Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

基于三维场景出图的拼接制作2.5维地图算法

针对目前2.5维电子地图的制作与其三维虚拟场景相对独立,且不易更新维护的问题,提出了对三维场景进行图片输出并拼接实现2.5维地图制作的算法。首先设定摄像机长宽值作为最小出图单位,在指定范围内,使用最小出图单位以任意水平角度和俯仰角度输出三维虚拟场景效果图,并记录相关空间信息。然后根据图片左上角点坐标值对所输出图片进行无缝拼接。实验结果表明,该方法在保证地图空间实体表现能力的同时,能够快速替换图中更新区域,提高2.5维地图制作效率。     

基于模糊支持向量机的剪接位点识别

为了提高模糊支持向量机(FSVM)对剪接位点的识别精度,提出一种计算样本隶属度的新方法。将样本到两聚类中心的距离比值作为样本的初始隶属度,采用K近邻(KNN)方法计算样本的紧密度,最后将初始隶属度与紧密度的乘积作为样本的最终隶属度,这样既提高了支持向量的隶属度,又降低了噪声样本的隶属度。将此方法应用到剪接位点的识别中,对组成性5′和3′剪接位点的识别精度分别达到了94.65%和 88.79%,与经典支持向量机相比,3′剪接位点的识别精度提高了7.94%。     

Experimental investigation of bond stress distribution and bond strength in unconfined UHPFRC lap splices under direct tension

Several studies on tension lap splices have shown the improvement of bond strength using Ultra-high performance Fibre Reinforced Concrete (UHPFRC). The bridging effect of fibres on cracks improves the bond splitting strength substantially in comparison to normal concrete. This paper investigates the influence of fibre content on the strength of tension lap splice of reinforcing bars in UHPFRC without additional transverse reinforcement. Different splice lengths and UHPFRC mixes were tested. Internal strain measurements were used to capture the force transfer mechanism and the evolution of longitudinal strain distribution and associated bond stresses. The bond performance is clearly related to the pre- and post-cracking tensile capacity of UHPFRC. At a distance exceeding 2 d_b from bar extremities, bond stress distribution at failure displayed a quasi-constant value regardless of the lap splice length up 10 d_b. This reveals for short lap splices that the bearing action of all ribs along the splice length contributes equally in resisting the applied force. This experimental program provides experimental results for understanding the local force transfer mechanism in UHPFRC lap splice and contribute for further developments on bond in UHPFRC.     

活性粉末混凝土中带肋钢筋搭接性能试验研究#br#

为明确活性粉末混凝土RPC（reactive powder concrete）中带肋钢筋搭接连接的受力性能,合理确定RPC中纵筋的搭接长度,以纵筋搭接长度、RPC强度、搭接钢筋净距和配箍率为试验参数,对39个RPC中的钢筋搭接连接试件进行对拉试验,获得各试验参数对RPC中带肋钢筋搭接连接性能的影响规律。结果表明：对拉荷载作用下,RPC中带肋钢筋搭接连接分别出现钢筋拔出和拉断两种破坏模式,对于保护层厚度小于2倍钢筋直径的拔出破坏试件,一般还伴随外围RPC劈裂裂缝的出现;对于拔出破坏试件,搭接区域的搭接强度随搭接长度增大而略有减小、随RPC强度和配箍率的增加而增大;相较于搭接长度为100mm的试件,搭接长度为150mm试件的搭接强度约减小5%;强度等级为100MPa、120MPa和150MPa的RPC与直径为20mm带肋钢筋间的搭接强度分别约为17.5MPa、19.5MPa和21.1MPa;相较于未配箍筋试件,配箍率为0.34%和0.75%试件的搭接强度分别提高7.8%和13.1%;相较于钢筋净距为20mm试件,净距为0和40mm试件的搭接强度分别约减小5%和8%,但净距40mm试件搭接强度的降低主要是由于试件RPC保护层厚度过小,使得钢筋外围RPC产生劈裂所致。根据试验结果,建立搭接区域钢筋表面搭接强度及临界搭接长度的计算公式,并以该文及其他研究者的试验结果验证了所提公式的适用性,据此可确定带肋钢筋在RPC中的临界搭接长度。     

HNC问答处理系统关键算法研究

HNC问答处理系统是一种崭新的问答处理模式,与传统的问答处理系统相比,它把对语言的处理深入到语言概念空间中进行,以求尽可能地减少语言中的同义和多义模糊。本文在介绍HNC问答处理系统整体构架的同时,设计和实现了问答系统中的3个关键算法,服务于问答系统的不同阶段处理需要。实际应用表明,在这些算法指导下的HNC问答处理系统具有良好的问题处理能力。     

IRB140型工业机器人连续轨迹控制的汉字绘制

编程实现Windows平台下TTF字库轮廓信息的提取;以机器人工作面为平面的情况出发,讨论位置插补,结合样条曲线的参数向量方程,利用等弦长的原理,给出插补算法;对于给定球面,进行姿态插补,结合三维坐标系的旋转变换,给出球面任一点的姿态参数;得出机器人绘制汉字的结果。     

1m厚44 m深地下连续墙的施工工艺

结合地下铁道工程施工技术标准，重点阐述了1m厚44m深地下连续墙的施工方法，对幅段接头、钢筋笼的制作及吊装进行了较深入的研究和探讨，对类似施工具有一定的参考价值。     

预制混凝土空心模剪力墙上下层插筋连接抗震性能试验研究

为研究预制混凝土空心模剪力墙上下层插筋连接的抗震性能,校验所取的搭接长度是否满足要求,对比不同的插筋形式,完成了4个预制混凝土空心模剪力墙试件的拟静力试验和2个试件的静力试验.试验结果表明:所有试件均为受弯破坏,承载力试验值与规范预测值的比值平均为1.31,试件极限位移角为1/85一1/55;试件根部水平滑移较小,对墙体整体抗震性能影响较小;由插筋及竖向分布筋的应变曲线、应变分布及试件整体抗震性能可知,采用的插筋连接及其搭接长度可以有效传递钢筋应力,满足抗震要求;采用双排插筋的试件抗震性能略好于采用单排插筋的试件.