电子自旋共振技术在生物领域的应用进展

电子顺磁共振(ESR)技术是一种研究顺磁性物质的未成对电子结构和动力学信息的波谱检测方法。近年来ESR技术在生物医学领域得到了广泛的应用,如解析含有过波金属离子的单分子磁体的构象与功能,金属蛋白酶结构和催化机理,自由基相关的电子传递过程等。目前,随着电子顺磁共振技术向微观世界探索的深入,一种基于NV的微观自旋磁共振技术日趋成熟,甚至达到了单分子单自旋的探测水平。本文综述了ESR技术在生物学领域应用的原理方法和研究进展,以及微观SER技术等的应用原理和进展,为更好地将ESR技术应用在蛋白质单分子结构解析与动力学研究、自由基反应途径解析,自旋标记分子的细胞内定位等提供参考和借鉴。     

冷冻电镜单颗粒技术的发展、现状与未来

近年来冷冻电子显微镜成像技术突飞猛进,越来越广泛地应用于生物大分子的高精度结构研究中,尤其在解析其他方法难以应对的蛋白质复合物的结构研究方面取得了瞩目的进展。文章对冷冻电镜单颗粒重构技术近年来的发展做了回顾和总结,重点介绍了冷冻电镜单颗粒重构技术中的基本流程及其使用的图像处理技术和算法,并对近年来人们重点关注的问题进行了讨论。最后对冷冻电镜单颗粒重构技术未来的发展趋势,尤其是对细胞内原位的分子结构以及蛋白质分子的动态信息的捕捉等方面进行了初步的探讨。     

单分子定位超分辨显微成像技术研究进展及展望(特邀综述)

随着新型荧光探针、先进激光、高灵敏光电探测器等相关领域的不断发展,突破衍射极限的超分辨光学显微技术为现代生物医学研究提供了新的有力工具,其中的单分子定位技术利用荧光分子的光开关效应,实现了亚细胞结构的纳米精度超分辨成像.本文介绍了单分子定位超分辨显微技术的基本原理与实现,例举了其在细胞生物学、组织生物学以及神经科学等方面的应用,讨论了该技术目前的发展趋势及可能的改进方向,为相关领域科学研究提供参考.超分辨光学显微技术的不断创新将推动生命科学的新发展.     

高分辨单颗粒分析在生物样品中的应用

冷冻电子显微学作为结构生物学主要工具之一,以解析承担生命活动中重要功能的各种蛋白质机器三维结构为手段,对其在生命活动中的功能机制进行研究。冷冻电子显微学的单颗粒分析法具有分辨率高、生物样品无需结晶、解析的结构接近生理状态等优点。近几年来,随着软、硬件的发展与革新,高分辨冷冻电镜单颗粒分析法在生物样品上的应用范围方面得到进一步扩展,囊括大至上百纳米的病毒颗粒,小至十纳米左右的蛋白质机器,同时单颗粒分析的分辨率也在稳步提高。目前,大量生物样品的结构解析能够常态地达到3~4 ?的准原子分辨率,足以阐明大部分生物问题。文章简要介绍了单颗粒分析的理论基础、发展过程、研究现状以及面临的更多挑战。     

多色单分子定位超分辨显微成像术

多色成像作为超分辨成像技术的重要延伸,极大地增强了人们研究亚细胞结构定位与交互关系的能力,从而有助于研究者深入理解细胞内复杂的生命现象与过程。基于单分子定位超分辨显微成像术(SMLM)工作原理的特殊性,已实现了激发依赖、激活依赖、分光依赖等数种有特点的多色成像方法。介绍6种主要的多色单分子定位超分辨显微成像技术,从分色能力、光谱窜扰、数据采集效率等角度分析了各方法的优缺点,并讨论了与多色成像相关的细胞固定方法,帮助研究人员根据自身实验需求选择合适可靠的多色成像手段研究相应的科学问题。     

冷冻电镜在分子生物物理学中的技术革命

冷冻电镜已经成为了一项应用越来越广泛的生物物理学技术。特别是近些年来,由于最新的信号探测器的应用,以及单颗粒三维重建算法的革新和不断改进,冷冻电镜技术取得了飞跃式的发展。通过该技术解析得到的生物大分子结构可以在单分子条件下达到近原子分辨率(4?)水平。随着越来越多具有重要生物医学功能的蛋白质及其复合体的高分辨结构被解析出来,冷冻电镜技术正在逐渐引发一场结构生物学革命,并引起全世界的关注。在该文中,作者重点介绍了冷冻电镜及单颗粒分析技术的发展历程,并以炎症复合体和剪接体为例,介绍一些最新的研究进展。     

