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This paper summarizes the autonomous guidance methods (AGMs) for pinpoint soft landing on celestial surfaces. We first review the development of powered descent guidance methods, focusing on their contributions for dealing with constraints and enhancing computational efficiency. With the increasing demand for reusable launchers and more scientific returns from space exploration, pinpoint soft landing has become a basic requirement. Unlike the kilometer-level precision for previous activities, the position accuracy of future planetary landers is within tens of meters of a target respecting all constraints of velocity and attitude, which is a very difficult task and arouses renewed interest in AGMs. This paper states the generalized three- and six-degree-of-freedom optimization problems in the powered descent phase and compares the features of three typical scenarios, i.e., the lunar, Mars, and Earth landing. On this basis, the paper details the characteristics and adaptability of AGMs by comparing aspects of analytical guidance methods, numerical optimization algorithms, and learning-based methods, and discusses the convexification treatment and solution strategies for non-convex problems. Three key issues related to AGM application, including physical feasibility, model accuracy, and real-time performance, are presented afterward for discussion. Many space organizations, such as those in the United States, China, France, Germany, and Japan, have also developed free-flying demonstrators to carry out related research. The guidance methods which have been tested on these demonstrators are briefly introduced at the end of the paper.

The CRISPR/Cas9 gene editing technology directs Cas9 protein to recognize, bind and cleave the target site specifically by using artificial single-guide RNA (sgRNA), through non-homologous end joining or homologous end-recombinant repair mechanisms of cells, which can be engineered to knockout or knock-in of genomes. RIG-I is a pattern recognition receptor that recognizes the 5'-triphosphate-containing RNA in the cytoplasm and activates IRF3/7 and NF-κB by interacting with the downstream signaling molecule MAVS, thus initiating the expression of type I interferons and inflammatory factors. Previous studies found that influenza B virus (IBV) can up-regulate the expression of RIG-I. In the present study, to explore whether RIG-I is the major receptor for IBV to active the antiviral innate immune response and its effect on IBV replication, RIG-I gene in 293T cells was knocked out by CRISPR-Cas9 system, and a stable RIG-I knockout 293T (RIG-I(-/-) 293T) cell line was screened by puromycin pressure. The results of Western blotting showed that RIG-I was not expressed in this cell line after IBV or Sendai virus (SeV) infection, indicating that the RIG-I(-/-) 293T cell line was successfully constructed. The transcription levels of interferons, inflammatory factors and interferon-stimulated genes in RIG-I(-/-) 293T cells which were infected by IBV decreased significantly compared with those in wild-type 293T cells. Moreover, the phosphorylation of p65 and IRF3 were not detected in IBV or SeV infected RIG-I(-/-) 293T cells. It is indicated that the expression of cytokines mainly depends on the RIG-I-mediated signaling pathway at the early stage of IBV infection. Furthermore, the multi-step growth curves of IBV in the wild type and RIG-I(-/-) 293T cells showed that RIG-I inhibited the replication of IBV. Collectively, the RIG-I knockout 293T cell line was successfully constructed. We found that RIG-I is the main receptor for IBV to active the antiviral innate immune response and is critical for inhibiting IBV replication, which lays the foundation for further study of IBV infection mechanism.CRISPR/Cas9 基因编辑技术是通过人工设计的单向导RNA(Single-guide RNA，sgRNA)指导Cas9 蛋白对目的基因靶位点进行特异性的识别、结合和切割后，通过细胞的非同源末端连接或同源末端重组修复机制来完成对基因组的敲除与敲入的编辑技术。RIG-I 是机体的一种模式识别受体，能够识别胞质中的含5′-三磷酸基团的RNA，并通过与下游信号分子MAVS 相互作用，激活IRF3/7 和NF-κB，从而启动I 型干扰素和炎性因子的表达。已有研究表明，B 型流感病毒(IBV)在感染早期能够上调RIG-I 的表达水平。为了探索RIG-I 是否为B 型流感病毒激活抗病毒天然免疫信号通路的主要受体及其对IBV 复制的影响，本研究利用CRISPR-Cas9 技术对293T 细胞中的RIG-I 基因进行了敲除，经嘌呤霉素压力筛选到了一株稳定敲除RIG-I 基因的293T (RIG-I(-/-) 293T)细胞系。Western blotting 检测发现，IBV 或仙台病毒感染后该细胞系中RIG-I 不再表达，说明该敲除细胞系构建成功。IBV感染RIG-I(-/-) 293T 细胞后，干扰素、炎性因子及干扰素刺激基因的转录水平与野生型293T 细胞相比明显下降，并且在RIG-I(-/-) 293T 细胞中检测不到p65 和IRF3 磷酸化，表明IBV 感染早期细胞因子的表达主要依赖于RIG-I信号通路的激活。IBV 在野生型及RIG-I(-/-) 293T 细胞中的多步生长曲线表明，RIG-I 可抑制 IBV 的复制。以上结果表明，RIG-I 敲除的293T 细胞系构建成功，RIG-I 是IBV 激活下游抗病毒天然免疫信号通路的主要受体之一，且对IBV 的复制具有负调控作用，该研究为探索IBV 的感染机制奠定了基础。.

