The guidance system of terminal flight is to guide the vehicle flies into the target precisely in a specific direction while satisfy all the constraints. A new adaptive proportion navigation guidance method is proposed. First the constraints are analyzed. To provide enough time for the lateral and longitudinal adjustments, a convergence strategy is designed and it improves the performance of proportion navigation guidance greatly. By considering the dynamics of vehicle, the execute errors of guidance commands are eliminated with an on-line navigation constants adaptive law. The angle rates of flight path angle and heading angle are converted into angle of attack and bank angle commands through command allocation. The simulation results show that the proposed terminal guidance method is precise and reliable.
A direct method is discussed for multistage launch vehicle ascent trajectory optimization. First the optimal control problem is modeled with the performance index as maximum terminal mass. A modified Gauss Pseudospectral method is used to design a rapid optimal algorithm for multistage launch vehicle ascent trajectory. The nonlinear terminal state constraints are converted into linear terminal state constraints through state equation matrix and Gauss weight coefficient. Based on linear gravity assumption, the analytical vacuum solution is obtained and used as initial guess. The simulation shows that the proposed algorithm can achieve the trajectory optimal goal with high precision and rapid convergence when all the terminal and path constraints are satisfied.
A formal analysis to footprint problem with effects of angle of attack (AOA) is presented. First a flexible and rapid standardized method for footprint generation is developed. Zero bank angle control strategy and the maximum crossrange method are used to obtain virtual target set; afterward, closed-loop bank angle guidance law is used to find footprint by solving closest approach problem for each element in virtual target set. Then based on quasi-equilibrium glide condition, the typical inequality reentry trajectory constraints are converted to angle of attack lower boundary constraint. Constrained by the lower boundary, an original and practical angle of attack parametric method is proposed. By using parametric angle of attack profile, optimization algorithm for angle of attack is designed and the impact of angle of attack to footprint is discussed. Simulations with different angle of attack profiles are presented to demonstrate the performance of the proposed footprint solution method and validity of optimal algorithm.
Background: Thrombosis is the chief culprit in the fatal event of atherosclerotic cardiovascular disease (ASCVDs). Neutrophil extracellular traps (NETs) closely link inflammation and thrombosis. The immune-related GTPase family M protein (IRGM) and its ortholog of mouse IRGM1 are positively correlated with plaque rupture during atherosclerosis process. However, whether and how IRGM/IRGM1 affects NETs formation and atherosclerotic thrombosis remains unknown, which will further promote the development of antithrombotic treatment tools.Methods: The thrombi images, platelet activation makers and NETs makers were detected in the serum of 193 STEMI patients and 43 controls. To futher investigate IRGM/IRGM1 affects NETs formation and atherosclerotic thrombosis in vivo, ApoE-/- Irgm1+/- and ApoE-/- mice received diets rich in fat and 2.5% FeCl3 was then used to induce experimental arterial thrombosis in an atherosclerosis background. In vitro, PMA and thrombin were used to stimulate neutrophils and platelets, respectively, and the expression of IRGM/IRGM1 were modified. To reveal the molecular mechanisms, MAPK- cPLA2 signals inhibitors were used.Results: Thrombi were observed in the offender lesions in almost all STEMI patients, and serum IRGM was positively correlated with platelet factor 4 and neutrophil elastase. Subsequently, Irgm1 deficient mice have a longer occlusion time and lower growth rate. In vitro, as expected, IRGM/Irgm1 deficiency inhibits platelet activation and platelet-neutrophil interaction. More importantly, IRGM promoted NETs production through activating MAPK-cPLA2 signals in PMA stimulated neuropils, whereas inhibiting the production of NETs eliminated the difference in platelet activation and thrombosis caused by IRGM/Irgm1 modification in vivo and vitro. Similarly, inhibition of platelet activation also eliminated the influence of IRGM/Irgm1 modification on NETs production.Conlusions: Overall, our data indicate that IRGM/Irgm1 deficiency in neuropils inhibits the intense interaction between neutrophils and platelets, and ultimately inhibits thrombosis. Targeting IRGM may represents a new therapeutic strategy that prevents and treats thrombosis during ASCVDs.Funding Information: This work was supported by the National Natural Science Foundation Projects [grant numbers 81870353 and 82170262 to S.F.], the Natural Science Foundation of Heilongjiang Province [grant number LH2020H048 and TD2020H001], and the 2nd Affiliated Hospital of Harbin Medical University, Harbin [grant number CX2016-21].Declaration of Interests: The authors have declared that no competing interest exists.Ethics Approval Statement: All experiments using human subjects were performed in accordance with the Declaration of Helsinki and approved by the Institutional Review Board Harbin Medical University. Written informed consent was obtained from participants before inclusion in the study.
