NIPALSTREE: a new hierarchical clustering approach for large compound libraries and its application to virtual screening

A hierarchical clustering algorithm--NIPALSTREE--was developed that is able to analyze large data sets in high-dimensional space. The result can be displayed as a dendrogram. At each tree level the algorithm projects a data set via principle component analysis onto one dimension. The data set is sorted according to this one dimension and split at the median position. To avoid distortion of clusters at the median position, the algorithm identifies a potentially more suited split point left or right of the median. The procedure is recursively applied on the resulting subsets until the maximal distance between cluster members exceeds a user-defined threshold. The approach was validated in a retrospective screening study for angiotensin converting enzyme (ACE) inhibitors. The resulting clusters were assessed for their purity and enrichment in actives belonging to this ligand class. Enrichment was observed in individual branches of the dendrogram. In further retrospective virtual screening studies employing the MDL Drug Data Report (MDDR), COBRA, and the SPECS catalog, NIPALSTREE was compared with the hierarchical k-means clustering approach. Results show that both algorithms can be used in the context of virtual screening. Intersecting the result lists obtained with both algorithms improved enrichment factors while losing only few chemotypes.     

CuSn合金熔体结构转变及其动力学行为探索

迄今为止,人们对合金在液相线之上的熔体结构转变过程的认识仍不清晰. 本文运用电阻法、DSC热分析等实验手段,对CuSn60wt%二元合金熔体在升温及保温条件下的结构转变动力学过程进行了研究,并通过相变动力学理论探讨了转变过程的特征与微观物理机制. 分析表明：合金熔体中温度诱导的结构转变过程符合“形核-长大”类型,其动力学过程为自动催化转变模式,其中液相中新结构原子团簇的“形核率”为转变速率的主导控制因素.     

杂质对溶胶-凝胶SiO2薄膜激光损伤的影响

采用溶胶-凝胶法制备了含有吸收性杂质和非吸收性杂质的SiO2增透膜,采用波长为1 064 nm的激光对其进行了小光斑激光预处理,对比研究了预处理前后的激光损伤差异,研究表明：激光预处理对于洁净的SiO2薄膜影响不大;含10 μm SiO2颗粒杂质的样品微透镜效应很明显,容易成为损伤起始的种子,激光预处理后情况有所改善;含有CeO2颗粒杂质的样品表现出了很强的吸收性质,损伤阈值降低到不足洁净样品的一半。所有样品激光预处理后损伤形貌未发生变化,透光率峰值均有约50 nm的蓝移。     

Measurement of the positive muon anomalous magnetic moment to 0.7 ppm

A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron, based on data collected in the year 2000. The result a(mu(+))=11 659 204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and has an error about one-half that of the combined previous data. The present world average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).     

激光器腔镜夹持方式对热变形的影响

 分析了当前大功率激光器腔镜采用的几种夹持方式特点，采用有限元软件计算了腔镜不同夹持方式下的镜面热变形和镜体最大应力，并对两种夹持方式下的应力破坏进行了分析。发现夹持方式对大功率激光器腔镜镜面变形影响很大，镜体边界沿径向固定的压圈法效果优于沿轴向固定的弹性压板法。     

Hyperfine structure,g j factors and lifetimes of excited2 P 1/2 states of Rb

The hyperfine structure of the 6² P _1/2 and 7² P _1/2 state of⁸⁵Rb and⁸⁷Rb and of the 6² P _3/2 state of⁸⁷Rb has been investigated with optical double resonance at intermediate magnetic fields. The magnetic interaction constants,g _j factors and lifetimes are: $$\begin{gathered} 6^2 P_{1/2} state: A\left( {^{85} Rb} \right) = 39.11\left( 3 \right) MHz,A\left( {^{87} Rb} \right) = 132.56 \left( 3 \right)MHz, \hfill \\ g_j = 0.6659\left( 3 \right), \tau = 1.14\left( {13} \right) \cdot 10^{ - 7} \sec , \hfill \\ 7^2 P_{1/2} state: A\left( {^{85} Rb} \right) = 17.68\left( 8 \right)MHz,A\left( {^{87} Rb} \right) = 59.92\left( 9 \right)MHz, \hfill \\ g_j = 0.6655\left( 5 \right), \hfill \\ 6^2 P_{3/2} state: g_j = 1.3337\left( {10} \right), \tau = 1.12\left( 8 \right) \cdot 10^{ - 7} \sec for ^{87} Rb. \hfill \\ \end{gathered} $$ From the hfs coupling constants of then ² P multiplets a 11.5% core polarization contribution to the magnetic hfs of then ² P _3/2 states is obtained, which is found to be independent from the main quantum numbern. The expectation values <r ^?3> _j for thenp valence electrons corrected for core polarization are compared with those derived from the² P fine structure separation. Good agreement is achieved for allnp levels with the choice ofZ _i =Z?3=34 for the effective nuclear charge number. The nuclear quadrupole moments of⁸⁵Rb and⁸⁷Rb are rederived on the basis of this more improved treatment for thep-electron-nucleus interaction yielding $$\begin{gathered} Q_N \left( {^{85} Rb} \right) = + 0.274\left( 2 \right) \cdot 10^{ - 24} cm^2 \hfill \\ Q_N \left( {^{85} Rb} \right) = + 0.132\left( 1 \right) \cdot 10^{ - 24} cm^2 \hfill \\ \end{gathered} $$ where the error does not include the remaining theoretical uncertainty of about 10%.     

