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Preventing autosomal-dominant hearing loss in Bth mice with CRISPR/CasRx-based RNA editing

Signal Transduction and Targeted Therapy 2022年第4期7卷 1258-1270页

作者： Ziwen Zheng Guo Li Chong Cui Fang Wang Xiaohan Wang Zhijiao Xu Huiping Guo yuxin chen Honghai Tang Daqi Wang Mingqian Huang Zheng-Yi chen Xingxu Huang Huawei Li Geng-Lin Li Xiaoxiang Hu Yilai Shu ENT Institute and Department of Otorhinolaryngology Eye&ENT HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China NHC Key Laboratory of Hearing Medicine(Fudan University) Shanghai 200032China State Key Laboratory of Agrobiotechnology China Agricultural UniversityBeijing 100193China College of Biological Sciences China Agricultural UniversityBeijing 100193China School of Life Science and Technology Southeast UniversityNanjing 210096China Department of Otolaryngology-Head and Neck Surgery Graduate Program in Speech and Hearing Bioscience and Technology and Program in NeuroscienceHarvard Medical SchoolBostonMA 02115USA Eaton-Peabody Laboratory Massachusetts Eye and Ear InfirmaryBostonMA 02114USA School of Life Science and Technology ShanghaiTech UniversityShanghai 200031China CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Institutes of Brain Science and the Collaborative Innovation Center for Brain Science Fudan UniversityShanghai 200031China

CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in Tmc1.We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1^(Bth)transcript by 90.8%,and the Tmc1 wild type transcript(Tmc1^(+))by 44.3%.We then injected a newly developed AAV vector(AAV-PHP.eB)based CasRx into the inner ears of neonatal Bth mice,and we found that Tmc1^(Bth)was reduced by 70.2%in 2 weeks with few off-target effects in the whole transcriptome.Consistently,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction current.Importantly,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 weeks.We,therefore,have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss,paving way for its further application in many other hereditary diseases in hearing and beyond.

关键词： CRISPR/Cas editing hearing

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基于图强化学习的配电网故障恢复决策

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电力系统自动化 2024年第2期48卷 151-158页

作者：张沛陈玉鑫王光华李晓影北京交通大学电气工程学院北京市100044 国网河北省电力有限公司保定供电分公司河北省保定市071000

针对配电网拓扑变化时启发式等算法在配电网故障恢复决策中求解效果与适应性变差的问题,提出了一种基于图强化学习的故障恢复决策方法。首先,利用图数据表征故障恢复中的决策信息,包括配电网拓扑结构与电气特征信息。然后,在图强化学习... 详细信息

针对配电网拓扑变化时启发式等算法在配电网故障恢复决策中求解效果与适应性变差的问题,提出了一种基于图强化学习的故障恢复决策方法。首先,利用图数据表征故障恢复中的决策信息,包括配电网拓扑结构与电气特征信息。然后,在图强化学习模型中设置前置图神经网络接收图数据输入,应对故障恢复过程中配电网的拓扑变化。最后,由内嵌图神经网络的强化学习智能体输出最终故障恢复策略以提高决策速度。采用改进的PG&E 69节点配电网算例进行验证,结果表明所提算法求解速度达到毫秒级,较启发式和遗传算法在求解效率上提高了6%~7%,故障恢复策略的负荷恢复率也更高。

关键词：图强化学习图神经网络强化学习配电网故障恢复

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基于编码视频的动态手势数据优化与识别

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北京邮电大学学报 2024年第2期47卷 90-96页

作者：谢晓燕曹盘宇夏浩陈雨馨西安邮电大学计算机学院西安710121

编码视频数据流中的运动矢量和残差等语法元素可用于替代光流进行运动表示,但其固有的像素噪声和特征稀疏性会影响精细动作的识别精度。对此,在对编码视频语法元素进行数据优化的基础上,设计了一个高精度、低复杂度的动态手势识别框架... 详细信息

