A high order compact scheme for hypersonic aerothermodynamics

A novel high order compact scheme for solving the compressible Navier-Stokes equations has been developed. The scheme is an extension of a method originally proposed for solving the Euler equations, and combines several techniques for the solution of compressible flowfields, such as upwinding, limiting and flux vector splitting, with the excellent properties of high order compact schemes. Extending the method to the Navier-Stokes equations is achieved via a Kinetic Flux Vector Splitting technique, which represents an unusual and attractive way to include viscous effects. This approach offers a more accurate and less computationally expensive technique than discretizations based on more conventional operator splitting. The Euler solver has been validated against several inviscid test cases, and results for several viscous test cases are also presented. The results confirm that the method is stable, accurate and has excellent shock-capturing capabilities for both viscous and inviscid flows

Construction of Modern Robust Nodal Discontinuous Galerkin Spectral Element Methods for the Compressible Navier-Stokes Equations

Discontinuous Galerkin (DG) methods have a long history in computational physics and engineering to approximate solutions of partial differential equations due to their high-order accuracy and geometric flexibility. However, DG is not perfect and there remain some issues. Concerning robustness, DG has undergone an extensive transformation over the past seven years into its modern form that provides statements on solution boundedness for linear and nonlinear problems. This chapter takes a constructive approach to introduce a modern incarnation of the DG spectral element method for the compressible Navier-Stokes equations in a three-dimensional curvilinear context. The groundwork of the numerical scheme comes from classic principles of spectral methods including polynomial approximations and Gauss-type quadratures. We identify aliasing as one underlying cause of the robustness issues for classical DG spectral methods. Removing said aliasing errors requires a particular differentiation matrix and careful discretization of the advective flux terms in the governing equations.Comment: 85 pages, 2 figures, book chapte

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

Compressibility effects on pressure fluctuation in compressible turbulent channel flows

We study compressibility effects on pressure fluctuations in wall-bounded turbulent flows using DNS data of compressible turbulent channel flows at various Mach numbers. We derive a pressure Poisson equation that allows splitting pressure fluctuations into the following terms: the rapid and slow terms as in incompressible flows, an additional mass-flux term related to the temporal and spatial variation of mass-flux fluctuations, and a viscous term related to fluctuating viscous stresses. As the bulk Mach number increases, the intensity of pressure fluctuations increases in the viscous sublayer and in the outer region, resulting from the intensification of the mass-flux term, whereas it decreases in the buffer layer and logarithmic layers, after weakening of the slow term. The rapid and slow terms are further split into their solenoidal and dilatational components using Helmholtz decomposition. The variances of the solenoidal components are found to be independent of the Mach number, whereas the dilatational components increase quadratically with the Mach number. The correlations between split pressure fluctuations and dilatational fluctuations show that the solenoidal-related pressure field turns turbulent kinetic energy into internal energy, whereas dilatational and viscous terms are responsible for reverse energy transfer

Genuine compressibility effects in wall-bounded turbulence

Compressible wall-bounded turbulence is generally assumed to be devoid of genuine compressibility effects, meaning that the effect of finite fluid dilatation is regarded as "small," at least in the absence of disturbing pressure gradients. In the present paper we attempt to answer the basic question of how small these effects are, by interrogating a DNS database of compressible channel flow and by using Helmholtz decomposition to infer the relative magnitude and correlations between the solenoidal and the dilatational parts of turbulence velocity fields. Not surprisingly, we find dilatational velocity fluctuations to be much smaller than solenoidal ones, but perhaps unexpectedly, we find that finite correlation between the two components accounts for a nonnegligible fraction (about 10%) of the turbulent shear stress near walls, and for up to 4% of the wall skin friction. Quadrant analysis of the dilatational velocity fluctuations shows that the largest contribution to the turbulent shear stress results from significant correlation between positive streamwise solenoidal velocity fluctuations (i.e., high-speed streaks), and positive vertical dilatational velocity fluctuations, which tend to mitigate the intensity of wall-ward sweep events

High-order, high-fidelity simulation of unsteady shock-wave/boundary layer interaction using flux reconstruction

In this work, a high-order implicit large-eddy simulation of an oblique shockwave/ boundary layer interaction at Mach 2.3 is performed. The high-order solver is based on the flux reconstruction method, allowing an arbitrary order of accuracy. A particular attention is paid to the shock-capturing technique which consists in a combination of a Laplacian artificial viscosity with the Ducros sensor. The ability of such a solver to accurately predict the flow features is assessed on both steady and unsteady fields. In particular, the typical lowfrequency motion of the reflected shock is reproduced. The shock-capturing methodology is proven to be efficient at resolving the shocks without damping the turbulence in the boundary layer. The results obtained give confidence in this solver to study in more details the shockwave/ boundary layer interaction phenomenon and future work is focused on the analysis of the oscillatory turbulent field in the interaction region

Expression of IGFBP-5 in neuroblastoma cells is regulated at the transcriptional level by c-Myb and B-Myb via direct and indirect mechanisms.

Neuroblastoma (NB), a malignant childhood tumor deriving from the embryonic neural crest, is sensitive to the growth-stimulating effects of insulin-like growth factors (IGFs). Aggressive cases of this disease often acquire autocrine loops of IGF production, but the mechanisms through which the different components of the IGF axis are regulated in tumor cells remain unclear. Upon conditional expression of c-Myb in a NB cell line, we detected up-regulation of IGF1, IGF1 receptor, and insulin-like growth factor-binding protein 5 (IGFBP-5) expression. Analysis of the IGFBP-5 promoter revealed two potential Myb binding sites at position −59 to −54 (M1) and −429 to −424 (M2) from the transcription start site; both sites were bound by c-Myb and B-Mybin vitro and in vivo. Reporter assays carried out using the proximal region of the human IGFBP-5 promoter demonstrated that c-Myb and B-Myb enhanced transcription. However, site-directed mutagenesis and deletion of the Myb binding sites coupled with reporter assays revealed that M2 but not M1 was important for Myb-dependent transactivation of the IGFBP-5promoter. The double mutant M1/M2 was still transactivated by c-Myb, suggesting the existence of Myb binding-independent mechanisms ofIGFBP-5 promoter regulation. A constitutively active AKT transactivated the IGFBP-5 promoter, whereas the phosphatidylinositol 3-kinase inhibitor LY294002 suppressed it. Moreover, the kinase dead dominant negative K179M AKT mutant was able to inhibit transcription from the M2 and M1/M2IGFBP-5 mutant promoters. Deletion analysis of theIGFBP-5 promoter revealed that the AKT-responsive region lies between nucleotides −334 and −83. Together, these data suggest that the Myb binding-independent transactivation of theIGFBP-5 promoter was due to the activation of the phosphatidylinositol 3-kinase/AKT pathway likely mediated by IGF1 receptor-dependent signals. Finally, IGFBP-5 was able to modulate proliferation of NB cells in a manner dependent on its concentration and on the presence of IGFs