Emerging Roles of Autophagy and Inflammasome in Ehrlichiosis

Human monocytic ehrlichiosis (HME) is a potentially life-threatening tick-borne rickettsial disease (TBRD) caused by the obligate intracellular Gram-negative bacteria, Ehrlichia. Fatal HME presents with acute ailments of sepsis and toxic shock-like symptoms that can evolve to multi-organ failure and death. Early clinical and laboratory diagnosis of HME are problematic due to non-specific flu-like symptoms and limitations in the current diagnostic testing. Several studies in murine models showed that cell-mediated immunity acts as a “double-edged sword” in fatal ehrlichiosis. Protective components are mainly formed by CD4 Th1 and NKT cells, in contrast to deleterious effects originated from neutrophils and TNF-α-producing CD8 T cells. Recent research has highlighted the central role of the inflammasome and autophagy as part of innate immune responses also leading to protective or pathogenic scenarios. Recognition of pathogen-associated molecular patterns (PAMPS) or damage-associated molecular patterns (DAMPS) triggers the assembly of the inflammasome complex that leads to multiple outcomes. Recognition of PAMPs or DAMPs by such complexes can result in activation of caspase-1 and -11, secretion of the pro-inflammatory cytokines IL-1β and IL-18 culminating into dysregulated inflammation, and inflammatory cell death known as pyroptosis. The precise functions of inflammasomes and autophagy remain unexplored in infections with obligate intracellular rickettsial pathogens, such as Ehrlichia. In this review, we discuss the intracellular innate immune surveillance in ehrlichiosis involving the regulation of inflammasome and autophagy, and how this response influences the innate and adaptive immune responses against Ehrlichia. Understanding such mechanisms would pave the way in research for novel diagnostic, preventative and therapeutic approaches against Ehrlichia and other rickettsial diseases

Application of WaSiM-ETH model to Northern German lowland catchments: model performance in relation to catchment characteristics and sensitivity to land use change

The hydrological catchment model WaSiM-ETH (Water Balance Simulation Model) is a spatially distributed, process- and grid-based hydrological catchment model which was primarily developed to simulate the water balance of mountainous catchments. In this study, the ability of WaSiM-ETH was tested to describe the hydrological processes of lowland catchments. In addition, the resulting model performance was related to subcatchment characteristics and the model's sensitivity to possible future land use change. The prediction of the hydrological effects of land use change is a major challenge in contemporary hydrological model applications. The study revealed that WaSiM-ETH is a suitable tool for the simulation of the hydrological behaviour of lowland catchments. However, for a few subcatchments model validation failed. Analysing the correlation between model performance and physiographic catchment characteristics revealed that WaSiM-ETH performs better in sloped catchments compared to plane ones. Modelling results were also better in heterogeneous catchments with respect to soils and vegetation compared to homogenous ones. However, the hydrological reaction to land use change scenarios was similar in all investigated catchments

Numerical Predictions of Fluid Flow and Heat Transfer in a Rotating Engine-Similar Two-Pass Internal Cooling Channel With Smooth and Ribbed Walls

Numerical investigations of a two-pass internal cooling channel with engine-similar cross-sections were conducted. The channel featured a trapezoidal inlet pass, a sharp 180° bend, and a nearly rectangular second pass. Calculations were conducted for a smooth and a ribbed channel (α = 45°, P/e = 10, e/dh=0.1) at Re = 50,000 and four different rotation numbers Ro = 0, 0.02, 0.05 and 0.1. The Reynolds-averaged Navier-Stokes (RANS) equations were solved by the DLR Research Code TRACE developed at Institute of Propulsion Technology of German Aerospace Centre Cologne. A Wilcox k-ω turbulence model with additional modifications for rotating flows and stagnation point behaviour was applied. Computations were performed using block-structured grids created with POINTWISE. Flow field measurements were independently performed at DLR using Particle Image Velocimetry. In the smooth channel, rotation had a large impact on secondary flows. Especially, rotation induced vortices completely changed the flow field. Rotation also changed flow impingement on tip wall and outlet pass side wall. Heat transfer in the outlet pass was strongly altered by the influence of rotation. In contrast to the smooth channel, rotation showed less influence on heat transfer in the ribbed channel. This was due to a strong secondary flow field induced by ribs. However, in the outlet pass Coriolis force markedly affected the rib induced secondary flow field. The influence of rotation on heat transfer was visible in particular in the bend region and in the second pass directly downstream of the bend

Numerical Predictions of the Effect of Rotation on Fluid Flow and Heat Transfer in an Engine-similar Two-pass Internal Cooling Channel with Smooth and Ribbed Walls

In the present study, a two-pass internal cooling channel with engine-similar cross-sections was investigated numerically. The channel featured a trapezoidal inlet pass, a sharp 180° bend and a nearly rectangular outlet pass. Calculations were conducted for a configuration with smooth walls and walls equipped with 45° skewed ribs (P/e = 10, e/dh = 0.1) at a Reynolds number of Re = 50,000. The present study focused on the effect of rotation on fluid flow and heat transfer. The investigated rotation numbers were Ro = 0.0 and 0.10. The computations were performed by solving the Reynolds-averaged Navier-Stokes equations (RANS method) with the commercial Finite-Volume solver FLUENT using a low-Re k-ω-SST turbulence model. The numerical grids were block-structured hexahedral meshes generated with POINTWISE. Flow field measurements were independently performed at DLR using Particle Image Velocimetry. In the smooth channel rotation had a large impact on secondary flows. Especially, rotation induced vortices completely changed the flow field. Rotation also changed flow impingement on tip and outlet pass side wall. Heat transfer in the outlet pass was strongly altered by rotation. In contrast to the smooth channel, rotation showed less influence on heat transfer in the ribbed channel. This is due to a strong secondary flow field induced by the ribs. However, in the outlet pass Coriolis force markedly affected the rib induced secondary flow field. The influence of rotation on heat transfer was visible in particular in the bend region and in the second pass directly downstream of the bend