Alessandra Nigro

A discontinuous Galerkin method for inviscid low Mach number flows

In this work we extend the high-order discontinuous Galerkin (DG) finite element method to inviscid low Mach number flows. The method here presented is designed to improve the accuracy and efficiency of the solution at low Mach numbers using both explicit and implicit schemes for the temporal discretization of the compressible Euler equations. The algorithm is based on a classical preconditioning technique that in general entails modifying both the instationary term of the governing equations and the dissipative term of the numerical flux function (full preconditioning approach). In the paper we show that full preconditioning is beneficial for explicit time integration while the implicit scheme turns out to be efficient and accurate using just the modified numerical flux function. Thus the implicit scheme could also be used for time accurate computations. The performance of the method is demonstrated by solving an inviscid flow past a NACA0012 airfoil at different low Mach numbers using various degrees of polynomial approximations. Computations with and without preconditioning are performed on different grid topologies to analyze the influence of the spatial discretization on the accuracy of the DG solutions at low Mach numbers.

Up to sixth-order accurate A-stable implicit schemes applied to the Discontinuous Galerkin discretized Navier–Stokes equations

Abstract In this paper a high-order implicit multi-step method, known in the literature as Two Implicit Advanced Step-point (TIAS) method, has been implemented in a high-order Discontinuous Galerkin (DG) solver for the unsteady Euler and Navier–Stokes equations. Application of the absolute stability condition to this class of multi-step multi-stage time discretization methods allowed to determine formulae coefficients which ensure A-stability up to order 6. The stability properties of such schemes have been verified by considering linear model problems. The dispersion and dissipation errors introduced by TIAS method have been investigated by looking at the analytical solution of the oscillation equation. The performance of the high-order accurate, both in space and time, TIAS-DG scheme has been evaluated by computing three test cases: an isentropic convecting vortex under two different testing conditions and a laminar vortex shedding behind a circular cylinder. To illustrate the effectiveness and the advantages of the proposed high-order time discretization, the results of the fourth- and sixth-order accurate TIAS schemes have been compared with the results obtained using the standard second-order accurate Backward Differentiation Formula, BDF2, and the five stage fourth-order accurate Strong Stability Preserving Runge–Kutta scheme, SSPRK4.

Time Integration in the Discontinuous Galerkin Code MIGALE - Unsteady Problems

This chapter presents recent developments of a high-order Discontinuous Galerkin (DG) method to deal with unsteady simulation of turbulent flows by using high-order implicit time integration schemes. The approaches considered during the IDIHOM project were the Implicit Large Eddy Simulation (ILES), where no explicit subgrid-scale (SGS) model is included and the DG discretization itself acts like a SGS model, and two hybrid approaches between Reynolds-averaged Navier- Stokes (RANS) and Large Eddy Simulation (LES) models, namely the Spalart-Allmaras Detached Eddy Simulation (SA-DES) and the eXtra- Large Eddy Simulation (X-LES). Accurate time integration is based on high-order linearly implicit Rosenbrock-type Runge-Kutta schemes, implemented in the DG code MIGALE up to sixth-order accuracy. Several high-order DG results of both incompressible and compressible 3D turbulent test cases proposed within the IDIHOM project demonstrate the capability of the method.

Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells.

BackgroundBergapten (5-methoxypsoralen), a natural psoralen derivative present in many fruits and vegetables, has shown antitumoral effects in a variety of cell types. In this study, it has been addressed how Bergapten in breast cancer cells induces autophagic process.ResultsIn MCF7 and ZR-75 breast cancer cells Bergapten exhibited anti-survival response by inducing the autophagic process increasing Beclin1, PI3KIII, UVRAG, AMBRA expression and conversion of LC3-I to LC3-II. LC3-GFP, Acridine orange assay and transmission electron microscopy even confirmed the increased autophagosome formations in treated cells. Bergapten-induced autophagy is dependent by PTEN up-regulation, since silencing this gene, the induction of Beclin1 and the p-AKT/p-mTOR signal down-regulation were reversed. PTEN is transcriptionally regulated by Bergapten through the involvement of p38MAPK/NF-Y, as evidenced by the use of p38MAPK inhibitor SB203580, site-direct mutagenesis of NF-Y element and NF-Y siRNA. Furthermore NF-Y knockdown prevented Bergapten-induced acid vesicular organelle accumulations (AVOs), strengthening the role of this element in mediating autophagy.ConclusionsOur data indicate PTEN as a key target of Bergapten action in breast cancer cells for the induction of autophagy. These findings add further details on the mechanism of action of Bergapten, therefore suggesting that phytochemical compounds may be implemented in the novel strategies for breast cancer treatment.

