Prediction of Low-Dose Aspirin-Induced Gastric Toxicity Using Nuclear Magnetic Resonance Spectroscopy-Based Pharmacometabolomics in Rats

Background: Low-dose aspirin (LDA) is the backbone for secondary prevention of coronary artery disease, although limited by gastric toxicity. This study aimed to identify novel metabolites that could predict LDA-induced gastric toxicity using pharmacometabolomics. Methods: Pre-dosed urine samples were collected from male Sprague-Dawley rats. The rats were treated with either LDA (10 mg/kg) or 1% methylcellulose (10 mL/kg) per oral for 28 days. The rats’ stomachs were examined for gastric toxicity using a stereomicroscope. The urine samples were analyzed using a proton nuclear magnetic resonance spectroscopy. Metabolites were systematically identified by exploring established databases and multivariate analyses to determine the spectral pattern of metabolites related to LDA-induced gastric toxicity. Results: Treatment with LDA resulted in gastric toxicity in 20/32 rats (62.5%). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) model displayed a goodness-of-fit (R²Y) value of 0.947, suggesting near-perfect reproducibility and a goodness-of-prediction (Q²Y) of −0.185 with perfect sensitivity, specificity and accuracy (100%). Furthermore, the area under the receiver operating characteristic (AUROC) displayed was 1. The final OPLS-DA model had an R²Y value of 0.726 and Q²Y of 0.142 with sensitivity (100%), specificity (95.0%) and accuracy (96.9%). Citrate, hippurate, methylamine, trimethylamine N-oxide and alpha-keto-glutarate were identified as the possible metabolites implicated in the LDA-induced gastric toxicity. Conclusion: The study identified metabolic signatures that correlated with the development of a low-dose Aspirin-induced gastric toxicity in rats. This pharmacometabolomic approach could further be validated to predict LDA-induced gastric toxicity in patients with coronary artery disease.     

Coupled frequencies of a rectangular hydroelastic system with two fluids

This paper deals with the study of behaviour of an idealized 2D hydroelastic system involving two inviscid liquids with an elastic rectangular container. The main objective is to investigate the influence of the physical parameters on eigenfrequencies and eigenmodes of the system. The study extends the previous results obtained for hydroelastic systems with one fluid. The governing equations describing the behaviour of the system are analyzed by using the concept of normal modes and their solutions presented in the form of infinite series. The expansion coefficients for the velocity potentials are calculated by employing a new inner product that allows the orthogonalisation of the normal modes. An eigenfrequency equation is then derived from the existence condition of a nontrivial solution. The numerical calculations are performed by varying only some relevant parameters.     

Stereoselective synthesis of (2E) 3‐amino‐2‐(1H‐benzimidazol‐2‐yl)acrylate and symmetric bisacrylates by transamination reactions

A range of various amines 2(a–i) was tested in transamination reactions using ethyl 2‐(1H‐benzimidazol‐2‐yl)‐3‐dimethylamino‐acrylate 1a. The (E)‐s‐cis/trans conformation of some representative products 4 was analyzed by ¹H and ¹³C NMR spectra. The C‐2/C‐3 bond of the compounds 3(a–i) is strongly polarized by a push‐pull effect. In the same manner, reactions of ethyl 2‐(benzoxazol‐2‐yl)‐3‐dimethylamino‐acrylate 1c with 1,4‐diaminobenzene 2i, ethylenediamine 2i, and 1,5‐diaminomaphthalene 2k have been investigated and gave directly the corresponding symmetric bis‐acrylates 4(a–c) in good yields. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 446–454, 1999     

Dynamics of multicomponent polymer mixtures: theoretical models

Theoretical models describing the dynamics of multicomponent polymer mixtures are reviewed. Some detailed derivations are shown to make the basic assumptions clear and to ease the comparison between these models. The effects of random noise and memory functions on the time evolution of dynamical correlation functions are examined. The long-range hydrodynamic interactions or mode-coupling effects are also included. A possible extension of these models to the kinetics of spinodal decomposition in solutions of polymer mixtures is briefly discussed.     

On the extremal values of the second largest Q-eigenvalue

We study extremal graphs for the extremal values of the second largest Q-eigenvalue of a connected graph. We first characterize all simple connected graphs with second largest signless Laplacian eigenvalue at most 3. The second part of the present paper is devoted to the study of the graphs that maximize the second largest Q-eigenvalue. We construct families of such graphs and prove that some of theses families are minimal for the fact that they maximize the second largest signless Laplacian eigenvalue.     

Large deviations from a macroscopic scaling limit for particle systems with Kac interaction and random potential

We consider a lattice gas in a periodic d-dimensional lattice of width γ⁻¹, γ>0, interacting via a Kac's type interaction, with range and strength γ^d, and under the influence of a random one body potential given by independent, bounded, random variables with translational invariant distribution. The system evolves through a conservative dynamics, i.e. particles jump to nearest neighbor empty sites, with rates satisfying detailed balance with respect to the equilibrium measures. In [M. Mourragui, E. Orlandi, E. Saada, Macroscopic evolution of particles systems with random field Kac interactions, Nonlinearity 16 (2003) 2123–2147] it has been shown that rescaling space as γ⁻¹ and time as γ⁻², in the limit γ→0, for dimensions d3, the macroscopic density profile ρ satisfies, a.s. with respect to the random field, a non-linear integral partial differential equation, having the diffusion matrix determined by the statistical properties of the external random field. Here we show an almost sure (with respect to the random field) large deviations principle for the empirical measures of such a process. The rate function, which depends on the statistical properties of the external random field, is lower semicontinuous and has compact level sets.     

Indefinite Stochastic Linear Quadratic Control with Markovian Jumps in Infinite Time Horizon

This paper studies a stochastic linear quadratic (LQ) control problem in the infinite time horizon with Markovian jumps in parameter values. In contrast to the deterministic case, the cost weighting matrices of the state and control are allowed to be indinifite here. When the generator matrix of the jump process – which is assumed to be a Markov chain – is known and time-invariant, the well-posedness of the indefinite stochastic LQ problem is shown to be equivalent to the solvability of a system of coupled generalized algebraic Riccati equations (CGAREs) that involves equality and inequality constraints. To analyze the CGAREs, linear matrix inequalities (LMIs) are utilized, and the equivalence between the feasibility of the LMIs and the solvability of the CGAREs is established. Finally, an LMI-based algorithm is devised to slove the CGAREs via a semidefinite programming, and numerical results are presented to illustrate the proposed algorithm.