Molecular spectroscopy: complexity of excited-state dynamics in DNA

Absorption of ultraviolet light by DNA is known to lead to carcinogenic mutations, but the processes between photon absorption and the photochemical reactions are poorly understood. In their study of the excited-stated dynamics of model DNA helices using femtosecond transient absorption spectroscopy, Crespo-Hernández et al. observe that the picosecond component of the transient signals recorded for the adenine-thymine oligonucleotide (dA)18.(dT)18 is close to that for (dA)18, but quite different from that for (dAdT)9.(dAdT)9; from this observation, they conclude that excimer formation limits excitation energy to one strand at a time. Here we use time-resolved fluorescence spectroscopy to probe the excited-state dynamics, which reveals the complexity of these systems and indicates that the interpretation of Crespo-Hernández et al. is an oversimplification. We also comment on the pertinence of separating base stacking and base pairing in excited-state dynamics of double helices and question the authors' assignment of the long-lived signal component found for (dA)18.(dT)18 to adenine excimers.     

Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers

Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL). The murine cancers acquire widespread recurrent amplifications and deletions targeting loci syntenic to those not only in human T-ALL but also in diverse human haematopoietic, mesenchymal and epithelial tumours. These results indicate that murine and human tumours experience common biological processes driven by orthologous genetic events in their malignant evolution. The highly concordant nature of genomic events encourages the use of genomically unstable murine cancer models in the discovery of biological driver events in the human oncogenome.     

Watching hydrogen-bond dynamics in a beta-turn by transient two-dimensional infrared spectroscopy

X-ray crystallography and nuclear magnetic resonance measurements provide us with atomically resolved structures of an ever-growing number of biomolecules. These static structural snapshots are important to our understanding of biomolecular function, but real biomolecules are dynamic entities that often exploit conformational changes and transient molecular interactions to perform their tasks. Nuclear magnetic resonance methods can follow such structural changes, but only on millisecond timescales under non-equilibrium conditions. Time-resolved X-ray crystallography has recently been used to monitor the photodissociation of CO from myoglobin on a subnanosecond timescale, yet remains challenging to apply more widely. In contrast, two-dimensional infrared spectroscopy, which maps vibrational coupling between molecular groups and hence their relative positions and orientations, is now routinely used to study equilibrium processes on picosecond timescales. Here we show that the extension of this method into the non-equilibrium regime allows us to observe in real time in a short peptide the weakening of an intramolecular hydrogen bond and concomitant opening of a beta-turn. We find that the rate of this process is two orders of magnitude faster than the 'folding speed limit' established for contact formation between protein side chains.     

Non-thermal melting in semiconductors measured at femtosecond resolution

Ultrafast time-resolved optical spectroscopy has revealed new classes of physical, chemical and biological reactions, in which directed, deterministic motions of atoms have a key role. This contrasts with the random, diffusive motion of atoms across activation barriers that typically determines kinetic rates on slower timescales. An example of these new processes is the ultrafast melting of semiconductors, which is believed to arise from a strong modification of the inter-atomic forces owing to laser-induced promotion of a large fraction (10% or more) of the valence electrons to the conduction band. The atoms immediately begin to move and rapidly gain sufficient kinetic energy to induce melting--much faster than the several picoseconds required to convert the electronic energy into thermal motions. Here we present measurements of the characteristic melting time of InSb with a recently developed technique of ultrafast time-resolved X-ray diffraction that, in contrast to optical spectroscopy, provides a direct probe of the changing atomic structure. The data establish unambiguously a loss of long-range order up to 900 A inside the crystal, with time constants as short as 350 femtoseconds. This ability to obtain the quantitative structural characterization of non-thermal processes should find widespread application in the study of ultrafast dynamics in other physical, chemical and biological systems.     

城镇及小区污水处理技术与应用

总结了十几年来国内外小型污水处理领域的技术发展和应用状况 ,着重讨论了强化一级处理、污水厌氧处理、好氧处理以及生物—化学结合处理等特点 ,指出市场化发展是我国今后一段时间小型污水处理发展的有效选择 .     

Fluorescence correlation spectroscopy in laser gradient field

Fluorescence correlation spectroscopy (FCS) is capable of probing dynamic processes in living biological systems. From photon fluctuation of fluorescing particles which diffuse through a small detection volume, FCS reveals information on the concentration and the structure of the particles, as well as information on microscopic environment. In this note, we study the radiation forces experienced by Rayleigh particles in a laser field in details, and analyze the effects of gradient field on FCS measurements.     

Experimental evidence for sub-3-fs charge transfer from an aromatic adsorbate to a semiconductor

The ultrafast timescale of electron transfer processes is crucial to their role in many biological systems and technological devices. In dye-sensitized solar cells, the electron transfer from photo-excited dye molecules to nanostructured semiconductor substrates needs to be sufficiently fast to compete effectively against loss processes and thus achieve high solar energy conversion efficiencies. Time-resolved laser techniques indicate an upper limit of 20 to 100 femtoseconds for the time needed to inject an electron from a dye into a semiconductor, which corresponds to the timescale on which competing processes such as charge redistribution and intramolecular thermalization of excited states occur. Here we use resonant photoemission spectroscopy, which has previously been used to monitor electron transfer in simple systems with an order-of-magnitude improvement in time resolution, to show that electron transfer from an aromatic adsorbate to a TiO(2) semiconductor surface can occur in less than 3 fs. These results directly confirm that electronic coupling of the aromatic molecule to its substrate is sufficiently strong to suppress competing processes.     

