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Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity

Signal Transduction and Targeted Therapy 2024年第1期9卷 259-270页

作者： Yan Sun Xiu-Na Yang Shuang-Shuang Yang Yi-Zhu Lyu Bing Zhang Kai-Wen Liu Na Li Jia-Chen Cui Guang-Xiang Huang Cheng-Lin Liu Jie Xu Jian-Qing Mi Zhu Chen xiao-Hu Fan sai-Juan Chen Shuo Chen Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of Hematology Second Hospital of Dalian Medical UniversityDalian 116023China National Facility for Protein Science Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China Legend Biotech China Nanjing 211112China Shanghai Immune Therapy Institute Shanghai Cancer InstituteState Key Laboratory of Oncogenes and Related GenesRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Wondercel Biotechnology Shenzhen 518052China

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across the cellular membrane.However,cell-surface antigeninduced multimerization(dubbed AIM herein)has not yet been consciously leveraged in chimeric antigen receptor(CAR)engineering for enriching T cell-based therapies.We co-developed ciltacabtagene autoleucel(cilta-cel),whose CAR incorporates two B-cell maturation antigen(BCMA)-targeted nanobodies in tandem,for treating multiple myeloma.Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity.Crystallographic analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution.BCMA-induced nanobody CAR multimerization enhanced cytotoxicity,alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release,towards myeloma-derived cells.Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.

关键词： cytotoxicity Antigen elevated

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A compact multi-pixel superconducting nanowire single-photon detector array supporting gigabit space-to-ground communications

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Light(Science & Applications) 2024年第2期13卷 254-266页

作者： Hao Hao Qing-Yuan Zhao Yang-Hui Huang Jie Deng Fan Yang sai-Ying Ru Zhen Liu Chao Wan Hao Liu Zhi-Jian Li Hua-Bing Wang Xue-Cou Tu La-Bao Zhang xiao-Qing Jia Xing-Long Wu Jian Chen Lin Kang Pei-Heng Wu Research Institute of Superconductor Electronics(RISE) School of Electronic Science and EngineeringNanjing UniversityNanjingJiangsu 210023China Purple Mountain Laboratories NanjingJiangsu 211111China Hefei National Laboratory HefeiAnhui 230088China National Laboratory of Solid State Microstructures and Department of Physics Nanjing UniversityNanjing 210023China

Classical and quantum space-to-ground communications necessitate highly sensitive receivers capable of extracting information from modulated photons to extend the communication distance from near-earth orbits to deep space explorations.To achieve gigabit data rates while mitigating strong background noise photons and beam drift in a highly attenuated free-space channel,a comprehensive design of a multi-functional detector is indispensable.In this study,we present an innovative compact multi-pixel superconducting nanowire single-photon detector array that integrates near-unity detection efficiency(91.6%),high photon counting rate(1.61 Gcps),large dynamic range for resolving different photon numbers(1-24),and four-quadrant position sensing function all within one device.Furthermore,we have constructed a communication testbed to validate the advantages offered by such an architecture.Through 8-PPM(pulse position modulation)format communication experiments,we have achieved an impressive maximum data rate of 1.5 Gbps,demonstrating sensitivities surpassing previous benchmarks at respective speeds.By incorporating photon number information into error correction codes,the receiver can tolerate maximum background noise levels equivalent to 0.8 photons/slot at a data rate of 120 Mbps—showcasing a great potential for daylight operation scenarios.Additionally,preliminary beam tracking tests were conducted through open-loop scanning techniques,which revealed clear quantitative dependence indicating sensitivity variations based on beam location.Based on the device characterizations and communication results,we anticipate that this device architecture,along with its corresponding signal processing and coding techniques,will be applicable in future space-to-ground communication tasks.

关键词： photon supporting correction

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论生成式人工智能侵权的责任主体——以集体主义为视角

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南昌大学学报（人文社会科学版） 2024年第1期55卷 119-131页

作者：陆小华陆赛赛天津大学新媒体与传播学院天津300072 天津大学法学院天津300072

生成式人工智能的快速发展与模糊的责任主体之间形成了巨大的责任鸿沟。生成式人工智能的多方参与者加剧了责任主体的不确定性,故有必要审视现有法律规范框架。侵权法所贯彻个人主义思想的侵权责任规范仍有适用空间,但适用范围有限。生... 详细信息

