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.     

Genetically Encoded Libraries of Constrained Peptides

Many therapeutic peptides can still be improved with respect to target specificity, target affinity, resistance to peptidases/proteases, physical stability, and capacity to pass through membranes required for oral delivery. Several modifications can improve the peptides’ properties, in particular those that impose (a) conformational constraint(s). Screening of constrained peptides and the identification of hits is greatly facilitated by the generation of genetically encoded libraries. Recent breakthrough bacterial, phage, and yeast display screening systems of ribosomally synthesized post-translationally constrained peptides, particularly those of lanthipeptides, are earning special attention. Here we provide an overview of display systems for constrained, genetically encoded peptides and indicate prospects of constrained peptide-displaying phage and bacterial systems as such in vivo.     

A novel technique for the preparation of secondary fatty amides

A technique for the synthesis of monosubstituted fatty amides at low temperature and ambient pressure was developed. This method involved the condensation of an amine with a triacylglycerol. The primary amine (ethyl,n-butyl,n-hexyl andn-octyl were tested) acted as reagent and solvent for the fatty substrates. No additional organic solvent or catalyst was added. Tallow, vegetable oils and fish oil all served well as substrates, as did pure tripalmitin. The rate of amidation was dependent upon temperature and the ratio of fat to amine. In a series of experiments conducted with tallow andn-butylamine at a fat:amine molar ratio of 1:16, amidation could be carried out at 20°C, producingn-butyltallowamide in 83% yield in 24 hr. When the fat:amine molar ratio was reduced to 1:8, and the temperature raised to 45°C, the amide yield was 87.6% in 24 hr. When the reaction was carried out at the boiling point ofn-butylamine (78°C) and at a fat:amine ratio of 1:8, the amide yield was 93.2% in 4 hr. The reaction progressed more rapidly with higher molecular weight amines. The identity and purity of the amides was assessed by thin-layer chromatography and confirmed by elemental analyses and infrared and C¹³ nuclear magnetic resonance spectroscopy.     

Fluidized Bed Air Drying: Experimental Study and Model Development

The presented study describes the processes and mechanisms of batch fluidized bed drying. The influencing factors of hot air drying are theoretically and experimentally examined, in order to present the relations between temperature and humidity profiles and all other drying parameters. A physical model is presented to facilitate the calculation of the drying processes under defined conditions. Three succeeding drying stages are therefore modeled. Mass and energy balances including all components taking part in the process are formulated. The model clarities the drying process under the assumption of pure heat transfer mechanisms. It does not contain adaptive parameters and takes into account an inactive bypass fraction of the fluidization and drying medium. The evaluation of the model was successful for two fluidized bed plants with nominal widths of 100 mm and 400 mm. The experiments showed sufficient accuracy and transferability of the model to equipment of application‐oriented dimensions.     

The influence of various reaction parameters on the performance of (α‐diimine)nickel(II) catalysts in ethylene oligomerization reactions

Modified (α‐diimine)nickel(II) catalysts are suitable for ethylene oligomerization reactions. Due to the mechanism (“chain running”), the formation of double‐bond isomers and branched olefins can be observed. The obtained oligomer mixtures show a Schulz–Flory distribution. Increasing ethylene pressure favors the selectivity of α‐olefin formation. The same effect can be observed when Lewis bases like thiophene or furane are added to the oligomerization reaction mixture. These results can be related to an interaction of the additives with the catalytic active species during the oligomerization process. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1356–1361, 2003     

Entwicklung und Erprobung eines Wäschersystems zur CO2‐Abreinigung aus Rauchgasen mithilfe alkalischer Reststoffe

An innovative, technical approach for the reduction of CO₂ emissions is presented that utilizes alkaline wastes to capture CO₂ from flue gases in stable mineral form. Comprehensive pilot‐scale experiments were conducted with the developed flue gas scrubbing system at a power plant site. By optimizing the process parameters gas flux, CO₂ partial pressure, circulation flux and suspension liquid‐to‐solid ratio, a CO₂ binding of 40 – 90 g kg^–1 waste could be reached and up to 25 % of the CO₂ could be captured. The new technique is economically advantageous especially when both alkaline waste and CO₂ are produced on site and when the carbonated products can be used as secondary resources.     

