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Quantitation and estimation of cooperation between target-binding sites in natural and antibody-dependent cell-mediated cytotoxicity by use of a mathematical transformation. Influence of interferon.

We have studied the use of a mathematical transformation, the Hill transformation, in natural and antibody-dependent cell-mediated cytotoxicity as a function of effector cell concentration. It can be concluded that when adherent cells are removed from the effector cell suspension, cooperation between binding sites for effector cells on the target cell changes from negative to zero. After stimulation of nonadherent cells with alpha-interferon, the binding sites still remain noninteracting. This is the case both in natural and in antibody-dependent cell-mediated cytotoxicity experiments. The Hill transformation seems to be an easy and easily reproducible way of quantitating cytotoxicity.

Antibody-Dependent Cell Cytotoxicity↗

A mathematical model of the Calvin photosynthesis cycle.

1. A mathematical model is presented for photosynthetic carbohydrate formation in C3 plants under conditions of light and carbon dioxide saturation. The model considers reactions of the Calvin cycle with triose phosphate export and starch production as main output processes, and treats concentrations of NADPH, NAD+, CO2, and H+ as fixed parameters of the system. Using equilibrium approximations for all reaction steps close to equilibrium steady-state and transient-state relationships are derived which may be used for calculation of reaction fluxes and concentrations of the 13 carbohydrate cycle intermediates, glucose 6-phosphate, glucose 1-phosphate, ATP, ADP, and inorganic (ortho)phosphate. 2. Predictions of the model were examined with the assumption that photosynthate export from the chloroplast occurs to a medium containing orthophosphate as the only exchangeable metabolite. The results indicate that the Calvin cycle may operate in a single dynamically stable steady state when the external concentration of orthophosphate does not exceed 1.9 mM. At higher concentrations of the external metabolite, the reaction system exhibits overload breakdown; the excessive rate of photosynthate export deprives the system of cycle intermediates such that the cycle activity progressively approaches zero. 3. Reactant concentrations calculated for the stable steady state that may obtain are in satisfactory agreement with those observed experimentally, and the model accounts with surprising accuracy for experimentally observed effects of external orthophosphate on the steady-state cycle activity and rate of starch production. 4. Control analyses are reported which show that most of the non-equilibrium enzymes in the system have a strong regulatory influence on the steady-state level of all of the cycle intermediates. Substrate concentration control coefficients for cycle enzymes may be positive, such that an increase in activity of an enzyme may raise the steady-state concentration of the substrate is consumes. 5. Under optimal external conditions (0.15-0.5 mM orthophosphate), reaction flux in the Calvin cycle is controlled mainly by ATP synthetase and sedoheptulose bisphosphatase; the cycle activity approaches the maximum velocity that can be supported by the latter enzyme. At lower concentrations of external orthophosphate the cycle activity is controlled almost exclusively by the phosphate translocator.(ABSTRACT TRUNCATED AT 400 WORDS)

Carbohydrates↗

Mathematical modelling of metabolic pathways affected by an enzyme deficiency. Energy and redox metabolism of glucose-6-phosphate-dehydrogenase-deficient erythrocytes.

The effects of various forms of glucose-6-phosphate dehydrogenase deficiency on erythrocyte metabolism have been studied on the basis of a complex mathematical model which comprises the main pathways of this cell: glycolysis, pentose pathway, reactions of the glutathione and adenine nucleotide metabolism. The calculated flux rates through the oxidative pentose pathway with and without methylene blue are in good accord with experimental results. The degree of deficiency as predicted by the model on the basis of calculated upper oxidative load boundaries, as well as of maximal methylene blue stimulation, correlates with the individual clinical manifestation of the metabolic disease. Therefore, the model allows one to judge the degree of metabolic disorder in the presence of glucose-6-phosphate dehydrogenase enzymopathies if the kinetic properties of the defect enzyme are known. Experimentally accessible parameters for an assessment of the oxidative load capacity of cells in vivo are proposed. It is pointed out that the threshold of tolerance as to energetic load is drastically reduced in the case of severe glucose-6-phosphate dehydrogenase deficiency.

Catalysis↗

Notulae seminologicae. 4. Mathematical evaluation of submicroscopical alterations in spermatozoa of sterile men with varicocele.

In this paper the mathematical formula recently proposed by Baccetti & Mirolli in this journal is used for the quantitative electron microscopical evaluation of six submicroscopical defects frequently present in the spermatozoa ejaculated by patients affected by various degrees of varicocele. All these characteristics are independent from each other and are in some way related to imperfect sperm maturation. They concern the shape and position of the acrosome, the status of the chromatin, of the mitochondria, of the axoneme, the individuality of the cell. The incidence in the sperm population of these submicroscopical characters is clearly related to the degree of the affection as estimated by usual clinical parameters. This demonstrates that the electron microscopical sperm analysis evaluated by the present formula is a very sensitive tool in revealing fine prognostical parameters.

