二价金属离子与YycFN相互作用的NMR研究

YycGF最早发现于枯草芽孢杆菌,是与细胞存活密切相关的双组分信号转导系统存在于少量低鸟嘌呤和胞嘧啶(G+C)含量的革兰氏阳性菌中,包括金黄色葡萄球菌和肺炎链球菌等人类病原菌,在外界环境刺激下,胞膜上的组氨酸激酶YycG通过自身组氨酸磷酸化活化,将磷酸根转移至反应调节蛋白YycF的N端调节区(YycF_N)使之磷酸化,调控下游基因表达,实现特定细胞应答反应.二价金属离子在双组分信号转导系统反应调节蛋白的磷酸化过程中起着非常关键的作用,但它们与YycF_N相互作用的机制尚不清楚.该文利用液体核磁共振(NMR)方法研究了Ca~(2+)、Mg~(2+)两种离子与YycF_N的相互作用,对详细的相互作用界面进行了分析,并计算了Ca~(2+)、Mg~(2+)与YycF_N的解离常数(K_d).发现金属离子的关键作用位点是Asp9、Asp16和Asp53等残基,蛋白的整体构象也发生了一定变化,为阐明二价金属离子在反应调节蛋白信号转导过程中的作用机制提供了重要线索.     

外磁场下XY模型中两量子位热纠缠的性质及其调控研究

在海森堡XY模型中,为了统一研究均匀磁场和非均匀磁场对系统热纠缠的影响,在两个量子位分别施加独立可控的外磁场(B+b)和(B-b). 发现在均匀磁场和低温条件下的纠缠度有一个稳定的平台区并发生纠缠突变. 控制磁场不均匀度b和选择合适的材料就可以获得最有利的纠缠,并大大提高系统退纠缠的临界温度T_c. 调节磁场的B值,可以在更宽的温度范围内实现此体系的纠缠开关. 关键词： 热纠缠度 密度矩阵 XY模型')" href="#">XY模型     

α稳定噪声驱动的非对称双稳随机共振现象

以微弱周期信号激励的非对称双稳系统为模型, 以信噪比增益为指标, 首先针对加性和乘性α 稳定噪声共同作用的随机共振现象展开了研究, 然后针对单独加性α 稳定噪声激励的随机共振现象进行了研究, 探究了α 稳定噪声特征指数α 和对称参数β 分别取不同值时, 系统结构参数a, b, 刻画双稳系统非对称性的偏度r以及α 稳定噪声强度放大系数Q或D对非对称双稳系统共振输出的作用规律. 研究结果表明, 无论在加性和乘性α 稳定噪声共同作用下还是在单独加性α 稳定噪声作用下, 通过调节a和b或者r均可诱导随机共振, 实现微弱信号的检测, 且有多个参数区间与之对应, 这些区间不随α 或β 的变化而变化; 在研究噪声诱导的随机共振现象时发现, 调节噪声强度放大系数也可使系统产生随机共振现象, 且达到共振状态时D的区间也不随α 或β 的变化而变化. 这些结论为α 稳定噪声环境下参数诱导随机共振中系统参数以及噪声诱导随机共振中噪声强度的合理选取提供了依据.     

二维非定常Sine-Gordon方程辛算法及其孤子数值模拟

在矩形域[-a,a]×[-a,a]内对微分算子L=(ə²)/(əx²)+(ə²)/(əy²)用5点差分格式将二维非定常Sine Gordon方程离散化为一个2×799²阶非线性Hamilton系统.对该系统使用Euler中心格式,得到一个非线性方程组.对此方程组建立迭代解法并给出了这个迭代方法的收敛条件和收敛速度.Sine Gordon方程单孤子和双孤子的数值模拟试验显示该辛算法是有效的.     

