CHIP相关基因与MPN患者心脑血管事件的风险分析

目的:分析骨髓增殖性肿瘤(MPN)患者不确定潜能的克隆性造血(CHIP)相关基因突变谱和临床特征,探讨CHIP相关基因与其心脑血管事件(CCE)的相关性及可能作用机制。方法:回顾性分析2019年8月-2022年7月首都医科大学附属北京安贞医院血液科收治的73例MPN患者的临床资料和二代测序结果,采用Logistic回归分析CHIP相关基因、炎症细胞因子对MPN患者CCE的影响。结果:55例(75.3%)MPN患者检出CHIP相关基因,原发性血小板增多症(ET)和真性红细胞增多症(PV)患者CHIP相关基因各突变频率差异无统计学意义。CHIP相关基因突变以单基因形式为主,检出率从高至低依次为JAK2V617F(63.0%,46/73)、ASXL1(16.4%,12/73)、TET2(11.0%,8/73)、DNMT3A(9.6%,7/73)、SRSF2(6.9%,5/73)、SF3B1(4.1%,3/73)、TP53(1.4%,1/73)和PPMID(1.4%,1/73)。年龄>60岁患者CHIP相关基因检出率明显高于≤60岁者[91.7%(33/36)vs 59.5%(22/37)]。27例(37.0%)MPN患者伴CCE(MPN/CCE),2次CCE者5例,均为动脉事件。CCE组患者年龄(62.8±12.8 vs 53.9±15.8岁,P=0.015)、IL-1β水平(17.7±26.0vs 4.3±8.6,P=0.012)、IL-8水平(360.7±598.6 vs 108.3±317.0,P=0.045)、血栓形成史(29.6%vs 2.2%,P=0.020)和CHIP相关基因检出率(88.9%vs 67.4%,P=0.040)高于无CCE组。多因素Logistic回归分析结果显示,年龄(OR=0.917,95%CI:0.843-0.999,P=0.047)、血栓形成史(OR=34.148,95%CI:2.392-487.535,P=0.009)、任何1个CHIP相关基因突变(OR=16.065,95%CI:1.217-212.024,P=0.035)和IL-1β水平升高(OR=0.929,95%CI:0.870-0.992,P=0.027)均是MPN/CCE的独立危险因素;CHIP相关单基因突变与MPN/CCE无关,但DNMT3A(OR=88.717,95%CI:2.690-292.482,P=0.012)、ASXL1(OR=7.941,95%CI:1.045-60.353,P=0.045)突变是PV/CCE的独立危险因素。结论:MPN患者CHIP相关基因突变率高,尤其是60岁以上患者;高龄、血栓形成史、CHIP相关基因突变和IL-1β水平升高是MPN发生CCE的独立危险因素。DNMT3A、ASXL1单基因突变是PV患者CCE的独立危险因素。CHIP相关基因突变及炎症细胞因子IL-1β升高是MPN新的CCE危险因素。

X波段GaAs MMIC低噪声放大器设计研究

文章针对雷达和卫星通信等微波系统需求,设计一种X波段GaAs单片微波集成电路(Monolithic Microwave Integrated Circuit,MMIC)低噪声放大器。该电路为两级放大器级联结构,采用自偏置电路结构,实现单电源3.5 V供电。通过电感峰化和宽带匹配等技术实现X波段的工作频率全覆盖,并实现较低的噪声系数。测试结果表明,在8~12 GHz频率范围内,低噪声放大器功率增益大于23 dB,噪声系数小于1.7 dB,输出1 dB压缩点功率大于13 dBm。

