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.
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.
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)).
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.
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.
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.
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.
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.
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.
Karakhim, S A
2012-01-01
The article is dedicated to analysis of equation which expresses apparent Michaelis constant K(m)app) of enzyme-catalysed reactions with activator participation by means of the substrate constant K(s) and rate constant of enzyme-substrate complex decomposition k(cat). It has been shown that although it is possible to record the mechanisms of such reactions as a scheme similar to Michaelis-Menten model and to derive equation of apparent Michaelis constant as K(m(app) = K(s) + k(cat)/k(1), but this approach cannot be used for investigation of all reactions with activator participation. The equation mentioned above is not obeyed in the general case, it may be true for some mechanisms only or under certain ratio of kinetic parameters of enzyme-catalysed reactions.
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.
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.
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.
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 ...
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.
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…
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
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).
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.
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...
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.
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.
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.
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.
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.
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.
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...
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.
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 ...
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.
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.
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).
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.
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…
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.
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.
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...
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...
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.
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.
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.
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.
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.
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%).
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.
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.
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.
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
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.
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…
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...
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
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.
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...
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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...
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.
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.
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.
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...
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.
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.
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…
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.
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…
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.
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.
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.
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.
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...
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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...
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.
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.
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 ...
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.
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...
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.
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.
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
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…
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).
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…
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...
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.
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…
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
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…
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.
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.
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.
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...
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.
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…
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...
A novel hydrogen peroxide biosensor based on hemoglobin-collagen-CNTs composite nanofibers.
Li, J; Mei, H; Zheng, W; Pan, P; Sun, X J; Li, F; Guo, F; Zhou, H M; Ma, J Y; Xu, X X; Zheng, Y F
2014-06-01
In this paper, carbon nanotubes (CNTs) were successfully incorporated in the composite composed of hemoglobin (Hb) and collagen using co-electrospinning technology. The formed Hb-collagen-CNTs composite nanofibers possessed distinct advantage of three-dimensional porous structure, biocompatibility and excellent stability. The Hb immobilized in the electrospun nanofibers retained its natural structure and the heterogeneous electron transfer rate constant (ks) of the direct electron transfer between Hb and electrodes was 5.3s(-1). In addition, the electrospun Hb-collagen-CNTs nanofibers modified electrodes showed good electrocatalytic properties toward H2O2 with a detection limit of 0.91μM (signal-to-noise ratio of 3) and the apparent Michaelis-Menten constant (Km(app)) of 32.6μM.
Faure, Mathilde; Sotta, Bruno; Gamby, Jean
2014-08-15
Real time monitoring of electrolyte resistance changes during hydrolysis of 4-nitrophenylphosphate (pNPP) by alkaline phosphatase (ALP) bound on paramagnetic-beads was performed into a small dielectric channel. The reaction kinetic fit with a non-competitive substrate-inhibition equation. Michaelis-Menten apparent constant, KM(app), was determined as 0.33±0.06mM and the maximum apparent rate, Vmax(app) as 98±5pMs(-1). The detection limits were 15fM for ALP and 0.75mM for pNPP. This miniaturized device constitutes a powerful tool for analysis of interaction between ligands. Copyright © 2014 Elsevier B.V. All rights reserved.
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
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.
Hong, Jun; Wang, Wei; Huang, Kun; Yang, Wei-Yun; Zhao, Ying-Xue; Xiao, Bao-Lin; Gao, Yun-Fei; Moosavi-Movahedi, Zainab; Ghourchian, Hedayatollah; Moosavi-Movahedi, Ali Akbar
2012-01-01
A nano-cluster with highly efficient peroxide activity was constructed based on nafion (NF) and cytochrome c (Cyt c). UV-Vis spectrometry and transmission electron microscopy (TEM) methods were utilized for characterization of the nano-structured enzyme or artificial peroxidase (AP). The nano-cluster was composed of a Chain-Ball structure, with an average ball size of about 40 nm. The Michaelis-Menten (K(m)) and catalytic rate (k(cat)) constants of the AP were determined to be 2.5 ± 0.4 µM and 0.069 ± 0.001 s(-1), respectively, in 50 mM PBS at pH 7.0. The catalytic efficiency of the AP was evaluated to be 0.028 ± 0.005 µM(-1) s(-1), which was 39 ± 5% as efficient as the native horseradish peroxidase (HRP). The AP was also immobilized on a functional multi-wall carbon nanotube (MWNCTs)-gold colloid nanoparticles (AuNPs) nano-complex modified glassy carbon (GC) electrode. The cyclic voltammetry of AP on the nano complex modified GC electrode showed a pair of well-defined redox peaks with a formal potential (E°') of -45 ± 2 mV (vs. Ag/AgCl) at a scan rate of 0.05 V/s. The heterogeneous electron transfer rate constant (k(s)) was evaluated to be 0.65 s(-1). The surface concentration of electroactive AP on GC electrode (Γ) was 7 × 10(-10) mol cm(-2). The apparent Michaelis-Menten constant (K(m)(app)) was 0.23 nM.
盛春; 张洋; 王璐; 贾能勤
2012-01-01
A novel biopolymer/room-temperature ionic liquid composite film based on carrageenan, room temperature ionic liquid （IL） [1-butyl-3-methylimidazolium tetrafluoroborate （[BMIM]BF4）] was explored for immobilization of hemoglobin （Hb） and construction of biosensor. Direct electrochemistry and electrocatalytic behaviors of Hb entrapped in the IL-carrageenan composite film on the surface of glassy carbon electrode （GCE） were investigated. UV-vis spectroscopy demonstrated that Hb in the IL-carrageenan composite film could retain its native secondary structure. A pair of well-defined redox peaks of Hb was obtained at the Hb-IL-carrageenan composite film modified electrode through direct electron transfer between the protein and the underlying electrode. The heterogeneous electron transfer rate constant （ks） was 2.02 s 1, indicating great facilitation of the electron transfer between Hb and IL-carrageenan composite film modified electrode. The modified electrode showed excellent electrocatalytic activity toward reduction of hydrogen peroxide with a linear range of 5.0 × 10-6 to 1.5 ×10-4 mol/L and the detection limit was 2.12 ×10 7 mol/L （S/N= 3）. The apparent Michaelis-Menten constant KM^app for hydrogen peroxide was estimated to be 0.02 mmol/L, indicating that the biosensor possessed high affinity to hydrogen peroxide. In addition, the proposed biosensor showed good reproducibility and stability.
Kim, Yong-Hak; Engesser, Karl-Heinrich
2005-02-15
Alkyl ether-degrading Rhodococcus sp. strain DEE5151, isolated from activated sewage sludge, has an activity for the oxidation of a variety of alkyl ethers, aralkyl ethers and dibenzyl ether. The whole cell activity for diethyl ether oxidation was effectively inhibited by 2,3-dihydrofurane, ethyl vinyl ether and glutaraldehyde. Glutaraldehyde of less than 30 microM inhibited the activity by a competitive manner with the inhibition constant, K(I) of 7.07+/-1.36 microM. The inhibition type became mixed at higher glutaraldehyde concentrations >30 microM, probably due to the inactivation of the cell activity by the Schiff-base formation. Structurally analogous ethyl vinyl ether inhibited the diethyl ether oxidation activity in a mixed manner with decreasing the apparent maximum oxidation rate, v(max)(app), and increasing the apparent Michaelis-Menten constant, K(M)(app). The mixed type inhibition by ethyl vinyl ether seemed to be introduced not only by the structure similarity with diethyl ether, but also by the reactivity of the vinyl ether with cellular components in the whole cell system.
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.
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....
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.
Zhang, Zhiqiang; Xia, Siqing; Leonard, Didier; Jaffrezic-Renault, Nicole; Zhang, Jiao; Bessueille, François; Goepfert, Yves; Wang, Xuejiang; Chen, Ling; Zhu, Zhiliang; Zhao, Jianfu; Almeida, M Gabriela; Silveira, Célia M
2009-02-15
A conductometric biosensor for nitrite detection was developed using cytochrome c nitrite reductase (ccNiR) extracted from Desulfovibrio desulfuricans ATCC 27774 cells immobilized on a planar interdigitated electrode by cross-linking with saturated glutaraldehyde (GA) vapour in the presence of bovine serum albumin, methyl viologen (MV), Nafion, and glycerol. The configuration parameters for this biosensor, including the enzyme concentration, ccNiR/BSA ratio, MV concentration, and Nafion concentration, were optimized. Various experimental parameters, such as sodium dithionite added, working buffer solution, and temperature, were investigated with regard to their effect on the conductance response of the biosensor to nitrite. Under the optimum conditions at room temperature (about 25 degrees C), the conductometric biosensor showed a fast response to nitrite (about 10s) with a linear range of 0.2-120 microM, a sensitivity of 0.194 microS/microM [NO(2)(-)], and a detection limit of 0.05 microM. The biosensor also showed satisfactory reproducibility (relative standard deviation of 6%, n=5). The apparent Michaelis-Menten constant (K(M,app)) was 338 microM. When stored in potassium phosphate buffer (100mM, pH 7.6) at 4 degrees C, the biosensor showed good stability over 1 month. No obvious interference from other ionic species familiar in natural waters was detected. The application experiments show that the biosensor is suitable for use in real water samples.
Gholivand, Mohammad Bagher; Khodadadian, Mehdi
2014-03-15
Cholesterol oxidase (ChOx) and catalase (CAT) were co-immobilized on a graphene/ionic liquid-modified glassy carbon electrode (GR-IL/GCE) to develop a highly sensitive amperometric cholesterol biosensor. The H2O2 generated during the enzymatic reaction of ChOx with cholesterol could be reduced electrocatalytically by immobilized CAT to obtain a sensitive amperometric response to cholesterol. The direct electron transfer between enzymes and electrode surface was investigated by cyclic voltammetry. Both enzymes showed well-defined redox peaks with quasi-reversible behaviors. An excellent sensitivity of 4.163 mA mM(-1)cm(-2), a response time less than 6s, and a linear range of 0.25-215 μM (R(2)>0.99) have been observed for cholesterol determination using the proposed biosensor. The apparent Michaelis-Menten constant (KM(app)) was calculated to be 2.32 mM. The bienzymatic cholesterol biosensor showed good reproducibility (RSDsanalytical performance for the determination of free cholesterol in human serum samples.
Ahmad, Rafiq; Tripathy, Nirmalya; Ahn, Min-Sang; Hahn, Yoon-Bong
2017-04-01
This study demonstrates a highly stable, selective and sensitive uric acid (UA) biosensor based on high aspect ratio zinc oxide nanorods (ZNRs) vertical grown on electrode surface via a simple one-step low temperature solution route. Uricase enzyme was immobilized on the ZNRs followed by Nafion covering to fabricate UA sensing electrodes (Nafion/Uricase-ZNRs/Ag). The fabricated electrodes showed enhanced performance with attractive analytical response, such as a high sensitivity of 239.67 μA cm-2 mM-1 in wide-linear range (0.01-4.56 mM), rapid response time (~3 s), low detection limit (5 nM), and low value of apparent Michaelis-Menten constant (Kmapp, 0.025 mM). In addition, selectivity, reproducibility and long-term storage stability of biosensor was also demonstrated. These results can be attributed to the high aspect ratio of vertically grown ZNRs which provides high surface area leading to enhanced enzyme immobilization, high electrocatalytic activity, and direct electron transfer during electrochemical detection of UA. We expect that this biosensor platform will be advantageous to fabricate ultrasensitive, robust, low-cost sensing device for numerous analyte detection.
A novel horseradish peroxidase biosensor towards the detection of dopamine: a voltammetric study.
Raghu, P; Reddy, T Madhusudana; Gopal, P; Reddaiah, K; Sreedhar, N Y
2014-04-10
A polymerized film of glycine (Gly) was prepared on the surface of carbon paste electrode (CPE) through the cyclic voltammetry (CV) technique. A novel biosensor for the determination of dopamine (DA) has been constructed based on horseradish peroxidase (HRP) and multiwalled carbon nanotubes (MWCNTs) immobilizing on Poly (Gly)/CPE through silica sol-gel (SiSG) entrapment. CV measurements were employed in order to understand the feasibility of poly (Gly) as an electron carrier between the immobilized peroxidase and the surface of CPE. By using differential pulse voltammetry (DPV) the calibration curves of DA was obtained in the range of 15-865 μM. The limit of detection (LOD) and limit of quantification (LOQ) of DA was found to be 6×10⁻⁷ M and 2×10⁻⁶ M respectively. The apparent Michaelis-Menten constant (Km(app)) was found to be 0.5 mM and illustrated that the good biological activity of the fixed enzyme. Electrochemical impedance spectroscopy (EIS) results confirmed the rapid electron transfer and also the immobilization of enzyme on the electrode surface. The biosensor showed high sensitivity, selectivity and reproducibility. This method has been used to determine DA in the presence of various interferences and in clinical preparations.
Flower like Bi structures on Pt surface facilitating effective cholesterol biosensing.
V C, Soorya; Berchmans, Sheela
2016-07-01
This work demonstrates effective biosensing of cholesterol with the help of an efficient inorganic H2O2 transducer based on Pt-Bi combined with the organic enzyme platform. It could be shown that the Bi (bismuth) adatoms modified Pt (platinum) surface displays enhanced catalytic oxidation of H2O2 at neutral pH and the catalytic oxidation of H2O2 occurs at a lower potential of 0.25V vs NCE (normal calomel electrode). The sensing platform is highly sensitive and shows linear response towards [H2O2] in the absence of any redox mediator or enzyme. The H2O2 sensing platform, further modified with cholesterol oxidase led to cholesterol biosensing with a sensitivity of 3.41μAmM(-1)cm(-2). The apparent Michaelis-Menten constant (Km(app)) was calculated to be 0.43mM which indicates high binding affinity with the substrate. The cholesterol biosensor does not suffer from the interferences due to other common electroactive species and is highly stable.
Zhybak, M; Beni, V; Vagin, M Y; Dempsey, E; Turner, A P F; Korpan, Y
2016-03-15
The use of a novel ammonium ion-specific copper-polyaniline nano-composite as transducer for hydrolase-based biosensors is proposed. In this work, a combination of creatinine deaminase and urease has been chosen as a model system to demonstrate the construction of urea and creatinine biosensors to illustrate the principle. Immobilisation of enzymes was shown to be a crucial step in the development of the biosensors; the use of glycerol and lactitol as stabilisers resulted in a significant improvement, especially in the case of the creatinine, of the operational stability of the biosensors (from few hours to at least 3 days). The developed biosensors exhibited high selectivity towards creatinine and urea. The sensitivity was found to be 85 ± 3.4 mAM(-1)cm(-2) for the creatinine biosensor and 112 ± 3.36 mAM(-1)cm(-2) for the urea biosensor, with apparent Michaelis-Menten constants (KM,app), obtained from the creatinine and urea calibration curves, of 0.163 mM for creatinine deaminase and 0.139 mM for urease, respectively. The biosensors responded linearly over the concentration range 1-125 µM, with a limit of detection of 0.5 µM and a response time of 15s. The performance of the biosensors in a real sample matrix, serum, was evaluated and a good correlation with standard spectrophotometric clinical laboratory techniques was found.
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.
Hydrolysis of used frying palm olein and sunflower oil catalyzed by porcine pancreatic lipase.
Arroyo, R; Sánchez-Muniz, F J; Cuesta, C; Burguillo, F J; Sánchez-Montero, J M
1996-11-01
The enzymatic hydrolysis of frying used vegetable oils with different degrees of alteration were measured using porcine pancreatic lipase (acylglycerol acylhydrolase EC 3.1.1.3). Successive frying of potatoes significantly increased the level of total polar lipid content in the palm olein from 9.3 +/- 0.1 mg/100 mg oil to 26.4 +/- 0.3 mg/100 mg oil after 90 fryings, and from 4.0 +/- 0.1 mg/100 mg oil to 27.7 +/- 0.3 mg/100 mg oil in sunflower oil after 60 fryings. Triacylglycerol polymers, triacylglycerol dimers, and oxidized triacylglycerols also increased 37-, 7.9-, and 7.5-times in palm olein, respectively, and 56-, 22-, and 4.7-times in sunflower oil, respectively. However, diacylglycerols and free fatty acid levels related to hydrolytic alteration did not increase with the number of fryings in both oils. The substrate concentration in the reactor was determined by calculating the molecular weight of each oil showing a different degree of alteration. We compared the methodology used by us and that used by other authors. The results show that the methods are reproducible and that the values obtained are in concordance with theoretical values. The kinetic parameters apparent Michaelis-Menten constant (KMapp) and apparent maximum velocity of hydrolysis (Vmaxapp) were different in unused palm olein (5.1 +/- 0.7 and 166 +/- 7.6, respectively) than in sunflower oil (2.2 +/- 0.3 and 62 +/- 2.2, respectively). However, changes in KMapp and Vmaxapp were not related to the degree of alteration of the oils.
The kinetics of denitrification in permeable sediments
Evrard, Victor; Glud, Ronnie N.; Cook, Perran L. M.
2013-01-01
on sediments taken from six shallow coastal sites in Port Phillip Bay, Victoria, Australia. The results showed that denitrification commenced rapidly (within 30 min) after the onset of anoxia and the kinetics could be well described by Michaelis-Menten kinetics with half saturation constants (apparent K...
Indices for the age of the creatine kinase M-chain in the blood
Wevers, R.A.; Hagelauer, U.; Stein, W.; Bohner, J.; Faust, U.; Landeghem, A.A.J. van; Soons, J.B.J.
1985-01-01
The apparent activation energy of the CK reaction as well as the Michaelis-Menten constants and the isoelectric point of CK MM can be used as indices for the mean age of the CK M-chain in the blood in vivo and in vitro. Modifications in the CK M-chain take place in vivo in the blood and in vitro
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 ...
Farmacokinetiek van urethaan bij de rat
Olling M; Zeijlmans PWM
1988-01-01
De kinetiek van urethaan volgt het Michaelis-Menten model, waarbij de Vmax na intraperitoneale toediening varieert van 7,1 mg/l.h bij een toediening van 100 mg/kg tot 38,2 mg/l.h na 1,25 g/kg. De Michaelis constante, Km, blijkt ver beneden de concentraties te liggen welke tijdens dit onderzoek k
Damour, Thibault Marie Alban Guillaume
2003-01-01
We review some string-inspired theoretical models which incorporate a correlated spacetime variation of coupling constants while remaining naturally compatible both with phenomenological constraints coming from geochemical data (Oklo; Rhenium decay) and with present equivalence principle tests. Barring unnatural fine-tunings of parameters, a variation of the fine-structure constant as large as that recently ``observed'' by Webb et al. in quasar absorption spectra appears to be incompatible with these phenomenological constraints. Independently of any model, it is emphasized that the best experimental probe of varying constants are high-precision tests of the universality of free fall, such as MICROSCOPE and STEP. Recent claims by Bekenstein that fine-structure-constant variability does not imply detectable violations of the equivalence principle are shown to be untenable.
Maggi, F.M.; Riley, W.J.
2009-06-01
The theoretical formulation of biological kinetic reactions in isotopic applications often assume first-order or Michaelis-Menten-Monod kinetics under the quasi-steady-state assumption to simplify the system kinetics. However, isotopic e ects have the same order of magnitude as the potential error introduced by these simpli cations. Both formulations lead to a constant fractionation factor which may yield incorrect estimations of the isotopic effect and a misleading interpretation of the isotopic signature of a reaction. We have analyzed the isotopic signature of denitri cation in biogeochemical soil systems by Menyailo and Hungate [2006], where high {sup 15}N{sub 2}O enrichment during N{sub 2}O production and inverse isotope fractionation during N{sub 2}O consumption could not be explained with first-order kinetics and the Rayleigh equation, or with the quasi-steady-state Michaelis-Menten-Monod kinetics. When the quasi-steady-state assumption was relaxed, transient Michaelis-Menten-Monod kinetics accurately reproduced the observations and aided in interpretation of experimental isotopic signatures. These results may imply a substantial revision in using the Rayleigh equation for interpretation of isotopic signatures and in modeling biological kinetic isotope fractionation with first-order kinetics or quasi-steady-state Michaelis-Menten-Monod kinetics.
Robinson, H.P.; Potter, Elinor
1971-03-01
This collection of mathematical data consists of two tables of decimal constants arranged according to size rather than function, a third table of integers from 1 to 1000, giving some of their properties, and a fourth table listing some infinite series arranged according to increasing size of the coefficients of the terms. The decimal values of Tables I and II are given to 20 D.
Sparavigna, Amelia Carolina
2012-01-01
As proposed in a previous paper, the decorations of ancient objects can provide some information on the approximate evaluations of constant {\\pi}, the ratio of circumference to diameter. Here we discuss some disks found in the tomb of Hemaka, the chancellor of a king of the First Dynasty of Egypt, about 3000 BC. The discussion is based on measurements of the dimensionless ratio of lengths.
Nader Sheibani
2013-07-01
Full Text Available Direct electron transfer of hemoglobin (Hb was realized by immobilizing Hb on a carboxyl functionalized multi-walled carbon nanotubes (FMWCNTs and gold nanoparticles (AuNPs nanocomplex-modified glassy carbon electrode. The ultraviolet-visible absorption spectrometry (UV-Vis, transmission electron microscopy (TEM and Fourier transform infrared (FTIR methods were utilized for additional characterization of the AuNPs and FMWCNTs. The cyclic voltammogram of the modified electrode has a pair of well-defined quasi-reversible redox peaks with a formal potential of −0.270 ± 0.002 V (vs. Ag/AgCl at a scan rate of 0.05 V/s. The heterogeneous electron transfer constant (ks was evaluated to be 4.0 ± 0.2 s−1. The average surface concentration of electro-active Hb on the surface of the modified glassy carbon electrode was calculated to be 6.8 ± 0.3 × 10−10 mol cm−2. The cathodic peak current of the modified electrode increased linearly with increasing concentration of hydrogen peroxide (from 0.05 nM to 1 nM with a detection limit of 0.05 ± 0.01 nM. The apparent Michaelis-Menten constant (Kmapp was calculated to be 0.85 ± 0.1 nM. Thus, the modified electrode could be applied as a third generation biosensor with high sensitivity, long-term stability and low detection limit.
Chen, Xiaoqian; Wang, Qingxiang; Wang, Liheng; Gao, Feng; Wang, Wei; Hu, Zhengshui
2015-04-15
A broccoli-like bismuth sulfide (bBi2S3) was synthesized via a solvothermal method using a self-made imidazoline derivative of 2-undecyl-1-dithioureido-ethyl-imidazoline as the soft template. The morphology and chemical constitution of the product were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM) and X-ray diffraction (XRD). Electrochemical characterization experiments show that the bBi2S3 has the higher specific surface area and standard heterogeneous electron transfer rate constant than the rod-like Bi2S3 (rBi2S3). Hemoglobin (Hb) was then chosen as a protein model to investigate the electrocatalytic property of the synthesized bBi2S3. The results show that Hb entrapped in the composite film of chitosan and bBi2S3 displays an excellent direct electrochemistry, and retains its biocatalytic activity toward the electro-reduction of hydrogen peroxide. The current response in the amperometry shows a linear response to H2O2 concentrations in the range from 0.4 to 4.8µM with high sensitivity (444µAmM(-1)) and low detection limit (0.096µM). The Michaelis-Menten constant (KM(app)) of the fabricated bioelectrode for H2O2 was determined as low as 1µM. These results demonstrate that the synthesized bBi2S3 offers a new path for the immobilization of redox-active protein and the construction of the third-generation biosensors. Copyright © 2014 Elsevier B.V. All rights reserved.
Zhao, Mei; Gao, Yue; Sun, Junyong; Gao, Feng
2015-03-03
Utilization of carbon nanodots (CNDs), newcomers to the world of carbonaceous nanomaterials, in the electrochemistry realm has rarely been reported so far. In this study, CNDs were used as immobilization supports and electron carriers to promote direct electron transfer (DET) reactions of glucose oxidase (GOx) and bilirubin oxidase (BOD). At the CNDs electrode entrapped with GOx, a high rate constant (k(s)) of 6.28 ± 0.05 s(-1) for fast DET and an apparent Michaelis-Menten constant (K(M)(app)) as low as 0.85 ± 0.03 mM for affinity to glucose were found. By taking advantage of its excellent direct bioelectrocatalytic performances to glucose oxidation, a DET-based biosensor for glucose detection ranging from 0 to 0.64 mM with a high sensitivity of 6.1 μA mM(-1) and a limit of detection (LOD) of 1.07 ± 0.03 μM (S/N = 3) was proposed. Additionally, the promoted DET of BOD immobilized on CNDs was also observed and effectively catalyzed the reduction of oxygen to water at the onset potential of +0.51 V (vs Ag/AgCl). On the basis of the facilitated DET of these two enzymes at CNDs electrodes, a mediator-free DET-type glucose/air enzymatic biofuel cell (BFC), in which CNDs electrodes entrapped with GOx and BOD were employed for oxidizing glucose at the bioanode and reducing oxygen at the biocathode, respectively, was successfully fabricated. The constructed BFC displayed an open-circuit voltage (OCV) as high as 0.93 V and a maximum power density of 40.8 μW cm(-2) at 0.41 V. These important features of CNDs have implied to be promising materials for immobilizing enzymes and efficient platforms for elaborating bioelectrochemical devices such as biosensors and BFCs.
Atypical cytochrome p450 kinetics: implications for drug discovery.
