Selective COX-2 inhibitors and risk of myocardial infarction

Selective inhibitors of cyclooxygenase- 2 ( COX- 2, ` coxibs') are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non- steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myocardial infarction and atherothrombotic events. This has led to the withdrawal of rofecoxib from global markets, and warnings have been issued by drug authorities about similar events during the use of celecoxib or valdecoxib/ parecoxib, bringing about questions of an inherent atherothrombotic risk of all coxibs and consequences that should be drawn by health care professionals. These questions need to be addressed in light of the known effects of selective inhibition of COX- 2 on the cardiovascular system. Although COX- 2, in contrast to the cyclooxygenase-1 ( COX- 1) isoform, is regarded as an inducible enzyme that only has a role in pathophysiological processes like pain and inflammation, experimental and clinical studies have shown that COX- 2 is constitutively expressed in tissues like the kidney or vascular endothelium, where it executes important physiological functions. COX- 2- dependent formation of prostanoids not only results in the mediation of pain or inflammatory signals but also in the maintenance of vascular integrity. Especially prostacyclin ( PGI(2)), which exerts vasodilatory and antiplatelet properties, is formed to a significant extent by COX- 2, and its levels are reduced to less than half of normal when COX- 2 is inhibited. This review outlines the rationale for the development of selective COX- 2 inhibitors and the pathophysiological consequences of selective inhibition of COX- 2 with special regard to vasoactive prostaglandins. It describes coxibs that are currently available, evaluates the current knowledge on the risk of atherothrombotic events associated with their intake and critically discusses the consequences that should be drawn from these insights. Copyright (C) 2005 S. Karger AG, Basel

Phase and Charge reentrant phase transitions in two capacitively coupled Josephson arrays with ultra-small junction

We have studied the phase diagram of two capacitively coupled Josephson junction arrays with charging energy, $E_c$, and Josephson coupling energy, $E_J$. Our results are obtained using a path integral Quantum Monte Carlo algorithm. The parameter that quantifies the quantum fluctuations in the i-th array is defined by $\alpha_i\equiv \frac{E_{{c}_i}}{E_{J_i}}$. Depending on the value of $\alpha_i$, each independent array may be in the semiclassical or in the quantum regime: We find that thermal fluctuations are important when $\alpha \lesssim 1.5$ and the quantum fluctuations dominate when $2.0 \lesssim \alpha$. We have extensively studied the interplay between vortex and charge dominated individual array phases. The two arrays are coupled via the capacitance $C_{{\rm inter}}$ at each site of the lattices. We find a {\it reentrant transition} in $\Upsilon(T,\alpha)$, at low temperatures, when one of the arrays is in the semiclassical limit (i.e. $\alpha_{1}=0.5$) and the quantum array has $2.0 \leq\alpha_{2} \leq 2.5$, for the values considered for the interlayer capacitance. In addition, when $3.0 \leq \alpha_{2} < 4.0$, and for all the inter-layer couplings considered above, a {\it novel} reentrant phase transition occurs in the charge degrees of freedom, i.e. there is a reentrant insulating-conducting transition at low temperatures. We obtain the corresponding phase diagrams and found some features that resemble those seen in experiments with 2D JJA.Comment: 25 Latex pages including 8 encapsulated poscript figures. Accepted for publication in Phys. Rev B (Nov. 2004 Issue

Zero-field Kondo splitting and quantum-critical transition in double quantum dots

Double quantum dots offer unique possibilities for the study of many-body correlations. A system containing one Kondo dot and one effectively noninteracting dot maps onto a single-impurity Anderson model with a structured (nonconstant) density of states. Numerical renormalization-group calculations show that while band filtering through the resonant dot splits the Kondo resonance, the singlet ground state is robust. The system can also be continuously tuned to create a pseudogapped density of states and access a quantum critical point separating Kondo and non-Kondo phases.Comment: 4 pages, 4 figures; Accepted for publication in Physical Review Letter

