Noise slows the rate of Michaelis-Menten reactions.
Van Dyken, J David
2017-10-07
Microscopic randomness and the small volumes of living cells combine to generate random fluctuations in molecule concentrations called "noise". Here I investigate the effect of noise on biochemical reactions obeying Michaelis-Menten kinetics, concluding that substrate noise causes these reactions to slow. I derive a general expression for the time evolution of the joint probability density of chemical species in arbitrarily connected networks of non-linear chemical reactions in small volumes. This equation is a generalization of the chemical master equation (CME), a common tool for investigating stochastic chemical kinetics, extended to reaction networks occurring in small volumes, such as living cells. I apply this equation to a generalized Michaelis-Menten reaction in an open system, deriving the following general result: 〈p〉≤p¯ and 〈s〉≥s¯, where s¯ and p¯ denote the deterministic steady-state concentration of reactant and product species, respectively, and 〈s〉 and 〈p〉 denote the steady-state ensemble average over independent realizations of a stochastic reaction. Under biologically realistic conditions, namely when substrate is degraded or diluted by cell division, 〈p〉≤p¯. Consequently, noise slows the rate of in vivo Michaelis-Menten reactions. These predictions are validated by extensive stochastic simulations using Gillespie's exact stochastic simulation algorithm. I specify the conditions under which these effects occur and when they vanish, therefore reconciling discrepancies among previous theoretical investigations of stochastic biochemical reactions. Stochastic slowdown of reaction flux caused by molecular noise in living cells may have functional consequences, which the present theory may be used to quantify. Copyright © 2017 Elsevier Ltd. All rights reserved.
Time-dependent corrections to effective rate and event statistics in Michaelis-Menten kinetics
Sinitsyn, N. A.; Nemenman, I.
2010-01-01
We generalize the concept of the geometric phase in stochastic kinetics to a noncyclic evolution. Its application is demonstrated on kinetics of the Michaelis-Menten reaction. It is shown that the nonperiodic geometric phase is responsible for the correction to the Michaelis-Menten law when parameters, such as a substrate concentration, are changing with time. We apply these ideas to a model of chemical reactions in a bacterial culture of a growing size, where the geometric correction qualita...
Time-dependent corrections to effective rate and event statistics in Michaelis-Menten kinetics.
Sinitsyn, N A; Nemenman, I
2010-11-01
The authors generalise the concept of the geometric phase in stochastic kinetics to a non-cyclic evolution. Its application is demonstrated on kinetics of the Michaelis-Menten reaction. It is shown that the non-periodic geometric phase is responsible for the correction to the Michaelis-Menten law when parameters, such as a substrate concentration, are changing with time. The authors apply these ideas to a model of chemical reactions in a bacterial culture of a growing size, where the geometric correction qualitatively changes the outcome of the reaction kinetics.
Perturbation theory in the catalytic rate constant of the Henri-Michaelis-Menten enzymatic reaction.
Bakalis, Evangelos; Kosmas, Marios; Papamichael, Emmanouel M
2012-11-01
The Henry-Michaelis-Menten (HMM) mechanism of enzymatic reaction is studied by means of perturbation theory in the reaction rate constant k (2) of product formation. We present analytical solutions that provide the concentrations of the enzyme (E), the substrate (S), as well as those of the enzyme-substrate complex (C), and the product (P) as functions of time. For k (2) small compared to k (-1), we properly describe the entire enzymatic activity from the beginning of the reaction up to longer times without imposing extra conditions on the initial concentrations E ( o ) and S ( o ), which can be comparable or much different.
About and beyond the Henri-Michaelis-Menten rate equation for single-substrate enzyme kinetics.
Bajzer, Zeljko; Strehler, Emanuel E
2012-01-20
For more than a century the simple single-substrate enzyme kinetics model and related Henri-Michaelis-Menten (HMM) rate equation have been thoroughly explored in various directions. In the present paper we are concerned with a possible generalization of this rate equation recently proposed by F. Kargi (BBRC 382 (2009) 157-159), which is assumed to be valid both in the case that the total substrate or enzyme is in excess and the quasi-steady-state is achieved. We demonstrate that this generalization is grossly inadequate and propose another generalization based on application of the quasi-steady-state condition and conservation equations for both enzyme and substrate. The standard HMM equation is derived by (a) assuming the quasi-steady-state condition, (b) applying the conservation equation only for the enzyme, and (c) assuming that the substrate concentration at quasi-steady-state can be approximated by the total substrate concentration [S](0). In our formula the rate is already expressed through [S](0), and we only assume that when quasi-steady-state is achieved the amount of product formed is negligible compared to [S](0). Numerical simulations show that our formula is generally more accurate than the HMM formula and also can provide a good approximation when the enzyme is in excess, which is not the case for the HMM formula. We show that the HMM formula can be derived from our expression by further assuming that the total enzyme concentration is negligible compared to [S](0). Copyright © 2011 Elsevier Inc. All rights reserved.
Pulkkinen, O
2016-01-01
Many chemical reactions in biological cells occur at very low concentrations of constituent molecules. Thus, transcriptional gene-regulation is often controlled by poorly expressed transcription-factors, such as E.coli lac repressor with few tens of copies. Here we study the effects of inherent concentration fluctuations of substrate-molecules on the seminal Michaelis-Menten scheme of biochemical reactions. We present a universal correction to the Michaelis-Menten equation for the reaction-rates. The relevance and validity of this correction for enzymatic reactions and intracellular gene-regulation is demonstrated. Our analytical theory and simulation results confirm that the proposed variance-corrected Michaelis-Menten equation predicts the rate of reactions with remarkable accuracy even in the presence of large non-equilibrium concentration fluctuations. The major advantage of our approach is that it involves only the mean and variance of the substrate-molecule concentration. Our theory is therefore accessi...
Liao, Fei; Zhu, Xiao-Yun; Wang, Yong-Mei; Zuo, Yu-Ping
2005-01-31
The estimation of enzyme kinetic parameters by nonlinear fitting reaction curve to the integrated Michaelis-Menten rate equation ln(S(0)/S)+(S(0)-S)/K(m)=(V(m)/K(m))xt was investigated and compared to that by fitting to (S(0)-S)/t=V(m)-K(m)x[ln(S(0)/S)/t] (Atkins GL, Nimmo IA. The reliability of Michaelis-Menten constants and maximum velocities estimated by using the integrated Michaelis-Menten equation. Biochem J 1973;135:779-84) with uricase as the model. Uricase reaction curve was simulated with random absorbance error of 0.001 at 0.075 mmol/l uric acid. Experimental reaction curve was monitored by absorbance at 293 nm. For both CV and deviation kinetic parameters and applicable for the characterization of enzyme inhibitors.
Golicnik, Marko
2011-01-01
The Michaelis-Menten rate equation can be found in most general biochemistry textbooks, where the time derivative of the substrate is a hyperbolic function of two kinetic parameters (the limiting rate "V", and the Michaelis constant "K"[subscript M]) and the amount of substrate. However, fundamental concepts of enzyme kinetics can be difficult to…
Golicnik, Marko
2011-01-01
The Michaelis-Menten rate equation can be found in most general biochemistry textbooks, where the time derivative of the substrate is a hyperbolic function of two kinetic parameters (the limiting rate "V", and the Michaelis constant "K"[subscript M]) and the amount of substrate. However, fundamental concepts of enzyme kinetics can be difficult to…
The integrated Michaelis-Menten rate equation: déjà vu or vu jàdé?
Goličnik, Marko
2013-08-01
A recent article of Johnson and Goody (Biochemistry, 2011;50:8264-8269) described the almost-100-years-old paper of Michaelis and Menten. Johnson and Goody translated this classic article and presented the historical perspective to one of incipient enzyme-reaction data analysis, including a pioneering global fit of the integrated rate equation in its implicit form to the experimental time-course data. They reanalyzed these data, although only numerical techniques were used to solve the model equations. However, there is also the still little known algebraic rate-integration equation in a closed form that enables direct fitting of the data. Therefore, in this commentary, I briefly present the integral solution of the Michaelis-Menten rate equation, which has been largely overlooked for three decades. This solution is expressed in terms of the Lambert W function, and I demonstrate here its use for global nonlinear regression curve fitting, as carried out with the original time-course dataset of Michaelis and Menten.
Pulkkinen, Otto; Metzler, Ralf
2015-12-04
Many chemical reactions in biological cells occur at very low concentrations of constituent molecules. Thus, transcriptional gene-regulation is often controlled by poorly expressed transcription-factors, such as E.coli lac repressor with few tens of copies. Here we study the effects of inherent concentration fluctuations of substrate-molecules on the seminal Michaelis-Menten scheme of biochemical reactions. We present a universal correction to the Michaelis-Menten equation for the reaction-rates. The relevance and validity of this correction for enzymatic reactions and intracellular gene-regulation is demonstrated. Our analytical theory and simulation results confirm that the proposed variance-corrected Michaelis-Menten equation predicts the rate of reactions with remarkable accuracy even in the presence of large non-equilibrium concentration fluctuations. The major advantage of our approach is that it involves only the mean and variance of the substrate-molecule concentration. Our theory is therefore accessible to experiments and not specific to the exact source of the concentration fluctuations.
Single-molecule Michaelis-Menten equations.
Kou, S C; Cherayil, Binny J; Min, Wei; English, Brian P; Xie, X Sunney
2005-10-20
This paper summarizes our present theoretical understanding of single-molecule kinetics associated with the Michaelis-Menten mechanism of enzymatic reactions. Single-molecule enzymatic turnover experiments typically measure the probability density f(t) of the stochastic waiting time t for individual turnovers. While f(t) can be reconciled with ensemble kinetics, it contains more information than the ensemble data; in particular, it provides crucial information on dynamic disorder, the apparent fluctuation of the catalytic rates due to the interconversion among the enzyme's conformers with different catalytic rate constants. In the presence of dynamic disorder, f(t) exhibits a highly stretched multiexponential decay at high substrate concentrations and a monoexponential decay at low substrate concentrations. We derive a single-molecule Michaelis-Menten equation for the reciprocal of the first moment of f(t), 1/, which shows a hyperbolic dependence on the substrate concentration [S], similar to the ensemble enzymatic velocity. We prove that this single-molecule Michaelis-Menten equation holds under many conditions, in particular when the intercoversion rates among different enzyme conformers are slower than the catalytic rate. However, unlike the conventional interpretation, the apparent catalytic rate constant and the apparent Michaelis constant in this single-molecule Michaelis-Menten equation are complicated functions of the catalytic rate constants of individual conformers. We also suggest that the randomness parameter r, defined as )2> / t2, can serve as an indicator for dynamic disorder in the catalytic step of the enzymatic reaction, as it becomes larger than unity at high substrate concentrations in the presence of dynamic disorder.
The Michaelis-Menten-Stueckelberg Theorem
Alexander N. Gorban
2011-05-01
Full Text Available We study chemical reactions with complex mechanisms under two assumptions: (i intermediates are present in small amounts (this is the quasi-steady-state hypothesis or QSS and (ii they are in equilibrium relations with substrates (this is the quasiequilibrium hypothesis or QE. Under these assumptions, we prove the generalized mass action law together with the basic relations between kinetic factors, which are sufficient for the positivity of the entropy production but hold even without microreversibility, when the detailed balance is not applicable. Even though QE and QSS produce useful approximations by themselves, only the combination of these assumptions can render the possibility beyond the “rarefied gas” limit or the “molecular chaos” hypotheses. We do not use any a priori form of the kinetic law for the chemical reactions and describe their equilibria by thermodynamic relations. The transformations of the intermediate compounds can be described by the Markov kinetics because of their low density (low density of elementary events. This combination of assumptions was introduced by Michaelis and Menten in 1913. In 1952, Stueckelberg used the same assumptions for the gas kinetics and produced the remarkable semi-detailed balance relations between collision rates in the Boltzmann equation that are weaker than the detailed balance conditions but are still sufficient for the Boltzmann H-theorem to be valid. Our results are obtained within the Michaelis-Menten-Stueckelbeg conceptual framework.
Michaelis-Menten equation and detailed balance in enzymatic networks.
Cao, Jianshu
2011-05-12
Many enzymatic reactions in biochemistry are far more complex than the celebrated Michaelis-Menten scheme, but the observed turnover rate often obeys the hyperbolic dependence on the substrate concentration, a relation established almost a century ago for the simple Michaelis-Menten mechanism. To resolve the longstanding puzzle, we apply the flux balance method to predict the functional form of the substrate dependence in the mean turnover time of complex enzymatic reactions and identify detailed balance (i.e., the lack of unbalanced conformational current) as a sufficient condition for the Michaelis-Menten equation to describe the substrate concentration dependence of the turnover rate in an enzymatic network. This prediction can be verified in single-molecule event-averaged measurements using the recently proposed signatures of detailed balance violations. The finding helps analyze recent single-molecule studies of enzymatic networks and can be applied to other external variables, such as force-dependence and voltage-dependence.
Optimal designs for Michaelis-Menten kinetic studies.
Matthews, J N S; Allcock, G C
2004-02-15
Many reactions in enzymology are governed by the Michaelis-Menten equation. Characterising these reactions requires the estimation of the parameters K(M) and V(max) which determine the Michaelis-Menten equation and this is done by observing rates of reactions at a set of substrate concentrations. The choice of substrate concentrations is investigated by determining Bayesian D-optimal designs for a model in which residuals have a normal distribution with constant variance. Designs which focus on alternative quantities, such as K(M) or the ratio V(max)/K(M) are also considered. The effect on the optimal designs of alternative error distributions is also considered.
Lu, Jian; Dong, Yuxia; Ng, Emily C; Siehl, Daniel L
2017-05-01
One of applications of directed evolution is to desensitize an enzyme to an inhibitor. kcat,1/KM and KI are three dimensions that when multiplied measure an enzyme's intrinsic capacity for catalysis in the presence of an inhibitor. The ideal values for the individual dimensions depend on substrate and inhibitor concentrations under the conditions of the application. When attempting to optimize those values by directed evolution, (kcat/KM)*KI can be an informative parameter for evaluating libraries of variants, but throughput is limited. We describe a manipulation of the Michaelis-Menten equation for competitive inhibition that isolates (kcat/KM)*KI on one side of the equation. If velocity is measured at constant enzyme and substrate concentrations with two different inhibitor concentrations (one of which can be 0), the data are sufficient to calculate (kcat/KM)*KI with just two rate measurements. The procedure is validated by correlating values obtained by the rapid method with those obtained by substrate saturation kinetics. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Michaelis-Menten relations for complex enzymatic networks.
Kolomeisky, Anatoly B
2011-04-21
Most biological processes are controlled by complex systems of enzymatic chemical reactions. Although the majority of enzymatic networks have very elaborate structures, there are many experimental observations indicating that some turnover rates still follow a simple Michaelis-Menten relation with a hyperbolic dependence on a substrate concentration. The original Michaelis-Menten mechanism has been derived as a steady-state approximation for a single-pathway enzymatic chain. The validity of this mechanism for many complex enzymatic systems is surprising. To determine general conditions when this relation might be observed in experiments, enzymatic networks consisting of coupled parallel pathways are investigated theoretically. It is found that the Michaelis-Menten equation is satisfied for specific relations between chemical rates, and it also corresponds to a situation with no fluxes between parallel pathways. Our results are illustrated for a simple model. The importance of the Michaelis-Menten relationship and derived criteria for single-molecule experimental studies of enzymatic processes are discussed.
Michaelis-Menten dynamics in protein subnetworks
Rubin, Katy J
2016-01-01
To understand the behaviour of complex systems it is often necessary to use models that describe the dynamics of subnetworks. It has previously been established using projection methods that such subnetwork dynamics generically involves memory of the past, and that the memory functions can be calculated explicitly for biochemical reaction networks made up of unary and binary reactions. However, many established network models involve also Michaelis-Menten kinetics, to describe e.g. enzymatic reactions. We show that the projection approach to subnetwork dynamics can be extended to such networks, thus significantly broadening its range of applicability. To derive the extension we construct a larger network that represents enzymes and enzyme complexes explicitly, obtain the projected equations, and finally take the limit of fast enzyme reactions that gives back Michaelis-Menten kinetics. The crucial point is that this limit can be taken in closed form. The outcome is a simple procedure that allows one to obtain ...
Michaelis-Menten dynamics in protein subnetworks.
Rubin, Katy J; Sollich, Peter
2016-05-07
To understand the behaviour of complex systems, it is often necessary to use models that describe the dynamics of subnetworks. It has previously been established using projection methods that such subnetwork dynamics generically involves memory of the past and that the memory functions can be calculated explicitly for biochemical reaction networks made up of unary and binary reactions. However, many established network models involve also Michaelis-Menten kinetics, to describe, e.g., enzymatic reactions. We show that the projection approach to subnetwork dynamics can be extended to such networks, thus significantly broadening its range of applicability. To derive the extension, we construct a larger network that represents enzymes and enzyme complexes explicitly, obtain the projected equations, and finally take the limit of fast enzyme reactions that gives back Michaelis-Menten kinetics. The crucial point is that this limit can be taken in closed form. The outcome is a simple procedure that allows one to obtain a description of subnetwork dynamics, including memory functions, starting directly from any given network of unary, binary, and Michaelis-Menten reactions. Numerical tests show that this closed form enzyme elimination gives a much more accurate description of the subnetwork dynamics than the simpler method that represents enzymes explicitly and is also more efficient computationally.
Michel, Denis
2013-01-01
The Michaelis-Menten enzymatic reaction is sufficient to perceive many subtleties of network modeling, including the concentration and time scales separations, the formal equivalence between bulk phase and single-molecule approaches, or the relationships between single-cycle transient probabilities and steady state rates. Seven methods proposed by different authors and yielding the same famous Michaelis-Menten equation, are selected here to illustrate the kinetic and probabilistic use of rate constants and to review basic techniques for handling them. Finally, the general rate of an ordered multistep reaction, of which the Michaelis-Menten reaction is a particular case, is deduced from a Markovian approach.
Michaelis-Menten kinetics of stiripentol in normal humans.
Levy, R H; Loiseau, P; Guyot, M; Blehaut, H M; Tor, J; Moreland, T A
1984-08-01
Michaelis-Menten kinetic parameters for stiripentol, and anticonvulsant, were assessed in six normal volunteers. Stiripentol was administered orally three times a day in dosage increments of 600, 1,200, and 1,800 mg/day for consecutive periods of 3, 4, and 7 days, respectively. Stiripentol steady-state levels at the three dosing rates increased more than proportionally with dose. The mean +/- SD oral clearance of stiripentol at 600 mg/day (1,090 +/- 624 L/day) was significantly greater (p less than 0.01) than at 1,200 (506 +/- 219 L/day) or 1,800 (405 +/- 151 L/day) mg/day. Average steady-state concentrations predicted from individually determined Vm and Km parameters were in good agreement with experimentally observed levels, indicating that the kinetics of stiripentol are of the Michaelis-Menten type. The mean Vm, Km, and Vm/Km ratio were 2,299 +/- 490 mg/day, 2.20 +/- 1.28 mg/L, and 1,241 +/- 837 L/day, respectively. Neuropsychological tests carried out before and after 14 days of stiripentol treatment showed a significant decline in verbal learning ability (p = 0.038) and a significant improvement in a test of memory and attention (p less than 0.01).
Michel, Denis; Ruelle, Philippe
2013-01-01
International audience; The Michaelis-Menten enzymatic reaction is sufficient to perceive many subtleties of network modeling, including the concentration and time scales separations, the formal equivalence between bulk phase and single-molecule approaches, or the relationships between single-cycle transient probabilities and steady state rates. Seven methods proposed by different authors and yielding the same famous Michaelis-Menten equation, are selected here to illustrate the kinetic and p...
Enzymatic reactions in microfluidic devices: Michaelis-Menten kinetics.
Ristenpart, William D; Wan, Jiandi; Stone, Howard A
2008-05-01
Kinetic rate constants for enzymatic reactions are typically measured with a series of experiments at different substrate concentrations in a well-mixed container. Here we demonstrate a microfluidic technique for measuring Michaelis-Menten rate constants with only a single experiment. Enzyme and substrate are brought together in a coflow microfluidic device, and we establish analytically and numerically that the initial concentration of product scales with the distance x along the channel as x5/2. Measurements of the initial rate of product formation, combined with the quasi-steady rate of product formation further downstream, yield the rate constants. We corroborate the x5/2 scaling result experimentally using the bioluminescent reaction between ATP and luciferase/luciferin as a model system.
Bozlee, Brian J.
2007-01-01
The impact of raising Gibbs energy of the enzyme-substrate complex (G[subscript 3]) and the reformulation of the Michaelis-Menten equation are discussed. The maximum velocity of the reaction (v[subscript m]) and characteristic constant for the enzyme (K[subscript M]) will increase with increase in Gibbs energy, indicating that the rate of reaction…
Amyloid-like fibril elongation follows michaelis-menten kinetics
Milto, Katazyna; Botyriute, Akvile; Smirnovas, Vytautas
2013-01-01
... are. We obtained experimental data on insulin amyloid-like fibril elongation at the conditions where other processes which may impact kinetics of fibril formation are minor and fitted it using Michaelis-Menten equation...
Costa, Rafael S; Machado, Daniel; Rocha, Isabel; Ferreira, Eugénio C
2010-05-01
The construction of dynamic metabolic models at reaction network level requires the use of mechanistic enzymatic rate equations that comprise a large number of parameters. The lack of knowledge on these equations and the difficulty in the experimental identification of their associated parameters, represent nowadays the limiting factor in the construction of such models. In this study, we compare four alternative modeling approaches based on Michaelis-Menten kinetics for the bi-molecular reactions and different types of simplified rate equations for the remaining reactions (generalized mass action, convenience kinetics, lin-log and power-law). Using the mechanistic model for Escherichia coli central carbon metabolism as a benchmark, we investigate the alternative modeling approaches through comparative simulations analyses. The good dynamic behavior and the powerful predictive capabilities obtained using the hybrid model composed of Michaelis-Menten and the approximate lin-log kinetics indicate that this is a possible suitable approach to model complex large-scale networks where the exact rate laws are unknown. 2010 Elsevier Ireland Ltd. All rights reserved.
Legitimacy of the stochastic Michaelis-Menten approximation.
Sanft, K R; Gillespie, D T; Petzold, L R
2011-01-01
Michaelis-Menten kinetics are commonly used to represent enzyme-catalysed reactions in biochemical models. The Michaelis-Menten approximation has been thoroughly studied in the context of traditional differential equation models. The presence of small concentrations in biochemical systems, however, encourages the conversion to a discrete stochastic representation. It is shown that the Michaelis-Menten approximation is applicable in discrete stochastic models and that the validity conditions are the same as in the deterministic regime. The authors then compare the Michaelis-Menten approximation to a procedure called the slow-scale stochastic simulation algorithm (ssSSA). The theory underlying the ssSSA implies a formula that seems in some cases to be different from the well-known Michaelis-Menten formula. Here those differences are examined, and some special cases of the stochastic formulas are confirmed using a first-passage time analysis. This exercise serves to place the conventional Michaelis-Menten formula in a broader rigorous theoretical framework.
Tang, J. Y
2015-01-01
The Michaelis-Menten kinetics and the reverse Michaelis-Menten kinetics are two popular mathematical formulations used in many land biogeochemical models to describe how microbes and plants would...
Schnell, Santiago
2014-01-01
The Michaelis-Menten equation is generally used to estimate the kinetic parameters, V and K(M), when the steady-state assumption is valid. Following a brief overview of the derivation of the Michaelis-Menten equation for the single-enzyme, single-substrate reaction, a critical review of the criteria for validity of the steady-state assumption is presented. The application of the steady-state assumption makes the implicit assumption that there is an initial transient during which the substrate concentration remains approximately constant, equal to the initial substrate concentration, while the enzyme-substrate complex concentration builds up. This implicit assumption is known as the reactant stationary assumption. This review presents evidence showing that the reactant stationary assumption is distinct from and independent of the steady-state assumption. Contrary to the widely believed notion that the Michaelis-Menten equation can always be applied under the steady-state assumption, the reactant stationary assumption is truly the necessary condition for validity of the Michaelis-Menten equation to estimate kinetic parameters. Therefore, the application of the Michaelis-Menten equation only leads to accurate estimation of kinetic parameters when it is used under experimental conditions meeting the reactant stationary assumption. The criterion for validity of the reactant stationary assumption does not require the restrictive condition of choosing a substrate concentration that is much higher than the enzyme concentration in initial rate experiments. © 2013 FEBS.
Thiopentone elimination in newborn infants: exploring Michaelis-Menten kinetics.
Larsson, P; Anderson, B J; Norman, E; Westrin, P; Fellman, V
2011-04-01
Thiopentone elimination has been described using Michaelis-Menten pharmacokinetics in adults after prolonged infusion or overdose, but there are few reports of elimination in neonates. Time-concentration profiles for neonates (n=37) given single-dose thiopentone were examined using both first-order (constant clearance) and mixed-order (Michaelis-Menten) elimination processes using nonlinear mixed effects models. These profiles included a 33-week post-menstrual age (PMA) neonate given an overdose. A two-compartment mamillary model was used to fit data. Parameter estimates were standardized to a 70 kg person using allometric models. There were 197 observations available for analysis from neonates with a mean post-menstrual age of 35 (SD 4.5) weeks and a mean weight of 2.5 (SD 0.9) kg. They were given a mean thiopentone dose of 3 (SD 0.4) mg/kg as a rapid bolus. Clearance at 26 weeks PMA was 0.015 l/min/70 kg and increased to 0.119 l/min/70 kg by 42 weeks PMA. The maximum rate of elimination (V(max)) at 26 weeks PMA was 0.22 mg/min/70 kg and increased to 4.13 mg/min/70 kg by 42 weeks PMA. These parameter estimates are approximately 40% adult values at term gestation. The Michaelis constant (K(m)) was 28.3 [between subject variability (BSV) 46.4%, 95% confidence interval (CI) 4.49-99.2] mg/l; intercompartment clearance was 0.44 (BSV 97.5%, 95% CI 0.27-0.63) l/min/70 kg; central volume of distribution was 46.4 (BSV 29.2%, 95% CI 41.7-59.8) l/70 kg; peripheral volume of distribution was 95.7 (BSV 70.3%, 95% CI 61.3-128) l/70 kg. Both first-order and mixed-order processes satisfactorily described elimination. First-order elimination adequately described the time-concentration profile in the premature neonate given an overdose. Clearance is immature in the pre-term neonate although there is rapid maturation around 40 weeks PMA, irrespective of post-natal age. © 2011 The Authors. Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.
Single molecule Michaelis-Menten equation beyond quasistatic disorder.
Xue, Xiaochuan; Liu, Fei; Ou-Yang, Zhong-Can
2006-09-01
The classic Michaelis-Menten equation describes the catalytic activities for ensembles of enzyme molecules very well. But recent single-molecule experiments showed that the waiting time distribution and other properties of single enzyme molecules were not consistent with the prediction based on the ensemble viewpoint. They have contributed to the slow conformational changes of a single enzyme in the catalytic processes. In this work, we study the general dynamics of single enzymes in the presence of dynamic disorder. We find that, within the time separation regimes, i.e., the slow reaction and nondiffusion limits, the Michaelis-Menten equation holds exactly. In particular, by employing the decoupling approximation we demonstrate analytically that the classic Michaelis-Menten equation is still an excellent approximation in the presence of general dynamic disorder.
Stochastic mapping of the Michaelis-Menten mechanism.
Dóka, Éva; Lente, Gábor
2012-02-07
The Michaelis-Menten mechanism is an extremely important tool for understanding enzyme-catalyzed transformation of substrates into final products. In this work, a computationally viable, full stochastic description of the Michaelis-Menten kinetic scheme is introduced based on a stochastic equivalent of the steady-state assumption. The full solution derived is free of restrictions on amounts of substance or parameter values and is used to create stochastic maps of the Michaelis-Menten mechanism, which show the regions in the parameter space of the scheme where the use of the stochastic kinetic approach is inevitable. The stochastic aspects of recently published examples of single-enzyme kinetic studies are analyzed using these maps.
Bueno, Paulo R; Watanabe, Ailton M; Faria, Ronaldo C; Santos, Márcio L; Riccardi, Carla S
2010-12-16
A piezoelectric detection of enzyme-modified surface was performed under Michaelis-Menten presumptions of steady-state condition. The approach herein presented showed promise in the study of enzymatic kinetics by measuring the frequency changes associated with mass changes at the piezoelectric crystal surface. Likewise, real-time frequency shifts, that is, dΔf/dt, indicated the rate of products formation from enzymatic reaction. In this paper, acetylcholinesterase was used as the enzymatic model and acetylcholine as substrate. The enzymatic rate has its maximum value for a short time during the kinetic reaction, for instance, during the first ten minutes of the reaction time scale. The values found for the kinetic constant rate and Michaelis-Menten constant were (1.4 ± 0.8) 10(5) s(-1) and (5.2 ± 3) 10(-4) M, respectively, in agreement with the values found in classical Michaelis-Menten kinetic experiments.
Sinitsyn, Nikolai A [Los Alamos National Laboratory
2008-01-01
We generalize the concept of the geometric phase in stochastic kinetics to a noncyclic evolution. Its application is demonstrated on kinetics of the Michaelis-Menten reaction. It is shown that the noncyclic geometric phase is responsible for the correction to the Michaelis-Menten law when parameters, such as a substrate concentration, are changing with time. We also discuss a model, where this correction qualitatively changes the outcome of reaction kinetics.
Conformational Nonequilibrium Enzyme Kinetics: Generalized Michaelis-Menten Equation.
Piephoff, D Evan; Wu, Jianlan; Cao, Jianshu
2017-08-03
In a conformational nonequilibrium steady state (cNESS), enzyme turnover is modulated by the underlying conformational dynamics. On the basis of a discrete kinetic network model, we use an integrated probability flux balance method to derive the cNESS turnover rate for a conformation-modulated enzymatic reaction. The traditional Michaelis-Menten (MM) rate equation is extended to a generalized form, which includes non-MM corrections induced by conformational population currents within combined cyclic kinetic loops. When conformational detailed balance is satisfied, the turnover rate reduces to the MM functional form, explaining its general validity. For the first time, a one-to-one correspondence is established between non-MM terms and combined cyclic loops with unbalanced conformational currents. Cooperativity resulting from nonequilibrium conformational dynamics can be achieved in enzymatic reactions, and we provide a novel, rigorous means of predicting and characterizing such behavior. Our generalized MM equation affords a systematic approach for exploring cNESS enzyme kinetics.
Role of substrate unbinding in Michaelis-Menten enzymatic reactions.
Reuveni, Shlomi; Urbakh, Michael; Klafter, Joseph
2014-03-25
The Michaelis-Menten equation provides a hundred-year-old prediction by which any increase in the rate of substrate unbinding will decrease the rate of enzymatic turnover. Surprisingly, this prediction was never tested experimentally nor was it scrutinized using modern theoretical tools. Here we show that unbinding may also speed up enzymatic turnover--turning a spotlight to the fact that its actual role in enzymatic catalysis remains to be determined experimentally. Analytically constructing the unbinding phase space, we identify four distinct categories of unbinding: inhibitory, excitatory, superexcitatory, and restorative. A transition in which the effect of unbinding changes from inhibitory to excitatory as substrate concentrations increase, and an overlooked tradeoff between the speed and efficiency of enzymatic reactions, are naturally unveiled as a result. The theory presented herein motivates, and allows the interpretation of, groundbreaking experiments in which existing single-molecule manipulation techniques will be adapted for the purpose of measuring enzymatic turnover under a controlled variation of unbinding rates. As we hereby show, these experiments will not only shed first light on the role of unbinding but will also allow one to determine the time distribution required for the completion of the catalytic step in isolation from the rest of the enzymatic turnover cycle.
Tang, Sanyi; Xiao, Yanni
2007-12-01
The purpose of this article is to provide the analytical solutions of one-compartment models with Michaelis-Menten elimination kinetics for three different inputs (single intravenous dose, multiple-dose bolus injection and constant). All analytical solutions obtained in present paper can be described by the well defined Lambert W function which can be easily implemented in most mathematical softwares such as Matlab and Maple. These results will play an important role in fitting the Michaelis-Menten parameters and in designing a dosing regimen to maintain steady-state plasma concentrations. In particular, the analytical periodic solution for multi-dose inputs is also given, and we note that the maximum and minimum values of the periodic solution depends on the Michaelis-Menten parameters, dose and time interval of drug administration. In practice, it is important to maintain a concentration above the minimum therapeutic level at all times without exceeding the minimum toxic concentration. Therefore, the one-compartment model with therapeutic window is proposed, and further the existence of periodic solution, analytical expression and its period are analyzed. The analytical formula of period plays a key role in designing a dose regimen to maintain the plasma concentration within a specified range over long periods of therapy. Finally, the completely analytical solution for the constant input rate is derived and discussed which depends on the relations between constant input rate and maximum rate of change of concentration.
Alternative Analysis of the Michaelis-Menten Equations
Krogstad, Harald E.; Dawed, Mohammed Yiha; Tegegne, Tadele Tesfa
2011-01-01
Courses in mathematical modelling are always in need of simple, illustrative examples. The Michaelis-Menten reaction kinetics equations have been considered to be a basic example of scaling and singular perturbation. However, the leading order approximations do not easily show the expected behaviour, and this note proposes a different perturbation…
Reexamining Michaelis-Menten Enzyme Kinetics for Xanthine Oxidase
Bassingthwaighte, James B.; Chinn, Tamara M.
2013-01-01
Abbreviated expressions for enzyme kinetic expressions, such as the Michaelis-Menten (M-M) equations, are based on the premise that enzyme concentrations are low compared with those of the substrate and product. When one does progress experiments, where the solute is consumed during conversion to form a series of products, the idealized conditions…
Alternative Analysis of the Michaelis-Menten Equations
Krogstad, Harald E.; Dawed, Mohammed Yiha; Tegegne, Tadele Tesfa
2011-01-01
Courses in mathematical modelling are always in need of simple, illustrative examples. The Michaelis-Menten reaction kinetics equations have been considered to be a basic example of scaling and singular perturbation. However, the leading order approximations do not easily show the expected behaviour, and this note proposes a different perturbation…
Reexamining Michaelis-Menten Enzyme Kinetics for Xanthine Oxidase
Bassingthwaighte, James B.; Chinn, Tamara M.
2013-01-01
Abbreviated expressions for enzyme kinetic expressions, such as the Michaelis-Menten (M-M) equations, are based on the premise that enzyme concentrations are low compared with those of the substrate and product. When one does progress experiments, where the solute is consumed during conversion to form a series of products, the idealized conditions…
Oscillatory enzyme reactions and Michaelis-Menten kinetics.
Goldbeter, Albert
2013-09-02
Oscillations occur in a number of enzymatic systems as a result of feedback regulation. How Michaelis-Menten kinetics influences oscillatory behavior in enzyme systems is investigated in models for oscillations in the activity of phosphofructokinase (PFK) in glycolysis and of cyclin-dependent kinases in the cell cycle. The model for the PFK reaction is based on a product-activated allosteric enzyme reaction coupled to enzymatic degradation of the reaction product. The Michaelian nature of the product decay term markedly influences the period, amplitude and waveform of the oscillations. Likewise, a model for oscillations of Cdc2 kinase in embryonic cell cycles based on Michaelis-Menten phosphorylation-dephosphorylation kinetics shows that the occurrence and amplitude of the oscillations strongly depend on the ultrasensitivity of the enzymatic cascade that controls the activity of the cyclin-dependent kinase. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Michaelis-Menten kinetics under non-isothermal conditions.
Lervik, Anders; Kjelstrup, Signe; Qian, Hong
2015-01-14
We extend the celebrated Michaelis-Menten kinetics description of an enzymatic reaction taking into consideration the presence of a thermal driving force. A coupling of chemical and thermal driving forces is expected from the principle of non-equilibrium thermodynamics, and specifically we obtain an additional term to the classical Michaelis-Menten kinetic equation, which describes the coupling in terms of a single parameter. A companion equation for the heat flux is also derived, which actually can exist even in the absence of a temperature difference. Being thermodynamic in nature, this result is general and independent of the detailed mechanism of the coupling. Conditions for the experimental verification of the new equation are discussed.
Design issues for the Michaelis-Menten model.
López-Fidalgo, J; Wong, Weng Kee
2002-03-07
We discuss design issues for the Michaelis-Menten model and use geometrical arguments to find optimal designs for estimating a subset of the model parameters, or a linear combination of the parameters. We propose multiple-objective optimal designs when the parameters have different levels of interest to the researcher. In addition, we compare six commonly used sequence designs in the biological sciences for estimating parameters and, propose optimal choices for the parameters for geometric designs using closed-form efficiency formulas.
Robust and efficient designs for the Michaelis-Menten model
Dette, Holger; Biedermann, Stefanie
2002-01-01
For the Michaelis-Menten model, we determine designs that maximize the minimum of the D-efficiencies over a certain interval for the nonlinear parameter. The best two point designs can be found explicitly, and a characterization is given when these designs are optimal within the class of all designs. In most cases of practical interest, the determined designs are highly efficient and robust with respect to misspecification of the nonlinear parameter. The results are illustrated and applied in...
Optimal designs for the Michaelis Menten model with correlated observations
Dette, Holger; Kunert, Joachim
2012-01-01
In this paper we investigate the problem of designing experiments for weighted least squares analysis in the Michaelis Menten model. We study the structure of exact D-optimal designs in a model with an autoregressive error structure. Explicit results for locally D-optimal are derived for the case where 2 observations can be taken per subject. Additionally standardized maximin D-optimal designs are obtained in this case. The results illustrate the enormous difficulties to find e...
The Michaelis-Menten-Stueckelberg Theorem
Gorban, Alexander N.; Muhammad Shahzad
2011-01-01
We study chemical reactions with complex mechanisms under two assumptions: (i) intermediates are present in small amounts (this is the quasi-steady-state hypothesis or QSS) and (ii) they are in equilibrium relations with substrates (this is the quasiequilibrium hypothesis or QE). Under these assumptions, we prove the generalized mass action law together with the basic relations between kinetic factors, which are sufficient for the positivity of the entropy production but hold even without mic...
Ochab-Marcinek, Anna
2010-04-21
The study of biochemical pathways usually focuses on a small section of a protein interactions network. Two distinct sources contribute to the noise in such a system: intrinsic noise, inherent in the studied reactions, and extrinsic noise generated in other parts of the network or in the environment. We study the effect of extrinsic noise entering the system through a nonlinear uptake reaction which acts as a nonlinear filter. Varying input noise intensity varies the mean of the noise after the passage through the filter, which changes the stability properties of the system. The steady-state displacement due to small noise is independent on the kinetics of the system but it only depends on the nonlinearity of the input function. For monotonically increasing and concave input functions such as the Michaelis-Menten uptake rate, we give a simple argument based on the small-noise expansion, which enables qualitative predictions of the steady-state displacement only by inspection of experimental data: when weak and rapid noise enters the system through a Michaelis-Menten reaction, then the graph of the system's steady states vs. the mean of the input signal always shifts to the right as noise intensity increases. We test the predictions on two models of lac operon, where TMG/lactose uptake is driven by a Michaelis-Menten enzymatic process. We show that as a consequence of the steady state displacement due to fluctuations in extracellular TMG/lactose concentration the lac switch responds in an asymmetric manner: as noise intensity increases, switching off lactose metabolism becomes easier and switching it on becomes more difficult. (c) 2009 Elsevier Ltd. All rights reserved.
Optimal design for goodness-of-fit of the Michaelis-Menten enzyme kinetic function
Wong, Weng Kee; Melas, Viatcheslav B.; Dette, Holger
2004-01-01
We construct efficient designs for the Michaelis-Menten enzyme kinetic model capable of checking model assumption. An extended model, called EMAX model is also considered for this purpose. This model is widely used in pharmacokinetics and reduces to the Michaelis- Menten model for a specific choice of the parameter setting. Our strategy is to find efficient designs for estimating the parameters in the EMAX model and at the same time test the validity of the Michaelis-Menten model against the ...
Determination of individual cell Michaelis-Menten constants.
Sunray, Merav; Zurgil, Naomi; Shafran, Yana; Deutsch, Mordechai
2002-01-01
A novel methodology for the measurement and analysis of apparent K(M) (Michaelis-Menten constant) and V(MAX) values of individual cells is suggested. It is based on a mathematical model that considers substrate influx into the cell, its intracellular enzymatic hydrolysis, and the product efflux. The mathematical formulation was approximated linearly in order to analyze intracellular substrate conversion characteristics via Michaelis-Menten theory. Utilizing static cytometry, the time dependence of the fluorescence intensity [FI(t)] emitted from prelocalized and defined FDA stained cells was recorded. This required frequent periodical measurements of the same cells, which are sequentially exposed to various fluorogenic substrate concentrations. Model simulations correlated with experimental results. Differences in distributions of individual K(M) and V(MAX) values of cells incubated with and without PHA were evident. Average K(M) and V(MAX) values of PHA-stimulated cells increased by 99% and 540%, respectively. This study may provide a tool for assessing intracellular enzymatic activity in individual intact cells under defined physiologic conditions. This may open new vistas in various areas, giving answers to critical questions arising in the field of cell and developmental biology, immunology, oncology, and pharmacology. Copyright 2001 Wiley-Liss, Inc.
Klinman, Judith P
2014-01-01
The final arbiter of enzyme mechanism is the ability to establish and test a kinetic mechanism. Isotope effects play a major role in expanding the scope and insight derived from the Michaelis-Menten equation. The integration of isotope effects into the formalism of the Michaelis-Menten equation began in the 1970s and has continued until the present. This review discusses a family of eukaryotic copper proteins, including dopamine β-monooxygenase, tyramine β-monooxygenase and peptidylglycine α-amidating enzyme, which are responsible for the synthesis of neuroactive compounds, norepinephrine, octopamine and C-terminally carboxamidated peptides, respectively. The review highlights the results of studies showing how combining kinetic isotope effects with initial rate parameters permits the evaluation of: (a) the order of substrate binding to multisubstrate enzymes; (b) the magnitude of individual rate constants in complex, multistep reactions; (c) the identification of chemical intermediates; and (d) the role of nonclassical (tunnelling) behaviour in C-H activation. © 2013 FEBS.
A comparison of the parameter estimating procedures for the Michaelis-Menten model.
Tseng, S J; Hsu, J P
1990-08-23
The performance of four parameter estimating procedures for the estimation of the adjustable parameters in the Michaelis-Menten model, the maximum initial rate Vmax, and the Michaelis-Menten constant Km, including Lineweaver & Burk transformation (L-B), Eadie & Hofstee transformation (E-H), Eisenthal & Cornish-Bowden transformation (ECB), and Hsu & Tseng random search (H-T) is compared. The analysis of the simulated data reveals the followings: (i) Vmax can be estimated more precisely than Km. (ii) The sum of square errors, from the smallest to the largest, follows the sequence H-T, E-H, ECB, L-B. (iii) Considering the sum of square errors, relative error, and computing time, the overall performance follows the sequence H-T, L-B, E-H, ECB, from the best to the worst. (iv) The performance of E-H and ECB are on the same level. (v) L-B and E-H are appropriate for pricesly measured data. H-T should be adopted for data whose error level are high. (vi) Increasing the number of data points has a positive effect on the performance of H-T, and a negative effect on the performance of L-B, E-H, and ECB.
Putz, Mihai V
2011-04-13
The conceptual and practical issues regarding the reduction of the Haldane-Radić enzymic mechanism, specific for cholinesterase kinetics, to the consecrated or logistically modified Michaelis-Menten kinetics, specific for some mutant enzymes, are here clarified as due to the limited initial substrate concentration, through detailed initial rate and progress curve analysis, even when other classical conditions for such equivalence are not entirely fulfilled.
Mihai V. Putz
2011-04-01
Full Text Available The conceptual and practical issues regarding the reduction of the Haldane-Radić enzymic mechanism, specific for cholinesterase kinetics, to the consecrated or logistically modified Michaelis-Menten kinetics, specific for some mutant enzymes, are here clarified as due to the limited initial substrate concentration, through detailed initial rate and progress curve analysis, even when other classical conditions for such equivalence are not entirely fulfilled.
Ever-fluctuating single enzyme molecules : Michaelis-Menten equation revisited
English, Brian P.; Min, Wei; Oijen, Antoine M. van; Lee, Kang Taek; Luo, Guobin; Sun, Hongye; Cherayil, Binny J.; Kou, S.C.; Xie, X. Sunney
2006-01-01
Enzymes are biological catalysts vital to life processes and have attracted century-long investigation. The classic Michaelis-Menten mechanism provides a highly satisfactory description of catalytic activities for large ensembles of enzyme molecules. Here we tested the Michaelis-Menten equation at
A note on the reverse Michaelis-Menten kinetics
Wang, Gangsheng [ORNL; Post, Wilfred M [ORNL
2013-01-01
We theoretically derive a general equation describing the enzyme kinetics that can be further simplified to the typical Michaelis-Menten (M-M) kinetics and the reverse M-M equation (RM-M) proposed by Schimel and Weintraub (2003). We discuss the conditions under which the RM-M is valid with this theoretical derivation. These conditions are contrary to the assumptions of Schimel and Weintraub (2003) and limit the applicability of the model in field soil environments. Nonetheless, Schimel and Weintraub s RM-M model is useful and has the ability to produce a non-linear response of SOM decomposition to enzyme concentration consistent with observations. Regardless of the theoretical basis, if we assume that the M-M and the RM-M could be equivalent, our sensitivity analysis indicates that enzyme plays a more sensitive role in the M-M kinetics compared with in the RM-M kinetics.
Amyloid-like fibril elongation follows michaelis-menten kinetics.
Milto, Katazyna; Botyriute, Akvile; Smirnovas, Vytautas
2013-01-01
A number of proteins can aggregate into amyloid-like fibrils. It was noted that fibril elongation has similarities to an enzymatic reaction, where monomers or oligomers would play a role of substrate and nuclei/fibrils would play a role of enzyme. The question is how similar these processes really are. We obtained experimental data on insulin amyloid-like fibril elongation at the conditions where other processes which may impact kinetics of fibril formation are minor and fitted it using Michaelis-Menten equation. The correlation of the fit is very good and repeatable. It speaks in favour of enzyme-like model of fibril elongation. In addition, obtained [Formula: see text] and [Formula: see text] values at different conditions may help in better understanding influence of environmental factors on the process of fibril elongation.
Eberwein, Jennifer; Shen, Weijun; Jenerette, G Darrel
2017-05-11
China experiences some of the highest rates of anthropogenic nitrogen deposition globally, with further increases projected. Understanding of soil feedbacks to the combined anthropogenic influences of climate change and nitrogen deposition in these systems is critical to improve predictive abilities for future climate scenarios. Here we used a Michaelis-Menten substrate-based kinetics framework to explore how soil CO2 production (Rsoil) responds to changes in temperature and available soil nitrogen (N) by combining field experiments with laboratory manipulations from sites experiencing elevated rates of anthropogenic N deposition but varying in soil N availabiltiy. The temperature sensitivity of Rsoil was strongly influenced by labile C additions. Furthermore, estimation of the temperature response of the Michaelis-Menten parameters supports the use of substrate-based kinetics in modeling efforts. Results from both field and laboratory experiments demonstrated a general decrease in Rsoil with increasing soil available N that was variably dependent on carbon (C) availability. Both the field and the laboratory measurements demonstrated a consistent decrease in the Michaelis-Menten parameter kM with increasing soil available N, indicating an increase in the efficiency of soil C decomposition with increasing N. Furthermore, these results provide evidence of interactions between N deposition and temperature sensitivity, which could influence C storage under combined anthropogenic global change drivers.
廖飞; 杨晓; 周岐新; 曾昭淳; 左渝萍
2003-01-01
Objective: To investigate the reliability for fast estimation of Michaelis-Menten constant (Km) with calibrated specific activity at only two medium concentrations of substrate by both simulation and experimentation with arylesterase (ArE)as model. Methods: Initial rates were simulated by randomly inserting uniform absolute error, and the experimental initial rates of ArE were determined by measuring the increaser of product absorbance. Calibrated specific activities at two substrate concentrations were obtained by regression analysis, and Km was calculated according to Michaelis-Menten equation. Results: By simulation with calibrated specific activities at two medium substrate concentrations, Km could be calculated according to Michaelis-Menten equation with reasonable precision and accuracy. By experimentation with substrates of 2-naphthyl acetate, phenyl acetate, and p-nitrophenyl acetate, there were no differences between the mean and SD of Km of ArE for either substrate by this linear kinetic method and the Lineweaver-Burk plot. Conclusion: This linear kinetic method was reliable for fast estimation of the Km of some specified enzyme on its substrate of lower solubility or lower sensitivity for quantification by common methods.
Stochastic Total Quasi-Steady-State Approximation for the Michaelis-Menten Scheme
Galstyan, Vahe
2015-01-01
In biochemical systems the Michaelis-Menten (MM) scheme is one of the best-known models of the enzyme- catalyzed kinetics. In the academic literature the MM approximation has been thoroughly studied in the context of differential equation models. At the level of the cell, however, molecular fluctuations have many important consequences, and thus, a stochastic investigation of the MM scheme is often necessary. In their work Barik et al. [Biophysical Journal, 95, 3563-3574, (2008)] presented a stochastic approximation of the MM scheme. They suggested a substitution of the propensity function in the reduced master equation with the total quasi-steady- state approximation (tQSSA) rate. The justification of the substitution, however, was provided for a special case only and did not cover the whole parameter domain of the tQSSA. In this manuscript we present a derivation of the stochastic tQSSA that is valid for the entire tQSSA parameter domain.
Relation between pulmonary clearance and particle burden: a Michaelis-Menten-like kinetic model.
Yu, R. C.; Rappaport, S.M.
1996-01-01
OBJECTIVES: To test the validity of a Michaelis-Menten-like kinetic model of pulmonary clearance of insoluble dusts. METHODS: Data were investigated from studies of pulmonary clearance in F344 rats exposed to antimony trioxide (Sb2O3), photocopy test toner, polyvinyl chloride powder (PVC), and diesel exhaust particles. The Michaelis-Menten-like model was used to develop a relation in which the pulmonary clearance half time was a linear function of lung burden. After combining all data, linear...
Extending the kinetic solution of the classic Michaelis-Menten model of enzyme action
BISPO, Jose Ailton Conceicao; Bonafe, Carlos Francisco Sampaio; SOUZA, Volnei Brito de; SILVA, Joao Batista de Almeida e; CARVALHO, Giovani Brandao Mafra de
2011-01-01
The principal aim of studies of enzyme-mediated reactions has been to provide comparative and quantitative information on enzyme-catalyzed reactions under distinct conditions. The classic Michaelis-Menten model (Biochem Zeit 49:333, 1913) for enzyme kinetic has been widely used to determine important parameters involved in enzyme catalysis, particularly the Michaelis-Menten constant (K (M) ) and the maximum velocity of reaction (V (max) ). Subsequently, a detailed treatment of the mechanisms ...
