Transduction Efficiency of AAV 2/6, 2/8 and 2/9 Vectors for Delivering Genes in Human Corneal Fibroblasts

In the present study, cellular tropism and relative transduction efficiency of AAV2/6, AAV2/8 and AAV2/9 vectors have been tested for the cornea using primary cultures of human corneal fibroblasts. The AAV6, AAV8 and AAV9 serotypes having AAV2 ITR plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Primary cultures of human corneal fibroblasts were exposed to AAV infectious particles at two different doses (1×105 and 2×105 MOI). Cytochemistry and enzyme assays were used to measure delivered transgene expression in samples collected at 4 and 30 hours after AAV infection by counting AP-stained cells or quantifying AP enzyme activity. Cellular toxicity of AAVs was evaluated with TUNEL and trypan blue assays. All three AAV serotypes transduced human corneal fibroblasts. The order of transduction efficiency was AAV2/6\u3e\u3e\u3eAAV2/9\u3eAAV2/8. The transduction efficiency of AAV2/6 was 30-50 fold higher (p \u3c0.001) for the human corneal fibroblasts compared to the AAV2/8 or AAV2/9 at two tested doses. The level of transgene expression at 4 hrs was considerably low compared to 30 hrs suggesting that the transgene delivery did not reach its peak at 4 hrs. Cultures exposed to any of the three AAV serotypes showed more than 97% cellular viability and less than 5 TUNEL positive cells suggesting that tested AAV serotypes do not induce significant cell death and are safe for corneal gene therapy

A Minkowski Type Trace Inequality and Strong Subadditivity of Quantum Entropy II: Convexity and Concavity

We revisit and prove some convexity inequalities for trace functions conjectured in the earlier part I. The main functional considered is \Phi_{p,q}(A_1,A_2,...,A_m) = (trace((\sum_{j=1}^m A_j^p)^{q/p}))^{1/q} for m positive definite operators A_j. In part I we only considered the case q=1 and proved the concavity of \Phi_{p,1} for 0 < p \leq 1 and the convexity for p=2. We conjectured the convexity of \Phi_{p,1} for 1< p < 2. Here we not only settle the unresolved case of joint convexity for 1 \leq p \leq 2, we are also able to include the parameter q\geq 1 and still retain the convexity. Among other things this leads to a definition of an L^q(L^p) norm for operators when 1 \leq p \leq 2 and a Minkowski inequality for operators on a tensor product of three Hilbert spaces -- which leads to another proof of strong subadditivity of entropy. We also prove convexity/concavity properties of some other, related functionals.Comment: Proof of a conjecture in math/0701352. Revised version replaces earlier draft. 18 pages, late

Magnetic Brane Solutions in AdS

We construct asymptotically AdS_5 solutions of Einstein-Maxwell theory dual to N=4 SYM theory on R^{3,1} in the presence of a background magnetic field. The solutions interpolate between AdS_5 and a near horizon AdS_3\times T^2. The central charge of the near horizon region, and hence low temperature entropy of the solution, is found to be \sqrt{4\over 3} times that of free N=4 SYM theory. The entropy vanishes at zero temperature. We also present the generalization of these solutions to arbitrary spacetime dimensionality.Comment: 17 page

Charged Magnetic Brane Solutions in AdS_5 and the fate of the third law of thermodynamics

We construct asymptotically AdS_5 solutions to 5-dimensional Einstein-Maxwell theory with Chern-Simons term which are dual to 4-dimensional gauge theories, including N=4 SYM theory, in the presence of a constant background magnetic field B and a uniform electric charge density \rho. For the solutions corresponding to supersymmetric gauge theories, we find numerically that a small magnetic field causes a drastic decrease in the entropy at low temperatures. The near-horizon AdS_2 \times R^3 geometry of the purely electrically charged brane thus appears to be unstable under the addition of a small magnetic field. Based on this observation, we propose a formulation of the third law of thermodynamics (or Nernst theorem) that can be applied to black holes in the AdS/CFT context. We also find interesting behavior for smaller, non-supersymmetric, values of the Chern-Simons coupling k. For k=1 we exhibit exact solutions corresponding to warped AdS_3 black holes, and show that these can be connected to asymptotically AdS_5 spacetime. For k\leq 1 the entropy appears to go to a finite value at extremality, but the solutions still exhibit a mild singularity at strictly zero temperature. In addition to our numerics, we carry out a complete perturbative analysis valid to order B^2, and find that this corroborates our numerical results insofar as they overlap.Comment: 45 pages v2: added note about subsequent results found in arXiv:1003.130

Dynamics of monatomic liquids

We present a theory of the dynamics of monatomic liquids built on two basic ideas: (1) The potential surface of the liquid contains three classes of intersecting nearly-harmonic valleys, one of which (the ``random'' class) vastly outnumbers the others and all whose members have the same depth and normal mode spectrum; and (2) the motion of particles in the liquid can be decomposed into oscillations in a single many-body valley, and nearly instantaneous inter-valley transitions called transits. We review the thermodynamic data which led to the theory, and we discuss the results of molecular dynamics (MD) simulations of sodium and Lennard-Jones argon which support the theory in more detail. Then we apply the theory to problems in equilibrium and nonequilibrium statistical mechanics, and we compare the results to experimental data and MD simulations. We also discuss our work in comparison with the QNM and INM research programs and suggest directions for future research.Comment: 53 pages, 16 figures. Differs from published version in using American English spelling and grammar (published version uses British English

