La gradation de lames de biopsie fournit des informations pronostiques essentielles pour le diagnostic et le traitement. La détection et le comptage manuel des mitoses est un travail fastidieux, sujet à des variations inter-et intra- observateur considérables. L'objectif principal de cette thèse de doctorat est le développement d'un système capable de fournir une détection des mitoses sur des images provenant de différents types de scanners rapides automatiques, ainsi que d'un microscope multispectral. L'évaluation des différents systèmes proposés est effectuée dans le cadre du projet MICO (MIcroscopie COgnitive, projet ANR TecSan piloté par notre équipe). Dans ce contexte, les systèmes proposés ont été testés sur les données du benchmark MITOS. En ce qui concerne les images couleur, notre système s'est ainsi classé en deuxième position de ce concours international, selon la valeur du critère F-mesure. Par ailleurs, notre système de détection de mitoses sur images multispectrales surpasse largement les meilleurs résultats obtenus durant le concours. / Digital pathology represents one of the major and challenging evolutions in modernmedicine. Pathological exams constitute not only the gold standard in most of medicalprotocols, but also play a critical and legal role in the diagnosis process. Diagnosing adisease after manually analyzing numerous biopsy slides represents a labor-intensive workfor pathologists. Thanks to the recent advances in digital histopathology, the recognitionof histological tissue patterns in a high-content Whole Slide Image (WSI) has the potentialto provide valuable assistance to the pathologist in his daily practice. Histopathologicalclassification and grading of biopsy samples provide valuable prognostic information thatcould be used for diagnosis and treatment support. Nottingham grading system is thestandard for breast cancer grading. It combines three criteria, namely tubule formation(also referenced as glandular architecture), nuclear atypia and mitosis count. Manualdetection and counting of mitosis is tedious and subject to considerable inter- and intrareadervariations. The main goal of this dissertation is the development of a framework ableto provide detection of mitosis on different types of scanners and multispectral microscope.The main contributions of this work are eight fold. First, we present a comprehensivereview on state-of-the-art methodologies in nuclei detection, segmentation and classificationrestricted to two widely available types of image modalities: H&E (HematoxylinEosin) and IHC (Immunohistochemical). Second, we analyse the statistical and morphologicalinformation concerning mitotic cells on different color channels of various colormodels that improve the mitosis detection in color datasets (Aperio and Hamamatsu scanners).Third, we study oversampling methods to increase the number of instances of theminority class (mitosis) by interpolating between several minority class examples that lietogether, which make classification more robust. Fourth, we propose three different methodsfor spectral bands selection including relative spectral absorption of different tissuecomponents, spectral absorption of H&E stains and mRMR (minimum Redundancy MaximumRelevance) technique. Fifth, we compute multispectral spatial features containingpixel, texture and morphological information on selected spectral bands, which leveragediscriminant information for mitosis classification on multispectral dataset. Sixth, we performa comprehensive study on region and patch based features for mitosis classification.Seven, we perform an extensive investigation of classifiers and inference of the best one formitosis classification. Eight, we propose an efficient and generic strategy to explore largeimages like WSI by combining computational geometry tools with a local signal measureof relevance in a dynamic sampling framework.The evaluation of these frameworks is done in MICO (COgnitive MIcroscopy, ANRTecSan project) platform prototyping initiative. We thus tested our proposed frameworks on MITOS international contest dataset initiated by this project. For the color framework,we manage to rank second during the contest. Furthermore, our multispectral frameworkoutperforms significantly the top methods presented during the contest. Finally, ourframeworks allow us reaching the same level of accuracy in mitosis detection on brightlightas multispectral datasets, a promising result on the way to clinical evaluation and routine.

