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.     

The vibrations of generally orthotropic beams,a finite element approach

This paper presents two finite element models for the prediction of free vibrational natural frequencies of fixed-free beams of general orthotropy. The discrete models include the transverse shear deformation effect and the rotary inertia effect. Numerical studies show that the convergence rate of the approximations calculated from the finite element analysis is dependent on the fibre orientation.     

Solvent complexes of jet-cooled β-phenylethylamine

Laser-induced fluorescence spectroscopy was used to investigate -phenylethylamine molecules that were cooled via supersonic gas expansions. The bare molecule spectra reveal 0-0 transitions that can be attributed to four separate conformers. Upon the addition of water or alcohol solvents, a series of new peaks is induced that appear to be built off separate bare molecule transitions. This is a pattern that is markedly different from the one seen for solvent addition to tyramine, which includes an-OH in the para position. As a result, definite hypotheses can be made to explain the influence of the para-OH in affecting solvent induced conformations.     

Droplet microfluidics

Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of "digital fluidic" operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as microreactors ranging from the nano- to femtoliter range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. This review will focus on the various droplet operations, as well as the numerous applications of the system. Due to advantages unique to droplet-based systems, this technology has the potential to provide novel solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.     

Low energy static Yang-Mills configurations

Non-singular static solutions for the SU(2) Yang-Mills field equations in the presence of external sources are presented. These solutions possess energies less than those of the magnetic dipole solutions, and can in fact have vanishingly small energies.     

Asymptotic Functional Form Preservation Method for the Perturbation Theory: Application to Anharmonic Oscillators

The asymptotic functional form preservation method is developed for the perturbation theory to obtain the energy eigenvalues of anharmonic oscillators. The conventional energy perturbative series expansion for the anharmonic oscillator is strongly divergent even if the anharmonicity is small. Employing a transformation containing an unphysical parameter, we analytically continue this series expansion into a new series expansion applicable to all the range of the perturbation parameter. The unphysical parameter is determined by the principle of minimal sensitivity. This new series expansion is reduced to the conventional energy perturbative series expansion for small anharmonicity, and it preserves the correct asymptotic functional form when the perturbation parameter tends to infinity. Then, we use the full‐range energy series expansion to calculate the energy eigenvalues of the anharmonic oscillator. In addition to excellent energy eigenvalues obtained for the oscillator with small and strong anharmonicity, accurate energy eigenvalues can be obtained using the full‐range energy series expansion when the perturbation parameter tends to infinity.