Entwicklung eines Transformationsmodells – Modularisierung schrittweise gedacht

For some years now, the process industry has been meeting the challenges of the markets with modular production and logistics concepts. This article presents this development process in the form of a four-stage transformation model. It is shown that the path towards modular production environments can be taken step by step. The motto is “evolution instead of revolution”. First, an overview of the state of the art of modularized production and logistics systems is given. Based on this, the article describes and classifies the four different stages of modularization.     

Antimicrobial Potential of Chiral Amide Derivatives of Ricinoleic and 3-Hydroxynonanoic Acid

The growing role of fatty acid amides in medicinal chemistry has recently been observed. Therefore, using simple and fast methods, a series of chiral amide derivatives (24 compounds) of ricinoleic and 3-hydroxynonanoic acid was obtained with 31–95% yields. Then, the evaluation of their antimicrobial activity against 13 microorganisms representing Gram-positive and Gram-negative bacteria, yeast, and molds was performed. The obtained compounds showed antimold potential; however, the tested species of molds were more susceptible to derivatives of 3-hydroxynonanoic acid than to amides obtained from ricinoleic acid (RA). Interestingly, hydroxamic acids derived from RA exhibited the best activity against Candida albicans and Candida tropicalis. On the other hand, hydroxamic acids derived from 3-hydroxynonanoic acid showed the best antimicrobial potential against the remaining tested microorganisms, especially against Pseudomonas cedrina. The obtained derivatives can be considered compounds of potential pharmacological significance, which is important due to the increasing problem of microbial resistance.     

Morphology of polymer blends in the melting section of co‐rotating twin screw extruders

The properties of polymer blends are largely determined by the morphological structure of the polymer combinations that are involved. In terms of extruder design, this means it is necessary to have models available for estimating the development of the morphology over the length of the screws. Since significant morphological changes are observed in the melting section, in particular, is it necessary to analyze not only the plasticizing process for binary material combinations but also the initial formation and further development of the morphology in this section of the extruder. In the framework of this study, experimental investigations were conducted into polypropylene/polyamide 6 (PP/PA6) blends with small components (by weight) of the disperse PA phase. Apart from varying the process conditions of screw speed and throughput, the viscosity ratio was also varied through the use of two different PP grades. The degree of melting and the development of the morphology over the length of the screws were determined for the individual tests. The study of blend morphology in the melting section reveals key findings that must be taken into account for modeling the initial formation and further development of the morphology. It is very clear that, on the second component, which melts at higher temperatures, a kind of melt film removal occurs at the surface of the granules as they melt. The drops of second component in the melting section, which are directly adjacent to components that have not yet fully melted in some cases, have already assumed dimensions (in the μm range) similar to those that are seen at the end of the extrusion process. This means that, in the melting section of the twin‐screw extruder, no volumes become detached from or are worn off the already‐molten granule surfaces. An evaluation of scanning electron micrographs also shows that, in the melting section of co‐rotating twin‐screw extruders, virtually all the degradation mechanisms that can essentially be distinguished, such as quasi‐steady drop breakup, folding, end pinching and decomposition through capillary instabilities, take place in parallel.     

Influence of the Multivalency of Ultrashort Arg‐Trp‐Based Antimicrobial Peptides (AMP) on Their Antibacterial Activity

Peptide dendrimers are a class of molecules of high interest in the search for new antibiotics. We used microwave‐assisted, copper(I)‐catalyzed alkyne–azide cycloaddition (CuAAC; “click” chemistry) for the simple and versatile synthesis of a new class of multivalent antimicrobial peptides (AMPs) containing solely arginine and tryptophan residues. To investigate the influence of multivalency on antibacterial activity, short solid‐phase‐ synthesized azide‐modified Arg‐Trp‐containing peptides were “clicked” to three different alkyne‐modified benzene scaffolds to access scaffolds with one, two, or three peptides. The antibacterial activity of 15 new AMPs was investigated by minimal inhibitory concentration (MIC) assays on five different bacterial strains, including a multidrug‐resistant Staphylococcus aureus (MRSA) strain. With ultrashort (2–3 residues) peptides, a clear synergistic effect of the trivalent display was observed, whereas this effect was not apparent with longer peptides. The best candidates showed activities in the low‐micromolar range against Gram‐positive MRSA. Surprisingly, the best activity against Gram‐negative Acinetobacter baumannii was observed with an ultrashort dipeptide on the trivalent scaffold (MIC: 7.5 μM ). The hemolytic activity was explored for the three most active peptides. At concentrations ten times the MIC values, <1 % hemolysis of red blood cells was observed.     

