An integrated modeling-experimental strategy for the analysis of metabolic pathways.

Abstract:

:An inherent problem in studying the behavior of a metabolic pathway is the impossibility of developing a complete, detailed model that includes all the cellular processes that have an impact on the set of fluxes in such a pathway. Lacking this, one requires some means of modeling the interactions between a metabolic pathway and other cellular processes for the purpose of analyzing pathway characteristics within the cell (e.g., determining sensitivity coefficients for various steps in the pathway) with a minimal amount of time and effort. A general framework is developed for studying these issues in a rigorous manner. Using this framework, detailed knowledge about a metabolic pathway (i.e., a set of rate expressions for steps in the pathway) can be combined with the results from a relatively simple set of experiments in order to obtain estimates for the sensitivity of the pathway to enzyme activities, inhibition constants, and other parameters that determine the pathway's behavior, while accounting for the pathway's interaction with the rest of the cellular metabolism. A model system representing amino acid production is used to illustrate the problem and to provide results based on computational experiments. The modeling strategy described here should be useful in genetic design to improve pathway fluxes and metabolic network selectivity.

journal_name

Math Biosci

journal_title

Mathematical biosciences

authors

Schlosser PM,Bailey JE

doi

10.1016/0025-5564(90)90049-5

subject

Has Abstract

pub_date

1990-06-01 00:00:00

pages

87-114

issue

1

eissn

0025-5564

issn

1879-3134

pii

0025-5564(90)90049-5

journal_volume

100

pub_type

杂志文章
  • Coding of information in models of tuberous electroreceptors.

    abstract::Weakly electric fish continuously emit a quasi-sinusoidal electric organ discharge (EOD) to probe their near environment (electrolocation). P-type tuberous receptors located on their skin respond to amplitude modulations of the EOD by varying their firing rate. These receptors, and the neuronal circuitry downstream fr...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2003.08.012

    authors: St-Hilaire M,Longtin A

    更新日期:2004-03-01 00:00:00

  • Probability density functions for axial ratios of sectioning profiles of anisotropically arranged elliptical microvessels.

    abstract::The article theoretically regards probability density functions (PDFs) for axial ratio (X/Y) of sectioning profiles of elliptical microvessels (MVs) arranged with anisotropy in a biological tissue volume. A technique for the PDF(X/Y) calculations in anisotropy of the elliptical MVs is described. The essence of this te...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2009.03.001

    authors: Krasnoperov RA,Gerasimov AN

    更新日期:2009-06-01 00:00:00

  • A Mathematical Model of Countercurrent Exchange of Oxygen Between Paired Arterioles and Venules.

    abstract::A mathematical model is formulated for diffusive countercurrent exchange of oxygen between paired arterioles and venules. A closed form solution of the problem is obtained by linearizing the nonlinear oxyhemoglobin dissociation curve at the inlet PO2 in the vessel. The closed form solution is compared with the corresp...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/0025-5564(88)90022-3

    authors: Sharan M,Popel AS

    更新日期:1988-09-01 00:00:00

  • Multi-timescale systems and fast-slow analysis.

    abstract::Mathematical models of biological systems often have components that vary on different timescales. This multi-timescale character can lead to problems when doing computer simulations, which can require a great deal of computer time so that the components that change on the fastest time scale can be resolved. Mathemati...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2016.07.003

    authors: Bertram R,Rubin JE

    更新日期:2017-05-01 00:00:00

  • Genetic oscillation deduced from Hopf bifurcation in a genetic regulatory network with delays.

    abstract::To understand how a gene regulatory network functioning as an oscillator is built, a genetic regulatory network with two transcriptional delays is investigated. We show by mathematical analysis and simulation that autorepression of mRNA and protein can provide a mechanism for the intracellular oscillator. Based on the...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2008.05.004

    authors: Xiao M,Cao J

    更新日期:2008-09-01 00:00:00

  • Quantification of the effect of control strategies on classical swine fever epidemics.

