Simulation of Rapidly-Exploring Random Trees in Membrane Computing with P-Lingua and Automatic Programming

Methods based on Rapidly-exploring Random Trees (RRTs) have been widely used in robotics to solve motion planning problems. On the other hand, in the membrane computing framework, models based on Enzymatic Numerical P systems (ENPS) have been applied to robot controllers, but today there is a lack of planning algorithms based on membrane computing for robotics. With this motivation, we provide a variant of ENPS called Random Enzymatic Numerical P systems with Proteins and Shared Memory (RENPSM) addressed to implement RRT algorithms and we illustrate it by simulating the bidirectional RRT algorithm. This paper is an extension of [21]a. The software presented in [21] was an ad-hoc simulator, i.e, a tool for simulating computations of one and only one model that has been hard-coded. The main contribution of this paper with respect to [21] is the introduction of a novel solution for membrane computing simulators based on automatic programming. First, we have extended the P-Lingua syntax –a language to define membrane computing models– to write RENPSM models. Second, we have implemented a new parser based on Flex and Bison to read RENPSM models and produce source code in C language for multicore processors with OpenMP. Finally, additional experiments are presented.Ministerio de Economía, Industria y Competitividad TIN2017-89842-

Simulation of Rapidly-Exploring Random Trees in Membrane Computing with P-Lingua and Automatic Programming

Methods based on Rapidly-exploring Random Trees (RRTs) have been widely used in robotics to solve motion planning problems. On the other hand, in the membrane computing framework, models based on Enzymatic Numerical P systems (ENPS) have been applied to robot controllers, but today there is a lack of planning algorithms based on membrane computing for robotics. With this motivation, we provide a variant of ENPS called Random Enzymatic Numerical P systems with Proteins and Shared Memory (RENPSM) addressed to implement RRT algorithms and we illustrate it by simulating the bidirectional RRT algorithm. This paper is an extension of [21]a. The software presented in [21] was an ad-hoc simulator, i.e, a tool for simulating computations of one and only one model that has been hard-coded. The main contribution of this paper with respect to [21] is the introduction of a novel solution for membrane computing simulators based on automatic programming. First, we have extended the P-Lingua syntax –a language to define membrane computing models– to write RENPSM models. Second, we have implemented a new parser based on Flex and Bison to read RENPSM models and produce source code in C language for multicore processors with OpenMP. Finally, additional experiments are presented

A new P-Lingua toolkit for agile development in membrane computing

Membrane computing is a massively parallel and non-deterministic bioinspired computing paradigm whose models are called P systems. Validating and testing such models is a challenge which is being overcome by developing simulators. Regardless of their heterogeneity, such simulators require to read and interpret the models to be simulated. To this end, P-Lingua is a high-level P system definition language which has been widely used in the last decade. The P-Lingua ecosystem includes not only the language, but also libraries and software tools for parsing and simulating membrane computing models. Each version of P-Lingua supported new types or variants of P systems. This leads to a shortcoming: Only a predefined list of variants can be used, thus making it difficult for researchers to study custom ones. Moreover, derivation modes cannot be user-defined, i.e, the way in which P system computations should be generated is determined by the simulation algorithm in the source code. The main contribution of this paper is a completely new design of the P-Lingua language, called P-Lingua 5, in which the user can define custom variants and derivation modes, among other improvements such as including procedural programming and simulation directives. It is worth mentioning that it has backward-compatibility with previous versions of the language. A completely new set of command-line tools is provided for parsing and simulating P-Lingua 5 files. Finally, several examples are included in this paper covering the most common P system types.Agencia Estatal de Investigación TIN2017-89842-

From Cellular Components to Living Cells (and Back): Evolution of Function in Biological Networks

