Ivan Mura | Universidad de los Andes (Colombia) (original) (raw)
Publications by Ivan Mura
Methods in molecular biology (Clifton, N.J.), 2016
The periodic oscillations in the activity of the cell cycle regulatory program, drives the timely... more The periodic oscillations in the activity of the cell cycle regulatory program, drives the timely activation of key cell cycle events. Interesting dynamical systems, such as oscillators, have been investigated by various theoretical and computational modeling methods. Thanks to the insights achieved by these modeling efforts we have gained considerable insights about the underlying molecular regulatory networks that can drive cell cycle oscillations. Here we review the basic features and characteristics of biological oscillators, discussing from a computational modeling point of view their specific architectures and the current knowledge about the dynamics that the life evolution selected to drive cell cycle oscillations.
Pathogens and Disease, 2015
Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the m... more Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most poisonous substances known to mankind. However, toxin regulation and signals triggering synthesis as well as the regulatory network and actors controlling toxin production are unknown. Experiments show that the neurotoxin gene is growth phase dependent for C. botulinum type A1 strain ATCC 19397, and toxin production is influenced both by culture conditions and nutritional status of the medium. Building mathematical models to describe the genetic and molecular machinery that drives the synthesis and release of BoNT requires a simultaneous description of the growth of the bacterium in culture. Here, we show four plausible modelling options which could be considered when constructing models describing the pattern of growth observed in a botulinum growth medium. Commonly used bacterial growth models are unsuitable to fit the pattern of growth observed, since they only include monotonic growth behaviour. We find that a model that includes both the nutritional status and the ability of the cells to sense their surroundings in a quorum-sensing manner is most successful at explaining the pattern of growth obtained for C. botulinum type A1 strain ATCC 19397.
HER members of the tyrosine-kinase family of trans-membrane receptors are initiators of signaling... more HER members of the tyrosine-kinase family of trans-membrane receptors are initiators of signaling cascades driving crucial cellular process, such as gene transcription, cell cycle progression, and apoptosis. Given their capacity of oncogenic transformation these receptors are the target of selective anticancer drugs, which in-vivo are however not as effective as anticipated by in-vitro experiments. Translating HER inhibitors into effective therapies to block the oncogenic signaling cascades will be facilitated by models that can provide reliable predictions for the evolution of the intricate HER mediated signaling networks. This work presents a process-algebra based approach to compactly specify and simulate HER signaling models. The proposed HER activation model can be easily reused as a building block in larger models of signaling.presents a process-algebra based approach to compactly specify and sim- ulate HER signaling models. The proposed HER activation model can be easily reus...
There are two popular approaches to modelling and verification of biological systems. In the firs... more There are two popular approaches to modelling and verification of biological systems. In the first one a system of ordinary differential equations (ODEs) is developed and solved through numerical integration techniques yielding a deterministic solution of the model. In the second one a stochastic (discrete-state) model is obtained and analysed through (stochastic) simulation techniques, yielding statistical estimates of the system behaviour. We propose an alternative approach based on probabilistic/stochastic model checking techniques. Relaying on temporal logic formalisms we investigate the possibility for a query language for stating biological properties of a system's model. Such queries are then automatically evaluated through existing model checking algorithms. To exemplify such approach we consider a biochemical oscillator taken from the literature. First we study such oscillator through the classical ODEs and stochastic simulation approaches. Then we develop a number of (probabilistic) queries that we verify against a Markov chain model of the oscillator, through the probabilistic model checler PRISM.
The Journal of Chemical Physics, Oct 28, 2008
In robust biological systems, wide deviations from highly controlled normal behavior may be rare,... more In robust biological systems, wide deviations from highly controlled normal behavior may be rare, yet they may result in catastrophic complications. While in silico analysis has gained an appreciation as a tool to offer insights into system-level properties of biological systems, analysis of such rare events provides a particularly challenging computational problem. This paper proposes an efficient stochastic simulation method to analyze rare events in biochemical systems. Our new approach can substantially increase the frequency of the rare events of interest by appropriately manipulating the underlying probability measure of the system, allowing high-precision results to be obtained with substantially fewer simulation runs than the conventional direct Monte Carlo simulation. Here, we show the algorithm of our new approach, and we apply it to the analysis of rare deviant transitions of two systems, resulting in several orders of magnitude speedup in generating high-precision estimates compared with the conventional Monte Carlo simulation.
