Hepatocytes may rupture after a drug overdose, and their intracellular contents act as damage-associated molecular patterns (DAMPs) that lead to additional leukocyte infiltration, amplifying the original injury. Necrosis-derived DNA can be recognized as a DAMP, activating liver non-parenchymal cells (NPCs). We hypothesized that NPCs react to DNA by releasing interferon (IFN)-1, which amplifies acetaminophen (APAP)-triggered liver necrosis. We orally overdosed different knockout mouse strains to investigate the pathways involved in DNA-mediated amplification of APAP-induced necrosis. Mice were imaged under intravital confocal microscopy to estimate injury progression, and hepatocytes and liver NPCs were differentially isolated for gene expression assays. Flow cytometry (FACS) using a fluorescent reporter mouse estimated the interferon-beta production by liver leukocytes under different injury conditions. We also treated mice with DNase to investigate the role of necrosis DNA signaling in IFN-1 production. Hepatocytes released a large amount of DNA after APAP overdose, which was not primarily sensed by these cells. However, liver NPCs promptly sensed such environmental disturbances and activated several DNA sensing pathways. Liver NPCs synthesized and released IFN-1, which was associated with concomitant hepatocyte necrosis. Ablation of IFN-1 recognition in interferon α/β receptor (IFNAR−/−) mice delayed APAP-mediated liver necrosis and dampened IFN-1 sensing pathways. We demonstrated a novel loop involving DNA recognition by hepatic NPCs and additional IFN-1 mediated hepatocyte death.
Este estudo tem como objetivo avaliar a eficácia da ferramenta TuPy Online na aprendizagem de disciplinas do curso de Ciência da Computação da Universidade do Estado do Rio de Janeiro (UERJ). O TuPy foi idealizado como uma ferramenta para visualização de execução de algoritmos, com ênfase na exibição de estruturas de dados em diferentes nı́veis de abstração. Este trabalho é o resultado da avaliação da aplicação sistemática da ferramenta em diversas turmas de Graduação e Pós-graduação. Utilizando a metodologia de Savi et al. para avaliação de aprendizagem, verificamos que a introdução da ferramenta produziu impacto positivo e, se considerado o aspecto de percepção dos alunos, um impacto ainda mais expressivo. Ambas análises foram validadas com significância estatı́stica.
Considerable effort has been made to create tools to support the teaching of programming logic, such as algorithm visualizers. One of them is TuPy Online which, besides having features for the representation of the state of variables for each step of the execution of a program, allows visualization of complex data structures, such as graphs or trees, in a convenient high level of abstraction. Moreover, the pseudo language employs a small set of commands, all in Portuguese language, complete enough to express any algorithm. In this work, we present TuPy Online and a study on the usability of this tool. We also measure its influence in the learning process of algorithms.Em 2018, um grupo de pesquisadores da Universidade do Estado do Rio de Janeiro (UERJ), idealizou a ferramenta TuPy Online 1 , como um software livre, para amparar e auxiliar estudantes na aprendizagem de algoritmos, e com três objetivos explícitos:
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