Clinical and Immunologic Correlates of Vasodilatory Shock Among Ebola Virus-Infected Nonhuman Primates in a Critical Care Model.

BACKGROUND: Existing models of Ebola virus infection have not fully characterized the pathophysiology of shock in connection with daily virologic, clinical, and immunologic parameters. We implemented a nonhuman primate critical care model to investigate these associations. METHODS: Two rhesus macaques received a target dose of 1000 plaque-forming units of Ebola virus intramuscularly with supportive care initiated on day 3. High-dimensional spectral cytometry was used to phenotype neutrophils and peripheral blood mononuclear cells daily. RESULTS: We observed progressive vasodilatory shock with preserved cardiac function following viremia onset on day 5. Multiorgan dysfunction began on day 6 coincident with the nadir of circulating neutrophils. Consumptive coagulopathy and anemia occurred on days 7 to 8 along with irreversible shock, followed by death. The monocyte repertoire began shifting on day 4 with a decline in classical and expansion of double-negative monocytes. A selective loss of CXCR3-positive B and T cells, expansion of naive B cells, and activation of natural killer cells followed viremia onset. CONCLUSIONS: Our model allows for high-fidelity characterization of the pathophysiology of acute Ebola virus infection with host innate and adaptive immune responses, which may advance host-targeted therapy design and evaluation for use after the onset of multiorgan failure.

Effects of crystallinity on residual stresses via molecular dynamics simulations.

Mechanical properties of materials are highly dependent on microstructure. One characteristic example is tensile stresses at the grain boundaries, which is one of the most critical factors in crack nucleation. Although experimental techniques have significantly evolved during the past decades with respect to obtaining high-resolution snapshots of the microstructure with methods such as scanning electron microscopy, the quantitative estimation of continuum quantities, such as localized stresses, still remains a very challenging task. The molecular dynamics simulation method has been proven to be a quite effective simulation tool for providing insights in such challenges due to its high spatial and temporal resolution. In this study, molecular dynamics simulations have been performed to obtain a spatial resolution of the residual stresses in solidified aluminum. A best-effort realistic microstructure was obtained by starting from a pure aluminum block which was initially melted and subsequently quenched under various cooling rates, and finally relaxed. The obtained results suggest that residual stresses are higher in absolute terms at the vicinity of grain boundaries than at the grain interiors, and higher crystallinity has been found to be correlated to lower residual stresses. Moreover, it has been shown both qualitatively and quantitatively that grain boundaries undergo tensile loading, in contrast to the grain interiors which are compressed; this result comes to support the conclusions of quite recent experimental investigations, showing that the residual stress is tensile at the grain boundaries and gradually transits into compressive in the grain interiors, and highlights the potential of molecular dynamics simulation to capture nanoscale physical phenomena.