International Telemetering Conference Proceedings / October 21, 2002 / Town & Country Hotel and Conference Center, San Diego, California / Ongoing work at National Aeronautics and Space Administration Goddard Space Flight Center (NASA/GSFC), seeks to apply standard Internet applications and protocols to meet the technology challenge of future satellite missions. Internet protocols and technologies are under study as a future means to provide seamless dynamic communication among heterogeneous instruments, spacecraft, ground stations, constellations of spacecraft, and science investigators. The primary objective is to design and demonstrate in the laboratory the automated end-to-end transport of files in a simulated dynamic space environment using off-the-shelf, low-cost, commodity-level standard applications and protocols. The demonstrated functions and capabilities will become increasingly significant in the years to come as both earth and space science missions fly more sensors and the present labor-intensive, mission-specific techniques for processing and routing data become prohibitively. This paper describes how an IP-based communication architecture can support all existing operations concepts and how it will enable some new and complex communication and science concepts. The authors identify specific end-to-end data flows from the instruments to the control centers and scientists, and then describe how each data flow can be supported using standard Internet protocols and applications. The scenarios include normal data downlink and command uplink as well as recovery scenarios for both onboard and ground failures. The scenarios are based on an Earth orbiting spacecraft with downlink data rates from 300 Kbps to 4 Mbps. Included examples are based on designs currently being investigated for potential use by the Global Precipitation Measurement (GPM) mission.

Prostate cancer (PCa) is the most common non-skin malignancy of men in developed countries. In spite of treatment with curative intent up to 30-40% of patients have disease recurrence after treatment, resulting from any combination of lymphatic, hematogenous, or contiguous local spread. The concept of early detection of PCa offer benefits in terms of reduced mortality, but at the cost of over-diagnosis and overtreatment of indolent disease. This is largely due to the random nature of conventional biopsies, with a risk of missing significant cancer and randomly hitting indolent disease. In the present thesis, diagnostic performance of MRI DWI and 11C Acetate PET/CT lymph node staging of intermediate and high risk PCa, was investigated, and additionally, predictive factors of regional lymph node metastases were evaluated. Further, additional value of targeted biopsies to conventional biopsies, for detection of clinically significant PCa, was investigated. In paper one and two, 53 and 40 patients with predominantly high risk PCa underwent 11C Acetate PET/CT and 3T MRI DWI, respectively, for lymph node staging, before extended pelvic lymph node dissection (ePLND). The sensitivity and specificity for PET/CT was 38% and 96% respectively. The sensitivity and specificity for MRI DWI was 55% and 90% respectively. In paper three, 53 patients with newly diagnosed PCa were included. All patients underwent multi-parametric MRI, followed by two cognitive targeted biopsies. Five more clinically significant cancers were detected by adding targeted biopsies to conventional biopsies. In paper four the value of quantitative and qualitative MRI DWI and 11C Acetate PET/CT parameters, alone and in combination, in predicting regional lymph node metastases were examined. ADCmean in lymph nodes and T-stage on MRI were independent predictors of lymph node metastases in multiple logistic regression analysis. In conclusion the specificity of diffusion weighted MRI and 11C Acetate PET/CT for lymph node staging was high, although the sensitivity was low. Predictive factors of regional lymph node metastases could be retrieved from diffusion weighted MRI and 11C Acetate PET/CT. By combining targeted biopsies with conventional biopsies the detection rate of clinically significant PCa could be increased.

Two trigonal tritopic ligands with different conformational degree of freedom: conformationally labile H3tcbpa (tris((4-carboxyl)phenylduryl)amine) and conformationally obstructed H3hmbqa (4,4′,4′′-(4,4,8,8,12,12-hexamethyl-8,12-dihydro-4H-benzo[9,1]quino-lizino[3,4,5,6,7-defg]acridine-2,6,10-triyl)tribenzoic acid) are assembled with square-planar paddle-wheel nodes with the aim of selective engineering of the frameworks with tbo and pto underlying net topologies. In the case of H3tcbpa, both topological types were obtained forming non-interpenetrated MOFs namely DUT-63 (tbo) and DUT-64 (pto). Whereas synthesis of DUT-63 proceeds under typical conditions, formation of DUT-64 requires an additional topology directing reagent (topological modifier). Solvothermal treatment of the conformationally hindered H3hmbqa ligand with the Cu-salt results exclusively in DUT-77 material, based on the single pto net. The possibility to insert the salen based metallated pillar ligand into networks with pto topology post-synthetically results in DUT-78 and DUT-79 materials (both ith-d) and opens new horizons for post-synthetic insertion of catalytically active metals within the above-mentioned topological type of frameworks.

