| 1. |
- Ghosh, S., et al.
(författare)
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Rule-based modelling of iron homeostasis in tuberculosis
- 2011
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Ingår i: Molecular BioSystems. - : Royal Society of Chemistry (RSC). - 1742-2051 .- 1742-206X. ; 7:10, s. 2750-2768
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Tidskriftsartikel (refereegranskat)abstract
- To establish itself within the host system, Mycobacterium tuberculosis (Mtb) has formulated various means of attacking the host system. One such crucial strategy is the exploitation of the iron resources of the host system. Obtaining and maintaining the required concentration of iron becomes a matter of contest between the host and the pathogen, both trying to achieve this through complex molecular networks. The extent of complexity makes it important to obtain a systems perspective of the interplay between the host and the pathogen with respect to iron homeostasis. We have reconstructed a systems model comprising 92 components and 85 protein-protein or protein-metabolite interactions, which have been captured as a set of 194 rules. Apart from the interactions, these rules also account for protein synthesis and decay, RBC circulation and bacterial production and death rates. We have used a rule-based modelling approach, Kappa, to simulate the system separately under infection and non-infection conditions. Various perturbations including knock-outs and dual perturbation were also carried out to monitor the behavioral change of important proteins and metabolites. From this, key components as well as the required controlling factors in the model that are critical for maintaining iron homeostasis were identified. The model is able to re-establish the importance of iron-dependent regulator (ideR) in Mtb and transferrin (Tf) in the host. Perturbations, where iron storage is increased, appear to enhance nutritional immunity and the analysis indicates how they can be harmful for the host. Instead, decreasing the rate of iron uptake by Tf may prove to be helpful. Simulation and perturbation studies help in identifying Tf as a possible drug target. Regulating the mycobactin (myB) concentration was also identified as a possible strategy to control bacterial growth. The simulations thus provide significant insight into iron homeostasis and also for identifying possible drug targets for tuberculosis.
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| 2. |
- Andersen, Jörgen H., et al.
(författare)
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A Machine Verified Distributed Sorting Algorithm
- 1996
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We present a verification of a distributed sorting algorithm in ALF, an implementation of Martin Löf's type theory. The implementation is expressed as a program in a priortized version of CBS, (the Calculus of Broadcasting Systems) which we have implemented in ALF. The specification is expressed in terms of an ALF type which represents the set of all sorted lists and an HML (Hennesey-Milner Logic) formula which expresses that the sorting program will input any number of data until it hears a value triggering the program to begin outputting the data in a sorted fashion. We gain expressive power from the type theory by inheriting the language of data, state expressions, and propositions.
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| 3. |
- Caprotti, Olga, 1964, et al.
(författare)
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High-quality translation: Molto tools and applications
- 2012
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Ingår i: The fourth Swedish Language Technology Conference (SLTC).
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Konferensbidrag (refereegranskat)abstract
- MOLTO (Multilingual On Line Translation, FP7-ICT-247914, www.molto-project.eu) is a European project focusing on translation on the web. MOLTO targets translation that has production quality, that is, usable for quick and reliable dissemination of information. MOLTO’s main focus is to increase the productivity of such translation systems, building on the technology of GF (Grammatical Framework) and its Resource Grammar Library. But MOLTO also develops hybrid methods which increase the quality of Statistical Machine Translation (SMT) by adding linguistic information, or bootstrap grammatical models from statistical models. This paper gives a brief overview of MOLTO’s latest achievements, many of which are more thoroughly described in separate papers and available as web-based demos and as open-source software.
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| 4. |
- Ghosh, Soma, et al.
