293 research outputs found

    Chimeric polyomavirus-derived virus-like particles: the immunogenicity of an inserted peptide applied without adjuvant to mice depends on its insertion site and its flanking linker sequence

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    We inserted the sequence of the carcinoembryonic antigen-derived T cell epitope CAP-1-6D (CEA) into different positions of the hamster polyomavirus major capsid protein VP1. Independently from additional flanking linkers, yeast-expressed VP1 proteins harboring the CEA insertion between VP1 amino acid residues 80 and 89 (site 1) or 288 and 295 (site 4) or simultaneously at both positions assembled to chimeric virus-like particles (VLPs). BALB/c mice immunized with adjuvant-free VLPs developed VP1- and epitope-specific antibodies. The level of the CEA-specific antibody response was determined by the insertion site, the number of inserts, and the flanking linker. The strongest CEA-specific antibody response was observed in mice immunized with VP1 proteins harboring the CEA insert at site 1. Moreover, the CEA-specific antibodies in these mice were still detectable 6 mo after the final booster immunization. Our results indicate that hamster polyomavirus-derived VLPs represent a highly immunogenic carrier for foreign insertions that might be useful for clinical and therapeutic applications

    SKY1 is involved in cisplatin-induced cell kill in Saccharomyces cerevisiae, and inactivation of its human homologue, SRPK1, induces cisplatin resistance in a human ovarian carcinoma cell line

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    The therapeutic potential of cisplatin, one of the most active and widely used anticancer drugs, is severely limited by the occurrence of cellular resistance. In this study, using budding yeast Saccharomyces cerevisiae as a model organism to identify novel drug resistance genes, we found that disruption of the yeast gene SKY1 (serine/arginine-rich protein-specific kinase from budding yeast) by either transposon insertion or one-step gene replacement conferred cellular resistance to cisplatin. Heterologous expression of the human SKY1 homologue SRPK1 (serine/arginine-rich protein-specific kinase) in SKY1 deletion mutant yeast cells restored cisplatin sensitivity, suggesting that SRPK1 is a cisplatin sensitivity gene, the inactivation of which could lead to cisplatin resistance. Subsequently, we investigated the role of SRPK1 in cisplatin sensitivity and resistance in human ovarian carcinoma A2780 cells using antisense oligodeoxynucleotides. Treatment of A2780 cells with antisense oligodeoxynucleotides directed against the translation initiation site of SRPK1 led to down-regulation of SRPK1 protein and conferred a 4-fold resistance to cisplatin. The human SRPK1 gene has not been associated with drug resistance before. Our new findings strongly suggest that SRPK1 is involved in cisplatin-induced cell kill and indicate that SRPK1 might potentially be of importance for studying clinical drug resistance

    Constructing Self-Dual Strings

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    We present an ADHMN-like construction which generates self-dual string solutions to the effective M5-brane worldvolume theory from solutions to the Basu-Harvey equation. Our construction finds a natural interpretation in terms of gerbes, which we develop in some detail. We also comment on a possible extension to stacks of multiple M5-branes.Comment: 1+19 pages, presentation improved, minor corrections, published versio

    The three-dimensional structure of Saturn's E ring

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    Saturn's diffuse E ring consists of many tiny (micron and sub-micron) grains of water ice distributed between the orbits of Mimas and Titan. Various gravitational and non-gravitational forces perturb these particles' orbits, causing the ring's local particle density to vary noticeably with distance from the planet, height above the ring-plane, hour angle and time. Using remote-sensing data obtained by the Cassini spacecraft in 2005 and 2006, we investigate the E-ring's three-dimensional structure during a time when the Sun illuminated the rings from the south at high elevation angles (> 15 degrees). These observations show that the ring's vertical thickness grows with distance from Enceladus' orbit and its peak brightness density shifts from south to north of Saturn's equator plane with increasing distance from the planet. These data also reveal a localized depletion in particle density near Saturn's equatorial plane around Enceladus' semi-major axis. Finally, variations are detected in the radial brightness profile and the vertical thickness of the ring as a function of longitude relative to the Sun. Possible physical mechanisms and processes that may be responsible for some of these structures include solar radiation pressure, variations in the ambient plasma, and electromagnetic perturbations associated with Saturn's shadow.Comment: 42 Pages, 13 Figures, modified to include minor proof correction