Evaluation of rate law approximations in bottom-up kinetic models of metabolism
Du, Bin; Zielinski, Daniel C.; Kavvas, Erol S.
2016-01-01
. These approximate rate laws were: 1) a Michaelis-Menten rate law with measured enzyme parameters, 2) a Michaelis-Menten rate law with approximated parameters, using the convenience kinetics convention, 3) a thermodynamic rate law resulting from a metabolite saturation assumption, and 4) a pure chemical reaction......Background: The mechanistic description of enzyme kinetics in a dynamic model of metabolism requires specifying the numerical values of a large number of kinetic parameters. The parameterization challenge is often addressed through the use of simplifying approximations to form reaction rate laws...... with reduced numbers of parameters. Whether such simplified models can reproduce dynamic characteristics of the full system is an important question. Results: In this work, we compared the local transient response properties of dynamic models constructed using rate laws with varying levels of approximation...
Ever-fluctuating single enzyme molecules: Michaelis-Menten equation revisited.
English, Brian P; Min, Wei; van Oijen, Antoine M; Lee, Kang Taek; Luo, Guobin; Sun, Hongye; Cherayil, Binny J; Kou, S C; Xie, X Sunney
2006-02-01
Enzymes are biological catalysts vital to life processes and have attracted century-long investigation. The classic Michaelis-Menten mechanism provides a highly satisfactory description of catalytic activities for large ensembles of enzyme molecules. Here we tested the Michaelis-Menten equation at the single-molecule level. We monitored long time traces of enzymatic turnovers for individual beta-galactosidase molecules by detecting one fluorescent product at a time. A molecular memory phenomenon arises at high substrate concentrations, characterized by clusters of turnover events separated by periods of low activity. Such memory lasts for decades of timescales ranging from milliseconds to seconds owing to the presence of interconverting conformers with broadly distributed lifetimes. We proved that the Michaelis-Menten equation still holds even for a fluctuating single enzyme, but bears a different microscopic interpretation.
Goličnik, Marko
2011-04-15
Various explicit reformulations of time-dependent solutions for the classical two-step irreversible Michaelis-Menten enzyme reaction model have been described recently. In the current study, I present further improvements in terms of a generalized integrated form of the Michaelis-Menten equation for computation of substrate or product concentrations as functions of time for more real-world, enzyme-catalyzed reactions affected by the product. The explicit equations presented here can be considered as a simpler and useful alternative to the exact solution for the generalized integrated Michaelis-Menten equation when fitted to time course data using standard curve-fitting software. Copyright © 2011 Elsevier Inc. All rights reserved.
Stroberg, Wylie; Schnell, Santiago
2016-12-01
The conditions under which the Michaelis-Menten equation accurately captures the steady-state kinetics of a simple enzyme-catalyzed reaction is contrasted with the conditions under which the same equation can be used to estimate parameters, KM and V, from progress curve data. Validity of the underlying assumptions leading to the Michaelis-Menten equation are shown to be necessary, but not sufficient to guarantee accurate estimation of KM and V. Detailed error analysis and numerical "experiments" show the required experimental conditions for the independent estimation of both KM and V from progress curves. A timescale, tQ, measuring the portion of the time course over which the progress curve exhibits substantial curvature provides a novel criterion for accurate estimation of KM and V from a progress curve experiment. It is found that, if the initial substrate concentration is of the same order of magnitude as KM, the estimated values of the KM and V will correspond to their true values calculated from the microscopic rate constants of the corresponding mass-action system, only so long as the initial enzyme concentration is less than KM. Copyright © 2016 Elsevier B.V. All rights reserved.
Moffitt, Jeffrey R; Bustamante, Carlos
2014-01-01
Enzyme-catalyzed reactions are naturally stochastic, and precision measurements of these fluctuations, made possible by single-molecule methods, promise to provide fundamentally new constraints on the possible mechanisms underlying these reactions. We review some aspects of statistical kinetics: a new field with the goal of extracting mechanistic information from statistical measures of fluctuations in chemical reactions. We focus on a widespread and important statistical measure known as the randomness parameter. This parameter is remarkably simple in that it is the squared coefficient of variation of the cycle completion times, although it places significant limits on the minimal complexity of possible enzymatic mechanisms. Recently, a general expression has been introduced for the substrate dependence of the randomness parameter that is for rate fluctuations what the Michaelis-Menten expression is for the mean rate of product generation. We discuss the information provided by the new kinetic parameters introduced by this expression and demonstrate that this expression can simplify the vast majority of published models. © 2013 FEBS.
The original Michaelis constant: translation of the 1913 Michaelis-Menten paper.
Michaelis, Leonor; Menten, Maud Leonora; Johnson, Kenneth A; Goody, Roger S
2011-10-04
Nearly 100 years ago Michaelis and Menten published their now classic paper [Michaelis, L., and Menten, M. L. (1913) Die Kinetik der Invertinwirkung. Biochem. Z. 49, 333-369] in which they showed that the rate of an enzyme-catalyzed reaction is proportional to the concentration of the enzyme-substrate complex predicted by the Michaelis-Menten equation. Because the original text was written in German yet is often quoted by English-speaking authors, we undertook a complete translation of the 1913 publication, which we provide as Supporting Information . Here we introduce the translation, describe the historical context of the work, and show a new analysis of the original data. In doing so, we uncovered several surprises that reveal an interesting glimpse into the early history of enzymology. In particular, our reanalysis of Michaelis and Menten's data using modern computational methods revealed an unanticipated rigor and precision in the original publication and uncovered a sophisticated, comprehensive analysis that has been overlooked in the century since their work was published. Michaelis and Menten not only analyzed initial velocity measurements but also fit their full time course data to the integrated form of the rate equations, including product inhibition, and derived a single global constant to represent all of their data. That constant was not the Michaelis constant, but rather V(max)/K(m), the specificity constant times the enzyme concentration (k(cat)/K(m) × E(0)).
Kosmidis, Kosmas; Karalis, Vangelis; Argyrakis, Panos; Macheras, Panos
2004-09-01
Two different approaches were used to study the kinetics of the enzymatic reaction under heterogeneous conditions to interpret the unusual nonlinear pharmacokinetics of mibefradil. Firstly, a detailed model based on the kinetic differential equations is proposed to study the enzymatic reaction under spatial constraints and in vivo conditions. Secondly, Monte Carlo simulations of the enzyme reaction in a two-dimensional square lattice, placing special emphasis on the input and output of the substrate were applied to mimic in vivo conditions. Both the mathematical model and the Monte Carlo simulations for the enzymatic reaction reproduced the classical Michaelis-Menten (MM) kinetics in homogeneous media and unusual kinetics in fractal media. Based on these findings, a time-dependent version of the classic MM equation was developed for the rate of change of the substrate concentration in disordered media and was successfully used to describe the experimental plasma concentration-time data of mibefradil and derive estimates for the model parameters. The unusual nonlinear pharmacokinetics of mibefradil originates from the heterogeneous conditions in the reaction space of the enzymatic reaction. The modified MM equation can describe the pharmacokinetics of mibefradil as it is able to capture the heterogeneity of the enzymatic reaction in disordered media.
Lee, Hye Jin; Wark, Alastair W; Goodrich, Terry T; Fang, Shiping; Corn, Robert M
2005-04-26
Real-time surface plasmon resonance (SPR) imaging measurements of surface enzymatic reactions on DNA microarrays are analyzed using a kinetics model that couples the contributions of both enzyme adsorption and surface enzyme reaction kinetics. For the case of a 1:1 binding of an enzyme molecule (E) to a surface-immobilized substrate (S), the overall enzymatic reaction can be described in terms of classical Langmuir adsorption and Michaelis-Menten concepts and three rate constants: enzyme adsorption (k(a)), enzyme desorption (k(d)) and enzyme catalysis (k(cat)). In contrast to solution enzyme kinetics, the amount of enzyme in solution is in excess as compared to the amount of substrate on the surface. Moreover, the surface concentration of the intermediary enzyme-substrate complex (ES) is not constant with time, but goes to zero as the reaction is completed. However, kinetic simulations show that the fractional surface coverage of ES on the remaining unreacted sites does reach a steady-state value throughout the course of the surface reaction. This steady-state value approaches the Langmuir equilibrium value for cases where k(a)[E] > k(cat). Experiments using the 3' --> 5' exodeoxyribonuclease activity of Exonuclease III on double-stranded DNA microarrays as a function of temperature and enzyme concentration are used to demonstrate how this model can be applied to quantitatively analyze the SPR imaging data.
Choi, I Y; Lee, S P; Kim, S G; Gruetter, R
2001-06-01
Glucose is the major substrate that sustains normal brain function. When the brain glucose concentration approaches zero, glucose transport across the blood-brain barrier becomes rate limiting for metabolism during, for example, increased metabolic activity and hypoglycemia. Steady-state brain glucose concentrations in alpha-chloralose anesthetized rats were measured noninvasively as a function of plasma glucose. The relation between brain and plasma glucose was linear at 4.5 to 30 mmol/L plasma glucose, which is consistent with the reversible Michaelis-Menten model. When the model was fitted to the brain glucose measurements, the apparent Michaelis-Menten constant, Kt, was 3.3 +/- 1.0 mmol/L, and the ratio of the maximal transport rate relative to CMRglc, Tmax/CMRglc, was 2.7 +/- 0.1. This Kt is comparable to the authors' previous human data, suggesting that glucose transport kinetics in humans and rats are similar. Cerebral blood flow (CBF) was simultaneously assessed and constant above 2 mmol/L plasma glucose at 73 +/- 6 mL 100 g(-1) min(-1). Extrapolation of the reversible Michaelis-Menten model to hypoglycemia correctly predicted the plasma glucose concentration (2.1 +/- 0.6 mmol/L) at which brain glucose concentrations approached zero. At this point, CBF increased sharply by 57% +/- 22%, suggesting that brain glucose concentration is the signal that triggers defense mechanisms aimed at improving glucose delivery to the brain during hypoglycemia.
Reduction for Michaelis-Menten-Henri kinetics in the presence of diffusion.
Kalachev, L.V.; Kaper, H.G.; Kaper, T.J.; Popovic, N.; Zagaris, A.
2007-01-01
Abstract: The Michaelis-Menten-Henri (MMH) mechanism is one of the paradigm reaction mechanisms in biology and chemistry. In its simplest form, it involves a substrate that reacts (reversibly) with an enzyme, forming a complex which is transformed (irreversibly) into a product and the enzyme. Given
A generalized Michaelis-Menten type equation for the analysis of growth
Lopez, S.; France, J.; Gerrits, W.J.J.; Dhanoa, M.S.; Humphries, D.J.; Dijkstra, J.
2000-01-01
The functional form W = (W0Kc Wf t(c)) /(Kc t(c)), where W is body size at age t, W0 and Wf are the zero- and infinite-time values of W, respectively, and K and c are constants, is derived. This new generalized Michaelis-Menten-type equation provides a flexible model for animal growth capable of
Reduction for Michaelis-Menten-Henri kinetics in the presence of diffusion
A. Zagaris (Antonios); L.V. Kalachev; H.G. Kaper; T.J. Kaper (Tasso Joost); N. Popovic
2007-01-01
textabstractThe Michaelis-Menten-Henri (MMH) mechanism is one of the paradigm reaction mechanisms in biology and chemistry. In its simplest form, it involves a substrate that reacts (reversibly) with an enzyme, forming a complex which is transformed (irreversibly) into a product and the enzyme.
A Simple Classroom Teaching Technique to Help Students Understand Michaelis-Menten Kinetics
Runge, Steven W.; Hill, Brent J. F.; Moran, William M.
2006-01-01
A new, simple classroom technique helps cell biology students understand principles of Michaelis-Menten enzyme kinetics. A student mimics the enzyme and the student's hand represents the enzyme's active site. The catalytic event is the transfer of marbles (substrate molecules) by hand from one plastic container to another. As predicted, increases…
Filobello-Nino, Uriel; Vazquez-Leal, Hector; Benhammouda, Brahim; Hernandez-Martinez, Luis; Khan, Yasir; Jimenez-Fernandez, Victor Manuel; Herrera-May, Agustin Leobardo; Castaneda-Sheissa, Roberto; Pereyra-Diaz, Domitilo; Cervantes-Perez, Juan; Agustin Perez-Sesma, Jose Antonio; Hernandez-Machuca, Sergio Francisco; Cuellar-Hernandez, Leticia
2014-01-01
In this article, Perturbation Method (PM) is employed to obtain a handy approximate solution to the steady state nonlinear reaction diffusion equation containing a nonlinear term related to Michaelis-Menten of the enzymatic reaction. Comparing graphics between the approximate and exact solutions, it will be shown that the PM method is quite efficient.
A two-substrate Michaelis-Menten model for the growth of self-replicating polymers.
Ferreira, R
1987-10-07
A two-substrate Michaelis-Menten model is proposed for the growth of autocatalytic self-replicating polymers. Selective growth depends on the existence of two complementary pairs of monomers. Discrimination among sequences results from different products of binding constants, KCGnKAUm. The results support an earlier renormalization group treatment (Ferreira & Tsallis, 1985).
Filobello-Nino, Uriel; Vazquez-Leal, Hector; Benhammouda, Brahim; Hernandez-Martinez, Luis; Khan, Yasir; Jimenez-Fernandez, Victor Manuel; Herrera-May, Agustin Leobardo; Castaneda-Sheissa, Roberto; Pereyra-Diaz, Domitilo; Cervantes-Perez, Juan; Agustin Perez-Sesma, Jose Antonio; Hernandez-Machuca, Sergio Francisco; Cuellar-Hernandez, Leticia
2014-01-01
In this article, Perturbation Method (PM) is employed to obtain a handy approximate solution to the steady state nonlinear reaction diffusion equation containing a nonlinear term related to Michaelis-Menten of the enzymatic reaction. Comparing graphics between the approximate and exact solutions, it will be shown that the PM method is quite efficient.
A Simple Classroom Teaching Technique to Help Students Understand Michaelis-Menten Kinetics
Runge, Steven W.; Hill, Brent J. F.; Moran, William M.
2006-01-01
A new, simple classroom technique helps cell biology students understand principles of Michaelis-Menten enzyme kinetics. A student mimics the enzyme and the student's hand represents the enzyme's active site. The catalytic event is the transfer of marbles (substrate molecules) by hand from one plastic container to another. As predicted, increases…
Houston, J B; Kenworthy, K E
2000-03-01
Strategies for the prediction of in vivo drug clearance from in vitro drug metabolite kinetic data are well established for the rat. In this animal species, metabolism rate-substrate concentration relationships can commonly be described by the classic hyperbola consistent with the Michaelis-Menten model and simple scaling of the parameter intrinsic clearance (CL(int) - the ratio of V(max) to K(m)) is particularly valuable. The in vitro scaling of kinetic data from human tissue is more complex, particularly as many substrates for cytochrome P450 (CYP) 3A4, the dominant human CYP, show nonhyperbolic metabolism rate-substrate concentration curves. This review critically examines these types of data, which require the adoption of an enzyme model with multiple sites showing cooperative binding for the drug substrate, and considers the constraints this kinetic behavior places on the prediction of in vivo pharmacokinetic characteristics, such as metabolic stability and inhibitory drug interaction potential. The cases of autoactivation and autoinhibition are discussed; the former results in an initial lag in the rate-substrate concentration profile to generate a sigmoidal curve whereas the latter is characterized by a convex curve as V(max) is not maintained at high substrate concentrations. When positive cooperativity occurs, we suggest the use of CL(max), the maximal clearance resulting from autoactivation, as a substitute for CL(int). The impact of heteroactivation on this approach is also of importance. In the case of negative cooperativity, care in using the V(max)/K(m) approach to CL(int) determination must be taken. Examples of substrates displaying each type of kinetic behavior are discussed for various recombinant CYP enzymes, and possible artifactual sources of atypical rate-concentration curves are outlined. Finally, the consequences of ignoring atypical Michaelis-Menten kinetic relationships are examined, and the inconsistencies reported for both different
Yan, Xiaoyu; Krzyzanski, Wojciech
2012-04-01
The Michaelis-Menten (M-M) approximation of the target-mediated drug disposition (TMDD) pharmacokinetic (PK) model was derived based on the rapid binding (RB) or quasi steady-state (QSS) assumptions that implied that the target and drug binding and dissociation were in equilibrium. However, the initial dose for an IV bolus injection for the M-M model did not account for a fraction bound to the target. We postulated a correction to an initial condition that was consistent with the assumptions underlying the M-M approximation. We determined that the difference between the injected dose and one that should be used for the initial condition is equal to the amount of drug bound to the target upon reaching the equilibrium. We also observed that the corrected initial condition made the internalization rate constant an identifiable parameter that was not for the original M-M model. Finally, we performed a simulation exercise to check if the correction will impact the model performance and the bias of the M-M parameter estimates. We used literature data to simulate plasma drug concentrations described by the RB/QSS TMDD model. The simulated data were refitted by both models. All the parameters estimated from the original M-M model were substantially biased. On the other hand, the corrected M-M is able to accurately estimate these parameters except for equilibrium constant K(m). Weighted sum of square residual and Akaike information criterion suggested a better performance of the corrected M-M model compared with the original M-M model. Further studies are necessary to determine the importance of this correction for the M-M model applications to analysis of TMDD driven PK data.
A Squared Michaelis-Menten Function of Substrate Concentration for Plant Mitochondrial Respiration 1
James, Alan T.; Wiskich, Joseph T.; Dry, Ian B.
1990-01-01
Dry and Wiskich ([1987] Arch Biochem Biophys 257: 92-99) have published data showing the response of plant mitochondrial respiration to increasing additions of oxaloacetate or malate when these substrates have been depleted by inhibition of succinate dehydrogenase by malonate, and coenzyme A (CoA) has been sequestered as acetyl-CoA by pyruvate dehydrogenase. In the presence of 2-oxoglutarate, it is shown that the response is given by a Michaelis-Menten curve, but in its absence, when malate has to supply substrate for dehydrogenation as well as to liberate CoA via malate dehydrogenase and citrate synthase, the response is presumably the product of two Michaelis-Menten functions, which can be approximated by the square of a single function. PMID:16667257
Wenzhen Gan
2013-01-01
Full Text Available This paper is concerned with the asymptotical behavior of solutions to the reaction-diffusion system under homogeneous Neumann boundary condition. By taking food ingestion and species' moving into account, the model is further coupled with Michaelis-Menten type functional response and nonlocal delay. Sufficient conditions are derived for the global stability of the positive steady state and the semitrivial steady state of the proposed problem by using the Lyapunov functional. Our results show that intraspecific competition benefits the coexistence of prey and predator. Furthermore, the introduction of Michaelis-Menten type functional response positively affects the coexistence of prey and predator, and the nonlocal delay is harmless for stabilities of all nonnegative steady states of the system. Numerical simulations are carried out to illustrate the main results.
Carvalho,Nakédia M. F.; Pires, Bianca M.; Antunes,Octavio A. C.; Roberto B Faria; Osório,Renata E. H. M. B.; Clovis Piovezan; Ademir Neves
2010-01-01
The Michaelis-Menten equation is used in many biochemical and bioinorganic kinetic studies involving homogeneous catalysis. Otherwise, it is known that determination of Michaelis-Menten parameters K M, Vmax, and k cat by the well-known Lineweaver-Burk double reciprocal linear equation does not produce the best values for these parameters. In this paper we present a discussion on different linear equations which can be used to calculate these parameters and we compare their results with the va...
Global stability of enzymatic chains of full reversible Michaelis-Menten reactions.
Belgacem, Ismail; Gouzé, Jean-Luc
2013-09-01
We consider a chain of metabolic reactions catalyzed by enzymes, of reversible Michaelis-Menten type with full dynamics, i.e. not reduced with any quasi-steady state approximations. We study the corresponding dynamical system and show its global stability if the equilibrium exists. If the system is open, the equilibrium may not exist. The main tool is monotone systems theory. Finally we study the implications of these results for the study of coupled genetic-metabolic systems.
Robustness of optimal designs for the Michaelis-Menten model under a variation of criteria
Dette, Holger; Kiss, Christine; Wong, Weng Kee
2009-01-01
The Michaelis-Menten model has and continues to be one of the most widely used models in many diverse fields. In the biomedical sciences, the model continues to be ubiquitous in biochemistry, enzyme kinetics studies, nutrition science and in the pharmaceutical sciences. Despite its wide ranging applications across disciplines, design issues for this model are given short shrift. This paper focuses on design issues and provides a variety of optimal designs of this model. In addition, we ...
Wenzhen Gan; Canrong Tian; Qunying Zhang; Zhigui Lin
2013-01-01
This paper is concerned with the asymptotical behavior of solutions to the reaction-diffusion system under homogeneous Neumann boundary condition. By taking food ingestion and species' moving into account, the model is further coupled with Michaelis-Menten type functional response and nonlocal delay. Sufficient conditions are derived for the global stability of the positive steady state and the semitrivial steady state of the proposed problem by using the Lyapunov functional. Our results show...
Optimal Designs for Discriminating Between some Extensions of the Michaelis-Menten Model
Jesus Lopez Fidalgo; Chiara Tommasi; Camelia Trandafir
2005-01-01
In this paper some results on the problem of computing optimal designs for discriminating between rival models are provided. Using T-optimality for two rival models a compound criterion is developed to discriminate between more than two models. Surprising results arise when T-optimal designs are compared with classical c-optimal designs for nonlinear models. In particular, some practical deviations of the Michaelis-Menten model are considered in order to measure and compare efficiencies of di...
Solution of the Michaelis-Menten equation using the decomposition method.
Sonnad, Jagadeesh R; Goudar, Chetan T
2009-01-01
We present a low-order recursive solution to the Michaelis-Menten equation using the decomposition method. This solution is algebraic in nature and provides a simpler alternative to numerical approaches such as differential equation evaluation and root-solving techniques that are currently used to compute substrate concentration in the Michaelis-Menten equation. A detailed characterization of the errors in substrate concentrations computed from decomposition, Runge-Kutta, and bisection methods over a wide range of s(0) : K(m) values was made by comparing them with highly accurate solutions obtained using the Lambert W function. Our results indicated that solutions obtained from the decomposition method were usually more accurate than those from the corresponding classical Runge-Kutta methods. Moreover, these solutions required significantly fewer computations than the root-solving method. Specifically, when the stepsize was 0.1% of the total time interval, the computed substrate concentrations using the decomposition method were characterized by accuracies on the order of 10(-8) or better. The algebraic nature of the decomposition solution and its relatively high accuracy make this approach an attractive candidate for computing substrate concentration in the Michaelis-Menten equation.
Widmer, L A; Stelling, J; Doyle, F J
2013-10-28
Using the (slow-scale) linear noise approximation, we give parameter-independent bounds to the substrate and product intrinsic noise variance for the stochastic Michaelis-Menten approximation at steady state.
无
2012-01-01
In this paper,the existence of eight periodic solutions to a Michaelis-Menten-type predator-prey system with delay and harvesting in patch environment is established using the analytical techniques and Mawhin's coincidence degree theory.
Biphasic character of ribosomal translocation and non-Michaelis-Menten kinetics of translation.
Xie, Ping
2014-12-01
We study theoretically the kinetics of mRNA translocation in the wild-type (WT) Escherichia coli ribosome, which is composed of a small 30S and large 50S subunit, and the ribosomes with mutations to some intersubunit bridges such as B1a, B4, B7a, and B8. The theoretical results reproduce well the available in vitro experimental data on the biphasic kinetics of the forward mRNA translocation catalyzed by elongation factor G (EF-G) hydrolyzing GTP, which can be best fit by the sum of two exponentials, and the monophasic kinetics of the spontaneous reverse mRNA translocation in the absence of the elongation factor, which can be best fit by a single-exponential function, in both the WT and mutant ribosomes. We show that both the mutation-induced increase in the maximal rate of the slow phase for the forward mRNA translocation and that in the rate of the spontaneous reverse mRNA translocation result from a reduction in the intrinsic energy barrier to resist the rotational movements between the two subunits, giving the same degree of increase in the two rates. The mutation-induced increase in the maximal rate of the fast phase for the forward mRNA translocation results mainly from the increase in the rate of the ribosomal unlocking, a conformational change in the ribosome that widens the mRNA channel for the mRNA translocation to take place, which could be partly due to the effect of the mutation on the intrasubunit 30S head rotation. Moreover, we study the translation rate of the WT and mutant ribosomes. It is shown that the translation rate versus the concentration of EF-G-GTP does not follow the Michaelis-Menten (MM) kinetics, which is in sharp contrast to the general property of other enzymes that the rate of the enzymatic reaction versus the concentration of a substrate follows the MM kinetics. The physical origin of this non-MM kinetics for the ribosome is revealed.
Mafrica, Stefano; Godiot, Stéphanie; Menouni, Mohsine; Boyron, Marc; Expert, Fabien; Juston, Raphaël; Marchand, Nicolas; Ruffier, Franck; Viollet, Stéphane
2015-03-09
In this paper, we present: (i) a novel analog silicon retina featuring auto-adaptive pixels that obey the Michaelis-Menten law, i.e. V=V(m) I(n)/I(n)+σ(n); (ii) a method of characterizing silicon retinas, which makes it possible to accurately assess the pixels' response to transient luminous changes in a ±3-decade range, as well as changes in the initial steady-state intensity in a 7-decade range. The novel pixel, called M(2)APix, which stands for Michaelis-Menten Auto-Adaptive Pixel, can auto-adapt in a 7-decade range and responds appropriately to step changes up to ±3 decades in size without causing any saturation of the Very Large Scale Integration (VLSI) transistors. Thanks to the intrinsic properties of the Michaelis-Menten equation, the pixel output always remains within a constant limited voltage range. The range of the Analog to Digital Converter (ADC) was therefore adjusted so as to obtain a Least Significant Bit (LSB) voltage of 2.35mV and an effective resolution of about 9 bits. The results presented here show that the M(2)APix produced a quasi-linear contrast response once it had adapted to the average luminosity. Differently to what occurs in its biological counterparts, neither the sensitivity to changes in light nor the contrast response of the M(2)APix depend on the mean luminosity (i.e. the ambient lighting conditions). Lastly, a full comparison between the M(2)APix and the Delbrück auto-adaptive pixel is provided.
Single-molecule enzymology à la Michaelis-Menten.
Grima, Ramon; Walter, Nils G; Schnell, Santiago
2014-01-01
Over the past 100 years, deterministic rate equations have been successfully used to infer enzyme-catalysed reaction mechanisms and to estimate rate constants from reaction kinetics experiments conducted in vitro. In recent years, sophisticated experimental techniques have been developed that begin to allow the measurement of enzyme-catalysed and other biopolymer-mediated reactions inside single cells at the single-molecule level. Time-course data obtained using these methods are considerably noisy because molecule numbers within cells are typically quite small. As a consequence, the interpretation and analysis of single-cell data requires stochastic methods, rather than deterministic rate equations. Here, we concisely review both experimental and theoretical techniques that enable single-molecule analysis, with particular emphasis on the major developments in the field of theoretical stochastic enzyme kinetics, from its inception in the mid-20th century to its modern-day status. We discuss the differences between stochastic and deterministic rate equation models, how these depend on enzyme molecule numbers and substrate inflow into the reaction compartment, and how estimation of rate constants from single-cell data is possible using recently developed stochastic approaches. © 2013 FEBS.
Selection between Michaelis-Menten and target-mediated drug disposition pharmacokinetic models.
Yan, Xiaoyu; Mager, Donald E; Krzyzanski, Wojciech
2010-02-01
Target-mediated drug disposition (TMDD) models have been applied to describe the pharmacokinetics of drugs whose distribution and/or clearance are affected by its target due to high binding affinity and limited capacity. The Michaelis-Menten (M-M) model has also been frequently used to describe the pharmacokinetics of such drugs. The purpose of this study is to investigate conditions for equivalence between M-M and TMDD pharmacokinetic models and provide guidelines for selection between these two approaches. Theoretical derivations were used to determine conditions under which M-M and TMDD pharmacokinetic models are equivalent. Computer simulations and model fitting were conducted to demonstrate these conditions. Typical M-M and TMDD profiles were simulated based on literature data for an anti-CD4 monoclonal antibody (TRX1) and phenytoin administered intravenously. Both models were fitted to data and goodness of fit criteria were evaluated for model selection. A case study of recombinant human erythropoietin was conducted to qualify results. A rapid binding TMDD model is equivalent to the M-M model if total target density R ( tot ) is constant, and R ( tot ) K ( D ) /(K ( D ) + C) ( 2 ) < 1 where K ( D ) represents the dissociation constant and C is the free drug concentration. Under these conditions, M-M parameters are defined as: V ( max ) = k ( int ) R ( tot ) V ( c ) and K ( m ) = K ( D ) where k ( int ) represents an internalization rate constant, and V ( c ) is the volume of the central compartment. R ( tot ) is constant if and only if k ( int ) = k ( deg,) where k ( deg ) is a degradation rate constant. If the TMDD model predictions are not sensitive to k ( int ) or k ( deg ) parameters, the condition of R ( tot ) K ( D ) /(K ( D ) + C) ( 2 ) < 1 alone can preserve the equivalence between rapid binding TMDD and M-M models. The model selection process for drugs that exhibit TMDD should involve a full mechanistic model as well as reduced models. The best model
Differences in Michaelis-Menten kinetics for different cultivars of maize during cyanide removal.
Yu, Xiao-Zhang; Gu, Ji-Dong
2007-06-01
Knowledge of the kinetic parameters, the half-saturation constant (K(m)) and the maximum metabolic capacity (v(max)), is very useful for the characterization of enzymes and biochemical processes. Little is known about rates of which vegetation metabolizes environmental chemicals. It is known, however, that vascular plants possess an enzyme system that detoxifies cyanide by converting it into the amino acid asparagine. This study investigated the differences in Michaelis-Menten kinetics of cyanide removal by different cultivars of maize. Detached leaves (1.0 g fresh weight) of seven different cultivars of maize (Zea mays L.) were kept in glass vessels with 100mL of aqueous solution spiked with potassium cyanide at 25+/-0.5 degrees C for 28 h. Four treatment concentrations of cyanide were used, ranging from 0.43 to 7.67 mgCNL(-1). The disappearance of cyanide from the aqueous solution was analyzed spectrophotometrically. Realistic values of K(m) and v(max) were estimated by a computer program using non-linear regression treatment. Lineweaver-Burk plots were also used to estimate the kinetic parameters for comparison. Using non-linear regression treatments, values of v(max) and K(m) were found to be between 10.80 and 22.80 mgCNkg(-1)h(-1), and 2.57 and 7.09 mgCNL(-1), respectively. The highest v(max) was achieved by the cultivars HengFen 1, followed by NongDa 108. The lowest v(max) was demonstrated by JingKe 8. The highest K(m) was found in NongDa 108, followed by HengFen 1. The lowest K(m) was associated with JingKe 8. Results from this study indicated that significant removal of cyanide from an aqueous solution was observed in the presence of plant materials without apparent phytotoxicity, even at the high concentration of cyanide used in this study. All maize cultivars used in this study were able to metabolize cyanide efficiently, although with different metabolic capacities. Results also showed a small variation of metabolic rates between the different cultivars
Bentz, Joe; Tran, Thuy Thanh; Polli, Joseph W; Ayrton, Andrew; Ellens, Harma
2005-10-01
Typically, the kinetics of membrane transport is analyzed using the steady-state Michaelis-Menten (or Eadie-Hofstee or Hanes) equations. This approach has been successful when the substrate is picked up from the aqueous phase, like a water-soluble enzyme, for which the Michaelis-Menten steady-state analysis was developed. For membrane transporters whose substrate resides in the lipid bilayer of the plasma membrane, like P-glycoprotein (P-gp), there has been no validation of the accuracy of the steady-state analysis because the elementary rate constants for transport were not known. Recently, we fitted the mass action elementary kinetic rate constants of P-gp transport of three different drugs through a confluent monolayer of MDCKII-hMDR1 cells. With these elementary rate constants in hand, we use computer simulations to assess the accuracy of the steady-state Michaelis-Menten parameters. This limits the simulation to parameter ranges known to be physiologically relevant. Using over 2,300 different vectors of initial elementary parameters spanning the space bounded by the three drugs, which defines 2,300 "virtual substrates", the concentrations of substrate transported were calculated and fitted to Eadie-Hofstee plots. Acceptable plots were obtained for 1,338 cases. The fitted steady-state Vmax values from the analysis correlated to within a factor of 2-3 with the values predicted from the elementary parameters. However, the fitted Km value could be generated by a wide range of underlying "molecular" Km values. This is because of the convolution of the drug passive permeability kinetics into the fitted Km. This implies that Km values measured in simpler systems, e.g., microsomes or proteoliposomes, even if accurate, would not predict the Km values for the confluent monolayer system or, by logical extension, in vivo. Reliable in vitro-in vivo extrapolation seems to require using the elementary rate constants rather than the Michaelis-Menten steady-state parameters.
Goličnik, Marko
2011-09-01
The exact closed-form solutions to the integrated rate equations for one-compartment pharmacokinetic models that obey Michaelis-Menten elimination kinetics were derived recently (Tang and Xiao in J Pharmacokin Pharmacodyn 34:807-827, 2007). These solutions are expressed in terms of the Lambert W(x)-omega function; however, unfortunately, most of the available computer programs are not set up to handle equations that involve the W(x) function. Therefore, in this article, I provide alternative explicit analytical equations expressed in terms of elementary mathematical functions that accurately approximate exact solutions and can be simply calculated using any optional standard software.
Michaelis-Menten speeds up tau-leaping under a wide range of conditions.
Wu, Sheng; Fu, Jin; Cao, Yang; Petzold, Linda
2011-04-07
This paper examines the benefits of Michaelis-Menten model reduction techniques in stochastic tau-leaping simulations. Results show that although the conditions for the validity of the reductions for tau-leaping remain the same as those for the stochastic simulation algorithm (SSA), the reductions result in a substantial speed-up for tau-leaping under a different range of conditions than they do for SSA. The reason of this discrepancy is that the time steps for SSA and for tau-leaping are determined by different properties of system dynamics.
Michaelis-Menten speeds up tau-leaping under a wide range of conditions
Wu, Sheng; Fu, Jin; Cao, Yang; Petzold, Linda
2011-04-01
This paper examines the benefits of Michaelis-Menten model reduction techniques in stochastic tau-leaping simulations. Results show that although the conditions for the validity of the reductions for tau-leaping remain the same as those for the stochastic simulation algorithm (SSA), the reductions result in a substantial speed-up for tau-leaping under a different range of conditions than they do for SSA. The reason of this discrepancy is that the time steps for SSA and for tau-leaping are determined by different properties of system dynamics.
Standardization of α-L-iduronidase enzyme assay with Michaelis-Menten kinetics.
Ou, Li; Herzog, Tyler L; Wilmot, Carrie M; Whitley, Chester B
2014-02-01
The lack of methodological uniformity in enzyme assays has been a long-standing difficulty, a problem for bench researchers, for the interpretation of clinical diagnostic tests, and an issue for investigational drug review. Illustrative of the problem, α-L-iduronidase enzyme catalytic activity is frequently measured with the substrate 4-methylumbelliferyl-α-L-iduronide (4MU-iduronide); however, final substrate concentrations used in different assays vary greatly, ranging from 25 μM to 1425 μM (Km ≈ 180 μM) making it difficult to compare results between laboratories. In this study, α-L-iduronidase was assayed with 15 different substrate concentrations. The resulting activity levels from the same specimens varied greatly with different substrate concentrations but, as a group, obeyed the expectations of Michaelis-Menten kinetics. Therefore, for the sake of improved comparability, it is proposed that α-L-iduronidase enzyme assays should be conducted either (1) under substrate saturating conditions; or (2) when concentrations are significantly below substrate saturation, with results standardized by arithmetic adjustment that considers Michaelis-Menten kinetics. The approach can be generalized to many other enzyme assays. Copyright © 2013 Elsevier Inc. All rights reserved.
Nakédia M. F. Carvalho
2010-01-01
Full Text Available The Michaelis-Menten equation is used in many biochemical and bioinorganic kinetic studies involving homogeneous catalysis. Otherwise, it is known that determination of Michaelis-Menten parameters K M, Vmax, and k cat by the well-known Lineweaver-Burk double reciprocal linear equation does not produce the best values for these parameters. In this paper we present a discussion on different linear equations which can be used to calculate these parameters and we compare their results with the values obtained by the more reliable nonlinear least-square fit.
Dutta, Annwesha; Chowdhury, Debashish
2017-05-01
The sequence of amino acid monomers in the primary structure of a protein is decided by the corresponding sequence of codons (triplets of nucleic acid monomers) on the template messenger RNA (mRNA). The polymerization of a protein, by incorporation of the successive amino acid monomers, is carried out by a molecular machine called ribosome. We develop a stochastic kinetic model that captures the possibilities of mis-reading of mRNA codon and prior mis-charging of a tRNA. By a combination of analytical and numerical methods, we obtain the distribution of the times taken for incorporation of the successive amino acids in the growing protein in this mathematical model. The corresponding exact analytical expression for the average rate of elongation of a nascent protein is a 'biologically motivated' generalization of the Michaelis-Menten formula for the average rate of enzymatic reactions. This generalized Michaelis-Menten-like formula (and the exact analytical expressions for a few other quantities) that we report here display the interplay of four different branched pathways corresponding to selection of four different types of tRNA.
Extended Parker-Sochacki method for Michaelis-Menten enzymatic reaction model.
Abdelrazik, Ismail M; Elkaranshawy, Hesham A
2016-03-01
In this article, a new approach--namely, the extended Parker-Sochacki method (EPSM)--is presented for solving the Michaelis-Menten nonlinear enzymatic reaction model. The Parker-Sochacki method (PSM) is combined with a new resummation method called the Sumudu-Padé resummation method to obtain approximate analytical solutions for the model. The obtained solutions by the proposed approach are compared with the solutions of PSM and the Runge-Kutta numerical method (RKM). The comparison proves the practicality, efficiency, and correctness of the presented approach. It serves as a basis for solving other nonlinear biochemical reaction models in the future. Copyright © 2015 Elsevier Inc. All rights reserved.
Explicit reformulations of time-dependent solution for a Michaelis-Menten enzyme reaction model.
Golicnik, Marko
2010-11-01
The exact closed-form solution to the Michaelis-Menten equation is expressed in terms of the Lambert W(x) function. However, the utility of this solution is limited because the W(x) function is not widely available in curve-fitting software. Based on various approximations to the W(x) function, different explicit equations expressed in terms of the elementary functions are proposed here as useful shortcuts to fit time depletion of substrate concentration directly to progress curves using commonly available nonlinear regression computer programs. The results are compared with those obtained by fitting other algebraic equations that have been proposed previously in the literature. 2010 Elsevier Inc. All rights reserved.
Michaelis-Menten kinetics, the operator-repressor system, and least squares approaches.
Hadeler, Karl Peter
2013-01-01
The Michaelis-Menten (MM) function is a fractional linear function depending on two positive parameters. These can be estimated by nonlinear or linear least squares methods. The non-linear methods, based directly on the defect of the MM function, can fail and not produce any minimizer. The linear methods always produce a unique minimizer which, however, may not be positive. Here we give sufficient conditions on the data such that the nonlinear problem has at least one positive minimizer and also conditions for the minimizer of the linear problem to be positive. We discuss in detail the models and equilibrium relations of a classical operator-repressor system, and we extend our approach to the MM problem with leakage and to reversible MM kinetics. The arrangement of the sufficient conditions exhibits the important role of data that have a concavity property (chemically feasible data).
Analysis of noise-induced bistability in Michaelis Menten single-step enzymatic cycle
Remondini, Daniel; Bazzani, Armando; Castellani, Gastone; Maritan, Amos
2011-01-01
In this paper we study noise-induced bistability in a specific circuit with many biological implications, namely a single-step enzymatic cycle described by Michaelis Menten equations with quasi-steady state assumption. We study the system both with a Master Equation formalism, and with the Fokker-Planck continuous approximation, characterizing the conditions in which the continuous approach is a good approximation of the exact discrete model. An analysis of the stationary distribution in both cases shows that bimodality can not occur in such a system. We discuss which additional requirements can generate stochastic bimodality, by coupling the system with a chemical reaction involving enzyme production and turnover. This extended system shows a bistable behaviour only in specific parameter windows depending on the number of molecules involved, providing hints about which should be a feasible system size in order that such a phenomenon could be exploited in real biological systems.
Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed reactions.
Atkins, William M
2005-01-01
The cytochrome P450 monooxygenases (CYPs) are the dominant enzyme system responsible for xenobiotic detoxification and drug metabolism. Several CYP isoforms exhibit non-Michaelis-Menten, or "atypical," steady state kinetic patterns. The allosteric kinetics confound prediction of drug metabolism and drug-drug interactions, and they challenge the theoretical paradigms of allosterism. Both homotropic and heterotropic ligand effects are now widely documented. It is becoming apparent that multiple ligands can simultaneously bind within the active sites of individual CYPs, and the kinetic parameters change with ligand occupancy. In fact, the functional effect of any specific ligand as an activator or inhibitor can be substrate dependent. Divergent approaches, including kinetic modeling and X-ray crystallography, are providing new information about how multiple ligand binding yields complex CYP kinetics.
Reith, David; Medlicott, Natalie J; Kumara De Silva, Rohana; Yang, Lin; Hickling, Jeremy; Zacharias, Mathew
2009-01-01
1. The aim of the present study was to perform an in vivo estimation of the Michaelis-Menten constants of the major metabolic pathways of paracetamol (APAP). 2. A two-occasion, single-dose cross-over trial was performed using 60 and 90 mg/kg doses of APAP in healthy patients undergoing third molar dental extraction. Plasma samples were collected over 24 h and urine was collected for 8 h after dosing. Twenty patients were enrolled in the study and complete data for plasma and urine were available for both doses for 13 volunteers who were included in the analysis; seven of the volunteers were men, the median age (range) was 22 years (19-31) and the median weight (range) was 68 kg (50-86). 3. The mean (95% CI) k(m) for APAP glucuronidation was 6.89 mmol/L (3.57-10.22) and the V(max) was 0.97 mmol/h per kg (0.65-1.28). The k(m) for APAP sulphation was 0.097 mmol/L (0.041-0.152) and the V(max) was 0.011 mmol/h per kg (0.009-0.013). For the combined excretion of APAP-cysteine and APAP-mercapturate, the k(m) was 0.303 mmol/L (0.131-0.475) and the V(max) was 0.004 mmol/h per kg (0.002-0.005). 4. The estimates for in vivo Michaelis-Menten constants for APAP glucuronidation and sulphation were in the order of those reported previously using in vitro methods.
Liao, Fei; Tian, Kao-Cong; Yang, Xiao; Zhou, Qi-Xin; Zeng, Zhao-Chun; Zuo, Yu-Ping
2003-03-01
The reliability of kinetic substrate quantification by nonlinear fitting of the enzyme reaction curve to the integrated Michaelis-Menten equation was investigated by both simulation and preliminary experimentation. For simulation, product absorptivity epsilon was 3.00 mmol(-1) L cm(-1) and K(m) was 0.10 mmol L(-1), and uniform absorbance error sigma was randomly inserted into the error-free reaction curve of product absorbance A(i) versus reaction time t(i) calculated according to the integrated Michaelis-Menten equation. The experimental reaction curve of arylesterase acting on phenyl acetate was monitored by phenol absorbance at 270 nm. Maximal product absorbance A(m) was predicted by nonlinear fitting of the reaction curve to Eq. (1) with K(m) as constant. There were unique A(m) for best fitting of both the simulated and experimental reaction curves. Neither the error in reaction origin nor the variation of enzyme activity changed the background-corrected value of A(m). But the range of data under analysis, the background absorbance, and absorbance error sigma had an effect. By simulation, A(m) from 0.150 to 3.600 was predicted with reliability and linear response to substrate concentration when there was 80% consumption of substrate at sigma of 0.001. Restriction of absorbance to 0.700 enabled A(m) up to 1.800 to be predicted at sigma of 0.001. Detection limit reached A(m) of 0.090 at sigma of 0.001. By experimentation, the reproducibility was 4.6% at substrate concentration twice the K(m), and A(m) linearly responded to phenyl acetate with consistent absorptivity for phenol, and upper limit about twice the maximum of experimental absorbance. These results supported the reliability of this new kinetic method for enzymatic analysis with enhanced upper limit and precision.
Bezerra, Rui M F; Fraga, Irene; Dias, Albino A
2013-01-01
Enzyme kinetic parameters are usually determined from initial rates nevertheless, laboratory instruments only measure substrate or product concentration versus reaction time (progress curves). To overcome this problem we present a methodology which uses integrated models based on Michaelis-Menten equation. The most severe practical limitation of progress curve analysis occurs when the enzyme shows a loss of activity under the chosen assay conditions. To avoid this problem it is possible to work with the same experimental points utilized for initial rates determination. This methodology is illustrated by the use of integrated kinetic equations with the well-known reaction catalyzed by alkaline phosphatase enzyme. In this work nonlinear regression was performed with the Solver supplement (Microsoft Office Excel). It is easy to work with and track graphically the convergence of SSE (sum of square errors). The diagnosis of enzyme inhibition was performed according to Akaike information criterion. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Accuracy of the Michaelis-Menten approximation when analysing effects of molecular noise.
Lawson, Michael J; Petzold, Linda; Hellander, Andreas
2015-05-06
Quantitative biology relies on the construction of accurate mathematical models, yet the effectiveness of these models is often predicated on making simplifying approximations that allow for direct comparisons with available experimental data. The Michaelis-Menten (MM) approximation is widely used in both deterministic and discrete stochastic models of intracellular reaction networks, owing to the ubiquity of enzymatic activity in cellular processes and the clear biochemical interpretation of its parameters. However, it is not well understood how the approximation applies to the discrete stochastic case or how it extends to spatially inhomogeneous systems. We study the behaviour of the discrete stochastic MM approximation as a function of system size and show that significant errors can occur for small volumes, in comparison with a corresponding mass-action system. We then explore some consequences of these results for quantitative modelling. One consequence is that fluctuation-induced sensitivity, or stochastic focusing, can become highly exaggerated in models that make use of MM kinetics even if the approximations are excellent in a deterministic model. Another consequence is that spatial stochastic simulations based on the reaction-diffusion master equation can become highly inaccurate if the model contains MM terms. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
Mechanistic interpretation of conventional Michaelis-Menten parameters in a transporter system.
Vivian, Diana; Polli, James E
2014-11-20
The aim was to elucidate how steps in drug translocation by a solute carrier transporter impact Michaelis-Menten parameters Km, Ki, and Vmax. The first objective was to derive a model for carrier-mediated substrate translocation and perform sensitivity analysis with regard to the impact of individual microrate constants on Km, Ki, and Vmax. The second objective was to compare underpinning microrate constants between compounds translocated by the same transporter. Equations for Km, Ki, and Vmax were derived from a six-state model involving unidirectional transporter flipping and reconfiguration. This unidirectional model is applicable to co-transporter type solute carriers, like the apical sodium-dependent bile acid transporter (ASBT) and the proton-coupled peptide cotransporter (PEPT1). Sensitivity analysis identified the microrate constants that impacted Km, Ki, and Vmax. Compound comparison using the six-state model employed regression to identify microrate constant values that can explain observed Km and Vmax values. Results yielded some expected findings, as well as some unanticipated effects of microrate constants on Km, Ki, and Vmax. Km and Ki were found to be equal for inhibitors that are also substrates. Additionally, microrate constant values for certain steps in transporter functioning influenced Km and Vmax to be low or high. Copyright © 2014 Elsevier B.V. All rights reserved.
Michaelis-Menten kinetics in shear flow: Similarity solutions for multi-step reactions.
Ristenpart, W D; Stone, H A
2012-03-01
Models for chemical reaction kinetics typically assume well-mixed conditions, in which chemical compositions change in time but are uniform in space. In contrast, many biological and microfluidic systems of interest involve non-uniform flows where gradients in flow velocity dynamically alter the effective reaction volume. Here, we present a theoretical framework for characterizing multi-step reactions that occur when an enzyme or enzymatic substrate is released from a flat solid surface into a linear shear flow. Similarity solutions are developed for situations where the reactions are sufficiently slow compared to a convective time scale, allowing a regular perturbation approach to be employed. For the specific case of Michaelis-Menten reactions, we establish that the transversally averaged concentration of product scales with the distance x downstream as x(5/3). We generalize the analysis to n-step reactions, and we discuss the implications for designing new microfluidic kinetic assays to probe the effect of flow on biochemical processes.
Müller, R; Babel, W
1980-01-01
Investigations of the 3-hexulosephosphate synthase (HPS) from different methylotrophic bacteria have revealed apparent discrepancies in kinetic behaviour. In all methanol-utilizing species investigated by us the kinetic characteristics showed intermediary plateau regions. Therefore, this behaviour is assumed to be a general feature of the HPS from all non-methane-utilizing methylotrophic bacteria. However, this assumption is in contrast to the results of other authors. Both for Methylomonas M15 (SAHM et al. 1976) and Methylomonas aminofaciens 77a (KATO et al. 1977, 1978) MICHAELIS-MENTEN kinetics of the HPS were stated. To check the validity of our assumption we have analyzed the kinetic data given by others. Indications of the existence of intermediary plateau regions could be found with the enzyme from Arthrobacter globiformis (BYKOVSKAYA and VORONKOV 1977) and Methylomonas aminofaciens 77a (KATO et al. 1978). Furthermore, biphasic ARRHENIUS plots indicate a multiple character of the HPS from these species as could already be demonstrated with the enzyme from Bacterium MB 58 and Pseudomonas oleovorans. In addition, causes which may obscure the detection of intermediary plateau regions are demonstrated.
eduction for Michaelis-Menten-Henri kinetics in the presence of diffusion
Leonid V. Kalachev
2007-05-01
Full Text Available The Michaelis-Menten-Henri (MMH mechanism is one of the paradigm reaction mechanisms in biology and chemistry. In its simplest form, it involves a substrate that reacts (reversibly with an enzyme, forming a complex which is transformed (irreversibly into a product and the enzyme. Given these basic kinetics, a dimension reduction has traditionally been achieved in two steps, by using conservation relations to reduce the number of species and by exploiting the inherent fast-slow structure of the resulting equations. In the present article, we investigate how the dynamics change if the species are additionally allowed to diffuse. We study the two extreme regimes of large diffusivities and of small diffusivities, as well as an intermediate regime in which the time scale of diffusion is comparable to that of the fast reaction kinetics. We show that reduction is possible in each of these regimes, with the nature of the reduction being regime dependent. Our analysis relies on the classical method of matched asymptotic expansions to derive approximations for the solutions that are uniformly valid in space and time.
