Eco‐Holonic 4.0 Circular Business Model to Conceptualize Sustainable Value Chain Towards Digital Transition

The purpose of this paper is to conceptualize a circular business model based on an Eco-Holonic Architecture, through the integration of circular economy and holonic principles. A conceptual model is developed to manage the complexity of integrating circular economy principles, digital transformation, and tools and frameworks for sustainability into business models. The proposed architecture is multilevel and multiscale in order to achieve the instantiation of the sustainable value chain in any territory. The architecture promotes the incorporation of circular economy and holonic principles into new circular business models. This integrated perspective of business model can support the design and upgrade of the manufacturing companies in their respective industrial sectors. The conceptual model proposed is based on activity theory that considers the interactions between technical and social systems and allows the mitigation of the metabolic rift that exists between natural and social metabolism. This study contributes to the existing literature on circular economy, circular business models and activity theory by considering holonic paradigm concerns, which have not been explored yet. This research also offers a unique holonic architecture of circular business model by considering different levels, relationships, dynamism and contextualization (territory) aspects

MITK-ModelFit: A generic open-source framework for model fits and their exploration in medical imaging -- design, implementation and application on the example of DCE-MRI

Many medical imaging techniques utilize fitting approaches for quantitative parameter estimation and analysis. Common examples are pharmacokinetic modeling in DCE MRI/CT, ADC calculations and IVIM modeling in diffusion-weighted MRI and Z-spectra analysis in chemical exchange saturation transfer MRI. Most available software tools are limited to a special purpose and do not allow for own developments and extensions. Furthermore, they are mostly designed as stand-alone solutions using external frameworks and thus cannot be easily incorporated natively in the analysis workflow. We present a framework for medical image fitting tasks that is included in MITK, following a rigorous open-source, well-integrated and operating system independent policy. Software engineering-wise, the local models, the fitting infrastructure and the results representation are abstracted and thus can be easily adapted to any model fitting task on image data, independent of image modality or model. Several ready-to-use libraries for model fitting and use-cases, including fit evaluation and visualization, were implemented. Their embedding into MITK allows for easy data loading, pre- and post-processing and thus a natural inclusion of model fitting into an overarching workflow. As an example, we present a comprehensive set of plug-ins for the analysis of DCE MRI data, which we validated on existing and novel digital phantoms, yielding competitive deviations between fit and ground truth. Providing a very flexible environment, our software mainly addresses developers of medical imaging software that includes model fitting algorithms and tools. Additionally, the framework is of high interest to users in the domain of perfusion MRI, as it offers feature-rich, freely available, validated tools to perform pharmacokinetic analysis on DCE MRI data, with both interactive and automatized batch processing workflows.Comment: 31 pages, 11 figures URL: http://mitk.org/wiki/MITK-ModelFi

Earth system modeling with endogenous and dynamic human societies: the copan:CORE open World-Earth modeling framework

Analysis of Earth system dynamics in the Anthropocene requires explicitly taking into account the increasing magnitude of processes operating in human societies, their cultures, economies and technosphere and their growing feedback entanglement with those in the physical, chemical and biological systems of the planet. However, current state-of-the-art Earth system models do not represent dynamic human societies and their feedback interactions with the biogeophysical Earth system and macroeconomic integrated assessment models typically do so only with limited scope. This paper (i) proposes design principles for constructing world-Earth models (WEMs) for Earth system analysis of the Anthropocene, i.e., models of social (world)-ecological (Earth) coevolution on up to planetary scales, and (ii) presents the copan:CORE open simulation modeling framework for developing, composing and analyzing such WEMs based on the proposed principles. The framework provides a modular structure to flexibly construct and study WEMs. These can contain biophysical (e.g., carbon cycle dynamics), socio-metabolic or economic (e.g., economic growth or energy system changes), and sociocultural processes (e.g., voting on climate policies or changing social norms) and their feedback interactions, and they are based on elementary entity types, e.g., grid cells and social systems. Thereby, copan:CORE enables the epistemic flexibility needed for contributions towards Earth system analysis of the Anthropocene given the large diversity of competing theories and methodologies used for describing socio-metabolic or economic and sociocultural processes in the Earth system by various fields and schools of thought. To illustrate the capabilities of the framework, we present an exemplary and highly stylized WEM implemented in copan:CORE that illustrates how endogenizing sociocultural processes and feedbacks such as voting on climate policies based on socially learned environmental awareness could fundamentally change macroscopic model outcomes

