Coupled Simulation of Seismic Wave Propagation and Failure Phenomena by Use of an MPS Method

The failure of brittle materials, for example glasses and rock masses, is commonly observed to be discontinuous. It is, however, difficult to simulate these phenomena by use of conventional numerical simulation methods, for example the finite difference method or the finite element method, because of the presence of computational grids or elements artificially introduced before the simulation. It is, therefore, important for research on such discontinuous failures in science and engineering to analyze the phenomena seamlessly. This study deals with the coupled simulation of elastic wave propagation and failure phenomena by use of a moving particle semi-implicit (MPS) method. It is simple to model the objects of analysis because no grid or lattice structure is necessary. In addition, lack of a grid or lattice structure makes it simple to simulate large deformations and failure phenomena at the same time. We first compare analytical and MPS solutions by use of Lamb’s problem with different offset distances, material properties, and source frequencies. Our results show that analytical and numerical seismograms are in good agreement with each other for 20 particles in a minimum wavelength. Finally, we focus our attention on the Hopkinson effect as an example of failure induced by elastic wave propagation. In the application of the MPS, the algorithm is basically the same as in the previous calculation except for the introduction of a failure criterion. The failure criterion applied in this study is that particle connectivity must be disconnected when the distance between the particles exceeds a failure threshold. We applied the developed algorithm to a suspended specimen that was modeled as a long bar consisting of thousands of particles. A compressional wave in the bar is generated by an abrupt pressure change on one edge. The compressional wave propagates along the interior of the specimen and is visualized clearly. At the other end of the bar, the spalling of the bar is reproduced numerically, and a broken piece of the bar is formed and falls away from the main body of the bar. Consequently, these results show that the MPS method effectively reproduces wave propagation and failure phenomena at the same time

Pharmacological Inhibition of Monoacylglycerol O-Acyltransferase 2 Improves Hyperlipidemia, Obesity, and Diabetes by Change in Intestinal Fat Utilization

<div><p>Monoacylglycerol O-acyltransferase 2 (MGAT2) catalyzes the synthesis of diacylglycerol (DG), a triacylglycerol precursor and potential peripheral target for novel anti-obesity therapeutics. High-throughput screening identified lead compounds with MGAT2 inhibitory activity. Through structural modification, a potent, selective, and orally bioavailable MGAT2 inhibitor, compound A (compA), was discovered. CompA dose-dependently inhibited postprandial increases in plasma triglyceride (TG) levels. Metabolic flux analysis revealed that compA inhibited triglyceride/diacylglycerol resynthesis in the small intestine and increased free fatty acid and acyl-carnitine with shorter acyl chains than originally labelled fatty acid. CompA decreased high-fat diet (HFD) intake in C57BL/6J mice. MGAT2-null mice showed a similar phenotype as compA-treated mice and compA did not suppress a food intake in MGAT2 KO mice, indicating that the anorectic effects were dependent on MGAT2 inhibition. Chronic administration of compA significantly prevented body weight gain and fat accumulation in mice fed HFD. MGAT2 inhibition by CompA under severe diabetes ameliorated hyperglycemia and fatty liver in HFD-streptozotocin (STZ)-treated mice. Homeostatic model assessments (HOMA-IR) revealed that compA treatment significantly improved insulin sensitivity. The proximal half of the small intestine displayed weight gain following compA treatment. A similar phenomenon has been observed in Roux-en-Y gastric bypass-treated animals and some studies have reported that this intestinal remodeling is essential to the anti-diabetic effects of bariatric surgery. These results clearly demonstrated that MGAT2 inhibition improved dyslipidemia, obesity, and diabetes, suggesting that compA is an effective therapeutic for obesity-related metabolic disorders.</p></div

Effect of compound A (compA) on postprandial triglyceride (TG) excursion.

<p>Fasted C57BL/6J mice were given a liquid meal orally with intraperitoneal injection of Pluronic F-127 to inhibit plasma TG lipolysis. (A) Structure of compA. Plasma samples were collected at 0, 2, and 4 h after oral gavage of a liquid meal. (B) Time course of changes in plasma chylomicron TG (CM/TG) levels and (C) postprandial TG excursion of 3 or 10 mg/kg compA at 6 h after dosing. (D) Time course of changes in plasma TG levels and (E) postprandial TG excursion of 30 mg/kg compA at 16 h after dosing. n = 6 (B, C), and n = 7 (D, E). #: <i>P</i> < 0.025 vs. vehicle group by one-tailed Williams’ test. **: <i>P</i> < 0.01, ***: <i>P</i> < 0.001 vs. vehicle group by Student’s t-test.</p