Reversed flow-injection manifold for the spectrophotometric determination of captopril based on its inhibitory effect on the Co(II)-2,2'-dipyridyl-2-pyridylhydrazone complex formation

The present work reports a new, simple and rapid reversed flow-injection (r-FI) method for the accurate and precise spectrophotometric determination of captopril (CPL) in pharmaceutical formulations. The method is based on the inhibitory effect of CPL on the complex formation of Co(II) with 2,2'-dipyridyl-2-pyridylhydrazone (DPPH). The chemical and FI variables were studied and optimized. The calibration graph was linear in the range 0-250 mg l(-1) CPL, at a sampling rate of 60 injections per hour. The method was found to be very precise [s(r)=0.8% at 100.0 mg l(-1) CPL (n=12)] and the 3sigma detection limit (c(L)=2.5 mg l(-1)) was quite satisfactory. Its application to commercially available pharmaceuticals produced excellent results, with a mean relative error of e(r)<1.0%.     

Membrane proteome analysis of the green-sulfur bacterium Chlorobium tepidum

An extensive proteomic approach relies on the possibility to visualize and analyze various types of proteins, including membrane proteins, which are rarely detectable on two-dimensional electrophoresis gels. In this study, different methods were employed for the enrichment of membrane proteins from Chlorobium tepidum prior to analysis with two-dimensional electrophoresis (2-DE). Isolated membranes were solubilized with Triton X-100 and from the supernatant we identified 58 unique proteins. The use of ionic sodium dodecyl sulfate (SDS) for protein solubilization, combined with acetone precipitation, resulted in an improved 2-DE pattern and the total number of the identified proteins was increased to 117. The use of acetone for protein precipitation improved the results by extracting compounds potentially deleterious to the resolution of 2-DE. However, the additional proteins detected by the use of SDS are in the majority more difficult to solubilize than less hydrophobic proteins. Further our attempts for selective extraction of the outer membrane proteins using the acid glycine method allowed the identification of 37 proteins of which 14 were predicted to have a signal sequence indicating their localization in the periplasmic space or in the outer membrane.     

Guided subwavelength plasmonic mode supported by a slot in a thin metal film

We demonstrate the existence of a bound optical mode supported by a slot in a thin metallic film deposited on a substrate, with slot dimensions much smaller than the wavelength. The modal size is almost completely dominated by the near field of the slot. Consequently, the size is very small compared with the wavelength, even when the dispersion relation of the mode approaches the light line of the surrounding media. In addition, the group velocity of this mode is close to the speed of light in the substrate, and its propagation length is tens of micrometers at the optical communication wavelength.     

Convergence rates for adaptive approximation of ordinary differential equations

Summary This paper constructs an adaptive algorithm for ordinary differential equations and analyzes its asymptotic behavior as the error tolerance parameter tends to zero. An adaptive algorithm, based on the error indicators and successive subdivision of time steps, is proven to stop with the optimal number, N, of steps up to a problem independent factor defined in the algorithm. A version of the algorithm with decreasing tolerance also stops with the total number of steps, including all refinement levels, bounded by . The alternative version with constant tolerance stops with total steps. The global error is bounded by the tolerance parameter asymptotically as the tolerance tends to zero. For a p-th order accurate method the optimal number of adaptive steps is proportional to the p-th root of the quasi-norm of the error density, while the number of uniform steps, with the same error, is proportional to the p-th root of the larger L ¹ -norm of the error density. Mathematics Subject Classification (2000):65Y20, 65L50, 65L70This work has been supported by the EU–TMR project HCL # ERBFMRXCT960033, the EU–TMR grant # ERBFMRX-CT98-0234 (Viscosity Solutions and their Applications), the Swedish Science Foundation, UdelaR and UdeM in Uruguay, the Swedish Network for Applied Mathematics, the Parallel and Scientific Computing Institute (PSCI) and the Swedish National Board for Industrial and Technical Development (NUTEK).     

Finite difference discretization of the Kuramoto-Sivashinsky equation

Summary We analyze a Crank-Nicolson-type finite difference scheme for the Kuramoto-Sivashinsky equation in one space dimension with periodic boundary conditions. We discuss linearizations of the scheme and derive second-order error estimates.Work supported by the Institute of Applied and Computational Mathematics of the Research Center of Crete-FORTH     

Three-dimensional PTx phase diagrams through interactive computer graphics

Interactive computer graphic techniques have been developed for the display of binary mixture phase diagrams. The diagrams are defined in temperature-pressure-composition space, and are portrayed as wireframe objects with depth perception in order to provide a three-dimensional effect. The displays used were vectro refresh workstations whose transformation hardware allows real-time rotation, rescaling, and translation of the diagrams, while software allows the extraction of constant property Px, Tx, PT and x - y plots. The equilibrium surfaces and the critical lines were calculated using the Redlich-Kwong equation of state and its Soave modification.     

