Development of low-loss lead-germanate glass for mid-infrared fiber optics: II. preform extrusion and fiber fabrication

For lead-germanate glass fibers, reducing the content of hydroxyl (OH) groups and the formation of metallic Pb species is essential to pave the way for their applications as low-loss mid-IR fiber optics since OH and metallic Pb species cause intense absorption and scattering loss, respectively, in the mid-IR spectral range. The first part of this study reported the optimization of the glass melting procedure to obtain low amount of OH while preventing formation of metallic Pb species in lead-germanate glass. Here, the second part of this study reports the investigation of the process conditions to fabricate low-loss lead-germanate glass fiber through further understanding of the co-effects of glass melting and heat treatment atmospheres on the formation of nano- and micron-scale metallic Pb species in both the as-produced and heat treated lead-germanate glasses. Finally, using this advance in knowledge, we successfully fabricated low-loss lead-germanate glass fibers with no presence of reduced metallic Pb particles by optimizing dehydration agent, glass melting, preform extrusion and fiber drawing conditions. The optimized fabrication conditions reduced the unstructured fiber loss by almost one order to <0.3 dB/m at 1.55 μm.     

α-Methylene-β-Lactone Scaffold for Developing Chemical Probes at the Two Ends of the Selectivity Spectrum

The utilities of an α-methylene-β-lactone (MeLac) moiety as a warhead composed of multiple electrophilic sites are reported. We demonstrate that a MeLac-alkyne not only reacts with diverse proteins as a broadly reactive measurement probe, but also recruits reduced endogenous glutathione (GSH) to assemble a selective chemical probe of GSH-β-lactone (GSH-Lac)-alkyne in live cells. Tandem mass spectrometry reveals that MeLac reacts with nucleophilic cysteine, serine, lysine, threonine, and tyrosine residues, through either Michael or acyl addition. A peptide-centric proteomics platform demonstrates that the proteomic selectivity profiles of orlistat and parthenolide, which have distinct reactivities, are measurable by MeLac-alkyne as a high-coverage probe. The GSH-Lac-alkyne selectively probes the glutathione S-transferase P responsible for multidrug resistance. The assembly of the GSH-Lac probe exemplifies a modular and scalable route to develop selective probes with different recognizing moieties.     

Production of Particle‐Stabilized Nonspherical Emulsion Drops in Simple Shear Flow

Nonspherical drops are of interest in the formation of microcapsules in life sciences like food, pharmacy, and cosmetics, agro and fine chemicals as well as material sciences. Out of many systems, particle‐stabilized emulsion drops, so‐called Pickering emulsions, exhibit an interesting formulation. Systems with Pickering particles applied in an excess amount were investigated. During deformation, the particles fully covered the enlarged drop interfaces and prevented its relaxation to a spherical drop shape. Nonspherical drops could be produced in simple shear flow using an adequate process routine. The production in a simple device is a promising high‐throughput alternative to microfluidic devices.     

Segmentation of Three-Dimensional Images with Parametric Active Surfaces and Topology Changes

In this paper, we introduce a novel parametric finite element method for segmentation of three-dimensional images. We consider a piecewise constant version of the Mumford–Shah and the Chan–Vese functionals and perform a region-based segmentation of 3D image data. An evolution law is derived from energy minimization problems which push the surfaces to the boundaries of 3D objects in the image. We propose a parametric scheme which describes the evolution of parametric surfaces. An efficient finite element scheme is proposed for a numerical approximation of the evolution equations. Since standard parametric methods cannot handle topology changes automatically, an efficient method is presented to detect, identify and perform changes in the topology of the surfaces. One main focus of this paper are the algorithmic details to handle topology changes like splitting and merging of surfaces and change of the genus of a surface. Different artificial images are studied to demonstrate the ability to detect the different types of topology changes. Finally, the parametric method is applied to segmentation of medical 3D images.     

Activation of the glmS Ribozyme Confers Bacterial Growth Inhibition

The ever‐growing number of pathogenic bacteria resistant to treatment with antibiotics call for the development of novel compounds with as‐yet unexplored modes of action. Here, we demonstrate the in vivo antibacterial activity of carba‐α‐d ‐glucosamine (CGlcN). In this mode of action study, we provide evidence that CGlcN‐mediated growth inhibition is due to glmS ribozyme activation, and we demonstrate that CGlcN hijacks an endogenous activation pathway, hence utilizing a prodrug mechanism. This is the first report describing antibacterial activity mediated by activating the self‐cleaving properties of a ribozyme. Our results open the path towards a compound class with an entirely novel and distinct molecular mechanism.     

Development of a method for the quantification of the molar gold concentration in tumour cells exposed to gold-containing drugs

The knowledge of the cellular molar concentration of a drug is an extremely important parameter for the discussion and interpretation of its efficacy and bioavailability. Concerning metal complexes, electrothermal atomic absorption spectroscopy (ETAAS) offers a valuable analytical tool. However, matrix effects often hamper proper quantification of the metal concentration in biological tissues. This paper describes the development of an ETAAS method for the quantification of the molar gold concentration in HT-29 colon carcinoma cells. ETAAS analytical conditions were optimised and a factor was developed which allows the calculation of the molar cellular gold concentration from the measured gold per cellular biomass value. The method was used to quantify the gold content in HT-29 cells after exposure to the gold drug auranofin. Results indicated a strong cellular uptake of auranofin (compared to other metal anticancer drugs), which significantly correlated with the antiproliferative effects triggered by this agent.     

Product Engineering am Beispiel extrudierter Instantpulver

Product Engineering in the Case of Extruded Instant Powders . Starch based instant powders are usually produced by cooking/gelatinizing in an excess of water with subsequent drying and milling. Important product attributes are the specific weight and the instant properties of the powder, as well as the taste, the viscosity, and the mouth-feel of the reconstituted gel. Cooking extrusion is an alternative energy saving process. Process development usually takes a long time and proves expensive due to the large number of different process parameters and their possible combinations. For two exemplary products it is demonstrated how the screw configuration and the target range of process parameters can be defined by statistical trial design. Final optimization (?fine tuning”?) and scale-up assure efficient process design according to product needs.     

Involvement of GPR17 in Neuronal Fibre Outgrowth

Characterization of new pharmacological targets is a promising approach in research of neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently been proposed as an interesting pharmacological target, e.g., in neuroregenerative processes. Using the well-established ex vivo model of organotypic slice co-cultures of the mesocortical dopaminergic system (prefrontal cortex (PFC) and substantia nigra/ventral tegmental area (SN/VTA) complex), the influence of GPR17 ligands on neurite outgrowth from SN/VTA to the PFC was investigated. The growth-promoting effects of Montelukast (MTK; GPR17- and cysteinyl-leukotriene receptor antagonist), the glial cell line-derived neurotrophic factor (GDNF) and of two potent, selective GPR17 agonists (PSB-16484 and PSB-16282) were characterized. Treatment with MTK resulted in a significant increase in mean neurite density, comparable with the effects of GDNF. The combination of MTK and GPR17 agonist PSB-16484 significantly inhibited neuronal growth. qPCR studies revealed an MTK-induced elevated mRNA-expression of genes relevant for neuronal growth. Immunofluorescence labelling showed a marked expression of GPR17 on NG2-positive glia. Western blot and RT-qPCR analysis of untreated cultures suggest a time-dependent, injury-induced stimulation of GPR17. In conclusion, MTK was identified as a stimulator of neurite fibre outgrowth, mediating its effects through GPR17, highlighting GPR17 as an interesting therapeutic target in neuronal regeneration.