SHIP-1 is an SH2 domain containing inositol-5-phosphatase that appears to be a negative regulator of hematopoiesis. To the potential effects of SHIP-1 on MMP2 secretion and migration of cancer cells, three murine SHIP...SHIP-1 is an SH2 domain containing inositol-5-phosphatase that appears to be a negative regulator of hematopoiesis. To the potential effects of SHIP-1 on MMP2 secretion and migration of cancer cells, three murine SHIP-1 mutants were made： △SH2-SHIP-1, △Ptase-SHIP-1, △Cter-SHIP-1. These mutant forms were subcloned as well as the wild type （WT） of murine SHIP-1 cDNA were subcloned into pcDNA3 expression vector, then transfected into and overexpressed SHIP-1 and its mutants in a Src-transformed 3Y1 cellline （SR3Y1）. The results showed that overexpression of wild type of SHIP-1 does not affect the MMP2 secretion in both SR3Y1 and 3Y1 cells, but can induce MMP9 secretion, while either WT SHIP-1, the SH2 domain, phosphatase domain, or C terminus deletion mutants could significantly block the MMP2 and MMP9 secretion in SR3Y1 cells and suppress cell invasion ability. The results confirmed SHIP-1 as a negative regulator for cell migration and invasion in transformed cells, and implied that it may function through each of its three domains.展开更多
The construction of the double-lane five-step ship lock of the Three Gorges Project （TGP） wascommenced in 1994, the excavation of the ship lock was completed by the end of 1999, and the ship lockwas put in operation...The construction of the double-lane five-step ship lock of the Three Gorges Project （TGP） wascommenced in 1994, the excavation of the ship lock was completed by the end of 1999, and the ship lockwas put in operation in June 2003. The side slopes of the ship lock are characterized by great height（170 m）, steepness （70 m in height of upright slope）, and great length （over 7000 m in total length）. Inassociation with the ship lock, the surrounding rocks in slope have a high potential to deform, withwhich the magnitude of deformation is restricted. Monitoring results show that the deformation of thefive-step ship lock high slopes of the TGP primarily occurred in excavation period, and deformationtended to be stable and convergent during operation period, suggesting the allowable ranges of deformation.At present, the slopes and lock chambers are stable, and the ship lock works well under normaloperation condition, enabling the social and economic benefits of the TGP. 2015 Institute of Rock and Soil Mechanics, Chinese Academy of Sciences. Production and hosting byElsevier B.V. All rights reserved.展开更多
Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR si...Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 （P3C） and Escherichia coli lipopolysaccharide （EcLPS） were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism （Pg1690） or TLR4 antagonism （Pg1449） and mutant E. coli LPS （LPxE/LPxF/WSK） were used. IL-lp, SH2-containing inositol phosphatase-1 （SHIP1） that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane （3AC） was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 （with SHIP1 activity） and mutant TLR4 ligands could enhance osteogenesis.展开更多
Contact nonlinear theory was researched. Contact problem was transformed into optimization problem containing Lagrange multiplier, and unsymmetrical stiffness matrix was transformed into symmetrical stiffness matrix. ...Contact nonlinear theory was researched. Contact problem was transformed into optimization problem containing Lagrange multiplier, and unsymmetrical stiffness matrix was transformed into symmetrical stiffness matrix. A finite element analysis （FEA） model defining more than 300 contact pairs for long nut-short screw locking mechanism of a large-scale vertical gear-rack typed ship-lift was built. Using augmented Lagrange method and symmetry algorithm of contact element stiffness, the FEA model was analyzed, and the contact stress of contact interfaces and the von Mises stress of key parts were obtained. The results show that the design of the locking mechanism meets the requirement of engineering, and this method is effective for solving large stole nonlinear contact pairs.展开更多
