Higher Lefschetz Traces and Spherical Euler Characteristics

Higher analogs of the Euler characteristic and Lefschetz number are introduced. It is shown that they possess a variety of properties generalizing known features of those classical invariants. Applications are then given. In particular, it is shown that the higher Euler characteristics are obstructions to homotopy properties such as the TNCZ condition, and to a manifold being homologically Kähler.

     

MTD-PLS: a PLS variant of the minimal topologic difference method. III. Mapping interactions between estradiol derivatives and the alpha estrogenic receptor

A homogeneous collection of 45 estrogen agonist derivatives with relative binding affinities measured to the estrogen receptor from Ratus norvegicus was used. The quantitative structure-activity relationships were derived using an improved minimal topologic difference (MTD) method in a partial least-squares (PLS) variant. The spatially assigned analysis of fragment properties can provide receptor site maps, within the limits of the existing series. A steric misfit was found for the steroidal position 2; benefic hydrophobic and van der Waals (enhanced by high polarizability) interactions were found for the 17alpha-CH=CH-X group. MTD-PLS mapping results are confirmed by the experimentally derived estradiol-estrogen receptor binding site contacts (based on X-ray crystallography). Our results suggest that this MTD-PLS method can yield useful results for interactions with receptors of unknown 3D structure and, generally, for the steric rigidity of receptor sites.     

A comparison of some integral methods

The integral methods proposed to compute the kinetic parameters of heterogeneous reactions under non-isothermal conditions are usually worked by the help of the least squares method and the obtained correlation coefficient is taken as a criterion to choose the best integral method.An analysis of several experimental data by mean of three different integral methods was performed by us and the results pointed out that this criterion, by itself, is not enough to provide reliable information on the kinetic parameters.It appears, thus, that the use of an integral method or another is a simple matter of researcher's choice.

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Zusammenfassung Integrationsmethoden zur Berechnung kinetischer Parameter von heterogenen Reaktionen unter nicht isothermen Bedingungen werden im allgemeinen nach der Methode der kleinsten Quadrate erarbeitet und der ermittelte Korrelationskoeffizient dient als ein Kriterium für die Auswahl der besten Integrationsmethode.Mittels drei verschiedenen Integrationsmethoden wurde eine Analyse verschiedener experimenteller Daten durchgeführt. Die Ergebnisse zeigen, daß dieses Kriterium allein nicht ausreicht, um ausreichende Informationen über die kinetischen Parameter zu liefern.Es scheint deshalb, daß die Verwendung der einen oder anderen Integrationsmethode einfach eine Wahl des Anwenders darstellt.

     

Mechano-chemische Reaktionen des Polyvinylchlorids 7. Einfluß einiger Faktoren auf die Zugfestigkeit der durch Walzen von PVC-S in Anwesenheit von aromatischen Diaminen erhaltenen Produkte

Zusammenfassung Die Möglichkeit von chemischen Reaktionen des Polyvinylchlorids mit niedermolekularen Beimischungen vom Typ aromatischer Diamine während der Verarbeitung des Polymeren durch Walzen wird besprochen.Die so erhaltenen Produkte weisen eine höhere Streckfestigkeit gegenüber dem ursprünglichen Polymeren auf; diese mechanische Eigenschaft wird als Auswirkung der Reaktion betrachtet. Es wird der Einfluß einiger Parameter des Verarbeitungsvorganges (Diaurin - Menge, Dauer, Temperatur) auf die Streckfestigkeit der so erhaltenen Erzeugnisse verfolgt.     

Quantifying the relationships among drug classes

The similarity of drug targets is typically measured using sequence or structural information. Here, we consider chemo-centric approaches that measure target similarity on the basis of their ligands, asking how chemoinformatics similarities differ from those derived bioinformatically, how stable the ligand networks are to changes in chemoinformatics metrics, and which network is the most reliable for prediction of pharmacology. We calculated the similarities between hundreds of drug targets and their ligands and mapped the relationship between them in a formal network. Bioinformatics networks were based on the BLAST similarity between sequences, while chemoinformatics networks were based on the ligand-set similarities calculated with either the Similarity Ensemble Approach (SEA) or a method derived from Bayesian statistics. By multiple criteria, bioinformatics and chemoinformatics networks differed substantially, and only occasionally did a high sequence similarity correspond to a high ligand-set similarity. In contrast, the chemoinformatics networks were stable to the method used to calculate the ligand-set similarities and to the chemical representation of the ligands. Also, the chemoinformatics networks were more natural and more organized, by network theory, than their bioinformatics counterparts: ligand-based networks were found to be small-world and broad-scale.     

Optimization of CAMD techniques 3. Virtual screening enrichment studies: a help or hindrance in tool selection?

Over the last few years many articles have been published in an attempt to provide performance benchmarks for virtual screening tools. While this research has imparted useful insights, the myriad variables controlling said studies place significant limits on results interpretability. Here we investigate the effects of these variables, including analysis of calculation setup variation, the effect of target choice, active/decoy set selection (with particular emphasis on the effect of analogue bias) and enrichment data interpretation. In addition the optimization of the publicly available DUD benchmark sets through analogue bias removal is discussed, as is their augmentation through the addition of large diverse data sets collated using WOMBAT.     

Obituary: Toshio Fujita,QSAR pioneer

This is the obituary for Toshio Fujita, pioneer of the quantitative structure activity relationship (QSAR) paradigm.     

Mechanochemically initiated polymerizations—5. Polymerization by vibratory milling of acrylamide and methacrylamide

Mechanochemical polymerization by vibratory milling of acrylamide and methacrylamide is discussed. The influences of duration, nature of medium and temperature are examined. The polymers are characterized by elemental analysis, i.r.-spectroscopy. X-ray and by determination of some properties. An anion-radical mechanism is proposed.