La formation des souvenirs repose sur un dialogue entre l’hippocampe et le cortex préfrontal médian (CPFm) qui se met en place progressivement et durablement après l’encodage de l’information. La lésion des noyaux reuniens et rhomboïde (ReRh), relai anatomo-fonctionnel entre ces deux structures, perturbe la consolidation à long terme d’un souvenir spatial. A ce jour, les mécanismes mis en jeu ne sont, pas connus. Nous avons donc étudié les processus moléculaires impliqués dans la formation d’un souvenir spatial, au sein de l’hippocampe et du CPFm, et les conséquences induites par la lésion des noyaux ReRh. Pour cela, nous avons lésé les noyaux ReRh de rats, puis nous les testés dans une tâche de piscine de Morris pendant trois jours. Nous avons alors effectué un séquençage des ARNm des sous-régions hippocampiques CA1 dorsale et ventrale, une analyse par RT-qPCR des ARNm du CPFm, ainsi qu’une analyse de l’activation de ces structures par quantification de la protéine issue du gène immédiat c-fos. Nos résultats montrent que la lésion des noyaux ReRh modifie les processus transcriptionnels et traductionnels qui prennent place dans l’hippocampe et le CPFm, dès trois jours d’apprentissage spatial. Ces résultats pourraient expliquer la non persistance d’un souvenir spatial et les déficits comportementaux qui en résultent à la suite d’une lésion des noyaux ReRh. / Memorization relies on a dialogue between the hippocampus and the medial prefrontal cortex (mPFC). This dialog takes place progressively after the encoding of an event. Given their connectivity, the thalamic nuclei named reuniens and rhomboid (ReRh) may modulate the functional loop between these two structures. Indeed, a lesion of these nuclei impairs the persistence of a spatial memory. The mechanisms underlying this process are still unknown. Therefore, we analyzed the molecular mechanisms underlying spatial memory consolidation within the hippocampus and the mPFC, and the consequences of a lesion of the ReRh nuclei. After a stereotaxic lesion of the ReRh nuclei, rats were subjected to three days of a spatial training in the Morris water maze. We then performed a RNA sequencing of the dorsal and ventral hippocampus (CA1 regions), RT-qPCR analysis of the mPCF, and a quantification of the expression of c-fos in these two structures. Results show that ReRh nuclei lesion impairs the transcriptional and translational mechanisms within the hippocampus and the mPFC as soon as after three days of a spatial learning. These alterations could lead to the retrieval deficit observed after a long post-acquisition delay.

Ce travail de thèse avait pour objectif d’étudier le rôle de l’hippocampe (HPC) ventral et des noyaux reuniens (Re) et rhomboïde (Rh) du thalamus dans les processus cognitifs qui sous-tendent la mémoire spatiale chez le Rat. Par l’utilisation d’approches complémentaires combinant l’imagerie cérébrale, la lésion excitotoxique, l’inactivation fonctionnelle réversible et des évaluations comportementales, nos résultats ont mis en évidence : (1) l’implication spécifique de l’HPC ventral uniquement dans le rappel d’informations spatiales ; (2) un rôle-clé des noyaux Re et Rh dans la persistance d’un souvenir spatial ; (3) l’implication des noyaux Re et Rh dans le labyrinthe du double-H, un nouveau test nécessitant d’une part, l’utilisation d’informations spatiales dépendant de l’intégrité de l’HPC dorsal, et d’autre part, une flexibilité comportementale, impliquant le cortex préfrontal médian. Ainsi, l’ensemble de ces résultats permet de proposer l’existence d’un circuit HPC-préfronto-thalamique impliqué dans divers aspects du traitement des informations spatiales. / The main objective of this thesis was to investigate the role of the ventral hippocampus (HPC) and the reuniens (Re) and rhomboid (Rh) thalamic nuclei in the cognitive processes underlying spatial memory in the Rat. If our results first confirmed, in the Morris water maze, the role of the dorsal HPC in the acquisition and retrieval of a spatial reference memory, we demonstrated the specific involvement of the ventral HPC only in the recall of spatial information. In addition, by using complementary approaches combining brain imaging, excitotoxic lesion and reversible functional inactivation, we were able to show for the first time a key role for the Re and Rh in the persistence of a spatial memory (25 days). Finally, the third set of experiments has highlighted the involvement of the Re and Rh in a mnemonic task performed in a new test, the double-H maze, which requires the use of spatial information depending on the integrity of the dorsal HPC, and a behavioral flexibility, involving the medial prefrontal cortex. Thus, taken together, these results suggest the involvement of a HPC-prefronto-thalamic network in various aspects of spatial information processing.

