Artificial neural network prediction of quantitative structure - retention relationships of polycyclic aromatic hydocarbons in gas chromatography

A feed-forward artificial neural network (ANN) model was used to link molecular structures (boiling points, connectivity indices and molecular weights) and retention indices of polycyclic aromatic hydrocarbons (PAHs) in linear temperature-programmed gas chromatography. A randomly taken subset of PAH retention data reported by Lee et al, [Anal. Chem. 51 (1979) 768], containing retention index data for 30 PAHs, was used to make the ANN model. The prediction ability of the trained ANN was tested on unseen data for 18 PAHs from the same article, as well as on the retention data for 7 PAHs experimentally obtained in this work. In addition, two different data sets with known retention indices taken from the literature were analyzed by the same ANN model. It has been shown that the relative accuracy as the degree of agreement between the measured and the predicted retention indices in all testing sets, for most of the studied PAHs, were within the experimental error margins (3 %)

Adsorption of Equimolar Mixtures of Cationic and Anionic Surfactants at the Water/Hexane Interface

In mixed solutions of anionic and cationic surfactants, called catanionics, ion pairs are formed which behave like non-ionic surfactants with a much higher surface activity than the single components. In equimolar mixtures of NaCnSO4 and CmTAB, all surface-active ions are paired. For mixtures with n + m = const, the interfacial properties are rather similar. Catanionics containing one long-chain surfactant and one surfactant with medium chain length exhibit a strong increase in surface activity as compared with the single compounds. In contrast, catanionics of one mediumand one short chain surfactant have a surface activity similar to that of the medium-chain surfactant alone. Both the Frumkin model and the reorientation model describe the experimental equilibrium data equally well, while the adsorption kinetics of the mixed medium- and short-chain surfactants can be well described only with the reorientation model

Syndecan-4 Is Essential for Development of Concentric Myocardial Hypertrophy via Stretch-Induced Activation of the Calcineurin-NFAT Pathway

Sustained pressure overload leads to compensatory myocardial hypertrophy and subsequent heart failure, a leading cause of morbidity and mortality. Further unraveling of the cellular processes involved is essential for development of new treatment strategies. We have investigated the hypothesis that the transmembrane Z-disc proteoglycan syndecan-4, a co-receptor for integrins, connecting extracellular matrix proteins to the cytoskeleton, is an important signal transducer in cardiomyocytes during development of concentric myocardial hypertrophy following pressure overload. Echocardiographic, histochemical and cardiomyocyte size measurements showed that syndecan-4−/− mice did not develop concentric myocardial hypertrophy as found in wild-type mice, but rather left ventricular dilatation and dysfunction following pressure overload. Protein and gene expression analyses revealed diminished activation of the central, pro-hypertrophic calcineurin-nuclear factor of activated T-cell (NFAT) signaling pathway. Cardiomyocytes from syndecan-4−/−-NFAT-luciferase reporter mice subjected to cyclic mechanical stretch, a hypertrophic stimulus, showed minimal activation of NFAT (1.6-fold) compared to 5.8-fold increase in NFAT-luciferase control cardiomyocytes. Accordingly, overexpression of syndecan-4 or introducing a cell-permeable membrane-targeted syndecan-4 polypeptide (gain of function) activated NFATc4 in vitro. Pull-down experiments demonstrated a direct intracellular syndecan-4-calcineurin interaction. This interaction and activation of NFAT were increased by dephosphorylation of serine 179 (pS179) in syndecan-4. During pressure overload, phosphorylation of syndecan-4 was decreased, and association between syndecan-4, calcineurin and its co-activator calmodulin increased. Moreover, calcineurin dephosphorylated pS179, indicating that calcineurin regulates its own binding and activation. Finally, patients with hypertrophic myocardium due to aortic stenosis had increased syndecan-4 levels with decreased pS179 which was associated with increased NFAT activation. In conclusion, our data show that syndecan-4 is essential for compensatory hypertrophy in the pressure overloaded heart. Specifically, syndecan-4 regulates stretch-induced activation of the calcineurin-NFAT pathway in cardiomyocytes. Thus, our data suggest that manipulation of syndecan-4 may provide an option for therapeutic modulation of calcineurin-NFAT signaling

Application of Consensus Scoring and Principal Component Analysis for Virtual Screening against β-Secretase (BACE-1)

BACKGROUND: In order to identify novel chemical classes of β-secretase (BACE-1) inhibitors, an alternative scoring protocol, Principal Component Analysis (PCA), was proposed to summarize most of the information from the original scoring functions and re-rank the results from the virtual screening against BACE-1. METHOD: Given a training set (50 BACE-1 inhibitors and 9950 inactive diverse compounds), three rank-based virtual screening methods, individual scoring, conventional consensus scoring and PCA, were judged by the hit number in the top 1% of the ranked list. The docking poses were generated by Surflex, five scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, and PMF_Score) were used for pose extraction. For each pose group, twelve scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, PMF_Score, LigScore1, LigScore2, PLP1, PLP2, jain, Ludi_1, and Ludi_2) were used for the pose rank. For a test set, 113,228 chemical compounds (Sigma-Aldrich® corporate chemical directory) were docked by Surflex, then ranked by the same three ranking methods motioned above to select the potential active compounds for experimental test. RESULTS: For the training set, the PCA approach yielded consistently superior rankings compared to conventional consensus scoring and single scoring. For the test set, the top 20 compounds according to conventional consensus scoring were experimentally tested, no inhibitor was found. Then, we relied on PCA scoring protocol to test another different top 20 compounds and two low micromolar inhibitors (S450588 and 276065) were emerged through the BACE-1 fluorescence resonance energy transfer (FRET) assay. CONCLUSION: The PCA method extends the conventional consensus scoring in a quantitative statistical manner and would appear to have considerable potential for chemical screening applications

