Biochemical interpretation of quantitative structure-activity relationships (QSAR) for biodegradation of N-heterocycles: a complementary approach to predict biodegradability

Prediction of the biodegradability of organic compounds is an ecologically desirable and economically feasible tool for estimating the environmental fate of chemicals. We combined quantitative structure-activity relationships (QSAR) with the systematic collection of biochemical knowledge to establish rules for the prediction of aerobic biodegradation of N-heterocycles. Validated biodegradation data of 194 N-heterocyclic compounds were analyzed using the MULTICASE-method which delivered two QSAR models based on 17 activating (OSAR 1) and on 16 inactivating molecular fragments (GSAR 2), which were statistically significantly linked to efficient or poor biodegradability, respectively. The percentages of correct classifications were over 99% for both models, and cross-validation resulted in 67.9% (GSAR 1) and 70.4% (OSAR 2) correct predictions. Biochemical interpretation of the activating and inactivating characteristics of the molecular fragments delivered plausible mechanistic interpretations and enabled us to establish the following biodegradation rules: (1) Target sites for amidohydrolases and for cytochrome P450 monooxygenases enhance biodegradation of nonaromatic N-heterocycles. (2) Target sites for molybdenum hydroxylases enhance biodegradation of aromatic N-heterocycles. (3) Target sites for hydratation by an urocanase-like mechanism enhance biodegradation of imidazoles. Our complementary approach represents a feasible strategy for generating concrete rules for the prediction of biodegradability of organic compounds.     

Knowledge Incorporation into Neural Networks From Fuzzy Rules

The incorporation of prior knowledge into neural networks can improve neural network learning in several respects, for example, a faster learning speed and better generalization ability. However, neural network learning is data driven and there is no general way to exploit knowledge which is not in the form of data input-output pairs. In this paper, we propose two approaches for incorporating knowledge into neural networks from fuzzy rules. These fuzzy rules are generated based on expert knowledge or intuition. In the first approach, information from the derivative of the fuzzy system is used to regularize the neural network learning, whereas in the second approach the fuzzy rules are used as a catalyst. Simulation studies show that both approaches increase the learning speed significantly.     

A Model for the Dynamic Interaction Between Evolution and Learning

The interaction between learning and evolution has elicited much interest particularly among researchers who use evolutionary algorithms for the optimization of neural structures. In this article, we will propose an extension of the existing models by including a developmental phase – a growth process – of the neural network. In this way, we are able to examine the dynamical interaction between genetic information and information learned during development. Several measures are proposed to quantitatively examine the benefits and the effects of such an overlap between learning and evolution. The proposed model, which is based on the recursive encoding method for structure optimization of neural networks, is applied to the problem domain of time series prediction. Furthermore, comments are made on problem domains which associate growing networks (size) during development with problems of increasing complexity.     

Basic intrusion protection: the first line of defense

Making your system safe is no cinch, but here's a guide to getting started. The article examines various system security methods, including: identification and authentication techniques; firewalls; audit trails; and automated intrusion detection systems     

Hepatic cholesterol metabolism in experimental nephrotic syndrome

Hypercholesterolemia is a consistent feature of the nephrotic syndrome. However, the mechanisms underlying this perturbation are unclear. In the present work, we have investigated different factors that influence hepatic cholesterol metabolism using the nephrotic rat as a model. The induction of nephrosis resulted in a severe and sustained hypercholesterolemia. However, no effect on the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase, could be detected. Further, plasma lathosterol/cholesterol ratio, a measure of cholesterol synthesis, was not altered. Also, plasma levels of mevalonate, both a substrate for cholesterogenesis beyond the rate-limiting step and a marker for cholesterol synthesis, did not differ between control rats and those with established hypercholesterolemia. There was no detectable change in the expression of low density lipoprotein (LDL) receptor between the two experimental groups. We conclude that the early increase in cholesterol synthesis reported after the induction of nephrosis is not necessary for the maintenance of hypercholeserolemia. Established hypercholesterolemia of the nephrotic syndrome seems to represent a steady state in which neither enhanced hepatic cholesterol synthesis nor retarded LDL cholesterol clearance is of major importance.     

