Substructure-based virtual screening for adenosine A2A receptor ligands

A virtual ligand-based screening approach was designed and evaluated for the discovery of new A(2A) adenosine receptor (AR) ligands. For comparison and evaluation, the procedures from a recently published virtual screening study that used the A(2A) AR X-ray crystal structure for the target-based discovery of new A(2A) ligands were largely followed. Several screening models were constructed by deriving the distinguishing structural features from selected sets of A(2A) AR antagonists, so-called frequent substructure mining. The best model in statistical terms was subsequently applied to large-scale virtual screens of a commercial vendor library. This resulted in the selection of 36 candidates for acquisition and testing. Of the selected candidates, eight compounds significantly inhibited radioligand binding at A(2A) AR (>30%) at 10 μM, corresponding to a "hit rate" of 22%. This hit rate is quite similar to that of the referenced target-based virtual screening study, while both approaches yield new, non-overlapping sets of ligands.     

Layered silicates nanocomposite matrix for improved fiber reinforced composites properties

Three-phase glass fiber reinforced composites (GFRP) consisting of traditional woven glass fiber and polyamide-6 (PA6) matrix dispersed with organically modified layered silicates were prepared and investigated in this study. The fabrication of GFRP with different weight percentages of layered silicates was successful when the matrix contains less than 5 wt% of the layered silicates. The improvement due to the high aspect ratio and high stiffness of the layered silicates is illustrated through the matrix-controlled properties of the GFRP. The results showed that the GFRP with 5 wt% layered silicates offer the largest improvement of approximately 30% increase in both flexural strength and compressive strength at elevated temperatures. On the other hand, the in-plane shear properties measured from [±45]_s laminates revealed that the layered silicates help improved both the in-plane shear strength and modulus appropriately. By utilizing a nanocomposite matrix, improvement of stiffness and strength, as well as thermal and barrier properties is obtained without any change in processing temperature of the fiber composites.     

A Dynamic Risk Assessment Methodology for Maintenance Decision Support

The failure mode and effect analysis (FMEA) is a widely applied technique for prioritizing equipment failures in the maintenance decision‐making domain. Recent improvements on the FMEA have largely focussed on addressing the shortcomings of the conventional FMEA of which the risk priority number is incorporated as a measure for prioritizing failure modes. In this regard, considerable research effort has been directed towards addressing uncertainties associated with the risk priority number metrics, that is occurrence, severity and detection. Despite these improvements, assigning these metrics remains largely subjective and mostly relies on expert elicitations, more so in instances where empirical data are sparse. Moreover, the FMEA results remain static and are seldom updated with the availability of new failure information. In this paper, a dynamic risk assessment methodology is proposed and based on the hierarchical Bayes theory. In the methodology, posterior distribution functions are derived for risk metrics associated with equipment failure of which the posterior function combines both prior functions elicited from experts and observed evidences based on empirical data. Thereafter, the posterior functions are incorporated as input to a Monte Carlo simulation model from which the expected cost of failure is generated and failure modes prioritized on this basis. A decision scheme for selecting appropriate maintenance strategy is proposed, and its applicability is demonstrated in the case study of thermal power plant equipment failures. Copyright © 2016 John Wiley & Sons, Ltd.     

Effects of phosphoglycerate kinase overproduction in Saccharomyces cerevisiae on the physiology and plasmid stability.

In this report the effects of phosphoglycerate kinase (PGK) overproduction on the physiology and plasmid stability in baker's yeast Saccharomyces cerevisiae containing the PGK1 gene on an episomal plasmid are described. This examination reveals that there is a preferred intracellular level for this enzyme, amounting to 10-15% of the total soluble protein. Strains containing the plasmid and the host strain were grown in non-selective batch cultures and continuous culture, under different growth conditions. Plasmid-containing yeast strains stabilize the copy number of the episomal plasmid at a level at which the PGK concentration is about 12%. This stabilization is due to an equilibrium between normal plasmid loss and selective pressure because of advantages resulting from the increased amount of PGK under glucose-limited conditions. During respiro-fermentative growth, PGK-overproducing cells showed an increased respiration rate and decreased fermentative activity, compared to the host strain. The PGK1 gene can be applied as a direct positive selection marker to obtain a high episomal plasmid stability during growth on glucose. The results are consistent with previously reported data on the physiology and gene stability of PGK-overproducing yeast cells that contain multiple copies of the PGK1 gene integrated into the genome.     

Model Studies with the Inversely Calculated lsochrones of Ventricular Depolarization

This paper describes experimental studies on the influence of inhomogeneities in the volume conductor, and model errors and measurement errors on the inversely calculated isochrones of ventricular depolarization. The results indicate that in the inverse problem the use of inhomogeneous models is essential, that knowledge of the exact heart geometry (shape and orientation) is important, and that signal error (noise) as encountered in normal ECG recordings is not critical. The number of (measurement) leads required is found to be on the order of 64.     