替普瑞酮通过E3泛素连接酶CHIP减轻LPS引起的心肌炎症反应和心功能障碍

目的:探究替普瑞酮又称香叶基香叶基丙酮,GGA)对脂多糖(LPS)诱导的心功能障碍的治疗作用及机制。方法:(1)取8周龄C57BL/6雄性野生型小鼠和热休克蛋白70(HSP70)羧基末端相互作用蛋白(CHIP)基因敲除小鼠,随机分为对照组、LPS组、LPS+GGA组和GGA组,每组8只。用腹腔注射LPS(25 mg/kg)的方法建立模型,于LPS刺激后1 h给予小鼠腹腔注射GGA(100 mg/kg)。利用小动物超声系统评估小鼠心脏功能;采集各组小鼠血清,检测血清肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)水平;HE染色观察病理学改变;ELISA检测心脏组织中炎症因子肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的水平;Western blot检测各组心脏组织HSP70、CHIP、核转运蛋白α2(KPNA2)、髓过氧化物酶(MPO)、血管细胞黏附分子(VCAM)和细胞间黏附分子(ICAM)的蛋白表达以及细胞核NF-κB的水平。(2)利用小鼠心肌细胞HL-1,建立LPS刺激的离体细胞炎症模型。ELISA检测细胞上清中TNF-α和IL-6的水平;Western blot检测心肌细胞中HSP70、CHIP和KPNA2蛋白表达;免疫荧光染色观察细胞核NF-κB的表达。结果:(1)GGA有效改善LPS刺激小鼠的心脏功能,显著提高射血分数和左室短轴缩短率(P<0.01),减少血清CK-MB和LDH含量(P<0.01),减轻心肌损伤。(2)GGA显著减少LPS引起的TNF-α和IL-6炎症因子的释放(P<0.01),以及NF-κB的入核,降低心肌组织中KPNA2、MPO、VCAM和ICAM蛋白表达,增加心肌组织和细胞HSP70的水平(P<0.01)。(3)在CHIP基因敲除的心肌细胞和小鼠中,GGA不能抑制LPS引起的炎症反应,失去了改善LPS刺激小鼠心脏功能的作用。结论:GGA能够减轻LPS引起的心功能障碍,其作用机制与升高HSP70的表达,促进CHIP的活化,减少NF-κB的入核,抑制炎症因子的释放有关。CHIP的敲除使GGA丧失了减轻LPS诱导的炎症反应和心肌损伤的作用。

一种X波段150W紧凑型功率放大器MMIC

基于0.35μm GaN高电子迁移率晶体管(HEMT)工艺平台设计了一款功率放大器单片微波集成电路(MMIC),采用双场板将HEMT的击穿电压提升至200 V;借助热电联合设计,优化HEMT的栅栅间距和末级HEMT布局,器件热阻降至0.55℃/W;输出匹配融合了功率分配/合成、阻抗变换和谐波调谐等功能,并通过多电容串联提高了击穿电压,增强了电路的鲁棒性;优化了版图布局,末级HEMT采用两两共地,并利用片上电感以缩短栅极偏置线,减小了芯片面积。最终,实现了饱和输出功率大于150 W、功率附加效率大于40%、功率增益大于22 dB的X波段功率放大器MMIC,其尺寸为3.8 mm×5.3 mm。该功率放大器MMIC可广泛应用于通信领域。

GaN功率放大器MMIC的近结区热阻解析模型

GaN功率放大器单片微波集成电路(MMIC)的热积累问题是制约其进一步高度集成和大功率化应用的主要技术瓶颈,针对该散热问题,提出了GaN功率放大器MMIC的近结区热阻解析模型。在简单多层叠加的热阻解析模型的基础上,细化至芯片的近结区域,引入了位置矫正因子矩阵和耦合系数矩阵,并通过加栅窗的方式建立了芯片近结区的热阻解析模型。该模型考虑了GaN功率放大器MMIC的特点以及衬底的晶格热效应,可以更准确地表征芯片结温。采用红外热成像仪对6种GaN功率放大器MMIC在不同工作条件下进行了热测试,对比仿真和测试结果发现,解析模型的结温预测误差在10%以内,说明该模型可以准确地表征GaN功率放大器MMIC的热特性,进而用于优化和指导电路拓扑设计。