Tanto a invasão local como o comprometimento de linfonodos cervicais tem grande impacto na sobrevida de pacientes portadores de carcinomas epidermóides de cabeça e pescoço. Em nosso trabalho nós primeiramente determinamos a expressão dos receptores de quimiocinas de CXCR1 a CXCR5, além de CCR7 e CX3CR1 pelo método do ensaio de proteção à ribonuclease (RPA) em 98 fragmentos de tumores primários, 91 fragmentos de mucosas adjacentes e 26 linfonodos comprometidos e correlacionamos estes dados com parâmetros anátomo-patológicos e sobrevida. CXCL12 ligante do receptor CXCR4 e CCL19 e CCL21 ambos ligantes de CCR7 foram determinados em 38 fragmentos de tumores, 33 mucosas adjacentes e 25 linfonodos comprometidos pela técnica de real-time PCR. Os tumores primários apresentam expressão aumentada do mRNA de CXCR1 (P=0.013), CXCR3 (P=0.008) e CXCR4 (P=0.025). Não observamos correlações entre status linfonodal ou tamanho de tumor. Os linfonodos comprometidos expressam mais mRNA dos receptores de quimiocinas CXCR4, CXCR5, CCR7 e CX3CR1 (todos com P<0.0001) em comparação aos tumores comprometidos. Observamos um aumento de sobrevida (P=0.048) e uma tendência a aumento de sobrevida livre de doença (P=0.074) nos pacientes negativos para a expressão de CX3CR1 (n=17) em comparação aos pacientes positivos (n=21) somente no subgrupo de pacientes portadores de carcinomas da cavidade oral. O mesmo foi observado com os pacientes CCR7 negativos também no subgrupo de pacientes portadores de carcinomas da cavidade oral, tanto em sobrevida global (P=0.024) como para sobrevida livre de doença (P=0.049). Em relação aos ligantes de quimiocinas observamos um aumento do mRNA de CCL21 em linfonodos comprometidos em relação aos tumores primários (P=0.059). Concluímos que a interação quimiotática entre CCR7 e de seu ligante CCL21, poderia ser um mecanismo de atração de células tumorais para os linfonodos em tumores de cavidade oral, além disso a negatividade da expressão do mRNA de CCR7 e CX3CR1 são candidatos marcadores de uma melhor sobrevida em carcinomas epidermóides de cavidade oral. / Local invasion and lymph nodal spread impact in the outcome of Head and Neck squamous cell carcinoma (HNSCC) patients (pts). We determined CXCR1-5, CCR7 and CX3CR1 mRNA expression by means of RNAse protection assay in 98 HNSCC primary tumors and 91 adjacent mucosa and 26 metastatic lymph nodes, correlating this data with outcome. CXCL12 and CCL19/CCL21, ligands for CXCR4 and CCR7, were determined in 38 tumor fragments, 33 adjacent mucosas and 25 de metastatic lymph nodes, by means of Quantitative Real-Time PCR. Tumors presented higher CXCR1 (P=0.013), CXCR3 (P=0.008) and CXCR4 mRNA (P=0.025) expression as compared to mucosa. No correlations are observed neither lymph nodal status nor tumor size impacted on chemokine receptor expression. Metastatic lymph nodes expressed more CXCR4, CXCR5, CCR7 and CX3CR1 (P<0.0001) as compared to matched tumors. We found a longer overall survival (OS) (P=0.048) and a trend toward longer disease free survival (DFS) (P=0.074) in CX3CR1 negative (n=17) as compared to positive pts (n=21) only in oral subgroup. The same occurred for CCR7 negative oral SCC, in terms of OS (P=0.024) and DFS (P=0.049). We conclude that, of the chemokine receptors here studied, CCR7 and CX3CR1 mRNA expression seems to better reflect outcome in oral subsite only. In addition, CCL21, a CCR7 ligand mRNAs is more expressed in metastatic lymph nodes than tumors (P=0.059). Further studies are warranted to confirm these results.

