MLCSB18

International Symposium on Molecular Logic and Computational Synthetic Biology

Santiago Chile, 17-18 December, 2018

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Overview

Synthetic biology aims at the design of biological systems in a systematic way, a process whose hallmark characteristics closely resemble the composition of software: off-the-shelf parts and devices with standard connections, the usual ingredients for assembling components into increasingly complex systems. Of course, a number of key enabling technologies are specifically biological, for example, DNA sequencing and fabrication. But, on the other hand, there is also a need for new models to cope with the complex and heterogeneous nature of biological systems. In this context, the Symposium starting point is to regard a network of interacting genes and proteins as a dynamic system evolving in time according to fundamental laws of reaction, diffusion and transport. These laws govern how a regulatory network, confronted by any set of stimuli, determines the appropriate response of a cell. The emerging behavioural patterns can be described in precise mathematical terms, combining discrete, continuous and stochastic features, and resorting both to specific or general-purpose analysis and verification techniques. Molecular logic, focussed on computing logical operations on molecules, a fruitful conceptual crossover between chemistry and computation with unsuspected applications, is a possible path in this research map. Actually, this Symposium emerged from a series of in- formal workshops on Molecular Logic which, for the last four years, have brought together researchers from different latitudes and backgrounds.

The new International Symposium aims at harnessing logical and algebraic methods for modelling and verifying systems on the interaction of Nature and Computation, around two main themes:

development of biological computation models and devices

application of new computing paradigms to the design of biological systems.

Original submissions are required in any topic from the following, non exclusive list:

Molecular logic

Chemistry, biology and computation

Quantum computing applications to biology

Computational synthetic biology

Control theory and/or algorithms for biological systems

Reconfigurability and adaptation

Probabilistic biological models

Hybrid systems for biology

Submissions on general computational models that are applicable to a biological context, such as probabilistic, hybrid, weighted, resource-based, and time-based are also welcome.

The workshop is promoted by the project Klee - Coalgebraic Modeling and Analysis for Computational Synthetic Biology (02/SAICT/2017), a R&D project supported by the Portuguese Foundation for Science and Technology

Important dates

8 September 2018 23 September 2018: Abstract deadline

15 September 2018 25 September 2018: Full paper deadline

15 October 2018 5 November 2018: Author notification

TBA: Final version deadline

TBA: Special issue invitation

Submissions and publications

Both fully mature contributions and work-in-progress submissions on the topics above are welcome. All contributions should be written in English, prepared in LATEX, using llncs style, and submitted as PDF files following instructions available from the symposium website. A page limit of 15 pages for full papers is established.

Extended abstracts with preliminarily results and work in progress (2-5 pages) are also welcomed for short presentations. They are subject to a light reviewing and will be available at the conference in an informal booklet.

All contributions must be original, unpublished and not submitted simultaneously for publication elsewhere. Both kinds of submissions should be done via the Online Conference System (OCS) of Springer using the link https://ocs.springer.com/ocs/home/MLCSB2018.

Proceedings with full papers will be published by Springer Lecture Notes in Computer Science Series. A journal Special Issue, with extended and revised versions of selected papers, is currently under negotiation.

Call for Papers
Second Call for Papers

MLCSB 2018 Post -Proceedings -- NEW!

LNCS 11415
eISBN 978-3-030-19432-1
Free online access for 4 weeks
(during May 2019)

• KLEE project

Chairs

• Manuel A. Martins (CIDMA, U.Aveiro, PT)
• Madalena Chaves, (Inria, France)

OC chairs

• Claudio Fuentes (U. Diego Portales, Chile)
• Daniel Figueiredo (U. Aveiro, Portugal)
• Pablo Razeto-Barry (IFICC, Chile)
• Tomás Veloz (IFICC, Chile)

Invited Speakers

• Marta Kwiatkowska (U. Oxford, U.K)
• Hidde de Jong (Inria, Grenoble, France)
• Alexandre Madeira (U. Minho, Portugal)

