Transformation in HaRe

HaRe [?] is a system developed at the University of Kent Computing Laboratory to support refactoring in Haskell. We also want HaRe to be an open platform to support general Haskell program transformation so it can be used by other researchers in the field. This paper demonstrates the facilities HaRe provides for program transformation by implementing a deforestation transformation as a case study

Contributions of the pore-forming toxin Listeriolysin O to Listeria monocytogenes pathogenesis

Listeriolysin O (LLO) is an essential determinant of Listeria monocytogenes pathogenesis that mediates the escape of L. monocytogenes from host cell vacuoles, thereby allowing replication in the cytosol without causing appreciable cell death. As a member of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins, LLO is unique in that it is secreted by a facultative intracellular pathogen, whereas all other CDCs are produced by pathogens that are largely extracellular. Deletion of the gene encoding LLO, hly, or replacement of LLO with other CDCs results in strains that are 10,000-fold less virulent during mouse infections. Deletion of LLO also results in a strain that is immunosuppressive in mice. LLO has structural and regulatory features that allow it to function intracellularly without causing cell death, most of which map to a unique N-terminal region of LLO referred to as the PEST-like sequence. Yet, while LLO has unique properties required for its intracellular site of action, extracellular LLO, like other CDCs, affects cells in myriad ways. Because all CDCs form pores in cholesterol-containing membranes that lead to rapid Ca2+ influx and K+ efflux, they consequently trigger a wide range of host cell responses, including MAPK activation, histone modification, and caspase-1 activation. There is no debate that extracellular LLO, like all other CDCs, can stimulate multiple cellular activities, but the primary question we wish to address is whether LLO secreted in the cytosol has an impact on pathogenesis.To address whether LLO secreted in the cytosol impacts the pathogenesis of L. monocytogenes we engineered a strain, referred to as hlyfl, that deletes hly after escape from phagocytic vacuoles. Using hlyfl, we determined that LLO secreted in the cytosol causes cytotoxicity that impairs the growth of L. monocytogenes in macrophages. However, this strain was less virulent in mice than WT L. monocytogenes because it had a defect in cell-to-cell spread. Furthermore, the strain was not as effective at inducing protective immunity in mice as a strain that was defective in cell-to-cell spread due to a defect in actin-based motility. We hypothesized that hlyfl was not as effective at inducing protective immunity because, like LLO-deficient strains, it induced IL-10. Administration of anti-IL-10 receptor blocking antibody improved the protective capacity of vaccination with hlyfl, indicating that bacterial localization in primary and secondary vacuoles leads to the induction of IL-10, which is immunosuppressive.To determine the bacterial components that lead to the induction of IL-10 by bacteria that cannot escape phagocytic vacuoles, we performed a genetic screen of transposon mutants for their ability to induce enhanced or diminished IL-10 from infected bone marrow-derived macrophages. We identified bacterial lipoproteins, which are recognized by TLR2, as the primary signal for IL-10 induction in macrophages. However, bacterial mutants that had increased lysis induced enhanced IL-10, which was dependent on signaling of endosomal TLRs. In mice, IL-10 induction and immune suppression was primarily mediated by endosomal TLRs. In summary, though LLO may cause some cytotoxicity it is absolutely required for escape from primary and secondary vacuoles. LLO-deficient mutants are avirulent, and they also lyse in vacuoles and induce expression of IL-10, which is immunosuppressive

On the pure state outcomes of Einstein-Podolsky-Rosen steering

In the Einstein--Podolsky--Rosen experiment, when Alice makes a measurement on her part of a bipartite system, Bob's part is collapsed to, or steered to, a specific ensemble. Moreover, by reading her measurement outcome, Alice can specify which state in the ensemble Bob's system is steered to and with which probability. The possible states that Alice can steer Bob's system to are called steered states. In this work, we study the subset of steered states which are pure after normalisation. We illustrate that these pure steered states, if they exist, often carry interesting information about the shared bipartite state. This information content becomes particularly clear when we study the purification of the shared state. Some applications are discussed. These include a generalisation of the fundamental lemma in the so-called `all-versus-nothing proof of steerability' for systems of arbitrary dimension.Comment: 7 pages, 0 figures; corrected typos and terminolog