O presente estudo teve como objetivo caracterizar as alterações histológicas de pele, linfonodo e baço, determinar a densidade de parasitas e de células iNOS+, assim como correlacionar o parasitismo com a expressão de iNOS em pele, baço e linfonodo de cães naturalmente acometidos por leishmaniose visceral. Foram selecionados aleatoriamente, 28 cães infectados com Leishmania (Leishmania) infantum chagasi, oriundos do Centro de Controle de Zoonoses do município de Araçatuba, os quais foram distribuídos em dois grupos, de acordo com sinais clínicos e exames laboratoriais, em sintomáticos (n=18) e assintomáticos (n=10). Um grupo de 6 animais oriundos de área não endêmica para leishmaniose visceral foram empregados como controle negativo. As alterações histológicas de pele foram similares em ambos os grupos clínicos, sintomáticos e assintomáticos, e se caracterizaram por um infiltrado inflamatório na derme, formado por células mononucleares (macrófagos, linfócitos e plasmócitos), que variou de discreto a intenso. No linfonodo, as alterações histológicas foram também semelhantes entre os grupos clínicos, e se caracterizaram por hiperplasia e hipertrofia da área cortical e para-cortical, que variou de discreta a intensa; e por hiperplasia e hipertrofia de macrófagos na região medular, caracterizando em muitos casos uma linfadenite granulomatosa. No baço, alterações histológicas da polpa branca e polpa vermelha foram similares entre os grupos sintomáticos e assintomáticos, com hipoplasia e atrofia de polpa branca e, hipertorfia e hiperplasia de macrófagos na polpa vermelha, variando de moderado a intenso. Quanto ao número de formas amastigotas/mm2 tanto na pele, como no linfonodo e baço, não houve diferença estatisticamente significativa entre os grupos clínicos (p=0,2104), (p=0,2401) e (p=0,8869), respectivamente. Em relação à densidade de células iNOS+(células/mm2), observamos que a infecção por Leishmania levou ao aumento do número destas células na pele, no baço e no linfonodo em relação ao controle (p < 0,05). Porém, quando analisamos a densidade de células iNOS+ entre os grupos clínicos, sintomáticos e assintomáticos, não observamos diferença significativa tanto na pele (p=0,3026), como em linfonodo (p=0,3257) e baço (p=0,5940). Observou-se correlação fraca e não significativa entre a densidade de parasitas e a densidade de células expressando iNOS+ no tegumento; porém no linfonodo, verificou-se correlação negativa moderada e significante (p=0,0034) entre o parasitismo e a expressão de células iNOS+, assim como no baço (p=0,0329), sugerindo que o óxido nítrico deve exercer um papel importante no controle do parasitismo em vísceras / The present study aimed the characterization the histological features in skin, lymph nodes and spleen; determination of the parasitism density and the cells expressing iNOS; and correlation between the parasitism and the expression of iNOS in the skin, lymph nodes and spleen of dogs naturally committed by visceral leishmaniasis. Twenty-eight naturally infected dogs by Leishmania (Leishmania) infantum chagasi were selected randomly from the Zoonosis Control Center of Araçatuba municipality and distributed in two groups according to the clinical signs and laboratory exams, symptomatic (n=18) and asymptomatic (n=10) animals. A group of six animals from non-endemic region for visceral leishmaniais was used as negative control. Histological changes in skin were similar in both clinical groups, symptomatic and asymptomatic, and were characterized by a focal and diffuse inflammatory infiltrate in the dermis of mononuclear cells (macrophages, lymphocytes, plasmocytes), that varied from discrete to intense. In lymph nodes, the histological changes were also similar in both clinical groups, and were characterized by hyperplasia and hypertrophy of the cortical and para-cortical area, that varied from discrete to intense; and hyperplasia and hypertrophy of macrophages in the medullar region characterizing in many cases a granulomatous lymphadenitis. In spleen, the histological alterations in the white pulp and red pulp were similar in both clinical groups, with hypoplasia and hypotrophy of the white pulp and hypertrophy and hyperplasia of macrophages in red pulp varying from moderate to intense. Regarding the results of parasitism density (amastigotes/mm2), we did not observe any significant difference between the clinical groups in skin (p=0.2104), lymph nodes (p=0.2401) and spleen (p=0.8869). Concerning to the density of iNOS+ cells, we observed that the infection by Leishmania caused an increase in the number of these cells in the skin, in spleen and lymph nodes in relation to the control group (p < 0.05). However, when we analyzed the density (cells /mm2) of iNOS+ expressing cells in clinical groups, symptomatic and asymptomatic, we did not observe any significant difference in the skin (p=0.3026), in lymph nodes (p=0.3257) and spleen (p=0.5940). A weak and non-significant correlation was observed between the parasite density and the density of iNOS+ cells in the skin. However, in the lymph node a significant and moderate correlation (p=0.0034) was observed between the parasitism and iNOS+ cells, as well as in the spleen (p=0.0329), suggesting that nitric oxide plays an important role in the control of the parasitism in the viscera

