Flid-solid multiphase flow simulator using a SPH-DEM coupled method in consideration of liquid bridge force related to water content

Most of the recent natural disasters such as landslide and tsunamis are complex phenomena in which fluid, ground, structures, etc. affect each other. Therefore, it is necessary to study from various mechanical viewpoints. Among them, in this research, we focus on “soilwater mixed phase flow” where fluid and soil affect each other, such as slope failure and ground collapse. In this study, ISPH method is applied for fluid simulation while DEM is applied for modelling of soil behavior. Then, a general-purpose fluid-solid multiphase flow simulator is developed using the ISPH-DEM coupling method. In addition, in DEM analysis, there are problems in consideration of apparent cohesion related to water content. In our analysis method, in order to adapt to unsaturated ground, the liquid bridge force model proposed in the powder technology field

Corrected ALE-ISPH with novel Neumann boundary condition and density-based particle shifting technique

It is well-known in the Smoothed Particle Hydrodynamics (SPH) community that correction in the gradient and Laplacian operators have the potential to drastically increase the accuracy of the method at the expense of computational stability. This paper proposes a stable implementation of such corrections in all derivative operators to the Arbitrary Lagrangian Eulerian incompressible SPH (ALE-ISPH) method, in addition to a novel Neumann boundary condition (BC) applied directly on the velocity (as opposed to traditional BCs where the constraint is applied on the acceleration). In this way, the pressure is solved for both water and wall particles simultaneously, leading to a pressure field that obeys non-penetration BC and divergence-free at the same time. Furthermore, to stabilize the method, we have developed a novel density-based particle shifting technique (PST), specifically designed to deal with incompressible fluids. In this formulation, the numerical density is given as one of the most critical constraint variables. As a result, the proposed density-based PST can maintain the fluid's overall volume for the whole simulation. In addition, it also provides numerical stability as it prevents particle clustering and leads the fluid domain to an isotropic composition. First, we verified the proposed corrected formulation with the novel Neumann BC for both non-penetration and non-slip conditions with the simulation of hydrostatic pressure and Poisenuille flow, respectively. Then, we tested the proposed density-based PST with the rotating square patch problem with results comparable to previous studies. Lastly, we verified the proposed method for the dam break with an obstacle test, a highly dynamic problem

Expression of human Gaucher disease gene GBA generates neurodevelopmental defects and ER stress in Drosophila eye.

Gaucher disease (GD) is the most common of the lysosomal storage disorders and is caused by defects in the GBA gene encoding glucocerebrosidase (GlcCerase). The accumulation of its substrate, glucocylceramide (GlcCer) is considered the main cause of GD. We found here that the expression of human mutated GlcCerase gene (hGBA) that is associated with neuronopathy in GD patients causes neurodevelopmental defects in Drosophila eyes. The data indicate that endoplasmic reticulum (ER) stress was elevated in Drosophila eye carrying mutated hGBAs by using of the ER stress markers dXBP1 and dBiP. We also found that Ambroxol, a potential pharmacological chaperone for mutated hGBAs, can alleviate the neuronopathic phenotype through reducing ER stress. We demonstrate a novel mechanism of neurodevelopmental defects mediated by ER stress through expression of mutants of human GBA gene in the eye of Drosophila

Feeding of ambroxol ameliorates neurodevelopmental defects and ER stress in the mutated hGBA induced <i>Drosophila</i> eye.