Tracy, Timothy S
2006-01-01
The Michaelis-Menten model is commonly used to estimate a drug's potential in vivo hepatic clearance based on in vitro data obtained during drug discovery and development. This paradigm assumes that the drug obeys 'typical' enzyme kinetics and thus can be described by this model. However, it is increasingly being recognised that a number of drugs metabolised not only by the cytochrome P450 enzymes but also by other enzymes and transporters can exhibit atypical kinetic profiles, and thus are not accurately modeled with the Michaelis-Menten model. Application of an incorrect model can then lead to mis-estimation of in vitro intrinsic clearance and thus affect the prediction of in vivo clearance. This review discusses several types of atypical kinetic profiles that may be observed, including examples of homotropic cooperativity (i.e. sigmoidal kinetics, biphasic kinetics and substrate inhibition kinetics) as well as heterotropic cooperativity (i.e. activation). Application of the incorrect kinetic model may profoundly affect estimations of intrinsic clearance. For example, incorrectly applying the Michaelis-Menten model to a kinetic profile exhibiting substrate inhibition kinetics will result in an underestimation of Km (Michaelis-Menten constant) and V(max) (maximal velocity), whereas application of the Michaelis-Menten model to sigmoidal kinetic data typically results in an overestimation of Km and V(max) at the lower substrate concentrations that are typically therapeutically relevant. One must also be careful of potential artefactual causes of atypical kinetic profiles, such as enzyme activation by solvents, buffer dependent kinetic profiles, or altered kinetic parameter estimates due to nonspecific binding of the substrate to proteins. Despite a plethora of data on the effects of atypical kinetic profiles in vitro, only modest effects have been noted in vivo (with the exception of substrate dependent inhibition). Thus, the clinical relevance of these phenomena
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
Li Yuanting
2012-09-01
Full Text Available Abstract Background Biosensors have attracted increasing attention as reliable analytical instruments in in situ monitoring of public health and environmental pollution. For enzyme-based biosensors, the stabilization of enzymatic activity on the biological recognition element is of great importance. It is generally acknowledged that an effective immobilization technique is a key step to achieve the construction quality of biosensors. Results A novel disposable biosensor was constructed by immobilizing laccase (Lac with silica spheres on the surface of multi-walled carbon nanotubes (MWCNTs-doped screen-printed electrode (SPE. Then, it was characterized in morphology and electrochemical properties by scanning electron microscopy (SEM and cyclic voltammetry (CV. The characterization results indicated that a high loading of Lac and a good electrocatalytic activity could be obtained, attributing to the porous structure, large specific area and good biocompatibility of silica spheres and MWCNTs. Furthermore, the electrochemical sensing properties of the constructed biosensor were investigated by choosing dopamine (DA as the typical model of phenolic compounds. It was shown that the biosensor displays a good linearity in the range from 1.3 to 85.5 μM with a detection limit of 0.42 μM (S/N = 3, and the Michaelis-Menten constant (Kmapp was calculated to be 3.78 μM. Conclusion The immobilization of Lac was successfully achieved with silica spheres to construct a disposable biosensor on the MWCNTs-doped SPE (MWCNTs/SPE. This biosensor could determine DA based on a non-oxidative mechanism in a rapid, selective and sensitive way. Besides, the developed biosensor could retain high enzymatic activity and possess good stability without cross-linking reagents. The proposed immobilization approach and the constructed biosensor offer a great potential for the fabrication of the enzyme-based biosensors and the analysis of phenolic compounds.
Direct electrochemistry of Penicillium chrysogenum catalase adsorbed on spectroscopic graphite.
Dimcheva, Nina; Horozova, Elena
2013-04-01
The voltammetric studies of Penicillium chrysogenum catalase (PcCAT) adsorbed on spectroscopic graphite, showed direct electron transfer (DET) between its active site and the electrode surface. Analogous tests performed with the commercially available bovine catalase revealed that mammalian enzyme is much less efficient in the DET process. Both catalases were found capable to catalyse the electrooxidation of phenol, but differed in the specifics of catalytic action. At an applied potential of 0.45V the non-linear regression showed the kinetics of the bioelectrochemical oxidation catalysed by the PcCAT obeyed the Hill equation with a binding constant K=0.034±0.002 M(2) (Hill's coefficient n=2.097±0.083, R(2)=0.997), whilst the catalytic action of the bovine catalase was described by the Michaelis-Menten kinetic model with the following parameters: V(max,app)=7.780±0.509 μA, and K(M,app)=0.068±0.070 mol L(-1). The performance of the electrode reaction was affected by the electrode potential, the pH, and temperature. Based on the effect of pH and temperature on the electrode response in presence of phenol a tentative reaction pathway of its bioelectrocatalytic oxidation has been hypothesised. The possible application of these findings in biosensing phenol up to concentration 30 mM at pHs below 7 and in absence of oxidising agents (oxygen or H(2)O(2)) was considered.
Li, Yonghong; Zeng, Xiandong; Liu, Xiaoying; Liu, Xinsheng; Wei, Wanzhi; Luo, Shenglian
2010-08-01
The direct electron transfer and electrocatalysis of hemoglobin (Hb) entrapped in the MCM-41 modified carbon ionic liquid electrode (CILE) were investigated by using cyclic voltammetry in 0.10 M pH 7.0 phosphate buffer solution (PBS). Due to its uniform pore structure, high surface areas and good biocompatibility, the mesoporous silica sieve MCM-41 provided a suitable matrix for immobilization of biomolecule. The MCM-41 modified CILE showed significant promotion to the direct electron transfer of Hb, which exhibited a pair of well defined and quasi-reversible peaks for heme Fe(III)/Fe(II) with a formal potential of -0.284 V (vs. Ag/AgCl). Additionally, the Hb immobilized on the MCM-41 modified carbon ionic liquid electrode showed excellent electrocatalytic activity toward H(2)O(2). The electrocatalytic current values were linear with increasing concentration of H(2)O(2) in a wide range of 5-310 microM and the corresponding detection limit was calculated to be 5 x 10(-8)M (S/N=3). The surface coverage of Hb immobilized on the MCM-41 modified carbon ionic liquid electrode was about 2.54 x 10(-9) molcm(-2). The Michaelis-Menten constant K(m)(app) of 214 microM indicated that the Hb immobilized on the modified electrode showed high affinity to H(2)O(2). The proposed electrode had high stability and good reproducibility due to the protection effect of MCM-41 and ionic liquid, and it would have wide potential applications in direct electrochemistry, biosensors and biocatalysis.
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
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.
Kinetics of propionate conversion in anaerobic continuously stirred tank reactors
Bangsø Nielsen, Henrik; Mladenovska, Zuzana; Ahring, Birgitte Kiær
2008-01-01
(max), and the half saturation constant, K-m, were initially estimated by applying the integrated Michaelis-Menten equation. A(max) was in the range from 22.8 to 29.1 mu mol gVS(-1) h(-1) while K-m, was in the range from 0.46-0.95 mM. In general, A(max) gave a good reflection of the reactor performances. Secondly...
无
2007-01-01
In this paper, differential pulse voltammetry (DPV) was applied to study the effects of aluminum Al(Ⅲ) on the lactate dehydrogenase (LDH) activity. Michaelis-Menten constant (KNADHm) and maximum velocity (vmax) in the enzyme promoting catalytic reaction of "pyruvate(Pyr) + NADH + H+ LDH(=) lactate + NAD+" under different conditions by monitoring DPV reduction current of NAD+ were reported.(C) 2007 Shu Ping Bi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Guo, Meiqing; Wang, Hefeng; Huang, Di; Han, Zhijun; Li, Qiang; Wang, Xiaojun; Chen, Jing
2014-06-01
A functionalized nitrogen-containing ordered mesoporous carbon (N-OMC), which shows good electrical properties, was synthesized by the carbonization of polyaniline inside a SBA-15 mesoporous silica template. Based on this, through entrapping laccase onto the N-OMC/polyvinyl alcohol (PVA) film a facilely fabricated amperometric biosensor was developed. Laccase from Trametes versicolor was assembled on a composite film of a N-OMC/PVA modified Au electrode and the electrochemical behavior was investigated. The results indicated that the N-OMC modified electrode exhibits electrical properties towards catechol. The optimum experimental conditions of a biosensor for the detection of catechol were studied in detail. Under the optimal conditions, the sensitivity of the biosensor was 0.29 A*M-1 with a detection limit of 0.31 μM and a linear detection range from 0.39 μM to 8.98 μM for catechol. The calibration curve followed the Michaelis-Menten kinetics and the apparent Michaelis-Menten \\left( K_{M}^{app} \\right) was 6.28 μM. This work demonstrated that the N-OMC/PVA composite provides a suitable support for laccase immobilization and the construction of a biosensor.
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.
Ion exchange equilibrium constants
Marcus, Y
2013-01-01
Ion Exchange Equilibrium Constants focuses on the test-compilation of equilibrium constants for ion exchange reactions. The book first underscores the scope of the compilation, equilibrium constants, symbols used, and arrangement of the table. The manuscript then presents the table of equilibrium constants, including polystyrene sulfonate cation exchanger, polyacrylate cation exchanger, polymethacrylate cation exchanger, polysterene phosphate cation exchanger, and zirconium phosphate cation exchanger. The text highlights zirconium oxide anion exchanger, zeolite type 13Y cation exchanger, and
Cosmological Constant, Fine Structure Constant and Beyond
Wei, Hao; Li, Hong-Yu; Xue, Dong-Ze
2016-01-01
In this work, we consider the cosmological constant model $\\Lambda\\propto\\alpha^{-6}$, which is well motivated from three independent approaches. As is well known, the evidence of varying fine structure constant $\\alpha$ was found in 1998. If $\\Lambda\\propto\\alpha^{-6}$ is right, it means that the cosmological constant $\\Lambda$ should be also varying. In this work, we try to develop a suitable framework to model this varying cosmological constant $\\Lambda\\propto\\alpha^{-6}$, in which we view it from an interacting vacuum energy perspective. We propose two types of models to describe the evolutions of $\\Lambda$ and $\\alpha$. Then, we consider the observational constraints on these models, by using the 293 $\\Delta\\alpha/\\alpha$ data from the absorption systems in the spectra of distant quasars, and the data of type Ia supernovae (SNIa), cosmic microwave background (CMB), baryon acoustic oscillation (BAO). We find that the model parameters can be tightly constrained to the narrow ranges of ${\\cal O}(10^{-5})$ t...
Generalized Pickands constants
Debicki, K.G.
2001-01-01
Pickands constants play an important role in the exact asymptotic of extreme values for Gaussian stochastic processes. By the {it generalized Pickands constant ${cal H_{eta$ we mean the limit begin{eqnarray* {cal H_{eta= lim_{T to inftyfrac{ {cal H_{eta(T){T, end{eqnarray* where ${cal H_{eta(T)= Exp
Chekin, Fereshteh; Leiva, Nélida; Raoof, Jahan Bakhsh; Gorton, Lo; Bülow, Leif
2010-10-01
In this study, direct electron transfer (ET) has been achieved between an immobilised non-symbiotic plant haemoglobin class II from Beta vulgaris (nsBvHb2) and three different screen-printed carbon electrodes based on graphite (SPCE), multi-walled carbon nanotubes (MWCNT-SPCE), and single-walled carbon nanotubes (SWCNT-SPCE) without the aid of any electron mediator. The nsBvHb2 modified electrodes were studied with cyclic voltammetry (CV) and also when placed in a wall-jet flow through cell for their electrocatalytic properties for reduction of H(2)O(2). The immobilised nsBvHb2 displayed a couple of stable and well-defined redox peaks with a formal potential (E°') of -33.5 mV (vs. Ag|AgCl|3 M KCl) at pH 7.4. The ET rate constant of nsBvHb2, k(s), was also determined at the surface of the three types of electrodes in phosphate buffer solution pH 7.4, and was found to be 0.50 s(-1) on SPCE, 2.78 s(-1) on MWCNT-SPCE and 4.06 s(-1) on SWCNT-SPCE, respectively. The average surface coverage of electrochemically active nsBvHb2 immobilised on the SPCEs, MWCNT-SPCEs and SWCNT-SPCEs obtained was 2.85 × 10(-10) mol cm(-2), 4.13 × 10(-10) mol cm(-2) and 5.20 × 10(-10) mol cm(-2). During the experiments the immobilised nsBvHb2 was stable and kept its electrochemical and catalytic activities. The nsBvHb2 modified electrodes also displayed an excellent response to the reduction of hydrogen peroxide (H(2)O(2)) with a linear detection range from 1 μM to 1000 μM on the surface of SPCEs, from 0.5 μM to 1000 μM on MWCNT-SPCEs, and from 0.1 μM to 1000 μM on SWCNT-SPCEs. The lower limit of detection was 0.8 μM, 0.4 μM and 0.1 μM at 3σ at the SPCEs, the MWCNT-SPCEs, and the SWCNT-SPCEs, respectively, and the apparent Michaelis-Menten constant, K(M)(app), for the H(2)O(2) sensors was estimated to be 0.32 mM , 0.29 mM and 0.27 mM, respectively.
黄琨; 洪军; 王玮; 肖保林; 赵莹雪; 杨卫云; 高云飞
2012-01-01
用阴离子表面活性剂十二烷基磺酸钠与细胞色素c自组装的方法构建了一种纳米超分子结构,观察到其具有显著的过氧化物酶活性,且在pH为10.5时达到最高.这种纳米结构过氧化物酶的催化效率为0.0219μmol/L·s.电化学方法测得其电子传递速率常数ks为0.586 s-1.这种以自组装方法构建的超分子结构不仅具有较高活性,可在天然过氧化物酶自杀性失活底物浓度较高时运用,且可固定化于电极上,实现与电极间的直接电子传递.%A nano-structured supermolecule or artificial enzyme was built self-assembly based on sodium dodecyl sulfate nano-micelle and cytochrome c. A significant peroxidase activity was observed and reached the maximum value at pH 10.5. Its catalytic efficiency was evaluated to be 0.0219 μmol/L·s. The immobilized nano-structured peroxidase modified electrode showed quasi-reversible electrochemical redox behaviors with a formal potential of (-38 ± 5) mV (vs. Ag/AgCI) at a scan rate of 0.05 V/s. The cathodic transfer coefficient and electron transfer rate constant were evaluated to be 0.51 and 0.59 s-1 respectively. The apparent Michaelis-Menten constant (Kmapp) was calculated to be 0.14 mmol/L. These results suggest that the nano-structured peroxidase not only perform a high activity as peroxidase and can be used in high concentration of hydrogen peroxide,but also can be immobilized on the electrode and realize direct electrochemical behavior.
用线性动力学方法考察黄嘌呤对尿酸酶的抑制作用%Inhibitory effects of xanthine on uricase analyzed by a linear kinetic method
赵利娜; 廖飞; 赵运胜
2005-01-01
目的:以米氏常数相差较大的两种尿酸酶为模型,考察用两个底物浓度下标定比活性确定酶动力学参数和筛选抑制剂的可靠性.方法:用293 nm吸收监测尿酸酶反应.通过两个底物浓度下标定比活性确定表观米氏常数(apparent michaelis-menten constant,Kmapp)和表观最大反应速度(apparent maximal reaction rate,Vmapp).据表观动力学参数随抑制剂浓度的变化确定抑制类型和抑制常数(inhibition constant,Ki).结果:只要所用尿酸浓度中较小者(the lower concentration of uric acid,SL)大于待测Km的0.8倍且较大者(the higher concentration of uric acid,SH)在SL的1.4倍以上,此线性动力学法能可靠测定Bacillusfastidiosus和Candida species尿酸酶的米氏常数,且与双倒数法结果一致.如SL大于Km的3.8倍而SH为SL的3倍,此线性动力学法所得Candida species尿酸酶Kmapp与抑制剂浓度成正比,Ki为(4.8±0.5)μmol/L,与双倒数法结果一致.Bacillus fastidiosus尿酸酶Km太高,底物浓度有限时不能用此方法筛选其抑制剂.结论:此线性动力学方法仅用高于Km的底物浓度也能可靠确定酶动力学参数,有利于用常规定量方法筛选对底物具有高亲合力特殊靶酶的抑制剂.
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
杨根生; 戚映丹; 欧志敏; 姚善泾
2009-01-01
The asymmetric hydrolyzation of racemic ibuprofen ester is one of the most important methods for chiral separation of ibuprofen. A catalytic antibody that accelerates the rate of enantioselective hydrolysis of ibuprofen methyl ester was successfully elicited against an immunogen consisting of tetrahedral sulfate hapten attached to bovine serum albumin (BSA). The rate constant enhancement factor Kcat/Kuncat was about 1.6x104. The catalytic activity of the catalytic antibody in a reverse micelle reaction system based on sodium b/s (2-ethylhexyl) sodium sulfosuccinate (AOT) in isooctane was studied. Kinetic analysis of the catalytic antibody-catalyzed reaction was found to be possible in this system. Kinetic studies showed that hydrolysis in the microemulsion system follow Michaelis-Menten kinetics. The catalytic antibody can also accelerate catalysis of S-ibuprofen methyl ester in the microemulsion system. Temperature effects, the pH profile, Km,app and Kcat were determined. The dependence of the catalytic antibody hydrolytic activity on the Wo (molar ratio of water to surfactant) showed a bell-shaped curve, presenting a maximum at about wo = 21.%根据过渡态理论设计和合成了能诱导产生催化选择性水解布洛芬甲酯的催化抗体的四面体硫酸盐半抗原,并与牛血清白蛋白(BSA)偶联制备成免疫源,通过免疫手段成功筛选出具有加速选择性水解生成S-布洛芬的特异性催化抗体.其Kcat,app/Kuncat,app达1.6x104.进一步地将催化抗体运用到W/O微乳体系(反胶束)中进行布洛芬酯的选择性水解研究,其动力学研究证明其催化过程同样遵循Michaelis.Menten方程.考察了pH值和温度对催化初速度影响,Wo(体系中水和琥珀酸二辛酯磺酸钠(AOT)的摩尔比)对催化初速度影响呈现为钟罩型,最适的Wo.为21.
Variation of Fundamental Constants
Flambaum, V. V.
2006-11-01
Theories unifying gravity with other interactions suggest temporal and spatial variation of the fundamental ``constants'' in expanding Universe. The spatial variation can explain a fine tuning of the fundamental constants which allows humans (and any life) to appear. We appeared in the area of the Universe where the values of the fundamental constants are consistent with our existence. We present a review of recent works devoted to the variation of the fine structure constant α, strong interaction and fundamental masses. There are some hints for the variation in quasar absorption spectra. Big Bang nucleosynthesis, and Oklo natural nuclear reactor data. A very promising method to search for the variation of the fundamental constants consists in comparison of different atomic clocks. Huge enhancement of the variation effects happens in transition between accidentally degenerate atomic and molecular energy levels. A new idea is to build a ``nuclear'' clock based on the ultraviolet transition between very low excited state and ground state in Thorium nucleus. This may allow to improve sensitivity to the variation up to 10 orders of magnitude! Huge enhancement of the variation effects is also possible in cold atomic and molecular collisions near Feshbach resonance.
Peselnick, L.; Robie, R.A.
1962-01-01
The recent measurements of the elastic constants of calcite by Reddy and Subrahmanyam (1960) disagree with the values obtained independently by Voigt (1910) and Bhimasenachar (1945). The present authors, using an ultrasonic pulse technique at 3 Mc and 25??C, determined the elastic constants of calcite using the exact equations governing the wave velocities in the single crystal. The results are C11=13.7, C33=8.11, C44=3.50, C12=4.82, C13=5.68, and C14=-2.00, in units of 1011 dyncm2. Independent checks of several of the elastic constants were made employing other directions and polarizations of the wave velocities. With the exception of C13, these values substantially agree with the data of Voigt and Bhimasenachar. ?? 1962 The American Institute of Physics.
Algorithm for structure constants
Paiva, F M
2011-01-01
In a $n$-dimensional Lie algebra, random numerical values are assigned by computer to $n(n-1)$ especially selected structure constants. An algorithm is then created, which calculates without ambiguity the remaining constants, obeying the Jacobi conditions. Differently from others, this algorithm is suitable even for poor personal computer. ------------- En $n$-dimensia algebro de Lie, hazardaj numeraj valoroj estas asignitaj per komputilo al $n(n-1)$ speciale elektitaj konstantoj de strukturo. Tiam algoritmo estas kreita, kalkulante senambigue la ceterajn konstantojn, obeante kondicxojn de Jacobi. Malsimile al aliaj algoritmoj, tiu cxi tauxgas ecx por malpotenca komputilo.
Radiographic constant exposure technique
Domanus, Joseph Czeslaw
1985-01-01
The constant exposure technique has been applied to assess various industrial radiographic systems. Different X-ray films and radiographic papers of two producers were compared. Special attention was given to fast film and paper used with fluorometallic screens. Radiographic image quality...... was tested by the use of ISO wire IQI's and ASTM penetrameters used on Al and Fe test plates. Relative speed and reduction of kilovoltage obtained with the constant exposure technique were calculated. The advantages of fast radiographic systems are pointed out...
Bosma, Wieb
2009-01-01
The average value of log s(n)/n taken over the first N even integers is shown to converge to a constant lambda when N tends to infinity; moreover, the value of this constant is approximated and proven to be less than 0. Here s(n) sums the divisors of n less than n. Thus the geometric mean of s(n)/n, the growth factor of the function s, in the long run tends to be less than 1. This could be interpreted as probabilistic evidence that aliquot sequences tend to remain bounded.
Is oral absorption of vigabatrin carrier-mediated?
Nøhr, M. K.; Juul, R. V.; Thale, Z. I.
2015-01-01
by mechanistic non-linear mixed effects modelling, evaluating PAT1-ligands as covariates on the PK parameters with a full covariate modelling approach. The oral absorption of vigabatrin was adequately described by a Michaelis-Menten type saturable absorption. Using a Michaelis constant of 32.8 mM, the model...... by significant increases in the apparent Michaelis constant. Based on the mechanistic model, a high capacity low affinity carrier is proposed to be involved in intestinal vigabatrin absorption. PAT1-ligands increased the Michaelis constant of vigabatrin after oral co-administration indicating that this carrier...
Scott, Tricia
2015-11-01
Compassion is a powerful word that describes an intense feeling of commiseration and a desire to help those struck by misfortune. Most people know intuitively how and when to offer compassion to relieve another person's suffering. In health care, compassion is a constant; it cannot be rationed because emergency nurses have limited time or resources to manage increasing demands.
Variation of fundamental constants
Flambaum, V V
2006-01-01
We present a review of recent works devoted to the variation of the fine structure constant alpha, strong interaction and fundamental masses. There are some hints for the variation in quasar absorption spectra, Big Bang nucleosynthesis, and Oklo natural nuclear reactor data. A very promising method to search for the variation of the fundamental constants consists in comparison of different atomic clocks. Huge enhancement of the variation effects happens in transition between accidentally degenerate atomic and molecular energy levels. A new idea is to build a ``nuclear'' clock based on the ultraviolet transition between very low excited state and ground state in Thorium nucleus. This may allow to improve sensitivity to the variation up to 10 orders of magnitude! Huge enhancement of the variation effects is also possible in cold atomic and molecular collisions near Feschbach resonance.
Sorensen, E
1940-01-01
The conventional axial blowers operate on the high-pressure principle. One drawback of this type of blower is the relatively low pressure head, which one attempts to overcome with axial blowers producing very high pressure at a given circumferential speed. The Schicht constant-pressure blower affords pressure ratios considerably higher than those of axial blowers of conventional design with approximately the same efficiency.
String Scale Cosmological Constant
Chalmers, Gordon
2006-01-01
The cosmological constant is an unexplained until now phenomena of nature that requires an explanation through string effects. The apparent discrepancy between theory and experiment is enourmous and has already been explained several times by the author including mechanisms. In this work the string theory theory of abolished string modes is documented and given perturbatively to all loop orders. The holographic underpinning is also exposed. The matching with the data of the LIGO and D0 experi...
Jackson, Neal
2015-01-01
I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. There are two broad categories of measurements. The first uses individual astrophysical objects which have some property that allows their intrinsic luminosity or size to be determined, or allows the determination of their distance by geometric means. The second category comprises the use of all-sky cosmic microwave background, or correlations between large samples of galaxies, to determine information about the geometry of the Universe and hence the Hubble constant, typically in a combination with other cosmological parameters. Many, but not all, object-based measurements give H0 values of around 72-74 km s(-1) Mpc(-1), with typical errors of 2-3 km s(-1) Mpc(-1). This is in mild discrepancy with CMB-based measurements, in particular those from the Planck satellite, which give values of 67-68 km s(-1) Mpc(-1) and typical errors of 1-2 km s(-1) Mpc(-1). The size of the remaining systematics indicate that accuracy rather than precision is the remaining problem in a good determination of the Hubble constant. Whether a discrepancy exists, and whether new physics is needed to resolve it, depends on details of the systematics of the object-based methods, and also on the assumptions about other cosmological parameters and which datasets are combined in the case of the all-sky methods.
Yongquan, Han
2016-10-01
The ideal gas state equation is not applicable to ordinary gas, it should be applied to the Electromagnetic ``gas'' that is applied to the radiation, the radiation should be the ultimate state of matter changes or initial state, the universe is filled with radiation. That is, the ideal gas equation of state is suitable for the Singular point and the universe. Maybe someone consider that, there is no vessel can accommodate radiation, it is because the Ordinary container is too small to accommodate, if the radius of your container is the distance that Light through an hour, would you still think it can't accommodates radiation? Modern scientific determinate that the radius of the universe now is about 1027 m, assuming that the universe is a sphere whose volume is approximately: V = 4.19 × 1081 cubic meters, the temperature radiation of the universe (cosmic microwave background radiation temperature of the universe, should be the closest the average temperature of the universe) T = 3.15k, radiation pressure P = 5 × 10-6 N / m 2, according to the law of ideal gas state equation, PV / T = constant = 6 × 1075, the value of this constant is the universe, The singular point should also equal to the constant Author: hanyongquan
Gulledge, Jay; Hrywna, Yarek; Cavanaugh, Colleen; Steudler, Paul A
2004-09-01
To determine whether repeated, long-term NH(4) (+) fertilization alters the enzymatic function of the atmospheric CH(4) oxidizer community in soil, we examined CH(4) uptake kinetics in temperate pine and hardwood forest soils amended with 150 kg N ha(-1) y(-1) as NH(4)NO(3) for more than a decade. The highest rates of atmospheric CH(4) consumption occurred in the upper 5 cm mineral soil of the control plots. In contrast to the results of several previous studies, surface organic soils in the control plots also exhibited high consumption rates. Fertilization decreased in situ CH(4) consumption in the pine and hardwood sites relative to the control plots by 86% and 49%, respectively. Fertilization increased net N mineralization and relative nitrification rates and decreased CH(4) uptake most dramatically in the organic horizon, which contributed substantially to the overall decrease in field flux rates. In all cases, CH(4) oxidation followed Michaelis-Menten kinetics, with apparent K(m) (K(m(app))) values typical of high-affinity soil CH(4) oxidizers. Both K(m(app)) and V(max(app)) were significantly lower in fertilized soils than in unfertilized soils. The physiology of the methane consumer community in the fertilized soils was distinct from short-term responses to NH(4) (+) addition. Whereas the immediate response to NH(4) (+) was an increase in K(m(app)), resulting from apparent enzymatic substrate competition, the long-term response to fertilization was a community-level shift to a lower K(m(app)), a possible adaptation to diminish the competitiveness of NH(4) (+) for enzyme active sites.
