A record-breaking heavy rainfall event that occurred in Zhengzhou,Henan province during 19–21 July 2021 is simulated using the Weather Research and Forecasting Model,and the large-scale precipitation efficiency(LSPE)...A record-breaking heavy rainfall event that occurred in Zhengzhou,Henan province during 19–21 July 2021 is simulated using the Weather Research and Forecasting Model,and the large-scale precipitation efficiency(LSPE)and cloud-microphysical precipitation efficiency(CMPE)of the rainfall are analyzed based on the model results.Then,the key physical factors that influenced LSPE and CMPE,and the possible mechanisms for the extreme rainfall over Zhengzhou are explored.Results show that water vapor flux convergence was the key factor that influenced LSPE.Water vapor was transported by the southeasterly winds between Typhoon In-Fa(2021)and the subtropical high,and the southerly flow of Typhoon Cempaka(2021),and converged in Zhengzhou due to the blocking by the Taihang and Funiu Mountains in western Henan province.Strong moisture convergence centers were formed on the windward slope of the mountains,which led to high LSPE in Zhengzhou.From the perspective of CMPE,the net consumption of water vapor by microphysical processes was the key factor that influenced CMPE.Quantitative budget analysis suggests that water vapor was mainly converted to cloud water and ice-phase particles and then transformed to raindrops through melting of graupel and accretion of cloud water by rainwater during the heavy precipitation stage.The dry intrusion in the middle and upper levels over Zhengzhou made the high potential vorticity descend from the upper troposphere and enhanced the convective instability.Moreover,the intrusion of cold and dry air resulted in the supersaturation and condensation of water vapor,which contributed to the heavy rainfall in Zhengzhou.展开更多
This study investigates the bond between seawater scoria aggregate concrete(SSAC)and stainless reinforcement(SR)through a series of pull-out tests.A total of 39 specimens,considering five experimental parameters—con-...This study investigates the bond between seawater scoria aggregate concrete(SSAC)and stainless reinforcement(SR)through a series of pull-out tests.A total of 39 specimens,considering five experimental parameters—con-crete type(SSAC,ordinary concrete(OC)and seawater coral aggregate concrete(SCAC)),reinforcement type(SR,ordinary reinforcement(OR)),bond length(3,5 and 8 times bar diameter),concrete strength(C25 and C30)and concrete cover thickness(42 and 67 mm)—were prepared.The typical bond properties(failure pattern,bond strength,bond-slip curves and bond stress distribution,etc.)of seawater scoria aggregate concrete-stainless rein-forcement(SSAC-SR)specimen were systematically studied.Generally,the failure pattern changed with the con-crete type used,and the failure surface of SSAC specimen was different from that of OC specimen.SSAC enhanced the bond strength of specimen,while its effect on the deformation of SSAC-SR was negative.On aver-age,the peak slip of SSAC specimens was 20%lower while the bond strength was 6.7%higher compared to OC specimens under the similar conditions.The effects of variables on the bond strength of SSAC–SR in increasing order are concrete type,bond length,concrete strength and cover thickness.The bond-slip curve of SSAC-SR specimen consisted of micro-slipping,slipping and declining stages.It can be obtained that SSAC reduced the curve curvature of bond-slip,and the decline of curve became steep after adopting SR.The typical distribution of bond stress along bond length changed with the types of concrete and reinforcement used.Finally,a specific expression of the bond stress-slip curve considering the effects of various variables was established,which could provide a basis for the practical application of reinforced SSAC.展开更多
