As a subsequent work of previous studies of authors, a new parallel computation approach is proposed to simulate the coupled dynamics of a rigid-flexible multibody system and compressible fluid. In this approach, the ...As a subsequent work of previous studies of authors, a new parallel computation approach is proposed to simulate the coupled dynamics of a rigid-flexible multibody system and compressible fluid. In this approach, the smoothed particle hydrodynamics(SPH) method is used to model the compressible fluid, the natural coordinate formulation(NCF) and absolute nodal coordinate formulation(ANCF) are used to model the rigid and flexible bodies, respectively. In order to model the compressible fluid properly and efficiently via SPH method, three measures are taken as follows. The first is to use the Riemann solver to cope with the fluid compressibility, the second is to define virtual particles of SPH to model the dynamic interaction between the fluid and the multibody system, and the third is to impose the boundary conditions of periodical inflow and outflow to reduce the number of SPH particles involved in the computation process. Afterwards, a parallel computation strategy is proposed based on the graphics processing unit(GPU) to detect the neighboring SPH particles and to solve the dynamic equations of SPH particles in order to improve the computation efficiency. Meanwhile, the generalized-alpha algorithm is used to solve the dynamic equations of the multibody system. Finally, four case studies are given to validate the proposed parallel computation approach.展开更多
Graded hypoxia is a common microenvironment in malignant solid tumors.As a central regulator in the hypoxic response,hypoxia-inducible factor-1(HIF-1)can induce multiple cellular processes including glycolysis,angioge...Graded hypoxia is a common microenvironment in malignant solid tumors.As a central regulator in the hypoxic response,hypoxia-inducible factor-1(HIF-1)can induce multiple cellular processes including glycolysis,angiogenesis,and necroptosis.How cells exploit the HIF-1 pathway to coordinate different processes to survive hypoxia remains unclear.We developed an integrated model of the HIF-1αnetwork to elucidate the mechanism of cellular adaptation to hypoxia.By numerical simulations and bifurcation analysis,we found that HIF-1αis progressively activated with worsening hypoxia due to the sequential deactivation of the hydroxylases prolyl hydroxylase domain enzymes and factor inhibiting HIF(FIH).Bistable switches control the activation and deactivation processes.As a result,glycolysis,immunosuppression,angiogenesis,and necroptosis are orderly elicited in aggravating hypoxia.To avoid the excessive accumulation of lactic acid during glycolysis,HIF-1αinduces monocarboxylate transporter and carbonic anhydrase 9 sequentially to export intracellular hydrogen ions,facilitating tumor cell survival.HIF-1α-induced miR-182 facilitates vascular endothelial growth factor production to promote angiogenesis under moderate hypoxia.The imbalance between accumulation and removal of lactic acid in severe hypoxia may result in acidosis and induce cell necroptosis.In addition,the deactivation of FIH results in the destabilization of HIF-1αin anoxia.Collectively,HIF-1αorchestrates the adaptation of tumor cells to hypoxia by selectively inducing its targets according to the severity of hypoxia.Our work may provide clues for tumor therapy by targeting the HIF-1 pathway.展开更多
基金supported by the 111 China Project(Grant No.B16003)the National Natural Science Foundation of China(Grant Nos.11290151,11702022,and 11221202)
文摘As a subsequent work of previous studies of authors, a new parallel computation approach is proposed to simulate the coupled dynamics of a rigid-flexible multibody system and compressible fluid. In this approach, the smoothed particle hydrodynamics(SPH) method is used to model the compressible fluid, the natural coordinate formulation(NCF) and absolute nodal coordinate formulation(ANCF) are used to model the rigid and flexible bodies, respectively. In order to model the compressible fluid properly and efficiently via SPH method, three measures are taken as follows. The first is to use the Riemann solver to cope with the fluid compressibility, the second is to define virtual particles of SPH to model the dynamic interaction between the fluid and the multibody system, and the third is to impose the boundary conditions of periodical inflow and outflow to reduce the number of SPH particles involved in the computation process. Afterwards, a parallel computation strategy is proposed based on the graphics processing unit(GPU) to detect the neighboring SPH particles and to solve the dynamic equations of SPH particles in order to improve the computation efficiency. Meanwhile, the generalized-alpha algorithm is used to solve the dynamic equations of the multibody system. Finally, four case studies are given to validate the proposed parallel computation approach.
基金supported by the National Natural Science Foundation of China(nos.12090052,11874209,11574139,and 11934008).
文摘Graded hypoxia is a common microenvironment in malignant solid tumors.As a central regulator in the hypoxic response,hypoxia-inducible factor-1(HIF-1)can induce multiple cellular processes including glycolysis,angiogenesis,and necroptosis.How cells exploit the HIF-1 pathway to coordinate different processes to survive hypoxia remains unclear.We developed an integrated model of the HIF-1αnetwork to elucidate the mechanism of cellular adaptation to hypoxia.By numerical simulations and bifurcation analysis,we found that HIF-1αis progressively activated with worsening hypoxia due to the sequential deactivation of the hydroxylases prolyl hydroxylase domain enzymes and factor inhibiting HIF(FIH).Bistable switches control the activation and deactivation processes.As a result,glycolysis,immunosuppression,angiogenesis,and necroptosis are orderly elicited in aggravating hypoxia.To avoid the excessive accumulation of lactic acid during glycolysis,HIF-1αinduces monocarboxylate transporter and carbonic anhydrase 9 sequentially to export intracellular hydrogen ions,facilitating tumor cell survival.HIF-1α-induced miR-182 facilitates vascular endothelial growth factor production to promote angiogenesis under moderate hypoxia.The imbalance between accumulation and removal of lactic acid in severe hypoxia may result in acidosis and induce cell necroptosis.In addition,the deactivation of FIH results in the destabilization of HIF-1αin anoxia.Collectively,HIF-1αorchestrates the adaptation of tumor cells to hypoxia by selectively inducing its targets according to the severity of hypoxia.Our work may provide clues for tumor therapy by targeting the HIF-1 pathway.
