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At least 307 records · Page 17Linked to original sources
PubMed2005

Bayesian inference for stochastic kinetic models using a diffusion approximation.

This article is concerned with the Bayesian estimation of stochastic rate constants in the context of dynamic models of intracellular processes. The underlying discrete stochastic kinetic model is replaced by a diffusion approximation (or stochastic differential equation approach) where a white noise term models stochastic behavior and the model is identified using equispaced time course data. The estimation framework involves the introduction of m- 1 latent data points between every pair of observations. MCMC methods are then used to sample the posterior distribution of the latent process and the model parameters. The methodology is applied to the estimation of parameters in a prokaryotic autoregulatory gene network.

Bayes Theorem↗
PubMed2005

Approximate linear confidence and curvature of a kinetic model of dodecanedioic acid in humans.

Dicarboxylic acids with an even number of carbon atoms have been proposed as an alternate energy substrate for enteral or parenteral nutrition in the acutely ill patient, due to their water solubility and their yielding TCA cycle intermediates upon beta-oxidation. In the present work, a nonlinear compartmental model of the kinetics of dodecanedioic acid is developed, and its parameters are estimated from time concentration experimental observations obtained from six healthy volunteers undergoing a per os administration of 3 g of the substance. Although the model is linear in the transfer of the free substance from plasma to the tissues, the exchange between gut and plasma compartments is represented as a saturable function. Albumin binding is then incorporated to obtain the final model in terms of the measured total concentrations. Estimates of the model's structural parameters were computed for each experimental subject, and the usual single-subject approximate confidence regions for the parameters were derived by inversion of the Hessian at the optimum. To verify the applicability of this approximation, the nonlinearity of the expectation surface at the optimum was measured by computing the normal (intrinsic) component of curvature. Because the model curvature was excessive in all subjects, the usual approximation could not be trusted to provide acceptable approximations to the parameter confidence regions. A suitable Monte Carlo simulation yielded empirical joint parameter distributions from which the approximate parameter variances could finally be obtained.

Computer Simulation↗
PubMed2005

Global kinetic model: a case study on the N-oxidation of alkylpyridines.

The homogeneous catalytic N-oxidation of two picolines and two lutidines by hydrogen peroxide has been studied calorimetrically using a heat flow and power compensation SIMULAR reaction calorimeter. The objective of this work was to extend a previously developed kinetic model [J. Sempere, R. Nomen, J.L. Rodriguez, M. Papadaki, Modelling of the reaction of 2-methylpyridine using hydrogen peroxide and a complex metal catalyst, Chem. Eng. Process. 37 (1998) 33-46] for 2-methylpyridine to more reactions in the same family. The kinetic model is in good agreement with our experimental data on beta-picoline. 3,5-Lutidine is in adequately good agreement with the model. However, the formation of two phases during the course of the reaction imposes the need for modifications to allow for mass transfer considerations. The N-oxidation of 2,6-lutidine is controlled by the addition or availability of hydrogen peroxide. A different reactor design is necessary for operation at the kinetic regime. High temperatures and catalyst concentrations enhance the selectivity towards N-oxidation of all alkylpyridines studied. The power evolution of all reactions has similar profiles thus indicating that similar kinetics are followed. The study of the N-oxidation of this family of compounds indicates that it is possible to design a process where hydrogen peroxide decomposition can be practically totally suppressed.

Calorimetry↗
PubMedDate not supplied

Kinetic modeling of brewery's spent grain autohydrolysis.

Isothermal autohydrolysis treatments of brewery's spent grain were used as a method for hemicellulose solubilization and xylo-oligosaccharides production. The time course of the concentrations of residual hemicelluloses (made up of xylan and arabinan) and reaction products were determined in experiments carried out at temperatures in the range from 150 to 190 degrees C using liquid-to-solid ratios of 8 and 10 g/g. To model the experimental findings concerning to brewery's spent grain autohydrolysis several kinetic models based on sequential pseudo-homogeneous first-order reactions were tested. Xylan and arabinan were assumed to yield oligosaccharides, monosaccharides (xylose or arabinose), furfural, and other decomposition products in consecutive reaction steps. The models proposed provide a satisfactory interpretation of the hydrolytic conversion of xylan and arabinan. An additional model merging the two proposed models for xylan and arabinan degradation assuming that furfural was formed from both pentoses was developed and the results obtained are discussed. The dependence of the calculated kinetic coefficients on temperature was established using Arrhenius-type equations.

