Accounts of debates in the House of Commons, March– April 1731, supplementary to the diary of the first earl of Egmont

John Perceval (1685–1748), 1st Viscount Perceval and (from 1733) 1st Earl of Egmont, was an assiduous recorder of his own life and times. His diaries, published by the Historical Manuscripts Commission from manuscripts in the British Library, are the best source for parliamentary debates at Westminster in the 1730s. For the years 1730-1733, when Perceval sat in the Commons (as an Irish peer) they are remarkably full. His practice seems to have been to prepare two versions (presumably on the basis of notes taken in the House), the first attributing speeches to individuals, and the second, entered up in the diary, which listed speakers and summarized all arguments on each side. His letterbooks for 1731 contain accounts of five debates that embody his first editing process, with speeches attributed to individuals. They were sent to an Irish correspondent, Marmaduke Coghill, and largely omitted from the diary because Perceval had already transcribed them elsewhere. They are new to historians and cast light on two main issues: the unsuccessful attempts by Perceval and the ‘Irish lobby’ to persuade the British parliament to settle the Irish woollen trade, a question bedevilling Anglo-Irish relations in this period; and an attempt by the opposition to stir up anger against perceived Spanish aggression against Gibraltar. One of the most interesting features is the insight afforded into the Commons performances of Sir Robert Walpole: his management of debates, his own style of speaking, and his sharp exchanges with opponents like William Pulteney.

Comparative effects of GLP-1 and GIP on cAMP production, insulin secretion, and in vivo antidiabetic actions following substitution of Ala8/Ala2 with 2-aminobutyric acid

The two major incretin hormones, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), are currently being considered as prospective drug candidates for treatment of type 2 diabetes. Interest in these gut hormones was initially spurred by their potent insulinotropic activities, but a number of other antihyperglycaemic actions are now established. One of the foremost barriers in progressing GLP-1 and GIP to the clinic concerns their rapid degradation and inactivation by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV). Here, we compare the DPP IV resistance and biological properties of Abu(8)/ Abu(2) (2-aminobutyric acid) substituted analogues of GLP-1 and GIP engineered to impart DPP IV resistance. Whereas (Abu(8))GLP-1 was completely stable to human plasma (half-life > 12h), GLP-1, GIP, and (Abu(2))GIP were rapidly degraded (half-lives: 6.2, 6.0, and 7.1 h, respectively). Native GIP, GLP-1, and particularly (Abu(8))GLP-1 elicited significant adenylate cyclase and insulinotropic activity, while (Abu(2))GIP was less effective. Similarly, in obese diabetic (ob/ob) mice, GIP, GLP-1, and (Abu(8))GLP-1 displayed substantial glucose-lowering and insulin -releasing activities, whereas (Abu(2))GIP was only weakly active. These studies illustrate divergent effects of penultimate amino acid Ala(8)/Ala(2) substitution with Abu on the biological properties of GLP-1 and GIP, suggesting that (Abu(8))GLP-1 represents a potential candidate for future therapeutic development. (C) 2004 Elsevier Inc. All rights reserved.

Identical extraction behavior and coordination of trivalent or hexavalent f-element cations using ionic liquid and molecular solvents

The extraction of both UO22+ and trivalent lanthanide and actinide ions (Am3+, Nd3+, Eu3+) by dialkylphosphoric or dialkylphosphinic acids from aqueous solutions into the ionic liquid, 1-decyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide has been studied and compared to extractions into dodecane. Radiotracer partitioning measurements show comparable patterns of distribution ratios for both the ionic liquid/aqueous and dodecane/aqueous systems, and the limiting slopes at low acidity indicate the partitioning of neutral complexes in both solvent systems. The metal ion coordination environment, elucidated from EXAFS and UV-visible spectroscopy measurements, is equivalent in the ionic liquid and dodecane solutions with coordination of the uranyl cation by two hydrogen-bonded extractant dimers, and of the trivalent cations by three extractant dimers. This is the first definitive report of a system where both the biphasic extraction equilibria and metal coordination environment are the same in an ionic liquid and a molecular organic solvent.