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Predicting intake and digestibility using mathematical models of ruminal function.

Intake and digestibility of feeds by ruminants are influenced by characteristics of the feed, animal and feeding situation. Integration of these characteristics in mathematical models is critical to future progress in forage evaluation and optimal formulation of diets for ruminants. The physiological and physical theories of intake regulation can be described by simple mathematical equations. These equations indicate that intake is a linear function of animal characteristics, such as body weight and production level, and a reciprocal function of feed characteristics, such as fill effect and energy content. Theoretical equations were developed to predict intake when the neutral detergent fiber and energy content of the diet and the energy requirements of the animal are known. The theoretical model also can be used to predict the maximum intake that will maintain a given level of animal production by solving the physiological and physical intake equations at their intersection. Psychogenic intake regulation, which is related to the animal's behavioral response to factors not related to physiological or physical characteristics, can be described mathematically as a multiplier. Digestibility can be predicted by summing the contents of ideal nutritive entities in feeds, which have true digestibilities near 100%, subtracting their associated endogenous losses and adding the variable digestible fiber content. Steady-state models indicate fractional rates of digestion and passage can be used to define ideal nutritive entities and predict digestibility over a range of kinetic characteristics. The steady-state solutions are particularly useful in understanding and predicting the depression in digestibility associated with changes in rates of passage at high levels of feed intake.

Animals↗

The role of hsp70 in protection and repair of luciferase activity in vivo; experimental data and mathematical modelling.

The stably transfected rat cell line HR24 expressing high levels of the inducible human hsp70 and its parental cell line Rat-1 were used for in vivo studies to analyse the role of hsp70 during thermal protein denaturation and the subsequent renaturation. In order to monitor denaturation and renaturation of a cellular protein in vivo, both cell lines were transiently transfected with firefly luciferase (Luc). The continuous monitoring of Luc activity during and after heat stress allowed a detailed analysis of the inactivation and reactivation kinetics in cells grown in monolayers. The aim of these studies was to distinguish a protective effect of increased hsp70 levels during heat shock-induced protein inactivation from a stimulation of reactivation. In this paper we show that in cells that are stably transfected with hsp70, thermal Luc inactivation decreased, and subsequent reactivation yielded higher activity levels, compared with the parental cells. The difference in early inactivation kinetics observed in the two cell lines suggests an immediate effect of the presence of an extra amount of hsp70 on enzyme inactivation. Using different mathematical models, the heat-induced inactivation and reactivation kinetics was compared with simulations of denaturation and renaturation. It is concluded that the model in which it is assumed that hsp70 is able to interact with partially denatured proteins, which did not yet lose their enzymatic activity, most optimally explains the experimental observations.

Animals↗

Mathematical modeling and computer simulation of erythrocytapheresis for SCD.

BACKGROUND: Erythrocytapheresis is used to prevent acute chest syndrome and stroke in patients with sickle cell disease (SCD). However, such regimens are associated with significant risks, such as iron overload and potential exposure to transfusion-transmitted infectious diseases. Computer modeling of erythrocytapheresis procedures may help optimize treatments and minimize risks. STUDY DESIGN AND METHODS: Mathematical models based upon material balance equations and patient-specific statistical analyses were developed to estimate HbS levels immediately after erythrocytapheresis and immediately before the next treatment. The equations were incorporated into a software application that was used to model the effects of various treatment values on four patients treated with 90 erythrocytapheresis procedures. RESULTS: Immediate postprocedure HbS values were accurately estimated with correlations between measured and calculated values ranging from R(2) = 0.83 to 0.96. Estimates of HbS just before the next treatment correlated well in three patients (R(2) = 0.71 to 0.83) but poorly in one (R(2) = 0.28 to 0.46). Varying the treatment values by computer simulation led to a wide variation in the number of RBC units and the net RBC volume transfused. CONCLUSION: Computer modeling of erythrocytapheresis can be used to optimize chronic treatment regimens for SCD patients and potentially to minimize the risks of overtransfusion.

Anemia, Sickle Cell↗

[Epidemiology of hepatitis A in Sardinia: mathematical model].