编码视频数据流中的运动矢量和残差等语法元素可用于替代光流进行运动表示,但其固有的像素噪声和特征稀疏性会影响精细动作的识别精度。对此,在对编码视频语法元素进行数据优化的基础上,设计了一个高精度、低复杂度的动态手势识别框架。首先,提出了关键P帧选择方法,通过选择信息量更高的编码帧解决了特征稀疏性问题;其次,提出了联合残差特征表示方法,利用残差得到精细的手势轮廓图,去除了运动矢量中手部以外的像素噪声;最后,设计了一种轻量而高效的动态手势识别模型,利用优化后的运动矢量和残差获得了类似于光流的计算效果。在viva,sheffield klnect gesture,NvGesture和EgoGesture等数据集上对所提方法进行了验证,实验结果显示,所提方法中仅使用RGB数据模式可达到的识别精度分别为82.94%、99.72%、81.12%和90.48%,降低了89%的存储开销,并且以4.7倍的运行速度获得了与先进方法相近的结果。

关键词：动态手势识别编码视频运动矢量残差数据优化

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时代新人培养:深刻意涵、理论溯源和培育路径

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思想战线 2024年第1期50卷 164-172页

作者：马福运陈雨昕河南师范大学马克思主义学院河南新乡453007

培养担当民族复兴大任的时代新人,是党和人民赋予新时代中国特色社会主义教育的战略任务。时代新人应具备有理想、有本领、有担当的核心特征,以践行社会主义核心价值观为基本遵循,做到德智体美劳全面发展,不负中华民族伟大复兴的历史使... 详细信息

培养担当民族复兴大任的时代新人,是党和人民赋予新时代中国特色社会主义教育的战略任务。时代新人应具备有理想、有本领、有担当的核心特征,以践行社会主义核心价值观为基本遵循,做到德智体美劳全面发展,不负中华民族伟大复兴的历史使命。培养时代新人这一命题的提出,可以从马克思主义科学理论、中华优秀传统文化、中国共产党百年奋斗历程和新时代十年的伟大变革中找到其理论根源和文化自信。而从理论命题转化为生动实践,则需要完善课堂、文化、实践和网络一体化培养机制,打造好课堂场域、实践场域、文化场域和网络场域的育人“生态圈”。

关键词：时代新人深刻内涵理论溯源培育路径

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Role of helicity of a-helical antimicrobia peptides to improve specificity

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Protein & Cell 2014年第8期5卷 631-642页

作者： Yibing Huang Liyan He Guirong Li Naicui Zhai Hongyu Jiang yuxin chen Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education Jilin University Changchun 130012 China National Engineering Laboratory for AIDS Vaccine Jilin University Changchun 130012 China School of Life Sciences Jilin University Changchun 130012 China The First Hospital Jilin University Changchun 130021 China

A major barrier to the use of antimicrobial peptides as antibiotics is the toxicity or ability to lyse eukaryotic cells. In this study, a 26-residue amphipathic a-helical antimicrobial peptide A12L/A20L （Ac-KWKSFLKTFKSLK KTVLHTLLKAISS-amide） was used as the framework to design a series of D- and L-diastereomeric peptides and study the relationships of helicity and biological activi- ties of o-helical antimicrobial peptides. Peptide helicity was measured by circular dichroism spectroscopy and demonstrated to correlate with the hydrophobicity of peptides and the numbers of D-amino acid substitu- tions. Therapeutic index was used to evaluate the selectivity of peptides against prokaryotic cells. By introducing D-amino acids to replace the original L-amino acids on the non-polar face or the polar face of the helix, the hemolytic activity of peptide analogs have been significantly reduced. Compared to the parent peptide, the therapeutic indices were improved of 44-fold and 22-fold against Gram-negative and Gram- positive bacteria, respectively. In addition, D- and L-diastereomeric peptides exhibited lower interaction with zwitterionic eukaryotic membrane and showed the significant membrane damaging effect to bacterial cells. Helicity was proved to play a crucial role on peptide specificity and biological activities. By simply replacing the hydrophobic or the hydrophilic amino acid residues on the non-polar or the polar face of these amphipathic derivatives of the parent peptide with D-amino acids, we demonstrated that this method could have excellent potential for the rational design of antimicrobial pep- tides with enhanced specificity.

