A. James Clark School of Engineering
Permanent URI for this communityhttp://hdl.handle.net/1903/1654
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
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Item Self-assembly of immune signals to program innate immunity through rational adjuvant design(Wiley, 2022-11-14) Bookstaver, Michelle L.; Zeng, Qin; Oakes, Robert S.; Kapnick, Senta M.; Saxena, Vikas; Edwards, Camilla; Venkataraman, Nishedhya; Black, Sheneil K.; Zeng, Xiangbin; Froimchuk, Eugene; Gebhardt, Thomas; Bromberg, Jonathan S.; Jewell, Christopher M.Recent clinical studies show activating multiple innate immune pathways drives robust responses in infection and cancer. Biomaterials offer useful features to deliver multiple cargos, but add translational complexity and intrinsic immune signatures that complicate rational design. Here a modular adjuvant platform is created using self-assembly to build nanostructured capsules comprised entirely of antigens and multiple classes of toll-like receptor agonists (TLRas). These assemblies sequester TLR to endolysosomes, allowing programmable control over the relative signaling levels transduced through these receptors. Strikingly, this combinatorial control of innate signaling can generate divergent antigen-specific responses against a particular antigen. These assemblies drive reorganization of lymph node stroma to a pro-immune microenvironment, expanding antigen-specific T cells. Excitingly, assemblies built from antigen and multiple TLRas enhance T cell function and antitumor efficacy compared to ad-mixed formulations or capsules with a single TLRa. Finally, capsules built from a clinically relevant human melanoma antigen and up to three TLRa classes enable simultaneous control of signal transduction across each pathway. This creates a facile adjuvant design platform to tailor signaling for vaccines and immunotherapies without using carrier components. The modular nature supports precision juxtaposition of antigen with agonists relevant for several innate receptor families, such as toll, STING, NOD, and RIG.Item CONTRIBUTIONS TO RESOLVING ISSUES IMPEDING THE OPERATION OF HIGH POWER MICROWAVE AND SUBMILLIMETER DEVICES(2014) Kashyn, Dmytro; Granatstein, Victor L.; Nusinovich, Gregory S.; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This thesis reports an experimental study aimed at extending high power, high efficiency gyrotron operation to submillimeter wavelengths. A series of experiments carried out both at the University of Maryland and the Institute of Applied Physics of the Russian Academy of Science, succeeded in demonstrating output power at 670 GHz of 180 kilowatts with 20% efficiency (gyrotron voltage was 57 kV and beam current was 16 amperes). The maximum output power achieved in the experiments was 210kW at somewhat higher voltage and current (viz. 58kV and 22A). The achieved output power and efficiency are twice as large as achieved in previous experiments in this frequency range with pulse duration in the range of tens of microseconds. These performance parameters are relevant to a previously proposed application of detecting concealed radioactive materials by air breakdown in a focused beam of sub-millimeter radiation. The 670 GHz gyrotron combined features of two lines of previous experiments: (a) to operate at the required frequency, pulsed solenoids producing 28T magnetic were employed and (b) to obtain high efficiency a very high order mode was used in the gyrotron cavity, as in the experiments with gyrotrons for plasma heating. Evidence of multimode beating was observed in submillimeter output envelope. The excitation of spurious modes, especially during the rise of the gyrotron voltage pulse, was analyzed and the method of avoiding this was proposed which also allows to reduce collector loading in gyrotrons operating in modulated regimes. The present study also includes theoretical analysis of the processes that deepens the understanding of microwave breakdown (arcing) in high power microwave devices. The effect of the dust particles microprotrusions on the device operation was analyzed. These microprotrusions were observed and their negative effects were remedied by careful polishing and machining of the resonator surface. Finally, the generated 670 GHz radiation was focused and used to study breakdown both in argon and in the air. This breakdown volume was theoretically analyzed and the effects of the atmospheric turbulence on the air breakdown were included.