Rational design of a dual-mode optical and chemical prodrug

Purpose. The purpose of this study is to demonstrate the rational design and behaviour of the first dual mode optical and chemical prodrug, exemplified by an acetyl salicylic acid-based system. Methods. A cyclic 1,4-benzodioxinone prodrug was synthesised by reaction of 3,5-dimethoxybenzoin and acetyl salicoyl chloride with pyridine. After purification by column chromatography and recrystallization, characterization was achieved using infrared and NMR spectroscopies, mass spectrometry, elemental analysis and single crystal X-ray diffraction. Light-triggered drug liberation was characterised via UV-visible spectroscopy following low-power 365 nm irradiation for controlled times. Chemical drug liberation was characterised via UV-visible spectroscopy in pH 5.5 solution. Results. The synthetic method yielded pure prodrug, with full supporting characterisation. Light-triggered drug liberation proceeded at a rate of 8.30 10j2 sj1, while chemical, hydrolytic liberation proceeded independently at 1.89 10j3 sj1. The photochemical and hydrolytic reactions were both quantitative. Conclusions. This study demonstrates the first rational dual-mode optical and chemical prodrug, using acetyl salicylic acid as a model, acting as a paradigm for future dual-mode systems. Photochemical drug liberation proceeds 44 times faster than chemical liberation, suggesting potential use in drug-eluting medical devices where an additional burst of drug is required at the onset of infection.

Distance and Proximity in Service to the Empire: Ulster and New Zealand between the Wars

This essay uses the concepts of ‘distance’ and ‘proximity’ to investigate and assess perceptions of community, nation and empire in inter-war New Zealand and Ulster (as well as Ireland and Northern Ireland) within a British imperial context, and explores the extent to which service of the empire (for example in the First World War) promoted both notions of imperial unity and local autonomy. It focuses on how these perceptions were articulated in the inter-war years during visits to Northern Ireland by three New Zealand premiers – Massey, Forbes and Coates – and to New Zealand by the Prime Minister of Northern Ireland, Lord Craigavon. It discusses the significant ways in which distance from their ‘home base’ and proximity to expatriate communities (in Craigavon's case) and Irish unionists and nationalists (in the case of the New Zealand premiers) inflected public statements during their visits. By examining these inter-war visits and investigating the rhetoric used and the cultural demonstrations associated with them, the factors of both distance and proximity can be used to evaluate similarities and difference across two parts of the empire. Thus, we can throw some light on the nature and dynamics of British imperial identity in the early twentieth century.

Signals of need in a cooperatively breeding mammal with mobile offspring

In many bird species with biparental care for young in the nest, hungry chicks beg repeatedly and parents adjust their feeding rate to the call rate of young. Repetitive calling also occurs in fledglings and in some mammals where offspring follow provisioners. It is not yet clear whether, in mobile systems with dispersed young where adults cannot compare the vocal behaviour of all young simultaneously, the calls represent a signal of need. We investigated repetitive begging by cooperatively reared meerkat, Suricata suricatta, pups that foraged with the group. Pups produced two types of begging calls: repeat calls over long periods and high-pitched calls mainly confined to feeding events. Food-deprived pups stayed closer to feeders, and begged for longer and more intensely by calling at a higher rate. Hungry pups increased both the rate of repeat calls, which were given continually, and the number of high-pitched bouts, but adults increased their food allocation only in relation to the rate of repeat calls. Our study indicates that hunger may lead to several changes in vocal behaviour, only some of which may be used by adults to assess need.

A Socio-Legal Analysis of Jihad

Since many offensive and defensive wars or acts of terrorism, such as the atrocities of 11 September in the United States and the July 2005 bombings in London, are committed under the banner of Islam and the duty of jihad, it is important to shed some light upon the Islamic laws of war in general, and the controversial concept of jihad in particular. This article traces the origins of, and rationale for, the use of force within the Islamic tradition, and assesses the meaning and evolution of the contentious concept of jihad within its historical context. Following an analysis of the opposing doctrinal views on the potential implications of jihad, the study argues that the concept of jihad should not be interpreted literally, but be adjusted in accordance with new historical and international conditions, and conducted by peaceful means, rather than by the sword.

Observation of high transient gain in the germanium x-ray laser at 19.6 nm

The transient-excitation pumping scheme, in which a picosecond duration pulse rapidly heats the plasma preformed by a low-intensity nanosecond pulse, was used to pump the Ne-like germanium, J = 0-1 transition at 19.6 nm. A small-signal gain coefficient of 30 cm(-1) was measured for targets less than or equal to 5 mm long. (C) 1998 Optical Society of America.

Influence of alpha-helicity, amphipathicity and D-amino acid incorporation on the peptide-induced mast cell activation

Mast cell activation by polycationic substances is believed to result from a direct activation of G protein alpha subunits and it was suggested that the adaption of amphipathic, alpha-helical conformations would allow the peptide to reach the cytosolic compartment to interact with G proteins (Mousli et al., 1994, Immunopharmacology 27, 1, for review). We investigated the histamine-releasing activity of model peptides as well as analogues of magainin 2 amide and neuropeptide Y with different amphipathicities and alpha-helix content on rat peritoneal mast cells. Amphipathic helicity is not a prerequisite for mast cell activation. Moreover, non-helical magainin peptides with high histamine-releasing activity were less active in the liberation of carboxyfluoresceine from negatively charged liposomes, indicating that peptide-induced mast cell activation and peptide-induced membrane perturbation do not correlate. In contrast to the negligible influence of the secondary structure, amino acid configuration may exert a striking influence on peptide-induced mast cell activation. Thus histamine-release by substance P was markedly impaired when the L-amino acids in the positively charged N-terminal region were replaced by D-amino acids, with [D-Arg(1)]substance P being the most inactive substance P diastereoisomer.

Antimicrobial peptide incorporated poly(2-hydroxyethyl methacrylate) hydrogels for the prevention of Staphylococcus epidermidis-associated biomaterial infections

The effectiveness of the antimicrobial peptide maximin-4, the ultrashort peptide H-Orn-Orn-Trp-Trp-NH(2) , and the lipopeptide C(12) -Orn-Orn-Trp-Trp-NH(2) in preventing adherence of pathogens to a candidate biomaterial were tested utilizing both matrix- and immersion-loaded poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogels. Antiadherent properties correlated to both the concentration released and the relative antimicrobial concentrations of each compound against Staphylococcus epidermidis ATCC 35984, at each time point. Immersion-loaded samples containing C(12) -Orn-Orn-Trp-Trp-NH(2) exhibited the lowest adherence profile for all peptides studied over 1, 4, and 24 h. The results outlined in this article show that antimicrobial peptides have the potential to serve as an important weapon against biomaterial associated infections. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.