A DNA Methyltransferase Modulator Inspired by Peyssonenyne Natural Product Structures

A novel epigenetic modulator that displays a DNMT1 inhibition and DNMT3A activation profile was characterized (compound 8 ). This compound is a derivative of palmitic acid that incorporates the putative reactive functional group (diynone) of the peyssonenyne natural products. Other analogues containing the diynone or an acetoxyenediyne did not show the same biological profile. In U937 human leukemia cells, diynone 8 induced cell differentiation and apoptosis, which correlated with the expression of Fas protein. Very surprisingly, diynone 8 was toxic to normal human fibroblasts (BJ) and mouse embryo fibroblasts (MEF), but not to immortalized human fibroblasts (BJEL); this unique effect was not observed with the classical DNMT inhibitor 5‐azacytidine. Therefore, compound 8 interferes in a very specific manner with signaling pathways, the activities of which differ between normal and immortalized cell types. This toxicity is reminiscent of the effects of Dnmt1 ablation on mouse fibroblasts. In fact, some of the genes deregulated by the loss of Dnmt1 are similarly deregulated by 8 , but not by the DNMT inhibitor SGI‐1027.     

Die patentierten Erfindungen von Wolfgang Gaede aus der Zeit von 1905 bis 1945

The Patented Inventions from Wolfgang Gaede from 1905 to 1945 The collection of Gaede's patents shows how successfully cooperation between science and industry could bee. Several up to now important inventions in vacuum technique have been made and this in sometimes hard and difficult circumstances. Even when Gaede has lost his chair at the university of Karlsruhe from illegal intrigues by the Nazis.     

Towards an optimised lab procedure for long-term oxidative ageing of asphalt mix specimen

Ageing of bitumen leads to increased stiffness and brittleness. Thus, bituminous bound pavements become more prone to failure by low-temperature and fatigue cracking. Therefore, the ageing behaviour of bitumen has a crucial impact on durability, as well as recyclability of pavements. To assess ageing of bitumen, the rolling thin film oven test and pressure ageing vessel are standardised methods for short-term and long-term ageing in the lab. For lab-ageing of hot mix asphalt (HMA), various methods have been developed in the last decades. This paper presents a study on the potential of employing a highly oxidant gas for simulating the long-term oxidative ageing of asphalt mix specimens in the lab. Based on the results, an optimised lab-ageing procedure (Viennese Ageing Procedure – VAPro) for compacted HMA specimens to assess mix performance of long-term lab-aged specimens is developed. Thus, it is possible to optimise mix design not only for short-term performance but to take into account effects of oxidative ageing during its in-service life. VAPro is based on a triaxial cell with forced flow of a gaseous oxidant agent through the specimen. The oxidant agent is enriched in ozone and nitric oxides to increase the rate of oxidation. It is shown by stiffness tests of unaged and lab-aged specimens, as well as by Dynamic Shear Rheometer tests of recovered binder from aged specimens that asphalt mixes can be long-term aged at moderate temperatures (+60°C) and within 4 days and a flow rate of 1 l/min by applying VAPro. Thus, an ageing procedure is at hand that can simulate long-term ageing at conditions that are representative of conditions that occur in the field within an efficient amount of time.     

Thioether Analogues of Disulfide‐Bridged Cyclic Peptides Targeting Death Receptor 5: Conformational Analysis,Dimerisation and Consequences for Receptor Activation

Cyclic peptides containing redox‐stable thioether bridges might provide a useful alternative to disulfide‐bridged bioactive peptides. We report the effect of replacing the disulfide bridge with a lanthionine linkage in a 16‐mer cyclic peptide that binds to death receptor 5 (DR5, TRAIL‐R2). Upon covalent oligomerisation, the disulfide‐bridged peptide has previously shown similar behaviour to that of TNF‐related apoptosis inducing ligand (TRAIL), by selectively triggering the DR5 cell death pathway. The structural and biological properties of the DR5‐binding peptide and its desulfurised analogue were compared. Surface plasmon resonance (SPR) data suggest that these peptides bind DR5 with comparable affinities. The same holds true for dimeric versions of these peptides: the thioether is able to induce DR5‐mediated apoptosis of BJAB lymphoma and tumorigenic BJELR cells, albeit to a slightly lower extent compared to its disulfide homologue. NMR analysis revealed subtle variation in the conformations of the two peptides and suggests that the thioether peptide is slightly less folded than its disulfide homologue. These observations could account for the different capability of the two dimers to cluster DR5 receptors on the cell surface and to trigger apoptosis. Nevertheless, our results suggest that the thioether peptide is a potential candidate for evaluation in animal models.     

Multispace and multilevel BDDC

The Balancing Domain Decomposition by Constraints (BDDC) method is the most advanced method from the Balancing family of iterative substructuring methods for the solution of large systems of linear algebraic equations arising from discretization of elliptic boundary value problems. In the case of many substructures, solving the coarse problem exactly becomes a bottleneck. Since the coarse problem in BDDC has the same structure as the original problem, it is straightforward to apply the BDDC method recursively to solve the coarse problem only approximately. In this paper, we formulate a new family of abstract Multispace BDDC methods and give condition number bounds from the abstract additive Schwarz preconditioning theory. The Multilevel BDDC is then treated as a special case of the Multispace BDDC and abstract multilevel condition number bounds are given. The abstract bounds yield polylogarithmic condition number bounds for an arbitrary fixed number of levels and scalar elliptic problems discretized by finite elements in two and three spatial dimensions. Numerical experiments confirm the theory.     

Polynomial approximation of shape function gradients from element geometries

A method is presented for the polynomial approximation of shape function gradients based solely on the geometry of finite element boundaries. The method is founded on a least squares approach which leads to an integration scheme satisfying a necessary condition for convergence. In its simplest form the method reduces to the well‐known uniform strain approach for finite elements. The method is applicable to a broad class of problems such as connecting dissimilar meshes, mesh adaptivity and transitioning, and the construction of finite elements with variable topologies. Finite elements based on the polynomial approximations are shown to pass patch tests of various orders. In contrast to standard elements, higher‐order patch tests are passed without the need for nodes internal to element boundaries. Less sensitivity to volumetric locking under plane strain conditions is demonstrated through comparisons with a standard element formulation. Copyright © 2001 John Wiley & Sons, Ltd.     

Collection of soot particles into aqueous suspension using a particle-into-liquid sampler

Steam collection devices collecting aerosol particles into liquid samples are frequently used to analyze water-soluble particulate material. The fate of water-insoluble components is often neglected. In this work, we show that fresh soot particles can be suspended into pure water using a steam collection device, the particle-into-liquid sampler (PILS, Weber et?al. 2001). The overall collection efficiency of freshly generated soot particles was found to be on the order of 20%. This shows that, depending on the analytic technique employed, the presence of insoluble, and/or hydrophobic particles in liquid samples from steam collection cannot be neglected.

Copyright © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC