A discrete event system is a dynamical system whose state evolves in time by the occurrence of events at possibly irregular time intervals. Timed Petri nets are a graphical and mathematical modeling tool applicable to...A discrete event system is a dynamical system whose state evolves in time by the occurrence of events at possibly irregular time intervals. Timed Petri nets are a graphical and mathematical modeling tool applicable to discrete event systems in order to represent its states evolution where the timing at which the state changes is taken into consideration. One of the most important performance issues to be considered in a discrete event system is its stability. Lyapunov theory provides the required tools needed to aboard the stability and stabilization problems for discrete event systems modeled with timed Petri nets whose mathematical model is given in terms of difference equations. By proving stability one guarantees a bound on the discrete event systems state dynamics. When the system is unstable, a sufficient condition to stabilize the system is given. It is shown that it is possible to restrict the discrete event systems state space in such a way that boundedness is achieved. However, the restriction is not numerically precisely known. This inconvenience is overcome by considering a specific recurrence equation, in the max-plus algebra, which is assigned to the timed Petri net graphical model.展开更多
Objective To investigate the chemical compositions of Maxing Shigan Decoction(麻杏石甘汤,MXSGD)and elucidate its anti-influenza A virus(IAV)mechanism from prediction to validation.Methods Ultra high-performance liquid...Objective To investigate the chemical compositions of Maxing Shigan Decoction(麻杏石甘汤,MXSGD)and elucidate its anti-influenza A virus(IAV)mechanism from prediction to validation.Methods Ultra high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was employed to analyze the chemical compositions of MXSGD.Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV.A protein-protein interaction(PPI)network was then constructed,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations.A total of 24 BALB/c mice were infected with IAV to build IAV mouse models.After successful modelling,the mouse models were randomly divided into model,MXSGD high-dose(2.8 g/kg),MXSGD low-dose(1.4 g/kg),and oseltamivir(20.14 mg/kg)groups,with an additional normal mice as control group(n=6 per group).The treatments were administered by gavage daily between 8:00 a.m.and 10:00 a.m.for five consecutive days.Upon completion of the administration,the body weight ratio,lung index,protein content in the bronchoalveolar lavage fluid(BALF),and the levels of inflammatory factors including interleukin(IL)-6 and tumor necrosis factor(TNF)-αin mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection.Furthermore,the expression levels of mechanistic target of rapamycin(mTOR),hypoxia inducible factor(HIF)-1α,and vascular endothelial growth factor(VEGF)proteins in the HIF-1 signaling pathway,which was enriched by network pharmacology,were detected by Western blot.Results A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method.These chemical components can be classified into 9 primary categories and 31 secondary categories.After intersecting the chemical component targets with IAV-related targets,a total of 567 potential MXSGD components targeting IAV were identified.The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways,including apoptosis,TNF,HIF-1,and IL-17 signaling pathways.The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α,mTOR,and VEGF were all lower than–5.0 kcal/mol.Furthermore,molecular dynamics simulations confirmed the structural stability of the resulting complexes.Animal experiments showed that compared with the normal controls,IAV-infected mice showed significantly reduced body weight ratio,markedly increased lung index,protein content in BALF,and the levels of inflammatory factors such as IL-6 and TNF-α(P<0.01),thereby causing damage to the lung tissue;consequently,the expression levels of mTOR,HIF-1α,and VEGF proteins in the lung tissues of these mice were significantly elevated(P<0.01).However,after MXSGD treatment,the mouse models presented a significant increase in body weight ratio,as well as marked decreases in lung index,protein content in BALF,and the levels of inflammatory factors including IL-6 and TNF-α(P<0.01).Furthermore,the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR,HIF-1α,and VEGF proteins in lung tissues(P<0.01 or P<0.05).Conclusion MXSGD exerts anti-IAV effects through multi-component,multi-target,and multi-pathway synergism.Among them,1-methoxyphaseollin is identified as a potential key component,which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway,providing experimental evidence for the clinical application of MXSGD.展开更多
The solution for the forward displacement analysis（FDA） of the general 6-6 Stewart mechanism（i.e., the connection points of the moving and fixed platforms are not restricted to lying in a plane） has been extensive...The solution for the forward displacement analysis（FDA） of the general 6-6 Stewart mechanism（i.e., the connection points of the moving and fixed platforms are not restricted to lying in a plane） has been extensively studied, but the efficiency of the solution remains to be effectively addressed. To this end, an algebraic elimination method is proposed for the FDA of the general 6-6 Stewart mechanism. The kinematic constraint equations are built using conformal geometric algebra（CGA）. The kinematic constraint equations are transformed by a substitution of variables into seven equations with seven unknown variables. According to the characteristic of anti-symmetric matrices, the aforementioned seven equations can be further transformed into seven equations with four unknown variables by a substitution of variables using the Grobner basis. Its elimination weight is increased through changing the degree of one variable, and sixteen equations with four unknown variables can be obtained using the Grobner basis. A 40th-degree univariate polynomial equation is derived by constructing a relatively small-sized 9 × 9 Sylvester resultant matrix. Finally, two numerical examples are employed to verify the proposed method. The results indicate that the proposed method can effectively improve the efficiency of solution and reduce the computational burden because of the small-sized resultant matrix.展开更多
文摘A discrete event system is a dynamical system whose state evolves in time by the occurrence of events at possibly irregular time intervals. Timed Petri nets are a graphical and mathematical modeling tool applicable to discrete event systems in order to represent its states evolution where the timing at which the state changes is taken into consideration. One of the most important performance issues to be considered in a discrete event system is its stability. Lyapunov theory provides the required tools needed to aboard the stability and stabilization problems for discrete event systems modeled with timed Petri nets whose mathematical model is given in terms of difference equations. By proving stability one guarantees a bound on the discrete event systems state dynamics. When the system is unstable, a sufficient condition to stabilize the system is given. It is shown that it is possible to restrict the discrete event systems state space in such a way that boundedness is achieved. However, the restriction is not numerically precisely known. This inconvenience is overcome by considering a specific recurrence equation, in the max-plus algebra, which is assigned to the timed Petri net graphical model.
