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This paper focuses on the non-zero sum differential game problem for Markovian jump systems with partially unknown transition probabilities. Firstly, a suboptimal control problem is studied by the free-connection weighting matrix method, and then the non-zero sum differential game problem is investigated on this basis. Several sufficient conditions for the existence of e -suboptimal control strategy and e -suboptimal Nash equilibrium strategies are provided, and their explicit expressions are designed. Moreover, the precise form for the upper bound of the cost function is also given. To facilitate the calculation, all conditions are converted into the corresponding equivalent linear matrix inequalities or bilinear matrix inequalities form. Finally, two numerical examples are utilized to demonstrate the effectiveness of the main results.

This paper investigates the asset-liability management problem for an ordinary robust insurance system between a reinsurer and an insurer under the Heston model with delay. The reinsurer, as the leader of the Stackelberg game, can price reinsurance premium and invest its wealth in a financial market that contains a risk-free asset and a risky asset whose price process is described by the Heston model. The insurer, as the follower of the Stackelberg game, can purchase proportional reinsurance from the reinsurer and invest in the same financial market. Under the consideration of the performance-related capital inflow/outflow, the wealth processes of the insurer and reinsurer are modeled by stochastic differential delay equations (SDDEs). This paper aims to find the equilibrium strategies for the reinsurer and insurer by maximizing the expected utility of the player’s terminal wealth with delay under the worst-case scenario of the alternative measures. By using the idea of backward induction and dynamic programming approach, the explicit expressions of the robust equilibrium strategies and value functions are derived. Finally, some numerical examples and sensitivity analysis to illustrate the effects of model parameters on the robust optimal reinsurance and investment strategies are performed.

Since the outbreak of 2019 novel coronavirus disease (COVID-19) induced by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pandemic has become a global catastrophe. Patients with cancer especially lung cancer are more vulnerable and susceptible to get infected by the virus SARS-CoV-2. The overwhelming impact of COVID-19 on lung cancer community may result in rise of the incidence and mortality of lung cancer. It would become more obvious in future retrospective studies. Lung cancer patients are believed at higher risk of COVID-19 due to immunosuppression and should be protected by vaccination with priority. Better understanding of SARS-CoV-2 could help develop more effective vaccines to eradicate this disease in the near future.

BACKGROUND To distinguish early-stage lung cancer from benign disease in pulmonary nodules, especially lesions with ground-glass opacity (GGO), we assessed gene mutations of ctDNA in peripheral blood using targeted next-generation sequencing (NGS). METHODS Single pulmonary nodule patients without mediastinal lymph nodes and symptoms that were hard to diagnose by chest CT and lung cancer biomarker measurement in multiple medical centers were enrolled into the study. All patients accepted minimally invasive surgery but refused preoperative biopsy. Gene mutations in preoperative blood samples were detected by targeted NGS. Mutations with significant differences between lung tumors and benign lesions, as grouped by postoperative pathology, were screened. Protein expression was determined by immunohistochemistry. Highly expressed genes were selected as biomarkers to verify the mutations in peripheral blood. RESULTS In the training set, the RNF213, KMT2D, CSMD3 and LRP1B genes were mutated more frequently in early-stage lung cancer (27 cases) than in benign nodules (15 cases) (P

Background Chemotherapy is one of the primary treatments for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), however, chemoresistance develops over time and is a bottleneck to effective chemotherapy worldwide. Therefore, the development of new potent therapeutic agents to overcome chemoresistance is of utmost importance. Triptolide is a natural component extracted from Tripterygium Wilfordii, a Chinese plant; our study aimed to evaluate its anti-tumor effects in taxol-resistant human lung adenocarcinoma and investigate its molecular mechanisms of chemoresistance. Methods Triptolide's inhibition of cell viability was detected by sulforhodamine B (SRB) assay. Cell cycle was measured by flow cytometry and cell apoptosis was assessed by flow cytometry and western blot. Expression of β-catenin was analyzed by western blot and immunofluorescence (IF). The anti-tumor effects of triptolide were determined using a subcutaneous in-vivo model. Cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. The expression level of p-p70S6K and p-GSK-3α/β was evaluated by western blot and IHC. Results Triptolide inhibited cell proliferation, induced S-phase cell cycle arrest and apoptosis in taxol-resistant A549 (A549/TaxR) cells. Moreover, intraperitoneal injection of triptolide resulted in a significant delay of tumor growth without obvious systemic toxicity in mice. Additionally, triptolide reversed epithelial-mesenchymal transition (EMT) through repression of the p70S6K/GSK3/β-catenin signaling pathway. Conclusions Our study provides evidence that triptolide can reverse EMT in taxol-resistant lung adenocarcinoma cells and impairs tumor growth by inhibiting the p70S6K/GSK3/β-catenin pathway, indicating that triptolide has potential to be used as a new therapeutic agent for taxol-resistant lung adenocarcinoma.

