Experimental design methodologies for the identification of Michaelis-Menten type kinetics

The main objective of this work was to investigate the application of experimental design techniques for the identification of Michaelis-Menten kinetic parameters. More specifically, this study attempts to elucidate the relative advantages/disadvantages of employing complex experimental design techniques in relation to equidistant sampling when applied to different reactor operation modes. All studies were supported by simulation data of a generic enzymatic process that obeys to the Michaelis-Menten kinetic equation. Different aspects were investigated, such as the influence of the reactor operation mode (batch, fed-batch with pulse wise feeding and fed-batch with continuous feeding) and the experimental design optimality criteria on the effectiveness of kinetic parameters identification. The following experimental design optimality criteria were investigated: 1) minimization of the sum of the diagonal of the Fisher information matrix (FIM) inverse (A-criterion), 2) maximization of the determinant of the FIM (D-criterion), 3) maximization of the smallest eigenvalue of the FIM (E-criterion) and 4) minimization of the quotient between the largest and the smallest eigenvalue (modified E-criterion). The comparison and assessment of the different methodologies was made on the basis of the Cramér-Rao lower bounds (CRLB) error in respect to the parameters vmax and Km of the Michaelis-Menten kinetic equation. In what concerns the reactor operation mode, it was concluded that fed-batch (pulses) is better than batch operation for parameter identification. When the former operation mode is adopted, the vmax CRLB error is lowered by 18.6 % while the Km CRLB error is lowered by 26.4 % when compared to the batch operation mode. Regarding the optimality criteria, the best method was the A-criterion, with an average vmax CRLB of 6.34 % and 5.27 %, for batch and fed-batch (pulses), respectively, while presenting a Km’s CRLB of 25.1 % and 18.1 %, for batch and fed-batch (pulses), respectively. As a general conclusion of the present study, it can be stated that experimental design is justified if the starting parameters CRLB errors are inferior to 19.5 % (vmax) and 45% (Km), for batch processes, and inferior to 42 % and to 50% for fed-batch (pulses) process. Otherwise equidistant sampling is a more rational decision. This conclusion clearly supports that, for fed-batch operation, the use of experimental design is likely to largely improve the identification of Michaelis-Menten kinetic parameters.

Environmental data management in the Sado Estuary

Estuaries are perhaps the most threatened environments in the coastal fringe; the coincidence of high natural value and attractiveness for human use has led to conflicts between conservation and development. These conflicts occur in the Sado Estuary since its location is near the industrialised zone of Peninsula of Setúbal and at the same time, a great part of the Estuary is classified as a Natural Reserve due to its high biodiversity. These facts led us to the need of implementing a model of environmental management and quality assessment, based on methodologies that enable the assessment of the Sado Estuary quality and evaluation of the human pressures in the estuary. These methodologies are based on indicators that can better depict the state of the environment and not necessarily all that could be measured or analysed. Sediments have always been considered as an important temporary source of some compounds or a sink for other type of materials or an interface where a great diversity of biogeochemical transformations occur. For all this they are of great importance in the formulation of coastal management system. Many authors have been using sediments to monitor aquatic contamination, showing great advantages when compared to the sampling of the traditional water column. The main objective of this thesis was to develop an estuary environmental management framework applied to Sado Estuary using the DPSIR Model (EMMSado), including data collection, data processing and data analysis. The support infrastructure of EMMSado were a set of spatially contiguous and homogeneous regions of sediment structure (management units). The environmental quality of the estuary was assessed through the sediment quality assessment and integrated in a preliminary stage with the human pressure for development. Besides the earlier explained advantages, studying the quality of the estuary mainly based on the indicators and indexes of the sediment compartment also turns this methodology easier, faster and human and financial resource saving. These are essential factors to an efficient environmental management of coastal areas. Data management, visualization, processing and analysis was obtained through the combined use of indicators and indices, sampling optimization techniques, Geographical Information Systems, remote sensing, statistics for spatial data, Global Positioning Systems and best expert judgments. As a global conclusion, from the nineteen management units delineated and analyzed three showed no ecological risk (18.5 % of the study area). The areas of more concern (5.6 % of the study area) are located in the North Channel and are under strong human pressure mainly due to industrial activities. These areas have also low hydrodynamics and are, thus associated with high levels of deposition. In particular the areas near Lisnave and Eurominas industries can also accumulate the contamination coming from Águas de Moura Channel, since particles coming from that channel can settle down in that area due to residual flow. In these areas the contaminants of concern, from those analyzed, are the heavy metals and metalloids (Cd, Cu, Zn and As exceeded the PEL guidelines) and the pesticides BHC isomers, heptachlor, isodrin, DDT and metabolits, endosulfan and endrin. In the remain management units (76 % of the study area) there is a moderate impact potential of occurrence of adverse ecological effects and in some of these areas no stress agents could be identified. This emphasizes the need for further research, since unmeasured chemicals may be causing or contributing to these adverse effects. Special attention must be taken to the units with moderate impact potential of occurrence of adverse ecological effects, located inside the natural reserve. Non-point source pollution coming from agriculture and aquaculture activities also seem to contribute with important pollution load into the estuary entering from Águas de Moura Channel. This pressure is expressed in a moderate impact potential for ecological risk existent in the areas near the entrance of this Channel. Pressures may also came from Alcácer Channel although they were not quantified in this study. The management framework presented here, including all the methodological tools may be applied and tested in other estuarine ecosystems, which will also allow a comparison between estuarine ecosystems in other parts of the globe.

