Modelling and simulating in systems biology: an approach based on multi-agent systems

Systems Biology is an innovative way of doing biology recently raised in bio-informatics contexts, characterised by the study of biological systems as complex systems with a strong focus on the system level and on the interaction dimension. In other words, the objective is to understand biological systems as a whole, putting on the foreground not only the study of the individual parts as standalone parts, but also of their interaction and of the global properties that emerge at the system level by means of the interaction among the parts. This thesis focuses on the adoption of multi-agent systems (MAS) as a suitable paradigm for Systems Biology, for developing models and simulation of complex biological systems. Multi-agent system have been recently introduced in informatics context as a suitabe paradigm for modelling and engineering complex systems. Roughly speaking, a MAS can be conceived as a set of autonomous and interacting entities, called agents, situated in some kind of nvironment, where they fruitfully interact and coordinate so as to obtain a coherent global system behaviour. The claim of this work is that the general properties of MAS make them an effective approach for modelling and building simulations of complex biological systems, following the methodological principles identified by Systems Biology. In particular, the thesis focuses on cell populations as biological systems. In order to support the claim, the thesis introduces and describes (i) a MAS-based model conceived for modelling the dynamics of systems of cells interacting inside cell environment called niches. (ii) a computational tool, developed for implementing the models and executing the simulations. The tool is meant to work as a kind of virtual laboratory, on top of which kinds of virtual experiments can be performed, characterised by the definition and execution of specific models implemented as MASs, so as to support the validation, falsification and improvement of the models through the observation and analysis of the simulations. A hematopoietic stem cell system is taken as reference case study for formulating a specific model and executing virtual experiments.

A Software Platform for Teaching Programming with Grading Systems

Красимир Манев, Милослав Средков, Петър Армянов - Състезателните системи (СС) са незаменимо средство за организация на състезания по програмиране. Напоследък СС се използват и в обучението по програмиране. В статията е предложена платформа, която да интегрира възможностите на СС, създадени или използвани от авторите. Целта е изграждането на проста и ефективна среда за обучение по програмиране, подпомагаща учебния процес. Специфицирани са основните елементи на платформата, като резултат от предходно изследване, и една нейна възможна архитектура.

Design principles of semantic binary database management systems

The Semantic Binary Data Model (SBM) is a viable alternative to the now-dominant relational data model. SBM would be especially advantageous for applications dealing with complex interrelated networks of objects provided that a robust efficient implementation can be achieved. This dissertation presents an implementation design method for SBM, algorithms, and their analytical and empirical evaluation. Our method allows building a robust and flexible database engine with a wider applicability range and improved performance. ^ Extensions to SBM are introduced and an implementation of these extensions is proposed that allows the database engine to efficiently support applications with a predefined set of queries. A New Record data structure is proposed. Trade-offs of employing Fact, Record and Bitmap Data structures for storing information in a semantic database are analyzed. ^ A clustering ID distribution algorithm and an efficient algorithm for object ID encoding are proposed. Mapping to an XML data model is analyzed and a new XML-based XSDL language facilitating interoperability of the system is defined. Solutions to issues associated with making the database engine multi-platform are presented. An improvement to the atomic update algorithm suitable for certain scenarios of database recovery is proposed. ^ Specific guidelines are devised for implementing a robust and well-performing database engine based on the extended Semantic Data Model. ^

A nested Petri net framework for modeling and analyzing multi-agent systems

In the past two decades, multi-agent systems (MAS) have emerged as a new paradigm for conceptualizing large and complex distributed software systems. A multi-agent system view provides a natural abstraction for both the structure and the behavior of modern-day software systems. Although there were many conceptual frameworks for using multi-agent systems, there was no well established and widely accepted method for modeling multi-agent systems. This dissertation research addressed the representation and analysis of multi-agent systems based on model-oriented formal methods. The objective was to provide a systematic approach for studying MAS at an early stage of system development to ensure the quality of design. ^ Given that there was no well-defined formal model directly supporting agent-oriented modeling, this study was centered on three main topics: (1) adapting a well-known formal model, predicate transition nets (PrT nets), to support MAS modeling; (2) formulating a modeling methodology to ease the construction of formal MAS models; and (3) developing a technique to support machine analysis of formal MAS models using model checking technology. PrT nets were extended to include the notions of dynamic structure, agent communication and coordination to support agent-oriented modeling. An aspect-oriented technique was developed to address the modularity of agent models and compositionality of incremental analysis. A set of translation rules were defined to systematically translate formal MAS models to concrete models that can be verified through the model checker SPIN (Simple Promela Interpreter). ^ This dissertation presents the framework developed for modeling and analyzing MAS, including a well-defined process model based on nested PrT nets, and a comprehensive methodology to guide the construction and analysis of formal MAS models.^

