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A theory of three-dimensional incompressible flow separation is presented in terms of the on-wall signatures of the flow. Some long-standing controversial issues are revisited and answers given, such as the inconsistency of the separation criteria based on the topological theory and “open separation,” and whether a separation line is an asymptote or envelope of neighboring skin-friction lines. General criteria for identifying an “open” or “closed” flow separation zone and separation line (including the initial point of the latter), steady and unsteady, are obtained, which apply to a generic smooth curved wall at any Reynolds numbers. The criteria are found to be most clearly given in terms of on-wall signatures of vorticity dynamics. These are then specified to steady boundary layer separation at large Reynolds numbers. A scale analysis under mild assumptions leads to a three-dimensional triple-deck structure near a generic boundary layer separation line. Criteria are presented for “separation watch,” which tells that a boundary-layer may soon break away, and for “separation warning,” which identifies the vorticity characteristics in an already formed boundary-layer separation zone and along a boundary-layer separation line. Flow behavior and its dependence on outer flow conditions are examined qualitatively. A numerical example is given which confirms the predictions of the theory.

Sepsis is characterized by organ dysfunction due to a dysregulated immune response to infection. Currently, no effective treatment for sepsis exists. Platelets are recognized as mediators of the immune response and may be a potential therapeutic target for the treatment of sepsis. We previously demonstrated that NLRP3 inflammasome activation in sepsis-induced activated platelets was associated with multi-organ injury in the cecal-ligation puncture (CLP) rat model of sepsis. In this study, we tested the hypothesis that inhibition of NLRP3 would inhibit platelet activation and attenuate multi-organ injury in the CLP rat. CLP (n = 10) or Sham (n = 10) surgery were performed in male and female Sprague-Dawley rats. A subset of CLP rats were treated with MCC950 (50mg/kg/d), a specific NLRP3 inhibitor (CLP+MCC950, n = 10). At 72 hrs. post-CLP, blood and organs were harvested for analysis of platelet activation, NLRP3 activation, inflammation and end organ damage. Platelet activation increased from 8±0.8% in Sham to 16±1% in CLP, and was reduced to 9±1% in CLP +M rats (p<0.05). NLRP3 activation was also increased in platelets of CLP vs Sham. NLRP3 expression was unchanged in kidney and lung after CLP, but Caspase 1 expression and IL-1β were increased. MCC950 treatment attenuated NLRP3 activation in platelets. Plasma, kidney, and lung levels of NLRP3 inflammasome associated cytokines, IL-1ß and IL-18, were significantly increased in CLP compared to Sham rats. Inhibition of NLRP3 normalized cytokine levels. Glomerular injury, pulmonary edema, and endothelial dysfunction markers were increased in CLP rats vs Sham. MCC950 treatment significantly decreased renal and pulmonary injury and endothelial dysfunction in CLP+M. Our results demonstrate a role for NLRP3 in contributing to platelet activation and multi-organ injury in sepsis.

Existing approximate Riemann solvers do not perform well when the grid is not aligned with strong shocks in the flow field. Three new approximate Riemann algorithms are investigated to improve solution accuracy and stability in the vicinity of strong shocks. The new algorithms are compared to the existing upwind algorithms in OVERFLOW 2.1. The new algorithms use a multidimensional pressure gradient based switch to transition to a more numerically dissipative algorithm in the vicinity of strong shocks. One new algorithm also attempts to artificially thicken captured shocks in order to alleviate the errors in the solution introduced by "stair-stepping" of the shock resulting from the approximate Riemann solver. This algorithm performed well for all the example cases and produced results that were almost insensitive to the alignment of the grid and the shock.