The interferon-stimulated gene IFITM3 restricts West Nile virus infection and pathogenesis

The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(−/−) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this, Ifitm3(−/−) fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infected Ifitm3(−/−) mice showed decreases in the total number of B cells, CD4(+) T cells, and antigen-specific CD8(+) T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells. IMPORTANCE As part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM) have been reported to inhibit multiple families of viruses in cell culture. However, few reports have evaluated the impact of IFITM genes on viral pathogenesis in vivo. In this study, we characterized the antiviral activity of Ifitm3 against West Nile virus (WNV), an encephalitic flavivirus, using mice with a targeted gene deletion of Ifitm3. Based on extensive virological and immunological analyses, we determined that Ifitm3 protects mice from WNV-induced mortality by restricting virus accumulation in peripheral organs and, subsequently, in central nervous system tissues. Our data suggest that Ifitm3 restricts WNV pathogenesis by multiple mechanisms and functions in part by controlling infection in different cell types

Emergent Quantum Near-Criticality from Baryonic Black Branes

We find new black 3-brane solutions describing the "conifold gauge theory" at nonzero temperature and baryonic chemical potential. Of particular interest is the low-temperature limit where we find a new kind of weakly curved near-horizon geometry; it is a warped product AdS_2 x R^3 x T^{1,1} with warp factors that are powers of the logarithm of the AdS radius. Thus, our solution encodes a new type of emergent quantum near-criticality. We carry out some stability checks for our solutions. We also set up a consistent ansatz for baryonic black 2-branes of M-theory that are asymptotic to AdS_4 x Q^{1,1,1}.Comment: 29 pages, 4 figures; v2 discussion of entropy revised, minor changes; v3 note added, minor improvements, version published in JHE

Chiral phase transitions and quantum critical points of the D3/D7(D5) system with mutually perpendicular E and B fields at finite temperature and density

We study chiral symmetry restoration with increasing temperature and density in gauge theories subject to mutually perpendicular electric and magnetic fields using holography. We determine the chiral symmetry breaking phase structure of the D3/D7 and D3/D5 systems in the temperature-density-electric field directions. A magnetic field may break the chiral symmetry and an additional electric field induces Ohm and Hall currents as well as restoring the chiral symmetry. At zero temperature the D3/D5 system displays a line of holographic BKT phase transitions in the density-electric field plane, while the D3/D7 system shows a mean-field phase transition. At intermediate temperatures, the transitions in the density-electric field plane are of first order at low density, transforming to second order at critical points as density rises. At high temperature the transition is only ever first order.Comment: 15 pages, 7 figures, v2: Added a referenc

d+idd+id Holographic Superconductors

A holographic model of $d+id$ superconductors based on the action proposed by Benini, Herzog, and Yarom [arXiv:1006.0731] is studied. This model has a charged spin two field in an AdS black hole spacetime. Working in the probe limit, the normalizable solution of the spin two field in the bulk gives rise to a $d+id$ superconducting order parameter at the boundary of the AdS. We calculate the fermion spectral function in this\ superconducting background and confirm the existence of fermi arcs for non-vanishing Majorana couplings. By changing the relative strength $\gamma$ of the $d$ and $id$ condensations, the position and the size of the fermi arcs are changed. When $\gamma =1$, the spectrum becomes isotropic and the spectral function is s-wave like. By changing the fermion mass, the fermi momentum is changed. We also calculate the conductivity for these holographic $d+id$ superconductors where time reversal symmetry has been broken spontaneously. A non-vanishing Hall conductivity is obtained even without an external magnetic field.Comment: 24 pages,17 figures, Add more discussions on hall conductivity, two new figures, Matched with published versio

Gauge gravity duality for d-wave superconductors: prospects and challenges

We write down an action for a charged, massive spin two field in a fixed Einstein background. Despite some technical problems, we argue that in an effective field theory framework and in the context of the AdS/CFT correspondence, this action can be used to study the properties of a superfluid phase transition with a d-wave order parameter in a dual strongly interacting field theory. We investigate the phase diagram and the charge conductivity of the superfluid phase. We also explain how possible couplings between the spin two field and bulk fermions affect the fermion spectral function.Comment: 42 pages, 6 figure