Network models pervade modern biology. From ecosystems down to molecular interactions in cells, they provide abstraction and explanation for biological processes. Thus, the relation between structure and function of networks is central to any comprehensive attempt for a theoretical understanding of life. Just as any living system, biological networks are shaped by evolutionary processes. In reverse, artificial evolution can be employed to reconstruct networks and to study their evolution. To this end, I have implemented an evolutionary algorithm specifically designed for the evolution of network models. With the developed evolutionary framework, a study of the evolution of information-processing networks was performed. It is shown that selection favours an organisational structure that is related to function, such that computations can be visualised as transitions between organisations. Furthermore, mathematical modelling is applied to extract reaction-kinetic constants from fluorescence microscopy data, and the model is presented and discussed in detail. Using this approach, a detailed quantitative model of exchange dynamics at PML nuclear bodies (NBs) is created, showing that PML NB components exhibit highly individual exchange kinetics. The FRAP data for PML NBs is additionally used as a test-case for automatic model inference using evolutionary methods, and a set of necessary and sufficient criteria for a good model fit is revealed. In the last part of this thesis, a stochastic analysis of the genetic regulatory system of DEF-like and GLO-like class B floral homeotic genes provides an explanation for their intricate regulatory wiring. The different potential regulatory architectures are investigated using Monte Carlo simulation, a simplified master-equation model, and fixedpoint analysis. It is shown that a positive autoregulatory loop via obligate heterodimerisation of transcription factor proteins reduces noise in cell-fate organ identity decisions.Netzwerkmodelle sind weit verbreitet in der modernen Biologie. In allen Teilgebieten - von der Ökologie bis hin zur Molekularbiologie - bieten sie die Möglichkeit, untersuchte Prozesse und Phänomene zu abstrahieren und damit auf theoretischer Ebene zugänglich zu machen. Es wird ein evolutionärer Algorithmus vorgestellt, der speziell für die Erzeugung von Netzwerkmodellen angepasst ist. Dafür wurde eine Genetische Programmierung der Netzwerkstruktur mit einer Evolutionsstrategie auf den kinetischen Parametern verknüpft. Mit dem neu entwickelten Evolutionären Algorithmus wurde dann eine Studie zur Evolution von informationsverarbeitenden Netzwerken durchgeführt. Selektion erzeugt eine funktionale Organisationsstruktur, in welcher eine Berechnung als Transition zwischen Organisationen abgebildet werden kann. Desweiteren wurden mathematische Modellierungsmethoden verwendet, um kinetische Reaktionskonstanten aus fluoreszenz-mikroskopischen Daten zu gewinnen. Die verwendete Methode wird im Detail vorgestellt und diskutiert. Auf diese Weise entstand ein detailliertes Modell des Proteinaustauschs an PML nuclear bodies (NBs), in welchem die Komponenten der PML NBs sehr differenzierte Austauschverhalten zeigen. Darüber hinaus werden die gewonnenen Daten genutzt, um die automatische Evolution von Netzwerkmodellen in einer realistischen Fallstudie zu testen. Zum Schluss wird eine stochastische Analyse des Zusammenspiels der DEF- und GLO-Gene in der Blütenentwicklung gezeigt, welche eine Erklärung für ihre überraschend komplexe Verschaltung liefert. Die verschiedenen möglichen Regulationsmechanismen werden mithilfe von Monte-Carlo-Simulation, einem Master-Equation-Ansatz und der Fixpunktanalyse verglichen. Es wird gezeigt, dass positive Autoregulation durch obligatorische Heterodimerisierung den Einfluss des Zufalls auf die Organidentität reduziert

Advances of Machine Learning in Materials Science: Ideas and Techniques

In this big data era, the use of large dataset in conjunction with machine learning (ML) has been increasingly popular in both industry and academia. In recent times, the field of materials science is also undergoing a big data revolution, with large database and repositories appearing everywhere. Traditionally, materials science is a trial-and-error field, in both the computational and experimental departments. With the advent of machine learning-based techniques, there has been a paradigm shift: materials can now be screened quickly using ML models and even generated based on materials with similar properties; ML has also quietly infiltrated many sub-disciplinary under materials science. However, ML remains relatively new to the field and is expanding its wing quickly. There are a plethora of readily-available big data architectures and abundance of ML models and software; The call to integrate all these elements in a comprehensive research procedure is becoming an important direction of material science research. In this review, we attempt to provide an introduction and reference of ML to materials scientists, covering as much as possible the commonly used methods and applications, and discussing the future possibilities.Comment: 80 pages; 22 figures. To be published in Frontiers of Physics, 18, xxxxx, (2023

Algorithms and Software for Biological MP Modeling by Statistical and Optimization Techniques

