DETECTION OF IRRADIATED CHICKEN MEAT BY ANALYSIS OF LIPID EXTRACTS FOR 2-SUBSTITUTED CYCLOBUTANONES USING AN ENZYME-LINKED-IMMUNOSORBENT-ASSAY

The means to detect the irradiation of food has been investigated for many years. In recent times radiolytic products, termed 2-alkylcyclobutanones (2-CBs), have been identified as excellent markers of irradiation in lipid-containing foods. An ELISA test was developed, which was capable of detecting a number of these compounds in irradiated chicken meat. A polyclonal antiserum was raised to a 2-CB containing a terminal carboxyl group conjugated to a carrier protein. This antiserum was highly specific for cyclobutanones containing C-10 and C-12 side chains. During assay validation the limit of detection of the assay was calculated to be 0.064 pg of 2-CB per gram of fat, within- and between-assay variations ranged from 6.7 to 18%. During experimental studies, chicken meat irradiated at doses ranging from 2.5 to 10 kGy were assayed and correctly identified as being treated. Quantitative comparisons between the ELISA and CC-MS revealed a good correlation (r(2) = 0.913) between the two methodologies in concentrations of 2-CB detected in irradiated samples.

Extracellular Loop 2 of the Free Fatty Acid Receptor 2 Mediates Allosterism of a Phenylacetamide Ago-Allosteric Modulator

Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molecular mechanisms mediating the activity of 4-chloro-alpha-(1-methylethyl)-N-2-thiazolylbenzeneacetamide (4-CMTB), a recently described phenylacetamide allosteric agonist and allosteric modulator of endogenous ligand function at human FFA2, by combining our previous knowledge of the orthosteric binding site with targeted examination of 4-CMTB structure-activity relationships and mutagenesis and chimeric receptor generation. Here we show that 4-CMTB is a selective agonist for FFA2 that binds to a site distinct from the orthosteric site of the receptor. Ligand structure-activity relationship studies indicated that the N-thiazolyl amide is likely to provide hydrogen bond donor/acceptor interactions with the receptor. Substitution at Leu(173) or the exchange of the entire extracellular loop 2 of FFA2 with that of FFA3 was sufficient to reduce or ablate, respectively, allosteric communication between the endogenous and allosteric agonists. Thus, we conclude that extracellular loop 2 of human FFA2 is required for transduction of cooperative signaling between the orthosteric and an as-yet-undefined allosteric binding site of the FFA2 receptor that is occupied by 4-CMTB.

A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action

Vaginal rings are currently being developed for the long-term (at least 30 days) continuous delivery of microbicides against human immunodeficiency virus (HIV). Research to date has mostly focused on devices containing a single antiretroviral compound, exemplified by the 25 mg dapivirine ring currently being evaluated in a Phase III clinical study. However, there is a strong clinical rationale for combining antiretrovirals with different mechanisms of action in a bid to increase breadth of protection and limit the emergence of resistant strains. Here we report the development of a combination antiretroviral silicone elastomer matrix-type vaginal ring for simultaneous controlled release of dapivirine, a non-nucleoside reverse transcriptase inhibitor, and maraviroc, a CCR5-targeted HIV-1 entry inhibitor. Vaginal rings loaded with 25 mg dapivirine and various quantities of maraviroc (50– 400 mg) were manufactured and in vitro release assessed. The 25 mg dapivirine and 100 mg maraviroc formulation was selected for further study. A 24-month pharmaceutical stability evaluation was conducted, indicating good product stability in terms of in vitro release, content assay, mechanical properties and related substances. This combination ring product has now progressed to Phase I clinical testing.

