SHOP2: An HTN Planning System

The SHOP2 planning system received one of the awards for distinguished performance in the 2002 International Planning Competition. This paper describes the features of SHOP2 which enabled it to excel in the competition, especially those aspects of SHOP2 that deal with temporal and metric planning domains

Nicotine and Cotinine – two pharmacologically active substances as parameters for the strain on fetuses and babies of mothers who smoke

Peer Reviewe

High-altitude migration of Heteroptera in Britain

Heteroptera caught during day and night sampling at a height of 200 m above ground at Cardington, Bedfordshire, UK, during eight summers (1999, 2000, and 2002-2007) were compared to high-altitude catches made over the UK and North Sea from the 1930s to the 1950s. The height of these captures indicates that individuals were engaged in windborne migration over distances of at least several kilometres and probably tens of kilometres. This conclusion is generally supported by what is known of the species' ecologies, which reflect the view that the level of dispersiveness is associated with the exploitation of temporary habitats or resources. The seasonal timing of the heteropteran migrations is interpreted in terms of the breeding/overwintering cycles of the species concerned

Fluorescent artificial receptor-based membrane assay (FARMA) for spatiotemporally resolved monitoring of biomembrane permeability

The spatiotemporally resolved monitoring of membrane translocation, e.g., of drugs or toxins, has been a long-standing goal. Herein, we introduce the fluorescent artificial receptor-based membrane assay (FARMA), a facile, label-free method. With FARMA, the permeation of more than hundred organic compounds (drugs, toxins, pesticides, neurotransmitters, peptides, etc.) through vesicular phospholipid bilayer membranes has been monitored in real time (µs-h time scale) and with high sensitivity (nM-µM concentration), affording permeability coefficients across an exceptionally large range from 10$^{-9}$–10$^{-3}$ cm s$^{-1}$. From a fundamental point of view, FARMA constitutes a powerful tool to assess structure-permeability relationships and to test biophysical models for membrane passage. From an applied perspective, FARMA can be extended to high-throughput screening by adaption of the microplate reader format, to spatial monitoring of membrane permeation by microscopy imaging, and to the compartmentalized monitoring of enzymatic activity

Rapid optical determination of β-lactamase and antibiotic activity

Background: The absence of rapid tests evaluating antibiotic susceptibility results in the empirical prescription of antibiotics. This can lead to treatment failures due to escalating antibiotic resistance, and also furthers the emergence of drug-resistant bacteria. This study reports a rapid optical method to detect β-lactamase and thereby assess activity of β-lactam antibiotics, which could provide an approach for targeted prescription of antibiotics. The methodology is centred on a fluorescence quenching based probe (β-LEAF – β-Lactamase Enzyme Activated Fluorophore) that mimics the structure of β-lactam antibiotics. Results: The β-LEAF assay was performed for rapid determination of β-lactamase production and activity of β-lactam antibiotic (cefazolin) on a panel of Staphylococcus aureus ATCC strains and clinical isolates. Four of the clinical isolates were determined to be lactamase producers, with the capacity to inactivate cefazolin, out of the twenty-five isolates tested. These results were compared against gold standard methods, nitrocefin disk test for β-lactamase detection and disk diffusion for antibiotic susceptibility, showing results to be largely consistent. Furthermore, in the sub-set of β-lactamase producers, it was demonstrated and validated that multiple antibiotics (cefazolin, cefoxitin, cefepime) could be assessed simultaneously to predict the antibiotic that would be most active for a given bacterial isolate. Conclusions: The study establishes the rapid β-LEAF assay for β-lactamase detection and prediction of antibiotic activity using S. aureus clinical isolates. Although the focus in the current study is β-lactamase-based resistance, the overall approach represents a broad diagnostic platform. In the long-term, these studies form the basis for the development of assays utilizing a broader variety of targets, pathogens and drugs