I sistemi biologici sono gruppi di entit\ue0 biologiche (es. molecole ed organismi), che interagiscono producendo specifiche dinamiche. Questi sistemi sono solitamente caratterizzati da una elevata complessit\ue0 perch\ue8 coinvolgono un elevato numero di componenti con molte interconnessioni. La comprensione dei meccanismi che governano i sistemi biologici e la previsione dei loro comportamenti in condizioni normali e patologiche \ue8 una sfida cruciale della biologia dei sistemi (in inglese detta systems biology), un'area di ricerca al confine tra biologia, medicina, matematica ed informatica. In questa tesi i P sistemi metabolici, detti brevemente sistemi MP, sono stati utilizzati come modello discreto per l'analisi di dinamiche biologiche. Essi sono una classe deterministica dei P sistemi classici, che utilizzano regole di riscrittura per rappresentare le reazioni chimiche e "funzioni di regolazioni di flusso" per regolare la reattivit\ue0 di ciascuna reazione rispetto alla quantita' di sostanze presenti istantaneamente nel sistema. Dopo un excursus sulla letteratura relativa ad alcuni modelli convenzionali (come le equazioni differenziali ed i modelli stocastici proposti da Gillespie) e non-convenzionali (come i P sistemi ed i P sistemi metabolici), saranno presentati i risultati della mia ricerca. Essi riguardano tre argomenti principali: i) l'equivalenza tra sistemi MP e reti di Petri ibride funzionali, ii) le prospettive statistiche e di ottimizzazione nella generazione di sistemi MP a partire da dati sperimentali, iii) lo sviluppo di un laboratorio virtuale chiamato MetaPlab, un software Java basato sui sistemi MP. L'equivalenza tra i sistemi MP e le reti di Petri ibride funzionali \ue8 stata dimostrata per mezzo di due teoremi ed alcuni esperimenti al computer per il caso di studio del meccanismo regolativo del gene operone lac nella pathway glicolitica. Il secondo argomento di ricerca concerne nuovi approcci per la sintesi delle funzioni di regolazione di flusso. La regressione stepwise e le reti neurali sono state impiegate come approssimatori di funzioni, mentre algoritmi di ottimizzazione classici ed evolutivi (es. backpropagation, algoritmi genetici, particle swarm optimization ed algoritmi memetici) sono stati impiegati per l'addestramento dei modelli. Una completo workflow per l'analisi dei dati sperimentali \ue8 stato presentato. Esso gestisce ed indirizza l'intero processo di sintesi delle funzioni di regolazione, dalla preparazione dei dati alla selezione delle variabili, fino alla generazione dei modelli ed alla loro validazione. Le metodologie proposte sono state testate con successo tramite esperimenti al computer sui casi di studio dell'oscillatore mitotico negli embrioni anfibi e del non photochemical quenching (NPQ). L'ultimo tema di ricerca \ue8 infine piu' applicativo e riguarda la progettazione e lo sviluppo di una architettura Java basata su plugin e di una serie di plugin che consentono di automatizzare varie fasi del processo di modellazione con sistemi MP, come la simulazione di dinamiche, la determinazione dei flussi e la generazione delle funzioni di regolazione.Biological systems are groups of biological entities, (e.g., molecules and organisms), that interact together producing specific dynamics. These systems are usually characterized by a high complexity, since they involve a large number of components having many interconnections. Understanding biological system mechanisms, and predicting their behaviors in normal and pathological conditions is a crucial challenge in systems biology, which is a central research area on the border among biology, medicine, mathematics and computer science. In this thesis metabolic P systems, also called MP systems, have been employed as discrete modeling framework for the analysis of biological system dynamics. They are a deterministic class of P systems employing rewriting rules to represent chemical reactions and "flux regulation functions" to tune reactions reactivity according to the amount of substances present in the system. After an excursus on the literature about some conventional (i.e., differential equations, Gillespie's models) and unconventional (i.e., P systems and metabolic P systems) modeling frameworks, the results of my research are presented. They concern three research topics: i) equivalences between MP systems and hybrid functional Petri nets, ii) statistical and optimization perspectives in the generation of MP models from experimental data, iii) development of the virtual laboratory MetaPlab, a Java software based on MP systems. The equivalence between MP systems and hybrid functional Petri nets is proved by two theorems and some in silico experiments for the case study of the lac operon gene regulatory mechanism and glycolytic pathway. The second topic concerns new approaches to the synthesis of flux regulation functions. Stepwise linear regression and neural networks are employed as function approximators, and classical/evolutionary optimization algorithms (e.g., backpropagation, genetic algorithms, particle swarm optimization, memetic algorithms) as learning techniques. A complete pipeline for data analysis is also presented, which addresses the entire process of flux regulation function synthesis, from data preparation to feature selection, model generation and statistical validation. The proposed methodologies have been successfully tested by means of in silico experiments on the mitotic oscillator in early amphibian embryos and the non photochemical quenching (NPQ). The last research topic is more applicative, and pertains the design and development of a Java plugin architecture and several plugins which enable to automatize many tasks related to MP modeling, such as, dynamics computation, flux discovery, and regulation function synthesis

