Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome,Boomerang Dysplasia,and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1–242), encompassing two calponin-homology domains (assigned CH1 and CH2). Primary variants in FLNB mostly occur in the domain (CH2) and surrounding the hinge-1 region. The four autosomal dominant disorders that are associated with FLNB variants are Larsen syndrome, atelosteogenesis type I (AOI), atelosteogenesis type III (AOIII), and boomerang dysplasia (BD). Despite the intense clustering of FLNB variants contributing to the LS-AO-BD disorders, the genotype-phenotype correlation is still enigmatic. In silico prediction tools and molecular dynamics simulation (MDS) approaches have offered the potential for variant classification and pathogenicity predictions. We retrieved 285 FLNB missense variants from the UniProt, ClinVar, and HGMD databases in the current study. Of these, five and 39 variants were located in the CH1 and CH2 domains, respectively. These variants were subjected to various pathogenicity and stability prediction tools, evolutionary and conservation analyses, and biophysical and physicochemical properties analyses. Molecular dynamics simulation (MDS) was performed on the three candidate variants in the CH2 domain (W148R, F161C, and L171R) that were predicted to be the most pathogenic. The MDS analysis results showed that these three variants are highly compact compared to the native protein, suggesting that they could affect the protein on the structural and functional levels. The computational approach demonstrates the differences between the FLNB mutants and the wild type in a structural and functional context. Our findings expand our knowledge on the genotype-phenotype correlation in FLNB-related LS-AO-BD disorders on the molecular level, which may pave the way for optimizing drug therapy by integrating precision medicine.     

Insights into high mobility group A (HMGA) proteins from Poaceae family: An in silico approach for studying homologs

High mobility group (HMG) proteins are the major architectural proteins. Among HMG proteins, High Mobility Group A (HMGA) is characterized by AT-hook (ATH) motifs, which have an affinity for AT-rich DNA. In this study, we characterized the plant HMGAs from the Poaceae family using in silico methods. The protein sequences for rice HMGAs were retrieved and the corresponding orthologs from grasses were extracted. The phylogenetic analysis identified three major evolutionary clades of grass HMGAs and their ATH motif analysis revealed that HMGAs from clade 1 and 2, except for clade 2 HMGAs, are devoid of high-affinity DNA-binding domain. The clade 2 HMGAs also displayed a highly conserved length of all the spacers and the length of the C-terminal tail following the last ATH. Moreover, the C-terminal tail in clade 2 HMGAs is smaller than HMGAs from any other clade. Unlike clade 2, other clades of Poaceae HMGAs displayed high variability in the length of spacers. Despite several differences among HMGAs of different clades in Poaceae, the H1/H5 domain was found to be highly conserved. This study has revealed the detailed analyses of Poaceae HMGAs and it will be useful for further investigation aiming at the determination of precise biological functions and molecular mechanisms of grass HMGAs.     

求解三维电磁问题的自适应区域分解FDTD方法

将三维电磁场问题的求解区域分解为若干独立的子区域,在各个子区域之间通过连接边界条件,进行自适应检测,当检测到波传播至检测边界上时,相应子区域被激活,并进行传统的FDTD迭代计算,否则该子区域置于休眠状态不参与场值迭代,从而减少计算时间.对三维微带互连结构的信号完整性仿真结果验证了这种采用边界检测的自适应区域分解时域有限差分(ADD-FDTD)方法在节省计算时间和解决复杂问题方面的有效性.     

一种新型微带光子带隙结构

提出一种新型微带光子带隙结构.该结构直接在微带信号线上刻蚀周期性结构,解决了该结构的封装问题,且不增加微带结构的尺寸.采用时域有限差分法分析该结构的S参数,并研究了几何参数与S参数之间的关系,得出了禁带中心频率、带宽随几何参数变化的趋势.     

基于近场时域谱的紧缩场口径优化设计

根据口径近场的时域谱,可以在全频段评估口径的绕射特征,从而建立紧缩场口径设计的一般准则.在X波段8～12GHz,计算了几种限度为5m×5m口径的近场时域谱.计算结果表明,在紧缩场设计中,为降低边缘绕射场电平,方口径优于圆口径,理想多项式锥削优于余弦锥削和均匀分布.提出两种工程化的边齿设计方法,在口径场均匀分布条件下,近场时域干扰谱分量均低于-25dB.口径近场计算均采用口径场卷积法.     

Electrochemical formation of cation-exchanging polypyrrole films within various hydrophilic–hydrophobic domains

The electrochemical polymerization technique has been successfully applied to produce conducting polymer film of controlled ion exchange properties. Polypyrrole films were prepared by electro-oxidative polymerization with doping some alkylsulfonates or Nafion. The ion exchange characteristics across polypyrrole films were examined by means of a novel electrochemical technique, namely, the in situ electrochemical quartz crystal microbalance (EQCM) method. According to EQCM measurements, exchanging ion species was found to be successfully controlled by changing the hydrophilic–hydrophobic balance of the incorporated sulfonated-based dopants. The film's characteristics became anion- to cation-exchanging as the dopants became more hydrophobic in nature. The polypyrrole–Nafion(poly(perfluoroethylene sulfonate)) composite film became to be a complete cation exchanger.     

时域下初始状态转换为激励

在信号与系统教科书中一般认为,复变换域中利用单边z变换或单边拉氏变换可以求解系统的零输入响应和零状态响应,而时域中的卷积运算只能求零状态响应。这是不全面的。本文通过在时域下将系统初始状态转换为激励信号,从而使得利用卷积运算不仅能够计算零状态响应而且可以求解完全响应和零输入响应。它使得时域分析更全面,丰富了时域分析的内容。也使得学生更好的理解时域分析的核心是卷积运算。     

软交换的安全问题及解决策略

软交换网络的安全和服务质量是实现可持续盈利的商业模式所必须要解决的基础性问题.本文分别从业务层设备、控制层设备、接入层设备以及软交换承载网的安全等几个方面对软交换网络的安全性进行了分析并给出了一些建议,同时强调了安全管理在解决软交换网络安全问题中的重要作用.文章最后对某运营商软交换试验网的安全方案进行了介绍.     

服务计算安全模型研究

服务计算是一种新的分布式计算模式。在服务计算中,跨组织广域分布的资源共享对安全提出了极大的挑战,特别是资源的动态变化及应用安全需求的动态变化对安全提出的挑战。本文给出了服务计算的安全模型,分析了这种应用逻辑与安全策略分离的基于信任域的安全模型的主要思想和优点。该模型可为信息栅格安全构建提供一种有效的解决思路。     

解单障碍问题的Lagrangian乘子非匹配网格区域分解法

针对二阶椭圆型单障碍问题提出了一类基于非匹配网格的Lagrang ian乘子非重叠型区域分解方法.并在适当条件下给出了该方法的收敛性分析和收敛速度估计.