IV. Referate

Ohne Zusammenfassung     

Referate

Ohne Zusammenfassung     

Referate

Ohne Zusammenfassung     

Referate

Ohne Zusammenfassung     

IV. Referate

Ohne Zusammenfassung     

Novel Furin Inhibitors with Potent Anti‐infectious Activity

New peptidomimetic furin inhibitors with unnatural amino acid residues in the P3 position were synthesized. The most potent compound 4‐guanidinomethyl‐phenylacteyl‐Arg‐Tle‐Arg‐4‐amidinobenzylamide (MI‐1148) inhibits furin with a K_i value of 5.5 pM . The derivatives also strongly inhibit PC1/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. A significant protective effect against anthrax and diphtheria toxin was observed in the presence of the furin inhibitors. Furthermore, the spread of the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of canine distemper virus was strongly inhibited. Inhibitor MI‐1148 was crystallized in complex with human furin. Its N‐terminal guanidinomethyl group in the para position of the P5 phenyl ring occupies the same position as that found previously for a structurally related inhibitor containing this substitution in the meta position, thereby maintaining all of the important P5 interactions. Our results confirm that the inhibition of furin is a promising strategy for a short‐term treatment of acute infectious diseases.     

Methoden zur Analyse des Bruchverhaltens hochfester Stahlfaserbetone

Methods for analyzing the fracture behavior of high‐strength steel fiber‐reinforced concretes High‐strength and ultra‐high strength fiber‐reinforced concretes are most suitable for applications with extreme mechanical loads. These extreme conditions require a ductile behavior under tensile loading, which is obtained solely by the addition of steel fibers and their working mechanism. Profound know ledge on the working mechanism of the steel fibers is necessary for optimizing this material. Usually, this knowledge is obtained by means of classical measuring techniques of destructive tests. Adopting measuring techniques from non‐destructive material testing helps to analyze and to identify the different stages of the fracture mechanism of high‐strength and ultra‐high strength fiber‐reinforced concretes in detail. The application of different non‐destructive measuring techniques is shown exemplary on tensile tests conducted on an ultra‐high strength fiber‐reinforced concrete and its applicability for analyzing the fracture behavior is discussed. The main focus is on the characterization of the relevant failure modes under tensile loading by the different measuring techniques and the comparison with classical measuring techniques (e. g. extensometer). The tensile tests have been analyzed by optical deformation measurements using digital image correlation (DIC), acoustic emission analysis (AE), and 3D computed tomography (CT).     

Combined exposure to cyanobacterial biomass, lead and the Newcastle virus enhances avian toxicity

Under environmental conditions, wild birds can be exposed to multiple stressors including natural toxins, anthropogenic pollutants and infectious agents at the same time.This experimental study was successful in testing the hypothesis that adverse effects of cyanotoxins, heavy metals and a non-pathogenic immunological challenge combine to enhance avian toxicity. Mortality occurred in combined exposures to naturally occurring cyanobacterial biomass and lead shots, lead shots and Newcastle vaccination as well as in single lead shot exposure. Mostly acute effects around day 10 were observed. On day 30 of exposure, there were no differences in the liver accumulation of lead in single and combined exposure groups. Interestingly, liver microcystin levels were elevated in birds co-exposed to cyanobacterial biomass together with lead or lead and the Newcastle virus. Significant differences in body weights between all Pb-exposed and Pb-non-exposed birds were found on days 10 and 20. Single exposure to cyanobacterial biomass resulted in hepatic vacuolar dystrophy, whereas co-exposure with lead led to more severe granular dystrophy. Haematological changes were associated with lead exposure, in particular. Biochemical analysis revealed a decrease in glucose and an increase in lactate dehydrogenase in single and combined cyanobacterial and lead exposures, which also showed a decreased antibody response to vaccination.The combined exposure of experimental birds to sub-lethal doses of individual stressors is ecologically realistic. It brings together new pieces of knowledge on avian health. In light of this study, investigators of wild bird die-offs should be circumspect when evaluating findings of low concentrations of contaminants that would not result in mortality on a separate basis. As such it has implications for wildlife biologists, veterinarians and conservationists of avian biodiversity.     

Aerobic Oxidative Coupling of o‐Xylene: Discovery of 2‐Fluoropyridine as a Ligand to Support Selective Pd‐Catalyzed C?H Functionalization

An improved method for the direct oxidative coupling of o‐xylene could provide streamlined access to an important monomer used in polyimide resins. The use of 2‐fluoropyridine as a ligand has been found to enable unprecedented levels of chemo‐ and regioselectivity in this palladium‐catalyzed aerobic oxidative coupling reaction. Preliminary insights have been obtained into the origin of the effectiveness of 2‐fluoropyridine as a ligand.