Biotechnology↗
PubMed2001

Kinetic model of protein-mediated ligand transport: influence of soluble binding proteins on the intermembrane diffusion of a fluorescent fatty acid.

The mechanism (or mechanisms) whereby fatty acids and other amphipathic compounds are transported from the plasma membrane to intracellular sites of biotransformation remains poorly defined. In an attempt to better characterize the role of cytosolic binding proteins in this process, a kinetic model of intermembrane ligand transport was developed in which diffusional transfer of ligand between membrane and protein is assumed. The model was tested by utilizing stopped-flow techniques to monitor the transfer of the fluorescent fatty acid analogue, 12-anthroyloxy stearate (12-AS), between model membrane vesicles. Studies were conducted in the presence or absence of bovine serum albumin (BSA), liver fatty acid-binding protein (L-FABP), and intestinal fatty acid-binding protein (I-FABP) in order to determine the effect of soluble proteins on the rate of intermembrane ligand transfer. As predicted by the model, the initial velocity of 12-AS arrival at the acceptor membrane increases in an asymptotic manner with the acceptor concentration. Furthermore, probe transfer velocity was found to decline asymptotically with increasing concentrations of BSA or L-FABP, proteins that exhibit diffusional transfer kinetics. This observation was found to hold true independent of whether donor or acceptor vesicles were preequilibrated with the protein. In contrast, 12-AS transfer velocity exhibited a linear correlation with the concentration of I-FABP, a protein that is thought to transport fatty acids, at least in part, via a collisional mechanism. Taken together, these findings validate the derived kinetic model of protein-mediated ligand transport and further suggest that the mechanism of ligand-protein interaction is a key determinant of the effect of cytosolic proteins on intracellular ligand diffusion.

Animals↗
PubMed2006

Kinetic modeling for the biosorption of copper by pretreated Aspergillus niger biomass.

In this present work, a kinetic model for biosorption of copper was developed considering the possibility of different forms of functional groups being present on the surface of the biomass prepared from Aspergillus niger. Results showed that metal uptake by A. niger was a mass transfer driven process, requiring only 30min to achieve 70% adsorption efficiency. Copper sorption by A. niger was influenced by the biomass dose, initial metal ion concentration, and pH of the solution. The Langmuir and Freundlich adsorption isotherms were used to describe the behavior of the system at different pH. The retention capacity of the biomass was determined at pH 6.0 to be equal to 23.62mg/g of biomass. The pretreatment with formalin improved the uptake of metal ion.

Adsorption↗
PubMed2005

Kinetic modeling of aerobic biodegradation of high oil and grease rendering wastewater.

Batch scale activated sludge kinetic studies were undertaken for the treatment of pet food wastewater characterized by oil and grease concentrations of up to 21,500 mg/L, COD and BOD concentrations of 75,000 and 60,000 mg/L, respectively as well as effluent from the batch dissolved air flotation (DAF) system. The conducted kinetics studies showed that Haldane Model fit the substrates and biomass data better than Monod model in DAF-pretreated wastewater, while the modified hydrolysis Monod model better fit the raw wastewater kinetic data. For the DAF pretreated batches, Haldane Model kinetic coefficients k, K(S), Y and Ki values of 1.28-5.35 g COD/g VSS-d, 17,833-23,477 mg/L, 0.13-0.41 mg VSS/mg COD and 48,168 mg/L, respectively were obtained reflecting the slow biodegradation rate. Modified hydrolysis Monod model kinetic constants for the raw wastewater i.e., k, K(S), Y, and K(H) varied from 1-1.3 g COD/g VSS-d, 5580-5600 mg COD/l, 0.08-0.85 mg VSS/mg COD, and 0.21-0.66 d(-1), respectively.