The excessive proliferation and migration of vascular smooth muscle cells (VSMCs) play vital roles in neointimal hyperplasia and vascular restenosis. In the present study, we aimed to investigate the function and mechanism of octamer-binding transcription factor 4 (OCT4, a key transcription factor for maintaining stem cells in de-differentiated state) on neointima formation in response to vascular injury. Quantitative reverse-transcription polymerase chain reaction and western blot results displayed a significant increase of OCT4 levels in injured carotid arteries. Immunohistochemistry and immunofluorescence assays confirmed that the increased OCT4 expression was primarily localized in α-SMA-positive VSMCs from neointima, and colocalized with PCNA in the nuclei of VSMCs. Adenovirus-mediated OCT4 overexpression in injured carotid arteries exacerbated intimal thickening, while OCT4 knockdown significantly inhibited intimal thickening. In-vitro experiments confirmed that the increased OCT4 expression in VMSCs could be induced by platelet-derived growth factor-BB (PDGF-BB) in a time-dependent manner. Overexpression of OCT4 greatly promoted VSMCs proliferation and migration, while OCT4 knockdown significantly retarded the PDGF-BB-induced excessive proliferation and migration of VSMCs. Bioinformatics analysis, dual-luciferase reporter assay, and chromatin immunoprecipitation assay confirmed that OCT4 could upregulate matrix metalloproteinases 2 (MMP2) expression through promoting its transcription. Moreover, knockdown of MMP2 significantly attenuated OCT4-mediated VSMCs proliferation and migration. These results indicated that OCT4 facilitated neointimal formation in response to vascular injury by MMP2-mediated VSMCs proliferation and migration, and targeting OCT4 in VSMCs might be a novel therapeutic strategy for vascular restenosis.

With the more complex investment environment of China’s power grid, the accurate prediction of the investment ability of power grid enterprises has become an important prerequisite for managers to make precise investment decisions. This paper first selects the factors affecting the investment capacity of the power grid from the internal and external environment, and establishes the index system of the factors affecting the investment capacity. Secondly, the path analysis is used to deeply explore the interaction relationship and influence degree of each index and investment capacity. Finally, the maximum investment capacity of the power network can be predicted based on the BP neural network prediction model. The results show that the BP neural network prediction model can achieve higher prediction accuracy when predicting the power grid investment capability.

Background To distinguish early‐stage lung cancer from benign disease in pulmonary nodules, especially lesions with ground‐glass opacity (GGO), we assessed gene mutations of ctDNA in peripheral blood using targeted next‐generation sequencing (NGS). Methods Single pulmonary nodule patients without mediastinal lymph nodes and symptoms that were hard to diagnose by chest CT and lung cancer biomarker measurement in multiple medical centers were enrolled into the study. All patients accepted minimally invasive surgery but refused preoperative biopsy. Gene mutations in preoperative blood samples were detected by targeted NGS. Mutations with significant differences between lung tumors and benign lesions, as grouped by postoperative pathology, were screened. Protein expression was determined by immunohistochemistry. Highly expressed genes were selected as biomarkers to verify the mutations in peripheral blood. Results In the training set, the RNF213, KMT2D, CSMD3 and LRP1B genes were mutated more frequently in early‐stage lung cancer (27 cases) than in benign nodules (15 cases) (P, We found a novel RNF213 gene with high specificity in peripheral blood ctDNA in assisted diagnosis of lung cancer. It may be helpful about assisted diagnosis and treatment of lung cancer.

Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed to evaluate the anticancer effects of curcumin on the RN5 MPM cell line. The inhibitory effects of curcumin on cell viability were determined using the sulforhodamine B assay. In addition, cell cycle progression was analyzed by propidium iodide (PI) staining and flow cytometry, and curcumin-induced apoptosis was measured by Annexin V/PI double staining. The translocation of apoptosis-inducing factor (AIF) was assessed by western blotting and immunofluorescence, and the expression levels of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (Akt)-mammalian target of rapamycin (mTOR) signaling pathway proteins and mitochondria-associated proteins were evaluated by western blotting. In vivo antitumor effects were evaluated in a subcutaneous murine model. Briefly, tumors were harvested from the mice, and immunohistochemistry was conducted to evaluate cell proliferation, apoptosis and angiogenesis. The results indicated that curcumin inhibited RN5 cell viability and induced apoptotic cell death. In addition the findings suggested that curcumin-induced cell apoptosis occurred via the mitochondrial pathway, and caspase-independent and AIF-dependent pathways. Further analysis revealed that curcumin may act as a PI3K-Akt-mTOR signaling pathway inhibitor by downregulating PI3K, p-Akt, p-mTOR and p-p70 ribosomal protein S6 kinase. Furthermore, curcumin inhibited tumor angiogenesis in vivo. In conclusion, curcumin may be potent enough to be developed as a novel therapeutic agent for the treatment of MPM.

Introduction To distinguish early stage lung cancer from benign disease of the lung nodules, especially the lesions with ground-glass opacity (GGO) or ground-glass nodule (GGN), we assessed gene mutations of the ctDNA in peripheral blood by using targeted next-generation sequencing (NGS). Methods Single lung nodule patients without mediastinal lymph nodes or symptoms hardly diagnosed by chest CT and biomarker of lung cancer were enrolled. All patients received minimally invasive surgery but refused preoperative biopsy. Gene mutations of pre-operative blood samples were detected by targeted NGS. Mutations with statistical differences were screened in lung cancer and benign disease grouped by postoperative pathology. Gene expression was determined by immunohistochemistry. Highly expressed genes were selected as biomarkers to verify the mutations in peripheral blood. Results In training set, RNF213, KMT2D, CSMD3 and LRP1B genes mutated more frequently in early stage lung cancer (25cases) than benign nodules (18cases) (P

Objective: The objective of this study was to investigate the molecular mechanisms involved in rapamycin-induced inhibition of tumor growth. Materials and Methods: Murine S180 sarcoma cells were subcutaneously injected into mice, and the tumor-bearing mice were randomly divided into three groups (vehicle control, 2 mg/kg rapamycin, and 4 mg/kg rapamycin). The effect of rapamycin on tumor growth was determined by measuring tumor volume. Mammalian target of rapamycin (mTOR), Beclin1, ULK1, LC3, Notch1, CD133, and CD90 expressions was confirmed using confocal microscopy and Western blotting. Results: The tumor growth inhibition rates induced by high-dose and low-dose rapamycin were 48.8% and 30.1%, respectively. Beclin1 and ULK1 expressions and the LC3-II/LC3-I ratio in tumor tissues were altered by rapamycin, whereas mTOR, Notch1, CD133, and CD90 expressions were significantly inhibited by rapamycin in immunofluorescence assays. Western blotting also showed similar results. Conclusion: Tumor growth delay induced by rapamycin may be associated with the suppression of the cancer stem cell phenotype (Notch1, CD133, and CD90) and promotion of autophagy (mTOR, Beclin1, ULK1, and LC3-II/LC3-I ratio) in the murine S180 sarcoma model.

Secondary lining cracking always occurs in existing tunnels when the tunnel passes through the weathered argillaceous siltstone layer, which seriously affects the safety of the tunnel. In order to study the mechanical properties of weathered argillaceous siltstone and the cracking law of the secondary lining, this study analyzes the relationship of accumulative plastic strain between the dynamic stress amplitude and static deviator stress, as well as the cracking law of the secondary lining of the sample. The results show that under cyclic loading, there are obvious accumulative plastic strain in weathered argillaceous siltstone; the bearing capacity of the secondary lining structure at the biased part shows an evident increase than that of others with cracking generating faster. The research results provide a reference for the safety and operation of the tunnel that runs through the weathered argillaceous siltstone layer.