Neal Jackson
2015-09-01
Full Text Available I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. There are two broad categories of measurements. The first uses individual astrophysical objects which have some property that allows their intrinsic luminosity or size to be determined, or allows the determination of their distance by geometric means. The second category comprises the use of all-sky cosmic microwave background, or correlations between large samples of galaxies, to determine information about the geometry of the Universe and hence the Hubble constant, typically in a combination with other cosmological parameters. Many, but not all, object-based measurements give H_0 values of around 72–74 km s^–1 Mpc^–1, with typical errors of 2–3 km s^–1 Mpc^–1. This is in mild discrepancy with CMB-based measurements, in particular those from the Planck satellite, which give values of 67–68 km s^–1 Mpc^–1 and typical errors of 1–2 km s^–1 Mpc^–1. The size of the remaining systematics indicate that accuracy rather than precision is the remaining problem in a good determination of the Hubble constant. Whether a discrepancy exists, and whether new physics is needed to resolve it, depends on details of the systematics of the object-based methods, and also on the assumptions about other cosmological parameters and which datasets are combined in the case of the all-sky methods.
Wolf, Joseph A
2010-01-01
This book is the sixth edition of the classic Spaces of Constant Curvature, first published in 1967, with the previous (fifth) edition published in 1984. It illustrates the high degree of interplay between group theory and geometry. The reader will benefit from the very concise treatments of riemannian and pseudo-riemannian manifolds and their curvatures, of the representation theory of finite groups, and of indications of recent progress in discrete subgroups of Lie groups. Part I is a brief introduction to differentiable manifolds, covering spaces, and riemannian and pseudo-riemannian geomet
Jackson Neal
2007-09-01
Full Text Available I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. In the last 20 years, much progress has been made and estimates now range between 60 and 75 km s^-1 Mpc^-1, with most now between 70 and 75 km s^-1 Mpc^-1, a huge improvement over the factor-of-2 uncertainty which used to prevail. Further improvements which gave a generally agreed margin of error of a few percent rather than the current 10% would be vital input to much other interesting cosmology. There are several programmes which are likely to lead us to this point in the next 10 years.
Beiu, V.
1997-04-01
In this paper the authors discuss several complexity aspects pertaining to neural networks, commonly known as the curse of dimensionality. The focus will be on: (1) size complexity and depth-size tradeoffs; (2) complexity of learning; and (3) precision and limited interconnectivity. Results have been obtained for each of these problems when dealt with separately, but few things are known as to the links among them. They start by presenting known results and try to establish connections between them. These show that they are facing very difficult problems--exponential growth in either space (i.e. precision and size) and/or time (i.e., learning and depth)--when resorting to neural networks for solving general problems. The paper will present a solution for lowering some constants, by playing on the depth-size tradeoff.
Constant Proportion Portfolio Insurance
Jessen, Cathrine
2014-01-01
Portfolio insurance, as practiced in 1987, consisted of trading between an underlying stock portfolio and cash, using option theory to place a floor on the value of the position, as if it included a protective put. Constant Proportion Portfolio Insurance (CPPI) is an option-free variation...... on the theme, originally proposed by Fischer Black. In CPPI, a financial institution guarantees a floor value for the “insured” portfolio and adjusts the stock/bond mix to produce a leveraged exposure to the risky assets, which depends on how far the portfolio value is above the floor. Plain-vanilla portfolio...... insurance largely died with the crash of 1987, but CPPI is still going strong. In the frictionless markets of finance theory, the issuer’s strategy to hedge its liability under the contract is clear, but in the real world with transactions costs and stochastic jump risk, the optimal strategy is less obvious...
Decay constants in geochronology
IgorM.Villa; PaulR.Renne
2005-01-01
Geologic time is fundamental to the Earth Sciences, and progress in many disciplines depends critically on our ability to measure time with increasing accuracy and precision. Isotopic geochronology makes use of the decay of radioactive nuclides as a help to quantify the histories of rock, minerals, and other materials. Both accuracy and precision of radioisotopic ages are, at present, limited by those of radioactive decay constants. Modem mass spectrometers can measure isotope ratios with a precision of 10-4 or better. On the other hand, the uncertainties associated with direct half-life determinations are, in most cases, still at the percent level. The present short note briefly summarizes progress and problems that have been encountered during the Working Group's activity.
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.
Effect in vitro of propoxur on kinetics of K+ stimulated PNPPase and protection by thiol reagents.
Babu, G R; Reddy, G R; Rajendra, W; Chetty, C S
1990-09-01
Kinetics analysis of K+ stimulated PNPPase was studied in the rat brain synaptosomes in the presence of propoxur. Non-competitive inhibition with respect to activation by PNPP was seen by the decreased maximal velocity (Vmax) without change in Michaelis-Menten Constant (Km). Activation energy values (delta E) were increased suggesting the decreased catalytic potential of the enzyme. It is also observed that dithiothrietol (DTT) (76 microM), cysteine (82 microM) and glutathione (120 microM) neutralized the inhibition of K(+)-PNPPase by propoxur to different extents.
Sushovan Chatterjee; Dipti Yadav; Lepakshi Barbora; Pinakeswar Mahanta; Pranab Goswami
2014-01-01
Biodiesel from sunflower oil using lipase chemically immobilized on silk-cocoon matrix in a packed-bed bioreactor was investigated. The immobilization was demonstrated by field-emission scanning electron microscopy and activity study. The lipase loading was 738.74 U (~0.01 g lipase powder)/g-lipase-immobilized matrix. The Km (Michaelis-Menten constant) of the free and the immobilized lipase was 451.26 μM and 257.26 μM, respectively. Low Km value of the immobilized lipase is attributed to the ...
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.
Characterization of CIM monoliths as enzyme reactors.
Vodopivec, Martina; Podgornik, Ales; Berovic, Marin; Strancar, Ales
2003-09-25
The immobilization of the enzymes citrate lyase, malate dehydrogenase, isocitrate dehydrogenase and lactate dehydrogenase to CIM monolithic supports was performed. The long-term stability, reproducibility, and linear response range of the immobilized enzyme reactors were investigated along with the determination of the kinetic behavior of the enzymes immobilized on the CIM monoliths. The Michaelis-Menten constant K(m) and the turnover number k(3) of the immobilized enzymes were found to be flow-unaffected. Furthermore, the K(m) values of the soluble and immobilized enzyme were found to be comparable. Both facts indicate the absence of a diffusional limitation in immobilized CIM enzyme reactors.
Yankov, D. ; Dobreva, E. ; Beschkov, V. ; Emanuilova, E
Study of optimum conditions and kinetics of starch hydrolysis by means of thermostable ed -amylase.
1986-11-01
The optimum conditions of starch hydrolysis, catalysed by a thermostable ..cap alpha..-amylase (EC 3.2.1.1) produced by the strain Bacillus licheniformis (MB 80) were determined. The kinetic constants in the Michaelis-Menten equation were determined in terms of substrate concentration and dextrose equivalent of the product. It was found that the enzyme action was inhibited by substrate at high concentrations and also by glucose. The enzyme studied is capable of use at an enhanced temperature of 100 degrees C thus enabling higher dextrose equivalents to be obtained than are possible with other less thermostable amylases restricted to temperatures no greater than 95 degrees C. 17 references.
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.
Purification and characterization of two glutathione S-aryltransferase activities from rat liver.
Askelöf, P; Guthenberg, C; Jakobson, I; Mannervik, B
1975-01-01
Two forms of glutathione S-aryltransferase were purified from rat liver. The only differences noted between the two forms were in the chromatographic and electrophoretic properties, which permitted the separation of the two species. The molecular weights of the enzyme and its subunits were estimated as about 50000 and 23000 respectively. The steady-state kinetics did no follow Michaelis-Menten kinetics when one substrate concentration was kept constant while the second substrate concentration was varied. Several S-substituted GSH derivatives were tested as inhibitors of the enzymic reaction. The enzyme was inactivated by thiol-group reagents. PMID:810139
Takayanagi, Toshiaki
2013-12-01
The basic model for chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection during therapy enables us to analyze short-term viral kinetics. However, the model is not useful for analyzing long-term viral kinetics. Here, I suggest a new model that was obtained by introducing Michaelis-Menten kinetics into the basic model. The new model can exhibit long-term viral kinetics without rebound and oscillation, unlike the basic model. The value of the parameter K in the new model is analogous to the Michaelis constant Km and is predicted to be approximately less than 10(10)/ml.
The Interacting and Non-constant Cosmological Constant
Verma, Murli Manohar
2009-01-01
We propose a time-varying cosmological constant with a fixed equation of state, which evolves mainly through its interaction with the background during most of the long history of the universe. However, such interaction does not exist in the very early and the late-time universe and produces the acceleration during these eras when it becomes very nearly a constant. It is found that after the initial inflationary phase, the cosmological constant, that we call as lambda parameter, rolls down from a large constant value to another but very small constant value and further dominates the present epoch showing up in form of the dark energy driving the acceleration.
Quantum Theory without Planck's Constant
Ralston, John P
2012-01-01
Planck's constant was introduced as a fundamental scale in the early history of quantum mechanics. We find a modern approach where Planck's constant is absent: it is unobservable except as a constant of human convention. Despite long reference to experiment, review shows that Planck's constant cannot be obtained from the data of Ryberg, Davisson and Germer, Compton, or that used by Planck himself. In the new approach Planck's constant is tied to macroscopic conventions of Newtonian origin, which are dispensable. The precision of other fundamental constants is substantially improved by eliminating Planck's constant. The electron mass is determined about 67 times more precisely, and the unit of electric charge determined 139 times more precisely. Improvement in the experimental value of the fine structure constant allows new types of experiment to be compared towards finding "new physics." The long-standing goal of eliminating reliance on the artifact known as the International Prototype Kilogram can be accompl...
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
Bormashenko Edward
2009-01-01
Full Text Available The status of fundamental physical constants is discussed. The nature of fundamental physical constants is cleared up, based on the analysis of the Boltzmann constant. A new definition of measurable values, 'mathematical' and 'physical' numbers and fundamental physical constants is proposed. Mathematical numbers are defined as values insensitive to the choice of both units and frames of reference, whereas 'physical numbers' are dimensionless values, insensitive to transformations of units and sensitive to the transformations of the frames of reference. Fundamental constants are classified as values sensitive to transformations of the units and insensitive to transformations of the frames of reference. It is supposed that a fundamental physical constant necessarily allows diminishing the number of independent etalons in a system of units.
Spectrophotometric determination of association constant
2016-01-01
Least-squares 'Systematic Trial-and-Error Procedure' (STEP) for spectrophotometric evaluation of association constant (equilibrium constant) K and molar absorption coefficient E for a 1:1 molecular complex, A + B = C, with error analysis according to Conrow et al. (1964). An analysis of the Charg...
Constant-Pressure Hydraulic Pump
Galloway, C. W.
1982-01-01
Constant output pressure in gas-driven hydraulic pump would be assured in new design for gas-to-hydraulic power converter. With a force-multiplying ring attached to gas piston, expanding gas would apply constant force on hydraulic piston even though gas pressure drops. As a result, pressure of hydraulic fluid remains steady, and power output of the pump does not vary.
Spectrophotometric determination of association constant
Spanget-Larsen, Jens
2016-01-01
Least-squares 'Systematic Trial-and-Error Procedure' (STEP) for spectrophotometric evaluation of association constant (equilibrium constant) K and molar absorption coefficient E for a 1:1 molecular complex, A + B = C, with error analysis according to Conrow et al. (1964). An analysis of the Charge...
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.
DETERMINATION OF STABILITY CONSTANTS OF MANGANESE (II ...
DR. AMINU
Keywords: Amino acids, dissociation constant, potentiometry, stability constant. INTRODUCTION ... constants of manganese (II) amino acid complexes using potentiometer. .... Principles of Biochemistry Third Edition,. Worth publishers, 41 ...
Varying constants, Gravitation and Cosmology
Uzan, Jean-Philippe
2010-01-01
Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. It is thus of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We thus detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describ...
Ruzsa's Constant on Additive Functions
Jin Hui FANG; Yong Gao CHEN
2013-01-01
A function f:N → R is called additive if f(mn) =f(m)+f(n) for all m,n with (m,n) =1.Let μ(x) =maxn≤x(f(n)-f(n + 1)) and v(x) =maxn≤x(f(n + 1)-f(n)).In 1979,Ruzsa proved that there exists a constant c such that for any additive function f,μ(x) ≤ cv(x2) + cf,where cf is a constant depending only on f.Denote by Raf the least such constant c.We call Raf Ruzsa's constant on additive functions.In this paper,we prove that Raf ≤ 20.
Naturally Time Dependent Cosmological Constant
Gregori, A
2004-01-01
In the light of the proposal of hep-th/0207195, we discuss in detail the issue of the cosmological constant, explaining how can string theory naturally predict the value which is experimentally observed, without low-energy supersymmetry.
Inflation and the cosmological constant
FENG Chaojun
2014-08-01
Full Text Available By assuming the cosmological “constant” is no longer a constant during the inflation epoch,it is found that the cosmological constant fine-tuning problem is solved.In the meanwhile,inflation models could predict a large tensor-to-scalar ratio,correct power spectral index and a larger running of it.Furthermore,the e-folding number is large enough to overcome the horizon,flatness problems in the Big Bang cosmology.
Varying Constants, Gravitation and Cosmology
Jean-Philippe Uzan
2011-03-01
Full Text Available Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. Thus, it is of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, solar system observations, meteorite dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.
Varying Constants, Gravitation and Cosmology.
Uzan, Jean-Philippe
2011-01-01
Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. Thus, it is of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, solar system observations, meteorite dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.
Varying Constants, Gravitation and Cosmology
Uzan, Jean-Philippe
2011-12-01
Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. Thus, it is of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, solar system observations, meteorite dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.
ZnO nanowire-based glucose biosensors with different coupling agents
Jung, Juneui [Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lim, Sangwoo, E-mail: swlim@yonsei.ac.kr [Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)
2013-01-15
Highlights: Black-Right-Pointing-Pointer Fabrication of ZnO nanowire-based glucose biosensors using different coupling agents. Black-Right-Pointing-Pointer Highest sensitivity for (3-aminopropyl)methyldiethoxysilane-treated biosensor. Black-Right-Pointing-Pointer Larger amount of glucose oxidase and lower electron transfer resistance for (3-aminopropyl)methyldiethoxysilane-treated biosensor. - Abstract: ZnO-nanowire-based glucose biosensors were fabricated by immobilizing glucose oxidase (GOx) onto a linker attached to ZnO nanowires. Different coupling agents were used, namely (3-aminopropyl)trimethoxysilane (APTMS), (3-aminopropyl)triethoxysilane (APTES), and (3-aminopropyl)methyldiethoxysilane (APS), to increase the affinity of GOx binding to ZnO nanowires. The amount of GOx immobilized on the ZnO nanowires, the performance, sensitivity, and Michaelis-Menten constant of each biosensor, and the electron transfer resistance through the biosensor were all measured in order to investigate the effect of the coupling agent on the ZnO nanowire-based biosensor. Among the different biosensors, the APS-treated biosensor had the highest sensitivity (17.72 {mu}A cm{sup -2} mM{sup -1}) and the lowest Michaelis-Menten constant (1.37 mM). Since APS-treated ZnO nanowires showed the largest number of C-N groups and the lowest electron transfer resistance through the biosensor, we concluded that these properties were the key factors in the performance of APS-treated glucose biosensors.
Kinetics of trypsin-catalyzed hydrolysis determined by isothermal titration calorimetry.
Maximova, Ksenia; Trylska, Joanna
2015-10-01
Isothermal titration calorimetry (ITC) was applied to determine enzymatic activity and inhibition. We measured the Michaelis-Menten kinetics for trypsin-catalyzed hydrolysis of two substrates, casein (an insoluble macromolecule substrate) and Nα-benzoyl-dl-arginine β-naphthylamide (a small substrate), and estimated the thermodynamic parameters in the temperature range from 20 to 37°C. The inhibitory activities of reversible (small molecule benzamidine) and irreversible (small molecule phenylmethanesulfonyl fluoride and macromolecule α1-antitrypsin) inhibitors of trypsin were also determined. We showed the usefulness of ITC for fast and direct measurement of inhibition constants and half-maximal inhibitory concentrations and for predictions of the mechanism of inhibition. ITC kinetic assays could be an easy and straightforward way to estimate Michaelis-Menten constants and the effectiveness of inhibitors as well as to predict the inhibition mechanism. ITC efficiency was found to be similar to that of classical spectrophotometric enzymatic assays. Copyright © 2015 Elsevier Inc. All rights reserved.
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.
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.
A new multi-wavelength model-based method for determination of enzyme kinetic parameters.
Sorouraddin, Mohammad-Hossein; Amini, Kaveh; Naseri, Abdolhossein; Vallipour, Javad; Hanaee, Jalal; Rashidi, Mohammad-Reza
2010-09-01
Lineweaver-Burk plot analysis is the most widely used method to determine enzyme kinetic parameters. In the spectrophotometric determination of enzyme activity using the Lineweaver-Burk plot, it is necessary to find a wavelength at which only the substrate or the product has absorbance without any spectroscopic interference of the other reaction components. Moreover, in this method, different initial concentrations of the substrate should be used to obtain the initial velocities required for Lineweaver-Burk plot analysis. In the present work, a multi-wavelength model-based method has been developed and validated to determine Michaelis-Menten constants for some enzyme reactions. In this method, a selective wavelength region and several experiments with different initial concentrations of the substrate are not required. The absorbance data of the kinetic assays are fitted by non-linear regression coupled to the numeric integration of the related differential equation. To indicate the applicability of the proposed method, the Michaelis-Menten constants for the oxidation of phenanthridine, 6-deoxypenciclovir and xanthine by molybdenum hydroxylases were determined using only a single initial concentration of the substrate, regardless of any spectral overlap.
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.
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
Learning Read-constant Polynomials of Constant Degree modulo Composites
Chattopadhyay, Arkadev; Gavaldá, Richard; Hansen, Kristoffer Arnsfelt;
2011-01-01
Boolean functions that have constant degree polynomial representation over a fixed finite ring form a natural and strict subclass of the complexity class \\textACC0ACC0. They are also precisely the functions computable efficiently by programs over fixed and finite nilpotent groups. This class...... is not known to be learnable in any reasonable learning model. In this paper, we provide a deterministic polynomial time algorithm for learning Boolean functions represented by polynomials of constant degree over arbitrary finite rings from membership queries, with the additional constraint that each variable...
Effective cosmological constant induced by stochastic fluctuations of Newton's constant
de Cesare, Marco; Lizzi, Fedele; Sakellariadou, Mairi
2016-09-01
We consider implications of the microscopic dynamics of spacetime for the evolution of cosmological models. We argue that quantum geometry effects may lead to stochastic fluctuations of the gravitational constant, which is thus considered as a macroscopic effective dynamical quantity. Consistency with Riemannian geometry entails the presence of a time-dependent dark energy term in the modified field equations, which can be expressed in terms of the dynamical gravitational constant. We suggest that the late-time accelerated expansion of the Universe may be ascribed to quantum fluctuations in the geometry of spacetime rather than the vacuum energy from the matter sector.
Effective cosmological constant induced by stochastic fluctuations of Newton's constant
de Cesare, Marco; Sakellariadou, Mairi
2016-01-01
We consider implications of the microscopic dynamics of spacetime for the evolution of cosmological models. We argue that quantum geometry effects may lead to stochastic fluctuations of the gravitational constant, which is thus considered as a macroscopic effective dynamical quantity. Consistency with Riemannian geometry entails the presence of a time-dependent dark energy term in the modified field equations, which can be expressed in terms of the dynamical gravitational constant. We suggest that the late-time accelerated expansion of the Universe may be ascribed to quantum fluctuations in the geometry of spacetime rather than the vacuum energy from the matter sector.
Nez, F
2005-06-15
This document reviews the theoretical and experimental achievements of the author since the beginning of his scientific career. This document is dedicated to the spectroscopy of hydrogen, deuterium and helium atoms. The first part is divided into 6 sub-sections: 1) the principles of hydrogen spectroscopy, 2) the measurement of the 2S-nS/nD transitions, 3) other optical frequency measurements, 4) our contribution to the determination of the Rydberg constant, 5) our current experiment on the 1S-3S transition, 6) the spectroscopy of the muonic hydrogen. Our experiments have improved the accuracy of the Rydberg Constant by a factor 25 in 15 years and we have achieved the first absolute optical frequency measurement of a transition in hydrogen. The second part is dedicated to the measurement of the fine structure constant and the last part deals with helium spectroscopy and the search for optical references in the near infrared range. (A.C.)
Mirror QCD and Cosmological Constant
Pasechnik, Roman; Teryaev, Oleg
2016-01-01
An analog of Quantum Chromo Dynamics (QCD) sector known as mirror QCD (mQCD) can affect the cosmological evolution and help in resolving the Cosmological Constant problem. In this work, we explore an intriguing possibility for a compensation of the negative QCD vacuum contribution to the ground state energy density of the universe by means of a positive contribution from the chromomagnetic gluon condensate in mQCD. The trace anomaly compensation condition and the form of the mQCD coupling constant in the infrared limit have been proposed by analysing a partial non-perturbative solution of the Einstein--Yang-Mills equations of motion.
Spatial Variations of Fundamental Constants
Barrow, John D; Barrow, John D.; Toole, Chris O'
1999-01-01
We show that observational limits on the possible time variation of constants of Nature are significantly affected by allowing for both space and time variation. Bekenstein's generalisation of Maxwell's equations to allow for cosmological variation of $alpha$ is investigated in a universe containing spherically symmetric inhomogeneities. The time variation of $alpha$ is determined by the local matter density and hence limits obtained in high-density geophysical enviroments are far more constraining than those obtained at high redshift. This new feature is expected to be a property of a wide class of theories for the variation of constants.
Bouncing universes with varying constants
Barrow, John D [DAMTP, Centre for Mathematical Sciences, Cambridge University, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Kimberly, Dagny [Theoretical Physics, Blackett Laboratory, Imperial College, Prince Consort Road, London SW7 2BZ (United Kingdom); Magueijo, Joao [Theoretical Physics, Blackett Laboratory, Imperial College, Prince Consort Road, London SW7 2BZ (United Kingdom)
2004-09-21
We investigate the behaviour of exact closed bouncing Friedmann universes in theories with varying constants. We show that the simplest BSBM varying alpha theory leads to a bouncing universe. The value of alpha increases monotonically, remaining approximately constant during most of each cycle, but increasing significantly around each bounce. When dissipation is introduced we show that in each new cycle the universe expands for longer and to a larger size. We find a similar effect for closed bouncing universes in Brans-Dicke theory, where G also varies monotonically in time from cycle to cycle. Similar behaviour occurs also in varying speed of light theories.
Bouncing Universes with Varying Constants
Barrow, J D; Magueijo, J; Barrow, John D.; Kimberly, Dagny; Magueijo, Joao
2004-01-01
We investigate the behaviour of exact closed bouncing Friedmann universes in theories with varying constants. We show that the simplest BSBM varying-alpha theory leads to a bouncing universe. The value of alpha increases monotonically, remaining approximately constant during most of each cycle, but increasing significantly around each bounce. When dissipation is introduced we show that in each new cycle the universe expands for longer and to a larger size. We find a similar effect for closed bouncing universes in Brans-Dicke theory, where $G$ also varies monotonically in time from cycle to cycle. Similar behaviour occurs also in varying speed of light theories.
Gravitational Instantons and Cosmological Constant
Cyriac, Josily
2015-01-01
The cosmological dynamics of an otherwise empty universe in the presence of vacuum fields is considered. Quantum fluctuations at the Planck scale leads to a dynamical topology of space-time at very small length scales, which is dominated by compact gravitational instantons. The Planck scale vacuum energy acts as a source for the curvature of the these compact gravitational instantons and decouples from the large scale energy momentum tensor of the universe, thus making the observable cosmological constant vanish. However, a Euclidean functional integral over all possible topologies of the gravitational instantons generates a small non-zero value for the large scale cosmological constant, which agrees with the present observations.
Decay Constants of Vector Mesons
LI Heng-Mei; WAN Shao-Long
2008-01-01
@@ The light vector mesons are studied within the framework of the Bethe-Salpeter equation with the vector-vectortype flat-bottom potential The Bethe-Salpeter wavefunctions and the decay constants of the vector mesons are obtained. All the obtained results, fρ, fφ, and fΚ* , are in agreement with the experimental values, respectively.
The 1% concordance Hubble constant
Bennett, C. L.; Larson, D.; Weiland, J. L. [Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States); Hinshaw, G., E-mail: cbennett@jhu.edu [Department of Physics and Astronomy, University of British Columbia, Vancouver, BC V6T 1Z1 (Canada)
2014-10-20
The determination of the Hubble constant has been a central goal in observational astrophysics for nearly a hundred years. Extraordinary progress has occurred in recent years on two fronts: the cosmic distance ladder measurements at low redshift and cosmic microwave background (CMB) measurements at high redshift. The CMB is used to predict the current expansion rate through a best-fit cosmological model. Complementary progress has been made with baryon acoustic oscillation (BAO) measurements at relatively low redshifts. While BAO data do not independently determine a Hubble constant, they are important for constraints on possible solutions and checks on cosmic consistency. A precise determination of the Hubble constant is of great value, but it is more important to compare the high and low redshift measurements to test our cosmological model. Significant tension would suggest either uncertainties not accounted for in the experimental estimates or the discovery of new physics beyond the standard model of cosmology. In this paper we examine in detail the tension between the CMB, BAO, and cosmic distance ladder data sets. We find that these measurements are consistent within reasonable statistical expectations and we combine them to determine a best-fit Hubble constant of 69.6 ± 0.7 km s{sup –1} Mpc{sup –1}. This value is based upon WMAP9+SPT+ACT+6dFGS+BOSS/DR11+H {sub 0}/Riess; we explore alternate data combinations in the text. The combined data constrain the Hubble constant to 1%, with no compelling evidence for new physics.
