Hinge peptide combinatorial libraries for inhilbitors of botulinum neurotoxins and saxitoxin: Deconvolution strategy

Combinatorial library screening offers a rapid process for identifying potential therapies to toxins. Hinge peptide libraries, which rely on conformational diversity rather than traditional molecular diversity, reduce the need for huge numbers of syntheses and screening steps and greatly expedite the discovery process of active molecules. Hinge peptide libraries having the structures: Acetyl-X₁–X₂–hinge–X₃–X₄–NH₂ (capped) and X₁–hinge–X₂–X₃ (uncapped), where X₁ through X₄ are near-equimolar mixtures of twelve L-amino acids and hinge = 4-aminobutyric acid, were screened for inhibitory activity in bioassays for botulinum neurotoxins A and B (BoNT/A, BoNT/B) and saxitoxin. The zinc protease activity of the reduced light chains of BoNT/A and /B was assayed by measuring the cleavage of synthetic substrates. Saxitoxin activity was measured by the restoration of the viability of neuroblastoma cells treated with ouabain and veratridine. Deconvolution of libraries was accomplished by fixing one position at a time beginning with the C-terminus. Primary library subsets in which position 4 was fixed showed moderate levels of inhibition for BoNT/A. Secondary library subsets showed stronger inhibition in the bioassays. In each of the bioassays, inhibitory potency was stronger when the second position to be fixed was on the opposite side of the hinge, rather than on the same side with respect to the C-terminus, suggesting that the hinge facilitates the interaction of side chains. Inhibitors for all three of the toxins studied were discovered within library subsets, although not necessarily in primary subsets. These studies demonstrate that (1) the best strategy for deconvoluting hinge peptide libraries is by fixing residues alternately on each side of the hinge moiety, and (2) it is essential to investigate secondary subsets even when primary subsets are inactive. The present findings support the concept that the increased flexibility imposed by the inclusion of a central hinge residue in small peptides increases the opportunity for side chain interactions, providing a distinct advantage for hinge peptide libraries over conventional peptide libraries. Hinge peptide libraries are a rich source of novel ligands for modulation of biomechanisms. The library subsets uncovered in this study may possess peptides that will lead to effective therapies to neurotoxin poisoning.     

A Pseudo-Stokes Mesh Motion Algorithm

This work presents a moving mesh methodology based on the solution of a pseudo flow problem. The mesh motion is modeled as a pseudo Stokes problem solved by an explicit finite element projection method. The mesh quality requirements are satisfied by employing a null divergent velocity condition. This methodology is applied to triangular unstructured meshes and compared to well known approaches such as the ones based on diffusion and pseudo structural problems. One of the test cases is an airfoil with a fully meshed domain. A specific rotation velocity is imposed as the airfoil boundary condition. The other test is a set of two cylinders that move toward each other. A mesh quality criterion is employed to identify critically distorted elements and to evaluate the performance of each mesh motion approach. The results obtained for each test case show that the pseudo-flow methodology produces satisfactory meshes during the moving process.     

一种复杂多边形最大内圆的快速查找算法

任意多边形的最大内圆的快速查找在多个领域有着重要的应用。首先给出了任意多边形的Voronoi图的生成方法,以及基于Voronoi图实现该多边形的最大内圆的寻找算法,在此基础上分别采用中线简化及并行化处理对算法进行了效率方面的改进,并重点研究了矢量数据并行化过程中的数据分配策略,给出了其最优数据划分策略——算法复杂度均衡法。最后对北美阿拉斯加地区的多个湖泊进行了最大内圆的查找实验,相应的实验结果表明,改进的方法能够很大程度地提高最大内圆的查找效率。     

一个新的四维混沌系统理论分析与电路实现

分析了一个新的复杂的四维混沌系统的基本特性，该系统每个方程中包含一个三次交叉乘积项，共有9个平衡点，它们相对于原点和坐标轴具有完美的对称性，并且相对于线性特性和不变流形具有很好的相似性.描述了两个同时共存的对称双翼吸引子.最后，设计了一个模拟电路来实现这个新的四维混沌系统，表明数值仿真和电路实现具有很好的一致性，同时说明在应用上由于频率不同导致的仿真与物理实现之间的重要区别. 关键词： 四维混沌系统 Lyapunov 指数 共存双翼吸引子 电路实现     