Confocal Microscopy: Applications in Materials Science

Confocal microscopy is increasingly becoming recognized as a valuable analytical tool in material science although long established in life sciences. It is shown that this technique can be employed successfully in investigating polymers, coatings, emulsions, etc. Using the scattered light not only for imaging but also for analysis in a Raman spectrometer chemical information from an exactly defined volume smaller than 1 μm³ within the sample can be achieved.     

Effect of Extrusion Cooking on Molecular Parameters of Corn Starch

By using a systems analytical model (SAM) and a fuzzy logic control software (fuzzy CIM) extrusion experiments were designed, that enabled a differentiation of the influence of the thermal energy input, expressed by the product temperature (PT), and the influence of the specific mechanical energy input (SME) on the molecular structure of extruded starch. The chromatographic examination of the molecular changes in the starch clearly revealed the influence of the extrusion cooking conditions on molecular degradation. The molecular size of extruded starch, expressed as the weight average of the molecular weight (M̄ _w), decreased exponentially when SME increased. In the range of 110—180 °C, PT had no significant influence on M̄ _w so that the observed reduction of M̄ _w was primarily dependent on the increase in SME. By contrast, the polydispersity depended both on PT and SME. The influence of PT on the polydispersity was of minor significance up to 160 °C, increasing more steeply at higher temperatures. PT increase above 180 °C resulted in increasing reducing power of the extruded starch, whereas SME had almost no effect on reducing power. Only at a PT of more than 180 °C small amounts of short chain molecules with a degree of polymerisation (DP) smaller than 6 could be determined.     

New Aromatic Azapentalenes: 3H‐ and 2H‐Imidazo[1,2‐d]tetrazoles

A number of title compounds ( 3a,c,4a—c ) were prepared by cyclization of 5‐aminotetrazolium salts having ketonic substituents ( 1,2 ). The following procedures were applied: a) for 3a, 4a,b : heating of 1a, 2a,b with acetic anhydride‐ base; b) for 3c,4c : heating of 1b,2b in a buffer solution of pH 6.5 (Tschitschibabin reaction). The proclivity for ring closure was more pronounced with the salts 2 . The 6‐unsubstituted representatives 3c and 4c underwent S_E‐reactions, the 2H‐isomer 4c being slightly more reactive; this was confirmed by AM1 calculations. The nitroso product 4g exists predominantly as the valence‐isomeric nitrile oxide 6 .     

Verlustfreie Katalysatorrezirkulation durch ein neuartiges Verfahrensprinzip bei der Hydroformylierung höhermolekularer Olefine

Free-of-loss Catalyst Recycling in the Hydroformylation of Higher Molecular Olefins by a Novel Process Technology In this paper a novel homogenous-heterogeneous procedure for the hydroformylation reaction of higher molecular olefins is presented, at which the reaction itself is homogeneously catalyzed and only after the reaction the catalyst complex is heterogenized only for separation. This procedure is achieved by using the lithium salt of triphenylphosphine monosulfonic acid (Li-TPPMS) as complex ligand for the hydroformylation catalyst and methanol as solubilizer. Li-TPPMS and its complexes with metal carbonyls are highly soluble in water and methanol, but completely insoluble in almost all other organic solvents. After the reaction the methanol is distilled off. The catalyst system becomes insoluble and can be separated from the reaction product by filtration or by extraction with water. The aqueous catalyst solution is evaporated to dryness and the catalyst system dissolved in methanol for a new reaction.     

Optisch aktive Amine durch Lipase-katalysierte Methoxyacetylierung

Optically Active Amines via Lipase-Catalyzed Methoxyacetylation Racemic amines can be efficiently resolved using ethylmethoxyacetate as acylating agent in a lipase-catalyzed reaction. The reaction of 1-phenyethylamine with ethylmethoxyacetate in the presence of a lipase from Burkholderia plantarii is presented. Excellent yields and selectivity and minimal amount of enzyme characterize this new process.