Reconfigurable intelligent surfaces (RISs) constitute a promising performance enhancement for next-generation (NG) wireless networks in terms of enhancing both their spectrum efficiency (SE) and energy efficiency (EE). We conceive a system for serving paired power-domain non-orthogonal multiple access (NOMA) users by designing the passive beamforming weights at the RISs. In an effort to evaluate the network performance, we first derive the best-case and worst-case of new channel statistics for characterizing the effective channel gains. Then, we derive the best-case and worst-case of our closed-form expressions derived both for the outage probability and for the ergodic rate of the prioritized user. For gleaning further insights, we investigate both the diversity orders of the outage probability and the high-signal-to-noise (SNR) slopes of the ergodic rate. We also derive both the SE and EE of the proposed network. Our analytical results demonstrate that the base station (BS)-user links have almost no impact on the diversity orders attained when the number of RISs is high enough. Numerical results are provided for confirming that: i) the high-SNR slope of the RIS-aided network is one; ii) the proposed RIS-aided NOMA network has superior network performance compared to its orthogonal counterpart., Comment: arXiv admin note: text overlap with arXiv:1910.00959

This study presents a direct trajectory optimization framework for a vertical takeoff and vertical landing (VTVL) reusable rocket with a two-stage structure for a launch mission to simultaneously d...

This study presents a trajectory optimization framework for lunar rover performing vertical takeoff vertical landing (VTVL) maneuvers in the presence of terrain using variable-thrust propulsion. First, a VTVL trajectory optimization problem with three-dimensional kinematics and dynamics model, boundary conditions, and path constraints is formulated. Then, a finite-element approach transcribes the formulated trajectory optimization problem into a nonlinear programming (NLP) problem solved by a highly efficient NLP solver. A homotopy-based backtracking strategy is applied to enhance the convergence in solving the formulated VTVL trajectory optimization problem. The optimal thrust solution typically has a “bang-bang” profile considering that bounds are imposed on the magnitude of engine thrust. An adaptive mesh refinement strategy based on a constant Hamiltonian profile is designed to address the difficulty in locating the breakpoints in the thrust profile. Four scenarios are simulated. Simulation results indicate that the proposed trajectory optimization framework has sufficient adaptability to handle VTVL missions efficiently.

In this letter, we study the outage performance of non-orthogonal multiple access (NOMA) with fixed power allocation over Nakagami- ${m}$ fading channels, where the fading parameters of NOMA users are different. In this scenario, new closed-form expressions are derived for the outage behavior of individual users and the system, respectively. Next, the diversity orders are obtained under high signal-to-noise ratio condition. The derived analytical expressions are exact and unprecedented in the earlier literature. Finally, simulations are conducted to confirm the validity of the analysis and show the outage performance of NOMA under different fading parameters of Nakagami- ${m}$ fading channels.

In this letter, we investigate the power allocation problem in nonorthogonal multiple access (NOMA) heterogeneous networks (HetNets), where the macrocell base station (MBS) and small cell base station (SBS) compete to maximize their own throughput with minimum rate requirement of each user. The throughput of MBS and SBS is formulated based on the equivalent channel gain, and the power allocation problem is captured as a Stackelberg game. A distributed power allocation algorithm is proposed to achieve the Stackelberg equilibrium. Simulation results demonstrate the convergence of the proposed algorithm. Meanwhile, it is verified that the combination of NOMA and HetNets possesses great potential to improve the spectrum efficiency compared to the orthogonal multiple access based HetNets.

To achieve more efficient spectrum utilization in the intelligent transportation system, non-orthogonal multiple access-enabled (NOMA-enabled) V2X communications have been emerging as a promising technology. In this paper, the resource allocation problem for NOMA-enabled V2X communications is investigated. For V2I links, in view of the user fairness and the different requirements of cellular users (CUEs), weighted max-min rate fairness for CUEs is applied, where both identical weights and different weights are considered. As for V2V users (VUEs), the minimum signal-to-interference-plus-noise ratio (SINR) requirements are imposed on the problem formulation. To solve the proposed optimization problem, it is decoupled into three stages: 1) power allocation for CUEs; 2) power control and subcarrier (SC) assignment for VUE pairs; 3) SC assignment and user clustering for CUEs. For the three stages, algorithms based on the Perron-Frobenius theorem, the Kuhn-Munkres algorithm, and the matching theory are proposed separately. Finally, an algorithm integrated the three stages is presented to obtain a joint solution. The convergence and the optimality of the proposed algorithms can be verified by theoretical analysis and simulations. Moreover, simulation results also indicate that each cluster of the optimal user clustering scheme is inclined to be occupied by the CUEs with diverse channel gains and the minimum weighted rate of all CUEs, $\tau $ , will decrease with the increase of the numbers of V2V links and the minimum SINR requirements of VUE pairs.