Earth system modeling with endogenous and dynamic human societies: the copan:CORE open World-Earth modeling framework

Analysis of Earth system dynamics in the Anthropocene requires to explicitly take into account the increasing magnitude of processes operating in human societies, their cultures, economies and technosphere and their growing feedback entanglement with those in the physical, chemical and biological systems of the planet. However, current state-of-the-art Earth System Models do not represent dynamic human societies and their feedback interactions with the biogeophysical Earth system and macroeconomic Integrated Assessment Models typically do so only with limited scope. This paper (i) proposes design principles for constructing World-Earth Models (WEM) for Earth system analysis of the Anthropocene, i.e., models of social (World) - ecological (Earth) co-evolution on up to planetary scales, and (ii) presents the copan:CORE open simulation modeling framework for developing, composing and analyzing such WEMs based on the proposed principles. The framework provides a modular structure to flexibly construct and study WEMs. These can contain biophysical (e.g. carbon cycle dynamics), socio-metabolic/economic (e.g. economic growth) and socio-cultural processes (e.g. voting on climate policies or changing social norms) and their feedback interactions, and are based on elementary entity types, e.g., grid cells and social systems. Thereby, copan:CORE enables the epistemic flexibility needed for contributions towards Earth system analysis of the Anthropocene given the large diversity of competing theories and methodologies used for describing socio-metabolic/economic and socio-cultural processes in the Earth system by various fields and schools of thought. To illustrate the capabilities of the framework, we present an exemplary and highly stylized WEM implemented in copan:CORE that illustrates how endogenizing socio-cultural processes and feedbacks could fundamentally change macroscopic model outcomes

Method for finding metabolic properties based on the general growth law. Liver examples. A General framework for biological modeling

We propose a method for finding metabolic parameters of cells, organs and whole organisms, which is based on the earlier discovered general growth law. Based on the obtained results and analysis of available biological models, we propose a general framework for modeling biological phenomena and discuss how it can be used in Virtual Liver Network project. The foundational idea of the study is that growth of cells, organs, systems and whole organisms, besides biomolecular machinery, is influenced by biophysical mechanisms acting at different scale levels. In particular, the general growth law uniquely defines distribution of nutritional resources between maintenance needs and biomass synthesis at each phase of growth and at each scale level. We exemplify the approach considering metabolic properties of growing human and dog livers and liver transplants. A procedure for verification of obtained results has been introduced too. We found that two examined dogs have high metabolic rates consuming about 0.62 and 1 gram of nutrients per cubic centimeter of liver per day, and verified this using the proposed verification procedure. We also evaluated consumption rate of nutrients in human livers, determining it to be about 0.088 gram of nutrients per cubic centimeter of liver per day for males, and about 0.098 for females. This noticeable difference can be explained by evolutionary development, which required females to have greater liver processing capacity to support pregnancy. We also found how much nutrients go to biomass synthesis and maintenance at each phase of liver and liver transplant growth. Obtained results demonstrate that the proposed approach can be used for finding metabolic characteristics of cells, organs, and whole organisms, which can further serve as important inputs for many applications in biology (protein expression), biotechnology (synthesis of substances), and medicine.Comment: 20 pages, 6 figures, 4 table

Blueprint: descrição da complexidade da regulação metabólica através da reconstrução de modelos metabólicos e regulatórios integrados

