Voltage-gated sodium channels （Navs） play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained h...Voltage-gated sodium channels （Navs） play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion （hDRG） tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Navl.7 （,-~ 50% of total Nav expression） and lower expres- sion of Navl.8 （~ 12%）, whereas the mouse DRG has higher expression of Nav 1.8 （- 45%） and lower expression of Navl.7 （- 18%）. To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary cultures with paclitaxel （0.1-1 μmol/L） for 24 h. Paclitaxel increased the Navl.7 but not Navl.8 expression and also increased the transient Na＋ currents and action potential firing frequency in small-diameter （〈50 ~tm） hDRG neurons. Thus, the hDRG provides a translational model in which to study ＂human pain in a dish＂ and test new pain therapeutics.展开更多
AIM: To determine if hyperpolarisation-activated nucleotide-gated(HCN) channels exist in human colon, and to investigate the expression of HCN channels in Hirschsprung's disease.METHODS:We investigated HCN1,HCN2,H...AIM: To determine if hyperpolarisation-activated nucleotide-gated(HCN) channels exist in human colon, and to investigate the expression of HCN channels in Hirschsprung's disease.METHODS:We investigated HCN1,HCN2,HCN3 and HCN4 protein expression in pull-through specimens from patients with Hirschsprung’s disease(HSCR,n=10)using the proximal-most ganglionic segment and distalmost aganglionic segment,as well as in healthy control specimens obtained at the time of sigmoid colostomy closure in children who had undergone anorectoplasty for imperforate anus(n=10).Fluorescent immunohistochemistry was performed to assess protein distribution,which was then visualized using confocal microscopy.RESULTS:No HCN1 channel expression was observed in any of the tissues studied.Both HCN2 and HCN4proteins were found to be equally expressed in the aganglionic and ganglionic bowel in HSCR and controls.HCN3 channel expression was found to be markedly decreased in the aganglionic colon vs ganglionic colon and controls.HCN2-4 channels were seen to be expressed within neurons of the myenteric and submucosal plexus of the ganglionic bowel and normal controls,and also co-localised to interstitial cells of Cajal in all tissues studied.CONCLUSION:We demonstrate HCN channel expression in human colon for the first time.Reduced HCN3expression in aganglionic bowel suggests its potential role in HSCR pathophysiology.展开更多
Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A ...Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion. The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period, and that activin A was shown to increase voltage-gated Na＋ current （/Na） in Neuro-2a cells, which was recorded by patch clamp technique. The present study revealed a novel mechanism for activin A, as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase.展开更多
In order to weaken the bias flow in the submerged entry nozzle （SEN） with slide- gate, the rotating magnetic field was imposed. The numerical method was employed to investigate the effect of rotating magnetic field ...In order to weaken the bias flow in the submerged entry nozzle （SEN） with slide- gate, the rotating magnetic field was imposed. The numerical method was employed to investigate the effect of rotating magnetic field on the flow field in the SEN and the mold under different slide-gate opening ratios. Numerical results showed that when the slide-gate opening ratio is smaller than 100%, the flow field in the SEN and the mold become asymmetry and there is an obvious circulation under the slide- gate in the SEN. With increasing exciting current, the divergent angle of liquid steel at the SEN outlet increases, the impact depth of liquid steel in the mold decreases. With increasing slide-gate opening ratio, the impact depth of liquid steel in the mold increases and the required exciting current to weaken the bias flow should increase.展开更多
Voltage-gated sodium channels （VGSCs） are known to be involved in the initiation and progression of many malignancies, and the different subtypes of VGSCs play important roles in the metastasis cascade of many tumor...Voltage-gated sodium channels （VGSCs） are known to be involved in the initiation and progression of many malignancies, and the different subtypes of VGSCs play important roles in the metastasis cascade of many tumors. This study investigated the functional expression of Nav1.5 and its effect on invasion behavior of human breast cancer cell line MDA-MB-231. The mRNA and protein expression of Nav1.5 was detected by real time PCR, Western Blot and immunofluorescence. The effects of Nav1.5 on cell proliferation, migration and invasion were respectively assessed by MTT and Transwell. The effects of Nav1.5 on the secretion of matrix metalloproteases （MMPs） by MDA-MB-231 were analyzed by RT-PCR. The over-expressed Nav 1.5 was present on the membrane of MDA-MB-231 cells. The invasion ability in vitro and the MMP-9 mRNA expression were respectively decreased to （47.82±0.53）% and （43.97±0.64）% （P〈0.05） respectively in MDA-MB-23 t cells treated with VGSCs specific inhibitor tetrodotoxin （TTX） by blocking Navl.5 activity. It was concluded that Navl.5 functional expression potentiated the invasive behavior of human breast cancer cell line MDA-MB-231 by increasing the secretion of MMP-9.展开更多