Program Committee

• Luís S. Barbosa (U. Minho, Portugal)
• Benjamin Bedregal (UFRN, Brasil)
• Mário Benevides (UFRJ, Brasil)
• Marcello Bonsangue (U. Leiden, Netherlands)
• Luca Cardelli (Microsoft Research, UK)
• Claudine Chaouiya (U.Aix-Marseille, France)
• Claudio Fuentes (U. Diego Portales, Chile)
• Sicun Gao (U. California, USA)
• Radu Grosu (Vienna U.T., Austria)
• Hidde de Jong (Inria, Grenoble, France)
• Masami Hagiya (U. Tokyo, Japan)
• Monika Heiner (Brandenburg TU, Germany)
• Marta Kwiatkowska (U. Oxford, U.K)
• Alexandre Madeira (U. Minho, Portugal)
• David Margulies (Weizmann I.S., Israel)
• Carlos Martín-Vide (U. Rovira i Virgili, Spain)
• Stefan Mitsch (Carnegie Mellon U., USA)
• Renato Neves (U. Minho, Portugal)
• Loic Pauleve (CNRS/LRI, France)
• Ion Petre (Abo Akademi Turku, Finland)
• Tatjana Petrov (U. Konstanz, Germany)
• Élisabeth Remy (IML Luminy, France)
• Eugénio Rocha (U. Aveiro, Portugal)
• Amilra P. de Silva (Queen’s U. Belfast, UK)
• Marie-France Sagot (ERABLE, Inria, France)
• Regivan Santiago (UFRN, Brasil)
• Ana Sokolova (U. Salzburg, Austria)
• Meng Sun (Peking University, China)
• Carolyn Talcott (SRI International, USA)
• Antonio Tallón (U. Seville, Spain)
• P.S. Thiagarajan (Harvard University, USA)
• Delfim F. M. Torres (U. Aveiro, Portugal)
• Adelinde Uhrmacher (U. Rostock, Germany)
• Boyan Yordanov (Microsoft Research, UK)
• Paolo Zuliani (Newcastle University, UK)

Invited talks

• Hidde de Jong
  INRIA Grenoble – Rhône-Alpes, France
  Natural and synthetic control of resource allocation in bacteria Abstract
  Abstract: Microorganisms adapt their physiology and growth rate to changes in nutrient availability in the environment. This involves changes in the expression of a large number of genes, encoding proteins with a variety of cellular functions. Fundamentally, the reorganization of gene expression in response to changes in environmental conditions is a resource allocation problem. It poses the question how microorganisms redistribute their protein synthesis capacity over different cellular functions when constrained by the changing environment. I will give an overview of recent work on resource allocation in bacteria, including novel insights gained by the application of optimal control theory. I will also present an approach to modify natural resource allocation schemes by putting the transcription of a key component of the gene expression machinery, RNA polymerase, under the control of an inducible promoter. By changing the inducer concentration in the medium, the RNA polymerase concentration can be adjusted and thereby bacterial growth switched between zero and the maximal growth rate supported by the medium. I will show that the proposed synthetic growth switch is a promising tool for gaining a better understanding of bacterial physiology and for applications in synthetic biology and biotechnology.
  

  • J. Izard, C. Gomez Balderas, D. Ropers, S. Lacour, X. Song, Y. Yang, A.B. Lindner, J. Geiselmann, H. de Jong. A synthetic growth switch based on controlled expression of RNA polymerase. Molecular Systems Biology, 11(11):840, 2015
    
  • N. Giordano, F. Mairet, J.-L. Gouzé, J. Geiselmann, H. de Jong. Dynamical allocation of cellular resources as an optimal control problem: Novel insights into microbial growth strategies. PLoS Computational Biology, 12(3): e1004802, 2016
    
  • H. de Jong, J. Geiselmann, D. Ropers . Resource reallocation in bacteria by reengineering the gene expression machinery. Trends in Microbiology, 25(6):480-93, 2017
    
  • I. Yegorov, F. Mairet, H. de Jong, J.-L. Gouzé. Optimal control of bacterial growth for the maximization of metabolite production. Journal of Mathematical Biology. To appear

