Dermatan sulfate released after injury is a potent promoter of fibroblast growth factor-2 function

Proteoglycans have been shown in vitro to bind multiple components of the cellular microenvironment that function during wound healing. To study the composition and function of these molecules when derived from an in vivo source, soluble proteoglycans released into human wound fluid were characterized and evaluated for influence on fibroblast growth factor-2 activity. Immunoblot analysis of wound fluid revealed the presence of syndecan-1, syndecan-4, glypican, decorin, perlecan, and versican. Sulfated glycosaminoglycan concentrations ranged from 15 to 65 microgram/ml, and treatment with chondroitinase B showed that a large proportion of the glycosaminoglycan was dermatan sulfate. The total glycosaminoglycan mixture present in wound fluid supported the ability of fibroblast growth factor-2 to signal cell proliferation. Dermatan sulfate, and not heparan sulfate, was the major contributor to this activity, and dermatan sulfate bound FGF-2 with Kd = 2.48 microM. These data demonstrate that proteoglycans released during wound repair are functionally active and provide the first evidence that dermatan sulfate is a potent mediator of fibroblast growth factor-2 responsiveness.     

Solution structure of nodularin. An inhibitor of serine/threonine-specific protein phosphatases

The three-dimensional solution structure of nodularin was studied by NMR and molecular dynamics simulations. The conformation in water was determined from the distance and dihedral data by distance geometry and refined by iterative relaxation matrix analysis. The cyclic backbone adopts a well defined conformation but the remote parts of the side chains of arginine as well as the amino acid derivative Adda have a large spatial dispersion. For the unusual amino acids the partial charges were calculated and nodularin was subjected to molecular dynamic simulations in water. A good agreement was found between experimental and computational data with hydrogen bonds, solvent accessibility, molecular motion, and conformational exchange. The three-dimensional structure resembles very closely that of microcystin-LR in the chemically equivalent segment. Therefore, it is expected that the binding of both microcystins and nodularins to serine/threonine-specific protein phosphatases is similar on an atomic level.     

Hybrid time domain solvers for the Maxwell equations in 2D

We present a new approach to time domain hybrid schemes for the Maxwell equations. By combining the classical FD‐TD scheme with two unstructured solvers, one explicit finite volume solver and one implicit finite element solver, we achieve a very efficient and flexible second‐order scheme. The second‐order accuracy of the hybrid scheme is verified through convergence studies on perfectly conducting as well as dielectric and diamagnetic circular cylinders. The numerical results also show its superiority to the FD‐TD scheme. Copyright © 2002 John Wiley & Sons, Ltd.     

Expression of a neutral horseradish peroxidase in Escherichia coli

Many measures of depression severity appear confounded by including depressive sub-typing features. We report the design of a brief (11 item) self-report scale of depression severity (the AUSSI), assessing both mood state and social impairment domains, and designed to be independent of sub-typing features. Mood severity and functional impairment scores demonstrated some independence in a sample of 360 patients. Patients with a 'melancholic' depressive type (categorised by four differing systems) differed from residual 'non-melancholic' depressed patients by having higher impairment scores, but the assigned groups did not differ, in the main, by mood severity scores. Advantages of the measure are summarised.     

Pharmacokinetics of cladribine in plasma and its 5''-monophosphate and 5''-triphosphate in leukemic cells of patients with chronic lymphocytic leukemia

PURPOSE: To determine whether microtubule- and actin-altering drugs, which have been shown to increase aqueous humor outflow, cause cellular contraction in human trabecular meshwork (HTM) cells. METHODS: HTM cells were plated in culture dishes containing a polymerized deformable silicone substrate. After 48 hours, the dishes were placed on an inverted microscope and treated with ethacrynic acid, colchicine, vinblastine, cytochalasin B, or 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and then recorded on videotape for 15 minutes. An increase in silicone substrate wrinkle size and/or number indicated a contraction. Sham controls were used. RESULTS: Cellular contraction was observed with ethacrynic acid, colchicine, and vinblastine in the 10(-5) to 10(-4) M dosage range. Pretreatment with H-7 blocked these effects. Cytochalasin B did not produce cellular contraction. CONCLUSIONS: Microtubule disruption causes cellular contraction in HTM cells, and this effect depends on an intact actin cytoskeleton network. Contraction of trabecular meshwork cells in response to various stimuli is an attractive hypothesis for possible homeostatic mechanisms in the outflow pathway, and this may serve as a focus for novel glaucoma drug development.     

