Voltage gated calcium channel(VGCC) antibodies are generally associated with Lambert-Eaton myasthenic syndrome. However the presence of this antibody has been associated with paraneoplastic as well as nonparaneoplasti...Voltage gated calcium channel(VGCC) antibodies are generally associated with Lambert-Eaton myasthenic syndrome. However the presence of this antibody has been associated with paraneoplastic as well as nonparaneoplastic cerebellar degeneration. Most patients with VGCC-antibody-positivity have small cell lung cancer(SCLC). Lambert-Eaton myasthenic syndrome(LEMS)is an autoimmune disease of the presynaptic part of the neuromuscular junction. Its classical clinical triadis proximal muscle weakness, areflexia and autonomic dysfunction. Fifty to sixty percent of LEMS patients have a neoplasia, usually SCLC. The co-occurrence of SCLC and LEMS causes more severe and progressive disease and shorter survival than non-paraneoplastic LEMS. Treatment includes 3,4 diaminopyridine for symptomatic purposes and immunotherapy with prednisolone, azathioprine or intravenous immunoglobulin in patients unresponsive to 3,4 diaminopyridine. Paraneoplastic cerebellar degeneration(PCD) is a syndrome characterized with severe, subacute pancerebellar dysfunction. Serum is positive for VGCC antibody in 41%-44% of patients, usually with the co-occurrence of SCLC. Clinical and electrophysiological features of LEMS are also present in 20%-40% of these patients. Unfortunately, PCD symptoms do not improve with immunotherapy. The role of VGCC antibody in the immunopathogenesis of LEMS is well known whereas its role in PCD is still unclear. All patients presenting with LEMS or PCD must be investigated for SCLC.展开更多
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
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
Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current ( named Ⅰf, Ⅰh, or Ⅰq). Recent studies have unveiled ...Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current ( named Ⅰf, Ⅰh, or Ⅰq). Recent studies have unveiled the molecular identity of HCN (HCN1-4) channels. HCN isoforms are unevenly expressed in the heart, even in the sinoatrial node. Features of HCN currents have been characterized in cardiac and other types of cells or in cell lines transfected with the HCN isoforms. The factors modulating Ih and the physiological significance of HCN channels in the heart have been extensively investigated in recent years. The hypothesis for transplanting and/or creating biological pacemakers to replace diseased sinoatrial and/or atrioventricular nodes has been postulated and tested in animal models. Local overexpression of HCN2 channels in the left atrium or in the left conductive bundle branch of the left ventricle via gene delivery induced significant Ⅰh and escape rhythms during vagal stimulation in canines. In addition, implantation of human mesenchymal stem cells with overexpression of HCN2 channels to the canine left ventricular wall was associated with formation of spontaneous escape rhythms of left-sided origin during vagal-stimulation-induced sinus arrest. This preliminary data suggest that the use of HCN channels may hold great promise in,the development of biological pacemakers.展开更多
Abstract Hyperpolarization-activated cyclic-nucleotide-gated ( HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current (named If, Ih, or Iq). Recent studies have unv...Abstract Hyperpolarization-activated cyclic-nucleotide-gated ( HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current (named If, Ih, or Iq). Recent studies have unveiled the molecular identity of HCN (HCN 1-4) channels. HCN isoforms are unevenly expressed in the heart, even in the sinoatrial node. Features of HCN currents have been characterized in cardiac and other types of cells or in cell lines transfected with the HCN isoforms. The factors modulating Ih and the physiological significance of HCN channels in the heart have been extensively investigated in recent years. The hypothesis for transplanting and/or creating biological pacemakers to replace diseased sinoatrial and/or atrioventricular nodes has been postulated and tested in animal models. Local overexpression of HCN2 channels in the left atrium or in the left conductive bundle branch of the left ventricle via gene delivery induced significant Ih and escape rhythms during vagal stimulation in canines. In addition, implantation of human mesenchymal stem cells with overexpression of HCN2 channels to the canine left ventricular wall was associated with formation of spontaneous escape rhythms of left-sided origin during vagal-stimulation-induced sinus arrest. This preliminary data suggest that the use of HCN channels may hold great promise in the development of biological pacemakers.展开更多