Pathogens and disease, 2015
Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the m... more Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most poisonous substances known to mankind. However, toxin regulation and signals triggering synthesis as well as the regulatory network and actors controlling toxin production are unknown. Experiments show that the neurotoxin gene is growth phase dependent for C. botulinum type A1 strain ATCC 19397, and toxin production is influenced both by culture conditions and nutritional status of the medium. Building mathematical models to describe the genetic and molecular machinery that drives the synthesis and release of BoNT requires a simultaneous description of the growth of the bacterium in culture. Here, we show four plausible modelling options which could be considered when constructing models describing the pattern of growth observed in a botulinum growth medium. Commonly used bacterial growth models are unsuitable to fit the pattern of growth observed, since they only include monotonic g...
Proceedings of IEEE International Computer Performance and Dependability Symposium, 1996
This work deals with analytical modelling of synchronisation delay experienced in multiprocessing... more This work deals with analytical modelling of synchronisation delay experienced in multiprocessing systems which execute redundant software to improve dependability figures. We propose a stochastic model based on a queuing network approach of system behaviour. We derive a bounded approximation of the distribution function of synchronisation delay by applying the matrix-geometric technique to analyse the model. An exact aggregation of
Journal of Bacteriology, 2015
Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the m... more Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most potent biological substances known to mankind. BoNTs are the agents responsible for botulism, a rare condition affecting the neuromuscular junction, causing a spectrum of diseases from mild cranial nerve palsies to acute respiratory failure and death. BoNTs are a potential bio-warfare threat and a public health hazard, since outbreaks of foodborne botulism are caused by the ingestion of preformed BoNTs in food. Currently, mathematical models relating to the hazards associated with C. botulinum, which are largely empirical, make major contributions to botulinum risk assessment. Evaluated using statistical techniques, these models simulate the response of the bacterium to environmental conditions. Though empirical models have been successfully incorporated into risk assessments to support food safety decision making, this process includes significant uncertainties so that relevant decision making is frequently conservative and inflexible. Progression involves encoding into the models cellular processes at a molecular level, especially the details of the genetic and molecular machinery. This addition drives the connection between biological mechanism and botulism risk assessment and hazard management strategies. This review brings together elements currently described in the literature which will be useful in building quantitative models of C. botulinum neurotoxin production. Subsequently, it outlines how the established form of modelling could be extended to include these new elements. Ultimately, this can offer further contributions into risk assessments to support food safety decision making.
2014 IEEE Colombian Conference on Communications and Computing (COLCOM), 2014
ABSTRACT This paper deals with the performance evaluation of systems whose service rates are depe... more ABSTRACT This paper deals with the performance evaluation of systems whose service rates are dependent on external variables, such as the level of resource availability in computing systems, the intensity of background traffic or the failures affecting telecommunications networks. A well-established class of performance models for systems belonging to this class is represented by Markov-modulated queuing networks. Motivated by a review of the results available in the literature, we propose in this work a very simple and generalizable analytical approach to compute the expected service time when the number of servers is very large and can be modeled as being infinite. Our analytical approach is a new one. With it, we are able to re-obtain in this paper results that are already known in the performance modeling and evaluation community. Moreover, we show through examples how the straightforward mathematical treatment we define can be applied to classes of models for which no analytical results are yet available.
Advances in Intelligent Systems and Computing, 2014
ABSTRACT HER members of the tyrosine-kinase family of trans-membrane receptors are initiators of ... more ABSTRACT HER members of the tyrosine-kinase family of trans-membrane receptors are initiators of signaling cascades driving crucial cellular process, such as gene transcription, cell cycle progression, and apoptosis. Given their capacity of oncogenic transformation these receptors are the target of selective anticancer drugs, which in-vivo are however not as effective as anticipated by in-vitro experiments. Translating HER inhibitors into effective therapies to block the oncogenic signaling cascades will be facilitated by models that can provide reliable predictions for the evolution of the intricate HER mediated signaling networks. This work presents a process-algebra based approach to compactly specify and simulate HER signaling models. The proposed HER activation model can be easily reused as a building block in larger models of signaling.presents a process-algebra based approach to compactly specify and sim- ulate HER signaling models. The proposed HER activation model can be easily reused as a building block in larger models of signaling.