    abstract::Emergency vaccination during an epidemic of classical swine fever virus (CSFV) has become a serious option because of the ethical problems of strategies with massive culling and the availability of a marker vaccine that reduces virus transmission. Here we present a model of between-herd CSFV transmission, which quanti...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2003.08.005

    authors: Klinkenberg D,Everts-van der Wind A,Graat EA,de Jong MC

    更新日期:2003-12-01 00:00:00

  • Effective rate models for the analysis of transport-dependent biosensor data.

    abstract::Optical biosensors, including the BIACORE, provide an increasingly popular method for determining reaction rates of biomolecules. In a flow chamber, with one reactant immobilized on a chip on the sensor surface, a solution containing the other reactant (the analyte) flows through the chamber. The time course of bindin...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/s0025-5564(99)00023-1

    authors: Mason T,Pineda AR,Wofsy C,Goldstein B

    更新日期:1999-07-01 00:00:00

  • Optimal input design: case study of the metabolic process.

    abstract::An optimal input of nutrients into the metabolic process of the individual subject so as to effect desired therapeutic results is particularly important for the critically ill. A patient-related, individualized nutrients optimization procedure is proposed here. The procedure is applicable to any time-invariant and det...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/0025-5564(89)90004-7

    authors: Giladi R,Sideman S

    更新日期:1989-12-01 00:00:00

  • A mathematical model of cancer chemotherapy with an optimal selection of parameters.

    abstract::An optimal parameter selection model of cancer chemotherapy is presented which describes the treatment of a tumor over a fixed period of time by the repeated administration of a single drug. The drug is delivered at evenly spaced intervals over the treatment period at doses to be selected by the model. The model const...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/0025-5564(90)90005-j

    authors: Martin RB,Fisher ME,Minchin RF,Teo KL

    更新日期:1990-05-01 00:00:00

  • Stochastic optimal therapy for enhanced immune response.

    abstract::Therapeutic enhancement of humoral immune response to microbial attack is addressed as the stochastic optimal control of a dynamic system. Without therapy, the modeled immune response depends upon the initial concentration of pathogens in a simulated attack. Immune response can be augmented by agents that kill the pat...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2004.06.004

    authors: Stengel RF,Ghigliazza R

    更新日期:2004-10-01 00:00:00

  • Yule-generated trees constrained by node imbalance.

    abstract::The Yule process generates a class of binary trees which is fundamental to population genetic models and other applications in evolutionary biology. In this paper, we introduce a family of sub-classes of ranked trees, called Ω-trees, which are characterized by imbalance of internal nodes. The degree of imbalance is de...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2013.08.008

    authors: Disanto F,Schlizio A,Wiehe T

    更新日期:2013-11-01 00:00:00

  • Investigation of the performance of fermentation processes using a mathematical model including effects of metabolic bottleneck and toxic product on cells.

    abstract::A number of recent research studies have focused on theoretical and experimental investigation of a bottleneck in a metabolic reaction network. However, there is no study on how the bottleneck affects the performance of a fermentation process when a product is highly toxic and remarkably influences the growth and deat...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2010.08.001

    authors: Sriyudthsak K,Shiraishi F

    更新日期:2010-11-01 00:00:00

  • The basic reproduction number and the probability of extinction for a dynamic epidemic model.

    abstract::We consider the spread of an epidemic through a population divided into n sub-populations, in which individuals move between populations according to a Markov transition matrix Σ and infectives can only make infectious contacts with members of their current population. Expressions for the basic reproduction number, R₀...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2012.01.002

    authors: Neal P

    更新日期:2012-03-01 00:00:00

  • Hopf bifurcation in pioneer-climax competing species models.

