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.

Análise comparativa de sistemas de classificação de doentes de reabilitação

RESUMO - Caracterização do problema: A inadequação e ineficácia do sistema de financiamento ―por diária‖ dos cuidados de reabilitação resultaram na necessidade de criação de sistemas de classificação de doentes de reabilitação em regime de internamento, em muitos países. Também em Portugal é necessário implementar um sistema de financiamento, baseado num sistema de classificação de doentes, ajustado pela complexidade e necessidade de cuidados destes doentes. Objectivos: Caracterização dos cuidados de reabilitação em Portugal, e do actual sistema de financiamento destes doentes; realização de uma revisão de literatura dos sistemas de classificação de doentes de reabilitação já existentes, de modo a compreender quais as variáveis de agrupamento utilizadas e qual a capacidade de previsão dos custos destes mesmos sistemas; perceber a importância da implementação de um dos sistemas de classificação em Portugal, e quais as suas vantagens. Metodologia: Da revisão de literatura efectuada, foram encontrados quatro sistemas de classificação de doentes implementados e/ou em vias de serem implementados como base para um sistema de financiamento, nos EUA, Austrália e Canadá. Foi efectuada uma extensa caracterização e análise crítica dos mesmos. Conclusões: Podemos concluir, que dos poucos sistemas de classificação de doentes de reabilitação existentes, optou-se pelo estudo de uma possível adopção do sistema norte-americano para a realidade portuguesa, por ser o único sistema de classificação já utilizado para fins de financiamento para todos os doentes de reabilitação desde 2002, o que inclui mais variáveis de decisão na classificação dos doentes, e o que permite a maior previsão dos custos dos doentes em termos percentuais.

Time series morphological analysis applied to biomedical signals events detection

Dissertation submitted in the fufillment of the requirements for the Degree of Master in Biomedical Engineering

Produção hospitalar : a importância da complexidade e da gravidade

RESUMO - A definição e medição da produção são questões centrais para a administração hospitalar. A produção hospitalar, quando se consideram os casos tratados, baseia-se em dois aspectos: a definição de sistemas de classificação de doentes como metodologia para identificar produtos e a criação de índices de casemix para se compararem esses mesmos produtos. Para a sua definição e implementação podem ser consideradas características relacionadas com a complexidade dos casos (atributo da oferta) ou com a sua gravidade (atributo da procura), ou ainda características mistas. Por sua vez, a análise do perfil e da política de admissões dos hospitais adquire um maior relevo no contexto de novas experiências previstas e em curso no SNS e da renovada necessidade de avaliação e regulação que daí decorrem. Neste estudo pretendeu-se discutir a metodologia para apuramento do índice de casemix dos hospitais, introduzindo- se a gravidade dos casos tratados como atributo relevante para a sua concretização. Assim, foi analisada uma amostra de 950 443 casos presentes na base de dados dos resumos de alta em 2002, tendo- -se dado particular atenção aos 31 hospitais posteriormente constituídos como SA. Foram considerados três índices de casemix: índice de complexidade (a partir do peso relativo dos DRGs), índice de gravidade (a partir da escala de mortalidade esperada do disease staging recalibrada para Portugal) e índice conjunto (média dos dois anteriores). Verificou-se que a análise do índice de complexidade, de gravidade e conjunto dá informações distintas sobre o perfil de admissões dos hospitais considerados. Os índices de complexidade e de gravidade mostram associações distintas às características dos hospitais e dos doentes tratados. Para além disso, existe uma diferença clara entre os casos com tratamento médico e cirúrgico. No entanto, para a globalidade dos hospitais analisados observou-se que os hospitais que tratam os casos mais graves tratam igualmente os mais complexos, tendo-se ainda identificado alguns hospitais em que tal não se verifica e, quando possível, apontado eventuais razões para esse comportamento.

Forest cover monitoring in the Bara district (Nepal) with remote sensing and geographic information systems

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies

Wetland Habitat Studies using various Classification Techniques on Multi-Spectral Landsat Imagery: Case study: Tram chim National Park, Dong Thap Vietnam

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies

The contribution of multitemporal information from multispectral satellite images for automatic land cover classification at the national scale

Thesis submitted to the Instituto Superior de Estatística e Gestão de Informação da Universidade Nova de Lisboa in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in Information Management – Geographic Information Systems

Development of new methodologies in sample treatment for proteomics workflow based on enzymatic probe sonication technology and mass spectrometry

Thesis submitted to the Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia, for the degree of Doctor of Philosophy in Biochemistry

Development of cyclodextrin-hydrogel polymeric systems in scCO2 for drug delivery