Investigation of the phase separation of PNIPAM using infrared spectroscopy together with multivariate data analysis

The use of vibrational spectroscopy to investigate complex structural changes in polymers yields chemically rich data, but interpretation can be challenging and subtle but meaningful spectral changes may be missed through visual inspection alone. Multivariate analysis is an efficient approach to gain an oversight of small but systematic spectral differences anywhere within the spectra, providing further insight into structural changes and associated transformation mechanisms. In this study, the novel analytical approach of infrared spectroscopy combined with principal component analysis and Gaussian peak fitting was used to investigate the structural changes in aqueous solutions of a polymer, using poly(N-isopropyl acrylamide) (PNIPAM) in the atactic form and with controlled tacticity as a model system. Subtle spectral changes associated with the dehydration and phase separation upon heating included peak shifts, an area ratio change of the amide I band to the amide II band and formation of a new peak in the amide I band were efficiently detected. Dehydration and phase separation of PNIPAM occurred in two temperature ranges, one for the atactic and one for isotactic rich part, both involving a complex re-organization of the hydrogen bonds and change of the hydration layer. The changes agreed with existing results from other techniques, and new insights were gained into the effect of controlled tacticity on phase transformation behaviour. The study demonstrates that infrared spectroscopy combined with the multivariate analytical method principal component analysis and Gaussian peak fitting is an efficient approach to probing structural change in polymers during heating. The simplicity of the presented approach could find excellent use in analysing and understanding the molecular environment of a range of stimuli-responsive polymers, for instance block or grafted types of polymers, as well as those with controlled tacticity.     

Ahp Cyclodepsipeptides: The Impact of the Ahp Residue on the “Canonical Inhibition” of S1 Serine Proteases

S1 serine proteases are by far the largest and most diverse family of proteases encoded in the human genome. Although recent decades have seen an enormous increase in our knowledge, the biological functions of most of these proteases remain to be elucidated. Chemical inhibitors have proven to be versatile tools for studying the functions of proteases, but this approach is hampered by the limited availability of inhibitor scaffold structures with the potential to allow rapid discovery of selective, noncovalent small‐molecule protease inhibitors. The natural product class of Ahp cyclodepsipeptides is an unusual class of small‐molecule canonical inhibitors; the incorporation of protease cleavage sequences into their molecular scaffolds enables the design of specific small‐molecule inhibitors that simultaneously target the S and S′ subsites of the protease through noncovalent mechanisms. Their synthesis is tedious, however, so in this study we have investigated the relevance of the Ahp moiety for achieving potent inhibition. We found that although the Ahp residue plays an important role in inhibition potency, appropriate replacement with β‐hydroxy amino acids results in structurally less complex derivatives that inhibit serine proteases in the low micromolar range.     

Iterative Antimicrobial Candidate Selection from Informed D‐/L‐Peptide Dimer Libraries

Growing resistance to antibiotics, as well as newly emerging pathogens, stimulate the investigation of antimicrobial peptides (AMPs) as therapeutic agents. Here, we report a new library design concept based on a stochastic distribution of natural AMP amino acid sequences onto half‐length synthetic peptides. For these compounds, a non‐natural motif of alternating D ‐ and L ‐backbone stereochemistry of the peptide chain predisposed for β‐helix formation was explored. Synthetic D ‐/L ‐peptides with permuted half‐length sequences were delineated from a full‐length starter sequence and covalently recombined to create two‐dimensional compound arrays for antibacterial screening. Using the natural AMP magainin as a seed sequence, we identified and iteratively optimized hit compounds showing high antimicrobial activity against Gram‐positive and Gram‐negative bacteria with low hemolytic activity. Cryo‐electron microscopy characterized the membrane‐associated mechanism of action of the new D ‐/L ‐peptide antibiotics.     

Dynamic modeling of CO2 absorption from coal-fired power plants into an aqueous monoethanolamine solution

Among carbon capture and storage (CCS), the post-combustion capture of carbon dioxide (CO₂) by means of chemical absorption is actually the most developed process. Steady state process simulation turned out as a powerful tool for the design of such CO₂ scrubbers. Besides steady state modeling, transient process simulations deliver valuable information on the dynamic behavior of the system. Dynamic interactions of the power plant with the CO₂ separation plant can be described by such models. Within this work a dynamic process simulation model of the absorption unit of a CO₂ separation plant was developed. For describing the chemical absorption of CO₂ into an aqueous monoethanolamine solution a rate based approach was used. All models were developed within the Aspen Custom Modeler^® simulation environment. Thermo physical properties as well as transport properties were taken from the electrolyte non-random-two-liquid model provided by the Aspen Properties^® database. Within this work two simulation cases are presented. In a first simulation the inlet temperature of the flue gas and the lean solvent into the absorber column was changed. The results were validated by using experimental data from the CO₂SEPPL test rig located at the Dürnrohr power station. In a second simulation the flue gas flow to the separation plant was increased. Due to the unavailability of experimental data a validation of the results from the second simulation could not be achieved.