Technology-transfer analysis of the materials research program “Matfo”

The commercial success of the German Federal Ministry's materials research program “Mafto” (1985–1994) was recently evaluated to determine the effectiveness of the direct-funding model in supporting innovative industrial research. Based on the results of a questionnaire, where a 97% return rate was achieved, it was found that the results obtained in 27% of the projects have already been commercialized to some degree, for 26% of the projects a commercialization of the results is planned but has not yet taken place, and for 54% of the projects no commercialization is planned. This study included only projects where at least four years had elapsed since project completion. The reasons why scientifically and technically successfully projects were not commercialized were also surveyed.     

A convenient method to discriminate between cytochrome P450 enzymes and flavin-containing monooxygenases in human liver microsomes

Liver microsomes are a frequently used probe to investigate the phase I metabolism of xenobiotics in vitro. Structures containing nucleophilic hetero-atoms are possible substrates for cytochrome P450 enzymes (P450) and flavin-containing monooxygenases (FMO). Both enzymes are located in the endoplasmatic reticulum of hepatocytes and both need oxygen and NADPH as cofactors. The common method to distinguish between the two enzyme systems is to use the thermal inactivation of FMO and to inhibit P450 completely with carbon monoxide, N-octylamine or N-benzylimidazole. In the literature no indication could be found that the heat inactivation of FMO does not affect any of the human P450 enzymes or that the overall P450 inhibitors inhibit the different human P450 enzymes sufficiently and do not affect the FMO. The effect of N-benzylimidazole and heat inactivation was tested on specific activities of seven P450 enzymes in human liver microsomes, 1A2, 2A6, 2C9, 2C19, 2D6, 3A4/5, and 2E1, using methoxyresorufin O-demethylation, coumarin 7-hydroxylation, (S)-warfarin 4-hydroxylation, (S)-(+)-mephenytoin 4-hydroxylation, dextrometorphan O-demethylation, oxidation of denitronifedipine, and chlorzoxazone 6-hydroxylation respectively. The sulfoxidation of methimazole (MMI) was used as a specific probe for the determination of FMO activity. Methimazole sulfoxidation was compared with the well known assay for FMO metabolism, the formation of N,N-dimethylaniline (DMA) N-oxide, to be confirmed as an exclusively FMO mediated reaction. The participation of P450 and FMO in the sulfoxidation of four sulfur containing peptides, ametryne; terbutryne, prometryne and methiocarb was investigated using human liver microsomes. All four reactions were demonstrated to be catalysed predominantly by cytochrome P450.     

On digital smoothing filters: A brief review of closed form solutions and two new filter approaches

The concept of smoothing noisy data using appropriate polynomials turns out to be equivalent to the application of suitable nonrecursive digital filters having the following properties: They process the data in such a way that the moments are conserved up to a desired order while the energy of their impulse response is minimum. Flatness constraints of their frequency response at =0 are equivalent to the moment condition. By using orthogonal polynomials, an explicit solution is known from the literature. A second approach which uses a special decomposition also yields closed form solutions. The realization is simplified, especially in the case where a large number of moments is supposed to be conserved.     

Zur Analytik von Zuckercouleuren I. Mitteilung: Differenzierung der Couleurklassen mittels Curiepunkt-Pyrolyse-Capillargaschromatographie-Massenspektrometrie

Summary After an introduction on the production, classification, legislative regulations, toxicology, and analysis of caramel colours, a report is given on the examination of these colourings by Curie-point pyrolysis-capillary gas chromatography-mass spectrometry. This method enables the differentiation between the four classes of caramel colours on the basis of the most concentrated of more than 100 identified pyrolysis products, which requires small quantities of substance (100 g) and short periods of time (1 h).

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Zur Analytik von Zuckercouleuren I. Mitteilung: Differenzierung der Couleurklassen mittels Curiepunkt-Pyrolyse-Capillargaschromatographie-Massenspektrometrie

Zusammenfassung Nach einer Einführung zur Herstellung, Klassifizierung, rechtlichen Stellung, Toxikologie und Analytik der Zuckercouleure wird über die Untersuchung dieser Farbstoffe mittels Curiepunkt-Pyrolyse-Capillargaschromatographie-Massenspektrometrie berichtet. Anhand der konzentrationsstärksten der über 100 identifizierten Pyrolyseprodukte ist es möglich, die vier Couleurklassen bei geringem Substanz- (100 g) and Zeitbedarf (1 h) sicher zu differenzieren.

     

Luminescent Amphiphilic Aminoglycoside Probes to Study Transfection

We report the characterization of amphiphilic aminoglycoside conjugates containing luminophores with aggregation-induced emission properties as transfection reagents. These inherently luminescent transfection vectors are capable of binding plasmid DNA through electrostatic interactions; this binding results in an emission “on” signal due to restriction of intramolecular motion of the luminophore core. The luminescent cationic amphiphiles effectively transferred plasmid DNA into mammalian cells (HeLa, HEK 293T), as proven by expression of a red fluorescent protein marker. The morphologies of the aggregates were investigated by microscopy as well as ζ-potential and dynamic light-scattering measurements. The transfection efficiencies using luminescent cationic amphiphiles were similar to that of the gold-standard transfection reagent Lipofectamine® 2000.     