Thesis for the Degree of Master of Science in Bioorganic Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Heat recovery from wastewater: numerical modelling of sewer systems

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente, perfil Engenharia Sanitária

Real-time labview assessment on adsorption systems

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

Autonomia funcional em idosos : caracterização multidimensional em idosos utentes de um centro de saúde urbano

RESUMO: Tivemos como objectivo do presente trabalho avaliar a capacidade funcional, e factores eventualmente a ela associados, numa amostra de 152 idosos ambulatórios, sem doenças agudas ou graves, utentes de um centro de saúde urbano. Cada avaliação consistiu numa entrevista, mediante um inquérito sobre capacidade funcional, morbilidade, estado mental e aspectos sociais, e no estudo da composição corporal. As perguntas referentes às variáveis estudadas foram por nós desenvolvidas e estruturadas com base em escalas internacionais validadas e de utilização comum na avaliação de idosos, excepto para as variáveis em que não encontrámos escalas com essas características. Os seus quesitos foram incluídos como perguntas e respostas estruturadas e pré-codificadas, permitindo a atribuição de uma pontuação a cada variável e a sua posterior divisão dicotómica. Aplicámos as escalas de Katz e de Lawton para a avaliação das actividades de autonomia física e instrumental da vida diária, a escala de Grimby para a avaliação da actividade física, a escala de Hamilton e o teste de Folstein para a avaliação do estado mental nas vertentes afectiva e cognitiva e a escala de Graffar para caracterizar a classe social, e perguntas sobre locomoção, autoavaliação da saúde, queixas de saúde presentes e rede social. Fizemos o registo da morbilidade segundo a International Classification of Primary Care - ICPC. A avaliação antropométrica constou da medição do peso, da altura, dos perímetros do braço, da cintura, da anca e proximal da coxa, e das pregas bicipital, tricipital, sub-escapular e supra-ilíaca. Foi também feita a estimativa da composição corporal por cálculos derivados de índices antropométricos e de bioimpedância eléctrica corporal total, o doseamento de algumas proteínas plasmáticas e a quantificação da força de preensão. Analisámos os resultados obtidos por grupos quanto ao sexo e à idade, dividida nos escalões etários 65 a 74 anos e mais do que 74 anos. Por regressão linear múltipla, foi testado o efeito do sexo e da idade sobre os valores medidos, para cada uma das variáveis e cada uma das suas pontuações parciais, sendo considerado como evidência de um efeito estaticamente significativo um valor “p” inferior a 0,05.Resumimos do seguinte modo os dados obtidos e a sua comparação com os dos estudos que seleccionámos como referência: A média de idades da amostra foi de 74 anos, sendo um terço destes do sexo masculino. Na sua maioria eram independentes em locomoção e funcionalidade, praticavam alguma actividade física, classificavam a sua saúde como razoável ou boa, apresentavam sintomatologia activa, não tinham depressão ou demência, tinham quem os acompanhasse embora cerca de metade apresentasse algum grau de isolamento, eram de baixa classe social, tinham excesso de peso, valores elevados de massa gorda, parâmetros plasmáticos proteicos compatíveis com ausência de doenças agudas ou graves e considerável força muscular de preensão. Na análise descritiva por grupos quanto ao sexo e/ou à idade, verificou-se que as mulheres e os mais idosos apresentavam maior isolamento social e os valores mais baixos de massa magra, hemoglobina e força de preensão. As mulheres tinham maior prevalência de dependência em autonomia física, depressão e valores mais baixos de transferrina. Os mais idosos apresentavam maior dependência em funcionalidade, menor actividade física, maior prevalência de demência, índice de massa corporal menos elevado, e valores mais baixos de albumina. Não se verificou prevalência de piores resultados dicotómicos nos homens nem no escalão etário menos idoso. Não teve relação com o sexo ou a idade o compromisso em autonomia instrumental, a presença de morbilidade ou a baixa classe social, assim como a não perturbação da locomoção e dos níveis de somatomedina-C. A análise comparativa com estudos multidimensionais em idosos portugueses e europeus ambulatórios revelou que a nossa amostra apresentava muitas características semelhantes às desses idosos. Assim, tinham elevada independência em locomoção, considerável independência em autonomia física e menor independência em autonomia instrumental; prática de actividade física ligeira, as mulheres dentro e os homens fora de casa; maior prevalência de morbilidade a nível dos aparelhos locomotor e cardiocirculatório, nos nossos idosos com pouca flutuação na autoavaliação de saúde; pequena prevalência de depressão e de demência; maior isolamento social nas mulheres e nas mais idosas; factores de classe social de baixo nível, diferindo apenas em relação aos idosos do norte da Europa que apresentavam elevada escolaridade e profissões mais diferenciadas; características biométricas sobreponíveis às dos idosos portugueses e às dos do sul da Europa, com tendência para o excesso de peso e proporção elevada de massa gorda; e doseamentos plasmáticos proteicos e força muscular de preensão compatíveis com ausência de doenças agudas ou crónicas graves. A comparação com os referidos estudos em relação ao risco de dependência, revelou semelhanças na associação entre dependência funcional e idade avançada, morbilidade, alteração do estado mental e isolamento social. Na amostra que estudámos não obtivemos associação entre dependência e o sexo feminino, facto que se verificou no estudo nacional de Almeida et al. e nos estudos multicêntricos europeus, ou o grau de escolaridade, como no estudo francês. Podemos concluir que, com o instrumento de avaliação que utilizámos, foi possível detectar e caracterizar perturbações numa amostra de idosos