1,939 research outputs found

    Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

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    Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage

    Different profiles of immune reconstitution in children and adults with HIV-infection after highly active antiretroviral therapy

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    BACKGROUND: Recent advances in characterizing the immune recovery of HIV-1-infected people have highlighted the importance of the thymus for peripheral T-cell diversity and function. The aim of this study was to investigate differences in immune reconstitution profiles after highly active antiretroviral therapy (HAART) between HIV-children and adults. METHODS: HIV patients were grouped according to their previous clinical and immunological status: 9 HIV-Reconstituting-adults (HIV-Rec-adults) and 10 HIV-Reconstituting-children (HIV-Rec-children) on HAART with viral load (VL) ≤400 copies/ml and CD4(+ )≥500 cells/μL at least during 6 months before the study and CD4(+ )≤300 cells/μL anytime before. Fifteen healthy-adults and 20 healthy-children (control subjects) were used to calculate Z-score values to unify value scales between children and adults to make them comparable. RESULTS: HIV-Rec-children had higher T-cell receptor excision circles (TREC) and lower interleukin (IL)-7 levels than HIV-Rec-adults (p < 0.05). When we analyzed Z-score values, HIV-Rec-children had higher TREC Z-score levels (p = 0.03) than HIV-Rec-adults but similar IL-7 Z-score levels. Regarding T-cell subsets, HIV-Rec-children had higher naïve CD4(+ )(CD4(+)CD45RA (hi+)CD27(+)), naïve CD8(+ )(CD8(+)CD45RA (hi+)CD27(+)), and memory CD8(+ )(CD8(+)CD45RO(+)) cells/μl than HIV-Rec-adults, but similar memory CD4(+ )(CD4(+)CD45RO(+)) counts. HIV-Rec-children had lower naïve CD8(+ )Z-score values than HIV-Rec-adults (p = 0.05). CONCLUSION: Our data suggest that HIV-Rec-children had better thymic function than HIV-Rec-adults and this fact affects the peripheral T-cell subsets. Thus, T-cell recovery after HAART in HIV-Rec-adults could be the consequence of antigen-independent peripheral T-cell expansion while in HIV-Rec-children thymic output could play a predominant role in immune reconstitution

    On the reflection of magnon bound states

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    We investigate the reflection of two-particle bound states of a free open string in the light-cone AdS_5 x S^5 string sigma model, for large angular momentum J=J_56 and ending on a D7 brane which wraps the entire AdS_5 and a maximal S^3 of S^5. We use the superspace formalism to analyse fundamental and two-particle bound states in the cases of supersymmetry-preserving and broken-supersymmetry boundaries. We find the boundary S-matrices corresponding to bound states both in the bulk and on the boundary.Comment: 35 pages, v2: few typos and ref corrected, accepted for publication in JHE

    Surprisingly Simple Spectra

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    The large N limit of the anomalous dimensions of operators in N=4{\cal N}=4 super Yang-Mills theory described by restricted Schur polynomials, are studied. We focus on operators labeled by Young diagrams that have two columns (both long) so that the classical dimension of these operators is O(N). At large N these two column operators mix with each other but are decoupled from operators with n2n\ne 2 columns. The planar approximation does not capture the large N dynamics. For operators built with 2, 3 or 4 impurities the dilatation operator is explicitly evaluated. In all three cases, in a certain limit, the dilatation operator is a lattice version of a second derivative, with the lattice emerging from the Young diagram itself. The one loop dilatation operator is diagonalized numerically. All eigenvalues are an integer multiple of 8gYM28g_{YM}^2 and there are interesting degeneracies in the spectrum. The spectrum we obtain for the one loop anomalous dimension operator is reproduced by a collection of harmonic oscillators. This equivalence to harmonic oscillators generalizes giant graviton results known for the BPS sector and further implies that the Hamiltonian defined by the one loop large NN dilatation operator is integrable. This is an example of an integrable dilatation operator, obtained by summing both planar and non-planar diagrams.Comment: 34 page