Biodegradation, Environmental↗
PubMed2002

Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach.

The selection of appropriate substrates for investigating the potential inhibition of CYP3A4 is critical as the magnitude of effect is often substrate-dependent, and a weak correlation is often observed among different CYP3A4 substrates. This feature has been attributed to the existence of multiple binding sites and, therefore, relatively complex in vitro data modeling is required to avoid erroneous evaluation and to allow prediction of drug-drug interactions. This study, performed in lymphoblast-expressed CYP3A4 with oxidoreductase, provides a systematic comparison of the effects of quinidine (QUI) and haloperidol (HAL) as modifiers of CYP3A4 activity using a selection of CYP3A4 substrates: testosterone (TST), midazolam (MDZ), nifedipine (NIF), felodipine (FEL), and simvastatin (SV). The effect of QUI and HAL on CYP3A4-mediated pathways was substrate-dependent, ranging from potent inhibition of NIF (K(i) = 0.25 and 5.3 micro M for HAL and QUI, respectively), weak inhibition (TST), minimal effect (HAL on MDZ/SV) to QUI activation of FEL and SV metabolism. Inhibition of TST metabolite formation occurred but its autoactivation properties were maintained, indicating binding of a QUI/HAL molecule to a distinct effector site. Various multisite kinetic models have been applied to elucidate the mechanism of the drug-drug interactions observed. Kinetic models with two substrate-binding sites have been found to be appropriate to a number of interactions, provided the substrates show hyperbolic (MDZ, FEL, and SV) or substrate inhibition kinetic properties (NIF). In contrast, a three-site model approach is required for TST, a substrate showing positive cooperativity in its binding to CYP3A4.

Binding Sites↗
PubMed1987

A kinetic model of chylomicron core lipid metabolism in rats: the effect of a single meal.

A detailed quantitative description of the metabolism of the core lipids of chylomicrons was developed with data obtained from rats injected intravenously with radioactive chylomicrons. Groups of recipient rats were starved or else fed a single meal that was either fat-free or contained 5% fat. The kinetic model included chains of delipidation compartments and a remnant particle. Compartments for recirculation of portions of triglyceride, cholesteryl ester, and unesterified fatty acid radioactivities were all included and necessary to obtain good fits to the data. Making the simplifying assumption that remnants could be represented as particles retaining cholesteryl esters but depleted in triglycerides, a 'delipidation index' was calculated as the ratio of the cholesteryl ester residence time divided by the triglyceride residence time. Significant differences were found in the delipidation index between the starved group and both the normal-fed and fat-free-fed groups. Compared with rats fed a meal of the usual diet which contained 5% fat, starved rats showed more extensive delipidation and a trend toward a longer residence time of remnant particles. A longer residence time of triglycerides in rats fed a fat-free meal was explained by less delipidation, but remnant removal appeared to be accelerated. The kinetic model makes possible an interpretation of the patterns of metabolism in terms of the known underlying physiological mechanisms.

Animals↗
PubMed1995

Size dependent liposome degradation in blood: in vivo/in vitro correlation by kinetic modeling.

The degradation of liposomes in blood circulation is important in regulating the releasing rate of encapsulated compounds. In this study, the effect of liposome size--one of the principal determining factors in liposome disposition--on their degradation in serum/blood was evaluated quantitatively both in vitro and in vivo. In the in vitro study, the time courses of the degradation of liposomes in fresh rat serum were measured continuously using 5(6)-carboxyfluorescein (CF) as an aqueous phase marker and were described by the kinetic model with the lag time (tau), first order degradation rate constant (k), and the maximum degradation (alpha). Both k and alpha increased with the increase of liposome size, which indicated a higher affinity of larger liposomes for complement activation. In the in vivo study, the degradation of liposomes was evaluated sensitively by a first order degradation rate constant (kd) in blood circulation. The kd was obtained by kinetically modeling the liposome degradation in vivo using 3H-inulin as an aqueous phase marker. The size dependent kd correlated well with the hepatic uptake clearance, which suggests an underlying complement activation mechanism common to both degradation and hepatic uptake of liposomes. There was a good correlation in the degradation rate constant between in vitro and in vivo trials. These kinetic analyses validate the quantitative evaluation of liposome degradation in blood circulation and provide a useful way to predict the degradation of liposomes in vivo from in vitro experiments.