  
  Hide abstract
• Marta Kwiatkowska
  University of Oxford, U.K
  Computing Reliably with Molecular Walkers Abstract
  Abstract: DNA computing is emerging as a versatile technology that promises a vast range of applications, including biosensing, drug delivery and synthetic biology. DNA logic circuits can be achieved in solution using strand displacement reactions, or by decision-making molecular robots-so called 'walkers'-that traverse tracks placed on DNA 'origami' tiles. Similarly to conventional silicon technologies, ensuring fault-free DNA circuit designs is challenging, with the difficulty compounded by the inherent unreliability of the DNA technology and lack of scientific understanding. This lecture will give an overview of computational models that capture DNA walker computation and demonstrate the role of quantitative verification and synthesis in ensuring the reliability of such systems. Future research challenges will also be discussed.
  Hide abstract
• Alexandre Madeira
  HASLab INESC TEC, U. Minho and
  CIDMA, U. Aveiro, Portugal
  Verification for everyone? An overview in Dynamic Logics Abstract
  Abstract: Alexandre Madeira HASLab INESC TEC, U. Minho CIDMA, U. Aveiro, Portugal madeira@ua.pt Abstract Propositional Dynamic Logic [2] was introduced in the 70’s by Pratt in [6] as a suitable logic to reason about, and verify, classic imperative programs. Since then, the original intuitions evolved to an entire family of logics, which became increasingly popular for assertional reasoning about a wide range of systems. This talk intends to make an overview on this path. Starting in the sem- inal motivations of Pratt, we present a method to the parametric generation of Graded Dynamic Logic. The dynamisation method [3, 4] contributed on this direction with a systematic parametric way to construct Multi-valued Dynamic Logics able to handle systems where the uncertainty is a prime concern. We con- clude the talk recalling other less conventional Dynamic Logics on the literature, including the Differential Dynamic Logic [5] and Quantum Dynamic Logic [1], opening the discussion about what and how these features can be useful on the goals of the current symposium.
  

  1. Baltag, A., Smets, S.: Quantum logic as a dynamic logic. Synthese 179(2), 285–306 (2011). 2. Harel, D., Kozen, D., Tiuryn, J.: Dynamic Logic. MIT Press (2000)
  3. Madeira, A., Neves, R., Martins, M.A.: An exercise on the genera- tion of many-valued dynamic logics. J. Log. Algebr. Meth. Program. 85(5), 1011–1037 (2016).
  4. Madeira, A., Neves, R., Martins, M.A., Barbosa, L.S.: A dynamic logic for ev- ery season. In: Braga, C., Martí-Oliet, N. (eds.) Formal Methods: Foundations and Applications - 17th Brazilian Symposium, SBMF 2014, Maceió, AL, Brazil, September 29-October 1, 2014. Proceedings. Lecture Notes in Computer Science, vol. 8941, pp. 130–145. Springer (2014).
  5. Platzer, A.: Logical Foundations of Cyber-Physical Systems. Springer (2018).
  6. Pratt, V.R.: Semantical considerations on floyd-hoare logic. In: 17th An- nual Symposium on Foundations of Computer Science, Houston, Texas, USA, 25-27 October 1976. pp. 109–121. IEEE Computer Society (1976).
  Hide abstract

Accepted contributions

Full papers

• Combinatorial dynamics for regulatory networks (Zane Huttinga, Bree Cummins, Tomas Gedeon) Abstract
  Abstract: Modeling dynamics of cellular networks presents significant challenges due to ill-defined nonlinearities, poorly characterized parameters, and noisy experimental data. Switching ODE systems are a modeling platform based on Boolean networks that allow the combinatorialization of dynamics and the parameter space, which in turn allows computing summaries of global dynamics across all parameters. In this contribution, we expand the class of cellular processes that can be modeled using this approach from direct transcriptional control to post-transcriptional modifications (PTM). We then show the relationship between parameter spaces of models with and without the PTM equations. We address the relationship between combinatorial representatives of dynamics and trajectories of the underlying ODE systems. We provide necessary and sufficient conditions that guarantee that representatives of equilibria correspond to equilibria of the dynamics, but also show that a phase space that correspond to a representative of a periodic orbit may not contain any bounded trajectory. Hide abstract
  
