On the Conversational Basis of Some Presuppositions

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Dynamic Pragmatics, or. Why We Shouldn't be Afraid of Embedded Implicature

This paper examines a particular case of embedded pragmatic effect, here dubbed "local pragmatic enrichment". I argue that local enrichment is fairly easily accommodated within semantic theories which take content to be structured. Two standard approaches to dynamic semantics, DRT and Heimian CCS, are discussed as candidates. Focusing on cases of local enrichment of disjuncts in clausal disjunctions, I point out that in these cases, local enrichment is driven by global felicity requirements, demonstrating that the local/global distinction is not a simple dichotomy

Disjunction and Anaphora

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Semantics and Pragmatics in the Interpretation of "or"

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An investigation of scalars in the antecedents of conditionals

An investigation of scalars in the antecedents of conditional

What projects and why

The empirical phenomenon at the center of this paper is projection, which we define (uncontroversially) as follows: (1) Definition of projection An implication projects if and only if it survives as an utterance implicatio

PentoRob: A Puzzle-Playing Robot for Dialogue Experiments

Hough J, Schlangen D. PentoRob: A Puzzle-Playing Robot for Dialogue Experiments. In: Hunter J, Simons M, Stone M, eds. Proceedings of JerSem: The 20th Workshop on the Semantics and Pragmatics of Dialogue. New Brunswick, NJ; 2016: 114-115

Design, computational studies, synthesis and in vitro antimicrobial evaluation of benzimidazole based thio-oxadiazole and thio-thiadiazole analogues

Background Two series of benzimidazole based thio-oxadiazole and thio-thiadiazole analogues were designed and synthesised as novel antimicrobial drugs through inhibition of phenylalanyl-tRNA synthetase (PheRS), which is a promising antimicrobial target. Compounds were designed to mimic the structural features of phenylalanyl adenylate (Phe-AMP) the PheRS natural substrate. Methods A 3D conformational alignment for the designed compounds and the PheRS natural substrate revealed a high level of conformational similarity, and a molecular docking study indicated the ability of the designed compounds to occupy both Phe-AMP binding pockets. A molecular dynamics (MD) simulation comparative study was performed to understand the binding interactions with PheRS from different bacterial microorganisms. The synthetic pathway of the designed compounds proceeded in five steps starting from benzimidazole. The fourteen synthesised compounds 5a-d, 6a-c, 8a-d and 9a-c were purified, fully characterised and obtained in high yield. Results In vitro antimicrobial evaluation against five bacterial strains showed a moderate activity of compound 8b with MIC value of 32 μg/mL against S. aureus, while all the synthesised compounds showed weak activity against both E. faecalis and P. aeruginosa (MIC 128 μg/mL). Conclusion Compound 8b provides a lead compound for further structural development to obtain high affinity PheRS inhibitors

Phenylalanyl tRNA synthetase (PheRS) substrate mimics: design, synthesis, molecular dynamics and antimicrobial evaluation

Antimicrobial resistance is a very challenging medical issue and identifying novel antimicrobial targets is one of the means to overcome this challenge. Phenylalanyl tRNA synthetase (PheRS) is a promising antimicrobial target owing to its unique structure and the possibility of selectivity in the design of inhibitors. Sixteen novel benzimidazole based compounds (5a–b), (6a–e), (7a–d), (9a–e) and three N,N-dimethyl-7-deazapurine based compounds (16a–c) were designed to mimic the natural substrate of PheRS, phenylalanyl adenylate (Phe-AMP), that was examined through flexible alignment. The compounds were successfully synthesised chemically in two schemes using 4 to 6-steps synthetic pathways, and evaluated against a panel of five microorganisms with the best activity observed against Enterococcus faecalis. To further investigate the designed compounds, a homology model of E. faecalis PheRS was generated, and PheRS-ligand complexes obtained through computational docking. The PheRS–ligand complexes were subjected to molecular dynamics simulations and computational binding affinity studies. As a conclusion, and using data from the computational studies compound 9e, containing the (2-naphthyl)-L-alanine and benzimidazole moieties, was identified as optimal with respect to occupancy of the active site and binding interactions within the phenylalanine and adenosine binding pockets