Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not...Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.展开更多
辅助驾驶和自动驾驶让汽车变得越来越智能,确保汽车安全驾驶的条件之一是要确保上位机和执行器即汽车电子控制单元(Electronic Control Unit,ECU)间的通信数据不被篡改。基于汽车开放系统架构(AUTomotive Open System ARchitecture,AUTO...辅助驾驶和自动驾驶让汽车变得越来越智能,确保汽车安全驾驶的条件之一是要确保上位机和执行器即汽车电子控制单元(Electronic Control Unit,ECU)间的通信数据不被篡改。基于汽车开放系统架构(AUTomotive Open System ARchitecture,AUTOSAR)的板端加密通信(Security Onboard Communication,SecOC)具有防重放和防篡改的特点,可以有效保护ECU间的通信信息。鉴于此,深入研究了SecOC车内网络安全通信,分析了SecOC每个模块的作用与原理,实现了SecOC车内网络安全通信,将该设计应用于某电动助力转向系统的产品中,并创建了基于控制器局域网(Controller Area Network,CAN)开发环境(CAN Open Environment,CANoe)的SecOC仿真模型。最后,通过测试证明了所提模型的有效性和可靠性。展开更多
Vertical GaN power MOSFET is a novel technology that offers great potential for power switching applications.Being still in an early development phase,vertical GaN devices are yet to be fully optimized and require car...Vertical GaN power MOSFET is a novel technology that offers great potential for power switching applications.Being still in an early development phase,vertical GaN devices are yet to be fully optimized and require careful studies to foster their development.In this work,we report on the physical insights into device performance improvements obtained during the development of vertical GaN-on-Si trench MOSFETs(TMOS’s)provided by TCAD simulations,enhancing the dependability of the adopted process optimization approaches.Specifically,two different TMOS devices are compared in terms of transfer-curve hysteresis(H)and subthreshold slope(SS),showing a≈75%H reduction along with a≈30%SS decrease.Simulations allow attributing the achieved improvements to a decrease in the border and interface traps,respectively.A sensitivity analysis is also carried out,allowing to quantify the additional trap density reduction required to minimize both figures of merit.展开更多
基金supported by grants from the National Health and Medical Research Council(NHMRC)of Australia(Nos.571100 and 1048082)the Baxter Charitable Foundation(to TCL)+1 种基金Medical Research grants from the Rebecca L.Cooper Medical Research Foundation(to MWW,TCL,and MDL)supported by a Charles D.Kelman,M.D.Postdoctoral Award(2010)from the International Retinal Research Foundation(USA)。
文摘Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.
文摘辅助驾驶和自动驾驶让汽车变得越来越智能,确保汽车安全驾驶的条件之一是要确保上位机和执行器即汽车电子控制单元(Electronic Control Unit,ECU)间的通信数据不被篡改。基于汽车开放系统架构(AUTomotive Open System ARchitecture,AUTOSAR)的板端加密通信(Security Onboard Communication,SecOC)具有防重放和防篡改的特点,可以有效保护ECU间的通信信息。鉴于此,深入研究了SecOC车内网络安全通信,分析了SecOC每个模块的作用与原理,实现了SecOC车内网络安全通信,将该设计应用于某电动助力转向系统的产品中,并创建了基于控制器局域网(Controller Area Network,CAN)开发环境(CAN Open Environment,CANoe)的SecOC仿真模型。最后,通过测试证明了所提模型的有效性和可靠性。
基金funding from the Electronic Component Systems for European Leadership Joint Undertaking (ECSEL JU),under grant agreement No.101007229support from the European Union’s Horizon 2020 Research and Innovation Programme,Germany,France,Belgium,Austria,Sweden,Spain,and Italy
文摘Vertical GaN power MOSFET is a novel technology that offers great potential for power switching applications.Being still in an early development phase,vertical GaN devices are yet to be fully optimized and require careful studies to foster their development.In this work,we report on the physical insights into device performance improvements obtained during the development of vertical GaN-on-Si trench MOSFETs(TMOS’s)provided by TCAD simulations,enhancing the dependability of the adopted process optimization approaches.Specifically,two different TMOS devices are compared in terms of transfer-curve hysteresis(H)and subthreshold slope(SS),showing a≈75%H reduction along with a≈30%SS decrease.Simulations allow attributing the achieved improvements to a decrease in the border and interface traps,respectively.A sensitivity analysis is also carried out,allowing to quantify the additional trap density reduction required to minimize both figures of merit.