Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels

Disrupted-in-schizophrenia 1 (DISC1) is a genetic susceptibility factor for schizophrenia and related severe psychiatric conditions. DISC1 is a multifunctional scaffold protein that is able to interact with several proteins, including the independently identified schizophrenia risk factor phosphodiesterase-4B (PDE4B). Here we report that the 100 kDa full-length DISC1 isoform (fl-DISC1) can bind members of each of the four gene, cAMP-specific PDE4 family. Elevation of intracellular cAMP levels, so as to activate protein kinase A, caused the release of PDE4D3 and PDE4C2 isoforms from fl-DISC1 while not affecting binding of PDE4B1 and PDE4A5 isoforms. Using a peptide array strategy, we show that PDE4D3 binds fl-DISC1 through two regions found in common with PDE4B isoforms, the interaction of which is supplemented because of the presence of additional PDE4B-specific binding sites. We propose that the additional binding sites found in PDE4B1 underpin its resistance to release during cAMP elevation. We identify, for the first time, a functional distinction between the 100 kDa long DISC1 isoform and the short 71 kDa isoform. Thus, changes in the expression pattern of DISC1 and PDE4 isoforms offers a means to reprogram their interaction and to determine whether the PDE4 sequestered by DISC1 is released after cAMP elevation. The PDE4B-specific binding sites encompass point mutations in mouse Disc1 that confer phenotypes related to schizophrenia and depression and that affect binding to PDE4B. Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology

Three-particle entanglement versus three-particle nonlocality

The notions of three-particle entanglement and three-particle nonlocality are discussed in the light of Svetlichny's inequality [Phys. Rev. D 35, 3066 (1987)]. It is shown that there exist sets of measurements which can be used to prove three-particle entanglement, but which are nevertheless useless at proving three-particle nonlocality. In particular, it is shown that the quantum predictions giving a maximal violation of Mermin's three-particle Bell inequality [Phys. Rev. Lett. 65, 1838 (1990)] can be reproduced by a hybrid hidden variables model in which nonlocal correlations are present only between two of the particles. It should be possible, however, to test the existence of both three-particle entanglement and three-particle nonlocality for any given quantum state via Svetlichny's inequality.Comment: REVTeX4, 4 pages, journal versio

Hydrogen-Helium Mixtures at High Pressure

The properties of hydrogen-helium mixtures at high pressure are crucial to address important questions about the interior of Giant planets e.g. whether Jupiter has a rocky core and did it emerge via core accretion? Using path integral Monte Carlo simulations, we study the properties of these mixtures as a function of temperature, density and composition. The equation of state is calculated and compared to chemical models. We probe the accuracy of the ideal mixing approximation commonly used in such models. Finally, we discuss the structure of the liquid in terms of pair correlation functions.Comment: Proceedings article of the 5th Conference on Cryocrystals and Quantum Crystals in Wroclaw, Poland, submitted to J. Low. Temp. Phys. (2004

Black holes and Hawking radiation in spacetime and its analogues

These notes introduce the fundamentals of black hole geometry, the thermality of the vacuum, and the Hawking effect, in spacetime and its analogues. Stimulated emission of Hawking radiation, the trans-Planckian question, short wavelength dispersion, and white hole radiation in the setting of analogue models are also discussed. No prior knowledge of differential geometry, general relativity, or quantum field theory in curved spacetime is assumed.Comment: 31 pages, 9 figures; to appear in the proceedings of the IX SIGRAV School on 'Analogue Gravity', Como (Italy), May 2011, eds. D. Faccio et. al. (Springer

Nuclear effects in the Drell-Yan process at very high energies

We study Drell-Yan (DY) dilepton production in proton(deuterium)-nucleus and in nucleus-nucleus collisions within the light-cone color dipole formalism. This approach is especially suitable for predicting nuclear effects in the DY cross section for heavy ion collisions, as it provides the impact parameter dependence of nuclear shadowing and transverse momentum broadening, quantities that are not available from the standard parton model. For p(D)+A collisions we calculate nuclear shadowing and investigate nuclear modification of the DY transverse momentum distribution at RHIC and LHC for kinematics corresponding to coherence length much longer than the nuclear size. Calculations are performed separately for transversely and longitudinally polarized DY photons, and predictions are presented for the dilepton angular distribution. Furthermore, we calculate nuclear broadening of the mean transverse momentum squared of DY dileptons as function of the nuclear mass number and energy. We also predict nuclear effects for the cross section of the DY process in heavy ion collisions. We found a substantial nuclear shadowing for valence quarks, stronger than for the sea.Comment: 46 pages, 18 figures, title changed and some discussion added, accepted for publication in PR

Pseudoscalar Higgs boson production associated with a single bottom quark at hadron colliders

We compute the complete next-to-leading order (NLO) SUSY-QCD corrections for the associated production of a pseudoscalar Higgs boson with a bottom quark via bottom-gluon fusion at the CERN Large Hadron Collider (LHC) and the Fermilab Tevatron. We find that the NLO QCD correction in the MSSM reaches $40$ at the LHC and $45$ at the Tevatron in our chosen parameter space

Exact Hypersurface-Homogeneous Solutions in Cosmology and Astrophysics

A framework is introduced which explains the existence and similarities of most exact solutions of the Einstein equations with a wide range of sources for the class of hypersurface-homogeneous spacetimes which admit a Hamiltonian formulation. This class includes the spatially homogeneous cosmological models and the astrophysically interesting static spherically symmetric models as well as the stationary cylindrically symmetric models. The framework involves methods for finding and exploiting hidden symmetries and invariant submanifolds of the Hamiltonian formulation of the field equations. It unifies, simplifies and extends most known work on hypersurface-homogeneous exact solutions. It is shown that the same framework is also relevant to gravitational theories with a similar structure, like Brans-Dicke or higher-dimensional theories.Comment: 41 pages, REVTEX/LaTeX 2.09 file (don't use LaTeX2e !!!) Accepted for publication in Phys. Rev.

Spherically Symmetric Braneworld Solutions with R_{4} term in the Bulk

An analysis of a spherically symmetric braneworld configuration is performed when the intrinsic curvature scalar is included in the bulk action; the vanishing of the electric part of the Weyl tensor is used as the boundary condition for the embedding of the brane in the bulk. All the solutions outside a static localized matter distribution are found; some of them are of the Schwarzschild-(A)dS_{4} form. Two modified Oppenheimer-Volkoff interior solutions are also found; one is matched to a Schwarzschild-(A)dS_{4} exterior, while the other does not. A non-universal gravitational constant arises, depending on the density of the considered object; however, the conventional limits of the Newton's constant are recovered. An upper bound of the order of TeV for the energy string scale is extracted from the known solar system measurements (experiments). On the contrary, in usual brane dynamics, this string scale is calculated to be larger than TeV.Comment: 23 pages, 1 figure, one minor chang

Global QCD Analysis and the CTEQ Parton Distributions

The CTEQ program for the determination of parton distributions through a global QCD analysis of data for various hard scattering processes is fully described. A new set of distributions, CTEQ3, incorporating several new types of data is reported and compared to the two previous sets of CTEQ distributions. Comparison with current data is discussed in some detail. The remaining uncertainties in the parton distributions and methods to further reduce them are assessed. Comparisons with the results of other global analyses are also presented.Comment: (Change in Latex style only: 2up style removed since many don't have it.) 35 pages, 23 figures separately submitted as uuencoded compressed ps-file; Michigan State Report # MSU-HEP/41024 and CTEQ 40