生成式人工智能的快速发展与模糊的责任主体之间形成了巨大的责任鸿沟。生成式人工智能的多方参与者加剧了责任主体的不确定性,故有必要审视现有法律规范框架。侵权法所贯彻个人主义思想的侵权责任规范仍有适用空间,但适用范围有限。生成式人工智能侵权的救济思维应当转向集体主义视角。尊重技术逻辑构建机器/人-机联合体,并依托侵权场景的类型化搭建多元责任主体的识别路径,进而在联合体内部将责任与经济利益相绑定,以此实现责任分配。

关键词：生成式人工智能人机交互联合体类型集体主义

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Publication scope and priorities of FESE in an evolving world: An editorial update and perspective

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Frontiers of Environmental Science & Engineering 2024年第1期18卷 169-171页

作者： Deng, Shubo Jin, Rencun Liang, sai Liu, Fudong Liu, Jinyong Lyu, Lai Ning, Daliang Pan, Bingcai van Hullebusch, Eric Wang, Bin Wen, Xianghua xiao, Kang Xu, Elvis Genbo Yang, Hong Ying, Qi Zhan, Xinmin Zhao, Dongye

Frontiers of Environmental Science&Engineering(FESE)is one of the flagship journals of the Chinese Academy of Engineering.It is an international peer-reviewed journal that publishes cutting-edge scientific work in all aspects of environmental disciplines.Since 2007,FESE has been an important platform for communicating the cutting-edge progress of theories,methods,technologies,and policies in environmental science and engineering.Its authors and readers involve scientists,engineers,and policymakers that are important stakeholders in dealing with environmental challenges.Prospective authors are encouraged to review recent issues of FESE to gain a deep understanding of the topics that are of great interest to the journal’s readers.In the cover letter,please clearly state the relevance to the journal’s publication scope and priorities.In particular,prospective authors are directed to the following instructions for further details on the scope,novelty and quality expectations,and minimum requirements.

关键词： journal please dealing

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Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children

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World Journal of Pediatrics 2024年第1期20卷 11-25页

作者： Xian-Li Zhang Xi Zhang Wang Hua Zheng-De Xie Han-Min Liu Hai-Lin Zhang Bi-Quan Chen Yuan Chen Xin Sun Yi Xu sai-Nan Shu Shun-Ying Zhao Yun-xiao Shang Ling Cao Yan-Hui Jia Luo-Na Lin Jiong Li Chuang-Li Hao xiao-Yan Dong Dao-Jiong Lin Hong-Mei Xu De-Yu Zhao Mei Zeng Zhi-Min Chen Li-Su Huang Department of Infectious Disease Children's HospitalZhejiang University School of Medicine3333 Binsheng RoadBinjiang DistrictHangzhou 310052China Clinical Research Unit Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Beijing Pediatric Research Institute Beijing Children's HospitalCapital Medical UniversityBeijingChina Department of Pediatric Pulmonology West China Second University HospitalSichuan UniversityChengduChina Department of Pediatric Pulmonology the Second Affiliated Hospital&Yuying Children's HospitalWenzhou Medical UniversityWenzhouChina Department of Infectious Disease Anhui Provincial Children's HospitalHefeiChina Department of Pediatrics the Second Hospital of Hebei Medical UniversityShijiazhuangChina Department of Pediatrics Xijing Hospitalthe Fourth Military Medical UniversityXi'anChina Department of Infectious Disease Guangzhou Women and Children's Medicine CenterGuangzhou Medicine UniversityGuangzhouChina Department of Pediatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Respiratory Disease Beijing Children's HospitalCapital Medical UniversityBeijingChina Department of Pediatric Respiratory Shengjing Hospital of China Medical UniversityShenyangChina Respiratory Department Children's Hospital Affiliated to Capital Institute of PediatricsBeijingChina Department of Clinical Epidemiology Aarhus UniversityAarhusDenmark Department of Respirology Children's Hospital of Soochow UniversitySuzhouChina Department of Respiratory Children's Hospital of ShanghaiChildren's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Infectious Disease Hainan Women and Children's Medical CenterHaikouChina Department of Infectious Disease Children's Hospital of Chongqing Medical UniversityChongqingChina Department of Respiratory Children's Hospital of Nanjing Medical UniversityNanjingChina Department of Infectious Di

Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years,representing a major global healthcare burden.There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life.A multidisciplinary consensus development group comprising experts in epidemiology,infectious diseases,respiratory medicine,and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.Data sources The evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,and the Cochrane Library,using variations in terms for"respiratory syncytial virus","RSV","lower respiratory tract infection","bronchiolitis","acute","viral pneumonia","neonatal","infant""children",and"pediatric".Results Evidence-based recommendations regarding diagnosis,treatment,and prevention were proposed with a high degree of consensus.Although supportive care remains the cornerstone for the management of RSV infections,new monoclonal antibodies,vaccines,drug therapies,and viral surveillance techniques are being rolled out.Conclusions This consensus,based on international and national scientific evidence,reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections.Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