飞秒激光在细胞纳米手术中的应用

激光类型不同,其与生物组织的作用机理也不同。其中飞秒激光由于脉冲持续时间短、瞬时功率大、聚焦尺寸小的特点,使得其在超快、超强和超精细领域有着广阔的应用前景。而结构微小的细胞的动力学研究,如有丝分裂、变形和凋亡,对于了解细胞的生物和发育行为有着重要作用。且生物大分子和水几乎不吸收近红外波长的光,故考虑应用近红外飞秒激光对细胞进行手术。这种激光手术技术已用于对细胞内结构进行切割和蚀除。介绍了该技术在细胞领域中的一些应用,如纳米手术、基因转染和染色体切割等。与传统技术相比,该技术精度高,可在不损伤细胞活性的前提下对细胞进行实验。     

带电纳米颗粒与相分离的带电生物膜之间相互作用的分子模拟

纳米颗粒在纳米医药、细胞成像等领域有着非常广泛的应用,深入理解纳米颗粒与生物膜之间相互作用的微观机制是纳米颗粒合成与应用的重要基础.本文采用粗粒化分子动力学模拟的方法研究了带电配体包裹的金纳米颗粒与相分离的带电生物膜之间的相互作用.结果表明,通过改变金纳米颗粒表面的配体密度、配体带电种类和比例,以及膜内带电脂分子的种类,可以方便地调控纳米颗粒在膜表面或膜内停留的位置和状态.进一步从自由能的角度分析了带电纳米颗粒与带电生物膜之间相互作用的微观物理机制.本文对纳米粒子在纳米医药、细胞成像等领域的应用具有一定的理论参考意义.     

光镊技术在气溶胶物理化学表征中的应用

有机气溶胶的热/动力学研究是多学科交叉的前沿研究领域,其核心问题主要是非理想混合包括挥发性、液-液相分离、非平衡传质动力学等,精确测量这些过程相关理化参数是目前研究的瓶颈。光镊系统可以悬浮气溶胶单颗粒,获得高信噪比受激拉曼光谱,在研究气溶胶物理化学性质与其大气效应中具有独到优势。被广泛用于有机及其与无机混合体系气溶胶的吸湿性、挥发性、水传质动力学、液-液相分离过程研究中。本文综述了激光悬浮气溶胶单颗粒技术的研究进展,主要包括光镊技术的原理和技术手段,以及在气溶胶关键物理化学参数测量中的应用。通过光镊系统,一方面可以获得重要理化参数的精确结果,另一方面可以对实际环境中悬浮液滴的状态进行模拟测量,从而为大气科学的研究与污染治理提供重要支撑。     

可饱和脉冲变压器及其在脉冲调制器中的应用

提出了采用多路绕组分组并联结构和同轴结构的两种新型可饱和脉冲变压器(SPT),用来取代寿命较短的气体开关,作为脉冲电容器或几百kV级脉冲调制器的充电变压器兼主开关。采用磁芯自动复位机制的新型SPT,初步解决了普通SPT难以兼具高升压倍数和绕组低饱和电感的问题,实现独立脉冲变压器和磁开关的集成紧凑化。采用初次级绕组间反向互感压制的物理机制,实现SPT次级绕组饱和电感降低到其固有饱和结构电感以下水平的重要特性,为实现低饱和电感磁开关探索了一条新技术路线。新型SPT已在螺旋Blumlein脉冲形成线(HBPFL)型高功率脉冲调制器中获得了应用:其作为变压器实现HBPFL充电200kV的目标;其作为HBPFL主开关形成了幅度为180kV、脉宽135ns、前沿时间60ns的准方波电压脉冲。此外,提出并验证了新型SPT应用于百kV级集成紧凑化Marx发生器及多路高电压脉冲ns同步等领域的新技术路线。     

