Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This thesis presents a study of Visible Near-infrared spectroscopy technique applied to predict soil properties. The purpose was to develop quantitative soil information due to the demand of digital soil mapping, environmental monitoring, agricultural production and for increasing spatial information on soil. Soil spectroscopy emerge as an alternative to revolutionize soil monitoring, allowing rapid, low-cost, non-destructive samples sampling, environmental-friendly, reproducible, and repeatable analysis. To improve the efficiency of soil prediction using spectral data, several spectral preprocessing techniques and multivariate models were exploited. A graphical user interface (GUI) in R, named Alrad Spectra, was developed to perform preprocessing, multivariate modeling and prediction using spectral data. Hereby, the objectives were: The objectives were: i) to predict soil properties to improve soil information using spectral data, ii) to compare the performance of spectral preprocessing and multivariate calibration methods in the prediction of soil organic carbon, iii) to obtain reliable soil organic carbon prediction, and iv) to develop a graphical user interface that performs spectral preprocessing and prediction of the soil property using spectroscopic data. A total of 595 soil samples were collected in central region of Santa Catarina State, Brazil. Soil spectral reflectance was obtained using a FieldSpec 3 spectroradiometer with a spectral range of 350–2500 nm with 1 nm of spectral resolution. The outcomes of the thesis have demonstrated the great performance of predicting soil properties using Vis-NIR spectroscopy. Apparently, soil properties that are directly related to the chromophores such as organic carbon presented superior prediction statistics than particle size. Spectral preprocessing applied in the soil spectra contribute to the development of high-level prediction model. Comparing different spectral preprocessing techniques for soil organic carbon (SOC) prediction revealed that the scatter–corrective preprocessing techniques presented superior prediction results compared to spectral derivatives. In scatter–correction technique, continuum removal is the most suitable preprocessing to be used for SOC prediction. In the calibration modeling, excepting for random forest, all of methods presented robust prediction, with emphasis on the support vector machine method. The systematic methodology applied in this study can improve the reliability of SOC estimation by examining how techniques of spectral preprocessing and multivariate methods affect the prediction performance using spectral analysis. The development of easy-to-use graphical user interface may benefit a large number of users, who will take advantage of this useful chemometrics analysis. Alrad Spectra is the first GUI of its kind and the expectation is that this tool can expand the application of the spectroscopy technique. / Esta tese apresenta um estudo da técnica de espectroscopia do visível ao infravermelho próximo aplicado à predição de propriedades do solo. O proposito foi de desenvolver informações quantitativas sobre o solo, devido à demanda do mapeamento digital de solos, monitoramento ambiental, produção agrícola e aumento das informações espaciais do solo. A espectroscopia surge como uma alternativa para revolucionar a monitorização do solo, permitindo uma amostragem rápida, de baixo custo, não destrutiva, ambientalmente amigável, reprodutível e repetitiva. Para melhorar a eficiência da predição do solo usando dados espectrais, várias técnicas de pré-processamento espectral e modelos multivariados foram explorados. Uma interface gráfica de usuário (GUI) no R, denominada Alrad Spectra, foi desenvolvida para realizar pré-processamento, modelagem multivariada e predição usando dados espectrais. Os objetivos foram: i) predizer as propriedades do solo para melhorar a informação do solo usando dados espectrais, ii) comparar os desempenhos dos pré-processamentos espectrais e métodos de calibração multivariada na predição do carbono orgânico do solo, iii) obter predições confiáveis do carbono orgânico do solo, e iv) desenvolver uma interface gráfica de usuário que realize o pré-processamento espectral e a predição do atributo solo usando dados espectroscópicos. Um total de 595 amostras de solo foram coletadas na região central do estado de Santa Catarina, Brasil. A reflectância espectral do solo foi obtida utilizando um espectrorradiômetro FieldSpec 3 com uma alcance espectral de 350-2500 nm com 1 nm de resolução espectral. Os resultados da tese demonstraram o grande desempenho da predição de propriedades do solo usando espectroscopia do vísivel ao infravermelho próximo. As propriedades do solo que estão diretamente relacionadas aos cromóforos, como o carbono orgânico, apresentaram predições superiores comparados com o tamanho de partículas. O pré-processamento espectral aplicado nos espectros do solo contribui para o desenvolvimento de um modelo de predição de alto nível. Comparando diferentes técnicas de pré-processamento espectral para a predição de carbono orgânico revelou que as técnicas de pré-processamento de correção de dispersão apresentaram resultados de predição superiores em comparação com as técnicas de derivação espectrais. Na técnica de correção de dispersão, a remoção do contínuo é o pré-processamento mais adequado a ser usado para a predição de carbono. Na modelagem de calibração, com exceção da floresta aleatória, todos os métodos apresentaram uma elevada predição, sendo destaque o método máquina de vetores de suporte. A metodologia sistemática aplicada neste estudo pode melhorar a confiabilidade da estimativa do carbono orgânico ao examinar como as técnicas de pré-processamento espectral e métodos multivariados afetam a performance da predição usando a análise espectral. O desenvolvimento da GUI de fácil utilização pode beneficiar um grande número de usuários, os quais podem tirar proveito desta análise quimiométrica. Alrad Spectra é a primeira GUI desse tipo e a expectativa é que esta ferramenta possa expandir a aplicação da técnica de espectroscopia.

