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Biosynthesis of novel thermoplastic polythioesters by engineered Escherichia coli

The development of non-petrochemical sources for the plastics industry continues to progress as large multinationals focus on renewable resources to replace fossil carbon. Many bacteria are known to accumulate polyoxoesters as water-insoluble granules in the cytoplasm. The thermoplastic and/or elastomeric behaviour of these biodegradable polymers holds promise for the development of various technological applications. Here, we report the synthesis and characterization of microbial polythioesters (PTEs), a novel class of biopolymers of general technological relevance. Biosynthesis of PTE homopolymers was achieved using a recombinant strain of Escherichia coli that expressed a non-natural pathway consisting of a butyrate kinase, a phosphotransbutyrylase, and a PHA synthase. Different homopolymers were produced, consisting of either 3-mercaptopropionate, 3-mercaptobutyrate, or 3-mercaptovalerate repeating units, if the respective mercaptoalkanoic acids were provided as precursor substrates to the fermentative process. The PTEs contributed up to 30% (w/w) of the cellular dry weight and were identified as hydrophobic inclusions in the cytoplasm. The chemical and stereochemical homogeneity of the purified PTEs were identified by different methods, and the estimated physical properties were compared to the oxypolyester equivalents, revealing low crystalline order and, for the poly(3-mercaptopropionate) improved thermal stability. The ability to produce PTEs through a biosynthetic route opens up new avenues in the field of biomaterials.     

4-Nitro-7-piperazino-2,1,3-benzoxadiazole as a reagent for monitoring of airborne isocyanates by liquid chromatography

4-Nitro-7-piperazino-2,1,3-benzoxadiazole (NBDPZ) is presented as a new reagent for the determination of mono- and diisocyanates in air samples. NBDPZ readily reacts with the airborne analytes, thus yielding the corresponding urea derivatives, which are subsequently separated by means of reversed-phase liquid chromatography. On a phenyl-modified stationary phase, excellent baseline separation for numerous mono- and diisocyanate derivatives is obtained. Both diode array and fluorescence detection are performed with limits of detection of 11-35 and 5-9 nmol/L for the individual derivatives, respectively. In contrast to established derivatizing agents for the analysis of isocyanates, NBDPZ provides for increased selectivity due to the favorable detection wavelengths in the visible range (UV/visible, absorption maximums approximately 480 nm; fluorescence, excitation maximums approximately 470 nm, emission maximums approximately 535 nm). In addition, the high molar absorptivities of the reagent and the derivatives provide excellent sensitivity that is superior to most literature-known methods. Finally, air sampling methods comprising both the use of impingers and test tubes are developed and successfully applied to the determination of isocyanates in gaseous samples. Excellent recovery reaching values of >90% is observed for each of the two techniques investigated.     

“To be recorded” analysis in reverse-mode automatic differentiation

The automatic generation of adjoints of mathematical models that are implemented as computer programs is receiving increased attention in the scientific and engineering communities. Reverse-mode automatic differentiation is of particular interest for large-scale optimization problems. It allows the computation of gradients at a small constant multiple of the cost for evaluating the objective function itself, independent of the number of input parameters. Source-to-source transformation tools apply simple differentiation rules to generate adjoint codes based on the adjoint version of every statement. In order to guarantee correctness, certain values that are computed and overwritten in the original program must be made available in the adjoint program. For their determination we introduce a static data-flow analysis called “to be recorded” analysis. Possible overestimation of this set must be kept minimal to get efficient adjoint codes. This efficiency is essential for the applicability of source-to-source transformation tools to real-world applications.     

Medizinethische Implikationen zukünftiger pharmakogenomischer Behandlungsstrategien

Zusammenfassung.   Gegenw?rtige Fortschritte in den pharmakologischen Wissenschaften erlauben einen ersten Ausblick auf eine individuelle, genotyp-basierende Arzneimitteltherapie, durch die sich die Effektivit?t der Medikamentenbenutzung weiter verbessern lie?e. Die genotypische Erfassung von genetischen Polymorphismen, die bei Medikamentenreaktionen beteiligt sind, verspricht die Arzneimitteltherapie grundlegend zu optimieren, wenn damit Patienten identifiziert werden, für die ein Medikament entweder nutzbringend und sicher angewandt oder aber aufgrund zu erwartender Nebenwirkungen nicht eingesetzt werden sollte. Die neuen pharmakogenomischen Behandlungsstrategien werfen komplexe ethische Fragestellungen auf, da durch ein genetisches Screening für Arzneimittelzwecke asymptomatische Patienten mit erh?htem Risiko für eine insgesamt schlechtere Prognose identifiziert werden k?nnten. Die Pharmakogenomik beeinflusst damit das Beziehungsverh?ltnis zwischen behandelnden Arzt und Patienten, das traditionell auf Diskretion, Vertraulichkeit und dem unbedingten Vorsatz, heilen und keinesfalls schaden zu wollen, beruht. Der vorliegende Aufsatz diskutiert einige ethische Aspekte im Bedeutungswandel der Arzt-Patienten-Beziehung, der durch diesen neuartigen pharmakogenomischen Behandlungsansatz ausgel?st wird.      

Motion Control of Mobile Robots—From Static Targets to Fast Drives in Moving Crowds

Motion control of vehicles under uncertain, noisy, and discontinuous positioning is essential in autonomous navigation in unknown environments. This article suggests two methods for motion control, where the initial parameters of the on-line control are physically explainable, the resulting trajectory as well as the control parameters are asymptotically converging and glitches in the localization are handled robustly. The differences to a known method based on Lyapunov functions are discussed theoretically as well as in terms of actual motion measurements. Physical experiments with landbound vehicles show the reliability and limitations of these different methods in setups employing static attractors, systematically moving targets and fast, unpredictable moving targets in highly dynamical environments. Mainly due to the physical meaning of the control parameters the adaptation to actual kinematics and dynamics is significantly simplified.     

The Forgotten “Old-Darwinian” Synthesis: The Evolutionary Theory of Ludwig H. Plate (1862–1937)

The German zoologist and geneticist Ludwig Plate was a pupil and successor of the “German Darwin” Ernst Haeckel as the director of the Institute of Zoology at Jena University. Plate campaigned for a revival of the original Darwinism. His research program, which he labelled “old-Darwinism”, proclaimed the synthesis of selectionism with “moderate Lamarckism” and orthogenesis.This article reconstructs and analyses Plate’s “old-Darwinian” synthesis and sheds light on Plate’s controversial biography, especially his conflict with Haeckel. Our research was supported by the Deutsche Forschungsgemeinschaft (HO 2143/5–2).     

Untersuchungen zum Kristallabbau bei der Reduktion von Wüstit

Reduktionsversuche an auf Eisen aufoxydiertem Wüstit mit Kohlenmonoxid-Kohlendioxid-Stickstoff- und Wasserstoff-Wasserdampf-Stickstoff-Gasgemischen. Mikroskopische Beobachtung der anreduzierten Wüstitoberfläche. Beeinflussung der Reduktion durch die Oberflächentopographie des Wüstits. Analogie der Wüstitreduktion unter gleichgewichtsnahen Bedingungen zur Kristallverdampfung.