A unified trajectory optimization framework with initialization strategies is proposed in this paper for lunar soft landing for various missions with specific requirements. Two main missions of interest are Apollo-like Landing from low lunar orbit and Vertical Takeoff Vertical Landing (a promising mobility method) on the lunar surface. The trajectory optimization is characterized by difficulties arising from discontinuous thrust, multi-phase connections, jump of attitude angle, and obstacles avoidance. Here R-function is applied to deal with the discontinuities of thrust, checkpoint constraints are introduced to connect multiple landing phases, attitude angular rate is designed to get rid of radical changes, and safeguards are imposed to avoid collision with obstacles. The resulting dynamic problems are generally with complex constraints. The unified framework based on Gauss Pseudospectral Method (GPM) and Nonlinear Programming (NLP) solver are designed to solve the problems efficiently. Advanced initialization strategies are developed to enhance both the convergence and computation efficiency. Numerical results demonstrate the adaptability of the framework for various landing missions, and the performance of successful solution of difficult dynamic problems.

Next-generation powered landing guidance for planetary soft landing needs multi-point-guidance capabilities. A novel trajectory optimization framework for planetary multi-point powered landing is presented in this study. First, the powered landing trajectory optimization problem with three-dimensional dynamics model, boundary conditions, and path constraints is formulated. The finite-element collocation approach with collocation based on Radau points is chosen to transcribe the formulated trajectory optimization problem into a nonlinear programming problem solved by Interior Point OPTimizer (IPOPT). The proposed trajectory optimization framework utilizes optimal sensitivity based on IPOPT to select the fuel-optimal landing aim point from candidate landing aim points by one optimization computation. Then, the optimal trajectory to the best landing aim point can be efficiently obtained based on the good initial value guess provided by the sensitivity analysis. Numerical results show that the proposed algorithm effectively and efficiently addresses the planetary multi-point powered landing problem and has potential for onboard implementation.

An extended-state-observer (ESO) based predictive control scheme is proposed for the autopilot of lunar landing. The slosh fuel masses exert forces and torques on the rigid body of lunar module (LM), such disturbances will dramatically undermine the stability of autopilot system. The fuel sloshing dynamics and uncertainties due to the time-varying parameters are considered as a generalized disturbance which is estimated by an ESO from the measured attitude signals and the control input signals. Then a continuous-time predictive controller driven by the estimated states and disturbances is designed to obtain the virtual control input, which is allocated to the real control actuators according to a deadband logic. The 6-DOF simulation results reveal the effectiveness of the proposed method when dealing with the fuel sloshing dynamics and parameter perturbations.

This paper investigates the allocation of resources, including subcarriers and spreading codes, as well as intercell interference (ICI) mitigation for multicell downlink multicarrier direct-sequence code division multiple-access systems, which aim to maximize the system's spectral efficiency (SE). The analytical benchmark scheme for resource allocation and ICI mitigation is derived by solving or closely solving a series of mixed integer non-convex optimization problems. Based on the optimization objectives the same as the benchmark scheme, we propose a novel distributed resource allocation assisted by ICI mitigation scheme referred to as resource allocation assisted by ICI mitigation (RAIM), which requires very low implementation complexity and demands little backhaul resource. Our RAIM algorithm is a fully distributed algorithm, which consists of the subcarrier allocation (SA) algorithm named RAIM-SA, spreading code allocation (CA) algorithm called RAIM-CA and the ICI mitigation algorithm termed RAIM-IM. The advantages of the RAIM are that its CA only requires limited binary ICI information of intracell channels, and it is able to make mitigation decisions without any knowledge of ICI information. Our simulation results show that the proposed RAIM scheme, with very low complexity required, achieves significantly better SE performance than other existing schemes, and its performance is very close to that obtained by the benchmark scheme.

In this paper, the application of non-orthogonal multiple access (NOMA) aided multiple unmanned aerial vehicles (UAVs) wireless networks is investigated in the downlink scenario. A new multiple UAVs framework, user-centric strategy for providing emergency services in the rural area, is proposed by utilizing a stochastic geometry model. In order to provide practical insights for the proposed NOMA assisted UAV framework, an imperfect successive interference cancelation (ipSIC) scenario is taken into account. For the user-centric strategy, we derive new exact expressions for the coverage probability. The derived analytical results explicitly indicate that the ipSIC coefficient is a dominant component in terms of coverage probability.

This paper investigates the guidance problem for powered landing of reusable rockets based on sliding mode control method. To track a reference trajectory, a nonsingular fast terminal sliding mode (NFTSM) surface is designed. Though traditional NFTSM controller is characterized by finite time convergence and high robustness against uncertainties, it results in high-frequency oscillation in control action, which is undesirable in engineering application. To address this issue, a super-twisting sliding mode controller is combined with the NFTSM surface to provide smoother control signal. The finite-time convergence of the proposed guidance law is proven using Lyapunov theorem. Taking parameter perturbations, initial state errors and wind disturbances into account, a 1000-run Monte Carlo simulation is performed. Simulation results illustrate the high tracking precision, strong robustness as well as low chattering property of the proposed controller.