L’évaluation de la performance des ouvrages hydrauliques en remblai est un enjeu majeur pour les gestionnaires en charge de leur sécurité. Qu'il s'agisse de digues ou de barrages, la présence de végétation arborescente représente un facteur de fragilité important. Deux types de mécanismes de détérioration peuvent ainsi être initiés ou aggravés : l’érosion interne et l’érosion externe. Or, ce facteur n’a été pris en compte que partiellement dans les modèles d’évaluation existants. De plus, les petits barrages en remblai peuvent avoir des dispositifs d’étanchéité différents et ne sont pas toujours équipés de drains et d’instruments d’auscultation: il est alors nécessaire d’adapter les modèles à chaque cas. L’objectif de la thèse est de répondre à ces verrous scientifiques. Les résultats de nos recherches concernent l’établissement de modèles d’évaluation de la performance basés sur des approches à base de connaissances.La démarche a été appliquée sur des ouvrages réels : 3 tronçons de digues de protection contre les inondations ainsi que 7 barrages en remblai ce qui nous a permis de montrer sa pertinence et donc son potentiel d’utilisation opérationnelle. / The performance assessment of embankment hydraulic works is a major challenge for managers in charge of their security. For both dikes and dams, the presence of trees represents an important fragility factor. Two types of deterioration mechanism can thus be initiated or aggravated: internal erosion or scouring. However, this factor has been taken only partially into account in existing assessment models. In addition, small embankment dams can have different sealing devices and are not always equipped with drains and monitoring instruments: it is thus necessary to customize the models in each case. The aim of the thesis was to remove these scientific obstacles. The results of our research concern the design of performance assessment models relying on knowledge-based approaches.The approach was implemented for real works: three sections of river dikes and seven small embankment dams which allowed us to show its relevance and therefore its operational potential.

Les huiles essentielles (HE) de lavande et de lavandin appartiennent au patrimoine de la région méditerranéenne. Comme tout produit naturel ou synthétique à valeur ajoutée, ces HE doivent être contrôlées pour justifier la qualité du produit. Ce contrôle qualité nécessite la mise en place d'une méthodologie analytique fiable. Dans cette étude, une nouvelle approche utilisant les techniques spectroscopiques et chromatographiques et le traitement de données à l'aide d'outils chimiométriques permet de différencier les HE de lavande et de lavandin par origine variétale. Cette discrimination s'effectue grâce à leur empreinte spectrale ou chromatographique. L’intérêt d’utiliser la chromatographie chirale associée à la détection polarimétrique et de la signature chiroptique acquise a également été étudié. Cette étude nous a permis d’identifier des marqueurs métabolomiques qui sont primordiaux pour caractériser les variétés. Les résultats montrent qu'il est possible de discriminer les HE de lavande et de lavandin selon leurs variétés avec une bonne justesse sur l'ensemble des techniques utilisées. / Lavender and lavandin essential oils (EOs) belong to the heritage of the Mediterranean region. Like any natural or synthetic product with an added value, these EOs must be controlled to justify the quality of the product. This quality control requires the establishment of a reliable analytical methodology. In this study, a new approach using spectroscopic and chromatographic techniques for data processing associated to chemometric tools allows to discriminate lavender and lavandin EOs. This discrimination is carried out thanks to their spectroscopic or chromatographic fingerprints. The interest to use the chiral chromatography combined with polarimetric detection and of acquired chiroptical signature was also studied. This methodology has allowed us to identify metabolomic markers which are paramount to characterize the varieties. The results show that it is possible to discriminate the lavender and lavandin EOs according to their varieties with good accuracy on all of the techniques used.