    Gravitational-wave astronomy: the high-frequency window

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    This contribution is divided in two parts. The first part provides a text-book level introduction to gravitational radiation. The key concepts required for a discussion of gravitational-wave physics are introduced. In particular, the quadrupole formula is applied to the anticipated ``bread-and-butter'' source for detectors like LIGO, GEO600, EGO and TAMA300: inspiralling compact binaries. The second part provides a brief review of high frequency gravitational waves. In the frequency range above (say) 100Hz, gravitational collapse, rotational instabilities and oscillations of the remnant compact objects are potentially important sources of gravitational waves. Significant and unique information concerning the various stages of collapse, the evolution of protoneutron stars and the details of the supranuclear equation of state of such objects can be drawn from careful study of the gravitational-wave signal. As the amount of exciting physics one may be able to study via the detections of gravitational waves from these sources is truly inspiring, there is strong motivation for the development of future generations of ground based detectors sensitive in the range from hundreds of Hz to several kHz.Comment: 21 pages, 5 figures, Lectures presented at the 2nd Aegean Summer School on the Early Universe, Syros, Greece, September 200

    Critical Dynamics of Magnets

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    We review our current understanding of the critical dynamics of magnets above and below the transition temperature with focus on the effects due to the dipole--dipole interaction present in all real magnets. Significant progress in our understanding of real ferromagnets in the vicinity of the critical point has been made in the last decade through improved experimental techniques and theoretical advances in taking into account realistic spin-spin interactions. We start our review with a discussion of the theoretical results for the critical dynamics based on recent renormalization group, mode coupling and spin wave theories. A detailed comparison is made of the theory with experimental results obtained by different measuring techniques, such as neutron scattering, hyperfine interaction, muon--spin--resonance, electron--spin--resonance, and magnetic relaxation, in various materials. Furthermore we discuss the effects of dipolar interaction on the critical dynamics of three--dimensional isotropic antiferromagnets and uniaxial ferromagnets. Special attention is also paid to a discussion of the consequences of dipolar anisotropies on the existence of magnetic order and the spin--wave spectrum in two--dimensional ferromagnets and antiferromagnets. We close our review with a formulation of critical dynamics in terms of nonlinear Langevin equations.Comment: Review article (154 pages, figures included

    D0-D4 brane tachyon condensation to a BPS state and its excitation spectrum in noncommutative super Yang-Mills theory

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    We investigate the D0-D4-brane system for different B-field backgrounds including the small instanton singularity in noncommutative SYM theory. We discuss the excitation spectrum of the unstable state as well as for the BPS D0-D4 bound state. We compute the tachyon potential which reproduces the complete mass defect. The relevant degrees of freedom are the massless (4,4) strings. Both results are in contrast with existing string field theory calculations. The excitation spectrum of the small instanton is found to be equal to the excitation spectrum of the fluxon solution on R^2_theta x R which we trace back to T-duality. For the effective theory of the (0,0) string excitations we obtain a BFSS matrix model. The number of states in the instanton background changes significantly when the B-field becomes self-dual. This leads us to the proposal of the existence of a phase transition or cross over at self-dual B-field.Comment: a4 11pt Latex2e 40 pages; v2: typos fixed, refined comments on renormalisation, refs added, v3: ref added, version publishe

    Couplings of light I=0 scalar mesons to simple operators in the complex plane

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    The flavour and glue structure of the light scalar mesons in QCD are probed by studying the couplings of the I=0 mesons σ(600)\sigma(600) and f0(980)f_0(980) to the operators qˉq\bar{q}q, αsG2\alpha_s G^2 and to two photons. The Roy dispersive representation for the ππ\pi\pi amplitude t00(s)t_0^0(s) is used to determine the pole positions as well as the residues in the complex plane. On the real axis, t00t_0^0 is constrained to solve the Roy equation together with elastic unitarity up to the K\Kbar threshold leading to an improved description of the f0(980)f_0(980). The problem of using a two-particle threshold as a matching point is discussed. A simple relation is established between the coupling of a scalar meson to an operator jSj_S and the value of the related pion form-factor computed at the resonance pole. Pion scalar form-factors as well as two-photon partial-wave amplitudes are expressed as coupled-channel Omn\`es dispersive representations. Subtraction constants are constrained by chiral symmetry and experimental data. Comparison of our results for the qˉq\bar{q}q couplings with earlier determinations of the analogous couplings of the lightest I=1 and I=1/2I=1/2 scalar mesons are compatible with an assignment of the σ\sigma, κ\kappa, a0(980)a_0(980), f0(980)f_0(980) into a nonet. Concerning the gluonic operator αsG2\alpha_s G^2 we find a significant coupling to both the σ\sigma and the f0(980)f_0(980).Comment: 31 pages, 5 figure
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