Hypersonic vehicle has an integrated frame-propulsion configuration.With strong nonlinear coupling between aerodynamic force and thrust,a feasible approach is proposed to obtain the optimal ascent trajectory.Based on zero sideslip assumption the ascent flight problem is modeled by means of optimal control theory.The mass is taken as state variable and the performance index is to minimize fuel consumption.The direction of body longitudinal axis is chosen as control input.The maximum principle is used for optimization.To solve the two point boundary value problem,the analytical mass point solution is taken as initial guess obtained by zero reference area assumption.Both finite difference method and modified Newton method are used to get the numerical solution.With the path constraint of attack of angle,the optimal trajectory is gotten through homotopy algorithm iteration finally.The simulation is conducted under the condition of the given initial and final constraints.The result shows that this method can minimize the fuel consumption for the ascent flight.And the iteration method taking reference area as the homotopy parameter can guarantee convergence of the algorithm.
A universal improved nonlinear longitudinal model of hypersonic developed by Langley lab is adopted. For the I/O linearizing model, a sliding mode controller is designed. This method can solve the uncertainty problem and insensitive to disturbance of outside. The index approach law used to drive the sliding mode to reach the sliding surface is adopted to eliminate the quiver. The simulation for tracking the height step and velocity step order at cruise condition show that the sliding mode controller with index approach law acquires satisfying tracking ability and strong robustness. The controller can not only track the single height step order or velocity step order accurately, but track the height step order and velocity step order together fleetly with zero error. In addition, the sliding controller with index law is better than the one with sign function in track speed and precision. Another result is also proved that the index approach law can eliminate the quiver perfectly.
Rationale: Atherosclerosis plaque rupture (PR) is the pathological basis and chief culprit of most acute cardiovascular events and death. Given the complex and important role of macrophage apoptosis and autophagy in affecting plaque stability, an important unanswered question include is whether, and how, immunity-related GTPase family M protein (IRGM) and its mouse orthologue IRGM1 affect macrophage survival and atherosclerotic plaque stability. Methods: To investigate whether serum IRGM of ST-segment elevation myocardial infarction (STEMI) patients is related to plaque morphology, we divided 85 STEMI patients into those with and without plaque rupture (PR and non-PR, respectively) based on OCT image analysis, and quantified the patients' serum IRGM levels. Next, we engineered Irgm1 deficient mice (Irgm1+/-) and chimera mice with Irgm1 deficiency in the bone marrow on an ApoE-/- background, which were then fed a high-fat diet for 16 weeks. Pathological staining was used to detect necrotic plaque cores, ratios of neutral lipids and cholesterol crystal, as well as collagen fiber contents in these mice to characterize plaque stability. In addition, immunofluorescence, immunohistochemical staining and western blot were used to detect the apoptosis of macrophages in the plaques. In vitro, THP-1 and RAW264.7 cells were stimulated with ox-LDL to mimic the in vivo environment, and IRGM/IRGM1 expression were modified by specific siRNA (knockdown) or IRGM plasmid (knocked-in). The effect of IRGM/Irgm1 on autophagy and apoptosis of macrophages induced by ox-LDL was then evaluated. In addition, we introduced inhibitors of the JNK/p38/ERK signaling pathway to verify the specific mechanism by which Irgm1 regulates RAW264.7 cell apoptosis. Results: The serum IRGM levels of PR patients is significantly higher than that of non-PR patients and healthy volunteers, which may be an effective predictor of PR. On a high-fat diet, Irgm1-deficient mice exhibit reduced necrotic plaque cores, as well as neutral lipid and cholesterol crystal ratios, with increased collagen fiber content. Additionally, macrophage apoptosis is inhibited in the plaques of Irgm1-deficient mice. In vitro, IRGM/Irgm1 deficiency rapidly inhibits ox-LDL-induced macrophage autophagy while inhibiting ox-LDL-induced macrophage apoptosis in late stages. Additionally, IRGM/Irgm1 deficiency suppresses reactive oxygen species (ROS) production in macrophages, while removal of ROS effectively inhibits macrophage apoptosis induced by IRGM overexpression. We further show that Irgm1 can affect macrophage apoptosis by regulating JNK/p38/ERK phosphorylation in the MAPK signaling pathway. Conclusions: Serum IRGM may be related to the process of PR in STEMI patients, and IRGM/Irgm1 deficiency increases plaque stability. In addition, IRGM/Irgm1 deficiency suppresses macrophage apoptosis by inhibiting ROS generation and MAPK signaling transduction. Cumulatively, these results suggest that targeting IRGM may represent a new treatment strategy for the prevention and treatment of acute cardiovascular deaths caused by PR.
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