0.6~18.0 GHz超宽带低噪声放大器MMIC

基于0.15μm GaAs E-pHEMT工艺设计并制备了一款0.6~18.0 GHz的低噪声放大器单片微波集成电路。该放大器使用一级共源共栅结构,通过负反馈实现宽带的匹配设计。同时在共栅晶体管栅极增加到地电容,共源管和共栅管漏极增加峰化电感,以提高高频增益,扩展带宽,改善噪声。常温在片测试结果表明,在3.3 V单电源供电下,0.6~18.0 GHz频带内该款低噪声放大器噪声系数典型值1.5 dB,小信号增益约15 dB,增益平坦度小于±0.9 dB,输入、输出电压驻波比典型值分别为1.7和1.8,1 dB压缩点输出功率典型值14 dBm,功耗72.6 mW,芯片面积1.5 mm×1.2 mm。

一种V波段高效率5W GaN功率放大器MMIC

基于0.13μm SiC基GaN高电子迁移率晶体管(HEMT)工艺,设计了一款V波段GaN功率放大器单片微波集成电路(MMIC)。该功率放大器MMIC采用三级放大拓扑结构以满足增益需求;使用高低阻抗微带传输线进行阻抗匹配,通过威尔金森功分器/合成器完成功率放大器的末端功率合成;通过对晶体管宽长比的设计与多胞晶体管的合成,实现了功率放大器的高功率稳定工作和高效率输出。经过测试,在59~61 GHz频率范围内,在占空比为20%、脉宽为100μs时,该功率放大器MMIC的饱和输出功率达到37 dBm以上,功率附加效率(PAE)大于21.1%,功率增益大于17 dB;连续波测试条件下输出功率大于36.8 dBm, PAE大于21%。该设计在输出功率和PAE上具有一定的优势。

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.

A Fully-Integrated Memristor Chip for Edge Learning

It is still challenging to fully integrate computing in memory chip as edge learning devices.In recent work published on Science,a fully-integrated chip based on neuromorphic memristors was developed for edge learning as artificial neural networks with functionality of synapses,dendrites,and somas.A crossbar-array memristor chip facilitated edge learning including hardware realization,learning algorithm,and cycle-parallel sign-and threshold-based learning(STELLAR)scheme.The motion control and demonstration platforms were executed to improve the edge learning ability for adapting to new scenarios.

Simplified quantitative analysis method and its application in the insitu synthesized copper-based azide chips

Copper-based azide(Cu(N_(3))2 or CuN_(3),CA)chips synthesized by in-situ azide reaction and utilized in miniaturized explosive systems has become a hot research topic in recent years.However,the advantages of in-situ synthesis method,including small size and low dosage,bring about difficulties in quantitative analysis and differences in ignition capabilities of CA chips.The aim of present work is to develop a simplified quantitative analysis method for accurate and safe analysis of components in CA chips to evaluate and investigate the corresponding ignition ability.In this work,Cu(N_(3))2 and CuN_(3)components in CA chips were separated through dissolution and distillation by utilizing the difference in solubility and corresponding content was obtained by measuring N_(3)-concentration through spectrophotometry.The spectrophotometry method was optimized by studying influencing factors and the recovery rate of different separation methods was studied,ensuring the accuracy and reproducibility of test results.The optimized method is linear in range from 1.0-25.0 mg/L,with a correlation coefficient R^(2)=0.9998,which meets the requirements of CA chips with a milligram-level content test.Compared with the existing ICP method,component analysis results of CA chips obtained by spectrophotometry are closer to real component content in samples and have satisfactory accuracy.Moreover,as its application in miniaturized explosive systems,the ignition ability of CA chips with different component contents for direct ink writing CL-20 and the corresponding mechanism was studied.This study provided a basis and idea for the design and performance evaluation of CA chips in miniaturized explosive systems.

A novel integrated microfluidic chip for on-demand electrostatic droplet charging and sorting

On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds,sample loss,and labor-intensive preparation procedures.Here,we demonstrate the development of a novel microfluidic chip that integrates droplet generation,on-demand electrostatic droplet charging,and high-throughput sorting.The charging electrode is a copper wire buried above the nozzle of the microchannel,and the deflecting electrode is the phosphate buffered saline in the microchannel,which greatly simplifies the structure and fabrication process of the chip.Moreover,this chip is capable of high-frequency droplet generation and sorting,with a frequency of 11.757 kHz in the drop state.The chip completes the selective charging process via electrostatic induction during droplet generation.On-demand charged microdroplets can arbitrarilymove to specific exit channels in a three-dimensional(3D)-deflected electric field,which can be controlled according to user requirements,and the flux of droplet deflection is thereby significantly enhanced.Furthermore,a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal.This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.

