Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients

Ab-inito study of a quasiperiodic Na monolayer on a fivefold i-AlPdMn surface

International audienceThe structure and stability of a quasiperiodic Na monolayer formed on a five-fold surface of an icosahedral AlPdMn quasicrystal have been investigated using ab-initio density-functional methods. The structural model of the adsorbed monolayer has been constructed on the basis of a mapping of the potential-energy landscape of an isolated adatom on the fivefold surface of i-AlPdMn. Na atoms adsorbed on the surface arranged to a highly regular quasiperiodic monolayer. The quasiperiodic ordering can be described by a tiling of decagons, hexagons, boats and pentagonal stars (DHBS). The coverage density of the adsorbed monolayer is 0.067 atoms/Å2</sup

Ab-inito study of a quasiperiodic Bi monolayer on a fivefold i-AlPdMn surface

International audienceThe structure and stability of a quasiperiodic Bi monolayer formed on a five-fold surface of an icosahedral AlPdMn quasicrystal have been investigated using ab-initio density-functional methods. The structural model of the adsorbed monolayer has been constructed on the basis of a mapping of the potential-energy landscape of an isolated adatom on the fivefold surface of i-AlPdMn. This leads to a structural model of the quasiperiodic adlayer with atoms at the vertices and mid-edge positions of the P1-tiling. The internal decoration of the tiles is enforced by the decoration of the circumference of the tiles

Alkaline-earth metal monolayers on fivefold i-Al-Pd-Mn surface: Influence of adatom size on quasiperiodic ordering

International audienceThe structure and stability of a quasiperiodic alkaline-earth metal monolayers formed on a five-fold surface of an icosahedral Al-Pd-Mn quasicrystal have been investigated using ab-initio density-functional methods. We study an influence of the size of adatom on the regularity of the quasiperiodic ordering. It was found that Ca adatoms at the coverage 0.066 atoms /Å2 (Θ=0.5) form on the i-Al-Pd-Mn surface a highly regular quasiperiodic monolayer with an ordering described by a decagonal DHBS tiling of decagons, hexagons, boats and pentagonal stars

Interatomic bonds and the tensile anisotropy of trialuminides in the elastic limit: A density functional study for Al₃(Sc,Ti,V,Cr)

International audienceThe tensile anisotropy in the elastic limit of Al3(Sc,Ti,V,Cr) intermetallic compounds in both L12 and D022 crystal structure have been investigated using first-principles density-functional calculations. In both both crystal structures the main bonding character comes from the saturation of dominant d3 (L12) and d4 (D022) hybrid orbitals located on the TM atoms. The series Al3Sc → Al3V corresponds to the gradually d-band filling and leads to a gradual increase of bond-strength and covalent bond formation. The magnetism of Cr breaks this trend in the Al3Cr compound (for both ferromagnetic and anti-ferromagnetic configurations). In this series, a trend towards an increased anisotropy of the elastic constants, Young modulus Y and Poisson ratio ν is observed. The easy and hard directions of tension can be simply identified by the variation of Y, which corresponds to the presence or absence of covalently bonded -Al-TM- chains. A high anisotropy of Poisson ratio arises also from an alternation of atoms in the lateral directions and can be understood in the same terms

Tkatchenko-Scheffler van der Waals correction method with and without self-consistent screening applied to solids

International audienceThe method proposed by Tkatchenko and Scheffler [Phys. Rev. Lett. 102, 073005 (2009)] to correct density functional calculations for the missing van derWaals interactions is implemented in the Vienna ab initio simulation package (VASP) code and tested on a wide range of solids, including noble-gas crystals, molecular crystals (alpha-N-2, sulfur dioxide, benzene, naphthalene, cytosine), layered solids (graphite, hexagonal boron nitride, vanadium pentoxide, MoS2, NbSe2), chain-like structures (selenium, tellurium, cellulose I), ionic crystals (NaCl, KI), and metals (nickel, zinc, cadmium). In addition to the original formulation expressing the van der Waals (vdW) corrections as pairwise potentials whose strength is derived from the rescaled polarizabilities of the neutral free atoms, the self-consistently screened (TS + SCS) [Phys. Rev. Lett. 108, 236402 (2012)] variant of the method involving electrodynamic response effects has been examined. Analytical expressions for the forces acting on the atoms and for the components of the stress tensor needed for the relaxation of the volume and shape of the unit cell using the TS + SCS method are derived. While the calculated structures are reasonably close to experiment, the van der Waals corrections to the binding energies are often found to be overestimated in comparison with experimental data. The TS + SCS approach leads to significantly better results in some problematic cases, such as the binding energy of graphite. However, there is room for further improvements, in particular for strongly ionic systems

Extending the applicability of the Tkatchenko-Scheffler dispersion correction via iterative Hirshfeld partitioning

International audienceRecently we have demonstrated that the applicability of the Tkatchenko-Scheffler (TS) method for calculating dispersion corrections to density-functional theory can be extended to ionic systems if the Hirshfeld method for estimating effective volumes and charges of atoms in molecules or solids (AIM's) is replaced by its iterative variant [T. Bucko, S. Lebegue, J. Hafner, and J. Angyan, J. Chem. Theory Comput. 9, 4293 (2013)]. The standard Hirshfeld method uses neutral atoms as a reference, whereas in the iterative Hirshfeld (HI) scheme the fractionally charged atomic reference states are determined self-consistently. We show that the HI method predicts more realistic AIM charges and that the TS/HI approach leads to polarizabilities and C-6 dispersion coefficients in ionic or partially ionic systems which are, as expected, larger for anions than for cations (in contrast to the conventional TS method). For crystalline materials, the new algorithm predicts polarizabilities per unit cell in better agreement with the values derived from the Clausius-Mosotti equation. The applicability of the TS/HI method has been tested for a wide variety of molecular and solid-state systems. It is demonstrated that for systems dominated by covalent interactions and/or dispersion forces the TS/HI method leads to the same results as the conventional TS approach. The difference between the TS/HI and TS approaches increases with increasing ionicity. A detailed comparison is presented for isoelectronic series of octet compounds, layered crystals, complex intermetallic compounds, and hydrides, and for crystals built of molecules or containing molecular anions. It is demonstrated that only the TS/HI method leads to accurate results for systems where both electrostatic and dispersion interactions are important, as illustrated for Li-intercalated graphite and for molecular adsorption on the surfaces in ionic solids and in the cavities of zeolites

Improved Density Dependent Correction for the Description of London Dispersion Forces

International audienceThe Tkatchenko-Scheffler method for calculating dispersion correction to standard density-functional theory, which uses fixed neutral atoms as a reference to estimate the effective volumes of atoms-in-molecule and to calibrate their polarizabilities and dispersion coefficients, fails to describe the structure and the energetics of ionic solids. Here, we propose a more appropriate partitioning, based on the iterative Hirshfeld scheme, where the fractionally charged atomic reference state is determined self-consistently. We show that our new method extends the applicability of the original method in particular to study ionic systems and adsorption phenomena on surfaces of ionic solids