利用系统级封装(System in Package,SiP)技术,可以将多个DDR芯片堆叠键合封装成DDR微组件,具有尺寸小、性能高等优点,应用广泛。DDR微组件结构、功能复杂,如何进行测试越来越得到关注。针对DDR微组件电路的测试和可靠性评价问题,设计一...利用系统级封装(System in Package,SiP)技术,可以将多个DDR芯片堆叠键合封装成DDR微组件,具有尺寸小、性能高等优点,应用广泛。DDR微组件结构、功能复杂,如何进行测试越来越得到关注。针对DDR微组件电路的测试和可靠性评价问题,设计一套DDR微组件电路测试系统。该测试系统包含相应的软件和硬件,能够同时实现对DDR3和DDR2微组件电路的实装测试,使用该测试系统能够筛选出故障电路,实现DDR微组件电路的可靠性评价。展开更多
Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through iso...Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.展开更多
为了解决现代计算机系统中双倍数据速率(double data rate,DDR)内存条稳定性与性能的问题,本文提出了一种并行压力自检方法,以提升DDR内存的商用质量。DDR自检测试是确保内存正常工作的关键工序,它不仅能识别和解决潜在的内存问题,还能...为了解决现代计算机系统中双倍数据速率(double data rate,DDR)内存条稳定性与性能的问题,本文提出了一种并行压力自检方法,以提升DDR内存的商用质量。DDR自检测试是确保内存正常工作的关键工序,它不仅能识别和解决潜在的内存问题,还能提高系统的可靠性和稳定性。传统的DDR自检测试一般采用遍历地址线和数据线的方法,这种方法较为简单,仅能发现易复现的故障,无法识别随机异常等较难复现的故障。为此,本文利用现场可编程门阵列(field programmable gate array,FPGA)内部实例化DDR知识产权模块(intellectual property,IP),实现了一种新的DDR高速内存管理方法。分析结果表明:该方法对提升产品的商用质量具有重要的参考价值。展开更多
存储器是构成计算系统的重要组成部分。DDR3内存容量大、带宽高、速度高,广泛应用在数字系统领域。片上网络(Network on Chip,NoC)占用资源少、功耗低,实现了复杂的片上功能单元的互连通信。在异构多节点片上网络中,各节点之间的信息交...存储器是构成计算系统的重要组成部分。DDR3内存容量大、带宽高、速度高,广泛应用在数字系统领域。片上网络(Network on Chip,NoC)占用资源少、功耗低,实现了复杂的片上功能单元的互连通信。在异构多节点片上网络中,各节点之间的信息交互机制对系统性能有重要影响。设计了面向NoC和DDR3控制器的网络接口,用于接收NoC各种请求类型的数据包,并通过AXI总线使DDR3控制器操作DDR3进行读写,向NoC路由器返回相应的响应包。经过前仿和后仿中大量读写操作的验证,表明网络接口读写操作符合NoC协议和AXI协议的时序要求,读写数据具有一致性,DDR3网络接口功能正确,实现了NoC和DDR3之间的高效通信。展开更多
Discoidin domain receptors(DDRs)are single-pass transmembrane proteins belonging to receptor tyrosine kinases(RTKs)family,which are activated by collagen ligands with unusual slow,sustained kinetics,distinguishing the...Discoidin domain receptors(DDRs)are single-pass transmembrane proteins belonging to receptor tyrosine kinases(RTKs)family,which are activated by collagen ligands with unusual slow,sustained kinetics,distinguishing them from canonical RTKs.While DDRs play critical roles in cell adhesion,differentiation,and cancer progression,their activation mechanisms remain partly understood.Here,we investigated the transmembrane domains(TMDs)of DDR1 and DDR2 to elucidate their interaction dynamics in membrane.Using bacterial adenylate cyclase two-hybrid(BACTH)assays,we demonstrated robust homotypic interactions and even stronger heterotypic associations between DDRTMDs.NMR spectroscopy of DDR1TMD and DDR2TMD reconstituted in lipid bilayer-mimetic bicelles showed obvious chemical shift alterations,further validating the stability of their heterocomplex formation.Systematic mutagenesis identified leucine zipper motifs rather than GXXXA motifs mediated both homo-and hetero-associations of DDR1TMD and DDR2TMD.These findings demonstrated the TMD as a critical mediator of DDRs oligomerization and revealed their interaction patterns within membrane.Our study advances the understanding of DDR signaling regulation and highlights transmembrane domain interactions as potential targets for modulating DDR-related pathologies.展开更多
文摘利用系统级封装(System in Package,SiP)技术,可以将多个DDR芯片堆叠键合封装成DDR微组件,具有尺寸小、性能高等优点,应用广泛。DDR微组件结构、功能复杂,如何进行测试越来越得到关注。针对DDR微组件电路的测试和可靠性评价问题,设计一套DDR微组件电路测试系统。该测试系统包含相应的软件和硬件,能够同时实现对DDR3和DDR2微组件电路的实装测试,使用该测试系统能够筛选出故障电路,实现DDR微组件电路的可靠性评价。
基金supported by the National Natural Science Foundation of China(Grant No.32170738)the National Medical Research Council of Singapore(Grant No.NMRC/CBRG/0013/2012).
文摘Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.
文摘存储器是构成计算系统的重要组成部分。DDR3内存容量大、带宽高、速度高,广泛应用在数字系统领域。片上网络(Network on Chip,NoC)占用资源少、功耗低,实现了复杂的片上功能单元的互连通信。在异构多节点片上网络中,各节点之间的信息交互机制对系统性能有重要影响。设计了面向NoC和DDR3控制器的网络接口,用于接收NoC各种请求类型的数据包,并通过AXI总线使DDR3控制器操作DDR3进行读写,向NoC路由器返回相应的响应包。经过前仿和后仿中大量读写操作的验证,表明网络接口读写操作符合NoC协议和AXI协议的时序要求,读写数据具有一致性,DDR3网络接口功能正确,实现了NoC和DDR3之间的高效通信。
基金supported by the National Natural Science Foundation of China(32471354 to T.C.and 82260400 to J.L)Natural Science Foundation of Hainan Province(No.822RC703 to J.L)。
文摘Discoidin domain receptors(DDRs)are single-pass transmembrane proteins belonging to receptor tyrosine kinases(RTKs)family,which are activated by collagen ligands with unusual slow,sustained kinetics,distinguishing them from canonical RTKs.While DDRs play critical roles in cell adhesion,differentiation,and cancer progression,their activation mechanisms remain partly understood.Here,we investigated the transmembrane domains(TMDs)of DDR1 and DDR2 to elucidate their interaction dynamics in membrane.Using bacterial adenylate cyclase two-hybrid(BACTH)assays,we demonstrated robust homotypic interactions and even stronger heterotypic associations between DDRTMDs.NMR spectroscopy of DDR1TMD and DDR2TMD reconstituted in lipid bilayer-mimetic bicelles showed obvious chemical shift alterations,further validating the stability of their heterocomplex formation.Systematic mutagenesis identified leucine zipper motifs rather than GXXXA motifs mediated both homo-and hetero-associations of DDR1TMD and DDR2TMD.These findings demonstrated the TMD as a critical mediator of DDRs oligomerization and revealed their interaction patterns within membrane.Our study advances the understanding of DDR signaling regulation and highlights transmembrane domain interactions as potential targets for modulating DDR-related pathologies.