ambulatórios, a maioria funcionalmente independentes, sem alterações do estado mental, mas apresentando morbilidade activa, tendência para a obesidade, e actividade física ligeira. Nos que apresentaram alterações, estas foram mais frequentes no sexo feminino e nos indivíduos com mais de 74 anos. A escala de funcionalidade desenvolvida foi sensível aos efeitos da idade e permitiu o cálculo do risco de dependência em relação às outras variáveis estudadas, sendo mais marcante a associação com baixa actividade física, presença de queixas de saúde, demência e índice de massa corporal elevado. Consideramos que a metodologia que empregámos poderá contribuir para a avaliação de capacidades, cujo conhecimento sistemático nos idosos se impõe. ------------- ABSTRACT: The main objective of the present work was to evaluate functional capacity and related factors, in a sample of 152 ambulatory elderly, free from acute or serious disease, attending an urban health centre. Each evaluation included an interview, with a questionnaire about functional capacity, morbidity, mental health and social aspects, and the study of body composition. The questions were developed and structured in accordance with international validated scales usually applied in the evaluation of the elderly, whenever there were scales for that purpose. Their items were included as structured pre-coded questions and answers, so that each variable could have its own quotation and be dichotomised. We employed Katz and Lawton scales for basic and instrumental activities of daily living, Grimby scale for physical activity, Hamilton scale for depression, Folstein’s Mini Mental State Examination for cognitive ability and Graffar scale for social class, and questions about walking, health perception, active complaints and social network. The symptoms register was done according to the International Classification of Primary Care - ICPC. The anthropometric exam involved the determination of height and weight, arm, waist, hip and proximal thigh circumferences, and biceps, triceps, subscapular and suprailiac skinfolds. For the body composition calculation we employed equations derived from anthropometric indices, and from measurement of total body bioelectric impedance. We also measured some plasma proteins and handgrip strength. The analysis of results was done by sex and age groups, separating those with 65 to 74 years from those older than 74 years. The effects of sex and age were tested by linear multiple regression, for each variable and its components. Presented "p" values being considered statistically significative if less than 0,05. The results we obtained and their comparison with the studies we choose as reference can be summarised as follows: Mean age of the sample was 74 years and about one third were men. Most of them were independent in gait and functionality, practised some physical activity, rate their health as fair or good, had physical complaints, had not depression or dementia, had some companionship although almost half of them with stigmas of isolation, belonged to low social class, were in the range of overweight, had raised values of fat mass, plasma proteins in accordance with no acute or serious disease, and considerable handgrip strength. The analysis of groups by sex and age revealed that women and the eldest had the greater social isolation and the lowest values of free fat mass, haemoglobin and handgrip strength. Women had the higher dependence in basic activities of daily living, more depression and lower levels of transferrin. The eldest were more dependent in functionality, had greater prevalence of dementia, less physical activity, less raised body mass index and lower levels of albumin. Men alone and the age range of 65 to 74 did not show any prevalence of the worse dichotomised results. There was no relationship between sex or age and instrumental activities of daily living, morbidity or low social class, and unaffected gait or somatomedin-C levels. The comparison of results with multidimensional studies in portuguese and european ambulatory elderly showed that our sample had many similarities with theirs. They were independent in gait and activities of daily living; practiced light physical activity, women indoors and men outdoors; had greater morbidity at locomotor and cardiovascular systems, with small latitude in health evaluation; low prevalence of depression and dementia; social isolation predominantly in older women; and low social class factors, witch is only different from those of north Europe who had higher education levels and professional carriers; biometric characteristics similar to other portuguese and south Europe elders, with tendency for overweight and high proportion of fat mass; and plasma protein levels and handgrip strength in accordance with no acute or chronic serious disease. The comparison to the referred studies in relation to dependency risk, showed similarities in the association of dependency and age, morbidity,altered mental state and social isolation. We did not find association between dependency and sex, as it was found in the portuguese study of Almeida et al. and the european multicentric studies, or the education level, as in the french study. We conclude that, with the evaluation battery we employed, it was possible to detect and characterise alterations in a sample of ambulatory elderly, most of whom were functionally independent and had no alterations in mental state, but had active morbidity, tendency to obesity, and only light physical activity. Those that had some alteration, were more frequently women and the eldest. The functionality scale we developed showed to be sensitive to age effects and suitable for the calculation of risk of dependency, being more important the association with low physical activity, active complaints, dementia and high body mass index. We consider that the methodology we applied can contribute to the evaluation of capabilities that should be systematically sought for in the elderly.

