The study of cellular signalling pathways and their deregulation in disease states, such as cancer, is a large and extremely complex task. Indeed, these systems involve many parts and processes but are studied piecewise and their literatures and data are consequently fragmented, distributed and sometimes--at least apparently--inconsistent. This makes it extremely difficult to build significant explanatory models with the result that effects in these systems that are brought about by many interacting factors are poorly understood. The rule-based approach to modelling has shown some promise for the representation of the highly combinatorial systems typically found in signalling where many of the proteins are composed of multiple binding domains, capable of simultaneous interactions, and/or peptide motifs controlled by post-translational modifications. However, the rule-based approach requires highly detailed information about the precise conditions for each and every interaction which is rarely available from any one single source. Rather, these conditions must be painstakingly inferred and curated, by hand, from information contained in many papers--each of which contains only part of the story. In this paper, we introduce a graph-based meta-model, attuned to the representation of cellular signalling networks, which aims to ease this massive cognitive burden on the rule-based curation process. This meta-model is a generalization of that used by Kappa and BNGL which allows for the flexible representation of knowledge at various levels of granularity. In particular, it allows us to deal with information which has either too little, or too much, detail with respect to the strict rule-based meta-model. Our approach provides a basis for the gradual aggregation of fragmented biological knowledge extracted from the literature into an instance of the meta-model from which we can define an automated translation into executable Kappa programs.
{"title":"A knowledge representation meta-model for rule-based modelling of signalling networks","authors":"Adrien Basso-Blandin, W. Fontana, Russell Harmer","doi":"10.4204/EPTCS.204.5","DOIUrl":"https://doi.org/10.4204/EPTCS.204.5","url":null,"abstract":"The study of cellular signalling pathways and their deregulation in disease states, such as cancer, is a large and extremely complex task. Indeed, these systems involve many parts and processes but are studied piecewise and their literatures and data are consequently fragmented, distributed and sometimes--at least apparently--inconsistent. This makes it extremely difficult to build significant explanatory models with the result that effects in these systems that are brought about by many interacting factors are poorly understood. \u0000The rule-based approach to modelling has shown some promise for the representation of the highly combinatorial systems typically found in signalling where many of the proteins are composed of multiple binding domains, capable of simultaneous interactions, and/or peptide motifs controlled by post-translational modifications. However, the rule-based approach requires highly detailed information about the precise conditions for each and every interaction which is rarely available from any one single source. Rather, these conditions must be painstakingly inferred and curated, by hand, from information contained in many papers--each of which contains only part of the story. \u0000In this paper, we introduce a graph-based meta-model, attuned to the representation of cellular signalling networks, which aims to ease this massive cognitive burden on the rule-based curation process. This meta-model is a generalization of that used by Kappa and BNGL which allows for the flexible representation of knowledge at various levels of granularity. In particular, it allows us to deal with information which has either too little, or too much, detail with respect to the strict rule-based meta-model. Our approach provides a basis for the gradual aggregation of fragmented biological knowledge extracted from the literature into an instance of the meta-model from which we can define an automated translation into executable Kappa programs.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"57 1","pages":"47-59"},"PeriodicalIF":0.0,"publicationDate":"2016-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89560025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Three reasonable hypotheses lead to the thesis that physical phenomena can be described and simulated with cellular automata. In this work, we attempt to describe the motion of a particle upon which a constant force is applied, with a cellular automaton, in Newtonian physics, in Special Relativity, and in General Relativity. The results are very different for these three theories.
{"title":"Free fall and cellular automata","authors":"P. Arrighi, Gilles Dowek","doi":"10.4204/EPTCS.204.1","DOIUrl":"https://doi.org/10.4204/EPTCS.204.1","url":null,"abstract":"Three reasonable hypotheses lead to the thesis that physical phenomena can be described and simulated with cellular automata. In this work, we attempt to describe the motion of a particle upon which a constant force is applied, with a cellular automaton, in Newtonian physics, in Special Relativity, and in General Relativity. The results are very different for these three theories.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"19 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2016-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77071358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Confluence is a critical property of computational systems which is related with determinism and non ambiguity and thus with other relevant computational attributes of functional specifications and rewriting system as termination and completion. Several criteria have been explored that guarantee confluence and their formalisations provide further interesting information. This work discusses topics and presents personal positions and views related with the formalisation of confluence properties in the Prototype Verification System PVS developed at our research group.