Real-time scheduling of embedded applications on multi-core platforms

For the past several decades, we have experienced the tremendous growth, in both scale and scope, of real-time embedded systems, thanks largely to the advances in IC technology. However, the traditional approach to get performance boost by increasing CPU frequency has been a way of past. Researchers from both industry and academia are turning their focus to multi-core architectures for continuous improvement of computing performance. In our research, we seek to develop efficient scheduling algorithms and analysis methods in the design of real-time embedded systems on multi-core platforms. Real-time systems are the ones with the response time as critical as the logical correctness of computational results. In addition, a variety of stringent constraints such as power/energy consumption, peak temperature and reliability are also imposed to these systems. Therefore, real-time scheduling plays a critical role in design of such computing systems at the system level. We started our research by addressing timing constraints for real-time applications on multi-core platforms, and developed both partitioned and semi-partitioned scheduling algorithms to schedule fixed priority, periodic, and hard real-time tasks on multi-core platforms. Then we extended our research by taking temperature constraints into consideration. We developed a closed-form solution to capture temperature dynamics for a given periodic voltage schedule on multi-core platforms, and also developed three methods to check the feasibility of a periodic real-time schedule under peak temperature constraint. We further extended our research by incorporating the power/energy constraint with thermal awareness into our research problem. We investigated the energy estimation problem on multi-core platforms, and developed a computation efficient method to calculate the energy consumption for a given voltage schedule on a multi-core platform. In this dissertation, we present our research in details and demonstrate the effectiveness and efficiency of our approaches with extensive experimental results.

A multi-purpose rainfall simulator for field infiltration and erosion studies

This paper describes a rainfall simulator developed for field and laboratory studies that gives great flexibility in plot size covered, that is highly portable and able to be used on steep slopes, and that is economical in its water use. The simulator uses Veejet 80100 nozzles mounted on a manifold, with the nozzles controlled to sweep to and from across a plot width of 1.5 m. Effective rainfall intensity is controlled by the frequency with which the nozzles sweep. Spatial uniformity of rainfall on the plots is high, with coefficients of variation (CV) on the body of the plot being 8-10%. Use of the simulator for erosion and infiltration measurements is discussed.

Guitar solo tracker

A motivação para este trabalho vem da necessidade que o autor tem em poder registar as notas tocadas na guitarra durante o processo de improviso. Quando o músico está a improvisar na guitarra, muitas vezes não se recorda das notas tocadas no momento, este trabalho trata o desenvolvimento de uma aplicação para guitarristas, que permita registar as notas tocadas na guitarra eléctrica ou clássica. O sinal é adquirido a partir da guitarra e processado com requisitos de tempo real na captura do sinal. As notas produzidas pela guitarra eléctrica, ligada ao computador, são representadas no formato de tablatura e/ou partitura. Para este efeito a aplicação capta o sinal proveniente da guitarra eléctrica a partir da placa de som do computador e utiliza algoritmos de detecção de frequência e algoritmos de estimação de duração de cada sinal para construir o registo das notas tocadas. A aplicação é desenvolvida numa perspectiva multi-plataforma, podendo ser executada em diferentes sistemas operativos Windows e Linux, usando ferramentas e bibliotecas de domínio público. Os resultados obtidos mostram a possibilidade de afinar a guitarra com valores de erro na ordem de 2 Hz em relação às frequências de afinação standard. A escrita da tablatura apresenta resultados satisfatórios, mas que podem ser melhorados. Para tal será necessário melhorar a implementação de técnicas de processamento do sinal bem como a comunicação entre processos para resolver os problemas encontrados nos testes efectuados.