Single event effects evaluation on convolution neural network in Xilinx 28 nm system on chip

Convolutional neural networks(CNNs) exhibit excellent performance in the areas of image recognition and object detection, which can enhance the intelligence level of spacecraft. However, in aerospace, energetic particles, such as heavy ions, protons, and alpha particles, can induce single event effects(SEEs) that lead CNNs to malfunction and can significantly impact the reliability of a CNN system. In this paper, the MNIST CNN system was constructed based on a 28 nm systemon-chip(SoC), and then an alpha particle irradiation experiment and fault injection were applied to evaluate the SEE of the CNN system. Various types of soft errors in the CNN system have been detected, and the SEE cross sections have been calculated. Furthermore, the mechanisms behind some soft errors have been explained. This research will provide technical support for the design of radiation-resistant artificial intelligence chips.

Efficient stochastic parallel gradient descent training for on-chip optical processor

In recent years,space-division multiplexing(SDM)technology,which involves transmitting data information on multiple parallel channels for efficient capacity scaling,has been widely used in fiber and free-space optical communication sys-tems.To enable flexible data management and cope with the mixing between different channels,the integrated reconfig-urable optical processor is used for optical switching and mitigating the channel crosstalk.However,efficient online train-ing becomes intricate and challenging,particularly when dealing with a significant number of channels.Here we use the stochastic parallel gradient descent(SPGD)algorithm to configure the integrated optical processor,which has less com-putation than the traditional gradient descent(GD)algorithm.We design and fabricate a 6×6 on-chip optical processor on silicon platform to implement optical switching and descrambling assisted by the online training with the SPDG algorithm.Moreover,we apply the on-chip processor configured by the SPGD algorithm to optical communications for optical switching and efficiently mitigating the channel crosstalk in SDM systems.In comparison with the traditional GD al-gorithm,it is found that the SPGD algorithm features better performance especially when the scale of matrix is large,which means it has the potential to optimize large-scale optical matrix computation acceleration chips.

Flip Chip技术在集成电路封装中的应用

阐述从集成电路封装发展现状、Flip Chip技术内涵、Flip Chip技术在集成电路封装中的应用剖析、市场发展展望等多个角度,探讨在集成电路封装中,应用Flip Chip技术的必要性和重要性。

V波段2W高效率GaN功率放大器MMIC的研制

由于氮化镓(GaN)具有高功率密度特性,因此GaN功率放大器在毫米波领域得到快速发展,其性能不断提升。基于此,采用0.13μm GaN工艺,研制了一款V波段高效率的GaN功率放大器单片微波集成电路(MMIC),对0.13μm GaN工艺和器件进行阐述。对功率放大器设计和制作进行研究,包括功率放大器的架构、电路实现以及功率合成和版图实现,并对功率放大器进行测试和结果分析,包括小信号特性和大信号特性。该功率放大器在40 GHz~75 GHz频段内,其饱和输出功率大于2 W,附加效率大于15%,功率增益大于18 dB,可广泛应用于毫米波雷达和通信领域。

Chiplet技术推动半导体产业可持续发展的研究

随着半导体产业面临莫尔定律的瓶颈,寻找新的技术推动力变得至关重要。文章将焦点放在Chiplet技术,这是一种可突破物理和经济限制、进一步提升性能的新兴技术。Chiplet技术利用模组化策略,不仅能提供更高的效能,且符合可持续发展的要求。文章深入探讨了Chiplet技术如何在莫尔定律遇到挑战的情况下推动半导体产业的可持续发展,并期望提供新的思维和发展方向。