{"title":"Formalising Confluence in PVS","authors":"M. Ayala-Rincón","doi":"10.4204/EPTCS.204.2","DOIUrl":"https://doi.org/10.4204/EPTCS.204.2","url":null,"abstract":"Confluence is a critical property of computational systems which is related with determinism and non ambiguity and thus with other relevant computational attributes of functional specifications and rewriting system as termination and completion. Several criteria have been explored that guarantee confluence and their formalisations provide further interesting information. This work discusses topics and presents personal positions and views related with the formalisation of confluence properties in the Prototype Verification System PVS developed at our research group.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"27 1","pages":"11-17"},"PeriodicalIF":0.0,"publicationDate":"2016-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80361293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mauricio Toro, A. Philippou, Sair Arboleda, María Puerta, S. CarlosM.Vélez
We define a mean-field semantics for S-PALPS, a process calculus for spatially-explicit, individualbased modeling of ecological systems. The new semantics of S-PALPS allows an interpretation of the average behavior of a system as a set of recurrence equations. Recurrence equations are a useful approximation when dealing with a large number of individuals, as it is the case in epidemiological studies. As a case study, we compute a set of recurrence equations capturing the dynamics of an individual-based model of the transmission of dengue in Bello (Antioquia), Colombia.
{"title":"Mean-Field Semantics for a Process Calculus for Spatially-Explicit Ecological Models","authors":"Mauricio Toro, A. Philippou, Sair Arboleda, María Puerta, S. CarlosM.Vélez","doi":"10.4204/EPTCS.204.7","DOIUrl":"https://doi.org/10.4204/EPTCS.204.7","url":null,"abstract":"We define a mean-field semantics for S-PALPS, a process calculus for spatially-explicit, individualbased modeling of ecological systems. The new semantics of S-PALPS allows an interpretation of the average behavior of a system as a set of recurrence equations. Recurrence equations are a useful approximation when dealing with a large number of individuals, as it is the case in epidemiological studies. As a case study, we compute a set of recurrence equations capturing the dynamics of an individual-based model of the transmission of dengue in Bello (Antioquia), Colombia.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"1 1","pages":"79-94"},"PeriodicalIF":0.0,"publicationDate":"2016-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89594001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Some notions in mathematics can be considered relative. Relative is a term used to denote when the variation in the position of an observer implies variation in properties or measures on the observed object. We know, from Skolem theorem, that there are first-order models where the set of real numbers is countable and some where it is not. This fact depends on the position of the observer and on the instrument/language the obserevr uses as well, i.e., it depends on whether he/she is inside the model or not and in this particular case the use of first-order logic. In this article, we assume that computation is based on finiteness rather than natural numbers and discuss Turing machines computable morphisms defined on top of the sole notion finiteness. We explore the relativity of finiteness in models provided by toposes where the Axiom of Choice (AC) does not hold, since Tarski proved that if AC holds then all finiteness notions are equivalent. Our toposes do not have natural numbers object (NNO) either, since in a topos with a NNO these finiteness notions are equivalent to Peano finiteness going back to computation on top of Natural Numbers. The main contribution of this article is to show that although from inside every topos, with the properties previously stated, the computation model is standard, from outside some of these toposes, unexpected properties on the computation arise, e.g., infinitely long programs, finite computations containing infinitely long ones, infinitely branching computations. We mainly consider Dedekind and Kuratowski notions of finiteness in this article.