Overcoming the “European Paradox”: The role of Regional Innovation Systems (RIS) in translating R&D investments into economic and employment growth

The emergence of the so-called “European Paradox” shows that R&D investment is not maximally effective and that increasing the scale of public R&D expenditures is not sufficient to generate employment and sustained economic growth. Increasing Governmental R&D Investment is far from being a “panacea” for stagnant growth. It is worth noting that Government R&D Investment does not have a statistically significant impact on employment, indicating the need to assess the trade-offs of policies that could lead to significant increases in government expenditure. Surprisingly, Governmental R&D Employment does not contribute to “mass-market” employment, despite its quite important role in reducing Youth-Unemployment. Despite the negative side-effects of Governmental R&D Employment on both GVA and GDP, University R&D Employment appears to have a quite important role in reducing Unemployment, especially Youth-Unemployment, while it also does not have a downside in terms of economic growth. Technological Capacity enhancement is the most effective instrument for reducing Unemployment and is a policy without any downside regarding sustainable economical development. In terms of wider policy implications, the results reinforce the idea that European Commission Research and Innovation policies must be restructured, shifting from a transnational framework to a more localised, measurable and operational approach.

An agent based architecture to support monitoring in plug and produce manufacturing systems using knowledge extraction

In recent years a set of production paradigms were proposed in order to capacitate manufacturers to meet the new market requirements, such as the shift in demand for highly customized products resulting in a shorter product life cycle, rather than the traditional mass production standardized consumables. These new paradigms advocate solutions capable of facing these requirements, empowering manufacturing systems with a high capacity to adapt along with elevated flexibility and robustness in order to deal with disturbances, like unexpected orders or malfunctions. Evolvable Production Systems propose a solution based on the usage of modularity and self-organization with a fine granularity level, supporting pluggability and in this way allowing companies to add and/or remove components during execution without any extra re-programming effort. However, current monitoring software was not designed to fully support these characteristics, being commonly based on centralized SCADA systems, incapable of re-adapting during execution to the unexpected plugging/unplugging of devices nor changes in the entire system’s topology. Considering these aspects, the work developed for this thesis encompasses a fully distributed agent-based architecture, capable of performing knowledge extraction at different levels of abstraction without sacrificing the capacity to add and/or remove monitoring entities, responsible for data extraction and analysis, during runtime.

Learning domain-specific sentiment lexicons with applications to recommender systems

Search is now going beyond looking for factual information, and people wish to search for the opinions of others to help them in their own decision-making. Sentiment expressions or opinion expressions are used by users to express their opinion and embody important pieces of information, particularly in online commerce. The main problem that the present dissertation addresses is how to model text to find meaningful words that express a sentiment. In this context, I investigate the viability of automatically generating a sentiment lexicon for opinion retrieval and sentiment classification applications. For this research objective we propose to capture sentiment words that are derived from online users’ reviews. In this approach, we tackle a major challenge in sentiment analysis which is the detection of words that express subjective preference and domain-specific sentiment words such as jargon. To this aim we present a fully generative method that automatically learns a domain-specific lexicon and is fully independent of external sources. Sentiment lexicons can be applied in a broad set of applications, however popular recommendation algorithms have somehow been disconnected from sentiment analysis. Therefore, we present a study that explores the viability of applying sentiment analysis techniques to infer ratings in a recommendation algorithm. Furthermore, entities’ reputation is intrinsically associated with sentiment words that have a positive or negative relation with those entities. Hence, is provided a study that observes the viability of using a domain-specific lexicon to compute entities reputation. Finally, a recommendation system algorithm is improved with the use of sentiment-based ratings and entities reputation.