Bingham fluid simulations using a physically consistent particle method

The Bingham fluid simulation model was constructed and validated using a physically consistent particle method, i.e., the Moving Particle Hydrodynamics (MPH) method. When a discrete particle system satisfies the fundamental laws of physics, the method is asserted as physically consistent. Since Bingham fluids sometimes show solid-like behaviors, linear and angular momentum conservation is especially important. These features are naturally satisfied in the MPH method. To model the Bingham feature, the viscosity of the fluid was varied to express the stress-strain rate relation. Since the solid-like part, where the stress does not exceed the yield stress, was modeled with very large viscosity, the implicit velocity calculation was introduced so as to avoid the restriction of the time step width with respect to the diffusion number. As a result, the present model could express the stopping and solid-like behaviors, which are characteristics of Bingham fluids. The proposed method was verified and validated, and its capability was demonstrated through calculations of the two-dimensional Poiseuille flow of a Bingham plastic fluid and the three-dimensional dam-break flow of a Bingham pseudoplastic fluid by comparing those computed results to theory and experiment

KAG-308, a newly-identified EP4-selective agonist shows efficacy for treating ulcerative colitis and can bring about lower risk of colorectal carcinogenesis by oral administration

AbstractAgonists for EP4 receptor, a prostaglandin E2 receptor subtype, appear to be a promising therapeutic strategy for ulcerative colitis (UC) due to their anti-inflammatory and epithelial regeneration activities. However, the clinical development of orally-available EP4 agonists for mild to moderate UC has not yet been reported. Furthermore, the possibility of an increased risk of colitis-associated cancer (CAC) through direct proliferative effects on epithelial cells via EP4 signaling has not been ruled out. Recently, we identified KAG-308 as an orally-available EP4-selective agonist. Here, we investigated the pharmacological and pharmacokinetic profiles of KAG-308. Then, we compared KAG-308 and sulfasalazine (SASP) for their abilities to prevent colitis and promote mucosal healing in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Finally, the effect of KAG-308 treatment on CAC was evaluated in an azoxymethane (AOM)/DSS-induced CAC mouse model. KAG-308 selectively activated EP4 and potently inhibited tumor necrosis factor-α production in peripheral whole blood and T cells. Oral administration of KAG-308, which showed relatively high bioavailability, suppressed the onset of DSS-induced colitis and promoted histological mucosal healing, while SASP did not. KAG-308 also prevented colorectal carcinogenesis by inhibiting colitis development and consequently decreasing mortality in a CAC model, whereas SASP had marginal effects. In contrast, MF-482, an EP4 antagonist, increased mortality. These results indicated that orally-administered KAG-308 suppressed colitis development and promoted mucosal healing. Moreover, it exhibited preventive effects on colorectal carcinogenesis, and thus may be a new therapeutic strategy for the management of UC that confers a reduced risk of colorectal carcinogenesis

A fluid lubrication analysis including negative pressure using a physically consistent particle method

In recent years, particle methods, which are good for moving boundary problems, have become an effective approach to understand and predict flows in complex geometry, such as lubrication behaviors in rolling bearings. This study adopted a physically consistent particle method, i.e., the moving particle hydrodynamics for incompressible flows (MPH-I) method. For capturing the free surface flows in lubrication, a surface tension model was included. In order to maintain the physical consistency in the MPH-I method, the surface tension model expressed with the two density potentials, which are cohesive pressure potential (CPP) and density gradient potential (DGP), was adopted. The MPH-I method with the two-potential-based surface tension model enabled to handle negative pressure and nearly incompressible flow with very large bulk modulus. In fact, the MPH-I method could successfully reproduce fundamental pressure generation effects in the fluid film lubrication, i.e., the wedge film and squeeze film effects. Furthermore, the computed lubrication pressure agreed well with the experimental results and the classic prediction with Reynolds equation. This implies that the present numerical method was validated under the fluid film lubrication problems

De novo DNA methylation independent establishment of maternal imprint on X chromosome in mouse oocytes.

In female mouse embryos, the paternal X chromosome (Xp) is preferentially inactivated during preimplantation development and trophoblast differentiation. This imprinted X-chromosome inactivation (XCI) is partly due to an activating imprint on the maternal X chromosome (Xm), which is set during oocyte growth. However, the nature of this imprint is unknown. DNA methylation is one candidate, and therefore we examined whether disruptions of the two de novo DNA methyltransferases in growing oocytes affect imprinted XCI. We found that accumulation of histone H3 lysine-27 trimethylation, a hallmark of XCI, occurs normally on the Xp, and not on the Xm, in female blastocysts developed from the mutant oocytes. Furthermore, the allelic expression patterns of X-linked genes including Xist and Tsix were unchanged in preimplantation embryos and also in the trophoblast. These results show that a maternal disruption of the DNA methyltransferases has no effect on imprinted XCI and argue that de novo DNA methylation is dispensable for Xm imprinting. This underscores the difference between imprinted XCI and autosomal imprinting