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.

BIVARIATE BINOMIAL SPATIAL MODELLING LOA loa PREVALENCE IN TROPICAL AFRICA

We present a state-of-the-art application of smoothing for dependent bivariate binomial spatial data to Loa loa prevalence mapping in West Africa. This application is special because it starts with the non-spatial calibration of survey instruments, continues with the spatial model building and assessment and ends with robust, tested software that will be used by the field scientists of the World Health Organization for online prevalence map updating. From a statistical perspective several important methodological issues were addressed: (a) building spatial models that are complex enough to capture the structure of the data but remain computationally usable; (b)reducing the computational burden in the handling of very large covariate data sets; (c) devising methods for comparing spatial prediction methods for a given exceedance policy threshold.

Infrastructure (Resilience-oriented) Modelling Language: I®ML A proposal for modelling infrastructures and their connections

The modelling of critical infrastructures (CIs) is an important issue that needs to be properly addressed, for several reasons. It is a basic support for making decisions about operation and risk reduction. It might help in understanding high-level states at the system-of-systems layer, which are not ready evident to the organisations that manage the lower level technical systems. Moreover, it is also indispensable for setting a common reference between operator and authorities, for agreeing on the incident scenarios that might affect those infrastructures. So far, critical infrastructures have been modelled ad-hoc, on the basis of knowledge and practice derived from less complex systems. As there is no theoretical framework, most of these efforts proceed without clear guides and goals and using informally defined schemas based mostly on boxes and arrows. Different CIs (electricity grid, telecommunications networks, emergency support, etc) have been modelled using particular schemas that were not directly translatable from one CI to another. If there is a desire to build a science of CIs it is because there are some observable commonalities that different CIs share. Up until now, however, those commonalities were not adequately compiled or categorized, so building models of CIs that are rooted on such commonalities was not possible. This report explores the issue of which elements underlie every CI and how those elements can be used to develop a modelling language that will enable CI modelling and, subsequently, analysis of CI interactions, with a special focus on resilience

ClimApp: A Novel Approach of an Intelligent HVAC Control System

This paper describes a novel deployment of an intelligent user-centered HVAC (Heating, Ventilating and Air Conditioner) control system. The main objective of this system is to optimize user comfort and to reduce energy consumption in office buildings. Existing commercial HVAC control systems work in a fixed and predetermined way. The novelty of the proposed system is that it adapts dynamically to the user and to the building environment. For this purpose the system architecture has been designed under the paradigm of Ambient Intelligence. A prototype of the system proposed has been tested in a real-world environment.

Modelling of chloride penetration into non-saturated concrete: Case study application for real marine off shore structures

The aim of this paper is to explain the chloride concentration profiles obtained experimentally from control samples of an offshore platform after 25 years of service life. The platform is located 12 km off the coast of the Brazilian province Rio Grande do Norte, in the north-east of Brazil. The samples were extracted at different orientations and heights above mean sea level. A simple model based on Fick’s second law is considered and compared with a finite element model which takes into account transport of chloride ions by diffusion and convection. Results show that convective flows significantly affect the studied chloride penetrations. The convection velocity is obtained by fitting the finite element solution to the experimental data and seems to be directly proportional to the height above mean sea level and also seems to depend on the orientation of the face of the platform. This work shows that considering solely diffusion as transport mechanism does not allow a good prediction of the chloride profiles. Accounting for capillary suction due to moisture gradients permits a better interpretation of the material’s behaviour.

Participatory modelling to support decision making in water management under uncertainty: Two comparative case studies in the Guadiana river basin, Spain.

A participatory modelling process has been conducted in two areas of the Guadiana river (the upper and the middle sub-basins), in Spain, with the aim of providing support for decision making in the water management field. The area has a semi-arid climate where irrigated agriculture plays a key role in the economic development of the region and accounts for around 90% of water use. Following the guidelines of the European Water Framework Directive, we promote stakeholder involvement in water management with the aim to achieve an improved understanding of the water system and to encourage the exchange of knowledge and views between stakeholders in order to help building a shared vision of the system. At the same time, the resulting models, which integrate the different sectors and views, provide some insight of the impacts that different management options and possible future scenarios could have. The methodology is based on a Bayesian network combined with an economic model and, in the middle Guadiana sub-basin, with a crop model. The resulting integrated modelling framework is used to simulate possible water policy, market and climate scenarios to find out the impacts of those scenarios on farm income and on the environment. At the end of the modelling process, an evaluation questionnaire was filled by participants in both sub-basins. Results show that this type of processes are found very helpful by stakeholders to improve the system understanding, to understand each others views and to reduce conflict when it exists. In addition, they found the model an extremely useful tool to support management. The graphical interface, the quantitative output and the explicit representation of uncertainty helped stakeholders to better understand the implications of the scenario tested. Finally, the combination of different types of models was also found very useful, as it allowed exploring in detail specific aspects of the water management problems.

