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The impacts of small woodlands on farmland biodiversity are less well studied than those of other habitats, such as hedgerows and field margins. Butterfly abundance and species richness were recorded along transects on two farms in southern England, one organic and one conventional, which had small woodlands. Woodland edges were particularly important for two species: comma Polygonia c-album and speckled wood Parare aegeria. Both were more abundant on woodland edges compared to hedgerows or field margins. A range of declining wider countryside species, including gatekeeper Pyronia tithonus and meadow brown Maniola jurtina, also frequented woodland edges. The quality of woodland edges was influential. Butterfly abundance was higher on woodland edges with a shrub layer. There was some evidence that bramble presence had a greater effect on butterfly abundance on the conventional compared to the organic farm. Small woodlands can make an important contribution to biodiversity conservation on farmland.

Organic farming, a low intensity system, may offer benefits for a range of taxa, but what affects the extent of those benefits is imperfectly understood. We explored the effects of organic farming and landscape on the activity density and species density of spiders and carabid beetles, using a large sample of paired organic and conventional farms in the UK. Spider activity density and species density were influenced by both farming system and surrounding landscape. Hunting spiders, which tend to have lower dispersal capabilities, had higher activity density, and more species were captured, on organic compared to conventional farms. There was also evidence for an interaction, as the farming system effect was particularly marked in the cropped area before harvest and was more pronounced in complex landscapes (those with little arable land). There was no evidence for any effect of farming system or landscape on web-building spiders (which include the linyphiids, many of which have high dispersal capabilities). For carabid beetles, the farming system effects were inconsistent. Before harvest, higher activity densities were observed in the crops on organic farms compared with conventional farms. After harvest, no difference was detected in the cropped area, but more carabids were captured on conventional compared to organic boundaries. Carabids were more species-dense in complex landscapes, and farming system did not affect this. There was little evidence that non-cropped habitat differences explained the farming system effects for either spiders or carabid beetles. For spiders, the farming system effects in the cropped area were probably largely attributable to differences in crop management; reduced inputs of pesticides (herbicides and insecticides) and fertilisers are possible influences, and there was some evidence for an effect of non-crop plant species richness on hunting spider activity density. The benefits of organic farming may be greatest for taxa with lower dispersal abilities generally. The evidence for interactions among landscape and farming system in their effects on spiders highlights the importance of developing strategies for managing farmland at the landscape-scale for most effective conservation of biodiversity.

Imatinib mesylate (Gleevec®, Novartis Pharma AG), an inhibitor of the c-Abl/Bcr-Abl, c-Kit, and PDGFR kinases, is an effective therapy for CML, GIST and HES. However, advanced stage CML and Ph+ ALL patients frequently relapse due to the development of resistance. In up to 50% of cases, imatinib resistance is the result of the clonal expansion of cells expressing Bcr-Abl kinase domain mutants and more than 30 such mutations have been detected. Different mutations display varying degrees of resistance, and although some are sensitive to increased concentrations of imatinib, new Abl kinase inhibitors with higher potency against wild-type and imatinib-resistant mutants of Bcr-Abl could have substantial clinical utility. Rational drug design based on the structural information obtained from the crystal structure of the Abl-imatinib complex and medicinal chemistry optimization of drug-like properties, resulted in the discovery of AMN107. The potencies of AMN107 and imatinib were compared with cellular assays using CML lines (K562 and KU812F) and Ba/F3 cells expressing either ‘wt’- or imatinib-resistant mutants of Bcr-Abl. AMN107 effectively reduced the cellular Bcr-Abl autophosphorylation in K562, KU812F and Ba/F3 Bcr-Abl cells with IC50s of 42, 60 and 23 nM, respectively (Gleevec: 470, 399 and 231 nM) The proliferation of these cells was inhibited with IC50s of 11, 8 and 23 nM (Gleevec: 272, 80 and 634 nM). Autophosphorylation of the Bcr-Abl mutants M351T, F317L and E255V was reduced by AMN107 with IC50s of 33, 43 and 245 nM (Gleevec: 595, 818 and 6499 nM), resulting in inhibition of cell proliferation with IC50s of 30, 77 and 684 nM (Gleevec: 1285, 1583 and 6294 nM). No effect could be observed below 8 μM against the T315I and G250E bcr-abl mutants. Similar to imatinib, AMN107 inhibited the cellular tyrosine kinase activity of PDGFR-β (A31 cells) and c-Kit (GIST882 cells), with IC50s of 85 and 192 nM (Gleevec: 74 and 96 nM). Control (Ba/F3) cell proliferation was unaffected by 10 μM AMN107, and added IL-3 abrogated the antiproliferative effects on Bcr-Abl expressing Ba/F3 cells. Furthermore, AMN107 (< 10 μM), did not effect unrelated kinases, e.g. c-erbB2 (BT474), Ins-R (A14) and IGF-1R (NWT-21), in cellular assays, consistent with its specificity and lack of general cytotoxicity. Based on these in vitro assays and preclinical in vivo and pharmacokinetic data to be presented separately, AMN107 represents a promising new tyrosine kinase inhibitor for testing in human clinical trials.

A review is presented of current and potentially applicable methods for the determination of oxygen, nitrogen, hydrogen and carbon in molybdenum, tungsten, niobium, and tantalum.

The platinum flux technique, well established for the determination of oxygen in titanium, was successfully applied to the analysis of zirconium for its oxygen content after a systematic study of the optimum experimental conditions. The extraction of oxygen was complete in 20 min in the temperature range of 1850 to 2100° with a ratio of flux to sample of about 4.5:1 to 8:1. Statistical analysis of the results on a homogeneous sample gave a standard deviation of 0.0038 weight % and a coefficient of variance of 2.9%atalevelof 0.131 weight % of oxygen in zirconium. The recommended experimental conditions are a 0.1-g sample, a 5:1 flux-to-sample ratio, and 20 min extraction at 1900°–1950°.

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