Romanticism and Blackwood's Magazine:'An Unprecedented Phenomenon'

Romanticism and Blackwood's Magazine is inspired by the ongoing critical fascination with Blackwood's Edinburgh Magazine, and the burgeoning recognition of its centrality to the Romantic age. Though the magazine itself was published continuously for well over a century and a half, this volume concentrates specifically on those years when William Blackwood was at the helm, beginning with his founding of the magazine in 1817 and closing with his death in 1834. These were the years when, as Samuel Taylor Coleridge put it in 1832, Blackwood's reigned as 'an unprecedented Phenomenon in the world of letters.' The magazine placed itself at the centre of the emerging mass media, commented decisively on all the major political and cultural issues that shaped the Romantic movement, and published some of the leading writers of the day, including Coleridge, Thomas De Quincey, John Galt, Felicia Hemans, James Hogg, Walter Scott, and Mary Shelley.

'This much-needed volume reminds us not only why Blackwood's was the most influential periodical publication of the time, but also how its writers, writings, and critical agendas continue to shape so many of the scholarly concerns of Romantic studies in the twenty-first century.' - Charles Mahoney, Associate Professor, University of Connecticut, USA

List of Illustrations
Acknowledgements
Abbreviations
Notes on Contributors
'A character so various, and yet so indisputably its own': A Passage to Blackwood's Edinburgh Magazine; R.Morrison & D.S.Roberts
PART I: BLACKWOOD'S AND THE PERIODICAL PRESS
Beginning Blackwood's: The Right Mix of Dulce and Ùtile; P.Flynn
John Gibson Lockhart and Blackwood's: Shaping the Romantic Periodical Press; T.Richardson
From Gluttony to Justified Sinning: Confessional Writing in Blackwood's and the London Magazine; D.Higgins
Camaraderie and Conflict: De Quincey and Wilson on Enemy Lines; R.Morrison
Selling Blackwood's Magazine, 1817-1834; D.Finkelstein
PART II: BLACKWOOD'S CULTURE AND CRITICISM
Blackwood's 'Personalities'; T.Mole
Communal Reception, Mary Shelley, and the 'Blackwood's School' of Criticism; N.Mason
Blackwoodian Allusion and the Culture of Miscellaneity; D.Stewart
Blackwood's Edinburgh Magazine in the Scientific Culture of Early Nineteenth-Century Edinburgh; W.Christie
The Art and Science of Politics in Blackwood's Edinburgh Magazine, c. 1817-1841; D.Kelly
Prosing Poetry: Blackwood's and Generic Transposition, 1820-1840; J.Camlot
PART III: BLACKWOOD'S FICTIONS
Blackwood's and the Boundaries of the Short Story; T.Killick
The Edinburgh of Blackwood's Edinburgh Magazine and James Hogg's Fiction; G.Hughes
'The Taste for Violence in Blackwood's Magazine'; M.Schoenfield
PART IV: BLACKWOOD'S AT HOME
John Wilson and Regency Authorship; R.Cronin
John Wilson and Sport; J.Strachan
William Maginn and the Blackwood's 'Preface' of 1826; D.E.Latané, Jr.
All Work and All Play: Felicia Hemans's Edinburgh Noctes; N.Sweet
PART V: BLACKWOOD'S ABROAD
Imagining India in Early Blackwood's; D.S.Roberts
Tales of the Colonies: Blackwood's, Provincialism, and British Interests Abroad; A.Jarrells
Selected Bibliography
Index

ROBERT MORRISON is Queen's National Scholar at Queen's University, Kingston, Ontario, Canada. His book, The English Opium-Eater: A Biography of Thomas De Quincey was a finalist for the James Tait Black Prize. He has edited writings by Jane Austen, Leigh Hunt, Thomas De Quincey, and John Polidori.
DANIEL SANJIV ROBERTS is Reader in English at Queen's University Belfast, UK. His publications include a monograph, Revisionary Gleam: De Quincey, Coleridge, and the High Romantic Argument (2000), and major critical editions of Thomas De Quincey's Autobiographic Sketches and Robert Southey's The Curse of Kehama; the latter was cited as a Distinguished Scholarly Edition by the MLA. He is currently working on an edition of Charles Johnstone's novel The History of Arsaces, Prince of Betlis for the Early Irish Fiction series.

