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).     

Mapping the human retina

The new therapeutic method of scotoma-based photocoagulation (SBP) developed at the Vienna Eye Clinic for diagnosis and treatment of age-related macular degeneration requires retinal maps from scanning laser ophthalmoscope images. This paper describes in detail all necessary image analysis steps for map generation. A prototype software system for fully automatic map generation has been implemented and tested on a representative dataset selected from a clinical study with 50 patients. The map required for the SBP treatment can be reliably extracted in all cases. Thus, algorithms presented in this paper should be directly applicable in daily clinical routine without major modifications.     

Retinal ganglion cell axon progression from the optic chiasm to initiate optic tract development requires cell autonomous function of GAP-43

Pathfinding mechanisms underlying retinal ganglion cell (RGC) axon growth from the optic chiasm into the optic tract are unknown. Previous work has shown that mouse embryos deficient in GAP-43 have an enlarged optic chiasm within which RGC axons were reportedly stalled. Here we have found that the enlarged chiasm of GAP-43 null mouse embryos appears subsequent to a failure of the earliest RGC axons to progress laterally through the chiasm-tract transition zone to form the optic tract. Previous work has shown that ventral diencephalon CD44/stage-specific embryonic antigen (SSEA) neurons provide guidance information for RGC axons during chiasm formation. Here we found that in the chiasm-tract transition zone, axons of CD44/SSEA neurons precede RGC axons into the lateral diencephalic wall and like RGC axons also express GAP-43. However unlike RGC axons, CD44/SSEA axon trajectories are unaffected in GAP-43 null embryos, indicating that GAP-43-dependent guidance at this site is RGC axon specific or occurs only at specific developmental times. To determine whether the phenotype results from loss of GAP-43 in RGCs or in diencephalon components such as CD44/SSEA axons, wild-type, heterozygous, or homozygous GAP-43 null donor retinal tissues were grafted onto host diencephalons of all three genotypes, and graft axon growth into the optic tract region was assessed. Results show that optic tract development requires cell autonomous GAP-43 function in RGC axons and not in cellular elements of the ventral diencephalon or transition zone.     

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.     

Glucose quantification in dried-down nanoliter samples using mid-infrared attenuated total reflection spectroscopy

The aim of this study was to determine the feasibility of minimally invasive glucose concentration measurement of a body fluid within the physiologically important range below 100 nL with a number of samples such as interstitial fluid, plasma, or whole blood using mid-infrared spectroscopy, but starting with preliminary measurements on samples of simple aqueous glucose solutions. The Fourier transform infrared spectrometer was equipped with a Golden Gate single reflection diamond attenuated total reflection (ATR) accessory and a room-temperature pyroelectric detector. As the necessary detection limits can be achieved only for dried samples within the spectrometric conditions realized by a commercial instrument, the work focused on the optimization of such ATR measurements. We achieved quantification of samples with volumes as low as 7 nL between 10 and 600 mg/dL. The standard error of prediction (SEP) for the concentration range 10-100 mg/dL is 3.2 mg/dL with full interval data between 1180 and 940 cm(-1). The performance of the prediction is given by a coefficient of variation of prediction (CV(pred) ) of 6.2%. When all samples within the whole concentration range are included, the SEP increases to 20.2 mg/dL, and hence the CV(pred) to 10.6% due to a nonlinear signal dependence on glucose concentration. A detection limit for glucose of 0.7 ng with a signal-to-noise ratio of 10 was obtained.