关键词： Consensus prevention Respiratory syncytial virus Treatment

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基于3D打印技术的舰船航行环境三维建模方法

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舰船科学技术 2024年第9期46卷 156-159页

作者：肖赛锋武汉华夏理工学院湖北武汉430000

通过模拟不同的舰船航行场景和紧急情况,操作人员可以在安全的虚拟环境中进行实践,提高应对实际航行中可能遇到的各种情况的能力,为此提出基于3D打印技术的舰船航行环境三维建模方法。该方法采集舰船航行区域卫星的测高数据,以该数据为... 详细信息

通过模拟不同的舰船航行场景和紧急情况,操作人员可以在安全的虚拟环境中进行实践,提高应对实际航行中可能遇到的各种情况的能力,为此提出基于3D打印技术的舰船航行环境三维建模方法。该方法采集舰船航行区域卫星的测高数据,以该数据为基础使用扰动重力反演方式对舰船航行环境的海底地形进行建模,对其进行纹理映射处理,得到舰船航行环境中的海底地形环境;再以舰船的尺寸、重量、材料等参数数据以及舰船场景图像作为基础,使用虚拟现实技术中的3Dmax软件构建舰船三维模型并纹理映射后,得到舰船三维模型,以舰船航行的海底地形三维模型和舰船三维模型为基础,采用光固化3D打印机打印海底地形三维模型和舰船三维模型后,得到现实的舰船航行环境三维建模结果。实验表明,该方法具备较强的扰动重力反演能力,可有效得到舰船航行的海底地形三维模型,以及建立舰船三维模型能力较佳,同时可有效运用3D打印机打印舰船三维模型和海底地形三维模型,应用效果较好。

关键词： 3D打印技术舰船航行环境三维建模扰动重力反演

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模糊整定PI参数的双柔性机械臂振动抑制

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东北大学学报（自然科学版） 2024年第2期45卷 217-225页

作者：李小彭周赛男刘佳琪尹猛东北大学机械工程与自动化学院辽宁沈阳110819 中国科学院深圳先进技术研究院广东深圳518055

机械臂伺服驱动系统中柔性因素的存在易导致机械臂输出转速波动,甚至引发系统谐振.为抑制系统转速波动,使机械臂传动系统性能稳定,使用模糊理论整定PI控制器参数的控制策略.根据假设模态法和拉格朗日动力学方程建立了考虑LuGre摩擦模型... 详细信息

机械臂伺服驱动系统中柔性因素的存在易导致机械臂输出转速波动,甚至引发系统谐振.为抑制系统转速波动,使机械臂传动系统性能稳定,使用模糊理论整定PI控制器参数的控制策略.根据假设模态法和拉格朗日动力学方程建立了考虑LuGre摩擦模型的双柔性机械臂传动系统动力学方程,并分析了动力学方程中耦合非线性项对系统传动特性的影响.使用极点配置策略确定PI控制器参数的取值范围,后根据模糊规则实时调整控制器参数,以减小伺服系统输出转速的波动,进而抑制系统谐振.最后,借助数值仿真分析和机械臂控制实验,与传统PI控制策略对比,发现本文所述控制策略可使电机端转角跟踪误差绝对值的平均值降低43.066%,柔性负载转角误差的标准差降低46.506%,更加验证了所提模糊规则整定PI控制器参数抑振方法的有效性.

关键词：双柔性机械臂柔性关节柔性负载模糊整定 PI控制

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含有柔性负载的电驱动系统建模与控制策略

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东北大学学报（自然科学版） 2024年第3期45卷 346-353,371页

作者：李小彭王浩哲尹猛周赛男东北大学机械工程与自动化学院辽宁沈阳110819 中国科学院深圳先进技术研究院广东深圳518055

为了抑制伺服电机启动和运行过程中产生的转速波动和振动,提出了一种基于极点配置的PI控制策略.首先,根据基尔霍夫电压定律和拉格朗日原理建立了伺服电机与柔性负载的整体动力学模型,并通过拉普拉斯变换计算系统的传递函数.其次,通过设... 详细信息

为了抑制伺服电机启动和运行过程中产生的转速波动和振动,提出了一种基于极点配置的PI控制策略.首先,根据基尔霍夫电压定律和拉格朗日原理建立了伺服电机与柔性负载的整体动力学模型,并通过拉普拉斯变换计算系统的传递函数.其次,通过设计控制器的参数,分析了采用相同幅值的极点配置方法对控制效果的影响.最后,通过与传统的Z-N方法和无控制方法进行对比,验证了该极点配置方法的优势.通过数值仿真和实验研究,实现了对伺服电机启动和运行过程中产生的角度误差的控制,有效抑制了电机转速的波动,保证了系统的稳定性.