Parallel Programming with Global Asynchronous Memory: Models, C++ APIs and Implementations

In the realm of High Performance Computing (HPC), message passing has been the programming paradigm of choice for over twenty years. The durable MPI (Message Passing Interface) standard, with send/receive communication, broadcast, gather/scatter, and reduction collectives is still used to construct parallel programs where each communication is orchestrated by the developer-based precise knowledge of data distribution and overheads; collective communications simplify the orchestration but might induce excessive synchronization. Early attempts to bring shared-memory programming model—with its programming advantages—to distributed computing, referred as the Distributed Shared Memory (DSM) model, faded away; one of the main issue was to combine performance and programmability with the memory consistency model. The recently proposed Partitioned Global Address Space (PGAS) model is a modern revamp of DSM that exposes data placement to enable optimizations based on locality, but it still addresses (simple) data- parallelism only and it relies on expensive sharing protocols. We advocate an alternative programming model for distributed computing based on a Global Asynchronous Memory (GAM), aiming to avoid coherency and consistency problems rather than solving them. We materialize GAM by designing and implementing a distributed smart pointers library, inspired by C++ smart pointers. In this model, public and pri- vate pointers (resembling C++ shared and unique pointers, respectively) are moved around instead of messages (i.e., data), thus alleviating the user from the burden of minimizing transfers. On top of smart pointers, we propose a high-level C++ template library for writing applications in terms of dataflow-like networks, namely GAM nets, consisting of stateful processors exchanging pointers in fully asynchronous fashion. We demonstrate the validity of the proposed approach, from the expressiveness perspective, by showing how GAM nets can be exploited to implement both standalone applications and higher-level parallel program- ming models, such as data and task parallelism. As for the performance perspective, preliminary experiments show both close-to-ideal scalability and negligible overhead with respect to state-of-the-art benchmark implementations. For instance, the GAM implementation of a high-quality video restoration filter sustains a 100 fps throughput over 70%-noisy high-quality video streams on a 4-node cluster of Graphics Processing Units (GPUs), with minimal programming effort

Infobiotics : computer-aided synthetic systems biology

Until very recently Systems Biology has, despite its stated goals, been too reductive in terms of the models being constructed and the methods used have been, on the one hand, unsuited for large scale adoption or integration of knowledge across scales, and on the other hand, too fragmented. The thesis of this dissertation is that better computational languages and seamlessly integrated tools are required by systems and synthetic biologists to enable them to meet the significant challenges involved in understanding life as it is, and by designing, modelling and manufacturing novel organisms, to understand life as it could be. We call this goal, where everything necessary to conduct model-driven investigations of cellular circuitry and emergent effects in populations of cells is available without significant context-switching, “one-pot” in silico synthetic systems biology in analogy to “one-pot” chemistry and “one-pot” biology. Our strategy is to increase the understandability and reusability of models and experiments, thereby avoiding unnecessary duplication of effort, with practical gains in the efficiency of delivering usable prototype models and systems. Key to this endeavour are graphical interfaces that assists novice users by hiding complexity of the underlying tools and limiting choices to only what is appropriate and useful, thus ensuring that the results of in silico experiments are consistent, comparable and reproducible. This dissertation describes the conception, software engineering and use of two novel software platforms for systems and synthetic biology: the Infobiotics Workbench for modelling, in silico experimentation and analysis of multi-cellular biological systems; and DNA Library Designer with the DNALD language for the compact programmatic specification of combinatorial DNA libraries, as the first stage of a DNA synthesis pipeline, enabling methodical exploration biological problem spaces. Infobiotics models are formalised as Lattice Population P systems, a novel framework for the specification of spatially-discrete and multi-compartmental rule-based models, imbued with a stochastic execution semantics. This framework was developed to meet the needs of real systems biology problems: hormone transport and signalling in the root of Arabidopsis thaliana, and quorum sensing in the pathogenic bacterium Pseudomonas aeruginosa. Our tools have also been used to prototype a novel synthetic biological system for pattern formation, that has been successfully implemented in vitro. Taken together these novel software platforms provide a complete toolchain, from design to wet-lab implementation, of synthetic biological circuits, enabling a step change in the scale of biological investigations that is orders of magnitude greater than could previously be performed in one in silico “pot”

Computational intelligence approaches to robotics, automation, and control [Volume guest editors]

No abstract available