Acrosome↗

Mathematical descriptions of AV nodal function curves in dogs.

Thirty-four anaestheized mongrel dogs subjected to thoracotomy were used to study AV node conduction during atrial pacing at increasing rates. Epicardial atrial electrodes were used, together with endocavitary recordings of His bundle electrogram. An analysis was made of the repercussions involved in using four different mathematical functions describing nodal conduction: three were nonlinear (exponential and hyperbolic A and B) and one linear. In the case of the first three, the consequences of using a direct nonlinear data-fitting procedure or an indirect procedure by linear transformations of the functions were studied. The exponential and hyperbolic B functions provided the least mean squared residual in quantifying nodal conduction (8.6 +/- 10.8 ms2 and 10.8 +/- 13.9 ms2, respectively). The use of nonlinear function transformation into a linear representation caused loss of precision in the fit to the data in the case of the exponential function (18.3 +/- 22.2 ms2 versus 8.6 +/- 10.8 ms2, p less than 0.01) and, to a lesser extent, in the case of the hyperbolic B function (12.5 +/- 16.4 ms2 versus 10.8 +/- 13.9 ms2, P less than 0.05).

Animals↗

A mathematical model of pattern formation by swimming microorganisms.

Bioconvection in suspensions of Tetrahymena pyriformis and Crypthecodinium cohnii is described and 2 new patterns, the toroid and the cat's-eye, which appear in shallow suspensions of C. cohnii, are reported. Except in very dense cultures, bioconvection does not arise unless the depth of the suspensions or the mean concentration exceed certain critical values, other things being equal. A mathematical model describing the hydrodynamics of suspension of negatively geotactic microorganisms is described which predicts the existence of critical depths and concentrations. The equations presented admit solutions describing the "polka-dot" patterns seen at low organism concentration in suspensions slightly deeper than the critical value. The discussion here is limited to the case of fairly dilute suspensions, but the basic approach can be applied also to richer cultures.

Dinoflagellida↗

Nutrition messages in language arts and mathematics textbooks used in English elementary schools in Montreal.

This analysis examined references to foods mentioned in elementary school textbooks used in Montreal English schools. A study of 58 language arts and mathematics textbooks used in grades one-six revealed 4,391 references to foods in words and pictures. A large proportion of the references were to sugar-rich foods. Eating with peers was depicted more frequently than eating with family, while a surprising number of children were depicted consuming their food alone in texts used in grades one-three. Results suggest that, because unintended information may influence children's nutritional habits, more attention should be directed at concomitant messages in elementary school textbooks.

Child↗

A mathematical model of fluid transport in the kidney.

A mathematical model of the rat kidney is developed from glomerular and tubular submodels. It is assumed that all nephrons are identical, that the hydraulic pressure in the tubules obeys Hagen-Poiseuille's law, that the rate of fluid reabsorption depends on the flow rate of tubular fluid, and that the tubules are distensible. The independent variables of the model are selected to comply with experimental measurements in the hydropenic rat. The model is used to evaluate the mechanism of glomerulotubular balance: changing the mean ultrafiltration pressure to the glomerular capillaries has a substantial influence on glomerular filtration rate (GFR). A change in the rate of fluid reabsorption in the proximal tubules has a strong influence on GFR notwithstanding that the change in GFR is smaller than that in the rate of fluid reabsorption. The calculated values for the hydraulic pressure profile in the tubular system and the interstitial pressure during ureteral obstruction are in close agreement with experimental measurements. Increasing the arterial haematocrit above normal causes a substantial decrease in GFR, whilst reducing it below normal has only a small effect on GRF.

Animals↗

Some factors of significance for respiratory gas exchange in muscle tissue. A mathematical analysis of a capillary model.

Morphological dimensions of the Krogh cylinder capillary model were calculated by mathematical simulation of respiratory gas exchange and blood flow in muscle tissue, using experimentally determined values for oxygen consumption (n'O2), blood flow (Q'), a-V O2 difference (a-v O2D) and pressure difference over the capillary (delta P), for resting and exercise conditions up to maximum performance. In the resting state a capillary radius, r1, of 3.5 (3-5) microgram a capillary density (CD) of 35 (30-90) capillaries/mm2 and a capillary length (L) of 900 (400-1000) microgram can satisfy experimentally determined values of the physiological variables. During muscular activity a maintained r1 and L with an increased CD allows higher n'O2. An increase in capillaries to about 600/mm2 can allow an n'O2 uptake 30 times the resting value (maximum performance). This increase cannot be achieved by an increase only in the r1. A shift to the right in the O2Hb dissociation curve during exercise has only a small effect on the O2 delivering capacity of the model, as has an increase in the diffusion constant for O2 in tissue. It is remarkable how limited a range of morphological dimensions, particularly of r1, is compatible with the known range of values for n'O2, O', a-v O2D and delta P, at rest and particularly during maximum performance of the muscle.