The feasibility of FTIR-based spectroscopy as a tool to measure cellular response to therapeutics was investigated. Fourier transform mid-infrared spectroscopy has been used in conjunction with multivariate analysis (MVA) to assess the chemistry of many clinically relevant biological materials; however, the technique has not yet found its place in a clinical setting. One issue that has held the technique back is due to the spectral distortions caused by resonant Mie scattering (RMieS), which affects the ability to confidently assign molecular assignments to the spectral signals from biomaterials. In the light of recently improved understanding of RMieS, resulting in a novel correction algorithm, the analytical robustness of corrected FTIR spectra was validated against multi-discipline methods to characterise a set of renal cell lines which were selected for their difference in morphology.After validation of the FTIR methodology by discriminating different cell lines, the second stage of analyses tested the sensitivity of FTIR technique by determining if discrete chemical differences could be highlighted within a cell population of the same origin. The renal carcinoma cell line 2245R contains a sub-population to contain a sub-population of cells displaying 'stem-cell like' properties. These stem-like cells, however, are difficult to isolate and characterise by conventional '-omic' means. Finally, cellular response to chemotherapeutics was investigated using the established renal cell lines CAKI-2 and A-498. For the model, 5-fluorouracil (5FU), an established chemotherapeutic agent with known mechanisms of action was used. Novel gold-based therapeutic compounds were also assessed in parallel to determine their efficacy against renal cell carcinoma. The novel compounds displayed initial activity, as the FTIR evidence suggested compounds were able to enter the cells in the first instance, evoking a cellular response. The long-term performance, tracked with standard proliferation assays and FTIR spectroscopy in the renal cancer cell model, however, was poor. Rather than dismissing the compounds as in-active, the compounds may simply be more effective in cancer cell types of a different nature. The FTIR-based evidence provided the means to suggest such a conclusion. Overall, the initial results suggest that the combination of FTIR and MVA, in the presence of the novel RMieS-EMSC algorithm can detect differences in cellular response to chemotherapeutics. The results were also in-line with complimentary biological-based techniques, demonstrating the powerful potential of the technique as a promising drug screening tool.

This work describes the results obtained from the phytochemical study, chemometric analysis and activity cytotoxic in vitro and in vivo of the leaves Guatteria pogonopus Mart., a species of Annonaceae that occurs in Sergipe. The leaves were subjected to two processes. In the first, the leaves were conducted extraction and the study of the chemical composition of the essential oil, considering the seasonality effect; in the second, the isolation of fixed compounds was performed on order to identify alkaloids. Both studies were evaluated towards the antitumor activity in vitro and in vivo. Yields of essential oils ranged from 0.34 % for the month of October/2012 to 0.10 % for the month of September/2012. This variation can be explained by the climate, which the rainfall was higher in September compared to October. This means that the greater the amount of precipitation, reduced yield. The sesquiterpene hydrocarbons were the main constituents of the oils in the samples, with the highest concentration in the month of July/2012 (71.93 %). They were identified as á- and â-pinene, bicyclogermacrene, germacrene B, ã-patchoulene, spathulenol, á-santalene, (E)-caryophyllene, ã-elemene and globulol. In Principal Component Analysis (PCA), both CP1 and CP2 components can explain 90 % of the total variance. It is remarkable that several compounds have focused on the right of the axis of CP1. This phenomenon explains the regularity of the percentage that appears in each month. The ã-patchouleno, spathulenol and bicyclogermacrene compounds protrude to the left of the axis of CP1. Which are the major compounds of the composition of essential oils predominant in all sampling months. In addition to these one can see (E)-caryophyllene and á-santalene, to a lesser prominence this axis. In Hierarchical Cluster Analysis (HCA) formed groups because of similarities. The results of the in vitro antitumor activity of essential oil showed pronounced cytotoxic activity against NCI-H358M, PC-3M and OVCAR-8 lines. In vivo study oil was able to inhibit tumor growth, thus indicating that the essential oil has a significant antitumor potential. Phytochemical study the alkaloidal sheets from the fraction of methanol extract was possible to date the isolation of six alkaloids encoded as GP-1 (nornuciferine), GP-2 (isocorydine), GP-3 (mixture of the nornuciferine and anonaine), GP-4 (lisycamine) and GP-5 (liriodinene). The identification of the alkaloids was performed by 1D/2D 1H and 13C NMR, MS and GC/MS, and comparison with authentic standards and literature data. The cytotoxicity assay performed with single concentration in the extracts and fractions (50 mg/ml) and basic substances (25 mg/mL) revealed promising results with minimal inhibition of 50 % of at least one tumor cell lines. Among the extracts, fractions and evaluated substance, the alkaloidal fraction and compounds GP-1 were the most active against strains B16-F10 and HepG2. Because the activities presented and in order to obtain the IC50 for these two samples front lines K562, HL-60 cells and PBMC were also evaluated. Both the alkaloidal fraction and the compound GP-1 showed good results. The results indicated that G. pogonopus is a biologically active cytotoxic properties with promising source of compounds. / Este trabalho descreve os resultados do estudo fitoquimico, analise quimiometrica e investigacao citotoxica in vitro e in vivo das folhas de Guatteria pogonopus Mart. uma especie de Annonaceae de ocorrencia em Sergipe. As folhas foram submetidas a dois processos: no primeiro, foi realizada a extracao e o estudo da composicao quimica do oleo essencial, levando em consideracao o efeito da sazonalidade. Enquanto que no segundo, foi realizado o isolamento de compostos fixos visando a identificacao de alcaloides. Ambos estudos foram avaliados frente a atividade antitumoral in vitro e in vivo. Os rendimentos dos oleos essenciais variaram de 0,34% para o mes de outubro/2012 a 0,10% para o mes de setembro/2012. Essa variacao pode ser explicada pelo clima, o qual o indice pluviometrico foi maior para setembro em relacao a outubro. Isso significa, que quanto maior a quantidade de precipitacao, menor o rendimento. Os sesquiterpenos hidrocarbonetos foram os constituintes majoritarios nas amostras dos oleos, com maior concentracao no mes de julho/2012 (71,93%). Os constituintes majoritarios identificados foram Ñ- e £]-pineno, biciclogermacreno, germacreno B, £^-patchouleno, espatulenol, £-santaleno, (E)-cariofileno, £^-elemeno e globulol. Na Analise de Componentes Principais (ACP), as duas componentes CP1 e CP2 conseguem explicar mais de 90% da variancia total dos dados. E possivel notar que varios compostos se concentraram na direita do eixo da CP1. Esse fenomeno explica a regularidade da porcentagem que aparece em cada mes. Os compostos £^-patchouleno, espatulenol e biciclogermacreno se sobressaem para esquerda do eixo da CP1. Os quais sao os compostos majoritarios da composicao dos oleos essenciais predominante em todos os meses de coleta. Na Analise de Agrupamento Hierarquico (AAH) formaram-se grupos devido a semelhancas. Os resultados da atividade antitumoral in vitro do oleo essencial indicaram pronunciada atividade citotoxica contra as linhagens de NCI-H358M, PC-3M e OVCAR-8. No estudo in vivo o oleo foi capaz de inibir o crescimento tumoral, indicando assim, que o oleo essencial apresenta um potencial antitumoral significativo. Do estudo fitoquimico da fracao alcaloidica do extrato metanolico foi possivel ate o momento o isolamento de seis alcaloides codificados como GP-1 (nornuciferina), GP-2 (isocoridina), GP-3 (nornuciferina e anonaina em mistura), GP-4 (lisicamina), GP-5 (liriodenina). A identificacao dos alcaloides foi realizada por RMN de 1H e 13C 1D/2D, EM e CG/EM, bem como comparacao com padroes autenticos e dados da literatura. O ensaio de atividade citotoxica em concentracao unica realizado com os extratos e fracoes (50 £gg/mL) e substancias puras (25 £gg/mL), revelaram resultados promissores com inibicao minima de 50% de pelo menos uma das linhagens tumorais. Entre os extratos, fracoes e substancia avaliadas, a fracao alcaloidica e o composto GP-1 foram os mais ativos contra as linhagens B16-F10 e HepG2. Devido as atividades apresentadas e com o objetivo de se obter a CI50 essas duas amostras tambem foram avaliadas frente as linhagens de celulas K562, HL-60 e PBMC. Tanto a fracao alcaloidica como o composto GP-1 apresentaram bons resultados. Os quais indicaram que G. pogonopus e uma fonte promissora de compostos biologicamente ativos com propriedades citotoxicas.

