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。     

基于多分辨分析的图像拼接并行算法

介绍了小波变换的概念和特性，并利用小波变换的多分辨分析给出了能同时兼顾光滑度和清晰度的图像拼接方法，在此基础上研究了图像拼接算法的并行化．实测结果证明了它的实用性．     

HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival

We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC) tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry. Levels of HE4 mRNA variants were measured by real-time PCR. Mean mRNA levels were compared among 16 normal endometrial samples, 14 grade 1 and 14 grade 3 endometrioid EC, 15 papillary serous EC, and 14 normal human tissue samples. The relationship between levels of HE4 variants and EC patient characteristics was analyzed with the use of Pearson correlation test. We found that, although all five HE4 mRNA variants are detectable in normal tissue samples, their expression is highly tissue-specific, with epididymis, trachea, breast and endometrium containing the highest levels. HE4-V0, -V1, and -V3 are the most abundant variants in both normal and malignant tissues. All variants are significantly increased in both endometrioid and papillary serous EC, with higher levels observed in grade 3 endometrioid EC. In the EC group, HE4-V1, -V3, and -V4 levels inversely correlate with EC patient survival, whereas HE4-V0 levels positively correlate with age. HE4 variants exhibit tissue-specific expression, suggesting that each variant may exert distinct functions in normal and malignant cells. HE4 levels appear to correlate with EC patient survival in a variant-specific manner. When using HE4 as a biomarker for EC management, the effects of age should be considered.     

空间网格结构装配式节点分类与发展需求

空间网格结构装配化发展的关键是装配式节点的研发,国内相关研究起步较晚,亟待更多创新。通过归纳总结网格结构中各种典型的及新发展的装配式节点,分析了其构造特征与现有分类思路,建议研发更完善和实用的分类体系。从节点的功能特性和市场需求出发,针对节点研发提出空间网格结构装配式节点应满足结构适用性、几何适应性、误差容忍性、外观效果和综合经济性要求,并以此为基础,对现有节点的综合性能和推广程度进行分类分析,给出了各类典型节点的定性评价,明确构造组成在节点设计方案中的重要性。通过评价结果与空间网格结构的实际装配化发展水平的对比,印证了所提出的对新型装配式节点性能要求的合理性。总结了网格结构装配式节点发展现状,对其新变化和新趋势进行了展望。