Encyclopedia of Systems Biology, 2013
Wireless Personal Communications, 2004
Page 1. Wireless Personal Communications 30: 7795, 2004. C 2004 Kluwer Academic Publishers. Prin... more Page 1. Wireless Personal Communications 30: 7795, 2004. C 2004 Kluwer Academic Publishers. Printed in the Netherlands. A Real-Time Monitoring and Intelligent Decisions-Making Platform for Enhanced Radio Resource Management in Wireless Cellular Systems ...
BMC Systems Biology, 2014
Background: Bacterial spores are important contaminants in food, and the spore forming bacteria a... more Background: Bacterial spores are important contaminants in food, and the spore forming bacteria are often implicated in food safety and food quality considerations. Spore formation is a complex developmental process involving the expression of more than 500 genes over the course of 6 to 8 hrs. The process culminates in the formation of resting cells capable of resisting environmental extremes and remaining dormant for long periods of time, germinating when conditions promote further vegetative growth. Experimental observations of sporulation and germination are problematic and time consuming so that reliable models are an invaluable asset in terms of prediction and risk assessment. In this report we develop a model which assists in the interpretation of sporulation dynamics.
Lecture Notes in Computer Science, 1997
Fork and join queueing network models can be used to represent and analyse the performance of dis... more Fork and join queueing network models can be used to represent and analyse the performance of distributed and parallel processing computer systems with concurrence and synchronisation constraints and shared resources. Concurrence and synchronisation make the solution of such performance models more complex than classical queueing network analysis. We consider parallel processing systems where a set of independent tasks are executed simultaneously and can be represented by fork and join queueing networks. We present an approximate method to analyse open fork and join queueing networks with general service time distribution represented by Coxian distribution. Specifically, we derive two approximations of the joint queue length distribution and closed form expressions for all the moments of this distribution. We prove that the method provides lower and upper bounds on the queue length moments.
Results: Gene expression is a fundamentally stochastic process with randomness in transcription a... more Results: Gene expression is a fundamentally stochastic process with randomness in transcription and translation. Usually, stochastic modelling techniques used in gene expression are based on the Gillespie approach, where the role of parameters and the ...
Page 1. CAUTION IST-2000-25352 D-4.3 Migration of CAUTION Platform for Efficient Resource Managem... more Page 1. CAUTION IST-2000-25352 D-4.3 Migration of CAUTION Platform for Efficient Resource Management in a Multi-system Wireless Networking Environment Contractual Date of Delivery to the CEC: 30 September 2002 (extension) ...
D-3.3 Traffic Load Scenario and Decision Making ... Contractual Date of Delivery to the CEC: 30 S... more D-3.3 Traffic Load Scenario and Decision Making ... Contractual Date of Delivery to the CEC: 30 September 2001 ... Actual Date of Delivery to the CEC: 15 October 2001 ... Author(s): Massimo Barbera1, Cristina Barbero1, Paola Dal Zovo1, Fernanda ...
This paper proposes a simplification of the stochastic Petri nets graphical notation with the pur... more This paper proposes a simplification of the stochastic Petri nets graphical notation with the purpose of defining a more compact and clearer graphical way of building formal models of biological phenomena. Three biological examples are first presented, then modeled with the classical SPN modeling formalism, and their key modeling patterns distilled to identify the main features that need to be represented in a stochastic model. The key features are then the object of the original part of the paper, in which a simplified and more concise, although formal, graphical notation, is proposed, and applied to the selected examples. The paper demonstrates the effectiveness of the simplified notation in producing more compact and understandable models of biological phenomena, still retaining the nice properties of Stochastic Petri Nets, i.e., their flexible abstraction level and formal semantics.