Orientadores: Juliana Azevedo Lima Pallone, Priscilla Efraim / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-26T22:17:20Z (GMT). No. of bitstreams: 1 Hashimoto_JulianaCampos_D.pdf: 1464157 bytes, checksum: dc1a53f725dfb7e2dbc0a615838c0c73 (MD5) Previous issue date: 2015 / Resumo: O desenvolvimento da cacauicultura no Brasil apresenta vários desafios no que se refere ao reconhecimento da qualidade e padronização da produção. Dois aspectos relevantes relacionados a essas dificuldades foram abordados nesta pesquisa. O primeiro aspecto trata da falta de informação referente à composição química das amêndoas de cacau produzidas em diferentes estados brasileiros e às características sensoriais dos produtos derivados. A este respeito, amostras de diferentes regiões produtoras (Bahia-BA, Pará-PA, Rondônia-RO e Costa do Marfim-CM) foram analisadas quanto a parâmetros físicos e químicos relevantes para a qualidade desta matéria prima, incluindo-se: número de amêndoas em 100 g, prova de corte, porcentagem de casca, pH, acidez, teores de umidade, lipídios, proteína, compostos fenólicos totais, teobromina e cafeína. A avaliação física das amêndoas de cacau por meio da prova de corte permitiu concluir que todas as amostras apresentaram padrão comercial satisfatório, porém, evidenciou-se a falta de padronização na etapa de pré-processamento. Diferenças significativas em relação à umidade, acidez, compostos fenólicos totais, teobromina e cafeína foram verificadas, as quais podem afetar diretamente a qualidade dos produtos derivados. A avaliação sensorial de chocolates elaborados a partir das amêndoas de origens distintas (BA, PA, RO, CM e Espírito Santo-ES) mostrou diferenças significativas entre as amostras, as quais foram percebidas tanto pelo painel sensorial treinado quanto pelo grupo de consumidores. As amostras de chocolates BA e CM mostraram diferenças importantes no perfil sensorial, enquanto as amostras RO e PA apresentaram similaridades e características intermediárias em relação às demais. Quanto à aceitação global, pequenas diferenças foram observadas, sendo que a amostra PA apresentou valor médio superior ao do chocolate BA, provavelmente devido à maior intensidade dos gostos ácido e amargo na amostra BA. O segundo aspecto abordado neste estudo trata da falta de métodos analíticos rápidos e objetivos para a avaliação da qualidade de amêndoas de cacau. Portanto, os dados das análises físico-químicas das 81 amostras de amêndoas de cacau obtidos na primeira etapa da pesquisa foram utilizados para a construção de modelos de calibração multivariada por meio da correlação com os espectros de reflectância difusa medidos na região do infravermelho próximo (10000-4000 cm-1). Nove modelos de regressão por Quadrados Mínimos Parciais foram desenvolvidos para a previsão de diversos parâmetros de composição química (umidade, porcentagem de casca, pH, acidez, lipídios, proteínas, compostos fenólicos totais, concentração de teobromina e cafeína) pela análise direta das amostras moídas e peneiradas, sem preparo adicional e geração de resíduos. Com exceção da concentração de cafeína, todos os parâmetros foram previstos com erros relativos médios menores que 10,2%, os quais são aceitáveis quando comparados aos coeficientes de variação dos métodos de referência usualmente utilizados. Dessa forma, os resultados obtidos demonstraram que o emprego da Espectroscopia no Infravermelho Próximo, aliada a quimiometria, é viável e indicado para o controle de qualidade de amêndoas de cacau em diversas etapas da cadeia produtiva / Abstract: The development of cocoa culture in Brazil presents several challenges with respect to recognition of the quality and production standardization. Two important aspects related to these difficulties were addressed in this study. The first aspect is the lack of information on the chemical composition of cocoa beans produced in different Brazilian states and sensory characteristics of derivatives. In this regard, samples from different producing regions (Bahia-BA, Pará-PA, Rondônia-RO and the Ivory Coast-CM) were analyzed for physical and chemical parameters relevant to the overall quality of this raw material, which included: bean count, cut test, pH, acidity and shell, moisture, total lipid, protein, phenolic compounds, theobromine and caffeine contents. Physical evaluation of cocoa beans by means of the cut test showed that all samples presented satisfactory commercial standard, however, revealed a lack of standardization in the post-harvesting practices. Significant differences in moisture, acidity, total phenolic compounds, theobromine and caffeine were found, which can directly affect the quality of derivatives. The sensory evaluation of chocolates manufactured with cocoa beans from different origins (BA, PA, RO, CM and Espírito Santo-ES) showed significant