    abstract::Two-dimensional pioneer-climax models of competing species differential equations are introduced and examined. The per capita growth rates are functions of weighted densities of the individual species. Constant rate forcing is added representing stocking or harvesting. The ensuring stability properties of interior equ...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/s0025-5564(96)00065-x

    authors: Sumner S

    更新日期:1996-10-01 00:00:00

  • Stability and Hopf bifurcation for a prey-predator model with prey-stage structure and diffusion.

    abstract::In this paper, we first propose a prey-predator model with prey-stage structure and diffusion. Then we discuss the following three problems: (1) stability of non-negative constant steady states for the reduced ODE system and the corresponding reaction diffusion system with homogeneous Neumann boundary conditions; (2) ...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2007.08.008

    authors: Wang M

    更新日期:2008-04-01 00:00:00

  • Some remarks on definition and validity of terms used in models for infectious disease spread.

    abstract::The epidemiology of infectious diseases makes use of a number of terms, such as exposure, infected, carrier, attack rate, and immunity. Researchers who intend to model the spread of epidemics should be aware of the problems with some of these terms. The role played by inapparent, or subclinical, infections is receivin...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/0025-5564(91)90001-y

    authors: Giesecke J

    更新日期:1991-12-01 00:00:00

  • A mathematical investigation of the effects of inhibitor therapy on three putative phosphorylation cascades governing the two-component system of the agr operon.

    abstract::Two-component systems (TCSs) are widely employed by bacteria to sense specific external signals and conduct an appropriate response via a phosphorylation cascade within the cell. The TCS of the agr operon in the bacterium Staphylococcus aureus forms part of a regulatory process termed quorum sensing, a cell-to-cell co...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2010.03.001

    authors: Jabbari S,King JR,Williams P

    更新日期:2010-06-01 00:00:00

  • A competition model for viral inhibition of host cell proliferation.

    abstract::Some viruses encode proteins that promote cell proliferation while others, such as the human immunodeficiency virus (HIV), encode proteins that prevent cell division. It has been hypothesized that the selective advantage determining which strategy evolves depends on the ability of the virus to induce a cellular enviro...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/s0025-5564(00)00020-1

    authors: Holtea S,Emerman M

    更新日期:2000-07-01 00:00:00

  • Spectra-based estimates of certain time-domain parameters of a bivariate stationary-point process.

    abstract::We consider estimates of certain time-domain parameters of a bivariate stationary-point process based on modified periodogram statistics. These estimates are shown to be asymptotically normal under regularity conditions. In the computations of the estimates, the advantage of using the FFT algorithm is demonstrated. Th...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/0025-5564(91)90061-m

    authors: Rigas AG

    更新日期:1991-05-01 00:00:00

  • Formulating spread of species with habitat dependent growth and dispersal in heterogeneous landscapes.

    abstract::Habitat heterogeneity can have profound effects on the spreading dynamics of invasive species. Using integro-difference equations, we investigate the spreading dynamics in a one-dimensional heterogeneous landscape comprising alternating favourable and unfavourable habitat patches or randomly generated habitat patches ...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2016.02.013

    authors: Ramanantoanina A,Hui C

    更新日期:2016-05-01 00:00:00

  • Equilibrium distributions and simulation methods for age structured populations.

    abstract::A simulation method is presented for the demographic and genetic variation of age structured haploid populations. First, we use matrix analytic methods to derive an equilibrium distribution for the age class sizes conditioned on the total population size. Knowledge of this distribution eliminates the need of a burn-in...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2015.08.003

    authors: Olsson F,Hössjer O

    更新日期:2015-10-01 00:00:00

  • Is the addition of higher-order interactions in ecological models increasing the understanding of ecological dynamics?

    abstract::Recent work has shown that higher-order terms in population dynamics models can increase the stability, promote the diversity, and better explain the dynamics of ecological systems. While it is known that these perceived benefits come from an increasing number of alternative solutions given by the nature of multivaria...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2019.108222

    authors: AlAdwani M,Saavedra S

    更新日期:2019-09-01 00:00:00

  • Closed-loop stability of pharmacokinetic-pharmacodynamic models.