During atmospheric entry, winds and atmospheric uncertainties may result in large dispersions at the beginning of powered landing of reusable rockets. To mitigate the effect of large initial dispersions and uncertainties, an optimal feedback guidance algorithm is presented for the powered landing of reusable rockets. The presented guidance algorithm implements receding-horizon trajectory optimization based on finite-element collocation approaches. The finite-element collocation approach fully discretizes the state and control variables of the powered landing guidance problem, leading to nonlinear programming (NLP) problems addressed by NLP solvers. The optimal trajectory of the powered landing is re-planned in each guidance period using the finite-element collocation approach. Results indicate the proposed optimal feedback guidance algorithm could guide the reusable rocket to land at a specified landing site in the presence of initial dispersion, model uncertainty, and disturbance.

The problem of lunar soft landing using variable-thrust propulsion is solved by the simultaneous dynamic optimization approach.We propose a novel adaptive mesh refinement strategy to address the difficulty of locating breakpoints in the thrust profile.Union property of R-function method is utilized to express discontinuous thrust profile. In this study, the problem of fuel-optimal lunar soft landing trajectory optimization using variable-thrust propulsion is considered. First, the lunar soft landing trajectory optimization problem with three-dimensional kinematics and dynamics model, boundary conditions, and path constraints strictly described is formulated. Then, the formulated trajectory optimization problem is solved by the simultaneous dynamic optimization approach. With bounds imposed on the magnitude of engine thrust, the optimal control solutions typically have a "bang-bang" thrust profile. The general simultaneous dynamic optimization approach has difficulty handling breakpoints in the control profiles. A novel adaptive mesh refinement strategy based on a constant Hamiltonian profile is proposed to address the difficulty of locating breakpoints in the thrust profile. Two cases are simulated. The engine of the first case is throttleable between zero and full thrust. The engine of the second case is throttleable between 10% and 60% of full thrust, and at full thrust. Union property of R-function method is utilized to express the thrust profile of the second case in the trajectory optimization problem. Simulation results show that the enhanced simultaneous dynamic optimization approach with adaptive mesh refinement strategy can effectively capture the breakpoints in the optimal thrust profile and obtain more refined lunar soft landing optimal solutions, compared with the results obtained by the general simultaneous dynamic optimization approach.

This paper presents a unified trajectory optimization framework for lunar ascent. Compared with prevailing and emerging studies on lunar ascent trajectory optimization with simplified lunar ascent process and simple constraints, our method formulates in detail the lunar ascent process with complex constraints in a unified manner. The kinematics and dynamics model of lunar ascent with mission-specific constraints explicitly expressed through equalities or inequalities form the fuel-optimal lunar ascent trajectory optimization problem. A proper direct trajectory optimization method is chosen to transcribe the original trajectory optimization problem into a nonlinear programming (NLP) problem solved by a highly efficient NLP solver. The homotopy-based backtracking initial value strategy is designed to enhance convergence of the solving process. First, a two-phase trajectory optimization problem including vertical-rise phase and orbit-insertion phase is solved in the proposed unified framework. Subsequently, to obtain terrain clearance, we directly incorporate terrain description into the lunar ascent problem to obtain the optimal lunar ascent trajectory. Simulation results indicate that the proposed unified trajectory optimization framework has enough adaptability to efficiently handle complex lunar ascent scenarios. The proposed framework may benefit future autonomous lunar ascent missions.

Aim To investigate the regulatory mechanism of glycogen synthase kinase 3β (GSK3β) in epithelial-mesenchymal transition (EMT) process after proliferative vitreoretinopathy (PVR) induction. Methods Experimental PVR was induced by intravitreal injection of retinal pigment epithelium (RPE) cells in the eyes of rabbits. A PI3K/Akt inhibitor (wortmannin) and a GSK3β inhibitor (LiCl) were also injected at different time during PVR progress. Electroretinogram (ERG), ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and LiCl were evaluated by ERG and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The vitreous was also collected for metabolomic analysis. Results Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3K/Akt pathways. Conclusion GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.

Rocket landing guidance under complex constraints is significant for reusable rocket. This paper presents a convex model predictive control strategy to generate the guidance command for fuel-optimal rocket landing problem. The performance of MPC is directly limited to its calculation speed and convergence, however the characteristics of convex optimization can make up for this problem. In this paper, we formulate the rocket landing problem in the longitudinal plane with nonlinear dynamics and nonconvex constraints, which could be convexified using successive linearization and relaxation respectively. Due to the free terminal time of this landing process, its time domain is mapped to a specific interval, and the terminal time is defined as additional control variable. A novel receding horizon strategy is proposed to obtain appropriate guidance command by changing the location of collocation points and objective function. Simulation results demonstrate that the proposed convex MPC method is very competitive that can make the rocket landing safely under complex constraints.

