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Programming the magnitude and persistence of antibody responses with innate immunity 总被引:1,自引:0,他引:1
Kasturi SP Skountzou I Albrecht RA Koutsonanos D Hua T Nakaya HI Ravindran R Stewart S Alam M Kwissa M Villinger F Murthy N Steel J Jacob J Hogan RJ García-Sastre A Compans R Pulendran B 《Nature》2011,470(7335):543-547
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. 相似文献
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针对常规PDP显示中的低灰度级轮廓问题,提出了一种新的PDP低灰度级图像增强算法.该算法根据PDP线性离散化的显示特点利用图像的表现率动态选择多种子场的编码,减少了图像伽马变化过程中灰度级的细节损失.针对PDP实际输出亮度相对于输入灰度级有反转的现象进行了理论分析和算法处理,消除了低灰度图像灰阶反转的现象.利用误差扩散算法最大限度地重现了图像的细节.实际结果表明该算法能够减少低灰度级轮廓,其显示效果明显优于传统方案. 相似文献
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基于曲率的自适应曲面数控磨削 总被引:1,自引:0,他引:1
利用等包络迹高度控制砂轮行走路径,实现了曲面的自适应数控成型磨削,以提高曲面的磨削效率.首先,根据曲面曲率建立自适应数控成型磨削的数控模式,然后,在比较等间距行走的数控磨削方式的基础上分析曲面曲率不同的成型磨削特征,最后,进行数控成型磨削试验和检测加工曲面的成形误差,验证该自适应数控成型磨削方法的有效性.分析结果表明,利用移动磨削点的包络成型磨削可以减小砂轮磨损对加工精度的影响.此外,等包络迹高度行走的数控磨削可以根据曲面曲率调节行走路经的间距,实现自适应磨削加工,提高曲面的加工效率,而且在加工曲率较大且提高加工精度时可以较大幅度地减少砂轮行走步数.试验结果表明,当等包络迹高度小至1μm时可以形成光顺的加工曲面,在100mm×40mm范围内形状误差PV值可以达到0.285mm. 相似文献
238.
雷达大地回波反射和散射系数的测量 总被引:2,自引:0,他引:2
介绍了雷达大地回波特性的一种测量方法 ,包括测量系统框图和基于回波波形的数据处理方法。利用该方法得出了一种地面的反射系数和散射系数 ,该结果对雷达高度表的设计和其它地面反射和散射系数测量均具有参考价值 相似文献
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Samuel CS Hewitson TD Unemori EN Tang ML 《Cellular and molecular life sciences : CMLS》2007,64(12):1539-1557
The peptide hormone relaxin is emerging as a multi-functional factor in a broad range of target tissues including several
non-reproductive organs, in addition to its historical role as a hormone of pregnancy. This review discusses the evidence
that collectively demonstrates the many diverse and vital roles of relaxin: the homeostatic role of endogenous relaxin in
mammalian pregnancy and ageing; its gender-related effects; the therapeutic effects of relaxin in the treatment of fibrosis,
inflammation, cardioprotection, vasodilation and wound healing (angiogenesis) amongst other pathophysiological conditions,
and its potential mechanism of action. Furthermore, translational issues using experimental models (to humans) and its use
in various clinical trials, are described, each with important lessons for the design of future trials involving relaxin.
The diverse physiological and pathological roles for relaxin have led to the search for its significance in humans and highlight
its potential as a drug of the future.
Received 12 December 2006; received after revision 12 February 2007; accepted 15 March 2007 相似文献