Towards large eddy simulation of dispersed gas -liquid two-phase turbulent flows

This study presents a detailed investigation of all essential components of computational and modeling issues necessary for a successful large-eddy simulation (LES) of dispersed two-phase turbulent flows. In particular, a two-layer concept is proposed to enable the LES capability in two-phase flows involving dispersed bubbles that are relatively large compared to the mesh size. The work comprises three major parts.;Part I focuses on the development and verification of a transient, three-dimensional, finite-volume-method (FVM) based accurate Navier-Stokes solver, named DREAM II (second generation of the DREAM code). Several high-order schemes are implemented for both the spatial and temporal discretization. Solution of the coupled partial differential equations is attacked with a fractional step (projection) method. The developed solver is verified against various benchmarks including Taylor\u27s vortex, free-shear layer, backward-facing step flow and square cavity. A second-order overall accuracy is achieved in both space and time.;Part II concerns the modeling and LES of single-phase turbulent flows. A review of the LES theory and subgrid-scale (SGS) models is presented. Three SGS models, namely, Smagorinsky model, dynamic model and implicit model, are implemented and investigated. Then turbulent channel flow, plane mixing layer, and flow past a square cylinder are simulated, and comparisons of the first-, second-order statistics, and characteristic flow structures are made with direct numerical simulation (DNS) and/or benchmark experiments. The test results show superior quality of the present LES.;Part III delves into the theory, modeling and simulation of dispersed two-phase flow systems. A conceptual review of the characteristics and description of such system is made, considering both Eulerian-Eulerian (E-E) and Eulerian-Lagrangian (E-L) approaches, but with an emphasis on the latter. Various hydrodynamic forces acting on particles or bubbles are summarized and interpreted. Formulations regarding interphase coupling is discussed in depth. Typical computational treatments of modeled two-way couplings in an E-L DNS/LES are reviewed. Issues related to the interpolation are addressed. A general Lagrangian particle-tracking (LPT) program, named PART, is developed and verified using analytical solutions. (Abstract shortened by UMI.)

Uncertainty assessment for CFD using error transport equation

While Computational Fluid Dynamics (CFD) is making extensive use of the power of computational technology, it is also facing a serious problem arising from the so-called numerical uncertainty. The overall uncertainty (or the global error) involved in CFD results can be due to different sources mainly contributed by (i) discretization error (or solution error due to incomplete grid convergence), (ii) iteration convergence error, (iii) grid generation errors (skewness, grid aspect and expansion ratio, coordinate transformation etc.), and (iv) round-off errors. In this study an in-depth discussion concerning these issues is presented with an emphasis on the discretization error in regard with the theoretical background, as well as the commonly used methods for identification and estimation of numerical errors.;The principal goal of this study is to develop a dynamic algorithm that can be used in conjunction with CFD simulation codes to quantify the discretization error in a selected process variable. The focus is on fluid dynamics applications where the conservation equations are solved for primary variables such as velocity, temperature and concentration etc., using finite difference and/or finite volume approach. A transport equation for the error (referred to as the error transport equation) is formulated and solved along with a localized residual estimation based on the modified equation concept. Spatiotemporal evolution of the error distribution is mapped and compared to exact error distributions for various benchmark test cases. A new method is proposed for deriving the error equation specifically aimed at using it with commercial CFD codes that use the finite volume approach. Finally, a blind test is performed on an unsteady 3D scalar transport problem subject to a rotational flow field. Excellent results are obtained in predicting the discretization error

Dysfunction of Bone Marrow Vascular Niche in Acute Graft-Versus-Host Disease after MHC-Haploidentical Bone Marrow Transplantation