Comprehensive assessment of slope safety based on catastrophe theory has been studied and improved in recent years, because of its advantage of simplicity and objective. However, as the evaluation index of slope safety, the result of catastrophe progression has problems on the accuracy and the threshold, and there is no solution available. So the ROC curve (receiver operating characteristic curve), which is commonly used in medical, has been used in the slope engineering for the first time. The ROC curve can intuitively reflect the accuracy of the evaluation method and calculate the threshold of catastrophe progression. Thus, the concept of degree of safety comes forward, which can quantify the safety of slope. The study results of engineering cases show that this method of results evaluation using ROC curve is simple and intuitive, and it plays a good role on the examination of evaluation method. Besides, it can be used as a comparative analysis of different evaluation methods, which provides a new idea for the assessment of evaluation methods of slope safety.

Combining the renewable energy system, the Energy Storage (ES) station can maintain stable power transfer between renewable energy systems and power grid. This paper works on real-time simulation for multiple energy storage systems under different operating modes. Then taking a large number of ES converters and power grid into account, a modified electromagnetic transient program (EMTP) algorithm is proposed which is fit for the field-programmable gate array (FPGA)-based real-time simulation. By compressing the steps of the traditional EMTP algorithm, the simulation can be completed only by updating the history current source in each simulation cycle. In the meantime, the system is decoupled and multiple subsystems are simulated independently. Furthermore, to fully utilize the high parallelism of FPGA, we design and build a CPU-FPGA-based real-time simulation platform to implement the ES station. Using the simulation platform, we build a model of ES station and connect to the grid through an inverter. The whole system is tested in a single FPGA under different scenarios.

This paper discusses linear quadratic Nash game of stochastic singular time-delay systems governed by Itô’s differential equation. Sufficient condition for the existence of Nash strategies is given by means of linear matrix inequality for the first time. Moreover, in order to demonstrate the usefulness of the proposed theory, stochastic H2∕H∞control with multiple decision makers is discussed as an immediate application.

In this paper, we deal with the Nash differential games of stochastic singular systems governed by Itô-type equation in finite-time horizon and infinite-time horizon, respectively. Firstly, the Nash differential game problem of stochastic singular systems in finite time horizon is formulated. By applying the results of stochastic optimal control problem, the existence condition of the Nash strategy is presented by means of a set of cross-coupled Riccati differential equations. Similarly, under the assumption of the admissibility of the stochastic singular systems, the existence condition of the Nash strategy in infinite-time horizon is presented by means of a set of cross-coupled Riccati algebraic equations. The results show that the strategies of each players interact.

For simulating and analyzing the input and output problem of national economy more accurately, this paper considers the fast and slow production processes during the course of social production development, takes stochastic economic risks into consideration, and constructs a H∞ robust control model to follow the production in the singularly perturbed dynamic input-output systems. Further introducing ideas of noncooperative differential game theory, the H∞ robust control model is transformed into a saddle-point equilibrium game model, and a new method for solving dynamic input-output problem by using saddle-point equilibrium strategies is obtained. A numerical result is presented in the end to illustrate the effectiveness of the method.

This paper discusses the infinite time horizon nonzero-sum linear quadratic (LQ) differential games of stochastic systems governed by Ito’s equation with state and control-dependent noise. First, the nonzero-sum LQ differential games are formulated by applying the results of stochastic LQ problems. Second, under the assumption of mean-square stabilizability of stochastic systems, necessary and sufficient conditions for the existence of the Nash strategy are presented by means of four coupled stochastic algebraic Riccati equations. Moreover, in order to demonstrate the usefulness of the obtained results, the stochastic H-two/H-infinity control with state, control and external disturbance-dependent noise is discussed as an immediate application.