Plataforma de gestão de incidentes

Mestrado em Engenharia Electrotécnica e de Computadores. Área de Especialização de Telecomunicações.

Distributed controllers modeling through Petri nets with multi-asynchronous-channels

This paper proposes the concept of multi-asynchronous-channel for Petri nets. Petri nets extended with multi-asynchronous-channels and time-domains support the specification of distributed controllers, where each controller has a synchronous execution but the global system is asynchronous (globally-asynchronous locally-synchronous systems). Each multi-asynchronous-channel specify the interaction between two or more distributed controllers. These channels, together with the time-domain concept, ensure the creation of network-independent models to support implementations using heterogeneous communication networks. The created models support not only the systems documentation but also their validation and implementation through simulation tools, verification tools, and automatic code generators. An application example illustrates the use of a Petri net class extended with the proposed channels. © 2015 IEEE.

RealCrono –sistema de difusão de resultados em tempo real na web

A velocidade de difusão de conteúdos numa plataforma web, assume uma elevada relevância em serviços onde a informação se pretende atualizada e em tempo real. Este projeto de Mestrado, apresenta uma abordagem de um sistema distribuído de recolher e difundir resultados em tempo real entre várias plataformas, nomeadamente sistemas móveis. Neste contexto, tempo real entende-se como uma diferença de tempo nula entre a recolha e difusão, ignorando fatores que não podem ser controlados pelo sistema, como latência de comunicação e tempo de processamento. Este projeto tem como base uma arquitetura existente de processamento e publicação de resultados desportivos, que apresentava alguns problemas relacionados com escalabilidade, segurança, tempos de entrega de resultados longos e sem integração com outras plataformas. Ao longo deste trabalho procurou-se investigar fatores que condicionassem a escalabilidade de uma aplicação web dando ênfase à implementação de uma solução baseada em replicação e escalabilidade horizontal. Procurou-se também apresentar uma solução de interoperabilidade entre sistemas e plataformas heterogêneas, mantendo sempre elevados níveis de performance e promovendo a introdução de plataformas móveis no sistema. De várias abordagens existentes para comunicação em tempo real sobre uma plataforma web, adotou-se um implementação baseada em WebSocket que elimina o tempo desperdiçado entre a recolha de informação e sua difusão. Neste projeto é descrito o processo de implementação da API de recolha de dados (Collector), da biblioteca de comunicação com o Collector, da aplicação web (Publisher) e sua API, da biblioteca de comunicação com o Publisher e por fim a implementação da aplicação móvel multi-plataforma. Com os componentes criados, avaliaram-se os resultados obtidos com a nova arquitetura de forma a aferir a escalabilidade e performance da solução criada e sua adaptação ao sistema existente.

Interactive spatial decision support for sustainable agroforestry management: a case study in East Kalimantan, Indonesia

Forest managers, stakeholders and investors want to be able to evaluate economic, environmental and social benefits in order to improve the outcomes of their decisions and enhance sustainable forest management. This research developed a spatial decision support system that provides: (1) an approach to identify the most beneficial locations for agroforestry projects based on the biophysical properties and evaluate its economic, social and environmental impact; (2) a tool to inform prospective investors and stakeholders of the potential and opportunities for integrated agroforestry management; (3) a simulation environment that enables evaluation via a dashboard with the opportunity to perform interactive sensitivity analysis for key parameters of the project; (4) a 3D interactive geographic visualization of the economic, environmental and social outcomes, which facilitate understanding and eases planning. Although the tool and methodology presented are generic, a case study was performed in East Kalimantan, Indonesia. For the whole study area, it was simulated the most suitable location for three different plantation schemes: monoculture of timber, a specific recipe (cassava, banana and sugar palm) and different recipes per geographic unit. The results indicate that a mixed cropping plantation scheme, with different recipes applied to the most suitable location returns higher economic, environmental and social benefits.