Magnetic solid phase extraction for chromatographic separation of carbamates

Magnetic solid phase extraction particles (MSPE) were produced using magnetite nanoparticles with diameters between 9 and 13 nm as nucleating agent. The produced particles with magnetite cores were smaller, and more irregular and poly‐dispersed, than those produced in the absence of the magnetite particles. The average diameters of the particles were 377 and 521 nm, respectively, for silica particles with and without magnetic core, whereas the diameters of the different grafted particles were of the same order of magnitude than the silica particles with magnetic cores. BET results indicated surface areas ranging between 9 and 37 m² g^?1 The TGA results showed that the particles contained about 10% water and other solvents, and between 5 to 6% grafted groups. The thermal decomposition of the particles (presented under Supplementary Information ) was autocatalytic with activation energies of 367, 546, and 616 kJ mol^?1 for particles grafted with cyanopropyl (cyano), octyl, and trimethyl (TMS), respectively. The order of dispersity of the particles in water followed the sequence cyano > PMA > TMS ? octyl, whereas the pesticides removing efficiency followed the reverse order.     

Properties and thermo-switch behaviour of LDPE mixed with carbon black,zinc metal and paraffin wax

This paper reports on the presence of wax and radiation-induced crosslinking on the morphology, thermal and mechanical properties, as well as electrical conductivity and thermo-switch properties of LDPE containing different amounts of carbon black (CB) or carbon black plus zinc metal as filler. Although the filler was generally well dispersed in the polymer or polymer/wax blend, there were clear indications of the formation of conductive pathways. Different combinations of polymer, wax, CB and zinc filler and radiation induced crosslinking gave rise to different extents of crystallinity and/or chain immobilization, which had an influence on the mechanical and thermo-mechanical properties, and on the electrical conductivity and thermo-switch behaviour. Most importantly, the presence of wax, and CB and CB/Zn fillers, gave rise to increased electrical conductivity. The thermal expansion in the composites did not seem to play a significant role in obtaining larger values of the positive temperature coefficient of resistivity (PTC). We found that the presence of a small amount of paraffin wax significantly increased the PTC coefficients of the LDPE based conductive composites, and that γ-radiation induced crosslinking provided the thermo-mechanical stability of the amorphous regions in LDPE needed to obtain a high PTC intensity, which would provide a cheap material with good thermo-switch functionality, which is something not observed before.     

Dissolved Silicon and Its Origin in Belgian Beers—A Multivariate Analysis

Beer is a quintessential part of Belgian heritage. We performed a detailed analysis of factors controlling Si content in Belgian beers as a case study to coincide with the 2011 IBiS meeting in Antwerp (Belgium). Beer is one of the richest dietary sources of Si. Three decades of research have yielded evidence of a role for Si in human physiology: it plays an essential role in bone mineral density and reduces the biological availability of aluminium. We analysed 119 Belgian beers: highest dissolved Si concentrations were found in high fermentation, traditionally brewed ales. Concentrations ranged between 214 and 2,071 μmol L^???1. This is probably due to the complexity and length of the brewing procedure: longer, more complicated processing and presence of brewing sediment in the bottle allows more Si to dissolve out of the base products like hop, barley or even rice. As a side effect of fermentation, alcohol content was related to Si content.     

Prevention of Clostridium outgrowth in heated and hermetically sealed meat products by nitrite – a review

This paper discusses several hypotheses regarding the inhibition of Clostridium in cured meat. It focuses on the binding of iron, as there is some evidence that inhibition of Clostridium botulinum outgrowth in nitrite-cured meat products is mainly due to iron binding in such a way that it is no longer available for outgrowth of Clostridium spores. This strong binding also explains the antioxidative properties of nitrite in these products. The binding of iron, in all probability, requires no more than a moderate amount of nitrite which, after binding as nitric oxide to the haem group, is unavailable for reactions leading to N-nitroso compounds either. Other reactions of nitrite, which also could lead to Clostridium inhibition, are not discussed in detail here.     

Stability of sulphadimidine during raw fermented sausage preparation: reaction of sulphadimine with nitrite

 Raw fermented sausage was prepared from a dough to which sulphadimidine (SDM), a drug frequently used in animal husbandry, was added. With the aid of thermospray-mass spectroscopy further evidence was obtained that, during preparation, reactions with nitrite added to the dough resulted in the formation of desamino-SDM and 4-hydroxydesamino-SDM. An indication was obtained that traces of chlorodesamino-SDM were present in the brine, but this observation could not be established. Received: 22 March 1999 / Revised version: 10 May 1999