Generalized Rule Induction Based on Immune Algorithm

A generalized rule induction mechanism, immune algorithm, for knowledge bases is building an inheritance hierarchy of classes based on the content of their knowledge objects. This hierarchy facilitates group-related processing tasks such as answering set queries, discriminating between objects, finding similarities among objects, etc. Building this hierarchy is a difficult task for knowledge engineers. Conceptual induction may be used to automate or assist engineers in the creation of such a classification structure. This paper introduces a new conceptual rule induction method, which addresses the problem of clustering large amounts of structured objects. The conditions under which the method is applicable are discussed.     

Quantum computation with ions in microscopic traps

We discuss a possible experimental realization of fast quantum gates with high fidelity with ions confined in microscopic traps. The original proposal of this physical system for quantum computation comes from Cirac and Zoller (Nature 404, 579 (2000)). In this paper we analyse a sensitivity of the ion-trap quantum gate on various experimental parameters which was omitted in the original proposal. We address imprecision of laser pulses, impact of photon scattering, nonzero temperature effects and influence of laser intensity fluctuations on the total fidelity of the two-qubit phase gate.     

斐索梯度折射率光纤透镜传感实验

采用LD泵浦的单纵模Nd：YVO4倍频激光器、梯度折射率光纤透镜等器件构成斐索梯度折射率光纤透镜传感实验仪．本文介绍了实验装置和实验原理，并给出了实验结果。     

Quantum Game with Restricted Matrix Strategies

We study a quantum game played by two players with restricted multiple strategies. It is found that in this restricted quantum game Nash equilibrium does not always exist when the initial state is entangled. At the same time,we find that when Nasli equilibrium exists the payoff function is usually different from that in the classical counterpart except in some special cases. This presents an explicit example showing quantum game and classical game may differ.When designing a quantum game with limited strategies, the allowed strategy should be carefully chosen according to the type of initial state.     

Design of interdigital transducers for crack detection in plates

Interdigital transducers (IDT) for non-destructive evaluation (NDE) of cracks in plates are designed based on an analytical model established previously. Key considerations include mode selectivity, excitation strength, collimation of wave and cost. The advantage of mode selectivity of IDT over PZT patch is presented both analytically and experimentally. Effects of parameters, namely finger spacing, width, length, number of fingers, and the size of IDT, on the excitation strength and mode selectivity are considered. This led to the design of a mobile double-sided IDT as an efficient device where excitation strength is strong and focused. The device was fabricated in-house using commercially available piezoelectric ceramics and used to develop a procedure for accurate identification of the direction and extent of cracks in plates. Three aluminum plates, one with a linear deep crack, another with a piecewise linear shallower crack and the third with a curved crack, were used to illustrate the accuracy and efficiency of both the proposed device and procedure for effective NDE.     

Correspondence between spin-dynamic phases and pulse program phases of NMR spectrometers

Spin state selective experiments have become very useful tools in solution NMR spectroscopy, particularly in the context of TROSY line narrowing. However, the practical implementation of such pulse sequences is frequently complicated by unexpected instrument behavior. Furthermore, a literal theoretical analysis of sequences published with specific phase settings can fail to rationalize such experiments and can seemingly contradict experimental findings. In this communication, we develop a practical approach to this ostensible paradox. Spin-dynamic design, rationalization, and simulation of NMR pulse sequences, as well as their confident and reliable implementation across current spectrometer hardware platforms, require precise understanding of the underlying nutation axis conventions. While currently often approached empirically, we demonstrate with a simple but general pulse program how to uncover these correspondences a priori in the general case. From this, we deduce a correspondence table between the spin-dynamic phases used in NMR theory and simulation on the one hand and pulse program phases of current commercial spectrometers on the other. As a practical application of these results, we analyze implementations of the original (1)H-(15)N TROSY experiment and illustrate how steady-state magnetization can be predictably, rather than empirically, added to a desired component. We show why and under which circumstances a literal adoption of phases from published sequences can lead to incorrect results. We suggest that pulse sequences should be consistently given with spin-dynamically correct (physical) phases, rather than in spectrometer-specific (software) syntax.