The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection,Regeneration, and Failure

Oncostatin M (OSM), a member of the interleukin-6 family, functions as a major mediator of cardiomyocyte remodeling under pathological conditions. Its involvement in a variety of human cardiac diseases such as aortic stenosis, myocardial infarction, myocarditis, cardiac sarcoidosis, and various cardiomyopathies make the OSM receptor (OSMR) signaling cascades a promising therapeutic target. However, the development of pharmacological treatment strategies is highly challenging for many reasons. In mouse models of heart disease, OSM elicits opposing effects via activation of the type II receptor complex (OSMR/gp130). Short-term activation of OSMR/gp130 protects the heart after acute injury, whereas chronic activation promotes the development of heart failure. Furthermore, OSM has the ability to integrate signals from unrelated receptors that enhance fetal remodeling (dedifferentiation) of adult cardiomyocytes. Because OSM strongly stimulates the production and secretion of extracellular proteins, it is likely to exert systemic effects, which in turn, could influence cardiac remodeling. Compared with the mouse, the complexity of OSM signaling is even greater in humans because this cytokine also activates the type I leukemia inhibitory factor receptor complex (LIFR/gp130). In this article, we provide an overview of OSM-induced cardiomyocyte remodeling and discuss the consequences of OSMR/gp130 and LIFR/gp130 activation under acute and chronic conditions.     

Spatially Resolved Characterization of the Gas Propagator in Monolithic Structured Catalysts Using NMR Diffusiometry

Gas diffusivity measurements in opaque porous media were performed using nuclear magnetic resonance. An optimized pulsed‐field gradient stimulated echo method with free volume selection was used to investigate the propagator of thermally polarized methane gas within commercial monolithic catalyst supports. Since signal losses due to T₂ relaxation were minimized by using a short echo time, diffusion processes could be characterized by the measured propagator functions and effective diffusion coefficients were determined for a broad range of observation times and in different spatial directions. The study of this noninvasive characterization of gas diffusion found a clear effect of the monolith type and its pore size and coating on the effective gas diffusion coefficient and the apparent tortuosity for a given observation time.     

Spurenstoffabtrennung mit keramischen Nanofiltrationsmembranen als Rotationsscheibenfilter

Reducing micropollutant pollution of water bodies is an important objective of water management and an integral part of environmental policy. Ceramic nanofiltration membranes were developed as multichannel membranes of increased membrane area and rotating disk filters. The membranes developed show retention of over 80 % for PEG 400. The membranes are currently being tested for the separation of micropollutants from wastewater contaminated with pharmaceuticals. With the help of a downstream oxidative process, the trace substances remaining in the permeate are degraded.     

Multicomponent gas diffusion in nonuniform tubes

In many technical processes gas, multicomponent diffusion takes place in confinements that are rarely uniform in direction of their long axis (e.g., catalysts pores). Here, we show that in conical tubes multicomponent diffusion is hindered. This effect increases with ratio of inlet to outlet cone radius Λ, indifferent of the orientation of the tube. Based on the Maxwell–Stefan equations, predictive analytical solution for ideal multicomponent diffusion in slightly tapered ducts is developed. In two‐bulb diffusion experiments on a uniform tube, the results of Duncan and Toor (1962) were reproduced. Comparison of model and experiment shows that the solution presented here provides a reliable quantitative prediction of the temporal change of H₂, N₂, and CO₂‐concentration for both tube geometries, uniform and slightly conical. In the demonstrated case (Λ = 3.16), mass diffusion is 68% delayed. Thus, for gaseous diffusion in “real,” typically tapered pores the transport limitation is more serious than considered so far. © 2014 American Institute of Chemical Engineers AIChE J, 61: 1404–1412, 2015     

A Prediction Method of the Behavior of Adhesively Bonded Structures under Cyclic Shear Loading Based on a Characterization of the Viscous Aspects of the Adhesive in an Assembly

The capabilities of structural bonding are more and more used. Estimating the abilities of an adhesive to endure repetitive loadings and to keep stable its mechanical properties along service life is an essential point to analyze in order to conduct fatigue assessments. The aim of this study is to develop a predictive tool for describing the fatigue behavior of an adhesive in an assembly under cyclic loadings. The approach developed analyzes the influence of viscosity on the mechanical behavior of an adhesive in an assembly based on monotonic and creep test results. Thanks to the evaluation of viscous phenomena, it is possible to predict the cyclic response of the adhesive. The experimental approach uses a unique bonded joint designed to limit the stress concentrations and with a maximum stress state in the center of the adhesive. In this paper, following the strategy developed under monotonic loading, experimental results under cyclic loading are presented for different types of loading using several load ratios and amplitudes. These results underline that the evolution of viscous deformations depends on the loading type. Under shear loading and for a ductile structural adhesive, the experimental results are well described using a viscoelastic–viscoplastic constitutive model with nonlinear viscous parameters. This model makes it possible to analyze the influence of different parameters on the mechanical response of bonded joints under cyclic shear loadings.     