关键词：伺服电机柔性负载极点配置 PI控制器速度环

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Atom-referenced and stabilized soliton microcomb

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Science China(Physics,Mechanics & Astronomy) 2024年第2期67卷 2-8页

作者： Rui Niu Shuai Wan Tian-Peng Hua Wei-Qiang Wang Zheng-Yu Wang Jin Li Zhu-Bo Wang Ming Li Zhen Shen Yu Robert Sun Shui-Ming Hu Brent ELittle sai Tak Chu Wei Zhao Guang-Can Guo Chang-Ling Zou Yun-Feng xiao Wen-Fu Zhang Chun-Hua Dong State Key Laboratory of Transient Optics and Photonics Xi’an Institute of Optics and Precision MechanicsChinese Academy of SciencesXi’an 710119China CAS Key Laboratory of Quantum Information University of Science and Technology of ChinaHefei 230026China CAS Center for Excellence in Quantum Information and Quantum Physics University of Science and Technology of ChinaHefei 230026China University of Chinese Academy of Sciences Beijing 100049China Department of Chemical Physics University of Science and Technology of ChinaHefei 230026China Department of Physics and Materials Science City University of Hong KongHong Kong 999077China State Key Laboratory for Mesoscopic Physics and Frontiers Science Center for Nano-optoelectronics School of PhysicsPeking UniversityBeijing 100871China

For the applications of the frequency comb in microresonators,it is essential to obtain a fully frequency-stabilized microcomb laser source.In this study,we present a system for generating a fully atom-referenced stabilized soliton microcomb.The pump light around 1560.48 nm is locked to an ultra-low-expansion(ULE)cavity.This pump light is then frequency-doubled and referenced to the atomic transition of87Rb.The repetition rate of the soliton microcomb is injection-locked to an atomic-clockstabilized radio frequency(RF)source,leading to mHz stabilization at 1 s.As a result,all comb lines have been frequencystabilized based on the atomic reference and the ULE cavity,achieving a very high precision of approximately 18 Hz at 1 s,corresponding to the frequency stability of 9.5×10^(-14).Our approach provides a fully stabilized microcomb experiment scheme with no requirement of f-2f technique,which could be easily implemented and generalized to various photonic platforms,thus paving the way towards the ultraprecise optical sources for high precision spectroscopy.

关键词： microcavity frequency comb dissipative Kerr solitons fully stabilized microcomb

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变长度柔性机械臂的双柔性伺服驱动系统振动抑制策略

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东北大学学报（自然科学版） 2024年第4期45卷 530-539页

作者：刘佳琪李小彭尹猛周赛男东北大学机械工程与自动化学院辽宁沈阳110819 中国科学院深圳先进技术研究院广东深圳518055

变长度的柔性机械臂在旋转运动过程中由于受到环境扰动以及自身柔性的影响导致了伺服驱动系统输出转速的波动现象,这会加剧柔性机械臂的振动,严重影响了柔性机械臂的运动精度.基于此,设计了一种基于干扰观测器的PI控制策略来抑制伺服驱... 详细信息

变长度的柔性机械臂在旋转运动过程中由于受到环境扰动以及自身柔性的影响导致了伺服驱动系统输出转速的波动现象,这会加剧柔性机械臂的振动,严重影响了柔性机械臂的运动精度.基于此,设计了一种基于干扰观测器的PI控制策略来抑制伺服驱动系统转速的波动.首先使用拉格朗日原理建立了双柔性伺服驱动系统的动力学模型并分析了双柔性伺服驱动系统的传动特性;其次将基于干扰观测器的PI控制策略应用于双柔性伺服驱动系统的速度环中,并通过鲁棒稳定性分析设计干扰观测器中的低通滤波器参数;最后开展了数值仿真分析和控制实验.实验结果验证了提出的控制策略能够有效减少变长度柔性机械臂的转速波动,提高伺服驱动系统的运动精度.

关键词：伺服驱动系统转速波动关节柔性控制策略 PI控制

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