A two-dimensional analytical subthreshold behavior model for junctionless dual-material cylindrical surrounding- gate （JLDMCSG） metal-oxide-semiconductor field-effect transistors （MOSFETs） is proposed. It is deriv...A two-dimensional analytical subthreshold behavior model for junctionless dual-material cylindrical surrounding- gate （JLDMCSG） metal-oxide-semiconductor field-effect transistors （MOSFETs） is proposed. It is derived by solving the two-dimensional Poisson＇s equation in two continuous cylindrical regions with any simplifying assumption. Using this analytical model, the subthreshold characteristics of JLDMCSG MOSFETs are investigated in terms of channel electro- static potential, horizontal electric field, and subthreshold current. Compared to junctionless single-material cylindrical surrounding-gate MOSFETs, JLDMCSG MOSFETs can effectively suppress short-channel effects and simultaneously im- prove carrier transport efficiency. It is found that the subthreshold current of JLDMCSG MOSFETs can be significantly reduced by adopting both a thin oxide and thin silicon channel. The accuracy of the analytical model is verified by its good agreement with the three-dimensional numerical simulator ISE TCAD.展开更多
A continuous yet analytic channel potential solution is proposed for doped symmetric double-gate （DG） MOSFETs from the accumulation to the strong-inversion region. Analytical channel potential relationship is derive...A continuous yet analytic channel potential solution is proposed for doped symmetric double-gate （DG） MOSFETs from the accumulation to the strong-inversion region. Analytical channel potential relationship is derived from the complete 1-D Poisson equation physically, and the channel potential solution of the DG MOSFET is obtained analytically. The extensive comparisons between the presented solution and the numerical simulation illustrate that the solution is not only accurate and continuous in the whole operation regime of DG MOSFETs, but also valid to wide doping concentration and various geometrical sizes, without employing any fitting parameter.展开更多
N and P-channel groove-gate MOSFETs based on a self-aligned CMOS process have been fabricated and characterized. For the devices with channel length of 140nm, the measured drain induced barrier lowering （DIBL） was 6...N and P-channel groove-gate MOSFETs based on a self-aligned CMOS process have been fabricated and characterized. For the devices with channel length of 140nm, the measured drain induced barrier lowering （DIBL） was 66mV/V for n-MOSFETs and 82mV/V for p-MOSFETs. The substrate current of a groove-gate n-MOSFET was 150 times less than that of a conventional planar n-MOSFET, These results demonstrate that groove-gate MOSFETs have excellent capabilities in suppressing short-channel effects. It is worth emphasizing that our groove-gate MOSFET devices are fabricated by using a simple process flow, with the potential of fabricating devices in the sub-100nm range.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
Self-aligned-gate heterostructure field-effect transistor（HFET） is fabricated using a wet-etching method.Titanium nitride（TiN） is one kind of thermal stable material which can be used as the gate electrode.A Ti/Au...Self-aligned-gate heterostructure field-effect transistor（HFET） is fabricated using a wet-etching method.Titanium nitride（TiN） is one kind of thermal stable material which can be used as the gate electrode.A Ti/Au cap layer is fixed on the gate and acts as an etching mask.Then the T-shaped gate is automatically formed through over-etching the TiN layer in 30% H2O2 solution at 95 ℃.After treating the ohmic region with an inductively coupled plasma（ICP） method,an Al layer is sputtered as an ohmic electrode.The ohmic contact resistance is approximately 0.3 Ω·mm after annealing at a low-temperature of 575 ℃ in N2 ambient for 1 min.The TiN gate leakage current is only 10^-8 A after the low-temperature ohmic process.The access region length of the self-aligned-gate（SAG） HFET was reduced from 2 μm to 0.3 μm compared with that of the gate-first HFET.The output current density and transconductance of the device which has the same gate length and width are also increased.展开更多
