Evaluating evolutionary algorithms and differential evolution for the online optimization of fermentation processes

Although important contributions have been made in recent years within the field of bioprocess model development and validation, in many cases the utility of even relatively good models for process optimization with current state-of-the-art algorithms (mostly offline approaches) is quite low. The main cause for this is that open-loop fermentations do not compensate for the differences observed between model predictions and real variables, whose consequences can lead to quite undesirable consequences. In this work, the performance of two different algorithms belonging to the main groups of Evolutionary Algorithms (EA) and Differential Evolution (DE) is compared in the task of online optimisation of fed-batch fermentation processes. The proposed approach enables to obtain results close to the ones predicted initially by the mathematical models of the process, deals well with the noise in state variables and exhibits properties of graceful degradation. When comparing the optimization algorithms, the DE seems the best alternative, but its superiority seems to decrease when noisier settings are considered.Fundo Europeu de Desenvolvimento Regional (FEDER)Fundação para a Ciência e a Tecnologia (FCT

Environmental sustainability in portuguese middle and high-schools : attitudes, perceptions and implementation

Dissertação de Mestrado em Cidadania Ambiental e Participação apresentada à Universidade AbertaTendo em conta os atuais desafios ambientais, sociais e económicos com que os cidadãos se deparam numa base diária, existe uma exigência imposta aos jovens de hoje e decisores do futuro no que concerne à sua preparação para lidar com os desafios de sustentabilidade ambiental vindouros. Impõe-se por propósitos ambientais, sociais e económicos, uma análise do atual estado da educação na sua componente ambiental, não estritamente curricular, e numa etapa menos destacada - o terceiro ciclo e ensino secundário. O atual estudo explora de uma forma global a sustentabilidade ambiental implementada e percecionada nas instituições de ensino de terceiro ciclo e ensino secundário Portuguesas, recorrendo a uma análise quantitativa e qualitativa. Os resultados do presente ensaio, discussão e conclusões, suportam-se num conceito de triangulação de dados. A recolha de dados baseou-se na aplicação e estudo de um inquérito por questionário enviado por correio eletrónico às diversas instituições de ensino do país e na realização e análise de um conjunto de entrevistas telefónicas a instituições selecionadas, tendo por base a primeira recolha dos dados do questionário. A discussão realizada e resultados obtidos, pela baixa taxa de retorno, não permitem compreender de forma fiável o panorama nacional, mas deixam antever grande heterogeneidade e o pequeno número de iniciativas ambientais realizadas pelas instituições escolares. A reduzida sensibilização em relação à temática é também comum. A sustentabilidade ambiental implementada é muitas vezes mínima, tendo frequentemente na sua génese a simples redução de custos, sem qualquer planeamento ambiental e integração associados. A interação entre as entidades de ensino e o tecido empresarial envolvente, juntas de freguesia, câmaras municipais e mesmo governo central, em relação a iniciativas de sustentabilidade ambiental, é diminuta. A existência de sistemas de gestão ambiental é escassa e frequentemente muito simplificada. Falta de motivação, orientação e fraca sensibilidade ambiental são problemas reconhecidos. No curto e médio prazo, no entanto, muitas soluções estão disponíveis, sendo propostas neste trabalho.The environmental, social and economic issues that citizens face in every-day life demand from the youth of today, - tomorrow decision-makers -, an adequate preparation to deal with the upcoming challenges. A study about the current non-curricular environmental education in middle and high-school institutions is essential at this time of great environmental challenges. This study explores the implemented environmentally sustainable measures and the attitudes toward them in Portuguese middle and high-school educational institutions, using both quantitative and qualitative analysis. This work´s results, discussion and conclusions, are supported through data triangulation. The relevant pillars of this investigation were the implementation and study of an e-mailed questionnaire survey to the several educational institutions in the country and the analysis of twenty two telephonic interviews, conducted to selected institutions based on data collected on the questionnaire. Given the low return rate of questionnaire responses, it was not possible to reliably understand the national panorama in this area of study. The data that were collected, however, pointed to a wide variety of implemented procedures, initiatives and knowledge, with a disappointing trend toward very little environmental awareness, commitment and responsibility, throughout Portuguese schools. Implemented environmental sustainability in Portuguese schools is often reduced to simple cost-reduction measures, with no other planning or integration. The interaction between educational institutions and the business and corporate structure of the region, as well as with municipalities, city-hall´s and even the central government, is almost non-existent. The implementation of environmental management systems is uncommon and usually oversimplified. Lack of motivation, guidance, and weak environmental awareness are recognized problems in Portuguese schools. In the short and medium-term, however, many solutions are available and are proposed in this work