深紫外分光光度检测系统的稳定性及灵敏度研究

现有的国标光度法无法直接测定流程工业中连续反应单元生产过程的污染物,主要原因是氧气在深紫外区对紫外光的吸收干扰了紫外分光光度计对目标物质的检测,导致检测结果存在一定程度偏差。因此,解决这一问题的关键核心是稳定获取深紫外区不同特征波长物质的高灵敏光度信息。在紫外分光光度计基础上加装氮气输配系统,同时设计了自动进样流通池及进样托盘以实现检测间隙自动进样功能,减少检测间隙氮气消耗。为提高仪器稳定性,分别精准控制通入仪器内部光学系统区、样品室和数据接收区三个腔体的氮气流量,数值分别为6,2和3 L·min-1,使仪器基线平直度平均值由0.108降低至0.010,较空气条件削减了90.7%。通过对比空气与氮气两种气氛下直接测定SO2-₄的吸光度、灵敏度、灵敏度变化量和线性范围的差异,发现氮气气氛下检测结果的吸光度和灵敏度在光程b=1~100 mm范围内均有提升,灵敏度变化量随b=1 mm时的10.42%增大至b=100 mm时30.65%,线性范围却随光程的增加由0.09 g·L-1缩短至0.03 g·L-1。说明氮气输配系统能够成功抑制检测过程中紫外光强度的衰减。与检测SO2-₄的常用方法之一的离子色谱法相比,该方法具有检测便捷、检测结果稳定可靠并且经济效益良好的优势,可为工业实际应用奠定基础。     

Bacillus subtilis转录因子CtsR蛋白中clpC操纵子结合区域的NMR研究

革兰氏阳性菌枯草芽孢杆菌（Bacillus subtilis）响应热刺激时,精氨酸激酶McsB磷酸化转录因子CtsR蛋白中clpC操纵子结合区域的Arg62（R）位点,使得CtsR与clpC操纵子解离,从而启动clpC相关基因的转录过程,以表达细菌应对热刺激所需的蛋白.本文以CtsR蛋白中结合clpC操纵子的区域（KRGGGG）为研究对象,通过对¹H NMR、¹H-¹H COSY、¹H-¹H TOCSY、¹H-¹⁵N HSQC和¹H-¹³C HSQC等谱图的综合分析,对其¹H、¹³C以及¹⁵N的化学位移进行归属,为该片段与clpC操纵子相互作用,以及精氨酸磷酸化调控机制的研究提供基础.     

双椭圆纳米金属棒构成的表面等离子体波导的传输特性分析

设计了一种双椭圆纳米金属棒表面等离子体波导,采用频域有限差分法,对这种波导所支持的基模的能流密度分布、有效折射率和传播长度随几何结构参数和工作波长的依赖关系进行了分析.结果表明,沿纵向的能流主要分布在两个椭圆金属棒所形成的中间区域,且越靠近金属棒的弧形边,沿纵向的能流越大.通过调节两个金属棒的中心距离以及它们的两个半轴的大小,可以调节模式的有效折射率和传播长度.在工作波长确定的条件下,相对于a=b的情形来说,在a<b时,场与金属表面接触的面积较大,场 关键词： 集成光学 光波导 表面等离子体波导     

变权小世界生物神经网络的兴奋及优化特性

根据实际生物神经网络具有小世界连接和神经元之间的连接强度随时间变化的特点,首先构造了一个以Hodgkin-Huxley方程为节点动力学模型的动态变权小世界生物神经网络模型,然后研究了该模型神经元的兴奋特性、权值变化特点和不同的学习系数对神经元的兴奋统计特性的影响.最有意义的结果是,在同样的网络结构、网络参数及外部刺激信号的条件下,学习系数b存在一个最优值b^*,使生物神经网络的兴奋度在b=b^*时达到最大. 关键词： 动态变权生物神经网络 小世界网络 Hodgkin-Huxley方程     