<div><p>Acute graft-versus-host disease (aGvHD) is the most common complication of allogeneic hematopoietic stem cell transplantation (HSCT), which is often accompanied by impaired hematopoietic reconstitution. Sinusoidal endothelial cells (SECs) constitute bone marrow (BM) vascular niche that plays an important role in supporting self-renewal capacity and maintaining the stability of HSC pool. Here we provide evidences that vascular niche is a target of aGvHD in a major histocompatibility complex (MHC)–haploidentical matched murine HSCT model. The results demonstrated that hematopoietic cells derived from GvHD mice had the capacity to reconstitute hematopoiesis in healthy recipient mice. However, hematopoietic cells from healthy donor mice failed to reconstitute hematopoiesis in GvHD recipient mice, indicating that the BM niche was impaired by aGvHD in this model. We further demonstrated that SECs were markedly reduced in the BM of aGvHD mice. High level of Fas and caspase-3 expression and high rate of apoptosis were identified in SECs, indicating that SECs were destroyed by aGvHD in this murine HSCT model. Furthermore, high Fas ligand expression on engrafted donor CD4⁺, but not CD8⁺ T cells, and high level MHC-II but not MHC-I expression on SECs, suggested that SECs apoptosis was mediated by CD4⁺ donor T cells through the Fas/FasL pathway.</p></div

Hematopoietic cells derived from GvHD mice are competent for hematopoietic reconstitution (A–E) Continuous transplantation.

<p>Analyses were performed on day 14 after second transplantation. (A) Continuous HSCT: To evaluate the effects of GvHD on hematopoietic cell competency, lethally irradiated C57BL/6 (CD45.2) mice received BM cells(5×10⁶) from either BMT or GvHD recipient mice of [B6.SJL (CD45.1)→CB6F1 (CD45.1/2)] model at 14 days after first transplantation. (B) Representative flow cytometry analysis of.B cells (B220⁺), granulocytes (Gr-1⁺), and monocytes (CD11b⁺) in the recipient BM cells after continuous transplantation. (C) MNC count per tibia. (D) Percentages of B cells, granulocytes and monocytes in MNCs. (E) Counts of B cells, granulocytes and monocytes. (F–L) Competitive transplantation. Analyses were performed on day 30 after second transplantation. (F) Competitive transplantation to further evaluate the competency of hematopoietic cells in GvHD mice: 14 days after the first transplantation, BM cells (2.5×10⁶) from the transplanted mice [B6.SJL (CD45.1)→CB6F1 (CD45.1/2)] were mixed with equal amount (2.5×10⁶) of BM cells from healthy C57BL/6 mice (CD45.2), and transplanted into C57BL/6 recipients (CD45.2) after 8Gy radiotherapy. (G) Total MNC counts and CD45.1 positive cell counts per tibia. (H) Representative flow cytometry profile of HSCs (Lin⁻CD48⁻CD150⁺) analysis. (I) Absolute number of Lin⁻CD48⁻CD150⁺ cells in CD45.1 positive cell. (J) The percentage of Lin⁻CD48⁻CD150⁺ cells in CD45.1 positive cell. (K) and (L) Percentages and absolute number of B cells (B220⁺), granulocytes (Gr-1⁺), and monocytes (CD11b⁺), respectively. All tests were performed on day 30 after transplantation. Data are shown as mean ± SD and from 1 of 3 experiments with similar results. NS: no significant (n = 4, <i>t</i>-test).</p

Impairment of BM hematopoietic niche during GvHD.

<p>(A) Re-transplantation: In order to evaluate the effects of GvHD on BM niche, recipient mice in the GvHD and BMT groups received a second transplantation from healthy C57BL/6 BM cells (CD45.2, 5×10⁵) after 200cGy TBI on days 14 after first transplantation. Hematopoiesis was analyzed on day 14 after re-transplantation. (B) Count of MNCs per tibia (left bars) and the percentage of C57BL/6 donor-derived CD45.2⁺ cells in MNCs (right bars). (C) Absolute number of donor-derived B cells (CD45.2⁺/B220⁺), monocytes (CD45.2⁺/CD11b⁺) and granulocytes (CD45.2⁺/Gr-1⁺). (D) Percentages of donor-derived B cells, monocytes and granulocytes in MNCs. Data are shown as mean ± SD and from 1 of 3 experiments with similar results. *<i>P</i><0.05; **<i>P</i><0.01; NS: no significant (n = 4, <i>t</i>-test).</p

Destruction of vascular niche in acute GvHD.