Animals↗
PubMed2000

Reduction and protonation of the secondary quinone acceptor of Rhodobacter sphaeroides photosynthetic reaction center: kinetic model based on a comparison of wild-type chromatophores with mutants carrying Arg-->Ile substitution at sites 207 and 217 in the L-subunit.

After the light-induced charge separation in the photosynthetic reaction center (RC) of Rhodobacter sphaeroides, the electron reaches, via the tightly bound ubiquinone QA, the loosely bound ubiquinone Q(B) After two subsequent flashes of light, Q(B) is reduced to ubiquinol Q(B)H2, with a semiquinone anion Q-(B) formed as an intermediate after the first flash. We studied Q(B)H2 formation in chromatophores from Rb. sphaeroides mutants that carried Arg-->Ile substitution at sites 207 and 217 in the L-subunit. While Arg-L207 is 17 A away from Q(B), Arg-L217 is closer (9 A) and contacts the Q(B)-binding pocket. From the pH dependence of the charge recombination in the RC after the first flash, we estimated deltaG(AB), the free energy difference between the Q-(A)Q(B) and Q(A)Q-(B) states, and pK212, the apparent pK of Glu-L212, a residue that is only 4 A away from Q(B). As expected, the replacement of positively charged arginines by neutral isoleucines destabilized the Q-(B) state in the L217RI mutant to a larger extent than in the L207RI one. Also as expected, pK212 increased by approximately 0.4 pH units in the L207RI mutant. The value of pK212 in the L217RI mutant decreased by 0.3 pH units, contrary to expectations. The rate of the Q-(A)Q-(B)-->Q(A)Q(B)H2 transition upon the second flash, as monitored by electrometry via the accompanying changes in the membrane potential, was two times faster in the L207RI mutant than in the wild-type, but remained essentially unchanged in the L217RI mutant. To rationalize these findings, we developed and analyzed a kinetic model of the Q-(A)Q-(B)-->Q(A)Q(B)H2 transition. The model properly described the available experimental data and provided a set of quantitative kinetic and thermodynamic parameters of the Q(B) turnover. The non-electrostatic, 'chemical' affinity of the QB site to protons proved to be as important for the attracting protons from the bulk, as the appropriate electrostatic potential. The mutation-caused changes in the chemical proton affinity could be estimated from the difference between the experimentally established pK2J2 shifts and the expected changes in the electrostatic potential at Glu-L212, calculable from the X-ray structure of the RC. Based on functional studies, structural data and kinetic modeling, we suggest a mechanistic scheme of the QB turnover. The detachment of the formed ubiquinol from its proximal position next to Glu-L212 is considered as the rate-limiting step of the reaction cycle.

Amino Acid Substitution↗
PubMedDate not supplied

A kinetic model for substrate and energy consumption of microbial growth under substrate-sufficient conditions.