A framework for the development of parallel and distributed real-time embedded systems

Embedded real-time applications increasingly present high computation requirements, which need to be completed within specific deadlines, but that present highly variable patterns, depending on the set of data available in a determined instant. The current trend to provide parallel processing in the embedded domain allows providing higher processing power; however, it does not address the variability in the processing pattern. Dimensioning each device for its worst-case scenario implies lower average utilization, and increased available, but unusable, processing in the overall system. A solution for this problem is to extend the parallel execution of the applications, allowing networked nodes to distribute the workload, on peak situations, to neighbour nodes. In this context, this report proposes a framework to develop parallel and distributed real-time embedded applications, transparently using OpenMP and Message Passing Interface (MPI), within a programming model based on OpenMP. The technical report also devises an integrated timing model, which enables the structured reasoning on the timing behaviour of these hybrid architectures.

On development of fractional calculus during the last fifty years

Fractional calculus generalizes integer order derivatives and integrals. During the last half century a considerable progress took place in this scientific area. This paper addresses the evolution and establishes an assertive measure of the research development.

Science metrics on fractional calculus development since 1966

During the last fifty years the area of Fractional Calculus verified a considerable progress. This paper analyzes and measures the evolution that occurred since 1966.

Análise estática não linear de um edifício em betão armado

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Civil

Teamwork and Gendered Work Cultures: The Case of Finland

In this article I focus on women workers’ experiences of transformation from line work to teamworking in Finnish clothing companies in the 1990s and also show what happened after this transformation in the clothing branch. The undertone of it is rather melancholic. Following an initial period of intensive and successful development, clothing work was moved from Finland to countries of cheap labour, such as Estonia, Latvia, Lithuania and Russia, and even China. In this type of network manufacturing, the development of modern information and communication technologies played a central role. My aim is to present the standpoint of women clothing workers in this process. The main body of the empirical data of my study consists of dialogues with clothing workers, union representatives, supervisors and managers. I also make use of my fieldwork notes, memos and research diaries from three companies over a period of five years. Furthermore, in the background lie the action research material from Scandinavian type work conferences and the survey material of an extensive mail inquiry that covered the whole branch in Finland. My own research started in 1991 as a mail inquiry and then continued as a case study in companies from 1992 to 2000, by employing action research and ethnographic methodologies.

Foresight methodologies to understand changes in the labour process. Experience from Portugal

The foresight and scenario building methods can be an interesting reference for social sciences, especially in terms of innovative methods for labour process analysis. A scenario – as a central concept for the prospective analysis – can be considered as a rich and detailed portrait of a plausible future world. It can be a useful tool for policy-makers to grasp problems clearly and comprehensively, and to better pinpoint challenges as well as opportunities in an overall framework. The features of the foresight methods are being used in some labour policy making experiences. Case studies developed in Portugal will be presented, and some conclusions will be drawn in order to organise a set of principles for foresight analysis applied to the European project WORKS on the work organisation re-structuring in the knowledge society, and on the work design methods for new management structures of virtual organisations.

Futures of automobile industry and challenges on sustainable development and mobility

Portugal had only very few foresight exercises on the automobile sector, and the most recent one was a survey held in a project on work organisation systems in the automobile industry, its recent historical paths and the special strategies of location of companies (the WorTiS project). This involved several teams with different disciplinary backgrounds and from two Portuguese universities. The provisional main results of the first round of a Delphi survey held in Portugal on the automotive sector were already published, but a further analysis was not yet done. This foresight survey was done under the WorTiS project, developed in 2004 by IET – Research Centre on Enterprise and Work Innovation (at FCT-UNL), and financed by the Portuguese Ministry of Science and Technology. Some of this experience on foresight analysis is also been transferred to other projects, namely the WORKS project on work organisation restructuring in the knowledge society that received the support from EC and still is running. The majority of experts considered having an average of less knowledge in almost all the scenario topics presented. This means that information on the automotive industry is not spread enough among academics or experts in related fields (regional scientists, innovation economists, engineers, sociologists). Some have a good knowledge but in very specialised fields. Others have expertise on foresight, or macroeconomics, or management sciences, but feel insecure on issues related with futures of automobile sector. Nevertheless, we considered specially the topics where the experts considered themselves to have some knowledge. There were no “irrelevant” topics considered as such by the expert panel. There are also no topics that are not considered a need for co-operation. The lack of technological infrastructures was not considered as a hindered factor for the accomplishment of any scenario. The experts’ panel considered no other international competence besides US, Japan or Germany in these topics. Special focus will be made in this paper on the topic 2. Public policy and automobile industries, and more specifically on the technological and/or research policies issues, where one can specify the automobile’s role in transport policies with further implications like environment, safety, energy, mobility.

