A Dual-Acting Nitric Oxide Donor and Phosphodiesterase 5 Inhibitor Activates Autophagy in Primary Skin Fibroblasts

Wound healing pathologies are an increasing problem in ageing societies. Chronic, non-healing wounds, which cause high morbidity and severely reduce the quality of life of affected individuals, are frequently observed in aged individuals and people suffering from diseases affected by the Western lifestyle, such as diabetes. Causal treatments that support proper wound healing are still scarce. Here, we performed expression proteomics to study the effects of the small molecule TOP-N53 on primary human skin fibroblasts and keratinocytes. TOP-N53 is a dual-acting nitric oxide donor and phosphodiesterase-5 inhibitor increasing cGMP levels to support proper wound healing. In contrast to keratinocytes, which did not exhibit global proteome alterations, TOP-N53 had profound effects on the proteome of skin fibroblasts. In fibroblasts, TOP-N53 activated the cytoprotective, lysosomal degradation pathway autophagy and induced the expression of the selective autophagy receptor p62/SQSTM1. Thus, activation of autophagy might in part be responsible for beneficial effects of TOP-N53.     

Investigation of liquid water in gas diffusion layers of polymer electrolyte fuel cells using X-ray tomographic microscopy

In polymer electrolyte fuel cells (PEFCs), condensation of water within the pore network of the gas diffusion layers (GDL) can influence the gas transport properties and thus reduce the electrochemical conversion rates. The use of X-ray tomographic microscopy (XTM), which allows for a resolution in the order of one micrometer is investigated for studying ex situ the local saturation in GDL's. The strength of XTM is the high spatial resolution with simultaneous contrast for water and carbon, allowing for non-destructive 3D-imaging of the solid and the contained water. The application of this method for imaging the ex situ water intrusion into the porous network of GDLs is explored using absorption and phase contrast methods. It is shown that the inhomogeneous filling behavior of GDL materials can indeed be visualized with sufficient resolution. For Toray paper TGP-H-060 the local saturation was measured as function of the water pressure. The results, evaluated in 1D, 2D and 3D show a liquid water retention effect at the denser layers near the surface. A comparison with established capillary pressure functions is presented. Altogether, the results show the potential of the XTM-method as a tool for studying the liquid water behavior in PEFC on a microscopic scale.     

Effect of the Proximity of Pt to Ce or Ba in Pt/Ba/CeO2 Catalysts on NO x Storage–Reduction Performance

The effect of Pt location in Pt/Ba/CeO₂ catalysts for NO _x storage–reduction (NSR) was analyzed. The Pt location on BaCO₃ or CeO₂ support was controlled by changing the angle (φ) between the two flame sprays producing these two components. As-prepared flame-made catalysts contain PtO _x which must be reduced during the fuel rich phase to become active for NO _x storage and reduction of NO _x . For Pt on BaCO₃ this process was significantly faster than for Pt on CeO₂. The increased reduction ability of Pt on Ba is reflected in the light off temperatures: for Pt on CeO₂ temperatures around 330 °C were needed to combust 20% of C₃H₆ in air while for Pt on BaCO₃ only 250 °C were required for the same conversion. The ability to control the location of Pt or other noble metals is, therefore, essential to optimize the catalysts for a given Pt/Ba/CeO₂ weight ratio. The best performance was observed when most of the Pt constituent was located near Ba-containing sites.     

Klinische Ethik als Partnerschaft �C oder wie eine ethische Leitlinie f��r den patientengerechten Einsatz von Ressourcen entwickelt und implementiert werden kann