The prevalence of antibodies to hepatitis A in South-Sardinia was determined in samples of students and workers. In 1987 sera were collected from the children who attended kindergarten and elementary schools, in 1988 from students 13-20 years old (high schools) and from a group of workers who went to the public health office to ask for a certificate of good health. As far as the workers are concerned, the force of infection can be taken as a constant. In childhood, on the contrary, our findings are suggestive for a different immunization model. In this research work the prevalence observed in the population is analyzed using a mathematical model. Our model is based on the assumption that the force of infection increases linearly with age. The estimated fraction of susceptibles to hepatitis A is denoted by Y (X). The parameter h (X) represents the force of infection, the per capita rate at which susceptible population acquires infection. We assume that susceptibility may be lost only by natural infection and that permanent immunity results from first infection. So the fraction of susceptible population is gamma = exp (- x o integral of h (chi) d chi) if the force of infection increases linearly with age h (X) = ax + b then Y = exp (aX2 + bX + c) We can write In Y = y We obtain y = aX2 + bX + c Goodness of fit has been tested using the coefficient of determination R2. The number of cases in the group of age X - X + 1 can be estimated, for 10000 inhabitants, as (Y (X) - Y(X + 1) * 10000) Our findings are suggestive for a linear increasing of the force of infection with the group of age (R2 = 0.974). This could result from an age-dependent force of infection presumably as a consequence of age-related changes in behavioural patterns. Another explication could be a time-dependent force of infection according to improvements in socioeconomic and hygienic conditions. There is clear need for further research to separate the variations attributable to age from those attributable to time. Case notifications records could be very useful, but these data are notoriously unreliable.

Adolescent↗

Mathematical model for in vivo pharmacodynamics integrating fluctuation of the response: application to the prolactin suppressant effect of the dopaminomimetic drug DCN 203-922.

We propose a general pharmacokinetic-pharmacodynamic model that integrates the rhythmic fluctuation of hormone secretion for the description of the hormone-lowering effect of a drug. The mathematical model takes into account the variation in response observed after administration of a placebo and the drug. It is assumed that the change with time in the physiological response during the placebo period results from fluctuations in the concentration of hypothetical endogenous molecules. The mathematical formulation for predicting the response after drug intake is derived assuming competitive interaction of these "molecules" with the active species for binding to receptors. The suggested "fluctuation model" was implemented in order to describe the time course of the prolactin (PRL) plasma level after administration of two oral doses (2.5 and 5.0 mg) of the dopaminomimetic compound DCN 203-922 (DCN) to 9 healthy male subjects. Its performance was compared with that of conventional modeling approaches, in which the circadian changes after placebo are neglected and the hormone baseline is assumed to be constant. The new model provided a better description of the time course of PRL in most subjects. It was used for prediction of the amplitude and duration of the PRL suppressant effect after single and chronic administration of DCN at various dosage regimens as well as after changes in drug absorption.

Adult↗

Experimental study and mathematical modeling of the interaction between antibodies and antigens on the surface of liposomes.

Unilamellar liposomes with incorporated hapten-phospholipid conjugates were proposed as models of polyvalent antigens with migrating determinants for quantitative analysis of their interaction with antibodies. The monovalent pesticide atrazine was used as a model antigen. For its incorporation into the lipid bilayer, the atrazine carboxylated derivative was conjugated with dimyristoylphosphatidylethanolamine (DMPE). Unilamellar liposomes were prepared with dimyristoylphosphatidylcholine/atrazine-DMPE at molar ratios of 90:10, 95:5, 98:2, 99:1 and 99.5:0.5. Their interaction with the peroxidase-labeled anti-atrazine antibodies was studied by enzyme immunoassay and polarization fluoroimmunoassay techniques. It was shown that the increase in hapten content in the liposomes from 0.5 to 10 mol% led to an increase in the equilibrium constants of the interaction with antibodies from 0.093 x 10(8) to 0.303 x 10(8)M-1. The association rate constants varied from 1.45 x 10(5) to 15.5 x 10(5)M-1 s-1 depending on the antigen content in liposomes and experimental conditions. The measured constants were applied for a mathematical model describing multi-step interaction between antibodies and polyvalent liposomal antigens. The model adequately describes the quantitative regularities of the influence of antigen content and the affinity of immunochemical interaction on the quantity and the dynamics of the immune complexes forming.

Animals↗

Polysaccharide production by plant cells in suspension: experiments and mathematical modeling.

Symphytum officinale L cells were grown in Erlenmeyer flasks at four different temperatures: 15, 20, 25, and 30 degrees C. A mathematical model of the culture growth is presented. The intracellular and extracellular products are considered in separate equations. An interrelation between fresh weight, dry weight, and viability is considered in the balances. The model includes a description of the changes in time of wet and dry biomass, cell viability, substrate concentration and polysaccharide concentration, both intra- and extracellular. The model was tested by fitting the numerical results to the data obtained.

Biomass↗

Intrathoracic pressure fluctuations move blood during CPR: comparison of hemodynamic data with predictions from a mathematical model.

