To investigate the seismic performance of a composite frame comprised of steel reinforced ultra high-strength concrete （SRUHSC） columns and steel reinforced concrete （SRC） beams, six interior frame joint specimens...To investigate the seismic performance of a composite frame comprised of steel reinforced ultra high-strength concrete （SRUHSC） columns and steel reinforced concrete （SRC） beams, six interior frame joint specimens were designed and tested under low cyclically lateral load. The effects of the axial load ratio and volumetric stirrup ratio were studied on the characteristics of the frame joint performance including crack pattern, failure mode, ductility, energy dissipation capacity, strength degradation and rigidity degradation. It was found that all joint specimens behaved in a ductile manner with flexural-shear failure in the joint core region while plastic hinges appeared at the beam ends. The ductility and energy absorption capacity of joints increased as the axial load ratio decreased and the volumetric stirIup ratio increased. The displacement ductility coefficient and equivalent damping coefficient of the joints fell between the corresponding coefficients of the steel reinforced concrete （SRC） frame joint and RC frame joint. The axial load ratio and volumetric stirrup ratio have less influence on the strength degradation and more influence on the stiffness degradation. The stiffness of the joint degrades more significantly for a low volumetric stirrup ratio and high axial load ratio. The characteristics obtained from the SRUHSC composite frame joint specimens with better seismic performance may be a useful reference in future engineering applications.展开更多
Aurora kinases are clearly implicated in tumorgenesis and have emerged as promising targets for cancer therapy in recent years.In a virtual screening attempt,22 compounds were identified from nearly 15,000 microbial n...Aurora kinases are clearly implicated in tumorgenesis and have emerged as promising targets for cancer therapy in recent years.In a virtual screening attempt,22 compounds were identified from nearly 15,000 microbial natural products as potential small-molecule inhib- itors of human Aurora-B kinase.When tested in yeast models,2 compounds(one is Jado- mycin B)showed preferential inhibition of ipl1-321(yeast Aurora kinase temperature sen- sitive mutant)than wild type yeast cell,suggesting these compounds are true Aurora kinase inhibitors.Further in vitro biochemical assay using purified recombinant Aurora-B kinase showed Jadomycin B inhibits Aurora-B activity in a dose-dependent fashion while two Jadomycin congeners,Jadomycin S and T,showed no activity.The marked differences in activities of Jadomycins were explained by docking analyses.Our results also showed that Jadomycin B competes with ATP for the kinase active center,which is consistent with our docking prediction.Like other Aurora kinase inhibitors,Jadomycin B also reduced the phos- phorylation of histone H3 on Ser10 in vivo.Cell culture based tests of Jadomycin B activity confirmed previous results that Jadomycin B could induce apoptosis of tumor cells without blocking cell cycle.Above results indicate that Jadomyicn B is a new Aurora B kinase inhibi- tor worthy of further investigation.The SAR(structure and activity relationship)analysis in- dicated that groups attached to the oxazolone ring of Jadomycin were important for its ability to enter the catalytic cleft and occupy the active site to inhibit Aurora-B kinase.Jadomycin offers an ideal scaffold to generate novel derivatives with a hydrophobic side chain on their oxazolone rings,from which we may find Aurora-B inhibitors with improved activity.展开更多
基金National Natural Science Foundation of China Under Grant No.50878037
文摘To investigate the seismic performance of a composite frame comprised of steel reinforced ultra high-strength concrete （SRUHSC） columns and steel reinforced concrete （SRC） beams, six interior frame joint specimens were designed and tested under low cyclically lateral load. The effects of the axial load ratio and volumetric stirrup ratio were studied on the characteristics of the frame joint performance including crack pattern, failure mode, ductility, energy dissipation capacity, strength degradation and rigidity degradation. It was found that all joint specimens behaved in a ductile manner with flexural-shear failure in the joint core region while plastic hinges appeared at the beam ends. The ductility and energy absorption capacity of joints increased as the axial load ratio decreased and the volumetric stirIup ratio increased. The displacement ductility coefficient and equivalent damping coefficient of the joints fell between the corresponding coefficients of the steel reinforced concrete （SRC） frame joint and RC frame joint. The axial load ratio and volumetric stirrup ratio have less influence on the strength degradation and more influence on the stiffness degradation. The stiffness of the joint degrades more significantly for a low volumetric stirrup ratio and high axial load ratio. The characteristics obtained from the SRUHSC composite frame joint specimens with better seismic performance may be a useful reference in future engineering applications.
文摘Aurora kinases are clearly implicated in tumorgenesis and have emerged as promising targets for cancer therapy in recent years.In a virtual screening attempt,22 compounds were identified from nearly 15,000 microbial natural products as potential small-molecule inhib- itors of human Aurora-B kinase.When tested in yeast models,2 compounds(one is Jado- mycin B)showed preferential inhibition of ipl1-321(yeast Aurora kinase temperature sen- sitive mutant)than wild type yeast cell,suggesting these compounds are true Aurora kinase inhibitors.Further in vitro biochemical assay using purified recombinant Aurora-B kinase showed Jadomycin B inhibits Aurora-B activity in a dose-dependent fashion while two Jadomycin congeners,Jadomycin S and T,showed no activity.The marked differences in activities of Jadomycins were explained by docking analyses.Our results also showed that Jadomycin B competes with ATP for the kinase active center,which is consistent with our docking prediction.Like other Aurora kinase inhibitors,Jadomycin B also reduced the phos- phorylation of histone H3 on Ser10 in vivo.Cell culture based tests of Jadomycin B activity confirmed previous results that Jadomycin B could induce apoptosis of tumor cells without blocking cell cycle.Above results indicate that Jadomyicn B is a new Aurora B kinase inhibi- tor worthy of further investigation.The SAR(structure and activity relationship)analysis in- dicated that groups attached to the oxazolone ring of Jadomycin were important for its ability to enter the catalytic cleft and occupy the active site to inhibit Aurora-B kinase.Jadomycin offers an ideal scaffold to generate novel derivatives with a hydrophobic side chain on their oxazolone rings,from which we may find Aurora-B inhibitors with improved activity.