Variation of fundamental constants: theory
Flambaum, Victor
2008-05-01
Theories unifying gravity with other interactions suggest temporal and spatial variation of the fundamental ``constants'' in expanding Universe. There are some hints for the variation of different fundamental constants in quasar absorption spectra and Big Bang nucleosynthesis data. A large number of publications (including atomic clocks) report limits on the variations. We want to study the variation of the main dimensionless parameters of the Standard Model: 1. Fine structure constant alpha (combination of speed of light, electron charge and Plank constant). 2. Ratio of the strong interaction scale (LambdaQCD) to a fundamental mass like electron mass or quark mass which are proportional to Higgs vacuum expectation value. The proton mass is propotional to LambdaQCD, therefore, the proton-to-electron mass ratio comes into this second category. We performed necessary atomic, nuclear and QCD calculations needed to study variation of the fundamental constants using the Big Bang Nucleosynthsis, quasar spectra, Oklo natural nuclear reactor and atomic clock data. The relative effects of the variation may be enhanced in transitions between narrow close levels in atoms, molecules and nuclei. If one will study an enhanced effect, the relative value of systematic effects (which are not enhanced) may be much smaller. Note also that the absolute magnitude of the variation effects in nuclei (e.g. in very narrow 7 eV transition in 229Th) may be 5 orders of magnitude larger than in atoms. A different possibility of enhancement comes from the inversion transitions in molecules where splitting between the levels is due to the quantum tunneling amplitude which has strong, exponential dependence on the electron to proton mass ratio. Our study of NH3 quasar spectra has already given the best limit on the variation of electron to proton mass ratio.
Varying Fine-Structure Constant and the Cosmological Constant Problem
Fujii, Y
2003-01-01
We start with a brief account of the latest analysis of the Oklo phenomenon providing the still most stringent constraint on time-variability of the fine- structure constant $\\alpha$. Comparing this with the recent result from the measurement of distant QSO's appears to indicate a non-uniform time-dependence, which we argue to be related to another recent finding of the accelerating universe. This view is implemented in terms of the scalar-tensor theory, applied specifically to the small but nonzero cosmological constant. Our detailed calculation shows that these two phenomena can be understood in terms of a common origin, a particular behavior of the scalar field, dilaton. We also sketch how this theoretical approach makes it appropriate to revisit non- Newtonian gravity featuring small violation of Weak Equivalence Principle at medium distances.
Varying Fine-Structure Constant and the Cosmological Constant Problem
Fujii, Yasunori
We start with a brief account of the latest analysis of the Oklo phenomenon providing the still most stringent constraint on time variability of the fine-structure constant α. Comparing this with the recent result from the measurement of distant QSO's appears to indicate a non-uniform time-dependence, which we argue to be related to another recent finding of the accelerating universe. This view is implemented in terms of the scalar-tensor theory, applied specifically to the small but nonzero cosmological constant. Our detailed calculation shows that these two phenomena can be understood in terms of a common origin, a particular behavior of the scalar field, dilaton. We also sketch how this theoretical approach makes it appropriate to revisit non-Newtonian gravity featuring small violation of Weak Equivalence Principle at medium distances.
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.
Miyamoto, Hirotaka; Matsueda, Satoshi; Moritsuka, Akihiro; Shimokawa, Kenta; Hirata, Haruna; Nakashima, Mikiro; Sasaki, Hitoshi; Fumoto, Shintaro; Nishida, Koyo
2015-10-01
The effect of hypothermia on the in vivo pharmacokinetics of midazolam was evaluated, with a focus on altered metabolism in the liver and binding to serum proteins. Rat primary hepatocytes were incubated with midazolam (which is metabolized mainly by CYP3A2) at 37, 32 or 28 °C. The Michaelis-Menten constant (Km) and maximum velocity (Vmax) of midazolam were estimated using the Michaelis-Menten equation. The Km of CYP3A2 midazolam remained unchanged, but the Vmax decreased at 28 °C. In rats, whose temperature was maintained at 37, 32 or 28 °C by a heat lamp or ice pack, the plasma concentrations of midazolam were higher, whereas those in the brain and liver were unchanged at 28 °C. The tissue/plasma concentration ratios were, however, increased significantly. The unbound fraction of midazolam in serum at 28 °C was half that at 37 °C. These pharmacokinetic changes associated with hypothermic conditions were due to reductions in CYP3A2 activity and protein binding.
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.
Nesakumar, Noel; Ramachandra, Bhat Lakshmishri; Sethuraman, Swaminathan; Krishnan, Uma Maheswari; Rayappan, John Bosco Balaguru
2016-02-01
A novel bio-analytical method has been devised based on the change in catalytic activity of acetylcholinesterase (AChE) enzyme induced by captan, carbosulfan, 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and pentachlorophenol (PCP) for the investigation of inhibition efficiency and sensitivity using Pt/ZnO/AChE/Chitosan bioelectrode. The inhibition curves of captan, carbosulfan, TCDD and PCP were similar to Michaelis-Menten curve. TCDD held the minimum inhibitor Michaelis-Menten constant ([Formula: see text]) value (10.2 nM) in comparison with PCP (10.9 nM), carbosulfan (14.5 nM) and captan (7.9 × 10(3) nM). The maximum inhibition of AChE enzyme by captan was about 100 %, which was much higher than that of TCDD (72.7 %), PCP (68.1 %) and carbosulfan (47.7 %). The calculated theoretical sensitivity was in the order of TCDD > PCP > carbosulfan > captan. Comparing with TCDD (35.3 %), PCP (47.8 %) and carbosulfan (20.9 %), only the inhibition efficiency of captan (55.0 %) was the maximum. The developed bioelectrode exhibited high recovery and low relative standard deviation in local tap water samples.
A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics.
Saaby, Lasse; Brodin, Birger
2017-09-01
Transport proteins expressed in the different barriers of the human body can have great implications on absorption, distribution, and excretion of drug compounds. Inhibition or saturation of a transporter can potentially alter these absorbtion, distribution, metabolism and elimination properties and thereby also the pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P-gp, ABCB1) is an efflux transporter which is present in most of the barriers of the body, including the small intestine, the blood-brain barrier, the liver, and the kidney. In all these tissues, P-gp may mediate efflux of drug compounds and may also be a potential site for drug-drug interactions. Consequently, there is a need to be able to predict the saturation and inhibition of P-gp and other transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis has been applied to estimate kinetic parameters, such as Km and Vmax, for carrier-mediated transport, whereas half-maximal inhibitor concentration (IC50) and the disassociation constant for an inhibitor/P-gp complex (Ki) have been determined to estimate P-gp inhibition. This review addresses in vitro methods commonly used to study P-gp transport kinetics and aims at providing a critical evaluation of the application of steady-state Michaelis-Menten analysis of kinetic parameters for substrate/P-gp interactions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Urmeela Taukoorah
2016-01-01
Full Text Available Aloe vera gel (AVG is traditionally used in the management of diabetes, obesity, and infectious diseases. The present study aimed to investigate the inhibitory potential of AVG against α-amylase, α-glucosidase, and pancreatic lipase activity in vitro. Enzyme kinetic studies using Michaelis-Menten (Km and Lineweaver-Burk equations were used to establish the type of inhibition. The antioxidant capacity of AVG was evaluated for its ferric reducing power, 2-diphenyl-2-picrylhydrazyl hydrate scavenging ability, nitric oxide scavenging power, and xanthine oxidase inhibitory activity. The glucose entrapment ability, antimicrobial activity, and total phenolic, flavonoid, tannin, and anthocyanin content were also determined. AVG showed a significantly higher percentage inhibition (85.56±0.91 of pancreatic lipase compared to Orlistat. AVG was found to increase the Michaelis-Menten constant and decreased the maximal velocity (Vmax of lipase, indicating mixed inhibition. AVG considerably inhibits glucose movement across dialysis tubes and was comparable to Arabic gum. AVG was ineffective against the tested microorganisms. Total phenolic and flavonoid contents were 66.06±1.14 (GAE/mg and 60.95±0.97 (RE/mg, respectively. AVG also showed interesting antioxidant properties. The biological activity observed in this study tends to validate some of the traditional claims of AVG as a functional food.
Use of CdSe/ZnS luminescent quantum dots incorporated within sol-gel matrix for urea detection
Duong, Hong Dinh [School of Applied Chemical Engineering, Research Center for Biophotonics, Chonnam National University, Yong-Bong dong 300, 500-757 Gwangju (Korea, Republic of); Rhee, Jong Il [School of Applied Chemical Engineering, Research Center for Biophotonics, Chonnam National University, Yong-Bong dong 300, 500-757 Gwangju (Korea, Republic of)], E-mail: jirhee@chonnam.ac.kr
2008-09-19
In this work, urea detection techniques based on the pH sensitivity of CdSe/ZnS QDs were developed using three types of sol-gel membranes: a QD-entrapped membrane, urease-immobilized membrane and double layer consisting of a QD-entrapped membrane and urease-immobilized membrane. The surface morphology of the sol-gel membranes deposited on the wells in a 24-well microtiter plate was investigated. The linear detection range of urea was in the range of 0-10 mM with the three types of sol-gel membranes. The urea detection technique based on the double layer consisting of the QD-entrapped membrane and urease-immobilized membrane resulted in the highest sensitivity to urea due to the Michaelis-Menten kinetic parameters. That is, the Michaelis-Menten constant (K{sub m} =2.0745 mM) of the free urease in the QD-entrapped membrane was about 4-fold higher than that (K{sub m} =0.549 mM) of the immobilized urease in the urease-immobilized membrane and about 12-fold higher than that (K{sub m} =0.1698 mM) of the immobilized urease in the double layer. The good stability of the three sol-gel membranes for urea sensing over 2 months showed that the use of sol-gel membranes immobilized with QDs or an enzyme is suitable for biomedical and environmental applications.
Taukoorah, Urmeela; Mahomoodally, M. Fawzi
2016-01-01
Aloe vera gel (AVG) is traditionally used in the management of diabetes, obesity, and infectious diseases. The present study aimed to investigate the inhibitory potential of AVG against α-amylase, α-glucosidase, and pancreatic lipase activity in vitro. Enzyme kinetic studies using Michaelis-Menten (K m) and Lineweaver-Burk equations were used to establish the type of inhibition. The antioxidant capacity of AVG was evaluated for its ferric reducing power, 2-diphenyl-2-picrylhydrazyl hydrate scavenging ability, nitric oxide scavenging power, and xanthine oxidase inhibitory activity. The glucose entrapment ability, antimicrobial activity, and total phenolic, flavonoid, tannin, and anthocyanin content were also determined. AVG showed a significantly higher percentage inhibition (85.56 ± 0.91) of pancreatic lipase compared to Orlistat. AVG was found to increase the Michaelis-Menten constant and decreased the maximal velocity (V max) of lipase, indicating mixed inhibition. AVG considerably inhibits glucose movement across dialysis tubes and was comparable to Arabic gum. AVG was ineffective against the tested microorganisms. Total phenolic and flavonoid contents were 66.06 ± 1.14 (GAE)/mg and 60.95 ± 0.97 (RE)/mg, respectively. AVG also showed interesting antioxidant properties. The biological activity observed in this study tends to validate some of the traditional claims of AVG as a functional food. PMID:26880905
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.
New Quasar Studies Keep Fundamental Physical Constant Constant
2004-03-01
Very Large Telescope sets stringent limit on possible variation of the fine-structure constant over cosmological time Summary Detecting or constraining the possible time variations of fundamental physical constants is an important step toward a complete understanding of basic physics and hence the world in which we live. A step in which astrophysics proves most useful. Previous astronomical measurements of the fine structure constant - the dimensionless number that determines the strength of interactions between charged particles and electromagnetic fields - suggested that this particular constant is increasing very slightly with time. If confirmed, this would have very profound implications for our understanding of fundamental physics. New studies, conducted using the UVES spectrograph on Kueyen, one of the 8.2-m telescopes of ESO's Very Large Telescope array at Paranal (Chile), secured new data with unprecedented quality. These data, combined with a very careful analysis, have provided the strongest astronomical constraints to date on the possible variation of the fine structure constant. They show that, contrary to previous claims, no evidence exist for assuming a time variation of this fundamental constant. PR Photo 07/04: Relative Changes with Redshift of the Fine Structure Constant (VLT/UVES) A fine constant To explain the Universe and to represent it mathematically, scientists rely on so-called fundamental constants or fixed numbers. The fundamental laws of physics, as we presently understand them, depend on about 25 such constants. Well-known examples are the gravitational constant, which defines the strength of the force acting between two bodies, such as the Earth and the Moon, and the speed of light. One of these constants is the so-called "fine structure constant", alpha = 1/137.03599958, a combination of electrical charge of the electron, the Planck constant and the speed of light. The fine structure constant describes how electromagnetic forces hold
Constant-bandwidth constant-temperature hot-wire anemometer.
Ligeza, P
2007-07-01
A constant-temperature anemometer (CTA) enables the measurement of fast-changing velocity fluctuations. In the classical solution of CTA, the transmission band is a function of flow velocity. This is a minor drawback when the mean flow velocity does not significantly change, though it might lead to dynamic errors when flow velocity varies over a considerable range. A modification is outlined, whereby an adaptive controller is incorporated in the CTA system such that the anemometer's transmission band remains constant in the function of flow velocity. For that purpose, a second feedback loop is provided, and the output signal from the anemometer will regulate the controller's parameters such that the transmission bandwidth remains constant. The mathematical model of a CTA that has been developed and model testing data allow a through evaluation of the proposed solution. A modified anemometer can be used in measurements of high-frequency variable flows in a wide range of velocities. The proposed modification allows the minimization of dynamic measurement errors.
Three pion nucleon coupling constants
Arriola, E Ruiz; Perez, R Navarro
2016-01-01
There exist four pion nucleon coupling constants, $f_{\\pi^0, pp}$, $-f_{\\pi^0, nn}$, $f_{\\pi^+, pn} /\\sqrt{2}$ and $ f_{\\pi^-, np} /\\sqrt{2}$ which coincide when up and down quark masses are identical and the electron charge is zero. While there is no reason why the pion-nucleon-nucleon coupling constants should be identical in the real world, one expects that the small differences might be pinned down from a sufficiently large number of independent and mutually consistent data. Our discussion provides a rationale for our recent determination $$f_p^2 = 0.0759(4) \\, , \\quad f_{0}^2 = 0.079(1) \\,, \\quad f_{c}^2 = 0.0763(6) \\, , $$ based on a partial wave analysis of the $3\\sigma$ self-consistent nucleon-nucleon Granada-2013 database comprising 6713 published data in the period 1950-2013.
Time-Varying Fundamental Constants
Olive, Keith
2003-04-01
Recent data from quasar absorption systems can be interpreted as arising from a time variation in the fine-structure constant. However, there are numerous cosmological, astro-physical, and terrestrial bounds on any such variation. These includes bounds from Big Bang Nucleosynthesis (from the ^4He abundance), the Oklo reactor (from the resonant neutron capture cross-section of Sm), and from meteoretic lifetimes of heavy radioactive isotopes. The bounds on the variation of the fine-structure constant are significantly strengthened in models where all gauge and Yukawa couplings vary in a dependent manner, as would be expected in unified theories. Models which are consistent with all data are severly challenged when Equivalence Principle constraints are imposed.
Why isn't the solar constant a constant?
Li, K J; Xu, J C; Gao, P X; Yang, L H; Liang, H F; Zhan, L S
2012-01-01
In order to probe the mechanism of variations of the Solar Constant on the inter-solar-cycle scale, total solar irradiance (TSI, the so-called Solar Constant) in the time interval of 7 November 1978 to 20 September 2010 is decomposed into three components through the empirical mode decomposition and time-frequency analyses. The first component is the rotation signal, counting up to 42.31% of the total variation of TSI, which is understood to be mainly caused by large magnetic structures, including sunspot groups. The second is an annual-variation signal, counting up to 15.17% of the total variation, the origin of which is not known at this point in time. Finally, the third is the inter-solar-cycle signal, counting up to 42.52%, which are inferred to be caused by the network magnetic elements in quiet regions, whose magnetic flux ranges from $(4.27-38.01)\\times10^{19}$ Mx.
Fine-structure constant: Is it really a constant?
Bekenstein, Jacob D.
1982-03-01
It is often claimed that the fine-structure "constant" α is shown to be strictly constant in time by a variety of astronomical and geophysical results. These constrain its fractional rate of change α˙α to at least some orders of magnitude below the Hubble rate H0. We argue that the conclusion is not as straightforward as claimed since there are good physical reasons to expect α˙α<
Cryptography in constant parallel time
Applebaum, Benny
2013-01-01
Locally computable (NC0) functions are 'simple' functions for which every bit of the output can be computed by reading a small number of bits of their input. The study of locally computable cryptography attempts to construct cryptographic functions that achieve this strong notion of simplicity and simultaneously provide a high level of security. Such constructions are highly parallelizable and they can be realized by Boolean circuits of constant depth.This book establishes, for the first time, the possibility of local implementations for many basic cryptographic primitives such as one-way func
Henry's law constants of polyols
S. Compernolle
2014-05-01
Full Text Available Henry's law constants (HLC are derived for several polyols bearing between 2 and 6 hydroxyl groups, based on literature data for water activity, vapour pressure and/or solubility. Depending on the case, infinite dilution activity coefficients (IDACs, solid state pressures or activity coefficient ratios are obtained as intermediary results. For most compounds, these are the first values reported, while others compare favourably with literature data in most cases. Using these values and those from a previous work (Compernolle and Müller, 2014, an assessment is made on the partitioning of polyols, diacids and hydroxy acids to droplet and aqueous aerosol.
Exact constants in approximation theory
Korneichuk, N
1991-01-01
This book is intended as a self-contained introduction for non-specialists, or as a reference work for experts, to the particular area of approximation theory that is concerned with exact constants. The results apply mainly to extremal problems in approximation theory, which in turn are closely related to numerical analysis and optimization. The book encompasses a wide range of questions and problems: best approximation by polynomials and splines; linear approximation methods, such as spline-approximation; optimal reconstruction of functions and linear functionals. Many of the results are base
Kepler's Constant and WDS Orbit
Siregar, S
2012-01-01
The aim of this work are to find a Kepler's constant by using polynomial regression of the angular separation \\rho = \\rho(t) and the position angle \\theta = \\theta(t). The Kepler's constant obtained is used to derive the element of orbit. As a case study the angular separation and the position angle of the WDS 00063 +5826 and the WDS 04403-5857 were investigated. For calculating the element of orbit the Thiele-Innes van den Bos method is used. The rough data of the angular separation \\rho(t) and the position angle \\theta(t) are taken from the US Naval Observatory, Washington. This work also presents the masses and absolute bolometric magnitudes of each star.These stars include into the main-sequence stars with the spectral class G5V for WDS04403-5857and the type of spectrum G3V for WDS 00063+5826. The life time of the primary star and the secondary star of WDS 04403-5857 nearly equal to 20 Gyr. The life time of the primary star and the secondary star of WDS 00063+5826 are 20 Gyr and 19 Gyr, respectively.
van Dam, E.R.; Haemers, W.H.
1995-01-01
A graph G has constant u = u(G) if any two vertices that are not adjacent have u common neighbours. G has constant u and u if G has constant u = u(G), and its complement G has constant u = u(G). If such a graph is regular, then it is strongly regular, otherwise precisely two vertex degrees occur. We
Cosmological constant and curved 5D geometry
Ito, M
2002-01-01
We study the value of cosmological constant in de Sitter brane embedded in five dimensions with positive, vanishing and negative bulk cosmological constant. In the case of negative bulk cosmological constant, we show that not zero but tiny four-dimensional cosmological constant can be realized by tiny deviation from bulk curvature of the Randall-Sundrum model.
Stability constant estimator user`s guide
Hay, B.P.; Castleton, K.J.; Rustad, J.R.
1996-12-01
The purpose of the Stability Constant Estimator (SCE) program is to estimate aqueous stability constants for 1:1 complexes of metal ions with ligands by using trends in existing stability constant data. Such estimates are useful to fill gaps in existing thermodynamic databases and to corroborate the accuracy of reported stability constant values.
Constant training in direct ophthalmoscopy
Younan HC
2017-08-01
Full Text Available Helen-Cara Younan, Rishi Iyer, Janaki Natasha DesaiFaculty of Medicine, Imperial College London, London, UKWe read with great interest the review by Ricci and Ferraz on the advances in training and practice in ophthalmoscopy simulation.1As final year medical students, we have recently experienced direct ophthalmoscopy teaching and agree with the authors that “simulation is a helpful tool in ophthalmoscopy training”.1 Indeed, in our experience, simulation is useful in teaching a wide variety of clinical skills including venepuncture, intravenous cannulation, and catheterization. We were taught all of these clinical skills in our first clinical year of study through use of simulation models. With regards to our direct ophthalmoscopy teaching, we were first taught to recognize the normal retina and different retinal pathologies using images, before practicing our technique and recognition of those images in a model similar to the THELMA (The Human Eye Learning Model Assistant described by the authors.1However, we feel that the use of simulation models alone is not enough to provide confidence and competency in direct ophthalmoscopy among medical students. The authors conclude that “constant training is a well-known strategy for skill enhancement”,1 and we have found that a lack of constant training in direct ophthalmoscopy is evident. After learning venepuncture, cannulation, and catheterization on the simulation models, we were able to observe doctors performing these skills before performing them on patients either in the wards or in theatre. These are skills that we are constantly trained in across a wide variety of medical and surgical attachments. However, opportunities to observe and practice ophthalmoscopy during our attachments are more limited, and thus we are not continuing to use the skills we learn.Authors' replyLucas Holderegger Ricci,1 Caroline Amaral Ferraz21Department of Ophthalmology, School of Medicine, Laureate
The fundamental constants a mystery of physics
Fritzsch, Harald
2009-01-01
The speed of light, the fine structure constant, and Newton's constant of gravity — these are just three among the many physical constants that define our picture of the world. Where do they come from? Are they constant in time and across space? In this book, physicist and author Harald Fritzsch invites the reader to explore the mystery of the fundamental constants of physics in the company of Isaac Newton, Albert Einstein, and a modern-day physicist
Coupling constant in dispersive model
R Saleh-Moghaddam; M E Zomorrodian
2013-11-01
The average of the moments for event shapes in + - → hadrons within the context of next-to-leading order (NLO) perturbative QCD prediction in dispersive model is studied. Moments used in this article are $\\langle 1 - T \\rangle, \\langle ρ \\rangle, \\langle B_{T} \\rangle$ and $\\langle B_{W} \\rangle$. We extract , the coupling constant in perturbative theory and α0 in the non-perturbative theory using the dispersive model. By fitting the experimental data, the values of $(M_{Z^{°}})$ = 0.1171 ± 0.00229 and 0 ($_{I} = 2{\\text{GeV}}$) = 0.5068 ± 0.0440 are found. Our results are consistent with the above model. Our results are also consistent with those obtained from other experiments at different energies. All these features are explained in this paper.
Constant Proportion Debt Obligations (CPDOs)
Cont, Rama; Jessen, Cathrine
2012-01-01
be made arbitrarily small—and thus the credit rating arbitrarily high—by increasing leverage, but the ratings obtained strongly depend on assumptions on the credit environment (high spread or low spread). More importantly, CPDO loss distributions are found to exhibit a wide range of tail risk measures......Constant Proportion Debt Obligations (CPDOs) are structured credit derivatives that generate high coupon payments by dynamically leveraging a position in an underlying portfolio of investment-grade index default swaps. CPDO coupons and principal notes received high initial credit ratings from...... the major rating agencies, based on complex models for the joint transition of ratings and spreads for all names in the underlying portfolio. We propose a parsimonious model for analysing the performance of CPDO strategies using a top-down approach that captures the essential risk factors of the CPDO. Our...
Henry's law constants of polyols
S. Compernolle
2014-12-01
Full Text Available Henry's law constants (HLC are derived for several polyols bearing between 2 and 6 hydroxyl groups, based on literature data for water activity, vapour pressure and/or solubility. While deriving HLC and depending on the case, also infinite dilution activity coefficients (IDACs, solid state vapour pressures or activity coefficient ratios are obtained as intermediate results. An error analysis on the intermediate quantities and the obtained HLC is included. For most compounds, these are the first values reported, while others compare favourably with literature data in most cases. Using these values and those from a previous work (Compernolle and Müller, 2014, an assessment is made on the partitioning of polyols, diacids and hydroxy acids to droplet and aqueous aerosol.
Omnidirectional antenna having constant phase
Sena, Matthew
2017-04-04
Various technologies presented herein relate to constructing and/or operating an antenna having an omnidirectional electrical field of constant phase. The antenna comprises an upper plate made up of multiple conductive rings, a lower ground-plane plate, a plurality of grounding posts, a conical feed, and a radio frequency (RF) feed connector. The upper plate has a multi-ring configuration comprising a large outer ring and several smaller rings of equal size located within the outer ring. The large outer ring and the four smaller rings have the same cross-section. The grounding posts ground the upper plate to the lower plate while maintaining a required spacing/parallelism therebetween.
Is There a Cosmological Constant?
Kochanek, Christopher
2002-07-01
The grant contributed to the publication of 18 refereed papers and 5 conference proceedings. The primary uses of the funding have been for page charges, travel for invited talks related to the grant research, and the support of a graduate student, Charles Keeton. The refereed papers address four of the primary goals of the proposal: (1) the statistics of radio lenses as a probe of the cosmological model (#1), (2) the role of spiral galaxies as lenses (#3), (3) the effects of dust on statistics of lenses (#7, #8), and (4) the role of groups and clusters as lenses (#2, #6, #10, #13, #15, #16). Four papers (#4, #5, #11, #12) address general issues of lens models, calibrations, and the relationship between lens galaxies and nearby galaxies. One considered cosmological effects in lensing X-ray sources (#9), and two addressed issues related to the overall power spectrum and theories of gravity (#17, #18). Our theoretical studies combined with the explosion in the number of lenses and the quality of the data obtained for them is greatly increasing our ability to characterize and understand the lens population. We can now firmly conclude both from our study of the statistics of radio lenses and our survey of extinctions in individual lenses that the statistics of optically selected quasars were significantly affected by extinction. However, the limits on the cosmological constant remain at lambda sigma confidence level, which is in mild conflict with the results of the Type la supernova surveys. We continue to find that neither spiral galaxies nor groups and clusters contribute significantly to the production of gravitational lenses. The lack of group and cluster lenses is strong evidence for the role of baryonic cooling in increasing the efficiency of galaxies as lenses compared to groups and clusters of higher mass but lower central density. Unfortunately for the ultimate objective of the proposal, improved constraints on the cosmological constant, the next large survey
Is There a Cosmological Constant?
