Human variants in the Neuronal Basic Helix-Loop-Helix/ Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function

Neuronal Per-Arnt-Sim homology (PAS) Factor 4 (NPAS4) is a neuronal activity-dependent transcription factor which heterodimerises with ARNT2 to regulate genes involved in inhibitory synapse formation. NPAS4 functions to maintain excitatory/inhibitory balance in neurons, while mouse models have shown it to play roles in memory formation, social interaction and neurodegeneration. NPAS4 has therefore been implicated in a number of neuropsychiatric or neurodegenerative diseases which are underpinned by defects in excitatory/inhibitory balance. Here we have explored a broad set of non-synonymous human variants in NPAS4 and ARNT2 for disruption of NPAS4 function. We found two variants in NPAS4 (F147S and E257K) and two variants in ARNT2 (R46W and R107H) which significantly reduced transcriptional activity of the heterodimer on a luciferase reporter gene. Furthermore, we found that NPAS4.F147S was unable to activate expression of the NPAS4 target gene BDNF due to reduced dimerisation with ARNT2. Homology modelling predicts F147 in NPAS4 to lie at the dimer interface, where it appears to directly contribute to protein/protein interaction. We also found that reduced transcriptional activation by ARNT2 R46W was due to disruption of nuclear localisation. These results provide insight into the mechanisms of NPAS4/ARNT dimerisation and transcriptional activation and have potential implications for cognitive phenotypic variation and diseases such as autism, schizophrenia and dementia.David C. Bersten, John B. Bruning, Daniel J. Peet, Murray L. Whitela

Stationary axisymmetric solutions of five dimensional gravity

We consider stationary axisymmetric solutions of general relativity that asymptote to five dimensional Minkowski space. It is known that this system has a hidden SL(3,R) symmetry. We identify an SO(2,1) subgroup of this symmetry group that preserves the asymptotic boundary conditions. We show that the action of this subgroup on a static solution generates a one-parameter family of stationary solutions carrying angular momentum. We conjecture that by repeated applications of this procedure one can generate all stationary axisymmetric solutions starting from static ones. As an example, we derive the Myers-Perry black hole starting from the Schwarzschild solution in five dimensions.Comment: 31 pages, LaTeX; references adde

Effect of Scalar Mass in the Absorption and Emission Spectra of Schwarzschild Black Hole

Following Sanchez's approach we investigate the effect of scalar mass in the absorption and emission problems of 4d Schwarzschild black hole. The absorption cross sections for arbitrary angular momentum of the scalar field are computed numerically in the full range of energy by making use of the analytic near-horizon and asymptotic solutions and their analytic continuations. The scalar mass makes an interesting effect in the low-energy absorption cross section for S-wave. Unlike the massless case, the cross section decreases with increasing energy in the extremely low-energy regime. As a result the universality, {\it i.e.} low-energy cross section for S-wave is equal to the horizon area, is broken in the presence of mass. If the scalar mass is larger than a critical mass, the absorption cross section becomes monotonically decreasing function in the entire range of energy. The Hawking emission is also calculated numerically. It turns out that the Planck factor generally suppresses the contribution of higher partial waves except S-wave. The scalar mass in general tends to reduce the emission rate.Comment: 20 pages, 8 figures, V2: few comments are added. version to appear in Classical and Quantum Gravit

Brane Baldness vs. Superselection Sectors

The search for intersecting brane solutions in supergravity is a large and profitable industry. Recently, attention has focused on finding localized forms of known `delocalized' solutions. However, in some cases, a localized version of the delocalized solution simply does not exist. Instead, localized separated branes necessarily delocalize as the separation is removed. This phenomenon is related to black hole no-hair theorems, i.e. `baldness.' We continue the discussion of this effect and describe how it can be understood, in the case of Dirichlet branes, in terms of the corresponding intersection field theory. When it occurs, it is associated with the quantum mixing of phases and lack of superselection sectors in low dimensional field theories. We find surprisingly wide agreement between the field theory and supergravity both with respect to which examples delocalize and with respect to the rate at which this occurs.Comment: 26 pages, ReVTeX, 2 figures, reference added, version to appear in PR

D-brane dynamics near compactified NS5-branes

We examine the dynamics of a $Dp$-brane in the background of $k$ coincident, parallel $NS$5-branes which have had one of their common transverse directions compactified. We find that for small energy, bound orbits can exist at sufficiently large distances where there will be no stringy effects. The orbits are dependent upon the energy density, angular momentum and electric field. The analysis breaks down at radial distances comparable with the compactification radius and we must resort to using a modified form of the harmonic function in this region.Comment: Latex, 20 pages, 6 figs, references adde

Black Holes and Five-brane Thermodynamics

The phase diagram for Dp-branes in M-theory compactified on $T^4$, $T^4/Z_2$, $T^5$, and $T^6$ is constructed. As for the lower-dimensional tori considered in our previous work (hep-th/9810224), the black brane phase at high entropy connects onto matrix theory at low entropy; we thus recover all known instances of matrix theory as consequences of the Maldacena conjecture. The difficulties that arise for $T^6$ are reviewed. We also analyze the D1-D5 system on $T^5$; we exhibit its relation to matrix models of M5-branes, and use spectral flow as a tool to investigate the dependence of the phase structure on angular momentum.Comment: 57 pages, 6 eps figures, latex. v2: DLCQ limit of 5-brane corrected; typos corrected, references added. v3: reference added, typos corrected v4: comments on DLCQ limit of 5-brane corrected one last time. Final version, to appear in Phys. Rev.

Hard Scattering and Gauge/String Duality

We consider high-energy fixed-angle scattering of glueballs in confining gauge theories that have supergravity duals. Although the effective description is in terms of the scattering of strings, we find that the amplitudes are hard (power law). This is a consequence of the warped geometry of the dual theory, which has the effect that in an inertial frame the string process is never in the soft regime. At small angle we find hard and Regge behaviors in different kinematic regions.Comment: 4 page

Wilson Loops and Minimal Surfaces

The AdS/CFT correspondence suggests that the Wilson loop of the large N gauge theory with N=4 supersymmetry in 4 dimensions is described by a minimal surface in AdS_5 x S^5. We examine various aspects of this proposal, comparing gauge theory expectations with computations of minimal surfaces. There is a distinguished class of loops, which we call BPS loops, whose expectation values are free from ultra-violet divergence. We formulate the loop equation for such loops. To the extent that we have checked, the minimal surface in AdS_5 x S^5 gives a solution of the equation. We also discuss the zig-zag symmetry of the loop operator. In the N=4 gauge theory, we expect the zig-zag symmetry to hold when the loop does not couple the scalar fields in the supermultiplet. We will show how this is realized for the minimal surface.Comment: 51 pages, 7 figure

Entropy and Action of Dilaton Black Holes

We present a detailed calculation of the entropy and action of $U(1)~2$ dilaton black holes, and show that both quantities coincide with one quarter of the area of the event horizon. Our methods of calculation make it possible to find an explanation of the rule $S = A/4$ for all static, spherically symmetric black holes studied so far. We show that the only contribution to the entropy comes from the extrinsic curvature term at the horizon, which gives $S = A/4$ independently of the charge(s) of the black hole, presence of scalar fields, etc. Previously, this result did not have a general explanation, but was established on a case-by-case basis. The on-shell Lagrangian for maximally supersymmetric extreme dilaton black holes is also calculated and shown to vanish, in agreement with the result obtained by taking the limit of the expression obtained for black holes with regular horizon.The physical meaning of the entropy is discussed in relation to the issue of splitting of extreme black holes.Comment: 15 p., SU-ITP-92-2