The aim of the thesis was to develop novel mono-labeled and dual-labeled imaging agents for targeting cancer tumors by Positron Emission Tomography (PET) and Optical Imaging (OI). Bispidines were used as Copper-64 and NOTA as Copper-64 as well as Gallium-68 chelators for PET. Fluorophore, IR 800 dye was used for OI. Amine-terminated ultrasmall Silicon nanoparticles (Si NPs) of size 3-5 nm were used as a multifunctional multimodal imaging core.:Chapter 1 Introduction 1 1.1 General introduction 1 1.2 Aims and objectives of the thesis 6 Chapter 2 Literature review and theoretical part 7 2.1 Molecular imaging of cancer 7 2.1.1 Positron Emission Tomography 8 2.1.2 Optical imaging 19 2.2 Multimodal molecular imaging 21 2.2.1 Silicon nanoparticles as multimodal imaging agents 23 2.2.2 Factors affecting the biodistribution and pharmacokinetics of NPs 27 2.2.3 Tumor targeting strategies for molecular imaging agents 30 2.2.4 Targeted functionalization of NPs and BFCAs for imaging purposes 32 Chapter 3 Results and Discussion 35 3.1 Synthesis, characterization and radiolabeling studies of hexadentate bispidine-based bifunctional chelating agents 37 3.1.1 Synthesis of hexadentate bispidine-based ligands 39 3.1.2 Radiochemistry of modified bispidine derivatives 59 3.1.3 Conclusions 61 3.2 Design and synthesis of Bispidine-based TATE and sd antibody bioconjugates 63 3.2.1 Bispidine-based bioconjugates of somatostatin agonist TATE 63 3.2.2 Bispidine-based EGFR targeting sdAb conjugates B5-sdAb 71 3.2.3 Conclusions 80 3.3 Synthesis and characterization of amine-terminated ultrasmall Si NPs 81 3.3.1 Synthesis of amine-terminated Si NPs 81 3.3.2 Characterization of Si NPs 82 3.3.3 Surface characterization of Si NPs 84 3.3.4 Conclusions 85 3.4 Synthesis, characterization, and biodistribution studies of Si NP-based mono-labeled PET and optical imaging agents 86 3.4.1 Si NP-NOTA derived PET imaging agent 88 3.4.2 Synthesis and characterization of Si NP-Bispidine (Si NP-B4) 93 3.4.3 Synthesis, characterization, in vitro and in vivo evaluation of Si NP-IR800 as an optical imaging probe 95 3.4.5 Conclusions 104 3.5 Development of dual-labeled Si NPs an its in vitro and in vivo evaluation 106 3.5.1 Synthesis and characterization of Si NP-IR800-NOTA conjugate 107 3.5.2 Photophysical characterization of Si NP-IR800-NOTA and comparison with mono-labeled imaging agents 109 3.5.3 Radiolabeling studies of dual-labeled Si NP-IR800-NOTA 110 3.5.4 Quantitative estimation of the amount of fluorophore and the radiolabel on the Si NP conjugate 111 3.5.5 Cell Cytotoxicity Studies of the Si NP-IR800-NOTA 114 3.5.6 In vivo PET analysis and biodistribution studies, urine analysis and ex vivo examination of [64Cu]Cu-Si NP-IR800-NOTA 115 3.5.7 Comparative analysis of [68Ga]Ga-Si NP-IR800-NOTA and [64Cu]Cu-Si NP-IR800-NOTA in A431 tumor bearing mice 121 3.5.8 Conclusions 127 3.6 Investigation of mono-labeled and dual-labeled Si NPs as targeted imaging agents 128 3.6.1 Synthesis of Si NP-PEG-5B9 peptide conjugates 128 3.6.2 Characterization of the targeted Si NP conjugates 129 3.6.3 Conclusions 134 Chapter 4 Conclusions and Outlook 135 4.1 Conclusions 135 4.2 Outlook 140 Chapter 5 Experimental Section 141 5.1 Chemicals and Materials 141 5.2 Analysis, characterization and purification techniques and methods 143 5.3 Radionuclide production (68Ga and 64Cu) 146 5.4 Syntheses 148 5.4.1 Synthesis of bispidines derivatives (B1-B11), intermediates (B1’, B3’, B8’, B9’, B11’) and bifunctional linkers (L1, L2) 148 5.4.2 Synthesis of bispidines-based bioconjugates B4-PEG-TATE and B5-sdAb-7C12 160 5.4.3 Synthesis and modification of Si NPs by hydrothermal method 161 5.5 Radiolabeling experiments 166 5.6 In vitro cell experiments 167 5.7 Cell binding studies 169 5.8 Animal experiments 170 Chapter 6 References 172 Chapter 7 Annex 192 7.1 Acronyms 192 7.2 Supplementary Data 195 Chapter 8 Publications, Conferences and Awards 203 Chapter 9 Acknowledgements 206 Chapter 10 Statement of declaration / Erklärungen 208