The mechanism of the locking of the E1 Nino event onset phase to boreal spring （from April to June） in an intermediate coupled ocean-atmosphere model is investigated. The results show that the seasonal variation of ...The mechanism of the locking of the E1 Nino event onset phase to boreal spring （from April to June） in an intermediate coupled ocean-atmosphere model is investigated. The results show that the seasonal variation of the zonal wind anomaly over the equatorial Pacific associated with the seasonal variation of the ITCZ is the mechanism of the locking in the model. From January to March of the E1 Nino year, the western wind anomaly over the western equatorial Pacific can excite the downwelling Kelvin wave that propagates eastward to the eastern and middle Pacific by April to June. From April to December of the year before the E1 Nifio year, the eastern wind anomaly over the equatorial Pacific forces the downwelling Rossby waves that modulate the ENSO cycle. The modulation and the reflection at the western boundary modulate the time of the transition from the cool to the warm phase to September of the year before the E1 Nifio year and cause the strongest downwelling Kelvin wave from the reflected Rossby waves at the western boundary to arrive in the middle and eastern equatorial Pacific by April to June of the E1 Nino year. The superposition of these two kinds of downwelling Kelvin waves causes the El Nino event to tend to occur from April to June.展开更多
While passing through a lock, a ship usually undergoes a steady forward motion at low speed. Owing to the size restriction of lock chamber, the shallow water and bank effects on the hydrodynamic forces acting on the s...While passing through a lock, a ship usually undergoes a steady forward motion at low speed. Owing to the size restriction of lock chamber, the shallow water and bank effects on the hydrodynamic forces acting on the ship may be remarkable, which may have an adverse effect on navigation safety. However, the complicated hydrodynamics is not yet fully understood. This paper focuses on the hydrodynamic forces acting on a ship passing through a lock. The unsteady viscous flow and hydrodynamic forces are calculated by applying an unsteady RANS code with a RNG k-e turbulence model. User-defined function （UDF） is compiled to define the ship motion. Meanwhile, the grid regeneration is dealt with by using the dynamic mesh method and sliding interface technique. Numerical study is carried out for a bulk carrier ship passing through the Pierre Vandamme Lock in Zeebrugge at the model scale. The proposed method is validated by comparing the numerical results with the data of captive model tests. By analyzing the numerical results obtained at different speeds, water depths and eccentricities, the influences of speed, water depth and eccentricity on the hydrodynamic forces are illustrated. The numerical method proposed in this paper can qualitatively predict the ship-lock hydrodynamic interaction. It can provide certain guidance on the manoeuvring and control of ships passing through a lock.展开更多
AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR...AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain-and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS MiR-155 directly bound to the 3'-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and proinflammatory secretions including IL-6, TNF-alpha, IL-1 beta, and IFN-gamma, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and in-flammatory response, were observed in the antagomiR-155-treated mice. CONCLUSION MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.展开更多
A comprehensive investigation was performed for repairing the different types of cracks appearing on the surface or inside the concrete lining at various depths.The mate- rial properties used in grouting and two metho...A comprehensive investigation was performed for repairing the different types of cracks appearing on the surface or inside the concrete lining at various depths.The mate- rial properties used in grouting and two methods for crack repair were discussed in details, and consequently reliable repair measures were proposed and implemented.It is a better choice to adopt the hole-drilling method for the relatively regular crack.The grouting pres- sure should not be too high and it is generally between 0.4～0.6 MPa.For the second time grouting,the pressure maybe increased to 0.8 MPa.Other method is the pasting nozzles method which is more suitable for irregular cracks such as cracks with intensive density and crossing cracks.Its grouting pressure is generally between 0.6～1.0 MPa.The in-situ tests in Three Gorges Project demonstrate favorably the feasibility and applicability of the proposed methods for crack repair within the lining concrete.展开更多
基金the Sasagawa Medical Fellowship from Japan-Sino Medical Association with funds from the Nippon Foundation.
