75 research outputs found

    6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol, a specific glutathione S-transferase inhibitor, overcomes the multidrug resistance (MDR)-associated protein 1-mediated MDR in small cell lung cancer

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    In the present work, we have investigated the antitumor activity of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) on aggressive small cell lung cancer. NBDHEX not only is cytotoxic toward the parental small cell lung cancer H69 cell line (LC50 of 2.3 +/- 0.6 mu mol/L) but also overcomes the multidrug resistance of its variant, H69AR, which overexpresses the ATP-binding cassette transporter multidrug resistance-associated protein 1 (MRP1; LC50 of 4.5 +/- 0.9 mu mol/L). Drug efflux experiments, done in the presence of a specific inhibitor of MRP1, confirmed that NBDHEX is not a substrate for this export pump. Interestingly, NBDHEX triggers two different types of cell death: a caspase-dependent apoptosis in the H69AR cells and a necrotic phenotype in the parental H69 cells. The apoptotic pathway triggered by NBDHEX in H69AR cells is associated with c-Jun NH2-terminal kinase and c-Jun activation, whereas glutathione oxidation and activation of p38(MAPK) is observed in the NBDHEX-treated H69 cells. In contrast to the parental cells, the higher propensity to die through apoptosis of the H69AR cell line may be related to the lower expression of the antiapoptotic protein Bcl-2. Therefore, down-regulation of a factor crucial for cell survival makes H69AR cells more sensitive to the cytotoxic action of NBDHEX, which is not a MRP1 substrate. We have previously shown that NBDHEX is cytotoxic toward P-glycoprotein-overexpressing tumor cell lines. Therefore, NBDHEX seems a very promising compound in the search for new molecules able to overcome the ATP-binding cassette family of proteins, one of the major mechanisms of multidrug resistance in cancer cells

    The Subleading Term of the Strong Coupling Expansion of the Heavy-Quark Potential in a N=4\mathcal N=4 Super Yang-Mills Plasma

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    Applying the AdS/CFT correspondence, the expansion of the heavy-quark potential of the N{\cal N} supersymmetric Yang-Mills theory at large NcN_c is carried out to the sub-leading term in the large 't Hooft coupling at nonzero temperatures. The strong coupling corresponds to the semi-classical expansion of the string-sigma model, the gravity dual of the Wilson loop operator, with the sub-leading term expressed in terms of functional determinants of fluctuations. The contributions of these determinants are evaluated numerically.Comment: 17 pages in JHEP3, typos fixed, updated version to be published in JHE

    The Final Fate of the Rolling Tachyon

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    We propose an alternative interpretation of the boundary state for the rolling tachyon, which may depict the time evolution of unstable D-branes in string theory. Splitting the string variable in the temporal direction into the classical part, which we may call "time" and the quantum one, we observe the time dependent behaviour of the boundary. Using the fermion representation of the rolling tachyon boundary state, we show that the boundary state correctly describes the time-dependent decay process of the unstable D-brane into a S-brane at the classical level.Comment: 9 pages, revte

    Can holography reproduce the QCD Wilson line?

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    Recently a remarkable agreement was found between lattice simulations of long Wilson lines and behavior of the Nambu Goto string in flat space-time. However, the latter fails to fit the short distance behavior since it admits a tachyonic mode for a string shorter than a critical length. In this paper we examine the question of whether a classical holographic Wilson line can reproduce the lattice results for Wilson lines of any length. We determine the condition on the the gravitational background to admit a Coulombic potential at short distances. We analyze the system using three different renormalization schemes. We perform an explicit best fit comparison of the lattice results with the holographic models based on near extremal D3 and D4 branes, non-critical near extremal AdS6 model and the Klebanov Strassler model. We find that all the holographic models examined admit after renormalization a constant term in the potential. We argue that the curves of the lattice simulation also have such a constant term and we discuss its physical interpretation

    Exact results for static and radiative fields of a quark in N=4 super Yang-Mills

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    In this work (which supersedes our previous preprint arXiv:1112.2345) we determine the expectation value of the N=4$ SU(N) SYM Lagrangian density operator in the presence of an infinitely heavy static particle in the symmetric representation of SU(N), by means of a D3-brane probe computation. The result that we obtain coincides with two previous computations of different observables, up to kinematical factors. We argue that these agreements go beyond the D-brane probe approximation, which leads us to propose an exact formula for the expectation value of various operators. In particular, we provide an expression for the total energy loss by radiation of a heavy particle in the fundamental representation.Comment: 14 pages. This submission supersedes our previous preprint arXiv:1112.2345. v2: numerical factors fixed, minor clarifications, added reference

