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.     

NKT cell-dependent glycolipid–peptide vaccines with potent anti-tumour activity

It is known that T cells can eliminate tumour cells through recognition of unique or aberrantly expressed antigens presented as peptide epitopes by major histocompatibility complex (MHC) molecules on the tumour cell surface. With recent advances in defining tumour-associated antigens, it should now be possible to devise therapeutic vaccines that expand specific populations of anti-tumour T cells. However there remains a need to develop simpler efficacious synthetic vaccines that possess clinical utility. We present here the synthesis and analysis of vaccines based on conjugation of MHC-binding peptide epitopes to α-galactosylceramide, a glycolipid presented by the nonpolymorphic antigen-presenting molecule CD1d to provoke the stimulatory activity of type I natural killer T (NKT) cells. The chemical design incorporates an enzymatically cleavable linker that effects controlled release of the active components in vivo. Chemical and biological analysis of different linkages with different enzymatic targets enabled selection of a synthetic vaccine construct with potent therapeutic anti-tumour activity in mice, and marked in vitro activity in human blood.     

Diagonal-preserving ring ⁎-isomorphisms of Leavitt path algebras

The graph groupoids of directed graphs E and F are topologically isomorphic if and only if there is a diagonal-preserving ring ?-isomorphism between the Leavitt path algebras of E and F.     

Steady-state analysis of the Anaerobic Digestion Model No. 1 (ADM1)

The steady-state behavior of the Anaerobic Digestion Model No. 1 (ADM1) with respect to dilution rate and substrate concentration is analyzed in this study. Thereby, up to ten coexisting steady-state solutions are observed under the same operating conditions. The parameter region of a methane producing operation is limited regarding high dilution rates as well as low or high substrate concentrations. The underlying mechanisms causing those limits are investigated in detail, and the common core is identified, namely a positive feedback loop between growth of acetate degraders and acetate itself. The difference lies in the activation mechanisms of this feedback loop, which differs in the three investigated cases. The comparison of the present results with literature studies of simpler two-step models reveals qualitative differences regarding the substrate concentration. Therefore, an alternative simplified model is suggested, which shows qualitatively the same bifurcation behavior as the ADM1 considering variation of the substrate concentration.     

Surface tensor estimation from linear sections

From Crofton's formula for Minkowski tensors we derive stereological estimators of translation invariant surface tensors of convex bodies in the n‐dimensional Euclidean space. The estimators are based on one‐dimensional linear sections. In a design based setting we suggest three types of estimators. These are based on isotropic uniform random lines, vertical sections, and non‐isotropic random lines, respectively. Further, we derive estimators of the specific surface tensors associated with a stationary process of convex particles in the model based setting.