Burchardt, Malte; Träuble, Markus; Wittstock, Gunther
2009-06-15
The formalism for simulating scanning electrochemical microscopy (SECM) experiments by boundary element methods in three space coordinates has been extended to allow consideration of nonlinear boundary conditions. This is achieved by iteratively refining the boundary conditions that are encoded in a boundary condition matrix. As an example, the simulations are compared to experimental approach curves in the SECM feedback mode toward samples modified with glucose oxidase (GOx). The GOx layer was prepared by the layer-by-layer assembly of polyelectrolytes using glucose oxidase as one of the polyelectrolytes. The comparison of the simulated and experimental curves showed that under a wide range of experimentally accessible conditions approximations of the kinetics at the sample by first order models yield misleading results. The approach curves differ also qualitatively from curves calculated with first order models. As a consequence, this may lead to severe deviations when such curves are fitted to first order kinetic models. The use of linear approximations to describe the enzymatic reaction in SECM feedback experiments is justified only if the ratio of the mediator and Michaelis-Menten constant is equal to or smaller than 0.1 (deviation less than 10%).
Park, Soohyung; Agmon, Noam
2008-05-15
We develop a uniform theory for the many-particle diffusion-control effects on the Michaelis-Menten scheme in solution, based on the Gopich-Szabo relaxation-time approximation (Gopich, I. V.; Szabo, A. J. Chem. Phys. 2002, 117, 507). We extend the many-particle simulation algorithm to the Michaelis-Menten case by utilizing the Green function previously derived for excited-state reversible geminate recombination with different lifetimes (Gopich, I. V.; Agmon, N. J. Chem. Phys. 2000, 110, 10433). Running the simulation for representative parameter sets in the time domain and under steady-state conditions, we find poor agreement with classical kinetics but excellent agreement with some of the modern theories for bimolecular diffusion-influenced reactions. Our simulation algorithm can be readily extended to the biologically interesting case of dense patches of membrane-bound enzymes.
Kumar, Ashutosh; Dua, Arti
2015-01-01
Recent fluorescence spectroscopy measurements of the turnover time distribution of single-enzyme turnover kinetics of $\\beta$-galactosidase provide evidence of Michaelis-Menten kinetics at low substrate concentration. However, at high substrate concentrations, the dimensionless variance of the turnover time distribution shows systematic deviations from the Michaelis-Menten prediction. This difference is attributed to conformational fluctuations in both the enzyme and the enzyme-substrate complex and to the possibility of both parallel and off-pathway kinetics. Here, we use the chemical master equation to model the kinetics of a single fluctuating enzyme that can yield a product through either parallel or off-pathway mechanisms. An exact expression is obtained for the turnover time distribution from which the mean turnover time and randomness parameters are calculated. The parallel and off-pathway mechanisms yield strikingly different dependences of the mean turnover time and the randomness parameter on the su...
Simon Brown
2010-06-01
Full Text Available The behavior of enzyme-catalyzed reactions is not made clear to many students by the standard mathematical description of enzyme kinetics. An enzyme-machine analogy is described that has made the details of the Michaelis-Menten mechanism and the associated kinetics more accessible with minimal use of mathematics. Students taught using the analogy appear to have fewer of the misconceptions than those taught using a more mathematical approach.
Simon Brown
2010-01-01
The behavior of enzyme-catalyzed reactions is not made clear to many students by the standard mathematical description of enzyme kinetics. An enzyme-machine analogy is described that has made the details of the Michaelis-Menten mechanism and the associated kinetics more accessible with minimal use of mathematics. Students taught using the analogy appear to have fewer of the misconceptions than those taught using a more mathematical approach.
2009-01-01
A different view of Henri-Michaelis-Menten (HMM) enzyme kinetics is presented. In the first part of the paper, a simplified but useful description that stresses the cyclic nature of the catalytic process is introduced. The time-dependence of the substrate concentration after the initial transient phase is derived in a simple way that dispenses the mathematical technique known as quasi-steady-state approximation. In the second part of the paper an exact one-dimensional formulation of HMM kinet...
Uso de equações lineares na determinação dos parâmetros de Michaelis-Menten
Carvalho,Nakédia M. F.; Pires, Bianca M.; Antunes,Octavio A. C.; Roberto B Faria; Osório,Renata E. H. M. B.; Piovezan, Clovis; Neves,Ademir
2010-01-01
The Michaelis-Menten equation is used in many biochemical and bioinorganic kinetic studies involving homogeneous catalysis. Otherwise, it is known that determination of Michaelis-Menten parameters K M, Vmax, and k cat by the well-known Lineweaver-Burk double reciprocal linear equation does not produce the best values for these parameters. In this paper we present a discussion on different linear equations which can be used to calculate these parameters and we compare their results with the va...
Statistical reconstruction of transcription factor activity using Michaelis-Menten kinetics.
Khanin, R; Vinciotti, V; Mersinias, V; Smith, C P; Wit, E
2007-09-01
The basic building block of a gene regulatory network consists of a gene encoding a transcription factor (TF) and the gene(s) it regulates. Considerable efforts have been directed recently at devising experiments and algorithms to determine TFs and their corresponding target genes using gene expression and other types of data. The underlying problem is that the expression of a gene coding for the TF provides only limited information about the activity of the TF, which can also be controlled posttranscriptionally. In the absence of a reliable technology to routinely measure the activity of regulators, it is of great importance to understand whether this activity can be inferred from gene expression data. We here develop a statistical framework to reconstruct the activity of a TF from gene expression data of the target genes in its regulatory module. The novelty of our approach is that we embed the deterministic Michaelis-Menten model of gene regulation in this statistical framework. The kinetic parameters of the gene regulation model are inferred together with the profile of the TF regulator. We also obtain a goodness-of-fit test to verify the fit of the model. The model is applied to a time series involving the Streptomyces coelicolor bacterium. We focus on the transcriptional activator cdaR, which is partly responsible for the production of a particular type of antibiotic. The aim is to reconstruct the activity profile of this regulator. Our approach can be extended to include more complex regulatory relationships, such as multiple regulatory factors, competition, and cooperativity.
Goličnik, Marko
2011-06-01
Many pharmacodynamic processes can be described by the nonlinear saturation kinetics that are most frequently based on the hyperbolic Michaelis-Menten equation. Thus, various time-dependent solutions for drugs obeying such kinetics can be expressed in terms of the Lambert W(x)-omega function. However, unfortunately, computer programs that can perform the calculations for W(x) are not widely available. To avoid this problem, the replacement of the integrated Michaelis-Menten equation with an empiric integrated 1--exp alternative model equation was proposed recently by Keller et al. (Ther Drug Monit. 2009;31:783-785), although, as shown here, it was not necessary. Simulated concentrations of model drugs obeying Michaelis-Menten elimination kinetics were generated by two approaches: 1) calculation of time-course data based on an approximation equation W2*(x) performed using Microsoft Excel; and 2) calculation of reference time-course data based on an exact W(x) function built in to the Wolfram Mathematica. I show here that the W2*(x) function approximates the actual W(x) accurately. W2*(x) is expressed in terms of elementary mathematical functions and, consequently, it can be easily implemented using any of the widely available software. Hence, with the example of a hypothetical drug, I demonstrate here that an equation based on this approximation is far better, because it is nearly equivalent to the original solution, whereas the same characteristics cannot be fully confirmed for the 1--exp model equation. The W2*(x) equation proposed here might have an important role as a useful shortcut in optional software to estimate kinetic parameters from experimental data for drugs, and it might represent an easy and universal analytical tool for simulating and designing dosing regimens.
Kumar, Ashutosh; Maity, Hiranmay; Dua, Arti
2015-07-09
Recent fluorescence spectroscopy measurements of the turnover time distribution of single-enzyme turnover kinetics of β-galactosidase provide evidence of Michaelis-Menten kinetics at low substrate concentration. However, at high substrate concentrations, the dimensionless variance of the turnover time distribution shows systematic deviations from the Michaelis-Menten prediction. This difference is attributed to conformational fluctuations in both the enzyme and the enzyme-substrate complex and to the possibility of both parallel- and off-pathway kinetics. Here, we use the chemical master equation to model the kinetics of a single fluctuating enzyme that can yield a product through either parallel- or off-pathway mechanisms. An exact expression is obtained for the turnover time distribution from which the mean turnover time and randomness parameters are calculated. The parallel- and off-pathway mechanisms yield strikingly different dependences of the mean turnover time and the randomness parameter on the substrate concentration. In the parallel mechanism, the distinct contributions of enzyme and enzyme-substrate fluctuations are clearly discerned from the variation of the randomness parameter with substrate concentration. From these general results, we conclude that an off-pathway mechanism, with substantial enzyme-substrate fluctuations, is needed to rationalize the experimental findings of single-enzyme turnover kinetics of β-galactosidase.
Hum, Ryan J; Jha, Prabhat; McGahan, Anita M; Cheng, Yu-Ling
2012-12-13
Life expectancy has risen sharply in the last 50 years. We applied the classic Michaelis-Menten enzyme kinetics to demonstrate a novel mathematical relationship of income to childhood (aged 0-5 years) and adult (aged 15-60 years) survival. We treat income as a substrate that is catalyzed to increase survival (from technologies that income buys) for 180 countries from 1970 and 2007. Michaelis-Menten kinetics permit estimates of maximal survival and, uniquely, the critical income needed to achieve half of the period-specific maximum. Maximum child and adult survival rose by about 1% per year. Critical incomes fell by half for children, but doubled for men. HIV infection and smoking account for some, but not all, of the rising critical incomes for adult survival. Altering the future cost curve for adult survival will require more widespread use of current interventions, most notably tobacco control, but also research to identify practicable low-cost drugs, diagnostics, and strategies.DOI:http://dx.doi.org/10.7554/eLife.00051.001.
André Rosa Martins
2014-11-01
Full Text Available The enzymatic processes according Michaelis-Menten kinetics have been studied from various approaches to describe the inhibition state. Proposals for inhibition were compared from a generic process, where kinetic constants have received unitary values, and the numeric value of the concentration of substrate was ten (10 times higher than the numerical value of the concentration of enzyme. For each inhibition model proposed, numerical solutions were obtained from nonlinear system of ordinary differential equations, generating results presents by graphs showing the variation of the enzyme and enzyme complexes, also the variation of substrate and product of the reaction. Also, was designed a model with performance, indicating similar behavior to that seen in the Michaelis-Menten kinetics, where complex of reaction is rapidly formed and throughout the process, tends to decay to zero. Thus, in this new proposed model, the effect of inhibition starts at zero and, throughout the process, tends to the nominal value of the initial enzyme concentration. Such responses have proved to be valid for different values of enzyme concentration and process time, showing robustness. The proposed model was applied to the hydrolysis of disaccharides, providing a setting with conservation of mass of the model at the end of the process regarding the responses of the carbohydrate concentration.
Wu, Xiaotian; Li, Jun; Nekka, Fahima
2015-04-01
The current study aims to provide the closed form solutions of one-compartment open models exhibiting simultaneous linear and nonlinear Michaelis-Menten elimination kinetics for single- and multiple-dose intravenous bolus administrations. It can be shown that the elimination half-time ([Formula: see text]) has a dose-dependent property and is upper-bounded by [Formula: see text] of the first-order elimination model. We further analytically distinguish the dominant role of different elimination pathways in terms of model parameters. Moreover, for the case of multiple-dose intravenous bolus administration, the existence and local stability of the periodic solution at steady state are established. The closed form solutions of the models are obtained through a newly introduced function motivated by the Lambert W function.
Reeve, Russell; Turner, J Rick
2013-05-01
The Hill equation is often used in dose-response or exposure-response modeling. Aliases for the Hill model include the Emax model, and the Michaelis-Menten model. There is confusion about the appropriate parameterization, how to interpret the parameters, what the meaning is of the various parameterizations found in the literature, and which parameterization best approximates the statistical inferences produced when fitting the Hill equation to data. In this paper, we present several equivalent versions of the Hill model; show that they are equivalent in terms of yielding the same prediction for a given dose, and are equivalent to the four-parameter logistic model in this same sense; and deduce which parameterization is optimal in the sense of having the least statistical curvature and preferable multicollinearity.
Yan, Shaomin; Wu, Guang
2011-10-01
In this study, we attempted to use the neural network to model a quantitative structure-K(m) (Michaelis-Menten constant) relationship for beta-glucosidase, which is an important enzyme to cut the beta-bond linkage in glucose while K(m) is a very important parameter in enzymatic reactions. Eight feedforward backpropagation neural networks with different layers and neurons were applied for the development of predictive model, and twenty-five different features of amino acids were chosen as predictors one by one. The results show that the 20-1 feedforward backpropagation neural network can serve as a predictive model while the normalized polarizability index as well as the amino-acid distribution probability can serve as the predictors. This study threw lights on the possibility of predicting the K(m) in beta-glucosidases based on their amino-acid features.
Garneau-Tsodikova, Sylvie; Shkel, Irina A; Tsodikov, Oleg V
2009-04-15
Most enzyme kinetic experiments are carried out under pseudo-first-order conditions, that is, when one of the reactant species (the enzyme or the substrate) is in a large excess of the other species. More accurate kinetic information about the system can be gained without the restrictions of the pseudo-first-order conditions. We present a practical and general method of analysis of the common two-step rapid equilibrium Michaelis-Menten mechanism. The formalism is exact in that it does not involve any other approximations such as the steady-state, limitations on the reactant concentrations or on reaction times. We apply this method to the global analysis of kinetic progress curves for bovine alkaline phosphatase assays carried out under both pseudo-first-order and pseudo-second-order conditions.
Blum, Philipp; Hunkeler, Daniel; Weede, Matthias; Beyer, Christof; Grathwohl, Peter; Morasch, Barbara
2009-04-01
At a former wood preservation plant severely contaminated with coal tar oil, in situ bulk attenuation and biodegradation rate constants for several monoaromatic (BTEX) and polyaromatic hydrocarbons (PAH) were determined using (1) classical first order decay models, (2) Michaelis-Menten degradation kinetics (MM), and (3) stable carbon isotopes, for o-xylene and naphthalene. The first order bulk attenuation rate constant for o-xylene was calculated to be 0.0025 d - 1 and a novel stable isotope-based first order model, which also accounted for the respective redox conditions, resulted in a slightly smaller biodegradation rate constant of 0.0019 d - 1 . Based on MM-kinetics, the o-xylene concentration decreased with a maximum rate of kmax = 0.1 µg/L/d. The bulk attenuation rate constant of naphthalene retrieved from the classical first order decay model was 0.0038 d - 1 . The stable isotope-based biodegradation rate constant of 0.0027 d - 1 was smaller in the reduced zone, while residual naphthalene in the oxic part of the plume further downgradient was degraded at a higher rate of 0.0038 d - 1 . With MM-kinetics a maximum degradation rate of kmax = 12 µg/L/d was determined. Although best fits were obtained by MM-kinetics, we consider the carbon stable isotope-based approach more appropriate as it is specific for biodegradation (not overall attenuation) and at the same time accounts for the dominant electron-accepting process. For o-xylene a field based isotope enrichment factor ɛfield of - 1.4 could be determined using the Rayleigh model, which closely matched values from laboratory studies of o-xylene degradation under sulfate-reducing conditions.
Blum, Philipp; Hunkeler, Daniel; Weede, Matthias; Beyer, Christof; Grathwohl, Peter; Morasch, Barbara
2009-04-01
At a former wood preservation plant severely contaminated with coal tar oil, in situ bulk attenuation and biodegradation rate constants for several monoaromatic (BTEX) and polyaromatic hydrocarbons (PAH) were determined using (1) classical first order decay models, (2) Michaelis-Menten degradation kinetics (MM), and (3) stable carbon isotopes, for o-xylene and naphthalene. The first order bulk attenuation rate constant for o-xylene was calculated to be 0.0025 d(-1) and a novel stable isotope-based first order model, which also accounted for the respective redox conditions, resulted in a slightly smaller biodegradation rate constant of 0.0019 d(-1). Based on MM-kinetics, the o-xylene concentration decreased with a maximum rate of k(max)=0.1 microg/L/d. The bulk attenuation rate constant of naphthalene retrieved from the classical first order decay model was 0.0038 d(-1). The stable isotope-based biodegradation rate constant of 0.0027 d(-1) was smaller in the reduced zone, while residual naphthalene in the oxic part of the plume further downgradient was degraded at a higher rate of 0.0038 d(-1). With MM-kinetics a maximum degradation rate of k(max)=12 microg/L/d was determined. Although best fits were obtained by MM-kinetics, we consider the carbon stable isotope-based approach more appropriate as it is specific for biodegradation (not overall attenuation) and at the same time accounts for the dominant electron-accepting process. For o-xylene a field based isotope enrichment factor epsilon(field) of -1.4 could be determined using the Rayleigh model, which closely matched values from laboratory studies of o-xylene degradation under sulfate-reducing conditions.
Igamberdiev, Abir U; Roussel, Marc R
2012-03-01
Rubisco, the most abundant protein serving as the primary engine generating organic biomass on Earth, is characterized by a low catalytic constant (in higher plants approx. 3s(-1)) and low specificity for CO(2) leading to photorespiration. We analyze here why this enzyme evolved as the main carbon fixation engine. The high concentration of Rubisco exceeding the concentration of its substrate CO(2) by 2-3 orders of magnitude makes application of Michaelis-Menten kinetics invalid and requires alternative kinetic approaches to describe photosynthetic CO(2) assimilation. Efficient operation of Rubisco is supported by a strong flux of CO(2) to the chloroplast stroma provided by fast equilibration of bicarbonate and CO(2) and forwarding the latter to Rubisco reaction centers. The main part of this feedforward mechanism is a thylakoidal carbonic anhydrase associated with photosystem II and pumping CO(2) from the thylakoid lumen in coordination with the rate of electron transport, water splitting and proton gradient across the thylakoid membrane. This steady flux of CO(2) limits photosynthesis at saturating CO(2) concentrations. At low ambient CO(2) and correspondingly limited capacity of the bicarbonate pool in the stroma, its depletion at the sites of Rubisco is relieved by utilizing O(2) instead of CO(2), i.e. by photorespiration, a process which supplies CO(2) back to Rubisco and buffers the redox state and energy level in the chloroplast. Thus, the regulation of Rubisco function aims to keep steady non-equilibrium levels of CO(2), NADPH/NADP and ATP/ADP in the chloroplast stroma and to optimize the condition of homeostatic photosynthetic flux of matter and energy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Yu, Xiao-Zhang; Zhang, Xue-Hong
2016-07-01
Hydroponic experiments were conducted with different species of plants (rice, maize, soybean and willow) exposed to ferri-cyanide to investigate the half-saturation constant (K M ) and the maximal metabolic capacity (v max ) involved in phyto-assimilation. Three varieties for each testing species were collected from different origins. Measured concentrations show that the uptake rates responded biphasically to ferri-cyanide treatments by showing increases linearly at low and almost constant at high concentrations from all treatments, indicating that phyto-assimilation of ferri-cyanide followed the Michaelis-Menten kinetics. Using non-linear regression, the highest v max was by rice, followed by willows. The lowest v max was found for soybean. All plants, except maize (DY26) and rice (XJ12), had a similar K M value, suggesting the same enzyme was active in phyto-assimilation of ferri-cyanide. Transcript level, by real-time quantitative PCR, of enzymes involved in degradation of cyanides showed that the analyzed genes were differently expressed during different cyanides exposure. The expression of CAS and ST genes responded positively to KCN exposure, suggesting that β-CAS and ST pathways were two possible pathways for cyanide detoxification in rice. The transcript level of NIT and ASPNASE genes also showed a remarkable up-regulation to KCN, implying the contribution to the pool of amino acid aspartate, which is an end product of CN metabolism. Up-regulation of GS genes suggests that acquisition of ammonium released from cyanide degradation may be an additional nitrogen source for plant nutrition. Results also revealed that the expressions of these genes, except for GS, were relatively constant during iron cyanide exposure, suggesting that they are likely metabolized by plants through a non-defined pathway rather than the β-CAS pathway.
Michaelis-Menten reaction scheme as a unified approach towards the optimal restart problem.
Rotbart, Tal; Reuveni, Shlomi; Urbakh, Michael
2015-12-01
We study the effect of restart, and retry, on the mean completion time of a generic process. The need to do so arises in various branches of the sciences and we show that it can naturally be addressed by taking advantage of the classical reaction scheme of Michaelis and Menten. Stopping a process in its midst-only to start it all over again-may prolong, leave unchanged, or even shorten the time taken for its completion. Here we are interested in the optimal restart problem, i.e., in finding a restart rate which brings the mean completion time of a process to a minimum. We derive the governing equation for this problem and show that it is exactly solvable in cases of particular interest. We then continue to discover regimes at which solutions to the problem take on universal, details independent forms which further give rise to optimal scaling laws. The formalism we develop, and the results obtained, can be utilized when optimizing stochastic search processes and randomized computer algorithms. An immediate connection with kinetic proofreading is also noted and discussed.
Michaelis-Menten reaction scheme as a unified approach towards the optimal restart problem
Rotbart, Tal; Reuveni, Shlomi; Urbakh, Michael
2015-12-01
We study the effect of restart, and retry, on the mean completion time of a generic process. The need to do so arises in various branches of the sciences and we show that it can naturally be addressed by taking advantage of the classical reaction scheme of Michaelis and Menten. Stopping a process in its midst—only to start it all over again—may prolong, leave unchanged, or even shorten the time taken for its completion. Here we are interested in the optimal restart problem, i.e., in finding a restart rate which brings the mean completion time of a process to a minimum. We derive the governing equation for this problem and show that it is exactly solvable in cases of particular interest. We then continue to discover regimes at which solutions to the problem take on universal, details independent forms which further give rise to optimal scaling laws. The formalism we develop, and the results obtained, can be utilized when optimizing stochastic search processes and randomized computer algorithms. An immediate connection with kinetic proofreading is also noted and discussed.
Verlindo de Araujo, Bibiana; Farias da Silva, Cristófer; Costa, Teresa Dalla
2010-01-01
the determination of oral bioavailability of drugs which follow nonlinear pharmacokinetics is difficult and few methods are available. In this work, an alternative approach to determine oral bioavailability of voriconazole (VRC), used as a model drug, is presented. VRC pharmacokinetics was investigated in Wistar rats after p.o. (40 mg/kg) and i.v. administration (2.5, 5 and 10 mg/kg). VRC elimination showed saturation in all doses investigated, except the lower i.v. dose in which case a 3-compartment model with linear elimination adequately fitted the data. Data for the 2 higher i.v. doses were best described by a 3-compartment model with Michaelis-Menten elimination. A 1-compartment disposition with a saturable metabolic elimination model described the oral profile. VRC absolute oral bioavailability was determined by simultaneous fitting of the i.v. and oral profiles. the Michaelis constant and the maximum velocity estimated after 5 and 10 mg/kg i.v. dosing were 0.54 +/- 0.25 microg/ml and 2.53 +/- 0.54 microg/h, and 0.62 +/- 0.12 microg/ml and 2.74 +/- 0.84 microg/h, respectively. VRC oral bioavailability was determined to be 82.8%. the approach presented is an alternative for determining the bioavailability of drugs with similar nonlinear behavior. 2010 S. Karger AG, Basel.
Lee, Byung-Yo; Kwon, Kwang-Il; Kim, Min-Soo; Baek, In-Hwan
2016-08-01
Etanercept was approved by the Food and Drug Administration (FDA) in 2010 as a biologic agent for the treatment of rheumatoid arthritis (RA). The aim of the study was to investigate the pharmacokinetic properties of etanercept after intravenous and subcutaneous injection in rats. The plasma concentration of etanercept was determined using an enzyme-linked immunosorbent assay (ELISA). Intravenous and subcutaneous administration of 2 mg/kg of etanercept to rats showed that etanercept was slowly absorbed (time to reach the peak drug concentration [T max] = 1.60 days, bioavailability [F] = 47.18 %) and slowly eliminated (half-life [t 1/2], 2.33 days after intravenous administration and 3.31 days after subcutaneous administration). The area under the curve values on day 13 (AUC13day) were 121.25 ± 14.37 and 48.56 ± 6.78 μg day/mL after intravenous and subcutaneous administration, respectively. A two-compartment model with Michaelis-Menten elimination kinetics (V max = 94.28 µg/day; K m = 10.88 µg/mL) was used to describe the pharmacokinetic profile of etanercept. Our results describe the pharmacokinetic profile of etanercept, and these results could be used for the development of etanercept biosimilars.
Chaudhury, Srabanti; Cherayil, Binny J
2007-09-14
Single-molecule equations for the Michaelis-Menten [Biochem. Z. 49, 333 (1913)] mechanism of enzyme action are analyzed within the Wilemski-Fixman [J. Chem. Phys. 58, 4009 (1973); 60, 866 (1974)] approximation after the effects of dynamic disorder--modeled by the anomalous diffusion of a particle in a harmonic well--are incorporated into the catalytic step of the reaction. The solution of the Michaelis-Menten equations is used to calculate the distribution of waiting times between successive catalytic turnovers in the enzyme beta-galactosidase. The calculated distribution is found to agree qualitatively with experimental results on this enzyme obtained at four different substrate concentrations. The calculations are also consistent with measurements of correlations in the fluctuations of the fluorescent light emitted during the course of catalysis, and with measurements of the concentration dependence of the randomness parameter.
Bringing metabolic networks to life: convenience rate law and thermodynamic constraints
Klipp Edda
2006-12-01
Full Text Available Abstract Background Translating a known metabolic network into a dynamic model requires rate laws for all chemical reactions. The mathematical expressions depend on the underlying enzymatic mechanism; they can become quite involved and may contain a large number of parameters. Rate laws and enzyme parameters are still unknown for most enzymes. Results We introduce a simple and general rate law called "convenience kinetics". It can be derived from a simple random-order enzyme mechanism. Thermodynamic laws can impose dependencies on the kinetic parameters. Hence, to facilitate model fitting and parameter optimisation for large networks, we introduce thermodynamically independent system parameters: their values can be varied independently, without violating thermodynamical constraints. We achieve this by expressing the equilibrium constants either by Gibbs free energies of formation or by a set of independent equilibrium constants. The remaining system parameters are mean turnover rates, generalised Michaelis-Menten constants, and constants for inhibition and activation. All parameters correspond to molecular energies, for instance, binding energies between reactants and enzyme. Conclusion Convenience kinetics can be used to translate a biochemical network – manually or automatically - into a dynamical model with plausible biological properties. It implements enzyme saturation and regulation by activators and inhibitors, covers all possible reaction stoichiometries, and can be specified by a small number of parameters. Its mathematical form makes it especially suitable for parameter estimation and optimisation. Parameter estimates can be easily computed from a least-squares fit to Michaelis-Menten values, turnover rates, equilibrium constants, and other quantities that are routinely measured in enzyme assays and stored in kinetic databases.
Liu, Ai-Lin; Zhou, Ting; He, Feng-Yun; Xu, Jing-Juan; Lu, Yu; Chen, Hong-Yuan; Xia, Xing-Hua
2006-06-01
We firstly transformed the traditional Michaelis-Menten equation into an off-line form which can be used for evaluating the Michaelis-Menten constant after the enzymatic reaction. For experimental estimation of the kinetics of enzymatic reactions, we have developed a facile and effective method by integrating an enzyme microreactor into direct-printing polymer microchips. Strong nonspecific adsorption of proteins was utilized to effectively immobilize enzymes onto the microchannel wall, forming the integrated on-column enzyme microreactor in a microchip. The properties of the integrated enzyme microreactor were evaluated by using the enzymatic reaction of glucose oxidase (GOx) with its substrate glucose as a model system. The reaction product, hydrogen peroxide, was electrochemically (EC) analyzed using a Pt microelectrode. The data for enzyme kinetics using our off-line form of the Michaelis-Menten equation was obtained (K(m) = 2.64 mM), which is much smaller than that reported in solution (K(m) = 6.0 mM). Due to the hydrophobic property and the native mesoscopic structure of the poly(ethylene terephthalate) film, the immobilized enzyme in the microreactor shows good stability and bioactivity under the flowing conditions.
Pereira, Félix Monteiro; Oliveira, Samuel Conceição
2016-11-01
In this article, the occurrence of dead core in catalytic particles containing immobilized enzymes is analyzed for the Michaelis-Menten kinetics. An assessment of numerical methods is performed to solve the boundary value problem generated by the mathematical modeling of diffusion and reaction processes under steady state and isothermal conditions. Two classes of numerical methods were employed: shooting and collocation. The shooting method used the ode function from Scilab software. The collocation methods included: that implemented by the bvode function of Scilab, the orthogonal collocation, and the orthogonal collocation on finite elements. The methods were validated for simplified forms of the Michaelis-Menten equation (zero-order and first-order kinetics), for which analytical solutions are available. Among the methods covered in this article, the orthogonal collocation on finite elements proved to be the most robust and efficient method to solve the boundary value problem concerning Michaelis-Menten kinetics. For this enzyme kinetics, it was found that the dead core can occur when verified certain conditions of diffusion-reaction within the catalytic particle. The application of the concepts and methods presented in this study will allow for a more generalized analysis and more accurate designs of heterogeneous enzymatic reactors.
Meyer, Markus R; Orschiedt, Tina; Maurer, Hans H
2013-02-27
The pharmacokinetics of various important drugs are known to be significantly influenced by the human ABC transporter P-glycoprotein (P-gp), which may lead to clinically relevant drug-drug interactions. In contrast to therapeutic drugs, emerging drugs of abuse (DOA) are sold and consumed without any safety pharmacology testing. Only some studies on their metabolism were published, but none about their affinity to the transporter systems. Therefore, 47 DOAs from various classes were tested for their P-gp affinity using human P-gp (hP-gp) to predict possible drug-drug interactions. DOAs were initially screened for general hP-gp affinity and further characterized by modeling classic Michaelis-Menten kinetics and assessing their K(m) and V(max) values. Among the tested drugs, 12 showed a stimulation of ATPase activity. The most intensive stimulating DOAs were further investigated and compared with the known P-gp model substrates sertraline and verapamil. ATPase stimulation kinetics could be modeled for the entactogen 3,4-methylenedioxy-α-ethylphenethylamine (3,4-BDB), the hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), the abused alkaloid glaucine, the opioid-like drugs N-iso-propyl-1,2-diphenylethylamine (NPDPA), and N-(1-phenylcyclohexyl)-3-ethoxypropanamine (PCEPA), with K(m) and V(max) values within the same range as for verapamil or sertraline. As a consequence interactions with other drugs being P-gp substrates might be considered to be very likely and further studies should be encouraged. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Utilization of Integrated Michaelis-Menten Equation to Determine Kinetic Constants
Bezerra, Rui M. F.; Dias, Albino A.
2007-01-01
Students of biochemistry and related biosciences are urged to solve problems where kinetic parameters are calculated from initial rates obtained at different substrate concentrations. Troubles begin when they go to the laboratory to perform kinetic experiments and realize that usual laboratory instruments do not measure initial rates but only…
Utilization of Integrated Michaelis-Menten Equation to Determine Kinetic Constants
Bezerra, Rui M. F.; Dias, Albino A.
2007-01-01
Students of biochemistry and related biosciences are urged to solve problems where kinetic parameters are calculated from initial rates obtained at different substrate concentrations. Troubles begin when they go to the laboratory to perform kinetic experiments and realize that usual laboratory instruments do not measure initial rates but only…
Non-Michaelis-Menten kinetics model for conductance of low-conductance potassium ion channels.
Tolokh, Igor S; Tolokh, Illya I; Cho, Hee Cheol; D'Avanzo, Nazzareno; Backx, Peter H; Goldman, Saul; Gray, C G
2005-02-01
A reduced kinetics model is proposed for ion permeation in low-conductance potassium ion channels with zero net electrical charge in the selectivity filter region. The selectivity filter is assumed to be the only conductance-determining part of the channel. Ion entry and exit rate constants depend on the occupancy of the filter due to ion-ion interactions. The corresponding rates are assumed slow relative to the rates of ion motion between binding sites inside the filter, allowing a reduction of the kinetics model of the filter by averaging the entry and exit rate constants over the states with a particular occupancy number. The reduced kinetics model for low-conductance channels is described by only three states and two sets of effective rate constants characterizing transitions between these states. An explicit expression for the channel conductance as a function of symmetrical external ion concentration is derived under the assumption that the average electrical mobility of ions in the selectivity filter region in a limited range of ion concentrations does not depend on these concentrations. The simplified conductance model is shown to provide a good description of the experimentally observed conductance-concentration curve for the low-conductance potassium channel Kir2.1, and also predicts the mean occupancy of the selectivity filter of this channel. We find that at physiological external ion concentrations this occupancy is much lower than the value of two ions observed for one of the high-conductance potassium channels, KcsA.
Stability in a diffusive food chain model with Michaelis-Menten functional response
Lin, Zhigui; Pedersen, Michael
2004-01-01
This paper deals with the behavior of positive solutions to a reaction-diffusion system with homogeneous Neumann boundary conditions describing a three species food chain. A sufficient condition for the local asymptotical stability is given by linearization and also a sufficient condition...... for the global asymptotical stability is given by a Lyapunov function. Our result shows that the equilibrium solution is globally asymptotically stable if the net birth rate of the first species is big enough and the net death rate of the third species is neither too big nor too small. (C) 2004 Elsevier Ltd. All...
Commemorating the 1913 Michaelis-Menten paper Die Kinetik der Invertinwirkung: three perspectives.
Deichmann, Ute; Schuster, Stefan; Mazat, Jean-Pierre; Cornish-Bowden, Athel
2014-01-01
Methods and equations for analysing the kinetics of enzyme-catalysed reactions were developed at the beginning of the 20th century in two centres in particular; in Paris, by Victor Henri, and, in Berlin, by Leonor Michaelis and Maud Menten. Henri made a detailed analysis of the work in this area that had preceded him, and arrived at a correct equation for the initial rate of reaction. However, his approach was open to the important objection that he took no account of the hydrogen-ion concentration (a subject largely undeveloped in his time). In addition, although he wrote down an expression for the initial rate of reaction and described the hyperbolic form of its dependence on the substrate concentration, he did not appreciate the great advantages that would come from analysis in terms of initial rates rather than time courses. Michaelis and Menten not only placed Henri's analysis on a firm experimental foundation, but also defined the experimental protocol that remains standard today. Here, we review this development, and discuss other scientific contributions of these individuals. The three parts have different authors, as indicated, and do not necessarily agree on all details, in particular about the relative importance of the contributions of Michaelis and Menten on the one hand and of Henri on the other. Rather than force the review into an unrealistic consensus, we consider it appropriate to leave the disagreements visible. © 2013 FEBS.
Multi-system Nernst-Michaelis-Menten model applied to bioanodes formed from sewage sludge.
Rimboud, Mickaël; Desmond-Le Quemener, Elie; Erable, Benjamin; Bouchez, Théodore; Bergel, Alain
2015-11-01
Bioanodes were formed under constant polarization at -0.2 V/SCE from fermented sewage sludge. Current densities reached were 9.3±1.2 A m(-2) with the whole fermented sludge and 6.2±0.9 A m(-2) with the fermented sludge supernatant. The bioanode kinetics was analysed by differentiating among the contributions of the three redox systems identified by voltammetry. Each system ensured reversible Nernstian electron transfer but around a different central potential. The global overpotential required to reach the maximum current plateau was not imposed by slow electron transfer rates but was due to the potential range covered by the different redox systems. The microbial communities of the three bioanodes were analysed by 16S rRNA gene pyrosequencing. They showed a significant microbial diversity around a core of Desulfuromonadales, the proportion of which was correlated with the electrochemical performance of the bioanodes. Copyright © 2015 Elsevier Ltd. All rights reserved.
Yunxian Dai; Yiping Lin; Huitao Zhao
2014-01-01
We consider a predator-prey system with Michaelis-Menten type functional response and two delays. We focus on the case with two unequal and non-zero delays present in the model, study the local stability of the equilibria and the existence of Hopf bifurcation, and then obtain explicit formulas to determine the properties of Hopf bifurcation by using the normal form method and center manifold theorem. Special attention is paid to the global continuation of local Hopf bifurcation when the delay...
Bezerra, Rui M F; Pinto, Paula A; Fraga, Irene; Dias, Albino A
2016-03-01
To determine initial velocities of enzyme catalyzed reactions without theoretical errors it is necessary to consider the use of the integrated Michaelis-Menten equation. When the reaction product is an inhibitor, this approach is particularly important. Nevertheless, kinetic studies usually involved the evaluation of other inhibitors beyond the reaction product. The occurrence of these situations emphasizes the importance of extending the integrated Michaelis-Menten equation, assuming the simultaneous presence of more than one inhibitor because reaction product is always present. This methodology is illustrated with the reaction catalyzed by alkaline phosphatase inhibited by phosphate (reaction product, inhibitor 1) and urea (inhibitor 2). The approach is explained in a step by step manner using an Excel spreadsheet (available as a template in Appendix). Curve fitting by nonlinear regression was performed with the Solver add-in (Microsoft Office Excel). Discrimination of the kinetic models was carried out based on Akaike information criterion. This work presents a methodology that can be used to develop an automated process, to discriminate in real time the inhibition type and kinetic constants as data (product vs. time) are achieved by the spectrophotometer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Sakoda, M; Hiromi, K
1976-09-01
The best-fit values of the Michaelis constant (Km) and the maximum velocity (V) in the Michaelis-Menten equation can be obtained by the method of least squares with the Taylor expansion for the sum of squares of the absolute residual, i.e., the difference between the observed velocity and the corresponding velocity by calculation. This method makes it possible to determine the values of Km and V not in a trial-and-error manner but in a deductive and unique manner after some iterative procedures starting from arbitrary approximate values of Km and V. These values can be said to be uniquely determined for a set of data as the finally converged values are no longer dependent upon the initial approximate values of Km and V. It is also very important to obtain initial approximate values of parameters for the application of the method described above. A simple method is proposed to estimate the approximate values of parameters involved in fractional functions. The method of rearrangement after canceling of denominator of a fractional function can be utilized to obtain approximate values, not only for cases of two unknown parameters such as the Michaelis-Menten equation, but also for cases with more than two unknowns.
Machado, Eustáquio José
2014-01-01
A equação hiperbólica, conhecida no contexto bioquímico como o modelo de Michaelis-Menten, é utilizada para descrever a velocidade de reações químicas envolvendo enzimas (cinética enzimática). Este estudo teve como objetivo comparar os ajustes do modelo de Michaelis-Menten (1913) que fez uso de dois modelos não-lineares e quatro modelos linearizados. Os dois modelos não-lineares (um utilizou o método clássico assintotico usual e o outro fez uso da abordagem "bootstrap"). Os modelos linearizad...
Moaty Sayed, A A; Hussein, M A; Becker, T
2010-04-01
Lattice Boltzmann models (LBM) are rapidly showing their ability to simulate a lot of fluid dynamics problems that previously required very complex approaches. This study presents a LBM for simulating diffusion-advection transport of substrate in a 2-D laminar flow. The model considers the substrate influx into a set of active cells placed inside the flow field. A new innovative method was used to simulate the cells activity using the LBM by means of Michaelis-Menten kinetics. The model is validated with some numerical benchmark problems and proved highly accurate results. After validation the model was used to simulate the transport of oxygen substrates that diffuse in water to feed a set of active cartilage cells inside a new designed bioreactor.
Coluzzi, Barbara; Bersani, Enrico
2016-01-01
We recall the perturbation expansion for Michaelis-Menten kinetics, beyond the standard quasi-steady-state approximation (sQSSA). Against this background, we are able to appropriately apply the alternative approach to the study of singularly perturbed differential equations that is based on the renormalization group (SPDERG), by clarifying similarities and differences. In the present demanding situation, we directly renormalize the bare initial condition value for the substrate. Our main results are: i) the 2nd order SPDERG uniform approximations to the correct solutions contain, up to 1st order, the same outer components as the known perturbation expansion ones; ii) the differential equation to be solved for the derivation of the 1st order outer substrate component is simpler within the SPDERG approach; iii) the approximations better reproduce the numerical solutions of the original problem in a region encompassing the matching one, because of the 2nd order terms in the inner components, calculated here for ...
Fowler, Stephen; Guerini, Elena; Qiu, NaHong; Cleary, Yumi; Parrott, Neil; Greig, Gerard; Mallalieu, Navita L
2017-01-01
Basimglurant, a novel mGlu5-negative allosteric modulator under development for the treatment of major depressive disorder, is cleared via cytochrome P450 (P450)-mediated oxidative metabolism. Initial enzyme phenotyping studies indicated that CYP3A4/5 dominates basimglurant metabolism and highlights a risk for drug-drug interactions when it is comedicated with strong CYP3A4/5 inhibitors or inactivators; however, a clinical drug-drug interaction (DDI) study using the potent and selective CYP3A4/5 inhibitor ketoconazole resulted in an area under the curve (AUC) AUCi/AUC ratio of only 1.24. A further study using the CYP3A4 inducer carbamazepine resulted in an AUCi/AUC ratio of 0.69. More detailed in vitro enzyme phenotyping and kinetics studies showed that, at the low concentrations attained clinically, basimglurant metabolic clearance is catalyzed mainly by CYP1A2. The relative contributions of the enzymes were estimated as 70:30 CYP1A2:CYP3A4/5. Using this information, a clinical study using the CYP1A2 inhibitor fluvoxamine was performed, resulting in an AUCi/AUC ratio of 1.60, confirming the role of CYP1A2 and indicating a balanced DDI risk profile. Basimglurant metabolism kinetics show enzyme dependency: CYP1A2-mediated metabolism follows Michaelis-Menten kinetics, whereas CYP3A4 and CYP3A5 follow sigmoidal kinetics [with similar constant (KM) and S50 values]. The interplay of the different enzyme kinetics leads to changing fractional enzyme contributions to metabolism with substrate concentration, even though none of the metabolic enzymes is saturated. This example demonstrates the relevance of non-Michaelis-Menten P450 enzyme kinetics and highlights the need for a thorough understanding of metabolism enzymology to make accurate predictions for human metabolism in vivo. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
Longatte, Guillaume; Guille-Collignon, Manon; Lemaître, Frédéric
2017-06-15
In the past years, many strategies have been implemented to benefit from oxygenic photosynthesis to harvest photosynthetic electrons and produce a significant photocurrent. Therefore, electrochemical tools were considered and have globally relied on the electron transfer(s) between the photosynthetic chain and a collecting electrode. In this context, we recently reported the implementation of an electrochemical set-up at the preparative scale to produce photocurrents from a Chlamydomonas reinhardtii algae suspension with an appropriate mediator (2,6-DCBQ) and a carbon gauze as the working electrode. In the present work, we wish to describe a mathematical modeling of the recorded photocurrents to better understand the effects of the experimental conditions on the photosynthetic extraction of electrons. In that way, we established a general model of an electrocatalytic mechanism at the preparative scale (that is, assuming a homogenous bulk solution at any time and a constant diffusion layer, both assumptions being valid under forced convection) in which the chemical step involves a Michaelis-Menten-like behaviour. Dependences of transient and steady-state corresponding currents were analysed as a function of different parameters by means of zone diagrams. This model was tested to our experimental data related to photosynthesis. The corresponding results suggest that competitive pathways beyond photosynthetic harvesting alone should be taken into account. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Padayachee, Letrisha; Pillay, Ché S
2016-07-01
The thioredoxin system, consisting of thioredoxin reductase, thioredoxin and NADPH, is present in most living organisms and reduces a large array of target protein disulfides. The insulin reduction assay is commonly used to characterise thioredoxin activity in vitro, but it is not clear whether substrate saturation datasets from this assay should be fitted and modeled with the Michaelis-Menten equation (thioredoxin enzyme model), or fitted to the thioredoxin system with insulin reduction described by mass-action kinetics (redox couple model). We utilized computational modeling and in vitro assays to determine which of these approaches yield consistent and accurate kinetic parameter sets for insulin reduction. Using computational modeling, we found that fitting to the redox couple model, rather than to the thioredoxin enzyme model, resulted in consistent parameter sets over a range of thioredoxin reductase concentrations. Furthermore, we established that substrate saturation in this assay was due to the progressive redistribution of the thioredoxin moiety into its oxidised form. We then confirmed these results in vitro using the yeast thioredoxin system. This study shows how consistent parameter sets for thioredoxin activity can be obtained regardless of the thioredoxin reductase concentration used in the insulin reduction assay, and validates computational systems biology modeling studies that have described the thioredoxin system with the redox couple modeling approach.
Youdim, K; Dodia, R
2010-04-01
Non-linear dose-exposure (supra-proportionality) occurs when plasma drug concentrations increase in a non-linear fashion with increasing dose. To predict the likelihood of this, an understanding is required of the K(M), which reflects a drug ability to saturate a specific enzyme involved in its metabolism. This study assessed the accuracy of K(M) and V(max) determinations for compounds using a substrate-depletion approach with those determined using the product-formation approach, using both recombinant human cytochrome P450 (CYP) enzymes and human liver microsomes. For the vast majority of the compounds studied, the K(M)'s using recombinant CYPs and human liver microsomes in the two approaches predicted within two-fold. Further comparisons between the K(M) and V(max)-values were made between those measured using the product-formation approach and those estimated following simultaneous fitting of the Michaelis-Menten equation to all substrate depletion plots. In each case values were comparable. In conclusion, the current study showed the substrate-depletion approach can be used to estimate K(M) and V(max) using both human liver microsomes and recombinant P450s. Estimation of these parameters during early discovery will aid in the understanding of dosages at which non-linearity may occur, but potentially aid predictions of likely clinical drug-drug interactions.
Li, Albert P; Schlicht, Kari E
2014-01-01
A higher throughput platform was developed for the determination of K(M) values for isoformselective P450 substrates in human hepatocytes via incubation of the hepatocytes with substrates in 384- well plates and metabolite quantification by RapidFire™ mass spectrometry. Isoform-selective P450 substrates were incubated at 8 concentrations in triplicate with cryopreserved human hepatocytes from 16 donors. The metabolic pathways examined were the CYP1A2-catalyzed tacrine 1-hydroxylation, CYP2B6-catalyzed bupropion hydroxylation, CYP2C8-catalyzed amodiaquine N-deethylation, CYP2C9- catalyzed diclofenac 4'-hydroxylation, CYP2D6-catalyzed dextromethorphan O-demethylation, and CYP3A4-catalyzed midazolam 1'-hydroxylation. Typical saturation enzyme kinetics was observed for all the pathways evaluated. Individual differences in the apparent V(max) and K(M) values were observed among the human hepatocytes from each of the 16 individual donors, with no statistically significant gender- or age-associated differences. A "composite" K(M) value was calculated for each of the pathways via normalizing the individual activities to their respective V(max) values to develop "relative activities" followed by Michaelis-Menten analysis of the mean relative activities of the 16 donors at each of the 8 substrate concentrations. The resulting "composite" K(M) values for the P450 substrates may be used to guide in vitro P450 inhibition and induction studies and kinetic modeling of in vivo drug-drug interaction.
磁流变阻尼器的米氏模型及试验验证%MICHAELIS-MENTEN MODEL OF MAGNETORHEOLOGICAL DAMPER AND TEST VERIFICATION
张香成; 徐赵东; 王绍安; 沙凌峰
2013-01-01
为研究磁流变阻尼器(MRD)非线性滞回性能的影响因素,建立精确的MRD力学模型,对MRD进行力学性能试验,并基于米氏方程提出一个综合考虑电流、位移和频率影响的力学模型——米氏模型.对所提模型和传统经典力学模型进行数值模拟,并与试验结果进行对比分析,结果表明:该模型可以模拟MRD的非线性滞回性能、体现位移和频率对阻尼力及非线性滞回性能的影响.%To find the effect factors of the nonlinear hysteresis capability of a magnetorheological damper (MRD) and establish a precise mathematical model, a Michaelis-Menten (MM) Model was presented based on the MM equation which considers the effects of current, amplitude and frequency. Numerical simulations of the MM Model and traditional classical mathematic model were carried out to compare with the test results. Comparison results indicate that the MM Model could simulate the hysteresis capability of MRD and reflect the effects of current, amplitude and frequency on damping force and nonlinear hysteresis capability.
Bezerra, Rui M F; Dias, Albino A
2004-03-01
The kinetics of exoglucanase (Cel7A) from Trichoderma reesei was investigated in the presence of cellobiose and 24 different enzyme/Avicel ratios for 47 h, in order to establish which of the eight available kinetic models best explained the factors involved. The heterogeneous catalysis was studied and the kinetic parameters were estimated employing integrated forms of Michaelis-Menten equations through the use of nonlinear least squares. It was found that cellulose hydrolysis follows a model that takes into account competitive inhibition by cellobiose (final product) with the following parameters: Km = 3.8 mM, Kic = 0.041 mM, kcat = 2 h-1 (5.6 x 10-4 s-1). Other models, such as mixed type inhibition and those incorporating improvements concerning inhibition by substrate and parabolic inhibition, increased the modulation performance very slightly. The results support the hypothesis that nonproductive enzyme substrate complexes, parabolic inhibition, and enzyme inactivation (Selwyn test) are not the principal constraints in enzymatic cellulose hydrolysis. Under our conditions, the increment in hydrolysis was not significant for substrate/enzyme ratios <6.5.
André Rosa Martins
2015-01-01
.... One model was obtained, among the evaluated proposals, with performance indicating behavior similar to the classical Michaelis-Menten model, where the reaction complex is rapidly formed and, along...
Gattu, Srikanth; Crihfield, Cassandra L; Holland, Lisa A
2017-01-03
Phospholipid nanogels enhance the stability and performance of the exoglycosidase enzyme neuraminidase and are used to create a fixed zone of enzyme within a capillary. With nanogels, there is no need to covalently immobilize the enzyme, as it is physically constrained. This enables rapid quantification of Michaelis-Menten constants (KM) for different substrates and ultimately provides a means to quantify the linkage (i.e., 2-3 versus 2-6) of sialic acids. The fixed zone of enzyme is inexpensive and easily positioned in the capillary to support electrophoresis mediated microanalysis using neuraminidase to analyze sialic acid linkages. To circumvent the limitations of diffusion during static incubation, the incubation period is reproducibly achieved by varying the number of forward and reverse passes the substrate makes through the stationary fixed zone using in-capillary electrophoretic mixing. A KM value of 3.3 ± 0.8 mM (Vmax, 2100 ± 200 μM/min) was obtained for 3'-sialyllactose labeled with 2-aminobenzoic acid using neuraminidase from Clostridium perfringens that cleaves sialic acid monomers with an α2-3,6,8,9 linkage, which is similar to values reported in the literature that required benchtop analyses. The enzyme cleaves the 2-3 linkage faster than the 2-6, and a KM of 2 ± 1 mM (Vmax, 400 ± 100 μM/min) was obtained for the 6'-sialyllactose substrate. An alternative neuraminidase selective for 2-3 sialic acid linkages generated a KM value of 3 ± 2 mM (Vmax, 900 ± 300 μM/min) for 3'-sialyllactose. With a knowledge of Vmax, the method was applied to a mixture of 2-3 and 2-6 sialyllactose as well as 2-3 and 2-6 sialylated triantennary glycan. Nanogel electrophoresis is an inexpensive, rapid, and simple alternative to current technologies used to distinguish the composition of 3' and 6' sialic acid linkages.