Methods in molecular biology (Clifton, N.J.), 2016
The periodic oscillations in the activity of the cell cycle regulatory program, drives the timely... more The periodic oscillations in the activity of the cell cycle regulatory program, drives the timely activation of key cell cycle events. Interesting dynamical systems, such as oscillators, have been investigated by various theoretical and computational modeling methods. Thanks to the insights achieved by these modeling efforts we have gained considerable insights about the underlying molecular regulatory networks that can drive cell cycle oscillations. Here we review the basic features and characteristics of biological oscillators, discussing from a computational modeling point of view their specific architectures and the current knowledge about the dynamics that the life evolution selected to drive cell cycle oscillations.
Pathogens and Disease, 2015
Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the m... more Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most poisonous substances known to mankind. However, toxin regulation and signals triggering synthesis as well as the regulatory network and actors controlling toxin production are unknown. Experiments show that the neurotoxin gene is growth phase dependent for C. botulinum type A1 strain ATCC 19397, and toxin production is influenced both by culture conditions and nutritional status of the medium. Building mathematical models to describe the genetic and molecular machinery that drives the synthesis and release of BoNT requires a simultaneous description of the growth of the bacterium in culture. Here, we show four plausible modelling options which could be considered when constructing models describing the pattern of growth observed in a botulinum growth medium. Commonly used bacterial growth models are unsuitable to fit the pattern of growth observed, since they only include monotonic growth behaviour. We find that a model that includes both the nutritional status and the ability of the cells to sense their surroundings in a quorum-sensing manner is most successful at explaining the pattern of growth obtained for C. botulinum type A1 strain ATCC 19397.
HER members of the tyrosine-kinase family of trans-membrane receptors are initiators of signaling... more HER members of the tyrosine-kinase family of trans-membrane receptors are initiators of signaling cascades driving crucial cellular process, such as gene transcription, cell cycle progression, and apoptosis. Given their capacity of oncogenic transformation these receptors are the target of selective anticancer drugs, which in-vivo are however not as effective as anticipated by in-vitro experiments. Translating HER inhibitors into effective therapies to block the oncogenic signaling cascades will be facilitated by models that can provide reliable predictions for the evolution of the intricate HER mediated signaling networks. This work presents a process-algebra based approach to compactly specify and simulate HER signaling models. The proposed HER activation model can be easily reused as a building block in larger models of signaling.presents a process-algebra based approach to compactly specify and sim- ulate HER signaling models. The proposed HER activation model can be easily reus...
There are two popular approaches to modelling and verification of biological systems. In the firs... more There are two popular approaches to modelling and verification of biological systems. In the first one a system of ordinary differential equations (ODEs) is developed and solved through numerical integration techniques yielding a deterministic solution of the model. In the second one a stochastic (discrete-state) model is obtained and analysed through (stochastic) simulation techniques, yielding statistical estimates of the system behaviour. We propose an alternative approach based on probabilistic/stochastic model checking techniques. Relaying on temporal logic formalisms we investigate the possibility for a query language for stating biological properties of a system's model. Such queries are then automatically evaluated through existing model checking algorithms. To exemplify such approach we consider a biochemical oscillator taken from the literature. First we study such oscillator through the classical ODEs and stochastic simulation approaches. Then we develop a number of (probabilistic) queries that we verify against a Markov chain model of the oscillator, through the probabilistic model checler PRISM.
The Journal of Chemical Physics, Oct 28, 2008
In robust biological systems, wide deviations from highly controlled normal behavior may be rare,... more In robust biological systems, wide deviations from highly controlled normal behavior may be rare, yet they may result in catastrophic complications. While in silico analysis has gained an appreciation as a tool to offer insights into system-level properties of biological systems, analysis of such rare events provides a particularly challenging computational problem. This paper proposes an efficient stochastic simulation method to analyze rare events in biochemical systems. Our new approach can substantially increase the frequency of the rare events of interest by appropriately manipulating the underlying probability measure of the system, allowing high-precision results to be obtained with substantially fewer simulation runs than the conventional direct Monte Carlo simulation. Here, we show the algorithm of our new approach, and we apply it to the analysis of rare deviant transitions of two systems, resulting in several orders of magnitude speedup in generating high-precision estimates compared with the conventional Monte Carlo simulation.