Chlorogenic acid（5-caffeoylquinic acid, CGA） is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to it...Chlorogenic acid（5-caffeoylquinic acid, CGA） is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to its notable biological functions against cardiovascular diseases, type-2 diabetes and inflammatory conditions, CGA was recently hypothesized to be an alternative for the treatment of neurological diseases such as Alzheimer＇s disease and neuropathic pain disorders. However, its mechanism of action is unclear.Voltage-gated potassium channel（Kv） is a crucial factor in the electro-physiological processes of sensory neurons. Kv has also been identified as a potential therapeutic target for inflammation and neuropathic pain disorders. In this study, we analysed the effects of CGA on the two main subtypes of Kv in trigeminal ganglion neurons, namely, the IK,Aand IK,Vchannels. Trigeminal ganglion（TRG）neurons were acutely disassociated from the rat TRG, and two different doses of CGA（0.2 and 1 mmol·L21） were applied to the cells.Whole-cell patch-clamp recordings were performed to observe alterations in the activation and inactivation properties of the IK,Aand IK,Vchannels. The results demonstrated that 0.2 mmol·L21CGA decreased the peak current density of IK,A. Both 0.2 mmol·L21and1 mmol·L21CGA also caused a significant reduction in the activation and inactivation thresholds of IK,Aand IK,V. CGA exhibited a strong effect on the activation and inactivation velocities of IK,Aand IK,V. These findings provide novel evidence explaining the biological effects of CGA, especially regarding its neurological effects.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
A large gate metal height technique is proposed to enhance breakdown voltage in GaN channel and AlGaN channel high-electron-mobility-transistors(HEMTs).For GaN channel HEMTs with gate-drain spacing LGD=2.5μm,the brea...A large gate metal height technique is proposed to enhance breakdown voltage in GaN channel and AlGaN channel high-electron-mobility-transistors(HEMTs).For GaN channel HEMTs with gate-drain spacing LGD=2.5μm,the breakdown voltage VBR increases from 518 V to 582 V by increasing gate metal height h from 0.2μm to 0.4μm.For GaN channel HEMTs with LGD=7μm,VBR increases from 953 V to 1310 V by increasing h from 0.8μm to 1.6μm.The breakdown voltage enhancement results from the increase of the gate sidewall capacitance and depletion region extension.For Al0.4Ga0.6N channel HEMT with LGD=7μm,VBR increases from 1535 V to 1763 V by increasing h from 0.8μm to 1.6μm,resulting in a high average breakdown electric field of 2.51 MV/cm.Simulation and analysis indicate that the high gate metal height is an effective method to enhance breakdown voltage in GaN-based HEMTs,and this method can be utilized in all the lateral semiconductor devices.展开更多
An analytical model for the channel potential and the threshold voltage of the short channel dual-material-gate lightly doped drain （DMG-LDD） metal-oxide-semiconductor field-effect transistor （MOSFET） is presented...An analytical model for the channel potential and the threshold voltage of the short channel dual-material-gate lightly doped drain （DMG-LDD） metal-oxide-semiconductor field-effect transistor （MOSFET） is presented using the parabolic approximation method. The proposed model takes into account the effects of the LDD region length, the LDD region doping, the lengths of the gate materials and their respective work functions, along with all the major geometrical parameters of the MOSFET. The impact of the LDD region length, the LDD region doping, and the channel length on the channel potential is studied in detail. Furthermore, the threshold voltage of the device is calculated using the minimum middle channel potential, and the result obtained is compared with the DMG MOSFET threshold voltage to show the improvement in the threshold voltage roll-off. It is shown that the DMG-LDD MOSFET structure alleviates the problem of short channel effects （SCEs） and the drain induced barrier lowering （DIBL） more efficiently. The proposed model is verified by comparing the theoretical results with the simulated data obtained by using the commercially available ATLASTM 2D device simulator.展开更多
Introduction: Antibodies to voltage-gated potassium channels have been implicated in causing a host of peripheral and central nervous system disorders. However, the presence of these antibodies has not been previously...Introduction: Antibodies to voltage-gated potassium channels have been implicated in causing a host of peripheral and central nervous system disorders. However, the presence of these antibodies has not been previously associated with motor neuropathy. We describe the first case of acquired motor neuron disease associated with voltage-gated potas-sium channel antibodies. Case Report: The patient is an 81-year-old female who developed signs and symptoms of an idiopathic motor neuron disease. The patient was found to have increased antibodies to voltage-gated potassium chan-nels in the absence of a known metastatic or autoimmune process. Magnetic resonance imaging of the cervical spine demonstrated increased signal in the anterior horn regions of the cervical and upper thoracic spinal cord on T2-weighted imaging. The patient’s disease progression was refractory to both intravenous immunoglobulin and ster-oid therapy. Conclusion: Voltage-gated potassium channels may be causal or simply associated with motor neuron disease;this relationship needs to be elucidated. Testing for these antibodies may be warranted in cases of idiopathic rapidly progressing motor neuron disease.展开更多
