An in silico approach for screening flavonoids as P-glycoprotein inhibitors based on a Bayesian-regularized neural network

P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter, functions as a biological barrier by extruding cytotoxic agents out of cells, resulting in an obstacle in chemotherapeutic treatment of cancer. In order to aid in the development of potential P-gp inhibitors, we constructed a quantitative structure-activity relationship (QSAR) model of flavonoids as P-gp inhibitors based on Bayesian-regularized neural network (BRNN). A dataset of 57 flavonoids collected from a literature binding to the C-terminal nucleotide-binding domain of mouse P-gp was compiled. The predictive ability of the model was assessed using a test set that was independent of the training set, which showed a standard error of prediction of 0.146 +/- 0.006 (data scaled from 0 to 1). Meanwhile, two other mathematical tools, back-propagation neural network (BPNN) and partial least squares (PLS) were also attempted to build QSAR models. The BRNN provided slightly better results for the test set compared to BPNN, but the difference was not significant according to F-statistic at p = 0.05. The PLS failed to build a reliable model in the present study. Our study indicates that the BRNN-based in silico model has good potential in facilitating the prediction of P-gp flavonoid inhibitors and might be applied in further drug design.

Small-Molecule Selectively Recognizes Human Telomeric G-Quadruplex DNA and Regulates Its Conformational Switch

Structural complexity is an inherent feature of the human telomeric sequence, and it presents a major challenge for developing ligands of pharmaceutical interest. Recent studies have pointed out that the induction of a quadruplex or change of a quadruplex conformation on binding may be the most powerful method to exert the desired biological effect. In this study, we demonstrate a quadruplex ligand that binds selectively to different forms of the human telomeric G-quadruplex structure and regulates its conformational switch. The results show that not only can oxazine750 selectively induce parallel quadruplex formation from a random coil telomeric oligonucleotide, in the absence of added cations, it also can easily surpass the energy barrier between two structures and change the G-quadruplex conformation in Na+ or K+ solution. The combination of its unique properties, including the size and shape of the G-quadruplex and the small molecule, is proposed as the predominant force for regulating the special structural formation and transitions.

Electrochemical design of ultrathin platinum-coated gold nanoparticle monolayer films as a novel nanostructured electrocatalyst for oxygen reduction

The deliberate tailoring of nanostructured metallic catalysts at the monolayer-level is an ongoing challenge and could lead to new electronic and catalytic properties, since surface-catalyzed reactions are extremely sensitive to the atomic-level details of the catalytic surface. In this article, we present a novel electrochemical strategy to nanoparticle-based catalyst design using the recently developed underpotential deposition (UPD) redox replacement technique. A single UPD Cu replacement with Pt2+ yielded a uniform Pt layer on colloid gold surfaces. The ultrathin (nominally monolayer-level) Pt coating of the novel nanostructured particles was confirmed by cyclic voltammetry and X-ray photoelectron spectra (XPS). The present results demonstrate that ultrathin Pt coating effects efficiently and behaves as the nanostructured monometallic Pt for electrocatalytic oxygen reduction, and also shows size-dependent, tunable electrocatalytic ability. The as-prepared ultrathin Pt-coated Au nanoparticle monolayer electrodes reduce O-2 predominantly by four electrons to H2O, as confirmed by the rotating ring-disk electrode (RRDE) technique.

基于场景的笔式界面设计工具的设计和实现

设计实现了一个基于数字笔的用户界面设计工具，该工具以面向笔式界面领域，基于场景的设计思想来设计系统中的界面场景组织关系以及场景之间的动态切换方式，设计者与工具间的交互自然流畅、快捷高效。通过手势识别技术，该工具可以将场景的设计结果转换为内部的界面描述语言，并通过相应的解释最终构造生成笔式用户界面。该工具可以快速生成界面原型，从而有效地提高了笔式交互系统的设计和开发效率。

基于场景方法的笔式界面软件设计工具

为缩短的笔式用户界面软件的开发周期,让设计人员对软件的整体构思在开发过程中得以保持,提高团队人员的交流效率,提出了有关笔式界面软件的文档描述规范PUIML(pen-based user interface modeling language),并设计实现了一个笔交互的笔式用户界面软件设计工具。以笔式操作平台为软件平台,以PUIML为数据模型,采用基于场景设计的开发方法,为设计人员和用户提供自然的纸笔交互方式,设计结果形成PUIML形式的文档,通过主控程序执行。实践结果表明,使用PUI Maker可以解决笔式用户界面开发中存在的以开发人员为中心,原始设计与开发结果不一致等问题,提高了笔式界面软件的开发效率。

一种面向基于属性存取的文件系统的设计与实现

基于属性的存取，对于在包含不同来源的大量文件的系统中进行有效的信息管理来说，是一种非常具有吸引力的特性。然而尽管在相当长的一段时间内其价值已广为人知，该特性的真正有实用价值的实现仍然非常之少。本文探讨了实现该特性时面临的主要挑战，以及它们是怎样在一种专为此目的设计的文件系统中，通过成功的应用各种原则而被妥善处理。

Optimization of Global Signal Networks for Island-Style FPGAs

We present a staggered buffer connection method that provides flexibility for buffer insertion while designing global signal networks using the tile-based FPGA design methodology. An exhaustive algorithm is used to analyze the trade-off between area and speed of the global signal networks for this staggered buffer insertion scheme, and the criterion for determining the design parameters is presented. The comparative analytic result shows that the methods in this paper are proven to be more efficient for FPGAs with a large array size.