Critical Currents of Josephson-Coupled Wire Arrays

We calculate the current-voltage characteristics and critical current I_c^{array} of an array of Josephson-coupled superconducting wires. The array has two layers, each consisting of a set of parallel wires, arranged at right angles, such that an overdamped resistively-shunted junction forms wherever two wires cross. A uniform magnetic field equal to f flux quanta per plaquette is applied perpendicular to the layers. If f = p/q, where p and q are mutually prime integers, I_c^{array}(f) is found to have sharp peaks when q is a small integer. To an excellent approximation, it is found in a square array of n^2 plaquettes, that I_c^{array}(f) \propto (n/q)^{1/2} for sufficiently large n. This result is interpreted in terms of the commensurability between the array and the assumed q \times q unit cell of the ground state vortex lattice.Comment: 4 pages, 4 figure

Possible Glassiness in a Periodic Long-Range Josephson Array

We present an analytic study of a periodic Josephson array with long-range interactions in a transverse magnetic field. We find that this system exhibits a first-order transition into a phase characterized by an extensive number of states separated by barriers that scale with the system size; the associated discontinuity is small in the limit of weak applied field, thus permitting an explicit analysis in this regime.Comment: 4 pages, 2 Postscript figures in a separate file

Danish values, the foundation of the Folkeskole

We have imaged with Hubble Space Telescope WFC3/UVIS the central 2′7 × 2′7 region of the giant elliptical galaxy M87, using the ultraviolet filter F275W. In combination with archival ACS/WFC data taken through the F606W and F814W filters, covering the same field, we have constructed integrated-light UV-optical colors and magnitudes for 1460 objects, most of which are believed to be globular clusters (GCs) belonging to M87. The purpose was to ascertain whether the multiple-populations syndrome, ubiquitous among Galactic GCs, also exists among the M87 family of clusters. To achieve this goal, we sought those GCs with exceptionally blue UV-to-optical colors because helium-enriched sub-populations produce a horizontal-branch morphology that is well populated at high effective temperature. For comparison, integrated, synthetic UV-optical and purely optical colors and magnitudes have been constructed for 45 Galactic GCs, starting from individual-star photometry obtained with the same instruments and the same filters. We identify a small group of M87 clusters exhibiting a radial UV-optical color gradient, representing our best candidate GCs hosting multiple populations with extreme helium content. We also find that the central spatial distribution of the bluer GCs is flattened in a direction parallel to the jet, while the distribution of redder GCs is more spherical. We release to the astronomical community our photometric catalog in F275W, F606W, and F814W bands and the high-quality image stacks in the same bands

An Experimentally Realizable Weiss Model for Disorder-Free Glassiness

We summarize recent work on a frustrated periodic long-range Josephson array in a parameter regime where its dynamical behavior is identical to that of the $p=4$ disordered spherical model. We also discuss the physical requirements imposed by the theory on the experimental realization of this superconducting network.Comment: 6 pages, LaTeX, 2 Postscript figure

Giant Shapiro Resonances in a Flux Driven Josephson Junction Necklace

We present a detailed study of the dynamic response of a ring of $N$ equally spaced Josephson junctions to a time-periodic external flux, including screening current effects. The dynamics are described by the resistively shunted Josephson junction model, appropriate for proximity effect junctions, and we include Faraday's law for the flux. We find that the time-averaged $I-V$ characteristics show novel {\em subharmonic giant Shapiro voltage resonances}, which strongly depend on having phase slips or not, on $N$, on the inductance and on the external drive frequency. We include an estimate of the possible experimental parameters needed to observe these quantized voltage spikes.Comment: 8 pages RevTeX, 3 figures available upon reques

Ballistic dynamics of a convex smooth-wall billiard with finite escape rate along the boundary

We focus on the problem of an impurity-free billiard with a random position-dependent boundary coupling to the environment. The response functions of such an open system can be obtained non-perturbatively from a supersymmetric generating functional. The derivation of this functional is based on averaging over the escape rates and results in a non-linear ballistic $\sigma$-model, characterized by system-specific parameters. Particular emphasis is placed on the {}``whispering gallery modes'' as the origin of surface diffusion modes in the limit of large dimensionless conductance.Comment: 12 pages, no figure