CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation and establishing laterality. Cilia motility defects cause primary ciliary dyskinesia (PCD, MIM244400), a disorder affecting 1:15,000-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive ciliary bending. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD-linked loci. Here we show that the zebrafish cilia paralysis mutant schmalhans (smh(tn222)) encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product. Screening 146 unrelated PCD families identified individuals in six families with reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated protein. These results identify Ccdc103 as a dynein arm attachment factor that causes primary ciliary dyskinesia when mutated.     

Computer analysis of arbitrary reinforced concrete cross-section under bieccentric load

The computational aspects of the problem of ultimate strength analysis of arbitrary reinforced concrete cross-sections under normal force and biaxial bending are considered. The cross-section secant stiffness derived here in sures the convergence of the solution for the equilibrium equations in any load case. The stress-strain relations of con crete and reinforcements are expressed in terms of the piece-wise continuous cubic polynomials. The coefficients of the cross-section equilibrium equations are evaluated numerically by applying the integration rules proposed by Rieckmann and Sommerfield. The present approach is demonstrated through several examples.     

面向组件的软件测试技术

使用组件,特别是第三方商业组件集成开发而成的软件越来越多,面向组件的测试技术的需求越来越大。UML是目前软件开发业应用最广泛的可视化标准建模语言,它能应用于整个软件开发过程的各阶段。UML的许多特点与面向组件的软件测试需求相吻合。基于UML的软件测试技术在对面向组件的软件开发具有广阔的研究和应用前景。     

无线网络中的高效空间-频率编码技术

循环延迟冗余技术(CDD)是OFDM系统中对抗码间串扰的一项重要技术.CDD在发送端采用多天线,不同天线采用不同的相位延迟,从而增加发送端等价的信道频率选择性.首先对CDD技术进行综合评述,然后分析了CDD中的最佳延迟选择,并和CDD技术和经典的Alamouti空时码进行性能比较.仿真结果显示最优延迟下CDD技术能达到更好的性能,并且对天线阵列的数目没有约束.     

基于脉冲切换控制的网络化控制系统设计

利用脉冲切换控制的平均驻留时间方法对基于模型的网络控制系统(Model-Based NetWorked Control System,MB-NCS)进行了研究.将基于模型的网络控制系统建模为一类脉冲切换系统;利用脉冲切换控制的平均驻留时间方法给出了使此脉冲切换系统指数稳定的充分条件;借助Lyapunov稳定性理论和线性矩阵不等式方法设计了使此脉冲切换系统稳定的控制器,并且通过仿真验证了所提出的方法的有效性.     

香港沉积物氧化过程对铅的约束作用

本项研究通过了３２ｄ（天）的连续充气实验,探索硫含量变化对Ｐｂ的影响,结果表明：沉积物充气氧化过程引起ＡＶＳ的迅速减少,同时,Ｐｂ,Ｅｈ,ＤＯ,ｐＨ也发生了明显的变化趋势。     

Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia

Primary ciliary dyskinesia most often arises from loss of the dynein motors that power ciliary beating. Here we show that DNAAF3 (also known as PF22), a previously uncharacterized protein, is essential for the preassembly of dyneins into complexes before their transport into cilia. We identified loss-of-function mutations in the human DNAAF3 gene in individuals from families with situs inversus and defects in the assembly of inner and outer dynein arms. Knockdown of dnaaf3 in zebrafish likewise disrupts dynein arm assembly and ciliary motility, causing primary ciliary dyskinesia phenotypes that include hydrocephalus and laterality malformations. Chlamydomonas reinhardtii PF22 is exclusively cytoplasmic, and a PF22-null mutant cannot assemble any outer and some inner dynein arms. Altered abundance of dynein subunits in mutant cytoplasm suggests that DNAAF3 (PF22) acts at a similar stage as other preassembly proteins, for example, DNAAF2 (also known as PF13 or KTU) and DNAAF1 (also known as ODA7 or LRRC50), in the dynein preassembly pathway. These results support the existence of a conserved, multistep pathway for the cytoplasmic formation of assembly competent ciliary dynein complexes.     

Biomimetic self-templating supramolecular structures

In nature, helical macromolecules such as collagen, chitin and cellulose are critical to the morphogenesis and functionality of various hierarchically structured materials. During tissue formation, these chiral macromolecules are secreted and undergo self-templating assembly, a process whereby multiple kinetic factors influence the assembly of the incoming building blocks to produce non-equilibrium structures. A single macromolecule can form diverse functional structures when self-templated under different conditions. Collagen type I, for instance, forms transparent corneal tissues from orthogonally aligned nematic fibres, distinctively coloured skin tissues from cholesteric phase fibre bundles, and mineralized tissues from hierarchically organized fibres. Nature's self-templated materials surpass the functional and structural complexity achievable by current top-down and bottom-up fabrication methods. However, self-templating has not been thoroughly explored for engineering synthetic materials. Here we demonstrate the biomimetic, self-templating assembly of chiral colloidal particles (M13 phage) into functional materials. A single-step process produces long-range-ordered, supramolecular films showing multiple levels of hierarchical organization and helical twist. Three distinct supramolecular structures are created by this approach: nematic orthogonal twists, cholesteric helical ribbons and smectic helicolidal nanofilaments. Both chiral liquid crystalline phase transitions and competing interfacial forces at the interface are found to be critical factors in determining the morphology of the templated structures during assembly. The resulting materials show distinctive optical and photonic properties, functioning as chiral reflector/filters and structural colour matrices. In addition, M13 phages with genetically incorporated bioactive peptide ligands direct both soft and hard tissue growth in a hierarchically organized manner. Our assembly approach provides insight into the complexities of hierarchical assembly in nature and could be expanded to other chiral molecules to engineer sophisticated functional helical-twisted structures.