Development of a computational platform for the simulation of low Prandtl number turbulent flows

Mathematical modeling of physical phenomena is at the basis of many scientific field researches. Complex systems show multiscale and multiphysics aspects that cannot be always taken into account in detail. In the past many numerical codes have been developed and specialized to solve different aspects of turbulence and, in general, fluid motion for a very wide range of engineering applications. Nowadays, numerical code coupling and computational platforms are gaining a lot of interest for the simulation of very complex phenomena. This PhD study focuses on modeling physical systems with coupled simulations, in particular turbulent heat transfer for liquid metals. This type of fluids, known as low Prandtl number fluids, requires more sophisticated turbulent heat transfer models since those used to simulate fluids such as air or water lead to a sensible heat transfer overestimation. Seeking an increased numerical stability, a four logarithmic parameter turbulence model is proposed, starting from a model that has already been validated with simulations of Lead-Bismuth-Eutectic (LBE) fully developed turbulent flows. The turbulence model has been implemented in the finite element code FEMuS to perform an extensive validation by comparing obtained results with Direct Numerical Simulations and experimental data. Many simulations are performed, for fully developed turbulent flows in plane channels, cylindrical pipes and 19 pin nuclear reactor bundles and for turbulent forced and mixed convection over a backward facing step. When conservation equations of mass, momentum and energy need be coupled with dynamic two-equation or thermal turbulence four-equation models the use of numerical coupling becomes important. In order to dispose of a greater choice of dynamical turbulence models, a computational platform containing OpenFOAM and FEMuS codes has been developed

Simulation of TALL-3D experimental facility with a multiscale and multiphysics computational platform

This work details the development of a computational platform in joint collaboration between the Italian National Agency for New Technologies, Energy and Sustainable Economic Development (enea) and the University of Bologna (unibo). The platform is based on the open-source SALOME software that integrates the CATHARE system code for nuclear safety, FEMUS and OpenFOAM CFD codes in a unique framework, with efficient methods for data exchange. The computational platform has been used to simulate complex multiscale and multiphysics systems, such as the tall-3d facility, with a defective boundary condition approach on overlapping domains. The tall-3d experimental facility has been realized with the purpose of providing reference results to be used for both standalone and coupled System Thermal-Hydraulic (STH) and Computational Fluid Dynamic (CFD) code validation. The transient phenomenon of unprotected loss of lead-bismuth eutectic (LBE) flow that has been experimentally simulated at tall-3d is here studied. The system code is used to simulate the tall-3d apparatus while the CFD code is used to get a better insight into the fluid streaming occurring in the main tank component and improve the system code predictions. A flow transition from forced to natural convection is used to validate the codes and the platform ability to reproduce the experimental data

FEMuS-Platform: a numerical platform for multiscale and multiphysics code coupling

Nowadays, many open-source numerical codes are available to solve physical problems in structural mechanics, fluid flow, heat transfer, and neutron diffusion. However, even if these codes are often highly specialized in the numerical simulation of a particular type of physics, none of them allows simulating complex systems involving all the physical problems mentioned above. In this work we present a numerical framework, based on the SALOME platform, developed to perform multiscale and multiphysics simulations involving all the mentioned physical problems. In particular, the developed numerical platform includes the multigrid finite element in-house code FEMuS for heat transfer, fluid flow, turbulence and fluid-structure modeling; the open-source finite volume CFD software OpenFOAM; the multiscale neutronic code DONJON-DRAGON; and a system-scale code used for thermal-hydraulic simulations. Efficient data exchange among these codes is performed within computer memory by using the MED libraries, provided by the SALOME platform

A Logarithmic Turbulent Heat Transfer Model in Applications with Liquid Metals for Pr = 0.01–0.025

The study of turbulent heat transfer in liquid metal flows has gained interest because of applications in several industrial fields. The common assumption of similarity between the dynamical and thermal turbulence, namely, the Reynolds analogy, has been proven to be invalid for these fluids. Many methods have been proposed in order to overcome the difficulties encountered in a proper definition of the turbulent heat flux, such as global or local correlations for the turbulent Prandtl number and four parameter turbulence models. In this work we assess a four parameter logarithmic turbulence model for liquid metals based on the Reynolds Averaged Navier-Stokes (RAN) approach. Several simulation results considering fluids with P r = 0.01 and P r = 0.025 are reported in order to show the validity of this approach. The Kays turbulence model is also assessed and compared with integral heat transfer correlations for a wide range of Peclet numbers

