Cell Invasion by Neisseria meningitidis Requires a Functional Interplay between the Focal Adhesion Kinase, Src and Cortactin

Entry of Neisseria meningitidis (the meningococcus) into human brain microvascular endothelial cells (HBMEC) is mediated by fibronectin or vitronectin bound to the surface protein Opc forming a bridge to the respective integrins. This interaction leads to cytoskeletal rearrangement and uptake of meningococci. In this study, we determined that the focal adhesion kinase (FAK), which directly associates with integrins, is involved in integrin-mediated internalization of N. meningitidis in HBMEC. Inhibition of FAK activity by the specific FAK inhibitor PF 573882 reduced Opc-mediated invasion of HBMEC more than 90%. Moreover, overexpression of FAK mutants that were either impaired in the kinase activity or were not capable of autophosphorylation or overexpression of the dominant-negative version of FAK (FRNK) blocked integrin-mediated internalization of N. meningitidis. Importantly, FAK-deficient fibroblasts were significantly less invaded by N. meningitidis. Furthermore, N. meningitidis induced tyrosine phosphorylation of several host proteins including the FAK/Src complex substrate cortactin. Inhibition of cortactin expression by siRNA silencing and mutation of critical amino acid residues within cortactin, that encompass Arp2/3 association and dynamin binding, significantly reduced meningococcal invasion into eukaryotic cells suggesting that both domains are critical for efficient uptake of N. meningitidis into eukaryotic cells. Together, these results indicate that N. meningitidis exploits the integrin signal pathway for its entry and that FAK mediates the transfer of signals from activated integrins to the cytoskeleton. A cooperative interplay between FAK, Src and cortactin then enables endocytosis of N. meningitidis into host cells

Freigabe linker Radwege Vorlaeufige Hinweise fuer eine nachtraegliche Freigabe strassenbegleitender Radwege zum Linksfahren

TIB Hannover: RN 9155(7,a) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Radverkehrsanlagen Empfehlungen fuer Planung, Entwurf und Betrieb von Radverkehrsanlagen. Erlaeuterungen und Begruendungen

SIGLETIB: RN 9155 (3) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Numerical Flow Investigation of Morphing Leading Edges for the Enhancement of Maneuverability of Unmanned Combat Air Vehicles

Observing the progress in the technology of unmanned combat aerial vehicles (UCAVs) than it can be foreseen that in the future the role of manned combat aircraft will be taken over more and more by unmanned systems. The abandonment of pilots allows for more freedom in the aerodynamic design of the vehicle in regard to weight and acceleration, however, new stealth constraints have a severe impact. The design of UCAV configurations is driven by the special requirements of upcoming missions, as for instance the capabilities of long endurance fl ights joined with a low observability. The new demands have a crucial impact on the aerodynamic shape, and, hence, require new solutions for maneuver con- trol in respect to integration of engine in- and outlets, actuators and other devices. Additionally the new capabilities of long endurance ights has to be joined with low observability. In particular UCAVs are suited to the exploitation of non-conventional control technologies, such as aerodynamic morphing, flow control, or thrust vectoring. This paper presents a numerical investigation of innovative morphing technologies for aircraft applications and explores the feasibility for such technologies to enhance the maneuverability of unmanned combat aerial vehicles. In Aerodynamics the morphing is understood as a smooth, continuous change in geometry of the outer surface, e.g. the twist of complete wing can be changed in order control role moments. In the considered case morphing is used to provide additional ow control mechanisms taking into account the constraint of fllow radar signature. In particular morphing can be used to change the geometry of the airfoil leading edge to control the ow around the wings in order to generate additional lift or induce role moments. This paper is concerned with the investigation of the feasibility and effectiveness of morphing devices for the aerodynamic control of UCAVs. Focal point of this work is the morphing of leading edges in order to generate additional lift or role moments for UCAVs flying in high angle of attack mode. Therefore, the objective of the numerical investigations is the evaluation of the potential of morphing leading edges especially for the enhancement of the maneuverability of Delta- and Lambda-wing configurations with their vortex-dominated ow field. Of special interest is ow control at high angles of attack (AoA) by targeting an minimized shape adaptation in order to generate a needed additional lift, to induce role moments or to reduce the risk of the potential deleterious effects of vortex breakdown. The morphing of the leading edge must not confused with classical Kruger leading edge flaps. Although very effective in regard to the increase of lift such fl aps can't be used for UCAVs since gaps between fl aps and the wing have to be avoided in order to fulll the hard conditions of radar camouflage . The presented work is part of the DLR Project FaUSST which is the successor of the DLRProject UCAV-2010. The UCAV-2010 project was set up to identify and assess UCAV relevant technologies. The investigations have covered the pre-design process with fast, low fidelity methods as well as the detailed examination using high fidelity methods like URANS simulations. The verification of the promissing technologies and tools have been done by virtual and experimental prototypes. The combined research has lead to a Lambda wing type UCAV configuration with a medium sweep of the leading edge. The outcoming DLR-F17 conguration has been mainly derived from the so called Saccon geometry developed by EADS-MAS for the RTO/AVT-161 task group. Since the capability of medium to high AoA maneuverability will be investigated the angle of attack has been varied from 6 to 16 degrees. After presentation of the technical part, the results of leading edge manipulation are discussed. One focal point is the comparison of the impact of differently morphed leading edge shapes on the fl ight performance at specific flight situations. The aerodynamical coefficients, in particular Cl, Cd and Cm, are related to morphing parameters of the changed shape of the leading edges. Another key aspect is the varied effective angle of attack of the middle part of the wings, see Figure 2. In case of a basic high angle of attack the effective AoA (due to morphing) can change the vortical flow above the deformed wings enormously, even when the geometrical angle of the airfoil has been morphed only slightly. This work discusses the effectiveness of counter-rotating morphing of leading edges, since the requirements in regard to radar signature do not allow large geometry changes. This point reduces the degree of freedom of any shape morphing drastically. Thereto, only proper combinations of left and associated right wing deformations have been analyzed and discussed. After the discussion of the most interesting deformations an evaluation of the presented test cases in regard to the maneuverability enhancement of UCAVs concludes the presentation