Gejl, Michael; Rungby, Jørgen; Brock, Birgitte; Gjedde, Albert
2014-08-01
Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic incretin hormone with both pancreatic and extrapancreatic effects. Studies of GLP-1 reveal significant effects in regions of brain tissue that regulate appetite and satiety. GLP-1 mimetics are used for the treatment of type 2 diabetes mellitus. GLP-1 interacts with peripheral functions in which the autonomic nervous system plays an important role, and emerging pre-clinical findings indicate a potential neuroprotective role of the peptide, for example in models of stroke and in neurodegenerative disorders. A century ago, Leonor Michaelis and Maud Menten described the steady-state enzyme kinetics that still apply to the multiple receptors, transporters and enzymes that define the biochemical reactions of the brain, including the glucose-dependent impact of GLP-1 on blood-brain glucose transfer and metabolism. This MiniReview examines the potential of GLP-1 as a molecule of interest for the understanding of brain energy metabolism and with reference to the impact on brain metabolism related to appetite and satiety regulation, stroke and neurodegenerative disorders. These effects can be understood only by reference to the original formulation of the Michaelis-Menten equation as applied to a chain of kinetically controlled steps. Indeed, the effects of GLP-1 receptor activation on blood-brain glucose transfer and brain metabolism of glucose depend on the glucose concentration and relative affinities of the steps both in vitro and in vivo, as in the pancreas. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Sudhamalla, Babu; Kumar, Mahesh; Roy, Karnati R; Kumar, R Sunil; Bhuyan, Abani K
2013-11-01
It is known that tandem domains of enzymes can carry out catalysis independently or by collaboration. In the case of cysteine proteases, domain sequestration abolishes catalysis because the active site residues are distributed in both domains. The validity of this argument is tested here by using isolated human ribosomal protein S4, which has been recently identified as an unorthodox cysteine protease. Cleavage of the peptide substrate Z-FR↓-AMC catalyzed by recombinant C-terminal domain of human S4 (CHS4) is studied by fluorescence-monitored steady-state and stopped-flow kinetic methods. Proteolysis and autoproteolysis were analyzed by electrophoresis. The CHS4 domain comprised of sequence residues 116-263 has been cloned and ovreexpressed in Escherichia coli. The purified domain is enzymatically active. Barring minor differences, steady-state kinetic parameters for catalysis by CHS4 are very similar to those for full-length human S4. Further, stopped-flow transient kinetics of pre-steady-state substrate binding shows that the catalytic mechanism for both full-length S4 and CHS4 obeys the Michaelis-Menten model adequately. Consideration of the evolutionary domain organization of the S4e family of ribosomal proteins indicates that the central domain (residues 94-170) within CHS4 is indispensable. The C-terminal domain can carry out catalysis independently and as efficiently as the full-length human S4 does. Localization of the enzyme function in the C-terminal domain of human S4 provides the only example of a cysteine endoprotease where substrate-mediated intramolecular domain interaction is irrelevant for catalytic activity. Copyright © 2013 Elsevier B.V. All rights reserved.
Button, D K; Robertson, Betsy; Gustafson, Elizabeth; Zhao, Xiaoming
2004-09-01
A theory for solute uptake by whole cells was derived with a focus on the ability of oligobacteria to sequester nutrients. It provided a general relationship that was used to obtain the kinetic constants for in situ marine populations in the presence of naturally occurring substrates. In situ affinities of 0.9 to 400 liters g of cells(-1) h(-1) found were up to 10(3) times smaller than those from a "Marinobacter arcticus " isolate, but springtime values were greatly increased by warming. Affinities of the isolate for usual polar substrates but not for hydrocarbons were diminished by ionophores. A kinetic curve or Monod plot was constructed from the best available data for cytoarchitectural components of the isolate by using the theory together with concepts and calculations from first principles. The order of effect of these components on specific affinity was membrane potential > cytoplasmic enzyme concentration > cytoplasmic enzyme affinity > permease concentration > area of the permease site > translation coefficient > porin concentration. Component balance was influential as well; a small increase in cytoplasmic enzyme concentration gave a large increase in the effect of permease concentration. The effect of permease concentration on specific affinity was large, while the effect on K(m) was small. These results are in contrast to the Michaelis-Menten theory as applied by Monod that has uptake kinetics dependent on the quality of the permease molecules, with K(m) as an independent measure of affinity. Calculations demonstrated that most oligobacteria in the environment must use multiple substrates simultaneously to attain sufficient energy and material for growth, a requirement consistent with communities largely comprising few species.
Huang, Hsuan-Ming; Ismail-Beigi, Faramarz; Muzic, Raymond F
2011-08-01
A new model is introduced that individually resolves the delivery, transport, and phosphorylation steps of metabolism of glucose and its analogs in skeletal muscle by interpreting dynamic positron emission tomography (PET) data. The model uniquely utilizes information obtained from the competition between glucose and its radiolabeled analogs. Importantly, the model avoids use of a lumped constant which may depend on physiological state. Four basic physiologic quantities constitute our model parameters, including the fraction of total tissue space occupied by interstitial space (f(IS)), a flow-extraction product and interstitial (IS(g)) and intracellular (IC(g)) glucose concentrations. Using the values of these parameters, cellular influx (CI) and efflux (CE) of glucose, glucose phosphorylation rate (PR), and maximal transport (V(G)) and phosphorylation capacities (V(H)) can all be determined. Herein, the theoretical derivation of our model is addressed and characterizes its properties via simulation. Specifically, the model performance is evaluated by simulation of basal and euglycemic hyperinsulinemic (EH) conditions. In fitting the model-generated, synthetic data (including noise), mean estimates of all but IC(g) of the parameter values are within 5% of their values for both conditions. In addition, mean errors of CI, PR, and V(G) are less than 5% whereas those of VH and CE are not. It is concluded that under the conditions tested, the novel model can provide accurate parameter estimates and physiological quantities, except IC(g) and two quantities that are dependent on IC(g), namely CE and VH. However, the ability to estimate IC(g) seems to improve with increases in intracellular glucose concentrations as evidenced by comparing IC(g) estimates under basal vs EH conditions.
Oldiges Marco
2009-01-01
Full Text Available Abstract Background To understand the dynamic behavior of cellular systems, mathematical modeling is often necessary and comprises three steps: (1 experimental measurement of participating molecules, (2 assignment of rate laws to each reaction, and (3 parameter calibration with respect to the measurements. In each of these steps the modeler is confronted with a plethora of alternative approaches, e. g., the selection of approximative rate laws in step two as specific equations are often unknown, or the choice of an estimation procedure with its specific settings in step three. This overall process with its numerous choices and the mutual influence between them makes it hard to single out the best modeling approach for a given problem. Results We investigate the modeling process using multiple kinetic equations together with various parameter optimization methods for a well-characterized example network, the biosynthesis of valine and leucine in C. glutamicum. For this purpose, we derive seven dynamic models based on generalized mass action, Michaelis-Menten and convenience kinetics as well as the stochastic Langevin equation. In addition, we introduce two modeling approaches for feedback inhibition to the mass action kinetics. The parameters of each model are estimated using eight optimization strategies. To determine the most promising modeling approaches together with the best optimization algorithms, we carry out a two-step benchmark: (1 coarse-grained comparison of the algorithms on all models and (2 fine-grained tuning of the best optimization algorithms and models. To analyze the space of the best parameters found for each model, we apply clustering, variance, and correlation analysis. Conclusion A mixed model based on the convenience rate law and the Michaelis-Menten equation, in which all reactions are assumed to be reversible, is the most suitable deterministic modeling approach followed by a reversible generalized mass action kinetics
Leonard, Erin M; Marentette, Julie R; Balshine, Sigal; Wood, Chris M
2014-03-01
Traditionally, water quality guidelines/criteria are based on lethality tests where results are expressed as a function of waterborne concentrations (e.g. LC50). However, there is growing interest in the use of uptake and binding relationships, such as biotic ligand models (BLM), and in bioaccumulation parameters, such as critical body residue values (e.g. CBR50), to predict metal toxicity in aquatic organisms. Nevertheless, all these approaches only protect species against physiological death (e.g. mortality, failed recruitment), and do not consider ecological death which can occur at much lower concentrations when the animal cannot perform normal behaviours essential for survival. Therefore, we investigated acute (96 h) Ni toxicity in two freshwater fish species, the round goby (Neogobius melanostomus) and rainbow trout (Oncorhynchus mykiss) and compared LC, BLM, and CBR parameters for various organs, as well as behavioural responses (spontaneous activity). In general, round goby were more sensitive. Ni bioaccumulation displayed Michaelis-Menten kinetics in most tissues, and round goby gills had lower Kd (higher binding affinity) but similar Bmax (binding site density) values relative to rainbow trout gills. Round goby also accumulated more Ni than did trout in most tissues at a given exposure concentration. Organ-specific 96 h acute CBR values tended to be higher in round goby but 96 h acute CBR50 and CBR10 values in the gills were very similar in the two species. In contrast, LC50 and LC10 values were significantly higher in rainbow trout. With respect to BLM parameters, gill log KNiBL values for bioaccumulation were higher by 0.4-0.8 log units than the log KNiBL values for toxicity in both species, and both values were higher in goby (more sensitive). Round goby were also more sensitive with respect to the behavioural response, exhibiting a significant decline of 63-75 % in movements per minute at Ni concentrations at and above only 8 % of the LC50 value
Long, Cormac G; Gilbertson, John D; Vijayaraghavan, Ganesh; Stevenson, Keith J; Pursell, Christopher J; Chandler, Bert D
2008-08-06
Thiol monolayer-protected Au clusters (MPCs) were prepared using dendrimer templates, deposited onto a high-surface-area titania, and then the thiol stabilizers were removed under H2/N2. The resulting Au catalysts were characterized with transmission electron microscopy, X-ray photoelectron spectroscopy, and infrared spectroscopy of adsorbed CO. The Au catalysts prepared via this route displayed minimal particle agglomeration during the deposition and activation steps. Structural data obtained from the physical characterization of the Au catalysts were comparable to features exhibited from a traditionally prepared standard Au catalyst obtained from the World Gold Council (WGC). A differential kinetic study of CO oxidation catalysis by the MPC-prepared Au and the standard WGC catalyst showed that these two catalyst systems have essentially the same reaction order and Arrhenius apparent activation energies (28 kJ/mol). However, the MPC-prepared Au catalyst shows 50% greater activity for CO oxidation. Using a Michaelis-Menten approach, the oxygen binding constants for the two catalyst systems were determined and found to be essentially the same within experimental error. To our knowledge, this kinetic evaluation is the first experimental determination of oxygen binding by supported Au nanoparticle catalysts under working conditions. The values for the oxygen binding equilibrium constant obtained from the Michaelis-Menten treatment (ca. 29-39) are consistent with ultra-high-vacuum measurements on model catalyst systems and support density functional theory calculations for oxygen binding at corner or edge atoms on Au nanoparticles and clusters.
Zhou, Chuanzheng; Chattopadhyaya, Jyoti
2010-04-02
In this study, 12 different native or LNA, carba-LNA-modified dinucleoside phosphates were designed as simple chemical models to study how carba-LNA modifications improve the 3'-exonuclease (SVPDE in this study) resistance of internucleotidic phosphate compared to those exhibited by LNA-modified and the native counterparts. Michaelis-Menten kinetic studies for dimers 3 - 7, in which the LNA or carba-LNA modifications are located at the 5'-end, showed that (i) increased 3'-exonuclease resistance of (5')[LNA-T](p)T (3) compared to the native (5')T(p)T (1) was mainly attributed to steric hindrance imposed by the LNA modification that retards the nuclease binding (K(M)) and (ii) digestion of (5')[carba-LNA-dT](p)T (4) and (5')[LNA-T](p)T (3), however, exhibit similar K(M)s, whereas the former shows a 100x decrease in K(cat) and is hence more stable than the latter. By studying the correlation between log k(cat) and pK(a) of the departing 3'(or 6')-OHs for 3-7, we found the pK(a) of 3'-OH of carba-LNA-T was 1.4 pK(a) units higher than that of LNA-T, and this relatively less acidic character of the 3'-OH in the former leads to the 100x decrease in the catalytic efficiency for the digestion of (5')[carba-LNA-T](p)T (4). In contrast, Michaelis-Menten kinetic studies for dimers 9-12, with the LNA or carba-LNA modifications at the 3'-end, showed that the digestion of (5')T(p)[LNA-T] (9) exhibited similar K(M) but k(cat) decreased around 40 times compared to that of the native (5')T(p)T (1). Similar k(cat) values have been observed for digestion of (5')T(p)[carba-LNA-T] (10) and (5')T(p)[LNA-T] (9). The higher stability of carba-LNA modified dimer 10 compared with LNA modified dimer 9 comes solely from the increased K(M).
André Rosa Martins
2015-06-01
Full Text Available ResumoOs processos enzimáticos que seguem o modelo cinético de Michaelis-Menten foram estudados a partir de diferentes propostas para descrever a etapa de inibição reversível. As propostas de inibição foram comparadas a partir de um processo genérico, onde as constantes cinéticas receberam valores unitários e o valor numérico da concentração de substrato foi dez (10 vezes superior ao valor numérico da concentração de enzima. Para cada proposta de modelo de inibição foram obtidas soluções numéricas a partir de sistema não linear de equações diferenciais ordinárias, gerando gráficos que apresentaram, separadamente, a variação das concentrações da enzima, dos complexos enzimáticos, do substrato e do produto da reação. Foi obtido um modelo, dentre as propostas avaliadas, com desempenho indicando comportamento similar ao verificado no modelo clássico de Michaelis-Menten, onde o complexo de reação é rapidamente formado e, ao longo do processo, decai até tender a zero. Em contrapartida, diferentemente do modelo clássico, na nova proposta de modelo o efeito de inibição começa em zero e, ao longo do processo, tende ao valor nominal da concentração inicial da enzima. Tais respostas mostraram-se válidas para valores distintos de concentração de enzima e de tempo de processo, mostrando robustez e indicando uma tendência do somatório do substrato e do produto atingir o valor nominal da concentração inicial do substrato ao longo do tempo de processamento.
Yusof, Siti R; Abbott, N Joan; Avdeef, Alex
2017-08-30
Most studies of blood-brain barrier (BBB) permeability and transport are conducted at a single pH, but more detailed information can be revealed by using multiple pH values. A pH-dependent biophysical model was applied to the mechanistic analysis of published pH-dependent BBB luminal uptake data from three opioid derivatives in rat: pentazocine (Suzuki et al., 2002a, 2002b), naloxone (Suzuki et al., 2010a), and oxycodone (Okura et al., 2008). Two types of data were processed: in situ brain perfusion (ISBP) and brain uptake index (BUI). The published perfusion data were converted to apparent luminal permeability values, Papp, and analyzed by the pCEL-X program (Yusof et al., 2014), using the pH-dependent Crone-Renkin equation (pH-CRE) to determine the impact of cerebrovascular flow on the Michaelis-Menten transport parameters (Avdeef and Sun, 2011). For oxycodone, the ISBP data had been measured at pH7.4 and 8.4. The present analysis indicates a 7-fold lower value of the cerebrovascular flow velocity, Fpf, than that expected in the original study. From the pyrilamine-inhibited data, the flow-corrected passive intrinsic permeability value was determined to be P0=398×10(-6)cm·s(-1). The uptake data indicate that the neutral form of oxycodone is affected by a transporter at pH8.4. The extent of the cation uptake was less certain from the available data. For pentazocine, the brain uptake by the BUI method had been measured at pH5.5, 6.5, and 7.4, in a concentration range 0.1-40mM. Under similar conditions, ISBP data were also available. The pH-CRE determined values of Fpf from both methods were nearly the same, and were smaller than the expected value in the original publication. The transport of the cationic pentazocine was not fully saturated at pH5.5 at 40mM. The transport of the neutral species at pH7.4 appeared to reach saturation at 40mM pentazocine concentration, but not at 12mM. In the case of naloxone, a pH-dependent Michaelis-Menten equation (p
Introducing Michaelis-Menten Kinetics through Simulation
Halkides, Christopher J.; Herman, Russell
2007-01-01
We describe a computer tutorial that introduces the concept of the steady state in enzyme kinetics. The tutorial allows students to produce graphs of the concentrations of free enzyme, enzyme-substrate complex, and product versus time in order to learn about the approach to steady state. By using a range of substrate concentrations and rate…
Introducing Michaelis-Menten Kinetics through Simulation
Halkides, Christopher J.; Herman, Russell
2007-01-01
We describe a computer tutorial that introduces the concept of the steady state in enzyme kinetics. The tutorial allows students to produce graphs of the concentrations of free enzyme, enzyme-substrate complex, and product versus time in order to learn about the approach to steady state. By using a range of substrate concentrations and rate…
Leonard, Erin M; Wood, Chris M
2013-06-01
We investigated the bioaccumulation and acute toxicity (48 h or 96 h) of Ni in four freshwater invertebrate species in two waters with hardness of 40 (soft water) and 140 mg L(-1) as CaCO(3) (hard water). Sensitivity order (most to least) was Lymnaea stagnalis > Daphnia pulex > Lumbriculus variegatus > Chironomus riparius. In all cases water hardness was protective against acute Ni toxicity with LC(50) values 3-3.5× higher in the hard water vs. soft water. In addition, higher water hardness significantly reduced Ni bioaccumulation in these organisms suggesting that competition by Ca and Mg for uptake at the biotic ligand may contribute to higher metal resistance. CBR50 values (Critical Body Residues) were less dependent on water chemistry (i.e. more consistent) than LC(50) values within and across species by ~2 fold. These data support one of the main advantages of the Tissue Residue Approach (TRA) where tissue concentrations are generally less variable than exposure concentrations with respect to toxicity. Whole body Ni bioaccumulation followed Michaelis-Menten kinetics in all organisms, with greater hardness tending to decrease B(max) with no consistent effect on K(d). Across species, acute Ni LC(50) values tended to increase with both K(d) and B(max) values - i.e. more sensitive species exhibited higher binding affinity and lower binding capacity for Ni, but there was no correlation with body size. With respect to biotic ligand modeling, log K(NiBL) values derived from Ni bioaccumulation correlated well with log K(NiBL) values derived from toxicity testing. Both whole body Na and Mg levels were disturbed, suggesting that disruption of ionoregulatory homeostasis is a mechanism of acute Ni toxicity. In L. stagnalis, Na depletion was a more sensitive endpoint than mortality, however, the opposite was true for the other organisms. This is the first study to show the relationship between Na and Ni. Copyright © 2013 Elsevier Inc. All rights reserved.
Sims, Paul A.
2009-01-01
The King-Altman method of deriving rate equations for enzymatic reactions is applied to the derivation of the Michaelis-Menten equation, along with an explanation for how (or why) the King-Altman method works in this case. The slightly more complicated cases of competitive inhibition and a two-substrate enzyme-catalyzed reaction are then treated…
Sims, Paul A.
2009-01-01
The King-Altman method of deriving rate equations for enzymatic reactions is applied to the derivation of the Michaelis-Menten equation, along with an explanation for how (or why) the King-Altman method works in this case. The slightly more complicated cases of competitive inhibition and a two-substrate enzyme-catalyzed reaction are then treated…
Modeling of Bacillus spores: Inactivation and Outgrowth
2011-03-01
52 Michaelis - Menten Kinetics ...of repair mechanism [36]. These models were based on Michaelis - Menten kinetics , which is also the foundation of the work in this research Michaelis ...catalyzed reactions. Michaelis - Menten kinetics is a model of enzyme kinetics . The Michaelis - Menten equation describes the rates of enzymatic reactions by
2017-01-01
The specific consumption rate of substrate, as well as the associated specific growth rate, is an essential parameter in the mathematical description of substrate-limited microbial growth. In this paper we develop a completely new kinetic model of substrate transport, based on recent knowledge on the structural biology of transport proteins, which correctly describes very accurate experimental results at near-zero substrate concentration values found in the literature, where the widespread Michaelis-Menten model fails. Additionally, our model converges asymptotically to Michaelis-Menten predictions as substrate concentration increases. Instead of the single active site enzymatic reaction of Michaelis-Menten type, the proposed model assumes a multi-site kinetics, simplified as an apparent all-or-none mechanism for the transport, which is controlled by means of the local substrate concentration in the close vicinity of the transport protein. Besides, the model also assumes that this local concentration is not equal to the mean substrate concentration experimentally determined in the culture medium. Instead, we propose that it fluctuates with a mostly exponential distribution of Weibull type. PMID:28187189
More Nuts and Bolts of Michaelis-Menten Enzyme Kinetics
Lechner, Joseph H.
2011-01-01
Several additions to a classroom activity are proposed in which an "enzyme" (the student) converts "substrates" (nut-bolt assemblies) into "products" (separated nuts and bolts) by unscrewing them. (Contains 1 table.)
Enzyme Kinetics and the Michaelis-Menten Equation
Biaglow, Andrew; Erickson, Keith; McMurran, Shawnee
2010-01-01
The concepts presented in this article represent the cornerstone of classical mathematical biology. The central problem of the article relates to enzyme kinetics, which is a biochemical system. However, the theoretical underpinnings that lead to the formation of systems of time-dependent ordinary differential equations have been applied widely to…
More Nuts and Bolts of Michaelis-Menten Enzyme Kinetics
Lechner, Joseph H.
2011-01-01
Several additions to a classroom activity are proposed in which an "enzyme" (the student) converts "substrates" (nut-bolt assemblies) into "products" (separated nuts and bolts) by unscrewing them. (Contains 1 table.)
Enzyme Kinetics and the Michaelis-Menten Equation
Biaglow, Andrew; Erickson, Keith; McMurran, Shawnee
2010-01-01
The concepts presented in this article represent the cornerstone of classical mathematical biology. The central problem of the article relates to enzyme kinetics, which is a biochemical system. However, the theoretical underpinnings that lead to the formation of systems of time-dependent ordinary differential equations have been applied widely to…
Cyclodextrin-based artificial oxidases with high rate accelerations and selectivity
Zhou, You; Lindbäck, Emil Anders; Pedersen, Christian Marcus
2014-01-01
Three cyclodextrin derivatives with one to four 2-O-formylmethyl groups attached to the secondary rim were prepared and investigated as catalysts for the oxidation of aminophenols in buffered dilute hydrogen peroxide. The derivatives were found to be Michaelis-Menten catalysts and to give rate ac....... The ability of one of the new artificial enzymes to oxidize selectively one aminophenol from a mixture of two was investigated giving substrate selectivities of up to 16:1. © 2014 Elsevier Ltd. All rights reserved....
Armstrong, Robert A.
2008-10-01
Pasciak and Gavis were first to propose a model of nutrient uptake that includes both physical transport by diffusion and active biological transport across the cell membrane. While the Pasciak-Gavis model is not complicated mathematically (it can be expressed in closed form as a quadratic equation), its parameters are not so easily interpretable biologically as are the parameters of the Michaelis-Menten uptake model; this lack of transparency is probably the main reason the Pasciak-Gavis model has not been adopted by ecologically oriented modelers. Here I derive a Michaelis-like approximation to the Pasciak-Gavis model, and show how the parameters of the latter map to those of the Michaelis-like model. The derived approximation differs from a pure Michaelis-Menten model in a subtle but potentially critical way: in a pure Michaelis-Menten model, the half-saturation constant for nutrient uptake is independent of the density of transporter (or "porter") proteins on the cell surface, while in the Pasciak-Gavis model and its Michaelis-like approximation, the half-saturation constant does depend on the density of porter proteins. The Pasciak-Gavis model predicts a unique relationship between cell size, nutrient concentration in the medium, the half-saturation constant of porter-limited nutrient uptake, and the resulting rate of uptake; the Michaelis-like approximation preserves the most important feature of that relationship, the size at which porter limitation gives way to diffusion limitation. Finally I discuss the implications for community structure that are implied by the Pasciak-Gavis model and its Michaelis-like approximation.
In situ measurements of volatile aromatic hydrocarbon biodegradation rates in groundwater
Cozzarelli, Isabelle M.; Bekins, Barbara A.; Eganhouse, Robert P.; Warren, Ean; Essaid, Hedeff I.
2010-01-01
Benzene and alkylbenzene biodegradation rates and patterns were measured using an in situ microcosm in a crude-oil contaminated aquifer near Bemidji, Minnesota. Benzene-D6, toluene, ethylbenzene, o-, m- and p-xylenes and four pairs of C 3- and C 4-benzenes were added to an in situ microcosm and studied over a 3-year period. The microcosm allowed for a mass-balance approach and quantification of hydrocarbon biodegradation rates within a well-defined iron-reducing zone of the anoxic plume. Among the BTEX compounds, the apparent order of persistence is ethylbenzene > benzene > m,p-xylenes > o-xylene ≥ toluene. Threshold concentrations were observed for several compounds in the in situ microcosm, below which degradation was not observed, even after hundreds of days. In addition, long lag times were observed before the onset of degradation of benzene or ethylbenzene. The isomer-specific degradation patterns were compared to observations from a multi-year study conducted using data collected from monitoring wells along a flowpath in the contaminant plume. The data were fit with both first-order and Michaelis-Menten models. First-order kinetics provided a good fit for hydrocarbons with starting concentrations below 1 mg/L and Michaelis-Menten kinetics were a better fit when starting concentrations were above 1 mg/L, as was the case for benzene. The biodegradation rate data from this study were also compared to rates from other investigations reported in the literature.
In situ measurements of volatile aromatic hydrocarbon biodegradation rates in groundwater
Cozzarelli, I.M.; Bekins, B.A.; Eganhouse, R.P.; Warren, E.; Essaid, H.I.
2010-01-01
Benzene and alkylbenzene biodegradation rates and patterns were measured using an in situ microcosm in a crude-oil contaminated aquifer near Bemidji, Minnesota. Benzene-D6, toluene, ethylbenzene, o-, m- and p-xylenes and four pairs of C3- and C4-benzenes were added to an in situ microcosm and studied over a 3-year period. The microcosm allowed for a mass-balance approach and quantification of hydrocarbon biodegradation rates within a well-defined iron-reducing zone of the anoxic plume. Among the BTEX compounds, the apparent order of persistence is ethylbenzene > benzene > m,p-xylenes > o-xylene ≥ toluene. Threshold concentrations were observed for several compounds in the in situ microcosm, below which degradation was not observed, even after hundreds of days. In addition, long lag times were observed before the onset of degradation of benzene or ethylbenzene. The isomer-specific degradation patterns were compared to observations from a multi-year study conducted using data collected from monitoring wells along a flowpath in the contaminant plume. The data were fit with both first-order and Michaelis-Menten models. First-order kinetics provided a good fit for hydrocarbons with starting concentrations below 1 mg/L and Michaelis-Menten kinetics were a better fit when starting concentrations were above 1 mg/L, as was the case for benzene. The biodegradation rate data from this study were also compared to rates from other investigations reported in the literature.
Association of State Laws and Healthcare Workers' Influenza Vaccination Rates.
Lin, Chyongchiou Jeng; Nowalk, Mary Patricia; Raymund, Mahlon; Sweeney, Patricia M; Zimmerman, Richard K
2016-02-01
State laws are being used to increase healthcare worker (HCW) influenza vaccine uptake. Approximately 40% of states have enacted such laws but their effectiveness has been infrequently studied. Data sources for this study were the 2000-2011 U.S. National Health Interview Survey Adult Sample File and a summary of U.S. state HCW influenza vaccination laws. Hierarchical linear modeling was used for two time periods: 1) 2000-2005 (before enactment of many state laws) and 2) 2006-2011 (a time of increased enactment of state HCW influenza vaccination legislation). During 2000-2005, two states had HCW influenza vaccination laws and HCW influenza vaccination rates averaged 22.5%. In 2006-2011, 19 states had such laws and vaccination rates averaged 50.9% (p law score. Although laws varied widely in scope and applicability, states with HCW influenza vaccination laws reported higher HCW vaccination rates.
谢晶; 刘晓丹
2006-01-01
对香菇分别在273 K、283 K和293 K的密闭容器中氧气和二氧化碳随时间、浓度的变化进行了测定,根据酶动力学原理,利用非线性估计法、多重回归分析分别获得气体成分的变化率曲线和米式方程,从而获得相应的参数,求得反映呼吸状态的呼吸熵动态变化规律以及温度影响参数--活化能,并以此求出在任意温度、有氧呼吸气体环境条件下果蔬的最大呼吸速率,为气调包装系统设计提供理论依据.
Inferring the Rate-Length Law of Protein Folding
Lane, Thomas J
2013-01-01
We investigate the rate-length scaling law of protein folding, a key undetermined scaling law in the analytical theory of protein folding. We demonstrate that chain length is a dominant factor determining folding times, and that the unambiguous determination of the way chain length corre- lates with folding times could provide key mechanistic insight into the folding process. Four specific proposed laws (power law, exponential, and two stretched exponentials) are tested against one an- other, and it is found that the power law best explains the data. At the same time, the fit power law results in rates that are very fast, nearly unreasonably so in a biological context. We show that any of the proposed forms are viable, conclude that more data is necessary to unequivocally infer the rate-length law, and that such data could be obtained through a small number of protein folding experiments on large protein domains.
Did Unilateral Divorce Laws Raise Divorce Rates in Western Europe?
Kneip, Thorsten; Bauer, Gerrit
2009-01-01
The increase in European divorce rates over the past decades was accompanied by several changes in divorce laws. Yet for European countries, research on the effects of divorce law on the divorce rate is scarce. Most of the existing studies are based on data from North America and provide numerous, but inconsistent, results. We use fixed-effects…
Use of Mushroom Tyrosinase to Introduce Michaelis-Menten Enzyme Kinetics to Biochemistry Students
Flurkey, William H.; Inlow, Jennifer K.
2017-01-01
An inexpensive enzyme kinetics laboratory exercise for undergraduate biochemistry students is described utilizing tyrosinase from white button mushrooms. The exercise can be completed in one or two three-hour lab sessions. The optimal amounts of enzyme, substrate (catechol), and inhibitor (kojic acid) are first determined, and then kinetic data is…
The Impact of Deviation from Michaelis-Menten Saturation on Mathematical Model Stability Properties
Blackwell, Charles; Kliss, Mark (Technical Monitor)
1998-01-01
Based on purely abstract ecological theory, it has been argued that a system composed of two or more consumers competing for the same resource cannot persist. By analysis on a Monod format mathematical model, Hubble and others demonstrated that this assertion is true for all but very special cases of such competing organisms which are determined by an index formed by a grouping of. the parameters which characterize the biological processes of the competing organisms. In the laboratory, using a bioreactor, Hansen and Hubble obtained confirmatory results for several cases of two competing species, and they characterized it as "qualitative confirmation" of the assertion. This result is amazing, since the analysis required the exact equality of the hey index, and it seems certain that no pair of organism species could have exactly equal values. It is quite plausible, however, that pairs of organism species could have approximately equal indices, and the question of how different they could be and still have coexistence of the two (or more) presents itself. In this paper, the pursuit of this question and a compatible resolution is presented.
The Nuts and Bolts of Michaelis-Menten Enzyme Kinetics: Suggestions and Clarifications
Silverstein, Todd
2011-01-01
Matthew Junker's recent article describes a useful and effective enzyme kinetics application and analogy in which students simulate enzyme activity by unscrewing nut-bolt "substrate molecules", thus, converting them into separate nuts and bolts "products". A number of suggestions and corrections are presented that improve the clarity and accuracy…
Specificity of non-Michaelis-Menten enzymes: necessary information for analyzing metabolic pathways.
Cornish-Bowden, Athel; Cárdenas, María Luz
2010-12-16
The specificity of an enzyme obeying the Michaelis−Menten equation is normally measured by comparing the kcat/Km for different substrates, but this is inappropriate for enzymes with a Hill coefficient h different from 1. The obvious alternative of generalizing Km in the expression as K0.5, the substrate concentration for half-saturation, is better, but it is not entirely satisfactory either, and here we show that kcat/K0.5(h) gives satisfactory results for analyzing the kinetic behavior of metabolic pathways. The importance of using kcat/K0.5(h) increases with the value of h, but even when h is small, it makes an appreciable difference, as illustrated for the mammalian hexokinases. Reinterpretation of data for the specificity of these enzymes in terms of the proposed definition indicates that hexokinase D, often believed highly specific for glucose, and accordingly called “glucokinase”, actually has the lowest preference for glucose over fructose of the four isoenzymes found in mammals.
Estimation of Michaelis-Menten constant of efflux transporter considering asymmetric permeability.
Sugano, Kiyohiko; Shirasaka, Yoshiyuki; Yamashita, Shinji
2011-10-14
It was previously reported that the apparent K(m) values of P-gp in apical to basal (A to B) and basal to apical (B to A) directions were different. The purpose of the present study was to derive a theoretical framework by which this asymmetric concentration-permeability profile can be explained using a single intrinsic K(m) value. A three compartment model was used to represent the apical, cytosol and basal compartments. The difference of passive permeability and the surface areas between the apical and basolateral membrane were explicitly taken into account. Applying the steady state approximation and considering the mass balance in the cytosol compartment, an open analytical solution was obtained. By using this equation, the asymmetric concentration-permeability profile was appropriately reproduced. In addition, the expression level dependency of apparent K(m) was also reproduced. Copyright © 2011 Elsevier B.V. All rights reserved.
Estudio de bioequivalencia de teofilina considerando cinética de Michaelis-Menten
Fagiolino, Pietro; Turlier, M.; Payssé, Helena; Aiache, Jean-Marc
1994-01-01
Se presenta un estudio de bioequivalencia de dos formas farmacéuticas de Teofilina de liberación prolongada, teniendo en cuenta la cinética no lineal de eliminación de esta droga. Una dosis de 300 mg de Teofilina fue administrada a 12 voluntarios sanos, en un diseno aleatorio, cruzado y compensado. Se utilizó una forma farmacéutica elixir, a los efectos de estimar los parámetros farmacocinéticos de eliminación en cada individuo. Como parámetros de evaluación de la biodisponibilidad se utilizó...
The Nuts and Bolts of Michaelis-Menten Enzyme Kinetics: Suggestions and Clarifications
Silverstein, Todd
2011-01-01
Matthew Junker's recent article describes a useful and effective enzyme kinetics application and analogy in which students simulate enzyme activity by unscrewing nut-bolt "substrate molecules", thus, converting them into separate nuts and bolts "products". A number of suggestions and corrections are presented that improve the clarity and accuracy…
SBMLsqueezer: A CellDesigner plug-in to generate kinetic rate equations for biochemical networks
Schröder Adrian
2008-04-01
Full Text Available Abstract Background The development of complex biochemical models has been facilitated through the standardization of machine-readable representations like SBML (Systems Biology Markup Language. This effort is accompanied by the ongoing development of the human-readable diagrammatic representation SBGN (Systems Biology Graphical Notation. The graphical SBML editor CellDesigner allows direct translation of SBGN into SBML, and vice versa. For the assignment of kinetic rate laws, however, this process is not straightforward, as it often requires manual assembly and specific knowledge of kinetic equations. Results SBMLsqueezer facilitates exactly this modeling step via automated equation generation, overcoming the highly error-prone and cumbersome process of manually assigning kinetic equations. For each reaction the kinetic equation is derived from the stoichiometry, the participating species (e.g., proteins, mRNA or simple molecules as well as the regulatory relations (activation, inhibition or other modulations of the SBGN diagram. Such information allows distinctions between, for example, translation, phosphorylation or state transitions. The types of kinetics considered are numerous, for instance generalized mass-action, Hill, convenience and several Michaelis-Menten-based kinetics, each including activation and inhibition. These kinetics allow SBMLsqueezer to cover metabolic, gene regulatory, signal transduction and mixed networks. Whenever multiple kinetics are applicable to one reaction, parameter settings allow for user-defined specifications. After invoking SBMLsqueezer, the kinetic formulas are generated and assigned to the model, which can then be simulated in CellDesigner or with external ODE solvers. Furthermore, the equations can be exported to SBML, LaTeX or plain text format. Conclusion SBMLsqueezer considers the annotation of all participating reactants, products and regulators when generating rate laws for reactions. Thus, for
Divorce Laws and Divorce Rate in the U.S.
Marcassa, Stefania
2013-01-01
International audience; At the end of the 1960s, the U.S. divorce law underwent major changes and the divorce rate almost doubled in all of the states. This paper shows that changes in property division, alimony transfers, and child custody assignments account for a substantial share of the increase in the divorce rate, especially for young, college educated couples with children. I solve and calibrate a model where agents make decisions on their marital status, savings, and labor supply. Und...
Divorce Laws and Divorce Rate in the U.S.
Marcassa, Stefania
2011-01-01
At the end of the 1960s, the U.S. divorce laws underwent major changes and the divorce rate more than doubled in all of the states. The new laws introduced unilateral divorce in most of the states and changes in divorce settlements in every state, such as property division, alimony transfers, and child custody assignments. The empirical literature so far has focused on the switch from consensual to unilateral divorce and found that this change cannot fully account for the increase in the divo...
CONVERGENCE RATES IN THE LAW OF LOGARITHM OF RANDOM ELEMENTS
梁汉营; 苏淳; 王岳宝
2001-01-01
We discuss the convergence rates in the law of logarithm for partial sums and randomly indexed partial sums of independent random variables in Banach space, and find the necessary and sufficient conditions on the convergence rates. The results of [1-3] for sums of i.i.d, real valued r.v.'s are extended; Yang's[4] result is generalized and the necessity part of Yang's result is also discussed; a conjecture for the i.i.d, real-valued r.v.'s of [5] is answered in Banach space.
Hadamard Transform Time-of-Flight Mass Spectrometry
2010-01-26
determined by direct fitting of the initial rates data to the Michaelis - Menten equation. Excellent agreement is shown amongst the values indicating that...of VGVKVR by trypsin at pH 8.5. The dashed red line in the figure shows a best fit to the Michaelis - Menten equation for the data collected. The
Hadamard Transform Time-of-Flight Spectroscopy
2010-01-26
system presented in Figure 13 were determined by direct fitting of the initial rates data to the Michaelis - Menten equation. Excellent agreement is...trypsin at pH 8.5. The dashed red line in the figure shows a best fit to the Michaelis - Menten equation for the data collected. The error bars in
Scaling laws in the dynamics of crime growth rate
Alves, Luiz G. A.; Ribeiro, Haroldo V.; Mendes, Renio S.
2013-06-01
The increasing number of crimes in areas with large concentrations of people have made cities one of the main sources of violence. Understanding characteristics of how crime rate expands and its relations with the cities size goes beyond an academic question, being a central issue for contemporary society. Here, we characterize and analyze quantitative aspects of murders in the period from 1980 to 2009 in Brazilian cities. We find that the distribution of the annual, biannual and triannual logarithmic homicide growth rates exhibit the same functional form for distinct scales, that is, a scale invariant behavior. We also identify asymptotic power-law decay relations between the standard deviations of these three growth rates and the initial size. Further, we discuss similarities with complex organizations.
Scaling laws in the dynamics of crime growth rate
Alves, Luiz Gustavo de Andrade; Mendes, Renio dos Santos
2013-01-01
The increasing number of crimes in areas with large concentrations of people have made cities one of the main source of violence. Understanding characteristics of how crime rate expands and its relations with the cities size goes beyond an academic question, being a central issue for the contemporary society. Here, we characterize and analyze quantitative aspects of murders in the period from 1980 to 2009 in Brazilian cities. We find that the distribution of the annual, biannual and triannual logarithmic homicide growth rates exhibit the same functional form for distinct scales, that is, a scale invariant behaviour. We also identify asymptotic power-law decay relations between the standard deviations of these three growth rates and the initial size. Further, we discuss similarities with complex organizations.
The effect of divorce laws on divorce rates in Europe
González, L.; Viitanen, T.K.
2006-01-01
This paper analyzes a panel of 18 European countries spanning from 1950 to 2003 to examine the extent to which the legal reforms leading to "easier divorce" that took place during the second half of the 20th century have contributed to the increase in divorce rates across Europe. We use a quasi-experimental set-up and exploit the different timing of the reforms in divorce laws across countries. We account for unobserved country-specific factors by introducing country fixed effects, and we inc...
New types of experimental data shape the use of enzyme kinetics for dynamic network modeling.
Tummler, Katja; Lubitz, Timo; Schelker, Max; Klipp, Edda
2014-01-01
Since the publication of Leonor Michaelis and Maude Menten's paper on the reaction kinetics of the enzyme invertase in 1913, molecular biology has evolved tremendously. New measurement techniques allow in vivo characterization of the whole genome, proteome or transcriptome of cells, whereas the classical enzyme essay only allows determination of the two Michaelis-Menten parameters V and K(m). Nevertheless, Michaelis-Menten kinetics are still commonly used, not only in the in vitro context of enzyme characterization but also as a rate law for enzymatic reactions in larger biochemical reaction networks. In this review, we give an overview of the historical development of kinetic rate laws originating from Michaelis-Menten kinetics over the past 100 years. Furthermore, we briefly summarize the experimental techniques used for the characterization of enzymes, and discuss web resources that systematically store kinetic parameters and related information. Finally, describe the novel opportunities that arise from using these data in dynamic mathematical modeling. In this framework, traditional in vitro approaches may be combined with modern genome-scale measurements to foster thorough understanding of the underlying complex mechanisms.
Gonze, Didier; Abou-Jaoudé, Wassim; Ouattara, Djomangan Adama; Halloy, José
2011-01-01
The recent advance of genetic studies and the rapid accumulation of molecular data, together with the increasing performance of computers, led researchers to design more and more detailed mathematical models of biological systems. Many modeling approaches rely on ordinary differential equations (ODE) which are based on standard enzyme kinetics. Michaelis-Menten and Hill functions are indeed commonly used in dynamical models in systems and synthetic biology because they provide the necessary nonlinearity to make the dynamics nontrivial (i.e., limit-cycle oscillations or multistability). For most of the systems modeled, the actual molecular mechanism is unknown, and the enzyme equations should be regarded as phenomenological. In this chapter, we discuss the validity and accuracy of these approximations. In particular, we focus on the validity of the Michaelis-Menten function for open systems and on the use of Hill kinetics to describe transcription rates of regulated genes. Our discussion is illustrated by numerical simulations of prototype systems, including the Repressilator (a genetic oscillator) and the Toggle Switch model (a bistable system). We systematically compare the results obtained with the compact version (based on Michaelis-Menten and Hill functions) with its corresponding developed versions (based on "elementary" reaction steps and mass action laws). We also discuss the use of compact approaches to perform stochastic simulations (Gillespie algorithm). On the basis of these results, we argue that using compact models is suitable to model qualitatively biological systems.
Nijland, G.O.; Schouls, J.; Goudriaan, J.
2008-01-01
Any agricultural production process is characterized by input¿output relations. In this paper we show that the production functions of Liebig, Mitscherlich and Liebscher for the relation between nutrient supply and crop production can be regarded as special variants of one 'integrated model'. The
Heering, Hendrik A
2012-10-01
Deconvolution of protein film voltammetric data by fitting multiple components (sigmoids, derivative peaks) often is ambiguous when features are partially overlapping, due to exchangeability between the width and the number of components. Here, a new method is presented to obtain the width of the components. This is based on the equivalence between the sigmoidal catalytic response as function of electrode potential, and the classical saturation curve obtained for the enzyme activity as function of the soluble substrate concentration, which is also sigmoidal when plotted versus log[S]. Thus, analysis of the catalytic voltammogram with Lineweaver-Burk, Eadie-Hofstee, and Hanes-Woolf plots is feasible. This provides a very sensitive measure of the cooperativity number (Hill coefficient), which for electrons equals the apparent (fractional) number of electrons that determine the width, and thereby the number of components (kinetic phases). This analysis is applied to the electrocatalytic oxygen reduction by Paracoccus denitrificans cytochrome aa(3) (cytochrome c oxidase). Four partially overlapping kinetic phases are observed that (stepwise) increase the catalytic efficiency with increasingly reductive potential. Translated to cell biology, the activity of the terminal oxidase stepwise adapts to metabolic demand for oxidative phosphorylation. Copyright © 2011 Elsevier B.V. All rights reserved.
Nijland, G.O.; Schouls, J.; Goudriaan, J.
2008-01-01
Any agricultural production process is characterized by input¿output relations. In this paper we show that the production functions of Liebig, Mitscherlich and Liebscher for the relation between nutrient supply and crop production can be regarded as special variants of one 'integrated model'. The mo
Sheiner, L B; Beal, S L
1980-12-01
Individual pharmacokinetic par parameters quantify the pharmacokinetics of an individual, while population pharmacokinetic parameters quantify population mean kinetics, interindividual variability, and residual intraindividual variability plus measurement error. Individual pharmacokinetics are estimated by fitting individual data to a pharmacokinetic model. Population pharmacokinetic parameters are estimated either by fitting all individual's data together as though there was no individual kinetic differences (the naive pooled data approach), or by fitting each individual's data separately, and then combining the individual parameter estimates (the two-stage approach). A third approach, NONMEM, takes a middle course between these, and avoids shortcomings of each of them. A data set consisting of 124 steady-state phenytoin concentration-dosage pairs from 49 patients, obtained in the routine course of their therapy, was analyzed by each method. The resulting population parameter estimates differ considerably (population mean Km, for example, is estimated as 1.57, 5.36, and 4.44 micrograms/ml by the naive pooled data, two-stage, and NONMEN approaches, respectively). Simulations of the data were analyzed to investigate these differences. The simulations indicate that the pooled data approach fails to estimate variabilities and produces imprecise estimates of mean kinetics. The two-stage approach produces good estimates of mean kinetics, but biased and imprecise estimates of interindividual variability. NONMEN produces accurate and precise estimates of all parameters, and also reasonable confidence intervals for them. This performance is exactly what is expected from theoretical considerations and provides empirical support for the use of NONMEM when estimating population pharmacokinetics from routine type patient data.
Did Unilateral Divorce Laws Raise Divorce Rates? A Reconciliation and New Results
Justin Wolfers
2003-01-01
Application of the Coase Theorem to marital bargaining suggests that shifting from a consent divorce regime to no-fault unilateral divorce laws should not affect divorce rates. Each iteration of the empirical literature examining the evolution of divorce rates across US states has yielded different conclusions about the effects of divorce law liberalization. I show that these results reflect a failure to jointly consider both the political endogeneity of these divorce laws and the dynamic res...
Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme
2011-03-18
inhibition, Michaelis - Menten constants, and rates of reactivation for wild-type and V146H/ L363E hCE1 against racemic cyclosarin and stereoisomers of...0017441.t002 Table 3. Inhibition and Michaelis - Menten constants for wild-type and V146H/L363E hCE1 against stereoisomers of sarin and soman model...6 | Issue 3 | e17441 where Km was the nerve agent model Michaelis - Menten constant, k2 the unimolecular phosphonylation rate constant, v the remaining
Soft Black Hole Absorption Rates as Conservation Laws
Avery, Steven G
2016-01-01
The absorption rate of low-energy, or soft, electromagnetic radiation by spherically symmetric black holes in arbitrary dimensions is shown to be fixed by conservation of energy and large gauge transformations. We interpret this result as the explicit realization of the Hawking-Perry-Strominger Ward identity for large gauge transformations in the background of a non-evaporating black hole. Along the way we rederive and extend previous analytic results regarding the absorption rate for the minimal scalar and the photon.
Power law distribution of seismic rates: theory and data
Saichev, A
2004-01-01
We report an empirical determination of the probability density functions P(r) of the number r of earthquakes in finite space-time windows for the California catalog, over fixed spatial boxes 5 x 5 km^2 and time intervals dt =1, 10, 100 and 1000 days. We find a stable power law tail P(r) ~ 1/r^{1+mu} with exponent mu \\approx 1.6 for all time intervals. These observations are explained by a simple stochastic branching process previously studied by many authors, the ETAS (epidemic-type aftershock sequence) model which assumes that each earthquake can trigger other earthquakes (``aftershocks''). An aftershock sequence results in this model from the cascade of aftershocks of each past earthquake. We develop the full theory in terms of generating functions for describing the space-time organization of earthquake sequences and develop several approximations to solve the equations. The calibration of the theory to the empirical observations shows that it is essential to augment the ETAS model by taking account of th...
Agbogbo Frank K
2010-03-01
Full Text Available Abstract Background Different mechanistic models have been used in the literature to describe the enzymatic hydrolysis of pretreated biomass. Although these different models have been applied to different substrates, most of these mechanistic models fit into two- and three-parameter mechanistic models. The purpose of this study is to compare the models and determine the activation energy and the enthalpy of adsorption of Trichoderma reesei enzymes on ammonia fibre explosion (AFEX-treated wheat straw. Experimental enzymatic hydrolysis data from AFEX-treated wheat straw were modelled with two- and three-parameter mechanistic models from the literature. In order to discriminate between the models, initial rate data at 49°C were subjected to statistical analysis (analysis of variance and scatter plots. Results For three-parameter models, the HCH-1 model best fitted the experimental data; for two-parameter models Michaelis-Menten (M-M best fitted the experimental data. All the three-parameter models fitted the data better than the two-parameter models. The best three models at 49°C (HCH-1, Huang and M-M were compared using initial rate data at three temperatures (35°, 42° and 49°C. The HCH-1 model provided the best fit based on the F values, the scatter plot and the residual sum of squares. Also, its kinetic parameters were linear in Arrhenius/van't Hoff's plots, unlike the other models. The activation energy (Ea is 47.6 kJ/mol and the enthalpy change of adsorption (ΔH is -118 kJ/mol for T. reesei enzymes on AFEX-treated wheat straw. Conclusion Among the two-parameter models, Michaelis-Menten model provided the best fit compared to models proposed by Humphrey and Wald. For the three-parameter models, HCH-1 provided the best fit because the model includes a fractional coverage parameter (ϕ which accounts for the number of reactive sites covered by the enzymes.
Scaling laws for the upper ocean temperature dissipation rate
Bogucki, D.J.; Huguenard, K.; Haus, B.K.; Özgökmen, T.M.; Reniers, A.J.H.M.; Laxague, N.J.M.
2015-01-01
Our understanding of temperature dissipation rate χ within the upper ocean boundary layer, which is critical for climate forecasts, is very limited. Near-surface turbulence also affects dispersion of contaminants and biogeochemical tracers. Using high-resolution optical turbulence measurements, scal
Kandasamy, Palani; Moitra, Ranabir; Mukherjee, Souti
2015-01-01
Experiments were conducted to determine the respiration rate of tomato at 10, 20 and 30 °C using closed respiration system. Oxygen depletion and carbon dioxide accumulation in the system containing tomato was monitored. Respiration rate was found to decrease with increasing CO2 and decreasing O2 concentration. Michaelis-Menten type model based on enzyme kinetics was evaluated using experimental data generated for predicting the respiration rate. The model parameters that obtained from the respiration rate at different O2 and CO2 concentration levels were used to fit the model against the storage temperatures. The fitting was fair (R2 = 0.923 to 0.970) when the respiration rate was expressed as O2 concentation. Since inhibition constant for CO2 concentration tended towards negetive, the model was modified as a function of O2 concentration only. The modified model was fitted to the experimental data and showed good agreement (R2 = 0.998) with experimentally estimated respiration rate.
