Preferential uptake of the non steroid anti-inflammatory drug diclofenac into inflamed tissues after a single oral dose in rats

BACKGROUND: Diclofenac is a nonsteroidal anti-inflammatory drug which is available as prescription (RX) and over-the-counter (OTC) medication for the systemic and topical treatment of painful and inflammatory conditions such as arthritis and back pain. This study was undertaken to investigate the distribution and retention of diclofenac and/or its metabolites in inflamed tissues, using the carrageenan-induced inflammation model and quantitative whole body autoradiography in rats. METHODS: [14C]diclofenac sodium was administrated as a single 2 mg/kg oral dose 1 h after injection of carrageenan into one front and one hind footpads and subcutaneously into the dorsum of the neck of rats. A control animal received saline injections. Three carrageenan-treated rats and one control rat were sacrificed at 1, 4, 8, and 24 h after [14C]diclofenac sodium administration (total of 4 rats/time point). The carcasses were immediately snap-frozen and prepared for cryosectioning. Lengthwise whole-body sections (40 microm thick), including all major tissues, were obtained from different levels across the body. The tissue concentrations of total radiolabeled components were determined using quantitative autoradioluminography. RESULTS: The radioactivity patterns demonstrated that diclofenac and/or its metabolites preferentially distributed into the inflamed tissues. In unharmed tissues the distribution was similar in control and treated animals. The exposure, based on the areas under the tissue concentration versus time (AUC(0-tlast)), was 26 and 53 fold higher in the inflamed neck and inflamed footpads of treated animals than in control rats; the exposures in unharmed tissues were similar in the treated and control rats, and the AUC(0-tlast) was 17 fold higher in the inflamed paws than in the non inflamed footpads of the carrageenan-treated rats. The higher exposure in the inflamed tissues may be explained partly to the fact that the elimination of total radiolabeled components from inflamed tissues (t(1/2) = 6 h) appeared lower than from the corresponding unharmed tissues (t(1/2) = 2 h). CONCLUSION: This animal study demonstrated that diclofenac and/or its metabolites were rapidly and preferentially taken up and retained in inflamed tissues. Although there were theoretical considerations that mildly acidic NSAID may show some preferential distribution in inflamed tissues there was no clear experimental proof for diclofenac until the present study

N=2 central charge superspace and a minimal supergravity multiplet

We extend the notion of central charge superspace to the case of local supersymmetry. Gauged central charge transformations are identified as diffeomorphisms at the same footing as space-time diffeomorphisms and local supersymmetry transformations. Given the general structure we then proceed to the description of a particular vector-tensor supergravity multiplet of 24+24 components, identified by means of rather radical constraints

Absence of Embedded Mass Shells: Cerenkov Radiation and Quantum Friction

We show that, in a model where a non-relativistic particle is coupled to a quantized relativistic scalar Bose field, the embedded mass shell of the particle dissolves in the continuum when the interaction is turned on, provided the coupling constant is sufficiently small. More precisely, under the assumption that the fiber eigenvectors corresponding to the putative mass shell are differentiable as functions of the total momentum of the system, we show that a mass shell could exist only at a strictly positive distance from the unperturbed embedded mass shell near the boundary of the energy-momentum spectrum.Comment: Revised version: a remark added at the end of Section

STAR: Sparse Trained Articulated Human Body Regressor

The SMPL body model is widely used for the estimation, synthesis, and analysis of 3D human pose and shape. While popular, we show that SMPL has several limitations and introduce STAR, which is quantitatively and qualitatively superior to SMPL. First, SMPL has a huge number of parameters resulting from its use of global blend shapes. These dense pose-corrective offsets relate every vertex on the mesh to all the joints in the kinematic tree, capturing spurious long-range correlations. To address this, we define per-joint pose correctives and learn the subset of mesh vertices that are influenced by each joint movement. This sparse formulation results in more realistic deformations and significantly reduces the number of model parameters to 20% of SMPL. When trained on the same data as SMPL, STAR generalizes better despite having many fewer parameters. Second, SMPL factors pose-dependent deformations from body shape while, in reality, people with different shapes deform differently. Consequently, we learn shape-dependent pose-corrective blend shapes that depend on both body pose and BMI. Third, we show that the shape space of SMPL is not rich enough to capture the variation in the human population. We address this by training STAR with an additional 10,000 scans of male and female subjects, and show that this results in better model generalization. STAR is compact, generalizes better to new bodies and is a drop-in replacement for SMPL. STAR is publicly available for research purposes at http://star.is.tue.mpg.de.Comment: ECCV 202

