Airway Delivery of Hydrogel-Encapsulated Niclosamide for the Treatment of Inflammatory Airway Disease

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl⁻ currents and intracellular Ca²⁺ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca²⁺ activated Cl⁻ channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca²⁺ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.     

Fast start-up of a diesel fuel processor for PEM fuel cells

Fuel cell systems based on liquid fuels are particularly suitable for auxiliary power generation due to the high energy density of the fuel and its easy storage. Together with industrial partners, Oel-Waerme-Institut is developing a 3 kW_el PEM fuel cell system based on diesel steam reforming to be applied as an APU for caravans and yachts. The start-up time of a fuel cell APU is of crucial importance since a buffer battery has to supply electric power until the system is ready to take over. Therefore, the start-up time directly affects the battery capacity and consequently the system size, weight, and cost.     

Produktschonende Betriebs‐ und Designparameter von Wärmeübertragern für temperaturempfindliche Prozessströme

To allow the calculation of product degradation rates as extension to the currently used thermotechnical design calculations for heat exchangers, a volume‐related, reaction‐kinetic approach was developed. Therefore, a model system was selected and the product protection design parameters were determined for a lab‐scale heat exchanger with the help of simulations. The validation was demonstrated in an experiment. Additionally, the product‐protecting operating parameters for the heat exchanger were calculated with a technically relevant set of compounds.     

Indikatorenbasierte Evaluierung von Fischhabitaten in alpinen Fließgewässern

The EU Water Framework Directive commits member states to achieve good ecological status in all waterbodies. Artificial or heavily modified waterbodies must reach at least its good ecological potential. In view of these requirements, simple and feasible methods are required in order to evaluate habitat suitability for relevant target species in larger river reaches. Well-developed models for determining the relationship between stream flows and habitat for target species mainly based on micro- and meso-scale already exist. However, the application of such models is complex and time-consuming and consequently limited to relatively short river segments. The objective of this study is to develop a simplified applicable assessment model to evaluate habitat conditions for selected target fish. This model uses hydro-morphological indicators for the habitat assessment and relies on correlative relations between habitat suitability and hydro-morphological features of river stretches (average Froude-number, relative flow width, mean bed slope, relative water depth and flow velocity). The indicators were determined as reach-related averages, derived from 2D model simulations (hydraulic and habitat-specific). Particular emphasis was laid on using a wide range of river stretches with different hydro-morphological characteristics (hydrology, bed substratum, bed structures, degree of braiding, sinuosity of the river course, mean bed width and bed slope). As a result, a set of model equations enables the evaluation of fish habitat conditions in river stretches as a function of flow and morphology. The habitat suitability assessment focuses on four preselected target species: brown trout, European grayling and for low slope rivers common nase and barbel.     

W-Hierarchies Defined by Symmetric Gates

The classes of the W-hierarchy are the most important classes of intractable problems in parameterized complexity. These classes were originally defined via the weighted satisfiability problem for Boolean circuits. Here, besides the Boolean connectives we consider connectives such as majority, not-all-equal, and unique. For example, a gate labelled by the majority connective outputs true if more than half of its inputs are true. For any finite set C\mathcal{C} of connectives we construct the corresponding W( C\mathcal{C} )-hierarchy. We derive some general conditions which guarantee that the W-hierarchy and the W( C\mathcal{C} )-hierarchy coincide levelwise. If C\mathcal{C} only contains the majority connective then the first levels of the hierarchies coincide. We use this to show that a variant of the parameterized vertex cover problem, the majority vertex cover problem, is W[1]-complete.     

Coal lumps vs. electrons: How do Chinese bulk energy transport decisions affect the global steam coal market?

This paper demonstrates the ways in which different Chinese bulk energy transport strategies affect the future steam coal market in China and in the rest of the world. An increase in Chinese demand for steam coal will lead to a growing need for additional domestic infrastructure as production hubs and demand centers are spatially separated, and domestic transport costs could influence the future Chinese steam coal supply mix. If domestic transport capacity is available only at elevated costs, Chinese power generators could turn to the global trade markets and further increase steam coal imports. Increased Chinese imports could then yield significant changes in steam coal market economics on a global scale. This effect is analyzed in China, where coal is mainly transported by railway, and in another setting where coal energy is transported as electricity. For this purpose, a spatial equilibrium model for the global steam coal market has been developed. One major finding is that if coal is converted into electricity early in the supply chain, worldwide marginal costs of supply are lower than if coal is transported via railway. Furthermore, China's dependence on international imports is significantly reduced in this context. Allocation of welfare changes particularly in favor of Chinese consumers while rents of international producers decrease.     

The role of classroom quality in ameliorating the academic and social risks associated with difficult temperament.

The present study examines the moderating role first grade classroom quality may have on the relations between children's difficult temperament (assessed in infancy) and their academic and social outcomes in early elementary school (first grade). Using data from the National Institute of Child Health and Human Development's Study of Early Child Care and Youth Development, 1032 children were rated by their mothers at 6 months of age on difficult temperament. The quality of first grade classroom environments were then observed and rated along three domains: emotional support, classroom organization, and instructional support. Regression analyses examined the statistical interactions between difficult temperament and classroom quality domains on children's academic and social outcomes. Results indicate high-quality classroom environments may ameliorate the academic and social risks associated with having a difficult temperament. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

A superoxide sensor based on a multilayer cytochrome c electrode

A novel multilayer cytochrome c electrode for the quantification of superoxide radical concentrations is introduced. The electrode consists of alternating layers of cytochrome c and poly(aniline(sulfonic acid)) on a gold wire electrode. The formation of multilayer structures was proven by SPR experiments. Assemblies with 2-15 protein layers showed electrochemical communication with the gold electrode. For every additional layer, a substantial increase in electrochemically active cytochrome c (cyt. c) was found. For electrodes of more than 10 layers, the increase was more than 1 order of magnitude as compared to monolayer electrode systems. Thermodynamic and kinetic parameters of the electrodes were characterized. The mechanism of electron transfer within the multilayer assembly was studied, with results suggesting a protein-protein electron-transfer model. Electrodes of 2-15 layers were applied to the in vitro quantification of enzymatically generated superoxide, showing superior sensitivity as compared to a monolayer-based sensor. An electrode with 6 cyt. c/PASA layers showed the highest sensitivity of the systems studied, giving an increase in sensitivity of half an order of magnitude versus the that of the monolayer electrode. The stability of the system was optimized using thermal treatment, resulting in no loss in sensor signal or protein loading after 10 successive measurements or 2 days of storage.