  
• Reactive models for biological regulatory networks (Daniel Figueiredo and Luis Barbosa) Abstract
  Abstract: A reactive model, as studied by Gabbay and his collaborators, can be regarded as a digraphs whose the set of edges may be altered whenever an edge is crossed. In this paper we show how reactive models can describe biological regulatory networks and compare them to Boolean networks and piecewise-linear models, which are some of the most common kinds of models used nowadays. In particular, we show that, with respect to the signaling of steady states, reactive models lie between piecewise linear models and Boolean networks. Finally, we consider the logic introduced by Gabbay & Marcelino and define a notion of reactive models equivalence (called bisimulation in the logical context) which gives us a notion of how to reduce large models. Hide abstract
  
  
• Temporal Logic Based Synthesis of Experimentally Constrained Interaction Networks (Hillel Kugler, Judah Goldfeder) Abstract
  Abstract: Synthesis methods based on formal reasoning are a powerful way to automate the process of constructing computational models of gene regulatory networks and increase predictive power by considering a set of consistent models. Previously, a formal reasoning approach enabling the synthesis and analysis of biological networks, where the precise interactions or update rules are unknown was developed. System dynamics can be constrained with specifications of some required behaviors, thereby providing a characterization of the set of all networks capable of reproducing some experimental observations. The synthesis method is supported by a tool, the Reasoning Engine for Interaction Networks (RE:IN). Starting with the synthesis framework provided by RE:IN, we provide translations to temporal logic and semantics of Abstract Boolean Networks that enable us to use of-theshelf model checking tools and algorithms. An initial prototype implementation we developed demonstrates this is a gainful approach, providing speed-up gains for some benchmarks, while also opening the way to study extensions of the experimental observations language currently supported in RE:IN by using the rich expressive power of temporal logics. Hide abstract
  
  
• A Logical Framework for Modelling Breast Cancer Progression (Joelle Despeyroux, Amy Felty, Pietro Lio, Carlos Olarte) Abstract
  Abstract: Data streams for a personalised breast cancer programme could include collections of image data, tumour genome sequencing, likely at the single cell level, and liquid biopsies (DNA and Circulating Tumour Cells (CTCs)). Although they are rich in information, the full power of these datasets will not be realised until we develop methods to model the cancer systems and conduct analyses that transect these streams. In addition to machine learning approaches, we believe that logical reasoning has the potential to provide help in clinical decision support systems for doctors. We develop a logical approach to modelling cancer progression, focusing on mutation analysis and CTCs, which include the appearance of driver mutations, the transformation of normal cells to cancer cells in the breast, their circulation in the blood, and their path to the bone. Our long term goal is to improve the prediction of survival of metastatic breast cancer patients. We model the behaviour of the CTCs as a transition system, and we use Linear Logic (LL) to reason about our model. We consider several important properties about CTCs and prove them in LL. In addition, we formalise our results in the Coq Proof Assistant, thus providing formal proofs of our model. We believe that our results provide a promising proof-ofprinciple and can be generalised to other cancer types and groups of driver mutations. Hide abstract
  
  
• Random chromatin neighborhoods in 2n=40 Mus m. domesticus meiotic cells: P-percolation and image segmentation (Soledad Berríos, Julio Lopez Fenner, Aude Maignan) Abstract
  Abstract: Dynamical organization of bivalents during meiosis may play a significant role in the appearance of joint genic expression, as the result of persistent overlapping domains of constitutive pericentromeric heterochromatin coming from different bivalents during pachytene. We present early findings of an ongoing research in which we apply standard global threshold segmentation techniques for assessing correlation between observed sizes of sets of overlapping heterochromatin domains in spreads of meiotic Mus m. domesticus 2n=40 spermatocytes during pachytene and their simulated counterparts. Simulated spreads were produced ad libitum using a special non homogeneous Bernoulli site percolation process, called P-Percolation, acting upon the fullerene's dual C'1200, in which clusters of pericentromeric heterochromatin are depicted by random chromatin neigborhoods (ranches) arising from a process characterized by a vector P of independent Bernoulli random variables. We show that under the hypothesis made, a vector P of at least three dimensions is needed for establishing coherence between observed and simulated values. Hide abstract
  
