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1. Lee, Youri. EFFECTS OF VACCINE PLATFORMS AND ADJUVANTS ON PROTECTIVE EFFICACY AGAINST HUMAN RESPIRATORY SYNCYTIAL VIRUS.

Degree: PhD, Biology, 2018, Georgia State University

Human respiratory syncytial virus (RSV) is responsible for several million hospitalizations and 199,000 deaths in young children worldwide. In 1960s clinical trials, children who were vaccinated with alum-adjuvanted, formalin-inactivated whole RSV (FI-RSV) developed vaccine-enhanced respiratory disease after RSV infection, resulting in tragic vaccine failure. There is no licensed RSV vaccine. The goals of my PhD thesis studies were to better understand pulmonary inflammation in vaccinated animals and to develop safe and effective RSV vaccines. In the first project, I investigated the vaccine efficacy of RSV fusion (F) proteins in a soluble form or on virus-like particle (F-VLP). F VLP preferentially elicited T helper type 1 (Th1) immune responses whereas alum-adjuvanted F protein induced Th2 responses. Despite lung viral clearance, F protein immune mice displayed weight loss and lung histopathology and high mucus production and eosinophils. In contrast, prime or prime-boost of F VLP prevented eosinophils’ infiltration and vaccine-associated disease. An intrinsic property of F VLP to prime Th1 type immune responses appears to prevent RSV vaccine-enhanced disease after RSV challenge. In the second project, I investigated the adjuvant effects of monophosphoryl lipid A (MPL, a TLR4 ligand) and oligodeoxynucleotide CpG (CpG, a TLR9 ligand) on vaccine-enhanced respiratory disease after F protein prime vaccination and RSV challenge in infant and adult mice. Combination CpG+MPL adjuvant in RSV F protein prime vaccination of infant and adult age mice promoted the induction of Th1 type immune responses, and lung viral clearance after challenge. Importantly, CpG+MPL adjuvant plus F protein priming of mice was effective in preventing inflammatory lung histopathology and Th2 cytokine-expressing CD4 T cell responses after RSV challenge. In the third project, I found that inactivated and detergent-split RSV vaccines exposed neutralizing epitopes at higher levels than inactivated whole virus. Split RSV vaccination of mice induced less lung histopathology compared to FI-RSV after RSV challenge. Split RSV vaccination of mice with CpG and MPL adjuvants was found to be most effective in increasing Th1 type IgG2a antibodies, neutralizing activity, and lung viral clearance as well as modulating immune responses to prevent pulmonary histopathology after RSV vaccination and challenge. Advisors/Committee Members: Sang-Moo Kang, Didier Merlin, Jian Dong Li.

Subjects/Keywords: Respiratory Syncytial Virus; Virus like particle; Fusion (F) protein; Detergent-split RSV vaccines; Vaccine enhanced-disease; T helper type 1 and 2 CD4 T cell response; Histopathology; Adjuvants

…12 1.2 RSV vaccine-enhanced respiratory disease and vaccine adjuvants ............. 13… …1.2.1 Formalin-inactivated whole RSV vaccine (FI-RSV) enhanced respiratory disease… …14 1.2.4 Split RSV vaccines… …VACCINE-ENHANCED PULMONARY HISTOPATHOLOGY AFTER A SINGLE DOSE VACCINATION WITH FUSION PROTEIN… …INACTIVATED SPLIT RESPIRATORY SYNCYTIAL VIRUS VACCINE IN MICE… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Lee, Y. (2018). EFFECTS OF VACCINE PLATFORMS AND ADJUVANTS ON PROTECTIVE EFFICACY AGAINST HUMAN RESPIRATORY SYNCYTIAL VIRUS. (Doctoral Dissertation). Georgia State University. Retrieved from https://scholarworks.gsu.edu/biology_diss/211

Chicago Manual of Style (16th Edition):

Lee, Youri. “EFFECTS OF VACCINE PLATFORMS AND ADJUVANTS ON PROTECTIVE EFFICACY AGAINST HUMAN RESPIRATORY SYNCYTIAL VIRUS.” 2018. Doctoral Dissertation, Georgia State University. Accessed October 25, 2020. https://scholarworks.gsu.edu/biology_diss/211.

MLA Handbook (7th Edition):

Lee, Youri. “EFFECTS OF VACCINE PLATFORMS AND ADJUVANTS ON PROTECTIVE EFFICACY AGAINST HUMAN RESPIRATORY SYNCYTIAL VIRUS.” 2018. Web. 25 Oct 2020.

Vancouver:

Lee Y. EFFECTS OF VACCINE PLATFORMS AND ADJUVANTS ON PROTECTIVE EFFICACY AGAINST HUMAN RESPIRATORY SYNCYTIAL VIRUS. [Internet] [Doctoral dissertation]. Georgia State University; 2018. [cited 2020 Oct 25]. Available from: https://scholarworks.gsu.edu/biology_diss/211.