Kochanek, Christopher; Oliversen, Ronald J. (Technical Monitor)
2002-01-01
The grant contributed to the publication of 18 refereed papers and 5 conference proceedings. The primary uses of the funding have been for page charges, travel for invited talks related to the grant research, and the support of a graduate student, Charles Keeton. The refereed papers address four of the primary goals of the proposal: (1) the statistics of radio lenses as a probe of the cosmological model (#1), (2) the role of spiral galaxies as lenses (#3), (3) the effects of dust on statistics of lenses (#7, #8), and (4) the role of groups and clusters as lenses (#2, #6, #10, #13, #15, #16). Four papers (#4, #5, #11, #12) address general issues of lens models, calibrations, and the relationship between lens galaxies and nearby galaxies. One considered cosmological effects in lensing X-ray sources (#9), and two addressed issues related to the overall power spectrum and theories of gravity (#17, #18). Our theoretical studies combined with the explosion in the number of lenses and the quality of the data obtained for them is greatly increasing our ability to characterize and understand the lens population. We can now firmly conclude both from our study of the statistics of radio lenses and our survey of extinctions in individual lenses that the statistics of optically selected quasars were significantly affected by extinction. However, the limits on the cosmological constant remain at lambda Labor and Munoz).
A Variant of Davenport's Constant
R Thangadurai
2007-05-01
Let be a prime number. Let be a finite abelian -group of exponent (written additively) and be a non-empty subset of $]n[:=\\{1,2,\\ldots,n\\}$ such that elements of are incongruent modulo and non-zero modulo . Let $k ≥ D(G)/|A|$ be any integer where () denotes the well-known Davenport’s constant. In this article, we prove that for any sequence $g_1,g_2,\\ldots,g_k$ (not necessarily distinct) in , one can always extract a subsequence $g_{i_1},g_{i_2},\\ldots,g_{i_l}$ with $1 ≤ l ≤ k$ such that $$\\sum\\limits_{j=1}^l a_j g_{i_j}=0 \\text{in} G,$$ where $a_j\\in A$ for all . We provide examples where this bound cannot be improved. Furthermore, for the cyclic groups, we prove some sharp results in this direction. In the last section, we explore the relation between this problem and a similar problem with prescribed length. The proof of Theorem 1 uses group-algebra techniques, while for the other theorems, we use elementary number theory techniques.
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
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
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
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 fundamental constants and quantum electrodynamics
Taylor, Barry N; Langenberg, D N
1969-01-01
Introduction ; review of experimental data ; least-squares adjustment to obtain values of the constants without QED theory ; implications for quantum electrodynamics ; final recommended set of fundamental constants ; summary and conclusions.
Temporal variation of coupling constants and nucleosynthesis
Oberhummer, Heinz; Fairbairn, M; Schlattl, H; Sharma, M M
2003-01-01
We investigate the triple-alpha process and the Oklo phenomenon to obtain constraints on possible cosmological time variations of fundamental constants. Specifically we study cosmological temporal constraints for the fine structure constant and nucleon and meson masses.
Capacitive Cells for Dielectric Constant Measurement
Aguilar, Horacio Munguía; Maldonado, Rigoberto Franco
2015-01-01
A simple capacitive cell for dielectric constant measurement in liquids is presented. As an illustrative application, the cell is used for measuring the degradation of overheated edible oil through the evaluation of their dielectric constant.
Temporal variation of coupling constants and nucleosynthesis
Oberhummer, H.; Csótó, A.; Fairbairn, M.; Schlattl, H.; Sharma, M. M.
2003-05-01
We investigate the triple-alpha process and the Oklo phenomenon to obtain constraints on possible cosmological time variations of fundamental constants. Specifically we study cosmological temporal constraints for the fine structure constant and nucleon and meson masses.
Capacitive Cells for Dielectric Constant Measurement
Aguilar, Horacio Munguía; Maldonado, Rigoberto Franco
2015-01-01
A simple capacitive cell for dielectric constant measurement in liquids is presented. As an illustrative application, the cell is used for measuring the degradation of overheated edible oil through the evaluation of their dielectric constant.
Anderegg, G
2013-01-01
Critical Survey of Stability Constants of EDTA Complexes focuses on the computations, values, and characteristics of stability constants. The book emphasizes that for a critical discussion of experimentally determined stability constants, it is important to consider the precision of the values that manifests the self-consistency of the constant, taking into consideration the random errors. The publication reviews the stability constants of metal complexes. The numerical calculations affirm the reactions and transformations of metal ions when exposed to varying conditions. The text also present
Improved Methodology for Parameter Inference in Nonlinear, Hydrologic Regression Models
Bates, Bryson C.
1992-01-01
A new method is developed for the construction of reliable marginal confidence intervals and joint confidence regions for the parameters of nonlinear, hydrologic regression models. A parameter power transformation is combined with measures of the asymptotic bias and asymptotic skewness of maximum likelihood estimators to determine the transformation constants which cause the bias or skewness to vanish. These optimized constants are used to construct confidence intervals and regions for the transformed model parameters using linear regression theory. The resulting confidence intervals and regions can be easily mapped into the original parameter space to give close approximations to likelihood method confidence intervals and regions for the model parameters. Unlike many other approaches to parameter transformation, the procedure does not use a grid search to find the optimal transformation constants. An example involving the fitting of the Michaelis-Menten model to velocity-discharge data from an Australian gauging station is used to illustrate the usefulness of the methodology.
Untangling Fixed Effects and Constant Regressors
Klaassen, F.; Teulings, R.
2015-01-01
Fixed effects (FE) in panel data models overlap each other and prohibit the identification of the impact of "constant" regressors. Think of regressors that are constant across countries in a country-time panel with time FE. The traditional approach is to drop some FE and constant regressors by
Searching for Kaprekar's constants: algorithms and results
Byron L. Walden
2005-01-01
Full Text Available We examine some new results on Kaprekar's constants, specifically establishing the unique 7-digit (in base 4 and 9-digit (in base 5 Kaprekar's constants and showing that there are no 15-, 21-, 27-, or 33-digit Kaprekar's constants.
Untangling Fixed Effects and Constant Regressors
Klaassen, F.; Teulings, R.
2015-01-01
Fixed effects (FE) in panel data models overlap each other and prohibit the identification of the impact of "constant" regressors. Think of regressors that are constant across countries in a country-time panel with time FE. The traditional approach is to drop some FE and constant regressors by norma
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.
Thullner, Martin; Kampara, Makeba; Richnow, Hans H; Harms, Hauke; Wick, Lukas Y
2008-09-01
The microbial degradation of organic substrates often exhibits a fractionation of stable isotopes which leads to an enrichment of the heavier isotope in the remaining substrate. The use of this effect to quantify the amount of biodegraded substrate in contaminated aquifers requires that the isotope fractionation factor is constant in time and space. In many natural and engineered systems the bioavailable concentration at the location of the enzymes differs from the average bulk concentration of the substrate. When enzymatically driven substrate degradation is coupled to a preceding transport step controlling the bioavailability of the substrate, the observed isotope fractionation becomes a function of the bulk substrate concentration. The sensitivity of the observed isotope fractionation factor toward such substrate concentration changes depends on the ratio of bulk substrate concentration and Michaelis-Menten constant and on the ratio between the specific affinity of the microorganisms toward the substrate and the first order rate constant of the bioavailability limiting transport process. Highest sensitivities toward substrate concentration were found for combinations of high substrate concentration with low substrate bioavailability (i.e., high ratios of substrate concentration and Michaelis-Menten constant, and high ratios of specific affinity and transport rate constant). As a consequence, changes in concentration and isotopic composition of a bioavailability limited substrate in batch experiments should not exhibit a linear relation in a Rayleigh plot, and the slope of the Rayleigh plot should show a decreasing trend with concentration decrease. When using isotope fractionation to quantify biodegradation along groundwater flow paths, changes in observed isotope fractionation might occur while contaminant concentration decreases along a flow path.
Non-Relativistic Spacetimes with Cosmological Constant
Aldrovandi, R.; Barbosa, A. L.; Crispino, L.C.B.; Pereira, J. G.
1998-01-01
Recent data on supernovae favor high values of the cosmological constant. Spacetimes with a cosmological constant have non-relativistic kinematics quite different from Galilean kinematics. De Sitter spacetimes, vacuum solutions of Einstein's equations with a cosmological constant, reduce in the non-relativistic limit to Newton-Hooke spacetimes, which are non-metric homogeneous spacetimes with non-vanishing curvature. The whole non-relativistic kinematics would then be modified, with possible ...
Cosmological constant and Brane New World
Nojiri, S; Odintsov, S D; Nojiri, Shin'ichi; Obregon, Octavio; Odintsov, Sergei D.
2001-01-01
The estimation of the cosmological constant in inflationary Brane New World models is done. It is shown that basically it is quite large, of the same order as in anomaly-driven inflation. However, for some fine-tuning of bulk gravitational constant and AdS scale parameter $l^2$ it may be reduced to sufficiently small value. Bulk higher derivative AdS gravity with quantum brane matter may also serve as the model where small positive cosmological constant occurs.
Singularities in universes with negative cosmological constant
Tipler, F.J.
1976-10-01
It is well known that many universes with negative cosmological constant contain singularities. We shall generalize this result by proving that all closed universes with negative cosmological constant are both future and past timelike geodesically incomplete if the strong energy condition holds. No global causality conditions or restrictions on the initial data are used in the proof. Furthermore, we shall show that all open universes with a Cauchy surface and a negative cosmological constant are singular if the strong energy condition holds. (AIP)
Coasting cosmologies with time dependent cosmological constant
Pimentel, L O; Pimentel, Luis O.
1999-01-01
The effect of a time dependent cosmological constant is considered in a family of scalar tensor theories. Friedmann-Robertson-Walker cosmological models for vacumm and perfect fluid matter are found. They have a linear expansion factor, the so called coasting cosmology, the gravitational "constant" decreace inversely with time; this model satisfy the Dirac hipotesis. The cosmological "constant" decreace inversely with the square of time, therefore we can have a very small value for it at present time.
On a time varying fine structure constant
Berman, M S; Berman, Marcelo S.; Trevisan, Luis A.
2001-01-01
By employing Dirac LNH, and a further generalization by Berman (GLNH), we estimate how should vary the total number of nucleons, the energy density, Newton Gravitational constant, the cosmological constant, the magnetic permeability and electric permitivity, of the Universe,in order to account for the experimentally observed time variation of the fine structure constant. As a bonus,we find an acceptable value for the deceleration parameter of the present Universe, compatible with the Supernovae observations.
A natural cosmological constant from chameleons
Horatiu Nastase
2015-07-01
Full Text Available We present a simple model where the effective cosmological constant appears from chameleon scalar fields. For a Kachru–Kallosh–Linde–Trivedi (KKLT-inspired form of the potential and a particular chameleon coupling to the local density, patches of approximately constant scalar field potential cluster around regions of matter with density above a certain value, generating the effect of a cosmological constant on large scales. This construction addresses both the cosmological constant problem (why Λ is so small, yet nonzero and the coincidence problem (why Λ is comparable to the matter density now.
Surprises in numerical expressions of physical constants
Amir, Ariel; Tokieda, Tadashi
2016-01-01
In science, as in life, `surprises' can be adequately appreciated only in the presence of a null model, what we expect a priori. In physics, theories sometimes express the values of dimensionless physical constants as combinations of mathematical constants like pi or e. The inverse problem also arises, whereby the measured value of a physical constant admits a `surprisingly' simple approximation in terms of well-known mathematical constants. Can we estimate the probability for this to be a mere coincidence, rather than an inkling of some theory? We answer the question in the most naive form.
A natural cosmological constant from chameleons
Nastase, Horatiu, E-mail: nastase@ift.unesp.br [Instituto de Física Teórica, UNESP-Universidade Estadual Paulista, R. Dr. Bento T. Ferraz 271, Bl. II, Sao Paulo 01140-070, SP (Brazil); Weltman, Amanda, E-mail: amanda.weltman@uct.ac.za [Astrophysics, Cosmology & Gravity Center, Department of Mathematics and Applied Mathematics, University of Cape Town, Private Bag, Rondebosch 7700 (South Africa)
2015-07-30
We present a simple model where the effective cosmological constant appears from chameleon scalar fields. For a Kachru–Kallosh–Linde–Trivedi (KKLT)-inspired form of the potential and a particular chameleon coupling to the local density, patches of approximately constant scalar field potential cluster around regions of matter with density above a certain value, generating the effect of a cosmological constant on large scales. This construction addresses both the cosmological constant problem (why Λ is so small, yet nonzero) and the coincidence problem (why Λ is comparable to the matter density now)
Constant Width Planar Computation Characterizes ACC0
Hansen, Kristoffer Arnsfelt
2006-01-01
We obtain a characterization of ACC0 in terms of a natural class of constant width circuits, namely in terms of constant width polynomial size planar circuits. This is shown via a characterization of the class of acyclic digraphs which can be embedded on a cylinder surface in such a way that all...
Constant Width Planar Computation Characterizes ACC0
Hansen, K.A.
2004-01-01
We obtain a characterization of ACC 0 in terms of a natural class of constant width circuits, namely in terms of constant width polynomial size planar circuits. This is shown via a characterization of the class of acyclic digraphs which can be embedded on a cylinder surface in such a way that all...
Chiral Corrections to Vector Meson Decay Constants
Bijnens, J; Talavera, P; Bijnens, Johan; Gosdzinsky, Peter; Talavera, Pere
1998-01-01
We calculate the leading quark mass corrections of order $m_q\\log(m_q)$, $m_q$ and $m_q^{3/2}$ to the vector meson decay constants within Heavy Vector Meson Chiral Perturbation Theory. We discuss the issue of electromagnetic gauge invariance and the heavy mass expansion. Reasonably good fits to the observed decay constants are obtained.
Constant Angle Surfaces in the Heisenberg Group
Johan FASTENAKELS; Marian Ioan MUNTEANU; Joeri VAN DER VEKEN
2011-01-01
In this article we extend the notion of constant angle surfaces in S2 × R and H2 × R to general Bianchi-Cartan-Vranceanu spaces. We show that these surfaces have constant Gaussian curvature and we give a complete local classification in the Heisenberg group.
The time constant of the somatogravic illusion.
Correia Grácio, B J; de Winkel, K N; Groen, E L; Wentink, M; Bos, J E
2013-02-01
Without visual feedback, humans perceive tilt when experiencing a sustained linear acceleration. This tilt illusion is commonly referred to as the somatogravic illusion. Although the physiological basis of the illusion seems to be well understood, the dynamic behavior is still subject to discussion. In this study, the dynamic behavior of the illusion was measured experimentally for three motion profiles with different frequency content. Subjects were exposed to pure centripetal accelerations in the lateral direction and were asked to indicate their tilt percept by means of a joystick. Variable-radius centrifugation during constant angular rotation was used to generate these motion profiles. Two self-motion perception models were fitted to the experimental data and were used to obtain the time constant of the somatogravic illusion. Results showed that the time constant of the somatogravic illusion was on the order of two seconds, in contrast to the higher time constant found in fixed-radius centrifugation studies. Furthermore, the time constant was significantly affected by the frequency content of the motion profiles. Motion profiles with higher frequency content revealed shorter time constants which cannot be explained by self-motion perception models that assume a fixed time constant. Therefore, these models need to be improved with a mechanism that deals with this variable time constant. Apart from the fundamental importance, these results also have practical consequences for the simulation of sustained accelerations in motion simulators.
Physical Properties of Triglycerides IV. Dielectric Constant
Gouw, T.H.; Vlugter, J.C.
1967-01-01
Dielectric constants at 20° and at 40° C of a number of triglycerides in the liquid state have been measured. A molar additive function of the dielectric constant, based on a relation derived by J. van Elk, was used in combination with a previously derived equation for triglycerides to give an equat
Decay constants from twisted mass QCD
Dimopoulos, P; Michael, C; Simula, S; Urbach, C
2008-01-01
We present results for chiral extrapolations of the mass and decay constants of the rho meson. The data sets used are the nf=2 unquenched gauge configurations generated with twisted mass fermions by the European Twisted Mass Collaboration. We describe a calculation of three decay constants in charmonium and explain why they are required.
String theory, cosmology and varying constants
Damour, Thibault
In string theory the coupling `constants' appearing in the low-energy effective Lagrangian are determined by the vacuum expectation values of some (a priori) massless scalar fields (dilaton, moduli). This naturally leads one to expect a correlated variation of all the coupling constants, and an associated violation of the equivalence principle. We review some string-inspired theoretical models which incorporate such a spacetime variation of coupling constants while remaining naturally compatible both with phenomenological constraints coming from geochemical data (Oklo; Rhenium decay) and with present equivalence principle tests. Barring a very unnatural fine-tuning of parameters, a variation of the fine-structure constant as large as that recently `observed' by Webb et al. in quasar absorption spectra appears to be incompatible with these phenomenological constraints. Independently of any model, it is emphasized that the best experimental probe of varying constants are high-precision tests of the universality of free fall, such as MICROSCOPE and STEP.
String theory, cosmology and varying constants
Damour, Thibault Marie Alban Guillaume
2002-01-01
In string theory the coupling ``constants'' appearing in the low-energy effective Lagrangian are determined by the vacuum expectation values of some (a priori) massless scalar fields (dilaton, moduli). This naturally leads one to expect a correlated variation of all the coupling constants, and an associated violation of the equivalence principle. We review some string-inspired theoretical models which incorporate such a spacetime variation of coupling constants while remaining naturally compatible both with phenomenological constraints coming from geochemical data (Oklo; Rhenium decay) and with present equivalence principle tests. Barring a very unnatural fine-tuning of parameters, a variation of the fine-structure constant as large as that recently ``observed'' by Webb et al. in quasar absorption spectra appears to be incompatible with these phenomenological constraints. Independently of any model, it is emphasized that the best experimental probe of varying constants are high-precision tests of the universa...
Cosmic Time Variation of the Gravitational Constant
Tomaschitz, R
2000-01-01
A pre-relativistic cosmological approach to electromagnetism and gravitation is explored that leads to a cosmic time variation of the fundamental constants. Space itself is supposed to have physical substance, which manifests by its permeability. The scale factors of the permeability tensor induce a time variation of the fundamental constants. Atomic radii, periods, and energy levels scale in cosmic time, which results in dispersionless redshifts without invoking a space expansion. Hubble constant and deceleration parameter are reviewed in this context. The time variation of the gravitational constant at the present epoch can be expressed in terms of these quantities. This provides a completely new way to restrain the deceleration parameter from laboratory bounds on the time variation of the gravitational constant. This variation also affects the redshift dependence of angular diameters and the surface brightness, and we study in some detail the redshift scaling of the linear sizes of radio sources. The effec...
General Relativity, Cosmological Constant and Modular Forms
Kraniotis, G V
2001-01-01
Strong field (exact) solutions of the gravitational field equations of General Relativity in the presence of a Cosmological Constant are investigated. In particular, a full exact solution is derived within the inhomogeneous Szekeres-Szafron family of space-time line element with a nonzero Cosmological Constant. The resulting solution connects, in an intrinsic way, General Relativity with the theory of modular forms and elliptic curves and thus to the theory of Taniyama-Shimura.The homogeneous FLRW limit of the above space-time elements is recovered and we solve exactly the resulting Friedmann Robertson field equation with the appropriate matter density for generic values of the Cosmological Constant $ \\Lambda $ and curvature constant $K$. A formal expression for the Hubble constant is derived. The cosmological implications of the resulting non-linear solutions are systematically investigated. Two particularly interesting solutions i) the case of a flat universe $K=0,\\Lambda \
Stiripentol kinetics in epilepsy: nonlinearity and interactions.
Levy, R H; Loiseau, P; Guyot, M; Blehaut, H M; Tor, J; Moreland, T A
1984-11-01
Stiripentol kinetics during oral therapy were assessed in six patients with epilepsy who were receiving other antiepileptic drugs. Steady-state levels at 600, 1200, and 2400 mg/day increased in a nonlinear fashion, indicating Michaelis-Menten kinetics. Oral clearance of stiripentol at 600 mg/day was 41.5 +/- 23.4 l/day/kg (mean +/- SD), greater than that at 1200 mg/day (20.3 +/- 8.8 l/day/kg; P less than 0.05) or 2400 mg/day (8.5 +/- 3.8 l/day/kg; P less than 0.01). The apparent in vivo Michaelis-Menten parameters were determined from three mean steady-state concentrations. The average velocity of conversion of stiripentol to its metabolites (Vm), Michaelis constant (Km), and the ratio Vm/Km were 49.3 +/- 13.1 mg/day/kg, 1.35 +/- 1.08 mg/l, and 50.2 +/- 27.5 l/day/kg. Stiripentol reduced the elimination clearances of concomitant antiepileptic drugs. Phenytoin clearance was reduced in all five subjects who received this drug, from a mean control of 29.5 +/- 13.4 l/day to 18.5 +/- 4.6 l/day at a stiripentol dose of 1200 mg/day (P = 0.05) and to 6.48 +/- 2.59 l/day at 2400 mg/day (P less than 0.01). Stiripentol reduced the clearance of carbamazepine in one subject from a control value of 209 l/day to 128 l/day (1200 mg/day) and 61 l/day (2400 mg/day). Stiripentol reduced phenobarbital clearance in two subjects from 3.8 and 5.1 l/day to 2.3 and 3.4 l/day (2400 mg/day). The Michaelis-Menten kinetics of stiripentol, as well as its interactions with other antiepileptic drugs, have important implications in the designing of controlled clinical trials.
Some Zero-Sum Constants with Weights
S D Adhikari; R Balasubramanian; F Pappalardi; P Rath
2008-05-01
For an abelian group , the Davenport constant () is defined to be the smallest natural number such that any sequence of elements in has a non-empty subsequence whose sum is zero (the identity element). Motivated by some recent developments around the notion of Davenport constant with weights, we study them in some basic cases. We also define a new combinatorial invariant related to $(\\mathbb{Z}/n\\mathbb{Z})^d$, more in the spirit of some constants considered by Harborth and others and obtain its exact value in the case of $(\\mathbb{Z}/n\\mathbb{Z})^2$ where is an odd integer.
EFFECTS OF CONSTANT EXCITATION ON LOCAL BIFURCATION
WU Zhi-qiang; CHEN Yu-shu
2006-01-01
The effects of the constant excitation on the local bifurcation of the periodic solutions in the 1:2 internal resonant systems were analyzed based on the singularity theory. It is shown that the constant excitation make influence only when there exist some nonlinear terms, in the oscillator with lower frequency. Besides acting as main bifurcation parameter, the constant excitation, together with coefficients of some nonlinear terms,may change the values of unfolding parameters and the type of the bifurcation. Under the non-degenerate cases, the effect of the third order terms can be neglected.
On the constants for some Sobolev imbeddings
Pizzocchero Livio
2001-01-01
Full Text Available We consider the imbedding inequality is the Sobolev space (or Bessel potential space of type and (integer or fractional order . We write down upper bounds for the constants , using an argument previously applied in the literature in particular cases. We prove that the upper bounds computed in this way are in fact the sharp constants if , , and exhibit the maximising functions. Furthermore, using convenient trial functions, we derive lower bounds on for in many cases these are close to the previous upper bounds, as illustrated by a number of examples, thus characterizing the sharp constants with little uncertainty.
The Determination of the Strong Coupling Constant
Dissertori, Günther
2016-10-01
The strong coupling constant is one of the fundamental parameters of the Standard Theory of particle physics. In this review I will briefly summarise the theoretical framework, within which the strong coupling constant is defined and how it is connected to measurable observables. Then I will give an historical overview of its experimental determinations and discuss the current status and world average value. Among the many different techniques used to determine this coupling constant in the context of quantum chromodynamics, I will focus in particular on a number of measurements carried out at the Large Electron-Positron Collider (LEP) and the Large Hadron Collider (LHC) at CERN.
Mathematical Modeling of Biosensors Based on an Array of Enzyme Microreactors
Juozas Kulys
2006-04-01
Full Text Available This paper presents a two-dimensional-in-space mathematical model ofbiosensors based on an array of enzyme microreactors immobilised on a single electrode.The modeling system acts under amperometric conditions. The microreactors were modeledby particles and by strips. The model is based on the diffusion equations containing a non-linear term related to the Michaelis-Menten kinetics of the enzymatic reaction. The modelinvolves three regions: an array of enzyme microreactors where enzyme reaction as well asmass transport by diffusion takes place, a diffusion limiting region where only the diffusiontakes place, and a convective region, where the analyte concentration is maintained constant.Using computer simulation, the influence of the geometry of the microreactors and of thediffusion region on the biosensor response was investigated. The digital simulation wascarried out using the finite difference technique.
Nova, Esteban; Montecinos, Felipe; Brunet, Juan E; Lagos, Rosalba; Monasterio, Octavio
2007-09-15
FtsZ (Filamentous temperature sensitivity Z) cell division protein from Escherichia coli binds the fluorescence probe DAPI. Bundling of FtsZ was facilitated in the presence of DAPI, and the polymers in solution remained polymerized longer time than the protofilaments formed in the absence of DAPI. DAPI decreased both the maximal velocity of the GTPase activity and the Michaelis-Menten constant for GTP, indicating that behaves like an uncompetitive inhibitor of the GTPase activity favoring the GTP form of FtsZ in the polymers. The results presented in this work support a cooperative polymerization mechanism in which the binding of DAPI favors protofilament lateral interactions and the stability of the resulting polymers.
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.
Wang, Min; Bao, Wen-Jing; Wang, Jiong; Wang, Kang; Xu, Jing-Juan; Chen, Hong-Yuan; Xia, Xing-Hua
2014-10-01
3D hierarchical layer double hydroxides (LDHs) have attracted extensive interest due to their unique electronic and catalytic properties. Unfortunately, the existing preparation methods require high temperature or toxic organic compounds, which limits the applications of the 3D hierarchical LDHs in biocatalysis and biomedicine. Herein, we present a green strategy to synthesize ``Desert Rose Stone''-like Mg-Al-CO3 LDH nanoflowers in situ deposited on aluminum substrates via a coprecipitation method using atmospheric carbon dioxide. Using this method, we construct a novel ``Desert Rose Stone''-like nanobiocatalytic system by using HRP as the model enzyme. Compared with the free HRP, the HRP/Mg-Al-LDH nanobiocatalytic system exhibits higher catalytic activity and stability. A smaller apparent Michaelis-Menten constant (0.16 mM) of this system suggests that the encapsulated HRP shows higher affinity towards H2O2.