    Quark--anti-quark potential in N=4 SYM

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    We construct a closed system of equations describing the quark--anti-quark potential at any coupling in planar N=4 supersymmetric Yang-Mills theory. It is based on the Quantum Spectral Curve method supplemented with a novel type of asymptotics. We present a high precision numerical solution reproducing the classical and one-loop string predictions very accurately. We also analytically compute the first 7 nontrivial orders of the weak coupling expansion. Moreover, we study analytically the generalized quark--anti-quark potential in the limit of large imaginary twist to all orders in perturbation theory. We demonstrate how the QSC reduces in this case to a one-dimensional Schrodinger equation. In the process we establish a link between the Q-functions and the solution of the Bethe-Salpeter equation.Comment: 31 pages, 1 figure; v2: minor correcton

    Generalized cusp in AdS_4 x CP^3 and more one-loop results from semiclassical strings

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    We evaluate the exact one-loop partition function for fundamental strings whose world-surface ends on a cusp at the boundary of AdS_4 and has a "jump" in CP^3. This allows us to extract the stringy prediction for the ABJM generalized cusp anomalous dimension Gamma_{cusp}^{ABJM} (phi,theta) up to NLO in sigma-model perturbation theory. With a similar analysis, we present the exact partition functions for folded closed string solutions moving in the AdS_3 parts of AdS_4 x CP^3 and AdS_3 x S^3 x S^3 x S^1 backgrounds. Results are obtained applying to the string solutions relevant for the AdS_4/CFT_3 and AdS_3/CFT_2 correspondence the tools previously developed for their AdS_5 x S^5 counterparts.Comment: 48 pages, 2 figures, version 3, corrected misprints in formulas 2.12, B.86, C.33, added comment on verification of the light-like limi

    The generalized cusp in ABJ(M) N = 6 Super Chern-Simons theories

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    We construct a generalized cusped Wilson loop operator in N = 6 super Chern-Simons-matter theories which is locally invariant under half of the supercharges. It depends on two parameters and interpolates smoothly between the 1/2 BPS line or circle and a pair of antiparallel lines, representing a natural generalization of the quark-antiquark potential in ABJ(M) theories. For particular choices of the parameters we obtain 1/6 BPS configurations that, mapped on S^2 by a conformal transformation, realize a three-dimensional analogue of the wedge DGRT Wilson loop of N = 4. The cusp couples, in addition to the gauge and scalar fields of the theory, also to the fermions in the bifundamental representation of the U(N)xU(M) gauge group and its expectation value is expressed as the holonomy of a suitable superconnection. We discuss the definition of these observables in terms of traces and the role of the boundary conditions of fermions along the loop. We perform a complete two-loop analysis, obtaining an explicit result for the generalized cusp at the second non-trivial order, from which we read off the interaction potential between heavy 1/2 BPS particles in the ABJ(M) model. Our results open the possibility to explore in the three-dimensional case the connection between localization properties and integrability, recently advocated in D = 4.Comment: 53 pages, 10 figures, added references, this is the version appeared on JHE

    The quark anti-quark potential and the cusp anomalous dimension from a TBA equation

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    We derive a set of integral equations of the TBA type for the generalized cusp anomalous dimension, or the quark antiquark potential on the three sphere, as a function of the angles. We do this by considering a family of local operators on a Wilson loop with charge L. In the large L limit the problem can be solved in terms of a certain boundary reflection matrix. We determine this reflection matrix by using the symmetries and the boundary crossing equation. The cusp is introduced through a relative rotation between the two boundaries. Then the TBA trick of exchanging space and time leads to an exact equation for all values of L. The L=0 case corresponds to the cusped Wilson loop with no operators inserted. We then derive a slightly simplified integral equation which describes the small angle limit. We solve this equation up to three loops in perturbation theory and match the results that were obtained with more direct approaches.Comment: 63 pages, 12 figures. v2: references added, typos correcte
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