Chapter Three – Host–Parasite Interactions and the Evolution of Immune Defense

Parasites and pathogens are ubiquitous and act as an important selection pressure on animals. Here, drawing primarily on our own research, mostly on insects, we illustrate how host-parasite interactions have played a role in the evolution of a range of phenomena, including animal coloration, social behavior, foraging ecology, sexual selection, and life-history tradeoffs, as well as how variation in host behavior and ecology can drive variation in parasitism risk and host allocation of resources to immunity and other antiparasite defenses. We conclude by identifying key areas for future study.

Prescription contraception use: a cross-sectional population study of psychosocial determinants

Objective: Many forms of contraception are available on prescription only for example, the oral contraceptive pill (OCP) and long-acting reversible contraceptives (LARCs). In this analysis we aim to identify key determinants of prescription contraceptive use.

Design: Cross-sectional population survey. Data on sociodemographic indices, concerns about the OCP and perceived barriers to access were collected.

Setting: Data set constructed from a representative population-based telephone survey of community dwelling adults in the Republic of Ireland (RoI)

Participants: 1515 women aged between 18 and 45 years

Main outcome measure: Self-reported user of the OCP or LARCs (intrauterine contraception, contraceptive injections or subdermal contraceptive implants) in the previous 12 months.

Results: For at least some of the previous year, 35% had used the OCP and 14% had used LARCs, while 3% had used two or more of these methods. OCP users were significantly younger, more likely to be unmarried and had higher income than non-users. Overall, 68% agreed with the statement ‘that taking a break from long-term use of the contraceptive pill is a good idea’ and 37% agreed with the statement that ‘the OCP has dangerous side effects’ and this was the strongest predictor variable of non-use of the OCP. Intrauterine contraception users were significantly older, more likely to be married and had lower income than non-users. Injections or subdermal contraceptive implant users were significantly younger, less likely to be married, had lower income and were less likely to agree that taking a break from long-term use of the pill is a good idea than non-users.

Conclusions: Prescription contraceptive use is sociodemographically patterned, with LARCs in particular being associated with lower incomes in the RoI. Concerns about the safety of the OCP remain prevalent and are important and modifiable determinants of contraceptive-related behaviour.

Quantum control of photodissociation using intense, femtosecond pulses shaped with third order dispersion

We demonstrate the ability to control the molecular dissociation rate using femtosecond pulses shaped with third-order dispersion (TOD). Explicitly, a significant 50% enhancement in the dissociation yield for the low lying vibrational levels (v ∼ 6) of an H+2 ion-beam target was measured as a function of TOD. The underlying mechanism responsible for this enhanced dissociation was theoretically identified as non-adiabatic alignment induced by the pre-pulses situated on the leading edge of pulses shaped with negative TOD. This control scheme is expected to work in other molecules as it does not rely on specific characteristics of our test-case H+2 molecule.

VentBase:Developing a consensus among stakeholders in the deep-sea regarding environmental impact assessment for deep-sea mining-A workshop report

Mining seafloor massive sulfides for metals is an emergent industry faced with environmental management challenges. These revolve largely around limits to our current understanding of biological variability in marine systems, a challenge common to all marine environmental management. VentBase was established as a forum where academic, commercial, governmental, and non-governmental stakeholders can develop a consensus regarding the management of exploitative activities in the deep-sea. Participants advocate a precautionary approach with the incorporation of lessons learned from coastal studies. This workshop report from VentBase encourages the standardization of sampling methodologies for deep-sea environmental impact assessment. VentBase stresses the need for the collation of spatial data and importance of datasets amenable to robust statistical analyses. VentBase supports the identification of set-asides to prevent the local extirpation of vent-endemic communities and for the post-extraction recolonization of mine sites. © 2013.