A Lattice-Boltzmann model for low-Mach reactive flows is presented, built upon our recently published model (Comb & Flame, 196, 2018). The approach is hybrid and couples a Lattice-Boltzmann solver ...for the resolution of mass and momentum conservation and a finite difference solver for the energy and species conservation. Having lifted the constant thermodynamic and transport properties assumptions, the model presented now fully accounts for the classical reactive flow thermodynamic closure: each component is assigned NASA coefficients for calculating its thermodynamic properties. A temperature-dependent viscosity is considered, from which are deduced thermo-diffusive properties via specification of Prandtl and component-specific Schmidt numbers. Another major improvement from our previous contribution is the derivation of an advanced collision kernel compatible of multi-component reactive flows stable in high shear flows. Validation is carried out first on premixed configurations, through simulation of the planar freely propagating flame, the growth of the associated Darrieus-Landau instability and three regimes of flame-vortex interaction. A double shear layer test case including a flow-stabilized diffusion flame is then presented and results are compared with DNS simulations, showing excellent agreement.
The cytotoxin-associated gene (Cag) pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori) that augments cancer risk. CagA translocates into the cytoplasm where it ...stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD) CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat). Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique approach to study H. pylori interaction with the human gastric epithelium. Here, we show that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation.
Breast cancer is one of the most common malignancies in human females in the world. One protein that has elevated enzymatic lipase activity in breast cancers in vitro is phospholipase D (PLD), which ...is also involved in cell migration. We demonstrate that the PLD2 isoform, which was analyzed directly in the tumors, is crucial for cell invasion that contributes critically to the growth and development of breast tumors and lung metastases in vivo. We used three complementary strategies in a SCID mouse model and also addressed the underlying molecular mechanism. First, the PLD2 gene was silenced in highly metastatic, aggressive breast cancer cells (MDA-MB-231) with lentivirus-based short hairpin RNA, which were xenotransplanted in SCID mice. The resulting mouse primary mammary tumors were reduced in size (65%, P<0.05) and their onset delayed when compared with control tumors. Second, we stably overexpressed PLD2 in low-invasive breast cancer cells (MCF-7) with a biscistronic MIEG retroviral vector and observed that these cells were converted into a highly aggressive phenotype, as primary tumors that formed following xenotransplantation were larger, grew faster and developed lung metastases more readily. Third, we implanted osmotic pumps into SCID xenotransplanted mice that delivered two different small-molecule inhibitors of PLD activity (5-fluoro-2-indolyl des-chlorohalopemide and N-2-(4-oxo-1-phenyl-1,3,8-triazaspiro4,5dec-8-yl)ethyl-2-naphthalenecarboxamide). These inhibitors led to significant (>70%, P<0.05) inhibition of primary tumor growth, metastatic axillary tumors and lung metastases. In order to define the underlying mechanism, we determined that the machinery of PLD-induced cell invasion is mediated by phosphatidic acid, Wiscott-Aldrich Syndrome protein, growth receptor-bound protein 2 and Rac2 signaling events that ultimately affect actin polymerization and cell invasion. In summary, this study shows for the first time that PLD2 has a central role in the development, metastasis and level of aggressiveness of breast cancer, raising the possibility that PLD2 could be used as a new therapeutic target.
The canonical interaction between a two-dimensional weak Gaussian disturbance (entropy spot, density spot, weak vortex) with an exothermic/endothermic planar shock wave is studied via the linear ...interaction approximation. To this end, a unified framework based on an extended Kovásznay decomposition that simultaneously accounts for non-acoustic density disturbances along with a poloidal–toroidal splitting of the vorticity mode and for heat release is proposed. An extended version of Chu’s definition for the energy of disturbances in compressible flows encompassing multi-component mixtures of gases is also proposed. This new definition precludes spurious non-normal phenomena when computing the total energy of extended Kovásznay modes. Detailed results are provided for three cases, along with fully general expressions for mixed solutions that combine incoming vortical, entropy and density disturbances.
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