磷酸化调控泛素单体与Rad23A/Ubiquilin-1中泛素结合域互作的检测

泛素（ubiquitin，Ub）是一种广泛存在、高度保守的信号蛋白质，它能够特异性识别成千上万种靶蛋白，以非共价方式行使不同的功能，其中包含蛋白质降解．Ubiquilin-1（Ubql-1）和Rad23A作为两种蛋白降解的转运因子，都包含有与泛素结合的结构域，被称为泛素结合域（ubiquitin-associated domain，UBA）．2014年，泛素S65位磷酸化修饰的特异性激酶PINK1被发现，磷酸化使泛素在溶液中呈现舒展态与收缩态两种互相转换的构象．本文通过核磁共振（nuclear magnetic resonance，NMR）技术对UBA和磷酸化泛素之间的相互作用进行检测，观测磷酸化对UBA和泛素结合的影响．实验结果表明Rad23A-UBA2与Ubql-1 UBA都特异性的与磷酸化泛素的舒展态相互作用，但是磷酸化未改变泛素与UBA之间的亲和力．值得注意的是与Ubql-1 UBA相互作用时，磷酸化促进了泛素收缩态向舒展态的转换．     

基于19F化学标记磷酸化泛素的温度传感器开发

泛素是一种真核细胞信号分子,主要参与蛋白质降解和DNA修复等生命活动.泛素Ser65位被磷酸化之后,在溶液中呈现两个稳定的溶液构象,这两种构象的比例能够被pH调控,本研究利用NMR进一步发现它还受到温度影响.基于该发现,对磷酸化泛素进行了¹⁹F化学标记,利用¹⁹F NMR方法表征了不同温度下磷酸化泛素两种构象的比例,发现两者比例变化与温度之间的关系可以通过线性方程来描述,利用该方程可以通过构象比例计算样品内部温度,因此可以作为一种基于NMR检测的温度传感器.本文所开发的基于¹⁹F化学标记磷酸化泛素的温度传感器不仅能够作为体外样品温度检测的有力工具,还有望用于检测细胞内部的温度.从而有助于揭示生物学特性和功能.     

A nonequilibrium phase transition in immune response

The dynamics of immune response correlated to signal transduction in immune thymic cells (T cells) is studied. In particular, the problem of the phosphorylation of the immune-receptor tyrosine-based activation motifs (ITAM) is explored. A nonlinear model is established on the basis of experimental observations. The behaviours of the model can be well analysed using the concepts of nonequilibrium phase transitions. In addition, the Riemann－Hugoniot cusp catastrophe is demonstrated by the model. Due to the application of the theory of nonequilibrium phase transitions, the biological phenomena can be clarified more precisely. The results can also be used to further explain the signal transduction and signal discrimination of an important type of immune T cell.     

1H- and 13C-NMR Study of Some 6,7-Dihaloquinolone Nucleosides and Their Derivatives

The ¹H- and ¹³C-NMR spectra of 6,7-dihalo-1,4-dihydro-4-oxo-1-(2,3,5-tri-0-benzoyl-pβ-D-ribofuranosyl)quinoline-3-carboxylic acids (3), (4), the ester (3a), 6-chloro-1-(2-deoxy-3,5-di-O-tolouyl-α- and β-D-erythropentofuranosyl)-7-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid (5), and its free a-nucleoside (5a) have been investigated. Resonance signals were assigned by homo- and heteronuclear two dimensional NMR methods (DQF-COSY, HMQC, and HMBC) for (3), (4), (5), and (5a). Ribosylation sites and anomeric configurations were identified from ROESY spectra.     