基金Natural Science Foundation of Hunan Province(2025JJ80078)Open Fund of Hunan University of Chinese Medicine(21PTKF1005)。
文摘Objective To investigate the chemical compositions of Maxing Shigan Decoction(麻杏石甘汤,MXSGD)and elucidate its anti-influenza A virus(IAV)mechanism from prediction to validation.Methods Ultra high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was employed to analyze the chemical compositions of MXSGD.Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV.A protein-protein interaction(PPI)network was then constructed,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations.A total of 24 BALB/c mice were infected with IAV to build IAV mouse models.After successful modelling,the mouse models were randomly divided into model,MXSGD high-dose(2.8 g/kg),MXSGD low-dose(1.4 g/kg),and oseltamivir(20.14 mg/kg)groups,with an additional normal mice as control group(n=6 per group).The treatments were administered by gavage daily between 8:00 a.m.and 10:00 a.m.for five consecutive days.Upon completion of the administration,the body weight ratio,lung index,protein content in the bronchoalveolar lavage fluid(BALF),and the levels of inflammatory factors including interleukin(IL)-6 and tumor necrosis factor(TNF)-αin mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection.Furthermore,the expression levels of mechanistic target of rapamycin(mTOR),hypoxia inducible factor(HIF)-1α,and vascular endothelial growth factor(VEGF)proteins in the HIF-1 signaling pathway,which was enriched by network pharmacology,were detected by Western blot.Results A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method.These chemical components can be classified into 9 primary categories and 31 secondary categories.After intersecting the chemical component targets with IAV-related targets,a total of 567 potential MXSGD components targeting IAV were identified.The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways,including apoptosis,TNF,HIF-1,and IL-17 signaling pathways.The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α,mTOR,and VEGF were all lower than–5.0 kcal/mol.Furthermore,molecular dynamics simulations confirmed the structural stability of the resulting complexes.Animal experiments showed that compared with the normal controls,IAV-infected mice showed significantly reduced body weight ratio,markedly increased lung index,protein content in BALF,and the levels of inflammatory factors such as IL-6 and TNF-α(P<0.01),thereby causing damage to the lung tissue;consequently,the expression levels of mTOR,HIF-1α,and VEGF proteins in the lung tissues of these mice were significantly elevated(P<0.01).However,after MXSGD treatment,the mouse models presented a significant increase in body weight ratio,as well as marked decreases in lung index,protein content in BALF,and the levels of inflammatory factors including IL-6 and TNF-α(P<0.01).Furthermore,the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR,HIF-1α,and VEGF proteins in lung tissues(P<0.01 or P<0.05).Conclusion MXSGD exerts anti-IAV effects through multi-component,multi-target,and multi-pathway synergism.Among them,1-methoxyphaseollin is identified as a potential key component,which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway,providing experimental evidence for the clinical application of MXSGD.
基金Supported by National Natural Science Foundation of China(Grant No.51375059)National Hi-tech Research and Development Program of China(863 Program,Grant No.2011AA040203)+1 种基金Special Fund for Agro-scientific Research in the Public Interest of China(Grant No.201313009-06)National Key Technology R&D Program of the Ministry of Science and Technology of China(Grant No.2013BAD17B06)
文摘The solution for the forward displacement analysis（FDA） of the general 6-6 Stewart mechanism（i.e., the connection points of the moving and fixed platforms are not restricted to lying in a plane） has been extensively studied, but the efficiency of the solution remains to be effectively addressed. To this end, an algebraic elimination method is proposed for the FDA of the general 6-6 Stewart mechanism. The kinematic constraint equations are built using conformal geometric algebra（CGA）. The kinematic constraint equations are transformed by a substitution of variables into seven equations with seven unknown variables. According to the characteristic of anti-symmetric matrices, the aforementioned seven equations can be further transformed into seven equations with four unknown variables by a substitution of variables using the Grobner basis. Its elimination weight is increased through changing the degree of one variable, and sixteen equations with four unknown variables can be obtained using the Grobner basis. A 40th-degree univariate polynomial equation is derived by constructing a relatively small-sized 9 × 9 Sylvester resultant matrix. Finally, two numerical examples are employed to verify the proposed method. The results indicate that the proposed method can effectively improve the efficiency of solution and reduce the computational burden because of the small-sized resultant matrix.