Thermal Diffusivity Measurements of Liquid Silicate Melts

The effect of structure on the thermal diffusivities/conductivities for liquid silicates have been summarized based on recent experimental work carried out by the Royal Institute of Technology, Stockholm and the Tokyo Institute of Technology using the laser-flash and the hot-wire methods, respectively. In the former case, the effective thermal diffusivity was measured by a three-layer method. The relationship proposed by Mills that the thermal conductivity of silicates increases with a decrease in the ratio of NBO/T (number of non-bridging oxygens per tetrahedrally coordinated atom) has been well supported by the effective thermal diffusivity data for the liquid CaO-Al₂O₃-SiO₂ slags. However, it has been shown that for the slags having a higher CaO/Al₂O₃ ratio, the effective thermal diffusivity is roughly constant independent of the ratios of NBO/T. It has been concluded that when the silicate network is largely broken down, the phonon mean free path is not affected by the structure. It has been found by the hot-wire method that the magnitudes of thermal resistivity are in the hierarchy Li₂O-SiO₂2O-SiO₂2O-SiO₂ despite their similar values of NBO/T. It has been concluded that the ionicity of non-bridging oxygen ions is also a factor controlling the thermal conductivity of silicates as well as the number of broken bridges in the silicate network. The effective thermal diffusivity was measured for the CaO-Al₂O₃-SiO₂-FeO system to elucidate the radiation contribution to the effective thermal diffusivity. It has been found that the effective thermal diffusivity increases with an increase in FeO content. It can be considered that the strong absorption and emission within the liquid slag films caused by the Fe²⁺ ions enhances the photon heat transfer.     

Simulation of runaway electrons during tokamak disruptions

When modeling the generation of runaway electrons in tokamak disruptions, it is essential to account for the evolution of the electric field in a self-consistent way. This is achieved by the ARENA code, which is described in the present paper. In this code, the relativistic electron kinetic equation is solved by the Monte Carlo method, supplemented with a weighting scheme to enhance the accuracy of the simulated fast-electron dynamics. Finite elements are employed to solve Maxwell's equations governing the electric field, and this solution is coupled to the Monte Carlo solution of the kinetic equation in a semi-implicit way in order to maintain numerical stability. This numerical scheme thus makes it possible, for the first time, to simulate runaway avalanche kinetics in a disruption self-consistently, accounting both for the acceleration of runaway electrons by the electric field and for the change in the electric field induced by the runaway current. The first results of such a simulation of a JET-like disruption are presented.     

Parabolic-confocal unstable-resonator semiconductor lasers-Modelingand experiments

Surface-emitting all-grating-based unstable-resonator lasers, suitable for integration with diffractive beam-forming elements, have been experimentally and theoretically studied. The lasers exhibit single spatial mode operation for a device width of 160 μm. The device performance is modeled using a beam propagation method, which accounts for spatial hole burning as well as thermal and carrier diffusion effects. Near- and far-field calculations are incorporated to facilitate the comparison with the experimental results. To achieve high-quality beam forming, it is essential that the wavefront of the guided optical mode is well defined and stable. Using the model, we study the dependence of the wavefront distortion on various parameters and show how these distortions affect the far-field characteristics. The results from the simulations agree well with the experimental work. We find that the laser performance is to a large extent controlled by thermal effects. At low-power operation, these effects can be compensated for, for a range of the injection current, by modifications of the resonator or outcoupler grating geometries