Escribano, Rubén; Bustos-Ríos, Evelyn; Hidalgo, Pamela; Morales, Carmen E.
2016-09-01
Zooplankton production is critical for understanding marine ecosystem dynamics. This work estimates copepod growth and production in the coastal upwelling and coastal transition zones off central-southern Chile (~35 to 37°S) during a 3-year time series (2004, 2005, and 2006) at a fixed shelf station, and from spring-summer spatial surveys during the same period. To estimate copepod production (CP), we used species-biomasses and associated C-specific growth rates from temperature dependent equations (food-saturated) for the dominant species, which we assumed were maximal growth rates (gmax). Using chlorophyll-a concentrations as a proxy for food conditions, we determined a size-dependent half-saturation constant with the Michaelis-Menten equation to derive growth rates (g) under the effect of food limitation. These food-dependent C-specific growth rates were much lower (absence of bottom-up control, allowing copepods to grow without limitation due to food resources.
Spectral Quasi-Equilibrium Manifold for Chemical Kinetics.
Kooshkbaghi, Mahdi; Frouzakis, Christos E; Boulouchos, Konstantinos; Karlin, Iliya V
2016-05-26
The Spectral Quasi-Equilibrium Manifold (SQEM) method is a model reduction technique for chemical kinetics based on entropy maximization under constraints built by the slowest eigenvectors at equilibrium. The method is revisited here and discussed and validated through the Michaelis-Menten kinetic scheme, and the quality of the reduction is related to the temporal evolution and the gap between eigenvalues. SQEM is then applied to detailed reaction mechanisms for the homogeneous combustion of hydrogen, syngas, and methane mixtures with air in adiabatic constant pressure reactors. The system states computed using SQEM are compared with those obtained by direct integration of the detailed mechanism, and good agreement between the reduced and the detailed descriptions is demonstrated. The SQEM reduced model of hydrogen/air combustion is also compared with another similar technique, the Rate-Controlled Constrained-Equilibrium (RCCE). For the same number of representative variables, SQEM is found to provide a more accurate description.
Degradation kinetics and metabolites in continuous biodegradation of isoprene.
Srivastva, Navnita; Singh, Ram S; Upadhyay, Siddh N; Dubey, Suresh K
2016-04-01
The kinetic parameters of isoprene biodegradation were studied in a bioreactor, comprising of bioscrubber and polyurethane foam packed biofilter in series and inoculated with Pseudomonas sp., using a Michaelis-Menten type model. The maximum elimination capacity, ECmax; substrate constant, Ks and ECmax/Ks values for bioscrubber were found to be 666.7 g m(-3) h(-1), 9.86 g m(-3) and 67.56 h(-1), respectively while those for biofilter were 3333 g m(-3) h(-1), 13.96 g m(-3) and 238.7 h(-1), respectively. The biofilter section exhibited better degradation efficiency compared to the bioscrubber unit. Around 62-75% of the feed isoprene got converted to carbon dioxide, indicating the efficient capability of bacteria to mineralize isoprene. The FTIR and GC-MS analyses of degradation products indicated oxidative cleavage of unsaturated bond of isoprene. These results were used for proposing a plausible degradation pathway for isoprene.
Enzymatic detection of γ-hydroxybutyrate using aldo-keto reductase 7A2.
Bendinskas, Kestutis; Sattelberg, Patricia; Crossett, Daniel; Banyikwa, Andrew; Dempsey, Daniel; MacKenzie, James A
2011-05-01
Gamma-hydroxybutyrate (GHB) is a prescribed medication as well as a drug of abuse. Its detection in various matrices for in-field forensic scientists remains a challenge. We have developed an assay that uses aldo-keto reductase 7A2 (AKR7A2) for the specific determination of GHB in various drinks. AKR7A2 was purified using Ni-affinity chromatography. The Michaelis-Menten constant for the GHB oxidation reaction was 10 mM, and the minimum detection limit was 4 mM. Ethanol was not a substrate for AKR7A2. In a coupled reaction with NADP(+), phenazine methosulfate (PMS), and 2,6-dichlorophenolindophenol, various beverages (orange juice, milk, soda, and numerous alcoholic drinks) containing GHB turned from blue to light yellow. In a second coupled reaction where diaphorase replaced PMS, the presence of GHB also caused the expected change of color in various beers.
Wei Ma; Wei Song; Dan Bi Tian
2009-01-01
Multi-walled carbon nanombes (MWCNTs) were coated with ZnO by a hydrothermal method. The resulting nanocomposites were mixed with the Nation solution to form a composite matrix for the fabrication of hemoglobin (Hb) biosensor. To prevent the leak of Hb molecules of the biosensor, silica sol-gel film was coated on the surface of the Hb/ZnO-MWCNTs/Nafion electrode. The silica sol-gel/Hb/ZnO-MWCNTs/Nation film exhibited a pair of well-defined, quasi-reversible redox peaks. This biosensor showed excellent electrocatalytic activity to H2O2. The sensitivity and apparent Michaelis-Menten constant of this Hb biosensor to H2O2 were 1.31 A/(M cm2) and 82.8 umol/L, respectively, which indicated that Hb had high affinity to H2O2.
Chitosan-g-polyaniline: a creatine amidinohydrolase immobilization matrix for creatine biosensor
2009-09-01
Full Text Available A novel matrix composed of chitosan-graft-polyaniline (CHIT-g-PANI was electrochemically prepared to investigate the immobilization of creatine amidinohydrolase (CAH. CAH enzyme was covalently immobilized with the CHIT-g-PANI matrix using glutaraldehyde as a linker. The resulting CAH/CHIT-g-PANI biomatrix was characterized with Fourier transform infrared spectroscopy (FTIR, atomic force microscopy (AFM, contact angle measurement and cyclic voltammetry (CV taking CHIT-g-PANI as a reference. The influence of various parameters on CAH enzyme activity within the matrix was investigated including pH, temperature, and time. The Michaelis-Menten constant and apparent activities for the CAH enzyme were calculated to be 0.51 mM and 83.59 mg/cm2, respectively; indicating CHIT-g-PANI matrix has a high affinity to immobilize CAH enzyme.
Cotton cellulose: enzyme adsorption and enzymic hydrolysis
Beltrame, P.L.; Carniti, P.; Focher, B.; Marzetti, A.; Cattaneo, M.
1982-01-01
The adsorption of a crude cellulase complex from Trichoderma viride on variously pretreated cotton cellulose samples was studied in the framework of the Langmuir approach at 2-8 degrees. The saturation amount of adsorbed enzyme was related to the susceptibility of the substrates to hydrolysis. In every case the adsorption process was faster by 2-3 orders of magnitude than the hydrolysis step to give end products. For ZnCl/sub 2/-treated cotton cellulose the Langmuir parameters correlated fairly well with the value of the Michaelis constant, measured for its enzymic hydrolysis, and the adsorptive complex was indistinguishable from the complex of the Michaelis-Menten model for the hydrolysis.
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.
A multivariate nonlinear mixed effects method for analyzing energy partitioning in growing pigs
Strathe, Anders Bjerring; Danfær, Allan Christian; Chwalibog, André
2010-01-01
Simultaneous equations have become increasingly popular for describing the effects of nutrition on the utilization of ME for protein (PD) and lipid deposition (LD) in animals. The study developed a multivariate nonlinear mixed effects (MNLME) framework and compared it with an alternative method...... for estimating parameters in simultaneous equations that described energy metabolism in growing pigs, and then proposed new PD and LD equations. The general statistical framework was implemented in the NLMIXED procedure in SAS. Alternative PD and LD equations were also developed, which assumed...... that the instantaneous response curve of an animal to varying energy supply followed the law of diminishing returns behavior. The Michaelis-Menten function was adopted to represent a biological relationship in which the affinity constant (k) represented the sensitivity of PD to ME above maintenance. The approach...
Structure and Function of Bovine and Camel Chymosin
Jensen, Jesper Langholm
The central step in cheese making is the separation of milk into curd and whey. This can be done enzymatically by hydrolysis of the Phe105-Met106 bond or nearby bonds in bovine κ-casein, which releases its hydrophilic C-terminal leading to coagulation of the milk. The preferred enzyme...... this difference through the study of the structures of bovine and camel chymosin, and preparation of catalytically inactive enzymes in complex with substrate. Their milk-clotting activities was determined using the traditional assay on skimmed milk, and a fluorescence resonance energy transfer (FRET) assay...... was developed and used to measure Michaelis-Menten kinetics towards a κ-casein derived peptide and to determine the inhibition constants of pepstatin towards the enzymes. In addition to this, the commercial products made by recombinant expression in Aspergillus niger (A. niger) were subjected to a detailed...
Byssus thread: a novel support material for urease immobilization.
Mishra, Neelam; Pithawala, Kespi; Bahadur, Anita
2011-12-01
Byssus threads are tough biopolymer produced by mussels (Mytilus viridis) to attach themselves to rocks. These were collected from mussels in their natural habitat (N) and from animals maintained in laboratory condition (L) as a novel support. Byssus thread surfaces were characterized by SEM analysis, chemically modified and used for adsorption of urease. The efficiency of the immobilization was calculated by examining the relative enzyme activity of free and the immobilized urease. The pH stabilities of immobilized urease were higher (0.5 unit) than free enzyme. Immobilized enzymes on byssus (both N and L) when stored at 6 °C retained 50% of its activity after 30 days, but they were more stable in dry condition. The optimum temperature of immobilized enzymes was found to increase (25 °C). A Michaelis-Menten constant (K (m)) value for immobilized urease was also elevated (2.08 mol).
Marshak waves: Constant flux vs constant T-a (slight) paradigm shift
Rosen, M.D.
1994-12-22
We review the basic scaling laws for Marshak waves and point out the differences in results for wall loss, albedo, and Marshak depth when a constant absorbed flux is considered as opposed to a constant absorbed temperature. Comparisons with LASNEX simulations and with data are presented that imply that a constant absorbed flux is a more appropriate boundary condition.
The time constant of the somatogravic illusion
Correia Grácio, B.J.; Winkel, K.N. de; Groen, E.L.; Wentink, M.; Bos, J.E.
2013-01-01
Met desdemona hebben we gevonden dat de tijd constante van de somatografische illusie rond twee seconden is. Dit resultaat verschilt van wat was gevonden in ander onderzoek dat gebruikt maakt van een gewone centrifuge
Black holes with constant topological Euler density
Bargueño, Pedro
2016-01-01
A class of four dimensional spherically symmetric and static geometries with constant topological Euler density is studied. These geometries are shown to solve the coupled Einstein-Maxwell system when non-linear Born-Infeld-like electrodynamics is employed.
STABILITY CONSTANT OF THE TRISGLYCINATO METAL ...
DR. AMINU
Department of Pure and Industrial Chemistry,Bayero University Kano, P. M. B. 3011, Kano, ... The stability constants of iron, manganese, cobalt, and nickel complexes of glycine have been ... bidentate ligand in its coordination with metal ions.
Interacting universes and the cosmological constant
Alonso-Serrano, A. [Centro de Física “Miguel Catalán”, Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas, Serrano 121, 28006 Madrid (Spain); Estación Ecológica de Biocosmología, Pedro de Alvarado 14, 06411 Medellín (Spain); Bastos, C. [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Avenida Rovisco Pais 1, 1049-001 Lisboa (Portugal); Bertolami, O. [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Avenida Rovisco Pais 1, 1049-001 Lisboa (Portugal); Departamento de Física e Astronomia, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto (Portugal); Robles-Pérez, S., E-mail: salvarp@imaff.cfmac.csic.es [Centro de Física “Miguel Catalán”, Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas, Serrano 121, 28006 Madrid (Spain); Estación Ecológica de Biocosmología, Pedro de Alvarado 14, 06411 Medellín (Spain); Física Teórica, Universidad del País Vasco, Apartado 644, 48080 Bilbao (Spain)
2013-02-12
In this Letter it is studied the effects that an interaction scheme among universes can have in the values of their cosmological constants. In the case of two interacting universes, the value of the cosmological constant of one of the universes becomes very close to zero at the expense of an increasing value of the cosmological constant of the partner universe. In the more general case of a chain of N interacting universes with periodic boundary conditions, the spectrum of the Hamiltonian splits into a large number of levels, each of them associated with a particular value of the cosmological constant, that can be occupied by single universes revealing a collective behavior that plainly shows that the multiverse is much more than the mere sum of its parts.
Determination of the gravitational constant G
HU Zhong-kun; LIU Qi; LUO Jun
2006-01-01
A precise knowledge of the Newtonian gravitational constant G has an important role in physics and is of considerable meteorological interest.Although G was the first physical constant to be introduced and measured in the history of science,it is still the least precisely determined of all the fundamental constants of nature.The 2002 CODATA recommended value for G,G=(6.6742±0.0010)×10-11m3·kg-1·s-2,has an uncertainty of 150 parts per million (ppm),much larger than that of all other fundamental constants.Reviewed here is the status of our knowledge of the absolute value of G,methods for determining G,and recent high precision experiments for determining G.
Prime rings with PI rings of constants
Kharchenko, V K; Rodríguez-Romo, S
1996-01-01
It is shown that if the ring of constants of a restricted differential Lie algebra with a quasi-Frobenius inner part satisfies a polynomial identity (PI) then the original prime ring has a generalized polynomial identitiy (GPI). If additionally the ring of constants is semiprime then the original ring is PI. The case of a non-quasi-Frobenius inner part is also considered.
Trialogue on the number of fundamental constants
Duff, Michael J; Veneziano, Gabriele
2002-01-01
This paper consists of three separate articles on the number of fundamental dimensionful constants in physics. We started our debate in summer 1992 on the terrace of the famous CERN cafeteria. In the summer of 2001 we returned to the subject to find that our views still diverged and decided to explain our current positions. LBO develops the traditional approach with three constants, GV argues in favor of just two, while MJD advocates zero.
The Origin of the Constant Carbohydrate Diet
Charles Herbert Read
2009-01-01
Full Text Available The Constant Carbohydrate diet, based entirely on carbohydrate exchanges, is now widely used in the dietary treatment of diabetes mellitus. Being based on sound scientific principles and simple in design, the Constant Carabohydrate diet is appropriate for all those having diabetes mellitus, young or old, no matter their ethncity. This report describes why and how it was developed in 1951. Its simplicity makes it adaptable to all ethnic diets.
The Origin of the Constant Carbohydrate Diet
Read CharlesHerbert
2008-01-01
Full Text Available The Constant Carbohydrate diet, based entirely on carbohydrate exchanges, is now widely used in the dietary treatment of diabetes mellitus. Being based on sound scientific principles and simple in design, the Constant Carabohydrate diet is appropriate for all those having diabetes mellitus, young or old, no matter their ethncity. This report describes why and how it was developed in 1951. Its simplicity makes it adaptable to all ethnic diets.
Compact phase space, cosmological constant, discrete time
Rovelli, Carlo
2015-01-01
We study the quantization of geometry in the presence of a cosmological constant, using a discretiza- tion with constant-curvature simplices. Phase space turns out to be compact and the Hilbert space finite dimensional for each link. Not only the intrinsic, but also the extrinsic geometry turns out to be discrete, pointing to discreetness of time, in addition to space. We work in 2+1 dimensions, but these results may be relevant also for the physical 3+1 case.
Inflationary Phase with Time Varying Fundamental Constants
Berman, M S; Berman, Marcelo S.; Trevisan, Luis A.
2002-01-01
Following Barrow, and Barrow and collaborators, we find a cosmological JBD model, with varying speed of light and varying fine structure constant, where the deceleration parameter is -1,causing acceleration of the Universe.Indeed, we have an exponential inflationary phase. Plancks time, energy, length,etc.,might have had different numerical values in the past, than those available in the litterature, due to the varying values for speed of light, and gravitational constant.
Beyond lensing by the cosmological constant
Faraoni, Valerio
2016-01-01
The long-standing problem of whether the cosmological constant affects directly the deflection of light caused by a gravitational lens is reconsidered. We use a new approach based on the Hawking quasilocal mass of a sphere grazed by light rays and on its splitting into local and cosmological parts. Previous literature restricted to the cosmological constant is extended to any form of dark energy accelerating the universe in which the gravitational lens is embedded.
Beyond lensing by the cosmological constant
Faraoni, Valerio; Lapierre-Léonard, Marianne
2017-01-01
The long-standing problem of whether the cosmological constant affects directly the deflection of light caused by a gravitational lens is reconsidered. We use a new approach based on the Hawking quasilocal mass of a sphere grazed by light rays and on its splitting into local and cosmological parts. Previous literature restricted to the cosmological constant is extended to any form of dark energy accelerating the universe in which the gravitational lens is embedded.
A constant elasticity of profit production function
Beard, Rodney
2007-01-01
Impact analysis of changes in production inputs may be simplified if one can apply a constant adjustment factor to profit. In particular, if a production function can be found for which the elasticity of profit is constant and this function has desirable properties, then one can use the input elasticity of profit to study the impact of input changes on profit. In this paper such a production function is derived from first principles.
RNA structure and scalar coupling constants
Tinoco, I. Jr.; Cai, Z.; Hines, J.V.; Landry, S.M.; SantaLucia, J. Jr.; Shen, L.X.; Varani, G. [Univ. of California, Berkeley, CA (United States)
1994-12-01
Signs and magnitudes of scalar coupling constants-spin-spin splittings-comprise a very large amount of data that can be used to establish the conformations of RNA molecules. Proton-proton and proton-phosphorus splittings have been used the most, but the availability of {sup 13}C-and {sup 15}N-labeled molecules allow many more coupling constants to be used for determining conformation. We will systematically consider the torsion angles that characterize a nucleotide unit and the coupling constants that depend on the values of these torsion angles. Karplus-type equations have been established relating many three-bond coupling constants to torsion angles. However, one- and two-bond coupling constants can also depend on conformation. Serianni and coworkers measured carbon-proton coupling constants in ribonucleosides and have calculated their values as a function of conformation. The signs of two-bond coupling can be very useful because it is easier to measure a sign than an accurate magnitude.
Johnson Type Bounds on Constant Dimension Codes
Xia, Shu-Tao
2007-01-01
Very recently, an operator channel was defined by Koetter and Kschischang when they studied random network coding. They also introduced constant dimension codes and demonstrated that these codes can be employed to correct errors and/or erasures over the operator channel. Constant dimension codes are equivalent to the so-called linear authentication codes introduced by Wang, Xing and Safavi-Naini when constructing distributed authentication systems in 2003. In this paper, we study constant dimension codes. It is shown that Steiner structures are optimal constant dimension codes achieving the Wang-Xing-Safavi-Naini bound. Furthermore, we show that constant dimension codes achieve the Wang-Xing-Safavi-Naini bound if and only if they are certain Steiner structures. Then, we derive two Johnson type upper bounds, say I and II, on constant dimension codes. The Johnson type bound II slightly improves on the Wang-Xing-Safavi-Naini bound. Finally, we point out that a family of known Steiner structures is actually a fam...
Inflation with a constant rate of roll
Motohashi, Hayato; Starobinsky, Alexei A.; Yokoyama, Jun'ichi
2015-09-01
We consider an inflationary scenario where the rate of inflaton roll defined by ̈phi/H dot phi remains constant. The rate of roll is small for slow-roll inflation, while a generic rate of roll leads to the interesting case of 'constant-roll' inflation. We find a general exact solution for the inflaton potential required for such inflaton behaviour. In this model, due to non-slow evolution of background, the would-be decaying mode of linear scalar (curvature) perturbations may not be neglected. It can even grow for some values of the model parameter, while the other mode always remains constant. However, this always occurs for unstable solutions which are not attractors for the given potential. The most interesting particular cases of constant-roll inflation remaining viable with the most recent observational data are quadratic hilltop inflation (with cutoff) and natural inflation (with an additional negative cosmological constant). In these cases even-order slow-roll parameters approach non-negligible constants while the odd ones are asymptotically vanishing in the quasi-de Sitter regime.
Environment-Dependent Fundamental Physical Constants
Terazawa, Hidezumi
2012-01-01
A theory of special inconstancy, in which some fundamental physical constants such as the fine-structure and gravitational constants may vary, is proposed in pregeometry. In the special theory of inconstancy, the \\alpha-G relation of \\alpha=3\\pi/[16ln(4\\pi/5GM_W^2)] between the varying fine-structure and gravitaional constants (where M_W is the charged weak boson mass) is derived from the hypothesis that both of these constants are related to the same fundamental length scale in nature. Furthermore, it leads to the prediction of dot{{\\alpha}}/\\alpha=(-0.8\\pm2.5)\\times10^{-14}yr^{-1} from the most precise limit of dot{G}/G=(-0.6\\pm2.0)\\times10^{-12}yr^{-1} by Thorsett, which is not only consistent with the recent observation of dot{{\\alpha}}/\\alpha=(0.5\\pm0.5)\\times10^{-14}yr^{-1} by Webb et al. but also feasible for future experimental tests. Also a theory of general inconstancy, in which any fundamental physical constants may vary, is proposed in "more general relativity", by assuming that the space-time is ...
Athermal nonlinear elastic constants of amorphous solids.
Karmakar, Smarajit; Lerner, Edan; Procaccia, Itamar
2010-08-01
We derive expressions for the lowest nonlinear elastic constants of amorphous solids in athermal conditions (up to third order), in terms of the interaction potential between the constituent particles. The effect of these constants cannot be disregarded when amorphous solids undergo instabilities such as plastic flow or fracture in the athermal limit; in such situations the elastic response increases enormously, bringing the system much beyond the linear regime. We demonstrate that the existing theory of thermal nonlinear elastic constants converges to our expressions in the limit of zero temperature. We motivate the calculation by discussing two examples in which these nonlinear elastic constants play a crucial role in the context of elastoplasticity of amorphous solids. The first example is the plasticity-induced memory that is typical to amorphous solids (giving rise to the Bauschinger effect). The second example is how to predict the next plastic event from knowledge of the nonlinear elastic constants. Using the results of our calculations we derive a simple differential equation for the lowest eigenvalue of the Hessian matrix in the external strain near mechanical instabilities; this equation predicts how the eigenvalue vanishes at the mechanical instability and the value of the strain where the mechanical instability takes place.
MID IR Optical Constants of Orthopyroxenes.
Rucks, M.; Glotch, T. D.
2014-12-01
Orthopyroxenes are common rock forming minerals that are present on many planetary bodies as well as meteorites and cosmic dust. The presence of these minerals can give implications to the petrogenic history of these planetary bodies. Optical constants, n and k, are essential inputs into radiative transfer models which are used in remote sensing techniques. [1,2] While optical constants have been determined for orthopyroxenes with high Mg content, Fe rich orthopyroxenes have not been studied as extensively. [3] The goal of this research is to determine the optical constants of orthopyroxenes ranging in composition along the enstatite-ferrosilite solid solution, to gain a more comprehensive list of these values. Specular reflectance spectra, in the range of 250-4000 cm-1, were obtained for several oriented single crystal samples at three crystallographic orientations for each sample. Optical constants, n and k, were then derived through modeling of measured spectra using the Matlab lsqcurvefit function. Preveous work has identified the optical constants for two Mg rich natural samples, enstatite and hypersthene. Current research applies the above methodology to synthetic ferrosilite, the Fe rich end-member of the orthopyroxene mineral series. Future studies will provide a more comprehensive look at the variation of n and k as a function of the Mg:Fe composition. [1] Arnold, J.A. et al (2013) (under review), [2] Glotch, T.D. and Rossman, G.R. (2009) Icarus, [3] Jäger, C. et al (1998) Astron. Astrophys.
The case for the cosmological constant
Varun Sahni
2000-07-01
I present a short overview of current observational results and theoretical models for a cosmological constant. The main motivation for invoking a small cosmological constant (or -term) at the present epoch has to do with observations of high redshift Type Ia supernovae which suggest an accelerating universe. A ﬂat accelerating universe is strongly favoured by combining supernovae observations with observations of CMB anisotropies on degree scales which give the `best-ﬁt’ values ≃ 0.7 and m ≃ 0.3. A time dependent cosmological -term can be generated by scalar ﬁeld models with exponential and power law potentials. Some of these models can alleviate the `ﬁne tuning’ problem which faces the cosmological constant.
Bounds on Gromov Hyperbolicity Constant in Graphs
José M Rodríguez; José M Sigarreta
2012-02-01
If is a geodesic metric space and 1,2,3 $\\in$ , a geodesic triangle ={1,2,3} is the union of the three geodesics [1,2], [2,3] and [31] in . The space is -hyperbolic (in the Gromov sense) if any side of is contained in a -neighborhood of the union of two other sides, for every geodesic triangle in . If is hyperbolic, we denote by () the sharp hyperbolicity constant of , i.e. ()=$inf{$≥ 0$ : is -hyperbolic}. In this paper we relate the hyperbolicity constant of a graph with some known parameters of the graph, as its independence number, its maximum and minimum degree and its domination number. Furthermore, we compute explicitly the hyperbolicity constant of some class of product graphs.
Construction and experimental testing of the constant-bandwidth constant-temperature anemometer.
Ligeza, P
2008-09-01
A classical constant-temperature hot-wire anemometer enables the measurement of fast-changing flow velocity fluctuations, although its transmission bandwidth is a function of measured velocity. This may be a source of significant dynamic errors. Incorporation of an adaptive controller into the constant-temperature system results in hot-wire anemometer operating with a constant transmission bandwidth. The construction together with the results of experimental testing of a constant-bandwidth hot-wire anemometer prototype are presented in this article. During the testing, an approximately constant transmission bandwidth of the anemometer was achieved. The constant-bandwidth hot-wire anemometer can be used in measurements of high-frequency variable flows characterized by a wide range of velocity changes.