  
• Oscillatory behaviour on a non-autonomous hybrid SIR-model (Eugénio Rocha) Abstract
  Abstract: We study the impact of some abstract agent intervention on the disease spread modelled by a SIR-model with linear growth infectivity. The intervention are meant to decrease the infectivity, which are activated by a threshold on the number of infected individuals. The coupled model is represented as a nonlinear non-autonomous hybrid system. Stability at each node is obtained using the notions of non-autonomous attractors, Bohl exponents, and dichotomy spectrum. Numerical examples are given where the number of infected individuals can oscillate around a equilibrium point or be a succession of bump functions, which are validated with a tool based on the notion of delta-complete decision procedures for solving satisfiability modulo theories problems over the real numbers and bounded delta-reachability. These findings seem to show that hybrid SIR-models are more flexible than standard models and generate a vast set of solution profiles. It also raise questions regarding the possibility of the agent intervention been somehow responsible for the shape and intensity of future outbreaks. Hide abstract
  
  
• On the existence of synergies and the separability of closed reaction networks (Tomas Veloz, Alejandro Bassi, Pedro Maldonado, Pablo Razeto) Abstract
  Abstract: It is well known that closure is a necessary topological property for a reaction network to be dynamically stable. In this work we combine notions of chemical organization theory with structural properties of reaction networks to distill a minimal set of closed reaction networks that encodes the non-trivial stable dynamical regimes of the network. In particular, these non-trivial closed sets are synergetic, in the sense that their dynamics cannot always be computed from the dynamics of its closed constituents. We introduce a notion of separability for reaction networks and prove that it is strictly related to the notion of synergy. In particular, we provide a characterization of the nontrivial closed reaction networks by means of their degree of internal synergy. The less trivial the dynamics of the reaction network, the less can be separated into constituents, and equivalently the more synergies the reaction network has. We also discuss the computational and analytical benefits of this new representation of the dynamical structure of a reaction network. Hide abstract

  Extended abstracts

  
  
• A Susceptible-Infected-Removed Model on Time Scales (Delfim F. M. Torres) Abstract
  Abstract: We investigate an epidemic model based on Bailey's continuous differential system. In the continuous time domain, we extend the classical model to time-dependent coefficients and present an alternative solution method to Gleissner's approach. If the coefficients are constant, both solution methods yield the same result. After a brief introduction to time scales, we formulate the SIR (susceptible-infected-removed) model in the general time domain (including the continuous, the discrete, and hybrid cases) and derive its solution. In the discrete case, this provides the solution to a new discrete epidemic system, which exhibits the same behavior as the continuous model. The last part is dedicated to the analysis of the limiting behavior of susceptible, infected, and removed, which contains biological relevance. Work done by: Martin Bohner, Sabrina Streipert and Delfim F. M. Torres. Hide abstract
  
  
• Logics for Petri nets with propagating failures (Leandro Rafael Gomes, Alexandre Madeira, Mario Benevides) Abstract
  Abstract: Petri nets play a central role in the formal analysis of a wide range of complex systems and scenarios. Their ability to handle with concurrency and resource awareness justifies their adoption in a number of distinct contexts and applications, from the formal development of software, to other less conventional domains, as chemistry or biology. However, as usual, the application to new situations raises new challenges and issues. The ubiquity of failures in biological systems (as triggered events that are not followed by the corresponding transition) entails not only the adjustment of these structures, but also to raise of new logics suitable to express and verify properties in these systems. This paper contributes to such challenge by introducing a new variants of Petri net prepared to handle a scenario with firing failures, endowed with Dynamic Logics for Petri Nets prepared to deal with such scenario. Technically, the results obtained for logic were achieved by exploring a combination of two previous works of the authors, namely the Propositional Dynamic Logic for Petri Nets [1] and a parametric construction of multi-valued dynamic logics presented in [16]. Hide abstract
  
