多运营商高铁隧道移动网络覆盖方案

高铁移动网络覆盖是国内三大通信运营商的一个重点,而高铁隧道内移动网络覆盖更是运营商的一大难点痛点。文章根据我国中部省份某高铁线路覆盖规划实例,采用“设备+POI+泄漏电缆”模式,即三家运营商信号源设备通过同一POI(point of interface,多系统接入平台)接入,信号输出到泄漏电缆进行隧道覆盖,隧道口场坪站安装宽频切换天线对隧道外进行延伸覆盖,通过链路预算合理布置各运营商主设备信号源,从而实现隧道到室外的无缝覆盖。最后,根据已有成熟网络覆盖解决方案,对未来5G高铁隧道移动网络覆盖方案进行了探讨。     

盖子环替换及定点突变提高菜豆环氧化物水解酶对邻甲基苯基缩水甘油醚的催化性能

菜豆环氧化物水解酶1和2（PvEH1、PvEH2）能够动力学拆分外消旋邻甲基苯基缩水甘油醚（rac-oMGE），从而保留(R)-oMGE。基于对PvEH1和PvEH2结构的同源模拟和分析，发现二者分子中的盖子环差异较大，故本文选择盖子环作为研究目标。经融合聚合酶链式反应（FPCR），获得了PvEH2的盖子环区域被PvEH1对应区域替换的杂合酶Pv2Pv1。用全细胞酶E. coli/pv2pv1催化rac-oMGE，当(S)-oMGE刚好水解完全时，产物(S)-3-邻甲苯基-1,2-丙二醇（(S)-oTPD）的ee_p由PvEH2的58.3%提高至75.5%。为进一步提高酶的性质，在Pv2Pv1中选取11个氨基酸位点进行丙氨酸(A)突变，获得最优突变子E. coli/pv2pv1^K176A，活性为E. coli/pv2pv1（4.2U/g）的2.1倍，且当S构型的底物刚好完全水解时，(S)-oTPD的ee_p进一步提高为80.3%。分子对接分析发现，盖子环替换和K176位点突变为A，均使(R)-oMGE环氧环中的C_α更易受到酶中D101位点的攻击。利用E. coli/pv2pv1^K176A催化150mmol/L rac-oMGE水解制备(R)-oMGE（ee_s＞99%）和(S)-oTPD（ee_p=80.4%），二者的产率Y_S和Y_P分别为32.7%和60.1%，时空产率STY_S和STY_P为1.6g/(L·h)和3.3g/(L·h)。本实验为改善EH的催化性质提供了一种有效策略。     

The Genetic Basis of Primary Myelofibrosis and Its Clinical Relevance

Among classical BCR-ABL-negative myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF) is the most aggressive subtype from a clinical standpoint, posing a great challenge to clinicians. Whilst the biological consequences of the three MPN driver gene mutations (JAK2, CALR, and MPL) have been well described, recent data has shed light on the complex and dynamic structure of PMF, that involves competing disease subclones, sequentially acquired genomic events, mostly in genes that are recurrently mutated in several myeloid neoplasms and in clonal hematopoiesis, and biological interactions between clonal hematopoietic stem cells and abnormal bone marrow niches. These observations may contribute to explain the wide heterogeneity in patients’ clinical presentation and prognosis, and support the recent effort to include molecular information in prognostic scoring systems used for therapeutic decision-making, leading to promising clinical translation. In this review, we aim to address the topic of PMF molecular genetics, focusing on four questions: (1) what is the role of mutations on disease pathogenesis? (2) what is their impact on patients’ clinical phenotype? (3) how do we integrate gene mutations in the risk stratification process? (4) how do we take advantage of molecular genetics when it comes to treatment decisions?     

Translational Read-Through Therapy of RPGR Nonsense Mutations

X-chromosomal retinitis pigmentosa (RP) frequently is caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. We evaluated the potential of PTC124 (Ataluren, Translama^TM) treatment to promote ribosomal read-through of premature termination codons (PTC) in RPGR. Expression constructs in HEK293T cells showed that the efficacy of read-through reagents is higher for UGA than UAA PTCs. We identified the novel hemizygous nonsense mutation c.1154T > A, p.Leu385* ({"type":"entrez-nucleotide","attrs":{"text":"NM_000328.3","term_id":"1677500221"}}NM_000328.3) causing a UAA PTC in RPGR and generated patient-derived fibroblasts. Immunocytochemistry of serum-starved control fibroblasts showed the RPGR protein in a dot-like expression pattern along the primary cilium. In contrast, RPGR was no longer detectable at the primary cilium in patient-derived cells. Applying PTC124 restored RPGR at the cilium in approximately 8% of patient-derived cells. RT-PCR and Western blot assays verified the pathogenic mechanisms underlying the nonsense variant. Immunofluorescence stainings confirmed the successful PTC124 treatment. Our results showed for the first time that PTC124 induces read-through of PTCs in RPGR and restores the localization of the RPGR protein at the primary cilium in patient-derived cells. These results may provide a promising new treatment option for patients suffering from nonsense mutations in RPGR or other genetic diseases.     

