OBJECTIVE Cardiotoxicity refers to drug-induced arrhythmia such as Torsades de pointes.Current single ion channel(hERG)-based assay generates-30% false results.The aim is to establish an advanced in vitro cardiotoxici...OBJECTIVE Cardiotoxicity refers to drug-induced arrhythmia such as Torsades de pointes.Current single ion channel(hERG)-based assay generates-30% false results.The aim is to establish an advanced in vitro cardiotoxicity assay by incorporating high throughput multiple cardiac ion channel screening and human cardiomyocytes-based validation.METHODS Effects of drugs were tested on multiple cell lines expressing hERG,Nav1.5 and Cav1.2 by automated patch clamping.Subsequently,the results were validated with human pluripotent stem cell(hPSC)-derived cardiomyocytes(hPSC-CMs)in which ion currents and action potentials were measured by manual patch clamping.RESULTS We have tested the cardiotoxicity of monomers extracted from various medical herbs.Mitragynine is the major bioactive compound isolated from kratom,a therapeutic herb from the rain forest of South East Asia.As a popular stimulant,it has been associated with a number of acute fatal incidences.We observed a typical torsadogenic hazard of mitragynine.It exerted a strong hERG inhibition in hERG-HEK293 cell line(IC50:5.2 μmol·L-1)and hPSC-CMs(IC50:0.91 μmol·L-1)without affecting other cardiac ion channels.Moreover,it caused a significant prolongation of action potential duration(APD)in hPSC-CMs(a-32.5%increase in APD at 50 and 90%repolarization).On the other hand,deoxylelephantopin,apotential anti-cancer reagent,demonstrated low cardiotoxicity.It exerted a week inhibition on hERG in HEK293 cells with an IC50 of 87.2 μmol·L-1,while the effective concentrations for suppressing the growth of cancer cells ranges from 2 to 20μmol·L-1.At 100μmol·L-1,deoxylelephantopin showed no effects on Cav1.2 and Nav1.5 and it failed to alter APD in hPSC-CMs.CONCLUSION We have successfully tested a newin vitro cardiotoxicity assay strategy which incorporates multiple cardiac ion channels screening and hPSC-CMs validation.This new strategy could facilitate the effective and efficient evaluation of existing and new drugs/reagents for potential pro-arrhythmic risk.展开更多
For realizing diffused anode attachment in pure nitrogen arcs, a special arc plasma generator was designed and combined with suitable working parameters such as gas flow rate and arc current. The anode has a flow-rest...For realizing diffused anode attachment in pure nitrogen arcs, a special arc plasma generator was designed and combined with suitable working parameters such as gas flow rate and arc current. The anode has a flow-restrictor channel of 2.8 mm diameter and downstream expansion half-angle of 8°, with the purpose of creating a dispersed nitrogen-arc column by strong gasdynamic expansion effect. Results show that, when thermal blocking condition existed in the flow restrictor and the cathode cavity pressure was higher than that in the exit chamber by at least 9 kPa, the action due to gasdynamic expansion could be much stronger than the self-magnetic contraction effect of the arc and the nitrogen arc column could be effectively dispersed to form a sufficiently diffused attachment on the water-cooled anode surface.展开更多
The technology of pressure relief gas drainage is one of the most effective and economic for preventing gas emissions in underground mines.Based on current understanding of strata breakage and fracture development in ...The technology of pressure relief gas drainage is one of the most effective and economic for preventing gas emissions in underground mines.Based on current understanding of strata breakage and fracture development in overlying strata,the current study divides the overlying strata into the following three longitudinal zones in terms of the state of gas flow:a turbulent channel zone,a transitional circulation channel zone and a seepage channel zone.According to the key strata discrimination theory of controlling the overlying strata,the calculation method establishes that the step-type expansion of the mining gas channel corresponds to the advancing distance of working face,and this research also confrms the expanding rule that the mining gas channel in overlying strata follows the advancing distance of mining working face.Based on the geological conditions of Xinjing Coal Mine of Yangquan,this paper researches the expanding rule of mining gas channel as well as the control action of the channel acting on the pressure relief flow under the condition of the remote protective layer,and got the distance using inversion that the step-type expanding of mining gas channel is corresponding to the advancing distance of working face,which verifes the accuracy and feasibility of theoretical calculation method proposed in this study.The research provides the theoretical basis for choosing the technology of pressure relief gas drainage and designing the parameters of construction.展开更多
Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorl...Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations （0.1, 1, 5 and 10 ng/mL） and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations （2, 4, 8, 24 and 48 hours） by studying voltage-gated Na＋ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na＋ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na＋channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.展开更多
基于Wi-Fi技术的方法以其无需穿戴、易于部署等优点日益成为动作识别领域的热门研究方向。然而在有干扰的情况下,Wi-Fi设备易受到影响从而造成识别精度的下降。据此设计一种基于信道状态信息(Channel Status Information,CSI)的高鲁棒...基于Wi-Fi技术的方法以其无需穿戴、易于部署等优点日益成为动作识别领域的热门研究方向。然而在有干扰的情况下,Wi-Fi设备易受到影响从而造成识别精度的下降。据此设计一种基于信道状态信息(Channel Status Information,CSI)的高鲁棒性动作识别方法。提出动态子载波选择算法,动态地选取与动作相关性最大的子载波;针对无线设备在干扰情况下数据采集质量不佳、分割不精确导致动作识别准确率下降的问题,提出分割辅助算法,有效提高动作区间的分割精度和分类准确性。实验结果显示,该方法在无干扰和有干扰的环境下对五种动作的识别准确度分别可达到92%和81%,具有较强的鲁棒性。展开更多
