Petri-net-based 2D Design of DNA Walker Circuits

We consider localised DNA computation, where a DNA strand walks along a binary decision graph to compute a binary function. One of the challenges for the design of reliable walker circuits consists in leakage transitions, which occur when a walker jumps into another branch of the decision graph. We automatically identify leakage transitions, which allows for a detailed qualitative and quantitative assessment of circuit designs, design comparison, and design optimisation. The ability to identify leakage transitions is an important step in the process of optimising DNA circuit layouts where the aim is to minimise the computational error inherent in a circuit while minimising the area of the circuit. Our 2D modelling approach of DNA walker circuits relies on coloured stochastic Petri nets which enable functionality, topology and dimensionality all to be integrated in one two-dimensional model. Our modelling and analysis approach can be easily extended to 3-dimensional walker systems

A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking

Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems

Automatic validation of computational models using pseudo-3D spatio-temporal model checking

This article has been made available through the Brunel Open Access Publishing Fund.Background: Computational models play an increasingly important role in systems biology for generating predictions and in synthetic biology as executable prototypes/designs. For real life (clinical) applications there is a need to scale up and build more complex spatio-temporal multiscale models; these could enable investigating how changes at small scales reflect at large scales and viceversa. Results generated by computational models can be applied to real life applications only if the models have been validated first. Traditional in silico model checking techniques only capture how non-dimensional properties (e.g. concentrations) evolve over time and are suitable for small scale systems (e.g. metabolic pathways). The validation of larger scale systems (e.g. multicellular populations) additionally requires capturing how spatial patterns and their properties change over time, which are not considered by traditional non-spatial approaches. Results: We developed and implemented a methodology for the automatic validation of computational models with respect to both their spatial and temporal properties. Stochastic biological systems are represented by abstract models which assume a linear structure of time and a pseudo-3D representation of space (2D space plus a density measure). Time series data generated by such models is provided as input to parameterised image processing modules which automatically detect and analyse spatial patterns (e.g. cell) and clusters of such patterns (e.g. cellular population). For capturing how spatial and numeric properties change over time the Probabilistic Bounded Linear Spatial Temporal Logic is introduced. Given a collection of time series data and a formal spatio-temporal specification the model checker Mudi (http://mudi.modelchecking.org) determines probabilistically if the formal specification holds for the computational model or not. Mudi is an approximate probabilistic model checking platform which enables users to choose between frequentist and Bayesian, estimate and statistical hypothesis testing based validation approaches. We illustrate the expressivity and efficiency of our approach based on two biological case studies namely phase variation patterning in bacterial colony growth and the chemotactic aggregation of cells. Conclusions: The formal methodology implemented in Mudi enables the validation of computational models against spatio-temporal logic properties and is a precursor to the development and validation of more complex multidimensional and multiscale models

Promoting Ancestry as Ecodomy in Romanian Eastern Orthodox Christianity. The Role of Ancestors in Contemporary Romanian Orthodox Rhetoric

For the most part, contemporary Romanian Orthodox spirituality is still heavily based on a rhetoric which builds on the notion of ancestry with the intention not only to provide Romanians with a safe comfort zone, but also to secure its privileges and influence over most of today’s Romanian society. In attempting to go back in history to demonstrate that the ancestry of Romanians is sufficient proof for their full and unconditional adherence to Eastern Orthodox Christianity in its local Romanian version as the Romanian Orthodox Church, most of today’s representatives of Romanian Orthodox spirituality—notably Dumitru Stăniloae, Ioan Rămureanu, and Teoctist, the former Patriarch of the Romanian Orthodox Church—focused on a rhetoric that, on the one hand, takes Romanians back to their Thracian, Dacian, and Roman ancestors, while on the other hand, seeks to inculcate the idea that an unflinching adherence to this specific ancestry, which is described as Christian by nature and birth, must be kept at all costs. Thus, this specific kind of rhetoric attempts to build a protective fence around Romanians, who are taught that they need to preserve their Eastern Orthodox Christianity and their allegiance to the Romanian Orthodox Church mostly because, since their ancestors were Christians, they are in fact born Christian. The process of building this protective wall around Romanians is described by means of the term ‘ecodomy’ and, unlike its general use in contemporary debates as focusing on positive aspects, the particular focus of the Romanian Orthodox Church on ecodomy based on the idea of ancestry is going to be revealed mostly through a chain of negative connotations. Thus, the contemporary rhetoric of the Romanian Orthodox Church based on the notion of ancestry as ecodomy—one may even call it negative ecodomy—is going to be explained in connection with three fundamental aspects, namely church, nation, and culture, all intended to preserve not only the influence of the Romanian Orthodox Church in nowadays Romanian society, but also a set of privileges in its relationship with the state.http://ext.sagepub.comhb2016Dogmatics and Christian Ethic