Publikationen

A supersaturated single-phase Cu–26 at.% Co alloy was produced by high-pressure torsion deformation, leading to a nanocrystalline microstructure with a grain size smaller than 100 nm. The nonequilibrium solid solution decomposed during subsequent isothermal annealing. In situ high-energy X-ray diffraction was used to map changes linked to the separating phases, and the development of a nanoscale Cu–Co composite structure was observed. To gain further information about the relationship of the microstructure and the mechanical properties after phase separation, uniaxial tensile tests were conducted on as-deformed and isothermally annealed samples. Based on the in situ diffraction data, different isothermal annealing temperatures were chosen. Miniaturized tensile specimens with a round cross section were tested, and an image-based data evaluation method enabled the evaluation of true stress–strain curves and strain hardening behavior. The main results are as follows: all microstructural states showed high strength and ductility, which was achieved by a combination of strain-hardening and strain-rate hardening.

The dynamics of processes of nanoparticles such as diffusion, attraction and repulsion, and self-assembly of structures of nanoparticles at the solid-liquid interfaces differ significantly from those occurring for bulk conditions and their fundamental physical rules are still unknown. Here, we used liquid phase scanning transmission electron microscopy (LP-STEM) to study several aspects of nanoparticle dynamics of colloidal chitosan coated gold nanoparticle (TCHIT-AuNP) clusters in a liquid layer enclosed between two SiN membranes. We found that upon beam irradiation using an electron flux of 0.9 e−/sÅ2, the AuNPs assembled in clusters that shifted and rotated with time. The newly formed clusters could join and form larger clusters via a mechanism of oriented attachment. By increasing the electron flux to 6.2 e−/sÅ2, we observed the fragmentation of some of the clusters and TCHIT-AuNPs were exchanged between clusters. At the highest electron flux studied 25 e−/sÅ2, we observed AuNPs moving at a very slow speed compared to Brownian motion in liquid even though they were not permanently attached or pinned to the liquid-enclosing membrane. Experiments using branched polyethylenimine (BPEI) coated AuNPs were carried out for comparison.

This work presents the design and implementation of a reusable-tapered optical fiber sensor (RFS). We used the RFS together with a white light source to analyze the metastability of gold nanoparticles. With the RFS we observed that reaction limited aggregation occurred when modifying the concentration of metastable gold nanoparticles (MAuNPs). This was detected by a red-shift and a broadening of the absorption band. The transition from a metastable to a stable state, regardless of the concentration of the MAuNPs, was achieved by the addition of glucose. The changes in the refractive index of the solution due to the presence of glucose and the stability of the MAuNPs were successfully detected by the RFS. Diffusion limited aggregation of the MAuNPs was rapidly triggered after the addition of insulin. Finally, to gain a better understanding of our results we used Raman spectroscopy together with a hollow core photonic crystal optical fiber (HC-PCF) and studied the chemical interactions between the MAuNPs and glucose and between the MAuNPs and insulin.

Abstract In this study, we introduce the mouse dorsal skinfold chamber model as a valuable approach for the in vivo evaluation of topical formulations. For this purpose, dorsal skinfold chambers were implanted into BALB/c mice. Tumor necrosis factor (TNF)-α was administered to the chamber tissue for the local induction of inflammation followed by the application of diclofenac-containing or diclofenac-free (control) gel onto the skin of the chamber backside. Intravital fluorescence microscopy was repetitively performed throughout an observation period of 24 hours to study macromolecular leakage, leucocyte-endothelial cell interactions and microhaemodynamic parameters. In addition, infiltration of the inflamed tissue with different immune cell subtypes was assessed by immunohistochemistry. In a second set of experiments, the effect of dermal application of a diclofenac-containing gel on photochemically induced thrombus formation was analysed. It was observed that macromolecular leakage, numbers of adherent leucocytes and tissue infiltrating myeloperoxidase (MPO)-positive neutrophilic granulocytes and CD68-positive macrophages were significantly reduced in dorsal skinfold chambers treated with diclofenac-containing gel when compared to controls. Moreover, the diclofenac-containing gel exerted an anti-thrombotic activity, as indicated by a significantly prolonged complete vessel occlusion time. These findings demonstrate that the mouse dorsal skinfold chamber represents a valid and versatile tool to evaluate the effects of topical formulations in vivo.

About 20% of breast cancer tumors over-express the HER2 receptor. Trastuzumab, an approved drug to treat this type of breast cancer, is a monoclonal antibody directly binding at the HER2 receptor and ultimately inhibiting cancer cell growth. The goal of our study was to understand the early impact of trastuzumab on HER2 internalization and recycling in the HER2-overexpressing breast cancer cell line SKBR3. To this end, fluorescence microscopy, monitoring the amount of HER2 expression in the plasma membrane, was combined with mathematical modeling to derive the flux of HER2 receptors from and to the membrane. We constructed a dynamic multi-compartment model based on ordinary differential equations. To account for cancer cell heterogeneity, a first, dynamic model was expanded to a second model including two distinct cell phenotypes, with implications for different conformational states of HER2, i.e. monomeric or homodimeric. Our mathematical model shows that the hypothesis of fast constitutive HER2 recycling back to the plasma membrane does not match the experimental data. It conclusively describes the experimental observation that trastuzumab induces sustained receptor internalization in cells with membrane ruffles. It is also concluded that for rare, non-ruffled (flat) cells, HER2 internalization occurs three orders of magnitude slower than for the bulk, ruffled cell population.

Reusable catalysts based on earth-abundant metals with a broad applicability in organic synthesis are a key to a more sustainable production of fine chemicals, pharmaceuticals and agrochemicals. Herein, we report on a nanostructured nickel catalyst for the general and selective synthesis of primary amines via reductive amination, employing ammonia dissolved in water. Our catalyst, which operates at low temperature and pressure, is highly active, reusable and easy to handle. The synthesis from a specific nickel complex and γ-Al2O3 is straightforward, with the ligand–metal combination of this complex being crucial. Aldehydes (including purely aliphatic ones), aryl–alkyl, dialkyl and diaryl ketones can all be converted smoothly into primary amines. In addition, the amination of pharmaceuticals, bioactive compounds and natural products is demonstrated. Many functional groups—including hydrogenation-sensitive examples—are tolerated. We expect that our findings will inspire others to develop reusable and nanostructured earth-abundant metal catalysts for complex organic transformations.