Isotropic-nematic phase transition in suspensions of filamentous virus and the neutral polymer Dextran

We present an experimental study of the isotropic-nematic phase transition in an aqueous mixture of charged semi-flexible rods (fd virus) and neutral polymer (Dextran). A complete phase diagram is measured as a function of ionic strength and polymer molecular weight. At high ionic strength we find that adding polymer widens the isotropic-nematic coexistence region with polymers preferentially partitioning into the isotropic phase, while at low ionic strength the added polymer has no effect on the phase transition. The nematic order parameter is determined from birefringence measurements and is found to be independent of polymer concentration (or equivalently the strength of attraction). The experimental results are compared with the existing theoretical predictions for the isotropic-nematic transition in rods with attractive interactions.Comment: 8 Figures. To be published in Phys. Rev. E. For more information see http://www.elsie.brandeis.ed

The Galactic Population of Low- and Intermediate-Mass X-ray Binaries

(abridged) We present the first study that combines binary population synthesis in the Galactic disk and detailed evolutionary calculations of low- and intermediate-mass X-ray binaries (L/IMXBs). We show that the formation probability of IMXBs with initial donor masses of 1.5--4 Msun is typically >~5 times higher than that of standard LMXBs, and suggest that the majority of the observed systems may have descended from IMXBs. Distributions at the current epoch of the orbital periods, donor masses, and mass accretion rates have been computed, as have orbital-period distributions of BMPs. Several significant discrepancies between the theoretical and observed distributions are discussed. The orbital-period distribution of observed BMPs strongly favors cases where the envelope of the neutron-star progenitor is more easily ejected during the common-envelope phase. However, this leads to a >~100-fold overproduction of the theoretical number of luminous X-ray sources relative to the total observed number of LMXBs. X-ray irradiation of the donor star may result in a dramatic reduction in the X-ray active lifetime of L/IMXBs, thus possibly resolving the overproduction problem, as well as the long-standing BMP/LMXB birthrate problem.Comment: 12 pages, emulateapj, submitted to Ap

V-T Theory of Self Dynamic Response in a Monatomic Liquid

A new theoretical model for self dynamic response is developed using Vibration-Transit (V-T) theory, and is applied to liquid sodium at all wavevectors q from the hydrodynamic regime to the free particle limit. In this theory the zeroth-order Hamiltonian describes the vibrational motion in a single random valley harmonically extended to infinity. This Hamiltonian is tractable, is evaluated a priori for monatomic liquids, and the same Hamiltonian (the same set of eigenvalues and eigenvectors) is used for equilibrium and nonequlibrium theory. Here, for the self intermediate scattering function Fself(q,t) we find the vibrational contribution is in near perfect agreement with molecular dynamics (MD) through short and intermediate times, at all q. This is direct confirmation that normal mode vibrational correlations are present in the motion of the liquid state. The primary transit effect is diffusive motion of the vibrational equilibrium positions, as the liquid transits rapidly among random valleys. This motion is modeled as a standard random walk, and the resulting theoretical Fself(q,t) is in excellent agreement with MD results at all q and t. In the limit for q to infinity, the theory automatically exhibits the correct approach to the free-particle limit. Also in the limit for q to zero, the hydrodynamic limit emerges as well. In contrast to the benchmark theories of generalized hydrodynamics and mode coupling, the present theory is near a priori, while achieving modestly better accuracy. Therefore, in our view, it constitutes an improvement over the traditional theories.Comment: 16 pages, 11 figures, Journal Paper. Following referee's comments, Section IID has been completely rewritten and a new Section IIE has been adde

Albany: Using Component-based Design to Develop a Flexible, Generic Multiphysics Analysis Code

Abstract: Albany is a multiphysics code constructed by assembling a set of reusable, general components. It is an implicit, unstructured grid finite element code that hosts a set of advanced features that are readily combined within a single analysis run. Albany uses template-based generic programming methods to provide extensibility and flexibility; it employs a generic residual evaluation interface to support the easy addition and modification of physics. This interface is coupled to powerful automatic differentiation utilities that are used to implement efficient nonlinear solvers and preconditioners, and also to enable sensitivity analysis and embedded uncertainty quantification capabilities as part of the forward solve. The flexible application programming interfaces in Albany couple to two different adaptive mesh libraries; it internally employs generic integration machinery that supports tetrahedral, hexahedral, and hybrid meshes of user specified order. We present the overall design of Albany, and focus on the specifics of the integration of many of its advanced features. As Albany and the components that form it are openly available on the internet, it is our goal that the reader might find some of the design concepts useful in their own work. Albany results in a code that enables the rapid development of parallel, numerically efficient multiphysics software tools. In discussing the features and details of the integration of many of the components involved, we show the reader the wide variety of solution components that are available and what is possible when they are combined within a simulation capability. Key Words: partial differential equations, finite element analysis, template-based generic programmin