Indiana University-Purdue University Indianapolis (IUPUI) / Over 5 million older adults have Alzheimer's disease (AD) in the US, and this number is projected to double by 2050. Clinical trials of potential pharmacological treatments for AD have largely shown that once cognitive decline has occurred, targeting AD pathology in the brain does not improve cognition. Therefore, it is likely that the most effective treatments for AD will need to be administered before cognitive symptoms occur, necessitating a biomarker for the early, preclinical stages of AD. Cerebral blood flow (CBF) is a promising early biomarker for AD. CBF is decreased in individuals with AD compared to their normally aging counterparts, and it has been shown that CBF is altered in mild cognitive impairment (MCI) and earlier stages and may occur prior to amyloid or tau aggregation. In addition, CBF can be measured using arterial spin labeled (ASL) MRI, a noninvasive imaging technique that can be safely repeated over time to track prognosis or treatment efficacy. The complex temporal and spatial patterns of altered CBF over the course of AD, as well as the relationships between CBF and AD-specific and -nonspecific factors, will be critical to elucidate in order for CBF to be an effective early biomarker of AD. Here, we begin to characterize the relationships between CBF and risk factors, pathologies, and symptoms of AD. Chapter 1 is a systematic review of published literature that compares CBF in individuals with AD and MCI to CBF in cognitively normal (CN) controls and assesses the relationship between CBF and cognitive function. Chapter 2 reports our original research assessing the relationships between CBF, hypertension, and race/ethnicity in older adults without dementia from the the Indiana Alzheimer’s Disease Research Center (IADRC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). Chapter 3 reports our original research assessing the relationships between CBF and amyloid beta and tau aggregation measured with PET, as well as whether hypertension or APOEε4 positivity affects these relationships, in older adults without dementia from the IADRC. Chapter 4 reports our original research assessing the relationship between the spatial distribution of tau and subjective memory concerns. / 2023-05-24

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The benefits of an active lifestyle are undisputed, yet our understanding of the contribution of physical activity (PA) to the daily energy budget is limited. The prevailing model of a linear relationship between PA and total energy expenditure (TEE) has been challenged by models that predict an upper limit of TEE (constrained) or a compensatory decrease elsewhere in the budget in response to increased PA (compensated). The purpose of this study was to determine the equation of best fit between PA and TEE using linear and non-linear modeling in the light of existing models. Secondarily, we sought to explore relationships between PA and postulated means of behavioral (time sedentary) and physiologic (i.e. Immune, reproductive) compensation. We measured TEE in 57 healthy weight stable adults (18 to 58 yrs., F = 28) who ranged from being sedentary to ultra-endurance trained runners (0 to 78 mi/wk.) using the doubly labeled water technique and PA and sedentary time using a waist mounted triaxial accelerometer during the same 14-day period. We obtained fasting serum (albumin, cortisol, TNFα, C-reactive protein, free testosterone, TSH and T3), plasma (leptin) and whole blood (WBC with differential) concentrations. Using linear and non-linear modeling, we observed a positive linear relationship between PA (Vector Magnitude Counts per