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.     

Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.     

玉米不同垅作及群体结构对产量影响初报

以玉米三种垅作形式为主要内容,研究不同垅作的增产机制及相应的群体结构,提高玉米大面积连片种植的单产水平。试验表明大垅和大小垅种植方式具有保持和提高土壤温度、水分、抗旱抗涝的作用,同时适于密植,光能利用率高等老年,吡常规小垅玉米增产１４．０％－２２．８５。适宜密度６－７万株／hm^2。图３,表２。     

浅谈城市轨道交通工程施工中450t提运架设备架梁的应用

文章针对广珠城际轨道交通工程施工中450 t提运架设备箱梁架设施工方法、工艺及技术保证措施展开论述。     

道路施工过程中的材料消耗控制

市场经济条件下,企业的最大目的就是取得理想的经济效益,公路建设成本控制是关键,控制好影响成本主要因素的材料使用数量是公路施工企业的重要工作之一.     

关于L-Fuzzy子集层仿紧性的注记

文[2]曾指出L－Fuzzy拓扑学中关于L－Fuzzy子集的几种仿紧性不是一般拓扑学中子集仿紧性的真正推广,即它们不以分明子集仿紧性为特款,进一步修正了几个定义并重新证明了有关的几个定理,在这篇文章中,我们拟对层仿紧性进行修正并重证相关的几个定理。     

Impact of the RMB Joining in the SDR Basket on Its Internationalization from the Perspective of Risk Spillover

For evaluating the influence of the Chinese renminbi(RMB) joining in the special drawing right(SDR) basket on RMB's internationalization, the authors systemically study the risk spillover networks and examine the dynamic relationship of exchange rates among the SDR currencies including the US dollar(USD), European Union euro(EUR), Japanese yen(JPY) and British pound(GBP).The empirical results demonstrate that the USD takes a dominant position and holds the biggest risk spillover to other currencies, and the RMB's inclusion to the SDR basket makes the risk spillover to get average, giving rise to the SDR currency system more stable to a certain degree. The inclusion of the RMB in the SDR not only can reduce the systematic risk of the SDR, but also has a certain impact on the international exchange rate markets. Nowadays, in front of the growing trade friction, more such researches could help to effectively deal with the currency disputes.     

交通荷载作用下低路堤动力特性试验研究

结合连盐高速低路堤,对路堤进行了动应力、振动响应等现场测试,分析了路基中附加动应力及振动位移的变化规律.并且通过应力控制的室内动三轴试验,采用一定的动应力频率、不同的循环应力比来模拟交通荷载,研究了在循环荷载作用下,连盐高速公路饱和软粘土的轴向累计应变、孔隙水压力和轴向周期应变软化的变化规律.实验结果表明:路堤中动应力和振动位移随行车速度和车重的增加而增加,随深度的增加而降低,有效影响深度达2.5 m;原状土的临界循环应力比远大于重塑土,承受循环应力能力高于重塑土.因此,要加强浅层路基强度,同时要减少对底部下卧层软粘土的扰动.其结果可为在软土地基上设计和施工低路堤高速公路提供有益的参考.