Epilepsy is described as the most common chronic brain disorder. A typical symptom of epilepsy results in uncontrolled convulsions caused by temporary excessive neuronal discharges. Although several new anticon-vulsan...Epilepsy is described as the most common chronic brain disorder. A typical symptom of epilepsy results in uncontrolled convulsions caused by temporary excessive neuronal discharges. Although several new anticon-vulsants have been introduced, some types of seizures have still not been adequately controlled with these new and current therapies. There is an urgent need to develop new anticonvulsant drugs to control the many different types of seizures. Many studies have shown that the epilepsies involve more than one mechanism and therefore may be responsible for the various types of observed seizures. Recently reported studies have shown that a group of newly synthesized 6 Hz active anticonvulsant fluorinated N-benzamide enaminones exhibited selective inhibitions of voltage-gated sodium (Nav) channels. Nav channels are responsible for the initial inward currents during the depolarization phases of the action potential in excitable cells. The activation and opening of Nav channels result in the initial phases of action potentials. We hypothesize that there is an essential pharmacophore model for the interactions between these enaminones and the active sites of Nav channels. The research reported here is focused on molecular docking studies of the interactions that occur between the fluorinated N-benzamide enaminones and the Nav channels. These studies may open an avenue for designing anticonvulsant drugs by inhibiting Nav channels.展开更多
In the present work, a two-dimensional（2D） analytical framework of triple material symmetrical gate stack（TMGS）DG-MOSFET is presented in order to subdue the short channel effects. A lightly doped channel along wit...In the present work, a two-dimensional（2D） analytical framework of triple material symmetrical gate stack（TMGS）DG-MOSFET is presented in order to subdue the short channel effects. A lightly doped channel along with triple material gate having different work functions and symmetrical gate stack structure, showcases substantial betterment in quashing short channel effects to a good extent. The device functioning amends in terms of improved exemption to threshold voltage roll-off, thereby suppressing the short channel effects. The encroachments of respective device arguments on the threshold voltage of the proposed structure are examined in detail. The significant outcomes are compared with the numerical simulation data obtained by using 2D ATLAS;device simulator to affirm and formalize the proposed device structure.展开更多
文摘Voltage gated calcium channel(VGCC) antibodies are generally associated with Lambert-Eaton myasthenic syndrome. However the presence of this antibody has been associated with paraneoplastic as well as nonparaneoplastic cerebellar degeneration. Most patients with VGCC-antibody-positivity have small cell lung cancer(SCLC). Lambert-Eaton myasthenic syndrome(LEMS)is an autoimmune disease of the presynaptic part of the neuromuscular junction. Its classical clinical triadis proximal muscle weakness, areflexia and autonomic dysfunction. Fifty to sixty percent of LEMS patients have a neoplasia, usually SCLC. The co-occurrence of SCLC and LEMS causes more severe and progressive disease and shorter survival than non-paraneoplastic LEMS. Treatment includes 3,4 diaminopyridine for symptomatic purposes and immunotherapy with prednisolone, azathioprine or intravenous immunoglobulin in patients unresponsive to 3,4 diaminopyridine. Paraneoplastic cerebellar degeneration(PCD) is a syndrome characterized with severe, subacute pancerebellar dysfunction. Serum is positive for VGCC antibody in 41%-44% of patients, usually with the co-occurrence of SCLC. Clinical and electrophysiological features of LEMS are also present in 20%-40% of these patients. Unfortunately, PCD symptoms do not improve with immunotherapy. The role of VGCC antibody in the immunopathogenesis of LEMS is well known whereas its role in PCD is still unclear. All patients presenting with LEMS or PCD must be investigated for SCLC.
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.