Single-Particle Tracking Reveals Anti-Persistent Subdiffusion in Cell Extracts

Single-particle tracking (SPT) has become a powerful tool to quantify transport phenomena in complex media with unprecedented detail. Based on the reconstruction of individual trajectories, a wealth of informative measures become available for each particle, allowing for a detailed comparison with theoretical predictions. While SPT has been used frequently to explore diffusive transport in artificial fluids and inside living cells, intermediate systems, i.e., biochemically active cell extracts, have been studied only sparsely. Extracts derived from the eggs of the clawfrog Xenopus laevis, for example, are known for their ability to support and mimic vital processes of cells, emphasizing the need to explore also the transport phenomena of nano-sized particles in such extracts. Here, we have performed extensive SPT on beads with 20 nm radius in native and chemically treated Xenopus extracts. By analyzing a variety of distinct measures, we show that these beads feature an anti-persistent subdiffusion that is consistent with fractional Brownian motion. Chemical treatments did not grossly alter this finding, suggesting that the high degree of macromolecular crowding in Xenopus extracts equips the fluid with a viscoelastic modulus, hence enforcing particles to perform random walks with a significant anti-persistent memory kernel.     

新能源变革背景下的超导电力技术发展前景

自从1911年超导体发现以来,人们一直梦想超导体能够在电力技术中得到大规模应用.20世纪60年代以来,随着NbTi超导线材,特别是氧化物高温超导带材达到商业化水平,世界范围内广泛地开展了超导电力技术的研究与应用示范.单从技术上讲,超导电力技术已经接近实用化水平.当今,人类社会正在经历一次新的能源变革,超导电力技术在应对能源变革带来的挑战方面将会发挥重要的作用.文章介绍了近年来超导电力技术的发展趋势,并就其在新能源变革背景下的发展前景进行了探讨.     

On the use of multiple interpolation series in scaled particle theory: improved predictions and limitations

We propose further modifications to recent formulations of the scaled particle theory (SPT) of hard particle fluids. In any formulation of SPT, a number of conditions are applied to the central function G. As the exact form of G is unknown, a form must be assumed. Representing G with more than one series has recently been shown (Siderius and Corti, J. Chem. Phys. 127, 144502, 2007) to lead to improved planar surface tension predictions with little change in the already accurate pressure, excess chemical potential and fluid structure predictions. Another condition on G that includes the curvature of the radial distribution at contact was not, however, invoked in this previous work. We incorporate here this additional condition into the multiple series approach, resulting in further improvements to the SPT predictions. We also consider a number of permutations of the multiple interpolation series to explore the limitations of this approach and again find that increasing the number of series will not by itself lead to better predictions of the properties of the hard sphere fluid.     

Internalisation of engineered nanoparticles into mammalian cells in vitro: influence of cell type and particle properties

Cellular internalisation of industrial engineered nanoparticles is undesired and a reason for concern. Here we investigated and compared the ability of seven different mammalian cell cultures in vitro to incorporate six kinds of engineered nanoparticles, focussing on the role of cell type and particle properties in particle uptake. Uptake was examined using light and electron microscopy coupled with energy dispersive X-ray spectroscopy (EDX) for particle element identification. Flow cytometry was applied for semi-quantitative analyses of particle uptake and for exploring the influence on uptake by the phagocytosis inhibitor Cytochalasin D (CytoD). All particles studied were found to enter each kind of cultured cells. Yet, particles were never found within cell nuclei. The presence of the respective particles within the cells was confirmed by EDX. Live-cell imaging revealed the time-dependent process of internalisation of technical nanoparticles, which was exemplified by tungsten carbide particle uptake into the human skin cells, HaCaT. Particles were found to co-localise with lysosomal structures within the cells. The incorporated nanoparticles changed the cellular granularity, as measured by flow cytometry, already after 3 h of exposure in a particle specific manner. By correlating particle properties with flow cytometry data, only the primary particle size was found to be a weakly influential property for particle uptake. CytoD, an inhibitor of actin filaments and therewith of phagocytosis, significantly inhibited the internalisation of particle uptake in only two of the seven investigated cell cultures. Our study, therefore, supports the notion that nanoparticles can enter mammalian cells quickly and easily, irrespective of the phagocytic ability of the cells.     

Spectroscopy of superfluid pairing in atomic fermi gases

We study the dynamic structure factor for density and spin within the crossover from BCS superfluidity of atomic fermions to the Bose-Einstein condensation of molecules. Both structure factors are experimentally accessible via Bragg spectroscopy and allow for the identification of the pairing mechanism: the spin structure factor allows for the determination of the two particle gap, while the collective sound mode in the density structure reveals the superfluid state.     