    abstract::In automatic feedback control of intravenous drug infusions, convergence to the setpoint is an important objective. This paper examines the stability of pharmacokinetic-pharmacodynamic models of patient response regulated with proportional integral feedback. The model consists of three components: linear compartmental...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/s0025-5564(97)00076-x

    authors: Wada DR

    更新日期:1997-12-01 00:00:00

  • Kinetics of the formation of a protein corona around nanoparticles.

    abstract::Interaction of metal or oxide nanoparticles (NPs) with biological soft matter is one of the central phenomena in basic and applied biology-oriented nanoscience. Often, this interaction includes adsorption of suspended proteins on the NP surface, resulting in the formation of the protein corona around NPs. Structurally...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2016.09.018

    authors: Zhdanov VP,Cho NJ

    更新日期:2016-12-01 00:00:00

  • Sharpening spots: correcting for bleedover in cDNA array images.

    abstract::For cDNA array methods that depend on imaging of a radiolabel, we show that bleedover of one spot onto another, due to the gap between the array and the imaging media, can be a major problem. The images can be sharpened, however, using a blind convolution method based on the EM algorithm. The sharpened images look lik...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/s0025-5564(01)00101-8

    authors: Therneau T,Tschumper RC,Jelinek D

    更新日期:2002-03-01 00:00:00

  • A novel algorithm for tracing the interaction of a track with molecular targets--use of Delaunay triangulation.

    abstract::This paper describes an efficient method for tracing interactions between a radiation track and molecular targets in a cell or nucleus. The method is efficient because it ensures that a minimal subset of interactions in the track needs to be tested for each score. It is most useful for high-energy particles since the ...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/s0025-5564(98)10045-7

    authors: Fitzsimons CJ,Nikjoo H,Bolton CE,Goodhead DT

    更新日期:1998-12-15 00:00:00

  • Incorporating bolus and infusion pharmacokinetics into the ICING insulin model.

    abstract::The ICING model has been successfully used to guide clinical decisions on insulin administration in critical illness. However, insulin pharmacokinetics in the ICING model can be improved to better describe both intravenous (IV) bolus and infusion insulin administration. Patient data from 217 Dynamic Insulin Sensitivit...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/j.mbs.2016.08.005

    authors: Fisk L,Docherty PD,Pretty C,Chase JG

    更新日期:2016-11-01 00:00:00

  • The principle of interval constraints: a generalization of the symmetric Dirichlet distribution.

    abstract::A structure for representing problems in decision analysis and in expert systems, which reason under uncertainty, is the influence diagram or causal network. A causal network consists of an underlying joint probability distribution and a directed acyclic graph in which a propositional variable that represents a margin...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/0025-5564(91)90089-2

    authors: Neapolitan RE

    更新日期:1991-02-01 00:00:00

  • Epidemiological models of Mycobacterium tuberculosis complex infections.

    abstract::The resurgence of tuberculosis in the 1990s and the emergence of drug-resistant tuberculosis in the first decade of the 21st century increased the importance of epidemiological models for the disease. Due to slow progression of tuberculosis, the transmission dynamics and its long-term effects can often be better obser...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.mbs.2012.02.003

    authors: Ozcaglar C,Shabbeer A,Vandenberg SL,Yener B,Bennett KP

    更新日期:2012-04-01 00:00:00

  • Effect of aggregating behavior on population recovery on a set of habitat islands.

    abstract::We consider a single-species model which is composed of several patches connected by linear migration rates and having logistic growth with a threshold. We show the existence of an aggregating mechanism that allows the survival of a species which is in danger of extinction due to its low population density. Numerical ...

    journal_title:Mathematical biosciences

    pub_type: 杂志文章

    doi:10.1016/s0025-5564(00)00005-5

    authors: Padrón V,Trevisan MC

    更新日期:2000-05-01 00:00:00