In this paper we study three classes of nite automata satisfying the properties that every bi- in... more In this paper we study three classes of nite automata satisfying the properties that every bi- innite word is the label of at most one, at least one and exactly one bi-innite path. In particular, we investigate the algorithmic complexity of testing if a given nite automaton has one of these properties. Also, when restricted to the rst class above,
Elevated temperatures cause proteins in living cells to misfold. They start forming larger and la... more Elevated temperatures cause proteins in living cells to misfold. They start forming larger and larger aggregates that can eventually lead to the cell’s death. The heat shock response is an evolutionary well conserved cellular response to massive protein misfolding and it is driven by the need to keep the level of misfolded proteins under control. We consider in this paper
ABSTRACT One approach to modelling complex biological systems is to start from an abstract repres... more ABSTRACT One approach to modelling complex biological systems is to start from an abstract representation of the biological process and then to incorporate more details regarding its reactions or reactants through an iterative refinement process. The refinement should be done so as to ensure the preservation of the numerical properties of the model, such as its numerical fit and validation. Such approaches are well established in software engineering: starting from a formal specification of the system, one refines it step-by-step towards an implementation that is guaranteed to satisfy a number of logical properties. We introduce here the concepts of (quantitative) data refinement and process refinement of a biomolecular, reaction-based model. We choose as a case study a recently proposed model for the heat shock response and refine it to include some details of its acetylation-induced control. Although the refinement process produces a substantial increase in the number of kinetic parameters and variables, the methodology we propose preserves all the numerical properties of the model with a minimal computational effort.
ABSTRACT The Pattern self-Assembly Tile set Synthesis (PATS) problem, which arises in the theory ... more ABSTRACT The Pattern self-Assembly Tile set Synthesis (PATS) problem, which arises in the theory of structured DNA self-assembly, is to determine a set of coloured tiles that, starting from a bordering seed structure, self-assembles to a given rectangular colour pattern. The task of finding minimum-size tile sets is known to be NP-hard. We explore several complete and incomplete search techniques for finding minimal, or at least small, tile sets and also assess the reliability of the solutions obtained according to the kinetic Tile Assembly Model.
IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2000
The heat shock response is a well-conserved defence mechanism against the accumulation of misfold... more The heat shock response is a well-conserved defence mechanism against the accumulation of misfolded proteins due to prolonged elevated heat. The cell responds to heat shock by raising the levels of heat shock proteins (hsp), which are responsible for chaperoning protein refolding. The synthesis of hsp is highly regulated at the transcription level by specific heat shock (transcription) factors (hsf). One of the regulation mechanisms is the phosphorylation of hsf's. Experimental evidence shows a connection between the hyper-phosphorylation of hsfs and the transactivation of the hsp-encoding genes. In this paper, we incorporate several (de)phosphorylation pathways into an existing well-validated computational model of the heat shock response. We analyze the quantitative control of each of these pathways over the entire process. For each of these pathways we create detailed computational models which we subject to parameter estimation in order to fit them to existing experimental data. In particular, we find conclusive evidence supporting only one of the analyzed pathways. Also, we corroborate our results with a set of computational models of a more reduced size.
In this paper we study three classes of nite automata satisfying the properties that every bi- in... more In this paper we study three classes of nite automata satisfying the properties that every bi- innite word is the label of at most one, at least one and exactly one bi-innite path. In particular, we investigate the algorithmic complexity of testing if a given nite automaton has one of these properties. Also, when restricted to the rst class above,
Elevated temperatures cause proteins in living cells to misfold. They start forming larger and la... more Elevated temperatures cause proteins in living cells to misfold. They start forming larger and larger aggregates that can eventually lead to the cell’s death. The heat shock response is an evolutionary well conserved cellular response to massive protein misfolding and it is driven by the need to keep the level of misfolded proteins under control. We consider in this paper
ABSTRACT One approach to modelling complex biological systems is to start from an abstract repres... more ABSTRACT One approach to modelling complex biological systems is to start from an abstract representation of the biological process and then to incorporate more details regarding its reactions or reactants through an iterative refinement process. The refinement should be done so as to ensure the preservation of the numerical properties of the model, such as its numerical fit and validation. Such approaches are well established in software engineering: starting from a formal specification of the system, one refines it step-by-step towards an implementation that is guaranteed to satisfy a number of logical properties. We introduce here the concepts of (quantitative) data refinement and process refinement of a biomolecular, reaction-based model. We choose as a case study a recently proposed model for the heat shock response and refine it to include some details of its acetylation-induced control. Although the refinement process produces a substantial increase in the number of kinetic parameters and variables, the methodology we propose preserves all the numerical properties of the model with a minimal computational effort.
ABSTRACT The Pattern self-Assembly Tile set Synthesis (PATS) problem, which arises in the theory ... more ABSTRACT The Pattern self-Assembly Tile set Synthesis (PATS) problem, which arises in the theory of structured DNA self-assembly, is to determine a set of coloured tiles that, starting from a bordering seed structure, self-assembles to a given rectangular colour pattern. The task of finding minimum-size tile sets is known to be NP-hard. We explore several complete and incomplete search techniques for finding minimal, or at least small, tile sets and also assess the reliability of the solutions obtained according to the kinetic Tile Assembly Model.
IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2000
The heat shock response is a well-conserved defence mechanism against the accumulation of misfold... more The heat shock response is a well-conserved defence mechanism against the accumulation of misfolded proteins due to prolonged elevated heat. The cell responds to heat shock by raising the levels of heat shock proteins (hsp), which are responsible for chaperoning protein refolding. The synthesis of hsp is highly regulated at the transcription level by specific heat shock (transcription) factors (hsf). One of the regulation mechanisms is the phosphorylation of hsf's. Experimental evidence shows a connection between the hyper-phosphorylation of hsfs and the transactivation of the hsp-encoding genes. In this paper, we incorporate several (de)phosphorylation pathways into an existing well-validated computational model of the heat shock response. We analyze the quantitative control of each of these pathways over the entire process. For each of these pathways we create detailed computational models which we subject to parameter estimation in order to fit them to existing experimental data. In particular, we find conclusive evidence supporting only one of the analyzed pathways. Also, we corroborate our results with a set of computational models of a more reduced size.
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Papers by Eugen Czeizler