    Asymptotically Lifshitz wormholes and black holes for Lovelock gravity in vacuum

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    Static asymptotically Lifshitz wormholes and black holes in vacuum are shown to exist for a class of Lovelock theories in d=2n+1>7 dimensions, selected by requiring that all but one of their n maximally symmetric vacua are AdS of radius l and degenerate. The wormhole geometry is regular everywhere and connects two Lifshitz spacetimes with a nontrivial geometry at the boundary. The dynamical exponent z is determined by the quotient of the curvature radii of the maximally symmetric vacua according to n(z^2-1)+1=(l/L)^2, where L corresponds to the curvature radius of the nondegenerate vacuum. Light signals are able to connect both asymptotic regions in finite time, and the gravitational field pulls towards a fixed surface located at some arbitrary proper distance to the neck. The asymptotically Lifshitz black hole possesses the same dynamical exponent and a fixed Hawking temperature given by T=z/(2^z pi l). Further analytic solutions, including pure Lifshitz spacetimes with a nontrivial geometry at the spacelike boundary, and wormholes that interpolate between asymptotically Lifshitz spacetimes with different dynamical exponents are also found.Comment: 19 pages, 1 figur

    Integrable Wilson loops

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    The generalized quark-antiquark potential of N=4 supersymmetric Yang-Mills theory on S^3 x R calculates the potential between a pair of heavy charged particles separated by an arbitrary angle on S^3 and also an angle in flavor space. It can be calculated by a Wilson loop following a prescribed path and couplings, or after a conformal transformation, by a cusped Wilson loop in flat space, hence also generalizing the usual concept of the cusp anomalous dimension. In AdS_5 x S^5 this is calculated by an infinite open string. I present here an open spin-chain model which calculates the spectrum of excitations of such open strings. In the dual gauge theory these are cusped Wilson loops with extra operator insertions at the cusp. The boundaries of the spin-chain introduce a non-trivial reflection phase and break the bulk symmetry down to a single copy of psu(2|2). The dependence on the two angles is captured by the two embeddings of this algebra into \psu(2|2)^2, i.e., by a global rotation. The exact answer to this problem is conjectured to be given by solutions to a set of twisted boundary thermodynamic Bethe ansatz integral equations. In particular the generalized quark-antiquark potential or cusp anomalous dimension is recovered by calculating the ground state energy of the minimal length spin-chain, with no sites. It gets contributions only from virtual particles reflecting off the boundaries. I reproduce from this calculation some known weak coupling perturtbative results.Comment: 40 pages, 11 figures; v2-some formulas corrected, results unchange

    Field theories with anisotropic scaling in 2D, solitons and the microscopic entropy of asymptotically Lifshitz black holes

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    Field theories with anisotropic scaling in 1+1 dimensions are considered. It is shown that the isomorphism between Lifshitz algebras with dynamical exponents z and 1/z naturally leads to a duality between low and high temperature regimes. Assuming the existence of gap in the spectrum, this duality allows to obtain a precise formula for the asymptotic growth of the number of states with a fixed energy which depends on z and the energy of the ground state, and reduces to the Cardy formula for z=1. The holographic realization of the duality can be naturally inferred from the fact that Euclidean Lifshitz spaces in three dimensions with dynamical exponents and characteristic lengths given by z, l, and 1/z, l/z, respectively, are diffeomorphic. The semiclassical entropy of black holes with Lifshitz asymptotics can then be recovered from the generalization of Cardy formula, where the ground state corresponds to a soliton. An explicit example is provided by the existence of a purely gravitational soliton solution for BHT massive gravity, which precisely has the required energy that reproduces the entropy of the analytic asymptotically Lifshitz black hole with z=3. Remarkably, neither the asymptotic symmetries nor central charges were explicitly used in order to obtain these results.Comment: 17 pages, no figures, references corrected and update

    Proactive environmental strategy in a supply chain context: The mediating role of investments

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    Abstract: There is a growing body of knowledge on the link between environmental management and supply chain management, but there is contradicting evidence on the impact of a proactive environmental strategy on environmental performance. Therefore, this paper investigates the impact of proactive environmental strategy on environmental performance as mediated by environmental investments. We also consider the antecedents of the adoption of proactive environmental strategy. We develop and test hypotheses, using data collected from 96 Turkish manufacturers through an online questionnaire. The model was tested using Partial Least Squares (PLS), a structural equation modelling method. The results show that a proactive environmental strategy leads to higher environmental investments; both internally and externally in collaboration with suppliers. Our findings support our hypothesis that environmental investments acts as a mediating variable between proactive environmental strategy and environmental performance. The results also show that customer pressure and, particularly, organizational commitment positively impact the extent to which firms adopt a proactive environmental strategy
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