This section introduces equipment level testing, which incorporates functional/performance and reliability testing.

Launch vehicle tests include many important activities, particularly during the development phase. However, when the rocket begins launch services, system level tests focus on avionics system integration after assembly, mainly by simulating flight processes, also known as general check in China. The general check is performed hierarchically. The control (or GNC) subsystem is checked first, and then other systems, such as the telemetry system, etc. The shutdown time of every stage may be controlled around the theoretical value by modeling the shutdown equation.

Simplifying test and control operation, reducing launch preparation time, and limiting technical support personnel required on site, are apparently contradictory to improving test coverage, reducing operation differences between ground test and onboard flight, and improving testing facility versatility, but these are all important issues for TLCS.

Testing and checking continue for the whole launcher life cycle, and it is difficult to introduce all issues related to testing. Test content is very complicated and involves many aspects. Many test activities are performed during the development process and are not repeated in follow-up services such as structural strength checks, whereas avionics or electrical system tests are implemented before every launch. Therefore, this section introduces electrical system test techniques.

In this letter, we adopt multi-objective optimization to investigate the tradeoff between energy efficiency (EE) and spectral efficiency (SE) in downlink orthogonal frequency division multiple access (OFDMA) systems. In the proposed model, $\alpha$ -fair utility function is applied to take account of the rate fairness among users. We then transfer the original multi-objective optimization into a single objective optimization employing the weighted sum method to obtain the solution set characterized as a Pareto set. The obtained Pareto set demonstrates the tradeoff between EE and SE while $\alpha$ -fairness guarantee is in place. We further consider price of fairness, as a metric to quantify the loss of EE due to enforcing fairness requirements. Such a metric enables the network operators to determine an acceptable operation point in terms of EE-SE tradeoff when certain level of fairness is required. Simulation results indicate that higher fairness results in lower system EE, and the price of fairness is significantly raised with the increase of overall SE.

In this paper, a novel "delay- and utility-oriented (DUO)" resource allocation algorithm for the mixture of real-time (RT) and non-real-time services in orthogonal frequency division multiple access systems is proposed. The proposed DUO algorithm considers delay-utility function and rate-utility function simultaneously, scheduling RT packets approaching the deadline first and then achieving as much aggregate rate-utility as possible. Simulation results reveal that it can not only satisfy RT users' delay requirements in terms of packet drop ratio, but also obtain much more aggregate rate-utility for mixed services than other reference algorithms. Besides, the rate-utility fairness of all users is also improved substantially.

While TGF-β1 is known to induce epithelial–mesenchymal transition (EMT), a major factor in the pathogenesis of proliferative vitreoretinopathy (PVR), in ARPE-19 cells. The molecular pathways involved in EMT formation have not yet to be fully characterized. In this study, we have found that TGF-β1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-β1 inhibited GSK-3β by accelerating phosphorylation at ser9. GSK-3β inhibitor or knockdown of GSK-3β resulted in enhanced TGF-β1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-3β overexpression and PI3K/AKT inhibitor. Importantly, GSK-3β also mediated metabolic reprogramming in TGF-β1-treated cells. Our results indicate that GSK-3β plays a pivotal role in TGF-β1-mediated EMT in ARPE-19 cells.

Purpose To describe an outbreak of intraocular inflammation caused by endotoxin-contaminated counterfeit bevacizumab in China. Design Retrospective, observational case series. Participants Patients undergoing intravitreal injection at a public hospital in September 2010. Methods The medical records and microbiology results of patients who presented with intraocular inflammation after injection with intravitreal counterfeit bevacizumab were reviewed. Main Outcome Measures The incidence of intraocular inflammation, results of pathogen cultures, and clinical features of inflammation. Results A total of 116 patients (70 men and 46 women) were injected from 3 vials of counterfeit bevacizumab. Intraocular inflammation developed in 80 patients. The estimated median incubation period was 12 hours (range, 2–24 hours), and the median duration of symptoms was 6 days (range, 3–22 days). All patients were treated initially with topical corticosteroid and antibiotics. Vitreous tap and intravitreal injection were performed on 43 patients. Twenty-one patients with hypopyon and significant vitreous inflammation underwent vitrectomy. Microscopic evaluations and microbiologic cultures of all ocular specimens were negative for bacterial and fungal contamination. The presence of endotoxin in specimens was confirmed by laboratory testing. We refer to this new clinical syndrome as "endotoxin-induced ocular toxic syndrome" (EOTS). The inflammation regressed rapidly after treatment, and 63 patients (78.8%) recovered their pre-injection vision. Conclusions This study implicates endotoxin as the cause of intraocular inflammation after the intravitreal injection of counterfeit bevacizumab. The EOTS appeared clinically distinct from typical infectious endophthalmitis. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Necroptosis is a recently discovered programmed necrosis. Evidence demonstrated the importance of necroptosis in neuronal cell death. Necrostatin-1 is a specific inhibitor of necroptosis. In this study, we investigated the role of necrostatin-1 on photoreceptor survival and functional protection after experimental retinal detachment (RD) in rats. Necrostatin-1/inactive analogue of necrostatin-1 was introduced into the subretinal space at RD induction and 6 hours afterward, respectively. We found that necrostatin-1 attenuated retinal histopathological damage and reduced plasma membrane breakdown (a morphological hallmark of necroptosis) in outer retinal layers. Transmission electron microscopy showed that necrostatin-1 directly protected neurons by inhibiting necroptotic, not apoptotic, cell death. Treatment with necrostatin-1 inhibited the induction of receptor-interacting protein kinase phosphorylation after RD (a biomarker of necroptosis). Finally, electroretinographic recording proved that necrostatin-1 contributed to objective functional improvement after RD. These findings indicate that necrostatin-1 is a promising therapeutic agent that protects photoreceptors from necroptosis and improves functional outcome.