(författare)
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Rule Based Modeling of Iron Homeostasis in Tuberculosis
- 2010
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Ingår i: The Eighth Asia Pacific Bioinformatics Conference, Bangalore, India (APBC2010).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Mycobacterium tuberculosis (Mtb), which causes Tuberculosis (TB), has evolved into manydrug resistant forms, and in symbiosis with AIDS and other diseases, has become a dreadedpathogen world-wide. In an attempt to find new drugs, researchers have turned to the study ofiron homeostasis in TB: iron is an important resource that Mtb steals from its host, and isinvolved in the manifestation of virulence. We have formally encoded the relevant molecularinteractions described in the literature, yielding a program to simulate these aspects of ironmetabolism in Mtb, in the host, and in the interaction between the two. Iron acquisition viasiderophores is featured in detail.The Kappa modeling language we use represents molecular interactions compactly by rules,these being generalisations of chemical equations. The Kappa tool tells us syntactically howthe reactions are related, so we can see which play a central role, and which are comparativelyisolated. Our simulation results, both pathways and concentrations of species, match thosedescribed in the literature. Our program can therefore be used as an unambiguousrepresentation to anchor discussions about iron and TB, and to predict the results ofhypothetical perturbations that might be of use in the search for new drugs. For example, theresults of changing the infection level are as expected.A future possibility would be to combine our model with a genetic algorithm to suggest waysin which Mtb might evolve resistance to planned interventions.
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| 5. |
- Harcourt, Ed, et al.
(författare)
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A Framework for Representing Parameterised Processes
- 1995
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We describe a faithful representation of value-passing recursive parametric CCS processes in Alf, an implementation of Martin-Lof's constructive type theory. The representation is interesting because we borrow as much as possible from Alf including the domain of value and state expressions and the ability to evaluate them. Usually substitution of either channel values for channel variables and processes for process variables play a necessary role in the semantics. However, substitution is also borrowed from Alf by using higher-order functions. The main importance of this representation is that it allows us to borrow Alf's off-the-shelf theorems about data types and provides a uniform setting for doing various kinds machine assisted proofs, such as bisimulation proofs, equational reasoning, verification of Hennessy-Milner logic formulas. 1 Introduction Machine checked proofs of CCS processes require finite representations of the processes. However, for infinite value and state domains,...
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| 6. |
- Kühn, Clemens, 1981, et al.
(författare)
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Formal Representation of the High Osmolarity Glycerol Pathway in Yeast
- 2009
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Ingår i: Genome informatics. International Conference on Genome Informatics. - 0919-9454. ; 22, s. 69-83
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Tidskriftsartikel (refereegranskat)abstract
- The high osmolarity glycerol (HOG) signalling system in yeast belongs to the class of Mitogen Activated Protein Kinase (MAPK) pathways that are found in all eukaryotic organisms. It includes at least three scaffold proteins that form complexes, and involves reactions that are strictly dependent on the set of species bound to a certain complex. The scaffold proteins lead to a combinatorial increase in the number of possible states. To date, representations of the HOG pathway have used simplifying assumptions to avoid this combinatorial problem. Such assumptions are hard to make and may obscure or remove essential properties of the system.This paper presents a detailed generic formal representation of the HOG system without such assumptions, showing the molecular interactions known from the literature. The model takes complexes into account, and summarises existing knowledge in an unambiguous and detailed representation. It can thus be used to anchor discussions about the HOG system. In the commonly used Systems Biology Markup Language (SBML), such a model would need to explicitly enumerate all state variables. The \emph{Kappa} modelling language which we use supports representation of complexes without such enumeration.To conclude, we compare \emph{Kappa} with a few other modelling languages and software tools that could also be used to represent and model the HOG system.
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| 7. |
- Ostrovsky, Karol, 1975, et al.
(författare)
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Towards a Primitive Higher Order Calculus of Broadcasting Systems
- 2002
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Ingår i: PPDP '02. - New York, NY : ACM Press. - 1581135289 ; , s. 2-13
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Konferensbidrag (refereegranskat)abstract
- Ethernet-style broadcast is a pervasive style of computer communication. In this style, the medium is a single nameless channel. Previous work on modelling such systems proposed a first order process calculus called CBS. In this paper, we propose a fundamentally different calculus called HOBS. Compared to CBS, HOBS 1) is higher order rather than first order, 2) supports dynamic subsystem encapsulation rather than static, and 3) does not require an "underlying language" to be Turing-complete. Moving to a higher order calculus is key to increasing the expressivity of the primitive calculus and alleviating the need for an underlying language. The move, however, raises the need for significantly more machinery to establish the basic properties of the new calculus. This paper develops the basic theory for HOBS and presents two example programs that illustrate programming in this language. The key technical underpinning is an adaptation of Howe's method to HOBS to prove that bisimulation is a congruence. From this result, HOBS is shown to embed the lazy λ-calculus.