differences between the samples, which were identified by both the trained sensory panel as the consumers. BA and CM chocolate samples showed important differences in the sensory profile, while the RO and PA samples presented similarities and intermediate characteristics in relation to the others. The overall acceptance presented little differences with the PA chocolate scored higher than the BA chocolate, probably due to the more intense acidic and bitter tastes in the BA sample. The second subject discussed in this study is the unavailability of rapid and objective analytical methods for assessing the quality of cocoa beans. For this, the physicochemical data of 81 cocoa bean samples acquired in the first stage of this research, were used for the construction of multivariate calibration models by correlation with diffuse reflectance spectra measured in the near infrared region (10000-4000 cm-1). Nine Partial Least Squares regression models were developed allowing the prediction of various chemical parameters (moisture, pH, acidity, total lipids, protein, shell content, total phenolic compounds, concentration of theobromine and caffeine) through direct analysis of samples milled and sieved without any additional preparation. With the exception of caffeine concentration, all of the parameters were predicted with relative errors smaller than an average of 10.2%, which is acceptable when compared to the coefficients of variation of the reference methods usually used. Thus, the results obtained demonstrate that the use of NIR in conjunction with chemometrics is feasible and recommended for the quality control of cocoa beans in various stages of the production chain / Doutorado / Ciência de Alimentos / Doutora em Ciência de Alimentos

[pt] A busca de níveis superiores de qualidade, tempo e competitividade é uma preocupação constante das agências econômicas e no setor agro - alimentar não poderia ser diferente. Um crescente número de pesquisas tem sido publicado detalhando o uso de técnicas analíticas para a determinação do conteúdo mineral, razões isotópicas ou de ambos como descritores geográficos de diferentes produtos agrícolas desde alimentos frescos até produtos processados. A pesquisa de vinhos no Brasil ainda é muito restrita aos pólos produtores de vinhos do país. E, a maior parte dos trabalhos tem como o objetivo a análise de parâmetros clássicos de controle de qualidade, sendo recente em nosso país a pesquisa envolvendo o desenvolvimento e/ou aplicações de metodologias que possam caracterizar o vinho e sua região produtora. Técnicas espectrométricas, como a ICP-OES, ICP-MS, são as mais utilizadas para este propósito e, foram utilizadas neste trabalho. Pela primeira vez o estudo das razões isotópicas de boro e chumbo foi aplicado aos vinhos brasileiros. A análise e classificação dos componentes principais (PCCA) e a análise de agrupamentos (CA), foram utilizadas no processamento dos dados. As regiões Sul e Nordeste puderam ser definidas utilizando tanto os dados da caracterização inorgânica quanto os isotópicos, mas não o suficiente para se definir as regiões produtoras de vinhos do Rio Grande do Sul, em especial o Vale dos Vinhedos. Ficou claro neste trabalho que o emprego da estatística multivariada aos dados obtidos através das determinações inorgânicas e isotópicas é uma poderosa ferramenta analítica. / [en] The search for higher levels of quality, time and competitiveness is a constant concern of economic agencies and agro - food could not be different. A growing body of research has been published detailing the use of analytical techniques for determining the mineral content, isotopic ratios or both as geographical descriptors of different agricultural products from fresh food to processed products. A search of wines in Brazil is still very restricted to the poles wine producers in the country. And, most of the work has as objective the analysis of classical parameters of quality control, and recent research in our country involving the development and / or application of methodologies that characterize the wine and its producing region. Spectrometric techniques such as ICP-OES, ICP-MS, are the most used for this purpose and were used in this study. For the first time the study of the isotopic ratios of lead and boron was applied to the Brazilian wines. The analysis and classification of the major components (PCCA) and cluster analysis (CA) were used for data processing. The South and Northeast could be identified using data from both inorganic as the isotopic characterization, but not enough to define the wine producing regions of Rio Grande do Sul, particularly the Valley of the Vineyards. It became clear in this study that the use of multivariate statistical data obtained through the inorganic and isotopic determinations is a powerful analytical tool.

