Toward a Self-replicating Metabolic P System

This work concerns the synthesis of a "minimal cell' by means of a P system, which is a distributed rewriting system inspired by the structure and the functioning of the biological cell. Specifically, we aim to define a dynamical system which exhibits a steady metabolic evolution, resulting in self-maintenance and self-reproduction. Metabolic P systems represent a class of P systems particularly promising to model a minimal cell in discrete terms, since they have already successfully modeled several metabolisms. The main further step is thus to find a simple way to obtain Metabolic P system self-replication. This paper deals with ideas presented at the BWMC11 (held in Seville, Feb 2011) and opens a new trend in membrane computing, based on computational synthetic biology oriented applications of P systems modeling. The framework is here outlined, and some problems to tackle the synthesis of a minimal cell are discussed. Moreover, an overview of literature and a list of appealing research directions is given, along with several references

Metabolinės P sistemos įgyvendinimo lauku programuojamomis loginėmis matricomis tyrimas

The advancement in the fields of electronics and nature inspired computing, including metabolic P (MP) systems, presents new possible solutions to existing problems,however there are still no implementations of MP systems in field programmable gate arrays (FPGA). Therefore, in this work the problem of lack of knowledge about the quality of MP systems implementation in FPGA together with absence of implementation technique for multiple and effective MP systems is solved. The object of the research is specialized MP system implementations in FPGA that operate in real-time. The main aspects of the research object investigated in the thesis are: implementation quality and techniques. The aim of the thesis is to offer original FPGA based MP system solutions by creating and investigating real-time metabolic process electronic system used for imitation and testing. In order to solve the stated problem and reach the aim of the thesis the following objectives are formulated: using theoretical results of MP systems and other best practices, offer original solutions for MP system transformation to FPGA structural elements and signal processing schemes; reveal quality characteristics of the transformation based on throughput, complexity and power consumption; create real-time metabolic process imitation and testing electronic system and perform its evaluation experiments. The dissertation consists of an introduction, four chapters and general conclusions.The first chapter reveals the fundamental knowledge on nature inspired computing,MP system definition and application, and FPGA implementation quality estimation.In the second chapter the quality criteria of calculation accuracy, throughput,resource usage, power consumption and interface complexity are selected for the evaluation of MP system FPGA implementation. New combined MP system quality metric ant its visualisation is also proposed. In the third chapter the common FPGA implementation techniques are adapted for MP systems and new unified technique is proposed. The evaluation of the developed MP system implementations in FPGA is presented in the fourth chapter. The experiments consist of a single MP system implementation using three different techniques and a multiple MP system implementation using two new developed unified implementation techniques. The main results of the thesis were published in 5 scientific publications: three of them were printed in peer-reviewed scientific journals, one of them in Clarivate Analytics Web of Science database, two articles – in conference proceedings. The research results were presented in 6 scientific conferences

Analysis of “SystemC” design flow for FPGA implementation

High level language termed as SystemC language is recently gaining popularity in VLSI industries especially in Hardware-Software co-design. Using SystemC, Hardware IPs can be modeled at system level which helps to reduce the time to market for SOCs. In most applications SystemC is utilized to verify functionality of the design. However there has been relatively less work done on the synthesis of equivalent hardware from SystemC. In this paper, Finite Impulse Response Filter and Greatest Common divisor are designed as examples in SystemC language and their corresponding synthesis flow from SystemC to FPGA is proposed. The proposed method of synthesis would be time saving than the conventional design and synthesis using HDL in RTL perspective

MP Modeling of Glucose-Insulin Interactions in the Intravenous Glucose Tolerance Test

The Intra Venous Glucose Tolerance Test (IVGTT) is an experimental pro- cedure in which a challenge bolus of glucose is administered intra-venously and plasma glucose and insulin concentrations are then frequently sampled. An open problem is to construct a model representing simultaneously the entire control system. In the last three decades, several models appeared in the literature. One of the mostly used one is known as the minimal model, which has been challenged by the dynamical model. However, both the models have not escape from criticisms and drawbacks. In this paper we apply Metabolic P systems theory for developing new physiologically based models of the glucose-insulin system which can be applied to the Intra Venous Glucose Tolerance Test. We considered ten data-sets obtained from literature and for each of them we found an MP model which ts the data and explains the regulations of the dynamics. Finally, further analysis are planned in order to de ne common patterns which explain, in general, the action of the glucose-insulin control system

Deterministic and stochastic P systems for modelling cellular processes

This paper presents two approaches based on metabolic and stochastic P systems, together with their associated analysis methods, for modelling biological sys- tems and illustrates their use through two case studies.Kingdom's Engineering and Physical Sciences Research Council EP/ E017215/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/D019613/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/F01855X/