Dynamics of Fundamental Matter in N=2* Yang-Mills Theory

We study the dynamics of quenched fundamental matter in $\mathcal{N}=2^\ast$ supersymmetric large $N$ SU(N) Yang-Mills theory at zero temperature. Our tools for this study are probe D7-branes in the holographically dual $\mathcal{N}=2^\ast$ Pilch-Warner gravitational background. Previous work using D3-brane probes of this geometry has shown that it captures the physics of a special slice of the Coulomb branch moduli space of the gauge theory, where the $N$ constituent D3-branes form a dense one dimensional locus known as the enhancon, located deep in the infrared. Our present work shows how this physics is supplemented by the physics of dynamical flavours, revealed by the D7-branes embeddings we find. The Pilch-Warner background introduces new divergences into the D7-branes free energy, which we are able to remove with a single counterterm. We find a family of D7-brane embeddings in the geometry and discuss their properties. We study the physics of the quark condensate, constituent quark mass, and part of the meson spectrum. Notably, there is a special zero mass embedding that ends on the enhancon, which shows that while the geometry acts repulsively on the D7-branes, it does not do so in a way that produces spontaneous chiral symmetry breaking.Comment: 24 pages, 8 figures. Corrected typos, added comment about counterterm. To appear in JHE

Holographic DC conductivities from the open string metric

We study the DC conductivities of various holographic models using the open string metric (OSM), which is an effective metric geometrizing density and electromagnetic field effect. We propose a new way to compute the nonlinear conductivity using OSM. As far as the final conductivity formula is concerned, it is equivalent to the Karch-O'Bannon's real-action method. However, it yields a geometrical insight and technical simplifications. Especially, a real-action condition is interpreted as a regular geometry condition of OSM. As applications of the OSM method, we study several holographic models on the quantum Hall effect and strange metal. By comparing a Lifshitz background and the Light-Cone AdS, we show how an extra parameter can change the temperature scaling behavior of conductivity. Finally we discuss how OSM can be used to study other transport coefficients, such as diffusion constant, and effective temperature induced by the effective world volume horizon.Comment: 33 page

Holographic bulk viscosity: GPR vs EO

Recently Eling and Oz (EO) proposed a formula for the holographic bulk viscosity, in arXiv:1103.1657, derived from the null horizon focusing equation. This formula seems different from that obtained earlier by Gubser, Pufu and Rocha (GPR) in arXiv:0806.0407 calculated from the IR limit of the two-point function of the trace of the stress tensor. The two were shown to agree only for some simple scaling cases. We point out that the two formulae agree in two non-trivial holographic theories describing RG flows. The first is the strongly coupled N=2* gauge theory plasma. The second is the semi-phenomenological model of Improved Holographic QCD.Comment: 21 pages, 2 figure

The Structure of the Non-SUSY Baryonic Branch of Klebanov-Strassler

We study the two-dimensional space of supergravity solutions corresponding to non-supersymmetric deformations of the baryonic branch of Klebanov-Strassler. By combining analytical methods with a numerical survey of the parameter space, we find that this solution space includes as limits the softly-broken N=1 solutions of Gubser et al. and those of Dymarsky and Kuperstein. We also identify a one-dimensional family of solutions corresponding to a natural non-supersymmetric generalisation of Klebanov-Strassler, and one corresponding to the limit in which supersymmetry is completely absent, even in the far UV. For almost all of the parameter space we find indications that much of the structure of the supersymmetric baryonic branch survives.Comment: 29 pages plus appendices, 11 figure

Semi-parametric estimation of the Wilshire creep life prediction model: an application to 2.25Cr-1Mo steel

The Wilshire equation is a recent addition to the literature on safe life prediction. While the effect of temperature on creep life is reasonably understood, the effect of stress isn’t. The Wilshire equation deals with this by partitioning over sub ranges of stress, but this approximation can lead to poor life time predictions. This paper introduces a semi-parametric procedure that allows the data itself to identify the stress relationship. When applied to 2.25Cr-1Mo steel it was found that the stress relationship is non-linear, and this semi-parametric version of the Wilshire model had better predictive performance compared to any partitioned Wilshire model. This approach contains a limit to valid extrapolation and the isothermal predictions for creep life have a more realistic pattern of behaviour