INTRODUÇÃO: O status axilar é o fator prognóstico mais importante em câncer de mama. A biópsia de linfonodo sentinela (BLS) tornou-se o procedimento padrão no estadiamento axilar em pacientes com axila clinicamente negativa. O procedimento recomendado para pacientes com metástase em linfonodo sentinela (LS) inclui a linfadenectomia axilar completa (LAC). Porém questiona-se a necessidade da LAC em todos os pacientes com metástase em LS (MLS), particularmente naqueles com baixo risco de metástase em linfonodos axilares adicionais (Não-LS). Estimar de forma precisa a probabilidade de MLS e metástase em Não-LS (MNão-LS) pode auxiliar em muito o processo de decisão terapêutica. Os dados publicados referentes aos fatores preditivos de MLS e MNão-LS são de certa forma escassos. A forma de como esses dados são apresentados – geralmente expressos como razão de chance (odds-ratio) – dificulta o cálculo de probabilidade de MLS ou MNão-LS para um paciente em específico. Nesta tese, dois modelos de previsão computadorizados de fácil utilização foram desenvolvidos, utilizando-se um grande número de casos, para facilitar o cálculo de probabilidade de MLS e MNão-LS. MÉTODOS: Todos os dados clínico-patológicos foram coletados do banco de dados prospectivo de LS do Memorial Sloan-Kettering Cancer Center (MSKCC), Nova York, EUA. Os projetos de desenvolvimento de ambos os modelos foram aprovados pelo Institutional Review Board do MSKCC. Dois modelos foram desenvolvidos: Modelo de MLS (Modelo LS) e Modelo de metástase em Não-LS (Modelo Não-LS). No Modelo LS, os achados clínico-patológicos de 4.115 procedimentos subseqüentes de BLS (amostra de modelagem) foram submetidos à análise de regressão logística multivariada para se criar um modelo de previsão de MLS. Um software baseado nesse modelo foi desenvolvido utilizando-se as variáveis: idade, tamanho do tumor, tipo histológico, invasão vásculo-linfática (IVL), localização do tumor e multifocalidade. Esse modelo foi validado em uma amostra distinta (amostra de validação) com 1.792 BLSs subseqüentes. No Modelo Não-LS, os achados patológicos do tumor primário e das MLS, obtidas de 702 procedimentos de BLS (amostra de modelagem) em pacientes submetidos à LAC, foram submetidos à análise de regressão logística multivariada para se criar um modelo de previsão de MNão-LS. Um nomograma e um software baseados nesse modelo foram desenvolvidos utilizando-se as variáveis: tamanho do tumor, tipo histológico, grau nuclear, IVL, multifocalidade, receptor de estrógeno, método de detecção da MLS, número de LS positivos, número de LS negativos. Esse modelo foi validado em uma amostra distinta (amostra de validação) com 373 casos subseqüentes. RESULTADOS: O software do Modelo LS na amostra de modelagem mostrou-se adequado, com a área sob a curva de características operacionais (ROC) de 0,76. Quando aplicado na amostra de validação, o Modelo LS também previu de forma acurada as probabilidades de MLS (ROC = 0,76). O software e o nomograma do Modelo Não-LS na amostra de modelagem apresentaram uma área ob a curva ROC de 0,76 e, na amostra de validação, 0,77. CONCLUSÕES: Dois softwares de fácil utilização foram desenvolvidos, utilizando-se informações comumente disponíveis pelo cirurgião para calcular para o paciente a probabilidade de MLS e MNão-LS de forma precisa, fácil e individualizada. O software do Modelo LS não deve ser utilizado, porém, para se evitar a BLS. Para download dos softawares clique em: <A HREF="http://www.mastologia.com" TARGET="_BLANK">www.mastologia.com . / INTRODUCTION: Axillary lymph node status is the most significant prognostic factor in breast cancer. Sentinel lymph node biopsy (SLNB) has become the standard of care as the axillary staging procedure in clinically node negative patients. The standard procedure for patients with sentinel lymph node (SLN) metastasis includes complete axillary lymph node dissection (ALND). However, many experts question the need for complete ALND in every patient with detectable SLN metastases, particularly those perceived to have a low risk of additional lymph node (Non-SLN) metastasis. Accurate estimates of the likelihood of SLN metastases and additional disease in the axilla could greatly assist in decision-making treatment. The published data on predictive factors for SLN and Non-SLN metastases is somewhat scarce. It is also difficult to apply these data – usually expressed as odds ratio – to calculate the probability of SLN or Non-SLN metastases for a specific patient. In this thesis, two user-friendly computerized prediction models based on large datasets were developed, to assist the prediction of the presence of