{"title":"Finiteness and Computation in Toposes","authors":"E. Haeusler","doi":"10.4204/EPTCS.204.6","DOIUrl":"https://doi.org/10.4204/EPTCS.204.6","url":null,"abstract":"Some notions in mathematics can be considered relative. Relative is a term used to denote when the variation in the position of an observer implies variation in properties or measures on the observed object. We know, from Skolem theorem, that there are first-order models where the set of real numbers is countable and some where it is not. This fact depends on the position of the observer and on the instrument/language the obserevr uses as well, i.e., it depends on whether he/she is inside the model or not and in this particular case the use of first-order logic. In this article, we assume that computation is based on finiteness rather than natural numbers and discuss Turing machines computable morphisms defined on top of the sole notion finiteness. We explore the relativity of finiteness in models provided by toposes where the Axiom of Choice (AC) does not hold, since Tarski proved that if AC holds then all finiteness notions are equivalent. Our toposes do not have natural numbers object (NNO) either, since in a topos with a NNO these finiteness notions are equivalent to Peano finiteness going back to computation on top of Natural Numbers. The main contribution of this article is to show that although from inside every topos, with the properties previously stated, the computation model is standard, from outside some of these toposes, unexpected properties on the computation arise, e.g., infinitely long programs, finite computations containing infinitely long ones, infinitely branching computations. We mainly consider Dedekind and Kuratowski notions of finiteness in this article.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"1 1","pages":"61-77"},"PeriodicalIF":0.0,"publicationDate":"2016-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89866069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Compositionality and process equivalence are both standard concepts of process algebra. Compositionality means that the behaviour of a compound system relies only on the behaviour of its components, i.e. there is no emergent behaviour. Process equivalence means that the explicit statespace of a system takes a back seat to its interaction patterns: the information that an environment can obtain though interaction. Petri nets are a classical, yet widely used and understood, model of concurrency. Nevertheless, they have often been described as a non-compositional model, and tools tend to deal with monolithic, globally-specified models. This tutorial paper concentrates on Petri Nets with Boundaries (PNB): a compositional, graphical algebra of 1-safe nets, and its applications to reachability checking within the tool Penrose. The algorithms feature the use of compositionality and process equivalence, a powerful combination that can be harnessed to improve the performance of checking reachability and coverability in several common examples where Petri nets model realistic concurrent systems.
{"title":"Compositional model checking of concurrent systems, with Petri nets","authors":"P. Sobocinski","doi":"10.4204/EPTCS.204.3","DOIUrl":"https://doi.org/10.4204/EPTCS.204.3","url":null,"abstract":"Compositionality and process equivalence are both standard concepts of process algebra. Compositionality means that the behaviour of a compound system relies only on the behaviour of its components, i.e. there is no emergent behaviour. Process equivalence means that the explicit statespace of a system takes a back seat to its interaction patterns: the information that an environment can obtain though interaction. \u0000Petri nets are a classical, yet widely used and understood, model of concurrency. Nevertheless, they have often been described as a non-compositional model, and tools tend to deal with monolithic, globally-specified models. \u0000This tutorial paper concentrates on Petri Nets with Boundaries (PNB): a compositional, graphical algebra of 1-safe nets, and its applications to reachability checking within the tool Penrose. The algorithms feature the use of compositionality and process equivalence, a powerful combination that can be harnessed to improve the performance of checking reachability and coverability in several common examples where Petri nets model realistic concurrent systems.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"45 1","pages":"19-30"},"PeriodicalIF":0.0,"publicationDate":"2016-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87681597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We study the problem of generating, ranking and unranking of unlabeled ordered trees whose nodes have maximum degree of $Delta$. This class of trees represents a generalization of chemical trees. A chemical tree is an unlabeled tree in which no node has degree greater than 4. By allowing up to $Delta$ children for each node of chemical tree instead of 4, we will have a generalization of chemical trees. Here, we introduce a new encoding over an alphabet of size 4 for representing unlabeled ordered trees with maximum degree of $Delta$. We use this encoding for generating these trees in A-order with constant average time and O(n) worst case time. Due to the given encoding, with a precomputation of size and time O(n^2) (assuming $Delta$ is constant), both ranking and unranking algorithms are also designed taking O(n) and O(nlogn) time complexities.
{"title":"Generation, Ranking and Unranking of Ordered Trees with Degree Bounds","authors":"M. Amani, A. Nowzari-Dalini","doi":"10.4204/EPTCS.204.4","DOIUrl":"https://doi.org/10.4204/EPTCS.204.4","url":null,"abstract":"We study the problem of generating, ranking and unranking of unlabeled ordered trees whose nodes have maximum degree of $Delta$. This class of trees represents a generalization of chemical trees. A chemical tree is an unlabeled tree in which no node has degree greater than 4. By allowing up to $Delta$ children for each node of chemical tree instead of 4, we will have a generalization of chemical trees. Here, we introduce a new encoding over an alphabet of size 4 for representing unlabeled ordered trees with maximum degree of $Delta$. We use this encoding for generating these trees in A-order with constant average time and O(n) worst case time. Due to the given encoding, with a precomputation of size and time O(n^2) (assuming $Delta$ is constant), both ranking and unranking algorithms are also designed taking O(n) and O(nlogn) time complexities.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"230 1","pages":"31-45"},"PeriodicalIF":0.0,"publicationDate":"2016-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80247525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Any algorithm (in the sense of Gurevich's abstract-state-machine axiomatization of classical algorithms) operating over any arbitrary unordered domain can be simulated by a dynamic cellular automaton, that is, by a pattern-directed cellular automaton with unconstrained topology and with the power to create new cells. The advantage is that the latter is closer to physical reality. The overhead of our simulation is quadratic.