Made available in DSpace on 2014-12-17T15:37:01Z (GMT). No. of bitstreams: 1 JoacilGS_DISSERT.pdf: 4166780 bytes, checksum: d28a491081df0a86a997a1a2664b7535 (MD5) Previous issue date: 2010-12-28 / Serotonin or 5-hydroxytryptamine (5-HT) is a substance found in many tissues of the body, including as a neurotransmitter in the nervous system, in which may exert varied post-synaptic actions. Inside the neuro-axis, the location of 5-HT neurons is almost restricted to the raphe nuclei of the brainstem, such that 5-HT-immunoreactivity can be considered a marker of the raphe nuclei. The raphe nuclei are located in the brainstem, at or near the midline. The serotonergic groups were originally alphanumerically classified as B1 to B9 towards caudorrostral in rats and can be divided into upper and lower groups. In this study the distribution of serotonergic neurons was studied using immunohistochemistry in the brain of the rock cavy (Kerodon rupestris), a species of rodent endemic to Northeastern Brazil. The cytoarchitectonic location of serotonergic neurons was established in series of adjacent coronal and sagittal sections stained by the Nissl method and immunohistochemistry for 5-HT. Thus, we defined the raphe rostral linear, caudal linear, dorsal, median, and paramedian pontine raphe nuclei, and B9 cluster, constituting the rostral group, and the interpositus, magnus, obscure and palidus, constituting the caudal part of the group, comparable to which has been described for other mammalian species / A serotonina ou 5-hidroxitriptamina (5-HT) ? uma subst?ncia encontrada em muitos tecidos do organismo, inclusive no sistema nervoso como neurotransmissor, onde pode exercer a??es p?s-sin?pticas variadas. Dentro do neuro-eixo, a localiza??o dos neur?nios 5-HT ? quase absoluta nos n?cleos da rafe do tronco encef?lico, de tal maneira que 5-HT neuronal pode ser considerada um marcador dos n?cleos da rafe. Os n?cleos da rafe est?o localizados no tronco encef?lico, na linha m?dia ou suas proximidades. Os grupamentos serotonin?rgicos foram originalmente classificados alfanumericamente como B1 a B9 no sentido caudorrostral no rato e podem ser divididos em grupos superior e inferior. Neste trabalho a distribui??o dos neur?nios serotonin?rgicos foi estudada com imunoistoqu?mica no c?rebro do moc? (Kerodon rupestris), uma esp?cie de roedor end?mica da regi?o Nordeste do Brasil. A localiza??o citoarquitet?nica dos neur?nios serotonin?rgicos foi estabelecida em s?ries de sec??es coronais e sagitais adjacentes submetidas a colora??o pelo m?todo de Nissl e imunoistoqu?mica para 5-HT. Assim, foram delimitados os n?cleos da rafe linear rostral, linear caudal, dorsal, mediano, paramediano e pontino da rafe e grupamento B9, compondo o grupo rostral, e os n?cleos interp?sito, magno, obscuro e p?lido, compondo o grupo caudal, compar?vel ao que j? foi descrito para outras esp?cies de mam?feros

Made available in DSpace on 2014-12-17T15:37:06Z (GMT). No. of bitstreams: 1 JoseRLPC_DISSERT.pdf: 5508734 bytes, checksum: 81d9b9240f44158090493b3b76b26129 (MD5) Previous issue date: 2011-10-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The 3-hydroxytyramine/dopamine (DA) is a monoamine of catecholamineric group and consists in the progenitor substantia of synthesis of noradrenaline and adrenaline, having the enzyme tyrosine hydroxylase as a regulator of this process. Nuclei of midbrain expressing DA are the retrorubral field (RRF, A8 group), the substantia nigra pars compacta (SNc, A9 group) and the ventral tegmental area (VTA, A10 group). These nuclei are involved in three complex circuitry called mesostriatal, mesocortical and mesolimbic, which are related directly with various behavioral manifestations such as motor control, reward signaling in behavioural learning, motivation and pathological manifestations of Parkinson s disease and schizophrenia. The aim of this study was describe the morphology of midbrain dopaminergic neurons (A8, A9 and A10) of the rock cavy (Kerodon rupestris), a rodent belonging to the family Caviidae typical of the Brazilian Northeast, which is being adopted as a model for neuroanatomical studies in laboratory of neuroanatomy of the Federal University of Rio Grande do Norte. Coronal sections of brains of the rock cavies were submitted to staining by Nissl s method and immunohistochemistry against tyrosine