SLN and Non-SLN metastases. METHODS: All clinical and pathological data were collected from the prospective SLN database of Memorial Sloan-Kettering Cancer Center (MSKCC), New York, USA. The development projects of both models were approved by the Institutional Review Board of MSKCC. Two models were developed: Model for predicting SLN metastases (SLN Model) and Model for predicting Non-SLN metastases (Non-SLN Model). In the SLN Model, clinical and pathological features of 4,115 sequential SLNB procedures (modeling sample) were assessed with multivariable logistic regression to predict the presence SLN metastases. A software based on the logistic regression model was created using age, tumor size, tumor type, lymphovascular invasion, tumor location and multifocality. This model was subsequently applied to another set of 1,792 sequential SLNBs (validation sample). In the Non-SLN Model, pathological features of the primary tumor and SLN metastases, identified in 702 SLNBs (modeling sample) on patients who underwent complete ALND, were assessed with multivariable logistic regression to predict the presence of additional disease in the Non-SLNs of these patients. A nomogram and a software were created using tumor size, tumor type and nuclear grade, lymphovascular invasion, multifocality, and estrogen-receptor status of the primary tumor; method of detection of SLN metastases; number of positive SLNs; and number of negative SLNs. This model was subsequently applied to another set of sequential 373 procedures (validation sample). RESULTS: The software of the SLN Model for the modeling sample was accurate and discriminating, with an area under the receiver operating characteristic (ROC) curve of 0.76. When applied to the validation sample, the SLN-Model accurately predicted likelihood of SLN metastases (ROC = 0.76). The software and nomogram of the Non-SLN Model was also accurately predicted likelihood of Non-SLN metastases, with an area under ROC curve of 0.76 for the modeling sample, and 0.77 for the validation sample. CONCLUSION: Two user-friendly softwares were developed, using information commonly available to the surgeon to easily and accurately calculate the likelihood of having SLN metastases or additional, Non-SLN metastases for individual patients. However, the software of the SLN Model should not be used to avoid SLNB. Click on <A HREF="http://www.mastologia.com" TARGET="_BLANK">www.mastologia.com to download these softwares.

Flextensional actuators assembled in association with piezoceramics feature the amplification of nanometric displacements generated by the ceramics energy conversion. For applications that require high precision positioning or vibration response attenuation, such as hard disc reading or atomic force microscopy, a response tracking control needs to be implemented. Shell and plate piezoactuators with vibration control have been extensively studied in literature, however the design of controlled piezoelectric systems by means of the Topology Optimization Method (TOM) has not been fully explored in literature yet, and is generally focused on the frequency domain transient analysis, which employs a model reduction method for the sake of computational implementation. Dealing with transient analysis of flextensional piezoelectric actuators, an active closed loop control design is more suited for the positioning and vibration problem, which consists on measuring the outputs of the system by the closed loop sensor layer, whose signal is modified by a control gain and eventually inputted into the actuator layer so the system response signal is modulated. Aiming to enhance the active feedback control in piezoelectric actuators (PEAs), this work targets the design of the flextensional microstructure considering an active velocity feedback control (AVFC), where the active piezoelectric sensing and actuating cycles imply in an extra damping to the system. Therefore, the flextensional mechanism compliance shall be distributed within the design domain by the allocation of void regions where there should be the flexible hinges. Such a design can be accomplished by means of the TOM, which employs a systematic analysis of the dynamic model through the finite element method (FEM). In this work, the finite element (FE) system model takes into account the piezoelectric ceramics intermediate nodes, what is denominated as non-collapsed piezoelectric nodes model, and whose induced voltage during the time domain dynamic response contributes to the active control of the system. The topology optimization (TO) problem is formulated for the system vibration suppression at the restoring position and at the actuated position (positioner) subject to material volume and design variables constraints. The TOM implemented is based on the solid isotropic material with penalization (SIMP), the dynamic adjoint sensitivity, and on the optimization solver known as sequential linear programming (SLP). To illustrate the method, bidimensional