Predicting users' first impressions of website aesthetics with a quantification of perceived visual complexity and colorfulness

Users make lasting judgments about a website's appeal within a split second of seeing it for the first time. This first impression is influential enough to later affect their opinions of a site's usability and trustworthiness. In this paper, we demonstrate a means to predict the initial impression of aesthetics based on perceptual models of a website's colorfulness and visual complexity. In an online study, we collected ratings of colorfulness, visual complexity, and visual appeal of a set of 450 websites from 548 volunteers. Based on these data, we developed computational models that accurately measure the perceived visual complexity and colorfulness of website screenshots. In combination with demographic variables such as a user's education level and age, these models explain approximately half of the variance in the ratings of aesthetic appeal given after viewing a website for 500ms only.Engineering and Applied Science

Factors influencing brightness and beam quality of conventional and distributed Bragg reflector tapered laser diodes in absence of self-heating

In this study, the authors examine some of the factors affecting the brightness and the beam quality of high-power tapered lasers. The large volume resonators required to achieve a high-power, high-brightness operation make the beam quality sensitive to carrier lensing and a multimode operation. These cause bleaching of the regions outside the ridge waveguide. The beam quality in the conventional and the distributed Bragg reflector tapered lasers is examined in the absence of the self-heating effects to investigate the effect of the carrier lensing effects. The influence of the front facet reflectivity and the taper angle on the beam quality is investigated. The beam quality was found to degrade with an increase in the front facet reflectivity and for the larger taper angles in the conventional tapered lasers, especially at low ridge waveguide currents. Finally, the performance of the conventional tapered lasers employing a beamspoiler was assessed. The beam quality was found to be comparable with that achieved in the DBR tapered lasers

The Effect of Helium Sedimentation on Galaxy Cluster Masses and Scaling Relations

Recent theoretical studies predict that the inner regions of galaxy clusters may have an enhanced helium abundance due to sedimentation over the cluster lifetime. If sedimentation is not suppressed (e.g., by tangled magnetic fields), this may significantly affect the cluster mass estimates. We use Chandra X-ray observations of eight relaxed galaxy clusters to investigate the upper limits to the effect of helium sedimentation on the measurement of cluster masses and the best-fit slopes of the Y_X - M_500 and Y_X - M_2500 scaling relations. We calculated gas mass and total mass in two limiting cases: a uniform, un-enhanced abundance distribution and a radial distribution from numerical simulations of helium sedimentation on a timescale of 11 Gyrs. The assumed helium sedimentation model, on average, produces a negligible increase in the gas mass inferred within large radii (r < r500) (1.3 +/- 1.2 per cent) and a (10.2 +/- 5.5) per cent mean decrease in the total mass inferred within r < r500. Significantly stronger effects in the gas mass (10.5 +/- 0.8 per cent) and total mass (25.1 +/- 1.1 per cent) are seen at small radii owing to a larger variance in helium abundance in the inner region, r < 0.1 r500. We find that the slope of the Y_X -M_500 scaling relation is not significantly affected by helium sedimentation.Comment: 11 pages, accepted for publication in Astronomy and Astrophysic

Bifurcations, Chaos, Controlling and Synchronization of Certain Nonlinear Oscillators

In this set of lectures, we review briefly some of the recent developments in the study of the chaotic dynamics of nonlinear oscillators, particularly of damped and driven type. By taking a representative set of examples such as the Duffing, Bonhoeffer-van der Pol and MLC circuit oscillators, we briefly explain the various bifurcations and chaos phenomena associated with these systems. We use numerical and analytical as well as analogue simulation methods to study these systems. Then we point out how controlling of chaotic motions can be effected by algorithmic procedures requiring minimal perturbations. Finally we briefly discuss how synchronization of identically evolving chaotic systems can be achieved and how they can be used in secure communications.Comment: 31 pages (24 figures) LaTeX. To appear Springer Lecture Notes in Physics Please Lakshmanan for figures (e-mail: [email protected]