Carboxyl-modified single-walled carbon nanotubes selectively induce human telomeric i-motif formation

As the leading nanodevice candidate, single-walled carbon nano-tubes (SWNTs) have potential therapeutic applications in gene therapy and novel drug delivery. We found that SWNTs can inhibit DNA duplex association and selectively induce human telomeric i-motif DNA formation by binding to the 5'-end major groove under physiological conditions or even at pH 8.0. SWNT binding to telomeric DNA was studied by UV melting, NMR, S1 nuclease cleavage, CD, and competitive FRET methods. These results suggest that SWNTs might have the intriguing potential to modulate human telomeric DNA structures in vivo, like biologically relevant B-A and B-Z DNA transitions, which is of great interest for drug design and cancer therapy.

PolydA and polyrA self-structured by a europium and amino acid complex

Different DNA selectivity was found for the newly synthesized europium-L-valine complex. Unexpected DNA and RNA selection results showed that europium-L-valine complex can cause single-stranded polydA and polyrA to self-structure. The sigmoidal melting curve profiles indicate the transition is cooperative, similar to the cooperative melting of a duplex DNA. This is different from another europium amino acid complex, europium-L-aspartic acid complex which can induce B-Z transition under the low salt condition. To our knowledge, there is no report to show that a metal-amino acid complex can cause the self-structuring of single-stranded DNA and RNA.

Synthesis, luminescence, energy transfer and Langmuir-Blodgett films of amphiphilic complexes of rare earths with monooctadecyl phthalate

Three new amphiphilic rare earth complexes with only two organic long chains Ln (MOP)(2)Cl (MOP=monooctadecyl phthalate, Ln=Eu, Tb, Gd) were synthesized and characterized by elemental analysis. The complexes (Eu, Tb) showed good luminescence property with long fluorescence lifetime, whereas the intensity and lifetime of Tb complex are greater than those of Eu complex, By measuring the triplet energy levels of ligand based on energy transfer mechanism, above phenomena have been well explained. The Langmuir films of the complexes on the air/water interface were also studied and the results show that all of them have good film-forming property.

基于耦合驱动蛇形机器人机构设计与抬起的方法

文中设计了模块化的新型蛇形机器人关节单元 .该单元具有三个自由度 ,其中摆动和俯仰自由度由耦合机构驱动来获得较大的力矩和活动空间 .由该单元组成的蛇形机器人具有很强的驱动能力 ,能够抬起较多的单元 .针对蛇形机器人的特点 ,给出了耦合机构的设计原则 .对蛇形机器人抬起方法作了分析 ,得出采用适当规划方法能够抬起的最大单元数量是直接抬起的最大单元数量的平方关系的结论 ,并在此基础上分析了最大关节角对机器人抬起的影响 ,最后结合实例验证了上面分析结果

Copolymerization of CO2 and propylene oxide under rare earth ternary catalyst: design of ligand in yttrium complex

Copolymerization of carbon dioxide and propylene oxide was carried out employing (RC6H4COO)(3)Y/glycerin/ZnEt2 (R = -H, -CH3, NO2, -OH) ternary catalyst systems. The feature of yttrium carboxylates (ligand, substituent and its position on the aromatic ring) is of great importance in the final copolymerization. Appropriate design of substituent and position of the ligand in benzoate-based yttrium complex can adjust the microstructure of aliphatic polycarbonate in a moderate degree, where the head-to-tail linkage in the copolymer is adjustable from 68.4 to 75.4%. The steric factor of the ligand in the yttrium complex is crucial for the molecular weight distribution of the copolymer, probably due to the fact that the substituent at 2 and 4-position would disturb the coordination or insertion of the monomer, lead the copolymer with broad molecular distribution. Based on the study of ultraviolet-visible spectra of the ternary catalyst in various solvents, it seems that the absorption band at 240-255 nm be closely related to the active species of the rare earth ternary catalysts.

Intensity Distribution Design for Laser-Induced Thermal Loading Based on Numerical Simulation

To accomplish laser-induced thermal loading simulation tests for pistons,the Gaussian beam was modulated into multi-circular beam with specific intensity distribution.A reverse method was proposed to design the intensity distribution for the laser-induced thermal loading based on finite element(FE) analysis.Firstly,the FE model is improved by alternating parameters of boundary conditions and thermal-physical properties of piston material in a reasonable range,therefore it can simulate the experimental resul...

Developing A Microfluidic-Based System To Quantify Cell Capture Efficiency

Micro-fabrication technology has substantial potential for identifying molecular markers expressed on the surfaces of tissue cells and viruses. It has been found in several conceptual prototypes that cells with such markers are able to be captured by their antibodies immobilized on microchannel substrates and unbound cells are flushed out by a driven flow. The feasibility and reliability of such a microfluidic-based assay, however, remains to be further tested. In the current work, we developed a microfluidic-based system consisting of a microfluidic chip, an image grabbing unit, data acquisition and analysis software, as well as a supporting base. Specific binding of CD59-expressed or BSA-coupled human red blood cells (RBCs) to anti-CD59 or anti-BSA antibody-immobilized chip surfaces was quantified by capture efficiency and by the fraction of bound cells. Impacts of respective flow rate, cell concentration, antibody concentration and site density were tested systematically. The measured data indicated that the assay was robust. The robustness was further confirmed by capture efficiencies measured from an independent ELISA-based cell binding assay. These results demonstrated that the system developed provided a new platform to effectively quantify cellular surface markers effectively, which promoted the potential applications in both biological studies and clinical diagnoses.