副溶血弧菌QsvR ChIP-qPCR方法的建立

目的:建立副溶血弧菌QsvR的染色质免疫共沉淀实时定量PCR(ChIP-qPCR)实验方法。方法:通过热激转化和转化结合将标记2×Flag标签的qsvR片段转入qsvR突变株(ΔqsvR)中,阿拉伯糖诱导表达QsvR-2×Flag蛋白,通过甲醛与基因组DNA进行交联形成2×Flag-QsvR-DNA复合物,将基因组DNA超声裂解为100~1000 bp大小不等的片段,通过特异性抗原抗体反应将蛋白质-DNA复合物沉淀下来,高盐和加热解交联,回收DNA进行qPCR定量DNA,分析副溶血弧菌体内QsvR与靶基因的结合情况。结果:成功构建出实验菌株ΔqsvR/pBAD33-qsvR-2×Flag,以不加阿拉伯糖诱导为对照,经阿拉伯糖诱导菌株的aphA、opaR、exsB和vtrA的免疫共沉淀量明显较高,表明在副溶血弧菌体内QsvR与aphA、opaR、exsB和vtrA具有结合作用。结论:成功建立了副溶血弧菌QsvR的ChIP-qPCR实验方法,可用于原核生物体内蛋白质-DNA相互作用的研究。

X波段平衡式限幅低噪声放大器MMIC

为满足接收机的小型化需求,基于GaAs赝配高电子迁移率晶体管(PHEMT)工艺设计了一款用于8~12 GHz的平衡式限幅低噪声放大器(LNA)单片微波集成电路(MMIC)。将Lange电桥、限幅器、LNA集成在同一衬底上,Lange电桥采用异形设计,芯片比传统尺寸降低30%以上;限幅器级间采用电感匹配结构,提升MMIC的工作带宽;LNA采用并联负反馈、源极电感负反馈以及电流复用拓扑结构,实现超低功耗和良好的稳定性。芯片采用整体最优化设计,在片测试结果表明,在工作频带内,限幅LNA MMIC芯片的增益为(25±0.2)dB(去除1 dB斜率),噪声系数小于1.6 dB,总功耗小于100 mW,耐功率大于46 dBm,该芯片尺寸为2.8 mm×2.4 mm,充分体现了集成工艺的性能和尺寸优势。

基于GaAs PHEMT工艺的超宽带多通道开关滤波器组MMIC

基于0.25μm GaAs赝配高电子迁移率晶体管(PHEMT)工艺,研制了一款超宽带7路开关滤波器组单片微波集成电路(MMIC)芯片。芯片内集成了开关、驱动电路和带通滤波器,实现了开关滤波功能。开关采用反射式串-并联混合结构;译码器和驱动电路控制某一支路开关的导通或关断;带通滤波器由集总电感和电容组成。该开关滤波器组芯片通带频率覆盖0.8~18 GHz。探针测试结果表明,开关滤波器组芯片各个支路的中心插入损耗均小于8.5 dB,通带内回波损耗小于10 dB,典型带外衰减大于40 dB。为后续研发尺寸更小、性能更优的开关滤波器组提供了参考。

2~6GHz高性能开关滤波器组MMIC

基于0.25μm GaAs E/D赝配高电子迁移率晶体管(PHEMT)工艺,设计了一款2~6 GHz开关滤波器组单片微波集成电路(MMIC)芯片。片上集成了8路带通滤波器、输入、输出单刀八掷(SP8T)开关、3-8译码器和驱动器。通过输入、输出SP8T开关进行通道选择,采用三串两并结构,提高了通道间隔离度。带通滤波器组采用多级LC谐振器实现,最小、最大相对带宽分别为18%和100%,可用于宽带及窄带滤波器设计,具有通带插入损耗小,阻带抑制度高等优点。末级级联低通滤波器,实现远端寄生通带抑制大于35 dBc。在片探针测试结果显示,该开关滤波器组芯片在2~6 GHz频率范围内,每个带通滤波器的插入损耗均小于8.5 dB,阻带衰减为40 dB。该芯片具有通道多、功能复杂、集成度高的特点,可应用于宽带雷达系统进行频率预选。