Nucleotide Spin Labeling for ESR Spectroscopy of ATP-Binding Proteins

Site-directed spin labeling of proteins by chemical modification of engineered cysteine residues with the molecule MTSSL (1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl methanethiosulfonate) has been an invaluable tool for conducting double electron electron resonance (DEER) spectroscopy experiments. However, this method is generally limited to recombinant proteins with a limited number of reactive Cys residues that when modified will not impair protein function. Here, we present a method that allows for spin labeling of protein-nucleotide-binding sites by adenosine diphosphate (ADP) modified with a nitroxide moiety on the β-phosphate (ADP-β-S-SL). The synthesis of this ADP analog is straightforward and isolation of pure product is readily achieved on a standard reverse-phase high-performance liquid chromatography (HPLC) system. Furthermore, analyses of isolated ADP-β-S-SL by LC–mass spectrometry confirm that the molecule is very stable under ambient conditions. The crystal structure of ADP-β-S-SL bound to the ATP pocket of the histidine kinase CheA reveals specific targeting of the probe, whose nitroxide moiety is mobile on the protein surface. Continuous wave and pulsed-ESR measurements demonstrate the capability of ADP-β-S-SL to report on active site environment and provide reliable DEER distance constraints.     

川续断中新七糖三萜皂苷的核磁共振研究

从中药川续断根部的乙醇提取物中分得一个新的三萜皂甙.经过测定,它为:3-O[α-L-吡喃鼠李糖(1→3)][-β-D吡喃葡萄糖(1→4)]-β-D吡喃葡萄糖(1→3)-α-L-吡喃鼠李糖(1→2)-β-L-吡喃阿拉伯糖-常春藤甙元-28-O-β-D-吡喃葡萄糖(1→6)-β-D-吡喃葡萄糖酯甙.本文采用一维SEMDY,旋转坐标NOE差谱和选择性远程DEPT新技术相结合测定该化合物的糖链结构.     

Influence of ultrasound pretreatment on the subsequent glycation of dietary proteins

The influence of ultrasound treatment on the subsequent glycation process of proteins is controversial. Glycation behaviors of bovine serum albumin (BSA), β-lactoglobulin (β-Lg) and β-casein (β-CN) after ultrasound pretreatment (UP) were compared by both evaluating glycation kinetics and analyzing structural changes of proteins. UP resulted in both unfolding and aggregation behavior in protein samples, which altered the accessibility of the Lys and Arg. Five cycles of UP up-regulated the glycation degree of BSA and β-Lg, possibly due to the unfolding behavior induced by UP, which exposed additional glycation sites. In contrast, 30 cycles of UP induced a dramatic increase (by 97.9 nm) in particle size of BSA, thus burying portions of glycation sites and suppressing the glycation process. Notably, UP had minimal influence on glycation kinetics of β-CN, due to its intrinsic disordered structure. Based on proteomics analysis, the preference of Lys and Arg during glycation was found to be changed by UP in BSA and β-Lg. Four, 3 and 3 unique carboxyethylated lysine residues were identified in glycated BSA after 0, 5 and 30 cycles of UP, respectively. This study suggests that the protein glycation can be affected by UP, depending on the ultrasonication duration and native structure of the protein.     

Whose Entropy: A Maximal Entropy Analysis of Phosphorylation Signaling

High throughput experiments, characteristic of studies in systems biology, produce large output data sets often at different time points or under a variety of related conditions or for different patients. In several recent papers the data is modeled by using a distribution of maximal information-theoretic entropy. We pose the question: ‘whose entropy’ meaning how do we select the variables whose distribution should be compared to that of maximal entropy. The point is that different choices can lead to different answers. Due to the technological advances that allow for the system-wide measurement of hundreds to thousands of events from biological samples, addressing this question is now part of the analysis of systems biology datasets. The analysis of the extent of phosphorylation in reference to the transformation potency of Bcr-Abl fusion oncogene mutants is used as a biological example. The approach taken seeks to use entropy not simply as a statistical measure of dispersion but as a physical, thermodynamic, state function. This highlights the dilemma of what are the variables that describe the state of the signaling network. Is what matters Boolean, spin-like, variables that specify whether a particular phosphorylation site is or is not actually phosphorylated. Or does the actual extent of phosphorylation matter. Last but not least is the possibility that in a signaling network some few specific phosphorylation sites are the key to the signal transduction even though these sites are not at any time abundantly phosphorylated in an absolute sense.     