In this study, it is aimed to determine the ranking importance levels of the stages to be taken into consideration for new product development on a global scale in the automotive design process. New product design act...In this study, it is aimed to determine the ranking importance levels of the stages to be taken into consideration for new product development on a global scale in the automotive design process. New product design activity and stage-gate process differences between local automotive firms (serial production factory and stage-gate department in Turkey) and global automotive companies (serial production factory and stage-gate department in Turkey) are examined comparatively in the research area. In the automotive industry, which has been developing for a century, the question of how the local company products operating in the last sixty years have not been able to spread globally or how to develop global products is the background question of the research. For this purpose, one on one interviews were held with the managers of 3 national and 3 international automotive companies, who worked in the same region and who had previously designed a new vehicle, with design and product development departments.?According to?the data obtained by the AHP (Analytic Hierarchy Process) in the automotive design process, the importance of the criteria that should be taken into account for global product development has revealed. According to the results of the study, it was found that design validation stages were the most important globalization criterion in automotive design process as a new study area. In the comprehensive survey of the study, no other publication has been encountered to measure or evaluate the stages in the automotive design and new product development process in other sectors, including the vehicle industry. As in every industry sector, in the automotive industry, with the new product companies provide market development or competitive advantage. The new product is the life channel of a company and in the realization of this new vehicle;the disciplines of the automotive industry are formed by a hundred years of experience.展开更多
基金supported in part by NIH RO1Grants NS87988,DE17794,and DE22743 to R.R.J and NS89479 to S.Y.L and R.R.J
文摘Voltage-gated sodium channels （Navs） play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion （hDRG） tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Navl.7 （,-~ 50% of total Nav expression） and lower expres- sion of Navl.8 （~ 12%）, whereas the mouse DRG has higher expression of Nav 1.8 （- 45%） and lower expression of Navl.7 （- 18%）. To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary cultures with paclitaxel （0.1-1 μmol/L） for 24 h. Paclitaxel increased the Navl.7 but not Navl.8 expression and also increased the transient Na＋ currents and action potential firing frequency in small-diameter （〈50 ~tm） hDRG neurons. Thus, the hDRG provides a translational model in which to study ＂human pain in a dish＂ and test new pain therapeutics.
基金Supported by National Children’s Research Centre/Children’s Medical Research Foundation,Ireland
文摘AIM: To determine if hyperpolarisation-activated nucleotide-gated(HCN) channels exist in human colon, and to investigate the expression of HCN channels in Hirschsprung's disease.METHODS:We investigated HCN1,HCN2,HCN3 and HCN4 protein expression in pull-through specimens from patients with Hirschsprung’s disease(HSCR,n=10)using the proximal-most ganglionic segment and distalmost aganglionic segment,as well as in healthy control specimens obtained at the time of sigmoid colostomy closure in children who had undergone anorectoplasty for imperforate anus(n=10).Fluorescent immunohistochemistry was performed to assess protein distribution,which was then visualized using confocal microscopy.RESULTS:No HCN1 channel expression was observed in any of the tissues studied.Both HCN2 and HCN4proteins were found to be equally expressed in the aganglionic and ganglionic bowel in HSCR and controls.HCN3 channel expression was found to be markedly decreased in the aganglionic colon vs ganglionic colon and controls.HCN2-4 channels were seen to be expressed within neurons of the myenteric and submucosal plexus of the ganglionic bowel and normal controls,and also co-localised to interstitial cells of Cajal in all tissues studied.CONCLUSION:We demonstrate HCN channel expression in human colon for the first time.Reduced HCN3expression in aganglionic bowel suggests its potential role in HSCR pathophysiology.
