In order to study the cross-linking density and aging constitutive relationship of HTPB coating during storage,the thermal accelerated aging tests at 0%,3%,6%and 9%prestrains were carried out.The crosslinking density ...In order to study the cross-linking density and aging constitutive relationship of HTPB coating during storage,the thermal accelerated aging tests at 0%,3%,6%and 9%prestrains were carried out.The crosslinking density of HTPB coating at different aging stages were tested using low-field^1 H NMR and the variation of cross-linking density was analyzed.The aging model of cross-linking density considering the chemical aging and the physical stretching factors was established.The uniaxial tensile tests were carried out on HTPB coating at different aging stages and the cross-linking density was introduced into Ogden hyperelastic constitutive model as a characterization parameter of correction coefficient.Combined with uniaxial tensile test results,a prestrain aging constitutive model of HTPB coating was established.The results show that the cross-linking density of HTPB coating increases rapidly at first and then slowly with the increase of thermal accelerated aging time without prestrain.Under prestrain conditions,the crosslinking density of HTPB coating decreases at the early stage,and increases rapidly at first and then slowly at the middle and late stages of thermal accelerated aging.The correlation coefficients of aging model of cross-linking density and aging constitutive model with test results are R>0.9500 and R>0.9900 respectively,which can be used to accurately describe the cross-linking density and aging constitutive relationship of HTPB coating under prestrain accelerated thermal aging conditions.展开更多
A new unsteady three-dimensional convective-diffusive mathematical model for the transportation of macromolecules and water across the arterial wall was proposed . After the formation of leaky junctions due to the mit...A new unsteady three-dimensional convective-diffusive mathematical model for the transportation of macromolecules and water across the arterial wall was proposed . After the formation of leaky junctions due to the mitosis of endothelial cell of the arterial wall, the macromolecular transport happens surrounding the leaky cells. The arterial wall was divided into four layers: the endothelial layer, the subendothelial intima, the internal elastic lamina and the media for the convenience of research. The time-dependent concentration growth, the effect of the shape of endothelial cell and the effect of physiological parameters were analyzed. The analytical solution of velocity field and pressure field of water flow across the arterial wall were obtained; and concentration distribution of three macromolecules; LDL, HRP and Albumin, were calculated with numerical simulation method. The new theory predicts, the maximum and distribution areas of time dependent concentration with round-shape endothelial cell are both larger than that with ellipse-shape endothelial cell. The model also predicts the concentration growth is much alike that of a two-dimensional model and it shows that the concentration reaches its peak at the leaky junction where atherosclerotic formation frequently occurs and falls down rapidly in a limited area beginning from its earlier-time growth to the state when macromolecular transfer approaches steadily. These predictions of the new model are in agreement with the experimental observation for the growth and concentration distribution of LDL and Albumin.展开更多
Von Willebrand factor(VWF)is a multimeric plasma glycoprotein that captures platelets to the sites of vascular injury.The adhesive activity of VWF is highly dependent on the size of VWF.Hemodynamic force converts coil...Von Willebrand factor(VWF)is a multimeric plasma glycoprotein that captures platelets to the sites of vascular injury.The adhesive activity of VWF is highly dependent on the size of VWF.Hemodynamic force converts coiled VWF to linear form,exposing the scissile bond Y1605-M1606 within A2 domain.ADAMTS13(A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif 13)inhibits excessive platelet aggregation by specifically cleaving the cryptic peptide bond of VWF to regulate its size.Deficiency of ADAMTS13 activity,caused by either mutations or by inhibitory autoantibody,results