Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome

Griscelli syndrome (GS, MIM 214450), a rare, autosomal recessive disorder, results in pigmentary dilution of the skin and the hair, the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes. Most patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome (known as haemophagocytic syndrome, HS), leading to death in the absence of bone-marrow transplantation. In contrast, early in life some GS patients show a severe neurological impairment without apparent immune abnormalities. We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients. Further linkage analysis suggested a second gene associated with GS was in the same chromosomal region. Homozygosity mapping in additional families narrowed the candidate region to a 3.1-cM interval between D15S1003 and D15S962. We detected mutations in RAB27A, which lies within this interval, in 16 patients with GS. Unlike MYO5A, the GTP-binding protein RAB27A appears to be involved in the control of the immune system, as all patients with RAB27A mutations, but none with the MYO5A mutation, developed HS. In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not. RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis.     

Control of neurulation by the nucleosome assembly protein-1-like 2

Neurulation is a complex process of histogenesis involving the precise temporal and spatial organization of gene expression. Genes influencing neurulation include proneural genes determining primary cell fate, neurogenic genes involved in lateral inhibition pathways and genes controlling the frequency of mitotic events. This is reflected in the aetiology and genetics of human and mouse neural tube defects, which are of both multifactorial and multigenic origin. The X-linked gene Nap1l2, specifically expressed in neurons, encodes a protein that is highly similar to the nucleosome assembly (NAP) and SET proteins. We inactivated Nap1l2 in mice by gene targeting, leading to embryonic lethality from mid-gestation onwards. Surviving mutant chimaeric embryos showed extensive surface ectoderm defects as well as the presence of open neural tubes and exposed brains similar to those observed in human spina bifida and anencephaly. These defects correlated with an overproduction of neuronal precursor cells. Protein expression studies showed that the Nap1l2 protein binds to condensing chromatin during S phase and in apoptotic cells, but remained cytoplasmic during G1 phase. Nap1l2 therefore likely represents a class of tissue-specific factors interacting with chromatin to regulate neuronal cell proliferation.     

基于设计者智能主体模型的产品开发过程仿真

产品开发过程仿真是对产品开发过程进行预测、管理、评价和改进的有效手段.为了对产品开发过程中的人与组织因素进行仿真,提出了一种设计者驱动的产品开发过程仿真原理.重点对设计者智能主体模型进行了研究,采用INTERRAP混合结构建立了设计者智能主体结构模型,用分层有色随机Petri网描述了设计者的个体行为过程与协作行为过程.最后进行了系列仿真实验,初步证明了模型的有效性.基于设计者智能主体模型的过程仿真可在过程预测与评价、人因及组织分析、设计过程改进等方面发挥重要作用.     

极小化加权总完工时间的同时加工排序问题

讨论了平行机串联工件同时加工排序问题。目标函数是极小化加权总完工时间,并假设满足每批均含有k个工件,并且每批的加工时间为该批中所有工件的加工时间之和。对平行机的情况,该问题是强NP难的。本文主要针对该问题的两种特殊情况:(1)所有工件的权相等;(2)所有工件的加工时间相等,分别给出了最优算法,分析了算法的时间复杂性,同时用数值例子作了说明。     

INFORMATION CHARACTERIZATION OF COMMUNICATION CHANNELS FOR SYSTEM IDENTIFICATION

This paper studies identification of systems in which the system output is quantized, transmitted through a digital communication channel, and observed afterwards. The concept of the CR Ratio is introduced to characterize impact of communication channels on identification. The relationship between the CR Ratio and Shannon channel capacity is discussed. Identification algorithms are further developed when the channel error probability is unknown.     

活性污泥对聚-β-羟基丁酸酯(PHB)积累能力的影响

为了实现活性污泥资源化,用序批式反应器,分析了典型周期内,聚-β-羟基丁酸酯(PHB)含量与化学需氧量(COD)和总磷(TP)浓度的相关性。用聚合酶链式反应与变性梯度凝胶电泳方法对系统中的活性污泥种群结构进行鉴定,并在好氧曝气条件下,通过投加高浓度碳源,比较了不同PHB含量的活性污泥再次积累PHB的能力。结果表明:COD去除、PHB积累、TP浓度变化符合序批式反应器系统积累PHB的典型模型;转化为PHB的COD量比降解的COD量多出含碳量1.32mmol/L,存在固定CO2的现象;光合细菌红杆菌属是该系统中的优势种群;PHB含量较低、较高的微生物将COD转化为PHB的效率分别为46.54%、29.04%。     

氯代-1,4-二羟基蒽醌类中间体的合成、表征与性质

以多种氯代苯酐和对苯二酚为起始原料、无水三氯化铝为催化剂，通过Ffiedel—Crafts反应合成了多种氯代-1，4-二羟基蒽醌，利用UV-Vis、IR和^1HNMR等对制得的化合物进行了结构表征．结果表明：苯环上的氯原子对氯代苯酐的酰化活性具有明显的致钝作用，氯原子数量越多致钝作用越强，α-氯原子的致钝作用明显高于β-氯原子，表明氯原子的共轭效应是影响氯代苯酐酰化活性的主导因素；氯代-1，4-二羟基蒽醌分子中，氯原子的共轭效应提高了羰基的电子云密度，使分子内的氢键缔合增强，氯原子的诱导效应降低了异环的电子云密度．     

框筒结构剪力滞后效应分析

剪力滞后现象是高层框筒结构的一个重要力学现象,本文采用能量变分法分析了薄壁箱形截面梁的剪力滞后效应,对影响剪力滞系数的几何参数进行了对比分析,得到了一些有用的结论,对结构设计与施工有一定的指导作用.     

宝钢三期热轧生产管理系统的设计与实现

Oracle7客户/服务器数据库平台以其良好的性能与完备的功能,迅速地在信息处理市场中得到广泛的应用。这里简单介绍了基于Oracle7平台上运用软件工程规范与数据库设计理论,怎样设计与实现宝钢三期工程热轧生产管理系统的经验和体会。     

两个数列中的素数

运用初等方法讨论了两个数列中的素数.