相变存储器单元皮秒测试信号完整性研究

针对相变存储器皮秒测试系统由于矩阵开关电路分布参数以及信号通道中阻抗突变所引起的反射,严重影响了皮秒脉冲信号的完整性,使施加在相变单元上的皮秒脉冲信号严重失真,为了消除失真,改善信号完整性,从2个方面提出了解决方案：一是采用性能优良的高频继电器构成矩阵开关;二是减小反射,采取了源端阻抗匹配、负载分支端阻抗补偿、菊花链双线拓扑结构等措施,使得反射的影响减小到最小.理论分析与仿真结果表明：皮秒脉冲信号波形质量良好,满足测试要求.本测试系统为研究皮秒编程脉冲作用下相变存储器的存储机理、速度、可靠性等提供了良好的平台,也可作为电阻式随机擦写存储器单元测试系统.     

采用分步傅立叶方法初始啁啾脉冲的孤子效应压缩

采用分步傅立方法数值模拟皮秒脉总冲在单模光纤中的传输,计算和分析了初始啁啾以坡秒脉冲的孤子效应压缩的影响。通过分析脉冲压缩比,最佳光纤长度,压缩后手脉冲峰值功率和脉冲压缩质量的变化,发现采用增大初始啁啾的办法,可以使皮秒脉冲得到更好的压缩。     

饱和非线性光纤中孤子传输特性的数值研究

文章以包含五阶非线性效应的高阶非线性薛定谔方程为模型,数值分析了饱和非线性光纤中孤子的传输特性.结果表明,五阶非线性效应影响下,皮秒孤子间的相互作用与不含五阶非线性效应孤子情况并不相同,其相互作用更为严重.这对光孤子通信系统是非常有害的.数值计算结果发现,同时采用不等振幅和不等位相法,选取合适的振幅比和相对相位可以对孤子间的相互作用进行有效的抑制.     

Quantitative dynamics and binding studies of the 20S proteasome by NMR

The machinery used by the cell to perform essential biological processes is made up of large molecular assemblies. One such complex, the proteasome, is the central molecular machine for removal of damaged and misfolded proteins from the cell. Here we show that for the 670-kilodalton 20S proteasome core particle it is possible to overcome the molecular weight limitations that have traditionally hampered quantitative nuclear magnetic resonance (NMR) spectroscopy studies of such large systems. This is achieved by using an isotope labelling scheme where isoleucine, leucine and valine methyls are protonated in an otherwise highly deuterated background in concert with experiments that preserve the lifetimes of the resulting NMR signals. The methodology has been applied to the 20S core particle to reveal functionally important motions and interactions by recording spectra on complexes with molecular weights of up to a megadalton. Our results establish that NMR spectroscopy can provide detailed insight into supra-molecular structures over an order of magnitude larger than those routinely studied using methodology that is generally applicable.     

半导体激光器短电脉冲调制光脉冲的产生与控制

对半导体激光器短电脉冲调制增益开关法产生皮秒光脉冲动力学过程进行理论分析和实验研究 .基于单模数率方程 ,采用相图 ( Phase Portraits)法分析激光器激射皮秒光脉冲时载流子浓度和光子密度变化的对应关系 .探讨直流参数、调制脉冲参数和器件寄生参量等对产生皮秒光脉冲的影响 .在此基础上 ,研究 In Ga As P/ In P激光器短电脉冲调制产生单发激光脉冲最佳的实验条件     

卟啉衍生物TMPyP4与单链DNA的结合机理研究

通过圆二色谱、稳态吸收光谱、稳态荧光光谱和皮秒时间分辩荧光光谱研究了meso-四(4-(N-甲基吡啶基))卟啉(TMPyP4)与端粒DNA5′-TTAGGG-3′(S6)的结合机理.稳态光谱实验结果表明,在没有金属离子的Tris-HCl缓冲溶液中,S6DNA以单链的形式存在,TMPyP4与单链DNA的结合常数为1.51×106(mol/L)-1,饱和结合数为1.2.通过时间分辨荧光光谱对二者相互作用的机理进行了进一步研究,推测了TMPyP4与单链S6DNA之间的结合模式.     

Increased thermohaline stratification as a possible cause for an ocean anoxic event in the Cretaceous period

Ocean anoxic events were periods of high carbon burial that led to drawdown of atmospheric carbon dioxide, lowering of bottom-water oxygen concentrations and, in many cases, significant biological extinction. Most ocean anoxic events are thought to be caused by high productivity and export of carbon from surface waters which is then preserved in organic-rich sediments, known as black shales. But the factors that triggered some of these events remain uncertain. Here we present stable isotope data from a mid-Cretaceous ocean anoxic event that occurred 112 Myr ago, and that point to increased thermohaline stratification as the probable cause. Ocean anoxic event 1b is associated with an increase in surface-water temperatures and runoff that led to decreased bottom-water formation and elevated carbon burial in the restricted basins of the western Tethys and North Atlantic. This event is in many ways similar to that which led to the more recent Plio-Pleistocene Mediterranean sapropels, but the greater geographical extent and longer duration (approximately 46 kyr) of ocean anoxic event 1b suggest that processes leading to such ocean anoxic events in the North Atlantic and western Tethys were able to act over a much larger region, and sequester far more carbon, than any of the Quaternary sapropels.     