The growth of heterotrophic microorganisms can be classified into substrate-limited and substrate-sufficient growth according to the relative availability of the substrate (carbon and energy source) and other nutrients. It is generally observed that the consumption rates of substrate and energy (ATP) are higher under substrate-sufficient conditions than under conditions of substrate limitation. The excess substrate and ATP consumption is often influenced by the residual concentration of substrate in a relatively wide range. To account for these effects, a kinetic model is proposed to describe substrate and ATP consumption rates of microbial growth under substrate-sufficient conditions. According to the model, the specific substrate consumption rate of a substrate-sufficient culture can be expressed as the sum of the substrate rate under substrate-limited conditions at the corresponding specific growth rate and an additional consumption rate due to excess substrate. The same kinetic form also applies to the specific ATP consumption rate and to the specific oxygen consumption rate of an aerobic culture, respectively. The linear equations for substrate and ATP consumption rates of Pirt and of Stouthammer and Bettenhousen can be used for substrate-limited growth. The excess of substrate and ATP consumption rates at carbon surplus can be described in a form similar to that of Michaelis-Menten kinetics. The proposed kinetic model has been verified with experimental data from three continuous cultures representing both anaerobic and aerobic microbial growth on substrates with low and high degrees of reductance. Using this model, the parameters maximum growth yield and maintenance requirement (both in terms of substrate and ATP) of a culture under different growth limitations can be better defined and quantified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed2006

A quantitative kinetic model for ATP-induced intracellular Ca2+ oscillations.

A quantitative kinetic model is proposed to simulate the ATP-induced intracellular Ca(2+) oscillations. The quantitative effect of ATP concentration upon the oscillations was successfully simulated. Our simulation results support previous experimental explanations that the Ca(2+) oscillations are mainly due to interaction of Ca(2+) release from the endoplasmic reticulum (ER) and the ATP-dependent Ca(2+) pump back into the ER, and the oscillations are prolonged by extracellular Ca(2+) entry that maintains the constant Ca(2+) supplies to its intracellular stores. The model is also able to simulate the sudden disappearance phenomenon of the Ca(2+) oscillations observed in some cell types by taking into account of the biphasic characteristic of the Ca(2+) release from the endoplasmic reticulum (ER). Moreover, the model simulation results for the Ca(2+) oscillations characteristics such as duration, peak [Ca(2+)](cyt), and average interval, etc., lead to prediction of some possible factors responsible for the variations of Ca(2+) oscillations in different types of cells.

Adenosine Triphosphate↗
PubMedDate not supplied

Simulation of CA3 region of hippocampus by kinetic models.

The global activities of the hippocampal CA3 field which are induced by stimuli coming from entorhinal cortex have been investigated through computional experiments. The simulations are based on a mathematical model formulated within the frame of a kinetic theory of neural systems. To obtain a description closer to the real biological system, the kinetic model has been supplemented with elements describing the dynamics of neurotransmitters in synaptic clefts. Because high frequency activities occur in the CA3 field, elements for the description of receptor saturation and vesicle depletion phenomena have also been taken into account. The computational experiments show that CA3 model reacts to simulated stimuli from entorhinal sources activating the pyramidal neurons. This activity self-organizes within some limited areas, and spreads to the whole CA3 as a patterned reverberation of short period which requires both excitatory and inhibitory neural populations. The reverberating activity is then stopped by massive inhibition produced by slow-inhibitory neural population. The relationships between the parameters linked to the synaptic dynamic and the elements characterizing these patterns have been investigated.

Computer Simulation↗
PubMed1993

An analysis of the single-pool urea kinetic model and estimation of errors.

The single-pool urea kinetic model assumes that urea is distributed within the body in a volume Vf at a uniform concentration. It may be used to describe the clearance of urea during and following haemodialysis, and to determine the value of the urea concentration at the end of dialysis Cf or the urea generation rate G, and the urea distribution volume Vf. The protein catabolic rate (PCR) is obtained using the ratio G/Vf. The sensitivity of the predictions of the model to small errors in the experimentally estimated model parameters is evaluated and suggests that the model prediction of Cf is relatively insensitive to errors in the estimate of G, but more sensitive to errors in Vf and dialyser clearance K. The determination of G from urea concentration measurements made during dialysis alone is very sensitive to errors. The accurate estimation of G requires the use of concentration measurements made between dialyses. The calculation of the PCR is very sensitive to errors in G and Vf since these are not independent and must be used with caution, particularly when used to compare values between patients.

Humans↗
PubMed1994

[Use of urea kinetic modeling in patients on maintenance hemodialysis].