hydroxylase. The nuclear organization of the midbrain dopaminergic nuclei of the rock cavy is very similar to that found in other animals of the order Rodentia, except by the presence of the tail of substantia nigra, which was found only in the studied species. We concluded that the midbrain dopaminergic nuclei are phylogenetically stable among species, but we think to be it necessary to expand the studies about the particularity found the rock cavy, investigating its occurrence in other species of rodents or investigating its functional relevance / A 3-hidroxitiramina/dopamina (DA) ? uma monoamina do grupo das catecolaminas e consiste na subst?ncia precursora da s?ntese de noradrenalina e adrenalina, tendo a enzima tirosinahidroxilase (TH) como reguladora deste processo. Os n?cleos do mesenc?falo que expressam DA s?o a zona retrorubral (RRF, grupo A8), a subst?ncia negra pars compacta (SNc, grupo A9) e a ?rea tegmental ventral (VTA, grupo A10). Tais n?cleos est?o envolvidos em tr?s complexas circuitarias, chamadas mesostriatal, mesol?mbica e mesocortical, as quais est?o relacionadas diretamente com diversas manifesta??es comportamentais como controle da motricidade, sinaliza??o de recompensa na aprendizagem comportamental, motiva??o e nas manifesta??es patol?gicas da Doen?a de Parkinson e esquizofrenia. O objetivo deste estudo foi descrever a morfologia dos n?cleos dopamin?rgicos do mesenc?falo (A8, A9 e A10) do moc? (Kerodon rupestris), um roedor pertencente ? fam?lia Caviidae t?pico da regi?o Nordeste do Brasil, que est? sendo adotado como modelo para estudos neuroanat?micos no Laborat?rio de Neuroanatomia da Universidade Federal do Rio Grande do Norte. Sec??es coronais do enc?falo do moc? foram submetidas ? colora??o pelo m?todo de Nissl e imunoistoqu?mica contra tirosina-hidroxilase. A organiza??o nuclear do sistema dopamin?rgico do mesenc?falo do moc? ? muito semelhante ao que foi encontrado em outros animais da ordem Rodentia, exceto na presen?a da cauda da subst?ncia negra, que foi encontrada apenas na esp?cie em quest?o. Conclu?mos que os n?cleos dopamin?rgicos do mesenc?falo s?o filogeneticamente est?veis entre as esp?cies, por?m percebemos a necessidade de se ampliar os estudos acerca da particularidade encontrada no moc?, seja investigando a sua ocorr?ncia em outras esp?cies de roedores, seja investigando a sua relev?ncia funcional

Les théories de réaction nucléaire décrivant la synthèse des noyaux superlourds ne sont pas fermement établies. Bien qu'un consensus existe sur les caractéristiques qualitatives de la fusion-évaporation, les prédictions quantitatives des modèles disponibles sont encore insatisfaisantes. La section efficace de production est le produit de la section efficace de capture, de la probabilité de formation et de la probabilité de survie. Des études antérieures ont établi que la partie dominante des divergences restantes provenait de notre incapacité à contraindre correctement la probabilité de formation. L'objectif principal de cette thèse est de contraindre théoriquement cette quantité. Celui-ci a été atteint en examinant les incertitudes associées à la section efficace de capture ainsi qu'à la probabilité de survie par le biais de l'analyse de régression. La barrière de fission étant le facteur le plus influent dans les calculs de probabilité de survie, on supposera qu'elle est la seule source de ses incertitudes. Et puisque la différence entre les masses du fondamental et du point-selle définit la barrière de fission, nous avons commencé par étudier les incertitudes d'un modèle de type goutte liquide afin d'obtenir les incertitudes sur les masses. Sur la base de cette analyse, nous avons affiné une méthode permettant de contraindre les énergies de correction de couches. Afin de déterminer les incertitudes sur les barrières de fission, un modèle microscopique-macroscopique simplifié a été utilisé. Les incertitudes sur la phase de capture ont été obtenues à l'aide d'un modèle basé sur une paramétrisation de la distribution de barrières. Les contraintes portant sur la probabilité de formation ont été ensuite déduites à partir de la propagation des incertitudes sur la section efficace de capture et sur la barrière de fission. Par ailleurs, les effets de l'inertie sur la probabilité de formation ont été étudiés en utilisant la théorie des perturbations et un nouveau mécanisme réduisant