Minute ) and TEE (R2=0.313, Y = 1.427*X + 1930 and adjusted for fat free mass (FFM) R2=0.363, Y = 1.151*X + 2155). We identified no association between PA and RMR ( R2=0.015 and adjusted for FFM R2=0.010). In addition, we observed an association between higher PA and lower % time sedentary (R2=0.723). Although inconsistent, there was a general trend for higher PA but not TEE or its components to be associated with lower immune and reproductive biomarkers. These findings support a conventional linear model though intervention studies will be needed to further address this issue. / Doctor of Philosophy / The health benefits of being physically active are well known. At the same time there is much that is not understood about the relationship between physical activity and how much energy we spend in a day (total energy expenditure). It has been assumed for a long time that the amount of energy we spend is a simple matter of adding the calories burned at rest, digesting food, and exercising and as we exercise more we continue to add an equal number of calories to the daily budget. We call this the linear or additive model – energy spent increases in a straight line as physical activity increases. Because we have techniques for measuring total energy expenditure in people going about their usual lives that were not widely available until recently due to cost, scientists have developed new ideas about how increases in physical activity affect total energy expenditure. The constrained model suggests that there is a cap on how many calories we can burn in a day and that our bodies will save energy in other parts of the budget if our physical activity remains high enough to reach or exceed that cap. The second idea is called the compensated model like the constrained model predicts that the rate we spend energy slows down as we exercise more because the body has saved energy in other parts of the budget (compensation). Researchers don't know for sure if either of these models are correct, so we conducted a study to determine how physical activity and total energy expenditure are related and if our findings agree with either of these models. We were also interested in determining how physical activity is related to energy spent at rest (resting metabolic rate ) and energy spent being active (physical activity energy expenditure). Finally, we wanted to determine ways that the body might compensate. One way is to spend more time sedentary. Another way is to save energy on less urgent needs like the immune and reproductive systems. Our main goal was to create an equation that explain how higher levels of physical activity are related to total energy expenditure and other parts of the energy budget (RMR and physical activity energy expenditure). We also created equations that explain how physical activity is related to sedentary behavior and immune and reproductive markers in the blood. We recruited 57 male and female volunteers that represent a wide range of physical activity levels – from sedentary to ultra-endurance trained runners who routinely run as much as 80 miles per week. We measured the energy they spent and physical activity over 2 weeks. In our sample, we found that physical activity was related to total energy expenditure and physical activity energy expenditure in a linear way. We did not find a cap on the amount of energy spent (constraint). We found that participants who exercised more spent less time sedentary not more meaning that we did not find behavioral compensation. It is possible that there was compensation from the immune system because some of the markers of immune function were lower in people who were more physically active, but it was not consistent in all of the blood markers. A larger study using an exercise intervention is needed to assign causation to the correlation we found.