The effect of urea kinetic modeling (u.k.m.) application on dialysis efficiency and metabolic status was evaluated in 50 maintenance dialyzed patients. U.k.m. sessions were performed once a month based on the self-developed computer program to control dialysis. The dialysis index (Kt/V), the time averaged concentration (TAC), protein catabolic rate (pcr) and dialysis effectiveness (Ct/Co) were evaluated and the results obtained at the beginning and after 2, 4, and 8 months of the study were compared. Kt/V had risen significantly in the modeled patients from 1.04 to 1.24 and was accompanied by 12% Ct/Co increase of urea removal after 8 months. The tendency of the moderate (non significant) decrease of TAC from 54.57 to 52.48 mg% BUN was observed during the study. According to the NCDS criteria the percentage of adequately dialyzed patients increased from 42% at the beginning to 64% after 80 months; underdialyzed patients decreased from 16% to 6% and malnourished also from 16% to 6%, respectively, after u.k.m. application. Dialysis effectiveness for creatinine and uric acid described by Ct/Co for the above after 4 and 8 months was significantly increased when compared with the results obtained at the beginning of the study. These results indicate that u.k.m. application allowed to take control over uremic toxemia and improved dialysis adequacy in patients on maintenance dialysis. Protein catabolic rate in studied patients increased from 1.18 to 1.24 g/kg/per day during the study and it was accompanied by a total blood protein and serum albumin increase. This could indicate improvement of the nutritional status of dialyzed subjects.

Adolescent↗
PubMed2006

Validation of a tracer kinetic model for the quantification of 5-HT(2A) receptors in human brain with [(11)C]MDL 100,907.

The positron emission tomography (PET) ligand [(11)C]MDL 100,907 has previously been introduced to image the serotonin 2A (5-HT(2A)) receptor in human brain. The aim of this work was to contribute to the verification of the tracer kinetic modelling in human studies. Five healthy volunteers were scanned twice after intravenous bolus injection of approximately 370 MBq [(11)C]MDL 100,907 using dynamic PET. One scan was performed under baseline condition, the other scan commenced 90 mins after a single oral dose of 30 mg of the antidepressant mirtazapine, which binds to the 5-HT(2A) receptor. There did not appear to be radiolabelled metabolites of [(11)C]MDL 100,907 in human plasma, which are likely to cross the blood-brain barrier. Total volumes of distribution VD in 11 different brain regions were estimated using a reversible, two tissue, four rate constants compartment model with a variable fractional blood volume term and the metabolite-corrected plasma input function. There were no significant changes of the VD in the cerebellum between the baseline and the blocked scans confirming the cerebellum as a region devoid of displaceable binding. Regional estimates of binding potential were then obtained indirectly using the cerebellar VD and occupancies calculated. The mean occupancy with this clinically effective dose of mirtazapine was 60% without significant regional differences. This study confirmed the use of an arterial input kinetic model for the quantification of 5-HT(2A) receptor binding with [(11)C]MDL 100,907 and the use of the cerebellum as a reference region for the free and nonspecific binding.

Adult↗
PubMed2003

Mechanism and kinetic model for the decolorization of the azo dye Reactive Black 5 by hydrogen peroxide and UV radiation.

A kinetic model for the decolorization of C.I. Reactive Black 5 by the combination of hydrogen peroxide and UV radiation was developed based on experimental results and known chemical and photochemical reactions. The observed kinetic reaction coefficient was determined and correlated as a function of hydrogen peroxide concentration and UV intensity. The validity of the rate expression was tested experimentally in a parameterization study. The decolorization rate follows pseudo-first order kinetics with respect to dye concentration. The rate increases linearly with UV intensity and nonlinearly with increasing hydrogen peroxide concentration, going from a linear relationship at low H(2)O(2) concentrations to a maximum as hydrogen peroxide concentration continues to increase. The decolorization rate expression derived from the proposed reaction mechanism was reconciled with that used for correlating the experimental data.

Azo Compounds↗