Factors influencing in vivo transduction by recombinant adeno-associated viral vectors expressing the human factor IX cDNA.

Long-term expression of coagulation factor IX (FIX) has been observed in murine and canine models following administration of recombinant adeno-associated viral (rAAV) vectors into either the portal vein or muscle. These studies were designed to evaluate factors that influence rAAV-mediated FIX expression. Stable and persistent human FIX (hFIX) expression (> 22 weeks) was observed from 4 vectors after injection into the portal circulation of immunodeficient mice. The level of expression was dependent on promoter with the highest expression, 10% of physiologic levels, observed with a vector containing the cytomegalovirus (CMV) enhancer/beta-actin promoter complex (CAGG). The kinetics of expression after injection of vector particles into muscle, tail vein, or portal vein were similar with hFIX detectable at 2 weeks and reaching a plateau by 8 weeks. For a given dose, intraportal administration of rAAV CAGG-FIX resulted in a 1.5-fold or 4-fold higher level of hFIX compared to tail vein or intramuscular injections, respectively. Polymerase chain reaction analysis demonstrated predominant localization of the rAAV FIX genome in liver and spleen after tail vein injection with a higher proportion in liver after portal vein injection. Therapeutic levels of hFIX were detected in the majority of immunocompetent mice (21 of 22) following intravenous administration of rAAV vector without the development of anti-hFIX antibodies, but hFIX was not detected in 14 immunocompetent mice following intramuscular administration, irrespective of strain. Instead, neutralizing anti-hFIX antibodies were detected in all the mice. These observations may have important implications for hemophilia B gene therapy with rAAV vectors

Rotationally-Driven Fragmentation for the Formation of the Binary Protostellar System L1551 IRS 5

Either bulk rotation or local turbulence is widely invoked to drive fragmentation in collapsing cores so as to produce multiple star systems. Even when the two mechanisms predict different manners in which the stellar spins and orbits are aligned, subsequent internal or external interactions can drive multiple systems towards or away from alignment thus masking their formation process. Here, we demonstrate that the geometrical and dynamical relationship between the binary system and its surrounding bulk envelope provide the crucial distinction between fragmentation models. We find that the circumstellar disks of the binary protostellar system L1551 IRS 5 are closely parallel not just with each other but also with their surrounding flattened envelope. Measurements of the relative proper motion of the binary components spanning nearly 30 yr indicate an orbital motion in the same sense as the envelope rotation. Eliminating orbital solutions whereby the circumstellar disks would be tidally truncated to sizes smaller than are observed, the remaining solutions favor a circular or low-eccentricity orbit tilted by up to $\sim$25$^\circ$ from the circumstellar disks. Turbulence-driven fragmentation can generate local angular momentum to produce a coplanar binary system, but which bears no particular relationship with its surrounding envelope. Instead, the observed properties conform with predictions for rotationally-driven fragmentation. If the fragments were produced at different heights or on opposite sides of the midplane in the flattened central region of a rotating core, the resulting protostars would then exhibit circumstellar disks parallel with the surrounding envelope but tilted from the orbital plane as is observed.Comment: Accepted for publication in Ap

No Go Theorem for Kinematic Self-Similarity with A Polytropic Equation of State

We have investigated spherically symmetric spacetimes which contain a perfect fluid obeying the polytropic equation of state and admit a kinematic self-similar vector of the second kind which is neither parallel nor orthogonal to the fluid flow. We have assumed two kinds of polytropic equations of state and shown in general relativity that such spacetimes must be vacuum.Comment: 5 pages, no figures. Revtex. One word added to the title. Final version to appear in Physical Review D as a Brief Repor

Microscopic analysis of the chemical reaction between Fe(Te,Se) thin films and underlying CaF2_2

To understand the chemical reaction at the interface of materials, we performed a transmission electron microscopy (TEM) observation in four types of Fe(Te,Se) superconducting thin films prepared on different types of substrates: CaF2 substrate, CaF2 substrate with a CaF2 buffer layer, CaF2 substrate with a FeSe buffer layer, and a LaAlO3 substrate with a CaF2 buffer layer. Based on the energy-dispersive X-ray spectrometer (EDX) analysis, we found possible interdiffusion between fluorine and selenium that has a strong influence on the superconductivity in Fe(Te,Se) films. The chemical interdiffusion also plays a significant role in the variation of the lattice parameters. The lattice parameters of the Fe(Te,Se) thin films are primarily determined by the chemical substitution of anions, and the lattice mismatch only plays a secondary role.Comment: 30 pages, 9 figur

High-pressure study on the superconducting pyrochlore oxide Cd2Re2O7

Superconducting and structural phase transitions in a pyrochlore oxide Cd2Re2O7 are studied under high pressure by x-ray diffraction and electrical resistivity measurements. A rich P-T phase diagram is obtained, which contains at least two phases with the ideal and slightly distorted pyrochlore structures. It is found that the transition between them is suppressed with increasing pressure and finally disappears at a critical pressure Pc = 3.5 GPa. Remarkable enhancements in the residual resistivity as well as the coefficient A of the AT 2 term in the resistivity are found around the critical pressure. Superconductivity is detected only for the phase with the structural distortion. It is suggested that the charge fluctuations of Re ions play a crucial role in determining the electronic properties of Cd2Re2O7.Comment: 5 pages, 5 figures, submitted to J. Phys. Soc. Jp

Convergence to a self-similar solution in general relativistic gravitational collapse

We study the spherical collapse of a perfect fluid with an equation of state $P=k\rho$ by full general relativistic numerical simulations. For 0, it has been known that there exists a general relativistic counterpart of the Larson-Penston self-similar Newtonian solution. The numerical simulations strongly suggest that, in the neighborhood of the center, generic collapse converges to this solution in an approach to a singularity and that self-similar solutions other than this solution, including a ``critical solution'' in the black hole critical behavior, are relevant only when the parameters which parametrize initial data are fine-tuned. This result is supported by a mode analysis on the pertinent self-similar solutions. Since a naked singularity forms in the general relativistic Larson-Penston solution for 0, this will be the most serious known counterexample against cosmic censorship. It also provides strong evidence for the self-similarity hypothesis in general relativistic gravitational collapse. The direct consequence is that critical phenomena will be observed in the collapse of isothermal gas in Newton gravity, and the critical exponent $\gamma$ will be given by $\gamma\approx 0.11$, though the order parameter cannot be the black hole mass.Comment: 22 pages, 15 figures, accepted for publication in Physical Review D, reference added, typos correcte

Specific heat amplitude ratios for anisotropic Lifshitz critical behaviors

We determine the specific heat amplitude ratio near a $m$-axial Lifshitz point and show its universal character. Using a recent renormalization group picture along with new field-theoretical $\epsilon_{L}$-expansion techniques, we established this amplitude ratio at one-loop order. We estimate the numerical value of this amplitude ratio for $m=1$ and $d=3$. The result is in very good agreement with its experimental measurement on the magnetic material $MnP$. It is shown that in the limit $m \to 0$ it trivially reduces to the Ising-like amplitude ratio.Comment: 8 pages, RevTex, accepted as a Brief Report in Physical Review