Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.     

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

基于杯[4]芳烃的选择性识别有机酸的荧光传感器

以杯[4]芳烃为平台、氨基吡啶基团为识别位点、萘环为荧光基团,合成了一类新型荧光化学传感器.采用红外光谱、质谱、核磁共振和元素分析方法对产物进行了表征,并对产物的性能及荧光分子识别有机酸的机理进行了研究.结果表明,所合成的荧光分子在乙腈溶液中能选择性识别芳香族有机酸,表现出荧光淬灭现象,其与有机酸络合能力的大小依次为:对氰基苯甲酸>对氯苯甲酸>对甲氧基苯甲酸>苯甲酸.     

基于网格的数据库研究

网格计算是一种重要的新的技术,网格上的大量数据需要使用数据库系统来管理。在介绍了与网格环境下数据库系统相关的研究壬作之后,讨论了网格数据库的研究内容,包括网格数据库管理系统、网格数据库集成和网格应用的新需求。建议数据库研究人员对网格数据库作更多的研究,致力于从网格应用中发现并解决网格数据库面临的新问题。     

不允许缺货瞬时补足的EOQ模型的灵敏度分析

分析了不允许缺货瞬时补足的EOQ模型中各参数对订货批量的影响程度以及订货批量对最优费用的影响程度．说明了EOQ公式的各参数对订货批量以及订货批量对最优费用的不敏感性,而这种不敏感性正体现了EOQ模型的实用价值。     

西湖凹陷西部斜坡带花港组、平湖组储层裂缝发育特征及有效裂缝测井识别

以西湖凹陷西斜坡花港组、平湖组致密砂岩储层为研究对象,通过录井资料分析及岩心和显微薄片观察,研究裂缝的宏观与微观发育特征及其影响因素.结果显示其主要发育层理缝和构造缝.层理缝主要为水平缝和低角度缝,且已被充填;构造缝主要为垂直缝和高角度缝,充填缝和未充填缝各占一半.裂缝的发育受岩性、单层厚度、断裂及地应力场的综合影响....     

Interpretation of the architectural design methods

文章结合笔者近年来的工作实践,从建筑设计因素入手,分析和阐述了建筑设计的几种方法,并提出了自己的一些看法.     

A two-tier location management mechanism for IMS

This paper proposed a two-tier location management mechanism(TTLM)by improving the currentregistration mechanism(CR)in IP Multimedia Subsystem(IMS).The TTLM includes the visited networkregistration and the home network registration,in which the visited network registration is responsible forre-registration in IMS.When subscriber roams,the location information of home network will be updatedby the visited network based on the change of user equipment(UE)' s IP address.Therefore the TTLMcan reduce the tim...