Achievable Rates and Scaling Laws for Cognitive Radio Channels
Natasha Devroye
2008-01-01
Full Text Available Cognitive radios have the potential to vastly improve communication over wireless channels. We outline recent information theoretic results on the limits of primary and cognitive user communication in single and multiple cognitive user scenarios. We first examine the achievable rate and capacity regions of single user cognitive channels. Results indicate that at medium SNR (0Ã¢Â€Â“20Ã¢Â€Â‰dB, the use of cognition improves rates significantly compared to the currently suggested spectral gap-filling methods of secondary spectrum access. We then study another information theoretic measure, the multiplexing gain. This measure captures the number of point-to-point Gaussian channels contained in a cognitive channel as the SNR tends to infinity. Next, we consider a cognitive network with a single primary user and multiple cognitive users. We show that with single-hop transmission, the sum capacity of the cognitive users scales linearly with the number of users. We further introduce and analyze the primary exclusive radius, inside of which primary receivers are guaranteed a desired outage performance. These results provide guidelines when designing a network with secondary spectrum users.
Achievable Rates and Scaling Laws for Cognitive Radio Channels
Devroye Natasha
2008-01-01
Full Text Available Abstract Cognitive radios have the potential to vastly improve communication over wireless channels. We outline recent information theoretic results on the limits of primary and cognitive user communication in single and multiple cognitive user scenarios. We first examine the achievable rate and capacity regions of single user cognitive channels. Results indicate that at medium SNR (0–20 dB, the use of cognition improves rates significantly compared to the currently suggested spectral gap-filling methods of secondary spectrum access. We then study another information theoretic measure, the multiplexing gain. This measure captures the number of point-to-point Gaussian channels contained in a cognitive channel as the SNR tends to infinity. Next, we consider a cognitive network with a single primary user and multiple cognitive users. We show that with single-hop transmission, the sum capacity of the cognitive users scales linearly with the number of users. We further introduce and analyze the primary exclusive radius, inside of which primary receivers are guaranteed a desired outage performance. These results provide guidelines when designing a network with secondary spectrum users.
Cristiane Fagundes
2013-03-01
Full Text Available In this study, the influence of storage temperature and passive modified packaging (PMP on the respiration rate and physicochemical properties of fresh-cut Gala apples (Malus domestica B. was investigated. The samples were packed in flexible multilayer bags and stored at 2 °C, 5 °C, and 7 °C for eleven days. Respiration rate as a function of CO2 and O2 concentrations was determined using gas chromatography. The inhibition parameters were estimated using a mathematical model based on Michaelis-Menten equation. The following physicochemical properties were evaluated: total soluble solids, pH, titratable acidity, and reducing sugars. At 2 °C, the maximum respiration rate was observed after 150 hours. At 5 °C and 7 °C the maximum respiration rates were observed after 100 and 50 hours of storage, respectively. The inhibition model results obtained showed a clear effect of CO2 on O2 consumption. The soluble solids decreased, although not significantly, during storage at the three temperatures studied. Reducing sugars and titratable acidity decreased during storage and the pH increased. These results indicate that the respiration rate influenced the physicochemical properties.
Persson, Inga-Lill; Nilsson, Mats B; Pastor, John; Eriksson, Tobias; Bergström, Roger; Danell, Kjell
2009-10-01
Large herbivores can affect the carbon cycle in boreal forests by changing productivity and plant species composition, which in turn could ultimately alter litter production, nutrient cycling, and the partitioning between aboveground and belowground allocation of carbon. Here we experimentally tested how moose (Alces alces) at different simulated population densities affected belowground respiration rates (estimated as CO2 flux) in young boreal forest stands situated along a site productivity gradient. At high simulated population density, moose browsing considerably depressed belowground respiration rates (24-56% below that of no-moose controls) except during June, where the difference only was 10%. Moose browsing depressed belowground respiration the most on low-productivity sites. Soil moisture and temperature did not affect respiration rates. Impact of moose on belowground respiration was closely linked to litter production and followed Michaelis-Menten dynamics. The main mechanism by which moose decrease belowground respiration rates is likely their effect on photosynthetic biomass (especially decreased productivity of deciduous trees) and total litter production. An increased productivity of deciduous trees along the site productivity gradient causes an unequal effect of moose along the same gradient. The rapid growth of deciduous trees may offer higher resilience against negative effects of moose browsing on litter production and photosynthate allocation to roots.
Klinich, Kathleen D; Benedetti, Marco; Manary, Miriam A; Flannagan, Carol A
2017-05-19
State laws regarding child passenger protection vary substantially. The objective of this study was to develop a scoring system to rate child passenger safety laws relative to best practice recommendations for each age of child. State child passenger safety and seat belt laws were retrieved from the LexisNexis database for the years 2002-2015. Text of the laws was reviewed and compared to current best practice recommendations for child occupant protection for each age of child. A 0-4 scale was developed to rate the strength of the state law relative to current best practice recommendations. A rating of 3 corresponds to a law that requires a restraint that is sufficient to meet best practice, and a rating of 4 is given to a law that specifies several options that would meet best practice. Scores of 0, 1, or 2 are given to laws requiring less than best practice to different degrees. The same scale is used for each age of child despite different restraint recommendations for each age. Legislation that receives a score of 3 requires rear-facing child restraints for children under age 2, forward-facing harnessed child restraints for children aged 2 to 4, booster seats for children 5 to 10, and primary enforcement of seat belt use in all positions for children aged 11-13. Legislation requiring use of a "child restraint system according to instructions" would receive a score of 1 for children under age 2 and a 2 for children aged 2-4 because it would allow premature use of a booster for children weighing more than 13.6 kg (30 lb). The scoring system developed in this study can be used in mathematical models to predict how child passenger safety legislation affects child restraint practices.
Yao, Yijun; Shen, Rui; Pennel, Kelly G; Suuberg, Eric M
2013-12-01
In subsurface vapor intrusion, aerobic biodegradation has been considered as a major environmental factor that determines the soil gas concentration attenuation factors for contaminants such as petroleum hydrocarbons. The site investigation has shown that oxygen can play an important role in this biodegradation rate, and this paper explores the influence of oxygen concentration on biodegradation reactions included in vapor intrusion (VI) models. Two different three dimensional (3-D) numerical models of vapor intrusion were explored for their sensitivity to the form of the biodegradation rate law. A second order biodegradation rate law, explicitly including oxygen concentration dependence, was introduced into one model. The results indicate that the aerobic/anoxic interface depth is determined by the ratio of contaminant source vapor to atmospheric oxygen concentration, and that the contaminant concentration profile in the aerobic zone was significantly influenced by the choice of rate law.
Emanuele Ricca
2014-01-01
Full Text Available The present paper addresses two crucial features in the industrial development of fructose production by enzymatic hydrolysis of inulin: the use of immobilized biocatalyst in the hydrolysis of crude extracts of chicory roots and the evaluation of the effect of degree of polymerization of inulin on the overall reaction rate. The immobilized biocatalyst consisted of inulinase covalently bound to Sepabeads® supports. It was demonstrated that its catalytic activity towards crude inulin extract (real substrate was much higher than that exhibited towards pure inulin (synthetic solution. Experiments revealed that, in applications of practical interest with real substrate, the activity of immobilized enzyme was as high as 63 % of that of free enzyme in homogeneous solution. This certainly was a driving force to potential industrial application of this immobilized enzyme preparation. Therefore, the effect of pure and crude substrates on the kinetics of the reaction catalysed by the immobilized enzyme was investigated. The kinetic analysis revealed a Michaelis-Menten dependence of the reaction rate on substrate concentration for both pure (high molecular mass and crude (low molecular mass inulin. Interesting results were derived from the comparison of Km and vmax values in the two cases. In particular, it was found that increasing degree of polymerization of the substrate caused vmax decrease and Km increase. After evaluation of mass transport effects, this was mainly associated with a different substrate/ enzyme affinity when exploiting inulin characterized by different (low or high degree of polymerization.
Ordens não inteiras em cinética química Non-integer orders in chemical kinetics
André P. Oliveira
2010-01-01
Full Text Available Starting from zero-, first-, and second-order integrated laws for chemical kinetics, some cases are shown which produce fractional orders. Taking the Michaelis-Menten mechanism as a first example, it is shown that substrate order can go from 1 to zero, depending on relative concentration of enzyme and substrate. Using other examples which show fractional orders higher than one and even negative (inhibition, it is shown that the presence of an equilibrium before or parallel to the rate determining step can be the reason for fractional orders, which is an indication of a more complex mechanism.
Posttranscriptional expression regulation: what determines translation rates?
Regina Brockmann
2007-03-01
Full Text Available Recent analyses indicate that differences in protein concentrations are only 20%-40% attributable to variable mRNA levels, underlining the importance of posttranscriptional regulation. Generally, protein concentrations depend on the translation rate (which is proportional to the translational activity, TA and the degradation rate. By integrating 12 publicly available large-scale datasets and additional database information of the yeast Saccharomyces cerevisiae, we systematically analyzed five factors contributing to TA: mRNA concentration, ribosome density, ribosome occupancy, the codon adaptation index, and a newly developed "tRNA adaptation index." Our analysis of the functional relationship between the TA and measured protein concentrations suggests that the TA follows Michaelis-Menten kinetics. The calculated TA, together with measured protein concentrations, allowed us to estimate degradation rates for 4,125 proteins under standard conditions. A significant correlation to recently published degradation rates supports our approach. Moreover, based on a newly developed scoring system, we identified and analyzed genes subjected to the posttranscriptional regulation mechanism, translation on demand. Next we applied these findings to publicly available data of protein and mRNA concentrations under four stress conditions. The integration of these measurements allowed us to compare the condition-specific responses at the posttranscriptional level. Our analysis of all 62 proteins that have been measured under all four conditions revealed proteins with very specific posttranscriptional stress response, in contrast to more generic responders, which were nonspecifically regulated under several conditions. The concept of specific and generic responders is known for transcriptional regulation. Here we show that it also holds true at the posttranscriptional level.
CONVERGENCE RATES IN THE STRONG LAWS FOR A CLASS OF DEPENDENT RANDOM FIFLDS
CaiGuanghui
2003-01-01
By using a Rosenthal type inequality established in this paper,the complete convergence rates in the strong laws for a class of dependent random fields are discussed.And the result obtained extends those for ρ--mixing random fields,ρ*-mixing random fields and negatively associated fields.
STRONG LAW OF LARGE NUMBERS AND GROWTH RATE FOR NOD SEQUENCES
MA Song-lin; WANG Xue-jun
2015-01-01
In the paper, we get the precise results of Hájek-Rényi type inequalities for the par-tial sums of negatively orthant dependent sequences, which improve the results of Theorem 3.1 and Corollary 3.2 in Kim (2006) and the strong law of large numbers and strong growth rate for negatively orthant dependent sequences.
Speed-invariant encoding of looming object distance requires power law spike rate adaptation.
Clarke, Stephen E; Naud, Richard; Longtin, André; Maler, Leonard
2013-08-13
Neural representations of a moving object's distance and approach speed are essential for determining appropriate orienting responses, such as those observed in the localization behaviors of the weakly electric fish, Apteronotus leptorhynchus. We demonstrate that a power law form of spike rate adaptation transforms an electroreceptor afferent's response to "looming" object motion, effectively parsing information about distance and approach speed into distinct measures of the firing rate. Neurons with dynamics characterized by fixed time scales are shown to confound estimates of object distance and speed. Conversely, power law adaptation modifies an electroreceptor afferent's response according to the time scales present in the stimulus, generating a rate code for looming object distance that is invariant to speed and acceleration. Consequently, estimates of both object distance and approach speed can be uniquely determined from an electroreceptor afferent's firing rate, a multiplexed neural code operating over the extended time scales associated with behaviorally relevant stimuli.
RATE LAW AND ITS MOMENT EXPRESSIONS FOR PELLICULAR ION EXCHANGE MATERIALS OF VARIOURS SHAPES
YangGengliang; ZhangXiaomin; 等
1994-01-01
In this paper,the kinetic moment expressions and rate laws are derived for pellicular ion exchange materials with various geometrical forms under the conditions that ion exchange rate is controlled by both the partical diffusion and the film diffusion in finite solution volume.In addition,for strong acidic cation ion exchange fibre,by using the equations obtained we calculated the partical diffusion coefficients and the transfer coefficients in the film under different experimental conditions.
A two thousand year annual record of snow accumulation rates for Law Dome, East Antarctica
J. Roberts
2014-11-01
AD 663–704, AD 933–975 and AD 1429–1468 were below average. The calculated snow accumulation rates show good correlation with atmospheric reanalysis estimates, and significant spatial correlation over a wide expanse of East Antarctica, demonstrating that the Law Dome record captures larger scale variability across a large region of East Antarctica well beyond the immediate vicinity of the Law Dome summit. Spectral analysis reveals periodicities in the snow accumulation record which may be related to ENSO and Interdecadal Pacific Oscillation frequencies.
A MODIFIED THERMAL VISCOPLASTIC CONSTITUTIVE LAW INVOLVING THE EFFECT OF TEMPERATURE RISE RATE
Huang Chenguang; Duan Zhuping
2000-01-01
At high temperature rise rate, the mechanical properties of 10 # steel were determined ex perimentally in a very wide range of temperature and strain rates. A new constitutive relationship was put for ward, which can fit with the experimental results and describe various phenomena observed in our experim ents. Meanwhile, some interesting characteristics about the temperature rise rate, strain and strain rate hard ening and thermal softening are also shown in this paper. Finally, the reliability of the constitutive law and the correctness of the constitutive parameters were verified by comparing the calculation results with the ex perimental data.
Afterslip and aftershocks in the rate-and-state friction law
Helmstetter, A; Helmstetter, Agnes; Shaw, Bruce E.
2007-01-01
We study how a stress perturbation generated by a mainshock affects a population of faults obeying a rate-state friction law. Depending on the model parameters and on the initial state, the fault exhibits aftershocks, slow earthquakes, or decaying afterslip. We found several regimes with slip rate decaying as a power-law of time, with different characteristic times and exponents. The complexity of the model makes it unrealistic to invert for the friction law parameters from afterslip data. We modeled afterslip measurements for the Southern California Superstition Hills earthquake using the complete rate-and-state law, and found a huge variety of model parameters that can fit the observed data. In particular, it is impossible to distinguish the stable velocity strengthening regime (A>B) from the (potentially) unstable velocity weakening regime (B>A and stiffness k
The effect of a power-law mantle viscosity on trench retreat rate
Holt, Adam F.; Becker, Thorsten W.
2017-01-01
The subduction of lithospheric plates is partitioned between subducting plate motion and lateral slab migration (i.e. trench retreat and advance). We use 3-D, dynamic models of subduction to address the role of a power-law mantle viscosity on subduction dynamics and, in particular, rates of trench retreat. For all numerical models tested, we find that a power-law rheology results in reduced rates of trench retreat, and elevated slab dip angles, relative to the equivalent isoviscous mantle model. We analyse the asthenospheric pressure distribution and the style of mantle flow, which exhibits only limited variability as a function of mantle rheology, in order to compute estimates of the mantle forces associated with subduction. The inclusion of a power-law rheology reduces the mantle shear force (which resists subducting plate motion) to a greater degree than it reduces the dynamic pressure gradient across the slab (which resists trench retreat). Therefore, the inclusion of a power-law mantle rheology favours a shift towards a subduction mode with a reduced trench retreat component, typically a relative reduction of order 25 per cent in our 3-D models. We suggest that this mechanism may be of importance for reducing the high trench retreat rates observed in many previous models to levels more in line with the average subduction partitioning observed on Earth at present (i.e. trench velocity ≤ plate velocity), for most absolute plate motion reference frames.
Ge, Hao; Qian, Hong
2017-01-01
This paper studies a mathematical formalism of nonequilibrium thermodynamics for chemical reaction models with N species, M reactions, and general rate law. We establish a mathematical basis for J. W. Gibbs' macroscopic chemical thermodynamics under G. N. Lewis' kinetic law of entire equilibrium (detailed balance in nonlinear chemical kinetics). In doing so, the equilibrium thermodynamics is then naturally generalized to nonequilibrium settings without detailed balance. The kinetic models are represented by a Markovian jumping process. A generalized macroscopic chemical free energy function and its associated balance equation with nonnegative source and sink are the major discoveries. The proof is based on the large deviation principle of this type of Markov processes. A general fluctuation dissipation theorem for stochastic reaction kinetics is also proved. The mathematical theory illustrates how a novel macroscopic dynamic law can emerges from the mesoscopic kinetics in a multi-scale system.
Woeger, Julia; Kinoshita, Shunichi; Wolfgang, Eder; Briguglio, Antonino; Hohenegger, Johann
2016-04-01
Operculina complanata was collected in 20 and 50 m depth around the Island of Sesoko belonging to Japans southernmost prefecture Okinawa in a series of monthly sampling over a period of 16 months (Apr.2014-July2015). A minimum of 8 specimens (4 among the smallest and 4 among the largest) per sampling were cultured in a long term experiment that was set up to approximate conditions in the field as closely as possible. A set up allowing recognition of individual specimens enabled consistent documentation of chamber formation, which in combination with μ-CT-scanning after the investigation period permitted the assignment of growth steps to specific time periods. These data were used to fit various mathematical models to describe growth (exponential-, logistic-, generalized logistic-, Gompertz-function) and chamber building rate (Michaelis-Menten-, Bertalanffy- function) of Operculina complanata. The mathematically retrieved maximum lifespan and mean chamber building rate found in cultured Operculina complanata were further compared to first results obtained by the simultaneously conducted "natural laboratory approach". Even though these comparisons hint at a somewhat stunted growth and truncated life spans of Operculina complanata in culture, they represent a possibility to assess and improve the quality of further cultivation set ups, opening new prospects to a better understanding of the their theoretical niches.
Tomlinson, Sean
2016-04-01
The calculation and comparison of physiological characteristics of thermoregulation has provided insight into patterns of ecology and evolution for over half a century. Thermoregulation has typically been explored using linear techniques; I explore the application of non-linear scaling to more accurately calculate and compare characteristics and thresholds of thermoregulation, including the basal metabolic rate (BMR), peak metabolic rate (PMR) and the lower (Tlc) and upper (Tuc) critical limits to the thermo-neutral zone (TNZ) for Australian rodents. An exponentially-modified logistic function accurately characterised the response of metabolic rate to ambient temperature, while evaporative water loss was accurately characterised by a Michaelis-Menten function. When these functions were used to resolve unique parameters for the nine species studied here, the estimates of BMR and TNZ were consistent with the previously published estimates. The approach resolved differences in rates of metabolism and water loss between subfamilies of Australian rodents that haven't been quantified before. I suggest that non-linear scaling is not only more effective than the established segmented linear techniques, but also is more objective. This approach may allow broader and more flexible comparison of characteristics of thermoregulation, but it needs testing with a broader array of taxa than those used here.
Contractive Interference Functions and Rates of Convergence of Distributed Power Control Laws
Johansson, Hamid Reza Feyzmahdavian 'and' Mikael
2012-01-01
The standard interference functions introduced by Yates have been very influential on the analysis and design of distributed power control laws. While powerful and versatile, the framework has some drawbacks: the existence of fixed-points has to be established separately, and no guarantees are given on the rate of convergence of the iterates. This paper introduces contractive interference functions, a slight reformulation of the standard interference functions that guarantees the existence and uniqueness of fixed-points along with geometric convergence. We show that many power control laws from the literature are contractive and derive, sometimes for the first time, analytical convergence rate estimates for these algorithms. We also prove that contractive interference functions converge when executed totally asynchronously and, under the assumption that the communication delay is bounded, derive an explicit bound on the convergence time penalty due to increased delay. Finally, we demonstrate that although all...
Yun, Ji-Yeong; Lee, Jung-Eun; Yang, Kyung-Mi; Cho, Suekyung; Kim, Arim; Kwon, Yong-Uk; Kwon, Yong-Euk; Park, Jin-Byung
2012-01-01
The effects of structural modification of cell wall on the biotransformation capability by recombinant Corynebacterium glutamicum cells, expressing the chnB gene encoding cyclohexanone monooxygenase of Acinetobacter calcoaceticus NCIMB 9871, were investigated. Baeyer-Villiger oxygenation of 2-(2'-acetoxyethyl) cyclohexanone (MW 170 Da) into R-7-(2'-acetoxyethyl)-2-oxepanone was used as a model reaction. The whole-cell biotransformation followed Michaelis-Menten kinetics. The V (max) and K (S) values were estimated as 96.8 U g(-1) of dry cells and 0.98 mM, respectively. The V (max) was comparable with that of cyclohexanone oxygenation, whereas the K (S) was almost eightfold higher. The K (S) value of 2-(2'-acetoxyethyl) cyclohexanone oxygenation was reduced by ca. 30% via altering the cell envelop structure of C. glutamicum with ethambutol, which inhibits arabinosyl transferases involved in the biosynthesis of cell wall arabinogalactan and mycolate layers. The higher whole-cell biotransformation rate was also observed in the oxygenation of ethyl 2-cyclohexanone acetate upon ethambutol treatment of the recombinant C. glutamicum. Therefore, it was assumed that the biotransformation efficiency of C. glutamicum-based biocatalysts, with respect to medium- to large-sized lipophilic organic substrates (MW > ca. 170), can be enhanced by engineering their cell wall outer layers, which are known to function as a formidable barrier to lipophilic molecules.
CONVERGENCE RATES IN THE STRONG LAWS OF ASYMPTOTICALLY NEGATIVELY ASSOCIATED RANDOM FIELDS
ZhangLixin; WangXiuyun
1999-01-01
In this paper, a notion of negative side p-mixing (p -mixing) which can be regardedas asymptotic negative association is defined, and some Rosenthal type inequalities for p -mix-ing random fields are established. The complete convergence and almost sure summability onthe convergence rates with respect to the strong law of large numbers are also discussed for p--mixing random fields. The results obtained extend those for negatively associated sequences andp" -mixing random fields.
Global observation of Omori-law decay in the rate of triggered earthquakes
Parsons, T.
2001-12-01
Triggered earthquakes can be large, damaging, and lethal as evidenced by the 1999 shocks in Turkey and the 2001 events in El Salvador. In this study, earthquakes with M greater than 7.0 from the Harvard CMT catalog are modeled as dislocations to calculate shear stress changes on subsequent earthquake rupture planes near enough to be affected. About 61% of earthquakes that occurred near the main shocks are associated with calculated shear stress increases, while ~39% are associated with shear stress decreases. If earthquakes associated with calculated shear stress increases are interpreted as triggered, then such events make up at least 8% of the CMT catalog. Globally, triggered earthquakes obey an Omori-law rate decay that lasts between ~7-11 years after the main shock. Earthquakes associated with calculated shear stress increases occur at higher rates than background up to 240 km away from the main-shock centroid. Earthquakes triggered by smaller quakes (foreshocks) also obey Omori's law, which is one of the few time-predictable patterns evident in the global occurrence of earthquakes. These observations indicate that earthquake probability calculations which include interactions from previous shocks should incorporate a transient Omori-law decay with time. In addition, a very simple model using the observed global rate change with time and spatial distribution of triggered earthquakes can be applied to immediately assess the likelihood of triggered earthquakes following large events, and can be in place until more sophisticated analyses are conducted.
Shape of Growth Rate Distribution determines the type of Non-Gibrat's Law
Ishikawa, Atushi; Mizuno, Takayuki
2010-01-01
In this study, by employing exhaustive business data on Japanese firms that approximately fully cover the middle- and large-scale ranges in terms of firm size, the authors confirm the following findings. Detailed Balance is observed not only in profits data but also in sales data. The growth-rate distribution of sales has wider tails than the linear growth-rate distribution of profits in log-log scale. On one hand, in the middle-scale range of profits, the probability of positive growth decreases and the probability of negative growth increases symmetrically as the initial value increases. This is called Non-Gibrat's First Law. On the other hand, in the middle-scale range of sales, the probability of positive growth decreases as the initial value increases, while the probability of negative growth hardly changes. This is called Non-Gibrat's Second Law. Under Detailed Balance, Non-Gibrat's First and Second Laws are analytically induced from the linear and quadratic growth-rate distributions in log-log scale, r...
Automated Prediction of Catalytic Mechanism and Rate Law Using Graph-Based Reaction Path Sampling.
Habershon, Scott
2016-04-12
In a recent article [ J. Chem. Phys. 2015 , 143 , 094106 ], we introduced a novel graph-based sampling scheme which can be used to generate chemical reaction paths in many-atom systems in an efficient and highly automated manner. The main goal of this work is to demonstrate how this approach, when combined with direct kinetic modeling, can be used to determine the mechanism and phenomenological rate law of a complex catalytic cycle, namely cobalt-catalyzed hydroformylation of ethene. Our graph-based sampling scheme generates 31 unique chemical products and 32 unique chemical reaction pathways; these sampled structures and reaction paths enable automated construction of a kinetic network model of the catalytic system when combined with density functional theory (DFT) calculations of free energies and resultant transition-state theory rate constants. Direct simulations of this kinetic network across a range of initial reactant concentrations enables determination of both the reaction mechanism and the associated rate law in an automated fashion, without the need for either presupposing a mechanism or making steady-state approximations in kinetic analysis. Most importantly, we find that the reaction mechanism which emerges from these simulations is exactly that originally proposed by Heck and Breslow; furthermore, the simulated rate law is also consistent with previous experimental and computational studies, exhibiting a complex dependence on carbon monoxide pressure. While the inherent errors of using DFT simulations to model chemical reactivity limit the quantitative accuracy of our calculated rates, this work confirms that our automated simulation strategy enables direct analysis of catalytic mechanisms from first principles.
Jeen-Hwa Wang
2009-01-01
The two one-state-variable, rate- and state-dependent friction laws, i.e., the slip and slowness laws, are compared on the basis of dynamical behavior of a one-degree-of-freedom spring-slider model through numerical simulations. Results show that two (normalized) model parameters, i.e., △(the normalized characteristic slip distance) and β-α (the difference in two normalized parameters of friction laws), control the solutions. From given values of △, β, and α, for the slowness laws, the solution exists and the unique non-zero fixed point is stable when △>(β-α), yet not when △<β-α). For the slip law, the solution exists for large ranges of model parameters and the number and stability of the non-zero fixed points change from one case to another. Results suggest that the slip law is more appropriate for controlling earthquake dynamics than the slowness law.
An upscaled rate law for magnesite dissolution in heterogeneous porous media
Wen, Hang; Li, Li
2017-08-01
Spatial heterogeneity in natural subsurface systems governs water fluxes and residence time in reactive zones and therefore determines effective rates of mineral dissolution. Extensive studies have documented mineral dissolution rates in natural systems, although a general rate law has remain elusive. Here we fill this gap by answering two questions: (1) how and to what extent does spatial heterogeneity affect water residence time and effectively-dissolving surface area? (2) what is the upscaled rate law that quantifies effective dissolution rates in natural, heterogeneous media? With data constraints from experimental work, 240 Monte-Carlo numerical experiments of magnesite dissolution within quartz matrix were run with spatial distributions characterized by a range of permeability variance σ2lnκ (0.5-6.0) and correlation length (2-50 cm). Although the total surface area and global residence time (τa) are the same in all experiments, the water fluxes through reactive magnesite zones varies between 0.7 and 72.8% of the total water fluxes. Highly heterogeneous media with large σ2lnκ and long λ divert water mostly into non-reactive preferential flow paths, therefore bypassing and minimizing flow in low permeability magnesite zones. As a result, the water residence time in magnesite zones (i.e., reactive residence time τa,r) is long and magnesite dissolution quickly reaches local equilibrium, which leads to small effective surface area and low dissolution rates. Magnesite dissolution rates in heterogeneous media vary from 2.7 to 100% of the rates in the equivalent homogeneous media, with effectively-dissolving surface area varying from 0.18 to 6.83 m2 (out of 51.71 m2 total magnesite surface area). Based on 240 numerical experiments and 45 column experiments, a general upscaled rate law in heterogeneous media, RMgCO3,ht =kAe,hm(1 - exp(-τa/τa,r))α , was derived to quantify effective dissolution rates. The dissolution rates in heterogeneous media are a
Modeling networks of coupled enzymatic reactions using the total quasi-steady state approximation.
Andrea Ciliberto
2007-03-01
Full Text Available In metabolic networks, metabolites are usually present in great excess over the enzymes that catalyze their interconversion, and describing the rates of these reactions by using the Michaelis-Menten rate law is perfectly valid. This rate law assumes that the concentration of enzyme-substrate complex (C is much less than the free substrate concentration (S0. However, in protein interaction networks, the enzymes and substrates are all proteins in comparable concentrations, and neglecting C with respect to S0 is not valid. Borghans, DeBoer, and Segel developed an alternative description of enzyme kinetics that is valid when C is comparable to S0. We extend this description, which Borghans et al. call the total quasi-steady state approximation, to networks of coupled enzymatic reactions. First, we analyze an isolated Goldbeter-Koshland switch when enzymes and substrates are present in comparable concentrations. Then, on the basis of a real example of the molecular network governing cell cycle progression, we couple two and three Goldbeter-Koshland switches together to study the effects of feedback in networks of protein kinases and phosphatases. Our analysis shows that the total quasi-steady state approximation provides an excellent kinetic formalism for protein interaction networks, because (1 it unveils the modular structure of the enzymatic reactions, (2 it suggests a simple algorithm to formulate correct kinetic equations, and (3 contrary to classical Michaelis-Menten kinetics, it succeeds in faithfully reproducing the dynamics of the network both qualitatively and quantitatively.
Karakhim, S A
2012-01-01
The Slater-Bonner method which is used for graphic determination of substrate constant (Ks) by linear dependence of apparent Michaelis constant (Km(app)) on the limiting rate (V(app)) of enzyme-catalysed reactions with activator participation has been critically analysed. It has been shown that although it is possible to record the mechanisms of such reactions as a scheme similar to Michaelis-Menten model which allow to find correlation Km(app) and V(app) as equation Km(app) = Ks + V(app)/k1[E]0 ([E]0 is a total enzyme concentration, k1 is a rate constant of enzyme-substrate complex formation from free enzyme and substrate) in order to calculate Ks and individual rate constants (k1, k(-1)), but this approach for investigation of all reactions with activator participation ought not to be used. The above equation is not obeyed in general, it may be true for some mechanisms only or under certain ratios of kinetic parameters of enzyme-catalysed reactions.
Do more hospital beds lead to higher hospitalization rates? a spatial examination of Roemer's Law.
Delamater, Paul L; Messina, Joseph P; Grady, Sue C; WinklerPrins, Vince; Shortridge, Ashton M
2013-01-01
Roemer's Law, a widely cited principle in health care policy, states that hospital beds that are built tend to be used. This simple but powerful expression has been invoked to justify Certificate of Need regulation of hospital beds in an effort to contain health care costs. Despite its influence, a surprisingly small body of empirical evidence supports its content. Furthermore, known geographic factors influencing health services use and the spatial structure of the relationship between hospital bed availability and hospitalization rates have not been sufficiently explored in past examinations of Roemer's Law. We pose the question, "Accounting for space in health care access and use, is there an observable association between the availability of hospital beds and hospital utilization?" We employ an ecological research design based upon the Anderson behavioral model of health care utilization. This conceptual model is implemented in an explicitly spatial context. The effect of hospital bed availability on the utilization of hospital services is evaluated, accounting for spatial structure and controlling for other known determinants of hospital utilization. The stability of this relationship is explored by testing across numerous geographic scales of analysis. The case study comprises an entire state system of hospitals and population, evaluating over one million inpatient admissions. We find compelling evidence that a positive, statistically significant relationship exists between hospital bed availability and inpatient hospitalization rates. Additionally, the observed relationship is invariant with changes in the geographic scale of analysis. This study provides evidence for the effects of Roemer's Law, thus suggesting that variations in hospitalization rates have origins in the availability of hospital beds. This relationship is found to be robust across geographic scales of analysis. These findings suggest continued regulation of hospital bed supply to assist in
A General Law of Moment Convergence Rates for Uniform Empirical Process
Qing Pei ZANG
2011-01-01
Let {Xn; n ≥ 1} be a sequence of independent and identically distributed U[0,1]-distributed random variables.Define the uniform empirical process Fn(t)=n-1/2∑ni=1(I{Xi≤t} -t),0 ≤ t ≤ 1,‖Fn‖ =sup0≤t≤1 ｜Fn(t)｜.In this paper,the exact convergence rates of a general law of weighted infinite series of E{‖Fn‖ - εgs(n)}+ are obtained.
Ivan Chang
Full Text Available Mitochondrial bioenergetic processes are central to the production of cellular energy, and a decrease in the expression or activity of enzyme complexes responsible for these processes can result in energetic deficit that correlates with many metabolic diseases and aging. Unfortunately, existing computational models of mitochondrial bioenergetics either lack relevant kinetic descriptions of the enzyme complexes, or incorporate mechanisms too specific to a particular mitochondrial system and are thus incapable of capturing the heterogeneity associated with these complexes across different systems and system states. Here we introduce a new composable rate equation, the chemiosmotic rate law, that expresses the flux of a prototypical energy transduction complex as a function of: the saturation kinetics of the electron donor and acceptor substrates; the redox transfer potential between the complex and the substrates; and the steady-state thermodynamic force-to-flux relationship of the overall electro-chemical reaction. Modeling of bioenergetics with this rate law has several advantages: (1 it minimizes the use of arbitrary free parameters while featuring biochemically relevant parameters that can be obtained through progress curves of common enzyme kinetics protocols; (2 it is modular and can adapt to various enzyme complex arrangements for both in vivo and in vitro systems via transformation of its rate and equilibrium constants; (3 it provides a clear association between the sensitivity of the parameters of the individual complexes and the sensitivity of the system's steady-state. To validate our approach, we conduct in vitro measurements of ETC complex I, III, and IV activities using rat heart homogenates, and construct an estimation procedure for the parameter values directly from these measurements. In addition, we show the theoretical connections of our approach to the existing models, and compare the predictive accuracy of the rate law with
Chang, Ivan; Heiske, Margit; Letellier, Thierry; Wallace, Douglas; Baldi, Pierre
2011-01-01
Mitochondrial bioenergetic processes are central to the production of cellular energy, and a decrease in the expression or activity of enzyme complexes responsible for these processes can result in energetic deficit that correlates with many metabolic diseases and aging. Unfortunately, existing computational models of mitochondrial bioenergetics either lack relevant kinetic descriptions of the enzyme complexes, or incorporate mechanisms too specific to a particular mitochondrial system and are thus incapable of capturing the heterogeneity associated with these complexes across different systems and system states. Here we introduce a new composable rate equation, the chemiosmotic rate law, that expresses the flux of a prototypical energy transduction complex as a function of: the saturation kinetics of the electron donor and acceptor substrates; the redox transfer potential between the complex and the substrates; and the steady-state thermodynamic force-to-flux relationship of the overall electro-chemical reaction. Modeling of bioenergetics with this rate law has several advantages: (1) it minimizes the use of arbitrary free parameters while featuring biochemically relevant parameters that can be obtained through progress curves of common enzyme kinetics protocols; (2) it is modular and can adapt to various enzyme complex arrangements for both in vivo and in vitro systems via transformation of its rate and equilibrium constants; (3) it provides a clear association between the sensitivity of the parameters of the individual complexes and the sensitivity of the system's steady-state. To validate our approach, we conduct in vitro measurements of ETC complex I, III, and IV activities using rat heart homogenates, and construct an estimation procedure for the parameter values directly from these measurements. In addition, we show the theoretical connections of our approach to the existing models, and compare the predictive accuracy of the rate law with our experimentally
The legality of unilateral increase of interest rate in banking loan contracts under Serbian law
Dudaš Atila I.
2016-01-01
circumstances which the debtor could not influence. In most cases the bank could have influenced these circumstance or at least taken them into consideration at the time of the formation of contract. If not, they still fall within the bank's sphere of control or the bank bears the risk of their occurrence. The uniform approach of the courts, both in respect to credit contracts in which the debtor is a consumer, and contracts in which the debtor does not qualify as consumer, is that these clauses in loan contracts are null and void, since they are contrary to principles of good faith and equal value of reciprocal obligations, on the one hand, and make the object of the contract unascertainable, on the other. The courts, however, hardly ever declare the contract null and void in its entirety, but rather apply the rules on partial invalidity. Until the adoption of the Law on the Protection of Financial Services Consumers in 2011, the courts could render their decisions based only on the rules of general contract law pursuant to the Law on Obligations from 1978. The Law on the Protection of Financial Services Consumers explicitly forbids the modification of variable interest rate due to changes in the business policy or internal acts of the bank and prescribes that only officially published data or criteria may be used as variable elements of the interest rate. By this means, stipulating the right of the bank to subsequently, unilaterally and, in fact, freely increase the interest rate, a practice frequently applied in cases in which it was not economically justified, became statutorily forbidden.
Halász, Adám M; Lai, Hong-Jian; McCabe Pryor, Meghan; Radhakrishnan, Krishnan; Edwards, Jeremy S
2013-01-01
True steady states are a rare occurrence in living organisms, yet their knowledge is essential for quasi-steady-state approximations, multistability analysis, and other important tools in the investigation of chemical reaction networks (CRN) used to describe molecular processes on the cellular level. Here, we present an approach that can provide closed form steady-state solutions to complex systems, resulting from CRN with binary reactions and mass-action rate laws. We map the nonlinear algebraic problem of finding steady states onto a linear problem in a higher-dimensional space. We show that the linearized version of the steady-state equations obeys the linear conservation laws of the original CRN. We identify two classes of problems for which complete, minimally parameterized solutions may be obtained using only the machinery of linear systems and a judicious choice of the variables used as free parameters. We exemplify our method, providing explicit formulae, on CRN describing signal initiation of two important types of RTK receptor-ligand systems, VEGF and EGF-ErbB1.
Negus, Charles H; Impelluso, Thomas J
2007-07-01
Recent research effort in bone remodeling has been directed toward describing interstitial fluid flow in the lacuno-canalicular system and its potential as a cellular stimulus. Regardless of the precise contents of the mechanotransduction "black box", it seems clear that the fluid flow on which the remodeling is predicated cannot occur under static loading conditions. In an attempt to help continuum remodeling simulations catch up with cellular and subcellular research, this paper presents a simple, strain rate driven remodeling algorithm for density allocation and principal material direction rotations. An explicit finite element code was written and deployed on a supercomputer which discretizes the remodeling process and uses an objective hypoelastic constitutive law to simulate trabecular realignment. Results indicate that a target strain rate for this dynamic approach is |D ( I )| = 1.7% per second which seems reasonable when compared to observed strain rates. Simulations indicate that a morpho-mechanically realistic three-dimensional bone can be synthesized by applying a few dynamic loads at the envelope of common daily physiological rates, even with no static loading component.
Rate law of Fe(II) oxidation under low O2 conditions
Kanzaki, Yoshiki; Murakami, Takashi
2013-12-01
Despite intensive studies on Fe(II) oxidation kinetics, the oxidation rate law has not been established under low O2 conditions. The importance of Fe(II) oxidation under low O2 conditions has been recently recognized; for instance, the Fe(II)/Fe(III) compositions of paleosols, ancient soils formed by weathering, can produce a quantitative pattern of the atmospheric oxygen increase during the Paleoproterozoic. The effects of partial pressure of atmospheric oxygen (PO2) on the Fe(II) oxidation rate were investigated to establish the Fe(II) oxidation rate - PO2 relationships under low O2 conditions. All oxidation experiments were carried out in a glove box by introducing Ar gas at ∼10-5-∼10-4 atm of PO2, pH 7.57-8.09 and 22 °C. Luminol chemiluminescence was adopted to measure low Fe(II) concentrations (down to ∼2 nM). Combining previous data under higher PO2 conditions (10-3-0.2 atm) with the present data, the rate law for Fe(II) oxidation over a wide range of PO2 (10-5-0.2 atm) was found to be written as: d[Fe(II)]/dt=-k[Fe(II)][[]2 where the exponent of [O2], x, and the rate constant, k, change from x = 0.98 (±0.04) and log k = 15.46 (±0.06) at ∼6 × 10-3-0.2 atm of PO2 to x = 0.58 (±0.02) and log k = 13.41 (±0.03) at 10-5-∼6 × 10-3 atm of PO2. The most plausible mechanism that explains the change in x under low O2 conditions is that, instead of O2, oxygen-derived oxidants, H2O2 and to some extent, O2rad -, dominate the oxidation reactions at oxygen in the Precambrian.
Chowdhury, Debashish
2014-01-01
Cytoskeletal motor proteins move on filamentous tracks by converting input chemical energy that they derive by catalyzing the hydrolysis of ATP. The ATPase site is the analogue of an engine and hydrolysis of ATP is the analogue of burning of chemical fuel. Moreover, the functional role of a segment of the motor is analogous to that of the transmission system of an automobile, which consists of a shaft, gear, clutch, etc. The operation of the engine is intrinsically 'noisy' and the motor faces a molecular 'hailstorm' in the aqueous medium. In this commemorative review, we celebrate the centenary of Michaelis and Menten's landmark paper of 1913 and the golden jubilee of Monod and colleagues classic paper of 1963 by highlighting their relevance with respect to explaining the operational mechanisms of the engine and the transmission system, respectively, of cytoskeletal motors. © 2013 FEBS.
Her, Cheenou; Alonzo, Aaron P.; Vang, Justin Y.; Torres, Ernesto; Krishnan, V. V.
2015-01-01
Enzyme kinetics is an essential part of a chemistry curriculum, especially for students interested in biomedical research or in health care fields. Though the concept is routinely performed in undergraduate chemistry/biochemistry classrooms using other spectroscopic methods, we provide an optimized approach that uses a real-time monitoring of the…
Her, Cheenou; Alonzo, Aaron P.; Vang, Justin Y.; Torres, Ernesto; Krishnan, V. V.
2015-01-01
Enzyme kinetics is an essential part of a chemistry curriculum, especially for students interested in biomedical research or in health care fields. Though the concept is routinely performed in undergraduate chemistry/biochemistry classrooms using other spectroscopic methods, we provide an optimized approach that uses a real-time monitoring of the…
Jensen, Michael Gejl; Rungby, Jørgen; Brock, Birgitte;
2014-01-01
Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic incretin hormone with pancreatic and extrapancreatic effects. Studies reveal significant effects in regions of brain tissue that regulate appetite and satiety. The effects cause that mimetics of GLP-1 serves as treatment of type 2 diabete...... and in vivo, as in pancreas. The apparent neuroprotective potential of GLP-1, indirectly acting through changes of cerebral blood flow, glucose metabolism or brain glucose concentration, or all of these, is worthy of close attention....
Ahluwalia, Arti
2017-02-01
About two decades ago, West and coworkers established a model which predicts that metabolic rate follows a three quarter power relationship with the mass of an organism, based on the premise that tissues are supplied nutrients through a fractal distribution network. Quarter power scaling is widely considered a universal law of biology and it is generally accepted that were in-vitro cultures to obey allometric metabolic scaling, they would have more predictive potential and could, for instance, provide a viable substitute for animals in research. This paper outlines a theoretical and computational framework for establishing quarter power scaling in three-dimensional spherical constructs in-vitro, starting where fractal distribution ends. Allometric scaling in non-vascular spherical tissue constructs was assessed using models of Michaelis Menten oxygen consumption and diffusion. The models demonstrate that physiological scaling is maintained when about 5 to 60% of the construct is exposed to oxygen concentrations less than the Michaelis Menten constant, with a significant concentration gradient in the sphere. The results have important implications for the design of downscaled in-vitro systems with physiological relevance.
Hartvig, Pål; Kjelsberg, Ellen
2009-01-01
In 1939, Lionel Penrose published a cross-sectional study from 18 European countries, including the Nordic, in which he demonstrated an inverse relationship between the number of mental hospital beds and the number of prisoners. He also found strong negative correlations between the number of mental hospital beds and the number of deaths attributed to murder. He argued that by increasing the number of mental institution beds, a society could reduce serious crimes and imprisonment rates. The aim of the study was to test Penrose's theories longitudinally by monitoring the capacity of all psychiatric institutions and prisons in a society over time. From official statistics, we collected and systematized all relevant information regarding the number of mental institution beds and prisoners in Norway during the years 1930-2004, along with major crime statistics for the same period. During the years 1930-59, there was a 2% population-adjusted increase in mental institution beds and a 30% decrease in the prison population. During 1960-2004, there was a 74% population-adjusted decrease in mental institution beds and a 52% increase in the prison population. The same period saw a 500% increase in overall crime and a 900% increase in violent crimes, with a concurrent 94% increase in the size of the country's police force. Penrose's law proved remarkably robust in the longitudinal perspective. As opposed to Penrose, however, we argue that the rise in crime rates only to a very limited extent can be attributed to mental health de-institutionalization.
Non-steady state population kinetics of intravenous phenytoin.
Frame, B; Beal, S L
1998-08-01
This observational study explored the effects of demographics, sickness, and polypharmacy on the non-steady state population pharmacokinetics of intravenous phenytoin. One hundred fifteen patients were studied. Models were developed using the NONMEM program with hybrid first-order conditional estimation. A Michaelis-Menten model with delayed induction was preferred over a Michaelis-Menten model without induction, a Michaelis-Menten model with immediate induction, or a linear model with delayed induction. When the data were fit to a Michaelis-Menten model with delayed induction, the volume of distribution (Vd) was found to depend on weight and serum albumin. The Vd was estimated to be 0.95 l/kg, assuming an albumin level of 3 g/dl. The Michaelis-Menten constant (km) was estimated to be 7.9 mg/l. The baseline maximum metabolic rate was 580 mg/day for a 70-kg patient. The average time to onset of induction was 59.5 hours. If a fever developed after induction began, it increased the extent of induction. This model was evaluated retrospectively in 26 additional patients, yielding a mean prediction error of -0.4 mg/l (-3.0-2.2 mg/l) and a mean absolute prediction error of 4.7 mg/l (3.2-6.2 mg/l) based on two-level feedback. Given the large interindividual variances in maximum metabolic rate, phenytoin levels should be measured frequently.
Scherer, Michael; Romano, Eduardo; Caldwell, Susan; Taylor, Eileen
2017-07-11
Driving under the influence (DUI) citations are still a serious concern among drivers aged 16-20 years and have been shown to be related to increased risk of fatal and non-fatal crashes. A battery of laws and policies has been enacted to address this concern. While numerous studies have evaluated these policies, there is still a need for comprehensive policy evaluations that take into account a variety of contextual factors. Previous effort by this research team examined the impact of 20 minimum legal drinking age (MLDA)-21 laws in the state of California, as they impacted alcohol-related crash rates among drivers under 21 years of age while at the same time accounting for alcohol and gas taxes, unemployment rates, sex distribution among drivers, and sobriety checkpoints. The current research seeks to expand this evaluation to the county level (San Diego, County). More specifically, we evaluate the impact of measures subject to County control such as Retail Beverage Service (RBS) laws and Social Host (SH) laws, as well as media coverage, city employment, alcohol outlet density, number of sworn officers, alcohol consumption, and taxation policies to determine the most effective point of intervention for communities seeking to reduce underage DUI citations. Annual DUI citation data (2000 to 2013), RBS and SH policies, and city-wide demographic, economic, and environmental information were collected and applied to each of the 20 cities in San Diego County, California. A structural equation model was fit to estimate the relative contribution of the variables of interest to DUI citation rates. Alcohol consumption and alcohol outlet density both demonstrated a significant increase in DUI rates, while RBS laws, SH laws, alcohol tax rates, media clusters, gas tax rates and unemployment rates demonstrated significant decreases in DUI rates. At the county level, although RBS, SH laws, and media efforts were found to contribute to a significant reduction in DUI rates, the
Global analysis of the stream power law parameters based on worldwide 10Be denudation rates
Harel, M.-A.; Mudd, S. M.; Attal, M.
2016-09-01
The stream power law, expressed as E = KAmSn - where E is erosion rate [LT - 1], K is an erodibility coefficient [T - 1L (1 - 2m)], A is drainage area [L 2], S is channel gradient [L/L], and m and n are constants - is the most widely used model for bedrock channel incision. Despite its simplicity and limitations, the model has proved useful for topographic evolution, knickpoint migration, palaeotopography reconstruction, and the determination of rock uplift patterns and rates. However, the unknown parameters K, m, and n are often fixed arbitrarily or are based on assumptions about the physics of the erosion processes that are not always valid, which considerably limits the use and interpretation of the model. In this study, we compile a unique global data set of published basin-averaged erosion rates that use detrital cosmogenic 10Be. These data (N = 1457) enable values for fundamental river properties to be empirically constrained, often for the first time, such as the concavity of the river profile (m/n ratio or concavity index), the link between channel slope and erosion rate (slope exponent n), and substrate erodibility (K). These three parameters are calculated for 59 geographic areas using the integral method of channel profile analysis and allow for a global scale analysis in terms of climatic, tectonic, and environmental settings. In order to compare multiple sites, we also normalize n and K using a reference concavity index m/n = 0.5. A multiple regression analysis demonstrates that intuitive or previously demonstrated local-scale trends, such as the correlation between K and precipitation rates, do not appear at a global scale. Our results suggest that the slope exponent is generally > 1, meaning that the relationship between erosion rate and the channel gradient is nonlinear and thus support the hypothesis that incision is a threshold controlled process. This result questions the validity of many regional interpretations of climate and/or tectonics where
Xiao Liu
2016-01-01
Full Text Available Random disturbance factors would lead to the variation of target acquisition point during the long distance flight. To acquire a high target acquisition probability and improve the impact precision, missiles should be guided to an appropriate target acquisition position with certain attitude angles and line-of-sight (LOS angle rate. This paper has presented a new midcourse guidance law considering the influences of random disturbances, detection distance restraint, and target acquisition probability with Monte Carlo simulation. Detailed analyses of the impact points on the ground and the random distribution of the target acquisition position in the 3D space are given to get the appropriate attitude angles and the end position for the midcourse guidance. Then, a new formulation biased proportional navigation (BPN guidance law with angular constraint and LOS angle rate control has been derived to ensure the tracking ability when attacking the maneuvering target. Numerical simulations demonstrates that, compared with the proportional navigation guidance (PNG law and the near-optimal spatial midcourse guidance (NSMG law, BPN guidance law demonstrates satisfactory performances and can meet both the midcourse terminal angular constraint and the LOS angle rate requirement.