关键词： antimicrobial peptides （AMPs） peptideantibiotics helicity secondary structure diastereomericpeptides specificity therapeutic index

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基于IGWO-SVR的地铁车站投资预测

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铁道学报 2024年第5期46卷 179-188页

作者：郝晶晶段鹏鑫陈雨欣段晓晨石家庄铁道大学土木工程学院河北石家庄050043 河北经贸大学数学与统计学学院河北石家庄050061 石家庄铁道大学管理学院河北石家庄050043

为快速准确地预测可行性研究阶段的地铁车站投资以给投资方提供决策支持,提出一种改进的灰狼算法,来优化支持向量回归机参数的方法。通过收集整理地铁车站案例数据并建立数据库作为预测原始样本,利用自助法扩充样本以解决小样本预测准... 详细信息

为快速准确地预测可行性研究阶段的地铁车站投资以给投资方提供决策支持,提出一种改进的灰狼算法,来优化支持向量回归机参数的方法。通过收集整理地铁车站案例数据并建立数据库作为预测原始样本,利用自助法扩充样本以解决小样本预测准确率低的问题;对灰狼算法的初始种群生成、收敛因子和位置更新方式进行改进以避免灰狼算法陷入局部最优的问题;使用改进的灰狼算法对支持向量回归机的参数进行优化,建立地铁车站投资预测模型;以车站实例验证预测模型有效性。结果表明,改进的灰狼算法优化参数的支持向量回归机的预测模型在测试集平均相对误差为4.33%,拟合优度为0.9440,改进的灰狼算法优化参数后预测模型优于未经优化的、粒子群优化的和灰狼算法优化的支持向量回归机预测模型。实例红高路车站相对误差为4.87%,证明提出的模型是有效的。

关键词：投资预测自助法灰狼算法支持向量回归机地铁车站

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Gene regulatory network stabilized by pervasive weak repressions: micro RNA functions revealed by the May–Wigner theory

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National Science Review 2019年第6期6卷 1176-1188页

作者： yuxin chen Yang Shen Pei Lin Ding Tong Yixin Zhao Stefano Allesina Xu Shen Chung-I Wu School of Life Science Sun Yat-Sen University Target Discovery Research Boehringer Ingelheim Pharma Gmb H & Co KG Department of Biostatistics School of Public Health Yale University Department of Ecology and Evolution University of Chicago

Food web and gene regulatory networks(GRNs) are large biological networks, both of which can be analyzed using the May–Wigner theory. According to the theory, networks as large as mammalian GRNs would require dedicated gene products for stabilization. We propose that micro RNAs(mi RNAs) are those products. More than 30% of genes are repressed by mi RNAs, but most repressions are too weak to have a phenotypic consequence. The theory shows that(i) weak repressions cumulatively enhance the stability of GRNs, and(ii) broad and weak repressions confer greater stability than a few strong ones. Hence, the diffuse actions of mi RNAs in mammalian cells appear to function mainly in stabilizing GRNs. The postulated link between m RNA repression and GRN stability can be seen in a different light in yeast, which do not have mi RNAs. Yeast cells rely on non-specific RNA nucleases to strongly degrade m RNAs for GRN stability. The strategy is suited to GRNs of small and rapidly dividing yeast cells, but not the larger mammalian cells. In conclusion, the May–Wigner theory, supplanting the analysis of small motifs, provides a mathematical solution to GRN stability, thus linking mi RNAs explicitly to ’developmental canalization’.

关键词： micro RNAs network stability canalization May–Wigner theory systems biology RNA crosstalk

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Chip-scale metalens microscope for wide-field and depth-of-field imaging

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Advanced Photonics 2022年第4期4卷 68-75页

作者： Xin Ye Xiao Qian yuxin chen Rui Yuan Xingjian Xiao chen chen Wei Hu Chunyu Huang Shining Zhu Tao Li Nanjing University College of Engineering and Applied SciencesNational Laboratory of Solid State MicrostructuresKey Laboratory of Intelligent Optical Sensing and IntegrationJiangsu Key Laboratory of Artificial Functional MaterialsNanjingChina Collaborative Innovation Center of Advanced Microstructures NanjingChina

