Alkaloids from stems of Esenbeckia leiocarpa Engl. (Rutaceae) as potential treatment for Alzheimer disease

Esenbeckia leiocarpa Engl. (Rutaceae), popularly known as guarant?, goiabeira, is a native tree from Brazil. Bioactivity-guided fractionation of the ethanol stems extract afforded the isolation of six alkaloids: leiokinine A, leptomerine, kokusaginine, skimmianine, maculine and flindersiamine. All isolated compounds were tested for acetyl cholinesterase inhibition, in vitro and displayed anticholinesterasic activity. The alkaloid leptomerine showed the highest activity (IC?? = 2.5 mM), similar to that of the reference compound galanthamine (IC?? = 1.7 mM). The results showed for the first time the presence of alkaloids leptomerine and skimmianine in E. leiocarpa (Engl.) with potent anticholinesterasic activity.     

Replacing 32 proline residues by a noncanonical amino acid results in a highly active DNA polymerase

Protein engineering may be achieved by rational design, directed evolution-based methods, or computational protein design. Mostly these methods make recourse to the restricted pool of the 20 natural amino acids. With the ability to introduce different new kinds of functionalities into proteins, the use of noncanonical amino acids became a promising new method in protein engineering. Here, we report on the generation of a multifluorinated DNA polymerase. DNA polymerases are highly dynamic enzymes that catalyze DNA synthesis in a template-dependent manner, thereby passing several conformational states during the catalytic cycle. Here, we globally replaced 32 proline residues by the noncanonical imino acid (4R)-fluoroproline in a DNA polymerase of 540 amino acids (KlenTaq DNA polymerase). Interestingly, the substitution level of the proline residues was very efficient (92%). Nonetheless, the introduction of (4R)-fluoroproline into the DNA polymerase resulted in a highly active fluorinated enzyme, which was investigated in primer extension and PCR assays to analyze activity, selectivity, and stability in comparison to the parental enzyme. The DNA polymerase retained fidelity, activity, and sensitivity as the parental wild-type enzyme accompanied by some loss in thermostability. These results demonstrate that a noncanonical amino acid can be used for substitutions of natural counterparts in a highly dynamic enzyme with high molecular weight without effecting crucial enzyme properties. Furthermore, the employed DNA polymerase represents a promising starting point for directed DNA polymerase evolution with noncanonical amino acids.     

On the Reconstruction and Computation of Dual-Phase Steel Microstructures Based on 3D EBSD Data

In this contribution we reconstruct the three dimensional microstructure of a dual-phase steel based on the tomographic experimental data provided by the 3D electron backscatter diffraction (3D EBSD) method. The cross sections of the resulting microstructure are compared to the 2D reconstruction, which are obtained directly from the 3D EBSD data. We also perform FE-simulations based on these geometries and observe comparable results in 2D and 3D. (© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

On the efficiency of the Asmussen–Kroese-estimator and its application to stop-loss transforms

Recently, Asmussen and Kroese [6] proposed efficient stochastic estimators to approximate the probability that a random sum exceeds a certain threshold. This article aims to extend the analysis of some of these estimators: Several questions induced by [6] for the threshold setting are discussed. In particular, it is shown that Asmussen and Kroese provide the first heavy-tailed example with vanishing relative error. Furthermore, estimators of similar type for the approximation of moments of stop-loss transforms are given. Their asymptotic performance is analysed and a numerical illustration is attached at the end.     

Frequency compensation for a class of DAE's arising in electrical circuits

Structured perturbations of regular pencils of the form , are considered which model the addition of a capacitance c in an electrical circuit in order to improve the frequency response. (© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Integrated design and optimization of a complex nonlinear hybrid electric powertrain including simulations in time domain

This paper deals with the design and optimization of hybrid electric powertrains. Therefore basic relations of the behavior of hybrid electric powertrain systems and the controller design are introduced. Based on models of typical hybrid electric system components principal optimization approaches with respect to performance parameters like efficiency, availability, lifetime, etc. are shown. Hereby an optimization algorithm based on a global optimization technique is applied. Using the example of a fuel cell based hybrid electric powertrain system the approaches are introduced and compared to each using time-domain simulations integrated in optimization algorithms. The results show that both approaches are appropriate to design the system as well as the controllers. (© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Enzymatic Synthesis of Organic‐Polymer‐Grafted DNA

To create bioorganic hybrid materials, interdisciplinary work in the fields of chemistry, biology and materials science is conducted. DNA block copolymers are promising hybrid materials due to the combination of properties intrinsic to both the polymer and the nucleic acid blocks. Until now, the coupling of DNA and organic polymers has been exercised post‐synthetically in solution or on solid support. Herein, we report the first enzyme‐catalysed synthesis of DNA–organic polymer chimeras. For this purpose, four novel 2′‐deoxyuridine triphosphates carrying polymer‐like moieties linked to the nucleobase were synthesised. Linear polyethylene glycol monomethyl ethers of different sizes ( 1 ) and branched polyamido dendrons with varying terminal groups ( 2 ) were chosen as building blocks. We investigated the ability of DNA polymerases to accept the copolymers in comparison to the natural substrate and showed, through primer extensions, polymerase chain reactions and rolling circle amplification, that these building blocks could serve as a surrogate for the natural thymidine. By this method, DNA hybrid materials with high molecular weight, modification density, and defined structure are accessible.