Constant force extensional rheometry of polymer solutions
Szabo, Peter; McKinley, Gareth H.; Clasen, Christian
2012-01-01
We revisit the rapid stretching of a liquid filament under the action of a constant imposed tensile force, a problem which was first considered by Matta and Tytus [J. Non-Newton. Fluid Mech. 35 (1990) 215–229]. A liquid bridge formed from a viscous Newtonian fluid or from a dilute polymer solution...... filament can be probed. In particular, we show that with this constant force pull (CFP) technique it is possible to readily impose very large material strains and strain rates so that the maximum extensibility of the polymer molecules may be quantified. This unique characteristic of the experiment...
Do the fundamental constants change with time ?
Kanekar, Nissim
2008-01-01
Comparisons between the redshifts of spectral lines from cosmologically-distant galaxies can be used to probe temporal changes in low-energy fundamental constants like the fine structure constant and the proton-electron mass ratio. In this article, I review the results from, and the advantages and disadvantages of, the best techniques using this approach, before focussing on a new method, based on conjugate satellite OH lines, that appears to be less affected by systematic effects and hence holds much promise for the future.
Porous low dielectric constant materials for microelectronics.
Baklanov, Mikhail R; Maex, Karen
2006-01-15
Materials with a low dielectric constant are required as interlayer dielectrics for the on-chip interconnection of ultra-large-scale integration devices to provide high speed, low dynamic power dissipation and low cross-talk noise. The selection of chemical compounds with low polarizability and the introduction of porosity result in a reduced dielectric constant. Integration of such materials into microelectronic circuits, however, poses a number of challenges, as the materials must meet strict requirements in terms of properties and reliability. These issues are the subject of the present paper.
The Cosmological Constant Problem (2/2)
CERN. Geneva
2015-01-01
I will review the cosmological constant problem as a serious challenge to our notion of naturalness in Physics. Weinberg’s no go theorem is worked through in detail. I review a number of proposals possibly including Linde's universe multiplication, Coleman's wormholes, the fat graviton, and SLED, to name a few. Large distance modifications of gravity are also discussed, with causality considerations pointing towards a global modification as being the most sensible option. The global nature of the cosmological constant problem is also emphasized, and as a result, the sequestering scenario is reviewed in some detail, demonstrating the cancellation of the Standard Model vacuum energy through a global modification of General Relativity.
The Cosmological Constant Problem (1/2)
CERN. Geneva
2015-01-01
I will review the cosmological constant problem as a serious challenge to our notion of naturalness in Physics. Weinberg’s no go theorem is worked through in detail. I review a number of proposals possibly including Linde's universe multiplication, Coleman's wormholes, the fat graviton, and SLED, to name a few. Large distance modifications of gravity are also discussed, with causality considerations pointing towards a global modification as being the most sensible option. The global nature of the cosmological constant problem is also emphasized, and as a result, the sequestering scenario is reviewed in some detail, demonstrating the cancellation of the Standard Model vacuum energy through a global modification of General Relativity.
A Memorandum Report: Physical Constants of MCE
2016-08-01
A MEMORANDUM REPORT: PHYSICAL CONSTANTS OF MCE ECBC-TR-1289 B.L. Harris CHEMICAL WARFARE SERVICE August 2016 Approved for public release...MCE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Harris , B.L. 5d. PROJECT NUMBER A 1.13 5e. TASK NUMBER 5f...original 1945 publication. Note from Reviewers This version is a reprint with corrections of Harris , B.L. A Memorandum Report: Physical Constants of
Variations of fundamental constants and multidimensional gravity
Bronnikova, K. A.; Skvortsova, M. V.
We try to explain the recently reported large-scale spatial variations of the fine structure constant α, in agreement with other cosmological observations, in the framework of curvature-nonlinear multidimensional gravity. The original theory is reduced to a scalar-tensor theory in four dimensions, and the corresponding isotropic cosmologies are considered in both Einstein and Jordan conformal frames. In the Jordan frame one obtains simultaneous variations of α and the gravitational constant G, equal in magnitude. Long-wave small inhomogeneous perturbations of isotropic models allow for explaining spatial variations of α.
Optimizing constant wavelength neutron powder diffractometers
Cussen, Leo D., E-mail: leo@cussenconsulting.com
2016-06-11
This article describes an analytic method to optimize constant wavelength neutron powder diffractometers. It recasts the accepted mathematical description of resolution and intensity in terms of new variables and includes terms for vertical divergence, wavelength and some sample scattering effects. An undetermined multiplier method is applied to the revised equations to minimize the RMS value of resolution width at constant intensity and fixed wavelength. A new understanding of primary spectrometer transmission (presented elsewhere) can then be applied to choose beam elements to deliver an optimum instrument. Numerical methods can then be applied to choose the best wavelength.
Degravitation of the Cosmological Constant in Bigravity
Platscher, Moritz
2016-01-01
In this article the phenomenon of degravitation of the cosmological constant is studied in the framework of bigravity. It is demonstrated that despite a sizable value of the cosmological constant its gravitational effect can be only mild. The bigravity framework is chosen for this demonstration as it leads to a consistent, ghost-free theory of massive gravity. We show that degravitation takes place in the limit where the physical graviton is dominantly a gauge invariant metric combination. We present and discuss several phenomenological consequences expected in this regime.
Black Ring with a Positive Cosmological Constant
Chu, C S; Chu, Chong-Sun; Dai, Shou-Huang
2007-01-01
We construct a black ring with a cosmological constant in the five dimensional N=4 de Sitter supergravity theory. The black ring preserves half of the de Sitter supersymmetries. Unlike the flat case, this black ring is not rotating and the stability against gravitational self-attraction is balanced by the cosmological repulsion due to the cosmological constant. The black ring carries a dipole charge and this charge contributes to the first law of thermodynamics. The black ring has an entropy and mass which conform to the entropic N-bound proposal and the maximal mass conjecture.
Cosmological constant, supersymmetry, nonassociativity, and big numbers
Dzhunushaliev, Vladimir [KazNU, Department of Theoretical and Nuclear Physics, Almaty (Kazakhstan); IETP, Al-Farabi KazNU, Almaty (Kazakhstan)
2015-02-01
The nonassociative generalization of supersymmetry is considered. It is shown that the associator of four supersymmetry generators has the coefficient ∝ ℎ/l{sub 0}{sup 2} where l0 is some characteristic length. Two cases are considered: (a) l{sub 0}{sup -2} coincides with the cosmological constant; (b) l{sub 0} is the classical radius of the electron. It is also shown that the scaled constant is of the order of 10{sup -120} for the first case and 10{sup -30} for the second case. The possible manifestation and smallness of nonassociativity is discussed. (orig.)
Flexible alternatives to constant frequency systems
Stewart-Wilson, John
The use of hybrid systems in which variable frequency is used as generated, with a proportion being converted to constant frequency by electronic conversion, is examined as a flexible alternative to constant frequency systems. Here, some practical solutions to the technical issues raised by adopting the more flexible approach to electrical system generation are presented. In particular, attention is given to the frequency ranges used, impact on aircraft equipment, motor-driven equipment, transformer rectifier units, lighting, and avionics. The discussion also covers fan-assisted galley ovens, system architecture, special airworthiness requirements, and power quality.
Atomic weights: no longer constants of nature
Coplen, Tyler B.; Holden, Norman E.
2011-01-01
Many of us were taught that the standard atomic weights we found in the back of our chemistry textbooks or on the Periodic Table of the Chemical Elements hanging on the wall of our chemistry classroom are constants of nature. This was common knowledge for more than a century and a half, but not anymore. The following text explains how advances in chemical instrumentation and isotopic analysis have changed the way we view atomic weights and why they are no longer constants of nature
Coulomb field in a constant electromagnetic background
Adorno, T C; Shabad, A E
2016-01-01
Nonlinear Maxwell equations are written up to the third-power deviations from a constant-field background, valid within any local nonlinear electrodynamics including QED with Euler-Heisenberg effective Lagrangian. Linear electric response to imposed static finite-sized charge is found in the vacuum filled by an arbitrary combination of constant and homogeneous electric and magnetic fields. The modified Coulomb field, corrections to the total charge and to the charge density are given in terms of derivatives of the effective Lagrangian with respect to the field invariants.
Du Pan; Liu Shuna; Wu Ping [College of Chemistry and Environmental Science, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing 210097 (China); Cai Chenxin [College of Chemistry and Environmental Science, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing 210097 (China)], E-mail: cxcai@njnu.edu.cn
2007-12-31
This paper reports a new type of nanocomposite of poly(nile blue A) with single-walled carbon nanotubes (PNb-SWNTs). This nanocomposite was fabricated by the functionalization of SWNTs with poly(nile blue A), which was formed by electropolymerizing an Nb monomer through the use of cyclic voltammetry. Scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV-vis), cyclic voltammetry and electrochemical impedance spectroscopy (EIS) were used to characterize the PNb-SWNTs. The cyclic voltammetric results indicated that PNb-SWNTs were able to electrocatalyze the oxidation of NADH at a very low potential (ca. -80 mV versus SCE) and lead to a substantial decrease in the overpotential by more than 700 mV compared with the bare glassy carbon (GC) electrode. A biosensor, ADH-PNb-SWNT/GC, was developed by immobilizing alcohol dehydrogenase (ADH) onto the PNb-SWNT/GC electrode surface. The biosensor showed electrocatalytic activity toward the oxidation of ethanol with a good stability, reproducibility, and higher biological affinity. Under optimal conditions, the electrochemical response to detect ethanol has the typical characteristics of Michaelis-Menten kinetics with an apparent Michaelis-Menten constant of K{sub M}{sup app} {approx} 6.30 mM, and depends linearly on the concentration of ethanol from 0.1 to 3.0 mM (with a correlation coefficient of 0.998), with a detection limit of {approx}50 {mu}M (at a signal-to-noise ratio of 3). The facile procedure of immobilizing ADH used in the present work can promote the development of electrochemical research for enzymes (proteins), biosensors, biofuel cells and other bioelectrochemical devices.
What can be observed in real time PCR and when does it show?
Chigansky, Pavel; Jagers, Peter; Klebaner, Fima C
2017-06-30
Real time, or quantitative, PCR typically starts from a very low concentration of initial DNA strands. During iterations the numbers increase, first essentially by doubling, later predominantly in a linear way. Observation of the number of DNA molecules in the experiment becomes possible only when it is substantially larger than initial numbers, and then possibly affected by the randomness in individual replication. Can the initial copy number still be determined? This is a classical problem and, indeed, a concrete special case of the general problem of determining the number of ancestors, mutants or invaders, of a population observed only later. We approach it through a generalised version of the branching process model introduced in Jagers and Klebaner (J Theor Biol 224(3):299-304, 2003. doi: 10.1016/S0022-5193(03)00166-8 ), and based on Michaelis-Menten type enzyme kinetical considerations from Schnell and Mendoza (J Theor Biol 184(4):433-440, 1997). A crucial role is played by the Michaelis-Menten constant being large, as compared to initial copy numbers. In a strange way, determination of the initial number turns out to be completely possible if the initial rate v is one, i.e all DNA strands replicate, but only partly so when [Formula: see text], and thus the initial rate or probability of succesful replication is lower than one. Then, the starting molecule number becomes hidden behind a "veil of uncertainty". This is a special case, of a hitherto unobserved general phenomenon in population growth processes, which will be adressed elsewhere.
Ultrasound mediated enzymatic hydrolysis of cellulose and carboxymethyl cellulose.
Sulaiman, Ahmad Ziad; Ajit, Azilah; Chisti, Yusuf
2013-01-01
A recombinant Trichoderma reesei cellulase was used for the ultrasound-mediated hydrolysis of soluble carboxymethyl cellulose (CMC) and insoluble cellulose of various particle sizes. The hydrolysis was carried out at low intensity sonication (2.4-11.8 W cm(-2) sonication power at the tip of the sonotrode) using 10, 20, and 40% duty cycles. [A duty cycle of 10%, for example, was obtained by sonicating for 1 s followed by a rest period (no sonication) of 9 s.] The reaction pH and temperature were always 4.8 and 50°C, respectively. In all cases, sonication enhanced the rate of hydrolysis relative to nonsonicated controls. The hydrolysis of CMC was characterized by Michaelis-Menten kinetics. The Michaelis-Menten parameter of the maximum reaction rate Vmax was enhanced by sonication relative to controls, but the value of the saturation constant Km was reduced. The optimal sonication conditions were found to be a 10% duty cycle and a power intensity of 11.8 W cm(-2) . Under these conditions, the maximum rate of hydrolysis of soluble CMC was nearly double relative to control. In the hydrolysis of cellulose, an increasing particle size reduced the rate of hydrolysis. At any fixed particle size, sonication at a 10% duty cycle and 11.8 W cm(-2) power intensity improved the rate of hydrolysis relative to control. Under the above mentioned optimal sonication conditions, the enzyme lost about 20% of its initial activity in 20 min. Sonication was useful in accelerating the enzyme catalyzed saccharification of cellulose. © 2013 American Institute of Chemical Engineers.
Hargono Hargono
2017-05-01
Full Text Available Starch is a potential substrate for this purpose, but the extra cost is needed to hydrolyze it into reducing sugar. As an alternative to the expensive and energy demanding conventional hydrolysis process, the low-temperature hydrolysis is being studied. Granular Starch Hydrolysing Enzyme (GSHE was used in the process to degrade starch into reducing sugar at 30°C and pH 4. The substrates included bitter cassava flour, sweet cassava starch, and gadung flour. Starch concentrations studied were 50, 100, 150, 200, 250, 300, 350, and 400 g/L, respectively, while concentration of enzyme was 1.5 % (w/w. The optimum condition of the process was hydrolysis using 200 g/L of substrate concentration and enzyme concentration of 1.5% for 12 h. It was found that the reducing sugar was 49.3 g/L and the productivity of reducing sugar (Qrs was 4.11 (gL-1 h-1. Lineweaver-Burk plot of Michaelis-Menten equation was used to study the inhibition kinetics. The Michaelis-Menten constants (Km for these three substrates were determined as 141.64 g/L, 137,64 g/L and 140.84 g/L for bitter cassava flour, sweet cassava starch, and gadung flour, respectively. The value of Vm/Km, which denotes the affinity of the enzyme to the substrate, were determined and compared, and the result showed that the affinity (Vm to the enzyme to this substrate followed the order of sweet cassava starch˃ bitter cassava flour˃ gadung flour, and all are non-competitive inhibitor, while the Ki value was 0.022 h -1.
Holzapfel, K.; Mueller, S.A.; Seidl, C.; Schwaiger, M.; Senekowitsch-Schmidtke, R. [Dept. of Nuclear Medicine, Technical Univ. of Munich (Germany); Grosu, A.L. [Dept. of Radiation Oncology, Technical Univ. of Munich (Germany)
2008-06-15
Background and purpose: choline positron emission tomography (PET) can help to optimize radiation treatment strategy of prostate cancer. Therefore, the aim of this study was to elucidate the effects of ionizing radiation on the choline uptake in an androgen-dependent (LNCaP) and an androgen-independent (PC3) prostate cancer cell line. Material and methods: uptake of [methyl-{sup 3}H]choline chloride was investigated between 4 and 96 h after irradiation with 6 Gy. Dose dependence of choline uptake was examined following irradiation with 2-12 Gy, and cell survival was analyzed via the clonogenic assay. Michaelis-Menten kinetics was determined 24 h (PC3) and 48 h (LNCaP) after irradiation with 6 Gy. Results: PC3 cells showed a significant transitory increase of [methyl-{sup 3}H]choline uptake with a maximum at 24 h after irradiation. In LNCaP cells irradiation induced a significant decrease with a minimum at 48 h. Changes in choline uptake in both cell lines were almost dose-independent up to 12 Gy. Following irradiation with 6 Gy, transport capacity (v{sub max}) increased and Michaelis-Menten constant (K{sub M}) decreased in PC3 cells, while in LNCaP cells the two parameters behaved vice versa. Conclusion: changes in choline uptake following irradiation might be due to metabolic changes associated with initiation of processes that finally cause cell death. Thus, changes in tumor choline uptake monitored by PET after radiotherapy might not exclusively reflect therapeutic success but also altered tracer uptake as a consequence of irradiation. (orig.)
LIU,Shu-Na; YIN,Ya-Jing; CAI,Chen-Xin
2007-01-01
The negatively charged(at pH 8.2)glucose oxidase(GOx,pl ca.4.2)was assembled onto the surface of single-walled carbon nanotubes(SWNT),which was covered(or wrapped)by a layer of positively charged polyelectrolyte poly(dimethyldiallylammonium chloride)(PDDA),via the electrostatic interaction forming GOx-PDDA-SWNT nanocomposites.Fourier transform infrared(FTIR),UV-Vis and electrochemical impedance spectroscopy (EIS)were used to characterize the growth processes of the nanocomposites.The results indicated that GOx retained its native secondary conformational structure after it was immobilized on the surface of PDDA-SWNT. A biosensor(Nation-GOx-PDDA-SWNT/GC)was developed by immobilization of GOx-PDDA-SWNT nanocomposites on the surface of glassy carbon(GC)electrode using Nation(5%)as a binder. The biosensor showed the electrocatalytic activity toward the oxidation of glucose under the presence of ferrocene monocarboxylic acid(FcM) as an electroactive mediator with a good stability,reproducibility and higher biological affinity.Under an optimal condition,the biosensor could be used to detection of glucose,presenting a typical characteristic of Michaelis-Menten kinetics with the apparent Michaelis-Menten constant of Kapp/M ca.4.5 mmol/L,with a linear range of the concentrafion of glucose from 0.5 to 5.5 mmol/L(with correlation coefficient of 0.999)and the detection Iimit of ca.83μmol/L(at a signal-to-noise ratio of 3). Thus the biosensor was useful in sensing the glucose concentration in serum since the normal glucose concentration in blood serum was around 4.6 mmol/L.The facile procedure of immobilizing GOx used in present work would promote the developments of electrochemical research for enzymes(proteins). biosensors,biofuel cells and other bioelectrochemical devices.
Temperature-sensitive molecularly imprinted microgels with esterase activity%具酯酶活性的温敏型分子印迹微凝胶
王红飞; 杨浩; 张黎明
2011-01-01
Temperature-sensitive molecularly imprinted microgels (MIGs) exhibiting esterase activity were prepared by a reverse emulsion method using dialdehyde dextran-histidine conjugate (PAD-His) as the functional macromonomer and p-nitrophenyl phosphate (NPP) as the stable transition state analogue (TSA) as well as Co2+ as the coordination center. The catalytic activity of MIGs was greatly influenced by the template amount, and could be modulated by temperature. The hydrolysis kinetics ofp-nitrophenyl acetate (NPA) in the presence of MIGs could be described by the Michaelis-Menten equation. The Michaelis-Menten constant and maximium velocity were found to be 2.2×105 mol/L and 2.04×108 mol/h,respectively. In addition, the MIGs were found to have a high catalytic selectivity to NPA.%以双醛葡聚糖-组氨酸偶连物(PAD-His)为功能大单体、过渡态类似物p-硝基苯磷酸酯(NPP)为模板分子、Co2+为中心离子,采用油包水反相乳液法首次制得具有酯酶活性的温敏型分子印迹微凝胶(MIGs).催化水解实验表明,MIGs催化活性受模板分子用量的影响,并可通过温度进行有效调控.MIGs催化p-硝基乙酸苯酯(NPA)水解反应行为可用Michaelis-Menten方程进行描述,其最大催化水解反应速率和Michaelis-Menten常数分别为2.04×10-8 mol/h和2.2×10-5 mol/L,且具有较好的催化选择性.
M Iyan Sofyan
2004-12-01
Full Text Available The objectives of this research were: 1 to determine aeration rate and substrate concentration of pure cellulose to produce maximum glucose by Trichoderma reesei QM 9414 at 30 oC, and agitation 150 rpm; 2 to study the kinetics of pure cellulose fermentation by Trichoderma reesei QM 9414 to glucose and its implication upon fermentation of the lignin free rice straw. The experiment was arranged in factorial randomized complete design in three times replication. Treatments consisted of three levels of aeration (1,00 vvm; 1,5 vvm; 2,0 vvm and three levels of substrate concentration (0,75 ; 1,00 ; 1,25 % w/v. The results showed that at the exponential phase the average specific growth of Trichoderma reesei QM 9414 was 0,05374 hour-1, the maximum glucose product concentration of pure cellulose was 0.1644 gL-1,and the oxygen transfer was 0,0328 mg L-1 hour-1. According to t-test, the kinetics of pure cellulose fermentation model just the same as the lignin free rice straw fermentation.The enzymes produced by Trichoderma reesei QM 9414 in pure cellulose fermentation media followed the Michaelis-Menten model. The enzyme kinetic parameters were the maximum growth rate was 37x10-3 hour-1 and Michaelis-Menten constant was Ã‚Â½ maximum μ =17,5x10-3 hour-1. The volumetric oxygen transfer (KLa using rice straw was 0,0337 mg.hour-1. The value of KLa could be used for conversion from bioreactor at laboratory scale to commercial scale design.
2014-04-04
were determined by Michaelis - Menten steady state kinetics using Prism Graphpad (Irvine, CA). Kinetic data for CMP hydrolysis was used as a metric to...against CMP, paraoxon and phenyl acetate versus G3C9 expression in E. coli (Table 1). A closer examination of the Michaelis - Menten parameters reveals...0.05% BSA 1.09 ± 0.06 45 ± 9 24 ± 5 Table 2. Michaelis - Menten parameters for G3C9 CMP hydrolysis. G3C9 expressed in mammalian cells displayed
Quenched heavy-light decay constants
Baxter, R.M.; Booth, S.P.; Bowler, K.C.; Collins, S.; Henty, D.S.; Kenway, R.D.; Richards, D.G.; Shanahan, H.P.; Simone, J.N.; Simpson, A.D.; Wilkes, B.E. (Department of Physics, The University of Edinburgh, Edinburgh EH9 3JZ (United Kingdom)); Ewing, A.K.; Lellouch, L.; Sachrajda, C.T.; Wittig, H. (Physics Department, The University, Southampton SO9 5NH (United Kingdom)); (UKQCD Collaboration)
1994-02-01
We present results for heavy-light decay constants, using both propagating quarks and the static approximation, in [ital O]([ital a])-improved, quenched lattice QCD. At [beta]=6.2 on a 24[sup 3][times]48 lattice we find [ital f][sub [ital D
Timelike Constant Mean Curvature Surfaces with Singularities
Brander, David; Svensson, Martin
2014-01-01
We use integrable systems techniques to study the singularities of timelike non-minimal constant mean curvature (CMC) surfaces in the Lorentz–Minkowski 3-space. The singularities arise at the boundary of the Birkhoff big cell of the loop group involved. We examine the behavior of the surfaces at ...
Timelike Constant Mean Curvature Surfaces with Singularities
Brander, David; Svensson, Martin
2014-01-01
We use integrable systems techniques to study the singularities of timelike non-minimal constant mean curvature (CMC) surfaces in the Lorentz–Minkowski 3-space. The singularities arise at the boundary of the Birkhoff big cell of the loop group involved. We examine the behavior of the surfaces...
Benjamin Constant. Ontdekker van de moderne vrijheid
de Hert, Paul; Kinneging, A.; Colette, M.
2015-01-01
In 1806 analyseerde de Zwitsers-Franse politicus, filosoof en essayist Benjamin Constant (1767-1830) de moderne samenleving in zijn bekende boek Principes de politique. Uit dit klassiek geworden werk spreekt Constant’s ambivalentie en gevoel van nuance en subtiliteit. De “moderne” individuele
Einstein Spacetimes with Constant Weyl Eigenvalues
Barnes, Alan
2014-01-01
Einstein spacetimes (that is vacuum spacetimes possibly with a non-zero cosmological constant {\\Lambda}) with constant non-zero Weyl eigenvalus are considered. For type Petrov II & D this assumption allows one to prove that the non-repeated eigenvalue necessarily has the value 2{\\Lambda}/3 and it turns out that the only possible spacetimes are some Kundt-waves considered by Lewandowski which are type II and a Robinson-Bertotti solution of type D. For Petrov type I the only solution turns out to be a homogeneous pure vacuum solution found long ago by Petrov using group theoretic methods. These results can be summarised by the statement that the only vacuum spacetimes with constant Weyl eigenvalues are either homogeneous or are Kundt space- times. This result is similar to that of Coley et al. who proved their result for general spacetimes under the assumption that all scalar invariants constructed from the curvature tensor and all its derivatives were constant. Some preliminary results are also presented f...
Limitations of constant-force-feedback experiments.
Elms, Phillip J; Chodera, John D; Bustamante, Carlos J; Marqusee, Susan
2012-10-03
Single-molecule force spectroscopy has provided important insights into the properties and mechanisms of biological molecules and systems. A common experiment is to measure the force dependence of conformational changes at equilibrium. Here, we demonstrate that the commonly used technique of force feedback has severe limitations when used to evaluate rapid macromolecular conformational transitions. By comparing the force-dependent dynamics of three major classes of macromolecules (DNA, RNA, and protein) using both a constant-force-feedback and a constant-trap-position technique, we demonstrate a problem in force-feedback experiments. The finite response time of the instrument's force feedback can modify the behavior of the molecule, leading to errors in the reported parameters, such as the rate constants and the distance to the transition state, for the conformational transitions. We elucidate the causes of this problem and provide a simple test to identify and evaluate the magnitude of the effect. We recommend avoiding the use of constant force feedback as a method to study rapid conformational changes in macromolecules.
Pion decay constants in dense skyrmion matter
Lee H.-J.
2010-10-01
Full Text Available According to the QCD, the hadronic matter can have various phases with matter density and temperature. In general, when there is phase transition in a matter, it is known that a symmetry in the matter changes. In case of the hadronic matter, the chiral symmetry in the matter is expected to be restored when the matter density (or temperature increases. The actual order parameter with respect to the chiral symmetry in the hadronic matter is known as the quark condensate from the QCD, but the pion decay constant, corresponding to the radius of the chiral circle, plays the role of the order parameter in an eﬀective ﬁeld theoretical approach to the QCD. In this paper, by using the skyrmion model which is an eﬀective theory to the QCD, we construct the skyrmion matter as a model of the hadronic matter (nuclear matter and calculate the pion decay constant in the matter. Because of presence of the matter, the pion decay constant is split into the two components, the temporal component and the spatial component. We discuss the phase transition in the skyrmion matter and behavior of the two components of the decay constant for massless pion with density of the skyrmion matter.