examples of optimized topologies are numerically obtained by employing different velocity feedback control gains, and the topologies efficiency are compared and contrasted. / Atuadores piezoelétricos flextensionais funcionam como amplificadores nanométricos dos deslocamentos gerados pela piezocerâmica. Em sistemas que necessitam de alta precisão de posicionamento final ou baixa energia de vibração após sofrer um impacto, como na leitura de um disco rígido ou na microscopia de força atômica, requer-se que o atuador conte com um fator de correção de posicionamento, o qual pode ser obtido através de uma lei de controle. A utilização de material piezoelétrico para o controle de vibração em dispositivos de casca e placa foi amplamente abordado na literatura, porém o projeto de sistemas piezoelétricos controlados utilizando-se do Método da Otimização Topológica (MOT) foi pouco explorado e em geral é focado na análise transiente no domínio da frequência, o qual necessita que o problema tenha que ser reduzido para que a implementação computacional torne-se viável. Tratando-se de análise transiente em atuadores piezoelétricos flextensionais pode-se considerar o emprego de um controle ativo, o qual captura informações do dispositivo através de piezo-sensores e as realimenta na forma de um sinal de entrada em piezo-atuadores para modulação do sinal de resposta. Visando aprimorar o efeito do controle ativo em atuadores piezelétricos, este trabalho é voltado para o projeto de sua estrutura flextensional considerando o controle ativo de realimentação de velocidade, em que o ciclo envolvendo sensoreamento e atuação piezoelétricos fornece um amortecimento extra ao sistema. Deseja-se portanto que a flexibilidade do mecanismo flextensional seja distribuída no domínio de projeto pré-definido alocando vazios em regiões ao redor de onde devem estar presentes articulações da estrutura flexível, o que é obtido pelo MOT. Para encontrar a distribuição otimizada de material no domínio de projeto, o MOT emprega a análise sistemática do modelo dinâmico através do Método dos Elementos Finitos (MEF). Neste trabalho a modelagem do sistema para o MEF leva em consideração a presença dos nós intermediários das cerâmicas piezoelétricas, denominada modelagem para nós não colapsados, cuja tensão gerada ao longo da resposta dinâmica temporal influencia no controle ativo do sistema. O problema de Otimização Topológica (OT) é formulado para a atenuação da vibração do sistema em posição neutra e em posição atuada (posicionador) sujeito a restrições de volume e a valores máximo e mínimo que as variaveis de projeto assumem. A implementação do MOT é baseada no modelo de material denominado Material Isotrópico Sólido com Penalização (MISP), no cálculo da sensibilidade dinâmica adjunta, e na rotina de otimização conhecida como Programação Linear Sequencial (PLS). Para ilustrar o método, são projetados dispositivos bidimensionais e diferentes ganhos de controle de realimentação de velocidade são utilizados para obtenção da topologia otimizada, analisando-se a eficiência em cada caso.

Les réseaux pair-à-pair (P2P) constituent un modèle de plus en plus populaire pour la programmation d’applications Internet car ils favorisent la décentralisation, le passage à l’échelle, la tolérance aux pannes et l’auto-organisation. à la différence du modèle traditionnel client-serveur, un réseau P2P est un système réparti décentralisé dans lequel tous les nœuds interagissent directement entre eux et jouent à la fois les rôles de fournisseur et d’utilisateur de services et de ressources. Une table de hachage distribuée (DHT) est réalisée par un réseauP2P et offre les mêmes services qu’une table de hachage classique, hormis le fait que les différents couples (clef, valeur) sont stockés dans différents nœuds du réseau. La fonction principale d’une DHT est la recherche d’une valeur associée à une clef donnée. Parmi les protocoles réalisant une DHT on peut nommer Chord, Pastry, Kademlia et Tapestry. Ces protocoles promettent de garantir certaines propriétés de correction et de performance ; or, les tentatives de démontrer formellement de telles propriétés se heurtent invariablement à des cas limites dans lesquels certaines propriétés sont violées. Tian-xiang Lu a ainsi décrit des problèmes de correction dans des versions publiées de Pastry. Il a conçu un modèle, appelé LuPastry, pour lequel il a fourni une preuve partielle, mécanisée dans l’assistant à la preuve TLA+ Proof System, démontrant que les messages de recherche de clef sont acheminés au bon nœud du réseau dans le cas sans départ de nœuds. En analysant la preuve de Lu j’ai découvert qu’elle contenait beaucoup d’hypothèses pour lesquelles aucune preuve n’avait été fournie, et j’ai pu trouver des contre-exemples à plusieurs de ces hypothèses. La présente thèse apporte trois contributions. Premièrement, je présente LuPastry+, une spécification TLA+ revue de LuPastry. Au-delà des corrections nécessaires d’erreurs, LuPastry+ améliore LuPastry en introduisant de nouveaux opérateurs et définitions, conduisant à une spécification plus modulaire et isolant la complexité de raisonnement à des parties circonscrites de la preuve, contribuant ainsi à automatiser davantage la preuve. Deuxièmement, je présente une preuve TLA+ complète de l’acheminement correct dans LuPastry+. Enfin, je démontre que l’étape finale du processus d’intégration de nœuds dans LuPastry (et LuPastry+) n’est pas nécessaire pour garantir la cohérence du protocole. Concrètement, j’exhibe une nouvelle spécification avec un processus simplifié d’intégration de nœuds, que j’appelle Simplified LuPastry+, et je démontre qu’elle garantit le bon acheminement de messages de recherche de clefs. La preuve de correction pour Simplified LuPastry+ est obtenue en réutilisant la preuve pour LuPastry+, et ceci représente un bon succès pour la réutilisation de preuves, en particulier considérant la taille de ces preuves. Chacune des deux preuves requiert plus de 30000 étapes interactives ; à ma connaissance, ces preuves constituent les preuves les plus longues écrites dans le langage TLA+ à ce jour, et les seuls exemples d’application de preuves mécanisées de théorèmes pour la vérification de protocoles DHT / A distributed hash table (DHT) is a peer-to-peer network that offers the function of a classic hash table, but where different key-value pairs are stored at different nodes on the network. Like a classic hash table, the main function provided by a DHT is key lookup, which retrieves the value stored at a given key. Examples of DHT protocols include Chord, Pastry, Kademlia and Tapestry. Such DHT protocols certain correctness and performance guarantees, but formal verification typically discovers border cases that violate those guarantees. In his PhD thesis, Tianxiang Lu reported correctness problems in published versions of Pastry and developed a model called {\LP}, for which he provided a partial proof of correct delivery of lookup messages assuming no node failure, mechanized in the {\TLA} Proof System. In analyzing Lu's proof, I discovered that it contained unproven assumptions, and found counterexamples to several of these assumptions. The contribution of this thesis is threefold. First, I present {\LPP}, a revised {\TLA} specification of {\LP}. Aside from needed bug fixes, {\LPP} contains new definitions that make the specification more modular and significantly improve proof automation. Second, I present a complete {\TLA} proof of correct delivery for {\LPP}. Third, I prove that the final step of the node join process of {\LP}/{\LPP} is not necessary to achieve consistency. In particular, I develop a new specification with a simpler node join process, which I denote by {\SLP}, and prove correct delivery of lookup messages for this new specification. The proof of correctness of {\SLP} is written by reusing the proof for {\LPP}, which represents a success story in proof reuse, especially for proofs of this size. Each of the two proofs amounts to over 32,000 proof steps; to my knowledge, they are currently the largest proofs written in the {\TLA} language, and---together with Lu's proof---the only examples of applying full theorem proving for the verification of DHT protocols

O presente estudo teve como objetivo caracterizar as alterações histológicas de pele, linfonodo e baço, determinar a densidade de parasitas e de células iNOS+, assim como correlacionar o parasitismo com a expressão de iNOS em pele, baço e linfonodo de cães naturalmente acometidos por leishmaniose visceral. Foram selecionados aleatoriamente, 28 cães infectados com Leishmania (Leishmania) infantum chagasi, oriundos do Centro de Controle de Zoonoses do município de Araçatuba, os quais foram distribuídos em dois grupos, de acordo com sinais clínicos e exames laboratoriais, em sintomáticos (n=18) e assintomáticos (n=10). Um grupo de 6 animais oriundos de área não endêmica para leishmaniose visceral foram empregados como controle negativo. As alterações histológicas de pele foram similares em ambos os grupos clínicos, sintomáticos e assintomáticos, e se caracterizaram por um infiltrado inflamatório na derme, formado por células mononucleares (macrófagos, linfócitos e plasmócitos), que variou de discreto a intenso. No linfonodo, as alterações histológicas foram também semelhantes entre os grupos clínicos, e se caracterizaram por hiperplasia e hipertrofia da área cortical e para-cortical, que variou de discreta a intensa; e por hiperplasia e hipertrofia de macrófagos na região medular, caracterizando em muitos casos uma linfadenite granulomatosa. No baço, alterações histológicas da polpa branca e polpa vermelha foram similares entre os grupos sintomáticos e assintomáticos, com hipoplasia e atrofia de polpa branca e, hipertorfia e hiperplasia de macrófagos na polpa vermelha, variando de moderado a intenso. Quanto ao número de formas amastigotas/mm2 tanto na pele, como no linfonodo e baço, não houve diferença estatisticamente