On the equation of state of polymer solutions

The theory formulated for single and multicomponent systems is applied to polymer solutions. This follows earlier investigations on mixtures of low molecular weight compounds and a binary compatible polymer mixture. The requisite analysis of the polymer constituents, namely polyisobutylene and poly(dimethylsiloxane) shows good agreement between experiment and theory. Similar conclusions apply to the solvents, namely cyclohexane, benzene and hexa(methyl disiloxane). For the solutions, the theory makes predictions at elevated pressures, based on the equation of state of the constituents and low pressure experimentation for the mixtures. Satisfactory results obtain in this manner with deviations increasing with temperature and pressure (maximally 1 kbar). At low pressures, the agreement between experiment and theory is good for all temperatures and compositions.     

Application of machine learning to improve the results of high-throughput docking against the HIV-1 protease

We have previously reported that the application of a Laplacian-modified naive Bayesian (NB) classifier may be used to improve the ranking of known inhibitors from a random database of compounds after High-Throughput Docking (HTD). The method relies upon the frequency of substructural features among the active and inactive compounds from 2D fingerprint information of the compounds. Here we present an investigation of the role of extended connectivity fingerprints in training the NB classifier against HTD studies on the HIV-1 protease using three docking programs: Glide, FlexX, and GOLD. The results show that the performance of the NB classifier is due to the presence of a large number of features common to the set of known active compounds rather than a single structural or substructural scaffold. We demonstrate that the Laplacian-modified naive Bayesian classifier trained with data from high-throughput docking is superior at identifying active compounds from a target database in comparison to conventional two-dimensional substructure search methods alone.     

Immobilization of protein on aldehyde-containing gels—II. Activation of pyridine rings with cyanogen bromide

Cyanogen bromide was used to convert pyridine rings in polymers to polyaldehyde. By reaction with NH₂-containing substances, the rings are rebuilt, resulting in a pyridinium compound. Thus proteins and other NH₂-containing substances can be covalently bound. This method provides a new means for a immobilization technique. Pyridine-gels based on polysaccharide and polyacrylamide matrices, as well as pyridine glass beads, were synthesized and used to study the conditions necessary for coupling. Trypsin and — chymotrypsin were used as test substances for immobilization of proteins. Some properties of the bound protein were studied and compared to native enzyme. Some general results on the applicability of these gels for affinity chromatography are also presented.     

Photochemical generation of vinylketenes by electrocyclic opening of cyclobutenones

4,4-Dich1oro-2-cyclobutenones , available by cycloaddition of acetylenes to dichloroketene, can be photolyzed in the presence of olefins or dienes to produce regiospecifically 2-vinylcyclobutanones . The photochemical reaction succeeds even in some cases where thermolysis fails and was shown to proceed by electrocyclic ring opening to a vinylketene. Stereochemically the results of photolysis of differ from thermolysis with identical olefinic substrates.     

Analytic continuation by summation-methods

The paper deals with the analytic continuation of the geometric series by a family of linear transformations into some special domains of the complex plane.     

Subtle differences in structural transitions between poly-L- and poly-D-amino acids of equal length in water

Mirror-image asymmetric molecules, i.e., chiral isomers or enantiomers, are classically considered as chemically identical. Recent studies, however, have indicated that parity violation by the nuclear weak force induces a tiny energy difference between chiral isomers. Upon combination with a massive amplification process, expansion of this difference to a detectable macroscopic level may be achieved. Yet, experimental tests of this possibility, where one enantiomer is compared to the other in solution, are hampered by the possible presence of undetectable impurities. In this study we have overcome this problem by comparing structural and dynamic features of synthetic D- and L-polyglutamic acid and polylysine molecules each of 24 identical residues. In these water-soluble polypeptides helix formation is an intramolecular autocatalytic process amplified by each turn, which is actually unaffected by low level of putative impurities in the solvent. The helix and random coil configurations and their transition were determined in this study by circular dichroism (CD) and isothermal titration calorimetry (ITC) in water and deuterium oxide. Distinct differences in structure and transition energies between the enantiomeric polypeptides were detected by both CD and ITC when dissolved in water. Intriguingly, these differences were by and large abolished in deuterium oxide. Our findings suggest that deviation from physical invariance between the D- and L-polyamino acids is induced in part by different hydration in water which is eliminated in deuterium oxide. Based on the recent findings by Tikhonov and Volkov (V. I. Tikhonov and A. A. Volkov, Science 2002, 296, 2363) we suggest that ortho-H(2)O, which constitutes 75% of bulk H(2)O, has a preferential affinity to L-enantiomers. Differential hydration of enantiomers may have played a role in the selection of L-amino acids by early forms of life.     

Enrichment of high-throughput screening data with increasing levels of noise using support vector machines, recursive partitioning, and laplacian-modified naive bayesian classifiers

High-throughput screening (HTS) plays a pivotal role in lead discovery for the pharmaceutical industry. In tandem, cheminformatics approaches are employed to increase the probability of the identification of novel biologically active compounds by mining the HTS data. HTS data is notoriously noisy, and therefore, the selection of the optimal data mining method is important for the success of such an analysis. Here, we describe a retrospective analysis of four HTS data sets using three mining approaches: Laplacian-modified naive Bayes, recursive partitioning, and support vector machine (SVM) classifiers with increasing stochastic noise in the form of false positives and false negatives. All three of the data mining methods at hand tolerated increasing levels of false positives even when the ratio of misclassified compounds to true active compounds was 5:1 in the training set. False negatives in the ratio of 1:1 were tolerated as well. SVM outperformed the other two methods in capturing active compounds and scaffolds in the top 1%. A Murcko scaffold analysis could explain the differences in enrichments among the four data sets. This study demonstrates that data mining methods can add a true value to the screen even when the data is contaminated with a high level of stochastic noise.     

Heterogeneous Electrofreezing Triggered by CO2 on Pyroelectric Crystals: Qualitatively Different Icing on Hydrophilic and Hydrophobic Surfaces

By performing icing experiments on hydrophilic and hydrophobic surfaces of pyroelectric amino acids and on the x‐cut faces of LiTaO₃, we discovered that the effect of electrofreezing of super cooled water is triggered by ions of carbonic acid. During the cooling of the hydrophilic pyroelectric crystals, a continuous water layer is created between the charged hemihedral faces, as confirmed by impedance measurements. As a result, a current of carbonic acid ions, produced by dissolved environmental CO₂, flows through the wetted layer towards the hemihedral faces and elevates the icing temperature. This proposed mechanism is based on the following: (i) on hydrophilic surfaces, water with dissolved CO₂ (pH 4) freezes at higher temperatures than pure water of pH 7. (ii) In the absence of the ionic current, achieved by linking the two hemihedral faces of hydrophilic crystals by a conductive paint, water of the two pH levels freeze at the same temperature. (iii) On hydrophobic crystals with similar pyroelectric coefficients, where there is no continuous wetted layer, no electrofreezing effect is observed.