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Search Results: 1 - 10 of 174121 matches for " Olivier E. Pardo "
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S6K2: The Neglected S6 Kinase Family Member
Olivier E. Pardo,Michael J. Seckl
Frontiers in Oncology , 2013, DOI: 10.3389/fonc.2013.00191
Abstract: S6 kinase 2 (S6K2) is a member of the AGC kinases super-family. Its closest homolog, S6K1, has been extensively studied along the years. However, due to the belief in the community that the high degree of identity between these two isoforms would translate in essentially identical biological functions, S6K2 has been largely neglected. Nevertheless, recent research has clearly highlighted that these two proteins significantly differ in their roles in vitro as well as in vivo. These findings are significant to our understanding of S6 kinase signaling and the development of therapeutic strategies for several diseases including cancer. Here, we will focus on S6K2 and review the protein–protein interactions and specific substrates that determine the selective functions of this kinase.
Targeting Class IA PI3K Isoforms Selectively Impairs Cell Growth, Survival, and Migration in Glioblastoma
Katrin H?land, Danielle Boller, Christian Hagel, Silvia Dolski, András Treszl, Olivier E. Pardo, Paulina ?wiek, Fabiana Salm, Zaira Leni, Peter R. Shepherd, Beata Styp-Rekowska, Valentin Djonov, André O. von Bueren, Karl Frei, Alexandre Arcaro
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0094132
Abstract: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is frequently activated in human cancer and plays a crucial role in glioblastoma biology. We were interested in gaining further insight into the potential of targeting PI3K isoforms as a novel anti-tumor approach in glioblastoma. Consistent expression of the PI3K catalytic isoform PI3K p110α was detected in a panel of glioblastoma patient samples. In contrast, PI3K p110β expression was only rarely detected in glioblastoma patient samples. The expression of a module comprising the epidermal growth factor receptor (EGFR)/PI3K p110α/phosphorylated ribosomal S6 protein (p-S6) was correlated with shorter patient survival. Inhibition of PI3K p110α activity impaired the anchorage-dependent growth of glioblastoma cells and induced tumor regression in vivo. Inhibition of PI3K p110α or PI3K p110β also led to impaired anchorage-independent growth, a decreased migratory capacity of glioblastoma cells, and reduced the activation of the Akt/mTOR pathway. These effects were selective, because targeting of PI3K p110δ did not result in a comparable impairment of glioblastoma tumorigenic properties. Together, our data reveal that drugs targeting PI3K p110α can reduce growth in a subset of glioblastoma tumors characterized by the expression of EGFR/PI3K p110α/p-S6.
Stable rank of Leavitt path algebras
P. Ara,E. Pardo
Mathematics , 2006,
Abstract: We characterize the values of the stable rank for Leavitt path algebras, by giving concrete criteria in terms of properties of the underlying graph.
Towards a K-theoretic characterization of graded isomorphisms between Leavitt path algebras
P. Ara,E. Pardo
Mathematics , 2012,
Abstract: Hazrat gave a K-theoretic invariant for Leavitt path algebras as graded algebras. Hazrat conjectured that this invariant classifies Leavitt path algebras up to graded isomorphism, and proved the conjecture in some cases. In this paper, we prove that a weak version of the conjecture holds for all finite essential graphs.
Primely generated refinement monoids
P. Ara,E. Pardo
Mathematics , 2014,
Abstract: We extend both Dobbertin's characterization of primely generated regular refinement monoids and Pierce's characterization of primitive monoids to general primely generated refinement monoids.
Compensated magnetism by design in double perovskite oxides
Victor Pardo,Warren E. Pickett
Physics , 2009, DOI: 10.1103/PhysRevB.80.054415
Abstract: Taking into account Goodenough's superexchange rules, including both full structural relaxation and spin-orbit coupling, and checking strong correlation effects, we look for compensated half metals within the class of oxide double perovskites materials. Identifying likely half metallic (or half semimetallic) antiferromagnets, the full complications including orbital magnetism are included in order to arrive at realistic predictions of designed magnetic compounds with (near) vanishing net moment. After sorting through several candidates that have not been considered previously, two materials, K$_2$MnRhO$_6$ and La$_2$CrWO$_6$, remain as viable candidates. An important factor is obtaining compounds either with very small induced orbital moment (helped by closed subshells) or with an orbital moment that compensates the spin-orbit driven degradation of half metallic character. While thermodynamic stability of these materials cannot be ensured, the development of layer-by-layer oxide deposition techniques does not require that materials be thermodynamically stable to be synthesized.