Definition of the problem Recently, ethical guidelines for clinical practice have gained increased popularity, but in order to become useful they require more pioneer??s work. Clinical-ethical guidelines need to be based on a scientific foundation and their practicability must be improved. We present and put to discussion the initial steps of the METAP Project about the development and practical implementation of a clinical-ethical guideline dedicated to a fair resource-allocation at the bedside. Arguments With its methodological orientation, the project represents a guideline which is based on both research and consensus-building, undergoing systematic evaluation and modification. In addition to the guideline, the project comes with a manual (a tool kit) including a procedural instrument for making decisions supporting deliberative aspects. It focuses on issues of micro-allocation; furthermore, it provides empirical, ethical and legal basics for making fair treatment decisions that should help to prevent overtreatment, undertreatment or discrimination in patient care. We propose an Escalation Model with various instruments serving as problem solving strategies that correspond to the respective needs; these instruments include a pocket-summary (??Leporello??) with the most important facts; further reading material; normative and procedural recommendations; ward-specific strategies, and also the option of clinical ethics consultation. Conclusion Clinical partners have been actively involved in the developmental process from the beginning and contributed to the practical applicability, acceptance and a valid need-orientation of the whole tool kit. This partnership and the participatory approach seem to have helped METAP to gain a foothold in the clinic.     

Observations on the role of vitamin E in the toxicity of oxidized fats

Studies are reported on the relative effects of in vivo oxidation produced by diets devoid of vitamin E and the consumption of oxidized fat. Rats of the Sprague-Dawley strain were raised from weaning on a sucrose-casein diet containing minerals and vitamins in the required amounts, supplemented with 10% of safflower oil, menhaden oil, hydrogenated coconut oil or no fat. Animals of ca. 185 g of the group fed the 10% safflower oil were then switched for 4 weeks to safflower or menhaden oil-supplemented diets that were allowed to oxidize by exposing them to room temperature in the dark for 2–8 days. For comparison with effects of in vivo oxidation, animals were raised from weaning on similar fresh diets devoid of vitamin E. Consumption of oxidized fat was accompanied by loss of weight, effects on the size of the organs, changes in triglyceride levels and production of TBA-reacting substances in the tissues. There was no effect on the induced swelling of liver mitochondria or the susceptibility of erythrocytes to hemolysis in these animals. Growth was also suppressed in the animals fed the vitamin E-free diets, and in vivo oxidation in these animals produced marked effects on the membrane properties of erythrocytes and liver mitochondria.     

Direct synthesis of maghemite,magnetite and wustite nanoparticles by flame spray pyrolysis

Magnetic iron-oxide nanoparticles have been prepared by flame spray pyrolysis (FSP) under controlled atmosphere. This way controlled and direct flame synthesis of Fe₂O₃ (maghemite), Fe₃O₄ (magnetite) and FeO (wustite) particles is possible by a scalable process. The Fe oxidation state was controlled by varying the fuel to air ratio during combustion as well as by varying the valence state of the applied Fe precursor. The as-prepared materials were characterized by electron microscopy, nitrogen adsorption, X-ray diffraction and Raman spectroscopy. Magnetic properties were investigated with SQUID, which unravelled superparamagnetic behaviour for all materials and typical features for the corresponding crystal structures and particle sizes. Maximum magnetisation was achieved for a mixture of maghemite and magnetite.     

Decoding a temporal population code

Encoding of sensory events in internal states of the brain requires that this information can be decoded by other neural structures. The encoding of sensory events can involve both the spatial organization of neuronal activity and its temporal dynamics. Here we investigate the issue of decoding in the context of a recently proposed encoding scheme: the temporal population code. In this code, the geometric properties of visual stimuli become encoded into the temporal response characteristics of the summed activities of a population of cortical neurons. For its decoding, we evaluate a model based on the structure and dynamics of cortical microcircuits that is proposed for computations on continuous temporal streams: the liquid state machine. Employing the original proposal of the decoding network results in a moderate performance. Our analysis shows that the temporal mixing of subsequent stimuli results in a joint representation that compromises their classification. To overcome this problem, we investigate a number of initialization strategies. Whereas we observe that a deterministically initialized network results in the best performance, we find that in case the network is never reset, that is, it continuously processes the sequence of stimuli, the classification performance is greatly hampered by the mixing of information from past and present stimuli. We conclude that this problem of the mixing of temporally segregated information is not specific to this particular decoding model but relates to a general problem that any circuit that processes continuous streams of temporal information needs to solve. Furthermore, as both the encoding and decoding components of our network have been independently proposed as models of the cerebral cortex, our results suggest that the brain could solve the problem of temporal mixing by applying reset signals at stimulus onset, leading to a temporal segmentation of a continuous input stream.