Whether blood flow during cardiopulmonary resuscitation (CPR) results from intrathoracic pressure fluctuations or direct cardiac compression remains controversial. We developed a mathematical model that predicts that blood flow due to intrathoracic pressure fluctuations should be insensitive to compression rate over a wide range but dependent on the applied force and compression duration. If direct compression of the heart plays a major role, however, the model predicts that flow should be dependent on compression rate and force, but above a threshold, insensitive to compression duration. These differences in hemodynamics produced by changes in rate and duration form a basis for determining whether blood flow during CPR results from intrathoracic pressure fluctuations or from direct cardiac compression. The model was validated for direct cardiac compression by studying the hemodynamics of cyclic cardiac deformation following thoracotomy in four anesthetized, 21-32-kg dogs. As predicted by the model, there was no change in myocardial or cerebral perfusion pressures when the duration of compression was increased from 15% to 45% of the cycle at a constant rate of 60/min. There was, however, a significant increase in perfusion pressures when rate was increased from 60 to 150/min at a constant duration of 45%. The model was validated for intrathoracic pressure changes by studying the hemodynamics produced by a thoracic vest (vest CPR) in eight dogs. The vest contained a bladder that was inflated and deflated. Vest CPR changed intrathoracic pressure without direct cardiac compression, since sternal displacement was less than 0.8 cm. As predicted by the model and opposite to direct cardiac compression, there was no change in perfusion pressures when the rate was increased from 60 to 150/min at a constant duration of 45% of the cycle. Manual CPR was then studied in eight dogs. There was no surgical manipulation of the chest. Myocardial and cerebral blood flows were determined with radioactive microspheres and behaved as predicted from the model of intrathoracic pressure, not direct cardiac compression. At nearly constant peak sternal force (378-426 N), flow was significantly increased when the duration of compression was increased from short (13%-19% of the cycle) to long (40%-47%), at a rate of 60/min. Flow was unchanged, however, for an increase in rate from 60 to 150/min at constant compression duration. In addition, myocardial and cerebral flow correlated with their respective perfusion pressures.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Mathematical models for the Aedes aegypti dispersal dynamics: travelling waves by wing and wind.

Biological invasion is an important area of research in mathematical biology and more so if it concerns species which are vectors for diseases threatening the public health of large populations. That is certainly the case for Aedes aegypti and the dengue epidemics in South America. Without the prospect of an effective and cheap vaccine in the near future, any feasible public policy for controlling the dengue epidemics in tropical climates must necessarily include appropriate strategies for minimizing the mosquito population factor. The present paper discusses some mathematical models designed to describe A. aegypti's vital and dispersal dynamics, aiming to highlight practical procedures for the minimization of its impact as a dengue vector. A continuous model including diffusion and advection shows the existence of a stable travelling wave in many situations and a numerical study relates the wavefront speed to a few crucial parameters. Strategies for invasion containment and its prediction based on measurable parameters are analysed.

Aedes↗

Mathematical modeling of calcium homeostasis in yeast cells.

In this study, based on currently available experimental observations on protein level, we constructed a mathematical model to describe calcium homeostasis in normally growing yeast cells (Saccharomyces cerevisiae). Simulation results show that tightly controlled low cytosolic calcium ion level can be a natural result under the general mechanism of gene expression feedback control. The calmodulin (a sensor protein) behavior in our model cell agrees well with relevant observations in real cells. Moreover, our model can qualitatively reproduce the experimentally observed response curve of real yeast cell responding to step-like disturbance in extracellular calcium ion concentration. Further investigations show that the feedback control mechanism in our model is as robust as it is in real cells.

Calcineurin↗

Mathematical models in microbial systems biology.

Systems biology aims at an understanding of the genotype-phenotype relations brought about by cellular networks. Mathematical models as formal representations are central for handling the associated complexity. Recently, model-based analysis of microorganisms has begun, for instance, to reveal functional modules in metabolic and transcriptional networks, to predict cellular behavior from genome-scale physicochemical constraints, and to suggest novel design principles for well-studied bacterial subsystems such as chemotaxis. Guided by common themes such as modularity, optimality and robustness, iterative model development promises further progress towards a system-level understanding.

Adaptation, Physiological↗

[Toxicity and anti-tumour efficacy of oxaliplatin on Glasgow osteosarcoma induced in mice: a mathematical model].

To study time-scheduled regimens in the treatment of tumours by cytotoxic drugs delivered by IV injection, we propose a mathematical model of the action of a chemotherapy on the population of tumoral cells on the one hand, on a population of fast renewing healthy cells on the other hand. We chose for model parameter identification the treatment by oxaliplatin of Glasgow Osteosarcoma in mice.

Animals↗

Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: a mathematical model.

