Lipophilicity and bio‐mimetic properties determination of phytoestrogens using ultra‐high‐performance liquid chromatography

This paper presents lipophilicity and bio‐mimetic property determination of 15 phytoestrogens, namely biochanin A, daidzein, formononetin, genistein, genistein‐4,7‐dimethylether, prunetin, 3,4,7‐trihydroxyisoflavon, 4,6,7‐trihydroxyisoflavon, 4,6,7‐trimethoxyisoflavon, daidzin, genistin, ononin, sissotrin, coumestrol and coumestrol dimethylether. High‐performance liquid chromatography with fast gradient elution and Caco‐2 cell line were used to determine the physicochemical properties of selected phytoestrogens. Lipophilicity was determined on octadecyl‐sylane stationary phase using pH 2.0 and pH 7.4 buffers. Immobilized artificial membrane chromatography was used for prediction of interaction with biological membranes. Protein binding was measured on human serum albumin and α‐1‐acid‐glycoprotein (AGP) stationary phases. Caco‐2 assay was used as a gold standard for assessing in vitro permeability. The obtained results differentiate phytoestrogens according to their structure where aglycones show significantly higher lipophilicity, immobilized artificial membrane partitioning, AGP binding and Caco‐2 permeability compared with glucosides. However, human serum albumin binding was very high for all investigated compounds. Furthermore, a good correlation between experimentally obtained chromatographic parameters and in silico prediction was obtained for lipophilicity and human serum albumin binding, while the somewhat greater difference was obtained for AGP binding and Caco‐2 permeability.     

NIFTy 3 – Numerical Information Field Theory: A Python Framework for Multicomponent Signal Inference on HPC Clusters

NIFTy , “Numerical Information Field Theory,” is a software framework designed to ease the development and implementation of field inference algorithms. Field equations are formulated independently of the underlying spatial geometry allowing the user to focus on the algorithmic design. Under the hood, NIFTy ensures that the discretization of the implemented equations is consistent. This enables the user to prototype an algorithm rapidly in 1D and then apply it to high‐dimensional real‐world problems. This paper introduces NIFTy  3, a major upgrade to the original NIFTy  framework. NIFTy  3 allows the user to run inference algorithms on massively parallel high performance computing clusters without changing the implementation of the field equations. It supports n‐dimensional Cartesian spaces, spherical spaces, power spaces, and product spaces as well as transforms to their harmonic counterparts. Furthermore, NIFTy  3 is able to handle non‐scalar fields, such as vector or tensor fields. The functionality and performance of the software package is demonstrated with example code, which implements a mock inference inspired by a real‐world algorithm from the realm of information field theory. NIFTy  3 is open‐source software available under the GNU General Public License v3 (GPL‐3) at https://gitlab.mpcdf.mpg.de/ift/NIFTy/tree/NIFTy_3 .     

A new endocytic model based on the co-rotational grid method

Endocytosis plays important roles in many cellular physiological processes, such as metabolism and immune. Many theoretical models have been proposed to study the endocytic process, but little has considered the tensile deformation of the membrane and the actin forces. In this paper, a new endocytic model is proposed based on the co-rotational grid method. Our model gives a direct estimation of the in-plane strain of the plasma membrane and provides a basis for the calculation of further scission process of the vesicle. The results fit well with experimental data in the literature. Moreover, it is suggested that the active forces of actin at the endocytic site is the main mechanism driving the invagination of the plasma membrane.     

Development and validation of an ultra‐high‐performance liquid chromatography–tandem mass spectrometry method to determine the bioavailability of warfarin and its major metabolite 7‐hydroxy warfarin in rats dosed with oral formulations containing different polymorphic forms

A simple, sensitive and rapid ultra‐high‐performance liquid chromatography–electrospray ionization–tandem mass spectrometry method was developed and validated for the quantification of warfarin and 7‐hydroxy warfarin in Sprague Dawley (SD) rats. Animals were administered a single dose of warfarin sodium formulations (crystalline and amorphous) at 12 mg/kg via oral gavage and blood was drawn over a 96‐h time course. Sample process recoveries, matrix effect and analyte stability were determined. The linearity for warfarin and 7‐hydroxy warfarin was from 5 to 2000 ng/mL in blank SD rat plasma. Correlation coefficients (r²) for standard calibration curves were >.98 and analytes quantified within ±15% of target at all calibrator concentrations. The average percent accuracy and precision for intra‐ and inter‐day were 93.7%–113.8% and ≤12.1%, respectively, for warfarin and 7‐hydroxy warfarin, across the quality control standards (5, 10, 500, 1800 and 2000 ng/mL). Acceptable analytical recovery (>55%) was achieved with process efficiencies >41.5% and matrix effects <139.9% over the analytical range. Both analytes were stable in stock solution, autosampler, benchtop and three cycles of freeze–thaw with percent accuracy ≥90.2% and precision (percent relative standard deviation) ≤14%. The validated method was successfully applied to a pre‐clinical bioavailability study of crystalline and amorphous warfarin sodium formulations in SD rats.     