文摘SHIP-1 is an SH2 domain containing inositol-5-phosphatase that appears to be a negative regulator of hematopoiesis. To the potential effects of SHIP-1 on MMP2 secretion and migration of cancer cells, three murine SHIP-1 mutants were made： △SH2-SHIP-1, △Ptase-SHIP-1, △Cter-SHIP-1. These mutant forms were subcloned as well as the wild type （WT） of murine SHIP-1 cDNA were subcloned into pcDNA3 expression vector, then transfected into and overexpressed SHIP-1 and its mutants in a Src-transformed 3Y1 cellline （SR3Y1）. The results showed that overexpression of wild type of SHIP-1 does not affect the MMP2 secretion in both SR3Y1 and 3Y1 cells, but can induce MMP9 secretion, while either WT SHIP-1, the SH2 domain, phosphatase domain, or C terminus deletion mutants could significantly block the MMP2 and MMP9 secretion in SR3Y1 cells and suppress cell invasion ability. The results confirmed SHIP-1 as a negative regulator for cell migration and invasion in transformed cells, and implied that it may function through each of its three domains.
文摘The construction of the double-lane five-step ship lock of the Three Gorges Project （TGP） wascommenced in 1994, the excavation of the ship lock was completed by the end of 1999, and the ship lockwas put in operation in June 2003. The side slopes of the ship lock are characterized by great height（170 m）, steepness （70 m in height of upright slope）, and great length （over 7000 m in total length）. Inassociation with the ship lock, the surrounding rocks in slope have a high potential to deform, withwhich the magnitude of deformation is restricted. Monitoring results show that the deformation of thefive-step ship lock high slopes of the TGP primarily occurred in excavation period, and deformationtended to be stable and convergent during operation period, suggesting the allowable ranges of deformation.At present, the slopes and lock chambers are stable, and the ship lock works well under normaloperation condition, enabling the social and economic benefits of the TGP. 2015 Institute of Rock and Soil Mechanics, Chinese Academy of Sciences. Production and hosting byElsevier B.V. All rights reserved.
基金supported by Elam M. and Georgina E.Hack Memorial Research Funds,Department of Periodontics,University of Washington,Seattle,WA,USAsupported by WVCTSI funds,West Virginia University,Morgantown,WV,USA
文摘Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 （P3C） and Escherichia coli lipopolysaccharide （EcLPS） were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism （Pg1690） or TLR4 antagonism （Pg1449） and mutant E. coli LPS （LPxE/LPxF/WSK） were used. IL-lp, SH2-containing inositol phosphatase-1 （SHIP1） that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane （3AC） was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 （with SHIP1 activity） and mutant TLR4 ligands could enhance osteogenesis.
基金Supported by the Key Research Project of StatePower Corporation (SPKJ 0l6-06)the Key Scientific ResearchProject of Hubei Province ( 2004AC101D31)
文摘Contact nonlinear theory was researched. Contact problem was transformed into optimization problem containing Lagrange multiplier, and unsymmetrical stiffness matrix was transformed into symmetrical stiffness matrix. A finite element analysis （FEA） model defining more than 300 contact pairs for long nut-short screw locking mechanism of a large-scale vertical gear-rack typed ship-lift was built. Using augmented Lagrange method and symmetry algorithm of contact element stiffness, the FEA model was analyzed, and the contact stress of contact interfaces and the von Mises stress of key parts were obtained. The results show that the design of the locking mechanism meets the requirement of engineering, and this method is effective for solving large stole nonlinear contact pairs.
基金This work was supported by The National Key Basic Reserch and Development Project of China(2004CB418303)Project 4023100 of the Major Research Program for Global Change and Regional ResponseNational Natural Science Foundation of China(Grant No.40231005).
