2,039 research outputs found

    Predicting the expected behavior of agents that learn about agents: the CLRI framework

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    We describe a framework and equations used to model and predict the behavior of multi-agent systems (MASs) with learning agents. A difference equation is used for calculating the progression of an agent's error in its decision function, thereby telling us how the agent is expected to fare in the MAS. The equation relies on parameters which capture the agent's learning abilities, such as its change rate, learning rate and retention rate, as well as relevant aspects of the MAS such as the impact that agents have on each other. We validate the framework with experimental results using reinforcement learning agents in a market system, as well as with other experimental results gathered from the AI literature. Finally, we use PAC-theory to show how to calculate bounds on the values of the learning parameters

    18F-4V for PET–CT Imaging of VCAM-1 Expression in Atherosclerosis

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    ObjectivesThe aim of this study was to iteratively develop and validate an 18F-labeled small vascular cell adhesion molecule (VCAM)-1 affinity ligand and demonstrate the feasibility of imaging VCAM-1 expression by positron emission tomography–computed tomography (PET-CT) in murine atherosclerotic arteries.BackgroundHybrid PET-CT imaging allows simultaneous assessment of atherosclerotic lesion morphology (CT) and may facilitate early risk assessment in individual patients. The early induction, confinement of expression to atherosclerotic lesions, and accessible position in proximity to the blood pool render the adhesion molecule VCAM-1 an attractive imaging biomarker for inflamed atheroma prone to complication.MethodsA cyclic, a linear, and an oligomer affinity peptide, internalized into endothelial cells by VCAM-1–mediated binding, were initially derivatized with DOTA to determine their binding profiles and pharmacokinetics. The lead compound was then 18F-labeled and tested in atherosclerotic apoE−/− mice receiving a high-cholesterol diet as well as wild type murine models of myocardial infarction and heart transplant rejection.ResultsThe tetrameric peptide had the highest affinity and specificity for VCAM-1 (97% inhibition with soluble VCAM-1 in vitro). In vivo PET-CT imaging using 18F-4V showed 0.31 ± 0.02 SUV in murine atheroma (ex vivo %IDGT 5.9 ± 1.5). 18F-4V uptake colocalized with atherosclerotic plaques on Oil Red O staining and correlated to mRNA levels of VCAM-1 measured by quantitative reverse transcription polymerase chain reaction (R = 0.79, p = 0.03). Atherosclerotic mice receiving an atorvastatin-enriched diet had significantly lower lesional uptake (p < 0.05). Furthermore, 18F-4V imaging in myocardial ischemia after coronary ligation and in transplanted cardiac allografts undergoing rejection showed high in vivo PET signal in inflamed myocardium and good correlation with ex vivo measurement of VCAM-1 mRNA by quantitative polymerase chain reaction.Conclusions 18F-4V allows noninvasive PET-CT imaging of VCAM-1 in inflammatory atherosclerosis, has the dynamic range to quantify treatment effects, and correlates with inflammatory gene expression

    Angiogenesis in Squamous Cervical Neoplasia: Comparative Study of two Endothelial Cells

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    Purpose: to compare the efficiency of anti-factor VIII and anti-CD34 antibodies as vascular makers in cervical cancer, in cervical intraepithelial neoplasia and in normal cervix. Methods: using an immunohistochemical method, factor VIII-related antigen and leukocyte antigen CD34, we performed microvascular counts in 18 squamous cell carcinomas, in 15 cervical high-grade intraepithelial neoplasia, in 15 low-grade intraepithelial lesions and in 10 normal cervices. Using light microscopy we counted microvessels per 400X field in the most active areas of neovascularization with higher microvessel density in each case. Results: the average of microvessels stained with anti-CD34 in invasive carcinoma, high-grade intraepithelial lesions, low-grade intraepithelial lesions and in the normal cervices was 154, 134, 112 and 93, respectively. When we used anti-factor VIII the average was 56, 44, 33 and 30 vessels, following the same order. High-grade intraepithelial lesions and invasive carcinomas showed greater means number of vessels than normal tissue. Conclusions: the use of anti-CD34 allowed the detection of a greater number of vessels when compared to anti-factor VIII. However, we could observe that anti-factor VIII staining was able to significantly discriminate high-grade from low-grade lesions.Objetivo: comparação entre a acurácia dos marcadores de células endoteliais anti-CD34 e anti-fator VIII em neoplasia cervical uterina, em lesões intra-epiteliais e no colo normal. Métodos: os antígenos CD34 e o fator VIII foram identificados, por meio de técnicas de imuno-histoquímica, em 18 fragmentos de neoplasia invasiva, 15 de lesão intra-epitelial de alto grau e 15 de baixo grau e 10 de colos normais, tidos como grupo controle. Fez-se a contagem dos vasos em 10 campos com aumento de 400X, na área de maior densidade vascular. O total de vasos de cada caso resultou da soma dos 10 campos. Resultados: as médias dos vasos corados com anti-CD34 no carcinoma invasivo, em lesão de alto grau, de baixo grau e no colo uterino normal foram 154, 135, 112 e 93 vasos, respectivamente. Com o uso do anti-fator VIII as médias das densidades vasculares foram 56, 44, 33 e 30 vasos, seguindo a mesma ordem das amostras. Lesões de alto grau e carcinomas invasivos do colo apresentaram médias de vasos maiores do que as de colos normais. Conclusões: o emprego do anti-CD34 permite detecção de maior número de vasos do que o uso de anti-fator VIII. Confirmou-se a utilidade de ambos os marcadores na avaliação da angiogênese. A angiogênese diferencia lesões de baixo e alto grau, utilizando-se anti-fator VIII, o que não ocorre com anti-CD34.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de GinecologiaUNIFESP, EPM, Depto. de GinecologiaSciEL
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