DNA interaction,cytotoxicity and molecular structure of cobalt complex of 4‐amino‐N‐(6‐chloropyridazin‐3‐yl)benzene sulfonamide in the presence of secondary ligand pyridine

Novel cobalt complex of 4‐amino‐N‐(6‐chloropyridazin‐3‐yl)benzene sulfonamide (sulfachloropyridazine) has been synthesized and characterized by elemental analysis, FT‐IR spectroscopy and magnetic susceptibility (VSM). Cobalt complex of Sulfachloropyridazine (Co‐SCP) crystallized in monoclinic space group P2₁/n with Z = 4. The structure is solved by direct method and refined to R = 0.099 for 4720 reflections with I ?4σ(I). The results of FT‐IR spectra suggest the binding of cobalt atom to the sulfonamide ligand which is in agreement with the crystal structure determination. In crystal structure, molecule is linked via, C‐H … π, C‐Cl … π and π … π intermolecular interactions. The computational studies like the optimization energy and root means square deviation compare with single crystal structure, frontier molecular orbital (Homo‐Lumo energy) and binding energy of the Co‐SCP has been carried out using DFT/B3LYP level of theory in gaseous phase. Hirshfeld surfaces and the 2D‐fingerprint analysis are performed to study the nature of interactions and their measurable contributions towards crystal packing. The interaction of the complex with DNA is investigated using viscosity measurement and absorption titration studies. The result shows the complex bind to DNA with intercalative mode with high DNA‐binding constant (K_b). Also, in vivo and in vitro cytotoxic studies are performed using S. pombe cells and brine shrimp lethality bioassay. DNA‐cleavage study shows better cleaving ability of the complex.     

Structural and phase characteristics of the diamond/matrix interfacial zone in high-resistant diamond composites

The structural-phase state of the contact zone and the factors that influence on the strength of diamond retention in the diamond carbide composites were determined. Composites were obtained by the new hybrid technology that eliminates the reheating of the metalized coating. The elaborated technology combines the thermal diffusion metallization of a diamond and the sintering by the scheme of self-dosed impregnation in a one-stage technological cycle. By the methods of electron microscopy, X-ray diffraction analysis, and Raman spectroscopy the structural and phase characteristics of the interphase boundary were investigated. The improvement of chemical and mechanical adhesion between the diamond and carbide matrix was obtained. It was shown that the specific productivity of the samples with a metalized diamond component is 39% higher than those without metallization.     

On the radius of spatial analyticity for the modified Kawahara equation on the line

First, by using linear and trilinear estimates in Bourgain type analytic and Gevrey spaces, the local well‐posedness of the Cauchy problem for the modified Kawahara equation on the line is established for analytic initial data that can be extended as holomorphic functions in a strip around the x‐axis. Next we use this local result and a Gevrey approximate conservation law to prove that global solutions exist. Furthermore, we obtain explicit lower bounds for the radius of spatial analyticity given by , where can be taken arbitrarily small and c is a positive constant.     

A dynamic free-entry oligopoly with sluggish entry and exit adjustments

We study a dynamic free-entry oligopoly with sluggish entry and exit of firms under general demand and cost functions. We show that the number of firms in a steady-state open-loop solution for a dynamic free-entry oligopoly is smaller than that at static equilibrium and that the number of firms in a steady-state memoryless closed-loop solution is larger than that in an open-loop solution.     

Contingent derivatives and regularization for noncoercive inverse problems

Abstract

We study the inverse problem of parameter identification in noncoercive variational problems that commonly appear in applied models. We examine the differentiability of the set-valued parameter-to-solution map using the first-order and the second-order contingent derivatives. We explore the inverse problem using the output least-squares and the modified output least-squares objectives. By regularizing the noncoercive variational problem, we obtain a single-valued regularized parameter-to-solution map and investigate its smoothness and boundedness. We also consider optimization problems using the output least-squares and the modified output least-squares objectives for the regularized variational problem. We give a complete convergence analysis showing that for the output least-squares and the modified output least-squares, the regularized minimization problems approximate the original optimization problems suitably. We also provide the first-order and the second-order adjoint method for the computation of the first-order and the second-order derivatives of the output least-squares objective. We provide discrete formulas for the gradient and the Hessian calculation and present numerical results.