Pathogens and disease, 2015
Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the m... more Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most poisonous substances known to mankind. However, toxin regulation and signals triggering synthesis as well as the regulatory network and actors controlling toxin production are unknown. Experiments show that the neurotoxin gene is growth phase dependent for C. botulinum type A1 strain ATCC 19397, and toxin production is influenced both by culture conditions and nutritional status of the medium. Building mathematical models to describe the genetic and molecular machinery that drives the synthesis and release of BoNT requires a simultaneous description of the growth of the bacterium in culture. Here, we show four plausible modelling options which could be considered when constructing models describing the pattern of growth observed in a botulinum growth medium. Commonly used bacterial growth models are unsuitable to fit the pattern of growth observed, since they only include monotonic g...
Proceedings of IEEE International Computer Performance and Dependability Symposium, 1996
This work deals with analytical modelling of synchronisation delay experienced in multiprocessing... more This work deals with analytical modelling of synchronisation delay experienced in multiprocessing systems which execute redundant software to improve dependability figures. We propose a stochastic model based on a queuing network approach of system behaviour. We derive a bounded approximation of the distribution function of synchronisation delay by applying the matrix-geometric technique to analyse the model. An exact aggregation of
Journal of Bacteriology, 2015
Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the m... more Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most potent biological substances known to mankind. BoNTs are the agents responsible for botulism, a rare condition affecting the neuromuscular junction, causing a spectrum of diseases from mild cranial nerve palsies to acute respiratory failure and death. BoNTs are a potential bio-warfare threat and a public health hazard, since outbreaks of foodborne botulism are caused by the ingestion of preformed BoNTs in food. Currently, mathematical models relating to the hazards associated with C. botulinum, which are largely empirical, make major contributions to botulinum risk assessment. Evaluated using statistical techniques, these models simulate the response of the bacterium to environmental conditions. Though empirical models have been successfully incorporated into risk assessments to support food safety decision making, this process includes significant uncertainties so that relevant decision making is frequently conservative and inflexible. Progression involves encoding into the models cellular processes at a molecular level, especially the details of the genetic and molecular machinery. This addition drives the connection between biological mechanism and botulism risk assessment and hazard management strategies. This review brings together elements currently described in the literature which will be useful in building quantitative models of C. botulinum neurotoxin production. Subsequently, it outlines how the established form of modelling could be extended to include these new elements. Ultimately, this can offer further contributions into risk assessments to support food safety decision making.
2014 IEEE Colombian Conference on Communications and Computing (COLCOM), 2014
ABSTRACT This paper deals with the performance evaluation of systems whose service rates are depe... more ABSTRACT This paper deals with the performance evaluation of systems whose service rates are dependent on external variables, such as the level of resource availability in computing systems, the intensity of background traffic or the failures affecting telecommunications networks. A well-established class of performance models for systems belonging to this class is represented by Markov-modulated queuing networks. Motivated by a review of the results available in the literature, we propose in this work a very simple and generalizable analytical approach to compute the expected service time when the number of servers is very large and can be modeled as being infinite. Our analytical approach is a new one. With it, we are able to re-obtain in this paper results that are already known in the performance modeling and evaluation community. Moreover, we show through examples how the straightforward mathematical treatment we define can be applied to classes of models for which no analytical results are yet available.
Advances in Intelligent Systems and Computing, 2014
ABSTRACT HER members of the tyrosine-kinase family of trans-membrane receptors are initiators of ... more ABSTRACT HER members of the tyrosine-kinase family of trans-membrane receptors are initiators of signaling cascades driving crucial cellular process, such as gene transcription, cell cycle progression, and apoptosis. Given their capacity of oncogenic transformation these receptors are the target of selective anticancer drugs, which in-vivo are however not as effective as anticipated by in-vitro experiments. Translating HER inhibitors into effective therapies to block the oncogenic signaling cascades will be facilitated by models that can provide reliable predictions for the evolution of the intricate HER mediated signaling networks. This work presents a process-algebra based approach to compactly specify and simulate HER signaling models. The proposed HER activation model can be easily reused as a building block in larger models of signaling.presents a process-algebra based approach to compactly specify and sim- ulate HER signaling models. The proposed HER activation model can be easily reused as a building block in larger models of signaling.