MAREX: A general purpose hardware architecture for membrane computing

Membrane computing is an unconventional computing paradigm that has gained much attention in recent decades because of its massively parallel character and its usefulness to build models of complex systems. However, until now, there was no generic hardware implementation of P systems. Computational frameworks to execute P systems up to this day rely on the simulation of the parallel working mechanisms of P systems by inherently sequential algorithms. Such algorithms can then be implemented as is or can be parallelized, up to a certain point, to run on parallel computers. However, this is not as efficient as a dedicated parallel hardware implementation. There have been ad hoc implementations of particular P systems for parallel hardware, but they lack to be problem-generic or they are not scalable enough to implement large P systems. In this paper, a first intrinsically parallel hardware architecture to implement generic P system models is introduced. It is designed to be straightforwardly implemented in programmable logic circuits like FPGAs. The feasibility and correct execution of our architecture has been verified by means of a simulator, and several simulation results for different P system examples have been analysed to foresee the pros and cons of this design.Ministerio de Ciencia e Innovacion of Spain and the AEI/FEDER (EU) project TIN2017-89842-P (MABICAP)Ministerio de Ciencia e Innovacion of Spain and the AEI/FEDER (EU) project PID2019-110455GB-I00 (Par-HoT

Membrane computing technology for self-organization of devices in the internet of things

Disertacijoje nagrinėjamos membraninių skaičiavimų ir daiktų interneto technologijos bei su jomis susieti metaeuristikos algoritmai, optimizavimo skruzdžių kolonijomis algoritmai, daiktų interneto informacijos valdymo ir skirstymo algoritmai. Membraniniai skaičiavimai – tai kompiuterių mokslų sritis, kurioje skaičiavimo idėjos ir modeliai abstrahuojami iš gyvų ląstelių struktūros. Daiktų internetas – nepriklausomų įrenginių rinkinys, kuris vartotojams pateikiamas kaip viena darni sistema (struktūra) skirta išmaniaisiais įrankiais jungtis prie jutiklių ir daugybės prietaisų, siekiant juos valdyti arba gauti pagrindinę jų informaciją. Daiktų interneto savitvarkos duomenų valdymo ir skirstymo problemos sprendimas yra aktualus siekiant, kad sistemos veiktų nenutrūkstamai ir darniai. Šios disertacijos tyrimo objektas yra daiktų interneto savitvarka. Darbo tikslas – pasiūlyti originalų metaeuristika grįstą P sistemos sprendimą, sukuriant ir ištiriant membraninių skaičiavimų imitavimo ir testavimo sistemą daiktų interneto sąlygomis. Darbas skirtas prisidėti vystant darnias daiktų interneto sistemas. Atliekama analitinė membraninių skaičiavimų ir daiktų interneto literatūros apžvalga, pagrindžiant darbe iškeltos problemos aktualumą ir galimus jos sprendimo būdus tolimesniems tyrimams. Remiantis atlikta apžvalga bei pritaikant natūralioje gamtoje vykstančius procesus pasiūloma nauja daiktų interneto savitvarkos max-min skruzdžių P sistema, metodika. Pasiūlytas metodas ištiriamas MATLABTM programinėje įrangoje sukuriant virtualų tinklą imituojantį daiktų internetą. Disertaciją sudaro įvadas, trys skyriai ir bendrosios išvados. Pirmame skyriuje pristatomos esminės teorinės žinios apie membraninius skaičiavimus ir daiktų internetą, analizuojamas saviorganizuojantis daiktų internetas, metaeuristikos algoritmai, formuluojami disertacijos uždaviniai, apibrėžiama daiktų interneto informacijos skirstymo ir valdymo problema. Antrame skyriuje pristatoma saviorganizuojančio daiktų interneto metodika grįsta gamtoje vykstančiais procesais, pateikiamos P sistemos evoliucijos taisyklės ir programos pseudokodas. Trečiame skyriuje yra suformuluojami kokybiniai vertinimo kriterijai, MATLABTM programinėje įrangoje atliekami eksperimentai ištiriant daiktų interneto informacijos skirstymo ir valdymo max-min P skruzdžių sistemą ir pateikiami eksperimentinio tyrimo rezultatai. Pagrindiniai disertacijos rezultatai paskelbti 5 mokslinėse publikacijose – 3 iš jų atspausdintos recenzuojamuose mokslo žurnaluose, 2 – konferencijų medžiagose. Rezultatai viešinti 6 mokslinėse konferencijose.Daktaro disertacij

An Algorithm for Initial Fluxes of Metabolic P Systems

A central issue in systems biology is the study of efficient methods inferring fluxes of biological reactions by starting from experimental data. Among the different techniques proposed in the last years, the theory of Metabolic P systems, which is based on the Log-Gain principle, proved to be helpful for deducing biologi- cal fluxes from temporal series of observed dynamics. According to this approach, the algebraic systems provided by the Log-Gain principle determine the reaction fluxes underlying a system dynamics when initial fluxes are known. Here we propose a heuristic algorithm for estimating the initial fluxes, that is tested in two case studies

Biological networks in metabolic P systems

Abstract The metabolic P algorithm is a procedure which determines, in a biochemically realistic way, the evolution of P systems representing biological phenomena. A new formulation of this algorithm is given and a graphical formalism is introduced which seems to be very natural in expressing biological networks by means of a two level representation: a basic biochemical level and a second one which regulates the dynamical interaction among the reactions of the first level. After some basic examples, the mitotic oscillator in amphibian embryos is considered as an important case study. Three formulations of this biological network are developed. The first two are directly derived by Goldbeter's differential equations representation. The last one, entirely deduced by translating the biological description of the phenomenon in our diagrams, exhibits an analogous pattern, but it is conceptually simpler and avoids many details on the kinetic aspects of the reactions

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