Modelling and forecasting fossil fuels, CO2 and electricity prices and their volatilities

In the current uncertain context that affects both the world economy and the energy sector, with the rapid increase in the prices of oil and gas and the very unstable political situation that affects some of the largest raw materials’ producers, there is a need for developing efficient and powerful quantitative tools that allow to model and forecast fossil fuel prices, CO2 emission allowances prices as well as electricity prices. This will improve decision making for all the agents involved in energy issues. Although there are papers focused on modelling fossil fuel prices, CO2 prices and electricity prices, the literature is scarce on attempts to consider all of them together. This paper focuses on both building a multivariate model for the aforementioned prices and comparing its results with those of univariate ones, in terms of prediction accuracy (univariate and multivariate models are compared for a large span of days, all in the first 4 months in 2011) as well as extracting common features in the volatilities of the prices of all these relevant magnitudes. The common features in volatility are extracted by means of a conditionally heteroskedastic dynamic factor model which allows to solve the curse of dimensionality problem that commonly arises when estimating multivariate GARCH models. Additionally, the common volatility factors obtained are useful for improving the forecasting intervals and have a nice economical interpretation. Besides, the results obtained and methodology proposed can be useful as a starting point for risk management or portfolio optimization under uncertainty in the current context of energy markets.

Integration of a data acquisition system based on FlexRIO technology with EPICS

EPICS (Experimental Physics and Industrial Control System) lies in a set of software tools and applications which provide a software infrastructure for building distributed data acquisition and control systems. Currently there is an increase in use of such systems in large Physics experiments like ITER, ESS, and FREIA. In these experiments, advanced data acquisition systems using FPGA-based technology like FlexRIO are more frequently been used. The particular case of ITER (International Thermonuclear Experimental Reactor), the instrumentation and control system is supported by CCS (CODAC Core System), based on RHEL (Red Hat Enterprise Linux) operating system, and by the plant design specifications in which every CCS element is defined either hardware, firmware or software. In this degree final project the methodology proposed in Implementation of Intelligent Data Acquisition Systems for Fusion Experiments using EPICS and FlexRIO Technology Sanz et al. [1] is used. The final objective is to provide a document describing the fulfilled process and the source code of the data acquisition system accomplished. The use of the proposed methodology leads to have two diferent stages. The first one consists of the hardware modelling with graphic design tools like LabVIEWFPGA which later will be implemented in the FlexRIO device. In the next stage the design cycle is completed creating an EPICS controller that manages the device using a generic device support layer named NDS (Nominal Device Support). This layer integrates the data acquisition system developed into CCS (Control, data access and communication Core System) as an EPICS interface to the system. The use of FlexRIO technology drives the use of LabVIEW and LabVIEW FPGA respectively. RESUMEN. EPICS (Experimental Physics and Industrial Control System) es un conjunto de herramientas software utilizadas para el desarrollo e implementación de sistemas de adquisición de datos y control distribuidos. Cada vez es más utilizado para entornos de experimentación física a gran escala como ITER, ESS y FREIA entre otros. En estos experimentos se están empezando a utilizar sistemas de adquisición de datos avanzados que usan tecnología basada en FPGA como FlexRIO. En el caso particular de ITER, el sistema de instrumentación y control adoptado se basa en el uso de la herramienta CCS (CODAC Core System) basado en el sistema operativo RHEL (Red Hat) y en las especificaciones del diseño del sistema de planta, en la cual define todos los elementos integrantes del CCS, tanto software como firmware y hardware. En este proyecto utiliza la metodología propuesta para la implementación de sistemas de adquisición de datos inteligente basada en EPICS y FlexRIO. Se desea generar una serie de ejemplos que cubran dicho ciclo de diseño completo y que serían propuestos como casos de uso de dichas tecnologías. Se proporcionará un documento en el que se describa el trabajo realizado así como el código fuente del sistema de adquisición. La metodología adoptada consta de dos etapas diferenciadas. En la primera de ellas se modela el hardware y se sintetiza en el dispositivo FlexRIO utilizando LabVIEW FPGA. Posteriormente se completa el ciclo de diseño creando un controlador EPICS que maneja cada dispositivo creado utilizando una capa software genérica de manejo de dispositivos que se denomina NDS (Nominal Device Support). Esta capa integra la solución en CCS realizando la interfaz con la capa EPICS del sistema. El uso de la tecnología FlexRIO conlleva el uso del lenguaje de programación y descripción hardware LabVIEW y LabVIEW FPGA respectivamente.

A dynamic, probabilistic model for city building

The problem of interdependence between housing and commuting in a city has been analysed within the framework of welfare economics. Uncertain changes overtime in the working population has been considered by means of a dynamic, probabilistic model. The characteristics of irreversibility and durability in city building have been explicitly dealt with. The ultimate objective is that the model after further development will be an auxiliary tool in city planning.