The solution strategy of the heuristic algorithm is pre-set and has good performance in the conventional cloud resource scheduling process.However,for complex and dynamic cloud service scheduling tasks,due to the diff...The solution strategy of the heuristic algorithm is pre-set and has good performance in the conventional cloud resource scheduling process.However,for complex and dynamic cloud service scheduling tasks,due to the difference in service attributes,the solution efficiency of a single strategy is low for such problems.In this paper,we presents a hyper-heuristic algorithm based on reinforcement learning(HHRL)to optimize the completion time of the task sequence.Firstly,In the reward table setting stage of HHRL,we introduce population diversity and integrate maximum time to comprehensively deter-mine the task scheduling and the selection of low-level heuristic strategies.Secondly,a task computational complexity estimation method integrated with linear regression is proposed to influence task scheduling priorities.Besides,we propose a high-quality candidate solution migration method to ensure the continuity and diversity of the solving process.Compared with HHSA,ACO,GA,F-PSO,etc,HHRL can quickly obtain task complexity,select appropriate heuristic strategies for task scheduling,search for the the best makspan and have stronger disturbance detection ability for population diversity.展开更多
AIM:To clarify whether histone deacetylase inhibitors histone deacetylase inhibitors(HDACIs)can sensitize hepatocellular carcinoma(HCC)cells to sorafenib treatment.METHODS:Bax,Bcl-2,ATG5-ATG12,p21,and p27protein level...AIM:To clarify whether histone deacetylase inhibitors histone deacetylase inhibitors(HDACIs)can sensitize hepatocellular carcinoma(HCC)cells to sorafenib treatment.METHODS:Bax,Bcl-2,ATG5-ATG12,p21,and p27protein levels in Hep3B,HepG2,and PLC/PRF/5 cells were examined by Western blot.CCK8 and a fluorometric caspase-3 assay were used to examine cellular viability and apoptosis levels.The effect of Beclin-1 on sensitization of HCC cells to sorafenib was examined by transfecting Beclin-1 siRNA into Hep3B,HepG2,and PLC/PRF/5 cells.RESULTS:Autophagy inhibition enhances the inhibitory effects of vorinostat and sorafenib alone or in combination on HCC cell growth.Vorinostat and sorafenib synergistically induced apoptosis and cell cycle alterations.Western blot data indicated that HDACIs and Beclin-1 knockdown increased the p53 acetylation level.The knockdown of Beclin-1 enhanced the synergistic effect of the combination of vorinostat with sorafenib.CONCLUSION:HDACIs can sensitize HCC cells to sorafenib treatment by regulating the acetylation level of Beclin-1.展开更多
A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plas...A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and re-extracted with dichloromethane, after which the analyte and triptorelin as an internal standard (IS) were separated on a 300SB-C18 column (150 mm 4.6 mm i.d., 5 mm particle size) using 0.1% formic acid:methanol (45:55, v/v) as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization (ESI) interface, was operated in the positive ion mode, and the multiple-reaction monitoring (MRM) transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5-249.3, respectively. The lower limit of quantification (LLOQ) was 1 ng/mL for 100 mL plasma sample and the assay was linear over the concentration range 1-1000 ng/mL. The accuracy was within a range from 0.4% to 0.5% in terms of relative error (RE) and the intra- and inter-day precisions in terms of relative standard deviation (RSD) were r2.92 and r3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin (0.5 mg/kg) to Chinese volunteers.展开更多
A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasm...A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasma using liquid chromatography–tandem mass spectrometry. Probenecid was used as internal standard and solid-phase extraction was selected for sample preparation. A chromatographic separation was performed on an Agilent Poroshell SB-C_(18) column(50 mm*4.6 mm i.d., 2.7 μm) by an optimized gradient elution at a flow rate of 0.9 mL/min. The total run time was 7 min. Electrospray ionization was used in negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 143.0→143.0 for valproic acid, m/z 140.9→140.9 for 2-enevalproic acid and 4-enevalproic acid for their poor fragments, and m/z 283.9→239.9 for probenecid. The results showed good linearity of valproic acid, 2-enevalproic acid and 4-enevalproic acid in their respective linear ranges.The correlation coef fi cients were more than 0.998. The intra- and inter-day precision of the assay was less than 11.0% and the accuracy ranged from 2% to 12%. This analytical method was successfully applied to assay plasma concentrations of valproic acid and its two ene-metabolites in epilepsy patient plasma and used for therapeutic drug monitoring.展开更多