Cette thèse se situe dans le domaine de graphes et de leurs applications, Elleest constitué de trois grandes parties, la première est consacrée à l’étude d’unnouveau type de coloration sommets distinguantes, les arête-colorations sommetsdistinguantespar écarte. Il consiste de trouver une valuation des arêtes qui permettede distinguer les sommets de graphes telle que chaque sommet v du graphe est identifiéde façon unique par la différence entre la plus grande et la plus petite des valeursincidentes à v. Le plus entier pour lequel le graphe G admet une arête-colorationsommets-distinguantes par écarte est le nombre chromatique par écart de G, notégap(G). Nous avons étudié ce paramètre pour diverses familles de graphes. Uneconjecture intéressante, proposée dans cette partie, suggère que le nombre chromatiquepar écart de tout graphe connexe d’ordre n > 2 vaut n - 1, n ou n + 1.La deuxième partie du manuscrit concerne le problème du placement de graphes.Nous proposons un état de l’art des problèmes de placement de graphes, puis nousintroduisons la nouvelle notion de placement de graphes étiquetés. Il s’agit d’unplacement de graphes qui préserve les étiquettes des sommets. Ensuite, nous proposonsdes encadrements de ce nouveau paramètre pour plusieurs classes de graphes.La troisième partie de la thèse s’intéresse au problème d’appariement d’arbres dansle cadre de la recherche d’information dans des documents structurés de type XML.Les algorithmes holistique de jointure structurelle est l’une des premières méthodesproposées pour résoudre l’appariement exact des documents XML. Ces algorithmessont souvent divisés en deux grandes étapes. La première étape permet de décomposerl’arbre de la requête en un ensemble de petites composantes connexes. Ensuite,des solutions intermédiaires pour chaque composante de la requête sont trouvées, cesrésultats intermédiaires sont joints pour obtenir la solution finale. Nous proposonsdans cette partie un nouvel algorithme appelé TwigStack++ qui vise principalementà diminuer le coût de la jointure et le calcule inutile recherche. Notre algorithmeobtient de meilleurs résultats en comparaison avec deux autres méthodes de l’étatde l’art. / In this thesis, we investigate some problems in graph theory, namelythe graph coloring problem, the graph packing problem and tree pattern matchingfor XML query processing. The common point between these problems is that theyuse labeled graphs.In the first part, we study a new coloring parameter of graphs called the gapvertex-distinguishing edge coloring. It consists in an edge-coloring of a graph G whichinduces a vertex distinguishing labeling of G such that the label of each vertex isgiven by the difference between the highest and the lowest colors of its adjacentedges. The minimum number of colors required for a gap vertex-distinguishing edgecoloring of G is called the gap chromatic number of G and is denoted by gap(G).We will compute this parameter for a large set of graphs G of order n and we evenprove that gap(G) 2 fn E 1; n; n + 1g.In the second part, we focus on graph packing problems, which is an area ofgraph theory that has grown significantly over the past several years. However, themajority of existing works focuses on unlabeled graphs. In this thesis, we introducefor the first time the packing problem for a vertex labeled graph. Roughly speaking,it consists of graph packing which preserves the labels of the vertices. We studythe corresponding optimization parameter on several classes of graphs, as well asfinding general bounds and characterizations.The last part deal with the query processing of a core subset of XML query languages:XML twig queries. An XML twig query, represented as a small query tree,is essentially a complex selection on the structure of an XML document. Matching atwig query means finding all the occurrences of the query tree embedded in the XMLdata tree. Many holistic twig join algorithms have been proposed to match XMLtwig pattern. Most of these algorithms find twig pattern matching in two steps. Inthe first one, a query tree is decomposed into smaller pieces, and solutions againstthese pieces are found. In the second step, all of these partial solutions are joinedtogether to generate the final solutions. In this part, we propose a novel holistictwig join algorithm, called TwigStack++, which features two main improvementsin the decomposition and matching phase. The proposed solutions are shown to beefficient and scalable, and should be helpful for the future research on efficient queryprocessing in a large XML database.

