction in work hour sitting time was not detrimental to work related outcomes. Decreased sitting was observed to potentially improve presenteeism and absenteeism. Additionally, physical activity was shown to modestly improve productivity, presenteeism and absenteeism. Poor sleep patterns were associated with work impairment and increased absenteeism.
ContributorsPark, Anna (Author) / Buman, Matthew (Thesis advisor) / Crespo, Noe (Committee member) / Chisum, Jack (Committee member) / Arizona State University (Publisher)
Created2014
Description
Flavivirus infections are emerging as significant threats to human health around the globe. Among them West Nile(WNV) and Dengue Virus (DV) are the most prevalent in causing human disease with WNV outbreaks occurring in all areas around the world and DV epidemics in more than 100 countries. WNV is a neurotropic virus capable of causing meningitis and encephalitis in humans. Currently, there are no therapeutic treatments or vaccines available. The expanding epidemic of WNV demands studies that develop efficacious therapeutics and vaccines and produce them rapidly and inexpensively. In response, our lab developed a plant-derived monoclonal antibody (mAb) (pHu-E16) against DIII (WNV antigen) that is able to neutralize and prevent mice from lethal infection. However, this drug has a short window of efficacy due to pHu-E16's inability to cross the Blood Brain Barrier (BBB) and enter the brain. Here, we constructed a bifunctional diabody, which couples the neutralizing activity of E16 and BBB penetrating activity of 8D3 mAb. We also produced a plant-derived E16 scFv-CH1-3 variant with equivalent specific binding as the full pHu-E16 mAb, but only requiring one gene construct for production. Furthermore, a WNV vaccine based on plant-derived DIII was developed showing proper folding and potentially protective immune response in mice. DV causes severe hemorrhaging diseases especially in people exposed to secondary DV infection from a heterotypic strain. It is hypothesized that sub-neutralizing cross-reactive antibodies from the first exposure aid the second infection in a process called antibody-dependent enhancement (ADE). ADE depends on the ability of mAb to bind Fc receptors (FcγRs), and has become a major roadblock for developing mAb-based therapeutics against DV. We aim to produce an anti-Dengue mAb (E60) in different glycoengineered plant lines that exhibit reduced/differential binding to FcγRs, therefore, reducing or eliminating ADE. We have successfully cloned the molecular constructs of E60, and expressed it in two plant lines with different glycosylation patterns. We demonstrated that both plant-derived E60 mAb glycoforms retained specific recognition and neutralization activity against DV. Overall, our study demonstrates great strives to develop efficacious therapeutics and potent vaccine candidates against Flaviviruses in plant expression systems.
ContributorsHurtado, Jonathan (Author) / Chen, Qiang (Thesis advisor) / Huffman, Holly A (Committee member) / Steele, Kelly P (Committee member) / Arizona State University (Publisher)
Created2014
Description
PURPOSE: This study aimed to identify whether increased Pokémon GO use resulted in increased daily steps, compared to days when an individual did not play. In addition, this study examined Pokémon GO as a use case for for the study of gamification, particularly whether traditionally identified game mechanics in gamification literature were successfully identified as elements players enjoy when playing Pokémon GO. METHODS: A mixed methods approach, with 17 participants taking part in a daily physical activity tracking study and 14 participants participating in semi-structured interviews. In the use study, participant steps were tracked for one week using the Apple Health Kit application, and participants were also asked to provide daily answers to a variety of questions assessing game preferences and daily use of Pokémon GO - using the application called PACO. The semi-structured interviews examined self-reported physical activity, and asked questions pertaining to use of Pokémon GO, such as motivation to play. RESULTS: Results assessed by t-test indicate a small but non-significant trend towards increased steps taken on days when a participant played vs. did not play (t(72)=- .56, p=.57, mplay=5,0153220, mnonplay=4,5152,959). This was confirmed with a mixed model test showing that when controlling for time and participant’s baseline level of steps, there was no significant effect on steps/day. Results from the daily surveys and also the semi-structured interviews, indicated that nostalgia (i.e., catching ones’ favorite childhood Pokémon), was a strong motivator for many to play the game, which was counter to theoretical expectations. In line with previous theory, results suggested that operant conditioning principles appeared to be at work in terms of fostering game play use. DISCUSSION: Results of this study, which was a primarily hypothesis generating endeavor, indicated possible trends toward increased steps on days when a person plays Pokémon G), but - with such a small sample, and short-term length of study - no firm conclusions can be drawn. Further, results indicate the particular value of nostalgia as a driver towards game play for Pokémon GO.