{"title":"Cellular Automata are Generic","authors":"N. Dershowitz, Evgenia Falkovich","doi":"10.4204/EPTCS.179.2","DOIUrl":"https://doi.org/10.4204/EPTCS.179.2","url":null,"abstract":"Any algorithm (in the sense of Gurevich's abstract-state-machine axiomatization of classical algorithms) operating over any arbitrary unordered domain can be simulated by a dynamic cellular automaton, that is, by a pattern-directed cellular automaton with unconstrained topology and with the power to create new cells. The advantage is that the latter is closer to physical reality. The overhead of our simulation is quadratic.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"2 1","pages":"17-32"},"PeriodicalIF":0.0,"publicationDate":"2015-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78465768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Due to their "inherent parallelism", interaction nets have since their introduction been considered as an attractive implementation mechanism for functional programming. We show that a simple highly-concurrent implementation in Haskell can achieve promising speed-ups on multiple cores.
{"title":"A Simple Parallel Implementation of Interaction Nets in Haskell","authors":"Wolfram Kahl","doi":"10.4204/EPTCS.179.3","DOIUrl":"https://doi.org/10.4204/EPTCS.179.3","url":null,"abstract":"Due to their \"inherent parallelism\", interaction nets have since their introduction been considered as an attractive implementation mechanism for functional programming. We show that a simple highly-concurrent implementation in Haskell can achieve promising speed-ups on multiple cores.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"8 1","pages":"33-47"},"PeriodicalIF":0.0,"publicationDate":"2015-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91018972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adriana B. Compagnoni, P. Giannini, Catherine Kim, Matthew Milideo, Vishakha Sharma
We define BioScapeL, a stochastic pi-calculus in 3D-space. A novel aspect of BioScapeL is that entities have programmable locations. The programmer can specify a particular location where to place an entity, or a location relative to the current location of the entity. The motivation for the extension comes from the need to describe the evolution of populations of biochemical species in space, while keeping a sufficiently high level description, so that phenomena like diffusion, collision, and confinement can remain part of the semantics of the calculus. Combined with the random diffusion movement inherited from BioScape, programmable locations allow us to capture the assemblies of configurations of polymers, oligomers, and complexes such as microtubules or actin filaments. Further new aspects of BioScapeL include random translation and scaling. Random translation is instrumental in describing the location of new entities relative to the old ones. For example, when a cell secretes a hydronium ion, the ion should be placed at a given distance from the originating cell, but in a random direction. Additionally, scaling allows us to capture at a high level events such as division and growth; for example, daughter cells after mitosis have half the size of the mother cell.
{"title":"A Calculus of Located Entities","authors":"Adriana B. Compagnoni, P. Giannini, Catherine Kim, Matthew Milideo, Vishakha Sharma","doi":"10.4204/EPTCS.144.4","DOIUrl":"https://doi.org/10.4204/EPTCS.144.4","url":null,"abstract":"We define BioScapeL, a stochastic pi-calculus in 3D-space. A novel aspect of BioScapeL is that entities have programmable locations. The programmer can specify a particular location where to place an entity, or a location relative to the current location of the entity. The motivation for the extension comes from the need to describe the evolution of populations of biochemical species in space, while keeping a sufficiently high level description, so that phenomena like diffusion, collision, and confinement can remain part of the semantics of the calculus. Combined with the random diffusion movement inherited from BioScape, programmable locations allow us to capture the assemblies of configurations of polymers, oligomers, and complexes such as microtubules or actin filaments. \u0000Further new aspects of BioScapeL include random translation and scaling. Random translation is instrumental in describing the location of new entities relative to the old ones. For example, when a cell secretes a hydronium ion, the ion should be placed at a given distance from the originating cell, but in a random direction. Additionally, scaling allows us to capture at a high level events such as division and growth; for example, daughter cells after mitosis have half the size of the mother cell.","PeriodicalId":88470,"journal":{"name":"Dialogues in cardiovascular medicine : DCM","volume":"51 4 1","pages":"41-56"},"PeriodicalIF":0.0,"publicationDate":"2014-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91012557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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