  
• Approximations of Interval Markov Chains via Sampling (Kris Ghosh) Abstract
  Abstract: System models of biological processes are stochastic. The probabilities in the system models are often approximately known given the uncertainty in the environmental conditions. Interval Markov chains are modeled to address the uncertainty in the form of intervalvalued transition probabilities. In this work, we construct a sampling-based polynomial algorithm which reduces a given interval Markov chain to a discrete time Markov chain within bounds. Hide abstract
  
  
• Quantum simulation of quantum chemistry: a case study using IBM Q (Carlos Tavares, Sofia Oliveira, Vitor Gonçalves) Abstract
  Abstract: As quantum computing finally comes of age, with its first commercial implementations, quantum simulation emerges as a ground-breaking technology for several domains, including biology and chemistry. The process, however, raises a number of conceptual and practical challenges at different layers: the Hamiltonian modelling of the molecular system, the Hamiltonian translation to a quantum circuit and finally, the actual execution of the circuit in a quantum device, which faces relevant technical issues. In this work we aim at going through all such steps, thus contributing to the better understanding of the issues and techniques involved. We do so, by exploring a case study of the conception and execution of a quantum simulation for the hydrogen (H2) and Lithium-hydride (LiH) molecules, in an actual commercially available quantum computer, the IBM Q, accessed through the QuantaLab UMinho Academic Q Hub, and resorting to Qiskit platform and the ACQUA framework. We calculate properties of interest of the Hamiltonians, such as the ground state and the dissociation energy, reviewing the relevant theory, tools and techniques along the way. Hide abstract
  
  
• Optimal control of a delayed HIV/AIDS-PrEP model (Cristiana J. Silva) Abstract
  Abstract: We propose a HIV/AIDS-PrEP model, given by a system of delayed differential equations (DDE), based in [2]. The stability of the equilibrium points of the DDE system is analyzed, for any positive time delay. The impact of the a delayed PrEP prevention policy on the number of new HIV infections is discussed. In order to find an optimal way to apply PrEP in a specific region, a delayed optimal control problem is formulated where the control function represents the fraction of susceptible individuals under PrEP and the objective is to minimize the number of new infections as well as the cost associated to PrEP. The optimal solutions are derived analytical and numerically, and the results are discussed from an epidemiological point of view. Hide abstract
  
  
• Efficient Parameter Delta-Reachability Bounded Hybrid Systems (Eugénio Rocha) Abstract
  Abstract: We extend a tool that deal with the bounded $\delta$-reachability problem by determining the most efficient choices of parameters for a given prescribed set of parameters and input/output generating functions. For a hybrid system $H=$, where flow, jump, inv, init are SMT formulas encoded as first-order logic formulas over the real numbers, any formula $\phi$ can have its $\delta$-perturbation counterpart $\phi^\delta$, by specifying a numerical error bound $\delta$; where such formulas are handled by implementing the framework of $\delta$-complete decision procedures. Then, a $\delta$-perturbation of $H$ is defined as $H^\delta= $ by relaxing the logic formulas in $H$. Hence, choosing $n\in\bkN$ to be a bound on the number of discrete mode changes, $T\in\bkR^+$ an upper bound on the time duration, and \textit{unsafe} to encode a subset of $X\times Q$, the bounded $\delta$-reachability problem asks for one of the following answers: (a) “safe” if $H$ cannot reach \textit{unsafe} in $n$ steps within time $T$; (b) ”$\delta$-unsafe” if $H^\delta$ can reach \textit{unsafe}$^\delta$ in $n$ steps within time $T$. A frontier analysis optimisation is then performed by obtaining a bounded $\delta$-reachability solution for each combination of parameters values in the given prescribed sets, producing the values of the input/output generating functions over parameters plus solution, and finally computing a relative ranking by some multidirectional analysis algorithm. Some examples will be presented. Indifferent Hide abstract
  