Microscopy is very important in research and industry,yet traditional optical microscopy suffers from the limited field-of-view(FOV)and depth-of-field(DOF)in high-resolution imaging.We demonstrate a simultaneous large FOV and DOF microscope imaging technology based on a chip-scale metalens device that is implemented by a SiNxmetalens array with a co-and cross-polarization multiplexed dual-phase design and dispersive spectrum zoom effect.A 4-mm×4-mm FOV is obtained with a resolution of 1.74μm and DOF of200μm within a wavelength range of 450 to 510 nm,which definitely exceeds the performance of traditional microscopes with the same resolution.Moreover,it is realized in a miniaturized compact prototype,showing an overall advantage for portable and convenient microscope technology.

关键词： metalens microscope wide-field imaging

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AED-Net:An Abnormal Event Detection Network

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Engineering 2019年第5期5卷 930-939页

作者： Tian Wang Zichen Miao yuxin chen Yi Zhou Guangcun Shan Hichem Snoussi School of Automation Science and Electrical Engineering Beihang UniversityBeijing 100191China Department of Electronic Engineering Dalian Maritime UniversityDalian 116026China School of Instrumentation Science and Opto-electronic Engineering&International Research Institute for Multidisciplinary Science Beihang UniversityBeijing 100191China Institute Charles Delaunay-LM2S-UMR STMR 6281 CNRS University of Technology of TroyesTroyes 10010France

It has long been a challenging task to detect an anomaly in a crowded scene.In this paper,a selfsupervised framework called the abnormal event detection network(AED-Net),which is composed of a principal component analysis network(PCAnet)and kernel principal component analysis(kPCA),is proposed to address this problem.Using surveillance video sequences of different scenes as raw data,the PCAnet is trained to extract high-level semantics of the crowd’s situation.Next,kPCA,a one-class classifier,is trained to identify anomalies within the scene.In contrast to some prevailing deep learning methods,this framework is completely self-supervised because it utilizes only video sequences of a normal situation.Experiments in global and local abnormal event detection are carried out on Monitoring Human Activity dataset from University of Minnesota(UMN dataset)and Anomaly Detection dataset from University of California,San Diego(UCSD dataset),and competitive results that yield a better equal error rate(EER)and area under curve(AUC)than other state-of-the-art methods are observed.Furthermore,by adding a local response normalization(LRN)layer,we propose an improvement to the original AED-Net.The results demonstrate that this proposed version performs better by promoting the framework’s generalization capacity.

关键词： Abnormal events detection Abnormal event detection network Principal component analysis network Kernel principal component analysis

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城市连续隧道交织区主线交织车辆换道点选择行为研究

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重庆交通大学学报（自然科学版） 2024年第5期43卷 46-52页

作者：邬岚陈雨欣陈茜赵顗李铭浩南京林业大学汽车与交通工程学院江苏南京210037 东南大学交通学院江苏南京210096

基于城市连续隧道交织区分析主线交织车辆换道点选择行为,以实地采集的车行轨迹数据为基础,利用随机森林模型分析主线车辆换道点选择行为特征及影响行为决策的影响因素,而后分别采用支持向量机模型与随机森林模型进行换道点选择行为决... 详细信息

基于城市连续隧道交织区分析主线交织车辆换道点选择行为,以实地采集的车行轨迹数据为基础,利用随机森林模型分析主线车辆换道点选择行为特征及影响行为决策的影响因素,而后分别采用支持向量机模型与随机森林模型进行换道点选择行为决策建模和对比分析。研究结果表明:影响主线交织车辆换道点选择的主要因素为目标车辆状态以及本车道的后车状态,且经特征筛选之后建立换道决策模型的精度更高,其中支持向量机模型可以较好的刻画换道行为,模型的预测精度不低于85%。研究成果有助于在仿真模型中更准确描述换道点选择行为,同时为城市连续隧道交织区的优化和辅助驾驶策略制定提供支撑。

关键词：交通运输工程城市连续隧道交织区换道点选择行为行为特征分析决策模型

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