A microscopic mass balance approach has been developed to predict the fraction dose absorbed of suspensions of poorly soluble compounds. The mathematical model includes four fundamental dimensionless parameters to estimate the fraction dose absorbed: initial saturation (Is), absorption number (An), dose number (Do), and dissolution number (Dn). The fraction dose absorbed (F) increases with increasing Is, An, and Dn and with decreasing Do. At higher Dn and lower Do, the fraction dose absorbed reaches the maximal F, which depends only on An. The dissolution number limit on F can appear at both lower Do and lower Dn. Likewise, at higher Do and Dn, the fraction dose absorbed reaches a Do limit. Initial saturation makes a significant difference in F at lower Do and Dn. It is shown that the extent of drug absorption is expected to be highly variable when Dn and Do are approximately one. Furthermore, by calculating these dimensionless groups for a given compound, a formulation scientist can estimate not only the extent of drug absorption but also the effect, if any, of particle size reduction on the extent of drug absorption.

Chemistry, Pharmaceutical↗

A family of mathematical models to describe the risk of infection by a sexually transmitted agent.

Several recent publications have used, without demonstrating its derivation, a mathematical model that describes the risk of being infected by a sexually transmitted agent as a function of four parameters: the number of partners, the number of contacts with each partner, the per-contact probability of transmission, and the probability of a partner being infected. The model is derived both from elementary probability concepts and, more formally, by using the binomial expansion and conditional probabilities. The assumptions involved in these derivations are brought out, as are the limitations they impose on the uses of the model. The model equations used so far in published studies are shown to be special cases of a general form that allows for more variability of the sexual behavior modeled. The different uses to which the model has been put are categorized, and some further ones are suggested.

Acquired Immunodeficiency Syndrome↗

Mathematical modelling of the citric acid cycle for the analysis of glutamine isotopomers from cerebellar astrocytes incubated with [1(-13)C]glucose.

A mathematical model of the citric acid cycle devoted to the analysis of 13C-NMR data was developed for determining the relative flux of molecules through the anaplerotic versus oxidative pathways and the relative pyruvate carboxylase versus pyruvate dehydrogenase activities. Different variants of the model were considered depending on the reversibility of the conversion of fumarate into malate and oxaloacetate. The model also included the possibility of orientation-conserved transfer of the four-carbon citric acid cycle intermediates, leading to conversion of succinyl-CoA C1 into either malate C1 or C4. It was used to analyse NMR data from glutamine isotopomers produced by cerebellar astrocytes incubated with [1-13C]glucose. Partial cycling (39%) between oxaloacetate and fumarate was evident from the analysis. Application of the model to glutamate isotopomers from granule cells incubated with [1-13C]glucose [Martin, M.. Portais, J.C.. Labouesse. J., Canioni. P, & Merle, M. (1993) Eur. J. Biochem. 217, 617-625] indicated that total cycling of oxaloacetate into fumarate was, in this case, required to get the best fit. The results emphasized some important differences in carbon metabolism between cerebellar astrocytes and granule cells concerning the sources of carbon fuelling the citric acid cycle and the carbon fluxes on different pathways.

Acetates↗

[An algorithm for construction of a mathematical model of coronary circulation disorders].

The paper shows how to improve the quality of diagnosing coronary heart disease (CHD). It proposes a mathematical model of coronary circulatory disorders, which is based on the definition of CHD as a cardiac abnormality caused by the imbalance of coronary blood flow and myocardial oxygen consumption, outlines an algorithm for construction of this model. With this model, a computer system has been designed for examining a patients with CHD, which permits the construction of a virtual model of coronary circulatory disorders.

Algorithms↗

Economic evaluation using mathematical models: the case of misoprostol prophylaxis.

Using misoprostol prophylaxis as an example, many of the methods employed in economic analyses that incorporate mathematical models were described. These included: decision analysis, cost effectiveness analysis (including incremental cost effectiveness analysis), one-way, multi-way, and probabilistic sensitivity analysis, and the estimation of quality adjusted life years for use in cost utility analysis. In the case of misoprostol prophylaxis, the cost effectiveness analysis demonstrated that, compared to the no prophylaxis alternative, prophylaxis cost an extra $650, on average, for every additional ulcer prevented, and was potentially cost saving for some high risk groups. The cost utility analysis demonstrated that prophylaxis resulted (on average) in modest additional costs and no additional quality of life benefits. Sensitivity analysis demonstrated that, at worst, prophylaxis reduced quality of life; at best, the incremental cost effectiveness ratio was $9333 for each quality adjusted life-year gained by prophylaxis compared to no prophylaxis. The results of the cost utility analysis also showed that prophylaxis may be cost saving in high risk groups, confirming the results of the cost effectiveness analysis. Finally, and perhaps most importantly, this analysis illustrated the importance of incorporating measures of health related quality of life into economic evaluation.

Cost-Benefit Analysis↗