Novel statistical approach for primary high-throughput screening hit selection

The standard activity threshold-based method (the "top X" approach), currently widely used in the high-throughput screening (HTS) data analysis, is ineffective at identifying good-quality hits. We have proposed a novel knowledge-based statistical approach, driven by the hidden structure-activity relationship (SAR) within a screening library, for primary hit selection. Application to an in-house ultrahigh-throughput screening (uHTS) campaign has demonstrated it can directly identify active scaffolds containing valuable SAR information with a greatly improved confirmation rate compared to the standard "top X" method (from 55% to 85%). This approach may help produce high-quality leads and expedite the hit-to-lead process in drug discovery.     

Discrete symmetries in SO(N) grand unified groups and the survival hypothesis

The possibility of introducing the discrete symmetry D is studied, which along with SU^c(3) × SU_L(2) × U(1)-symmetry, remains after the breaking of SO(N) grand unified symmetry by the Higgs fields vevs ～ 10¹⁵ GeV. The D quantum number distinguishes the fermions coupled with W-bosons via left and right currents. As a result, the presence of low-mass fermions in the theory is provided.     

Paramagnetic defects in manganese-doped lead tungstate

In manganese-doped PbWO₄ crystals, low-intensity signals of triclinic clusters Mn⁴⁺-V _O and Fe³⁺-V _Pb have been revealed in addition to signals of Mn²⁺ tetragonal centers. The Mn⁴⁺-V _O cluster is formed by a Mn⁴⁺ ion in the W⁶⁺ position, which is associated with a vacancy of the nearest neighbor O^2?ion, and the Fe³⁺-V _Pb cluster consists of a Fe³⁺ ion substituting for Pb²⁺ with a local compensation of by a lead vacancy. It has been shown that, in PbWO₄: Mn, there is also a small amount of Mn⁴⁺ tetragonal centers located in the Pb²⁺ position with a nonlocal compensation of an excess charge.     

Edge-detection algorithm based on DCT continuous extension technique

A new computational approach to the edge-detection problem, based on the continuous extension of discrete cosine transform (CEDCT) technique is proposed. This technique has some attractive properties, and other things being equal, it has more precise results than the usual discrete Fourier or discrete cosine transforms, especially at the intermediate points. That is why this technique allows one to estimate numerically a finite number of a derivatives of a discrete set of multidimensional points, using some specified properties of CEDCT. Because of using the spectrum of a given set of points, this approach is applicable to a wide area of signal-and image-processing problems. The results obtained by the proposed approach are compared with the well-known and widely used Canny algorithm. Some 1D and 2D numerical examples are given. The text was submitted by the authors in English.     

Thermochemistry of methyl and ethyl nitro, RNO2, and nitrite, RONO, organic compounds

Computational quantum theory is employed to determine the thermochemical properties of n-alkyl nitro and nitrite compounds: methyl and ethyl nitrites, CH3ONO and C2H5ONO, plus nitromethane and nitroethane, CH3NO2 and C2H5NO2, at 298.15 K using multilevel G3, CBS-QB3, and CBS-APNO composite methods employing both atomization and isodesmic reaction analysis. Structures and enthalpies of the corresponding aci-tautomers are also determined. The enthalpies of formation for the most stable conformers of methyl and ethyl nitrites at 298 K are determined to be -15.64 +/- 0.10 kcal mol-1 (-65.44 +/- 0.42 kJ mol-1) and -23.58 +/- 0.12 kcal mol-1 (-98.32 +/- 0.58 kJ mol-1), respectively. DeltafHo(298 K) of nitroalkanes are correspondingly evaluated at -17.67 +/- 0.27 kcal mol-1 (-74.1 +/- 1.12 kJ mol-1) and -25.06 +/- 0.07 kcal mol-1 (-121.2 +/- 0.29 kJ mol-1) for CH3NO2 and C2H5NO2. Enthalpies of formation for the aci-tautomers are calculated as -3.45 +/- 0.44 kcal mol-1 (-14.43 +/- 0.11 kJ mol-1) for aci-nitromethane and -14.25 +/- 0.44 kcal mol-1 (-59.95 +/- 1.84 kJ mol-1) for the aci-nitroethane isomers, respectively. Data are evaluated against experimental and computational values in the literature with recommendations. A set of thermal correction parameters to atomic (H, C, N, O) enthalpies at 0 K is developed, to enable a direct calculation of species enthalpy of formation at 298.15 K, using atomization reaction and computation outputs.     

