Corrosion fatigue behavior of electron beam melted iron in simulated body fluid

Pure iron is very attractive as a biodegradable implant material due to its high biocompatibility. In combination with additive manufacturing, which facilitates great flexibility of the implant design, it is possible to selectively adjust the microstructure of the material in the process, thereby control the corrosion and fatigue behavior. In the present study, conventional hot-rolled (HR) pure iron is compared to pure iron manufactured by electron beam melting (EBM). The microstructure, the corrosion behavior and the fatigue properties were studied comprehensively. The investigated sample conditions showed significant differences in the microstructures that led to changes in corrosion and fatigue properties. The EBM iron showed significantly lower fatigue strength compared to the HR iron. These different fatigue responses were observed under purely mechanical loading as well as with superimposed corrosion influence and are summarized in a model that describes the underlying failure mechanisms

Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations

Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or the determination of an acceptable daily intake (ADI). To overcome this limitation, an in vitro/in silico method was established that predicts the risk of human DILI in relation to oral doses and blood concentrations. This method can be used to estimate DILI risk if the maximal blood concentration (Cmax) of the test compound is known. Moreover, an ADI can be estimated even for compounds without information on blood concentrations. To systematically optimize the in vitro system, two novel test performance metrics were introduced, the toxicity separation index (TSI) which quantifies how well a test differentiates between hepatotoxic and non-hepatotoxic compounds, and the toxicity estimation index (TEI) which measures how well hepatotoxic blood concentrations in vivo can be estimated. In vitro test performance was optimized for a training set of 28 compounds, based on TSI and TEI, demonstrating that (1) concentrations where cytotoxicity first becomes evident in vitro (EC10) yielded better metrics than higher toxicity thresholds (EC50); (2) compound incubation for 48 h was better than 24 h, with no further improvement of TSI after 7 days incubation; (3) metrics were moderately improved by adding gene expression to the test battery; (4) evaluation of pharmacokinetic parameters demonstrated that total blood compound concentrations and the 95%-population-based percentile of Cmax were best suited to estimate human toxicity. With a support vector machine-based classifier, using EC10 and Cmax as variables, the cross-validated sensitivity, specificity and accuracy for hepatotoxicity prediction were 100, 88 and 93%, respectively. Concentrations in the culture medium allowed extrapolation to blood concentrations in vivo that are associated with a specific probability of hepatotoxicity and the corresponding oral doses were obtained by reverse modeling. Application of this in vitro/in silico method to the rat hepatotoxicant pulegone resulted in an ADI that was similar to values previously established based on animal experiments. In conclusion, the proposed method links oral doses and blood concentrations of test compounds to the probability of hepatotoxicity

Steuerung der Beitragspolitik im Sportverein

Wicker P, Breuer C, Ebbert S. Steuerung der Beitragspolitik im Sportverein. In: Braun S, Hansen S, eds. Steuerung im organisierten Sport. Jahrestagung der dvs-Sektion Sportsoziologie vom 25. - 27. September 2006 in Paderborn . Schriften der Deutschen Vereinigung für Sportwissenschaft. Vol 170. Hamburg: Czwalina; 2008: 207-216

Resolution of minor size differences in a family of heteroleptic coordination cages by trapped ion mobility ESI-MS

We report a complex system of heteroleptic coordination cages based on the combination of four bismonodentate ligands whose backbones only slightly differ in shape and length. cis-[Pd2L2L’2] assemblies cleanly form after addition of PdII cations to a 1 : 1 mixture of two shape-complementary ligands, each. When three or even all four ligands are used in combination, the unambiguous discrimination of all individual species in the product mixture becomes difficult by conventional NMR spectroscopic and mass spectrometric methods. Due to steric constraints, the system is restricted to the formation of ten different coordination cages in total, two of which are isomeric. We show that high-resolution trapped ion mobility mass spectrometry (TIMS) allows the clear differentiation of all ten species. Observed size trends could be readily reproduced by the calculation of theoretical values for collisional cross sections (CCS) from geometry-optimized models

Endohedrally Functionalized Heteroleptic Coordination Cages for Phosphate Ester Binding

Metallosupramolecular hosts of nanoscopic dimensions, which are able to serve as selective receptors and catalysts, are usually composed of only one type of organic ligand, restricting diversity in terms of cavity shape and functional group decoration. We report a series of heteroleptic [Pd$_2$A$_2$B$_2$] coordination cages that self-assemble from a library of shape complementary bis-monodentate ligands in a non-statistical fashion. Ligands A feature an inward pointing NH function, able to engage in hydrogen bonding and amenable to being functionalized with amide and alkyl substituents. Ligands B comprise tricyclic aromatic backbones of different shape and electronic situation. The obtained heteroleptic coordination cages were investigated for their ability to bind phosphate diesters as guests. All-atom molecular dynamics (MD) simulations in explicit solvent were conducted to understand the mechanistic relationships behind the experimentally determined guest affinities