基金The project supported by National Medical Research Council(NMRC CG12Aug09&NMRC EDG10may050)National Research Foundation(NRF2008-CRP003-02)of Singapore and Ministry of Science,Technology and Innovation Malaysia(Sciencefund Grant to Tan Mei Lan)
文摘OBJECTIVE Cardiotoxicity refers to drug-induced arrhythmia such as Torsades de pointes.Current single ion channel(hERG)-based assay generates-30% false results.The aim is to establish an advanced in vitro cardiotoxicity assay by incorporating high throughput multiple cardiac ion channel screening and human cardiomyocytes-based validation.METHODS Effects of drugs were tested on multiple cell lines expressing hERG,Nav1.5 and Cav1.2 by automated patch clamping.Subsequently,the results were validated with human pluripotent stem cell(hPSC)-derived cardiomyocytes(hPSC-CMs)in which ion currents and action potentials were measured by manual patch clamping.RESULTS We have tested the cardiotoxicity of monomers extracted from various medical herbs.Mitragynine is the major bioactive compound isolated from kratom,a therapeutic herb from the rain forest of South East Asia.As a popular stimulant,it has been associated with a number of acute fatal incidences.We observed a typical torsadogenic hazard of mitragynine.It exerted a strong hERG inhibition in hERG-HEK293 cell line(IC50:5.2 μmol·L-1)and hPSC-CMs(IC50:0.91 μmol·L-1)without affecting other cardiac ion channels.Moreover,it caused a significant prolongation of action potential duration(APD)in hPSC-CMs(a-32.5%increase in APD at 50 and 90%repolarization).On the other hand,deoxylelephantopin,apotential anti-cancer reagent,demonstrated low cardiotoxicity.It exerted a week inhibition on hERG in HEK293 cells with an IC50 of 87.2 μmol·L-1,while the effective concentrations for suppressing the growth of cancer cells ranges from 2 to 20μmol·L-1.At 100μmol·L-1,deoxylelephantopin showed no effects on Cav1.2 and Nav1.5 and it failed to alter APD in hPSC-CMs.CONCLUSION We have successfully tested a newin vitro cardiotoxicity assay strategy which incorporates multiple cardiac ion channels screening and hPSC-CMs validation.This new strategy could facilitate the effective and efficient evaluation of existing and new drugs/reagents for potential pro-arrhythmic risk.
基金supported by the National Natural Science Foundation of China (11575273)
文摘For realizing diffused anode attachment in pure nitrogen arcs, a special arc plasma generator was designed and combined with suitable working parameters such as gas flow rate and arc current. The anode has a flow-restrictor channel of 2.8 mm diameter and downstream expansion half-angle of 8°, with the purpose of creating a dispersed nitrogen-arc column by strong gasdynamic expansion effect. Results show that, when thermal blocking condition existed in the flow restrictor and the cathode cavity pressure was higher than that in the exit chamber by at least 9 kPa, the action due to gasdynamic expansion could be much stronger than the self-magnetic contraction effect of the arc and the nitrogen arc column could be effectively dispersed to form a sufficiently diffused attachment on the water-cooled anode surface.
基金the National Basic Research Programs of China (No. 2011CB201204)the National Natural Science Foundation of China (Nos. 51074160)+1 种基金the Fundamental Research Funds for the Central Universities (No. 2010QNA03)Project Funded by the Priority Academic Program Development of Jiangsu Higher Education institutions for their support for this project
文摘The technology of pressure relief gas drainage is one of the most effective and economic for preventing gas emissions in underground mines.Based on current understanding of strata breakage and fracture development in overlying strata,the current study divides the overlying strata into the following three longitudinal zones in terms of the state of gas flow:a turbulent channel zone,a transitional circulation channel zone and a seepage channel zone.According to the key strata discrimination theory of controlling the overlying strata,the calculation method establishes that the step-type expansion of the mining gas channel corresponds to the advancing distance of working face,and this research also confrms the expanding rule that the mining gas channel in overlying strata follows the advancing distance of mining working face.Based on the geological conditions of Xinjing Coal Mine of Yangquan,this paper researches the expanding rule of mining gas channel as well as the control action of the channel acting on the pressure relief flow under the condition of the remote protective layer,and got the distance using inversion that the step-type expanding of mining gas channel is corresponding to the advancing distance of working face,which verifes the accuracy and feasibility of theoretical calculation method proposed in this study.The research provides the theoretical basis for choosing the technology of pressure relief gas drainage and designing the parameters of construction.
基金supported by a grant from the National Natural Science Foundation of China,No.30972766,31170852,81001322,81172795,81173048the Specialized Research Fund for the Doctoral Program of Colleges and Universities,No.20094402110004
文摘Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations （0.1, 1, 5 and 10 ng/mL） and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations （2, 4, 8, 24 and 48 hours） by studying voltage-gated Na＋ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na＋ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na＋channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.
文摘基于Wi-Fi技术的方法以其无需穿戴、易于部署等优点日益成为动作识别领域的热门研究方向。然而在有干扰的情况下,Wi-Fi设备易受到影响从而造成识别精度的下降。据此设计一种基于信道状态信息(Channel Status Information,CSI)的高鲁棒性动作识别方法。提出动态子载波选择算法,动态地选取与动作相关性最大的子载波;针对无线设备在干扰情况下数据采集质量不佳、分割不精确导致动作识别准确率下降的问题,提出分割辅助算法,有效提高动作区间的分割精度和分类准确性。实验结果显示,该方法在无干扰和有干扰的环境下对五种动作的识别准确度分别可达到92%和81%,具有较强的鲁棒性。