·AIM:To assess the effect of 0.01%atropine eye drops on intraocular pressure(IOP)in myopic children.·METHODS:A placebo-controlled,double-masked,randomized study.Totally 220 children aged 6 to 12 y with myopi...·AIM:To assess the effect of 0.01%atropine eye drops on intraocular pressure(IOP)in myopic children.·METHODS:A placebo-controlled,double-masked,randomized study.Totally 220 children aged 6 to 12 y with myopia ranging from-1.00 to-6.00 D in both eyes were enrolled.Children were randomized in a 1:1 ratio to either 0.01%atropine eye drops or a placebo group using generated random numbers.All participants underwent the examination of IOP and cycloplegic refraction at baseline,6 and 12 mo.The change of IOP and the proportion of subjects with increased IOP in atropine and placebo groups were compared.·RESULTS:Of 220 children,117 were boys(53.2%).A total of 159(72.3%)participants completed the follow-up at the 1-year study.At baseline,the mean IOP was 15.74 mm Hg(95%CI,15.13 to 16.34 mm Hg)for the 0.01%atropine group and 15.59 mm Hg(95%CI,15.00 to 16.19 mm Hg)for placebo group(mean difference,0.14 mm Hg;P=0.743)after adjusting for central corneal thickness at baseline.At one year follow-up,the mean change of IOP was 0.16 mm Hg(95%CI,-0.43 to 0.76 mm Hg)for the 0.01%atropine group and-0.11 mm Hg(95%CI,-0.71 to 0.50 mm Hg)for placebo group(mean difference,0.27 mm Hg;P=0.525)after adjusting for central corneal thickness.The 51.4%of children have increased IOP in the 0.01%atropine group,compared with 45.9%in the placebo group(P=0.511).·CONCLUSION:The 0.01%atropine eye drops do not significantly affect the risk of elevated IOP.It is relatively safer to use in the studies that try to minimize myopia progression.However,a further long-duration study is required to be validated.展开更多
基金supported by the National Key Research and Development Program of China(Grant Nos.2018YFC1506801 and 2018YFF0300102)the National Natural Science Foundation of China(NSFC)(Grant No.42105013).
文摘A record-breaking heavy rainfall event that occurred in Zhengzhou,Henan province during 19–21 July 2021 is simulated using the Weather Research and Forecasting Model,and the large-scale precipitation efficiency(LSPE)and cloud-microphysical precipitation efficiency(CMPE)of the rainfall are analyzed based on the model results.Then,the key physical factors that influenced LSPE and CMPE,and the possible mechanisms for the extreme rainfall over Zhengzhou are explored.Results show that water vapor flux convergence was the key factor that influenced LSPE.Water vapor was transported by the southeasterly winds between Typhoon In-Fa(2021)and the subtropical high,and the southerly flow of Typhoon Cempaka(2021),and converged in Zhengzhou due to the blocking by the Taihang and Funiu Mountains in western Henan province.Strong moisture convergence centers were formed on the windward slope of the mountains,which led to high LSPE in Zhengzhou.From the perspective of CMPE,the net consumption of water vapor by microphysical processes was the key factor that influenced CMPE.Quantitative budget analysis suggests that water vapor was mainly converted to cloud water and ice-phase particles and then transformed to raindrops through melting of graupel and accretion of cloud water by rainwater during the heavy precipitation stage.The dry intrusion in the middle and upper levels over Zhengzhou made the high potential vorticity descend from the upper troposphere and enhanced the convective instability.Moreover,the intrusion of cold and dry air resulted in the supersaturation and condensation of water vapor,which contributed to the heavy rainfall in Zhengzhou.
基金funded by the National Natural Science Foundation of China(Nos.51408346,51978389)the Systematic Project of Guangxi Key Laboratory of Disaster Prevention and Structural Safety(2019ZDK035)the Opening Foundation of Shandong Key Laboratory of Civil Engineering Disaster Prevention and Mitigation(No.CDPM2019KF12).