An evaluation of residues at an oil refinery site following fires

Soil pollution at the oil refinery at Novi Sad following destruction of crude oil and its products in storage tanks during the Kosovo conflict was investigated. More than 100, 000 t of crude oil and its products were destroyed, and about 90% of these were burnt off, 10% leached and 130 t recovered. The acute injection of polycyclic aromatic hydrocarbons (PAHs) to the air of the town was widespread depending on the weather conditions and ranged from 1-431,000 ng/m(3). The presence of PAHs, polychlorinated biphenyls (PCBs), and elements in the surface zone and soil core samples taken from various sites were determined up to a depth of 100 cm. Concentrations of PAHs were in the range between 0.75 and 86.19 mug/g dry soil. The contaminated soil can be expected to act as a permanent pollution source, while the mobile constituents are likely to cause groundwater pollution

Trace metal distribution in surface soils of Novi Sad and bank sediment of the Danube river

Concentration of Cu, Cd, Pb, Zn, As, Mn, and Fe in the Novi Sad city urban area surface soil samples and the Danube bank sediment sample were measured in 2001. The results correspond to a network of six representative sampling sites in which the main soil properties, organic matter, water content, pH, and particle size have also been determined. The geometric mean content of Zn, Cu, Cd, and Pb obtained from soil samples throughout the Novi Sad urban area (61.32, 28.39, 0.151, and 2.70 mg/kg, respectively) was compared with the geometric mean concentration in world soils. it was revealed only one site (sampling site No. 3) with Zn and Cu content higher than the allowed ones set by Dutch authorities used for investigation of a site for possible rehabilitation (Dutch A values)

Toxic and essential elements in soft wheat grain cultivated in Serbia

A survey was carried out with the aim of assessing the level of some toxic (Cd, Pb, Hg and As) and essential (Cu, Zn, Fe and Mn) elements in wheat grown in Serbia. A total of 433 samples of soft winter wheat grain from all the Serbian wheat-growing regions were pooled into 52 representative samples for 2002 harvest. After wet digestion, Cd, As, and Pb were determined by graphite furnace atomic absorption spectrometry (GFAAS), whereas Cu, Zn, Fe and Mn were determined by flame atomic absorption spectrometry (FAAS). Vapour generation accessory was used for Hg determination. The mean and median contents of all samples were (on a dry weight basis) 29 and 24 mu g/kg for Cd, 137 and 87 mu g/kg for Pb, 7 and LT 0.1 mu g/kg for Hg, 55 and 59 mu g/kg for As, 4.1 and 4.0 mg/kg for Cu, 24 and 24 mg/kg for Zn, 53 and 53 mg/kg for Fe, 34 and 33 mg/kg for Mn. The calculated mean and median levels of contamination were compared with the recommended or regulated maximum levels according to the European Commission and the national legislation. The average intake of eight selected elements from wheat-based products was estimated for the Serbian population

Mobility of heavy metals originating from bombing of industrial sites

Surface soil samples from the NIS Jugopetrol fuel storage sites has been studied. The aim of this work has been the detection of heavy and inorganic metals including As, Pb, Cd, Ni, Zn, Cr, and Cu in soils after bombing present due to outflow, burning or leaking of crude oil and oil products at five chosen locations: Belgrade-Cukarica, Smederevo, Ni, Bor and Prahovo. In order to get information of the future environmental and health risks, sampling was repeated after several months at the same locations. Certain locations present a threat on environment because of the possible transport of contaminants during higher water levels

Improved MR phase-contrast velocimetry using a novel nine-point balanced motion-encoding scheme with increased robustness to eddy current effects

Phase-contrast MRI (PC-MRI) velocimetry is a noninvasive, high-resolution motion assessment tool. However, high motion sensitivity requires strong motion-encoding magnetic gradients, making phase-contrast-MRI prone to baseline shift artifacts due to the generation of eddy currents. In this study, we propose a novel nine-point balanced velocity-encoding strategy, designed to be more accurate in the presence of strong and rapidly changing gradients. The proposed method was validated using a rotating phantom, and its robustness and precision were explored and compared with established approaches through computer simulations and in vivo experiments. Computer simulations yielded a 39-57% improvement in velocity-noise ratio (corresponding to a 27-33% reduction in measurement error), depending on which method was used for comparison. Moreover, in vivo experiments confirmed this by demonstrating a 26-53% reduction in accumulated velocity error over the R-R interval. The nine-point balanced phase-contrast-MRI-encoding strategy is likely useful for settings where high spatial and temporal resolution and/or high motion sensitivity is required, such as in high-resolution rodent myocardial tissue phase mapping. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc