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Scale Relativity Theory and . . . : 1 Founding principles and scale laws
, 2008
"... In these two companion papers, we provide an overview and a brief history of the multiple roots, current developments and recent advances of integrative systems biology and identify multiscale integration as its grand challenge. Then we introduce the fundamental principles and the successive steps ..."
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In these two companion papers, we provide an overview and a brief history of the multiple roots, current developments and recent advances of integrative systems biology and identify multiscale integration as its grand challenge. Then we introduce the fundamental principles and the successive steps that have been followed in the construction of the scale relativity theory, and discuss how scale laws of increasing complexity can be used to model and understand the behaviour of complex biological systems. In scale relativity theory, the geometry of space is considered to be continuous but non-differentiable, therefore fractal (i.e., explicitly scale-dependent). One writes the equations of motion in such a space as geodesics equations, under the constraint of the principle of relativity of all scales in nature. To this purpose, covariant derivatives are constructed that implement the various effects of the non-differentiable and fractal geometry. In this first review paper, the scale laws that describe the new dependence on resolutions of physical quantities are obtained as solutions of differential equations acting in the scale space. This leads to several possible levels of description for these laws, from the simplest scale invariant laws to generalized laws with variable fractal dimensions. Initial applications of
Simulation The Activity-tracking paradigm in
"... discrete-event modeling and simulation: The case of spatially continuous distributed systems ..."
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discrete-event modeling and simulation: The case of spatially continuous distributed systems
Dynamical Modelling Of Feedback Gene Regulatory Networks
, 2009
"... Living cells are made up of networks of interacting genes, proteins and other bio-molecules. Simple interactions between network components in forms of feedback regulations can lead to complex collective dynamics. A key task in cell biology is to gain a thorough understanding of the dynamics of intr ..."
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Living cells are made up of networks of interacting genes, proteins and other bio-molecules. Simple interactions between network components in forms of feedback regulations can lead to complex collective dynamics. A key task in cell biology is to gain a thorough understanding of the dynamics of intracellular systems and processes. In this thesis, a combined approach of mathematical modelling, computational simulation and analytical techniques, has been used to obtain a deeper insight into the dynamical aspects of a variety of feedback systems commonly encountered in cells. These systems range from model system with detailed available molecular knowledge to general regulatory motifs with varying network structures. Deterministic as well as stochastic modelling techniques have been employed, depending primarily on the specific questions asked. The first part of the thesis focuses on dissecting the principles behind the regulatory design of the Tryptophan Operon system in Escherichia coli. It has evolved three negative feedback loops, namely repression, attenuation and enzyme inhibition, as core regulator mechanisms to control the intracellular level of tryptophan amino acid, which is taken up for protein
METHODOLOGY ARTICLE Open Access
"... Rule-based multi-level modeling of cell biological systems ..."
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STATEMENT BY AUTHOR
, 2009
"... requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this thesis are allowable without special permission, provided that accurate acknowledgment of source is mad ..."
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requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this thesis are allowable without special permission, provided that accurate acknowledgment of source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the copyright holder. SIGNED:
COMPUTATIONAL ANALYSIS OF THE SIMPLE SEQUENCE REPEATS IN MUCIN-6 OF FOVEOLAR CELLS
"... In this study, a computational analysis has been carried out to investigate the patterns of the simple sequence repeats (SSRs) in mucin-6 mRNA gene of human foveolar cells. The computational analysis of SSRs is important because it can provide insight into the diseases generated by SSRs. Our results ..."
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In this study, a computational analysis has been carried out to investigate the patterns of the simple sequence repeats (SSRs) in mucin-6 mRNA gene of human foveolar cells. The computational analysis of SSRs is important because it can provide insight into the diseases generated by SSRs. Our results show that mucin-6 mRNA has a high relative frequency of dinucleotide and trinucleotide SSR motifs. The trinucleotide SSRs have special significance because they constitute the amino acid in the coding region of the gene. The analysis of trinucleotide SSRs shows that the motifs from the category T9 is highly repetitive. This research may provide insights into the biomedical research in the stomach pathogenesis that is implicated by SSRs in mucin-6 gene.
Review Spatial Simulations in Systems Biology: From Molecules to Cells
, 2012
"... Abstract: Cells are highly organized objects containing millions of molecules. Each biomolecule has a specific shape in order to interact with others in the complex machinery. Spatial dynamics emerge in this system on length and time scales which can not yet be modeled with full atomic detail. This ..."
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Abstract: Cells are highly organized objects containing millions of molecules. Each biomolecule has a specific shape in order to interact with others in the complex machinery. Spatial dynamics emerge in this system on length and time scales which can not yet be modeled with full atomic detail. This review gives an overview of methods which can be used to simulate the complete cell at least with molecular detail, especially Brownian dynamics simulations. Such simulations require correct implementation of the diffusion-controlled reaction scheme occurring on this level. Implementations and applications of spatial simulations are presented, and finally it is discussed how the atomic level can be included for instance in multi-scale simulation methods.
CHALLENGES FOR MODELING AND SIMULATION METHODS IN SYSTEMS BIOLOGY
"... Systems Biology is aimed at analyzing the behavior and interrelationships of biological systems and is characterized by combining experimentation, theory, and computation. Dedicated to exploring current challenges, the panel brings together people from a variety of disciplines whose perspectives ill ..."
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Systems Biology is aimed at analyzing the behavior and interrelationships of biological systems and is characterized by combining experimentation, theory, and computation. Dedicated to exploring current challenges, the panel brings together people from a variety of disciplines whose perspectives illuminate diverse facets of Systems Biology and the challenges for modeling and simulation methods. 1
PREDICTION OF IN VITRO HEPATIC BILIARY EXCRETION USING STOCHASTIC AGENT-BASED MODELING AND FUZZY CLUSTERING
"... We present a method for estimating (predicting) parameter values for an agent-based model of in silico hepatocytes (ISH). The method enables the ISH to interact with simulated drugs to reasonably match results from in vitro hepatocyte excretion studies. Further, we make the estimation method availab ..."
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We present a method for estimating (predicting) parameter values for an agent-based model of in silico hepatocytes (ISH). The method enables the ISH to interact with simulated drugs to reasonably match results from in vitro hepatocyte excretion studies. Further, we make the estimation method available to the model, itself, to enable it to reasonably anticipate (predict) the biliary transport and excretion properties of a new compound based on the acceptable parameter values for previously encountered compounds. We use Fuzzy c-Means (FCM) classification algorithm to determine the degree of similarity between previously tuned compounds and the new compound. Specifically, a set of simulation parameters for enkephalin was predicted using the tuned parameter values of salicylate, taurocholate, and methotrexate. The feature space for the FCM classification is the physicochemical properties of the compounds. 1
An Analysis Tool Library for Biochemical Modeling on E-Cell System Version 3
"... E-Cell Analysis Toolkit, a library of mathematical analysis scripts for E-Cell Simulation Environment Version 3 (Takahashi et al. [1]), provides fundamental functions and useful demonstration programs for analyzing mathematical models in system biology. Recently, a large number of biochemical models ..."
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E-Cell Analysis Toolkit, a library of mathematical analysis scripts for E-Cell Simulation Environment Version 3 (Takahashi et al. [1]), provides fundamental functions and useful demonstration programs for analyzing mathematical models in system biology. Recently, a large number of biochemical models have been constructed with the study of complex biological systems, and the development of in silico