Electron Confinement, Orbital Ordering, and Orbital Moments in $d^0$-$d^1$ Oxide Heterostructures
Victor Pardo,Warren E. Pickett
Physics , 2010, DOI: 10.1103/PhysRevB.81.245117
Abstract: The (SrTiO$_3$)$_m$/(SrVO$_3$)$_n$ $d^0-d^1$ multilayer system is studied with first principles methods through the observed insulator-to-metal transition with increasing thickness of the SrVO$_3$ layer. When correlation effects with reasonable magnitude are included, crystal field splittings from the structural relaxations together with spin-orbit coupling (SOC) determines the behavior of the electronic and magnetic structures. These confined slabs of SrVO$_3$ prefer $Q_{orb}$=($\pi,\pi$) orbital ordering of $\ell_z = 0$ and $\ell_z = -1$ ($j_z=-1/2$) orbitals within the plane, accompanied by $Q_{spin}$=(0,0) spin order (ferromagnetic alignment). The result is a SOC-driven ferromagnetic Mott insulator. The orbital moment of 0.75 $\mu_B$ strongly compensates the spin moment on the $\ell_z = -1$ sublattice. The insulator-metal transition for $n = 1 \to 5$ (occurring between $n$=4 and $n$=5) is reproduced. Unlike in the isoelectronic $d^0-d^1$ TiO$_2$/VO$_2$ (rutile structure) system and in spite of some similarities in orbital ordering, no semi-Dirac point [{\it Phys. Rev. Lett.} {\bf 102}, 166803 (2009)] is encountered, but the insulator-to-metal transition occurs through a different type of unusual phase. For n=5 this system is very near (or at) a unique semimetallic state in which the Fermi energy is topologically determined and the Fermi surface consists of identical electron and hole Fermi circles centered at $k$=0. The dispersion consists of what can be regarded as a continuum of radially-directed Dirac points, forming a "Dirac circle".
Quantum Confinement Induced Molecular Mott Insulating State in La$_4$Ni$_3$O$_8$
Victor Pardo,Warren E. Pickett
Physics , 2010, DOI: 10.1103/PhysRevLett.105.266402
Abstract: The recently synthesized layered nickelate La$_4$Ni$_3$O$_8$, with its cuprate-like NiO$_2$ layers, seemingly requires a Ni1 ($d^8$)+2Ni2 ($d^9$) charge order, together with strong correlation effects, to account for its insulating behavior. Using density functional methods including strong intra-atomic repulsion (Hubbard U), we obtain an insulating state via a new mechanism: {\it without charge order}, Mott insulating behavior arises based on quantum coupled, spin-aligned Ni2-Ni1-Ni2 $d_{z^2}$ states across the trilayer (rather than based on atomic states), with antiferromagnetic ordering within layers. The weak and frustrated magnetic coupling between cells may account for the small spin entropy that is removed at the N\'eel transition at 105 K and the lack of any diffraction peak at the N\'eel point.
Pressure-induced metal-insulator and spin-state transition in low-valence layered nickelates
Victor Pardo,Warren E. Pickett
Physics , 2011, DOI: 10.1103/PhysRevB.85.045111
Abstract: Ab initio calculations predict a metal-insulator transition at zero temperature to occur in La$_4$Ni$_3$O$_8$ at moderate pressures as a result of a pressure-induced spin-state transition. The spin-state transition that is seen at 105 K at ambient pressure from a low-temperature high-spin state to a high-temperature low-spin state has been observed to be shifted to lower temperatures as pressure is applied. From our calculations we find that a smaller unit cell volume favors the metallic low-spin state, which becomes more stable at 5 GPa. Similar physics should take place in the related compound La$_3$Ni$_2$O$_6$, but on a different energy scale, which may account for why the transition has not been observed in this material.
Magnetism from $2p$ States in Alkaline Earth Monoxides: Trends with Varying N Impurity Concentration
V. Pardo,W. E. Pickett
Physics , 2008, DOI: 10.1103/PhysRevB.78.134427
Abstract: $2p$-based magnetic moments and magnetic coupling are studied with density functional based methods for substitutional N in the alkaline earth monoxide series MgO, CaO, SrO, BaO. The hole is rather strongly localized near the N$^{2-}$ ion, being somewhat more so when strong on-site interactions are included in the calculations. Strong magnetic coupling is obtained in the itinerant electron limit but decreases strongly in the localized limit in which the Coulomb repulsion within the N $2p$ shell (U) is much greater than the N $2p$ impurity bandwidth (W). We find that this limit is appropriate for realistic N concentrations. Ordering on a simple cubic sublattice may maximize the magnetic coupling due to its high directionality.
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