Non-Linear Unsteady Aerodynamic Response Approximation Using Multi-Layer Functionals

Non-linear functional representation of the aerodynamic response provides a convenient mathematical model for motion-induced unsteady transonic aerodynamic loads response, that accounts for both complex non-linearities and time-history effects. A recent development, based on functional approximation theory, has established a novel functional form; namely, the multi-layer functional. For a large class of non-linear dynamic systems, such multi-layer functional representations can be realised via finite impulse response (FIR) neural networks. Identification of an appropriate FIR neural network model is facilitated by means of a supervised training process in which a limited sample of system input-output data sets is presented to the temporal neural network. The present work describes a procedure for the systematic identification of parameterised neural network models of motion-induced unsteady transonic aerodynamic loads response. The training process is based on a conventional genetic algorithm to optimise the network architecture, combined with a simplified random search algorithm to update weight and bias values. Application of the scheme to representative transonic aerodynamic loads response data for a bidimensional airfoil executing finite-amplitude motion in transonic flow is used to demonstrate the feasibility of the approach. The approach is shown to furnish a satisfactory generalisation property to different motion histories over a range of Mach numbers in the transonic regime.

Modeling small-scale dairy farms in central Mexico using multi-criteria programming

Milk supply from Mexican dairy farms does not meet demand and small-scale farms can contribute toward closing the gap. Two multi-criteria programming techniques, goal programming and compromise programming, were used in a study of small-scale dairy farms in central Mexico. To build the goal and compromise programming models, 4 ordinary linear programming models were also developed, which had objective functions to maximize metabolizable energy for milk production, to maximize margin of income over feed costs, to maximize metabolizable protein for milk production, and to minimize purchased feedstuffs. Neither multicriteria approach was significantly better than the other; however, by applying both models it was possible to perform a more comprehensive analysis of these small-scale dairy systems. The multi-criteria programming models affirm findings from previous work and suggest that a forage strategy based on alfalfa, rye-grass, and corn silage would meet nutrient requirements of the herd. Both models suggested that there is an economic advantage in rescheduling the calving season to the second and third calendar quarters to better synchronize higher demand for nutrients with the period of high forage availability.

Weaning diet induces sustained metabolic phenotype shift in the pig and influences host response to Bifidobacterium lactis NCC2818

Background The process of weaning causes a major shift in intestinal microbiota and is a critical period for developing appropriate immune responses in young mammals.Objective To use a new systems approach to provide an overview of host metabolism and the developing immune system in response to nutritional intervention around the weaning period.Design Piglets (n=14) were weaned onto either an egg-based or soya-based diet at 3 weeks until 7 weeks, when all piglets were switched onto a fish-based diet. Half the animals on each weaning diet received Bifidobacterium lactis NCC2818 supplementation from weaning onwards. Immunoglobulin production from immunologically relevant intestinal sites was quantified and the urinary (1)H NMR metabolic profile was obtained from each animal at post mortem (11 weeks).Results Different weaning diets induced divergent and sustained shifts in the metabolic phenotype, which resulted in the alteration of urinary gut microbial co-metabolites, even after 4 weeks of dietary standardisation. B lactis NCC2818 supplementation affected the systemic metabolism of the different weaning diet groups over and above the effects of diet. Additionally, production of gut mucosa-associated IgA and IgM was found to depend upon the weaning diet and on B lactis NCC2818 supplementation.ConclusionThe correlation of urinary (1)H NMR metabolic profile with mucosal immunoglobulin production was demonstrated, thus confirming the value of this multi-platform approach in uncovering non-invasive biomarkers of immunity. This has clear potential for translation into human healthcare with the development of urine testing as a means of assessing mucosal immune status. This might lead to early diagnosis of intestinal dysbiosis and with subsequent intervention, arrest disease development. This system enhances our overall understanding of pathologies under supra-organismal control.

A multi-objective programming approach for the optimal operation of distributed generation considering uncertainty

Due to the renewed interest in distributed generation (DG), the number of DG units incorporated in distribution systems has been rapidly increasing in the past few years. This situation requires new analysis tools for understanding system performance, and taking advantage of the potential benefits of DG. This paper presents an evolutionary multi-objective programming approach to determine the optimal operation of DG in distribution systems. The objectives are the minimization of the system power losses and operation cost of the DG units. The proposed approach also considers the inherent stochasticity of DG technologies powered by renewable resources. Some tests were carried out on the IEEE 34 bus distribution test system showing the robustness and applicability of the proposed methodology. © 2011 IEEE.