Seismic earth thrust against massive building walls

The problem of earth thrust for a massive building in a seismic environment is analysed. Intertial and kinematic soil-structure interactions are considered by modelling the soil and the structure together. The problem is solved in the frequency domain by using the computer code FLUSH. Results show that the horizontal component of the seismic earth thrust is much greater than that obtained when applying the Mononobe-Okabe theory. This study establishes a set of conclusicns and recommendations for both design and practical purposes, and proposes future lines of investigation.

Determination of the influence of specific building regulations in smart buildings

The automation of domestic services began to be implemented in buildings since the late nineteenth century, and today we are used to terms like ‘intelligent buildings’, ‘digital home’ or ‘domotic buildings’. These concepts tell us about constructions which integrate new technologies in order to improve comfort, optimize energy consumption or enhance the security of users. In conjunction, building regulations have been updated to suit the needs of society and to regulate these new facilities in such structures. However, we are not always sure about how far, from the quantitative or qualitative point of view, legislation should regulate certain aspects of the building activity. Consequently, content analysis is adopted in this research to determine the influence of building regulations in the implementation of new technologies in the construction process. This study includes the analysis of different European regulations, the collection and documentation of such guidelines that have been established and a study of the impact that all of these have had in the way we start thinking an architectural project. The achievements of the research could be explained in terms of the regulatory requirements that must be taken into account in order to achieve a successful implementation of a home automation system, and the key finding has been the confirmation of how the design of smart buildings may be promoted through specific regulatory requirements while other factors, such as the global economic situation, do not seem to affect directly the rate of penetration of home automation in construction.

Building an ontology catalogue for smart cities

Apart from providing semantics and reasoning power to data, ontologies enable and facilitate interoperability across heterogeneous systems or environments. A good practice when developing ontologies is to reuse as much knowledge as possible in order to increase interoperability by reducing heterogeneity across models and to reduce development effort. Ontology registries, indexes and catalogues facilitate the task of finding, exploring and reusing ontologies by collecting them from different sources. This paper presents an ontology catalogue for the smart cities and related domains. This catalogue is based on curated metadata and incorporates ontology evaluation features. Such catalogue represents the first approach within this community and it would be highly useful for new ontology developments or for describing and annotating existing ontologies.

Assessment of urban parameterizations in the WRF model for air quality modelling purposes in Madrid (Spain)

This study aims to assess the performance or multi-layer canopy parameterizations implemented in the mesoscale WRF model in order to understand their potential contribution to improve the description of energy fluxes and wind fields in the Madrid city. It was found that the Building Energy Model (BEP+BEM) parameterization yielded better results than the bulk standard scheme implemented in the Noah LSM, but very close to those of the Building Energy Parameterization (BEP). The later was deemed as the best option since data requirements and CPU time were smaller. Two annual runs were made to feed the CMAQ chemical-transport model to assess the impact of this feature in routinely air quality modelling activities.

Urban microclimate and thermal comfort modelling: strategies for urban renovation

The urban microclimate plays an important role in building energy consumption and thermal comfort in outdoor spaces. Nowadays, cities need to increase energy efficiency, reduce pollutant emissions and mitigate the evident lack of sustainability. In light of this, attention has focused on the bioclimatic concepts use in the urban development. However, the speculative unsustainability of the growth model highlights the need to redirect the construction sector towards urban renovation using a bioclimatic approach. The public space plays a key role in improving the quality of today’s cities, especially in terms of providing places for citizens to meet and socialize in adequate thermal conditions. Thermal comfort affects perception of the environment, so microclimate conditions can be decisive for the success or failure of outdoor urban spaces and the activities held in them. For these reasons, the main focus of this work is on the definition of bioclimatic strategies for existing urban spaces, based on morpho-typological components, urban microclimate conditions and comfort requirements for all kinds of citizens. Two case studies were selected in Madrid, in a social housing neighbourhood constructed in the 1970s based on Rational Architecture style. Several renovation scenarios were performed using a computer simulation process based in ENVI-met and diverse microclimate conditions were compared. In addition, thermal comfort evaluation was carried out using the Universal Thermal Climate Index (UTCI) in order to investigate the relationship between microclimate conditions and thermal comfort perception. This paper introduces the microclimate computer simulation process as a valuable support for decision-making for neighbourhood renovation projects in order to provide new and better solutions according to the thermal quality of public spaces and reducing energy consumption by creating and selecting better microclimate areas.

A Knowledge-based System for Intelligent Support in Pharmacogenomics Evidence Assessment: Ontology-driven Evidence Representation, Retrieval, Classification and Interpretation

Thesis (Ph.D.)--University of Washington, 2016-06