Nakonezny, Paul A.; And Others
1995-01-01
Studied no-fault divorce law effects on the divorce rate. Results revealed that no-fault divorce laws led to measurable increases in divorce rates. Median family income was the only significant predictor of change in divorce rate; the adjusted post-no-fault divorce rate increased as median family income increased. (RJM)
Lavee, J; Ashkenazi, T; Stoler, A; Cohen, J; Beyar, R
2013-03-01
Israel's organ donation rate has always been among the lowest in Western countries. In 2008 two new laws relevant to organ transplantation were introduced. The Brain-Respiratory Death Law defines the precise circumstances and mechanisms to determine brain death. The Organ Transplantation Law bans reimbursing transplant tourism involving organ trade, grants prioritization in organ allocation to candidates who are registered donors and removes disincentives for living donation by providing modest insurance reimbursement and social supportive services. The preliminary impact of the gradual introduction and implementation of these laws has been witnessed in 2011. Compared to previous years, in 2011 there was a significant increase in the number of deceased organ donors directly related to an increase in organ donation rate (from 7.8 to 11.4 donors per million population), in parallel to a significant increase in the number of new registered donors. In addition the number of kidney transplantations from living donors significantly increased in parallel to a significant decrease in the number of kidney transplantations performed abroad (from 155 in 2006 to 35 in 2011). The new laws have significantly increased both deceased and living organ donation while sharply decreasing transplant tourism. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.
Andric, Pavle; Meyer, Anne S.; Jensen, Peter Arendt
2010-01-01
, during 96 h of reaction. When glucose was removed by dialysis during the enzymatic hydrolysis, the cellulose conversion rates and glucose yields increased. In fact, with dialytic in situ glucose removal, the rate of enzyme-catalyzed glucose release during 48-72 h of reaction recovered from 20......-40% to become approximate to 70% of the rate recorded during 6-24 h of reaction. Although Michaelis-Menten kinetics do not suffice to model the kinetics of the complex multi-enzymatic degradation of cellulose, the data for the glucose inhibition were surprisingly well described by simple Michaelis......-Menten inhibition models without great significance of the inhibition mechanism. Moreover, the experimental in situ removal of glucose could be simulated by a Michaelis-Menten inhibition model. The data provide an important base for design of novel reactors and operating regimes which include continuous product...
Wang, M; Sun, X Z; Tang, S X; Tan, Z L; Pacheco, D
2013-06-01
Water-soluble components of feedstuffs are mainly utilized during the early phase of microbial fermentation, which could be deemed an important determinant of gas production behavior in vitro. Many studies proposed that the fractional rate of degradation (FRD) estimated by fitting gas production curves to mathematical models might be used to characterize the early incubation for in vitro systems. In this study, the mathematical concept of FRD was developed on the basis of the Logistic-Exponential (LE) model, with initial gas volume being zero (LE0). The FRD of the LE0 model exhibits a continuous increase from initial (FRD 0) toward final asymptotic value (FRD F) with longer incubation time. The relationships between the FRD and gas production at incubation times 2, 4, 6, 8, 12 and 24 h were compared for four models, in addition to LE0, Generalization of the Mitscherlich (GM), c th order Michaelis-Menten (MM) and Exponential with a discrete LAG (EXPLAG). A total of 94 in vitro gas curves from four subsets with a wide range of feedstuffs from different laboratories and incubation periods were used for model testing. Results indicated that compared with the GM, MM and EXPLAG models, the FRD of LE0 model consistently had stronger correlations with gas production across the four subsets, especially at incubation times 2, 4, 6, 8 and 12 h. Thus, the LE0 model was deemed to provide a better representation of the early fermentation rates. Furthermore, the FRD 0 also exhibited strong correlations (P < 0.05) with gas production at early incubation times 2, 4, 6 and 8 h across all four subsets. In summary, the FRD of LE0 model provides an alternative to quantify the rate of early stage incubation, and its initial value could be an important starting parameter of rate.
Generic Enzymatic Rate Equation%酶反应速率方程的普适形式
徐岷涓; 朱晓梅; 林保宏; 敖平
2011-01-01
Kinetic modeling of large-scale metabolic network require a generic enzymatic rate equation. In the generic form, kinetic parameters are clear and precise enough to correlate to experimental data and construct a database. Such a uniform form is easy to deal with arbitrary number of substrates and products in computation of dynamic modeling. The generic rate equation is symmetrical in both directions of reversible reaction and formally exact under the quasi-steady state condition. Here presented the rigorous derivation of generic rate equation from further three classical enzymatic rate equations and discussed the characters and uses of the generic form.%酶反应速率方程的普适形式是应用于相互关联的大规模代谢途径动力学建模的重要方法.把酶反应速率方程写成Michaelis-Menten-King-Altman方程形式可以使得动力学参数(或函数)容易与数据库中的实验数据相接轨,并可以处理任意数量的底物和产物,有利于大规模的计算.普适形式可以同时描述正、负反应方向,并能精确地用于准稳态条件.展示了在三类生物体系中广泛存在的酶反应机制中普适方程的严格推导过程,并讨论了普适方程的特点,针对不可逆反应酶反应产生的产物抑制效应可以自然消除,总结了在普适速率方程中体现调节剂的作用和协同作用.
Gratz, Andrew J.; Bird, Peter
1993-01-01
The range of the measured quartz dissolution rates, as a function of temperature and pOH, extent of saturation, and ionic strength, is extended to cover a wider range of solution chemistries, using the negative crystal methodology of Gratz et al. (1990) to measure the dissolution rate. A simple rate law describing the quartz dissolution kinetics above the point of zero charge of quartz is derived for ionic strengths above 0.003 m. Measurements were performed on some defective crystals, and the mathematics of step motion was developed for quartz dissolution and was compared with rough-face behavior using two different models.
Mao, You-An; Zhong, Ke-Jun; Wei, Wan-Zhi; Wei, Xin-Liang; Lu, Hong-Bing
2005-02-01
The effect of N'-nitrosonornicotine (NNN), one of the tobacco-specific nitrosamines, on the catalytic activity of glutamate dehydrogenase (GLDH) in the alpha-ketoglutarate amination, using reduced nicotinamide adenine dinucleotide as coenzyme, was studied by a chronoamperometric method. The maximum reaction rate of the enzyme-catalyzed reaction and the Michaelis-Menten constant, or the apparent Michaelis-Menten constant, were determined in the absence and presence of NNN. NNN remarkably inhibited the bio-catalysis activity of GLDH, and was a reversible competitive inhibitior with K(i), estimated as 199 micromol l(-1) at 25 degrees C and pH 8.0.
The Effect of Saquinavir on the Rate of Metabolism of Midazolam
2013-01-31
Hensyl, 1990). Saquinavir and Midazolam 8 Ki The inhibition constant for Michaelis - Menten kinetics which describes the ability of a drug to inhibit...Redacted] PREFACE This study was conducted to provide information regarding the kinetic interaction between midazolam and saquinavir. Midazolam is a...the catalysis of a second drug (Fabre et. al., 1988). Km The Michaelis constant that describes the affinity of an enzyme to a particular substrate
RENEWAL OF BASIC LAWS AND PRINCIPLES FOR POLAR CONTINUUM THEORIES(Ⅶ)-INCREMENTAL RATE TYPE
戴安民
2003-01-01
The purpose is to establish the rather complete equations of motion, boundary conditions and equation of energy rate of incremental rate type for micropolar continua. To this end the rather complete definitions for rates of deformation gradient and its inverse are made. The new relations between various stress and couple stress rate tensors are derived.Finally, the coupled equations of motion, boundary conditions and equation of energy rate of incremental rate type for continuum mechanics are obtained as a special case.
Noda, H.
2016-05-01
Pressure solution creep (PSC) is an important elementary process in rock friction at high temperatures where solubilities of rock-forming minerals are significantly large. It significantly changes the frictional resistance and enhances time-dependent strengthening. A recent microphysical model for PSC-involved friction of clay-quartz mixtures, which can explain a transition between dilatant and non-dilatant deformation (d-nd transition), was modified here and implemented in dynamic earthquake sequence simulations. The original model resulted in essentially a kind of rate- and state-dependent friction (RSF) law, but assumed a constant friction coefficient for clay resulting in zero instantaneous rate dependency in the dilatant regime. In this study, an instantaneous rate dependency for the clay friction coefficient was introduced, consistent with experiments, resulting in a friction law suitable for earthquake sequence simulations. In addition, a term for time-dependent strengthening due to PSC was added which makes the friction law logarithmically rate-weakening in the dilatant regime. The width of the zone in which clasts overlap or, equivalently, the interface porosity involved in PSC plays a role as the state variable. Such a concrete physical meaning of the state variable is a great advantage in future modelling studies incorporating other physical processes such as hydraulic effects. Earthquake sequence simulations with different pore pressure distributions demonstrated that excess pore pressure at depth causes deeper rupture propagation with smaller slip per event and a shorter recurrence interval. The simulated ruptures were arrested a few kilometres below the point of pre-seismic peak stress at the d-nd transition and did not propagate spontaneously into the region of pre-seismic non-dilatant deformation. PSC weakens the fault against slow deformation and thus such a region cannot produce a dynamic stress drop. Dynamic rupture propagation further down to
Buttram, Mance E; Kurtz, Steven P; Dart, Richard C; Margolin, Zachary R
2017-09-01
Recent limited epidemiologic and case reports suggest that gabapentin is being misused, especially among prescription opioid misusers. However, no apparent studies have reported data from law enforcement on the diversion and misuse of gabapentin. Case report data are drawn from a quarterly survey of prescription drug diversion completed by a national sample of law enforcement and regulatory agencies who engage in drug diversion investigations. Rates of gabapentin diversion per 100 000 population were calculated for each quarter from 2002 through 2015. Qualitative data are drawn from a brief questionnaire completed by a subsample of survey respondents and were organized and presented by theme. In total, 407 new cases of diverted gabapentin were reported during the time period, with diversion rates steadily increasing from zero cases in the first 2 quarters of 2002 to a high of 0.027 cases per 100 000 population in the fourth quarter of 2015. Qualitative data suggest that gabapentin is being misused in conjunction with prescription opioids and that gabapentin and heroin are being combined and consumed together. Law enforcement reporters found these drug use trends to be contributing to gabapentin diversion. The recent increase in gabapentin diversion appears to be related to the opioid epidemic, based on law enforcement descriptions of gabapentin being misused in combination with opioids. Yet epidemiological data related to this finding is limited and research conducted among gabapentin misusers is needed to understand this problem in more depth. Greater monitoring of gabapentin abuse and diversion appear warranted. Copyright © 2017 John Wiley & Sons, Ltd.
Okun's Law, Creation of Money and the Decomposition of the Rate of Unemployment
Stéphane Mussard; Bernard Philippe
2006-01-01
In this paper, we show that the rate of unemployment in period t depends on GDP and inflation rate in period t-1. We then show that GDP is related to money creation, and subsequently that the rate of unemployment is a decreasing function of this creation.
Ruthenium(III Catalysis in Perborate Oxidation of 5-Oxoacids
S. Shree Devi
2014-01-01
Full Text Available Ruthenium(III catalyzes perborate oxidation of substituted 5-oxoacids in acidic solution. The catalyzed oxidation is first order with respect to the oxidant and catalyst. The rate of ruthenium(III catalyzed oxidation displays the Michaelis-Menten kinetics on the reductant and is independent of [H+] of the medium. Hydrogen peroxide is the reactive species of perborate and the kinetic results reveal formation of ruthenium(III peroxo species-5-oxoacid complex. Electron-releasing substituents accelerate the reaction rate and electron-withdrawing substituents retard it. The order of reactivity among the studied 5-oxoacids is p-methoxy ≫ p-methyl > p-phenyl > −H > p-chloro > p-bromo > m-nitro. Activation parameters are evaluated using Arrhenius and Eyring’s plots. A mechanism consistent with the observed kinetic data is proposed and discussed. A suitable rate law is derived based on the mechanism.
Do More Hospital Beds Lead to Higher Hospitalization Rates? A Spatial Examination of Roemer’s Law
Delamater, Paul L.; Messina, Joseph P.; Grady, Sue C.; WinklerPrins, Vince; Shortridge, Ashton M.
2013-01-01
Background Roemer’s Law, a widely cited principle in health care policy, states that hospital beds that are built tend to be used. This simple but powerful expression has been invoked to justify Certificate of Need regulation of hospital beds in an effort to contain health care costs. Despite its influence, a surprisingly small body of empirical evidence supports its content. Furthermore, known geographic factors influencing health services use and the spatial structure of the relationship between hospital bed availability and hospitalization rates have not been sufficiently explored in past examinations of Roemer’s Law. We pose the question, “Accounting for space in health care access and use, is there an observable association between the availability of hospital beds and hospital utilization?” Methods We employ an ecological research design based upon the Anderson behavioral model of health care utilization. This conceptual model is implemented in an explicitly spatial context. The effect of hospital bed availability on the utilization of hospital services is evaluated, accounting for spatial structure and controlling for other known determinants of hospital utilization. The stability of this relationship is explored by testing across numerous geographic scales of analysis. The case study comprises an entire state system of hospitals and population, evaluating over one million inpatient admissions. Results We find compelling evidence that a positive, statistically significant relationship exists between hospital bed availability and inpatient hospitalization rates. Additionally, the observed relationship is invariant with changes in the geographic scale of analysis. Conclusions This study provides evidence for the effects of Roemer’s Law, thus suggesting that variations in hospitalization rates have origins in the availability of hospital beds. This relationship is found to be robust across geographic scales of analysis. These findings suggest
A. Adetoro
2011-10-01
Full Text Available The kinetics of the oxidation of Pyrocatechol violet (PCVH by nitrite ion (NO2- in aqueous acidic medium has been studied at 24±1ºC, I = 0.50 mol/dm3(NaCl, [H+] = 1.0×10-3 mol/dm3. The reaction is first order to [PCVH] and half order to [NO2-]. The redox reaction displayed a 1:1 stoichiometry and obeys the rate law: d[PCVH]/dt = (a + b[H+] [PCVH][NO2-]½. The second-order rate constant increases with increase in acid concentration and ionic strength. This system displayed positive salt effect while spectroscopic investigation and Michaelis-Menten plot showed evidence of intermediate complex formation in the course of the reaction. A plausible mechanism has been proposed for the reaction.
Kuykendall, Katherine
2011-07-01
Constitutive laws commonly used to model friction stir welding have been evaluated, both qualitatively and quantitatively, and a new application of a constitutive law which can be extended to materials commonly used in FSW is presented. Existing constitutive laws have been classified as path-dependent or path-independent. Path-independent laws have been further classified according to the physical phenomena they capture: strain hardening, strain rate hardening, and/or thermal softening. Path-dependent laws can track gradients in temperature and strain rate characteristic to friction stir welding; however, path-independent laws cannot. None of the path-independent constitutive laws evaluated has been validated over the full range of strain, strain rate, and temperature in friction stir welding. Holding all parameters other than constitutive law constant in a friction stir weld model resulted in temperature differences of up to 21%. Varying locations for maximum temperature difference indicate that the constitutive laws resulted in different temperature profiles. The Sheppard and Wright law is capable of capturing saturation but incapable of capturing strain hardening with errors as large as 57% near yield. The Johnson-Cook law is capable of capturing strain hardening; however, its inability to capture saturation causes over-predictions of stress at large strains with errors as large as 37% near saturation. The Kocks and Mecking model is capable of capturing strain hardening and saturation with errors less than 5% over the entire range of plastic strain. The Sheppard and Wright and Johnson-Cook laws are incapable of capturing transients characteristic of material behavior under interrupted temperature or strain rate. The use of a state variable in the Kocks and Mecking law allows it to predict such transients. Constants for the Kocks and Mecking model for AA 5083, AA 3004, and Inconel 600 were determined from Atlas of Formability data. Constants for AA 5083 and AA
A Simple Rate Law Experiment Using a Custom-Built Isothermal Heat Conduction Calorimeter
Wadso, Lars; Li, Xi.
2008-01-01
Most processes (whether physical, chemical, or biological) produce or consume heat: measuring thermal power (the heat production rate) is therefore a typical method of studying processes. Here we describe the design of a simple isothermal heat conduction calorimeter built for use in teaching; we also provide an example of its use in simultaneously…
Moment Convergence Rates in the Law of the Logarithm for Dependent Sequences
Ke-Ang Fu; Xiao-Rong Yang
2009-06-01
Let $\\{X_n;n≥ 1\\}$ be a strictly stationary sequence of negatively associated random variables with mean zero and finite variance. Set $S_n=\\sum^n_{k=1}X_k,M_n=\\max_{k≤ n}|S_k|,n≥ 1$. Suppose $^2=EX^2_1+2\\sum^∞_{k=2}EX_1X_k(0 < < ∞)$. In this paper, the exact convergence rates of a kind of weighted infinite series of $E\\{M_n-\\sqrt{n\\log n}\\}_+$ and $E\\{|S_n|-\\sqrt{n\\log n}\\}_+$ as $\\searrow 0$ and $E\\{\\sqrt{\\frac{^2 n}{8\\log n}}-M_n\\}_+$ as $\
Cristiane Fagundes
2013-03-01
Full Text Available In this study, the influence of storage temperature and passive modified packaging (PMP on the respiration rate and physicochemical properties of fresh-cut Gala apples (Malus domestica B. was investigated. The samples were packed in flexible multilayer bags and stored at 2 °C, 5 °C, and 7 °C for eleven days. Respiration rate as a function of CO2 and O2 concentrations was determined using gas chromatography. The inhibition parameters were estimated using a mathematical model based on Michaelis-Menten equation. The following physicochemical properties were evaluated: total soluble solids, pH, titratable acidity, and reducing sugars. At 2 °C, the maximum respiration rate was observed after 150 hours. At 5 °C and 7 °C the maximum respiration rates were observed after 100 and 50 hours of storage, respectively. The inhibition model results obtained showed a clear effect of CO2 on O2 consumption. The soluble solids decreased, although not significantly, during storage at the three temperatures studied. Reducing sugars and titratable acidity decreased during storage and the pH increased. These results indicate that the respiration rate influenced the physicochemical properties.Neste estudo, a influência da temperatura de armazenamento e da embalagem com atmosfera modificada passiva (AMP na taxa respiratória e nas propriedades físico-químicas de maçãs da variedade Gala (Malus domestica, B. minimamente processadas foi investigada. As amostras foram acondicionadas em embalagens flexíveis e armazenados a 2 °C, 5 °C e 7 °C, durante 11 dias. A taxa de respiração foi gerada para diferentes concentrações de O2 e CO2, obtidas por cromatografia gasosa. Os parâmetros de inibição foram estimados por um modelo matemático baseado na equação de Michaelis-Menten. Foram avaliadas as seguintes propriedades físico-químicas: sólidos solúveis totais, pH, acidez titulável e açúcares redutores. A 2 °C, a taxa de respiração máxima foi
Van Poppel, F; De Beer, J
1991-06-01
"This article examines the effects of three juridical changes [in 1838, 1883, and 1971] on the divorce rate in the Netherlands.... For this purpose intervention variables were added to a statistical time-series...model. If it is assumed that the effects of the 1883 and 1971 reforms have been permanent, the total effect of the juridical reforms has been considerable. However, even though the model based on the assumption of permanent effects provides the best fit of the data, changes occurring some years after the immediate effects suggest that it may be reasonable to assume that the effects were temporary only." An English-language version of the article is available from the author. (SUMMARY IN ENG)
Ketobemidone prodrugs for buccal delivery
Hansen, L.B.; Christrup, Lona Louring; Bundgaard, H.
1992-01-01
conditions ensuring maximal esterase activity, was studied as a function of ester concentration at 37°C. The kinetics of hydrolysis could be accounted for in terms of the Michaelis-Menten equation and the rate parameters K(m) and V(max) were determined. Due to the occurrence of zero-order kinetics...
This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights ...
This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights ...
Manipulating single enzymes by an external harmonic force
Lomholt, Michael A; Urbakh, Michael; Metzler, Ralf
2007-01-01
We study a Michaelis-Menten reaction for a single two-state enzyme molecule, whose transition rates between the two conformations are modulated by an harmonically oscillating external force. In particular, we obtain a range of optimal driving frequencies for changing the conformation of the enzyme...
KINETICS OF QUERCETIN NITRATIO N BY HORSERADISH PEROXIDASE
Andrija Šmelcerović
2013-03-01
Full Text Available In this study we investigated the kinetics of the nitration of quercetin by horseradish peroxidase. Quercetin nitration reaction was followed by recording the spectral changes over the time at 380 nm. The reaction rate increases with increasing of the quercetin concentration and follows the Michaelis-Menten type kinetics. Kinetic parameters of the studied enzymatic reaction were determined.
An, C.; Parker, G.; Fu, X.
2015-12-01
River morphology evolves in response to trade-offs among a series of environmental forcing factors, and this evolution will be disturbed if such environmental factors change. One example of response to chronic disturbance is the intensive river evolution after earthquakes in southwest China's mountain areas. When simulating river morphological response to environmental disturbance, an exponential rate law with a specified characteristic response time is often regarded as a practical tool for quantification. As conceptual models, empirical rate law formulations can be used to describe broad brush morphological response, but their physically basis is not solid in that they do not consider the details of morphodynamic processes. Meanwhile, river evolution can also be simulated with physically-based morphodynamic models which conserve sediment via the Exner equation. Here we study the links between the rate law formalism and the Exner equation through solving the Exner equation mathematically and numerically. The results show that, when implementing a very simplified form of a relation for bedload transport, the Exner equation can be reduced to the diffusion equation, the solution of which is a Gaussian function. This solution coincides with the solution associated with rate laws, thus providing a physical basis for such formulations. However, when the complexities of a natural river are considered, the solution of the Exner equation will no longer be a simple Gaussian function. Under such circumstances, the rate law becomes invalid, and a full understanding of the response of rivers to earthquakes requires a complete morphodynamic model.
The Law of the Tendency of the Rate of Profit to Fall and the End User Communication Technology
Peter Sekloča
2015-03-01
Full Text Available The author critically analyses the contemporary debate about the law of the tendential fall in the rate of profit in which Marx summed up the central contradiction of the capitalist mode of production. The results of the analysis are then applied on the business strategies of the informational capitalism in the segment of end users of the informational and communicational technology. Unpaid labor of users for digital media platform owners as well as hardware and software purchase both resemble peculiar counteracting tendencies for the “law”. The analysis indicates that the immaterial labor and outsourcing of equipment may truly increase the profit rate in a way that was rather inconceivable in Marx's day, but this still does not undermine the “law’s” validity. Counteracting tendencies have their own limits and that is also why the capital does not allow them to reach their end and restore conditions for a “new” central contradiction conceptualized by Italian autonomists.
Gómez-Uribe, Carlos A; Verghese, George C; Tzafriri, Abraham R
2008-12-28
Widely different time scales are common in systems of chemical reactions and can be exploited to obtain reduced models applicable to the time scales of interest. These reduced models enable more efficient computation and simplify analysis. A classic example is the irreversible enzymatic reaction, for which separation of time scales in a deterministic mass action kinetics model results in approximate rate laws for the slow dynamics, such as that of Michaelis-Menten. Recently, several methods have been developed for separation of slow and fast time scales in chemical master equation (CME) descriptions of stochastic chemical kinetics, yielding separate reduced CMEs for the slow variables and the fast variables. The paper begins by systematizing the preliminary step of identifying slow and fast variables in a chemical system from a specification of the slow and fast reactions in the system. The authors then present an enhanced time-scale-separation method that can extend the validity and improve the accuracy of existing methods by better accounting for slow reactions when equilibrating the fast subsystem. The resulting method is particularly accurate in systems such as enzymatic and protein interaction networks, where the rates of the slow reactions that modify the slow variables are not a function of the slow variables. The authors apply their methodology to the case of an irreversible enzymatic reaction and show that the resulting improvements in accuracy and validity are analogous to those obtained in the deterministic case by using the total quasi-steady-state approximation rather than the classical Michaelis-Menten. The other main contribution of this paper is to show how mass fluctuation kinetics models, which give approximate evolution equations for the means, variances, and covariances of the concentrations in a chemical system, can feed into time-scale-separation methods at a variety of stages.
A. Farmany; H. Noorizadeh; S.S. Mortazavi
2011-01-01
The semi-classical black hole tunneling radiation （Parikh-Wilczek tunneling proposal） is calculated under a minimal length uncertainty analysis. It is shown that, the generalized second law of thermodynamics may bound the tunneling probability radiation of a Reissner-Nordstrom black hole radiation.
Luz Helena Guamanzara Torres
2013-01-01
Full Text Available This paper provides a review of the book The Law of Secrets, of the author Juan Carlos Martínez-Villalba Riofrío studying the secrets and how law does protect. To this end, the author has analyzed the general theory of secrecy, secrets and methodology, its overall rating, essential elements and their different legal dimensions, the secret as a subjective right. It also establishes that professional secrecy is protected by constitutional principles such as the right to privacy.
K. S. Adegbie; F. I. Alao
2012-01-01
A mathematical model for thermal explosion in a combustible dusty gas containing fuel droplets with general Arrhenius reaction-rate laws, convective and radiative heat losses, and interphase heat exchange between gas and inert solid particles is investigated. The objective of the study is to examine the effects of interphase heat exchange between the gas and solid particles on (i) ignition of reacting gas, (ii) accumulation of heat by the solid particles during combustion process (iii) evapor...
马中良; 李艳利; 鲍真真; 王旻
2005-01-01
在生物化学试验中,酶的米氏常数的测定实验是经典的实验.通过Km 测定这一实验的改进,指导学生怎样认识和把握理论知识,并将之应用科学研究中.在生物化学实验教学中,注意提高学生的动手能力,提高解决问题和分析问题的能力,从而形成对待实验结果和教材的正确观点.
林中; 苏银法
2004-01-01
目的: 获得(一级并行)米氏消除药物静脉注射给药时的血药浓度近似解.方法: 根据四阶Runge-Kutta算法,采用Excel软件编写基于药动学参数的程序.结果:输出某周期或稳态任一次给药后的预期血药浓度.结论:方法操作简单,结果可靠,可作为(一级并行)米氏消除药物静脉注射给药时药动学方程的数值解法.
苏银法; 杜乐燕
2006-01-01
目的获得(一级并行)米氏消除药物血管外给药时的血药浓度近似值.方法根据四阶Runge-Kutta算法,采用Excel软件编写基于药动学参数的血药浓度近似解表格程序.结果通过实例演示,可以输出第n周期(或稳态)第s次血管外给药后每间隔0.005 h的预期血药浓度.结论该法是(一级并行)米氏消除药物血管外给药动力学方程的一种可靠的数值解法.
祁兵; 黄大贶
2003-01-01
@@ Michaelis-Menten消除动力学(下称米氏型消除)是非线性药物动力学中的重要部分.大量临床研究表明[1],呈药动学非线性特征的药物,尤有必要进行血药浓度监测.本文对静注多次给药情况下的稳态动力学特征进行了研究,得到了稳态浓度存在的必要条件及稳态浓度的精确表达式,为临床用药提供了理论依据.
易洪雷; 丁辛
2001-01-01
Focused on various BP algorithms with variable learning rate based on network system error gradient, a modified learning strategy for training non-linear network models is developed with both the incremental and the decremental factors of network learning rate being adjusted adaptively and dynamically. The golden section law is put forward to build a relationship between the network training parameters, and a series of data from an existing model is used to train and test the network parameters. By means of the evaluation of network performance in respect to convergent speed and predicting precision, the effectiveness of the proposed learning strategy can be illustrated.
Föh, Kennet Fischer; Mandøe, Lene; Tinten, Bjarke
Business Law is a translation of the 2nd edition of Erhvervsjura - videregående uddannelser. It is an educational textbook for the subject of business law. The textbook covers all important topic?s within business law such as the Legal System, Private International Law, Insolvency Law, Contract law......, Instruments of debt and other claims, Sale of Goods and real estate, Charges, mortgages and pledges, Guarantees, Credit agreements, Tort Law, Product liability and Insurance, Company law, Market law, Labour Law, Family Law and Law of Inheritance....
Sendzik, Mark Edward
2002-01-01
The analysis explores the environmental justice impacts of the 1998 Illinois Retail Rate Law and Cook County waste-to-energy siting proposals on the Chicago metropolitan area. Particular attention is given to the dynamics of the grassroots environmental organizations which emerged to fight the siting proposals. The organizations are examined in the context of NIMBYism, the antitoxic movement, the environmental justice movement, and mainstream environmentalism. In addition, the underlying causes for the unintended consequences of the Retail Rate Law are analyzed against the backdrop of market and government failure. Face-to-face and telephone interviews were conducted with forty-one persons familiar with the battles over the Cook County siting proposals and the efforts to repeal the Retail Rate Law. The term "environmental justice" became controversial as siting opponents and supporters both appropriated the issue to support dueling positions on the proposed sitings. However, environmental justice did not play an instrumental role in repealing the Retail Rate Law or the siting proposals. Economic concerns led to the repeal of the legislation and demise of the original siting proposals. The circumstances of the siting battles and opposition groups raise questions about the future effectiveness of the environmental justice movement. A combination of market and government failure led to the unintended consequences from the retail Rate Law. Strategic maneuvering by state legislative leaders delayed the repeal of the legislation by several years. The resulting delay placed considerable cost on individuals, communities, corporations, and the State of Illinois. A bivariate analysis was conducted to examine whether the distribution patterns of ground level concentrations from the proposed facilities would have had a disproportionate distribution in lower-income and minority populations in the Chicago metropolitan area. The statistical analysis did discover evidence that
Jawad, Abdul [COMSATS Institute of Information Technology, Department of Mathematics, Lahore (Pakistan); Videla, Nelson [FCFM, Universidad de Chile, Departamento de Fisica, Santiago (Chile); Gulshan, Faiza [Lahore Leads University, Department of Mathematics, Lahore (Pakistan)
2017-05-15
In the present work, we study the consequences of considering a new family of single-field inflation models, called power-law plateau inflation, in the warm inflation framework. We consider the inflationary expansion is driven by a standard scalar field with a decay ratio Γ having a generic power-law dependence with the scalar field φ and the temperature of the thermal bath T given by Γ(φ,T) = C{sub φ}(T{sup a})/(φ{sup a-1}). Assuming that our model evolves according to the strong dissipative regime, we study the background and perturbative dynamics, obtaining the most relevant inflationary observable as the scalar power spectrum, the scalar spectral index and its running and the tensor-to-scalar ratio. The free parameters characterizing our model are constrained by considering the essential condition for warm inflation, the conditions for the model evolves according to the strong dissipative regime and the 2015 Planck results through the n{sub s}-r plane. For completeness, we study the predictions in the n{sub s}-dn{sub s}/d ln k plane. The model is consistent with a strong dissipative dynamics and predicts values for the tensor-to-scalar ratio and for the running of the scalar spectral index consistent with current bounds imposed by Planck and we conclude that the model is viable. (orig.)
Altman-Palm, Nancy; Tremblay, Carol Horton
1998-01-01
Explores the effects of legislation requiring parental consent for a minor's abortion and the risk of acquiring AIDS on adolescent pregnancy and abortion rates. Finds lower pregnancy and abortion rates for women 15-17 in states with parental involvement legislation, while abortion doubles and pregnancy rates decline with the incidence of AIDS.…
Föh, Kennet Fischer; Mandøe, Lene; Tinten, Bjarke
Business Law is a translation of the 2nd edition of Erhvervsjura - videregående uddannelser. It is an educational textbook for the subject of business law. The textbook covers all important topic?s within business law such as the Legal System, Private International Law, Insolvency Law, Contract law...
Farazdaghi, Hadi
2011-02-01
Photosynthesis is the origin of oxygenic life on the planet, and its models are the core of all models of plant biology, agriculture, environmental quality and global climate change. A theory is presented here, based on single process biochemical reactions of Rubisco, recognizing that: In the light, Rubisco activase helps separate Rubisco from the stored ribulose-1,5-bisphosphate (RuBP), activates Rubisco with carbamylation and addition of Mg²(+), and then produces two products, in two steps: (Step 1) Reaction of Rubisco with RuBP produces a Rubisco-enediol complex, which is the carboxylase-oxygenase enzyme (Enco) and (Step 2) Enco captures CO₂ and/or O₂ and produces intermediate products leading to production and release of 3-phosphoglycerate (PGA) and Rubisco. PGA interactively controls (1) the carboxylation-oxygenation, (2) electron transport, and (3) triosephosphate pathway of the Calvin-Benson cycle that leads to the release of glucose and regeneration of RuBP. Initially, the total enzyme participates in the two steps of the reaction transitionally and its rate follows Michaelis-Menten kinetics. But, for a continuous steady state, Rubisco must be divided into two concurrently active segments for the two steps. This causes a deviation of the steady state from the transitional rate. Kinetic models are developed that integrate the transitional and the steady state reactions. They are tested and successfully validated with verifiable experimental data. The single-process theory is compared to the widely used two-process theory of Farquhar et al. (1980. Planta 149, 78-90), which assumes that the carboxylation rate is either Rubisco-limited at low CO₂ levels such as CO₂ compensation point, or RuBP regeneration-limited at high CO₂. Since the photosynthesis rate cannot increase beyond the two-process theory's Rubisco limit at the CO₂ compensation point, net photosynthesis cannot increase above zero in daylight, and since there is always respiration at
郑丹平; 吴艳阳; 吴群河; 罗昊; 张恒军; 张仁铎
2013-01-01
设计了层状底泥的连续流动培养实验装置,经调试后用于对珠江广州河段的沉积物样品进行连续流动培养实验r通过检测培养出水和稳定状态时硝氮还原速率和氨氮生成速率,运用Michaelis-Menten方程计算珠江底泥的潜在硝氮还原速率和氨氮生成速率,并结合氨氮生成和硝氮还原理论配比分析硝氮还原的主要途径.结果显示,珠江广州河段整体的潜在硝氮还原速率为1410 nmol· (h·mL)-1,硝氮还原动力参数为5.0 mmol·L-1；潜在氨氮生成速率为0.665 nmol·(h·mL)-1,氨氮生成动力参数为0.137 mmol·L-1；厌氧氨氧化作用和硝氮异化还原作用是珠江底泥中硝氮还原的主要途径.%Flow-through reactors ( FTR) were designed and debugged for the incubation experiments of sediment slices. After being constructed, the FTR with sediments were run for different concentrations of nitrate-inflow incubation experiments. Time-series concentrations of nitrate and ammonium were monitored in the outflow, and the nitrate reduction rates (NRR) and ammonium production rates (APR) were calculated when reaching a equilibrium-steady state. After that, the potential maximum nitrate reduction rate and ammonium production rate were calculated out according to Michaelis-Menten equation. The conclusions are as follows: the potential NRR in Pearl River sediment was 1410 nmol· (h·mL)-1, and the kinetic parameter of nitrate reduction was 5. 0 mmol·L-1; the potential APR was 0. 665 nmol· ( h · mL) -1, while the kentic parameter was 0.137 mmol·L-1. The anaerobic ammonium oxidation(Anammox) and the dissimilatory nitrate reduction to ammonium (DNRA) are likely to be the two principle pathways for nitrate reduction in river sediments.
Gudavalli, Ravi; Katsenovich, Yelena; Wellman, Dawn M.; Lagos, Leonel; Tansel, Berrin
2013-09-05
ABSTRACT: Hydrogen carbonate is one of the most significant components within the uranium geochemical cycle. In aqueous solutions, hydrogen carbonate forms strong complexes with uranium. As such, aqueous bicarbonate may significantly increase the rate of uranium release from uranium minerals. Quantifying the relationship of aqueous hydrogen carbonate solutions to the rate of uranium release during dissolution is critical to understanding the long-term fate of uranium within the environment. Single-pass flow-through (SPTF) experiments were conducted to estimate the rate of uranium release from Na meta-autunite as a function of bicarbonate solutions (0.0005-0.003 M) under the pH range of 6-11 and temperatures of 5-60oC. Consistent with the results of previous investigation, the rate of uranium release from sodium autunite exhibited minimal dependency on temperature; but were strongly dependent on pH and increasing concentrations of bicarbonate solutions. Most notably at pH 7, the rate of uranium release exhibited 370 fold increases relative to the rate of uranium release in the absence of bicarbonate. However, the effect of increasing concentrations of bicarbonate solutions on the release of uranium was significantly less under higher pH conditions. It is postulated that at high pH values, surface sites are saturated with carbonate, thus the addition of more bicarbonate would have less effect on uranium release. Results indicate the activation energies were unaffected by temperature and bicarbonate concentration variations, but were strongly dependent on pH conditions. As pH increased from 6 to 11, activation energy values were observed to decrease from 29.94 kJ mol-1 to 13.07 kJ mol-1. The calculated activation energies suggest a surface controlled dissolution mechanism.
Edo, María; Marchionni, Mariana; Garganta, Santiago
2017-01-01
Argentina has traditionally stood out in terms of educational outcomes among its Latin American counterparts. Schooling of older children, however, still shows room for improvement especially among the more vulnerable. Fortunately, during the last years a sizeable improvement in attendance rates for children aged 15 through 17 took place. This…
Langsted, Lars Bo; Garde, Peter; Greve, Vagn
<> book contains a thorough description of Danish substantive criminal law, criminal procedure and execution of sanctions. The book was originally published as a monograph in the International Encyclopaedia of Laws/Criminal Law....... book contains a thorough description of Danish substantive criminal law, criminal procedure and execution of sanctions. The book was originally published as a monograph in the International Encyclopaedia of Laws/Criminal Law....
Manipulating single enzymes by an external harmonic force
Lomholt, Michael A; Urbakh, Michael; Metzler, Ralf
2007-01-01
We study a Michaelis-Menten reaction for a single two-state enzyme molecule, whose transition rates between the two conformations are modulated by an harmonically oscillating external force. In particular, we obtain a range of optimal driving frequencies for changing the conformation of the enzyme......, thereby controlling the enzymatic activity (i.e., product formation). This analysis demonstrates that it is, in principle, possible to obtain information about particular rates within the kinetic scheme....
Harold J. Berman
1999-03-01
Full Text Available In the third millennium of the Christian era, which is characterised by the emergence of a world economy and eventually a world society, the concept of world law is needed to embrace not only the traditional disciplines of public international law, and comparative law, but also the common underlying legal principles applicable in world trade, world finance, transnational transfer of technology and other fields of world economic law, as well as in such emerging fields as the protection of the world's environment and the protection of universal human rights. World law combines inter-state law with the common law of humanity and the customary law of various world communities.
K. S. Adegbie
2012-01-01
Full Text Available A mathematical model for thermal explosion in a combustible dusty gas containing fuel droplets with general Arrhenius reaction-rate laws, convective and radiative heat losses, and interphase heat exchange between gas and inert solid particles is investigated. The objective of the study is to examine the effects of interphase heat exchange between the gas and solid particles on (i ignition of reacting gas, (ii accumulation of heat by the solid particles during combustion process (iii evaporation of the liquid fuel droplets, and (iv consumption of reacting gas concentration. The equations governing the physical model with realistic assumptions are stated and nondimensionalised leading to an intractable system of first-order coupled nonlinear differential equations, which is not amenable to exact methods of solution. Therefore, we present numerical solutions as well as different qualitative effects of varying interphase heat exchange parameter. Graphs and Table feature prominently to explain the results obtained.
Sousa Jr R.
2004-01-01
Full Text Available Partial hydrolysis of whey proteins by enzymes immobilized on an inert support can either change or evidence functional properties of the produced peptides, thereby increasing their applications. The hydrolysis of sweet cheese whey proteins by alcalase, which is multipoint-immobilized on agarose gel, is studied here. A Michaelis-Menten model that takes into account competitive inhibition by the product was fitted to experimental data. The influence of pH on the kinetic parameters in the range 6.0 to 11.0 was assessed, at 50ºC. Initial reaction-rate assays in a pHstat at different concentrations of substrate were used to estimate kinetic and Michaelis-Menten parameters, k and K M. Experimental data from long-term batch assays were used to quantify the inhibition parameter, K I. The fitting of the model to the experimental data was accurate in the entire pH range.
Hydrolysis of Toxic Natural Glucosides Catalyzed by Cyclodextrin Dicyanohydrins
Bjerre, Jeannette; Nielsen, Erik Holm; Bols, Mikael
2008-01-01
The hydrolysis of toxic 7-hydroxycoumarin glucosides and other aryl and alkyl glucosides, catalyzed by modified a- and ß-cyclodextrin dicyanohydrins, was investigated using different UV, redox, or HPAEC detection assays. The catalyzed reactions all followed Michaelis-Menten kinetics, and an impre......The hydrolysis of toxic 7-hydroxycoumarin glucosides and other aryl and alkyl glucosides, catalyzed by modified a- and ß-cyclodextrin dicyanohydrins, was investigated using different UV, redox, or HPAEC detection assays. The catalyzed reactions all followed Michaelis-Menten kinetics......, and an impressive rate increase of up to 7569 (kcat/kuncat) was found for the hydroxycoumarin glucoside substrate 4-MUGP. Good and moderate degrees of catalysis (kcat/kuncat) of up to 1259 were found for the natural glucosides phloridzin and skimmin. By using a newly developed catechol detection UV-assay, a weak...
Modeling Heavy Metal Removal in Wetlands.
1992-05-01
1976 a,b,c) and Pettersson (1976) treated heavy metals uptake according to Michaelis-Menten kinetics ( Lehninger , 1975), discussed later in detail...copper kinetics equation as used in this modeling effort is presented below, after Lehninger (1975): dv_ dV, Ca (5) dt dt C.+K, where: v = rate of copper...the bulk solution, Cb, using either the Lineweaver-Burk double reciprocal or Eadie-Hofstee graphical methods ( Lehninger , 1975). Nielsen (1976 b) used
A Century of Enzyme Kinetic Analysis, 1913 to 2013
Johnson, Kenneth A.
2013-01-01
This review traces the history and logical progression of methods for quantitative analysis of enzyme kinetics from the 1913 Michaelis and Menten paper to the application of modern computational methods today. Following a brief review of methods for fitting steady state kinetic data, modern methods are highlighted for fitting full progress curve kinetics based upon numerical integration of rate equations, including a re-analysis of the original Michaelis-Menten full time course kinetic data. ...
Powell, B J
2015-01-01
There is longstanding fundamental interest in 6-fold coordinated $d^6$ ($t_{2g}^6$) transition metal complexes such as [Ru(bpy)$_3$]$^{2+}$ and Ir(ppy)$_3$, particularly their phosphorescence. This interest has increased with the growing realisation that many of these complexes have potential uses in applications including photovoltaics, imaging, sensing, and light-emitting diodes. In order to design new complexes with properties tailored for specific applications a detailed understanding of the low-energy excited states, particularly the lowest energy triplet state, $T_1$, is required. Here we describe a model of pseudo-octahedral complexes based on a pseudo-angular momentum representation and show that the predictions of this model are in excellent agreement with experiment - even when the deviations from octahedral symmetry are large. This model gives a natural explanation of zero-field splitting of $T_1$ and of the relative radiative rates of the three sublevels in terms of the conservation of time-revers...
Daria Roithmayr
2015-06-01
Full Text Available Until recently, theorists considering the evolution of human cooperation have paid little attention to institutional punishment, a defining feature of large-scale human societies. Compared to individually-administered punishment, institutional punishment offers a unique potential advantage: the ability to control how quickly legal rules of punishment evolve relative to social behavior that legal punishment regulates. However, at what rate should legal rules evolve relative to society to maximize compliance? We investigate this question by modeling the co-evolution of law and cooperation in a public goods game with centralized punishment. We vary the rate at which States update their legal punishment strategy relative to Citizens’ updating of their contribution strategy and observe the effect on Citizen cooperation. We find that when States have unlimited resources, slower State updating lead to more Citizen cooperation: by updating more slowly, States force Citizens to adapt to the legal punishment rules. When States depend on Citizens to finance their punishment activities, however, we find evidence of a ‘Goldilocks’ effect: optimal compliance is achieved when legal rules evolve at a critical evolutionary rate that is slow enough to force citizens to adapt, but fast enough to enable states to quickly respond to outbreaks of citizen lawlessness.
Leahy, Catherine M; Peterson, Ray F; Wilson, Ian G; Newbury, Jonathan W; Tonkin, Anne L; Turnbull, Deborah
2010-07-01
The aim of this research was to assess tertiary student distress levels with regards to (i) comparisons with normative population data, and (ii) the effects of discipline, year level, and student characteristics. Self-reported treatment rates and level of concern regarding perceived distress were also collected. Students from all six years of an undergraduate medical course were compared with samples from Psychology, Law and Mechanical Engineering courses at the University of Adelaide, Australia. Students participated in one of three studies that were either web-based or paper-based. All studies included Kessler's Measure of Psychological Distress (K10), and questions pertaining to treatment for any mental health problems and concern regarding distress experienced. Of the 955 tertiary students who completed the K10, 48% were psychologically distressed (a K10 score > or = 22) which equated to a rate 4.4 times that of age-matched peers. The non-health disciplines were significantly more distressed than the health disciplines. Distress levels were statistically equivalent across all six years of the medical degree. Of tertiary students, 11% had been treated for a mental health problem. Levels of concern correlated with the K10 score. The results from this research suggest that high distress levels among the tertiary student body may be a phenomenon more widely spread than first thought. Low treatment rates suggest that traditional models of support may be inadequate or not appropriate for tertiary cohorts.
Berman, Harold J.; Robert W. Woodruff; James Barr Ames
1999-01-01
In the third millennium of the Christian era, which is characterised by the emergence of a world economy and eventually a world society, the concept of world law is needed to embrace not only the traditional disciplines of public international law, and comparative law, but also the common underlying legal principles applicable in world trade, world finance, transnational transfer of technology and other fields of world economic law, as well as in such emerging fields as the protection of the ...
Phenomenological analysis of ATP dependence of motor proteins.
Yunxin Zhang
Full Text Available In this study, through phenomenological comparison of the velocity-force data of processive motor proteins, including conventional kinesin, cytoplasmic dynein and myosin V, I found that, the ratio between motor velocities of two different ATP concentrations is almost invariant for any substall, superstall or negative external loads. Therefore, the velocity of motors can be well approximated by a Michaelis-Menten like formula V = [ATP]k(FL([ATP] + K(M, with L the step size, and k(F the external load F dependent rate of one mechanochemical cycle of motor motion in saturated ATP solution. The difference of Michaelis-Menten constant K(M for substall, superstall and negative external load indicates, the configurations at which ATP molecule can bind to motor heads for these three cases might be different, though the expression of k(F as a function of F might be unchanged for any external load F. Verifications of this Michaelis-Menten like formula has also been done by fitting to the recent experimental data.
Phenomenological analysis of ATP dependence of motor protein
Zhang, Yunxin
2011-01-01
In this study, through phenomenological comparison of the velocity-force data of processive motor proteins, including conventional kinesin, cytoplasmic dynein and myosin V, we found that, the ratio between motor velocities of two different ATP concentrations is almost invariant for any substall, superstall or negative external loads. Therefore, the velocity of motor can be well approximated by a Michaelis-Menten like formula $V=\\atp k(F)L/(\\atp +K_M)$, with $L$ the step size, and $k(F)$ the external load $F$ dependent rate of one mechanochemical cycle of motor motion in saturated ATP solution. The difference of Michaelis-Menten constant $K_M$ for substall, superstall and negative external load indicates, the ATP molecule affinity of motor head for these three cases are different, though the expression of $k(F)$ as a function of $F$ might be unchanged for any external load $F$. Verifications of this Michaelis-Menten like formula has also been done by fitting to the recent experimental data.
Enzymatic Reactions in Microfluidic Devices
Ristenpart, W. D.; Wan, J.; Stone, H. A.
2008-11-01
We establish simple scaling laws for enzymatic reactions in microfluidic devices, and we demonstrate that kinetic parameters obtained conventionally using multiple stop-flow experiments may instead be extracted from a single microfluidic experiment. Introduction of an enzyme and substrate species in different arms of a Y-shaped channel allows the two species to diffuse across the parallel streamlines and to begin reacting. Measurements of the product concentration versus distance down the channel provide information about the kinetics of the reaction. In the limit where the enzyme is much larger (and thus less diffusive) than the substrate, we show that near the entrance the total amount of product (P) formed varies as a power law in the distance x down the channel. For reactions that follow standard Michaelis-Menten kinetics, the power law takes the form P˜(Vmax/Km) x^5/2, where Vmax and Km are the maximum reaction rate and Michaelis constant respectively. If a large excess of substrate is used, then Km is identified by measuring Vmax far downstream where the different species are completely mixed by diffusion. Numerical simulations and experiments using the bioluminescent reaction between luciferase and ATP as a model system are both shown to accord with the model. We discuss the implications for significant savings in the amount of time and enzyme required for determination of kinetic parameters.
Kawamura, Hikaru; Kakui, Shingo; Morimoto, Syouji; Yamamoto, Takumi
2016-01-01
Statistical properties of the homogeneous one-dimensional spring-block (Burridge-Knopoff) model of earthquakes obeying the rate and state dependent friction law are studied by extensive computer simulations. The quantities computed include the magnitude distribution, the rupture-length distribution, the mainshock recurrence-time distribution, the seismic time correlations before and after the mainshock, the mean slip amount and the mean stress drop at the mainshock, etc. Events of the model can be classified into two distinct categories. One tends to be unilateral with its epicenter located at the rim of the rupture zone of the preceding event, while the other tends to be bilateral with enhanced "characteristic" features resembling the so-called "asperity". For both types events, the distribution of the rupture length L_r exhibits an exponential behavior at larger sizes, exp[-L_r/L_0] with a characteristic "seismic correlation length" L_0. The continuum limit of the model is examined, where the model is found...
Shiraki, Ryoji; Brantley, Susan L.
1995-04-01
Three affinity-based rate models based upon physical growth mechanisms were used to fit surface-controlled precipitation rate data for calcite using a continuously stirred tank reactor in NaOHCaCl 2CO 2H 2O solutions at 100°C and 100 bars total pressure between pH 6.38 and 6.98. At higher stirring speeds, when a H 2CO 3∗ was smaller than 2.33 × 10 -3, rate showed a parabolic dependence upon exp( Δ G/RT) for exp( Δ G/RT) 1.72 and followed a rate law based upon the assumption that surface nucleation is rate-limiting. When α H 2CO 3∗ was greater than 5.07 × 10 -3, the rate showed a linear dependence upon exp( Δ G/RT), suggesting growth by a simple surface adsorption mechanism. The rate of these three mechanisms at 100°C can be expressed by the following equations: ( spiral growth) R ppt = 10 -9.00±0.15expΔG/RT- 1 1.93±0.14, ( adsorption) R ppt = 10 -8.64±0.07expΔG/RT- 1 1.09±0.10, ( surface nucleation) R ppt = 10 -7.28±0.49exp- 2.36±0.21/ΔG/RT. The mechanistic model of Plummer et al. (1978) given by R net = k 1a H+ + k 2a H2CO3∗ + k 3a H2O - k 4a Ca2+a HCO-3 also describes the precipitation rate when growth followed the spiral growth equation. The rate constant for precipitation, k4, ranges between 7.08 × 10 -4 to 1.01 × 10 -3 moles cm -2 s -1 in the a H 2CO 3∗ range studied. This work shows that precipitation at 100°C in the spiral growth regime is well fit by both the mechanistic model of Plummer et al. (1978), based on multiple elementary reactions, and by a model derived for growth at screw dislocations. Outside of the regime of spiral growth, however, the model of Plummer et al. (1978) fails, suggesting that different elementary reactions control growth in the adsorption or two-dimensional nucleation regimes. However, the model of Plummer et al. (1978), based upon individual elementary reactions, accurately predicts both dissolution and precipitation of calcite under certain conditions; tests of the affinity based models
Goodman, Michael L.; Kwan, Chiman; Ayhan, Bulent; Shang, Eric L.