Council of Science Editors:

Lee Y. EFFECTS OF VACCINE PLATFORMS AND ADJUVANTS ON PROTECTIVE EFFICACY AGAINST HUMAN RESPIRATORY SYNCYTIAL VIRUS. [Doctoral Dissertation]. Georgia State University; 2018. Available from: https://scholarworks.gsu.edu/biology_diss/211


Brigham Young University

2. Hakala, Tim. Settling-Time Improvements in Positioning Machines Subject to Nonlinear Friction Using Adaptive Impulse Control.

Degree: PhD, 2006, Brigham Young University

A new method of adaptive impulse control is developed to precisely and quickly control the position of machine components subject to friction. Friction dominates the forces affecting fine positioning dynamics. Friction can depend on payload, velocity, step size, path, initial position, temperature, and other variables. Control problems such as steady-state error and limit cycles often arise when applying conventional control techniques to the position control problem. Studies in the last few decades have shown that impulsive control can produce repeatable displacements as small as ten nanometers without limit cycles or steady-state error in machines subject to dry sliding friction. These displacements are achieved through the application of short duration, high intensity pulses. The relationship between pulse duration and displacement is seldom a simple function. The most dependable practical methods for control are self-tuning; they learn from online experience by adapting an internal control parameter until precise position control is achieved. To date, the best known adaptive pulse control methods adapt a single control parameter. While effective, the single parameter methods suffer from sub-optimal settling times and poor parameter convergence. To improve performance while maintaining the capacity for ultimate precision, a new control method referred to as Adaptive Impulse Control (AIC) has been developed. To better fit the nonlinear relationship between pulses and displacements, AIC adaptively tunes a set of parameters. Each parameter affects a different range of displacements. Online updates depend on the residual control error following each pulse, an estimate of pulse sensitivity, and a learning gain. After an update is calculated, it is distributed among the parameters that were used to calculate the most recent pulse. As the stored relationship converges to the actual relationship of the machine, pulses become more accurate and fewer pulses are needed to reach each desired destination. When fewer pulses are needed, settling time improves and efficiency increases. AIC is experimentally compared to conventional PID control and other adaptive pulse control methods on a rotary system with a position measurement resolution of 16000 encoder counts per revolution of the load wheel. The friction in the test system is nonlinear and irregular with a position dependent break-away torque that varies by a factor of more than 1.8 to 1. AIC is shown to improve settling times by as much as a factor of two when compared to other adaptive pulse control methods while maintaining precise control tolerances.

Subjects/Keywords: control; position; adaptive; impulsive; settling-time; nonlinear friction; pulses; displacements; precise; tolerances; log-spaced; update; distributed; learning; Coulomb; Stribeck; Tomizuka; Yang; AIC; PID; MRAC; STR; RTAI; Linux; FreeBSD; kernel modules; microcontroller; convergence; practical; self-tuning; methods; techniques; limit-cycles; steady-state; error; zero; stable; stability; bound; envelope; partitioned; scheme; lookup-table; multi-point; adaptation; repeatable; mean; servo; motor; exponential; square-law; rise-time; real-time; log-log interpolation; pro-forma; curve-fit; sensitivity; compliance; variable; static; dynamic response; torque; acceleration; velocity; optical encoder; parameters; evolution; fixed-law; enhanced split; weighting; initialization; trajectory; layered processes; Mechanical Engineering

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Hakala, T. (2006). Settling-Time Improvements in Positioning Machines Subject to Nonlinear Friction Using Adaptive Impulse Control. (Doctoral Dissertation). Brigham Young University. Retrieved from https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=2060&context=etd

Chicago Manual of Style (16th Edition):

Hakala, Tim. “Settling-Time Improvements in Positioning Machines Subject to Nonlinear Friction Using Adaptive Impulse Control.” 2006. Doctoral Dissertation, Brigham Young University. Accessed October 25, 2020. https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=2060&context=etd.

MLA Handbook (7th Edition):

Hakala, Tim. “Settling-Time Improvements in Positioning Machines Subject to Nonlinear Friction Using Adaptive Impulse Control.” 2006. Web. 25 Oct 2020.

Vancouver:

Hakala T. Settling-Time Improvements in Positioning Machines Subject to Nonlinear Friction Using Adaptive Impulse Control. [Internet] [Doctoral dissertation]. Brigham Young University; 2006. [cited 2020 Oct 25]. Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=2060&context=etd.

Council of Science Editors:

Hakala T. Settling-Time Improvements in Positioning Machines Subject to Nonlinear Friction Using Adaptive Impulse Control. [Doctoral Dissertation]. Brigham Young University; 2006. Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=2060&context=etd

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