Numerical and Experimental Analysis of the Intake Flow in a High Performance Four-Stroke Motorcycle Engine: Influence of the Two-Equation Turbulence Models

An experimental and numerical analysis of the intake system of a production high performance four-stroke motorcycle engine was carried out. The aim of the work was to characterize the fluid dynamic behavior of the engine during the intake phase and to evaluate the capability of the most commonly used two-equation turbulence models to reproduce the in-cylinder flow field for a very complex engine head. Pressure and mass flow rates were measured on a steady-flow rig. Furthermore, velocity measurements were obtained within the combustion chamber using laser Doppler anemometry (LDA). The experimental data were compared to the numerical results using four two-equation turbulence models (standard k-e, realizable k-e, Wilcox k-w, and SST k-ω models). All the investigated turbulence models well predicted the global performances of the intake system and the mean flow structure inside the cylinder. Some differences between measurements and computations were found close to the cylinder head while an improving agreement was evident moving away from the engine head. Furthermore, the Wilcox k-w model permitted the flow field inside the combustion chamber of the engine to be reproduced and the overall angular momentum of the flux with respect to the cylinder axis to be quantified more properly.

Recombinant Arabidopsis HSP70 Sustains Cell Survival and Metastatic Potential of Breast Cancer Cells

The chaperone HSP70 protein is widely present in many different tumors and its expression correlates with an increased cell survival, low differentiation, and poor therapeutic outcome in human breast cancer. The intracellular protein has prevalently a cytoprotective function, while the extracellular HSP70 mediates immunologic responses. Evolutionarily, HSPs are well conserved from prokaryotes to eukaryotes, and human HSP70 shows a strong similarity to that of plant origin. In the current article, we have tested the potential effect of recombinant HSP70, from Arabidopsis thaliana, on cell survival and metastatic properties of breast cancer cells. Our data show that HSP70 sustains cell viability in MCF-7 and MDA-MB-231 breast tumoral cells and increases Cyclin D1 and Survivin expression. The extracellular HSP70 triggers cell migration and the activation of MMPs particularly in MDA-MB-231 cells. Furthermore, under UV-induced stress condition, the low levels of phospho-AKT were increased by exogenous HSP70, together with the upregulation of Cyclin D1, particularly in the tumoral cell phenotype. On the other hand, UV increased TP53 expression, and the coincubation of HSP70 lowers the TP53 levels similar to the control. These findings correlate with the cytoprotective and antiapoptotic role of HSPs, as reported in different cellular contexts. This is the first study on mammary cells that highlights how the heterologous HSP70 from Arabidopsis thaliana sustains cell survival prevalently in breast cancer cell types, thus maintaining their metastatic potential. Therefore, targeting HSP70 would be of clinical importance since HSP70 blocking selectively targets tumor cells, in which it supports cell growth and survival. Mol Cancer Ther; 15(5); 1063–73. ©2016 AACR.

High-Order Discontinuous Galerkin Solution of Unsteady Flows by Using an Advanced Implicit Method

The aim of this paper is to investigate and evaluate a multi-stage and multi-step method that is an evolution of the more common Backward Differentiation Formulae (BDF). This new class of formulae, called Two Implicit Advanced Step-point (TIAS), has been applied to a high-order Discontinuous Galerkin (DG) discretization of the Navier-Stokes equations, coupling the high temporal accuracy gained by the TIAS scheme with the high space accuracy of the DG method. The performance of the DG-TIAS scheme has been evaluated by means of two test cases: an inviscid isentropic convecting vortex and a laminar vortex shedding behind a circular cylinder. The advantages of the high-order time discretization are illustrated comparing the sixth-order accurate TIAS scheme with the second-order accurate BDF scheme using the same spatial discretization.