文摘The mechanism of the locking of the E1 Nino event onset phase to boreal spring （from April to June） in an intermediate coupled ocean-atmosphere model is investigated. The results show that the seasonal variation of the zonal wind anomaly over the equatorial Pacific associated with the seasonal variation of the ITCZ is the mechanism of the locking in the model. From January to March of the E1 Nino year, the western wind anomaly over the western equatorial Pacific can excite the downwelling Kelvin wave that propagates eastward to the eastern and middle Pacific by April to June. From April to December of the year before the E1 Nifio year, the eastern wind anomaly over the equatorial Pacific forces the downwelling Rossby waves that modulate the ENSO cycle. The modulation and the reflection at the western boundary modulate the time of the transition from the cool to the warm phase to September of the year before the E1 Nifio year and cause the strongest downwelling Kelvin wave from the reflected Rossby waves at the western boundary to arrive in the middle and eastern equatorial Pacific by April to June of the E1 Nino year. The superposition of these two kinds of downwelling Kelvin waves causes the El Nino event to tend to occur from April to June.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.51061130548 and 51179019)
文摘While passing through a lock, a ship usually undergoes a steady forward motion at low speed. Owing to the size restriction of lock chamber, the shallow water and bank effects on the hydrodynamic forces acting on the ship may be remarkable, which may have an adverse effect on navigation safety. However, the complicated hydrodynamics is not yet fully understood. This paper focuses on the hydrodynamic forces acting on a ship passing through a lock. The unsteady viscous flow and hydrodynamic forces are calculated by applying an unsteady RANS code with a RNG k-e turbulence model. User-defined function （UDF） is compiled to define the ship motion. Meanwhile, the grid regeneration is dealt with by using the dynamic mesh method and sliding interface technique. Numerical study is carried out for a bulk carrier ship passing through the Pierre Vandamme Lock in Zeebrugge at the model scale. The proposed method is validated by comparing the numerical results with the data of captive model tests. By analyzing the numerical results obtained at different speeds, water depths and eccentricities, the influences of speed, water depth and eccentricity on the hydrodynamic forces are illustrated. The numerical method proposed in this paper can qualitatively predict the ship-lock hydrodynamic interaction. It can provide certain guidance on the manoeuvring and control of ships passing through a lock.
文摘AIM To explore the mechanism by which microRNA-155 (miR-155) regulates the pathogenesis of experimental colitis. METHODS A luciferase assay was performed to confirm the binding of miR-155 to the SHIP-1 3'-UTR. MiR-155 mimics, negative controls and SHIP-1 expression/knockdown vectors were established and then utilized in gain-and loss-of-function studies performed in raw264.7 cells and primary bone marrow-derived macrophages (BMDMs). Thereafter, dextran sulfate sodium (DSS)-induced colitis mouse model with or without antagomiR-155 treatment was established, and the levels of miR-155 and SHIP-1, as well as the pro-inflammatory capabilities, were measured by western blot, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS MiR-155 directly bound to the 3'-UTR of SHIP-1 mRNA and induced a significant decrease in SHIP-1 expression in both raw264.7 cells and primary BMDMs. MiR-155 markedly promoted cell proliferation and proinflammatory secretions including IL-6, TNF-alpha, IL-1 beta, and IFN-gamma, whereas these effects could be reversed by the restoration of SHIP-1 expression. In vivo studies showed that antagomiR-155 administration could alleviate DSS-induced intestinal inflammation in Balb/c mice. Moreover, significantly increased SHIP-1 expression, as well as decreased Akt activation and in-flammatory response, were observed in the antagomiR-155-treated mice. CONCLUSION MiR-155 promotes experimental colitis by repressing SHIP-1 expression. Thus, the inhibition of miR-155 might be a promising strategy for therapy.
基金the National Natural Science Foundation of China(10602049)
文摘A comprehensive investigation was performed for repairing the different types of cracks appearing on the surface or inside the concrete lining at various depths.The mate- rial properties used in grouting and two methods for crack repair were discussed in details, and consequently reliable repair measures were proposed and implemented.It is a better choice to adopt the hole-drilling method for the relatively regular crack.The grouting pres- sure should not be too high and it is generally between 0.4～0.6 MPa.For the second time grouting,the pressure maybe increased to 0.8 MPa.Other method is the pasting nozzles method which is more suitable for irregular cracks such as cracks with intensive density and crossing cracks.Its grouting pressure is generally between 0.6～1.0 MPa.The in-situ tests in Three Gorges Project demonstrate favorably the feasibility and applicability of the proposed methods for crack repair within the lining concrete.