<p>Ambroxol can recover morphological defects and decrease ER stress in transgenic flies. (A) Less fluorescence emitted by the eye imaginal discs of hGBA^RecNciI transgenic combinations treated with, than without 1 mM Ambroxol. (B) Values generated by different transgenic combinations at fixed quantities of fluorescence intensity (n = 12–43 eye imaginal discs of third instar larvae per transgenic combination). Error bars represent SE. *Significant difference compared with controls (all without Ambroxol) (***P<0.001; Student's t test). (C) Ambroxol (1 mM) decreases expression levels of dBiP mRNA in the heads of hGBA^RecNciI transgenic combinations (n  =  about 30 fly heads per transgenic combination). Internal control was dRpL32. Error bars represent SE. (D) Eye phenotypes of hGBA^RecNciI transgenic combinations incubated without or with 1 mM Ambroxol. Size and shape of ocelli were uniform, and layout uniformity was more similar to that of normal fly eyes treated with 1 mM Ambroxol. (E) Size histograms of ocelli in hGBA^RecNciI transgenic combinations treated with or without 1 mM Ambroxol. (n = 6–10 flies per transgenic combination; about 400 ocelli each). Dispersion analysis showed significant differences from hGBA^RecNciI transgenic combinations treated with and without 1 mM Ambroxol (F = 2.07–3.35; P<0.001; Levene's test).</p

Neurodevelopmental defects in the <i>Drosophila</i> eye caused by expression of hGBA carrying the RecNciI mutation.

<p>We investigated the effects of overexpression to mutated hGBAs in fly eyes. (A) Phenotype of eyes overexpressing hGBA^WT transgenic combination do not significantly differ from those of GMR control. Phenotype of eyes overexpressing hGBA^R120W transgenic combinations occasionally differed in terms of morphology in some flies compared with control. Eye morphology is obviously affected in hGBA^RecNciI transgenic combinations compared with control. (B) Size histograms of ocelli in transgenic combinations (n = 3–5 flies each, about 100 ocelli each). Dispersion analysis showed obvious differences in variance of the sizes of ocelli between the hGBA^RecNciI transgenic combinations and the GMR control (F = 29.50–37.19; P<0.001; Levene's test).</p

Endoplasmic reticulum (ER) stress detected in the mutated hGBA induced <i>Drosophila</i> eye.

<p>We used xbp1-EGFP as an ER stress marker in which EGFP is expressed in frame only after ER stress <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069147#pone.0069147-Ryoo1" target="_blank">[31]</a>. (A) Weak fluorescence is generated in eye imaginal discs expressing the hGBA^WT construct. The eye imaginal discs of hGBA^R120W transgenic combinations emitted more fluorescence than that of hGBA^WT transgenic combination. The eye imaginal discs of hGBA^RecNciI transgenic combinations emitted the most intense fluorescence. (B) Values generated by different transgenic combinations with fixed quantities of fluorescence intensity (n = 7–15 eye imaginal discs from third instar larvae per transgenic combination). Error bars represent SE. *Significant difference compared with values from GMR control (***P<0.001; Student's t test). (C) Endoplasmic reticulum stress marker gene, dBiP (major ER chaperone) mRNA expression in hGBA^R120W and hGBA^RecNciI transgenic combinations was upregulated (n  =  about 30 fly heads per transgenic combination). Internal control was dRpL32. Error bars represent SE. *Significant difference compared with GMR control (*P<0.05; Student's t test). (D) High levels of hGBAs are expressed in whole bodies of heat-shocked flies. Expression levels of dBiP mRNA of hGBA^R120W and hGBA^RecNciI transgenic combinations were also upregulated (n  =  about 30 flies per transgenic combination). Internal control was dRpL32. Error bars represent SE. *Significant difference compared with hs control (*P<0.05; **P<0.01; ***P<0.001; Student's t test).</p

Generation of transgenic flies carrying hGBA variants.

<p>(A) Sequence of hGBA. Blue and red fonts show R120W and RecNciI mutations, respectively. (B) Expression levels of hGBA mRNA confirmed by quantitative RT-PCR (n  =  about 30 fly heads per transgenic combination) with dRpL32 as internal control. Error bars represent SE. (C) Levels of hGBA protein confirmed by Western blotting (n  =  about 100 fly heads per transgenic combination). Total amounts of hGBA protein were decreased in hGBA^R120W, and significantly decreased in hGBA^RecNciI transgenic combinations, compared with hGBA^WT transgenic combination.</p