Multi-bump solutions in a neural field model with external inputs

"Available online 3 March 2016"We study the conditions for the formation of multiple regions of high activity or “bumps” in a one-dimensional, homogeneous neural field with localized inputs. Stable multi-bump solutions of the integro-differential equation have been proposed as a model of a neural population representation of remembered external stimuli. We apply a class of oscillatory coupling functions and first derive criteria to the input width and distance, which relate to the synaptic couplings that guarantee the existence and stability of one and two regions of high activity. These input-induced patterns are attracted by the corresponding stable one-bump and two-bump solutions when the input is removed. We then extend our analytical and numerical investigation to NN-bump solutions showing that the constraints on the input shape derived for the two-bump case can be exploited to generate a memory of N>2N>2 localized inputs. We discuss the pattern formation process when either the conditions on the input shape are violated or when the spatial ranges of the excitatory and inhibitory connections are changed. An important aspect for applications is that the theoretical findings allow us to determine for a given coupling function the maximum number of localized inputs that can be stored in a given finite interval.The work received financial support from FCT through a PhD grant (SFRH/BD/41179/2007) and from the EU-FP7 ITN project NETT: Neural Engineering Transformative Technologies (nr. 289146)

Inference in credal networks: branch-and-bound methods and the A/R+ algorithm

AbstractA credal network is a graphical representation for a set of joint probability distributions. In this paper we discuss algorithms for exact and approximate inferences in credal networks. We propose a branch-and-bound framework for inference, and focus on inferences for polytree-shaped networks. We also propose a new algorithm, A/R+, for outer approximations in polytree-shaped credal networks

A pipeline for the reconstruction and evaluation of context-specific human metabolic models at a large-scale

Constraint-based (CB) metabolic models provide a mathematical framework and scaffold for in silico cell metabolism analysis and manipulation. In the past decade, significant efforts have been done to model human metabolism, enabled by the increased availability of multi-omics datasets and curated genome-scale reconstructions, as well as the development of several algorithms for context-specific model (CSM) reconstruction. Although CSM reconstruction has revealed insights on the deregulated metabolism of several pathologies, the process of reconstructing representative models of human tissues still lacks benchmarks and appropriate integrated software frameworks, since many tools required for this process are still disperse across various software platforms, some of which are proprietary.In this work, we address this challenge by assembling a scalable CSM reconstruction pipeline capable of integrating transcriptomics data in CB models. We combined omics preprocessing methods inspired by previous efforts with in-house implementations of existing CSM algorithms and new model refinement and validation routines, all implemented in the Troppo Python-based open-source framework. The pipeline was validated with multi-omics datasets from the Cancer Cell Line Encyclopedia (CCLE), also including reference fluxomics measurements for the MCF7 cell line.We reconstructed over 6000 models based on the Human-GEM template model for 733 cell lines featured in the CCLE, using MCF7 models as reference to find the best parameter combinations. These reference models outperform earlier studies using the same template by comparing gene essentiality and fluxomics experiments. We also analysed the heterogeneity of breast cancer cell lines, identifying key changes in metabolism related to cancer aggressiveness. Despite the many challenges in CB modelling, we demonstrate using our pipeline that combining transcriptomics data in metabolic models can be used to investigate key metabolic shifts. Significant limitations were found on these models ability for reliable quantitative flux prediction, thus motivating further work in genome-wide phenotype prediction.Author summary Genome-scale models of human metabolism are promising tools capable of contextualising large omics datasets within a framework that enables analysis and manipulation of metabolic phenotypes. Despite various successes in applying these methods to provide mechanistic hypotheses for deregulated metabolism in disease, there is no standardized workflow to extract these models using existing methods and the tools required to do so are mostly implemented using proprietary software.We have assembled a generic pipeline to extract and validate context-specific metabolic models using multi-omics datasets and implemented it using the troppo framework. We first validate our pipeline using MCF7 cell line models and assess their ability to predict lethal gene knockouts as well as flux activity using multi-omics data. We also demonstrate how this approach can be generalized for large-scale transcriptomics datasets and used to generate insights on the metabolic heterogeneity of cancer and relevant features for other data mining approaches. The pipeline is available as part of an open-source framework that is generic for a variety of applications.Competing Interest StatementThe authors have declared no competing interest.The authors thank the PhD scholarships co-funded by national funds and the European Social Fund through the Portuguese Foundation for Science and Technology (FCT), with references: SFRH/BD/118657/2016 (V.V.), SFRH/BD/133248/2017 (J.F.). This study was also supported by the FCT under the scope of the strategic funding of UIDB/04469/2020 unit.info:eu-repo/semantics/publishedVersio