文摘This study investigates the bond between seawater scoria aggregate concrete(SSAC)and stainless reinforcement(SR)through a series of pull-out tests.A total of 39 specimens,considering five experimental parameters—con-crete type(SSAC,ordinary concrete(OC)and seawater coral aggregate concrete(SCAC)),reinforcement type(SR,ordinary reinforcement(OR)),bond length(3,5 and 8 times bar diameter),concrete strength(C25 and C30)and concrete cover thickness(42 and 67 mm)—were prepared.The typical bond properties(failure pattern,bond strength,bond-slip curves and bond stress distribution,etc.)of seawater scoria aggregate concrete-stainless rein-forcement(SSAC-SR)specimen were systematically studied.Generally,the failure pattern changed with the con-crete type used,and the failure surface of SSAC specimen was different from that of OC specimen.SSAC enhanced the bond strength of specimen,while its effect on the deformation of SSAC-SR was negative.On aver-age,the peak slip of SSAC specimens was 20%lower while the bond strength was 6.7%higher compared to OC specimens under the similar conditions.The effects of variables on the bond strength of SSAC–SR in increasing order are concrete type,bond length,concrete strength and cover thickness.The bond-slip curve of SSAC-SR specimen consisted of micro-slipping,slipping and declining stages.It can be obtained that SSAC reduced the curve curvature of bond-slip,and the decline of curve became steep after adopting SR.The typical distribution of bond stress along bond length changed with the types of concrete and reinforcement used.Finally,a specific expression of the bond stress-slip curve considering the effects of various variables was established,which could provide a basis for the practical application of reinforced SSAC.
基金supported in part by the National Key R&D Program of China under Grant 2017YFB1302400the Jinan“20 New Colleges and Universities”Funded Scientific Research Leader Studio under Grant 2021GXRC079+2 种基金the Major Agricultural Applied Technological Innovation Projects of Shandong Province underGrant SD2019NJ014the Shandong Natural Science Foundation under Grant ZR2019MF064the Beijing Advanced Innovation Center for Intelligent Robots and Systems under Grant 2019IRS19.
文摘The solution strategy of the heuristic algorithm is pre-set and has good performance in the conventional cloud resource scheduling process.However,for complex and dynamic cloud service scheduling tasks,due to the difference in service attributes,the solution efficiency of a single strategy is low for such problems.In this paper,we presents a hyper-heuristic algorithm based on reinforcement learning(HHRL)to optimize the completion time of the task sequence.Firstly,In the reward table setting stage of HHRL,we introduce population diversity and integrate maximum time to comprehensively deter-mine the task scheduling and the selection of low-level heuristic strategies.Secondly,a task computational complexity estimation method integrated with linear regression is proposed to influence task scheduling priorities.Besides,we propose a high-quality candidate solution migration method to ensure the continuity and diversity of the solving process.Compared with HHSA,ACO,GA,F-PSO,etc,HHRL can quickly obtain task complexity,select appropriate heuristic strategies for task scheduling,search for the the best makspan and have stronger disturbance detection ability for population diversity.
基金Supported by Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University
文摘AIM:To clarify whether histone deacetylase inhibitors histone deacetylase inhibitors(HDACIs)can sensitize hepatocellular carcinoma(HCC)cells to sorafenib treatment.METHODS:Bax,Bcl-2,ATG5-ATG12,p21,and p27protein levels in Hep3B,HepG2,and PLC/PRF/5 cells were examined by Western blot.CCK8 and a fluorometric caspase-3 assay were used to examine cellular viability and apoptosis levels.The effect of Beclin-1 on sensitization of HCC cells to sorafenib was examined by transfecting Beclin-1 siRNA into Hep3B,HepG2,and PLC/PRF/5 cells.RESULTS:Autophagy inhibition enhances the inhibitory effects of vorinostat and sorafenib alone or in combination on HCC cell growth.Vorinostat and sorafenib synergistically induced apoptosis and cell cycle alterations.Western blot data indicated that HDACIs and Beclin-1 knockdown increased the p53 acetylation level.The knockdown of Beclin-1 enhanced the synergistic effect of the combination of vorinostat with sorafenib.CONCLUSION:HDACIs can sensitize HCC cells to sorafenib treatment by regulating the acetylation level of Beclin-1.