A directional mutation operator for differential evolution algorithms

Differential evolution (DE) is widely studied in the past decade. In its mutation operator, the random variations are derived from the difference of two randomly selected different individuals. Difference vector plays an important role in evolution. It is observed that the best fitness found so far by DE cannot be improved in every generation. In this article, a directional mutation operator is proposed. It attempts to recognize good variation directions and increase the number of generations having fitness improvement. The idea is to construct a pool of difference vectors calculated when fitness is improved at a generation. The difference vector pool will guide the mutation search in the next generation once only. The directional mutation operator can be applied into any DE mutation strategy. The purpose is to speed up the convergence of DE and improve its performance. The proposed method is evaluated experimentally on CEC 2005 test set with dimension 30 and on CEC 2008 test set with dimensions 100 and 1000. It is demonstrated that the proposed method can result in a larger number of generations having fitness improvement than classic DE. It is combined with eleven DE algorithms as examples of how to combine with other algorithms. After its incorporation, the performance of most of these DE algorithms is significantly improved. Moreover, simulation results show that the directional mutation operator is helpful for balancing the exploration and exploitation capacity of the tested DE algorithms. Furthermore, the directional mutation operator modifications can save computational time compared to the original algorithms. The proposed approach is compared with the proximity based mutation operator as both are claimed to be applicable to any DE mutation strategy. The directional mutation operator is shown to be better than the proximity based mutation operator on the five variants in the DE family. Finally, the applications of two real world engineering optimization problems verify the usefulness of the proposed method.     

Evolution on neutral networks accelerates the ticking rate of the molecular clock

Large sets of genotypes give rise to the same phenotype, because phenotypic expression is highly redundant. Accordingly, a population can accept mutations without altering its phenotype, as long as the genotype mutates into another one on the same set. By linking every pair of genotypes that are mutually accessible through mutation, genotypes organize themselves into neutral networks (NNs). These networks are known to be heterogeneous and assortative, and these properties affect the evolutionary dynamics of the population. By studying the dynamics of populations on NNs with arbitrary topology, we analyse the effect of assortativity, of NN (phenotype) fitness and of network size. We find that the probability that the population leaves the network is smaller the longer the time spent on it. This progressive ‘phenotypic entrapment’ entails a systematic increase in the overdispersion of the process with time and an acceleration in the fixation rate of neutral mutations. We also quantify the variation of these effects with the size of the phenotype and with its fitness relative to that of neighbouring alternatives.     

金属配合物与核酸作用机理的理论计算

通过计算机模拟金属配合物与核酸作用机理,对其理论模型能量计算和结构优化。在不同的化学环境条件下得到不同的实验模拟结果,对真实的化学反应过程有重要的指导意义和参考意义。通过Gaussian03,Gauss View等软件的结合应用,分别应用于优化计算和理论建模,熟悉了对化学软件操作应用。     

数据库垄断的成因及对策分析

学术数据库市场被少数几个出版商掌握，新的数据库商难以加入到竞争中来，因此导致了学术数据库市场的垄断问题。本文通过叙述学术数据库垄断的四个问题，即数据库定价的不合理、数据库许可权的滥用、经营者集中和数据库用户受限，提出通过开放获取、图书馆联合与立法保护来应对数据库市场的垄断问题。     

具有双通道数据包丢失的Delta算子系统故障检测

研究同时存在双通道数据包丢失和时变时延的Delta算子网络控制系统（NCSs）故障检测问题.假定数据包丢失发生在控制器到执行器、传感器至控制器的数据传输过程中，并且利用两个相互独立的伯努利随机变量描述是否发生丢包.将上述的NCSs建模为网络切换系统，提出任意切换律下故障检测滤波器的设计方法.利用线性矩阵不等式（LMIs）方法、Lyapunov-Krasovskii泛函和平均驻留时间等得出所考虑的网络切换系统具备指数均方稳定性的充分条件.证明了所用的网络切换系统满足H_∞性能，并推导出了滤波器参数的显式表达.数值仿真结果验证了所提方法的有效性.     

基于变异测试的错误定位研究进展

随着软件规模和复杂度的不断提高，软件的质量问题成为了关注的焦点，如何高效地找出软件中的错误成为一个亟需解决的问题。错误定位是软件质量保证的重要途径之一，近年来已经成为软件工程中一个非常重要的研究课题。基于变异测试的错误定位通过比较原程序和对应变异体的差异来计算每条语句的怀疑度，再由怀疑度大小进行排序，程序员根据排序逐个检查找出错误语句。汇总近7年（2012-2018）国内外的基于变异测试的错误定位技术的研究成果，介绍了错误定位的基本方法，介绍基于变异测试的错误定位思想，从变异算子、变异体及等价变异体3个方面对已有的研究工作进行分类归纳和总结，探讨了基于变异测试的错误定位未来可能的研究方向、机遇和挑战。