2017-01-01
A data driven, near photospheric, 3 D, non-force free magnetohydrodynamic model predicts time series of the complete current density, and the resistive heating rate Q at the photosphere in neutral line regions (NLRs) of 14 active regions (ARs). The model is driven by time series of the magnetic field B observed by the Helioseismic and Magnetic Imager on the Solar Dynamics Observatory (SDO) satellite. Spurious Doppler periods due to SDO orbital motion are filtered out of the time series for B in every AR pixel. Errors in B due to these periods can be significant. The number of occurrences N(q) of values of Q > or = q for each AR time series is found to be a scale invariant power law distribution, N(Q) / Q-s, above an AR dependent threshold value of Q, where 0.3952 or = E obeys the same type of distribution, N(E) / E-S, above an AR dependent threshold value of E, with 0.38 < or approx. S < or approx. 0.60, also with little variation among ARs. Within error margins the ranges of s and S are nearly identical. This strong similarity between N(Q) and N(E) suggests a fundamental connection between the process that drives coronal flares and the process that drives photospheric NLR heating rates in ARs. In addition, results suggest it is plausible that spikes in Q, several orders of magnitude above background values, are correlated with times of the subsequent occurrence of M or X flares.
R. Ramachandrappa
2013-01-01
Full Text Available A kinetic study on RuCl3-catalysed oxidation of levocarnitine (LC by sodium N-bromo-p-toluenesulphonamide or bromamine-T (BAT has been carried out in HCl medium at 303 K. The reaction rate shows a first order dependence on [BAT]0 and fractional order with respect to both [LC]0 and [H+]. Addition of the reaction product, p-toluenesulphonamide, retards the rate. The addition of RuCl3 and chloride ions to the reaction mixture shows an increase in the rate of the reaction. The dielectric effect is positive. The variation of ionic strength of the medium has no significant effect on the rate of the reaction. The reaction fails to initiate polymerization of acrylamide. Michaelis-Menten type of kinetics has been proposed. Thermodynamic parameters have been computed from Arrhenius plot by studying the reaction at different temperatures. The reaction stoichiometry and oxidation products were identified. Based on the experimental observations a suitable mechanism was proposed and rate law deduced.
Hezbollah: The Dynamics of Recruitment
2011-05-19
fundamental Michaelis - Menten kinetic interaction of the enzyme- substrate complex over time. As substrates are converted by enzymes 0 to the intermediate... Michaelis - Menten , Sensitivity Analysis, Nonlinear Differential Equations 16. PRICE CODE 17. SECURITY CLASSIFICATION UNCLASSIFIED OF REPORT 18...Illustrations Figures Figure 1. Concentration over time for the Michaelis - Menten equations. ...................................... 38 Figure 2
Dean Lueck; Thomas J. Miceli
2004-01-01
This chapter examines the economics of property rights and property law. Property law is a fundamental part of social organization and is also fundamental to the operation of the economy because it defines and protects the bundle of rights that constitute property. Property law thereby creates incentives to protect and invest in assets and establishes a legal framework within which market exchange of assets can take place. The purpose of this chapter is to show how the economics of property r...
Manitoba Dept. of Education, Winnipeg.
This publication outlines a law course intended as part of a business education program in the secondary schools of Manitoba, Canada. The one credit course of study should be taught over a period of 110-120 hours of instruction. It provides students with an introduction to the principles, practices, and consequences of law with regard to torts,…
Sadl, Urska
2013-01-01
Reasoning of the Court of Justice of the European Union – Constr uction of arguments in the case-law of the Court – Citation technique – The use of formulas to transform case-law into ‘law’ – ‘Formulaic style’ – European citizenship as a fundamental status – Ruiz Zambrano – Reasoning from...
Study on zeroing the curvature rate of differential geometric guidance law%基于零化曲率变化率的微分几何制导律研究
叶继坤; 雷虎民; 薛东风; 李炯; 邵雷
2011-01-01
Based on the idea of zeroing the curvature rate ,a new differential geometirc guidance law was proposed in order to intercept the maneuver target. Firstly, the triangle geometric relation of the missile and the target was analyzed, the shape invariability criterion of the triangle was used to design the guidance law in the Ferent coordinate based on the idea of zeroing the curvature rate,also the definite iteration algorithm was given. Secondly,the plane geometry theory was used to construct the function of Lya-punov in order to prove the stability of the derived differential geometric guidance law. Simulation results show that, compared with the proportional guidance law and integrated guidance and control method, the differential geometric guidance law has high precision, the intercept time is shorter,and the rate of the trajectory curve converges to zero in the end. Also it overcomes the load increasing sharply caused by the sight line rate divergence.%基于零化拦截器弹道曲率变化率的思想设计了一种微分几何制导律.论文首先分析了弹目拦截的几何三角形,以三角形形状的不变性为基本思想确定拦截器的飞行方向,在伏雷内(Frenet)标架内得到拦截器的制导指令,并给出每个时刻拦截器飞行方向确定的迭代算法.其次结合平面几何知识,通过构造李亚普诺夫(Liapunov)函数对设计的制导律稳定性进行理论证明推导.仿真结果表明,相对于比例导引,基于零化曲率的微分几何制导律具有较高的制导精度,弹道较为平直,末端弹道曲率变化率趋近于零,克服了比例导引末端视线角速率发散的情况,降低了执行机构的要求.
Doranda Maracineanu
2009-06-01
Full Text Available The law system of a State represents the body of rules passed or recognized by that State inorder to regulate the social relationships, rules that must be freely obeyed by their recipients, otherwisethe State intervening with its coercive power. Throughout the development of the society, pedants havebeen particularly interested in the issue of law systems, each supporting various classifications; theclassification that has remained is the one distinguishing between the Anglo-Saxon, the Roman-German,the religious and respectively the communist law systems. The third main international law system is theMuslim one, founded on the Muslim religion – the Islam. The Islam promotes the idea that Allah createdthe law and therefore it must be preserved and observed as such. Etymologically, the Arabian word“Islam” means “to be wanted, to obey” implying the fact that this law system promotes total andunconditioned submission to Allah. The Islamic law is not built on somebody of laws or leading cases,but has as source. The Islam is meant as a universal religion, the Koran promoting the idea of the unityof mankind; thus, one of the precepts in the Koran asserts that “all men are equal (…, there is nodifference between a white man and a black man, between one who is Arabian and one who is not,except for the measure in which they fear God.” The Koran is founded mainly on the Talmud, Hebrewsource of inspiration, and only on very few Christian sources. The Islam does not forward ideas whichcannot be materialized; on the contrary its ideas are purely practical, easy to be observed by the commonman, ideas subordinated to the principle of monotheism. The uncertainties and gaps of the Koran, whichhave been felt along the years, imposed the need for another set of rules, meant to supplement it – that isSunna. Sunna represents a body of laws and, consequently, the second source of the Koran. Sunnanarrates the life of the prophet Mohamed, the model to
Ian M. Sandeman
2014-09-01
Full Text Available Ocean acidification is impacting the calcification of corals, but the mechanisms of calcification are still unclear. To explore the relationship between calcification and pH, small pieces of coral were suspended from a torsion microbalance in gently stirred, temperature controlled, seawater in a closed chamber. Net calcification rate and pH were continuously monitored while light, temperature or pH could be manipulated. The coral pieces were from the edges of thin plates of Agaricia agaricites and were studied alive and freshly collected. Unexpectedly, when calcification was taking place (n=9, 0.082 mg.hr-1.cm-2, as determined by weight increase, the pH of the surrounding seawater medium changed little (n=10, -0.0047 pH units.hr-1.cm-2. When calcification was not taking place the decrease of seawater pH was an order of magnitude higher, -0.013 pH units.hr-1.cm-2. This is the opposite of what is expected when calcium carbonate (CaCO3 forms. Similarly, fresh skeleton initially showed no change of pH in the seawater medium although the rates of weight gain were high (upto 1.0 mg hr-1.cm-2. After 10 hours, as the rate of deposition decreased following a generalized Michaelis-Menten growth curve, the pH began to decrease dramatically indicating an increase of CO2 in the seawater. These unexpected results can be explained if unstable calcium bicarbonate (Ca(HCO³2 is formed in the organic matrix/carbonic anhydrase surface and slowly transforms later to CaCO3. Pieces of living coral monitored in the chamber for 30 hours gained weight during the day and loss it at night. The loss would be consistent with the transformation of Ca(HCO³2 to CaCO3 with the release of CO2. The mean calcification rate of live coral was greater (n=8, p=0.0027 in high light (120 μmol.s-1.m-2 at 0.098 mg.hr-1.cm-2, compared to 0.063 mg.hr-1.cm-2 in low light (12 μmol.s-1.m-2. However, at the same time the mean rate of pH change was -0.0076 under low light compared to -0
Signaling Cascades: Consequences of Varying Substrate and Phosphatase Levels
Feliu, Elisenda; Knudsen, Michael; Wiuf, Carsten Henrik
2012-01-01
We study signaling cascades with an arbitrary number of layers of one-site phosphorylation cycles. Such cascades are abundant in nature and integrated parts of many pathways. Based on the Michaelis-Menten model of enzyme kinetics and the law of mass-action, we derive explicit analytic expressions...... for how the steady state concentrations and the total amounts of substrates, kinase, and phosphatates depend on each other. In particular, we use these to study how the responses (the activated substrates) vary as a function of the available amounts of substrates, kinase, and phosphatases. Our results...
Permeation mechanism of a two-state potassium channel
WANG Xiangqun; ZHAO Tongjun; SONG Yang; ZHAN Yong
2007-01-01
A two-state hopping model was proposed to study the permeation of ion channel.The Nemst equation in equilibrium and the Michaelis-Menten relation in steady state were derived from the two-state kinetic model.The currentvoltage relationship obtained in the symmetrical solutions case was linear when the applied potential was less than 100 mV,which met Ohm's law.The conductance-concentration relationship exhibited the saturation property.Moreover,the characteristic time reaching the steady state of the KcsA channel was also discussed.
王静; 张立纳; 王金利
2011-01-01
我国涉法涉诉信访案件频发的原因是多样化的，而我国涉法涉诉信访案件的评查制度尚没有完全建立。坚持实事求是、依法评查并严格遵守法律程序的评查原则，建立涉法涉诉信访案件评查网络信息管理系统，明确评查主体和评查任务，实现评查机制的灵活多样和评查过程的公开透明．建立一评终局的评查终局制度方能缓解我国涉法涉诉信访案件当前的混乱状态。%The law and litigation related petition case frequently occur for a variety of reasons. China has not fully established rating and checking system of law and litigation related petition cases. To alleviate current confusion of law and litigation related c
A Relationship between Lotka's Law, Bradford's Law, and Zipf's Law.
Chen, Ye-Sho; Leimkuhler, Ferdinand F.
1986-01-01
A common functional relationship among Lotka's law, Bradford's law, and Zipf's law is derived. The proof takes explicit account of the sequences of observed values of the variables by means of an index. This approach results in a more realistic and precise formulation of each law. (Author/EM)
Gudavalli, Ravi; Katsenovich, Yelena; Wellman, Dawn M.; Idarraga, Melina; Lagos, Leonel; Tansel, Berrin
2013-08-02
Bicarbonate is one of the most significant components within the uranium geochemical cycle. In aqueous solutions, bicarbonate forms strong complexes with uranium. As such, aqueous bicarbonate may significantly increase the rate of uranium release from uranium minerals. Quantifying the relationship of aqueous bicarbonate concentration to the rate of uranium release during dissolution is critical to understanding the long-term fate of uranium within the environment. Single-pass flow-through (SPTF) experiments were conducted to estimate the rate of uranium release from Na meta-autunite as a function of bicarbonate (0.0005-0.003 M) under the pH range of 6-11 and a temperature range of 5-60oC. Consistent with the results of previous investigation, the rate of uranium release exhibited minimal dependency on temperature; but were strongly dependent on pH. Increasing aqueous bicarbonate concentrations afforded comparable increases in the rate of release of uranium. Most notably under low pH conditions the aqueous bicarbonate resulted in up to 370 fold increases in the rate of uranium release in relative to the rate of uranium release in the absence of bicarbonate. However, the effect of aqueous bicarbonate on the release of uranium was significantly less under higher pH conditions. It is postulated that at high pH values, surface sites are saturated with carbonate, thus the addition of more bicarbonate would have less effect on uranium release.
Hay, Carter; Evans, Michelle M.
2006-01-01
Rates of serious crime in the United States dropped greatly throughout the 1990s for virtually all offenses. John Donohue and Steven Levitt have argued that this reduction relates strongly to the 1973 "Roe v. Wade" decision that legalized the abortion of unwanted pregnancies. If such pregnancies result in children with higher lifetime risks of…
Hay, Carter; Evans, Michelle M.
2006-01-01
Rates of serious crime in the United States dropped greatly throughout the 1990s for virtually all offenses. John Donohue and Steven Levitt have argued that this reduction relates strongly to the 1973 "Roe v. Wade" decision that legalized the abortion of unwanted pregnancies. If such pregnancies result in children with higher lifetime risks of…
Administrative Law: The Hidden Comparative Law Course.
Strauss, Peter L.
1996-01-01
Argues that the main contribution of the Administrative Law course to law students is that it presents problems which contrast with those of the standard court-centered curriculum and can illuminate other areas of law, repeatedly confronting students with doctrinal differences. Offers several examples from civil procedure, constitutional law, and…
Javed, F.; Hainzl, S.; Aoudia, A.; Qaisar, M.
2016-05-01
We model the spatial and temporal evolution of October 8, 2005 Kashmir earthquake's aftershock activity using the rate-and-state dependent friction model incorporating uncertainties in computed coseismic stress perturbations. We estimated the best possible value for frictional resistance " Aσ n", background seismicity rate " r" and coefficient of stress variation "CV" using maximum log-likelihood method. For the whole Kashmir earthquake sequence, we measure a frictional resistance Aσ n ~ 0.0185 MPa, r ~ 20 M3.7+ events/year and CV = 0.94 ± 0.01. The spatial and temporal forecasted seismicity rate of modeled aftershocks fits well with the spatial and temporal distribution of observed aftershocks that occurred in the regions with positive static stress changes as well as in the apparent stress shadow region. To quantify the effect of secondary aftershock triggering, we have re-run the estimations for 100 stochastically declustered catalogs showing that the effect of aftershock-induced secondary stress changes is obviously minor compared to the overall uncertainties, and that the stress variability related to uncertain slip model inversions and receiver mechanisms remains the major factor to provide a reasonable data fit.
Ensemble velocity of non-processive molecular motors with multiple chemical states
Vilfan, Andrej
2014-01-01
We study the ensemble velocity of non-processive motor proteins, described with multiple chemical states. In particular, we discuss the velocity as a function of ATP concentration. Even a simple model which neglects the strain-dependence of transition rates, reverse transition rates and nonlinearities in the elasticity can show interesting functional dependencies, which deviate significantly from the frequently assumed Michaelis-Menten form. We discuss how the oder of events in the duty cycle can be inferred from the measured dependence. The model also predicts the possibility of velocity reversal at a certain ATP concentration if the duty cycle contains several conformational changes of opposite directionalities.
Manhart, Angelika; Schmeiser, Christian
2017-01-01
A model for the dynamics of actin filament ends along the leading edge of the lamellipodium is analyzed. It contains accounts of nucleation by branching, of deactivation by capping, and of lateral flow along the leading edge by polymerization. A nonlinearity arises from a Michaelis-Menten type modeling of the branching process. For branching rates large enough compared to capping rates, the existence and stability of nontrivial steady states is investigated. The main result is exponential convergence to nontrivial steady states, proven by investigating the decay of an appropriate Lyapunov functional.
José L. Gómez
2005-01-01
Full Text Available A new method for determining the intrinsic parameters of reaction in processes involving a high initial rate has been developed. The usefulness of this alternative, which consists of determining several sets of apparent parameters at different times and then extrapolating these to time zero, is demonstrated proved by the linear dependence obtained between the apparent parameters and the reaction time. The method permitted the values of the intrinsic parameters (enzyme specific activity and Michaelis-Menten constants of both substrates to be obtained for the system under study and was checked with experimental reaction rate data for the soybean peroxidase/phenol/hydrogen peroxide system.
Klieve, Helen; Barnes, Michael; De Leo, Diego
2009-04-01
Observed reductions in firearm suicides in Australia have been linked to the 1997 national firearms agreement (NFA) introduced following the 1996 Port Arthur massacre. The NFA placed strong access restrictions on firearms. To assess the impact of legislative restrictions on the incidence of firearm suicide in Queensland and explore alternative or contributory factors behind observed declines. The Queensland suicide register (QSR) provided detailed information on all male suicides in Queensland (1990-2004), with additional data for Australia (1968-2004) accessed from other official sources. Trends in suicide rates pre/post NFA, and in method selection, were assessed using negative binomial regressions. Changing method selection patterns were examined using a cohort analysis of 5 years of age classes for Australian males. The observed reduction in firearms suicides was initiated prior to the 1997 introduction of the NFA in Queensland and Australia, with a clear decline observed in Australian figures from 1988. No significant difference was found in the rate pre/post the introduction of the NFA in Queensland; however, a significant difference was found for Australian data, the quality of which is noticeably less satisfactory. A marked age-difference in method choice was observed through a cohort analysis demonstrating both time and age influences. Within sequential birth cohorts, rates of firearms suicides decreased in younger males but increased in hanging suicides; this trend was far less marked in older males. The implemented restrictions may not be responsible for the observed reductions in firearms suicide. Data suggest that a change in social and cultural attitudes could have contributed to the shift in method preference.
Allen, Linda J. S.
2016-09-01
Dr. Chowell and colleagues emphasize the importance of considering a variety of modeling approaches to characterize the growth of an epidemic during the early stages [1]. A fit of data from the 2009 H1N1 influenza pandemic and the 2014-2015 Ebola outbreak to models indicates sub-exponential growth, in contrast to the classic, homogeneous-mixing SIR model with exponential growth. With incidence rate βSI / N and S approximately equal to the total population size N, the number of new infections in an SIR epidemic model grows exponentially as in the differential equation,
Benford's law theory and applications
Miller, Steven J
2015-01-01
Benford's law states that the leading digits of many data sets are not uniformly distributed from one through nine, but rather exhibit a profound bias. This bias is evident in everything from electricity bills and street addresses to stock prices, population numbers, mortality rates, and the lengths of rivers. Here, Steven Miller brings together many of the world's leading experts on Benford's law to demonstrate the many useful techniques that arise from the law, show how truly multidisciplinary it is, and encourage collaboration. Beginning with the general theory, the contributors explain t
Kagan, Yan Y.
2010-01-01
We consider two statistical regularities that were used to explain Omori's law of the aftershock rate decay: the Levy and Inverse Gaussian (IGD) distributions. These distributions are thought to describe stress behavior influenced by various random factors: post-earthquake stress time history is described by a Brownian motion. Both distributions decay to zero for time intervals close to zero. But this feature contradicts the high immediate aftershock level according to Omori's law. We propose...
Non-linear response of soil carbon gas (CO2, CH4) flux to oxygen availability
Mcnicol, G.; Silver, W. L.
2013-12-01
Soil oxygen (O2) concentration can impact soil carbon (C) fluxes of carbon dioxide (CO2) and methane (CH4), and is an important chemical gradient across the terrestrial-aquatic interface that drives large differences in ecosystem C storage. Few studies have established quantitative relationships between gas-phase O2 concentration and soil C fluxes in controlled settings. Though standard Michaelis-Menten enzyme kinetics would predict a highly non-linear relationship between O2 concentration and microbial consumption, existing studies have imposed coarse changes in O2 concentration that necessarily prevent detection of non-linearity. We report on the results of laboratory incubations designed to explore the short-term sensitivity of soil C emissions to a wide range of gas-phase O2 concentrations. Organic-rich soil was collected from a drained peatland and subjected to seven O2 concentration treatments ranging from 0.03 % - 20 % O2. We compared the fit of the observed C flux response to O2 concentration to linear, log-linear, and Michaelis-Menten functions using MSE and residual fits as performance metrics. We found that both CO2 and CH4 emissions were highly sensitive to O2 concentration, with emission rates increasing and decreasing, respectively, at higher O2. Net CH4 emission rates were attenuated at higher O2 concentrations most likely due to stimulation of gross CH4 consumption. A log-linear or Michaelis-Menten model better fit data than a linear model by both performance metrics, demonstrating, empirically, a non-linear relationship between O2 concentration and soil CO2 and CH4 fluxes. Our results suggest high O2 sensitivity of C-rich soils at the terrestrial-aquatic interface and show that the microbial response to soil redox chemistry must be measured over a biophysically meaningful range of conditions to derive relationships that accurately predict soil C fluxes.
莫秋云
2009-01-01
文章从工业环境噪声对人体心率影响的角度,研究噪声对人体负荷影响规律的方法及实现问题,并开发数据处理系统.在研究方法中,依据工业企业噪声现状选择声级、频率范围;采用能够反映微小变化的心率变异(HRV)作为评价指标,获得噪声对人体心脏的影响规律.该方法与系统实现强调影响劳动安全的人体心脏负荷问题,可从工程生理学与心理学双重角度更为全面科学地研究噪声的影响规律.%This paper studies the influence law of human body' s load and its realization in industrial noise environment from the aspect of the noise influencing heart rate, and develops a date processing system. This method choose the studied noise level and their frequency coverage, and take the heart rate variability (HRV) as an assessment index, because HRV more reflect a tiny change and obtain a exact law of the heart change influenced by noise. This method and it' s system realization more emphasizes person' s psychological load at influencing labor security. The influence is discussed on the point of engineering psychology and psychology.
Louis Kaplow; Steven Shavell
2005-01-01
This entry for the forthcoming The New Palgrave Dictionary of Economics (Second Edition) surveys the economic analysis of five primary fields of law: property law; liability for accidents; contract law; litigation; and public enforcement and criminal law. It also briefly considers some criticisms of the economic analysis of law.
Holko, David A.
1982-01-01
Presents a complete computer program demonstrating the relationship between volume/pressure for Boyle's Law, volume/temperature for Charles' Law, and volume/moles of gas for Avagadro's Law. The programing reinforces students' application of gas laws and equates a simulated moving piston to theoretical values derived using the ideal gas law.…
A Century of Enzyme Kinetic Analysis, 1913 to 2013
Johnson, Kenneth A.
2013-01-01
This review traces the history and logical progression of methods for quantitative analysis of enzyme kinetics from the 1913 Michaelis and Menten paper to the application of modern computational methods today. Following a brief review of methods for fitting steady state kinetic data, modern methods are highlighted for fitting full progress curve kinetics based upon numerical integration of rate equations, including a re-analysis of the original Michaelis-Menten full time course kinetic data. Finally, several illustrations of modern transient state kinetic methods of analysis are shown which enable the elucidation of reactions occurring at the active sites of enzymes in order to relate structure and function. PMID:23850893
Oakes, Jesse; Nguyen, Tina; Britt, B Mark
2003-06-01
Ellman's method was used to determine the Michaelis-Menten parameters for the hydrolysis of acetylthiocholine by Electrophorus electricus acetylcholinesterase from 12 to 37 degrees C. Arrhenius analysis revealed that the activation energy for formation of the enzyme/substrate complex is 22.2 +/- 1.1 kJ/mole. The Arrhenius plot of k(cat) is markedly curved and attributed to comparable rates of acylation and deacylation due to the absence of evidence for a temperature-dependent enzyme conformational change by differential scanning calorimetry.
Esterification of phenolic acids catalyzed by lipases immobilized in organogels.
Zoumpanioti, M; Merianou, E; Karandreas, T; Stamatis, H; Xenakis, A
2010-10-01
Lipases from Rhizomucor miehei and Candida antarctica B were immobilized in hydroxypropylmethyl cellulose organogels based on surfactant-free microemulsions consisting of n-hexane, 1-propanol and water. Both lipases kept their catalytic activity, catalyzing the esterification reactions of various phenolic acids including cinnamic acid derivatives. High reaction rates and yields (up to 94%) were obtained when lipase from C. antarctica was used. Kinetic studies have been performed and apparent kinetic constants were determined showing that ester synthesis catalyzed by immobilized lipases occurs via the Michaelis-Menten mechanism.
Lipase-catalyzed ethanolysis of fish oils: multi-response kinetics.
Torres, Carlos F; Moeljadi, Marlina; Hill, Charles G
2003-08-05
The kinetics of the lipase-catalyzed (Pseudomonas cepacia) ethanolysis of fish oil has been studied in a batch reactor using menhaden oil, tuna oil, and acylglycerol mixtures derived from menhaden oil. Multi-response models derived from a generalized Michaelis-Menten mechanism were developed to describe the rates of formation of ethyl esters of the primary fatty acids present in the precursor oil. A first-order model for deactivation of the lipase was fit simultaneously to one of the data sets.
Chan-Huot, Monique; Lesot, Philippe; Pelupessy, Philippe; Duma, Luminita; Bodenhausen, Geoffrey; Duchambon, Patricia; Toney, Michael D; Reddy, U Venkateswara; Suryaprakash, N
2013-05-07
We report the in situ and real-time monitoring of the interconversion of L- and D-alanine-d3 by alanine racemase from Bacillus stearothermophilus directly observed by (2)H NMR spectroscopy in anisotropic phase. The enantiomers are distinguished by the difference of their (2)H quadrupolar splittings in a chiral liquid crystal containing short DNA fragments. The proof-of-principle, the reliability, and the robustness of this new method is demonstrated by the determination of the turnover rates of the enzyme using the Michaelis-Menten model.
A century of enzyme kinetic analysis, 1913 to 2013.
Johnson, Kenneth A
2013-09-02
This review traces the history and logical progression of methods for quantitative analysis of enzyme kinetics from the 1913 Michaelis and Menten paper to the application of modern computational methods today. Following a brief review of methods for fitting steady state kinetic data, modern methods are highlighted for fitting full progress curve kinetics based upon numerical integration of rate equations, including a re-analysis of the original Michaelis-Menten full time course kinetic data. Finally, several illustrations of modern transient state kinetic methods of analysis are shown which enable the elucidation of reactions occurring at the active sites of enzymes in order to relate structure and function.
A kinetic model for the penicillin biosynthetic pathway in
Nielsen, Jens; Jørgensen, Henrik
1996-01-01
A kinetic model for the first two steps in the penicillin biosynthetic pathway, i.e. the ACV synthetase (ACVS) and the isopenicillin N synthetase (IPNS) is proposed. The model is based on Michaelis-Menten type kinetics with non-competitive inhibition of the ACVS by ACV, and competitive inhibition...... of the IPNS by glutathione. The model predicted flux through the pathway corresponds well with the measured rate of penicillin biosynthesis. From the kinetic model the elasticity coefficients and the flux control coefficients are calculated throughout a fed-batch cultivation, and it is found...
Nguyen, Tung Viet; Reinhard, Martin; Gin, Karina Yew-Hoong
2013-05-01
The degradation of perfluorochemicals (PFCs) by hydroxyl radical ((·)OH) follows complex pathways resulting in stable products. Kinetic models are needed to predict the product distribution of (·)OH-initiated PFC degradation under environmental and treatment conditions. The bimolecular rate constants were measured in water for the reaction of (·)OH and N-ethyl perfluorooctane sulfonamidoethanol (N-EtFOSE), and intermediates, N-ethyl perfluorooctane sulfonamidoacetate (N-EtFOSAA), N-ethyl perfluorooctane sulfonamide (N-EtFOSA) and perfluorooctane sulfonamidoacetate (FOSAA). Under standard conditions (pH = 6, 25 ± 2 °C, Co PFC = 5-10 μg L(-1), Co H2O2 = 10 mM, irradiation intensity = 765 W m(-2)), the measured constants for N-EtFOSE, N-EtFOSAA, N-EtFOSA and FOSAA were (1.05 ± 0.12) × 10(9) M(-1) s(-1), (0.68 ± 0.05) × 10(9) M(-1) s(-1), (0.68 ± 0.05) × 10(9) M(-1) s(-1) and (0.53 ± 0.05) × 10(9) M(-1) s(-1), respectively. Constants in the pH range from 1 to 10 varied within a factor of 2-4 for most compounds. Over a period of 2-days, N-EtFOSE reacted directly (without forming long-lived intermediates) to perfluorooctane sulfonamide (FOSA) (18.8%) and perfluorooctanoic acid (PFOA) (39.1%). N-EtFOSE reacted via oxidation of the ethanolic hydroxyl group to N-EtFOSAA (12.4%) and N-dealkylation to N-EtFOSA (13.3%) and FOSAA (0.2%) and unknown intermediates. In sunlit surface waters, the (·)OH-induced transformation of N-substituted sulfonamide compounds to photostable products occurs on a time scale of days to weeks by model prediction.
Abernathy, Thomas J., Jr.; Arcus, Margaret E.
1977-01-01
Divorce rates in North America have increased sharply during the last century. Though this fact may best be understood as the result of many factors, one of them is the law. This paper provides a brief history of Canadian divorce laws and their relationship to divorce rates. (Author)
李华; 霍瑞贞
2000-01-01
In experiment,the polyphenoloxidase was extracted from mushroom by using acetone precipitating method threetimes. And then, it was immobilized by using the absorbentdeposition method with porous glass powder as carriers,It wasstudied to catalize p-chlorophenol oxidizing reaction inchloroform, complys with Michaelis-Menten dynamicmodel.And themoisture content in organic solvent directly affected thecatalytic activity of mushroom polyphenoloxidase. Theoptimum reaction condition for the catalyrtic oxidation of p-chlorophenol in chloroform was determined: pH:7, temperature:25°C, moisture content: 0.5%(v/v).The measured value of dynamic parameters was 29.45kJ. mol-1 for apparent activationenergy,1.058mol. L-1 for Michaelis-Menten kinetics and 9.074×10-2 min-1 for the maximum reaction rate.% 本文用丙酮沉淀法从蘑菇中提取多酚氧化酶,以多孔玻璃粉为载体,用吸附沉积法将酶固定,研究了该酶在氯仿介质中催化对氯苯酚氧化反应的机理遵循米氏(Michaelis-Menten)动力学方程；而且,在有机介质中含水率大小直接影响酶的催化活性.实验测得反应的最佳条件为pH=7.0,温度为25°C,含水率为0.5%(v/v)；表观活化能Ea=29.54kJ . mol-1,米氏常数Km=1.058mol . dm-3,最大反应速率rmax=90.74×10-3min-1.
Kinetic Measurements for Enzyme Immobilization.
Cooney, Michael J
2017-01-01
Enzyme kinetics is the study of the chemical reactions that are catalyzed by enzymes, with a focus on their reaction rates. The study of an enzyme's kinetics considers the various stages of activity, reveals the catalytic mechanism of this enzyme, correlates its value to assay conditions, and describes how a drug or a poison might inhibit the enzyme. Victor Henri initially reported that enzyme reactions were initiated by a bond between the enzyme and the substrate. By 1910, Michaelis and Menten were advancing their work by studying the kinetics of an enzyme saccharase which catalyzes the hydrolysis of sucrose into glucose and fructose. They published their analysis and ever since the Michaelis-Menten equation has been used as the standard to describe the kinetics of many enzymes. Unfortunately, soluble enzymes must generally be immobilized to be reused for long times in industrial reactors. In addition, other critical enzyme properties have to be improved like stability, activity, inhibition by reaction products, and selectivity towards nonnatural substrates. Immobilization is by far the chosen process to achieve these goals.Although the Michaelis-Menten approach has been regularly adapted to the analysis of immobilized enzyme activity, its applicability to the immobilized state is limited by the barriers the immobilization matrix places upon the measurement of compounds that are used to model enzyme kinetics. That being said, the estimated value of the Michaelis-Menten coefficients (e.g., V max, K M) can be used to evaluate effects of immobilization on enzyme activity in the immobilized state when applied in a controlled manner. In this review enzyme activity and kinetics are discussed in the context of the immobilized state, and a few novel protocols are presented that address some of the unique constraints imposed by the immobilization barrier.
Optimum PN Guidance Law for Maneuvering Target
SUN Bao-cai; QI Zai-kang
2007-01-01
An optimum PN guidance law for maneuvering target is developed using optimal control theory. By estimating the target position and setting the cost function, the guidance law can be deduced even without knowing the missile lateral acceleration. Since the quadratic cost function can make a compromise between the miss distance andthe control constraint, the optimum guidance law obtained is more general. Also, introduced line of sight rate as the input, a practical form of this guidance law is derived. The simulation results show the effectiveness of the guidance laws.
Kansas Data Access and Support Center — Law Enforcement Locations in Kansas Any location where sworn officers of a law enforcement agency are regularly based or stationed. Law enforcement agencies "are...
Edlund, Hans Henrik
2003-01-01
Report on Danish Tenancy Law. Contribution to a research project co-financed by the Grotius Programme for Judicial Co-Operation in Civil Matters. http://www.iue.it/LAW/ResearchTeaching/EuropeanPrivateLaw/Projects.shtml......Report on Danish Tenancy Law. Contribution to a research project co-financed by the Grotius Programme for Judicial Co-Operation in Civil Matters. http://www.iue.it/LAW/ResearchTeaching/EuropeanPrivateLaw/Projects.shtml...
Hesselink, M.W.
2015-01-01
This article discusses the normative relationship between contract law and democracy. In particular, it argues that in order to be legitimate contract law needs to have a democratic basis. Private law is not different in this respect from public law. Thus, the first claim made in this article will be that also for contract law a democratic basis is a necessary condition for legitimacy. A fully democratic basis may also be a sufficient condition for a legitimate and just contract law. However,...
Moate, P J; Boston, R C; Jenkins, T C; Lean, I J
2008-02-01
Previous investigations into ruminal lipolysis of triacylglycerol and ruminal biohydrogenation (BH) of unsaturated long-chain fatty acids have generally quantified these processes with either zero-order or first-order kinetics. This investigation examined if Michaelis-Menten and other nonlinear kinetics might be useful for quantifying these processes. Data from 2 previously published in vitro experiments employing rumen fluid from sheep to investigate the lipolysis of trilinolein, the BH of cis-9, cis-12 linoleic acid (LA), and the BH of fatty acids derived from the lipolysis of trilinolein were used for the development of a multi-compartmental model. The model described the lipolysis of triacylglycerol well. The model also provided a good mathematical description of the resulting production of nonesterified fatty acids, the isomerization of nonesterified LA, and subsequent production of rumenic acid (RA), vaccenic acid (VA), and stearic acid (SA). However, the model described poorly the patterns of the concentrations of LA, RA, VA, and SA after incubation of trilinolein in rumen fluid. The model is consistent with known stoichiometry and biochemistry and is parsimonious in that it employs a minimal number of parameters to describe all of the major aspects of lipolysis and BH. The first step in the lipolysis of trilinolein was described by Michaelis-Menten kinetics (Vmax = 529 +/- 16 mg/L per h; Km = 698 +/- 41 mg/L). Both subsequent lipolysis steps were approximated by a first-order (linear kinetics) rate constant (k = 2.64 +/- 0.041 /h). Isomerization of LA to RA was modeled by simple Michaelis-Menten kinetics (Vmax = 2,421 +/- 83 mg/L per h; Km = 440 +/- 22 mg/L). The kinetics of the BH of RA to VA was described by a Michaelis-Menten-type process involving competitive inhibition by VA (Vmax = 492 +/- 6.5 mg/L per h; Km = 1 mg/L). The final step, the BH of VA to SA, was modeled by a quasi-first-order process (k = 0.533 +/- 0.021 /h), but as the concentration of
2011-03-01
interactions [9] at the Michaelis - Menten state [14]. These interactions enable the protonation of the adenine ring at N3 [9] by the cationic Arg180 of RTA...bound and unbound states. a (top left): overlay of the apo RTA (green, 1IFT [32]) with the oligonucleotide-bound RTA at the Michaelis - Menten state...box atop in the less populated bound conformation (1IFS [32]); d (bottom right): overlay of the oligonucleotide-bound RTA at the Michaelis - Menten state
Development of Optimized Guidelines for Therapeutic Strategies for Organophosphate Poisoning
2011-03-01
Hoang, 1995). Metabolism is a complex mechanism, but is implemented into PBPK models in the form of zero order, first order, or Michaelis - Menten ...kinetics. The Vmax and Km required in the Michaelis - Menten equation are derived from in vitro and in vivo 22 measurements. Most PBPK models...metabolism occurs in the liver and follows Michaelis - Menten kinetics (Hoang, 1995). PBPK modeling of organophosphates The consideration of developing a
2009-01-01
with phenyl acetate and paraoxonwere determined by Michaelis - Menten steady state kinetics . The data from four or more independent experiments were fit...paraoxon was followed atA412 for 20 min at room temperature as described above. The data were fit using Michaelis - Menten steady state kinetics to derive...for 4 h at room temperature as described above. The data were fit using Michaelis - Menten steady state kinetics to derive the KM and Vmax values of
Modeling of Complex Mixtures: JP-8 Toxicokinetics
2008-10-01
diffusion, including metabolic loss via the cytochrome P-450 system, described by non-linear Michaelis - Menten kinetics as shown in the following...point. Inhalation and iv were the dose routes for the rat study. The modelers used saturable ( Michaelis - Menten ) kinetics as well as a second... Michaelis - Menten liver metabolic constants for n-decane have been measured (Km = 1.5 mg/L and Vmax = 0.4 mg/hour) using rat liver slices in a vial
Arizmendi, Octavio
2012-01-01
We determine which Boolean stable law is freely infinitely divisible and which is not. Some positive Boolean stable laws and a mixture of them have completely monotonic densities and they are both freely and classically infinitely divisible. Freely infinitely divisible Boolean stable laws and the corresponding free stable laws are non trivial examples whose free divisibility indicators are infinity.
Tsindeliani, Imeda A.
2016-01-01
The article deals with consideration of the actual theoretic problems of the subject and system of tax law in Russia. The theoretical approaches to determination of the nature of separate institutes of tax law are represented. The existence of pandect system intax law building as financial law sub-branch of Russia is substantiated. The goal of the…
Hesselink, M.W.
2015-01-01
This article discusses the normative relationship between contract law and democracy. In particular, it argues that in order to be legitimate contract law needs to have a democratic basis. Private law is not different in this respect from public law. Thus, the first claim made in this article will
1993-01-01
Law* implications. R-5 3. Wills for both spouses. 4. Powers of Attorney. 5. Consumer law issues. B. 1ypically readiness exercises and rapid...Soldiers’ & Sailors’ Civil Relief Act JA 261 Real Property Guide JA 262 Wills Guide JA 263 Family Law Guide JA 265 Consumer Law Guide JA 267 Legal
Greffet, Jean-Jacques; Brucoli, Giovanni; Sakat, Emilie; Marquier, François
2016-01-01
Thermal emission can be conveniently described using Kirchhoff law which states that the emissivity is equal to the absorptivity for isothermal bodies. For a finite size system, absorptivity is replaced by an absorption cross section. Here, we study the link between thermal emission and absorption by a finite size object which is not isothermal. We define a local absorption rate for a given incident plane wave and we prove that it is equal to the local emissivity rate. Hence, Kirchhoff law can be extended to anisothermal media. A practical consequence is the possibility of analysing thermal radiation by a variety of non-equilibrium systems such as microwave radiation in geophysical remote sensing or X-UV radiation by plasmas. This result provides a theoretical framework to analyse thermal emission by hot electrons in quantum wells, tunnel junctions or graphene. It paves the way to the design of a new generation of incandescent emitters made of subwavelength hot emitters coupled to cold antennas. The antennas ...
Andraško, Richard
2011-01-01
Principles of private law The reason of choosing "Principles of private law" for my thesis is that private law is built on untouchable values. For example, basic values like freedom and equality, which are represented by these principles. Many of them are indispensable in the relation of functionality of the whole system of law. Most of them have Roman law origin. The purpose of my thesis is to describe and summarize the main principles of private law that mostly appear in Czech law, especial...
of participants keen to work together to promote research and policy development in such a lively forum." - Professor Steve Saxby PhD, Cert Ed., MBCS Professor of IT Law and Public Policy, Solicitor, Deputy Head of School (Research), Faculty of Business and Law, University of Southampton, Editor...... not only the original themes of Legal, Security and Privacy Issues in IT Law and International Law and Trade but more recently two new conferences on International Public and Private Law. The papers in this volume then represent the contributions to all these fields and reflect the strong desire......-in-Chief, The Computer Law & Security Review - The International Journal of Technology Law and Practice (Elsevier), www.elsevier.com/locate/clsr, Editor, The Encyclopedia of Information Technology Law (Sweet & Maxwell), Director ILAWS - Institute for Law and the Web - School of Law, Southampton University, www...
Kagan, Yan Y
2010-01-01
We consider two statistical regularities that were used to explain Omori's law of the aftershock rate decay: the Levy and Inverse Gaussian (IGD) distributions. These distributions are thought to describe stress behavior influenced by various random factors: post-earthquake stress time history is described by a Brownian motion. Both distributions decay to zero for time intervals close to zero. But this feature contradicts the high immediate aftershock level according to Omori's law. We propose that these statistical distributions are influenced by the power-law stress distribution near the earthquake focal zone and we derive new distributions as a mixture of power-law stress with the exponent psi and Levy as well as IGD distributions. Such new distributions describe the resulting inter-earthquake time intervals and closely resemble Omori's law. The new Levy distribution has a pure power-law form with the exponent -(1+psi/2) and the mixed IGD has two exponents: the same as Levy for small time intervals and -(1+...
Nielsen, Ruth
The focus in this book is upon EU labour law and its interaction with national and international labour law. The book provides an analysis of the framework and sources of European labour law. It covers a number of substantive topics, notably collective labour law, individual employment contracts......, discrimination on grounds of sex and on other grounds, free movement of persons, restructuring of enterprises, working environment and enforcement of rights derived from EU labour law....
无
2009-01-01
China’s draft Energy Law is now under consideration China’s draft Energy Law has been submitted to the State Council’s Legislative Affairs Office and will be considered at this year’s executive meeting, said a key member of the expert panel drafting the law. If the law makes it through the council, the National People’s Congress (NPC), China’s supreme law-making body, will vote on it.
Andreea Lorena Ponaru
2007-01-01
This article attempts to present and explain the main features of the japanese law system. Japanese Law system was reformed during the domination of Tokugawa shogun family. In 1870, Foreign Governmental Systems Study Office was founded. By judicial sentences many french laws were introduced in Japanese law system. Roma-Tokyo-Berlin Alliance (1936) introduced a strong German influence in the law system. The Japanese judicial system has known five periods. In the first (1869-1888) were introduc...
Power laws, Pareto distributions and Zipf's law
Newman, M E J
2004-01-01
When the probability of measuring a particular value of some quantity varies inversely as a power of that value, the quantity is said to follow a power law, also known variously as Zipf's law or the Pareto distribution. Power laws appear widely in physics, biology, earth and planetary sciences, economics and finance, computer science, demography and the social sciences. For instance, the distributions of the sizes of cities, earthquakes, solar flares, moon craters, wars and people's personal ...
International Private Law and Communitarian Law
Abelardo Posso Serrano
2013-01-01
Full Text Available Private international law is justified at a time when the legal systems of nation states seeking a way to extend their areas and competencies. This desire led to the conflict between national laws, which grew smaller as did the novel concept of "international community", but did not suppress national relativism. A new law began to settle, then, with the progress of the integration process. Community laws have mechanisms to be applied, even when states would try to ignore them or to fulfill a relative way.
Predictive implications of Gompertz's law
Richmond, Peter; Roehner, Bertrand M.
2016-04-01
Gompertz's law tells us that for humans above the age of 35 the death rate increases exponentially with a doubling time of about 10 years. Here, we show that the same law continues to hold up to age 106. At that age the death rate is about 50%. Beyond 106 there is so far no convincing statistical evidence available because the number of survivors are too small even in large nations. However, assuming that Gompertz's law continues to hold beyond 106, we conclude that the mortality rate becomes equal to 1 at age 120 (meaning that there are 1000 deaths in a population of one thousand). In other words, the upper bound of human life is near 120. The existence of this fixed-point has interesting implications. It allows us to predict the form of the relationship between death rates at age 35 and the doubling time of Gompertz's law. In order to test this prediction, we first carry out a transversal analysis for a sample of countries comprising both industrialized and developing nations. As further confirmation, we also develop a longitudinal analysis using historical data over a time period of almost two centuries. Another prediction arising from this fixed-point model, is that, above a given population threshold, the lifespan of the oldest persons is independent of the size of their national community. This prediction is also supported by empirical evidence.
Bath's law Derived from the Gutenberg-Richter law and from Aftershock Properties
Helmsttetter, A; Helmsttetter, Agnes; Sornette, Didier
2003-01-01
The empirical Bath's law states that the average magnitude difference between a mainshock and its largest aftershock is 1.2, regardless of the mainshock magnitude. We first point out that the standard interpretation of Bath's law in terms of the two largest events of a self-similar set of independent events is incorrect, because it neglects the selection procedure entering the definition of aftershocks. We reconcile Bath's law with (i) the existence of a universal Gutenberg-Richter law for all earthquakes and (ii) with the empirical observation (productivity law) that each earthquake of magnitude m triggers other earthquakes at a rate ~10^(alpha m) with alpha~0.8.
Zipf's law and maximum sustainable growth
Malevergne, Y; Sornette, D
2010-01-01
Zipf's law states that the number of firms with size greater than S is inversely proportional to S. Most explanations start with Gibrat's rule of proportional growth but require additional constraints. We show that Gibrat's rule, at all firm levels, yields Zipf's law under a balance condition between the effective growth rate of incumbent firms (which includes their possible demise) and the growth rate of investments in entrant firms. Remarkably, Zipf's law is the signature of the long-term optimal allocation of resources that ensures the maximum sustainable growth rate of an economy.
D.N. Bakhrakh
2006-03-01
Full Text Available The question about the subjects of law branches is concerning the number of most important and difficult in law science. Its right decision influences on the subject of law regulation, precise definition of addressees of law norms, the volume of their rights and duties, the limits of action of norms of Main part of the branch, its principles. Scientific investigations, dedicated to law subjects system, promote the development of recommendations for the legislative and law applying activity; they are needed for scientific work organization and student training, for preparing qualified lawyers.
Predictive implications of Gompertz's law
Richmond, Peter
2015-01-01
Gompertz's law tells us that for humans above the age of 35 the death rate increases exponentially with a doubling time of about 10 years. Here, we show that the same law continues to hold even for ages over 100. Beyond 106 there is so far no statistical evidence available because the number of survivors is too small even in the largest nations. However assuming that Gompertz's law continues to hold beyond 106, we conclude that the mortality rate becomes equal to 1 at age 120 (meaning that there are 1,000 deaths in a population of one thousand). In other words, the upper bound of human life is near 120. The existence of this fixed-point has interesting implications. It allows us to predict the form of the relationship between death rates at age 35 and the doubling time of Gompertz's law. In order to test this prediction, we first carry out a transversal analysis for a sample of countries comprising both industrialized and developing nations. As further confirmation, we also develop a longitudinal analysis usi...
Studies on the kinetics of plasminogen activation by tissue plasminogen activator.
Rånby, M
1982-06-24
The steady-state rate of plasminogen activation by tissue plasminogen activator has been determined at various plasminogen concentrations. A plasmin substrate method similar to that presented by Christensen and Müllertz (Biochim. Biophys. Acta 480 (1977) 257-281) was used. The reaction was studied using one-chain type and two-chain type tissue plasminogen activator, N-terminal glutamic acid and N-terminal lysine plasminogen in the presence and in the absence of fibrin (eight studies). The kinetic data were fitted to a general Wong-Hanes equation and the simplest equation with significant parameters was found. In the absence of fibrin N-terminal glutamic acid plasminogen activation obeyed the Michaelis-Menten rate equation (Km 4.9 and 7.6 micro M and kcat 0.0013 and 0.0078 s-1 for one-chain type and two-chain type tissue plasminogen activator, respectively. In the absence of fibrin the activation of N-terminal lysine plasminogen activation failed to obey the Michaelis-Menten rate equation. Fibrin was found to stimulate greatly (up to 1000-fold) the steady-state activation rate. A theory for the fibrin stimulating mechanism is presented.
2008-01-01
The National People’s Congress(NPC)published China’s new draft Food Safety Law on April 20 for public discussion.The draft law covers food safety evaluation,monitoring, and recall and information release.
The Administrative Law Judges conduct hearings and render decisions in proceedings between the EPA and persons, businesses, government entities, and other organizations which are or are alleged to be regulated under environmental laws.
Petz, Thomas; Sagaert, Vincent; Østergaard, Kim
2004-01-01
In this section authors from various European countries report the recent case law in their country on the field of private patrimonial law, that is decisions on the law of property, juridical acts, the law of obligations, contract law and prescription. The European Review of Private Law (ERPL......) started this section in 2003. The section aims to give our readers an overview of what is happening in the most recent European case law. We have asked the national reporters to report the juridical essence of the decisions given by the highest courts in their country. These national reports...... not relate the facts of the decision, nor the personal opinion of the reporter. One can find discussions on the most important decisions of European courts in ERPL’s case note section. The recent case law section gives overviews of decisions published in periods of four months. The period of January...
Petz, Thomas; Sagaert, Vincent; Østergaard, Kim
2004-01-01
In this section authors from various European countries report the recent case law in their country on the field of private patrimonial law, that is decisions on the law of property, juridical acts, the law of obligations, contract law and prescription. The European Review of Private Law (ERPL......) started this section in 2003. The section aims to give our readers an overview of what is happening in the most recent European case law. We have asked the national reporters to report the juridical essence of the decisions given by the highest courts in their country. These national reports...... not relate the facts of the decision, nor the personal opinion of the reporter. One can find discussions on the most important decisions of European courts in ERPL’s case note section. The recent case law section gives overviews of decisions published in periods of four months. The period of January...
Christoffersen, Lisbet
2017-01-01
An analysis of the degree and content of statutory law regulation of Nordic Lutheran majority churches in 2017......An analysis of the degree and content of statutory law regulation of Nordic Lutheran majority churches in 2017...
Health care law versus constitutional law.
