Inaug.--diss.--Kiel. / Lebensgang.

The effect of charge geometry on the structural response of right circular cylinders, subjected to internal blast loading, was investigated. Thin-walled, seamless 304 stainless steel cylinders were subjected to blast loads from partially confined bare cylindrical PE4 charges with different diameter and aspect ratios(charges length to charge diameter). The diameters of interest were: 25 mm (aspect ratios of 0.5 -3). 30 mm (aspect ratios of 0.5 -1.6). 35 mm (aspect ratios of 0.5 - 1.1). 40 mm (aspect ratios of 0.5 - 0.9). The effect of aspect ratio, for the constant diameter or constant mass cases, on the structural response of the cylinders (that is, diametric deflection, axial impulse, and axial shortening) is reported. Cylindrical charges with an aspect ratio of 1, were compared to spherical charges of equivalent mass. For charges with constant diameter with varying length: The diametric deflection increased with increasing aspect ratio. The axial shortening increased with increasing aspect ratio. The axial impulse increased with increasing aspect ratio. For charges with constant mass with varying diameter and length: The long charges (that is, charges with aspect ratios greater than 1) caused larger diametric deflections than their mass equivalent short (that is, charges with aspect ratios less than 1) charges. This is because the long charges had more side effective charge mass (that is, the mass of the charge that contributes directly to the diametric deflection of a cylinder) than the shorter charges. The short charges transferred more axial impulse to the ballistic pendulum, because they had more axial effective charge mass (that is, the mass of the charge that contributes directly to the axial impulse that is transferred to a ballistic pendulum) than their mass equivalent long charges. It was observed that a lighter charge can diametrically deflect a cylinder more effectively than a heavier charge, if its side effective charge mass is greater than that of the heavier charge. The structural responses of the cylinders obtained from cylindrical charge detonations were greater than those obtained from the mass equivalent spherical charge detonations. The deflections resulting from the cylindrical charges were also more localised compared to the spherical charges.

An attractive strategy to improve efficacy of current Influenza A Virus (IAV) vaccines is to promote protective CD4 T cell responses. Antiviral CD4 T cell responses are predominantly classified as strong IFN-gamma producing T helper type 1 (Th1) cells. Yet, the role of IFN-gamma in protection against IAV is still unclear, suggesting absolute Th1 polarization may be expendable for effective IAV immunity. Here we test this hypothesis using models that restrict the deficiency of known transcriptional regulators of Th1 immunity in only CD4 T cells, avoiding indirect impact on other immune cell responses. We find the 'master regulator' of Th1 cells, the T-box transcription factor T-bet (Tbx21), to be dispensable for CD4 T cell-mediated protection from lethal IAV but important for maximizing the magnitude of effector responses by regulating cell trafficking to the lung. While donor Tbx21-/- responses gain Th17 characteristics, they still produce substantial IFN-gamma, suggesting their Th1 attributes may still be required for protection. Interestingly, Tbx21-/- cells expressed more Eomesodermin (Eomes), a paralog of T-bet, but Eomes-/- cells retain WT-like responses suggesting minor roles for Eomes in presence of T-bet. In contrast, Tbx21-/-Eomes-/- cells, completely lose their Th1 identity but remarkably exhibit stronger inflammation-induced Th17 attributes than Tbx21-/- cells. Strikingly, we find in vitro Th17-primed Tbx21-/-Eomes-/- effectors lose their plasticity to become Th1 but instead strengthen their Th17-ness in IAV infected mice but still protect. Finally, we observed that protection of previously primed Tbx21-/- and Tbx21-/-Eomes-/- mice from a lethal unrelated IAV strain required T cell mediated immunity. Our observations thus demonstrate novel roles for Eomes in broadening the scope of protective mechanisms against IAV. Furthermore, we decisively demonstrate protective roles for prototypical non-plastic Th17 responses in primary and secondary responses, thus increasing the scope of target mechanisms relevant for CD4 T-cell based vaccination strategies against viral pathogens.

A synthesis is described for a number of 16,16-dimethyl analogs of the prostacyclin and related 6-keto prostaglandin types. Included are l6, l6-dimethyl-PGI2 sodium salt (XLIV), 6α-l6, l6-dimethyl-PGI1(XLV), 6β-l6, l6-dimethyl-PGI1 (XLVII), 6-keto-l6, l6-dimethyl-PGF1-α (XLIX), and 6-keto-l6, l6-dimethyl PGE1 (LV). Done, but not included, is the activity for these analogs in the blood platelet aggregation inhibition assay. This activity was consistently less than for the corresponding 16, 16-dihydro compounds.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.