In resource constrained wireless systems, achieving higher spectral efficiency (SE) and energy efficiency (EE), and greater rate fairness are conflicting objectives. Here, a general framework is presented to analyze the tradeoff among these three performance metrics in cooperative OFDMA systems with decode-and-forward relaying, where subcarrier pairing and allocation, relay selection, choice of transmission strategy, and power allocation are jointly considered. In our analytical framework, rate fairness is represented utilizing the $\alpha $ -fairness model, and the resource allocation problem is formulated as a multi-objective optimization problem. We then propose a cross-layer resource allocation algorithm across application and physical layers, and further devise a heuristic algorithm to tackle the computational complexity issue. The SE-EE tradeoff is characterized as a Pareto optimal set, and the efficiency and fairness tradeoff is investigated through the price of fairness. Simulations indicate that higher fairness results in a worse SE-EE tradeoff. It is also shown imposing fairness helps to reduce the outage probability. For a fixed number of relays, by increasing circuit power, the performance of SE-EE tradeoff is degraded. Interestingly, by increasing the number of relays, although the total circuit power is increased, the SE-EE tradeoff is not necessarily degraded. This is thanks to the extra degree of freedom provided in relay selection.

In this study, the fuel-optimal trajectory optimization problem of lunar soft landing using variable-thrust propulsion is considered. First, we formulate the trajectory optimization problem of lunar soft landing with three-dimensional kinematics and dynamics, boundary constraints, and path constraints strictly described. The formulated trajectory optimization problem is then solved by the simultaneous dynamic optimization approach. With bounds imposed on the magnitude of the engine thrust, the optimal thrust profile typically has a “bang-bang” profile. The general simultaneous dynamic optimization approach has difficulty handling breakpoints of control profiles. A novel adaptive mesh refinement strategy based on a constant Hamiltonian profile is proposed to address the difficulty of locating breakpoints of the thrust profile. Simulation results show that the enhanced simultaneous dynamic optimization approach with the adaptive mesh refinement strategy can effectively capture breakpoints of the optimal thrust profile and obtain more refined optimal solutions, compared with the general simultaneous dynamic optimization approach.

Purpose: To quantitatively analyze the collagen produced by rabbit keratocytes treated with mitomycin C (MMC) and/or transforming growth factor-beta (TGF-β1), and to investigate the collagen arrangement in situ, using second harmonic generation (SHG) microscopy.Methods: Keratocytes were divided into four groups: The keraotocytes in group rabbit keratocytes were treated with serum free medium containing 1% methylcellulose as controls. The cells in group TGF were received with TGF-β1 (at 2 ng/ml) and the same medium as the control. After exposure to MMC at 0.02 mg/ml for 5 minutes, the cells in group MMC were received with the same treatment as controls. In group TGF-MMC, the cells were exposed to MMC at 0.02 mg/ml for 5 minutes first, and then treated as group TGF. The signals of collagen were detected by SHG at 2 and 4 weeks post-treatment. The collagen content, as well as the keratocyte numbers, was calculated by MetaMorph Offline.Results: The collagen arrangement could be detected clearly by SHG...

This paper proposes a simultaneous trajectory optimization framework to determine the optimal trajectory of lunar ascent with terrain. By considering the influence of the rotation of the moon, a three-dimensional kinematics and dynamics model for the lunar ascent process is given. To ensure flight safety, the terrain model is considered the collision-free path constraints of this trajectory optimization problem. Moreover, the terminal position and velocity are transformed into orbit elements as terminal insertion constraints. The maximum angular rate of the pitch and yaw angle is also constrained. Given that lunar ascent is subject to the tradeoff between fuel and payload, as well as to conserve fuel for possible contingencies, minimum fuel use is used as the performance index. The formulated trajectory optimization problem is discretized into a nonlinear programming (NLP) problem by the hp-adaptive pseudospectral method, which is used to deal with the complex terrain constraints. The initial values for solving the NLP problem are generated by the homotopy-based backtracking strategy. Four scenarios are designed to test the capability of the proposed simultaneous trajectory optimization framework for lunar ascent with terrain. Simulation results indicate that the proposed simultaneous trajectory optimization framework has enough adaptability to efficiently address the lunar ascent trajectory optimization problem with complex terrain constraints. The results of this study will benefit future autonomous lunar ascent missions.