Hall, Mark A
2013-04-01
National Federation of Independent Business v. Sebelius, the Supreme Court's ruling on the Patient Protection and Affordable Care Act, is a landmark decision - both for constitutional law and for health care law and policy. Others will study its implications for constitutional limits on a range of federal powers beyond health care. This article considers to what extent the decision is also about health care law, properly conceived. Under one view, health care law is the subdiscipline that inquires how courts and government actors take account of the special features of medicine that make legal or policy issues especially problematic - rather than regarding health care delivery and finance more generically, like most any other economic or social enterprise. Viewed this way, the opinions from the Court's conservative justices are mainly about general constitutional law principles. In contrast, Justice Ruth Bader Ginsburg's dissenting opinion for the four more liberal justices is just as much about health care law as it is about constitutional law. Her opinion gives detailed attention to the unique features of health care finance and delivery in order to inform her analysis of constitutional precedents and principles. Thus, the Court's multiple opinions give a vivid depiction of the compelling contrasts between communal versus individualistic conceptions of caring for those in need, and between health care and health insurance as ordinary commodities versus ones that merit special economic, social, and legal status.
A Finite-Difference Solution of Solute Transport through a Membrane Bioreactor
B. Godongwana
2015-01-01
Full Text Available The current paper presents a theoretical analysis of the transport of solutes through a fixed-film membrane bioreactor (MBR, immobilised with an active biocatalyst. The dimensionless convection-diffusion equation with variable coefficients was solved analytically and numerically for concentration profiles of the solutes through the MBR. The analytical solution makes use of regular perturbation and accounts for radial convective flow as well as axial diffusion of the substrate species. The Michaelis-Menten (or Monod rate equation was assumed for the sink term, and the perturbation was extended up to second-order. In the analytical solution only the first-order limit of the Michaelis-Menten equation was considered; hence the linearized equation was solved. In the numerical solution, however, this restriction was lifted. The solution of the nonlinear, elliptic, partial differential equation was based on an implicit finite-difference method (FDM. An upwind scheme was employed for numerical stability. The resulting algebraic equations were solved simultaneously using the multivariate Newton-Raphson iteration method. The solution allows for the evaluation of the effect on the concentration profiles of (i the radial and axial convective velocity, (ii the convective mass transfer rates, (iii the reaction rates, (iv the fraction retentate, and (v the aspect ratio.
Forte, David F.
1978-01-01
A brief look at Columbia, Harvard, and Notre Dame law schools shows that the American tradition in teaching natural law has not been strong. The value of teaching natural law is discussed, a separate course or seminar is seen as the most effective option, and a selection of available sources for such a course is appended. (JMD)
J. Klijnsma
2015-01-01
This article examines the implications for contract law of Rawls' theory of justice as fairness. It argues that contract law as an institution is part of the basic structure of society and as such subject to the principles of justice. Discussing the basic structure in relation to contract law is par
Terra, B.J.M.; Wattel, P.J.
2008-01-01
This book is intended as a reference book for tax law and EC law pratitioners, tax administrators, academics, the judiciary and tax or Community law policy makers. For students, an abridged student edition textbook is available. The book offers a systematic survey of the tax implications of the EC T
Lawyers' Wives of Wisconsin, Racine.
The pamphlet briefly describes various facets of the law and legal system in Wisconsin, and defines many legal terms. The objective is to further public understanding of the law and of the legal profession, particularly in Wisconsin. No attempt is made to answer specific legal questions. Sections cover civil and criminal law; the federal court…
2002-03-26
designations (Note: Soldiers may no longer use the “By Law” designation.) 3. Wills for both spouses. 4. Powers of Attorney. 5. Consumer law issues. 6...Guide JA 263 Family Law Guide JA 265 Consumer Law Guide JA 267 Legal Assistance Office Directory JA 271 Legal Assistance Office Administration
Basse, Ellen Margrethe
Modern Danish environmental law has a strong international dimension due to membership of EU and participation in global and regional agreements. The concept of transnational law that includes EU environmental law that has vertical as well as horizontal effects across jurisdictions binding national...
Breuer, Daniel
2012-07-01
The publication considers the problem within the European and German legal boundary conditions. There may be a conflict of targets between teh economic cost theory and the standards of energy law or cartel law. To solve a potential conflict between economic rationality and legal regulations, the balancing of free emission certificates is looked into as it may provide information on the rationality and legal acceptability of pricing at the full stock exchange price. (orig./RHM)
Edao, Yuki; Iwai, Yasunori; Sato, Katsumi; Hayashi, Takumi
2016-08-01
A passive reactor for tritium oxidation at room temperature has been widely studied in nuclear engineering especially for a detritiation system (DS) of a tritium process facility taking possible extraordinary situation severely into consideration. We have focused on bacterial oxidation of tritium by hydrogen-oxidizing bacteria in natural soil to realize the passive oxidation reactor. The purpose of this study was to examine the feasibility of a bioreactor with hydrogen-oxidizing bacteria in soil from a point of view of engineering. The efficiency of the bioreactor was evaluated by kinetics. The bioreactor packed with natural soil shows a relative high conversion rate of tritium under the saturated moisture condition at room temperature, which is obviously superior to that of a Pt/Al2O3 catalyst generally used for tritium oxidation in the existing tritium handling facilities. The order of reaction for tritium oxidation with soil was the pseudo-first order as assessed with Michaelis-Menten kinetics model. Our engineering suggestion to increase the reaction rate is the intentional addition of hydrogen at a small concentration in the feed gas on condition that the oxidation of tritium with soil is expressed by the Michaelis-Menten kinetics model.
A mathematical model of liver metabolism: from steady state to dynamic
Calvetti, D; Kuceyeski, A [Case Western Reserve University, Department of Mathematics, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Somersalo, E [Helsinki University of Technology, Institute of Mathematics, P. O. Box 1100, FIN-02015 HUT (Finland)], E-mail: daniela.calvetti@case.edu, E-mail: amy.kuceyeski@case.edu, E-mail: erkki.somersalo@hut.fi
2008-07-15
The increase in Type 2 diabetes and other metabolic disorders has led to an intense focus on the areas of research related to metabolism. Because the liver is essential in regulating metabolite concentrations that maintain life, it is especially important to have good knowledge of the functions within this organ. In silico mathematical models that can adequately describe metabolite concentrations, flux and transport rates in the liver in vivo can be a useful predictive tool. Fully dynamic models, which contain expressions for Michaelis-Menten reaction kinetics can be utilized to investigate different metabolic states, for example exercise, fed or starved state. In this paper we describe a two compartment (blood and tissue) spatially lumped liver metabolism model. First, we use Bayesian Flux Balance Analysis (BFBA) to estimate the values of flux and transport rates at steady state, which agree closely with values from the literature. These values are then used to find a set of Michaelis-Menten parameters and initial concentrations which identify a dynamic model that can be used for exploring different metabolic states. In particular, we investigate the effect of doubling the concentration of lactate entering the system via the hepatic artery and portal vein. This change in lactate concentration forces the system to a new steady state, where glucose production is increased.
Zhu, Rencheng; Li, Shunyi; Bao, Xiaofeng; Dumont, Éric
2017-02-01
The performances of two identical biofilters, filled with a new composite packing material (named CM-5) embedded with functional microorganisms or sterilized CM-5 without microorganisms, were investigated for H2S treatment. Running parameters in terms of microbial counts, pressure drops, and inlet and outlet H2S concentrations were measured. The results show that the microbial count of the CM-5 was approximately ×105 CFU/g before being filled into the biofilter, while that of the sterilized CM-5 was negligible. The functional microorganisms embedded in CM-5 adapted to the environment containing H2S quickly. In most cases, pressure drops of the CM-5 biofilter were slightly higher than those of the sterilized CM-5 biofilter when the gas flow rate was 0.6-2.5 m3/h. The maximum elimination capacity (EC) of the CM-5 biofilter in treating H2S could reach up to 65 g/(m3·h) when the loading rate (LR) was approximately 80 g/(m3·h). If the LR was much higher, the measured EC showed a slight downward trend. The experimental ECs of biofilters were fitted by two typical dynamic models: the Michaelis-Menten model and the Haldane model. Compared with the Michaelis-Menten model, the Haldane model fit the experimental ECs better for the two biofilters because of the presence of the substrate inhibition behaviour.
Modeling uptake kinetics of cadmium by field-grown lettuce
Chen Weiping [Department of Environmental Sciences, University of California, 900 University Avenue, Riverside, CA 92521 (United States)], E-mail: chenweip@yahoo.com.cn; Li Lianqing [Institute of Resources, Ecosystem and Environment of Agriculture, Nanjing Agricultural University, Nanjing 210095 (China); Chang, Andrew C.; Wu Laosheng [Department of Environmental Sciences, University of California, 900 University Avenue, Riverside, CA 92521 (United States); Kwon, Soon-Ik [Agricultural Environmental and Ecology Division, National Institute of Agricultural Science and Technology, Suwon 441-707 (Korea, Republic of); Bottoms, Rick [Desert Research and Extension Center, 1004 East Holton Road, El Centro, CA 92243 (United States)
2008-03-15
Cadmium uptake by field grown Romaine lettuce treated with P-fertilizers of different Cd levels was investigated over an entire growing season. Results indicated that the rate of Cd uptake at a given time of the season can be satisfactorily described by the Michaelis-Menten kinetics, that is, plant uptake increases as the Cd concentration in soil solution increases, and it gradually approaches a saturation level. However, the rate constant of the Michaelis-Menten kinetics changes over the growing season. Under a given soil Cd level, the cadmium content in plant tissue decreases exponentially with time. To account for the dynamic nature of Cd uptake, a kinetic model integrating the time factor was developed to simulate Cd plant uptake over the growing season: C{sub Plant} = C{sub Solution} . PUF{sub max} . exp[-b . t], where C{sub Plant} and C{sub Solution} refer to the Cd content in plant tissue and soil solution, respectively, PUF{sub max} and b are kinetic constants. - A kinetic model was developed to evaluate the uptake of Cd under field conditions.
Zhu, Rencheng; Li, Shunyi; Bao, Xiaofeng; Dumont, Éric
2017-01-01
The performances of two identical biofilters, filled with a new composite packing material (named CM-5) embedded with functional microorganisms or sterilized CM-5 without microorganisms, were investigated for H2S treatment. Running parameters in terms of microbial counts, pressure drops, and inlet and outlet H2S concentrations were measured. The results show that the microbial count of the CM-5 was approximately ×105 CFU/g before being filled into the biofilter, while that of the sterilized CM-5 was negligible. The functional microorganisms embedded in CM-5 adapted to the environment containing H2S quickly. In most cases, pressure drops of the CM-5 biofilter were slightly higher than those of the sterilized CM-5 biofilter when the gas flow rate was 0.6–2.5 m3/h. The maximum elimination capacity (EC) of the CM-5 biofilter in treating H2S could reach up to 65 g/(m3·h) when the loading rate (LR) was approximately 80 g/(m3·h). If the LR was much higher, the measured EC showed a slight downward trend. The experimental ECs of biofilters were fitted by two typical dynamic models: the Michaelis-Menten model and the Haldane model. Compared with the Michaelis-Menten model, the Haldane model fit the experimental ECs better for the two biofilters because of the presence of the substrate inhibition behaviour. PMID:28198800
The Interplay between international law and labour law in South ...
This article investigates the interplay between labour law and international law in ... be included in diplomatic contracts of employment after ratification of a treaty, ... law; interplay; inviolability; labour law; principle of extraterritoriality; receiving ...
Approximation law for discrete-time variable structure control systems
Yan ZHENG; Yuanwei JING
2006-01-01
Two approximation laws of sliding mode for discrete-time variable structure control systems are proposed to overcome the limitations of the exponential approximation law and the variable rate approximation law. By applying the proposed approximation laws of sliding mode to discrete-time variable structure control systems, the stability of origin can be guaranteed, and the chattering along the switching surface caused by discrete-time variable structure control can be restrained effectively. In designing of approximation laws, the problem that the system control input is restricted is also considered, which is very important in practical systems. Finally a simulation example shows the effectiveness of the two approximation laws proposed.
Aishwarya Singh Chauhan
2015-01-01
Full Text Available Trichoderma spp. have been reported earlier for their excellent capacity of secreting extracellular α-galactosidase. This communication focuses on the optimization of culture conditions for optimal production of enzyme and its characterization. The evaluation of the effects of different enzyme assay parameters such as stability, pH, temperature, substrate concentrations, and incubation time on enzyme activity has been made. The most suitable buffer for enzyme assay was found to be citrate phosphate buffer (50 mM, pH 6.0 for optimal enzyme activity. This enzyme was fairly stable at higher temperature as it exhibited 72% activity at 60°C. The enzyme when incubated at room temperature up to two hours did not show any significant loss in activity. It followed Michaelis-Menten curve and showed direct relationship with varying substrate concentrations. Higher substrate concentration was not inhibitory to enzyme activity. The apparent Michaelis-Menten constant (Km, maximum rate of reaction (Vmax, Kcat, and catalytic efficiency values for this enzyme were calculated from the Lineweaver-Burk double reciprocal plot and were found to be 0.5 mM, 10 mM/s, 1.30 U mg−1, and 2.33 U mg−1 mM−1, respectively. This information would be helpful in understanding the biophysical and biochemical characteristics of extracellular α-galactosidase from other microbial sources.
Exploration of two-enzyme coupled catalysis system using scanning electrochemical microscopy.
Wu, Zeng-Qiang; Jia, Wen-Zhi; Wang, Kang; Xu, Jing-Juan; Chen, Hong-Yuan; Xia, Xing-Hua
2012-12-18
In biological metabolism, a given metabolic process usually occurs via a group of enzymes working together in sequential pathways. To explore the metabolism mechanism requires the understanding of the multienzyme coupled catalysis systems. In this paper, an approach has been proposed to study the kinetics of a two-enzyme coupled reaction using SECM combining numerical simulations. Acetylcholine esterase and choline oxidase are immobilized on cysteamine self-assembled monolayers on tip and substrate gold electrodes of SECM via electrostatic interactions, respectively. The reaction kinetics of this two-enzyme coupled system upon various separation distance precisely regulated by SECM are measured. An overall apparent Michaelis-Menten constant of this enzyme cascade is thus measured as 2.97 mM at an optimal tip-substrate gap distance of 18 μm. Then, a kinetic model of this enzyme cascade is established for evaluating the kinetic parameters of individual enzyme by using the finite element method. The simulated results demonstrate the choline oxidase catalytic reaction is the rate determining step of this enzyme cascade. The Michaelis-Menten constant of acetylcholine esterase is evaluated as 1.8 mM. This study offers a promising approach to exploring mechanism of other two-enzyme coupled reactions in biological system and would promote the development of biosensors and enzyme-based logic systems.
Pugh, C. Preston; Pouncey, Dakota L; Hartman, Jessica H.; Nshimiyimana, Robert; Desrochers, Linda P.; Goodwin, Thomas E.; Boysen, Gunnar; Miller, Grover P.
2014-01-01
The widely used anticoagulant Coumadin (R/S-warfarin) undergoes oxidation by cytochromes P450 into hydroxywarfarins that subsequently become conjugated for excretion in urine. Hydroxywarfarins may modulate warfarin metabolism transcriptionally or through direct inhibition of cytochromes P450 and thus, UGT action toward hydroxywarfarin elimination may impact levels of the parent drugs and patient responses. Nevertheless, relatively little is known about conjugation by UDP-glucuronosyltransferases in warfarin metabolism. Herein, we identified probable conjugation sites, kinetic mechanisms and hepatic UGT isoforms involved in microsomal glucuronidation of R- and S-7-hydroxywarfarin. Both compounds underwent glucuronidation at C4 and C7 hydroxyl groups based on elution properties and spectral characteristics. Their formation demonstrated regio- and enantioselectivity by UGTs and resulted in either Michaelis-Menten or substrate inhibition kinetics. Glucuronidation at the C7 hydroxyl group occurred more readily than at the C4 group, and the reaction was overall more efficient for R-7-hydroxywarfarin due to higher affinity and rates of turnover. The use of these mechanisms and parameters to model in vivo clearance demonstrated that contributions of substrate inhibition would lead to underestimation of metabolic clearance than that predicted by Michaelis-Menten kinetics. Lastly, these processes were driven by multiple UGTs indicating redundancy in glucuronidation pathways and ultimately metabolic clearance of R- and S-7-hydroxywarfarin. PMID:25447818
Modeling nitrate removal in a denitrification bed.
Ghane, Ehsan; Fausey, Norman R; Brown, Larry C
2015-03-15
Denitrification beds are promoted to reduce nitrate load in agricultural subsurface drainage water to alleviate the adverse environmental effects associated with nitrate pollution of surface water. In this system, drainage water flows through a trench filled with a carbon media where nitrate is transformed into nitrogen gas under anaerobic conditions. The main objectives of this study were to model a denitrification bed treating drainage water and evaluate its adverse greenhouse gas emissions. Field experiments were conducted at an existing denitrification bed. Evaluations showed very low greenhouse gas emissions (mean N2O emission of 0.12 μg N m(-2) min(-1)) from the denitrification bed surface. Field experiments indicated that nitrate removal rate was described by Michaelis-Menten kinetics with the Michaelis-Menten constant of 7.2 mg N L(-1). We developed a novel denitrification bed model based on the governing equations for water flow and nitrate removal kinetics. The model evaluation statistics showed satisfactory prediction of bed outflow nitrate concentration during subsurface drainage flow. The model can be used to design denitrification beds with efficient nitrate removal which in turn leads to enhanced drainage water quality.
Inhibition of serotonin transport by (+)McN5652 is noncompetitive
Hummerich, Rene [Biochemical Laboratory, Central Institute of Mental Health, 68159 Mannheim (Germany); Schulze, Oliver [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Raedler, Thomas [Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Mikecz, Pal [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Reimold, Matthias [Department of Nuclear Medicine, University Hospital Tuebingen, D-72076 Tuebingen (Germany); Brenner, Winfried [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Clausen, Malte [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Schloss, Patrick [Biochemical Laboratory, Central Institute of Mental Health, 68159 Mannheim (Germany); Buchert, Ralph [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany)]. E-mail: buchert@uke.uni-hamburg.de
2006-04-15
Introduction: Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [{sup 11C}] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [{sup 11}C] (+)McN5652 and serotonin at the SERT. The aim of the present study therefore was to pharmacologically characterize the interaction of [{sup 11}C] (+)McN5652 and serotonin at the SERT. Methods: In vitro saturation analyses of [{sup 3}H]serotonin uptake into HEK293 cells stably expressing the human SERT were performed in the absence and presence of unlabelled (+)McN5652. Data were evaluated assuming Michaelis-Menten kinetics. Results: Unlabelled (+)McN5652 significantly reduced the maximal rate of serotonin transport V {sub max} of SERT without affecting the Michaelis-Menten constant K {sub M}. Conclusions: This finding indicates that (+)McN5652 inhibits serotonin transport through the SERT in a noncompetitive manner. This might suggest that [{sup 11}C] (+)McN5652 PET is not significantly affected by endogenous serotonin.
Entrapment of glucoamylase by sol-gel technique in PhTES/TEOS hybrid matrixes
B. Vlad-Oros
2007-12-01
Full Text Available Mesoporous silica particles were prepared by the sol-gel method from different alkoxysilane precursors and used as a host matrix for encapsulation of glucoamylase, an enzyme widely used in fermentative industry. The aim was to investigate the physico-chemical properties of the different silica powders and their effect on the enzyme kinetics. The encapsulated enzymes followed Michaelis-Menten kinetics. The Michaelis constant (KM and the maximum rate of starch hydrolysis reaction (Vmax were calculated according to the Michaelis-Menten and Lineweaver-Burke plots. The values of the Michaelis constant (KM of the encapsulated enzymes were higher than those of the free enzyme. The temperature and pH inﬂ uence on the activity of free and immobilized glucoamylase were also compared. The results of this study show that the enzymes immobilized in organic/inorganic hybrid silica matrixes (obtained by the sol-gel method, allowing the entrapped glucoamylase to retain its biological activity, are suitable for many different applications, (medicinal, clinical, analytical.
Narasimhan, T.N.
2007-10-17
In a world with water resources severely impacted bytechnology, science must actively contribute to water law. To this end,this paper is an earth scientist s attempt to comprehend essentialelements of water law, and to examine their connections to science.Science and law share a common logical framework of starting with apriori prescribed tenets, and drawing consistent inferences. In science,observationally established physical laws constitute the tenets, while inlaw, they stem from social values. The foundations of modern water law inEurope and the New World were formulated nearly two thousand years ago byRoman jurists who were inspired by Greek philosophy of reason.Recognizing that vital natural elements such as water, air, and the seawere governed by immutable natural laws, they reasoned that theseelements belonged to all humans, and therefore cannot be owned as privateproperty. Legally, such public property was to be governed by jusgentium, the law of all people or the law of all nations. In contrast,jus civile or civil law governed private property. Remarkably, jusgentium continues to be relevant in our contemporary society in whichscience plays a pivotal role in exploiting vital resources common to all.This paper examines the historical roots of modern water law, followstheir evolution through the centuries, and examines how the spirit ofscience inherent in jus gentium is profoundly influencing evolving waterand environmental laws in Europe, the United States and elsewhere. In atechnological world, scientific knowledge has to lie at the core of waterlaw. Yet, science cannot formulate law. It is hoped that a philosophicalunderstanding of the relationships between science and law willcontribute to their constructively coming together in the service ofsociety.
Besnik Murati
2015-07-01
Full Text Available The state as an international entity and its impact on the individual’s right has been and still continues to be a crucial factor in the relationship between private and public persons. States vary in terms of their political system, however, democratic states are based on the separation of powers and human rights within the state. Rule of law is the product of many actors in a state, including laws, individuals, society, political system, separation of powers, human rights, the establishment of civil society, the relationship between law and the individual, as well as, individual-state relations. Purpose and focus of this study is the importance of a functioning state based on law, characteristics of the rule of law, separation of powers and the basic concepts of the rule of law.
Statistical laws in linguistics
Altmann, Eduardo G
2015-01-01
Zipf's law is just one out of many universal laws proposed to describe statistical regularities in language. Here we review and critically discuss how these laws can be statistically interpreted, fitted, and tested (falsified). The modern availability of large databases of written text allows for tests with an unprecedent statistical accuracy and also a characterization of the fluctuations around the typical behavior. We find that fluctuations are usually much larger than expected based on simplifying statistical assumptions (e.g., independence and lack of correlations between observations).These simplifications appear also in usual statistical tests so that the large fluctuations can be erroneously interpreted as a falsification of the law. Instead, here we argue that linguistic laws are only meaningful (falsifiable) if accompanied by a model for which the fluctuations can be computed (e.g., a generative model of the text). The large fluctuations we report show that the constraints imposed by linguistic laws...
Rigon, Riccardo; Rodriguez-Iturbe, Ignacio; Maritan, Amos; Giacometti, Achille; Tarboton, David G.; Rinaldo, Andrea
1996-11-01
Hack's law is reviewed, emphasizing its implications for the elongation of river basins as well as its connections with their fractal characteristics. The relation between Hack's law and the internal structure of river basins is investigated experimentally through digital elevation models. It is found that Hack's exponent, elongation, and some relevant fractal characters are closely related. The self-affine character of basin boundaries is shown to be connected to the power law decay of the probability of total contributing areas at any link and to Hack's law. An explanation for Hack's law is derived from scaling arguments. From the results we suggest that a statistical framework referring to the scaling invariance of the entire basin structure should be used in the interpretation of Hack's law.
Doranda Maracineanu
2009-06-01
Full Text Available The internal law of a State is the expression of the sovereign will of that Sate; however, thereare some features common to all law systems. The evolution of the society as a whole gave rise tointernational bodies (such as the European Union, through which the signatory countries haveassimilated certain unitary regulations in the internal law system. The origin of this law system is thelaw book of Justinian, during whose time the Roman law was codified. Thus, in the year 528 a. d.Justinian arranged the legal rules of those times in a unitary whole, adapted to the realities of those days.In our country, as per the fundamental law - the Constitution, the treaties and conventions ratified byRomania prevail in case of a conflict between them and the internal legislation regarding the humanrights.
Evaluation of the Massachusetts Smoke-free Workplace Law
Connolly, DMD, MPH, Gregory N; Carpenter, MS, Carrie; Alpert, ScM., BSc, Hillel R.; Skeer, MSW, MPH, Margie; Travers, Mark
2005-01-01
STUDY OBJECTIVES This report describes an evaluation of the Massachusetts Smoke-Free Workplace Law. The main objectives were to: (1) assess the change in indoor air quality that occurred in a sample of hospitality venues pre and post the law; (2) determine compliance with the law after implementation; and (3) evaluate economic changes pre and post the law, including patronage, sales revenue, and employment rates.
Zipf's law, power laws and maximum entropy
Visser, Matt
2013-04-01
Zipf's law, and power laws in general, have attracted and continue to attract considerable attention in a wide variety of disciplines—from astronomy to demographics to software structure to economics to linguistics to zoology, and even warfare. A recent model of random group formation (RGF) attempts a general explanation of such phenomena based on Jaynes' notion of maximum entropy applied to a particular choice of cost function. In the present paper I argue that the specific cost function used in the RGF model is in fact unnecessarily complicated, and that power laws can be obtained in a much simpler way by applying maximum entropy ideas directly to the Shannon entropy subject only to a single constraint: that the average of the logarithm of the observable quantity is specified.
Zipf's law, power laws, and maximum entropy
Visser, Matt
2012-01-01
Zipf's law, and power laws in general, have attracted and continue to attract considerable attention in a wide variety of disciplines - from astronomy to demographics to economics to linguistics to zoology, and even warfare. A recent model of random group formation [RGF] attempts a general explanation of such phenomena based on Jaynes' notion of maximum entropy applied to a particular choice of cost function. In the present article I argue that the cost function used in the RGF model is in fact unnecessarily complicated, and that power laws can be obtained in a much simpler way by applying maximum entropy ideas directly to the Shannon entropy subject only to a single constraint: that the average of the logarithm of the observable quantity is specified.
Haselmann, Rainer; Pistor, Katharina; Vig, Vikrant
2006-01-01
A voluminous literature seeks to explore the relation between law and finance, but offers little insights into dynamic relation between legal change and behavioral outcomes or about the distributive effects of law on different market participants. The current paper disentangles the law-finance relation by using disaggregate data on banks’ lending patterns in 12 transition countries over a 8 year period. This allows us to control for country level heterogeneity and differentiate between differ...
JAVIER DE LUCAS
2014-06-01
Full Text Available This article explores the relationship between violence, law and borders by analyzing both the violence at the borders and the violence of the borders. In both cases, the author states that violence exerted by means of law, as well as migratory and asylum policies, threaten the universal human rights of the most vulnerable people and cannot be seen as exercising the legitimate monopoly of force, resulting in the destruction of the Rule of Law.
Gabrielsen, Jonas
The bond between law and rhetoric is as old as the subjects themselves. Especially the ancient works on legal rhetoric afford, however, a too narrow depiction of the interaction between law and rhetoric as a purely instrumental discipline of communication in court. In this paper I challenge...... this narrow understanding of legal rhetoric and outline three distinct frames of understanding the relation between law and rhetoric...
Малярчук, Назар Вікторович
2013-01-01
In this course we tried to shed some light on the most important issues of the environmental law: notion, subject, method, system and sources of environmental law, we revealed the context of government management in the field of the protection of environment, legal regulation of conducting environmental examination. The separate subjects determines legal regime of each environmental law objects: lands, water, mineral wealth, forests, air, flora and fauna, natural protection fund of Ukraine. ...
Engel, Christoph
2004-01-01
Hardly any of the law's subjects know the text of the provisions that govern their conduct. Even less would they be able to handle this text properly, were they to get access to it. Nonetheless the law firmly believes that it is not feckless. This paper solves the puzzle by drawing on four bodies of knowledge: neurobiology, developmental psychology, the psychology of learning, and work form social scientists on learning.The paper makes the following claim: typically the law reaches its addres...
Bjerre, Henrik Jøker
2005-01-01
of the concept of enjoyment is instructive, and looking at it more closely makes it possible to spell out why obedience in itself does not suffice for a moral existence. Subjecting ourselves to the prescriptions of positive law might actually function as a way of escaping the insatiable demands of the moral law....... In this case, the positive law not only sustains our enjoyment (by securing basic liberties), but also comes to function as an object of enjoyment itself....
Langsted, Lars Bo; Garde, Peter; Greve, Vagn
Derived from the renowned multi-volume International Encyclopaedia of Laws, this book provides a practical analysis of criminal law in Denmark. An introduction presents the necessary background information about the framework and sources of the criminal justice system, and then proceeds...... resource for criminal lawyers, prosecutors, law enforcement officers, and criminal court judges handling cases connected with Denmark. Academics and researchers, as well as the various international organizations in the field, will welcome this very useful guide, and will appreciate its value in the study...... of comparative criminal law....
This volume, the third in the series, contains the proceedings of the conference 'Law before Gratian' and covers a wide range of topics from individual and local studies to broader reflections on the status and function of law in medieval European societies before the scholastic legal 'revolution......' of the later twelfth century. Seeking to broaden our view of what constituted law in this period, the articles examine these earlier developments in their own right and provide new insights into the variety and complexity of early and high medieval approaches to law and jurisprudence. Contributors...
Langsted, Lars Bo; Garde, Peter; Greve, Vagn
resource for criminal lawyers, prosecutors, law enforcement officers, and criminal court judges handling cases connected with Denmark. Academics and researchers, as well as the various international organizations in the field, will welcome this very useful guide, and will appreciate its value in the study......Derived from the renowned multi-volume International Encyclopaedia of Laws, this book provides a practical analysis of criminal law in Denmark. An introduction presents the necessary background information about the framework and sources of the criminal justice system, and then proceeds...... of comparative criminal law....
Thinking law: thinking law in motion
Laura Beth Nielsen
2014-01-01
This essay argues that one way to “think law” is to think “law in motion”. I will argue that a “law in motion” perspective embodies four core elements or ‘multiplicities’ which are: (1) multiple methodologies; (2) multiple perspectives; (3) multiple vocalities; and (4) multiple media including objects. As will become evident by the number of inspiring colleagues that have articulated rationales and perspectives for each of these multiplicities, these are not original ideas for which I can cla...
F-rough law and the discovery of rough law
Qiu Jinming; Shi Kaiquan
2009-01-01
By using function one direction S-rough sets (function one direction singular rough sets), this article presents the concepts of F-law, F-rough law, and the relation metric of rough law; by using these concepts, this article puts forward the theorem of F-law relation metric, two orders theorem of F-rough law relation metric, the attribute theorem of F-rough law band, the extremum theorem of F-rough law relation metric, the discovery principle of F-rough law and the application of F-rough law.
Farber, D.A.; Peeters, Marjan
2016-01-01
This book brings together over seventy fifty authors for a comprehensive examination of the emerging global regime of climate change law. Despite the relative youth of climate change law, we can already begin to see the outlines of legal regimes addressing climate change mitigation and adaptation (a
Social Studies: Law Education.
Curriculum Review, 1979
1979-01-01
Reviews 11 series, texts, supplements, kits, and professional references for law instruction, including civil and criminal law, the Bill of Rights, and controversial legal issues: arson, gun control, capital punishment, and euthanasia. While all grade levels are covered, the emphasis is on secondary-level materials. (SJL)
Harper, Steven J.
2013-01-01
The Law School Admission Council recently reported that applications were heading toward a 30-year low, reflecting, as a "New York Times" article put it, "increased concern over soaring tuition, crushing student debt, and diminishing prospects of lucrative employment upon graduation." Since 2004 the number of law-school…
Meulen, van der B.M.J.
2014-01-01
The twenty-first century has witnessed a fundamental reform of food law in the European Union, to the point where modern EU food law has now come of age. This book presents the most significant elements of these legal developments with contributions from a highly qualified team of academics and
Haramaya Law Review: Submissions
The Haramaya Law Review (HLR) is seeking original submissions in English ... including analysis of domestic or international laws and cases, the African Union ... In general, three consecutive words or more copied from a source should be treated .... If submitting to a peer-reviewed section of the journal, the instructions in ...
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2006-01-01
Beijing has begun work on laws and regulations to guarantee the smooth operation of the 2008 Olympics One of the major tasks for Beijing as host of the 2008 Olympic Games is to establish regulations and laws to govern the preparations for and conduct of the Games. Thus, on April 10 the Olympic Legislation Coordinating
Desmoulin-Canselier, Sonia; Lacour, Stéphanie
Law and nanotechnology form a vast subject. The aim here will be to examine them from the societal standpoint of nanoethics, if necessary without due reference to the work that has been undertaken. For while law differs from ethics, as we shall attempt to explain throughout this reflection, it must also be studied in its relationship with social realities.
Juan M.C. Larrosa
2016-12-01
Full Text Available The valuation of a social network is an issue that has been addressed based on simplifying approaches. Various value laws have been stipulated, which are largely atheoretical but have been effectively used to estimate the potential economic value of social network-based firms. This review highlights the various contributions used in the recent literature on networks valuation laws.
Teaching Information Technology Law
Taylor, M. J.; Jones, R. P.; Haggerty, J.; Gresty, D.
2009-01-01
In this paper we discuss an approach to the teaching of information technology law to higher education computing students that attempts to prepare them for professional computing practice. As information technology has become ubiquitous its interactions with the law have become more numerous. Information technology practitioners, and in particular…
Meulen, van der B.M.J.; Velde, van der M.; Szajkowska, A.; Verbruggen, R.
2008-01-01
This handbook analyses and explains the institutional, substantive and procedural elements of EU food law, taking the General Food Law as a focus point. Principles are discussed as well as specific rules addressing food as a product, the processes related to food and communication about food through
Meulen, van der B.M.J.
2014-01-01
The twenty-first century has witnessed a fundamental reform of food law in the European Union, to the point where modern EU food law has now come of age. This book presents the most significant elements of these legal developments with contributions from a highly qualified team of academics and prac
Social Studies: Law Education.
Curriculum Review, 1979
1979-01-01
Reviews 11 series, texts, supplements, kits, and professional references for law instruction, including civil and criminal law, the Bill of Rights, and controversial legal issues: arson, gun control, capital punishment, and euthanasia. While all grade levels are covered, the emphasis is on secondary-level materials. (SJL)
Gazzaniga, Michael S
2008-11-06
Some of the implications for law of recent discoveries in neuroscience are considered in a new program established by the MacArthur Foundation. A group of neuroscientists, lawyers, philosophers, and jurists are examining issues in criminal law and, in particular, problems in responsibility and prediction and problems in legal decision making.
Harper, Steven J.
2013-01-01
The Law School Admission Council recently reported that applications were heading toward a 30-year low, reflecting, as a "New York Times" article put it, "increased concern over soaring tuition, crushing student debt, and diminishing prospects of lucrative employment upon graduation." Since 2004 the number of law-school…
Gibbons, John
1999-01-01
Discusses the language of law and its general interest to the field of applied linguistics. Specific focus is on legal language, the problems and remedies of legal communication (e.g., language and disadvantage before the law, improving legal communication) the legislation of language (e.g., language rights, language crimes), and forensic…
Information Law and Copyright.
Marx, Peter A.
1986-01-01
Because of information law's inability to keep up with rapid changes in information technology and impreciseness of the law, copyrighting of databases poses unique problems. Interpretation of fair use doctrine, privately owned computer "downloading," impact of federal electronic filing, and questions concerning information businesses need to be…
Potter, William Gray
1981-01-01
Discusses the literature that has become associated with Lotka's Law of Scientific Productivity (a general theoretical estimate of author productivity in the sciences) and attempts to identify the important factors of Lotka's original methodology that should be considered when attempting to test applicability of Lotka's Law. Forty-seven references…
1997-01-01
WOMEN’S rights concern the world over. Even though China has a different legal tradition and social system, participants from the Beijing Sino-British Women and Law Symposium discovered that both Chinese and foreign scholars could reach agreement and understanding on many issues. Enacting Laws for Women Professor Yang Dawen, from the
Unilateralism in International Law
Hartmann, Jacques
2015-01-01
international law. This note considers when and how a State or a regional organisation may legitimately take unilateral measures to protect the environment. The note will does not consider the legality of including foreign aircraft within the ETS, which has been dealt with elsewhere. Instead, it will focus...... on the legality and importance of unilateral acts for the development of international law....
[Law 6/84: "an inappropriate law"].
Barroco, L E
1994-01-01
The intervention of Dr. Luis Elmano Barroco was evaluated at a meeting on March 19, 1994, on the topic of the state of abortion after 10 years of the new abortion law. Some aspects of the law of 1984 are characterized as inappropriate and inadequate because of the experience of the maternity ward of Dr. Alfredo da Costa. It was expected that in the wake of the publication of the law, official health care institutions would provide services for termination of pregnancy in accordance with legal indications. However, a survey carried out by the Association for Family Planning in July 1993 revealed that more than 50% of hospitals did not perform abortions because of the inexistence of specialized services or lack of resources or on grounds of conscientious objection. Even a revision of the abortion law does not take into consideration the fact that before 12 weeks of gestation it is difficult to precisely confirm grave lesions or the physical and psychological state of health of the pregnant woman which could be potentially life threatening. It was not taken into account either that it is impossible to diagnose definitively chromosomal aberrations, severe diseases, and fetal malformation before the 16th week. The law did not contemplate the prevailing socioeconomical conditions either that lead to clandestine abortion with high morbidity and mortality from cervical lesions, uterine perforation, infections, sepsis, and salpingitis. Prenatal diagnosis for eugenic abortion can be carried out by cytogenetic analysis of the amniotic fluid and ecography, but such diagnosis probably amounts to only 30-40% of risk cases in the whole country. A recent study by the Johns Hopkins University indicated that the chance of survival of a child born before 24 weeks is nil, therefore the limit of induced abortion should be extended to the 24th week to facilitate diagnosis of possible genetic abnormalities.
The impact of EU law on Belgian consumer law terminology
Cauffman, C.
2012-01-01
The implementation of EU directives in the field of consumer law distorted the Belgian legal terminology. In particular, consumer law terminology often differs from civil law terminology. The meaning of traditional civil law concepts is no longer respected in the field of consumer law. Moreover, the
The impact of EU law on Belgian consumer law terminology
Cauffman, C.
2012-01-01
The implementation of EU directives in the field of consumer law distorted the Belgian legal terminology. In particular, consumer law terminology often differs from civil law terminology. The meaning of traditional civil law concepts is no longer respected in the field of consumer law. Moreover, the
1991-01-01
This book covers: Historical origins of civil code legal systems; Modern civil law practice for mineral lawyers; Treaties and agreements for protection of international investments; Europe 1992-toward a single energy market; Dispute resolution in international agreements; Assessment of political risk; Reducing political risk; Protecting mineral investments from upheaval in developing countries; Typical world petroleum arrangements; government take in the Pacific Rim - Papua New Guinea; Mineral base of the USSR and prospects of investment; International taxation for the mining practitioner; Tax considerations - branch versus subsidiary; Doing business in the host country - nontax considerations; Impact of host-country laws on operations and profits; Mineral development and native rights - New Zealand; Designing the investment vehicle: mining; International oil and gas joint ventures; Selected U.S. laws with extraterritorial effect; U.S. tax and securities laws applied to foreign joint venturers; and Extraterritorial effect of U.S. laws.
Mayoral Diaz-Asensio, Juan Antonio; Jaremba, Urszula; Nowak, Tobias
2014-01-01
The judicial protection system in the European Union (EU) is premised on the fact that national judges are supposed to act as decentralized EU judges. This role is exercised through tools enshrined in, inter alia, primacy, direct and indirect effect of EU law, and the preliminary ruling procedure....... However, a number of studies show that national judges experience difficulties in exercising EU competences due to their lack of knowledge in the field of EU law. In this contribution we study the differences in the level of self-evaluation of EU law knowledge among judges, which consequently influence...... the way judges approach EU law. For that purpose we question the relevance of several institutional and socio-legal factors, such as organization of the judiciary, generation, the system of legal education and judicial training and practical experience with EU law. Our analysis is based on data collected...
2012-01-01
chloroethene mineralization under nomi- nally anoxic conditions can exhibit saturation type ( Michaelis - Menten ) kinetics over the range of environmentally...relevant concentrations. The Michaelis - Menten parameters, Vmax and ks, are sensitive to a number of environmental factors and vary according to in
Dynamical Systems and Control Theory Inspired by Molecular Biology
2011-02-20
is odd) steady states, there never are more than 2n − 1 steady states, that for parameters near the standard Michaelis - Menten quasi-steady state...conditions, there are at most n + 1 steady states and that for parameters far from the standard Michaelis - Menten quasi-steady state conditions, there is at
Jensen, Michael Gejl; Lerche, Susanne; Egefjord, Lærke
2013-01-01
hypoglycemia study and our previous hyperglycemia study to estimate the Michaelis-Menten constants of glucose transport and metabolism. The GLP-1 treatment lowered the vascular volume of brain tissue. Loading data from hypo- to hyperglycemia into the Michaelis-Menten equation, we found increased maximum...
The total quasi-steady-state approximation for complex enzyme reactions
Pedersen, Morten Gram; Bersani, A. M.; Bersani, E.
2008-01-01
Biochemistry in general and enzyme kinetics in particular have been heavily influenced by the model of biochemical reactions known as Michaelis-Menten kinetics. Assuming that the complex concentration is approximately constant after a short transient phase leads to the usual Michaelis-Menten (MM...
Plankton Dynamics and Mesoscale Turbulence
2010-06-29
dependending on available nutri- ents through a Holling type-II (or Michaelis - Menten ) functional response, by a Holling type III grazing by zooplankton, by...phytoplankton, using a Michaelis - Menten (or Monod) functional form. The con- stants ρ1 and ρ2 are used to transform phytoplankton biomass into nutrient
The Practice of Transnational Law
2000-01-01
Contents :"The new law merchant and the global market place" by Klaus Peter Berger, "The CENTRAL enquiry on the use of transnational law in international contract law and arbitration", "The UNIDROIT principles and transnational law" by Michael Joachim Bonell, "Examples for the practical application of transnational law", "The questionnaire and results of the CENTRAL enquiry"
Chemical Laws, Idealization and Approximation
Tobin, Emma
2013-01-01
This paper examines the notion of laws in chemistry. Vihalemm ("Found Chem" 5(1):7-22, 2003) argues that the laws of chemistry are fundamentally the same as the laws of physics they are all "ceteris paribus" laws which are true "in ideal conditions". In contrast, Scerri (2000) contends that the laws of chemistry are…
Lapas, Luciano C; Ferreira, Rogelma M S; Rubí, J Miguel; Oliveira, Fernando A
2015-03-14
We analyze the temperature relaxation phenomena of systems in contact with a thermal reservoir that undergoes a non-Markovian diffusion process. From a generalized Langevin equation, we show that the temperature is governed by a law of cooling of the Newton's law type in which the relaxation time depends on the velocity autocorrelation and is then characterized by the memory function. The analysis of the temperature decay reveals the existence of an anomalous cooling in which the temperature may oscillate. Despite this anomalous behavior, we show that the variation of entropy remains always positive in accordance with the second law of thermodynamics.
Lando, Ole
2007-01-01
In the article it is argued that the wish to preserve the cultural values of national law should not prevent the EU from preparing a Code or an Optional Instrument. The no-code countries on the British Isles and in Scandinavia are the most ardent opponents to the idea of unifying European Contract...... Law by way of a code on Contracts. In both these regions however the absence of a code causes problems. In England a prominent writer has found that the major weakness of the judge-made law is its immense diffusion and the consequent difficulty of access to it and the Nordic countries face the same...
Elsmore, Matthew James
2013-01-01
-border setting, with a particular focus on small business and consumers. The article's overall message is to call for a rethink of received wisdom suggesting that trade marks are effective trade-enabling devices. The case is made for reassessing how we think about European trade mark law.......First, this article argues that trade mark law should be approached in a supplementary way, called reconfiguration. Second, the article investigates such a reconfiguration of trade mark law by exploring the interplay of trade marks and service transactions in the Single Market, in the cross...
Fomcenco, Alex; Werlauff, Erik
This book is a must-have for any business advisor that operates on a cross-border level in the European Union, EU. Regardless of whether you already have solid knowledge about doing business in the EU or you are just taking your first steps on this corporate scene, Business Law, Europe should...... be the book within your reach. We call it “Our Corporate Bible”. In an easily comprehendible way we address some of the most essential issues of business law, and provide guidelines and clarity for understanding and proper application of the legal provisions that govern business law in Europe....
Lapas, Luciano C.; Ferreira, Rogelma M. S.; Rubí, J. Miguel; Oliveira, Fernando A.
2015-03-01
We analyze the temperature relaxation phenomena of systems in contact with a thermal reservoir that undergoes a non-Markovian diffusion process. From a generalized Langevin equation, we show that the temperature is governed by a law of cooling of the Newton's law type in which the relaxation time depends on the velocity autocorrelation and is then characterized by the memory function. The analysis of the temperature decay reveals the existence of an anomalous cooling in which the temperature may oscillate. Despite this anomalous behavior, we show that the variation of entropy remains always positive in accordance with the second law of thermodynamics.
Fomcenco, Alex; Werlauff, Erik
This book is a must-have for any business advisor that operates on a cross-border level in the European Union, EU. Regardless of whether you already have solid knowledge about doing business in the EU or you are just taking your first steps on this corporate scene, Business Law, Europe should...... be the book within your reach. We call it “Our Corporate Bible”. In an easily comprehendible way we address some of the most essential issues of business law, and provide guidelines and clarity for understanding and proper application of the legal provisions that govern business law in Europe....
The Effects of Laws on Divorce in American States
Stetson, Dorothy M.; Wright, Gerald C., Jr.
1975-01-01
Explores the extent to which state divorce laws have an independent effect on divorce rates. Two findings, using regression analysis, are (1) a strong relationship exists between permissiveness of divorce laws and divorce rates; (2) the relationship remains when effects of variations in economic development and social costs are controlled. (Author)
F-generation law and recognition of system law
Shi Kaiquan; Yao Bingxue
2007-01-01
If a system is not disturbed (or invaded) by some law, there is no doubt that each system will move according to the expected law and keep stable. Although such a fact often appears, some unknown law breaks into the system and leads it into turbulence. Using function one direction S-rough sets, this article gives the concept of the F-generation law in the system, the generation model of the F-generation law and the recognition method of the system law. Function one direction singular rough sets is a new theory and method in recognizing the disturbance law existing in the system and recognizing the system law.
Structural simplification of chemical reaction networks in partial steady states.
Madelaine, Guillaume; Lhoussaine, Cédric; Niehren, Joachim; Tonello, Elisa
2016-11-01
We study the structural simplification of chemical reaction networks with partial steady state semantics assuming that the concentrations of some but not all species are constant. We present a simplification rule that can eliminate intermediate species that are in partial steady state, while preserving the dynamics of all other species. Our simplification rule can be applied to general reaction networks with some but few restrictions on the possible kinetic laws. We can also simplify reaction networks subject to conservation laws. We prove that our simplification rule is correct when applied to a module of a reaction network, as long as the partial steady state is assumed with respect to the complete network. Michaelis-Menten's simplification rule for enzymatic reactions falls out as a special case. We have implemented an algorithm that applies our simplification rules repeatedly and applied it to reaction networks from systems biology.
Costonis, John J.
2002-01-01
Introduces papers from a conference focused on the bijural programs of Louisiana State University Law Center and McGill University Faculty of Law. The programs educate all first-degree law students in both the common law and civil law traditions, preparing them for the increasing globalization of legal practice. (EV)
Lawful Permanent Residents - Annual Report
Department of Homeland Security — A lawful permanent resident (LPR) or 'green card' recipient is defined by immigration law as a person who has been granted lawful permanent residence in the United...
Makuch, Karen E; Pereira, Ricardo, Dr
2012-01-01
"Environmental & Energy Law attempts to bridge the knowledge gap between legal developments designed to achieve environmental and/or energy-related objectives and the practical, scientific and technical...
Finnis, John
1986-01-01
A discussion of natural law outlines some of the theory and tradition surrounding it and examines its relationship to the social science and legal curriculum and to the teaching of jurisprudence. (MSE)
Zinoviev, Yury M
2012-01-01
The equations of the relativistic causal Newton gravity law for the planets of the solar system are studied in the approximation when the Sun rests at the coordinates origin and the planets do not iteract between each other.
secondly to consider the quest for enacting a freedom of information law in ... Zambia; and thirdly, to highlight the principles of the Freedom of Information. Bill that was ..... contract negotiations, or place them at a competitive disadvantage.
Nielsen, Sandro
2012-01-01
Online dictionaries that assist users in writing legal texts in English as a foreign language are important lexicographic tools. They can help law students bridge the factual and linguistic gaps between the two legal universes involved. However, existing online law dictionaries with English...... as the target language primarily focus on terms, but students also need to write the remainder of the texts in factually and linguistically correct English. It is therefore important to have a sound theoretical foundation before embarking on a dictionary project that aims to help law students communicate...... by containing the types of data that can best satisfy the needs of students at the three stages of legal text production: draft writing, revising and editing. The theoretical aspects discussed are supported by examples from the online CISG Dictionary, which is a lexicographic tool developed to help Danish law...
US Fish and Wildlife Service, Department of the Interior — The Union Slough National Wildlife Refuge Law Enforcement Plan clarifies U.S. Fish and Wildlife enforcement policies as they apply to the Refuge. It provides...
Reforming Ethiopia's Expropriation Law
Muradu_Abdo
Ethiopia is increasingly using expropriation as the single most important device .... contesting public purpose or for cultural reasons, general anti-expropriation .... expropriation law in the sense of permanent physical takeover of farmland by.
... Policies & Laws | Español Search Stopbullying.gov WHAT IS BULLYING Definition The Roles Kids Play Other Types of Aggressive Behavior CYBER BULLYING What is Cyberbullying? Prevent Cyberbullying Report Cyberbullying WHO ...
Levin, Sandy
1989-01-01
Presents learning activities and resources for teaching senior level criminal law courses. Topics covered include arrest, search and seizure, bail, trial procedures, sentencing, and prisons. Objective is to encourage students to address societal issues. (LS)
Health Law: Notifiable diseases
Gastón Casaux
2014-07-01
Full Text Available This work made up the ultimate Health Law, latest new law branch from older date in the whole world but recently appearance in our country. As usual in other cases, we increase one of de most relevant events: the endless number of diseases that we advise obligatory, because they have been regulated for consecutive by-laws en the codex from 1946, 1958 and 2004. Since 2012 in order of the successful transformations in the modern technology with the change of rules in our order-law, it was necessary to recall their contents and we achieve in order of the promulgation the decree number 41/12 dated in February 16. In the second chapter we analyse one of the most bothersome contents: the diseases becoming from the food habitudes (named eia´s, whatever we considered a real significance for the common of the citizens and consumers, because they prevail notoriously in the human health.