Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-induced peripheral neuropathy. Results show that local or systemic administration of 4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl}morpholine (PrNMI) dose-dependently suppressed CIPN mechanical and cold allodynia. Orally administered PrNMI also dose-dependently suppressed CIPN allodynia symptoms in both male and female rats without any CNS side effects. Co-administration with selective cannabinoid receptor subtype blockers revealed that PrNMI's anti-allodynic effects are mediated by CB1 receptor (CB1R) activation. Expression of CB2Rs was reduced in dorsal root ganglia from CIPN rats, whereas expression of CB1Rs and various endocannabinoid synthesizing and metabolizing enzymes was unaffected. Daily PrNMI treatment of CIPN rats for two weeks showed a lack of appreciable tolerance to PrNMI's anti-allodynic effects. In an operant task which reflects cerebral processing of pain, PrNMI also dose-dependently suppressed CIPN pain behaviors. Our results demonstrate that PRCBs exemplified by PrNMI may represent a viable option for the treatment of CIPN pain symptoms

Design of an actively cooled grid system to improve efficiency in inertial electrostatic confinement fusion reactors

Traditional inertial electrostatic confinement (IEC) fusion reactor designs utilize an ion accelerating grid fabricated out of a refractory metal capable of operating at high temperatures to radiate off heat imparted by ion-grid collisions. Unfortunately, the high gird temperature allows for a substantial thermionic electron emission current, requiring a high power draw and significantly reducing reactor efficiency. Further, electrons emitted from the grid are accelerated into the reactor shell where they generate a significant amount of bremsstrahlung x-rays requiring additional shielding and increasing system size and weight. Presented is a novel modification to the traditional implementation of IEC fusion reactor, designed to improve operating efficiency by reducing electron emission from the grid. A liquid cooled grid design is utilized to reduce thermionic electron emission, allowing for higher plasma densities, and greater input power while improving system efficiency and reducing x-ray output. The resulting low grid temperatures substantially reduce thermionic electron emission and greatly improve reactor efficiency by reducing current draw from the central grid. The reduction of thermionic electron emission will eliminate the majority of bremsstrahlung x-ray generation thereby reducing shielding requirements. By measuring the heat deposited into the coolant, the grid cooling system may also be used as a diagnostic tool to study the physics involved in IEC reactors. In this manner, grid transparency may be directly measured as a function of ion bombardment heating. By modifying the confinement scheme of the reactor and subsequently evaluating the energy flux to the grid through ion collisions, greater energy and particle confinement times may be obtained.Committee Member/Second Reader: Dwayne Blaylock; Faculty Mentor: Chandra Rama

DESIGN OF A RESONANT SOFT SWITCHING POWER SUPPLY FOR STABILIZED DC IMPULSE DELIVERY

This thesis addresses the issues involved in the design and construction of a multiphase resonant switching power supply for delivery of a high voltage, high current stabilized DC impulse. Such a power supply may be used in place a pulse forming network (PFN) to drive a high power klystron amplifier, which typically requires voltages near -100kV at 10s of amps of current. Unlike an LC PFN, a switchmode power supply (SMPS) allows greater control over pulse duration while still allowing generation of longer duration pulses on the order of 10ms with constant output voltage by use of feedback regulation. Specifically, the thesis documents the results from the design of a loosely coupled boost transformer with a parallel LC resonator on the secondary, a microcontroller based control system for feedback stabilization and techniques of harmonic mitigation to reduce switching noise on the output waveform

Precipitate Size in GRCop-84 Gas Atomized Powder and Laser Powder Bed Fusion Additively Manufactured Material

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