Six-coordinate nitrato complexes of iron(III) porphyrins

The interaction of tetrahydrofuran (THF) with thin films of the nitrato complexes Fe(III)(Por)(eta(2)-O(2)NO) [Por = meso-tetraphenylporphyrinato (TPP) and meso-tetratolylporphyrinato (TTP) dianion] at low temperature leads to the formation of the six-coordinate nitrato complex Fe(Por)(THF)(NO(3)), which was characterized by IR and UV-visible spectroscopies. Formation of the THF adduct was accompanied by nitrate linkage isomerization from bidentate to monodentate coordination. The iron(III) center remains in a high spin state in contrast with the previously observed low-spin nitratonitrosyl complex Fe(TPP)(NO)(eta(10-ONO(2)). Upon warming, THF dissociates to restore the initial five-coordinate bidentate nitrato complex.     

Interaction of nitrogen bases with iron-porphyrin nitrito complexes Fe(Por)(ONO) in sublimed solids

The reactions of the nitrogen Lewis bases (B) 1-methylimidazole (1-MeIm), pyridine (Py), and NH3 as gases with sublimed layers containing the 5-coordinate nitrito iron(III)-porphyrinato complexes Fe(Por)(eta1-ONO) (1) are described (Por = meso-tetraphenyl-porphyrinato or meso-tetra-p-tolyl-porphyrinato dianions). In situ FTIR and optical spectra are used to characterize the formation of the 6-coordinate nitro complexes formed by the reaction of 1 with B = 1-MeIm, Py, or NH3. These represent the first examples of 6-coordinate amino-nitro complexes with sterically unprotected iron-porphyrins. The interaction of ammonia with Fe(Por)(ONO) at 140 K initially led to the nitrito species Fe(Por)(NH3)(eta1-ONO), and this species isomerized to the nitro complexes Fe(Por)(NH3)(eta1-NO2) upon warming to 180 K. When the latter were warmed to room temperature under intense pumping, the initial nitrito complexes Fe(Por)(eta1-ONO) were restored. Assignments of vibrational frequencies for the coordinated nitro group in 6-coordinate iron-porphyrin complexes are given and confirmed using 15N-labeled nitrogen dioxide to identify characteristic infrared bands. For M(Por)(B)(NO2) complexes (M = Fe or Co), an inverse correlation between the net charge transfer from the axial ligand B to the nitro group and the value of Deltanu = nua(NO2) - nus(NO2) is proposed. These observations are discussed in the context of growing interest in potential physiological roles of nitrite ion reactions with ferro- and ferri-heme proteins.     

Application of High-Frequency Electron Paramagnetic Resonance/Electron Spin Echo for the Identification of the Impurity Composition and Electronic Structure of Ceramics Based Garnets

Physics of the Solid State - Electron paramagnetic resonance (EPR) spectra of Ce3+, Yb3+, Cr3+, and Gd3+ impurity ions in yttrium aluminum garnet Y3Al5O12 (YAG) ceramics were detected and...     

Monoclinic centers of rare-earth <Emphasis Type="Italic">S</Emphasis> ions in yttrium orthoaluminate crystals

The ESR spectrum of Gd³⁺ and Eu²⁺ monoclinic centers, which substitute for yttrium ions in YAlO₃ crystals doped with europium and zirconium, has been investigated. Parameters of the fine structure of these centers are determined. The hyperfine-interaction parameters are determined for the centers with ¹⁵¹Eu isotope, and the hyperfine structure of the centers with ¹⁵³Eu isotope is discussed.