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.     

A Review on Metal‐Free Doped Carbon Materials Used as Oxygen Reduction Catalysts in Solid Electrolyte Proton Exchange Fuel Cells

Within the last decade, metal‐free heteroatom doped carbon nanomaterials have gained attention as effective electrocatalysts for the oxygen reduction reaction (ORR) in many electrochemical systems. Since then, reports have stated that the ORR catalytic activity, onset potential, and H₂O production selectivity of these materials is similar to that of platinum‐based catalysts. These statements rely on cyclic voltammetry (CV) and rotating disc electrode (RDE) measurements in liquid alkaline electrolyte. However, fuel cell researchers aim to replace the costly platinum catalysts in the more prominent acidic solid electrolyte proton exchange fuel cell (PEFC). In this respect, there are only a few reports of unpromising activity, stability, and H₂O production selectivity. In addition, only few reports have been presented on the implementation of such materials in cathode catalyst layers of actual PEFC devices. This mini‐review aims to summarize and evaluate results of these reports. Material synthesis, cell power, open circuit voltage, stability properties, and proposed active sites are reviewed. To date, the highest reported PEFC power densities with guaranteed metal‐free heteroatom doped carbon cathode catalysts have reached up to 321 mW cm⁻²; which although a promising value is substantially short of values obtained for platinum based catalysts.     

Efficiency improvement of dye-sensitized solar cells based on electrodeposited TiO2 films by low temperature post-treatment

Porous crystalline TiO₂ films can be prepared at low temperatures (80 °C) by surfactant-assisted electrodeposition from TiCl₃ solution. Nevertheless, up to now calcination at high temperatures (typically 450 °C) was still necessary to establish a good performance of these films in dye-sensitized solar cells (DSSC). With this study we report that water vapour treatment at much lower temperatures (150 °C) for 1 week improves the performance of the films in DSSC to the same degree as calcination although the overall crystallinity remains lower. Reason for the good efficiency is that the porous structure stays intact and thus the dye molecules can be better adsorbed. Avoiding high temperatures during the preparation process of TiO₂ films for the application in DSSC enables the use of polymer substrates for the fabrication of flexible solar cells.     

Fabrication of CdSe‐Nanofibers with Potential for Biomedical Applications

The design and synthesis of nanostructured functional hybrid biomaterials are essential for the next generation of advanced diagnostics and the treatment of disease. A simple route to fabricate semiconductor nanofibers by self‐assembled, elastin‐like polymer (ELP)‐templated semiconductor nanoparticles is reported. Core–shell nanostructures of CdSe nanoparticles with a shell of ELPs are used as building blocks to fabricate functional one‐dimensional (1D) nanostructures. The CdSe particles are generated in situ within the ELP matrix at room temperature. The ELP controls the size and the size‐distribution of the CdSe nanoparticles in an aqueous medium and simultaneously directs the self‐assembly of core–shell building blocks into fibril architectures. It was found that the self‐assembly of core–shell building blocks into nanofibers is strongly dependent on the pH value of the medium. Results of cytotoxicity and antiproliferation of the CdSe‐ELP nanofibers demonstrate that the CdSe‐ELP does not exhibit any toxicity towards B14 cells. Moreover, these are found to be markedly capable of crossing the cell membrane of B14. In contrast, unmodified CdSe nanoparticles with ELPs cause a strong toxic response and reduction in the cell proliferation. This concept is valid for the fabrication of a variety of metallic and semiconductor 1D‐architectures. Therefore, it is believed that these could be used not only for biomedical purposes but for application in a wide range of advanced miniaturized devices.     

The Yin and Yang of VEGF and PEDF: Multifaceted Neurotrophic Factors and Their Potential in the Treatment of Parkinson's Disease

Over the last few decades, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) have emerged as multifaceted players in not only the pathogenesis, but potential treatment, of numerous diseases. They activate diverse intracellular signaling cascades known to have extensive crosstalk, and have been best studied for their effects in cardiology and cancer biology. Recent work with the two factors indicates that the activity of one growth factor is often directly related to the action of the other. Their respective neuroprotective effects, in particular, raise important questions regarding the treatment of neurodegenerative disorders, including Parkinson's disease.     

Moving Bed Heat Exchangers for Use With Heat Storage in Concentrating Solar Plants: A Multiphase Model

Heat storage based on particulate materials is a promising option to provide a demand-oriented electricity production with utility-scale solar power plants. For energy storage discharge, a moving bed heat exchanger is considered and its design is investigated. As a basis for a flexible design tool, a multiphase model based on the Eulerian continuum approach was set up to describe the bulk flow and the thermal performance. The model was applied to an example heat exchanger layout, and the simulation results were compared with an empirical model, confirming the validity of the approach. Initial parameter variations identify the key parameters and their effect on the thermal performance.     

Dietary and host-related factors influencing carotenoid bioaccessibility from spinach (Spinacia oleracea)

Several dietary and host related factors potentially influencing carotenoid (beta-carotene, lutein and zeaxanthin) bioaccessibility from spinach, including different concentrations of sodium, calcium and magnesium, were systematically investigated by means of an in vitro digestion model. Bioaccessibility was highest when milk (4% fat) and lowest when skimmed milk or more complex food matrices such as sausage were added to the meal. Micellarisation significantly depended on the presence and concentration of bile salts and pancreatin (p < 0.001, Bonferroni) but was unaffected by pepsin. Micellarisation significantly decreased to 61.4 ± 3.0% of control (p < 0.001, Dunnett’s) at high cholesterol (114 mg/test meal) but not at similar stigmasterol concentrations. Calcium and magnesium ?13.8 mM individually inhibited micelle formation ( >40% on average), presumably due to the generation of insoluble soaps with fatty acids and bile salts. Increased sodium concentrations (280 and 460 mM) altered carotenoid micellarisation patterns, favoring beta-carotene isomers (p < 0.001, Bonferroni) but decreasing lutein and zeaxanthin (p < 0.001 and p < 0.05, respectively, Bonferroni). This study suggests that minerals may impact carotenoid bioavailability.     

Dynamic Min-Max Problems

In this paper a method to check the solvability of a set of linear equations in the (max, min, +) algebra is described. Then, extensions to dynamic (or periodic) systems in the (max, min, +) algebra are provided. Further, some results regarding the uniqueness of solutions in both cases are given. Finally, we address a more general quasi periodic problem and provide an algorithm for its solution.