l'entrave à la fusion a été décrit comme un décalage de la condition initiale dans l'approximation de Smoluchowski. Enfin, sur la base de cette approche, une explication de la dépendance en énergie du point d'injection phénoménologique a été obtenue. / The nuclear reaction theories describing the synthesis of superheavy nuclei are not firmly established. Although, the basic qualitative features of fusion-evaporation have reached a consensus, the quantitative predictions of the available models are still unsatisfactory. The production cross-section is the product of the capture cross-section, the formation probability and survival probability. Previous studies have shown that the dominating part of the remaining discrepancies came from our inability to properly constrain the formation probability. The main goal of this thesis is to theoretically constrain this quantity. This is achieved by examining the uncertainties in the capture cross-section and the survival probability using regression analysis. The fission barrier being the most influential factor in survival probability calculations, it is assumed to be the only source of uncertainties. Since the fission barrier is the difference between the ground-state and saddle-point masses, we started investigating the uncertainties in the liquid drop model. Based on this analysis we have refined a method to constrain the shell correction energies. To determine the uncertainties in the fission barriers, a simplified phenomenological macroscopic-microscopic model was used. The uncertainties in the capture step were determined using a model based on a parametrization of the barrier distribution. From the propagation of the uncertainties in the capture cross-section and fission barrier, the constraints on the formation probability were determined. Separately, the effects of inertia on the formation probability were investigated using perturbation theory and a new mechanism reducing fusion hindrance was described as a shift in the initial condition within the Smoluchowski approximation. Additionally, based on this approach, an explanation for the phenomenological energy dependent parametrization of the injection point was found.

Made available in DSpace on 2014-10-09T12:45:29Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:01Z (GMT). No. of bitstreams: 1 07295.pdf: 6617875 bytes, checksum: 02bc676c5e25a80397e40d7d6eecf61d (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Estudos prévios demonstram projeções dos núcleos da rafe para áreas clássicas relacionadas ao controle do sistema cardiovascular, como locus coeruleus, núcleo do trato solitário, coluna intermédio lateral da medula espinal, núcleos motor dorsal do vago e ambíguo. Baseado nesta informação este estudo investigou a participação dos núcleos da rafe nas respostas adaptativas a estímulos de hipervolemia e hipovolemia. Foram utilizados ratos machos (Wistar), adultos, mantidos em biotério sob condições controladas, divididos em cinco grupos: hipovolemia (Hipo, submetidos à punção cardíaca com remoção sangüínea), controle da hipovolemia (C hipo, submetidos à punção cardíaca sem remoção sangüínea), hipervolemia (Hiper, submetidos à cirurgia para canulação da veia jugular externa e adição de solução salina no sexto dia pós-cirúrgico), controle da hipervolemia (C hiper, submetidos à cirurgia para canulação da veia jugular externa sem adição de solução salina) e basal (BS). Após 90 minutos do estímulo, os animais foram profundamente anestesiados e perfundidos transcardiacamente com salina seguida de fixador Paraformaldeído + Bórax 4%, 4ºC, pH 9,5. Os encéfalos foram removidos pós-fixados, crioprotegidos e seccionados em cortes coronais de 40 µm e processados com técnicas de imunohistoquímica contra Fos e 5-HT. Os estímulos de hipo e hipervolemia não causaram aumento significativo dos neurônios Fos-imunoreativos ou 5HT/Fos-imunoreativos. Nos núcleos Li, DR, MnR, RMg e ROb o grupo C hipo apresentou maior número de neurônios Fos-IR e 5HT/Fos-IR em relação ao grupo C hiper. Os resultados sugerem que os núcleos da rafe não participam nas repostas adaptativas aos estímulos aplicados. Entretanto, os mesmos parecem estar envolvidos em processos de nocicepção, seja através da 5-HT ou de outras substâncias neuroativas, presentes nestes núcleos. / Previous studies presented projections from the raphe nuclei to