Heterologous prime-boost immunization strategies can evoke powerful T cell immune responses and may be of value in developing an improved tuberculosis vaccine. We show that recombinant modified vaccinia virus Ankara, expressing Mycobacterium tuberculosis Ag 85A (M.85A), strongly boosts bacille Calmette-Guérin (BCG)-induced Ag 85A specific CD4+ and CD8+ T cell responses in mice. A comparison of intranasal (i.n.) and parenteral immunization of BCG showed that while both routes elicited comparable T cell responses in the spleen, only i.n. delivery elicited specific T cell responses in the lung lymph nodes, and these responses were further boosted by i.n. delivery of M.85A. Following aerosol challenge with M. tuberculosis, i.n. boosting of BCG with either BCG or M.85A afforded unprecedented levels of protection in both the lungs (2.5 log) and spleens (1.5 log) compared with naive controls. Protection in the lung correlated with the induction of Ag 85A-specific, IFN-γ-secreting T cells in lung lymph nodes. These findings support further evaluation of mucosally targeted prime-boost vaccination approaches for tuberculosis.
Abstract-In this paper, we present our experiences in using symbolic model checking to analyze a specification of a software system for aircraft collision avoidance. Symbolic model checking has been highly successful when applied to hardware systems. We are interested in whether model checking can be effectively applied to large software specifications. To investigate this, we translated a portion of the state-based system requirements specification of Traffic Alert and Collision Avoidance System II (TCAS II) into input to a symbolic model checker (SMV). We successfully used the symbolic model checker to analyze a number of properties of the system. We report on our experiences, describing our approach to translating the specification to the SMV language, explaining our methods for achieving acceptable performance, and giving a summary of the properties analyzed. Based on our experiences, we discuss the possibility of using model checking to aid specification development by iteratively applying the technique early in the development cycle. We consider the paper to be a data point for optimism about the potential for more widespread application of model checking to software systems.
In this paper, we prove new upper bounds on the complexity of the certified write-all problem with respect to an adaptive adversary. Our strongest result is that for any ǫ > 0, there exists an O(p 1+ǫ) work algorithm for the p-processor p-memory cell write-all. We also give a randomized O(p 2 log p) work algorithm for a p-processor p 2-memory cell write-all.
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