Sensitivity computations by automatic differentiation of a CFD code based on spectral differences

We compute flow sensitivities by modifying a CFD code which is spatially-discretized with spectral differences. Our discrete approach relies on algorithmic differentiation. We obtain two transformed codes, one for each differentiation mode : tangent and adjoint. Both codes compute sensitivities in an unsteady test case of two-dimensional incompressible flow inside a periodic cube with an initial double-shear profile. The sensitivities from both codes agree to within machine accuracy, and compare well with those approximated by finite difference computations. We discuss execution times and describe our strategy to automatically differentiate in adjoint mode a parallel code containing MPI instructions

The temporal evolution of the energy flux across scales in homogeneous turbulence

A temporal study of energy transfer across length scales is performed in 3D numerical simulations of homogeneous shear flow and isotropic turbulence. The average time taken by perturbations in the energy flux to travel between scales is measured and shown to be additive. Our data suggests that the propagation of disturbances in the energy flux is independent of the forcing and that it defines a `velocity' that determines the energy flux itself. These results support that the cascade is, on average, a scale-local process where energy is continuously transmitted from one scale to the next in order of decreasing size.Comment: Accepted for publication as a Letter in Physics of Fluid

Sensitivity computations by algorithmic differentiation of a high-­order cfd code based on spectral differences

We compute flow sensitivities by differentiating a high-­order computational fluid dynamics code. Our fully discrete approach relies on automatic differentiation (AD) of the original source code. We obtain two transformed codes by using the AD tool Tapenade (INRIA), one for each differentiation mode: tangent and adjoint. Both differentiated codes are tested against each other by computing sensitivities in an unsteady test case. The results from both codes agree to within machine accuracy, and compare well with those approximated by finite differences. We compare execution times and discuss the encountered technical difficulties due to 1) the code parallelism and 2) the memory overhead caused by unsteady problems

Pharmacological modulation of CXCR4 cooperates with BET bromodomain inhibition in diffuse large B-cell lymphoma

Constitutive activation of the chemokine receptor CXCR4 has been associated with tumor progression, invasion, and chemotherapy resistance in different cancer subtypes. Although the CXCR4 pathway has recently been suggested as an adverse prognostic marker in diffuse large B-cell lymphoma, its biological relevance in this disease remains underexplored. In a homogeneous set of 52 biopsies from patients, an antibody-based cytokine array showed that tissue levels of CXCL12 correlated with high microvessel density and bone marrow involvement at diagnosis, supporting a role for the CXCL12-CXCR4 axis in disease progression. We then identified the tetra-amine IQS-01.01RS as a potent inverse agonist of the receptor, preventing CXCL12-mediated chemotaxis and triggering apoptosis in a panel of 18 cell lines and primary cultures, with superior mobilizing properties in vivo than those of the standard agent. IQS-01.01RS activity was associated with downregulation of p-AKT, p-ERK1/2 and destabilization of MYC, allowing a synergistic interaction with the bromodomain and extra-terminal domain inhibitor, CPI203. In a xenotransplant model of diffuse large B-cell lymphoma, the combination of IQS-01.01RS and CPI203 decreased tumor burden through MYC and p-AKT downregulation, and enhanced the induction of apoptosis. Thus, our results point out an emerging role of CXCL12-CXCR4 in the pathogenesis of diffuse large B-cell lymphoma and support the simultaneous targeting of CXCR4 and bromodomain proteins as a promising, rationale-based strategy for the treatment of this disease

Lymphomas of the head and neck region: an update

The field of haematopathology is rapidly evolving and for the non-specialized pathologist receiving a specimen with the possibility of a lymphoid malignancy may be a daunting experience. The coincidence of the publication, in 2017, of the WHO monographies on head and neck and haematopoietic and lymphoid tumours prompted us to write this review. Although not substantially different from lymphomas elsewhere, lymphomas presenting in this region pose some specific problems and these are central to the review. In addition, differences in subtype frequency and morphological variations within the same entity are discussed. The difficulty in diagnosis related to some specimens led us to briefly mention common subtypes of systemic lymphomas presenting in the head and neck region.info:eu-repo/semantics/publishedVersio