基金the National Natural Science Foundation of China, No.30903123, 30901329the Project of Science and Technology of Jilin Province, No.20090741, 20090185
文摘Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion. The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period, and that activin A was shown to increase voltage-gated Na＋ current （/Na） in Neuro-2a cells, which was recorded by patch clamp technique. The present study revealed a novel mechanism for activin A, as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase.
基金financially supported by the National High Technical Research and Development Programme of China (No. 2009AA03Z530)the National Natural Science Foundation of China and Shanghai Baosteel (No. 50834010)+3 种基金the National Natural Science Foundation of China (Nos. 51174058, 51104047 and 51004035)111 Project (No. B07015)the Fundamental Research Funds for the Central Universities(No. N100409007)the Doctor Startup Foundation of Liaoning Province (No.20111009)
文摘In order to weaken the bias flow in the submerged entry nozzle （SEN） with slide- gate, the rotating magnetic field was imposed. The numerical method was employed to investigate the effect of rotating magnetic field on the flow field in the SEN and the mold under different slide-gate opening ratios. Numerical results showed that when the slide-gate opening ratio is smaller than 100%, the flow field in the SEN and the mold become asymmetry and there is an obvious circulation under the slide- gate in the SEN. With increasing exciting current, the divergent angle of liquid steel at the SEN outlet increases, the impact depth of liquid steel in the mold decreases. With increasing slide-gate opening ratio, the impact depth of liquid steel in the mold increases and the required exciting current to weaken the bias flow should increase.
文摘Voltage-gated sodium channels （VGSCs） are known to be involved in the initiation and progression of many malignancies, and the different subtypes of VGSCs play important roles in the metastasis cascade of many tumors. This study investigated the functional expression of Nav1.5 and its effect on invasion behavior of human breast cancer cell line MDA-MB-231. The mRNA and protein expression of Nav1.5 was detected by real time PCR, Western Blot and immunofluorescence. The effects of Nav1.5 on cell proliferation, migration and invasion were respectively assessed by MTT and Transwell. The effects of Nav1.5 on the secretion of matrix metalloproteases （MMPs） by MDA-MB-231 were analyzed by RT-PCR. The over-expressed Nav 1.5 was present on the membrane of MDA-MB-231 cells. The invasion ability in vitro and the MMP-9 mRNA expression were respectively decreased to （47.82±0.53）% and （43.97±0.64）% （P〈0.05） respectively in MDA-MB-23 t cells treated with VGSCs specific inhibitor tetrodotoxin （TTX） by blocking Navl.5 activity. It was concluded that Navl.5 functional expression potentiated the invasive behavior of human breast cancer cell line MDA-MB-231 by increasing the secretion of MMP-9.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61204092 and 61076101)the Fundamental Research Funds for the Central Universities of Ministry of Education of China(Grant No.K50511250001)
文摘A two-dimensional analytical subthreshold behavior model for junctionless dual-material cylindrical surrounding- gate （JLDMCSG） metal-oxide-semiconductor field-effect transistors （MOSFETs） is proposed. It is derived by solving the two-dimensional Poisson＇s equation in two continuous cylindrical regions with any simplifying assumption. Using this analytical model, the subthreshold characteristics of JLDMCSG MOSFETs are investigated in terms of channel electro- static potential, horizontal electric field, and subthreshold current. Compared to junctionless single-material cylindrical surrounding-gate MOSFETs, JLDMCSG MOSFETs can effectively suppress short-channel effects and simultaneously im- prove carrier transport efficiency. It is found that the subthreshold current of JLDMCSG MOSFETs can be significantly reduced by adopting both a thin oxide and thin silicon channel. The accuracy of the analytical model is verified by its good agreement with the three-dimensional numerical simulator ISE TCAD.