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| 8. |
- Prasad, K V S, 1952
(författare)
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A Calculus of Broadcasting Systems
- 1995
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Ingår i: Science of Computer Programming. - 0167-6423. ; 25:2-3, s. 285-327
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Tidskriftsartikel (refereegranskat)abstract
- CBS is a simple and natural CCS-like calculus where processes speak one at a time and are heard instantaneously by all others. Speech is autonomous, contention between speakers being resolved non-deterministically, but hearing only happens when someone else speaks. Observationally meaningful laws differ from those of CCS. The change from handshake communication in CCS to broadcast in CBS permits several advances.1. Priority, which attaches only to autonomous actions, is simply added to CBS in contrast to CCS, where such actions are the result of communication.2. A CBS simulator runs a process by returning a list of values it broadcasts. This permits a powerful combination, CBS with the host language. It yields several elegant algorithms. Only processes with a unique response to each input are needed in practice, so weak bisimulation is a congruence.3. CBS subsystems are interfaced by translators; by mapping messages to silence, these can restrict hearing and hide speech.Reversing a translator turns its scope inside out. This permits a new specification for a communication link: the environment of each user should behave like the other user.This paper reports the stable aspects of an evolving study.
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| 9. |
- Prasad, K V S, 1952
(författare)
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A Calculus of Broadcasting Systems
- 1991
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Ingår i: Samson Abramsky, T. S. E. Maibaum (Eds.): TAPSOFT'91: Proceedings of the International Joint Conference on Theory and Practice of Software Development, Brighton, UK, April 8-12, 1991, Volume 1: Colloquium on Trees in Algebra and Programming (CAAP'91). Springer 1991 Lecture Notes in Computer Science. - 3540539824 ; , s. 338-358
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Konferensbidrag (refereegranskat)abstract
- CBS is a simple and natural CCS-like calculus where processes speak one at a time and are heard instantaneously by all others. Speech is autonomous, contention between speakers being resolved nondeterministically,but hearing only happens when someone else speaks.Observationally meaningful laws dier from those of CCS. The changefrom handshake communication in CCS to broadcast in CBS permits severaladvances. (1) Priority, which attaches only to autonomous actions,is simply added to CBS in contrast to CCS, where such actions are theresult of communication. (2) A CBS simulator runs a process by returninga list of values it broadcasts. This permits a powerful combination,CBS with the host language. It yields several elegant algorithms. Onlyprocesses with a unique response to each input are needed in practice, soweak bisimulation is a congruence. (3) CBS subsystems are interfaced bytranslators; by mapping messages to silence, these can restrict hearingand hide speech. Reversing a translator turns its scope inside out. Thispermits a new specification for a communication link: the environmentof each user should behave like the other user.This paper reports the stable aspects of an evolving study.
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| 10. |
- Prasad, K V S, 1952
(författare)
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A Calculus of Value Broadcasts
- 1993
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Ingår i: Arndt Bode, Mike Reeve, Gottfried Wolf (Eds.): PARLE '93, Parallel Architectures and Languages Europe, 5th International PARLE Conference, Munich, Germany, June 14-17, 1993, Proceedings. Springer 1993 Lecture Notes in Computer Science. - 3540568913 ; , s. 391-402
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Konferensbidrag (refereegranskat)abstract
- Computation can be modelled as a sequence of values, each broadcast by one agent and instantaneously audible to all those in parallel with it. Listening agents receive the value; others lose it. Subsystems interface via translators; these can scramble values and thus hide or restrict them. Examples show the calculus describing this model to be a powerful and natural programming tool. Weak bisimulation, a candidate for observational equivalence, is defined on the basis that receiving a value can be matched by losing it.
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