Tese de doutoramento em Biomedical EngineeringUm modelo metabólico consegue prever o fenótipo de um organismo. No entanto, estes modelos podem obter previsões incorretas, pois alguns processos metabólicos são controlados por mecanismos reguladores. Assim, várias metodologias foram desenvolvidas para melhorar os modelos metabólicos através da integração de redes regulatórias. Todavia, a reconstrução de modelos regulatórios e metabólicos à escala genómica para diversos organismos apresenta diversos desafios. Neste trabalho, propõe-se o desenvolvimento de diversas ferramentas para a reconstrução e análise de modelos metabólicos e regulatórios à escala genómica. Em primeiro lugar, descreve-se o Biological networks constraint-based In Silico Optimization (BioISO), uma nova ferramenta para auxiliar a curação manual de modelos metabólicos. O BioISO usa um algoritmo de relação recursiva para orientar as previsões de fenótipo. Assim, esta ferramenta pode reduzir o número de artefatos em modelos metabólicos, diminuindo a possibilidade de obter erros durante a fase de curação. Na segunda parte deste trabalho, desenvolveu-se um repositório de redes regulatórias para procariontes que permite suportar a sua integração em modelos metabólicos. O Prokaryotic Transcriptional Regulatory Network Database (ProTReND) inclui diversas ferramentas para extrair e processar informação regulatória de recursos externos. Esta ferramenta contém um sistema de integração de dados que converte dados dispersos de regulação em redes regulatórias integradas. Além disso, o ProTReND dispõe de uma aplicação que permite o acesso total aos dados regulatórios. Finalmente, desenvolveu-se uma ferramenta computacional no MEWpy para simular e analisar modelos regulatórios e metabólicos. Esta ferramenta permite ler um modelo metabólico e/ou rede regulatória, em diversos formatos. Esta estrutura consegue construir um modelo regulatório e metabólico integrado usando as interações regulatórias e as ligações entre genes e proteínas codificadas no modelo metabólico e na rede regulatória. Além disso, esta estrutura suporta vários métodos de previsão de fenótipo implementados especificamente para a análise de modelos regulatórios-metabólicos.Genome-Scale Metabolic (GEM) models can predict the phenotypic behavior of organisms. However, these models can lead to incorrect predictions, as certain metabolic processes are controlled by regulatory mechanisms. Accordingly, many methodologies have been developed to extend the reconstruction and analysis of GEM models via the integration of Transcriptional Regulatory Network (TRN)s. Nevertheless, the perspective of reconstructing integrated genome-scale regulatory and metabolic models for diverse prokaryotes is still an open challenge. In this work, we propose several tools to assist the reconstruction and analysis of regulatory and metabolic models. We start by describing BioISO, a novel tool to assist the manual curation of GEM models. BioISO uses a recursive relation-like algorithm and Flux Balance Analysis (FBA) to evaluate and guide debugging of in silico phenotype predictions. Hence, this tool can reduce the number of artifacts in GEM models, decreasing the burdens of model refinement and curation. A state-of-the-art repository of TRNs for prokaryotes was implemented to support the reconstruction and integration of TRNs into GEM models. The ProTReND repository comprehends several tools to extract and process regulatory information available in several resources. More importantly, this repository contains a data integration system to unify the regulatory data into standardized TRNs at the genome scale. In addition, ProTReND contains a web application with full access to the regulatory data. Finally, we have developed a new modeling framework to define, simulate and analyze GEnome-scale Regulatory and Metabolic (GERM) models in MEWpy. The GERM model framework can read a GEM model, as well as a TRN from different file formats. This framework assembles a GERM model using the regulatory interactions and Genes-Proteins-Reactions (GPR) rules encoded into the GEM model and TRN. In addition, this modeling framework supports several methods of phenotype prediction designed for regulatory-metabolic models.I would like to thank Fundação para a Ciência e Tecnologia for the Ph.D. studentship I was awarded with (SFRH/BD/139198/2018)

Computational and Mathematical Modelling of the EGF Receptor System

This chapter gives an overview of computational and mathematical modelling of the EGF receptor system. It begins with a survey of motivations for producing such models, then describes the main approaches that are taken to carrying out such modelling, viz. differential equations and individual-based modelling. Finally, a number of projects that applying modelling and simulation techniques to various aspects of the EGF receptor system are described