Nanotechnology has promising applications in biomedicine, such as in drug delivery, diagnosis, and tissue engineering. The pharmacokinetics of nanomaterials significantly affects their biological behavior in vivo, affecting their biomedical applications and potential nanotoxicity. In this review, we highlight some recent advances in the pharmacokinetic studies of representative nanomaterials. We focus on the relationships between the physicochemical properties of nanomaterials and physiological consequences.

The Jin Ping arch dam foundation exhibits large differences in the stiffness between left and right bank due to a fault in the valley and unloading, relaxation and rock crushing effects in the left abutment. An extremely complex engineering problem appears by achieving mechanical balance for the dam body. To reinforce the left dam foundation concrete pads refilling faults, huge concrete piles and consolidation grouting together with grout and drainage curtains are investigated and executed. The numerical results show that these reinforcement measures for the excavated dam foundation improved significantly the rock mass deformability and its stability. A suitable excavation sequence for reinforcement tunnels and caverns is studied and the stability of these tunnels is analysed. The influence of consolidation grouting on the slope stability is investigated by varying spacing and number of active grouting holes. During the construction of the reinforcement tunnels the vibrations induced by blasting are simulated and measured. For different distances between tunnels and slope to tunnels respectively, the maximum quantity of explosives for single drives is studied.

The induction of autophagy by nanoparticles causes nanotoxicity, but appropriate modulation of autophagy by nanoparticles may have therapeutic potential. Multiwalled carbon nanotubes (MWCNTs) interact with cell membranes and membrane-associated molecules before and after internalization. These interactions alter cellular signaling and impact major cell functions such as cell cycle, apoptosis, and autophagy. In this work, we demonstrated that MWCNT-cell interactions can be modulated by varying densely distributed surface ligands on MWCNTs. Using a fluorescent autophagy-reporting cell line, we evaluated the autophagy induction capability of 81 surface-modified MWCNTs. We identified strong and moderate autophagy-inducing MWCNTs as well as those that did not induce autophagy. Variation of the surface ligand structure of strong autophagy nanoinducers led to the induction of different autophagy-activating signaling pathways, presumably through their different interactions with cell surface receptors.

Parameter estimation for linear continuous stochastic systems is studied via Haar wavelet. Wavelet transforms is equivalent to applying a family of low-pass filters with decreasing cutoff frequency on the resulting signal. This advantage results from wavelet. which the other orthogonal functions don't have, is used to study the Wiener process (WP). We show that the approximation process of WP with Haar wavelet is stationary and its covariance matrix is very spare and has a nice structure. Markov method and its recursive algorithms are presented. Numerical simulation results of the method are given.

In order to alleviate the increasing contradictions between the service supply of service zone and service demand of service object, and maintain the efficient, comfortable and safe highway, logical extension of Highway service zone is imperative. This paper researches on the service zone of Beijing-Hong Kong-Macao (B-HK-M) Expressway in Guangdong section through qualitative analysis and quantitative analysis. Qualitative analysis includes analyzing on the characteristic of service objects and services demand, and quantitative analysis is mainly to build up the mathematic model according to the current data of service zone, and to estimate the drive-in traffic volume. The result can be used to determine the functional configuration and type of proposed service zone, and shows that the extension of service zone of B-HK-M Expressway in Guangdong section is feasible and lucrative, providing scientific basis to the future design and space outlay of service zone of B-HK-M Expressway in Guangdong section.

In this paper, decentralized adaptive control problem is studied for a class of stochastic nonlinear large-scale systems in parametric non-strict-feedback forms. By employing the stochastic Lyapunov-like theorem and the backstepping design technique, the adaptive state feedback decentralized controller and parameters adaptive law are developed. It is shown that such an adaptive control scheme can guarantee that the closed-loop, large-scale, interconnected stochastic nonlinear system is globally bounded stable in probability.

The reaction mechanism of (CH 3 ) 3 CO with CO has been theoretically investigated using den-sity-functional theory (DFT) calculations at B3LYP/6-31G * level. In order to get more reliable energy values the single-point energy is evaluated at CCSD (T)/6-31++G ** level. The results show that the reaction is multi-channel and the reaction of (CH 3 ) 3 CO radical with CO mostly produces (CH 3 ) 3 C + CO 2 . The reaction could play a role in eliminating air pollution.