Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11

The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration.     

The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation

A challenging task for the adaptive immune system of vertebrates is to identify and eliminate intracellular antigens. Therefore a highly specialized antigen presentation machinery has evolved to display fragments of newly synthesized proteins to effector cells of the immune system at the cell surface. After proteasomal degradation of unwanted proteins or defective ribosome products, resulting peptides are translocated into the endoplasmic reticulum by the transporter associated with antigen processing and loaded onto major histocompatibility complex (MHC) class I molecules. Peptide-MHC I complexes are transported via the secretory pathway to the cell surface where they are then inspected by cytotoxic T lymphocytes, which can trigger an immune response. This review summarizes the current view of the intracellular machinery of antigen processing and of viral immune escape mechanisms to circumvent destruction by the host. Received 4 October 2005; received after revision 19 November 2005; accepted 24 November 2005     

Signaling in the Chemosensory Systems

The mammalian olfactory system is not uniformly organized but consists of several subsystems each of which probably serves distinct functions. Not only are the two major nasal chemosensory systems, the vomeronasal organ and the main olfactory epithelium, structurally and functionally separate entities, but the latter is further subcompartimentalized into overlapping expression zones and projection-related subzones. Moreover, the populations of ‘OR37’ neurons not only express a unique type of olfactory receptors but also are segregated in a cluster-like manner and generally project to only one receptor-specific glomerulus. The septal organ is an island of sensory epithelium on the nasal septum positioned at the nasoplatine duct; it is considered as a ‘mini-nose’ with dual function. A specific chemosensory function of the most recently discovered subsystem, the so-called Grueneberg ganglion, is based on the expression of olfactory marker protein and the axonal projections to defined glomeruli within the olfactory bulb. This complexity of distinct olfactory subsystems may be one of the features determining the enormous chemosensory capacity of the sense of smell.     

On the self-association potential of transmembrane tight junction proteins

Tight junctions seal intercellular clefts via membrane-related strands, hence, maintaining important organ functions. We investigated the self-association of strand-forming transmembrane tight junction proteins. The regulatory tight junction protein occludin was differently tagged and cotransfected in eucaryotic cells. These occludins colocalized within the plasma membrane of the same cell, coprecipitated and exhibited fluorescence resonance energy transfer. Differently tagged strand-forming claudin-5 also colocalized in the plasma membrane of the same cell and showed fluorescence resonance energy transfer. This demonstrates self-association in intact cells both of occludin and claudin-5 in one plasma membrane. In search of dimerizing regions of occludin, dimerization of its cytosolic C-terminal coiledcoil domain was identified. In claudin-5, the second extracellular loop was detected as a dimer. Since the transmembrane junctional adhesion molecule also is known to dimerize, the assumption that homodimerization of transmembrane tight junction proteins may serve as a common structural feature in tight junction assembly is supported. Received 6 October 2005; received after revision 14 December 2005; accepted 27 December 2005 †These authors contributed equally to this work.     

爆破冲击波在隧道变截面断面的传播特性

为研究爆破冲击波在隧道内复杂环境下的传播规律,以老营盘隧道为依托,通过建立三维数值模型,在LS-DYNA软件中分析了隧道断面变化不同系数下冲击波的传播规律。研究结果表明：冲击波经过变截面后,总体上以平面波的形式向前传播;冲击波传播至隧道断面扩大界面时,冲击波超压衰减速度加快,超压峰值降低;当断面扩大1.5倍时,冲击波冲量衰减系数为1.158,冲击波能量残留比率为74.5%;断面扩大倍数越大,冲击波超压衰减速度越大,能量衰减幅度越大;冲击波传播至隧道断面缩小界面时,冲击波超压增大,其衰减速度减缓,导致冲击波造成的损伤程度增加;当断面缩小系数取0.5时,冲击波冲量增强系数为0.687,冲击波能量放大系数为2.122;断面缩小系数越小,冲击波造成的损伤越大。     

基于网格技术的多用户多任务模拟训练系统

针对信息化条件下的武器装备模拟训练问题提出了一种多用户多任务模拟训练系统的概念,这种模式的系统能够满足大规模、多人次的装备教学和训练需求。首先,建立了面向大规模训练的两级用户管理体制,以及B/S与HLA结合的系统体系结构;然后,综合利用Web技术、网格技术（Globus Toolkit 4,GT4）和分布仿真技术（HLA/RTI）等解决了HLA联邦资源共享与整合、系统组织与协同等核心问题,实现了在同一套模拟训练系统上多组用户同时进行相同或者不同训练任务的设计目标;最后,面向通用雷达装备设计并实现了一个原型系统,它具有资源利用率高、重用性强、用户容量大等特点,在XX实验室建设的应用中取得了良好的效果。