Single-molecule fluorescence imaging of membrane-bound proteins for studies of cell signal transduction

Fluorescence imaging of single molecules is becoming a powerful tool to examine biological processes at the molecular level.Using total internal reflection fluorescence microscopy (TIRFM),it has been possible to study the dynamic behavior of single molecules on living cell membranes.Herein,we briefly review the application of TIRFM-based single-molecule imaging in studies of membrane receptors involved in signal transduction.Furthermore,we discuss several examples of our own research on growth factor receptors,including TGF-β receptors,HER2,and EGFR,and speculate possible applications of this technique to investigate other cellular events occurring on or near the plasma-membrane.     

Two-state kinetics characterized by image analysis of nuclear magnetic resonance spectra

Nuclear magnetic resonance (NMR) spectroscopy has become an important tool in modern biological research. NMR spectra image analysis can be used to analyze the kinetics of biomacromolecular conformational changes.The relationship between the image parameters and the protein dynamics was investigated by using a small globular protein ω-conotoxin SO3 (ω-CTX SO3). The physical meanings of the image parameters were characterized from the results. Comparison of the data from the traditional integral area of specific resonance peaks method and the NMR image analysis method showed the advantages of using NMR spectra image analysis for kinetic analysis of two-state processes monitored by 1D proton NMR.     

Effect of solvents on the barrierless reaction in the excited state of cyanine dye

UV－Vis,fluorescence spectroscopy and time resolved spectroscopic technique on picosecond and femto-second scales have been utilized to investigate the effect of steric hindrance and multiple hydroxyl groups of solvents on the barreierless isomerization in excited state of 3,3 ′-di(3-sulfopropyl)thiacyanine triethylamminium salt,The results show that the factors mentioned above may be responsible for a different “short-time behavior “of the bleaching signal on the ground state and nonlinear viscosity dependence of the excited-state lifetime in ispropanol and glycol,These phenomena are distinguished from the situation repored in the long-chained monhydroxyl alcoloh solvents.However,the dye molecule still exhibits the analyzing-wavelength dependence of the observed fluorescence lifetime,that is ,the fluorescence lifetime increases with the increasing of analyzing-wavelength ,The conclusions are in agreement with those drawn from femtosecond upconversion fluorescence experiments and further exemplify the barrierless isomerization model in the excited state.     

Dynamics of crystallization and dissolution of calcium orthophosphates at the near-molecular level

Although extensive investigations of biogenic and geological calcium phosphate crystallization/dissolution and their phase transformations have been performed,the mechanisms of crystallization and dissolution of sparingly soluble calcium phosphates in geological settings have not been completely determined at the near-molecular level.In particular,an understanding of the physical-chemical processes at the earliest nucleation stage and the subsequent crystal surface dynamics in soil solutions is lacking.This review focuses on the earliest events in homo/heterogeneous nucleation from an initial supersaturated solution phase,the subsequent growth of calcium phosphate phases,and the relevant influences of the presence of additional inorganic and organic molecules in both geological and biological settings.These studies have implications for the understanding of the complex processes of calcium phosphate transformations in soils,and provide possible physical-chemical mechanisms for the biogeochemical behavior of phosphorus at the near-molecular level.     

Genomic analysis of metastasis reveals an essential role for RhoC

The most damaging change during cancer progression is the switch from a locally growing tumour to a metastatic killer. This switch is believed to involve numerous alterations that allow tumour cells to complete the complex series of events needed for metastasis. Relatively few genes have been implicated in these events. Here we use an in vivo selection scheme to select highly metastatic melanoma cells. By analysing these cells on DNA arrays, we define a pattern of gene expression that correlates with progression to a metastatic phenotype. In particular, we show enhanced expression of several genes involved in extracellular matrix assembly and of a second set of genes that regulate, either directly or indirectly, the actin-based cytoskeleton. One of these, the small GTPase RhoC, enhances metastasis when overexpressed, whereas a dominant-negative Rho inhibits metastasis. Analysis of the phenotype of cells expressing dominant-negative Rho or RhoC indicates that RhoC is important in tumour cell invasion. The genomic approach allows us to identify families of genes involved in a process, not just single genes, and can indicate which molecular and cellular events might be important in complex biological processes such as metastasis.     

SOS微微秒光导开关的结构设计及实验结果

本文讨论了微微秒光导开关电路参数对开关响应速度的影响。给出了微微秒光导开关的结构设计和实验结果。本文报道的ＳＯＳ微微秒光导开关输出电脉冲半强宽小于５ｐｓ，电脉冲幅度为ｍｖ量级。