Search for Lorentz and CPT violation effects in Muon spin precession

The spin precession frequency of muons stored in the (g-2) storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for a nonzero delta omega a(=omega a mu+ - omega a mu-) and a sidereal variation of omega a mu+/-). No significant effect is found, and the following limits on the standard-model extension parameters are obtained: bZ = -(1.0+/-1.1) x 10(-23) GeV; (m mu dZ0 + HXY)=(1.8+/-6.0) x 10(-23) GeV; and the 95% confidence level limits b perpendicular mu+ <1.4 x 10(-24) GeV and b perpendicular mu- <2.6 x 10(-24) GeV.     

反相高效液相法测定大鼠肝组织中DNA的碱基含量

 利用反相高效液相法 ,采用SupelcosilLC 18柱 (2 5 0mm× 4 6mmi d ,5 μm) ,以甲醇 0 0 5mol/LKH2 PO4缓冲液 (体积比为 2 0∶80 )为流动相 ,流速 0 8mL/min ,在 2 5 4nm波长处检测 ,对生活在高原 (海拔 2 3km)的习服大鼠肝组织中脱氧核糖核酸 (DNA)的碱基含量进行了检测 ,发现各碱基在DNA中所占的比例是相对稳定的 :腺嘌呤 (A) 2 8 8%、鸟嘌呤 (G) 2 3 3%、胞嘧啶 (C) 17 4 %、胸腺嘧啶 (T) 2 5 3% ,并利用内标法对DNA甲基化水平进行了测定。     

Desymmetrised pentaporphyrinic gears mounted on metallo-organic anchors

Mastering intermolecular gearing is crucial for the emergence of complex functional nanoscale machineries. However, achieving correlated motion within trains of molecular gears remains highly challenging, due to the multiple degrees of freedom of each cogwheel. In this context, we designed and synthesised a series of star-shaped organometallic molecular gears incorporating a hydrotris(indazolyl)borate anchor to prevent diffusion on the surface, a central ruthenium atom as a fixed rotation axis, and an azimuthal pentaporphyrinic cyclopentadienyl cogwheel specifically labelled to monitor its motion by non-time-resolved Scanning Tunneling Microscopy (STM). Desymmetrisation of the cogwheels was first achieved sterically, i.e. by introducing one tooth longer than the other four. For optimal mechanical interactions, chemical labelling was also investigated as a preferential way to induce local contrast in STM images, and the electronic properties of one single paddle were modulated by varying the porphyrinic scaffold or the nature of the central metal. To reach such a structural diversity, our modular synthetic approach relied on sequential cross-coupling reactions on a penta(p-halogenophenyl)cyclopentadienyl ruthenium(ii) key building block, bearing a single pre-activated p-iodophenyl group. Chemoselective Sonogashira or more challenging Suzuki–Miyaura reactions allowed the controlled introduction of the tagged porphyrinic tooth, and the subsequent four-fold cross-couplings yielded the prototypes of pentaporphyrinic molecular gears for on-surface studies, incorporating desymmetrised cogwheels over 5 nm in diameter.

Star-shaped cogwheel prototypes incorporating one sterically- or chemically-labelled porphyrinic paddle were designed and synthesised with the aim of achieving intermolecular gearing on surfaces.     

Ultrasensitive Direct Quantification of Nucleobase Modifications in DNA by Surface‐Enhanced Raman Scattering: The Case of Cytosine

Recognition of chemical modifications in canonical nucleobases of nucleic acids is of key importance since such modified variants act as different genetic encoders, introducing variability in the biological information contained in DNA. Herein, we demonstrate the feasibility of direct SERS in combination with chemometrics and microfluidics for the identification and relative quantification of 4 different cytosine modifications in both single‐ and double‐stranded DNA. The minute amount of DNA required per measurement, in the sub‐nanogram regime, removes the necessity of pre‐amplification or enrichment steps (which are also potential sources of artificial DNA damages). These findings show great potentials for the development of fast, low‐cost and high‐throughput screening analytical devices capable of detecting known and unknown modifications in nucleic acids (DNA and RNA) opening new windows of activity in several fields such as biology, medicine and forensic sciences.