areas related to the cardiovascular control, like the locus coeruleus, nucleus of the solitary tract, spinal cord intermedium lateral column, dorsal motor vagus and ambiguus nuclei. Based in this information, the present work analyzed the participation of the raphe nuclei in the adaptative responses to hypovolaemia and hypervolaemia. Were used wistar rats, kept in controlled conditions, divided in 5 groups: hypovolaemia (Hypo, cardiac puncture and blood extraction), hypovolaemia control (C Hypo, cardiac puncture without blood extraction), hypervolaemia (Hyper, external jugular vein canulation surgery and saline addition), hypervolaemia control (C Hyper, external jugular vein canulation surgery and no saline addition) and basal condition (BS). Ninety minutes after the stimulus, the animals were anesthetized and perfused with saline followed by 4% paraformaldehyde plus borax, pH 9.5 at 4ºC. The brains were removed, pos-fixated, cryoprotected, sectioned in 40µm thickness coronal slices and proceeded with double-labeling immunohistochemistry techniques against Fos protein and serotonin. The Hypo and Hyper stimuli presented no significant increase of Fos-IR and double-labeled neurons. The C Hypo group presented higher number of labeled neurons in the Li, DR, MnR, RMg and ROb nuclei in comparison to the group C Hyper. These results suggest that the raphe nuclei have no participation in the adaptative responses to the volemy stimuli. However, this nuclei seems to be related to the nociception no modulated just by the serotonin but by others neurotransmitters too.

Foram medidos os momentos magnéticos dos estados da banda rotacional do estado fundamental do ANTPOT 159 Tb, através da técnica da distribuição angular perturbada, utilizando-se o campo magnético transiente. Os estados do ANTPOT. 159 Tb foram populados via excitação coulombiana com feixe de ANTPOT. 35 Cl a 88 Me V, sendo os raios -y, emitidos na desexcitação dos estados, observados em coincidência com as partículas retroespalhadas do feixe. Os momentos magnéticos medidos neste trabalho, foram comparados com as previsões de modelos híbridos (rotor+partícula e rotor triaxial+quase-partícula), nos quais a hamiltoniana do núcleo é separada em uma parte fenomenológica que descreve o caroço e uma parte microscópica que leva em conta o movimento da partícula desemparelhada. Os resultados experimentais também foram interpretados com um cálculo puramente microscópico, baseado no modelo de camadas com projeção de momento angular. Os níveis de energia da banda do estado fundamental são bem descritos pelos modelos, embora o staggering em energia previsto pelo modelo rotor triaxial+quase-partícula apresente uma fase de oscilação oposta à observada. Os momentos magnéticos experimentais são bem reproduzidos pelos modelos, nos quais a inclusão de outras configurações sugere uma pequena oscilação, observada nos resultados experimentais. As probabilidades de transição magnéticas B(M1) não são bem descritas por nenhum dos modelos, nos quais a inclusão de várias configurações atenua os valores calculados. / Magnetic moments of the levels in the ground state rotational band of 159Tb were measured using the transient magnetic field perturbed angular distribution technique. The levels in 159Tb were populated by Coulomb excitation with an 88 MeV beam and the deexciting rays were observed in coincidence with backscattered projectiles. The magnetic moments measured in this work were compared with hybrid models (rotor+particle and triaxial rotor+quasiparticle) in which the Hamiltonian of the nucleus is separated in a phenomenological part describing the core and a rnicroscopic part which takes into acconnt the movement of the unpaired particle. The experimental results were also interpreted with a purely microscopic calculation based on the angular momentum projection shell model. The energy levels in the ground state band are well described by the models, although the energy staggering predicted in the triaxial rotor+quasi-particle calculation has a phase opposite to the observed one. The experimental magnetic moments are well reproduced by the models, with the band miring suggesting a slight oscillation as observed in the experimental data. The magnetic transition probabilities B(M1) are not well described by the models, in which the band mixing attenuates the calculated values.

