577 research outputs found

    Hilbert-Post completeness for the state and the exception effects

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    In this paper, we present a novel framework for studying the syntactic completeness of computational effects and we apply it to the exception effect. When applied to the states effect, our framework can be seen as a generalization of Pretnar's work on this subject. We first introduce a relative notion of Hilbert-Post completeness, well-suited to the composition of effects. Then we prove that the exception effect is relatively Hilbert-Post complete, as well as the "core" language which may be used for implementing it; these proofs have been formalized and checked with the proof assistant Coq.Comment: Siegfried Rump (Hamburg University of Technology), Chee Yap (Courant Institute, NYU). Sixth International Conference on Mathematical Aspects of Computer and Information Sciences , Nov 2015, Berlin, Germany. 2015, LNC

    The chloroplast RNA helicase ISE2 is required for multiple chloroplast RNA processing steps in Arabidopsis thaliana

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    INCREASED SIZE EXCLUSION LIMIT2 (ISE2) is a chloroplast-localized RNA helicase that is indispensable for proper plant development. Chloroplasts in leaves with reduced ISE2expression have previously been shown to exhibit reduced thylakoid contents and increased stromal volume, indicative of defective development. It has recently been reported that ISE2 is required for the splicing of group II introns from chloroplast transcripts. The current study extends these findings, and presents evidence for ISE2’s role in multiple aspects of chloroplast RNA processing beyond group II intron splicing. Loss of ISE2 from Arabidopsis thaliana leaves resulted in defects in C-to-U RNA editing, altered accumulation of chloroplast transcripts and chloroplast-encoded proteins, and defective processing of chloroplast ribosomal RNAs. Potential ISE2 substrates were identified by RNA immunoprecipitation followed by next-generation sequencing (RIP-seq), and the diversity of RNA species identified supports ISE2’s involvement in multiple aspects of chloroplast RNA metabolism. Comprehensive phylogenetic analyses revealed that ISE2 is a non-canonical Ski2-like RNA helicase that represents a separate sub-clade unique to green photosynthetic organisms, consistent with its function as an essential protein. Thus ISE2’s evolutionary conservation may be explained by its numerous roles in regulating chloroplast gene expression

    On coalgebras with internal moves

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    In the first part of the paper we recall the coalgebraic approach to handling the so-called invisible transitions that appear in different state-based systems semantics. We claim that these transitions are always part of the unit of a certain monad. Hence, coalgebras with internal moves are exactly coalgebras over a monadic type. The rest of the paper is devoted to supporting our claim by studying two important behavioural equivalences for state-based systems with internal moves, namely: weak bisimulation and trace semantics. We continue our research on weak bisimulations for coalgebras over order enriched monads. The key notions used in this paper and proposed by us in our previous work are the notions of an order saturation monad and a saturator. A saturator operator can be intuitively understood as a reflexive, transitive closure operator. There are two approaches towards defining saturators for coalgebras with internal moves. Here, we give necessary conditions for them to yield the same notion of weak bisimulation. Finally, we propose a definition of trace semantics for coalgebras with silent moves via a uniform fixed point operator. We compare strong and weak bisimilation together with trace semantics for coalgebras with internal steps.Comment: Article: 23 pages, Appendix: 3 page

    Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression

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    <p>Abstract</p> <p>Background</p> <p>Neuropilin-2 (Nrp2) is a receptor for vascular endothelial growth factor-C (VEGF-C), which is a well-known lymphangiogenic factor and plays an important role in lymph node metastasis of various human cancers, including breast cancer. Recently, Nrp2 was shown to play a role in cancer by promoting tumor cell metastasis. CXC chemokine receptor 4 (CXCR4) also promotes tumor metastasis. In the previous studies, we demonstrated that VEGF-C and cytoplasmic CXCR4 expressions were correlated with poorer patient prognosis (BMC Cancer 2008,8:340; Breast Cancer Res Treat 2005, 91:125–132).</p> <p>Methods</p> <p>The relationship between Nrp2 expression and lymph node metastasis, VEGF-C expression, CXCR4 expression, and other established clinicopathological variables (these data were cited in our previous papers), including prognosis, was analyzed in human breast cancer. Effects of neutralizing anti-Nrp2 antibody on CXCR4 expression and chemotaxis were assessed in MDA-MB-231 breast cancer cells.</p> <p>Results</p> <p>Nrp2 expression was observed in 53.1% (60 of 113) of the invasive breast carcinomas. Nrp2 expression was significantly correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Survival curves determined by the Kaplan-Meier method showed that Nrp2 expression was associated with reduced overall survival. In multivariate analysis, Nrp2 expression emerged as a significant independent predictor for overall survival. Neutralizing anti-Nrp2 antibody blocks cytoplasmic CXCR4 expression and CXCR4-induced migration in MDA-MB-231 cells.</p> <p>Conclusion</p> <p>Nrp2 expression was correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Nrp2 expression may serve as a significant prognostic factor for long-term survival in breast cancer. Our data also showed a role for Nrp2 in regulating cytoplasmic CXCR4 expression <it>in vitro</it>.</p

    Synthesis and Biological Evaluation of 2-Methyl-4,5-Disubstituted Oxazoles as a Novel Class of Highly Potent Antitubulin Agents

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    Antimitotic agents that interfere with microtubule formation are one of the major classes of cytotoxic drugs for cancer treatment. Multiple 2-methyl-4-(3′,4′,5′-trimethoxyphenyl)-5-substituted oxazoles and their related 4-substituted-5-(3′,4′,5′-trimethoxyphenyl) regioisomeric derivatives designed as cis-constrained combretastatin A-4 (CA-4) analogues were synthesized and evaluated for their antiproliferative activity in vitro against a panel of cancer cell lines and, for selected highly active compounds, interaction with tubulin, cell cycle effects and in vivo potency. Both these series of compounds were characterized by the presence of a common 3′,4′,5′-trimethoxyphenyl ring at either the C-4 or C-5 position of the 2-methyloxazole ring. Compounds 4g and 4i, bearing a m-fluoro-p-methoxyphenyl or p-ethoxyphenyl moiety at the 5-position of 2-methyloxazole nucleus, respectively, exhibited the greatest antiproliferative activity, with IC50 values of 0.35-4.6 nM (4g) and 0.5–20.2 nM (4i), which are similar to those obtained with CA-4. These compounds bound to the colchicine site of tubulin and inhibited tubulin polymerization at submicromolar concentrations. Furthermore, 4i strongly induced apoptosis that follows the mitochondrial pathway. In vivo, 4i in a mouse syngeneic model demonstrated high antitumor activity which significantly reduced the tumor mass at doses ten times lower than that required for CA-4P, suggesting that 4i warrants further evaluation as a potential anticancer drug
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