Reversal of Tabun Toxicity Enabled by a Triazole-Annulated Oxime Library—Reactivators of Acetylcholinesterase

Acetylcholinesterase (AChE), an enzyme that degrades the neurotransmitter acetylcholine, when covalently inhibited by organophosphorus compounds (OPs), such as nerve agents and pesticides, can be reactivated by oximes. However, tabun remains among the most dangerous nerve agents due to the low reactivation efficacy of standard pyridinium aldoxime antidotes. Therefore, finding an optimal reactivator for prophylaxis against tabun toxicity and for post-exposure treatment is a continued challenge. In this study, we analyzed the reactivation potency of 111 novel nucleophilic oximes mostly synthesized using the CuAAC triazole ligation between alkyne and azide building blocks. We identified several oximes with significantly improved in vitro reactivating potential for tabun-inhibited human AChE, and in vivo antidotal efficacies in tabun-exposed mice. Our findings offer a significantly improved platform for further development of antidotes and scavengers directed against tabun and related phosphoramidate exposures, such as the Novichok compounds.     

Reasoning and proof in geometry: effects of a learning environment based on heuristic worked-out examples

We analyze heuristic worked-out examples as a tool for learning argumentation and proof. Their use in the mathematics classroom was motivated by findings on traditional worked-out examples, which turned out to be efficient for learning algorithmic problem solving. The basic idea of heuristic worked-out examples is that they encourage explorative processes and thus reflect explicitly different phases while performing a proof. We tested the hypotheses that teaching with heuristic examples is more effective than usual classroom instruction in an experimental classroom study with 243 grade 8 students. The results suggest that heuristic worked-out examples were more effective than the usual mathematics instruction. In particular, students with an insufficient understanding of proof were able to benefit from this learning environment.     

Strategies to foster students’ competencies in constructing multi-steps geometric proofs: teaching experiments in Taiwan and Germany

In this article, we discuss the complexity of geometric proofs with respect to a theoretical analysis and empirical results from studies in Taiwan and Germany. Based on these findings in both countries, specific teachings experiments with junior high school students were developed, conducted, and evaluated. According to the different classroom and learning culture in East Asia and Western Europe, the interventions differed in their way of organizing the learning activities during regular mathematics lessons. The statistical analysis of the pre–post-test data indicated that both interventions were successful in fostering students’ proof competence.     

The compound Poisson risk model with multiple thresholds

In this paper we consider a multi-threshold compound Poisson risk model. A piecewise integro-differential equation is derived for the Gerber-Shiu discounted penalty function. We then provide a recursive approach to obtain general solutions to the integro-differential equation and its generalizations. Finally, we use the probability of ruin to illustrate the applicability of the approach.     

TLC Retention Behavior of Brodifacoum,Bromadiolone, and Coumatetralyl and their Impurities on Different Adsorbents

JPC – Journal of Planar Chromatography – Modern TLC - The chromatographic behavior of three biocidal technical materials, rodenticide active ingredients brodifacoum, bromadiolone, and...     

Nanomedicine—Challenge and Perspectives

The application of nanotechnology concepts to medicine joins two large cross‐disciplinary fields with an unprecedented societal and economical potential arising from the natural combination of specific achievements in the respective fields. The common basis evolves from the molecular‐scale properties relevant to the two fields. Local probes and molecular imaging techniques allow surface and interface properties to be characterized on a nanometer scale at predefined locations, while chemical approaches offer the opportunity to elaborate and address surfaces, for example, for targeted drug delivery, enhanced biocompatibility, and neuroprosthetic purposes. However, concerns arise in this cross‐disciplinary area about toxicological aspects and ethical implications. This Review gives an overview of selected recent developments and applications of nanomedicine.     

Convergence of an Interior Point Algorithm for Continuous Minimax

We propose an algorithm for the constrained continuous minimax problem. The algorithm uses a quasi-Newton search direction, based on subgradient information, conditional on maximizers. The initial problem is transformed to an equivalent equality constrained problem, where the logarithmic barrier function is used to ensure feasibility. In the case of multiple maximizers, the algorithm adopts semi-infinite programming iterations toward epiconvergence. Satisfaction of the equality constraints is ensured by an adaptive quadratic penalty function. The algorithm is augmented by a discrete minimax procedure to compute the semi-infinite programming steps and ensure overall progress when required by the adaptive penalty procedure. Progress toward the solution is maintained using merit functions.     

On the synthesis of chlorine pentafluoride

The reaction between chlorine trifluoride and elemental fluorine was studied in order to find the optimal reaction conditions for the synthesis of chlorine pantafluoride. It has been found that nickel difluoride is a very effective catalyst for the mentioned reaction. The obtained results are expressed as space-time-yield of chlorine pentafluoride.     

Determination of partition coefficients of metals in the Sava River environment

Site specific data and partition coefficients of stable elements in the Sava River environment have been measured. Distribution of metals in periphyton was similar to those found in sediments from the same locations. The concentration ratios of periphyton over sediments for Zn, As, Cd and Pb exceeded one. Thus the content of these metals in periphyton provides more information about anthropogenic pollution than either sediment or water samples collected at the periphyton site. In addition, the enrichment factors of the most abundant metals in the sediment samples have been calculated.     

The combined effect of numerical integration and approximation of the boundary in the finite element method for eigenvalue problems

Summary. The paper deals with the finite element analysis of second order elliptic eigenvalue problems when the approximate domains are not subdomains of the original domain and when at the same time numerical integration is used for computing the involved bilinear forms. The considerations are restricted to piecewise linear approximations. The optimum rate of convergence for approximate eigenvalues is obtained provided that a quadrature formula of first degree of precision is used. In the case of a simple exact eigenvalue the optimum rate of convergence for approximate eigenfunctions in the -norm is proved while in the -norm an almost optimum rate of convergence (i.e. near to is achieved. In both cases a quadrature formula of first degree of precision is used. Quadrature formulas with degree of precision equal to zero are also analyzed and in the case when the exact eigenfunctions belong only to the convergence without the rate of convergence is proved. In the case of a multiple exact eigenvalue the approximate eigenfunctions are compard (in contrast to standard considerations) with linear combinations of exact eigenfunctions with coefficients not depending on the mesh parameter . Received September 18, 1993 / Revised version received September 26, 1994