344 research outputs found

    Comparison of adeno-associated virus pseudotype 1, 2, and 8 vectors administered by intramuscular injection in the treatment of murine phenylketonuria

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    Phenylketonuria (PKU) is caused by hepatic phenylalanine hydroxylase (PAH) deficiency and is associated with systemic accumulation of phenylalanine (Phe). Previously we demonstrated correction of murine PKU after intravenous injection of a recombinant type 2 adeno-associated viral vector pseudotyped with type 8 capsid (rAAV2/8), which successfully directed hepatic transduction and Pah gene expression. Here, we report that liver PAH activity and phenylalanine clearance were also restored in PAH-deficient mice after simple intramuscular injection of either AAV2 pseudotype 1 (rAAV2/1) or rAAV2/8 vectors. Serotype 2 AAV vector (rAAV2/2) was also investigated, but long-term phenylalanine clearance has been observed only for pseudotypes 1 and 8. Therapeutic correction was shown in both male and female mice, albeit more effectively in males, in which correction lasted for the entire period of the experiment (>1 year). Although phenylalanine levels began to rise in female mice at about 8-10 months after rAAV2/8 injection they remained only mildly hyperphenylalaninemic thereafter and subsequent supplementation with synthetic tetrahydrobiopterin resulted in a transient decrease in blood phenylalanine. Alternatively, subsequent administration of a second vector with a different AAV pseudotype to avoid immunity against the previously administrated vector was also successful for long-term treatment of female PKU mice. Overall, this relatively less invasive gene transfer approach completes our previous studies and allows comparison of complementary strategies in the development of efficient PKU gene therapy protocols

    Asymptotes in SU(2) Recoupling Theory: Wigner Matrices, 3j3j Symbols, and Character Localization

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    In this paper we employ a novel technique combining the Euler Maclaurin formula with the saddle point approximation method to obtain the asymptotic behavior (in the limit of large representation index JJ) of generic Wigner matrix elements DMMJ(g)D^{J}_{MM'}(g). We use this result to derive asymptotic formulae for the character χJ(g)\chi^J(g) of an SU(2) group element and for Wigner's 3j3j symbol. Surprisingly, given that we perform five successive layers of approximations, the asymptotic formula we obtain for χJ(g)\chi^J(g) is in fact exact. This result provides a non trivial example of a Duistermaat-Heckman like localization property for discrete sums.Comment: 36 pages, 3 figure

    On the Propagation of Slip Fronts at Frictional Interfaces

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    The dynamic initiation of sliding at planar interfaces between deformable and rigid solids is studied with particular focus on the speed of the slip front. Recent experimental results showed a close relation between this speed and the local ratio of shear to normal stress measured before slip occurs (static stress ratio). Using a two-dimensional finite element model, we demonstrate, however, that fronts propagating in different directions do not have the same dynamics under similar stress conditions. A lack of correlation is also observed between accelerating and decelerating slip fronts. These effects cannot be entirely associated with static local stresses but call for a dynamic description. Considering a dynamic stress ratio (measured in front of the slip tip) instead of a static one reduces the above-mentioned inconsistencies. However, the effects of the direction and acceleration are still present. To overcome this we propose an energetic criterion that uniquely associates, independently on the direction of propagation and its acceleration, the slip front velocity with the relative rise of the energy density at the slip tip.Comment: 15 pages, 6 figure

    Matching gauge theory and string theory in a decoupling limit of AdS/CFT

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    We identify a regime of the AdS/CFT correspondence in which we can quantitatively match N=4 super Yang-Mills (SYM) for small 't Hooft coupling with weakly coupled type IIB string theory on AdS_5 x S^5. We approach this regime by taking the same decoupling limit on both sides of the correspondence. On the gauge theory side only the states in the SU(2) sector survive, and in the planar limit the Hamiltonian is given by the XXX_{1/2} Heisenberg spin chain. On the string theory side we show that the decoupling limit corresponds to a non-relativistic limit. In this limit some of the bosonic modes and all of the fermionic modes of the string become infinitely heavy and decouple. We first take the decoupling limit of the string sigma-model classically. This enables us to identify a semi-classical regime with semi-classical string states even though we are in a regime corresponding to small 't Hooft coupling. We furthermore analyze the quantum corrections that enter in taking the limit. From this we infer that gauge theory and string theory match, both in terms of the action and the spectrum, for the leading part and the first correction away from the semi-classical regime. Finally we consider the implications for the hitherto unexplained matching of the one-loop contribution to the energy of certain gauge theory and string theory states, and we explain how our results give a firm basis for the matching of the Hagedorn temperature in hep-th/0608115.Comment: 29 pages, 1 figure. v2: Version published in JHEP, section 4 improve

