QUASI: a novel method for simultaneous superposition of multiple flexible ligands and virtual screening using partial similarity

The structure of many receptors is unknown, and only information about diverse ligands binding to them is available. A new method is presented for the superposition of such ligands, derivation of putative receptor site models and utilization of the models for screening of compound databases. In order to generate a receptor model, the similarity of all ligands is optimized simultaneously taking into account conformational flexibility and also the possibility that the ligands can bind to different regions of the site and only partially overlap. Ligand similarity is defined with respect to a receptor site model serving as a common reference frame. The receptor model is dynamic and coevolves with the ligand alignment until an optimal self-consistent superposition is achieved. When ligand conformational flexibility is permitted, different superposition models are possible and consistent with the data. Clustering of the superposition solutions is used to obtain diverse models. When the models are used to screen a database of compounds, high enrichments are obtained, comparable to those obtained in docking studies.     

Structure-fluorescence contrast relationship in cyanine DNA intercalators: toward rational dye design

The fluorescence enhancement mechanisms of a series of DNA stains of the oxazole yellow (YO) family have been investigated in detail using steady-state and ultrafast time-resolved fluorescence spectroscopy. The strong increase in the fluorescence quantum yield of these dyes upon DNA binding is shown to originate from the inhibition of two distinct processes: 1) isomerisation through large-amplitude motion that non-radiatively deactivates the excited state within a few picoseconds and 2) formation of weakly emitting H-dimers. As the H-dimers are not totally non-fluorescent, their formation is less efficient than isomerisation as a fluorescent contrast mechanism. The propensity of the dyes to form H-dimers and thus to reduce their fluorescence contrast upon DNA binding is shown to depend on several of their structural parameters, such as their monomeric (YO) or homodimeric (YOYO) nature, their substitution and their electric charge. Moreover, these parameters also have a substantial influence on the affinity of the dyes for DNA and on the ensuing sensitivity for DNA detection. The results give new insight into the development and optimisation of fluorescent DNA probes with the highest contrast.     

K6Pb8Cd: A Zintl Phase with Oligomers of Pb4 Tetrahedra Interconnected by Cd Atoms

Unprecedented (Pb ₄ )Cd(Pb ₄ )Cd(Pb ₄ )Cd(Pb ₄ ) tetramers (see picture) are present in the structure of the title compound, in which they coexist with isolated Pb₄ tetrahedra. Since Cs₆Ge₈Zn has the same stoichiometry as K₆Pb₈Cd but contains exclusively (Ge₄)₂Zn dimers, this can be viewed as a disproportionation reaction of the type (a).     

Arsenic Speciation in Urine and Blood Reference Materials

Acute and chronic exposure to arsenic is a growing problem in the industrialized world. Arsenic is a potent carcinogen and toxin in humans. In the body, arsenic is metabolized to produce several species, including inorganic forms, such as trivalent (As^III) and pentavalent (As^V), and the methylated metabolites such as monomethylarsonic acid, (MMA^V), and dimethylarsinic acid (DMA^V), in addition to arsenobetaine (AsB) which is ingested and excreted from the body in the same form. Each of these species has been reported to possess a specific but different degree of toxicity. Thus, not only is the measurement of total As required, but also quantification of the individual metabolites is necessary to evaluate the toxicity and risk assessment of this element. There are a large number of reference materials that are used to validate methodology for the analysis of As in blood and urine, but they are limited to total As concentrations. In this study, the speciation of five arsenic metabolites is reported in blood and urine from commercial available control materials certified for total arsenic levels. The separation was performed with an anion exchange column using inductively coupled plasma mass spectrometry as a detector. Baseline separation was achieved for As^III, As^V, MMA^V, DMA^V, and AsB, allowing us to quantify all five species. Excellent agreement between the total arsenic levels and the sum of the speciated As levels was obtained.     

A thermoanalytical study on some compounds of Zr(IV) with azopyrazolonic derivatives

Thermoanalytical data on six reagents and on their compounds with Zr(IV) are reported. Except for H acid, all reagents were azopyrazolonic derivatives obtained by synthesis. The purpose of this study was to obtain data on the thermal stabilities of the reagents and their zirconium compounds, and to establish the reagent: zirconium: water combination ratio.

