Abstract multiplicity results for (p,q)(p,q)-Laplace equations with two parameters

We investigate the existence and multiplicity of abstract weak solutions of the equation $-\Delta_p u -\Delta_q u=\alpha |u|^{p-2}u + \beta |u|^{q-2}u$ in a bounded domain under zero Dirichlet boundary conditions, assuming $1<q<p$ and $\alpha,\beta \in \mathbb{R}$. We determine three generally different ranges of parameters $\alpha$ and $\beta$ for which the problem possesses a given number of distinct pairs of solutions with a prescribed sign of energy. As auxiliary results, which are also of independent interest, we provide alternative characterizations of variational eigenvalues of the $q$-Laplacian using narrower and larger constraint sets than in the standard minimax definition.Comment: 29 pages, 3 figure

Simulation of Helicopter Rotors On Unstructured Mixed Meshes Using Edge-Based Reconstruction Schemes

The paper gives a detailed description of the developed numerical method for simulating the turbulent flow around a helicopter rotor and calculating its aerodynamic characteristics. The method is based on the original vertex-centered finite-volume EBR schemes. The features of these schemes are their higher accuracy that is achieved through the use of edge-based reconstruction of variables on extended quasi-one-dimensional stencils, and a moderate computational cost that allows for serial computations. When dealing with discontinuities or solutions with large gradients, a quasi-one-dimensional EBR-WENO scheme is used. The methods are implemented in the in-house code NOISEtte within the hybrid MPI&shy;OpenMP parallel model. Validation of the developed techniques is carried out by simulating several cases for hovering and forward-flight regimes of helicopter rotors

Advanced fluorescence microscopy reveals disruption of dynamic CXCR4 dimerization by subpocket-specific inverse agonists

Funding: This research was funded by European Union’s Horizon2020 Marie Skłodowska-Curie Actions (MSCA) Program under Grant Agreement 641833 (ONCORNET) and European Cooperation in Science and Technology (COST) Action CA18133 European Research Network on Signal Transduction (ERNEST). A. Inoue was funded by the Leading Advanced Projects for Medical Innovation (LEAP) JP19gm0010004 from the Japan Agency for Medical Research and Development.Although class A G protein−coupled receptors (GPCRs) can function as monomers, many of them form dimers and oligomers, but the mechanisms and functional relevance of such oligomerization is ill understood. Here, we investigate this problem for the CXC chemokine receptor 4 (CXCR4), a GPCR that regulates immune and hematopoietic cell trafficking, and a major drug target in cancer therapy. We combine single-molecule microscopy and fluorescence fluctuation spectroscopy to investigate CXCR4 membrane organization in living cells at densities ranging from a few molecules to hundreds of molecules per square micrometer of the plasma membrane. We observe that CXCR4 forms dynamic, transient homodimers, and that the monomer−dimer equilibrium is governed by receptor density. CXCR4 inverse agonists that bind to the receptor minor pocket inhibit CXCR4 constitutive activity and abolish receptor dimerization. A mutation in the minor binding pocket reduced the dimer-disrupting ability of these ligands. In addition, mutating critical residues in the sixth transmembrane helix of CXCR4 markedly diminished both basal activity and dimerization, supporting the notion that CXCR4 basal activity is required for dimer formation. Together, these results link CXCR4 dimerization to its density and to its activity. They further suggest that inverse agonists binding to the minor pocket suppress both dimerization and constitutive activity and may represent a specific strategy to target CXCR4.Publisher PDFPeer reviewe

Simulation of massively separated flows and rotating machine flows using hybrid models

RANS, DES, hybrid RANS/DVMS and DDES/DVMS models are introduced in low dissipation schemes. They are compared for the simulation of vortex shedding flows around a NACA0021 at high angle of attack and a Caradonna-Tung helix

Simulation d'écoulements massivement séparés et d'écoulements en machine tournantes à l'aide de modèles hybrides

International audienceRANS, DES, hybrid RANS/DVMS and DDES/DVMS models are introduced in low dissipation schemes. They are compared for the simulation of vortex shedding flows around a NACA0021 at high angle of attack and a Caradonna-Tung helix