in the accumulation of ultra-large VWF in plasma,leading to excessive platelet aggregation and disseminated VWF/plateletrich thrombus formation,which is the characteristic of thrombotic thrombocytopenic purpura(TTP).Previous studies showed that,circulating ADAMTS13 generally adopts a closed conformation by the interaction of its TSP8-CUB domain and Spacer domain.This auto-inhibition is relieved when VWF D4-CK domain binds to C-termini of ADAMTS13 disrupting the interaction between TSP8-CUB domain and Spacer domain.As a result,ADAMTS13 changes into an open conformation,exposing more VWF binding sites.Open conformation of ADAMTS13 is considered as a hallmark of acute acquired TTP.However,the dynamic process of conformational transition of ADAMTS13 has not been fully understood.Besides,there are variable natural truncations of ADAMTS13 in circulation,including the truncations lacking the metalloprotease domain.The role of these truncations without enzyme activity in hemostasis is still unknown.Given that there are multiple binding sites in both VWF and open ADAMTS13,we hypothesize that open ADAMTS13 promotes the cross-linking of VWF.Atomic force microscopy(AFM)was employed to prove our hypothesis at single molecule level.The N-termini of ADAMTS13 was immobilized on the polystyrene surface,while the C-termini was stretched by AFM tip.The force required for unfolding was measured and the molecular length increment was obtained by fitting the data with worm-like chain model.In addition,both the polystyrene surface and cantilever were coated with VWF,the adhesion frequency of VWF-VWF interaction were measured in the presence or absence of soluble DisC(a ADAMTS13 truncation that lacks the metalloprotease domain).Our results show that,the rupture force required for ADAMTS13 unfolding is^22 pN.The length increment is mainly in the range of 0-50 nm,and the peak value is 22.6±1.8 nm,consistent with the predicted value of homologous modeling(~27 nm)in literature.The adhesion frequency of two VWF molecules increased in the presence of DisC in a concentration-dependent manner.With or without DisC in solution,the rupture force of the VWF molecules was^20 pN.The bond lifetime of two VWF declined with force increasing,the characteristic of a'slip'bond.In contrast,in the presence of DisC,the bond lifetime firstly increased as force increasing and then decreased as force increasing further,which is the characteristic of a'catch-slip'bond.The distinct patterns of bond lifetime vs force in the presence and absence of DisC indicate that DisC promotes the cross-linking of two VWF molecules.Our data suggest that open ADAMTS13 stabilizes the network of VWF multimers and promotes platelet adhesion.展开更多
基金supported by the National Defense Pre-Research Foundation of China[grant number ZS2015070132A12002]。
文摘In order to study the cross-linking density and aging constitutive relationship of HTPB coating during storage,the thermal accelerated aging tests at 0%,3%,6%and 9%prestrains were carried out.The crosslinking density of HTPB coating at different aging stages were tested using low-field^1 H NMR and the variation of cross-linking density was analyzed.The aging model of cross-linking density considering the chemical aging and the physical stretching factors was established.The uniaxial tensile tests were carried out on HTPB coating at different aging stages and the cross-linking density was introduced into Ogden hyperelastic constitutive model as a characterization parameter of correction coefficient.Combined with uniaxial tensile test results,a prestrain aging constitutive model of HTPB coating was established.The results show that the cross-linking density of HTPB coating increases rapidly at first and then slowly with the increase of thermal accelerated aging time without prestrain.Under prestrain conditions,the crosslinking density of HTPB coating decreases at the early stage,and increases rapidly at first and then slowly at the middle and late stages of thermal accelerated aging.The correlation coefficients of aging model of cross-linking density and aging constitutive model with test results are R>0.9500 and R>0.9900 respectively,which can be used to accurately describe the cross-linking density and aging constitutive relationship of HTPB coating under prestrain accelerated thermal aging conditions.
