Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Dehydrogenation of Light Alkanes Over Rhenium Catalysts on Conventional and Mesoporous MFI Supports

Recently, Re/HZSM-5 (Si/Al = 15) was shown to be an efficient catalyst for ethane dehydrogenation and aromatization at 823 K and atmospheric pressure. In this reaction, the major initial products were benzene, toluene and xylene (BTX), but increasing amounts of ethene were produced with time on stream due to deactivation of the catalyst. We show that by use of rhenium impregnated MFI supports with very few or no acidic sites (Si/Al > 500), highly selective ethane dehydrogenation catalysts are obtained with ethene selectivities of 98%. By use of mesoporous MFI supports (Si/Al >500) the lifetime of the catalyst appears to be slightly improved compared to conventional MFI crystals. The beneficial effect of a mesoporous MFI support is convincingly demonstrated in propane dehydrogenation, where both conversion and selectivities on the mesoporous MFI (Si/Al > 500) impregnated with Re are significantly higher than on Re supported on a comparable conventional MFI support.     

An optimality criteria based method for discrete design optimization taking into account buildability constraints

This paper presents a heuristic design optimization method specifically developed for practicing structural engineers. Practical design optimization problems are often governed by buildability constraints. The majority of optimization methods that have recently been proposed for design optimization under buildability constraints are based on evolutionary computing. While these methods are generally easy to implement, they require a large number of function evaluations (finite element analyses), and they involve algorithmic parameters that require careful tuning. As a consequence, both the computation time and the engineering time are high. The discrete design optimization algorithm presented in this paper is based on the optimality criteria method for continuous optimization. It is faster than an evolutionary algorithm and it is free of tuning parameters. The algorithm is successfully applied to two classical benchmark problems (the design of a ten-bar truss and an eight-story frame) and to a practical truss design optimization problem.     

A New $H_{{bm infty}}$ Stabilization Criterion for Networked Control Systems

This note is concerned with robust H_infin control of linear networked control systems with time-varying network-induced delay and data packet dropout. A new Lyapunov-Krasovskii functional, which makes use of the information of both the lower and upper bounds of the time-varying network-induced delay, is proposed to drive a new delay-dependent H_infin stabilization criterion. The criterion is formulated in the form of a non-convex matrix inequality, of which a feasible solution can be obtained by solving a minimization problem in terms of linear matrix inequalities. In order to obtain much less conservative results, a tighter bounding for some term is estimated. Moreover, no slack variable is introduced. Finally, two numerical examples are given to show the effectiveness of the proposed design method.     

Robust exponential stability conditions for retarded systems with Lipschitz nonlinear stochastic perturbations

This paper investigates robust mean‐square exponential stability of a class of uncertain stochastic state‐delayed systems with Lipschitz nonlinear stochastic perturbation. Based on Lyapunov–Krasovskii functional (LKF) method and free‐weighting matrix technique, some new delay‐dependent stability conditions are established in terms of linear matrix inequalities (LMIs). In order to reduce the conservatism, (1) the delay is divided into several segments, i.e. the delay decomposition method is applied; (2) cross terms estimation is avoided; (3) some information of the cross terms relationships which has not been involved in Reference (IET Control Theory Appl. 2008; 2(11):966–973) is considered. Moreover, from the mathematical point of view, the results obtained by free‐weighting matrix technique can be equivalently re‐formulated by simpler ones without involving any additional free matrix variables. The effectiveness of the method is demonstrated by numerical examples. Copyright © 2010 John Wiley & Sons, Ltd.     

Effects of auditory,haptic and visual feedback on performing gestures by gaze or by hand

Modern interaction techniques like non-intrusive gestures provide means for interacting with distant displays and smart objects without touching them. We were interested in the effects of feedback modality (auditory, haptic or visual) and its combined effect with input modality on user performance and experience in such interactions. Therefore, we conducted two exploratory experiments where numbers were entered, either by gaze or hand, using gestures composed of four stroke elements (up, down, left and right). In Experiment 1, a simple feedback was given on each stroke during the motor action of gesturing: an audible click, a haptic tap or a visual flash. In Experiment 2, a semantic feedback was given on the final gesture: the executed number was spoken, coded by haptic taps or shown as text. With simultaneous simple feedback in Experiment 1, performance with hand input was slower but more accurate than with gaze input. With semantic feedback in Experiment 2, however, hand input was only slower. Effects of feedback modality were of minor importance; nevertheless, semantic haptic feedback in Experiment 2 showed to be useless at least without extensive training. Error patterns differed between both input modes, but again not dependent on feedback modality. Taken together, the results show that in designing gestural systems, choosing a feedback modality can be given a low priority; it can be chosen according to the task, context and user preferences.     

Linear programming based approximation algorithms for feedback set problems in bipartite tournaments

We consider the feedback vertex set and feedback arc set problems on bipartite tournaments. We improve on recent results by giving a 2-approximation algorithm for the feedback vertex set problem. We show that this result is the best that we can attain when using optimal solutions to a certain linear program as a lower bound on the optimal value. For the feedback arc set problem on bipartite tournaments, we show that a recent 4-approximation algorithm proposed by Gupta (2008) [8] is incorrect. We give an alternative 4-approximation algorithm based on an algorithm for the feedback arc set on (non-bipartite) tournaments given by van Zuylen and Williamson (2009) [14].     

Efficient Sequence Alignment with Side-Constraints by Cluster Tree Elimination

Aligning DNA and protein sequences is a core technique in molecular biology. Often, it is desirable to include partial prior knowledge and conditions in an alignment. Going beyond prior work, we aim at the integration of such side constraints in free combination into alignment algorithms. The most common and successful technique for efficient alignment algorithms is dynamic programming (DP). However, a weakness of DP is that one cannot include additional constraints without specifically tailoring a new DP algorithm. Here, we discuss a declarative approach that is based on constraint techniques and show how it can be extended by formulating additional knowledge as constraints. We take special care to obtain the efficiency of DP for sequence alignment. This is achieved by careful modeling and applying proper solving strategies. Finally, we apply our method to the scanning for RNA motifs in large sequences. This case study demonstrates how the new approach can be used in real biological problems. A prototypic implementation of the method is available at .