KDM2B/FBXL10 targets c-Fos for ubiquitylation and degradation in response to mitogenic stimulation.

KDM2B (also known as FBXL10) controls stem cell self-renewal, somatic cell reprogramming and senescence, and tumorigenesis. KDM2B contains multiple functional domains, including a JmjC domain that catalyzes H3K36 demethylation and a CxxC zinc-finger that recognizes CpG islands and recruits the polycomb repressive complex 1. Here, we report that KDM2B, via its F-box domain, functions as a subunit of the CUL1-RING ubiquitin ligase (CRL1/SCF(KDM2B)) complex. KDM2B targets c-Fos for polyubiquitylation and regulates c-Fos protein levels. Unlike the phosphorylation of other SCF (SKP1-CUL1-F-box)/CRL1 substrates that promotes substrates binding to F-box, epidermal growth factor (EGF)-induced c-Fos S374 phosphorylation dissociates c-Fos from KDM2B and stabilizes c-Fos protein. Non-phosphorylatable and phosphomimetic mutations at S374 result in c-Fos protein which cannot be induced by EGF or accumulates constitutively and lead to decreased or increased cell proliferation, respectively. Multiple tumor-derived KDM2B mutations impaired the function of KDM2B to target c-Fos degradation and to suppress cell proliferation. These results reveal a novel function of KDM2B in the negative regulation of cell proliferation by assembling an E3 ligase to targeting c-Fos protein degradation that is antagonized by mitogenic stimulations

High-density QCD and Cosmic Ray Air Showers

We discuss particle production in the high-energy, small-x limit of QCD where the gluon density of hadrons is expected to become nonperturbatively large. Strong modifications of the phase-space distribution of produced particles as compared to leading-twist models are predicted which reflect in the properties of cosmic ray induced air showers in the atmosphere. Assuming hadronic primaries, our results suggest a light composition near GZK cutoff energies. We also show that cosmic ray data discriminate among various QCD evolution scenarios for the rate of increase of the gluon density at small x, such as fixed-coupling and running-coupling BFKL evolution. There are clear indications for a slower growth of the gluon density as compared to RHIC and HERA, due e.g. to running-coupling effects.Comment: 5 pages, 1 figur

Incommensurate Magnetic Fluctuations in YBa2Cu3O6.6

We use inelastic neutron scattering to demonstrate that at low temperatures, the low frequency magnetic fluctuations in YBa_2Cu_3O_{6.6} ($T_c=62.7$ K) are incommensurate, being found at positions displaced by $\pm\delta$ ($0.057\pm 0.006$ r.l.u.) along the $[\pi,\pi]$ direction from the wave vector $(\pi,\pi)$ associated with the antiferromagnetic order of the parent insulator, YBa_2Cu_3O_{6}. The dynamical susceptibility $\chi''(q,\omega)$ at the incommensurate positions increases on cooling below $T_c$, accompanied by a suppression of magnetic fluctuations at the commensurate points.Comment: 11 pages, Latex, 4 figure

Model of C-Axis Resistivity of High-\Tc Cuprates

We propose a simple model which accounts for the major features and systematics of experiments on the $c$-axis resistivity, $\rho_c$, for \lsco, \ybco and \bsco . We argue that the $c$-axis resistivity can be separated into contributions from in-plane dephasing and the $c$-axis ``barrier'' scattering processes, with the low temperature semiconductor-like behavior of $\rho_c$ arising from the suppression of the in-plane density of states measured by in-plane magnetic Knight shift experiments. We report on predictions for $\rho_c$ in impurity-doped \ybco materials.Comment: 10 pages + figures, also see March Meeting J13.1

On the Bilayer Coupling in the Yttrium-Barium Family of High Temperature Superconductors

We present and solve a model for the susceptibility of two CuO2 planes coupled by an interplane coupling J_perp and use the results to analyze a recent "cross-relaxation" NMR experiment on Y2Ba4Cu7O15. We deduce that in this material the product of J_perp and the maximum value of the in-plane susceptibility chi_max varies from approximately 0.2 at T = 200 K to 0.4 at T = 120 K and that this implies the existence of a temperature dependent in-plane spin correlation length. Using estimates of chi_max from the literature we find 5 meV < J_perp < 20 meV. We discuss the relation of the NMR results to neutron scattering results which have been claimed to imply that in YBa2Cu3O_{6+x} the two planes of a bilayer are perfectly anticorrelated. We also propose that the recently observed 41 meV excitation in YBa2Cu3O7 is an exciton pulled down below the superconducting gap by J_perp.Comment: 11 pages, 3 postscript figures (uuencoded and compressed

C24 Sphingolipids Govern the Transbilayer Asymmetry of Cholesterol and Lateral Organization of Model and Live-Cell Plasma Membranes