文摘A new unsteady three-dimensional convective-diffusive mathematical model for the transportation of macromolecules and water across the arterial wall was proposed . After the formation of leaky junctions due to the mitosis of endothelial cell of the arterial wall, the macromolecular transport happens surrounding the leaky cells. The arterial wall was divided into four layers: the endothelial layer, the subendothelial intima, the internal elastic lamina and the media for the convenience of research. The time-dependent concentration growth, the effect of the shape of endothelial cell and the effect of physiological parameters were analyzed. The analytical solution of velocity field and pressure field of water flow across the arterial wall were obtained; and concentration distribution of three macromolecules; LDL, HRP and Albumin, were calculated with numerical simulation method. The new theory predicts, the maximum and distribution areas of time dependent concentration with round-shape endothelial cell are both larger than that with ellipse-shape endothelial cell. The model also predicts the concentration growth is much alike that of a two-dimensional model and it shows that the concentration reaches its peak at the leaky junction where atherosclerotic formation frequently occurs and falls down rapidly in a limited area beginning from its earlier-time growth to the state when macromolecular transfer approaches steadily. These predictions of the new model are in agreement with the experimental observation for the growth and concentration distribution of LDL and Albumin.
基金supported by National Natural Science Foundation of China ( 31500759,31771012)the Guangzhou Science Technology Program ( 201707010062)
文摘Von Willebrand factor(VWF)is a multimeric plasma glycoprotein that captures platelets to the sites of vascular injury.The adhesive activity of VWF is highly dependent on the size of VWF.Hemodynamic force converts coiled VWF to linear form,exposing the scissile bond Y1605-M1606 within A2 domain.ADAMTS13(A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif 13)inhibits excessive platelet aggregation by specifically cleaving the cryptic peptide bond of VWF to regulate its size.Deficiency of ADAMTS13 activity,caused by either mutations or by inhibitory autoantibody,results in the accumulation of ultra-large VWF in plasma,leading to excessive platelet aggregation and disseminated VWF/plateletrich thrombus formation,which is the characteristic of thrombotic thrombocytopenic purpura(TTP).Previous studies showed that,circulating ADAMTS13 generally adopts a closed conformation by the interaction of its TSP8-CUB domain and Spacer domain.This auto-inhibition is relieved when VWF D4-CK domain binds to C-termini of ADAMTS13 disrupting the interaction between TSP8-CUB domain and Spacer domain.As a result,ADAMTS13 changes into an open conformation,exposing more VWF binding sites.Open conformation of ADAMTS13 is considered as a hallmark of acute acquired TTP.However,the dynamic process of conformational transition of ADAMTS13 has not been fully understood.Besides,there are variable natural truncations of ADAMTS13 in circulation,including the truncations lacking the metalloprotease domain.The role of these truncations without enzyme activity in hemostasis is still unknown.Given that there are multiple binding sites in both VWF and open ADAMTS13,we hypothesize that open ADAMTS13 promotes the cross-linking of VWF.Atomic force microscopy(AFM)was employed to prove our hypothesis at single molecule level.The N-termini of ADAMTS13 was immobilized on the polystyrene surface,while the C-termini was stretched by AFM tip.The force required for unfolding was measured and the molecular length increment was obtained by fitting the data with worm-like chain model.In addition,both the polystyrene surface and cantilever were coated with VWF,the adhesion frequency of VWF-VWF interaction were measured in the presence or absence of soluble DisC(a ADAMTS13 truncation that lacks the metalloprotease domain).Our results show that,the rupture force required for ADAMTS13 unfolding is^22 pN.The length increment is mainly in the range of 0-50 nm,and the peak value is 22.6±1.8 nm,consistent with the predicted value of homologous modeling(~27 nm)in literature.The adhesion frequency of two VWF molecules increased in the presence of DisC in a concentration-dependent manner.With or without DisC in solution,the rupture force of the VWF molecules was^20 pN.The bond lifetime of two VWF declined with force increasing,the characteristic of a'slip'bond.In contrast,in the presence of DisC,the bond lifetime firstly increased as force increasing and then decreased as force increasing further,which is the characteristic of a'catch-slip'bond.The distinct patterns of bond lifetime vs force in the presence and absence of DisC indicate that DisC promotes the cross-linking of two VWF molecules.Our data suggest that open ADAMTS13 stabilizes the network of VWF multimers and promotes platelet adhesion.