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the National Natural Science Foundation of China(No.30470559,30330230,30240059)the National Basic Research Development Program(973)of China(No.2007CB512501)Beijing Natural Science Foundation(No.7052039)
文摘Dorsal root ganglion(DRG)neurons have peripheral terminals in skin,muscle,and other peripheral tissues,andcentral
文摘Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current ( named Ⅰf, Ⅰh, or Ⅰq). Recent studies have unveiled the molecular identity of HCN (HCN1-4) channels. HCN isoforms are unevenly expressed in the heart, even in the sinoatrial node. Features of HCN currents have been characterized in cardiac and other types of cells or in cell lines transfected with the HCN isoforms. The factors modulating Ih and the physiological significance of HCN channels in the heart have been extensively investigated in recent years. The hypothesis for transplanting and/or creating biological pacemakers to replace diseased sinoatrial and/or atrioventricular nodes has been postulated and tested in animal models. Local overexpression of HCN2 channels in the left atrium or in the left conductive bundle branch of the left ventricle via gene delivery induced significant Ⅰh and escape rhythms during vagal stimulation in canines. In addition, implantation of human mesenchymal stem cells with overexpression of HCN2 channels to the canine left ventricular wall was associated with formation of spontaneous escape rhythms of left-sided origin during vagal-stimulation-induced sinus arrest. This preliminary data suggest that the use of HCN channels may hold great promise in,the development of biological pacemakers.
文摘Abstract Hyperpolarization-activated cyclic-nucleotide-gated ( HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current (named If, Ih, or Iq). Recent studies have unveiled the molecular identity of HCN (HCN 1-4) channels. HCN isoforms are unevenly expressed in the heart, even in the sinoatrial node. Features of HCN currents have been characterized in cardiac and other types of cells or in cell lines transfected with the HCN isoforms. The factors modulating Ih and the physiological significance of HCN channels in the heart have been extensively investigated in recent years. The hypothesis for transplanting and/or creating biological pacemakers to replace diseased sinoatrial and/or atrioventricular nodes has been postulated and tested in animal models. Local overexpression of HCN2 channels in the left atrium or in the left conductive bundle branch of the left ventricle via gene delivery induced significant Ih and escape rhythms during vagal stimulation in canines. In addition, implantation of human mesenchymal stem cells with overexpression of HCN2 channels to the canine left ventricular wall was associated with formation of spontaneous escape rhythms of left-sided origin during vagal-stimulation-induced sinus arrest. This preliminary data suggest that the use of HCN channels may hold great promise in the development of biological pacemakers.
基金supported by the National Science Foundation of China (Grant No. 81000456)the Science and Technology Department of Sichuan Province (Grant No. 2009SZ0171)
文摘Chlorogenic acid（5-caffeoylquinic acid, CGA） is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to its notable biological functions against cardiovascular diseases, type-2 diabetes and inflammatory conditions, CGA was recently hypothesized to be an alternative for the treatment of neurological diseases such as Alzheimer＇s disease and neuropathic pain disorders. However, its mechanism of action is unclear.Voltage-gated potassium channel（Kv） is a crucial factor in the electro-physiological processes of sensory neurons. Kv has also been identified as a potential therapeutic target for inflammation and neuropathic pain disorders. In this study, we analysed the effects of CGA on the two main subtypes of Kv in trigeminal ganglion neurons, namely, the IK,Aand IK,Vchannels. Trigeminal ganglion（TRG）neurons were acutely disassociated from the rat TRG, and two different doses of CGA（0.2 and 1 mmol·L21） were applied to the cells.Whole-cell patch-clamp recordings were performed to observe alterations in the activation and inactivation properties of the IK,Aand IK,Vchannels. The results demonstrated that 0.2 mmol·L21CGA decreased the peak current density of IK,A. Both 0.2 mmol·L21and1 mmol·L21CGA also caused a significant reduction in the activation and inactivation thresholds of IK,Aand IK,V. CGA exhibited a strong effect on the activation and inactivation velocities of IK,Aand IK,V. These findings provide novel evidence explaining the biological effects of CGA, especially regarding its neurological effects.
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.
基金Project supported by the National Key Science&Technology Special Project of China(Grant No.2017ZX01001301)the National Key Research and Development Program of China(Grant No.2016YFB0400100)the National Natural Science Foundation of China(Grant Nos.51777168 and 61801374).