In this paper, the problem of fuel-optimal lunar ascent trajectory optimization using constant-thrust propulsion is considered. The whole lunar ascent process is divided into two phases: vertical-rise phase and orbit-insertion phase, respectively. Considering the influence of rotation of the moon, a three-dimensional kinematics and dynamics model for lunar ascent is established. The fuel-optimal lunar ascent trajectory optimization problem is posed as a two-phase constrained nonlinear trajectory optimization problem solved by using Gauss pseudospectral method. Initial guesses for this trajectory optimization problem are obtained by solving a subproblem where the angular rate of pitch angle and yaw angel is not constrained. Four scenarios of the two-phase lunar ascent trajectory optimization problem are designed. The simulation results show that all state and control variables satisfy the related constraints and practical engineering condition in each scenario. The developed direct trajectory optimization framework has the adaptability to address various scenarios of the two-phase lunar ascent mission.

The photosensitive polyimide film, Durimide, is a common component of retinal prostheses; however, retinal cell response to Durimide has not been effectively studied This work assessed the in vitro biocompatibility of a retinal prosthesis containing platinum-electrode embedded Durimide film.Biocompatibility evaluation assessed cytotoxicity, attachment, and proliferation of two cell lines: a human retinal pigmented epithelium cell line (CRL) and a rhesus monkey choroid- retinal endothelial cell line (RF/6A). Cells were cultured with the platinum-electrode embedded Durimide film, with tissue-culture treated polystyrene plates (TCPS) used as a control substrate for cell growth. The effect of a Durimide-exposed medium on cell apoptosis and life cycle was assessed using flow cytometry (FCM).The indirect cytotoxicity evaluation revealed no toxic effect of the prosthesis on cells. The attachment and proliferation of CRL and RF/6A cells cultured with the Durimide prostheses showed no significant differences to the control. The FCM experiments demonstrated a liquid medium exposed to the prosthesis had no effects on apoptosis or cell life cycle in comparison with the control (p0.05).The results demonstrate that Durimide has good biocompatibility with retinal cell lines CRL and RF/6A. In conclusion, while further in vitro and in vivo studies are required to clarify long-term effects, Durimide is indicated as a promising material with suitable biocompatibility for retinal implants.

Fifth Generation (5G) networks will compromise of heterogeneous networks (HetNets) with macrocell overlaid with lower power small cells to achieve higher throughput by offloading users with low signal-to-noise-ratio from macrocell to the small cells. In this paper, we proposed a multi-objective optimization problem (MOP) to jointly investigate the tradeoff between throughput and backhaul energy efficiency (BEE) using ω-fair utility function for two different backhauling technologies in downlink transmission scheme of a two-tier HetNets. We then transform the proposed MOP into a single objective optimization problem (SOP) employing the weighted sum method to obtain the complete Pareto Frontier solution set with minimum QoS requirements and rate fairness level ω. The transformed SOP is solved in an iterative manner using Lagrangian Dual Decomposition (LDD) with a subgradient method providing a near-optimal solution. Simulation results demonstrate the effectiveness of our proposed approach in reducing the total area power consumption irrespective of the backhauling technology by dynamically adjusting weighting coefficient α and rate fairness level ω. Our numerical results also demonstrate the fundamental tradeoff between throughput and BEE for different parameters such as weighting coefficient α and rate fairness level ω.

Cooperative communication has been identified as an important component in the 5G system. This paper considers a decode-and-forward (DF) relaying wireless cooperative network, in which the self-energy recycling relay is powered by radio-frequency (RF) signal from the source and its transmitted power from the loop-back channel. The harvested energy is used to support the relay transmissions. Based on a self-energy recycling relaying protocol, we study the optimization of energy efficiency in wireless cooperative networks. Although the formulated optimization problem is not convex, it can be re-constructed to a parametric problem in the convex form by using the non-linear fractional programming, to which closed form solutions can be found by using the Lagrange multiplier method. The simulation results are presented to verify the effectiveness of this solution proposed in this paper.

During soft landing process of planet lander, it will encounter many obstacles need to control precisely. For traditional off-line design, it's very hard to handle many constrains with uncertainty. So this paper give out an online trajectory planning and guidance method to realize the autonomous obstacle avoidance to achieve flight safety. This method is an improved optimal feedback guidance algorithm based on multiple waypoints optimization algorithm. The obstacle avoidance problem is transformed into a navigation point constraint problem and derived with the specific waypoints constraint expressions to realize autonomous obstacle avoidance. Simulation results show that this method can effectively avoid the obstacles in the most fuel-efficient cases to achieve a safe landing.