HB-EGF–EGFR Signaling in Bone Marrow Endothelial Cells Mediates Angiogenesis Associated with Multiple Myeloma

Epidermal growth factor receptor (EGFR) and its ligand heparin-binding EGF-like growth factor (HB-EGF) sustain endothelial cell proliferation and angiogenesis in solid tumors, but little is known about the role of HB-EGF–EGFR signaling in bone marrow angiogenesis and multiple myeloma (MM) progression. We found that bone marrow endothelial cells from patients with MM express high levels of EGFR and HB-EGF, compared with cells from patients with monoclonal gammopathy of undetermined significance, and that overexpressed HB-EGF stimulates EGFR expression in an autocrine loop. We also found that levels of EGFR and HB-EGF parallel MM plasma cell number, and that HB-EGF is a potent inducer of angiogenesis in vitro and in vivo. Moreover, blockade of HB-EGF–EGFR signaling, by an anti-HB-EGF neutralizing antibody or the EGFR inhibitor erlotinib, limited the angiogenic potential of bone marrow endothelial cells and hampered tumor growth in an MM xenograft mouse model. These results identify HB-EGF–EGFR signaling as a potential target of anti-angiogenic therapy, and encourage the clinical investigation of EGFR inhibitors in combination with conventional cytotoxic drugs as a new therapeutic strategy for MM

High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment

Multiple myeloma (MM) is a genetically heterogeneous disease that includes a subgroup of 10–15% of patients facing dismal survival despite the most intensive treatment. Despite improvements in biological knowledge, MM is still an incurable neoplasia, and therapeutic options able to overcome the relapsing/refractory behavior represent an unmet clinical need. The aim of this review is to provide an integrated clinical and biological overview of high-risk MM, discussing novel therapeutic perspectives, targeting the neoplastic clone and its microenvironment. The dissection of the molecular determinants of the aggressive phenotypes and drug-resistance can foster a better tailored clinical management of the high-risk profile and therapy-refractoriness. Among the current clinical difficulties in MM, patients’ management by manipulating the tumor niche represents a major challenge. The angiogenesis and the stromal infiltrate constitute pivotal mechanisms of a mutual collaboration between MM and the non-tumoral counterpart. Immuno-modulatory and anti-angiogenic therapy hold great efficacy, but variable and unpredictable responses in high-risk MM. The comprehensive understanding of the genetic heterogeneity and MM high-risk ecosystem enforce a systematic bench-to-bedside approach. Here, we provide a broad outlook of novel druggable targets. We also summarize the existing multi-omics-based risk profiling tools, in order to better select candidates for dual immune/vasculogenesis targeting

Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores the angiogenic homeostasis and suppresses tumor progression

Interactions of malignant multiple myeloma (MM) plasma cells (MM-cells) with the microenvironment control MM-cell growth, survival, drug-resistance and dissemination. As in MM microvascular density increases in the bone marrow (BM), we investigated whether BM MM endothelial cells (MMECs) control disease progression via the junctional adhesion molecule A (JAM-A). Membrane and cytoplasmic JAM-A levels were upregulated in MMECs in 111 newly diagnosed (NDMM) and 201 relapsed-refractory (RRMM) patients compared to monoclonal gammopathy of undetermined significance (MGUS) and healthy controls. Elevated membrane expression of JAM-A on MMECs predicted poor clinical outcome. Mechanistically, addition of recombinant JAM-A to MMECs increased angiogenesis whereas its inhibition impaired angiogenesis and MM growth in 2D and 3D in vitro cell culture and chorioallantoic membrane-assays. To corroborate these findings, we treated MM bearing mice with JAM-A blocking mAb and demonstrated impaired MM progression corresponding to decreased MM-related vascularity. These findings support JAM-A as an important mediator of MM progression through facilitating MM-associated angiogenesis. Collectively, elevated JAM-A expression on bone marrow endothelial cells is an independent prognostic factor for patient survival in both NDMM and RRMM. Blocking JAM-A restricts angiogenesis in vitro, in embrio and in vivo and represents a suitable druggable molecule to halt neoangiogenesis and MM progression