Capillary Permeability↗

A mathematical description of the myogenic response in the microcirculation.

A mathematical model for description of static and dynamic myogenic responses to change of vascular transmural pressure in the arterioles of skeletal muscle was developed for the purpose of elucidating some basic characteristics of the myogenic vascular control system which have proved difficult to reveal by physiological observations alone. The model, which is a refined version of a previous one (Borgström & Grände 1979), is based on a force-equilibrium in the arteriolar wall, including passive forces related to vascular transmural pressure, wall elasticity, and wall viscosity, an active force related to resting vascular tone, and the active static and dynamic myogenic forces considered to be related to and triggered by wall tension (force) and its rate of change as indicated by our previous results. The effects of biological inertia, of shifts along the length--tension curve of the smooth muscle, and of pressure induced reactions in the more proximal arterial vessels were taken into account in the present force-equilibrium equation for the arterioles. Arteriolar wall viscosity was assumed to decrease with increasing rate of wall movement, a behaviour predicted by the model and corroborated by in vitro observations on larger vessels. The model was found capable of faithfully simulating microvascular myogenic responses in cat skeletal muscle in vivo in response to ramp as well as impulse transmural pressure stimuli over the entire biological range from maximum constriction to dilatation. With such characteristics, it can serve as a useful complement to physiological approaches in attempts to define more precisely the mode of operation of the myogenic control system and to reveal inherent complexities of biophysical factors and of interaction of other control mechanisms in microvascular regulation in vivo, as exemplified by presented tests and preliminary results.

Animals↗

Likely mechanism of the hydrophobic sensitizer accumulation in tumor cells: mathematical models.

Two mathematical models describing the accumulation kinetics of hydrophobic sensitizers in the cell membrane and cytoplasm and the influence of intra- and extracellular pH values on intracellular accumulation are suggested. Numerical calculations were done for hematoporphyrin (Hp) as an example. When compared with the experimental data, both models gave satisfactory results describing the accumulation time and level. A biphasic character of the sensitizer accumulation process was obtained as a result of the difference in the accumulation times characteristic for the plasma membrane and cytoplasm. The ratio of characteristic times was determined by the ratio of membrane and cytoplasm volumes and a "water-lipid" partition coefficient reflecting the height of the membrane barrier for the sensitizer penetration through the plasma membrane lipid bilayer. Generally, the enhanced uptake of Hp molecules by cells was obtained when both extracellular and intracellular pH (pHin) values were lower than the physiological ones. A "selectivity" of accumulation was achieved in "tumor" cells for reasonable pHin values (about 6.0). But when compared with the experimental data, the value of selectivity was not high enough, indicating that, though the pH value is an important factor in Hp intracellular accumulation, it might be less important as a factor for selectivity of Hp accumulation in tumors.

Chemical Phenomena↗

Evaluation of electrical conductivity-temperature curves using a mathematical model: temperature-dependent changes during thawing of frozen aqueous pharmaceuticals.

The information contained in the electrical conductivity curves of pharmaceuticals measured as a function of temperature can be represented by a small set of parameters. This is achieved by approximating the electrical conductivity curve as a number of consecutive steps, using a suitable empirical model. The three parameters describing each step are: transition temperature, slope factor and step height. The validity of the calculated transition temperatures was established by applying the model to electrical conductivity curves measured on aqueous solutions of KCl, NaCl and on a KCl-NaCl mixture. It appears that the transition temperatures calculated for these inorganic salts are in good agreement with the respective eutectic temperatures reported in the literature. Subsequently, the method was applied to the corticosteroids prednisolone sodium succinate and prednisolone disodium phosphate. The mathematical model yields a satisfactory fit for both experimental conductivity curves. The actual consequences of freeze-drying an aqueous solution of prednisolone sodium succinate below and above the respective transition temperatures calculated are discussed in relation to the experimental conductivity data.

Chemistry, Pharmaceutical↗

The effect of animated diagrams on the understanding of a mathematical demonstration in 11- to 14-year-old pupils.

One hundred and eight children from 11 to 14 years were given instruction on shears and rotations, and how these transformations could be used to show the truth of Pythagoras's Theorem. The experimental group, which saw a computer-presented animated display of the transformations, scored more highly on a subsequent test than either of two control groups, the first of which saw no computer at all, but only a diagram sheet which was in the possession of all the children. The second control group saw a computer-presented display which showed only the same ten discrete stages of the transformations as the diagram sheet. It was concluded that animation per se can facilitate the understanding of a mathematical task.

Achievement↗

A mathematical model for conduction of action potentials along bifurcating axons.