Numerical characterization and experimental verification of an in-plane MEMS-actuator with thin-film aluminum heater

In this paper, a novel concept of a thermo-mechanical MEMS actuator using aluminum thin-film heaters on a thermal oxide for electrical insulation is presented. The actuator is part of an universal tensile testing platform for thermo-mechanical material characterization of one dimensional materials on a micro- and nano-scopic scale under different environmental conditions, as varying temperatures, pressure, moisture or even vacuum and is realised in BDRIE technology. It is shown, that the actuator concept fulfills the requirements for the use in a tensile loading stage along with heterogeneously integrated nanofunctional elements, following a specimen centered approach in line with bottom-up self-assembly processes. Simulation and experiment agree very well in the thermal and mechanical domain and allow subsequent optimisation of the actuator performance.     

New inhibitors of the Tat-TAR RNA interaction found with a "fuzzy" pharmacophore model

TAR RNA is a potential target for AIDS therapy. Ligand-based virtual screening was performed to retrieve novel scaffolds for RNA-binding molecules capable of inhibiting the Tat-TAR interaction, which is essential for HIV replication. We used a "fuzzy" pharmacophore approach (SQUID) and an alignment-free pharmacophore method (CATS3D) to carry out virtual screening of a vendor database of small molecules and to perform "scaffold-hopping". A small subset of 19 candidate molecules were experimentally tested for TAR RNA binding in a fluorescence resonance energy transfer (FRET) assay. Both methods retrieved molecules that exhibited activities comparable to those of the reference molecules acetylpromazine and chlorpromazine, with the best molecule showing ten times better binding behavior (IC50 = 46 microM). The hits had molecular scaffolds different from those of the reference molecules.     

Engineering of functional supramacromolecular complexes of proteins (enzymes) using reversed micelles as matrix microreactors

The size of the inner water cavity of reversed micelles formedin a triple system ‘water-surfactant-organic solvent’can be widely varied by changing the degree of surfactant hydration.This gives grounds to use reversed micelles as matrix microreactorsfor the design of supramolecular complexes of proteins. Usingultracentrifugation analysis, it has been demonstrated thatthe oligomeric composition of various enzymes (ketoglutaratedehydrogenase, alkaline phosphatase, lactic dehydrogenase, glyceraldehyde-3-phosphatedehydrogenase) solubilized in reversed micelles of Aerosol OT[sodium bis(2-ethylehexyl)sulfosuccinate] in octane changesupon variation of the degree of hydration. An oligomeric complexforms under conditions when the radius of the micelle innercavity is big enough to incorporate this complex as a whole.At lower degrees of hydration the micelles ‘uncouple’such complexes to their components. The catalytic propertiesof various oligomeric complexes have been studied. Possibilitiesof using reversed micelles for the separation of subunits ofoligomeric enzymes under non-denaturating conditions have beendemonstrated. In particular, the isolated subunits of alkalinephosphatase, lactic dehydrogenase and glyceralde-hyde-3-phosphatedehydrogenase have been found to be active in Aerosol OT reversedmicelles. The dependences of the catalytic activity of oligomericenzymes represent saw-like curves. The maxima of the catalyticactivity observed at these curves relate to the functioningof various oligomeric forms of an enzyme. The radii of the micelleinner cavity under conditions when these maxima are observedcorrelate with the linear dimensions of the enzyme oligomericforms. Correlation of the position of a maximum with the shapeof an oligomeric complex is discussed.     

Towards language-to-language transformation

This paper proposes a simplicity-oriented approach and framework for language-to-language transformation of, in particular, graphical languages. Key to simplicity is the decomposition of the transformation specification into sub-rule systems that separately specify purpose-specific aspects. We illustrate this approach by employing a variation of Plotkin’s Structural Operational Semantics (SOS) for pattern-based transformations of typed graphs in order to address the aspect ‘computation’ in a graph rewriting fashion. Key to our approach are two generalizations of Plotkin’s structural rules: the use of graph patterns as the matching concept in the rules, and the introduction of node and edge types. Types do not only allow one to easily distinguish between different kinds of dependencies, like control, data, and priority, but may also be used to define a hierarchical layering structure. The resulting Type-based Structural Operational Semantics (TSOS) supports a well-structured and intuitive specification and realization of semantically involved language-to-language transformations adequate for the generation of purpose-specific views or input formats for certain tools, like, e.g., model checkers. A comparison with the general-purpose transformation frameworks ATL and Groove, illustrates along the educational setting of our graphical WebStory language that TSOS provides quite a flexible format for the definition of a family of purpose-specific transformation languages that are easy to use and come with clear guarantees.

     

Extended bisection method for parameter identification of the transient heat conduction equation for thermo-elastic deformations during drilling

A new interdisciplinary approach is discribed to identifying unknown parameters using an extended version of the known interval bisection method. This developed method is based on the use of finite elements for calibrating the simulation calculation. The resulting thermo-elastic deformations which occur in drilling processes with impaired cooling lubrication are to be used as correction values for tool positioning in the NC control. Based on the strong impact on workpiece temperature of machining, a simulation approach is presented for calculating the temperature fields and their thermo-elastic consequences. In addition, methods are presented to correct these effects. This paper particularly deals with the temperature fields of drilling operations. Special attention is paid to the technique employed for iterative numerical determination of the unknown heat flux η _w and heat transfer coefficient \(\bar {\gamma }\) values. Finally, the data obtained from experiments are compared with those achieved by numerical simulation in order to verify the efficiency of simulation and determination of parameters.