  
• Molecular Logic and the Problem of Computational Implementation (Claudio Fuentes) Abstract
  Abstract: De Silva defines the Molecular Logic-based Computation, as "(...) an approach that deals with molecules and chemical systems that have an innate ability to compute, at least in a rudimentary way, as machines based on transistors, semiconductors or people "[2013: 12]." The criticism that can be raised is that conceptualization is trying to elucidate the notion of logic in terms of the notion of computing. The elucidation of this question then shifts to what we are going to understand by computation. The issue is important, especially in light of the abundant specialized literature on the concept of computing, and the meaning of expressions of the type "the S system performs a computational process C". Depending on the way in which the notion of computing is understood, the thesis that living systems have a "logic", in the sense that they perform certain computational processes, can be a trivial and philosophically uninteresting thesis (see, for example: Piccini, G. (2015) The mechanistic conceptualization (Piccinini 2007, 2015, Kaplan 2011, Milkowski 2013) explains the concrete calculation in terms of the mechanical properties of a system. According to the mechanistic account, concrete computer systems are functional mechanisms of a special type, that is, mechanisms that perform specific calculations. A given calculation can be implemented in multiple physical media (eg, cells), provided that the media possess a sufficient number of dimensions of variation (or degrees of freedom) that can be appropriately accessible and manipulated and that the components of the mechanism are functionally organized in the proper way The objects studied in the mathematical theory of computation - Turing machines, algorithms, etc. - are usually implemented by specific physical systems. This poses a problem: how can a particular physical system perform a calculation when the calculation is defined by an abstract mathematical formalism? This can be called the problem of computational implementation. Hide abstract
  
  
• An essay on weighted state transition models with reactivity (Daniel Figueiredo) Abstract
  Abstract: The term reactivity is used by Gabbay to refer state transition systems whose accessibility relation is not fixed but can vary according to the edges crossed. On this work, the possibility of assign weights to edges is considered. In particular, we are interested into apply these ideas to biological modeling and we discuss about the theoretical tools we would need. Furthermore, the possibility of using the software PRISM to study such models is discussed and we consider already some initial results obtained for simple toy models. Hide abstract
  
  
• Proteins as dynamic architectural patterns (Alejandro Sanchez, Luís Barbosa) Abstract
  Abstract: Predicting and designing the dynamics of proteins is a challenging task, which has a number of similarities to the problem of architecturally designing distributed, heterogeneous and dynamically reconfigurable software systems. We exploit such a similarity by addressing the problem using an architectural description language called ARCHERY. The language allows modelling hierarchical architectures in terms of architectural patterns, as well as the specification of reconfiguration scripts and constraints. Scripts are intended to model the dynamics of architectures, and constraints are used to both verify that design principles are preserved and to describe conditions for triggering reconfiguration scripts. A derived labelled transition system enables the animation and verification of the resulting model. Hide abstract
  