Scaled particle theory for bulk and confined fluids: A review

More than half a century after its first formulation by Reiss, Frisch and Lebowitz in 1959, scaled particle theory (SPT) has proven its immense usefulness and has become one of the most successful theories in liquid physics. In recent years, we have strived to extend SPT to fluids confined in a variety of random porous matrices. In this article, we present a timely review of these developments. We have endeavored to present a formulation that is pedagogically more accessible than those presented in various original papers, and we hope this benefits newcomers in their research work. We also use more consistent notations for different cases. In addition, we discuss issues that have been scarcely considered in the literature, e.g., the one-fluid structure of SPT due to the isomorphism between the equation of state for a multicomponent fluid and that for a one-component fluid or the pure-confinement scaling relation that provides a connection between a confined and a bulk fluid.     

共聚焦显微拉曼光谱在木质纤维细胞壁预处理中的应用进展

在能源紧缺和环境恶化的双重压力下,利用农林生物质替代化石资源生产生物燃料、生物基化学品和材料逐步发展成为世界范围内的研究热点,而细胞壁中纤维素、半纤维素、木质素以及其他少量组分的空间分布不均一性和化学结构复杂性构成了天然抗降解屏障,严重阻碍生物质的转化效率,因此需要对木质纤维原料进行预处理,以期破坏细胞壁的宏观壁垒,实现生物质的低成本高效转化。在此过程中,全面了解木质纤维细胞壁的化学组成、结构特性及其在生物质转化过程中的解构机理是高效利用农林生物质的重要前提。由于拉曼光谱具有样品制备要求低、灵敏度高、且能在原位状态下对样品进行定性、定量分析等特点,使得拉曼光谱成为研究木质细胞壁结构的有力工具。尤其与显微技术相结合时,可以同时获得木质纤维细胞壁主要组分的微区分布与超分子结构信息,实现生物质转化过程中化学组分动态变化的可视化研究。首先介绍了拉曼光谱成像的工作原理,并对纤维素、半纤维素和木质素的拉曼特征信号进行了归属。其次,总结了近几年拉曼光谱在生物质转化领域内的应用与研究进展,综述了拉曼光谱在未处理状态下以及稀酸、水热、稀碱等不同预处理过程中的分析方法,对细胞壁主要组分的分布进行表征,以揭示预处理过程中各组分的溶出过程及迁移规律,为在细胞及亚细胞水平探究预处理诱导细胞壁主要组分动态溶解机制提供了有效路径。此外,针对检测中收集的光谱数量过多、分析难等问题,文章重点介绍了主成分聚类分析法和顶点成分分析法两种拉曼数据分析方法,用于提取特征信息并对光谱进行分类研究,以深入探究特定组分的空间分布和分子结构。最后,根据上述分析展望了拉曼光谱在生物质转化领域的研究趋势,为相关研究提供技术参考。     

Micromagnetic recording field analysis of fast-switching single-pole-type heads for bit-patterned media

A Landau–Lifshitz–Gilbert (LLG) micromagnetic analysis of the recording field of single-pole-type (SPT) heads was carried out. The whole volume comprising the SPT head and the double-layered medium was treated micromagnetically using the finite-difference method with cubic cells as small as 5 nm, giving a total number of cells of more than 10.8 million. A parallelized fast Fourier transform (FFT) method was used to solve this large-scale problem. Dynamic recording fields were calculated for various head structures and head materials. The timing (synchronization) between the dynamic head field and land location in bit-patterned media (BPM) is discussed and the design methodology is discussed for a fast-switching SPT head.     

弹性壳结构静力与动力分析的光滑粒子法

本文通过采用移动最小二乘函数作为近似函数 和完全拉格朗日方程作为近似方程来改善光滑粒子法的稳定性和数值精度; 在此基础上, 提出了壳结构静力分析的光滑粒子法, 并完善了壳结构动力分析方法; 最后, 采用国际公认的壳结构的标准测试模型对静力和动力问题分别进行了验证, 所得结果与已有数据吻合良好, 证明了本文数值模型的有效性和可靠性, 为光滑粒子法进一步在裂纹、破碎等非线性壳结构中的应用提供参考. 关键词： 弹性壳 静力与动力分析 光滑粒子法 完备性和稳定性