significativa entre os grupos clínicos (p=0,2104), (p=0,2401) e (p=0,8869), respectivamente. Em relação à densidade de células iNOS+(células/mm2), observamos que a infecção por Leishmania levou ao aumento do número destas células na pele, no baço e no linfonodo em relação ao controle (p < 0,05). Porém, quando analisamos a densidade de células iNOS+ entre os grupos clínicos, sintomáticos e assintomáticos, não observamos diferença significativa tanto na pele (p=0,3026), como em linfonodo (p=0,3257) e baço (p=0,5940). Observou-se correlação fraca e não significativa entre a densidade de parasitas e a densidade de células expressando iNOS+ no tegumento; porém no linfonodo, verificou-se correlação negativa moderada e significante (p=0,0034) entre o parasitismo e a expressão de células iNOS+, assim como no baço (p=0,0329), sugerindo que o óxido nítrico deve exercer um papel importante no controle do parasitismo em vísceras / The present study aimed the characterization the histological features in skin, lymph nodes and spleen; determination of the parasitism density and the cells expressing iNOS; and correlation between the parasitism and the expression of iNOS in the skin, lymph nodes and spleen of dogs naturally committed by visceral leishmaniasis. Twenty-eight naturally infected dogs by Leishmania (Leishmania) infantum chagasi were selected randomly from the Zoonosis Control Center of Araçatuba municipality and distributed in two groups according to the clinical signs and laboratory exams, symptomatic (n=18) and asymptomatic (n=10) animals. A group of six animals from non-endemic region for visceral leishmaniais was used as negative control. Histological changes in skin were similar in both clinical groups, symptomatic and asymptomatic, and were characterized by a focal and diffuse inflammatory infiltrate in the dermis of mononuclear cells (macrophages, lymphocytes, plasmocytes), that varied from discrete to intense. In lymph nodes, the histological changes were also similar in both clinical groups, and were characterized by hyperplasia and hypertrophy of the cortical and para-cortical area, that varied from discrete to intense; and hyperplasia and hypertrophy of macrophages in the medullar region characterizing in many cases a granulomatous lymphadenitis. In spleen, the histological alterations in the white pulp and red pulp were similar in both clinical groups, with hypoplasia and hypotrophy of the white pulp and hypertrophy and hyperplasia of macrophages in red pulp varying from moderate to intense. Regarding the results of parasitism density (amastigotes/mm2), we did not observe any significant difference between the clinical groups in skin (p=0.2104), lymph nodes (p=0.2401) and spleen (p=0.8869). Concerning to the density of iNOS+ cells, we observed that the infection by Leishmania caused an increase in the number of these cells in the skin, in spleen and lymph nodes in relation to the control group (p < 0.05). However, when we analyzed the density (cells /mm2) of iNOS+ expressing cells in clinical groups, symptomatic and asymptomatic, we did not observe any significant difference in the skin (p=0.3026), in lymph nodes (p=0.3257) and spleen (p=0.5940). A weak and non-significant correlation was observed between the parasite density and the density of iNOS+ cells in the skin. However, in the lymph node a significant and moderate correlation (p=0.0034) was observed between the parasitism and iNOS+ cells, as well as in the spleen (p=0.0329), suggesting that nitric oxide plays an important role in the control of the parasitism in the viscera

A expressão de E-caderina (Ecad) pode ser regulada pré ou pós transcricionalmente por Snail e Hakai, respectivamente. Nosso objetivo foi determinar a expressão de Ecad, Snail e Hakai, em células epiteliais (CE) de tecido tumoral e peritumoral de pacientes com carcinoma ductal invasivo da mama e correlacionar sua expressão ao comprometimento linfonodal axilar (LN+). As CE de amostras de tecidos de 45 pacientes (52% LN+) foram extraídas por método imunomagnético, o RNA foi extraído por RT-PCR em tempo real e utilizou-se primers específicos para a moléculas. A expressão de Ecad, Snail e Hakai não variou entre o tecido tumoral e peritumoral e não houve correlação com comprometimento linfonodal / E-cadherin (Ecad) expression may be transcriptionally or post-transcriptionally regulated by Snail and Hakai. Our aim was to determine the expression of Ecad, Snail and Hakai, in epithelial cells (EC) obtained from tumor and its adjacent tissue from women with invasive ductal breast carcinoma (IDC) and evaluate their correlation to the axillary's lymph node (LN+) involvement. Tissue from 45 patients (52% LN+) had their EC recovered by immunomagnetic antibody process, RNA was extracted and real-time RT-PCR was performed using specific primers. Ecad, Snail and Hakai mRNA expression did not vary between tumoral and peritumoral samples and their expression was not correlated to LN involvement