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- All Subjects: Environmental engineering
- All Subjects: Nanoparticles
- Member of: Theses and Dissertations
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Perpetual Pavements, if properly designed and rehabilitated, it can last longer than 50 years without major structural rehabilitation. Fatigue endurance limit is a key parameter for designing perpetual pavements to mitigate bottom-up fatigue cracking. The endurance limit has not been implemented in the Mechanistic Empirical Pavement Design Guide software, currently known as DARWin-ME. This study was conducted as part of the National Cooperative Highway Research Program (NCHRP) Project 9-44A to develop a framework and mathematical methodology to determine the fatigue endurance limit using the uniaxial fatigue test. In this procedure, the endurance limit is defined as the allowable tensile strains at which a balance takes place between the fatigue damage during loading, and the healing during the rest periods between loading pulses. The viscoelastic continuum damage model was used to isolate time dependent damage and healing in hot mix asphalt from that due to fatigue. This study also included the development of a uniaxial fatigue test method and the associated data acquisition computer programs to conduct the test with and without rest period. Five factors that affect the fatigue and healing behavior of asphalt mixtures were evaluated: asphalt content, air voids, temperature, rest period and tensile strain. Based on the test results, two Pseudo Stiffness Ratio (PSR) regression models were developed. In the first model, the PSR was a function of the five factors and the number of loading cycles. In the second model, air voids, asphalt content, and temperature were replaced by the initial stiffness of the mix. In both models, the endurance limit was defined when PSR is equal to 1.0 (net damage is equal to zero). The results of the first model were compared to the results of a stiffness ratio model developed based on a parallel study using beam fatigue test (part of the same NCHRP 9-44A). The endurance limit values determined from uniaxial and beam fatigue tests showed very good correlation. A methodology was described on how to incorporate the second PSR model into fatigue analysis and damage using the DARWin-ME software. This would provide an effective and efficient methodology to design perpetual flexible pavements.
Scaled Formulations of Succinate based Polymeric particles for Eventual Testing in Clinical Settings
With an estimated 19.3 million cases and nearly 10 million deaths from cancer in a year worldwide, immunotherapies, which stimulate the immune system so that it can attack and kill cancer cells, are of interest. Tumors are produced from the uncontrolled and rapid proliferation of cells in the body. Cancer cells rely heavily on glutamine for proliferation due to its contribution of nitrogen for nucleotides and amino acids. Glutamine enters the tricarboxylic acid (TCA) cycle as α-ketoglutarate via glutaminolysis, in which glutamine is converted into glutamate by the enzyme glutaminase (GLS). Cancer cell proliferation may be limited by using glutaminase inhibitor CB-839. However, immune cells also rely on these metabolic pathways. Thus, a method for restarting the metabolic pathways in the presence of inhibitors is attractive. Succinate, a key metabolite in the TCA cycle, has been shown to stimulate the immune system despite the presence of metabolic inhibitors, such as CB-839. A delivery method of succinate is through microparticles (MPs) or nanoparticles (NPs) which may be coated in polyethylene glycol (PEG) for improved hydrophilicity. Polyethylene glycol succinate (PEGS) MPs were generated and tested in vivo and were shown to reduce tumor growth and prolong mouse survival. With the success in stimulating the immune system with MPs, NPs were investigated for an improved immune response due to their smaller size. These PES NPs were generated in this study. For clinical settings, it is necessary to scale-up the production of particles. Two methods of scale-up were proposed: (1) a combination of multiple small batches into a mixed batch, and (2) a singular, big batch. Size and release properties were compared to a small batch of PES NPs, and it was concluded that the big batch more closely resembled the small batch compared to the mixed batch. Thus, it was concluded that batch-to-batch variability plays a larger role than volume changes when scaling-up. In clinical settings, it is recommended to produce the particles in a big batch rather than a mixed batch.