pony - The occam-pi Network Environment

Although concurrency is generally perceived to be a `hard' subject, it can in fact be very simple --- provided that the underlying model is simple. The occam-pi parallel processing language provides such a simple yet powerful concurrency model that is based on CSP and the pi-calculus. This paper presents pony, the occam-pi Network Environment. occam-pi and pony provide a new, unified, concurrency model that bridges inter- and intra-processor concurrency. This enables the development of distributed applications in a transparent, dynamic and highly scalable way. The first part of this paper discusses the philosophy behind pony, explains how it is used, and gives a brief overview of its implementation. The second part evaluates pony's performance by presenting a number of benchmarks

Process-Oriented Collective Operations

Distributing process-oriented programs across a cluster of machines requires careful attention to the effects of network latency. The MPI standard, widely used for cluster computation, defines a number of collective operations: efficient, reusable algorithms for performing operations among a group of machines in the cluster. In this paper, we describe our techniques for implementing MPI communication patterns in process-oriented languages, and how we have used them to implement collective operations in PyCSP and occam-pi on top of an asynchronous messaging framework. We show how to make use of collective operations in distributed processoriented applications. We also show how the process-oriented model can be used to increase concurrency in existing collective operation algorithms

To boldly go:an occam-π mission to engineer emergence

Future systems will be too complex to design and implement explicitly. Instead, we will have to learn to engineer complex behaviours indirectly: through the discovery and application of local rules of behaviour, applied to simple process components, from which desired behaviours predictably emerge through dynamic interactions between massive numbers of instances. This paper describes a process-oriented architecture for fine-grained concurrent systems that enables experiments with such indirect engineering. Examples are presented showing the differing complex behaviours that can arise from minor (non-linear) adjustments to low-level parameters, the difficulties in suppressing the emergence of unwanted (bad) behaviour, the unexpected relationships between apparently unrelated physical phenomena (shown up by their separate emergence from the same primordial process swamp) and the ability to explore and engineer completely new physics (such as force fields) by their emergence from low-level process interactions whose mechanisms can only be imagined, but not built, at the current time

Understanding tissue morphology: model repurposing using the CoSMoS process

We present CoSMoS as a way of structuring thinking on how to reuse parts of an existing model and simulation in a new model and its implementation. CoSMoS provides a lens through which to consider, post-implementation, the assumptions made during the design and implementation of a software simulation of physical interactions in the formation of vascular structures from endothelial cells. We show how the abstract physical model and its software implementation can be adapted for a different problem: the growth of cancer cells under varying environmental perturbations. We identify the changes that must be made to adapt the model to its new context, along with the gaps in our knowledge of the domain that must be filled by wet-lab experimentation when recalibrating the model. Through parameter exploration, we identify the parameters that are critical to the dynamic physical structure of the modelled tissue, and we calibrate these parameters using a series of in vitro experiments. Drawing inspiration from the CoSMoS project structure, we maintain confidence in the repurposed model, and achieve a satisfactory degree of model reuse within our in silico experimental system

Dense agent-based HPC simulation of cell physics and signaling with real-time user interactions

Introduction: Distributed simulations of complex systems to date have focused on scalability and correctness rather than interactive visualization. Interactive visual simulations have particular advantages for exploring emergent behaviors of complex systems. Interpretation of simulations of complex systems such as cancer cell tumors is a challenge and can be greatly assisted by using “built-in” real-time user interaction and subsequent visualization.Methods: We explore this approach using a multi-scale model which couples a cell physics model with a cell signaling model. This paper presents a novel communication protocol for real-time user interaction and visualization with a large-scale distributed simulation with minimal impact on performance. Specifically, we explore how optimistic synchronization can be used to enable real-time user interaction and visualization in a densely packed parallel agent-based simulation, whilst maintaining scalability and determinism. We also describe the software framework created and the distribution strategy for the models utilized. The key features of the High-Performance Computing (HPC) simulation that were evaluated are scalability, deterministic verification, speed of real-time user interactions, and deadlock avoidance.Results: We use two commodity HPC systems, ARCHER (118,080 CPU cores) and ARCHER2 (750,080 CPU cores), where we simulate up to 256 million agents (one million cells) using up to 21,953 computational cores and record a response time overhead of ≃350 ms from the issued user events.Discussion: The approach is viable and can be used to underpin transformative technologies offering immersive simulations such as Digital Twins. The framework explained in this paper is not limited to the models used and can be adapted to systems biology models that use similar standards (physics models using agent-based interactions, and signaling pathways using SBML) and other interactive distributed simulations

A Transactional Architecture for Simulation

Abstract-We are developing a concurrent, agent-based approach to complex systems simulation as part of the CoSMoS project. In such simulations an agent's behaviour can typically be characterised as a series of queries and updates to its environment-a "transactional" pattern of interaction familiar to programmers of database systems. We explore how ideas from the field of databases, such as optimistic approaches to consistency and replication, may profitably be applied to the field of simulation, and how the constraints of modern databases can be relaxed to yield better performance while maintaining simulation validity

Macrophage transactivation for chemokine production identified as a negative regulator of granulomatous inflammation using agent-based modeling

Cellular activation in trans by interferons, cytokines and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and / or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani-infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation

Engineering simulations for cancer systems biology

Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions

Modelling fungal colonies and communities:challenges and opportunities

This contribution, based on a Special Interest Group session held during IMC9, focuses on physiological based models of filamentous fungal colony growth and interactions. Fungi are known to be an important component of ecosystems, in terms of colony dynamics and interactions within and between trophic levels. We outline some of the essential components necessary to develop a fungal ecology: a mechanistic model of fungal colony growth and interactions, where observed behaviour can be linked to underlying function; a model of how fungi can cooperate at larger scales; and novel techniques for both exploring quantitatively the scales at which fungi operate; and addressing the computational challenges arising from this highly detailed quantification. We also propose a novel application area for fungi which may provide alternate routes for supporting scientific study of colony behaviour. This synthesis offers new potential to explore fungal community dynamics and the impact on ecosystem functioning