Mammalian sphingolipids, primarily with C24 or C16 acyl chains, reside in the outer leaflet of the plasma membrane. Curiously, little is known how C24 sphingolipids impact cholesterol and membrane microdomains. Here, we present evidence that C24 sphingomyelin, when placed in the outer leaflet, suppresses microdomains in giant unilamellar vesicles and also suppresses submicron domains in the plasma membrane of HeLa cells. Free energy calculations suggested that cholesterol has a preference for the inner leaflet if C24 sphingomyelin is in the outer leaflet. We indeed observe that cholesterol enriches in the inner leaflet (80%) if C24 sphingomyelin is in the outer leaflet. Similarly, cholesterol primarily resides in the cytoplasmic leaflet (80%) in the plasma membrane of human erythrocytes where C24 sphingolipids are naturally abundant in the outer leaflet. We conclude that C24 sphingomyelin uniquely interacts with cholesterol and regulates the lateral organization in asymmetric membranes, potentially by generating cholesterol asymmetry

A GPU-based hyperbolic SVD algorithm

A one-sided Jacobi hyperbolic singular value decomposition (HSVD) algorithm, using a massively parallel graphics processing unit (GPU), is developed. The algorithm also serves as the final stage of solving a symmetric indefinite eigenvalue problem. Numerical testing demonstrates the gains in speed and accuracy over sequential and MPI-parallelized variants of similar Jacobi-type HSVD algorithms. Finally, possibilities of hybrid CPU--GPU parallelism are discussed.Comment: Accepted for publication in BIT Numerical Mathematic

First-Principles Calculations of Hyperfine Interactions in La_2CuO_4

We present the results of first-principles cluster calculations of the electronic structure of La_2CuO_4. Several clusters containing up to nine copper atoms embedded in a background potential were investigated. Spin-polarized calculations were performed both at the Hartree-Fock level and with density functional methods with generalized gradient corrections to the local density approximation. The distinct results for the electronic structure obtained with these two methods are discussed. The dependence of the electric-field gradients at the Cu and the O sites on the cluster size is studied and the results are compared to experiments. The magnetic hyperfine coupling parameters are carefully examined. Special attention is given to a quantitative determination of on-site and transferred hyperfine fields. We provide a detailed analysis that compares the hyperfine fields obtained for various cluster sizes with results from additional calculations of spin states with different multiplicities. From this we conclude that hyperfine couplings are mainly transferred from nearest neighbor Cu^{2+} ions and that contributions from further distant neighbors are marginal. The mechanisms giving rise to transfer of spin density are worked out. Assuming conventional values for the spin-orbit coupling, the total calculated hyperfine interaction parameters are compared to informations from experiments.Comment: 23 pages, 9 figure

Coherent `ab' and `c' transport theory of high-TcT_{c} cuprates

We propose a microscopic theory of the `$c$'-axis and in-plane transport of copper oxides based on the bipolaron theory and the Boltzmann kinetics. The fundamental relationship between the anisotropy and the spin susceptibility is derived, $\rho_{c}(T,x)/\rho_{ab}(T,x)\sim x/\sqrt{T}\chi_{s}(T,x)$. The temperature $(T)$ and doping $(x)$ dependence of the in-plane, $\rho_{ab}$ and out-of-plane, $\rho_{c}$ resistivity and the spin susceptibility, $\chi_{s}$ are found in a remarkable agreement with the experimental data in underdoped, optimally and overdoped $La_{2-x}Sr_{x}CuO_{4}$ for the entire temperature regime from $T_{c}$ up to $800K$. The normal state gap is explained and its doping and temperature dependence is clarified.Comment: 12 pages, Latex, 3 figures available upon reques

NMR and Neutron Scattering Experiments on the Cuprate Superconductors: A Critical Re-Examination

We show that it is possible to reconcile NMR and neutron scattering experiments on both LSCO and YBCO, by making use of the Millis-Monien-Pines mean field phenomenological expression for the dynamic spin-spin response function, and reexamining the standard Shastry-Mila-Rice hyperfine Hamiltonian for NMR experiments. The recent neutron scattering results of Aeppli et al on LSCO (x=14%) are shown to agree quantitatively with the NMR measurements of $^{63}T_1$ and the magnetic scaling behavior proposed by Barzykin and Pines. The reconciliation of the $^{17}T_1$ relaxation rates with the degree of incommensuration in the spin fluctuation spectrum seen in neutron experiments is achieved by introducing a new transferred hyperfine coupling $C'$ between oxygen nuclei and their next nearest neighbor $Cu^{2+}$ spins; this leads to a near-perfect cancellation of the influence of the incommensurate spin fluctuation peaks on the oxygen relaxation rates of LSCO. The inclusion of the new $C'$ term also leads to a natural explanation, within the one-component model, the different temperature dependence of the anisotropic oxygen relaxation rates for different field orientations, recently observed by Martindale $et~al$. The measured significant decrease with doping of the anisotropy ratio, $R= ^{63}T_{1ab}/^{63}T_{1c}$ in LSCO system, from $R =3.9$ for ${\rm La_2CuO_4}$ to $R ~ 3.0$ for LSCO (x=15%) is made compatible with the doping dependence of the shift in the incommensurate spin fluctuation peaks measured in neutron experiments, by suitable choices of the direct and transferred hyperfine coupling constants $A_{\beta}$ and B.Comment: 24 pages in RevTex, 9 figures include