1. A mathematical model based on the Hodgkin-Huxley equations is derived to describe quantitatively the propagation of action potentials in a branching axon. 2. The model treats the case of a bifurcating axon with branches of different diameters. The solution takes into account the changes in space constant in the different regions. 3. The model allows for investigating parameters leading to preferential conduction of action potentials in one daughter branch as seen experimentally. 4. Assuming that the only difference between the various daughter branches is in their diameters, conduction blocks should occur simultaneously rather than differentially into all daughter branches when the geometrical ratio is greater than 10. 5. In order to obtain differential conduction into the two branches changes in ionic concentrations due to the repetitive action potentials had to be introduced into the equations. 6. We find that conditions which allow differential buildup of K concentration around the two branches, produce differential conduction block. These conditions may be different periaxonal spaces around the branches or different time constant for recovery processes that eliminate K from the periaxonal space. 7. The effects of an inexcitable branch on conduction of action potentials in the second branch are described. 8. We find that the membrane current which is associated with the action potential is much more sensitive than the action potential itself and shows more distinct changes near regions of inhomogeneity such as a branch point, a step increase in diameter or an inexcitable branch.

Action Potentials↗

Three-dimensional kinematic modelling of the human shoulder complex--Part II: Mathematical modelling and solution via optimization.

In this paper, individual joint sinus cones associated with the sternoclavicular, claviscapular, and glenohumeral joints of the three-dimensional kinematic model introduced in Part I for the human shoulder complex are quantitatively determined. First, mathematical description of the humerus orientation with respect to torso is given in terms of eight joint variables. Since the system is a kinematically redundant one, solution for the joint variables satisfying a prescribed humerus orientation is possible only if additional requirements are imposed; and the "minimum joint motion" criterion is introduced for this purpose. Two methods, namely the Lagrange multipliers and flexible tolerance methods, are formulated and tested for the optimization problem. The statistical in-vivo data base for the circumductory motion of the upper arm is employed to determine a set of joint variables via optimization, which are then utilized to establish the sizes and orientations of the elliptical cones for the individual joint sinuses. The results are discussed and compared with those given on the basis of measurements made on cadaveric specimens.

Biomechanical Phenomena↗

O2 transport in cerebral microregions (mathematical simulation).

The effects of the circulation rate in capillaries, the intensity of O2 consumption by nerve cells and the capillary network density on the O2 tension distribution in the cerebral cortex have been studied, utilizing a mathematical model simulating actual neuron-capillary relationships. The model has been written as a system of equations in partial derivatives, its solution obtained by the net-point method. Regulatory variations of the capillary circulation rate in certain cerebral microregions have been shown to ensure similar changes in oxygen supply throughout the region. A drop of the pO2 level in a cerebral microregion with a rising O2 consumption by nerve cells is shown to be due, by 75 percent, to the increase of O2 consumption and by 25 percent, to the lower pO2 in the capillaries. Conversely, an increase in pO2 in microregions resulting from a lower O2 consumption by neurons is due by 75 percent, to a pO2 rise in capillaries and by 25 percent, at the expense of an O2 consumption decrease. In cerebral regions differing in capillary network density by 20 percent, changes in the conditions for oxygen supply to tissue are due by 1/3 to pO2 variations in the capillaries and by 2/3 to alterations in the diffusion distances.

Biological Transport, Active↗

Mathematical method for determining kVp from x-ray attenuation measurements.

A mathematical analysis of the shape of x-ray attenuation curves is presented that suggests a new method of determining the kVp of bremsstrahlung beams. The main result is a simple analytic formula which gives an excellent approximation to the attenuation curve for large thickness of high-Z absorber. From this, a graphical procedure is derived which yields a straight line whose slope is related to the mass attenuation coefficient evaluated at the peak energy. Included are corrections for aluminum filtration, ion-chamber energy dependence, and coherent scattering. The method is limited to beams generated by a constant potential and with negligible characteristic photons in the filtered spectrum. Numerical data are given for using copper absorber below 70 kVcp and tin above 90 kVcp.

Mathematics↗

Mathematical predictions of electroacoustic frequency response of in situ hearing aids.

The amplitude spectrum of an acoustic signal presented to the microphone of a hearing aid is altered drastically before it finally reaches the user's eardrum. A major part of this alteration is due to the interaction of various mechanical and acoustic resonances which are characteristic of the hearing-aid receiver and the sound transmission system linking the receiver with the eardrum. Because of the complexity of this phenomenon, there is yet no means for predicting, a priori, the true shape of the sound spectrum that will occur at the user's eardrum. This paper reports on the development and testing of just such a scheme. The accuracy of this scheme--a computer-aided mathematical technique--is measured in the laboratory on real and artificial ears. The results of those measurements show good agreement between experimental and computer-generated data below 5000 Hz.

Acoustics↗