Calculation of Thermochemical Constants of Propellants
K. P. Rao
1979-01-01
Full Text Available A method for calculation of thermo chemical constants and products of explosion of propellants from the knowledge of molecular formulae and heats of formation of the ingredients is given. A computer programme in AUTOMATH-400 has been established for the method. The results of application of the method for a number of propellants are given.
Cosmological constant influence on cosmic string spacetime
Abbassi, Amir H; 10.1103/physRevD.67.103504
2008-01-01
We investigate the line element of spacetime around a linear cosmic string in the presence of a cosmological constant. We obtain the metric and argue that it should be discarded because of asymptotic considerations. Then a time dependent and consistent form of the metric is obtained and its properties are discussed.
Hamiltonian constants for several new entire solutions
2008-01-01
Using the Hamiltonian identities and the corresponding Hamilto- nian constants for entire solutions of elliptic partial differential equations, we investigate several new entire solutions whose existence were shown recently, and show interesting properties of the solutions such as formulas for contact angles at infinity of concentration curves.
Can compactifications solve the cosmological constant problem?
Hertzberg, Mark P. [Institute of Cosmology, Department of Physics and Astronomy, Tufts University,574 Boston Ave, Medford, MA 02155 (United States); Center for Theoretical Physics, Department of Physics,Massachusetts Institute of Technology,77 Massachusetts Ave, Cambridge, MA 02139 (United States); Masoumi, Ali [Institute of Cosmology, Department of Physics and Astronomy, Tufts University,574 Boston Ave, Medford, MA 02155 (United States)
2016-06-30
Recently, there have been claims in the literature that the cosmological constant problem can be dynamically solved by specific compactifications of gravity from higher-dimensional toy models. These models have the novel feature that in the four-dimensional theory, the cosmological constant Λ is much smaller than the Planck density and in fact accumulates at Λ=0. Here we show that while these are very interesting models, they do not properly address the real cosmological constant problem. As we explain, the real problem is not simply to obtain Λ that is small in Planck units in a toy model, but to explain why Λ is much smaller than other mass scales (and combinations of scales) in the theory. Instead, in these toy models, all other particle mass scales have been either removed or sent to zero, thus ignoring the real problem. To this end, we provide a general argument that the included moduli masses are generically of order Hubble, so sending them to zero trivially sends the cosmological constant to zero. We also show that the fundamental Planck mass is being sent to zero, and so the central problem is trivially avoided by removing high energy physics altogether. On the other hand, by including various large mass scales from particle physics with a high fundamental Planck mass, one is faced with a real problem, whose only known solution involves accidental cancellations in a landscape.
Early publications about nonzero cosmological constant
Horvath, I
2012-01-01
In 2011 the Nobel Prize in Physics was awarded for the 1998 discovery of the nonzero cosmological constant. This discovery is very important and surely worth to receive the Nobel Prize. However, years earlier several papers had been published (Paal, Horvath, & Lukacs 1992; Holba et al. 1992, Holba et al. 1994) about a very similar discovery from observational data.
Teaching Nanochemistry: Madelung Constants of Nanocrystals
Baker, Mark D.; Baker, A. David
2010-01-01
The Madelung constants for binary ionic nanoparticles are determined. The computational method described here sums the Coulombic interactions of each ion in the particle without the use of partial charges commonly used for bulk materials. The results show size-dependent lattice energies. This is a useful concept in teaching how properties such as…
Discrete Higgs and the Cosmological Constant
Amore, Paolo; Diaz-Cruz, J Lorenzo
2008-01-01
It is proposed that the Higgs vacuum possesses a small-scale structure that can explain the large discrepancy between the predicted electroweak vacuum energy density and the observed cosmological constant. An effective Lagrangian description is employed to obtain modifications to the Standard Model predictions that can be tested at collider experiments.
Quantum electrodynamics and the fundamental constants
Peter J. Mohr
2000-07-01
Full Text Available the results of critical experiments and the theoretical expressions for these results written in terms of the constants. Many of the theoretical expressions are based on quantum electrodynamics (QED, so the consistency of the comparison provides a critical test of the validity of the theory.
LIOUVILLE'S THEOREM FOR LPDO WITH CONSTANT COEFFICIENTS
Han Yazhou; Luo Xuebo
2005-01-01
In this note, the authors consider a class of linear partial differential operators P(θ) with constant coefficients and prove that the operator P(θ) has Liouville property if and only if the polynomial P(iξ) doesn't have roots in Rn\\{O}.
The fine structure constant and habitable planets
Sandora, McCullen
2016-01-01
© 2016 IOP Publishing Ltd and Sissa Medialab srl .We use the existence of habitable planets to impose anthropic requirements on the fine structure constant, α. To this effect, we present two considerations that restrict its value to be very near the one observed. The first, that the end product...
Constant capacitance in nanopores of carbon monoliths.
García-Gómez, Alejandra; Moreno-Fernández, Gelines; Lobato, Belén; Centeno, Teresa A
2015-06-28
The results obtained for binder-free electrodes made of carbon monoliths with narrow micropore size distributions confirm that the specific capacitance in the electrolyte (C2H5)4NBF4/acetonitrile does not depend significantly on the micropore size and support the foregoing constant result of 0.094 ± 0.011 F m(-2).
Monopoly price discrimination with constant elasticity demand
Aguirre Pérez, Iñaki; Cowan, Simon George
2013-01-01
This paper presents new results on the welfare e¤ects of third-degree price discrimination under constant elasticity demand. We show that when both the share of the strong market under uniform pricing and the elasticity di¤erence between markets are high enough,then price discrimination not only can increase social welfare but also consumer surplus.
Cosmological models with constant deceleration parameter
Berman, M.S.; de Mello Gomide, F.
1988-02-01
Berman presented elsewhere a law of variation for Hubble's parameter that yields constant deceleration parameter models of the universe. By analyzing Einstein, Pryce-Hoyle and Brans-Dicke cosmologies, we derive here the necessary relations in each model, considering a perfect fluid.
Supersymmetry Breaking and the Cosmological Constant
Banks, T
2014-01-01
I review three attempts to explain the small value of the cosmological constant, and their connection to SUSY breaking. They are The String Landscape, Supersymmetric Large Extra Dimensions (SLED), and the Holographic Space-time Formalism invented by Fischler and myself.
Monopoly price discrimination with constant elasticity demand
Aguirre Pérez, Iñaki; Cowan, Simon George
2013-01-01
This paper presents new results on the welfare e¤ects of third-degree price discrimination under constant elasticity demand. We show that when both the share of the strong market under uniform pricing and the elasticity di¤erence between markets are high enough,then price discrimination not only can increase social welfare but also consumer surplus.
The Elastic Constants for Wrought Aluminum Alloys
Templin, R L; Hartmann, E C
1945-01-01
There are several constants which have been devised as numerical representations of the behavior of metals under the action of loadings which stress the metal within the range of elastic action. Some of these constants, such as Young's modulus of elasticity in tension and compression, shearing modulus of elasticity, and Poisson's ratio, are regularly used in engineering calculations. Precise tests and experience indicate that these elastic constants are practically unaffected by many of the factors which influence the other mechanical properties of materials and that a few careful determinations under properly controlled conditions are more useful and reliable than many determinations made under less favorable conditions. It is the purpose of this paper to outline the methods employed by the Aluminum Research Laboratories for the determination of some of these elastic constants, to list the values that have been determined for some of the wrought aluminum alloys, and to indicate the variations in the values that may be expected for some of the commercial products of these alloys.
Variation of the fine structure constant
Lipovka, Anton A
2016-01-01
In present paper we evaluate the fine structure constant variation which should take place as the Universe is expanded and its curvature is changed adiabatically. This changing of the fine structure constant is attributed to the energy lost by physical system (consist of baryonic component and electromagnetic field) due to expansion of our Universe. Obtained ratio (d alpha)/alpha = 1. 10{-18} (per second) is only five times smaller than actually reported experimental limit on this value. For this reason this variation can probably be measured within a couple of years. To argue the correctness of our approach we calculate the Planck constant as adiabatic invariant of electromagnetic field, from geometry of our Universe in the framework of the pseudo- Riemannian geometry. Finally we discuss the double clock experiment based on Al+ and Hg+ clocks carried out by T. Rosenband et al. (Science 2008). We show that in this particular case there is an error in method and this way the fine structure constant variation c...
Microwave spectrum and molecular constants of indole
Nesvadba, Radim; Studecký, Tomáš; Uhlíková, Tereza; Urban, Štěpán
2017-09-01
Every single person has a certain characteristic group of scent molecules. The microwave spectra of the organic compounds of scent could be useful for the identification of people, but a database of spectra of scent molecules needs to be created first. The spectrum of indole, that is among the human scent molecules, was measured in the frequency range of 7.5-19 GHz under the conditions of supersonic expansion in a pulse emission Fourier Transform Microwave Spectrometer (FTMW) with a Fabry-Perot resonator. The high resolution of the spectrometer enables the detection of rotational transitions with hyperfine splitting. A total of 37 new rotational transitions were measured and analyzed using the PGOPHER software to derive the rotational and centrifugal distortion constants, as well as the 14N nuclear quadrupole coupling constants. The molecular constants were determined with approximately two orders of magnitude greater accuracy as compared with some earlier studies of indole. The obtained data and constants of indole are the first step towards the development of a database of the human scent molecules.
When is the growth index constant?
Polarski, David; Starobinsky, Alexei A.; Giacomini, Hector
2016-12-01
The growth index γ is an interesting tool to assess the phenomenology of dark energy (DE) models, in particular of those beyond general relativity (GR). We investigate the possibility for DE models to allow for a constant γ during the entire matter and DE dominated stages. It is shown that if DE is described by quintessence (a scalar field minimally coupled to gravity), this behaviour of γ is excluded either because it would require a transition to a phantom behaviour at some finite moment of time, or, in the case of tracking DE at the matter dominated stage, because the relative matter density Ωm appears to be too small. An infinite number of solutions, with Ωm and γ both constant, are found with wDE = 0 corresponding to Einstein-de Sitter universes. For all modified gravity DE models satisfying Geff >= G, among them the f(R) DE models suggested in the literature, the condition to have a constant wDE is strongly violated at the present epoch. In contrast, DE tracking dust-like matter deep in the matter era, but with Ωm G and an example is given using scalar-tensor gravity for a range of admissible values of γ. For constant wDE inside GR, departure from a quasi-constant value is limited until today. Even a large variation of wDE may not result in a clear signature in the change of γ. The change however is substantial in the future and the asymptotic value of γ is found while its slope with respect to Ωm (and with respect to z) diverges and tends to ‑∞.
Pawlowski, F; Jorgensen, P; Olsen, Jeppe
2002-01-01
-Fock vibration-rotation interaction constants have an accuracy similar to that obtained by a direct minimization of the CCSD(T) energy. The most accurate vibration-rotation interaction constants are those calculated at the CCSD(T)/cc-pVQZ level. The equilibrium bond distances determined from these interaction...
Chen,Guochu; Zhang,Lin; Hao,Ninmei; Liu,Xianguang; Wang,Junhong
2003-01-01
Guided by the principle of neural network, an intelligent PID controller based on neural network is devised and applied to control of constant temperature and constant liquidlevel system. The experiment results show that this controller has high accuracy and strong robustness and good characters.
Moura, Clarissa de Almeida; Lima, Jéssica Polyana da Silva; Silveira, Vanessa Augusta Magalhães; Miguel, Mário André Leocadio; Luchiari, Ana Carolina
2017-02-20
The ability to learn about the signs of variability in space and time is known as time place learning (TPL). To adjust their circadian rhythms, animals use stimuli that change regularly, such as the light-dark cycle, temperature, food availability or even social stimuli. Because light-dark cycle is the most important environmental temporal cue, we asked how a diurnal animal would perform TPL if this cue was removed. Zebrafish has been extensively studied in the chronobiology area due to it diurnal chronotype, thus, we studied the effects of constant light and constant dark on the time-place learning and activity profile in zebrafish. Our data show that while under constant light and dark condition zebrafish was not able of TPL, after 30days under the constant conditions, constant light led to higher activity level and less significant (robust) 24h rhythm.
Frequency Dependence of Attenuation Constant of Dielectric Materials
A. S. Zadgaonkar
1975-01-01
Full Text Available Different dielectric materials have been studied for frequency dependence of attenuation constant. The sensitive cathode ray oscillograph method has been used to evaluate to the dielectric constant and loss factor, and from these attenuation constants have been calculated. The temperature remaining constant, a regular increase has been observed in attenuation constant, at higher frequencies of electro-magnetic propagating wave.
Fat Euclidean Gravity with Small Cosmological Constant
Sundrum, Raman
2003-01-01
The cosmological constant problem is usually considered an inevitable feature of any effective theory capturing well-tested gravitational and matter physics, without regard to the details of short-distance gravitational couplings. In this paper, a subtle effective description avoiding the problem is presented in a first quantized language, consistent with experiments and the Equivalence Principle. First quantization allows a minimal domain of validity to be carved out by cutting on the proper length of particle worldlines. This is facilitated by working in (locally) Euclidean spacetime, although considerations of unitarity are still addressed by analytic continuation from Lorentzian spacetime. The new effective description demonstrates that the cosmological constant problem {\\it is} sensitive to short-distance details of gravity, which can be probed experimentally. ``Fat Gravity'' toy models are presented, illustrating how gravity might shut off at short but testable distances, in a generally covariant manner...
Negative Energy Cosmology and the Cosmological Constant
Prokopec, Tomislav
2011-01-01
It is well known that string theories naturally compactify on anti-de Sitter spaces, and yet cosmological observations show no evidence of a negative cosmological constant in the early Universe's evolution. In this letter we present two simple nonlocal modifications of the standard Friedmann cosmology that can lead to observationally viable cosmologies with an initial (negative) cosmological constant. The nonlocal operators we include are toy models for the quantum cosmological backreaction. In Model I an initial quasiperiodic oscillatory epoch is followed by inflation and a late time matter era, representing a dark matter candidate. The backreaction in Model II quickly compensates the negative cosmological term such that the Ricci curvature scalar rapidly approaches zero, and the Universe ends up in a late time radiation era.
Pole placement with constant gain output feedback
Sridhar, B.; Lindorff, D. P.
1972-01-01
Given a linear time invariant multivariable system with m inputs and p outputs, it was shown that p closed loop poles of the system can be preassigned arbitrarily using constant gain output feedback provided (A circumflex, B circumflex) is controllable. These data show that if (A circumflex, B circumflex, C circumflex) is controllable and observable, and Rank B circumflex = m, Rank C circumflex = p, then max (m,p) poles of the system can be assigned arbitarily using constant gain output feedback. Further, it is shown that in some cases more than max (m,p) poles can be arbitrarily assigned. A least square design technique is outlined to approximate the desired pole locations when it is not possible to place all the poles.
Lattice Boltzmann model with nearly constant density.
Fang, Hai-ping; Wan, Rong-zheng; Lin, Zhi-fang
2002-09-01
An improved lattice Boltzmann model is developed to simulate fluid flow with nearly constant fluid density. The ingredient is to incorporate an extra relaxation for fluid density, which is realized by introducing a feedback equation in the equilibrium distribution functions. The pressure is dominated by the moving particles at a node, while the fluid density is kept nearly constant and explicit mass conservation is retained as well. Numerical simulation based on the present model for the (steady) plane Poiseuille flow and the (unsteady) two-dimensional Womersley flow shows a great improvement in simulation results over the previous models. In particular, the density fluctuation has been reduced effectively while achieving a relatively large pressure gradient.
Quantum Exclusion of Positive Cosmological Constant?
Dvali, Gia
2014-01-01
We show that a positive cosmological constant is incompatible with the quantum-corpuscular resolution of de Sitter metric in form of a coherent state. The reason is very general and is due to the quantum self-destruction of the coherent state because of the scattering of constituent graviton quanta. This process creates an irreversible quantum clock, which precludes eternal de Sitter. It also eliminates the possibility of Boltzmann brains and Poincare recurrences. This effect is expected to be part of any microscopic theory that takes into account the quantum corpuscular structure of the cosmological background. This observation puts the cosmological constant problem in a very different light, promoting it, from a naturalness problem, into a question of quantum consistency. We are learning that quantum gravity cannot tolerate exceedingly-classical sources.
Mechanism for a Decaying Cosmological Constant
Bisabr, Y
2002-01-01
A mechanism is introduced to reduce a large cosmological constant to a sufficiently small value consistent with observational upper limit. The basic ingradient in this mechanism is a distinction which has been made between the two unit systems used on cosmology and particle physics. We have used a conformal invariant gravitational model to define a particular conformal frame in terms of the large scale properties of the universe. It is then argued that the contributions of mass scales in particle physics to the vacuum energy density should be considered in a different conformal frame. In this manner a cancellation mechanism is presented in which the conformal factor plays a key role to relax the large effective cosmological constant.
Cosmological Constant or Variable Dark Energy?
XU Li-Xin; ZHANG Cheng-Wu; LIU Hong-Ya
2007-01-01
@@ Selection statics of the Akaike information criterion (AIC) model and the Bayesian information criterion (BIC)model are applied to the Λ-cold dark matter (ΛCDM) cosmological model, the constant equation of state of dark energy, w =constant, and the parametrized equation of state of dark energy, w(z) = w0 + w1z/(1 + z),to determine which one is the better cosmological model to describe the evolution of the universe by combining the recent cosmic observational data including Sne Ia, the size of baryonic acoustic oscillation (BAO) peak from SDSS, the three-year WMAP CMB shift parameter. The results show that AIC, BIC and current datasets are not powerful enough to discriminate one model from the others, though odds suggest differences between them.
Regular Black Holes with Cosmological Constant
MO Wen-Juan; CAI Rong-Gen; SU Ru-Keng
2006-01-01
We present a class of regular black holes with cosmological constant Λ in nonlinear electrodynamics. Instead of usual singularity behind black hole horizon, all fields and curvature invariants are regular everywhere for the regular black holes. Through gauge invariant approach, the linearly dynamical stability of the regular black hole is studied. In odd-parity sector, we find that the Λ term does not appear in the master equations of perturbations, which shows that the regular black hole is stable under odd-parity perturbations. On the other hand, for the even-parity sector, the master equations are more complicated than the case without the cosmological constant. We obtain the sufficient conditions for stability of the regular black hole. We also investigate the thermodynamic properties of the regular black hole, and find that those thermodynamic quantities do not satisfy the differential form of first law of black hole thermodynamics. The reason for violating the first law is revealed.
Hyperscaling violation and the shear diffusion constant
Kolekar, Kedar S.; Mukherjee, Debangshu; Narayan, K.
2016-09-01
We consider holographic theories in bulk (d + 1)-dimensions with Lifshitz and hyperscaling violating exponents z , θ at finite temperature. By studying shear gravitational modes in the near-horizon region given certain self-consistent approximations, we obtain the corresponding shear diffusion constant on an appropriately defined stretched horizon, adapting the analysis of Kovtun, Son and Starinets. For generic exponents with d - z - θ > - 1, we find that the diffusion constant has power law scaling with the temperature, motivating us to guess a universal relation for the viscosity bound. When the exponents satisfy d - z - θ = - 1, we find logarithmic behaviour. This relation is equivalent to z = 2 +deff where deff =di - θ is the effective boundary spatial dimension (and di = d - 1 the actual spatial dimension). It is satisfied by the exponents in hyperscaling violating theories arising from null reductions of highly boosted black branes, and we comment on the corresponding analysis in that context.
Cylindrical wormholes with positive cosmological constant
Richarte, Mart'\\in G
2013-01-01
We construct cylindrical, traversable wormholes with finite radii by taking into account the cut-and-paste procedure for the case of cosmic string manifolds with a positive cosmological constant. Under reasonable assumptions about the equation of state of the matter located at the shell, we find that the wormhole throat undergoes a monotonous evolution provided it moves at a constant velocity. In order to explore the dynamical nonlinear behaviour of the wormhole throat, we consider that the matter at the shell is supported by anisotropic Chaplygin gas, anti-Chaplygin gas, or a mixed of Chaplygin and anti-Chaplygin gases implying that wormholes could suffer an accelerated expansion or contraction but the oscillatory behavior seems to be forbidden.
Cylindrical wormholes with positive cosmological constant
Richarte, Martín G.
2013-07-01
We construct cylindrical, traversable wormholes with finite radii by taking into account the cut-and-paste procedure for the case of cosmic string manifolds with a positive cosmological constant. Under reasonable assumptions about the equation of state of the matter located at the shell, we find that the wormhole throat undergoes a monotonous evolution provided it moves at a constant velocity. In order to explore the dynamical nonlinear behavior of the wormhole throat, we consider that the matter of the shell is supported by anisotropic Chaplygin gas, anti-Chaplygin gas, or a mixture of Chaplygin and anti-Chaplygin gases, implying that wormholes could suffer an accelerated expansion or contraction, but that oscillatory behavior seems to be forbidden.
The Cosmological Constant in the Quantum Multiverse
Larsen, Grant; Roberts, H L L
2011-01-01
Recently, a new framework for describing the multiverse has been proposed which is based on the principles of quantum mechanics. The framework allows for well-defined predictions, both regarding global properties of the universe and outcomes of particular experiments, according to a single probability formula. This provides complete unification of the eternally inflating multiverse and many worlds in quantum mechanics. In this paper we elucidate how cosmological parameters can be calculated in this framework, and study the probability distribution for the value of the cosmological constant. We consider both positive and negative values, and find that the observed value is consistent with the calculated distribution at an order of magnitude level. In particular, in contrast to the case of earlier measure proposals, our framework prefers a positive cosmological constant over a negative one. These results depend only moderately on how we model galaxy formation and life evolution therein.
Some Dynamical Effects of the Cosmological Constant
Axenides, M.; Floratos, E. G.; Perivolaropoulos, L.
Newton's law gets modified in the presence of a cosmological constant by a small repulsive term (antigravity) that is proportional to the distance. Assuming a value of the cosmological constant consistent with the recent SnIa data (Λ~=10-52 m-2), we investigate the significance of this term on various astrophysical scales. We find that on galactic scales or smaller (less than a few tens of kpc), the dynamical effects of the vacuum energy are negligible by several orders of magnitude. On scales of 1 Mpc or larger however we find that the vacuum energy can significantly affect the dynamics. For example we show that the velocity data in the local group of galaxies correspond to galactic masses increased by 35% in the presence of vacuum energy. The effect is even more important on larger low density systems like clusters of galaxies or superclusters.
Lectures on the Cosmological Constant Problem
Padilla, Antonio
2015-01-01
These lectures on the cosmological constant problem were prepared for the X Mexican School on Gravitation and Mathematical Physics. The problem itself is explained in detail, emphasising the importance of radiative instability and the need to repeatedly fine tune as we change our effective description. Weinberg's no go theorem is worked through in detail. I review a number of proposals including Linde's universe multiplication, Coleman's wormholes, the fat graviton, and SLED, to name a few. Large distance modifications of gravity are also discussed, with causality considerations pointing towards a global modification as being the most sensible option. The global nature of the cosmological constant problem is also emphasized, and as a result, the sequestering scenario is reviewed in some detail, demonstrating the cancellation of the Standard Model vacuum energy through a global modification of General Relativity.
Incompressible flows with piecewise constant density
Danchin, Raphaël
2012-01-01
We investigate the incompressible Navier-Stokes equations with variable density. The aim is to prove existence and uniqueness results in the case of discontinuous ini- tial density. In dimension n = 2, 3, assuming only that the initial density is bounded and bounded away from zero, and that the initial velocity is smooth enough, we get the local-in-time existence of unique solutions. Uniqueness holds in any dimension and for a wider class of velocity fields. Let us emphasize that all those results are true for piecewise constant densities with arbitrarily large jumps. Global results are established in dimension two if the density is close enough to a positive constant, and in n-dimension if, in addition, the initial velocity is small. The Lagrangian formula- tion for describing the flow plays a key role in the analysis that is proposed in the present paper.
The fine structure constant and numerical alchemy
Dattoli, Giuseppe
2010-01-01
We comment on past and more recent efforts to derive a formula yielding the fine structure constant in terms of integers and transcendent numbers. We analyse these "exoteric" attitudes and describe the myths regarding {\\alpha}, which seems to have very ancient roots, tracing back to Cabbala and to medieval alchemic conceptions. We discuss the obsession for this constant developed by Pauli and the cultural "environment" in which such an "obsession" grew. We also derive a simple formula for {\\alpha} in terms of two numbers {\\pi} and 137 only. The formula we propose reproduces the experimental values up to the last significant digit, it has not any physical motivation and is the result of an alchemic combination of numbers. We make a comparison with other existing formulae, discuss the relevant limits of validity by comparison with the experimental values and discuss a criterion to recover a physical meaning, if existing, from their mathematical properties.
Constant envelope chirped OFDM power efficiency
Dida, Mussa A.; Hao, Huan; Anjum, M. R.; Ran, Tao
2016-10-01
Fractional Fourier OFDM or simply chirped OFDM performs better in time-frequency selective channel than its convectional OFDM. Although chirped OFDM outperforms OFDM it still inherits Peak to Average Power Ratio (PAPR) drawback as a convectional OFDM. To eliminate PAPR drawback Constant Envelope OFDM was developed and for better performance in time frequency selective channel Constant Envelope Fractional Fourier OFDM (CE-COFDM) is used. Its BER performance is analyzed and compared to chirped OFDM and OFDM in AWGN and Rayleigh channel. The simulations show the BER performance of CE-COFDM is the same as chirped OFDM and OFDM. The power efficiency of CE-COFDM is also studied and different simulations performed shows CE-COFDM is more power efficient than chirped OFDM and convectional OFDM for class A and class B Linear Power Amplifier (LPA).
Daylight calculations using constant luminance curves
Betman, E. [CRICYT, Mendoza (Argentina). Laboratorio de Ambiente Humano y Vivienda
2005-02-01
This paper presents a simple method to manually estimate daylight availability and to make daylight calculations using constant luminance curves calculated with local illuminance and irradiance data and the all-weather model for sky luminance distribution developed in the Atmospheric Science Research Center of the University of New York (ARSC) by Richard Perez et al. Work with constant luminance curves has the advantage that daylight calculations include the problem's directionality and preserve the information of the luminous climate of the place. This permits accurate knowledge of the resource and a strong basis to establish conclusions concerning topics related to the energy efficiency and comfort in buildings. The characteristics of the proposed method are compared with the method that uses the daylight factor. (author)