Application of an allosteric ternary complex model to the technique of pharmacological resultant analysis

A simple ternary complex model of drug-receptor interaction has been used to extend the procedure of pharmacological resultant analysis, enabling the quantitation of interactions between allosteric modulators and orthosteric antagonists. Equations derived in the theoretical treatment were used to analyse functional data for the interaction between the allosteric modulator gallamine and the orthosteric antagonist scopolamine, with oxotremorine as the agonist, at rat tracheal muscarinic acetylcholine receptors. Quantitative estimates of the affinity of gallamine for the allosteric site (pKz = 4.7) and the extent of negative, heterotropic co-operativity between gallamine and scopolamine (alpha' = 13.1) were obtained. Furthermore, an alternative direct, model-fitting approach, that does not rely on the determination of concentration ratios, was also developed, and yielded similar results. It is suggested that the approach presented in this paper is useful for quantifying interactions between orthosteric antagonists and allosteric modulators, particularly when the extent of co-operativity is low or the modulators possess multiple pharmacological properties, or both.     

Complement resistance of capsulated strains of Aeromonas salmonicida

1. We investigated the effect of exercise on plasma adrenomedullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects. 2. The exercise protocol consisted of two fixed work loads (40 and 80 W) for 4 min each and venous blood samples were taken at rest, during each exercise stage and after exercise while monitoring the mean arterial pressure (MAP) and heart rate (HR). In MI, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and cardiac output (CO) were measured throughout exercise. 3. Adrenomedullin levels did not significantly increase with exercise. Adrenomedullin levels correlated with PAP and PCWP at rest (P < 0.05). Atrial natriuretic peptide levels correlated with PAP, PCWP and LVEDP throughout exercise (P < 0.05) but, on multiple regression analysis, PCWP correlated only with ANP (P < 0.01). Brain natriuretic peptide levels correlated with LVEDP throughout exercise (P < 0.01) and its increment correlated closely with basal BNP levels at rest (P < 0.01). 4. These results suggest that adrenomedullin does not respond to the acute haemodynamic changes of exercise, whereas ANP responds to it and PCWP is the major stimulus factor. Brain natriuretic peptide responds to exercise in proportion to the basal synthesis of BNP in patients with left ventricular dysfunction and LVEDP may play a role in increasing BNP during exercise.     

Anatomical data fusion for quantitative reconstruction inmyocardial tomoscintigraphy using a spline model of the thorax organs

The authors present the fusion of anatomical data as a method for improving the reconstruction in single photon emission computed tomography (SPECT). Anatomical data is used to deduce a parameterized model of organs in a reconstructed slice using spline curves. This model allows the authors to define the imaging process, i.e., the direct problem, more adequately, and furthermore to restrict the reconstruction to the emitting zones. Instead of the usual square pixels, the authors use a new kind of discretization pixel, which fits to the contour in the region of interest. In the reconstruction phase, the authors estimate the activity in the emitting zones and also the optimum parameters of their model. Concentrating on the left ventricular (LV) wall activity, the simulation and phantom results show an accurate estimation of both the myocardial shape and the radioactive emission     

The large deflection dynamic plastic response of rectangular plates

By assuming a kinematically admissible, time-dependent velocity field and considering the global equilibrium of all the forces acting on each rigid segment during large deflection of a plate, a complete theoretical investigation is undertaken herein to trace the large deflection dynamic plastic response (including the transient phase) of simply-supported or fully-clamped rectangular plates. This procedure deduces two modifying factors ƒ₁ and ƒ₂ which reflect the effect of the membrane forces and are employed to formulate the governing equations in the case of large deflections. The present prediction of the final plate deflection coincides excellently with the corresponding experimental results for deflections up to 5–10 times the plate thickness. This theory greatly improves the estimates based on the bending-only theory and provides a new way to trace the transient phase of dynamically loaded plates when the effect of membrane forces is significant.     

A new method of excitation control based on fuzzy set theory

The synthesis of the structure of the power system stabiliser (PSS) and its parametrization are based entirely on methods of linear system theory. Thus the desired effect of the PSS is limited to a bounded area around one system operating point. The use of a controller based on fuzzy set theory introduces an event controlled excitation of the synchronous machine taking into account the power system operation. The desired response of the fuzzy controller is given by a set of rules which are obtained from the limits of the voltage regulator and the undesired performance of the conventional excitation control. A fuzzy controller has been developed for which simulation results are provided. These results support the concept of a fuzzy controller for the purpose of excitation control. They show that a well designed fuzzy controller is superior to a fast excitation control with an additional PSS     

Kinetic behaviour of muscle LDH immobilized in nylon tubing

Immobilization was carried out of the lactate dehydrogenase (LDH) from rabbit muscle (EC 1.1.1.27), cross-linked through the bifunctional reactive glutar-aldehyde on to nylon tubing (1 m long, 53cm² internal surface area). Immobilized LDH inactivation kinetics are of first order (t_1/2 = 3·6 years, k = 5·4,e^?4 day^?1 to 5°C). The smaller effect of pH on activity than in the case of LDH in solution can be explained on the basis of limitation to proton diffusion towards the support. A limiting effect to free external diffusion of the substrate towards and products from the support was also observed, an effect which seems to determine the effective kinetic behaviour of immobilized LDH. The apparent optimum temperature is centred around 40°C, observing a clear inactivation (thermal denaturation) above this temperature. In the temperature range studied (10–40°C), the co-existence was seen of a kinetic control accompanied by another control, involving diffusional transport of substrates and products, on the global activity of the immobilized enzyme. This makes the Arrhenius profiles curvilinear. Both graphic and statistical non-linear regression analysis of the kinetic data—rate, v, versus substrate concentration [S]—carried out under conditions in which the diffusional limitations can be considered negligible (high recirculation flow rate), permitted investigation of the intrinsic kinetic behaviour of immobilized LDH. In this sense, it can be deduced that the rate equation to which these data seem to be fitted is of the polynomial quotient type in [S] of minimum degree 2:2. Although the diffusional limitations have a marked effect on the type of global kinetics shown by immobilized LDH, temperature was not found to affect its v[S] behaviour. The experimental evidence obtained thus indicates that the rate equation in the 10-40°C temperature range continues to be a rational equation of at least degree 2:2 in [S].     

Specimen size effect during tensile testing of an unreinforced polymer

Various specimen sizes of an unreinforced polymer, Hercules 3501 -6 thermosetting epoxy, were subjected to a tensile test. The general specimen geometry was a rectangular dog-bone shape with constant gauge length, but with each specimen size having a different crosssectional area. These cross-sectional areas were obtained by varying the thickness of the epoxy during casting, and the gauge section width during grinding. The resulting failure surfaces of the specimens were observed and photographed using scanning electron microscopy. The results indicate that failure stress, dimensions of the critical flaw which caused failure, and a quantity which is proportional to the fracture toughness, are all correlated with specimen size.     

Measurement of synchronous machine rotor angle from analysis ofzero sequence harmonic components of machine terminal voltage

Generator rotor angle measurement is useful in identification of electric machine parameters in the d and q axes and as an indicator of stability of the operating condition. Rotor angle measurements with the appropriate bandwidth are also very useful in observation of rotor torsional oscillations both for monitoring and protection against undamped torsional modes, and for use in control schemes designed to damp torsional oscillations. A method of measurement of synchronous machine rotor angle from an analysis of the phase angle of zero sequence harmonic components of terminal voltage is presented