La médecine de précision (MP) est un nouveau paradigme qui révolutionne la pratique médicale actuelle et remodèle complètement la médecine de demain. La MP aspire à placer le patient au centre du parcours de soins en y intégrant les données médicales et biologiques individuelles tout en tenant compte de la grande diversité interindividuelle. La prédiction des états pathologiques chez les patients nécessite une compréhension dynamique et systémique. Les erreurs innées du métabolisme (EIM) sont des troubles génétiques résultant de défauts dans une voie biochimique donnée en raison de la déficience d'une enzyme, de son cofacteur ou d’un transporteur. Les EIM ne sont plus considérées comme des maladies monogéniques mais tendent à être plus complexes et multifactorielles. Le profil métabolomique permet le dépistage d’une pathologie, la recherche de biomarqueurs et l’exploration des voies métaboliques mises en jeu. Dans ce travail de thèse, nous avons utilisé l’approche métabolomique qui est particulièrement pertinente pour les EIM compte tenu de leur physiopathologie de base qui est étroitement liée au métabolisme. Ce travail a permis la mise en place d’une méthodologie métabolomique non ciblée basée sur une stratégie analytique multidimensionnelle comportant la spectrométrie de masse à haute résolution couplée à la chromatographie liquide ultra-haute performance et la mobilité ionique. La mise en place de la méthodologie de prétraitement, d’analyse et d’exploitation des données générées avec des outils de design expérimental et d’analyses multivariées ont été aussi établies. Enfin, cette approche a été appliquée pour l’exploration des EIM avec les mucopolysaccharidoses comme preuve de concept. Les résultats obtenus suggèrent un remodelage majeur du métabolisme des acides aminés dans la mucopolysaccharidose de type I. En résumé, la métabolomique pourrait être un outil complémentaire pertinent en appui à l’approche génomique dans l’exploration des EIM. / The new field of precision medicine is revolutionizing current medical practice and reshaping future medicine. Precision medicine intends to put the patient as the central driver of healthcare by broadening biological knowledge and acknowledging the great diversity of individuals. The prediction of physiological and pathological states in patients requires a dynamic and systemic understanding of these interactions. Inborn errors of metabolism (IEM) are genetic disorders resulting from defects in a given biochemical pathway due to the deficiency of an enzyme, its cofactor or a transporter. IEM are no longer considered to be monogenic diseases, which adds another layer of complexity to their characterization and diagnosis. To meet this need for faster screening, the metabolic profile can be a promising candidate given its ability in disease screening, biomarker discovery and metabolic pathway investigation. In this thesis, we used a metabolomic approach which is particularly relevant for IEM given their basic pathophysiology that is tightly related to metabolism. This thesis allowed the implementation of an untargeted metabolomic methodology based on a multidimensional analytical strategy including high-resolution mass spectrometry coupled with ultra-high-performance liquid chromatography and ion mobility. This work also set a methodology for preprocessing, analysis and interpretation of the generated data using experimental design and multivariate data analysis. Finally, the strategy is applied to the exploration of IEM with mucopolysaccharidoses as a proof of concept. The results suggest a major remodeling of the amino acid metabolisms in mucopolysaccharidosis type I. In summary, metabolomic is a relevant complementary tool to support the genomic approach in the functional investigations and diagnosis of IEM.

When microalgae are exposed to changing environmental conditions, e.g., light-dark cycles or oscillations in nutrient availability (CO2, nitrogen, phosphate or silicate) they respond with metabolic changes in the carbon allocation pattern. Short time regulations in the time range of few seconds to minutes can be mirrored best by mass spectroscopy based metabolomics. However, these snap shots do not reflect the alterations in the carbon flow to the cellular macromolecules like protein, carbohydrate or lipid. In this review it is shown how the combination of FTIR spectroscopy and Chla-in-vivo-fluorescence based electron transport rates can reveal changes in the metabolic flux rates of carbon during a shift of the environmental conditions. The review will demonstrate in which time range FTIR spectroscopy can deliver significant information and how FTIR spectroscopy data can synergistically support metabolome analysis by mass-spectroscopy.

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