A cross‐cultural comparison of colour emotion for two‐colour combinations

Psychophysical experiments were conducted in the UK, Taiwan, France, Germany, Spain, Sweden, Argentina, and Iran to assess colour emotion for two‐colour combinations using semantic scales warm/cool, heavy/light, active/passive, and like/dislike. A total of 223 observers participated, each presented with 190 colour pairs as the stimuli, shown individually on a cathode ray tube display. The results show consistent responses across cultures only for warm/cool, heavy/light, and active/passive. The like/dislike scale, however, showed some differences between the observer groups, in particular between the Argentinian responses and those obtained from the other observers. Factor analysis reveals that the Argentinian observers preferred passive colour pairs to active ones more than the other observers. In addition to the cultural difference in like/dislike, the experimental results show some effects of gender, professional background (design vs. nondesign), and age. Female observers were found to prefer colour pairs with high‐lightness or low‐chroma values more than their male counterparts. Observers with a design background liked low‐chroma colour pairs or those containing colours of similar hue more than nondesign observers. Older observers liked colour pairs with high‐lightness or high‐chroma values more than young observers did. Based on the findings, a two‐level theory of colour emotion is proposed, in which warm/cool, heavy/light, and active/passive are identified as the reactive‐level responses and like/dislike the reflective‐level response. © 2010 Wiley Periodicals, Inc. Col Res Appl, 2012     

Interaction of 1-allyl-3-methyl-imidazolium chloride and carbon black and its influence on carbon black filled rubbers

The interactions of the ionic liquid 1-allyl-3-methyl-imidazolium chloride (AMIMCl) with different grades of carbon black have been investigated using rheological measurements, differential scanning calorimetry and Raman spectroscopy. We could prove strong attractive interactions of AMIMCl with the carbon black surface, which result, for example, in the formation of an AMIMCl–carbon black–bucky gel and in an increased glass transition temperature of the ionic liquid in the presence of carbon black. Raman spectroscopy revealed that the AMIMCl is preferably attached to the edges of graphitic crystals at the carbon black surface, which have the highest adsorption energies. A surface treatment of different grades of carbon black with AMIMCl led to significant changes of the mechanical and electrical properties of different rubber compounds filled with carbon black, which can be attributed to a decreased filler–polymer interaction and a local plasticising effect of the AMIMCl at the carbon black surface.     

Solution Structure and Dynamics of the Small Protein HVO_2922 from Haloferax volcanii

Past sequencing campaigns overlooked small proteins as they seemed to be irrelevant due to their small size. However, their occurrence is widespread, and there is growing evidence that these small proteins are in fact functionally very important in organisms found in all kingdoms of life. Within a global proteome analysis for small proteins of the archaeal model organism Haloferax volcanii, the HVO_2922 protein has been identified. It is differentially expressed in response to changes in iron and salt concentrations, thus suggesting that its expression is stress-regulated. The protein is conserved among Haloarchaea and contains an uncharacterized domain of unknown function (DUF1508, UPF0339 family protein). We elucidated the NMR solution structure, which shows that the isolated protein forms a symmetrical dimer. The dimerization is found to be concentration-dependent and essential for protein stability and most likely for its functionality, as mutagenesis at the dimer interface leads to a decrease in stability and protein aggregation.     

Click-Chemistry (CuAAC) Trimerization of an αvβ6 Integrin Targeting Ga-68-Peptide: Enhanced Contrast for in-Vivo PET Imaging of Human Lung Adenocarcinoma Xenografts

α_vβ₆ Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with α_vβ₆ integrin-dependent TGF-β dysregulation, such as fibrosis. We have designed a trimeric Ga-68-labeled TRAP conjugate of the α_vβ₆-specific cyclic pentapeptide SDM17 (cyclo[RGD-Chg-E]-CONH₂) to enhance α_vβ₆ integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17)₃ showed a 28-fold higher α_vβ₆ affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC₅₀ of 0.26 vs. 7.4 nM, respectively), a 13-fold higher IC₅₀-based selectivity over the related integrin α_vβ₈ (factors of 662 vs. 49), and a threefold higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments with H2009 tumor-bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17)₃ holds promise for improved clinical PET diagnostics of carcinomas and fibrosis.     

Effect of N3 modifications on the affinity of spin label ç for abasic sites in duplex DNA

Noncovalent site‐directed spin labeling (NC‐SDSL) of abasic sites in duplex DNAs with the spin label ç , a cytosine analogue, is a promising approach for spin‐labeling nucleic acids for EPR spectroscopy. In an attempt to increase the affinity of ç for abasic sites, several N3 derivatives were prepared, and their binding affinities were determined by EPR spectroscopy. Most of the N3 substituents had a detrimental effect on binding. The triazole‐linked polyethylene‐glycol derivative ( 12 a ) showed a 15‐fold decrease in affinity, whereas the binding affinities of ethyl azido ( 8 b ) and hydroxyl ( 8 c ) derivatives were five‐ to sixfold lower. The spin‐labeled nucleoside Ç showed only a twofold decrease, thus binding better than 8 c , even though it contains the larger 2′‐deoxyribose substituent at N3 instead of a 2‐hydroxyethyl group. N3 derivatives that contained the basic ethyl amino ( 9 ) or ethyl guanidino ( 10 ) substituents had both higher binding affinity and solubility, attributed to their cationic charge at neutral pH. Compounds 9 and 10 are promising candidates for NC‐SDSL of nucleic acids, for distance measurements by pulsed EPR spectroscopy.