A pipeline for the reconstruction and evaluation of context-specific human metabolic models at a large-scale

Constraint-based (CB) metabolic models provide a mathematical framework and scaffold for in silico cell metabolism analysis and manipulation. In the past decade, significant efforts have been done to model human metabolism, enabled by the increased availability of multi-omics datasets and curated genome-scale reconstructions, as well as the development of several algorithms for context-specific model (CSM) reconstruction. Although CSM reconstruction has revealed insights on the deregulated metabolism of several pathologies, the process of reconstructing representative models of human tissues still lacks benchmarks and appropriate integrated software frameworks, since many tools required for this process are still disperse across various software platforms, some of which are proprietary. In this work, we address this challenge by assembling a scalable CSM reconstruction pipeline capable of integrating transcriptomics data in CB models. We combined omics preprocessing methods inspired by previous efforts with in-house implementations of existing CSM algorithms and new model refinement and validation routines, all implemented in the Troppo Python-based open-source framework. The pipeline was validated with multi-omics datasets from the Cancer Cell Line Encyclopedia (CCLE), also including reference fluxomics measurements for the MCF7 cell line. We reconstructed over 6000 models based on the Human-GEM template model for 733 cell lines featured in the CCLE, using MCF7 models as reference to find the best parameter combinations. These reference models outperform earlier studies using the same template by comparing gene essentiality and fluxomics experiments. We also analysed the heterogeneity of breast cancer cell lines, identifying key changes in metabolism related to cancer aggressiveness. Despite the many challenges in CB modelling, we demonstrate using our pipeline that combining transcriptomics data in metabolic models can be used to investigate key metabolic shifts. Significant limitations were found on these models ability for reliable quantitative flux prediction, thus motivating further work in genome-wide phenotype prediction.The authors thank the PhD scholarships co-funded by national funds and the European Social Fund through the Portuguese Foundation for Science and Technology (FCT), with references: SFRH/BD/118657/2016 (V.V.), SFRH/BD/133248/ 2017 (J.F.). This study was also supported by the FCT under the scope of the strategic funding of UIDB/04469/2020 unit and by LABBELS - Associate Laboratory in Biotechnology, Bioengineering and Microelectromechnaical Systems, LA/P/0029/2020.info:eu-repo/semantics/publishedVersio

Evolutionary algorithms for static and dynamic optimization of fed-batch fermentation processes

In this work, Evolutionary Algorithms (EAs) are used to control a recombinant bacterial fed-batch fermentation process, that aims at producing a bio-pharmaceutical product. In a first stage, a novel EA is used to optimize the process, prior to its start, by simultaneously adjusting the feeding trajectory, the duration of the fermentation and the initial conditions of the process. In a second stage, dynamic optimization is proposed, where the EA is running simultaneously with the fermentation process, receiving information regarding from the process, updating its internal model, reaching new solutions that will be used for online control

Metropolitan Morphology and Discontinuities

The main purpose of this research consists in the development and validation, through the application to a case study, of new methods for the definition of territorial discontinuities and morphologies, using the most recent scientific and technological developments that have been made in the fields of remote sensing, geographical information systems and statistics in general. These methods should allow the development of applications for environmental planning and land management. Due to its large dynamics and constant mutation, the Lisbon Metropolitan Area (AML) was chosen as a case study. This research is being conducted in the Geography and Regional Planning Department of the New University of Lisbon (DGPR/UNL) in a close direct relationship with the AML.info:eu-repo/semantics/publishedVersio

Effect of soliton interaction on timing jitter in communication systems

Timing jitter in soliton communication systems is studied, taking into account both soliton interaction and amplifier noise, Deviations from Gordon-Haus jitter for closely spaced solitons are observed. A new analytical model for the timing jitter is proposed, The model presented considers interaction in a random sequence of solitons and the effect of the amplified spontaneous emission noise added in each amplification stage, We obtain a good agreement between the new analytical model and simulation results for practical communication systems