Pour comprendre les mécanismes microscopiques du renforcement dans les nanocomposites, nous avons mis en œuvre un système nanocomposite modèle composé de nanoparticules de silice incorporées dans une matrice du copolymère PMMA/PBuA. La formation des échantillons se fait par évaporation du solvant -l'eau- du système colloïdal mixte latex et silice. La structure de la charge peut être contrôlée par le pH et la fraction volumique de la silice. La combinaison de diffusion de neutrons aux petits angles et microscopie électronique à transmission nous a permis d'établir un diagramme de phases du nombre d'agrégation de la silice. Les tests mécaniques en traction uni-axiale sur des nanocomposites de structure définie nous ont donné accès à la relation entre la structure des charges et la rhéologie. L'augmentation du nombre d'agrégation moyen augmente le renforcement du module de Young, et mène à une rupture précoce des films. Un optimum entre fort renforcement et grande déformation avant rupture peut être trouvé en s'intéressant à l'énergie de rupture. Lorsque l'on s'intéresse à la structure des chaînes dans les nanocomposites, il faut créer le contraste moyen nul pour la silice en introduisant des chaînes deutériées D. Nous avons pu suivre l'interdiffusion des chaînes H et D durant le recuit dans deux systèmes. Pour suivre la dissolution des billes de latex dans le polymère fondu, nous avons mis en place une modélisation des données structurales. La présence de la silice limite la mobilité des chaînes dans les nanocomposites. / To improve the understanding of the reinforcement effect in nanocomposites, we have set up a model system made of a latex matrix (PMMA-PBuA copolymer) with incorporated nanosilica beads. The nanocomposite films are made by evaporating the aqueous solvent of mixture of silica/latex colloidal solutions. The structure of the network is well controlled by the pH and volume fraction of silica. We have established a phase diagram of the aggregation number of the silica by small angle neutron scattering and scanning electron microscopy. The rheological properties of silica-latex nanocomposites have been tested by uni-axial stress-strain isotherms and correlated to the silica structure. The increase of the average aggregation number reinforces the Young modulus and decreases the elongation at the breaking point. An optimum has been found by determining the energy needed until rupture. We have studied the chain structure in the nanocomposites by creatin g zero-average contrast conditions for the silica, using mixtures of D- and H-latex. The interdiffusion of the H and D chains during the annealing could be measured in two systems and intermediate structure modelled. The presence of the nanosilica particles reduces the mobility of the polymer chains.

A produtividade de soja no mundo aumenta há décadas, em razão do avanço genético e das técnicas de cultivo e, em especial, pelo avanço da ciência na melhoria da fixação biológica de nitrogênio (FBN), nutriente exigido em grande quantidade pela soja. Existe a hipótese que a quantidade de nitrogênio (N) fornecida pela FBN e pelo solo não sejam suficientes para dar continuidade ao aumento da produtividade média hoje atingida (3 Mg ha-1), ou seja, o N seria o fator limitante para a soja. Essa hipótese é reforçada quando consideramos que o cultivo de soja é realizado em solos com baixo fornecimento de N, e em condições subótimas para a FBN. Neste contexto, seria necessário a adubação nitrogenada para complementar a demanda da cultura pelo nutriente. Dessa forma, caberia o uso da adubação nitrogenada para complementar a demanda da soja pelo N? A demanda de N pela soja, pode até ser complementada via fertilização. Entretanto, a mesma só faz sentido se não houver prejuízo à FBN, processo que sempre deve ser priorizado. Esta pesquisa teve como objetivo verificar a produtividade da soja e, compreender a resposta da planta à fertilização nitrogenada, no que diz respeito ao aproveitamento do N do fertilizante e sua influência na FBN. Para tanto, foram realizados dois anos de experimentos em ambiente tropical (Cerrado, Estado do Mato Grosso) e subtropical (sul do Estado de São Paulo). As fontes de variação experimentais foram doses (0, 20, 40, 80 e 120 kg ha-1) de N, e épocas de aplicação do fertilizante (VE, e R3) utilizando ureia aplicada com incorporação ao solo. Outro experimento foi realizado com a aplicação de ureia em baixas doses (650, 1300 e 1950 g ha-1 de N) em R1 ou R3 em Ambiente subtropical. Em ambos experimentos, foi utilizado o N marcado com o isótopo 15N. Não houve resposta produtiva da soja às doses de N aplicadas. Entre as épocas de aplicação, foi verificado que em uma das safras no Cerrado, houve maior produtividade (400 kg ha-1) com o fornecimento de N em R3. Porém essa resposta é obtida em determinadas condições ambientais, ou seja, o fornecimento de N não é garantia de aumento de produção, e a resposta é incerta. Houve redução da FBN, em porcentagem (% de N na planta derivado da atmosfera), da ordem de 15% entre a soja sem N e a soja com 120 kg N ha-1. A extração de N total foi 8% maior com a adubação em R3. O aumento do N (20 kg ha-1) da parte aérea