Objective The essential role of platelet activation in haemostasis and thrombotic diseases focuses attention on unveiling the underlying intracellular signals of platelet activation. Disabled-2 (Dab2) has been implicated in platelet aggregation and in the control of clotting responses. However, there is not yet any in vivo study to provide direct evidence for the role of Dab2 in haemostasis and platelet activation. Approach and Results Megakaryocyte lineage-restricted Dab2 knockout (Dab2−/−) mice were generated to delineate in vivo functions of Dab2 in platelets. Dab2−/− mice appeared normal in size with prolonged bleeding time and impaired thrombus formation. Although normal in platelet production and granule biogenesis, Dab2−/− platelets elicited a selective defect in platelet aggregation and spreading on fibrinogen in response to low concentrations of thrombin, but not other soluble agonists. Investigation of the role of Dab2 in thrombin signaling revealed that Dab2 has no effect on the expression of thrombin receptors and the outside-in signaling. Dab2−/− platelets stimulated by low concentrations of thrombin were normal in Gαq-mediated calcium mobilization and PKC activation but were defective in Gα12/13-mediated RhoA-ROCKII activation. The attenuated Gα12/13 signaling led to impaired ADP release, Akt-mTOR and integrin αIIbβ3 activation, fibrinogen binding, and clot retraction. The defective responses of Dab2−/− platelets to low concentrations of thrombin stimulation may contribute to the impaired haemostasis and thrombosis of Dab2−/− mice. Conclusions This study sheds new insight in platelet biology and represents the first report demonstrating that Dab2 is a key regulator of haemostasis and thrombosis by functional interplay with Gα12/13-mediated thrombin signaling.
PrefaceNetworked control systems (NCSs) are a type of distributed control systems where sensors, actuators, and controllers are interconnected through a communication network. This system setup has the advantage of low cost, flexibility, and less wiring, but it also inevitably invites some delays and data loss into the design procedure.The focus of this book is to address the problem of analysis and design of NCSs when the communication delays are varying in a random fashion. This random feature of the time delays is typical for commercially used networks, such as a DeviceNet TM (which is a controller area network (CAN)) and EtherNet TM network. Models for communication network delays are first developed, in which Markov processes are used to model these random networkinduced delays. Based on such models, we establish novel methodologies for stability analysis, control with disturbance attenuation, filter design, and fault estimation for a class of uncertain linear/nonlinear uncertain NCSs with random communication network-induced delays in both sensor-to-controller and controller-to-actuator channels. Data packet dropouts in the communication channels also have been taken into consideration in the modeling and design procedure.The main technique used in this book is based on the Lyapunov-Razumikhin method, which results in delay-dependent controllers. We first consider the design problems for uncertain linear NCSs. In this case, state feedback controllers and dynamic output feedback controllers are designed to satisfy both stability and disturbance attenuation requirements for this class of NCSs. A robust filter design problem is also considered. Moreover, a robust fault estimator that ensures the fault estimation error is less than a prescribed performance level is designed. We further go on to address the control problems for uncertain nonlinear NCSs. The nonlinear plant is first described by the Takagi-Sugeno (T-S) fuzzy model. Based on this model, stability analysis, disturbance attenuation, filter design, and fault estimation problems are studied for uncertain nonlinear NCSs in parallel. It should be noted that system uncertainties, disturbances and noises are addressed in both cases. VI PrefaceThe existence of such controllers, filters, and fault estimators are given in terms of the solvability of bilinear matrix inequalities (BMIs). Iterative algorithms are proposed to change this non-convex problem into quasi-convex optimization problems, which can be solved effectively by available mathematical tools.Finally, to demonstrate the effectiveness and advantages of the proposed design methodologies in this book, numerical examples are given in each designed control systems. The simulation results show that the proposed design methodologies can achieve the prescribed performance requirements.
This paper studies the remote Kalman filtering problem for a distributed system setting with multiple sensors that are located at different physical locations. Each sensor encapsulates its own measurement data into one single packet and transmits the packet to the remote filter via a lossy distinct channel. For each communication channel, a time-homogeneous Markov chain is used to model the normal operating condition of packet delivery and losses. Based on the Markov model, a necessary and sufficient condition is obtained, which can guarantee the stability of the mean estimation error covariance. Especially, the stability condition is explicitly expressed as a simple inequality whose parameters are the spectral radius of the system state matrix and transition probabilities of the Markov chains. In contrast to the existing related results, our method imposes less restrictive conditions on systems. Finally, the results are illustrated by simulation examples.
The effects of laser scanning speed on the microstructure, microhardness, and corrosion behavior of Ni45 coatings were investigated by using optical microscopy (OM), scanning electron microscopy (SEM), X-ray diffraction (XRD), microhardness, and electrochemical measurements. The results showed that increasing laser scanning speed promotes the transformation from planar crystals to dendrites and refines the grains concurrently. The γ-(Ni, Fe), FeNi3, and M23(C,B)6 are identified as the primary phase composition in the Ni45 coatings regardless of the laser scanning speed. Thereinto, the formation and growth of M23(C,B)6 precipitates can be inhibited with increasing laser scanning speed due to the higher cooling rate, which affects the microhardness distribution and corrosion resistance of the coating. On the one hand, the microhardness of the whole coating presents a downtrend with increasing laser scanning speed due to the reduction of M23(C,B)6 phase. On the other hand, the corrosion resistance in 0.5 M NaCl solution is improved to some extent at higher laser scanning speed because the less precipitation of M23(C,B)6 reduces the depletion of Cr around the precipitates. In contrast, all the coatings exhibit undifferentiated but poor corrosion resistance in the highly corrosive 0.5 M NaCl + 0.5 M H2SO4 solution.
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