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Zusammenfassung Thermoanalytische Daten von 6 Reagenzien und deren Verbindungen mit Zr(IV) werden mitgeteilt. Außer H-Säure waren alle Reagenzien durch Synthese erhaltene Azopyrazolon-Derivate. Zweck der Untersuchung war, Daten über die thermische Stabilität dieser Reagenzien und ihrer Zirkonverbindungen zu erhalten und das Verhältnis Reagens: Zirkon: Wasser festzustellen.

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Sediment Assessment of the Pchelina Reservoir,Bulgaria

The temporal dynamics of anthropogenic impacts on the Pchelina Reservoir is assessed based on chemical element analysis of three sediment cores at a depth of about 100–130 cm below the surface water. The ¹³⁷Cs activity is measured to identify the layers corresponding to the 1986 Chernobyl accident. The obtained dating of sediment cores gives an average sedimentation rate of 0.44 cm/year in the Pchelina Reservoir. The elements’ depth profiles (Ti, Mn, Fe, Zn, Cr, Ni, Cu, Mo, Sn, Sb, Pb, Co, Cd, Ce, Tl, Bi, Gd, La, Th and U_nat) outline the Struma River as the main anthropogenic source for Pchelina Reservoir sediments. The principal component analysis reveals two groups of chemical elements connected with the anthropogenic impacts. The first group of chemical elements (Mn, Fe, Cr, Ni, Cu, Mo, Sn, Sb and Co) has increasing time trends in the Struma sediment core and no trend or decreasing ones at the Pchelina sampling core. The behavior of these elements is determined by the change of the profile of the industry in the Pernik town during the 1990s. The second group of elements (Zn, Pb, Cd, Bi and U_nat) has increasing time trends in Struma and Pchelina sediment cores. The increased concentrations of these elements during the whole investigated period have led to moderate enrichments for Pb and U_nat, and significant enrichments for Zn and Cd at the Pchelina sampling site. The moderately contaminated, according to the geoaccumulation indexes, Pchelina Reservoir surface sediment samples have low ecotoxicity.     

γ-Active Constraints in Convex Semi-Infinite Programming

In this article, we extend the definition of γ-active constraints for linear semi-infinite programming to a definition applicable to convex semi-infinite programming, by two approaches. The first approach entails the use of the subdifferentials of the convex constraints at a point, while the second approach is based on the linearization of the convex inequality system by means of the convex conjugates of the defining functions. By both these methods, we manage to extend the results on γ-active constraints from the linear case to the convex case.     

Protter-Morawetz multidimensional problems

About 50 years ago M.H. Protter introduced boundary value problems that are multidimensional analogues of the classical plane Morawetz problems for equations of mixed hyperbolic-elliptic type that model transonic fluid flows. Up to now there are no general existence results for the Protter-Morawetz multidimensional problems, and an understanding of the situation is not at hand. At the same time, Protter also formulated boundary value problems in the hyperbolic part of the domain??the nonhomogeneous wave equation is studied in a (3+1)-D domain bounded by two characteristic cones and a non-characteristic ball. These problems could be considered as multidimensional variants of the Darboux problem in ?². In the frame of classical solvability the hyperbolic Protter problem is not Fredholm, because it has an infinite-dimensional cokernel. On the other hand, it is known that the unique generalized solution of a Protter problem may have a strong power-type singularity even for some very smooth right-hand side functions. This singularity is isolated at the vertex O of the boundary light cone and does not propagate along the characteristic cone. In the general case of smooth right-hand side function, some necessary and sufficient conditions for the existence of a bounded solution are given and a priori estimates for the solution are found. The semi-Fredholm solvability of the problem is proved.     

Separating the solution sets of analytical and polynomial systems

A linear inequality system with infinitely many constraints is polynomial (analytical) if its index set is a compact interval of the real line and all its coefficients are polynomial (analytical, respectively) functions of the index on this interval. This paper provides an example of analytical system whose solution set cannot be the solution set of any polynomial system. Research supported by DGES of Spain and FEDER of UE, Grant BFM2002-04114-C02-01. Research supported by CONACyT of Mexico, Grant 130036. Research partially supported by CONACyT of Mexico, Grant 44003.