Control Coefficients (control + coefficient)

Distribution by Scientific Domains


Selected Abstracts


Expression of the pyrG gene determines the pool sizes of CTP and dCTP in Lactococcus lactis

FEBS JOURNAL, Issue 12 2004
Casper M. Jørgensen
The pyrG gene from Lactococcus lactis encodes CTP synthase (EC 6.4.3.2), an enzyme converting UTP to CTP. A series of strains were constructed with different levels of pyrG expression by insertion of synthetic constitutive promoters with different strengths in front of pyrG. These strains expressed pyrG levels in a range from 3 to 665% relative to the wild-type expression level. Decreasing the level of CTP synthase to 43% had no effect on the growth rate, showing that the capacity of CTP synthase in the cell is in excess in a wild-type strain. We then studied how pyrG expression affected the intracellular pool sizes of nucleotides and the correlation between pyrG expression and nucleotide pool sizes was quantified using metabolic control analysis in terms of inherent control coefficients. At the wild-type expression level, CTP synthase had full control of the CTP concentration with a concentration control coefficient close to one and a negative concentration control coefficient of ,0.28 for the UTP concentration. Additionally, a concentration control coefficient of 0.49 was calculated for the dCTP concentration. Implications for the homeostasis of nucleotide pools are discussed. [source]


The effect of thiamine supplementation on tumour proliferation

FEBS JOURNAL, Issue 15 2001
A metabolic control analysis study
Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted on the basis of correction of the pre-existing level of thiamine deficiency (42%), as assayed by the cofactor/enzyme ratio. Interestingly, at very high overdoses of thiamine, ,,2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth. This effect was heightened, resulting in a 36% decrease, when thiamine supplementation was administered from the 7th day prior to tumour inoculation. Our results show that thiamine supplementation sufficient to correct existing thiamine deficiency stimulates tumour proliferation as predicted by MCA. The tumour inhibitory effect at high doses of thiamine is unexplained and merits further study. [source]


Adaptive output feedback control for a class of planar nonlinear systems,

ASIAN JOURNAL OF CONTROL, Issue 5 2009
Fang Shang
Abstract This paper is concerned with the problem of global adaptive stabilization by output feedback for a class of planar nonlinear systems with uncertain control coefficient and unknown growth rate. The control coefficient is not supposed to have known upper bound, and this relaxes the corresponding requirement in the existing literature (see e.g. 1, 2. First, by the universal control method, an observer is constructed based on the dynamic high-gain K-filters. Then, the control design procedure is developed to obtain the stabilizing controller and dynamic compensator for the uncertainties in the control coefficient. It is shown that the global stability of the closed-loop system can be guaranteed by the appropriate choice of the design parameters. A simulation example is also provided to illustrate the correctness of the theoretical results. © 2009 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society. [source]


Expression of the pyrG gene determines the pool sizes of CTP and dCTP in Lactococcus lactis

FEBS JOURNAL, Issue 12 2004
Casper M. Jørgensen
The pyrG gene from Lactococcus lactis encodes CTP synthase (EC 6.4.3.2), an enzyme converting UTP to CTP. A series of strains were constructed with different levels of pyrG expression by insertion of synthetic constitutive promoters with different strengths in front of pyrG. These strains expressed pyrG levels in a range from 3 to 665% relative to the wild-type expression level. Decreasing the level of CTP synthase to 43% had no effect on the growth rate, showing that the capacity of CTP synthase in the cell is in excess in a wild-type strain. We then studied how pyrG expression affected the intracellular pool sizes of nucleotides and the correlation between pyrG expression and nucleotide pool sizes was quantified using metabolic control analysis in terms of inherent control coefficients. At the wild-type expression level, CTP synthase had full control of the CTP concentration with a concentration control coefficient close to one and a negative concentration control coefficient of ,0.28 for the UTP concentration. Additionally, a concentration control coefficient of 0.49 was calculated for the dCTP concentration. Implications for the homeostasis of nucleotide pools are discussed. [source]


Adaptive synchronization of GLHS with unknown parameters

INTERNATIONAL JOURNAL OF CIRCUIT THEORY AND APPLICATIONS, Issue 8 2009
Yan-Wu Wang
Abstract In this paper, an adaptive controller for the synchronization of two generalized Lorenz hyperchaos systems (GLHSs) is designed by using the Lyapunov method. In the synchronization schema, the parameters of the drive system are unknown and different from those of the response system. By introducing update laws for both the control coefficients and the parameters of the response system, the adaptive controller proposed in this paper is brand new compared with the former relative works. The proposed adaptive controller is feasible for any possible parameters of GLHS. Numerical simulation is carried out to verify and illustrate the analytical result. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Robust adaptive control for a class of uncertain strict-feedback nonlinear systems

INTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 7 2009
F. Hong
Abstract In this paper, robust adaptive control is presented for a class of perturbed strict-feedback nonlinear systems with both completely unknown control coefficients and parametric uncertainties. The proposed design method does not require the a priori knowledge of the signs of the unknown control coefficients. For the first time, the key technical Lemma is proven when the Nussbaum function is chosen by N(,)=,2cos(,), based on which the proposed robust adaptive scheme can guarantee the global uniform ultimate boundedness of the closed-loop system signals. Simulation results show the validity of the proposed scheme. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Structural and functional organization of Complex I in the mitochondrial respiratory chain

BIOFACTORS, Issue 1-4 2003
Cristina Bianchi
Abstract Metabolic flux control analysis of NADH oxidation in bovine heart submitochondrial particles revealed high flux control coefficients for both Complex I and Complex III, suggesting that the two enzymes are functionally associated as a single enzyme, with channelling of the common substrate, Coenzyme Q. This is in contrast with the more accepted view of a mobile diffusable Coenzyme Q pool between these enzymes. Dilution with phospholipids of a mitochondrial fraction enriched in Complexes I and III, with consequent increased theoretical distance between complexes, determines adherence to pool behavior for Coenzyme Q, but only at dilution higher than 1:5 (protein:phospholipids), whereas, at lower phospholipid content, the turnover of NADH cytochrome c reductase is higher than expected by the pool equation. [source]


Metabolic Control Analysis of Monoclonal Antibody Synthesis

BIOTECHNOLOGY PROGRESS, Issue 2 2001
Ramon Gonzalez
A general route for protein synthesis in eukaryotic cells has been proposed and applied to monoclonal antibody (MAb) synthesis. It takes into account transcription of the gene, binding of ribosomes to mRNA, and polypeptide elongation including binding to SRP (signal recognition particles) and SRP-receptor, competing translocation, folding and glycosylation, assembly of the heavy and light chains in a tetrameric protein and Golgi processing and secretion. A comprehensive model was built on the basis of the proposed pathway. The model takes into account the mechanism of each step. Metabolic control analysis (MCA) principles were applied to the general pathway using the proposed model, and control coefficients were calculated. The results show a shared flux control (of both pathway flux and flux ratio at the branch) among different steps, i.e., transcription, folding, glycosylation, translocation and building blocks synthesis. The steps sharing the control depend on the concentration of building blocks, pathway flux and levels of OST (oligosacharyl transferase), BiP (heavy chain binding protein) and PDI (protein disulfide isomerase). Model predictions compare well with experimental data for MAb synthesis, explaining the control structure of the route and the heterogeneity of the product and also addressing future targets for improvement of the production rate of MAbs. [source]