Adaptações metodológicas e pedagógicas no ensino da Técnica de Dança Clássica : estudo de caso com uma aluna com Síndrome de Down na Escola de Dança Ana Luísa Mendonça

Relatório Final de Estágio apresentado à Escola Superior de Dança, com vista à obtenção do grau de Mestre em Ensino de Dança.

A interdisciplinaridade no 2º Ciclo do Ensino Regular e Ensino Vocacional de Dança no âmbito da disciplina de Expressão Criativa na Escola de Dança do Orfeão de Leiria

Relatório Final de Estágio apresentado à Escola Superior de Dança, com vista à obtenção do grau de Mestre em Ensino de Dança.

Automatic learning for the classification of chemical reactions and in statistical thermodynamics

This Thesis describes the application of automatic learning methods for a) the classification of organic and metabolic reactions, and b) the mapping of Potential Energy Surfaces(PES). The classification of reactions was approached with two distinct methodologies: a representation of chemical reactions based on NMR data, and a representation of chemical reactions from the reaction equation based on the physico-chemical and topological features of chemical bonds. NMR-based classification of photochemical and enzymatic reactions. Photochemical and metabolic reactions were classified by Kohonen Self-Organizing Maps (Kohonen SOMs) and Random Forests (RFs) taking as input the difference between the 1H NMR spectra of the products and the reactants. The development of such a representation can be applied in automatic analysis of changes in the 1H NMR spectrum of a mixture and their interpretation in terms of the chemical reactions taking place. Examples of possible applications are the monitoring of reaction processes, evaluation of the stability of chemicals, or even the interpretation of metabonomic data. A Kohonen SOM trained with a data set of metabolic reactions catalysed by transferases was able to correctly classify 75% of an independent test set in terms of the EC number subclass. Random Forests improved the correct predictions to 79%. With photochemical reactions classified into 7 groups, an independent test set was classified with 86-93% accuracy. The data set of photochemical reactions was also used to simulate mixtures with two reactions occurring simultaneously. Kohonen SOMs and Feed-Forward Neural Networks (FFNNs) were trained to classify the reactions occurring in a mixture based on the 1H NMR spectra of the products and reactants. Kohonen SOMs allowed the correct assignment of 53-63% of the mixtures (in a test set). Counter-Propagation Neural Networks (CPNNs) gave origin to similar results. The use of supervised learning techniques allowed an improvement in the results. They were improved to 77% of correct assignments when an ensemble of ten FFNNs were used and to 80% when Random Forests were used. This study was performed with NMR data simulated from the molecular structure by the SPINUS program. In the design of one test set, simulated data was combined with experimental data. The results support the proposal of linking databases of chemical reactions to experimental or simulated NMR data for automatic classification of reactions and mixtures of reactions. Genome-scale classification of enzymatic reactions from their reaction equation. The MOLMAP descriptor relies on a Kohonen SOM that defines types of bonds on the basis of their physico-chemical and topological properties. The MOLMAP descriptor of a molecule represents the types of bonds available in that molecule. The MOLMAP descriptor of a reaction is defined as the difference between the MOLMAPs of the products and the reactants, and numerically encodes the pattern of bonds that are broken, changed, and made during a chemical reaction. The automatic perception of chemical similarities between metabolic reactions is required for a variety of applications ranging from the computer validation of classification systems, genome-scale reconstruction (or comparison) of metabolic pathways, to the classification of enzymatic mechanisms. Catalytic functions of proteins are generally described by the EC numbers that are simultaneously employed as identifiers of reactions, enzymes, and enzyme genes, thus linking metabolic and genomic information. Different methods should be available to automatically compare metabolic reactions and for the automatic assignment of EC numbers to reactions still not officially classified. In this study, the genome-scale data set of enzymatic reactions available in the KEGG database was encoded by the MOLMAP descriptors, and was submitted to Kohonen SOMs to compare the resulting map with the official EC number classification, to explore the possibility of predicting EC numbers from the reaction equation, and to assess the internal consistency of the EC classification at the class level. A general agreement with the EC classification was observed, i.e. a relationship between the similarity of MOLMAPs and the similarity of EC numbers. At the same time, MOLMAPs were able to discriminate between EC sub-subclasses. EC numbers could be assigned at the class, subclass, and sub-subclass levels with accuracies up to 92%, 80%, and 70% for independent test sets. The correspondence between chemical similarity of metabolic reactions and their MOLMAP descriptors was applied to the identification of a number of reactions mapped into the same neuron but belonging to different EC