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Title: Model reduction and physical understanding of slowly oscillating processes : the circadian cycle.

Abstract

A differential system that models the circadian rhythm in Drosophila is analyzed with the computational singular perturbation (CSP) algorithm. Reduced nonstiff models of prespecified accuracy are constructed, the form and size of which are time-dependent. When compared with conventional asymptotic analysis, CSP exhibits superior performance in constructing reduced models, since it can algorithmically identify and apply all the required order of magnitude estimates and algebraic manipulations. A similar performance is demonstrated by CSP in generating data that allow for the acquisition of physical understanding. It is shown that the processes driving the circadian cycle are (i) mRNA translation into monomer protein, and monomer protein destruction by phosphorylation and degradation (along the largest portion of the cycle); and (ii) mRNA synthesis (along a short portion of the cycle). These are slow processes. Their action in driving the cycle is allowed by the equilibration of the fastest processes; (1) the monomer dimerization with the dimer dissociation (along the largest portion of the cycle); and (2) the net production of monomer+dimmer proteins with that of mRNA (along the short portion of the cycle). Additional results (regarding the time scales of the established equilibria, their origin, the rate limiting steps, the couplings among themore » variables, etc.) highlight the utility of CSP for automated identification of the important underlying dynamical features, otherwise accessible only for simple systems whose various suitable simplifications can easily be recognized.« less

Authors:
 [1];
  1. (Ploutonos 7, Palaio Faliro, Greece)
Publication Date:
Research Org.:
Sandia National Laboratories
Sponsoring Org.:
USDOE
OSTI Identifier:
951695
Report Number(s):
SAND2006-1015J
TRN: US200913%%101
DOE Contract Number:
AC04-94AL85000
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proposed for publication in Multiscale Modeling and Simulation.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ACCURACY; DIMERIZATION; DIMERS; DISSOCIATION; DROSOPHILA; MONOMERS; ORIGIN; PERFORMANCE; PHOSPHORYLATION; PRODUCTION; PROTEINS; SYNTHESIS

Citation Formats

Goussis, Dimitris A., and Najm, Habib N. Model reduction and physical understanding of slowly oscillating processes : the circadian cycle.. United States: N. p., 2006. Web. doi:10.1137/060649768.
Goussis, Dimitris A., & Najm, Habib N. Model reduction and physical understanding of slowly oscillating processes : the circadian cycle.. United States. doi:10.1137/060649768.
Goussis, Dimitris A., and Najm, Habib N. Sun . "Model reduction and physical understanding of slowly oscillating processes : the circadian cycle.". United States. doi:10.1137/060649768.
@article{osti_951695,
title = {Model reduction and physical understanding of slowly oscillating processes : the circadian cycle.},
author = {Goussis, Dimitris A. and Najm, Habib N.},
abstractNote = {A differential system that models the circadian rhythm in Drosophila is analyzed with the computational singular perturbation (CSP) algorithm. Reduced nonstiff models of prespecified accuracy are constructed, the form and size of which are time-dependent. When compared with conventional asymptotic analysis, CSP exhibits superior performance in constructing reduced models, since it can algorithmically identify and apply all the required order of magnitude estimates and algebraic manipulations. A similar performance is demonstrated by CSP in generating data that allow for the acquisition of physical understanding. It is shown that the processes driving the circadian cycle are (i) mRNA translation into monomer protein, and monomer protein destruction by phosphorylation and degradation (along the largest portion of the cycle); and (ii) mRNA synthesis (along a short portion of the cycle). These are slow processes. Their action in driving the cycle is allowed by the equilibration of the fastest processes; (1) the monomer dimerization with the dimer dissociation (along the largest portion of the cycle); and (2) the net production of monomer+dimmer proteins with that of mRNA (along the short portion of the cycle). Additional results (regarding the time scales of the established equilibria, their origin, the rate limiting steps, the couplings among the variables, etc.) highlight the utility of CSP for automated identification of the important underlying dynamical features, otherwise accessible only for simple systems whose various suitable simplifications can easily be recognized.},
doi = {10.1137/060649768},
journal = {Proposed for publication in Multiscale Modeling and Simulation.},
number = ,
volume = ,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}
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