com a aplicação em R3 no Cerrado, acompanhou o aumento de produtividade, mas esse aumento não foi provocado pelo N derivado do fertilizante (Ndff). A eficiência de uso do N (NUE) apresentou valores próximos a 50%, e, foi semelhante entre as duas épocas de aplicação de N em ambos os ambientes. No outro experimento, o fornecimento de N foliar não aumentou a produtividade, embora a NUE seja alta, com média de 64%. / The soybean yield in the world has been increasing for decades, due to the cultivation techniques, the cultivars, and the advancement of science in improving the biological nitrogen fixation (BNF), nutrient required in large quantities for soybeans. There is hypothesis that the quantity of nitrogen (N) provided by the BNF and soil are not enough to continue to increase yields today achieved (3 Mg ha-1), or N would be the limiting factor for soybeans. This hypothesis is reinforced when we consider that soybean cultivation is carried out in soils with low N supply, and suboptimal conditions for BFN. In this scenario, it would be the use of nitrogen fertilizer to supplement the soybean demand for N? The demand of N by soybeans may even be supplemented via fertilization. However, it only makes sense if there is (NUE) o damage to the BFN, a process that should always be prioritized. Many experiments with supply of mineral N have been conducted. Some tested negative, others positive. Producers are also conducting nitrogen fertilization in soybean, without proper knowledge of the subject. This study aimed to evaluate the production of soybean response, and understand the reaction of the plant to nitrogen fertilization, with regard to the use of N fertilizer and its influence on BFN. For that, two years of experiments were performed in tropical environment (Cerrado, Mato Grosso) and subtropical (southern state of São Paulo). The experimental variation sources were nitrogen rates, and fertilizer application times, using N marked with the 15N isotope. The application of nutrients has been tried in the soil, and also in soybean leaves. Verified productive soybean response to the supply of N in the Cerrado where the amount of N available to the crop is low. However such response is achieved under certain environmental conditions or N supply is no guarantee production increase, and the response is uncertain. The BFN is reduced, if not in absolute terms (kg ha-1 de N fixed by FBN), in percentages (% of N at plant from atmosphere). The total N extraction was always higher with fertilization in R3, and the Cerrado environment the application at this stage caused increased yeld, but only in one crop season. Increasing Number of shoot with the application in R3 in Primavera do Leste, accompanied the increase in productivity, but this increase was not caused by N fertilizer (Ndff). The N use efficiency showed values close to 50% and was similar between the two N application timing in both environments. In the tropical environment NUE decreased with increasing N rate. In subtropical environment NUE was constant. The supply of leaf N did not increase productivity, although the NUE is high, averaging 64%.

Este trabalho objetivou o estudo de rotas de formação de metabólitos secundários utilizando precursores isotopicamente marcados com 13C. Os experimentos de crescimento com adição de [1-13C]acetato, [1,2-13C2]acetato e [U-13C315N1]-L-cisteína para o fungo do ambiente marinho Penicillium sp. DRF2 mostrou que as ciclotiocurvularinas são provenientes da rota de formação de policetídeos e pela incorporação de L-cisteína, depois da transformação desta em 3-mercaptopiruvato. Os resultados sugerem que a formação das ciclotiocurvularinas provém de um processo de detoxificação da α,β-desidrocurvularina. O estudo do metabolismo secundário de Aspergillus sp. DLM3-8, também do ambiente marinho, mostrou que o seu perfil metabólico produzido em experimentos de crescimento sob diferentes condições é constante. Os experimentos de incorporação de precursores isotopicamente marcados com 13C na naftoquinonaimina, produzida por Aspergillus sp. DLM3-8 foram inconclusivos, indicando que outras abordagens experimentais devem ser realizadas para se investigar a biossíntese deste metabólito. / This investigation aimed investigated the formation routes of secondary metabolites using 13C-labelled precursors. Feeding experiments with [1-13C]acetate, [1,2-13C2]acetate and [U-13C315N1]-L-cysteine within the growth medium of the marine-derived fungi Penicillium sp. DRF2 showed that cyclothiocurvularins are derived from polyketides and from the incorporation of a L-cysteine residue, after its transformation into 3-mercaptopyruvate. The results suggest that the formation of cyclothiocurvularins is derived from a detoxification process ofα,β-dehydrocurvularin. Investigation of the secondary metabolism of a marine-derived Aspergillus sp. DLM3-8 indicated a stable metabolic profile under a variety of growth conditions. Feeding experiments with 13C-labelled precursors for the biosynthesis investigation of naphthoquinoneimine were inconclusive, indicating that other methodologies should be envisaged in order to investigate the biosynthesis of this metabolite.