Synthesis and Biopharmaceutical Evaluation of Imatinib Analogues Featuring Unusual Structural Motifs

A convenient synthesis of imatinib, a potent inhibitor of ABL1 kinase and widely prescribed drug for the treatment of a variety of leukemias, was devised and applied to the construction of a series of novel imatinib analogues featuring a number of non‐aromatic structural motifs in place of the parent molecule's phenyl moiety. These analogues were subsequently evaluated for their biopharmaceutical properties (e.g., ABL1 kinase inhibitory activity, cytotoxicity). The bicyclo[1.1.1]pentane‐ and cubane‐containing analogues were found to possess higher themodynamic solubility, whereas cubane‐ and cyclohexyl‐containing analogues exhibited the highest inhibitory activity against ABL1 kinase and the most potent cytotoxicity values against cancer cell lines K562 and SUP‐B15. Molecular modeling was employed to rationalize the weak activity of the compounds against ABL1 kinase, and it is likely that the observed cytotoxicity of these agents arises through off‐target effects.     

Characterization of products from fast and isothermal hydrothermal liquefaction of microalgae

We investigated nonisothermal (fast) and nominally isothermal hydrothermal liquefaction (HTL) of Nannochloropsis sp. microalgae for the production of biocrude. Biocrude yields ranged from 36 to 45 wt % (dry weight), with fast HTL with low mass loading giving the highest yield. This condition also gave the biocrude with the lowest heating value, which indicates there are compromises to be made between biocrude quantity and quality. The aqueous phase and biocrude product fractions were characterized using elemental analysis and Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR MS). This detailed level of analysis identified more than 30,000 unique molecular products. The aqueous phase products included compounds with the same molecular formulae as known herbicides, which may inform efforts in genetic engineering of algae and/or bacteria for cultivation on the aqueous phase. This detailed molecular‐level characterization provides some clues regarding the types of reactions that may take place during HTL. © 2016 American Institute of Chemical Engineers AIChE J, 62: 815–828, 2016     

Unipolar Fatigue Behavior of BCTZ Lead‐Free Piezoelectric Ceramics

(Ba,Ca)(Ti,Zr)O₃ lead‐free piezoelectric ceramics have been considered to be one of the most potential lead‐free alternatives for PZT in the room‐temperature range. The stability of the piezoelectric performance during unipolar cycling is investigated in this study. It is found that the unipolar fatigue behavior is similar to soft PZT. Developments of bias field, offset polarization, asymmetry in strain, and dielectric hysteresis loops are observed during bipolar measurements. The changes are mainly contributed to the migration of charge carriers to the grain boundaries driven by the unscreened depolarization field. Redistribution of the accumulated charge carriers by bipolar electric cycling or thermal annealing can significantly recover the unipolar fatigued state. The unipolar strain response stabilized after 1000 cycles at 0.053% for an electric field of 0.6 kV/mm (d₃₃*= 883 pm/V), which is a good characteristic for actuator applications.     

Synthetic Indolactam V Analogues as Inhibitors of PAR2‐Induced Calcium Mobilization in Triple‐Negative Breast Cancer Cells

Human proteinase‐activated receptor 2 (PAR2), a transmembrane G‐protein‐coupled receptor (GPCR), is an attractive target for a novel anticancer therapy, as it plays a critical role in cell migration and invasion. Selective PAR2 inhibitors therefore have potential as anti‐metastatic drugs. Knowing that the natural product teleocidin A2 is able to inhibit PAR2 in tumor cells, the goal of the present study was to elaborate structure–activity relationships and to identify potent PAR2 inhibitors with lower activity against the adverse target, protein kinase C (PKC). For this purpose, an efficient gram‐scale total synthesis of indolactam V (i.e., the parent structure of all teleocidins) was developed, and a library of derivatives was prepared. Some compounds were indeed found to exhibit high potency as PAR2 inhibitors at low nanomolar concentrations with improved selectivity (relative to teleocidin A2). The pseudopeptidic fragment bridging the C3 and C4 positions of the indole core proved to be essential for target binding, whereas activity and target selectivity depends on the substituents at N1 or C7. This study revealed novel derivatives that show high efficacy in PAR2 antagonism combined with increased selectivity.     

Phosphorus availability on many organically managed farms in Europe

Maintaining sufficient soil phosphorus (P) levels for non-limiting crop growth is challenging in organic systems since off-farm inputs of P are restricted. This study assessed the status of P on organic farms in Europe using soil test results for extractable P. Data was obtained from published literature, unpublished theses, and various national and regional databases of soil test values. Most of the data (15,506 observations) came from field scale soil tests, but in some cases (1272 observations) values had been averaged across a farm. Farm scale and field scale data were analysed separately and the impact of farm type (arable, dairy, grassland, horticulture, mixed, poultry, unknown) was assessed. Soil test results were assigned to P classes from very low (P class 1) to very high (P class 5). The farm scale data came primarily from Norway, Sweden and Switzerland and did not indicate deficiencies in extractable P; 93% of farms fell into class 3 or above. The majority of the field scale data came from Germany and indicated sufficient or higher levels of P availability for arable and grassland systems on 60% of fields; the remaining fields had low or very low available P. Adaptations in organic systems may improve P uptake and utilization efficiency allowing yields to be maintained in the short-term, nevertheless there is cause for concern about the long-term P sustainability of some organic farming systems in Europe. This highlights the need to reassess allowable P inputs in organic farming systems to improve overall sustainability.