  
• Synchronous searching for DNA patterns (Leandro Rafael Gomes) Abstract
  Abstract: The uniqueness of each living organism is reflected in its DNA pattern. In that sense, it is of core importance for biologists to study the genome of living beings, in order to understand their growth, functioning and reproduction. We have seen, in particular, that the process of searching for a specific sequence of nucleotides in a DNA molecule become indispensable in biological research [1]. Its range of applications varies from diverse fields such as medical diagnosis, forensics and synthetic biology [9]. For the last one, the methods used in DNA sequencing are relevant in distinct directions: they provide information of natural organisms, which can be used to construct synthetic parts and devices; it is used to verify fabricated systems; facilitates detection and identification of synthetic organisms [11]. String matching techniques, which are basis of DNA sequencing, can be found in the literature divided in two distinct approaches: exact matching [2] and approximate matching [12]. Approximate DNA matching techniques [3] are becoming more relevant than the ones based on exact matching, as they can address very common situations like acquisition errors, small differences in the sequences due to mutations or evolutionary modifications, or even present themselves useful to reconstruct phylogenetic trees [7]. The long tradition of finite state automata in many text search methods make them suitable computational models to address problems related with DNA matching, either exact [5] or approximate [10]. Parallel computation is nowadays a pervasive paradigm to several application domains. Consequently, formalisms to model these kinds of computations begun to emerge, namely, Concurrent Kleene algebra (CKA) [4] and Synchronous Kleene algebra (SKA) [8], The notion of synchronism was added to Kleene algebras in [8], combining the expressiveness of Kleene algebras for axiomatising regular expressions and finite automata, with an operator to model parallelism. In SKA, the notion of parallelism is based in the process algebra CCS calculus [6], where two independent actions are processed at the same time. In [8], the author directed the work on SKA in two phases: first, its semantics was given by sets of synchronous strings; then, he presented a new construction for nondeterministic finite automata, based on the semantics of the synchronous operator of SKA. Hide abstract
• Reaction network modeling of endosymbiotic interactions (Daniela Flores, Tomas Veloz) Abstract
  Abstract: The theory of endosymbiosis developed by Lynn Margulis, describes the origin of plastids and mitochondria from prokaryotes that were acquired and conserved within host cells giving rise to eukaryotic cells. Although structural, biochemical and morphological evidence has focused on mitochondria and chloroplasts to demonstrate their prokaryotic ancestry, it has been postulated that several organelles and more structurally complex organisms have been originated by endosymbiosis, giving rise to new species and lineages (Margulis \& Sagan., 2000). An endosymbiosis study model corresponds to the interrelation between corals (Cnidaria, Anthozoa) and photosynthetic algae of the genus Symbiodinium (also known as Zooxanthellae), which correspond to the most common endosymbionts among coral reefs (Trench., 1997; Rowan ., 1998). In this coupling between host and endosymbiont, the alga acquires nutrients through the host and produces organic compounds to satisfy not only the requirement of the endosymbionts, but also the energy demanded by the host, which provides an advantage to both organisms in warm, shallow waters and with low nutrient availability, which has allowed the success and survival of coral reef communities despite recent climate changes (Yellowlees et al., 2008, Baker et al., 2004). In general, the establishment of this type of interaction gives rise to new properties, structures, morphologies and competencies for the organisms that underlie the relationship. The latter hinders the experimental study of this phenomenon because the members cannot be studied separately. For this reason, a framework to this phenomenon from a mathematical and computational perspective would be crucial importance, but unfortunately no framework of this kind has been yet developed. In the present study we propose such framework to model endosymbiotic relationship. In particular, we provide a simple model of the interaction between anthozoan corals and symbiont algae of the genus Symbiodinium by means of a framework based on reaction networks (Chemical Organization Theory) that has recently proposed to represent ecological interactions at the mechanistic level, and we discuss the capabilities of this framework to model endosymbiotic interactions in general. Hide abstract

  A Survey

  
  
• Molecular Logic: Brief Introduction and Some Philosophical Considerations (Claudio Fuentes, Patricio Fuentes) Abstract
  Abstract: In the present article a brief historical and systematic introduction to the field of molecular logic is proposed. There are also some relevant philosophical consequences, derived from the technical treatment of this topic. These consequences are made explicit in three fundamental questions. Some of the proposed methods for the representation of the intracellular molecular dynamics are also presented and the advantages and limitations that the different methods exhibit when modeling natural biological circuits are evaluated. The Boolean approach to molecular logic is considered with special attention in this article, emphasizing that "logic gates" have proven to be functionally appropriate for analyzing experimental information, however, they present limitations to capture complex biological processes. In relation to this last point, the problem presented by the modeling of continuous variables through discrete systems is studied in depth. It is explained then the need to have adequate logic to the phenomenon and its characteristics. Hide abstract

  (Informal) Book of abstracts

  (with the Extended Abstracts and a short article by A.Parsanna de Silva )

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