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Item Antenna Design and SAR Analysis on Human Head Phantom Simulation for Future Clinical Applications(Scientific Research Publishing, 2017-09) Perez, Felipe Pablo; Bandeira, Joseph Paul; Morisaki, Jorge J.; Krishna Peddinti, Seshasai Vamsi; Salama, Paul; Rizkalla, James; Rizkalla, Maher E.; Medicine, School of MedicineBackground The rapid development of a variety of devices that emit Radiofrequency Electromagnetic fields (RF-EMF) has sparked growing interest in their interaction with biological systems and the beneficial effects on human health. As a result, investigations have been driven by the potential for therapeutic applications, as well as concern for any possible negative health implications of these EM energies [-]. Recent results have indicated specific tuning of experimental and clinical RF exposure may lead to their clinical application toward beneficial health outcomes []. Method In the current study, a mathematical and computer simulation model to analyze a specific RF-EMF exposure on a human head model was developed. Impetus for this research was derived from results of our previous experiments which revealed that Repeated Electromagnetic Field Stimulation (REMFS) decreased the toxic levels of beta amyloid (Aβ) in neuronal cells, thereby suggesting a new potential therapeutic strategy for the treatment of Alzheimer's disease (AD). Throughout development of the proposed device, experimental variables such as the EM frequency range, specific absorption rate (SAR), penetration depth, and innate properties of different tissues have been carefully considered. Results RF-EMF exposure to the human head phantom was performed utilizing a Yagi-Uda antenna type possessing high gain (in the order of 10 dbs) at a frequency of 64 MHz and SAR of 0.6 W/Kg. In order to maximize the EM power transmission in one direction, directors were placed in front of the driven element and reflectors were placed behind the driven element. So as to strategically direct the EM field into the center of the brain tissue, while providing field linearity, our analysis considered the field distribution for one versus four antennas. Within the provided dimensions of a typical human brain, results of the Bioheat equation within COMSOL Multiphysics version 5.2a software demonstrated less than a 1 m˚K increase from the absorbed EM power.Item Structure-Guided Optimization of Replication Protein A (RPA)–DNA Interaction Inhibitors(American Chemical Society, 2020-01-02) Gavande, Navnath S.; VanderVere-Carozza, Pamela S.; Pawelczak, Katherine S.; Vernon, Tyler L.; Jordan, Matthew R.; Turchi, John J.; Medicine, School of MedicineReplication protein A (RPA) is the major human single stranded DNA (ssDNA)-binding protein, playing essential roles in DNA replication, repair, recombination, and DNA-damage response (DDR). Inhibition of RPA-DNA interactions represents a therapeutic strategy for cancer drug discovery and has great potential to provide single agent anticancer activity and to synergize with both common DNA damaging chemotherapeutics and newer targeted anticancer agents. In this letter, a new series of analogues based on our previously reported TDRL-551 (4) compound were designed to improve potency and physicochemical properties. Molecular docking studies guided molecular insights, and further SAR exploration led to the identification of a series of novel compounds with low micromolar RPA inhibitory activity, increased solubility, and excellent cellular up-take. Among a series of analogues, compounds 43, 44, 45, and 46 hold promise for further development of novel anticancer agents.