The SH2 domain-containing protein tyrosine phosphatase 2(SHP2,also known as PTP2C),encoded by PTPN11,is ubiquitously expressed and has context-specific effects.It promotes RAS/MAPK signaling downstream of receptor tyr...The SH2 domain-containing protein tyrosine phosphatase 2(SHP2,also known as PTP2C),encoded by PTPN11,is ubiquitously expressed and has context-specific effects.It promotes RAS/MAPK signaling downstream of receptor tyrosine kinases,cytokine receptors,and extracellular matrix proteins,and was shown in various lineages to modulate cell survival,proliferation,differentiation,and migration.Over the past decade,PTPN11 inactivation in chondrocytes was found to cause metachondromatosis,a rare disorder characterized by multiple enchondromas and osteochondroma-like lesions.Moreover,SHP2 inhibition was found to mitigate osteoarthritis pathogenesis in mice,and abundant but incomplete evidence suggests that SHP2 is crucial for cartilage development and adult homeostasis,during which its expression and activity are tightly regulated transcriptionally and posttranslationally,and by varying sets of functional partners.Fully uncovering SHP2 actions and regulation in chondrocytes is thus fundamental to understanding the mechanisms underlying both rare and common cartilage diseases and to designing effective disease treatments.We here review current knowledge,highlight recent discoveries and controversies,and propose new research directions to answer remaining questions.展开更多
针对PTP(precise time protocol)协议在应用层获取软件时间戳导致时钟同步精度下降的问题,提出一种基于MAC(media access control)层获取硬件时间戳的PTP同步优化方案。设计了以STM32F407微处理器为核心的PTP时钟应用平台,在MAC层实现...针对PTP(precise time protocol)协议在应用层获取软件时间戳导致时钟同步精度下降的问题,提出一种基于MAC(media access control)层获取硬件时间戳的PTP同步优化方案。设计了以STM32F407微处理器为核心的PTP时钟应用平台,在MAC层实现了硬件时间戳获取,避免了由于协议栈软件处理延时产生的不确定性;针对PTP时钟晶振老化导致的时间同步偏差及网络延迟抖动问题,采用迭代方法优化了本地时钟频率调节算法,提高了频率校正精度。经实际测试,主从时钟偏差的RMS(root mean square)优于20 ns,提升了时钟同步精度。展开更多
本文探讨了一种采用通用IT服务器平台实现专业媒体网络下IP流时钟同步精度分析和监测方法,实现对基于SMPTE ST 2110、SMPTE ST 2022-6等多种专业媒体网络IP流的时钟锁定精度状态进行实时监测和分析,同时该平台具备多通道IP流同时分析的...本文探讨了一种采用通用IT服务器平台实现专业媒体网络下IP流时钟同步精度分析和监测方法,实现对基于SMPTE ST 2110、SMPTE ST 2022-6等多种专业媒体网络IP流的时钟锁定精度状态进行实时监测和分析,同时该平台具备多通道IP流同时分析的能力,并提供信息上报接口。展开更多
基金NIH and NIAMS Grants R21 AR081642(W.Y.),R01 AR066746(W.Y.),R01 AR080062(V.L.)and R01 AR83245(V.L.)supported by the Rhode Island Hospital Orthopaedic Foundation(W.Y.).
文摘The SH2 domain-containing protein tyrosine phosphatase 2(SHP2,also known as PTP2C),encoded by PTPN11,is ubiquitously expressed and has context-specific effects.It promotes RAS/MAPK signaling downstream of receptor tyrosine kinases,cytokine receptors,and extracellular matrix proteins,and was shown in various lineages to modulate cell survival,proliferation,differentiation,and migration.Over the past decade,PTPN11 inactivation in chondrocytes was found to cause metachondromatosis,a rare disorder characterized by multiple enchondromas and osteochondroma-like lesions.Moreover,SHP2 inhibition was found to mitigate osteoarthritis pathogenesis in mice,and abundant but incomplete evidence suggests that SHP2 is crucial for cartilage development and adult homeostasis,during which its expression and activity are tightly regulated transcriptionally and posttranslationally,and by varying sets of functional partners.Fully uncovering SHP2 actions and regulation in chondrocytes is thus fundamental to understanding the mechanisms underlying both rare and common cartilage diseases and to designing effective disease treatments.We here review current knowledge,highlight recent discoveries and controversies,and propose new research directions to answer remaining questions.
文摘针对PTP(precise time protocol)协议在应用层获取软件时间戳导致时钟同步精度下降的问题,提出一种基于MAC(media access control)层获取硬件时间戳的PTP同步优化方案。设计了以STM32F407微处理器为核心的PTP时钟应用平台,在MAC层实现了硬件时间戳获取,避免了由于协议栈软件处理延时产生的不确定性;针对PTP时钟晶振老化导致的时间同步偏差及网络延迟抖动问题,采用迭代方法优化了本地时钟频率调节算法,提高了频率校正精度。经实际测试,主从时钟偏差的RMS(root mean square)优于20 ns,提升了时钟同步精度。