<p>In order to verify vascular niche is the target of aGvHD, BM SECs from recipient mice were tested by flow cytometric and histological analysis. (A) Representative flow cytometry profile of SECs (Sca-1-VEGFR2+VEGFR3+). (B) Absolute number of BM SECs per tibia. (C) Percentages of BM SECs in MNCs. (D) HE and Immunohistochemistry analysis of disrupted vascular niche in acute GvHD vs BMT control. Arrows indicate SECS. (E) Representative flow cytometry analysis to assess apoptosis SECs. (F) Apoptosis of SECs, expressed by Annexin V⁺/PI⁻ and Annexin V⁺/PI⁺ to SSC^low/VEGFR3⁺. (G and H) Proliferation assay of SECs by measuring Ki67 by flow cytometry and percentage of proliferating SECs (VEGFR3⁺/Ki-67⁺ cells) in MNCs. Data are shown as mean ± SD and from 1 of 3 experiments with similar results. **<i>P</i><0.01 (n = 4, <i>t</i>-test).</p

Dysfunction of vascular niche in acute GvHD.

<p>To evaluate the expression of CXCR4/SDF-1 and SCF/c-Kit in BM cells, flow cytometry and RT-PCR analysis were performed at 14 days after transplantation. (A) Representative flow cytometry profile of CXCR4 expression in Lin⁻CD48⁻CD150⁺ cells. (B–D): Analysis of CXCR4/SDF-1 and SCF/c-Kit pathways. (B) Percentage of CXCR4⁺ cells in HSCS. (C) Percentage of SDF-1⁺ cells in VEGFR3⁺ endothelial cells. (D) RT-PCR for measuring the expression of SCF in sorted BM SECs. Data are shown as mean ± SD. Experiments were performed at least twice. *<i>P</i><0.05; **<i>P</i><0.01; NS: no significant (n = 4 for CXCR4/SDF-1 analysis and n = 3 for SCF/C-Kit analysis, <i>t</i>-test).</p

MHC-haploidentical murine GvHD model and suppression of hematopoiesis during GvHD.

<p>(A) A MHC-haploidentical murine GVHD model was established by transplanting BM cells (5×10⁶) plus splenocyts (6×10⁷) from B6.SJL donor mice (CD45.1) into lethally irradiated CB6F1 recipient mice (CD45.1/2) [B6.SJL (CD45.1)→CB6F1 (CD45.1/2)]. Recipent mice received BM cells alone as control groups. (B) Survival of mice receiving HSCT with donor BM plus splenocytes or donor BM only (<i>P</i><0.05, Log-rank test). (C) Body weight of mice receiving HSCT (N = 20 in each group on day 3; n = 4 in GvHD and n = 20 in BMT respectively on day 21 post-transplantation). (D) Engraftment of donor-derived cells after HSCT in a GvHD mouse. (E–G) Kinetics of WBC, Hgb, and platelet counts after HSCT. (H) MNCs count on day 14 and day 21 after HSCT. (I) Count of Lin⁻/CD48⁻/CD150⁺ cells after HSCT. (J) Percentage of Lin⁻/CD48⁻/CD150⁺ cells in MNCs after HSCT. Data are shown as mean ± SD and from 1 of 3 experiments with similar results. *<i>P</i><0.05; **<i>P</i><0.01 (n = 4, <i>t</i>-test).</p

CD4⁺ T-cell mediated vascular niche damage in GvHD.

<p>(A) Percentages of CD4⁺ and CD8⁺ donor T cells in MNCs in BM at 14 days after transplantation. (B) MHC-II expression in BM SECs. (C) MHC-I expression in BM SECs. (D) Representative flow cytometry profile of Fas expression in BM SECs. (E) Percentages of Fas⁺ cells in SECs. (F) Expression of Fas and caspase-3 in BM SECs measured by RT-PCR. (G) Representative flow cytometry profile of caspase-3 expression in BM SECs. (H) Percentages of caspase-3 positive cells in SECs. (I) Representative flow cytometry of FasL in donor CD4⁺ T cells. (J) Percentages of FasL⁺ CD4⁺ donor T cells in MNCs. Data are shown as mean ± SD and from 1 of 3 experiments with similar results (Only one experiment for caspase-3 expression). **<i>P</i><0.01; NS: no significant (n = 4, <i>t</i>-test).</p