3,511 research outputs found
Mass conserved elementary kinetics is sufficient for the existence of a non-equilibrium steady state concentration
Living systems are forced away from thermodynamic equilibrium by exchange of
mass and energy with their environment. In order to model a biochemical
reaction network in a non-equilibrium state one requires a mathematical
formulation to mimic this forcing. We provide a general formulation to force an
arbitrary large kinetic model in a manner that is still consistent with the
existence of a non-equilibrium steady state. We can guarantee the existence of
a non-equilibrium steady state assuming only two conditions; that every
reaction is mass balanced and that continuous kinetic reaction rate laws never
lead to a negative molecule concentration. These conditions can be verified in
polynomial time and are flexible enough to permit one to force a system away
from equilibrium. In an expository biochemical example we show how a
reversible, mass balanced perpetual reaction, with thermodynamically infeasible
kinetic parameters, can be used to perpetually force a kinetic model of
anaerobic glycolysis in a manner consistent with the existence of a steady
state. Easily testable existence conditions are foundational for efforts to
reliably compute non-equilibrium steady states in genome-scale biochemical
kinetic models.Comment: 11 pages, 2 figures (v2 is now placed in proper context of the
excellent 1962 paper by James Wei entitled "Axiomatic treatment of chemical
reaction systems". In addition, section 4, on "Utility of steady state
existence theorem" has been expanded.
MetaboTools: A comprehensive toolbox for analysis of genome-scale metabolic models
Metabolomic data sets provide a direct read-out of cellular phenotypes and
are increasingly generated to study biological questions. Our previous work
revealed the potential of analyzing extracellular metabolomic data in the
context of the metabolic model using constraint-based modeling. Through this
work, which consists of a protocol, a toolbox, and tutorials of two use cases,
we make our methods available to the broader scientific community. The protocol
describes, in a step-wise manner, the workflow of data integration and
computational analysis. The MetaboTools comprise the Matlab code required to
complete the workflow described in the protocol. Tutorials explain the
computational steps for integration of two different data sets and demonstrate
a comprehensive set of methods for the computational analysis of metabolic
models and stratification thereof into different phenotypes. The presented
workflow supports integrative analysis of multiple omics data sets.
Importantly, all analysis tools can be applied to metabolic models without
performing the entire workflow. Taken together, this protocol constitutes a
comprehensive guide to the intra-model analysis of extracellular metabolomic
data and a resource offering a broad set of computational analysis tools for a
wide biomedical and non-biomedical research community
Conditions for duality between fluxes and concentrations in biochemical networks
Mathematical and computational modelling of biochemical networks is often
done in terms of either the concentrations of molecular species or the fluxes
of biochemical reactions. When is mathematical modelling from either
perspective equivalent to the other? Mathematical duality translates concepts,
theorems or mathematical structures into other concepts, theorems or
structures, in a one-to-one manner. We present a novel stoichiometric condition
that is necessary and sufficient for duality between unidirectional fluxes and
concentrations. Our numerical experiments, with computational models derived
from a range of genome-scale biochemical networks, suggest that this
flux-concentration duality is a pervasive property of biochemical networks. We
also provide a combinatorial characterisation that is sufficient to ensure
flux-concentration duality. That is, for every two disjoint sets of molecular
species, there is at least one reaction complex that involves species from only
one of the two sets. When unidirectional fluxes and molecular species
concentrations are dual vectors, this implies that the behaviour of the
corresponding biochemical network can be described entirely in terms of either
concentrations or unidirectional fluxes
A Study of Sequence Distribution of a Painted Globule as a Model for Proteins with Good Folding Properties
In this paper we present a method to study the folding structure of a simple model consisting of two kinds of monomers, hydrophobic and hydrophilic. This method has three main steps: an efficient simulation method to bring an open sequence of homopolymer to a folded state, the application of a painting method called regular hull to the folded globule and the refolding process of the obtained copolymer sequence. This study allows us to suggest a theoretical function of disorder distribution for copolymer sequences that give rise to a compacted and well micro-phase separated globule
A Study of Sequence Distribution of a Painted Globule as a Model for Proteins with Good Folding Properties
In this paper we present a method to study the folding structure of a simple model consisting of two kinds of monomers, hydrophobic and hydrophilic. This method has three main steps: an efficient simulation method to bring an open sequence of homopolymer to a folded state, the application of a painting method called regular hull to the folded globule and the refolding process of the obtained copolymer sequence. This study allows us to suggest a theoretical function of disorder distribution for copolymer sequences that give rise to a compacted and well micro-phase separated globule
The difference in patterns of motor and cognitive function in chronic fatigue syndrome and severe depressive illness
Background. Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) share many symptoms and aetiological factors but may have different neurobiological underpinnings. We wished to determine the profile of the biological variables disturbed in CFS and MDD, and identify any critical factors that differentiate the disorders. Methods. Thirty patients with CFS, 20 with MDD and 15 healthy controls – matched group-wise for age and sex – were recruited. Subjects were given a detailed battery of motor and cognitive tests, including measures of psychomotor speed, memory and maximal voluntary muscle contraction in both the morning and evening that were balanced to avoid order effects. Results. CFS patients generally performed worse on cognitive tests than healthy controls, but better than patients with MDD. Both patient groups had markedly impaired motor function compared with healthy controls. MDD subjects showed a significantly greater diurnal improvement in maximal voluntary contraction than healthy controls. Conclusions. Patients with CFS and MDD show similarly substantial motor impairment, but cognitive deficits are generally more marked in MDD. Diurnal changes in some functions in MDD may differentiate the disorder from CFS
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