Assessment of the determination of water-soluble ionic composition of atmospheric aerosols from the analysis of crossed halves of filters

The water-soluble ionic composition of atmospheric aerosols is a key parameter for estimating its anthropogenic or natural origin. This evaluation depends on the reliability of the performed measurements. The differential approach for the evaluation of the measurement uncertainty was used for estimating, separately, the uncertainty associated with the extraction step, by difference from the observed intermediate precision and the combination of all the other uncertainty components affecting the estimated intermediate precision. The intermediate precision was estimated from the difference of results of the analysis, in different days, of several pairs of filters resulting from cross-changing of their halves. The precision associated with the symmetry of filters division, affecting the homogeneity of studied combined pairs of filters, was subtracted from the observed dispersion of results. The resulting detailed model of measurement performance allowed defining strategies for cost of analysis or magnitude of measurement uncertainty reduction. Measurements are fit for the analysis of urban aerosols since the expanded relative measurement uncertainty is smaller than a target value of 30 %.     

Measuring Tollmien–Schlichting waves using phase-averaged particle image velocimetry

This article addresses the direct experimental measurement of Tollmien?CSchlichting waves on a flat plate, when the laminar boundary layer is excited by velocity perturbations; the free stream velocity was 16?m/s, the excitation frequency 250?Hz. The two-dimensional velocity field in proximity of the flat plate was captured using a conventional PIV system; however, the image recording was phase locked with the disturbance source and ensemble averaging was used to obtain characteristics of the Tollmien?CSchichting waves. In particular, after subtraction of the mean velocity, the characteristics of the excited waves in terms of streamlines were extracted, revealing that the investigated waves represented velocity deviations with an order of magnitude of 1?% of the undisturbed free stream flow. This study is a prelude to the use of the same technique to visualize the effect of dielectric barrier discharge plasma actuators on the suppression of such Tollmien?CSchlichting waves, which is difficult using other measurement techniques.     

Correction to "combinatiorial properties of some classes of matrices over GF(2)"

Due to my oversight in checking the galley proofs, an error has occured in Tran [1]. The wording of proposition 4.2 on page 162 should read.     

Management and analysis of DNA microarray data by using weighted trees

We investigate discrete structures and combinatoric modeling of weighted prefix trees for managing and analyzing DNA microarray data. We describe the algorithms to construct the weighted trees for these data. Using these weighted trees with our algorithms, we propose methods to compute the appearance probability of a DNA microarray, to compare the informational distances in the expression of genes between the DNA microarrays, to search the characteristic microarrays and the group of candidate genes suggestive of a pathology.     

Small molecule microarray identifies inhibitors of tyrosyl-DNA phosphodiesterase 1 that simultaneously access the catalytic pocket and two substrate binding sites

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a member of the phospholipase D family of enzymes, which catalyzes the removal of both 3′- and 5′-DNA phosphodiester adducts. Importantly, it is capable of reducing the anticancer effects of type I topoisomerase (TOP1) inhibitors by repairing the stalled covalent complexes of TOP1 with DNA. It achieves this by promoting the hydrolysis of the phosphodiester bond between the Y723 residue of human TOP1 and the 3′-phosphate of its DNA substrate. Blocking TDP1 function is an attractive means of enhancing the efficacy of TOP1 inhibitors and overcoming drug resistance. Previously, we reported the use of an X-ray crystallographic screen of more than 600 fragments to identify small molecule variations on phthalic acid and hydroxyquinoline motifs that bind within the TDP1 catalytic pocket. Yet, the majority of these compounds showed limited (millimolar) TDP1 inhibitory potencies. We now report examining a 21 000-member library of drug-like Small Molecules in Microarray (SMM) format for their ability to bind Alexa Fluor 647 (AF647)-labeled TDP1. The screen identified structurally similar N,2-diphenylimidazo[1,2-a]pyrazin-3-amines as TDP1 binders and catalytic inhibitors. We then explored the core heterocycle skeleton using one-pot Groebke–Blackburn–Bienayme multicomponent reactions and arrived at analogs having higher inhibitory potencies. Solving TDP1 co-crystal structures of a subset of compounds showed their binding at the TDP1 catalytic site, while mimicking substrate interactions. Although our original fragment screen differed significantly from the current microarray protocol, both methods identified ligand–protein interactions containing highly similar elements. Importantly inhibitors identified through the SMM approach show competitive inhibition against TDP1 and access the catalytic phosphate-binding pocket, while simultaneously providing extensions into both the substrate DNA and peptide-binding channels. As such, they represent a platform for further elaboration of trivalent ligands, that could serve as a new genre of potent TDP1 inhibitors.

Using small molecule microarray TDP1 inhibitors have been identified that bind in a trivalent mode.