Made available in DSpace on 2017-07-21T14:19:33Z (GMT). No. of bitstreams: 1 Juscelino Izidoro Oliveira.pdf: 622255 bytes, checksum: 54447b380bca4ea8e2360060669d5cff (MD5) Previous issue date: 2012-07-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Multivariate data analysis allows the researcher to verify the interaction among a lot of attributes that can influence the behavior of a response variable. That analysis uses models that can be induced from experimental data set. An important issue in the induction of multivariate regressors and classifers is the sample size, because this determines the reliability of the model for tasks of regression or classification of the response variable. This work approachs the sample size issue through the Theory of Probably Approximately Correct Learning, that comes from problems about machine learning for induction of models. Given the importance of agricultural modelling, this work shows two procedures to select variables. Variable Selection by Principal Component Analysis is an unsupervised procedure and allows the researcher to select the most relevant variables from the agricultural data by considering the variation in the data. Variable Selection by Supervised Principal Component Analysis is a supervised procedure and allows the researcher to perform the same process as in the previous procedure, but concentrating the focus of the selection over the variables with more influence in the behavior of the response variable. Both procedures allow the sample complexity informations to be explored in variable selection process. Those procedures were tested in five experiments, showing that the supervised procedure has allowed to induce models that produced better scores, by mean, than that models induced over variables selected by unsupervised procedure. Those experiments also allowed to verify that the variables selected by the unsupervised and supervised procedure showed reduced indices of multicolinearity. / A análise multivariada de dados permite verificar a interação de vários atributos que podem influenciar o comportamento de uma variável de resposta. Tal análise utiliza modelos que podem ser induzidos de conjuntos de dados experimentais. Um fator importante na indução de regressores e classificadores multivariados é o tamanho da amostra, pois, esta determina a contabilidade do modelo quando há a necessidade de se regredir ou classificar a variável de resposta. Este trabalho aborda a questão do tamanho da amostra por meio da Teoria do Aprendizado Provavelmente Aproximadamente Correto, oriundo de problemas sobre o aprendizado de máquina para a indução de modelos. Dada a importância da modelagem agrícola, este trabalho apresenta dois procedimentos para a seleção de variáveis. O procedimento de Seleção de Variáveis por Análise de Componentes Principais, que não é supervisionado e permite ao pesquisador de agricultura selecionar as variáveis mais relevantes de um conjunto de dados agrícolas considerando a variação contida nos dados. O procedimento de Seleção de Variáveis por Análise de Componentes Principais Supervisionado, que é supervisionado e permite realizar o mesmo processo do primeiro procedimento, mas concentrando-se apenas nas variáveis que possuem maior infuência no comportamento da variável de resposta. Ambos permitem que informações a respeito da complexidade da amostra sejam exploradas na seleção de variáveis. Os dois procedimentos foram avaliados em cinco experimentos, mostrando que o procedimento supervisionado permitiu, em média, induzir modelos que produziram melhores pontuações do que aqueles modelos gerados sobre as variáveis selecionadas pelo procedimento não supervisionado. Os experimentos também permitiram verificar que as variáveis selecionadas por ambos os procedimentos apresentavam índices reduzidos de multicolinaridade..