基金Project supported by the National Natural Science Foundation of China(Grant No.60876027)the Open Funds of Jiangsu Province Key Lab of ASIC Design(JSICK1007)
文摘A continuous yet analytic channel potential solution is proposed for doped symmetric double-gate （DG） MOSFETs from the accumulation to the strong-inversion region. Analytical channel potential relationship is derived from the complete 1-D Poisson equation physically, and the channel potential solution of the DG MOSFET is obtained analytically. The extensive comparisons between the presented solution and the numerical simulation illustrate that the solution is not only accurate and continuous in the whole operation regime of DG MOSFETs, but also valid to wide doping concentration and various geometrical sizes, without employing any fitting parameter.
基金Project supported by the National Natural Science Foundation of China （Grant No 60376024）.
文摘N and P-channel groove-gate MOSFETs based on a self-aligned CMOS process have been fabricated and characterized. For the devices with channel length of 140nm, the measured drain induced barrier lowering （DIBL） was 66mV/V for n-MOSFETs and 82mV/V for p-MOSFETs. The substrate current of a groove-gate n-MOSFET was 150 times less than that of a conventional planar n-MOSFET, These results demonstrate that groove-gate MOSFETs have excellent capabilities in suppressing short-channel effects. It is worth emphasizing that our groove-gate MOSFET devices are fabricated by using a simple process flow, with the potential of fabricating devices in the sub-100nm range.
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Self-aligned-gate heterostructure field-effect transistor（HFET） is fabricated using a wet-etching method.Titanium nitride（TiN） is one kind of thermal stable material which can be used as the gate electrode.A Ti/Au cap layer is fixed on the gate and acts as an etching mask.Then the T-shaped gate is automatically formed through over-etching the TiN layer in 30% H2O2 solution at 95 ℃.After treating the ohmic region with an inductively coupled plasma（ICP） method,an Al layer is sputtered as an ohmic electrode.The ohmic contact resistance is approximately 0.3 Ω·mm after annealing at a low-temperature of 575 ℃ in N2 ambient for 1 min.The TiN gate leakage current is only 10^-8 A after the low-temperature ohmic process.The access region length of the self-aligned-gate（SAG） HFET was reduced from 2 μm to 0.3 μm compared with that of the gate-first HFET.The output current density and transconductance of the device which has the same gate length and width are also increased.
文摘In this study, it is aimed to determine the ranking importance levels of the stages to be taken into consideration for new product development on a global scale in the automotive design process. New product design activity and stage-gate process differences between local automotive firms (serial production factory and stage-gate department in Turkey) and global automotive companies (serial production factory and stage-gate department in Turkey) are examined comparatively in the research area. In the automotive industry, which has been developing for a century, the question of how the local company products operating in the last sixty years have not been able to spread globally or how to develop global products is the background question of the research. For this purpose, one on one interviews were held with the managers of 3 national and 3 international automotive companies, who worked in the same region and who had previously designed a new vehicle, with design and product development departments.?According to?the data obtained by the AHP (Analytic Hierarchy Process) in the automotive design process, the importance of the criteria that should be taken into account for global product development has revealed. According to the results of the study, it was found that design validation stages were the most important globalization criterion in automotive design process as a new study area. In the comprehensive survey of the study, no other publication has been encountered to measure or evaluate the stages in the automotive design and new product development process in other sectors, including the vehicle industry. As in every industry sector, in the automotive industry, with the new product companies provide market development or competitive advantage. The new product is the life channel of a company and in the realization of this new vehicle;the disciplines of the automotive industry are formed by a hundred years of experience.