Encyclopedia of Systems Biology, 2013
Wireless Personal Communications, 2004
Page 1. Wireless Personal Communications 30: 7795, 2004. C 2004 Kluwer Academic Publishers. Prin... more Page 1. Wireless Personal Communications 30: 7795, 2004. C 2004 Kluwer Academic Publishers. Printed in the Netherlands. A Real-Time Monitoring and Intelligent Decisions-Making Platform for Enhanced Radio Resource Management in Wireless Cellular Systems ...
BMC Systems Biology, 2014
Background: Bacterial spores are important contaminants in food, and the spore forming bacteria a... more Background: Bacterial spores are important contaminants in food, and the spore forming bacteria are often implicated in food safety and food quality considerations. Spore formation is a complex developmental process involving the expression of more than 500 genes over the course of 6 to 8 hrs. The process culminates in the formation of resting cells capable of resisting environmental extremes and remaining dormant for long periods of time, germinating when conditions promote further vegetative growth. Experimental observations of sporulation and germination are problematic and time consuming so that reliable models are an invaluable asset in terms of prediction and risk assessment. In this report we develop a model which assists in the interpretation of sporulation dynamics.
Lecture Notes in Computer Science, 1997
Fork and join queueing network models can be used to represent and analyse the performance of dis... more Fork and join queueing network models can be used to represent and analyse the performance of distributed and parallel processing computer systems with concurrence and synchronisation constraints and shared resources. Concurrence and synchronisation make the solution of such performance models more complex than classical queueing network analysis. We consider parallel processing systems where a set of independent tasks are executed simultaneously and can be represented by fork and join queueing networks. We present an approximate method to analyse open fork and join queueing networks with general service time distribution represented by Coxian distribution. Specifically, we derive two approximations of the joint queue length distribution and closed form expressions for all the moments of this distribution. We prove that the method provides lower and upper bounds on the queue length moments.
Results: Gene expression is a fundamentally stochastic process with randomness in transcription a... more Results: Gene expression is a fundamentally stochastic process with randomness in transcription and translation. Usually, stochastic modelling techniques used in gene expression are based on the Gillespie approach, where the role of parameters and the ...
Page 1. CAUTION IST-2000-25352 D-4.3 Migration of CAUTION Platform for Efficient Resource Managem... more Page 1. CAUTION IST-2000-25352 D-4.3 Migration of CAUTION Platform for Efficient Resource Management in a Multi-system Wireless Networking Environment Contractual Date of Delivery to the CEC: 30 September 2002 (extension) ...
D-3.3 Traffic Load Scenario and Decision Making ... Contractual Date of Delivery to the CEC: 30 S... more D-3.3 Traffic Load Scenario and Decision Making ... Contractual Date of Delivery to the CEC: 30 September 2001 ... Actual Date of Delivery to the CEC: 15 October 2001 ... Author(s): Massimo Barbera1, Cristina Barbero1, Paola Dal Zovo1, Fernanda ...
This paper proposes a simplification of the stochastic Petri nets graphical notation with the pur... more This paper proposes a simplification of the stochastic Petri nets graphical notation with the purpose of defining a more compact and clearer graphical way of building formal models of biological phenomena. Three biological examples are first presented, then modeled with the classical SPN modeling formalism, and their key modeling patterns distilled to identify the main features that need to be represented in a stochastic model. The key features are then the object of the original part of the paper, in which a simplified and more concise, although formal, graphical notation, is proposed, and applied to the selected examples. The paper demonstrates the effectiveness of the simplified notation in producing more compact and understandable models of biological phenomena, still retaining the nice properties of Stochastic Petri Nets, i.e., their flexible abstraction level and formal semantics.