The complement and neutrophil defense systems, as major components of innate immunity, are activated during inflammation and infection. For neutrophil migration to the inflamed region, we hypothesized that the complement activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure of human neutrophils to C5a, dose- and time-dependently resulted in a rapid C5a receptor-1 (C5aR1)-dependent shape-change, indicated by enhanced flow cytometric forward-scatter area values. Similar changes were observed after incubation with zymosan-activated serum and in blood neutrophils during murine sepsis, but not in mice lacking the C5aR1. In human neutrophils, Amnis high-resolution digital imaging revealed a C5a-induced decrease in circularity and increase in the cellular length/width ratio. Biomechanically, microfluid optical stretching experiments indicated significantly increased neutrophil deformability early after C5a stimulation. The C5a-induced shape changes were inhibited by pharmacological blockade of either the Cl−/HCO3−-exchanger or the Cl−-channel. Furthermore, actin polymerization assays revealed that C5a exposure resulted in a significant polarization of the neutrophils. The functional polarization process triggered by ATP–P2X/Y-purinoceptor interaction was also involved in the C5a-induced shape changes, because pre-treatment with suramin blocked not only the shape changes but also the subsequent C5a-dependent chemotactic activity. In conclusion, the data suggest that the anaphylatoxin C5a regulates basic neutrophil cell processes by increasing the membrane elasticity and cell size as a consequence of actin-cytoskeleton polymerization and reorganization, transforming the neutrophil into a migratory cell able to invade the inflammatory site and subsequently clear pathogens and molecular debris.
We have developed an inducible and reversible hepatic LDLR knockdown mouse model of atherosclerosis regression. Although cholesterol reduction decreased early en face lesions in the aortic arches, macrophage area was reduced in both early and late lesions within the aortic sinus after reversal of hypercholesterolemia. Our model circumvents many of the challenges associated with current mouse models of regression. The use of this technology will potentially expedite studies of atherosclerosis and regression without use of mice with genetic defects in lipid metabolism.
Developed societies have a high level of preparedness for natural or man-made disasters. But such incidents cannot be completely prevented, and when an incident like an earthquake or an accident in a chemical or nuclear plant hits a populated area, rescue teams need to be employed. In such situations it is a necessity for rescue teams to get a quick overview of the situation in order to identify possible locations of victims that need to be rescued and dangerous locations that need to be secured. Rescue forces must operate quickly in order to save lives, and they often need to operate in dangerous environments. Hence, robot-supported systems are increasingly used to support and accelerate search operations. The objective of the SENEKA concept is to network the various robots and sensor systems used by first responders in order to make the search for victims and survivors more quick and efficient. SENEKA targets the integration of the robot-sensor network into the operation procedures of the rescue teams. The aim of this paper is to inform on the goals and first research results of the ongoing joint research project SENEKA
We propose a robust method to handle kinematic and algorithmic singularities of any kinematically redundant robot under task-space hierarchical control with ordered equalities and inequalities. Our main idea is to exploit a second order model of the non-linear kinematic function, in the sense of the Newton's method in optimization. The second order information is provided by a hierarchical BFGS algorithm omitting the heavy computation required for the true Hessian. In the absence of singularities, which is robustly detected, we use the Gauss-Newton algorithm that has quadratic convergence. In all cases we keep a least-squares formulation enabling good computation performances. Our approach is demonstrated in simulation with a simple robot and a humanoid robot, and compared to state-of-the-art algorithms.
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