Is There a Place in OR for Intelligent Tutoring Systems?

Intelligent tutoring systems (ITS) have recently found a wide range of potential applications across a multitude of disciplines and subject areas. This paper investigates the suitability and feasibility of developing ITS in the general context of OR as well as in a specific OR activity, simulation. It also examines how a current teaching aid for simulation model debugging can be transformed into an ITS and proposes a specification for the transformation process. The paper concludes that ITS could be useful in OR either for use as prime training systems or integrated in existing OR teaching packages. However, the field of ITS is in its infancy and development efforts are likely to be labour-intensive.     

Engineered chimeric enzymes as tools for drug discovery: generating reliable bacterial screens for the detection, discovery, and assessment of estrogen receptor modulators

Engineered protein-based sensors of ligand binding have emerged as attractive tools for the discovery of therapeutic compounds through simple screening systems. We have previously shown that engineered chimeric enzymes, which combine the ligand-binding domains of nuclear hormone receptors with a highly sensitive thymidylate synthase reporter, yield simple sensors that report the presence of hormone-like compounds through changes in bacterial growth. This work describes an optimized estrogen sensor in Escherichia coli with extraordinary reliability in identifying diverse estrogenic compounds and in differentiating between their agonistic/antagonistic pharmacological effects. The ability of this system to assist the discovery of new estrogen-mimicking compounds was validated by screening a small compound library, which led to the identification of two structurally novel estrogen receptor modulators and the accurate prediction of their agonistic/antagonistic biocharacter in human cells. Strong evidence is presented here that the ability of our sensor to detect ligand binding and recognize pharmacologically critical properties arises from allosteric communication between the artificially combined protein domains, where different ligand-induced conformational changes in the receptor are transmitted to the catalytic domain and translated to distinct levels of enzymic efficiency. To the best of our knowledge, this is one of the first examples of an engineered enzyme with the ability to sense multiple receptor conformations and to be either activated or inactivated depending on the nature of the bound effector molecule. Because the proposed mechanism of ligand dependence is not specific to nuclear hormone receptors, we anticipate that our protein engineering strategy will be applicable to the construction of simple sensors for different classes of (therapeutic) binding proteins.     

Sequential injection affinity chromatography utilizing an albumin immobilized monolithic column to study drug-protein interactions

In this study, sequential injection affinity chromatography was used for drug-protein interactions studies. The analytical system used consisted of a sequential injection analysis (SIA) manifold directly connected with convective interaction media (CIM) monolithic epoxy disks modified by ligand-immobilization of protein. A non-steroidal, anti-inflammatory drug, naproxen (NAP) and bovine serum albumin (BSA) were selected as model drug and protein, respectively. The SIA system was used for sampling, introduction and propulsion of drug towards to the monolithic column. Association equilibrium constants, binding capacity at various temperatures and thermodynamic parameters (free energy DeltaG, enthalpy DeltaH) of the binding reaction of naproxen are calculated by using frontal analysis mathematics. The variation of incubation time and its effect in on-line binding mode was also studied. The results indicated that naproxen had an association equilibrium constant of 2.90 x 10(6)M(-1) at pH 7.4 and 39 degrees C for a single binding site. The associated change in enthalpy (DeltaH) was -27.36 kcal mol(-1) and the change in entropy (DeltaS) was -73 cal mol(-1)K(-1) for a single type of binding sites. The location of the binding region was examined by competitive binding experiments using a biphosphonate drug, alendronate (ALD), as a competitor agent. It was found that the two drugs occupy the same class of binding sites on BSA. All measurements were performed with fluorescence (lambda(ext)=230 nm, lambda(em)=350 nm) and spectrophotometric detection (lambda=280 nm).     

Open-cage fullerene derivatives having 11-, 12-, and 13-membered-ring orifices: chemical transformations of the organic addends on the rim of the orifice

A novel open-cage [60]fullerene derivative, having two sulfur atoms on the rim of its 13-membered-ring orifice, has been isolated and characterized. Extensive studies on the N-MEM group reactivity of this as well as other previously reported open-cage [60]fullerene derivatives led to several new open-cage [60]fullerene adducts.