Second derivative time integration methods for discontinuous Galerkin solutions of unsteady compressible flows

In this paper we investigate the possibility of using the high-order accurate A(α)-stable Second Derivative (SD) schemes proposed by Enright for the implicit time integration of the Discontinuous Galerkin (DG) space-discretized Navier–Stokes equations. These multistep schemes are A-stable up to fourth-order, but their use results in a system matrix difficult to compute. Furthermore, the evaluation of the nonlinear function is computationally very demanding. We propose here a Matrix-Free (MF) implementation of Enright schemes that allows to obtain a method without the costs of forming, storing and factorizing the system matrix, which is much less computationally expensive than its matrix-explicit counterpart, and which performs competitively with other implicit schemes, such as the Modified Extended Backward Differentiation Formulae (MEBDF). The algorithm makes use of the preconditioned GMRES algorithm for solving the linear system of equations. The preconditioner is based on the ILU(0) factorization of an approximated but computationally cheaper form of the system matrix, and it has been reused for several time steps to improve the efficiency of the MF Newton–Krylov solver. We additionally employ a polynomial extrapolation technique to compute an accurate initial guess to the implicit nonlinear system. The stability properties of SD schemes have been analyzed by solving a linear model problem. For the analysis on the Navier–Stokes equations, two-dimensional inviscid and viscous test cases, both with a known analytical solution, are solved to assess the accuracy properties of the proposed time integration method for nonlinear autonomous and non-autonomous systems, respectively. The performance of the SD algorithm is compared with the ones obtained by using an MF-MEBDF solver, in order to evaluate its effectiveness, identifying its limitations and suggesting possible further improvements.

Towards the Identification of Novel Breast Cancer Inhibitors Specific for GPER-Expressing Cells

Together with estrogen receptors ERα and ERβ, the G protein‐coupled estrogen receptor (GPER) mediates important pathophysiological signaling pathways induced by estrogens and is currently regarded as a promising target for ER‐negative (ER−) and triple‐negative (TN) breast cancer. Only a few selective GPER modulators have been reported to date, and their use in cancer cell lines has often led to contradictory results. Herein we report the application of virtual screening and cell‐based studies for the identification of new chemical scaffolds with a specific antiproliferative effect against GPER‐expressing breast cancer cell lines. Out of the four different scaffolds identified, 8‐chloro‐4‐(4‐chlorophenyl)pyrrolo[1,2‐a]quinoxaline 14 c was found to be the most promising compound able to induce: 1) antiproliferative activity in GPER‐expressing cell lines (MCF7 and SKBR3), similarly to G15; 2) no effect on cells that do not express GPER (HEK293); 3) a decrease in cyclin D1 expression; and 4) a sustained induction of cell‐cycle negative regulators p53 and p21.

MATRIX-FREE MODIFIED EXTENDED BACKWARD DIFFERENTIATION FORMULAE APPLIED TO THE DISCONTINUOUS GALERKIN SOLUTION OF COMPRESSIBLE UNSTEADY VISCOUS FLOWS

In this work a matrix-free modified extended backward differentiation time integration method has been implemented in a high-order discontinuous Galerkin solver for the unsteady Navier-Stokes equations. The resulting non-linear systems at each time step are solved iteratively using a preconditioned inexact Newton/Krylov method. In order to speed-up the solution process a frozen preconditioner formulation and a polynomial extrapolation technique for computing a better initial guess for the Newton iterations have been considered. Numerical results for compressible inviscid and viscous test cases show the effectiveness of the proposed numerical strategies and the performance advantages of the matrix-free method compared to its matrix-explicit counterpart for this class of implicit multi-stage time schemes. Furthermore, the influence of some physical (low Mach) and space discretization (stretched grid) aspects is examined to highlight pros and cons of the proposed time integration algorithm and its potential in solving non-stiff and stiff systems with respect to the widely used explicit Runge-Kutta schemes.