    Magnetic Heisenberg-chain/pp-wave correspondence

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    We find a decoupling limit of planar N=4 super Yang-Mills (SYM) on R x S^3 in which it becomes equivalent to the ferromagnetic XXX_{1/2} Heisenberg spin chain in an external magnetic field. The decoupling limit generalizes the one found in hep-th/0605234 corresponding to the case with zero magnetic field. The presence of the magnetic field is seen to break the degeneracy of the vacuum sector and it has a non-trivial effect on the low energy spectrum. We find a general connection between the Hagedorn temperature of planar N=4 SYM on R x S^3 in the decoupling limit and the thermodynamics of the Heisenberg chain. This is used to study the Hagedorn temperature for small and large value of the effective coupling. We consider the dual decoupling limit of type IIB strings on AdS_5 x S^5. We find a Penrose limit compatible with the decoupling limit that gives a magnetic pp-wave background. The breaking of the symmetry by the magnetic field on the gauge theory side is seen to have a geometric counterpart in the derivation of the Penrose limit. We take the decoupling limit of the pp-wave spectrum and succesfully match the resulting spectrum to the low energy spectrum on the gauge theory side. This enables us to match the Hagedorn temperature of the pp-wave to the Hagedorn temperature of the gauge theory for large effective coupling. This generalizes the results of hep-th/0608115 to the case of non-zero magnetic field.Comment: 35 pages, 2 figures. v2: Refs. adde

    A Monte-Carlo study of the AdS/CFT correspondence: an exploration of quantum gravity effects

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    In this paper we study the AdS/CFT correspondence for N=4 SYM with gauge group U(N), compactified on S^3 in four dimensions using Monte-Carlo techniques. The simulation is based on a particular reduction of degrees of freedom to commuting matrices of constant fields, and in particular, we can write the wave functions of these degrees of freedom exactly. The square of the wave function is equivalent to a probability density for a Boltzman gas of interacting particles in six dimensions. From the simulation we can extract the density particle distribution for each wave function, and this distribution can be interpreted as a special geometric locus in the gravitational dual. Studying the wave functions associated to half-BPS giant gravitons, we are able to show that the matrix model can measure the Planck scale directly. We also show that the output of our simulation seems to match various theoretical expectations in the large N limit and that it captures 1/N effects as statistical fluctuations of the Boltzman gas with the expected scaling. Our results suggest that this is a very promising approach to explore quantum corrections and effects in gravitational physics on AdS spaces.Comment: 40 pages, 7 figures, uses JHEP. v2: references adde

    BF models, Duality and Bosonization on higher genus surfaces

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    The generating functional of two dimensional BFBF field theories coupled to fermionic fields and conserved currents is computed in the general case when the base manifold is a genus g compact Riemann surface. The lagrangian density L=dBAL=dB{\wedge}A is written in terms of a globally defined 1-form AA and a multi-valued scalar field BB. Consistency conditions on the periods of dBdB have to be imposed. It is shown that there exist a non-trivial dependence of the generating functional on the topological restrictions imposed to BB. In particular if the periods of the BB field are constrained to take values 4πn4\pi n, with nn any integer, then the partition function is independent of the chosen spin structure and may be written as a sum over all the spin structures associated to the fermions even when one started with a fixed spin structure. These results are then applied to the functional bosonization of fermionic fields on higher genus surfaces. A bosonized form of the partition function which takes care of the chosen spin structure is obtainedComment: 17 page
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