classes, which demonstrated the ability of the MOLMAP/SOM approach to verify the internal consistency of classifications in databases of metabolic reactions. RFs were also used to assign the four levels of the EC hierarchy from the reaction equation. EC numbers were correctly assigned in 95%, 90%, 85% and 86% of the cases (for independent test sets) at the class, subclass, sub-subclass and full EC number level,respectively. Experiments for the classification of reactions from the main reactants and products were performed with RFs - EC numbers were assigned at the class, subclass and sub-subclass level with accuracies of 78%, 74% and 63%, respectively. In the course of the experiments with metabolic reactions we suggested that the MOLMAP / SOM concept could be extended to the representation of other levels of metabolic information such as metabolic pathways. Following the MOLMAP idea, the pattern of neurons activated by the reactions of a metabolic pathway is a representation of the reactions involved in that pathway - a descriptor of the metabolic pathway. This reasoning enabled the comparison of different pathways, the automatic classification of pathways, and a classification of organisms based on their biochemical machinery. The three levels of classification (from bonds to metabolic pathways) allowed to map and perceive chemical similarities between metabolic pathways even for pathways of different types of metabolism and pathways that do not share similarities in terms of EC numbers. Mapping of PES by neural networks (NNs). In a first series of experiments, ensembles of Feed-Forward NNs (EnsFFNNs) and Associative Neural Networks (ASNNs) were trained to reproduce PES represented by the Lennard-Jones (LJ) analytical potential function. The accuracy of the method was assessed by comparing the results of molecular dynamics simulations (thermal, structural, and dynamic properties) obtained from the NNs-PES and from the LJ function. The results indicated that for LJ-type potentials, NNs can be trained to generate accurate PES to be used in molecular simulations. EnsFFNNs and ASNNs gave better results than single FFNNs. A remarkable ability of the NNs models to interpolate between distant curves and accurately reproduce potentials to be used in molecular simulations is shown. The purpose of the first study was to systematically analyse the accuracy of different NNs. Our main motivation, however, is reflected in the next study: the mapping of multidimensional PES by NNs to simulate, by Molecular Dynamics or Monte Carlo, the adsorption and self-assembly of solvated organic molecules on noble-metal electrodes. Indeed, for such complex and heterogeneous systems the development of suitable analytical functions that fit quantum mechanical interaction energies is a non-trivial or even impossible task. The data consisted of energy values, from Density Functional Theory (DFT) calculations, at different distances, for several molecular orientations and three electrode adsorption sites. The results indicate that NNs require a data set large enough to cover well the diversity of possible interaction sites, distances, and orientations. NNs trained with such data sets can perform equally well or even better than analytical functions. Therefore, they can be used in molecular simulations, particularly for the ethanol/Au (111) interface which is the case studied in the present Thesis. Once properly trained, the networks are able to produce, as output, any required number of energy points for accurate interpolations.

Accessibility and Local Development: Interaction between Cross-border Accessibility and Local Development in Portugal and Spain

One of de EU major concerns is cohesion and cross-border regional development. Usually cross-border regions are less dynamic, acting as bottlenecks mainly in peripheral territories. This paper is focused on the Portuguese-Spanish border using socio-economic and accessibility data. It considers Spatial Econometrics to produce statistical evidence on the relationship between accessibility and development at a local scale. A pilot study is conducted on North and Center region using variables such as population age, graduation characteristics, migrations, unemployment and daily accessibility to main towns in future this evaluation will be applied to the entire cross-border area between Portugal and Spain.

Measuring and evaluating the impacts of TOD measures: searching for evidence of TOD characteristics in Azambuja train line

TOD (Transit Oriented Development) is typically defined as a high density mixed area (residential and commercial) within easy walking distance of a high capacity public transport station (typically within an 800m buffer area). TOO is viewed as a set of strategies to increase the use of public transport, increasing walking activity, containing urban sprawl, and creating more liveable places. It is believed that this type of combined strategies will improve sustainable growth. This work is an exploratory work for evidence of TOD characteristics in train station areas in Azambuja train line, setting further methodologies to evaluate the success of TOD areas.

Development of Chitosan and Poly (Vinyl Alcohol) Blended scaffolds for cell culture using supercritical fluids technology

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Mestrado Integrado em Engenharia Química e Bioquímica