Tendo como referência uma concepção de Geografia que assume que o espaço geográfico é componente constituinte da sociedade, uma instância da sociedade (Milton Santos) ou uma dimensão transversal da sociedade (Jacques Lévy), o trabalho procura qualificar a reestruturação da cidade de São Paulo (que se inicia nos anos 1980) a partir da imensa disseminação do uso do automóvel particular. O trabalho investe na caracterização da natureza dos novos espaços produzidos como resultado da relação cidade automóvel, do mesmo modo que avalia como a cidade é inflexionada pelos espaços do automóvel. A referência específica para essa caracterização é a definição de cidade como espaço principal de convivialidade humana, processo esse apreendido pelo conceito de urbanidade e como a forma mais eficiente de administração da distância espacial (Jacques Lévy), cujos espaços se estruturam de dois modos principais: a forma territorial (predomínio da contigüidade) e a forma reticular (redes, predomínio lacunar). A difusão do automóvel favorece, em São Paulo, a formação de redes geográficas que fragmentam a cidade e criam um horizonte de separações e segregações. Nessa reconfiguração da cidade a estrutura espacial mais característica é o que denominamos de núcleos de baixa territorialização associados ao uso do automóvel. São núcleos de rede que negam a cidade, assim como os subúrbios americanos negavam os centros das cidades americanas. Funcionam como se fossem subúrbios encravados no interior do núcleo denso da cidade. Por essa razão esses núcleos de baixa territorialização (mantém um baixo nível de relações com os espaços contíguos) também são denominados por nós como subúrbios internos. Essa reestruturação rebaixa a urbanidade da cidade, deteriorando os espaços públicos e abrindo caminho para o domínio das soluções privadas frente às dificuldades das cidades. / Taking as reference a concept of Geography that views geographical space as a building block of society, as an instance of society (Milton Santos) or a transversal dimension of society (Jacques Lévy), this paper seeks to qualify the restructuring of the city of São Paulo, begun in the 1980s, which resulted from the vast dissemination of private automobile usage. This paper addresses itself to characterize the nature of the new spaces arising from the city automobile relationship, and to assess how the city is modulated by the spaces of the automobile. Our specific reference will be the definition of city as the key space for human sociability, a process apprehended by the concept of urbanity and seen as the most efficient form of managing spatial distance (Jacques Lévy), wherein spaces are structured in two main modes: the territorial form (predominance of contiguity) and the reticular form (networks, predominance of lacunae). In São Paulo, the dissemination of the automobile contributes to establish geographical networks that fragment the city and create an urban horizon of separations and segregations. In such a framework, the most typical spatial structure comprises what we call nuclei of low territorialization, which are associated with the use of the automobile. These network nuclei deny the city, much as the U.S. suburbs negated the city centers of American towns, and function as if they were suburbs grafted into the dense nucleus of the city. For this reason, they can also be called internal suburbs, inasmuch as they maintain minimal relationships with contiguous spaces. This type of restructuring degrades the urbanity of a city, deteriorates public spaces and opens the way for the predominance of private solutions to the predicaments of cities.