ContributorsBiel, Alexander M (Author) / Hekler, Eric (Thesis advisor) / Ainsworth, Barbara (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2016
Description
Pitchers are a vital part of the game of baseball and may account for up to two-thirds of the variance in win percentage. As they rise through the ranks of competition, physical skill set becomes less of a factor when compared to mentality. Pitchers are the “first line of defense” for keeping opponents from having an opportunity to score, as well as for holding onto their own team’s lead. Baseball pitchers not only face pressure to perform, but also experience stress from factors such as low pay, adjusting to higher levels of competition, and internal team competition for a limited number of spots. Athletes are often resistant to seeking aid from sport psychologists and often turn to unfavorable means to cope (i.e. drugs/alcohol, excessive exercise) with stress instead. Meditation has been shown to have beneficial effects on psychological factors associated with performance including emotional regulation, anxiety, confidence, focus, and mindfulness. Mobile applications have become a popular means of delivering mindfulness. The purpose of this study was to determine the feasibility and preliminary effectiveness of delivering a mindful meditation intervention using a mobile meditation application to improve psychological factors associated with performance (i.e. emotional regulation, anxiety (somatic and cognitive), confidence, focus, mindfulness) to minor league baseball pitchers. Pitchers in instructional league (Phase one) and off season (Phase two) were asked to meditate daily for 10-minutes each day for three weeks (Phase one) and eight weeks (Phase two). Pitchers were asked to complete self-report questionnaires and satisfaction surveys at pre- and post-intervention. Pitchers in phase one reported enjoying meditation, had improvements in self-confidence and sport confidence, and reported moderate decreases in cognitive anxiety and concentration disruption. Pitchers in phase two also enjoyed meditating (94.7%) and had improvements in self-confidence and moderate decreases in somatic anxiety. Low adherence due to timing (off-season) of intervention may have been a contributing factor to fewer outcomes. Future research should explore the feasibility and effectiveness of implementing meditation during the baseball season.
ContributorsDowling, Tiffany (Author) / Huberty, Jennifer (Thesis advisor) / Ransdell, Lynda (Committee member) / Buman, Matthew (Committee member) / Michel, Jesse (Committee member) / Arizona State University (Publisher)
Created2018
Description
Physical activity, sedentary behaviors, and sleep are often associated with cardiometabolic biomarkers commonly found in metabolic syndrome. These relationships are well studied, and yet there are still questions on how each activity may affect cardiometabolic biomarkers. The objective of this study was to examine data from the BeWell24 studies to evaluate the relationship between objectively measured physical activity and sedentary behaviors and cardiometabolic biomarkers in middle age adults, while also determining if sleep quality and duration mediates this relationship. A group of inactive participants (N = 29, age = 52.1 ± 8.1 years, 38% female) with increased risk for cardiometabolic disease were recruited to participate in BeWell24, a trial testing the impact of a lifestyle-based, multicomponent smartphone application targeting sleep, sedentary, and more active behaviors. During baseline, interim (4 weeks), and posttest visits (8 weeks), biomarker measurements were collected for weight (kg), waist circumference (cm), glucose (mg/dl), insulin (uU/ml), lipids (mg/dl), diastolic and systolic blood pressures (mm Hg), and C reactive protein (mg/L). Participants wore validated wrist and thigh sensors for one week intervals at each time point to measure sedentary behavior, physical activity, and sleep outcomes. Long bouts of sitting time (>30 min) significantly affected triglycerides (beta = .15 (±.07), p<.03); however, no significant mediation effects for sleep quality or duration were present. No other direct effects were observed between physical activity measurements and cardiometabolic biomarkers. The findings of this study suggest that reductions in long bouts of sitting time may support reductions in triglycerides, yet these effects were not mediated by sleep-related improvements.
ContributorsLanich, Boyd (Author) / Buman, Matthew (Thesis advisor) / Ainsworth, Barbara (Committee member) / Huberty, Jennifer (Committee member) / Arizona State University (Publisher)
Created2017
Description
Influenza is a deadly disease that poses a major threat to global health. The surface proteins of influenza A, the type most often associated with epidemics and pandemics, mutate at a very high frequency from season to season, reducing the efficacy of seasonal influenza vaccines. However, certain regions of these proteins are conserved between strains of influenza A, making them attractive targets for the development of a ‘universal’ influenza vaccine. One of these highly conserved regions is the ectodomain of the influenza matrix 2 protein (M2e). Studies have shown that M2e is poorly immunogenic on its own, but when properly adjuvanted it can be used to induce protective immune responses against many strains of influenza A. In this thesis, M2e was fused to a pair experimental ‘vaccine platforms’: an antibody fusion protein designed to assemble into a recombinant immune complex (RIC) and the hepatitis B core antigen (HBc) that can assemble into virus-like particles (VLP). The two antigens were produced in Nicotiana benthamiana plants through the use of geminiviral vectors and were subsequently evaluated in mouse trials. Mice were administered three doses of either the VLP alone or a 1:1 combination of the VLP and the RIC, and recipients of both the VLP and RIC exhibited endpoint anti-M2e antibody titers that were 2 to 3 times higher than mice that received the VLP alone. While IgG2a:IgG1 ratios, which can suggest the type of immune response (TH1 vs TH2) an antigen will elicit, were higher in mice vaccinated solely with the VLP, the higher overall titers are encouraging and demonstrate a degree of interaction between the RIC and VLP vaccines. Further research is necessary to determine the optimal balance of VLP and RIC to maximize IgG2a:IGg1 ratios as well as whether such interaction would be observed through the use of a variety of diverse antigens, though the results of other studies conducted in this lab suggests that this is indeed the case. The results of this study demonstrate not only the successful development of a promising new universal influenza A vaccine, but also that co-delivering different types of recombinant vaccines could reduce the total number of vaccine doses needed to achieve a protective immune response.
ContributorsFavre, Brandon Chetan (Author) / Mason, Hugh S (Thesis advisor) / Mor, Tsafrir (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2019