To achieve the planetary safe landing, the ability of evaluating new landing sites, redesigning trajectory and maneuvering to a new and safe site must be ensured while hazards are detected in the nominal landing site. This paper investigates the hazard avoidance scheme employing the three-dimensional optimal zero-effect-miss/zero-effect-velocity feedback guidance algorithm for its robustness and easy to implement. Meanwhile, by introducing the bisection search method, with the auxiliary of the numerical results of the feedback guidance algorithm, the open-loop optimal time-to-go can be determined in real time, which reduces fuel consumption a lot. The accessibility and optimality evaluation of the candidate new landing sites, which acquired by applying the scheme, lay the foundation for selection of the new landing site. The performance of the scheme proposed is demonstrated through numerical simulation examples and Monte Carlo simulations, and the results indicate that the fuel-optimal redesigned trajectory can always be found.

Summary We conducted a pilot test of polymer flooding in the Shuanghe reservoir located in the southeast Henan oil field, China. The target reservoir has a net thickness of 15.56 m (50 ft), an average permeability of 420 md, and a temperature of 75°C (167°F). The polymers used are two types of modified partially hydrolyzed Polyacrylamides, named S525 and S625, which have molecular weights of 16,700,000 and 19,670,000 daltons, respectively. The objective of this pilot test is to investigate the feasibility of polymer flooding for improving oil recovery in an elevated-temperature reservoir. The polymer flooding started in February 1994. Through December 1995, a total of 246 tons (about 0.5 × 106 lbm) of dry polymer had been used with an injection concentration of 900 to 1,100 ppm. The pore volume (PV) injected reached 0.2164. As a result, oil production increased by 22,000 tons (184,000 bbl) and water production decreased by 153,000 tons (962,000 bbl), which accounts for the incremental oil recovery of 3.8% and water-cut reduction of 5.6% in the test block. We estimate that, by the end of this project, the ultimate increase in oil production will exceed 63,000 tons (528,000 bbl) with the enhanced oil recovery going up to 9.8%. The yield is 0.2 tons more oil produced per kilogram of polymer injected or 0.7 barrel of oil produced per pound of polymer. We attribute the success of the pilot test to the techniques used during the implementation of the flooding, including prevention of polymer-thermal degradation, good reservoir description, and the profile modification carried out before and after the polymer injection. This pilot test illustrates a case where polymers with extra-high molecular weight are successfully injected in an elevated-temperature reservoir to control the mobility ratio and modify the permeability profile.

Background The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. Methodology/Principal Findings Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. Conclusions/Significance Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity., Author Summary Macrophages play critical roles in modulating Mycobacterium leprae (M. leprae) infection. In this study, we investigated the immune status of macrophages stimulated with live M. leprae or killed M. leprae. We found that live M. leprae-infected macrophages polarized toward the regulatory M2-type, preferentially primed Treg responses, and downregulated Th1 and cytotoxic T cell responses. Furthermore, our ex vivo data confirmed these findings. These results revealed novel mechanisms of M. leprae infection.

To observe the effects of a single intravitreal rhEPO injection on light-induced retinal damage in rats and to explore the possible mechanisms.Male Sprague-Dawley rats were randomly divided into a normal group, a control group (PBS intravitreal injection), and a number of treatment groups (intravitreal rhEPO injection at 0.625, 1.25, 2.5, 5, 10, or 20 U). After dark adaptation for 24 h, rats were exposed to white light (2800 lx) for 5 h. Based on the effects of rhEPO on the ERG-b wave, an optimal dose (5U) was chosen for further experiments that included histopathological examination and outer nuclear layer (ONL) counting at 5 and 10 days after light exposure. Cell apoptosis and proteins (caspase-3, bcl-xL) were also examined at 3 days. Some cell signaling related proteins (AKT, ERK1/2 and STAT5) were also analyzed. In another experiment, rats received intravitreal injection of rhEPO (5U) at 30 min after light exposure. ERG and morphological changes were examined at 3 days after light exposure.ERG-b wave amplitudes are well preserved in rats receiving 2.5, 5, or 10 U rhEPO, in comparison with the PBS control. The dose-effect relationship was bell-shaped, with the maximum effect at 5 U. Less apoptotic cells were in the ONL in the 5U group. The rats receiving 5 U rhEPO at 30 min after light exposure also had higher b-wave amplitude. Caspase-3 expression was down-regulated and Bcl-xL was up-regulated in the rhEPO group. Phosphorylated ERK(1,2) was reduced in the rhEPO group.A single intravitreal injection of rhEPO can postpone photoreceptor light damage in rats. The optimal dose was 5 U in this study. The effective time window was from 24 h prior to light exposure to 5 h after. RhEPO may be involved in the regulation of the expression of Caspase-3 and Bcl-xL. The possible cell signal transduction maybe through the ERK1/2 pathway.