Programming the magnitude and persistence of antibody responses with innate immunity

Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines, which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for >1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques.     

A Pluto-like radius and a high albedo for the dwarf planet Eris from an occultation

The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1?AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163?±?6?kilometres, density 2.52?±?0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ～1?nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun.     

A terahertz metamaterial with unnaturally high refractive index

Controlling the electromagnetic properties of materials, going beyond the limit that is attainable with naturally existing substances, has become a reality with the advent of metamaterials. The range of various structured artificial 'atoms' has promised a vast variety of otherwise unexpected physical phenomena, among which the experimental realization of a negative refractive index has been one of the main foci thus far. Expanding the refractive index into a high positive regime will complete the spectrum of achievable refractive index and provide more design flexibility for transformation optics. Naturally existing transparent materials possess small positive indices of refraction, except for a few semiconductors and insulators, such as lead sulphide or strontium titanate, that exhibit a rather high peak refractive index at mid- and far-infrared frequencies. Previous approaches using metamaterials were not successful in realizing broadband high refractive indices. A broadband high-refractive-index metamaterial structure was theoretically investigated only recently, but the proposed structure does not lend itself to easy implementation. Here we demonstrate that a broadband, extremely high index of refraction can be realized from large-area, free-standing, flexible terahertz metamaterials composed of strongly coupled unit cells. By drastically increasing the effective permittivity through strong capacitive coupling and decreasing the diamagnetic response with a thin metallic structure in the unit cell, a peak refractive index of 38.6 along with a low-frequency quasi-static value of over 20 were experimentally realized for a single-layer terahertz metamaterial, while maintaining low losses. As a natural extension of these single-layer metamaterials, we fabricated quasi-three-dimensional high-refractive-index metamaterials, and obtained a maximum bulk refractive index of 33.2 along with a value of around 8 at the quasi-static limit.     

铜胁迫下两种来源野胡萝卜的膜脂过氧化水平比较

研究了在不同浓度的铜处理下,两种来源野胡萝卜(矿区:湖北铜绿山铜矿;正常土壤:湖北武汉严西湖)膜脂过氧化水平和生长情况.结果表明:在相同浓度的铜处理下,非矿区种的丙二醛(MDA)、氧自由基以及过氧化氢含量明显高于矿区种,显示非矿区种体内膜脂过氧化水平较高,受到较严重的过氧化伤害;矿区海洲香薷更能耐受铜胁迫,矿区种已经形成了抗性生态型.     

Displacement Discontinuity Method in 3D Problems of Fracture Mechanics

The present paper suggests a modification of boundary elements numerical method, which uses displacement discontinuity method in 3D space. The current method can effectively decrease the computational elements number in 3D space because final elements are placed only on the surface of a fracture simulating the discontinuity of elastic medium. Thus the dimension of the problem is decreased. The new fundamental solutions were developed based on double layer potentials. The method proved to be effective for hydraulic fractures modeling and their interaction with natural faults in host rock formations.     

青藏高原土地利用与覆被变化的时空特征

青藏高原土地利用与土地覆被变化(LUCC)研究是区域土地科学与全球变化科学研究的重要内容,也是保障高原生态安全屏障功能稳定与提升的科学基础.本文通过对已有LUCC数据与成果的再分析,研究了高原整体LUCC时空特征、典型区LUCC的时空过程及典型类型的变化过程与机制.结果表明:青藏高原土地利用与土地覆被结构稳定,一级地类变化面积比例低于7%,并以单次变化为主,土地覆被状况总体改善.近年来高寒草地覆被状况整体好转、局部退化,林地恢复良好,耕地基本稳定,建设用地显著扩张,裸地轻微减少.人口较为密集的河湟谷地与"一江两河"地区,建设用地、耕地、人工林地等增加明显;藏北高原和三江源等牧区,超载过牧和生态建设的作用均有体现;珠穆朗玛峰国家级自然保护地区土地覆被类型多样、变化复杂,并表现出对气候变化和人类活动有较强的敏感性.高原土地变化研究中还存在现有数据产品数量不足、精度不高,土地利用变化过程及其环境效应认识不够深入等问题,需要加强野外监测和遥感技术的结合,关注LULC在不同时空尺度下的变化特征,同时注重土地利用与土地覆被类型转化和类内渐变,使高原LUCC研究更好地服务于高原生态安全屏障建设和区域可持续发展.     

半挂铰接列车山区高速路段协同水平分析

现阶段半挂铰接列车动力性能不足,导致山区高速公路设计指标与车辆行驶性能存在协同水平低的问题.文章以东风天龙半挂铰接列车为研究对象,开展了自然驾驶实车连续行驶试验,根据车辆运行状态参数及道路纵面高程变化,剖析了纵坡路段下车辆连续速度、平衡车速以及短下坡-上坡衔接路段速度变化特征,并以20 km·h-1作为速度折减量,获取...     

虚拟现实技术支持下的三维地形仿真系统设计研究

将虚拟现实技术应用到地形仿真中的相关理论与关键技术,确定了系统实现的技术路线,并以黑龙江省8511农场数据作为本系统的实验数据,以武汉吉奥公司的CCGIS4.0作为二次开发平台,使用Visual Basic6.0重新定制与开发了三维地形仿真系统,在普通PC机上成功建立了桌面型虚拟现实系统.系统实现了三维场景的漫游、查询定位、空间分析和视频输出等功能,达到了虚拟三维场景实时动态显示与交互的目的.     

Biological weapons

Brucella has traditionally been considered a biological weapon. It was the subject of extensive offensive research in the past, and still belongs to category B pathogens on most lists. Its propensity for airborne transmission and induction of chronic debilitating disease requiring combined antibiotic regimens for treatment, its abundance around the world and its vague clinical characteristics defying rapid clinical diagnosis are some of the characteristics that apply to the pathogen's weapons potential. Yet minimal mortality, availability of treatment options, protracted inoculation period and the emergence of new, more virulent potential weapons means that its inclusion among agents of bioterrorism is nowadays mainly of historical significance. Nevertheless, in the interest of literacy and of avoiding panic, physicians and the public both should be aware of the most common zoonosis worldwide.     

Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets

We present the first analysis of the human proteome with regard to interactions between proteins. We also compare the human interactome with the available interaction datasets from yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans) and fly (Drosophila melanogaster). Of >70,000 binary interactions, only 42 were common to human, worm and fly, and only 16 were common to all four datasets. An additional 36 interactions were common to fly and worm but were not observed in humans, although a coimmunoprecipitation assay showed that 9 of the interactions do occur in humans. A re-examination of the connectivity of essential genes in yeast and humans indicated that the available data do not support the presumption that the number of interaction partners can accurately predict whether a gene is essential. Finally, we found that proteins encoded by genes mutated in inherited genetic disorders are likely to interact with proteins known to cause similar disorders, suggesting the existence of disease subnetworks. The human interaction map constructed from our analysis should facilitate an integrative systems biology approach to elucidating the cellular networks that contribute to health and disease states.