文摘A large gate metal height technique is proposed to enhance breakdown voltage in GaN channel and AlGaN channel high-electron-mobility-transistors(HEMTs).For GaN channel HEMTs with gate-drain spacing LGD=2.5μm,the breakdown voltage VBR increases from 518 V to 582 V by increasing gate metal height h from 0.2μm to 0.4μm.For GaN channel HEMTs with LGD=7μm,VBR increases from 953 V to 1310 V by increasing h from 0.8μm to 1.6μm.The breakdown voltage enhancement results from the increase of the gate sidewall capacitance and depletion region extension.For Al0.4Ga0.6N channel HEMT with LGD=7μm,VBR increases from 1535 V to 1763 V by increasing h from 0.8μm to 1.6μm,resulting in a high average breakdown electric field of 2.51 MV/cm.Simulation and analysis indicate that the high gate metal height is an effective method to enhance breakdown voltage in GaN-based HEMTs,and this method can be utilized in all the lateral semiconductor devices.
文摘An analytical model for the channel potential and the threshold voltage of the short channel dual-material-gate lightly doped drain （DMG-LDD） metal-oxide-semiconductor field-effect transistor （MOSFET） is presented using the parabolic approximation method. The proposed model takes into account the effects of the LDD region length, the LDD region doping, the lengths of the gate materials and their respective work functions, along with all the major geometrical parameters of the MOSFET. The impact of the LDD region length, the LDD region doping, and the channel length on the channel potential is studied in detail. Furthermore, the threshold voltage of the device is calculated using the minimum middle channel potential, and the result obtained is compared with the DMG MOSFET threshold voltage to show the improvement in the threshold voltage roll-off. It is shown that the DMG-LDD MOSFET structure alleviates the problem of short channel effects （SCEs） and the drain induced barrier lowering （DIBL） more efficiently. The proposed model is verified by comparing the theoretical results with the simulated data obtained by using the commercially available ATLASTM 2D device simulator.
文摘Introduction: Antibodies to voltage-gated potassium channels have been implicated in causing a host of peripheral and central nervous system disorders. However, the presence of these antibodies has not been previously associated with motor neuropathy. We describe the first case of acquired motor neuron disease associated with voltage-gated potas-sium channel antibodies. Case Report: The patient is an 81-year-old female who developed signs and symptoms of an idiopathic motor neuron disease. The patient was found to have increased antibodies to voltage-gated potassium chan-nels in the absence of a known metastatic or autoimmune process. Magnetic resonance imaging of the cervical spine demonstrated increased signal in the anterior horn regions of the cervical and upper thoracic spinal cord on T2-weighted imaging. The patient’s disease progression was refractory to both intravenous immunoglobulin and ster-oid therapy. Conclusion: Voltage-gated potassium channels may be causal or simply associated with motor neuron disease;this relationship needs to be elucidated. Testing for these antibodies may be warranted in cases of idiopathic rapidly progressing motor neuron disease.
文摘Epilepsy is described as the most common chronic brain disorder. A typical symptom of epilepsy results in uncontrolled convulsions caused by temporary excessive neuronal discharges. Although several new anticon-vulsants have been introduced, some types of seizures have still not been adequately controlled with these new and current therapies. There is an urgent need to develop new anticonvulsant drugs to control the many different types of seizures. Many studies have shown that the epilepsies involve more than one mechanism and therefore may be responsible for the various types of observed seizures. Recently reported studies have shown that a group of newly synthesized 6 Hz active anticonvulsant fluorinated N-benzamide enaminones exhibited selective inhibitions of voltage-gated sodium (Nav) channels. Nav channels are responsible for the initial inward currents during the depolarization phases of the action potential in excitable cells. The activation and opening of Nav channels result in the initial phases of action potentials. We hypothesize that there is an essential pharmacophore model for the interactions between these enaminones and the active sites of Nav channels. The research reported here is focused on molecular docking studies of the interactions that occur between the fluorinated N-benzamide enaminones and the Nav channels. These studies may open an avenue for designing anticonvulsant drugs by inhibiting Nav channels.
文摘In the present work, a two-dimensional（2D） analytical framework of triple material symmetrical gate stack（TMGS）DG-MOSFET is presented in order to subdue the short channel effects. A lightly doped channel along with triple material gate having different work functions and symmetrical gate stack structure, showcases substantial betterment in quashing short channel effects to a good extent. The device functioning amends in terms of improved exemption to threshold voltage roll-off, thereby suppressing the short channel effects. The encroachments of respective device arguments on the threshold voltage of the proposed structure are examined in detail. The significant outcomes are compared with the numerical simulation data obtained by using 2D ATLAS;device simulator to affirm and formalize the proposed device structure.