基金the National Natural Science Foundation (30973587)the China Postdoctoral Science Foundation (20110491328)the National Natural Science Funds for Young Scholar (81102383)for financial support
文摘A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and re-extracted with dichloromethane, after which the analyte and triptorelin as an internal standard (IS) were separated on a 300SB-C18 column (150 mm 4.6 mm i.d., 5 mm particle size) using 0.1% formic acid:methanol (45:55, v/v) as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization (ESI) interface, was operated in the positive ion mode, and the multiple-reaction monitoring (MRM) transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5-249.3, respectively. The lower limit of quantification (LLOQ) was 1 ng/mL for 100 mL plasma sample and the assay was linear over the concentration range 1-1000 ng/mL. The accuracy was within a range from 0.4% to 0.5% in terms of relative error (RE) and the intra- and inter-day precisions in terms of relative standard deviation (RSD) were r2.92 and r3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin (0.5 mg/kg) to Chinese volunteers.
文摘A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasma using liquid chromatography–tandem mass spectrometry. Probenecid was used as internal standard and solid-phase extraction was selected for sample preparation. A chromatographic separation was performed on an Agilent Poroshell SB-C_(18) column(50 mm*4.6 mm i.d., 2.7 μm) by an optimized gradient elution at a flow rate of 0.9 mL/min. The total run time was 7 min. Electrospray ionization was used in negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 143.0→143.0 for valproic acid, m/z 140.9→140.9 for 2-enevalproic acid and 4-enevalproic acid for their poor fragments, and m/z 283.9→239.9 for probenecid. The results showed good linearity of valproic acid, 2-enevalproic acid and 4-enevalproic acid in their respective linear ranges.The correlation coef fi cients were more than 0.998. The intra- and inter-day precision of the assay was less than 11.0% and the accuracy ranged from 2% to 12%. This analytical method was successfully applied to assay plasma concentrations of valproic acid and its two ene-metabolites in epilepsy patient plasma and used for therapeutic drug monitoring.
基金Supported by the National Natural Science Foundation of China(No.82071000)the Beijing Science Foundation for Distinguished Yong Scholars(No.JQ20029)+2 种基金the Capital Health Research and Development of Special(No.2020-2-1081)Supported by the Beijing Municipal Administration of Hospitals Incubating Program(No.PX2022007)the Primary Scientific Research Foundation for the Junior Researcher in Beijing Tongren Hospital,Capital Medical University(No.2020-YJJ-ZZL-011)。
文摘·AIM:To assess the effect of 0.01%atropine eye drops on intraocular pressure(IOP)in myopic children.·METHODS:A placebo-controlled,double-masked,randomized study.Totally 220 children aged 6 to 12 y with myopia ranging from-1.00 to-6.00 D in both eyes were enrolled.Children were randomized in a 1:1 ratio to either 0.01%atropine eye drops or a placebo group using generated random numbers.All participants underwent the examination of IOP and cycloplegic refraction at baseline,6 and 12 mo.The change of IOP and the proportion of subjects with increased IOP in atropine and placebo groups were compared.·RESULTS:Of 220 children,117 were boys(53.2%).A total of 159(72.3%)participants completed the follow-up at the 1-year study.At baseline,the mean IOP was 15.74 mm Hg(95%CI,15.13 to 16.34 mm Hg)for the 0.01%atropine group and 15.59 mm Hg(95%CI,15.00 to 16.19 mm Hg)for placebo group(mean difference,0.14 mm Hg;P=0.743)after adjusting for central corneal thickness at baseline.At one year follow-up,the mean change of IOP was 0.16 mm Hg(95%CI,-0.43 to 0.76 mm Hg)for the 0.01%atropine group and-0.11 mm Hg(95%CI,-0.71 to 0.50 mm Hg)for placebo group(mean difference,0.27 mm Hg;P=0.525)after adjusting for central corneal thickness.The 51.4%of children have increased IOP in the 0.01%atropine group,compared with 45.9%in the placebo group(P=0.511).·CONCLUSION:The 0.01%atropine eye drops do not significantly affect the risk of elevated IOP.It is relatively safer to use in the studies that try to minimize myopia progression.However,a further long-duration study is required to be validated.
