An unusual nicotinamide derivative, 4-pyridone-3-carboxamide ribonucleoside (4PYR), is a novel endothelial toxin and oncometabolite

Our recent studies identified a novel pathway of nicotinamide metabolism that involves 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) and demonstrated its endothelial cytotoxic effect. This study tested the effects of 4PYR and its metabolites in experimental models of breast cancer. Mice were divided into groups: 4T1 (injected with mammary 4T1 cancer cells), 4T1 + 4PYR (4PYR-treated 4T1 mice), and control, maintained for 2 or 21 days. Lung metastasis and endothelial function were analyzed together with blood nucleotides (including 4PYR), plasma amino acids, nicotinamide metabolites, and vascular ectoenzymes of nucleotide catabolism. 4PYR metabolism was also evaluated in cultured 4T1, MDA-MB-231, MCF-7, and T47D cells. An increase in blood 4PYR in 4T1 mice was observed at 2 days. 4PYR and its metabolites were noticed after 21 days in 4T1 only. Higher blood 4PYR was linked with more lung metastases in 4T1 + 4PYR vs. 4T1. Decreased L-arginine, higher asymmetric dimethyl-L-arginine, and higher vascular ecto-adenosine deaminase were observed in 4T1 + 4PYR vs. 4T1 and control. Vascular relaxation caused by flow-dependent endothelial activation in 4PYR-treated mice was significantly lower than in control. The permeability of 4PYR-treated endothelial cells was increased. Decreased nicotinamide but enhanced nicotinamide metabolites were noticed in 4T1 vs. control. Reduced N-methylnicotinamide and a further increase in Met2PY were observed in 4T1 + 4PYR vs. 4T1 and control. In cultured breast cancer cells, estrogen and progesterone receptor antagonists inhibited the production of 4PYR metabolites. 4PYR formation is accelerated in cancer and induces metabolic disturbances that may affect cancer progression and, especially, metastasis, probably through impaired endothelial homeostasis. 4PYR may be considered a new oncometabolite.Subject terms: Mechanisms of disease, Pathogenesis, Breast cancer     

On the Statistical Discrepancy and Affinity of Priority Vector Heuristics in Pairwise-Comparison-Based Methods

There are numerous priority deriving methods (PDMs) for pairwise-comparison-based (PCB) problems. They are often examined within the Analytic Hierarchy Process (AHP), which applies the Principal Right Eigenvalue Method (PREV) in the process of prioritizing alternatives. It is known that when decision makers (DMs) are consistent with their preferences when making evaluations concerning various decision options, all available PDMs result in the same priority vector (PV). However, when the evaluations of DMs are inconsistent and their preferences concerning alternative solutions to a particular problem are not transitive (cardinally), the outcomes are often different. This research study examines selected PDMs in relation to their ranking credibility, which is assessed by relevant statistical measures. These measures determine the approximation quality of the selected PDMs. The examined estimates refer to the inconsistency of various Pairwise Comparison Matrices (PCMs)—i.e., W = (w_ij), w_ij > 0, where i, j = 1,…, n—which are obtained during the pairwise comparison simulation process examined with the application of Wolfram’s Mathematica Software. Thus, theoretical considerations are accompanied by Monte Carlo simulations that apply various scenarios for the PCM perturbation process and are designed for hypothetical three-level AHP frameworks. The examination results show the similarities and discrepancies among the examined PDMs from the perspective of their quality, which enriches the state of knowledge about the examined PCB prioritization methodology and provides further prospective opportunities.     

Vibration of a Beam on Random and Microperiodic Subsoil Caused by Moving Load

The subject of the analysis is a vibration problem of an infinitive beam resting on a foundation with periodic and stochastic parameters under a stochastic moving load. The problem is solved using the Tolerance Averaging Approximation procedure and also concept of a stochastic dynamic influence function. In this way we obtained an effective solution which may be applied in the railway engineering. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

From Colloidal Dispersions of Zeolite Monolayers to Effective Solid Catalysts in Transformations of Bulky Organic Molecules: Role of Freeze-Drying and Dialysis

We investigated the properties and catalytic activity of zeolites with MWW topology obtained by unprecedented liquid exfoliation of the MCM-56 zeolite into solutions of monolayers and isolation/reassembly of the dispersed layers by various methods, with optional purification by dialysis or ammonium exchange. The layers were recovered by flocculation with alcohol or ammonium nitrate and freeze-drying. Flocculation alone, even with ammonium nitrate, did not ensure removal of residual sodium cations resulting in catalysts with low activity. Dialysis of the solutions with dispersed monolayers proved to be efficient in removing sodium cations and preserving microporosity. The monolayers were also isolated as solids by freeze-drying. The highest BET area and pore volume obtained with the freeze-dried sample confirmed lyophilization efficiency in preserving layer structure. The applied test reaction, Friedel–Crafts alkylation of mesitylene, showed high benzyl alcohol conversion due to increased concentration of accessible acid centers caused by the presence of secondary mesoporosity. The applied treatments did not change the acid strength of the external acid sites, which are the most important ones for converting bulky organic molecules. Zeolite acidity was not degraded in the course of exfoliation into monolayers, showing the potential of such colloid dispersions for the formation of active catalysts.     

Inductive charge dispersal in the solvolysis of 2-exo- and 2-endo-norbornyl toluenesulfonates.

The effect of substituents at C4, 5, 6 and 7 on solvolysis rates and products of 2-exo- and 2-endo-norbornyl tosylates confirms that differential carbon participation is responsible for varying exo/endo rate and product ratios.     

Crystal and molecular structure of phenylbenzyl-1-(2,2,3-trimethylcyclopropyl)phosphine oxide

The title compound crystallizes in the orthorhombic space groupPna2₁, witha=15.576(2),b=19.134(3),c=5.693(1) Å andz=4. The structure was solved by direct methods, and refined to a finalR value of 0.059. This study confirms both the structure and stereochemistry of the title compound.     

Hidden symmetry and correlated states of electrons and holes in quantum dots

We describe hidden symmetry and its application to the construction of exact correlated states of electrons and holes in quantum dots. The hidden symmetry is related to degenerate single particle energy shells and symmetric interactions. Both can be engineered in a quantum dot. We focus on hidden symmetry involving spin singlet pairing of electrons and spin singlet pairing of holes. Detailed calculations for a third shell are presented to illustrate the mechanism of pairing.     

A note on the asymptotic expansion of Feynman amplitudes

Employing the technique given by Bergere and Lam, we determine the asymptotic expansion of Feynman amplitude (in the Schwinger integral representation) when the masses of any subset of internal lines tend to zero.