苦皮藤中两个新的 β-二氢沉香呋喃型化合物的 NMR 数据解析

从南蛇藤属植物苦皮藤中分离出两个新的β-二氢沉香呋喃型化合物：1β,2β,15-三乙酰氧基-8α-(α-甲基)-丁酰氧基-9β-苯甲酰氧基-4α,6α-二羟基-β-二氢沉香呋喃（化合物I）和1β,15-二乙酰氧基-8α-(α-甲基)-丙酰氧基-2β,9β-二苯甲酰氧基-4α,6α-二羟基-β-二氢沉香呋喃（化合物II）．通过核磁共振（NMR，包括¹H NMR、¹³C NMR、DEPT、¹H-¹H COSY、NOESY、HSQC、HMBC）技术对化合物所有的¹H和¹³C NMR信号进行了全归属和详细解析.     

Comparison of CID, ETD and metastable atom-activated dissociation (MAD) of doubly and triply charged phosphorylated tau peptides

The fragmentation behavior of the 2+ and 3+ charge states of eleven different phosphorylated tau peptides was studied using collision-induced dissociation (CID), electron transfer dissociation (ETD) and metastable atom-activated dissociation (MAD). The synthetic peptides studied contain up to two known phosphorylation sites on serine or threonine residues, at least two basic residues, and between four and eight potential sites of phosphorylation. CID produced mainly b-/y-type ions with abundant neutral losses of the phosphorylation modification. ETD produced c-/z-type ions in highest abundance but also showed numerous y-type ions at a frequency about 50% that of the z-type ions. The major peaks observed in the ETD spectra correspond to the charge-reduced product ions and small neutral losses from the charge-reduced peaks. ETD of the 2+ charge state of each peptide generally produced fewer backbone cleavages than the 3+ charge state, consistent with previous reports. Regardless of charge state, MAD achieved more extensive backbone cleavage than CID or ETD, while retaining the modification(s) in most cases. In all but one case, unambiguous modification site determination was achieved with MAD. MAD produced 15-20% better sequence coverage than CID and ETD for both the 2+ and 3+ charge states and very different fragmentation products indicating that the mechanism of fragmentation in MAD is unique and complementary to CID and ETD.     

Study of spatial signal transduction in bistable switches

Bistable switch modules are among the most important fundamental motifs in signal-transduction pathways. To better understand their spatial signal transduction, we model the diffusion process in the one-dimensional (1–D) domain. We find that when none of the elements diffuse, the response of the system exhibits a spatial switch–like property. However, when one of the elements is highly diffusible, the response of the system does not show any spatial switching behavior. Furthermore, we observe that the spatial responses of the system are more sensitive to the time constant of the switch when none of the elements are diffusible. Further, a slow loop keeps the system in the high steady state more positions than that in the fast loop. Finally, we consolidate our numerical results analytically by performing a mathematical method.     

Azimuthal sound localization using coincidence of timing across frequency on a robotic platform

An algorithm for localizing a sound source with two microphones is introduced and used in real-time situations. This algorithm is inspired by biological computation of interaural time difference as occurring in the barn owl and is a modification of the algorithm proposed by Liu et al. [J. Acoust. Soc. Am. 110, 3218-3231 (2001)] in that it creates a three-dimensional map of coincidence location. This eliminates localization artifacts found during tests with the original algorithm. The source direction is found by determining the azimuth at which the minimum of the response in an azimuth-frequency matrix occurs. The system was tested with a pan-tilt unit in real-time in an office environment with signal types ranging from broadband noise to pure tones. Both open loop (pan-tilt unit stationary) and closed loop experiments (pan-tilt unit moving) were conducted. In real world situations, the algorithm performed well for all signal types except pure tones. Subsequent room simulations showed that localization accuracy decreases with decreasing direct-to-reverberant ratio.