A carbamazepine-indomethacin (1:1) cocrystal produced by milling

An X-ray amorphous mixture of carbamazepine and indomethacin transforms upon annealing to produce a novel 1:1 cocrystal, whose structure has been determined from laboratory powder X-ray diffraction (PXRD) data.

Variation in the sensitivity of Callosobruchus (Coleoptera: Bruchidae) acetylcholinesterase to the organophosphate insecticide malaoxon: effect of species, geographical strain and food type

BACKGROUND: Bruchid beetles, Callosobruchus species, are serious pests of economically important grain legumes; their activity in stores is often controlled by use of synthetic insecticides. Esterases are known to be involved in insecticide resistance in insects. However, there is dearth of information on esterase activity in the genus Callosobruchus. In this study we investigated the effect of species, geographical strain and food type on the variation of acetylcholinesterase (AChE) activity and its inhibition by malaoxon (malathion metabolite) using an in vitro spectrophotometric method. RESULT: AChE activity varied significantly among species and strains and also among legume type used for rearing them. Generally irrespective of species, strain or food type, the higher the AChE activity of a population, the higher its inhibition by malaoxon. C. chinensis had the highest AChE activity of the species studied and in the presence of malaoxon it had the lowest remaining AChE activity, while C. rhodesianus retained the highest activity. CONCLUSION: A firsthand knowledge of AChE activity in regional Callosobruchus in line with the prevailing food types should be of utmost importance to grain legume breeders, researchers on plant materials for bruchid control and pesticide manufacturer/applicators for a robust integrated management of these bruchids.

RACORO extended-term, aircraft observations of boundary-layer clouds

A first-of-a-kind, extended-term cloud aircraft campaign was conducted to obtain an in-situ statistical characterization of continental boundary-layer clouds needed to investigate cloud processes and refine retrieval algorithms. Coordinated by the Atmospheric Radiation Measurement (ARM) Aerial Facility (AAF), the Routine AAF Clouds with Low Optical Water Depths (CLOWD) Optical Radiative Observations (RACORO) field campaign operated over the ARM Southern Great Plains (SGP) site from 22 January to 30 June 2009, collecting 260 h of data during 59 research flights. A comprehensive payload aboard the Center for Interdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS) Twin Otter aircraft measured cloud microphysics, solar and thermal radiation, physical aerosol properties, and atmospheric state parameters. Proximity to the SGP's extensive complement of surface measurements provides ancillary data that supports modeling studies and facilitates evaluation of a variety of surface retrieval algorithms. The five-month duration enabled sampling a range of conditions associated with the seasonal transition from winter to summer. Although about two-thirds of the cloud flights occurred in May and June, boundary-layer cloud fields were sampled under a variety of environmental and aerosol conditions, with about 77% of the flights occurring in cumulus and stratocumulus. Preliminary analyses illustrate use of these data to analyze cloud-aerosol relationships, characterize the horizontal variability of cloud radiative impacts, and evaluate surface-based retrievals. We discuss how an extended-term campaign requires a simplified operating paradigm that is different from that used for typical, short-term, intensive aircraft field programs.

Numerical-asymptotic boundary integral methods in high-frequency acoustic scattering

In this article we describe recent progress on the design, analysis and implementation of hybrid numerical-asymptotic boundary integral methods for boundary value problems for the Helmholtz equation that model time harmonic acoustic wave scattering in domains exterior to impenetrable obstacles. These hybrid methods combine conventional piecewise polynomial approximations with high-frequency asymptotics to build basis functions suitable for representing the oscillatory solutions. They have the potential to solve scattering problems accurately in a computation time that is (almost) independent of frequency and this has been realized for many model problems. The design and analysis of this class of methods requires new results on the analysis and numerical analysis of highly oscillatory boundary integral operators and on the high-frequency asymptotics of scattering problems. The implementation requires the development of appropriate quadrature rules for highly oscillatory integrals. This article contains a historical account of the development of this currently very active field, a detailed account of recent progress and, in addition, a number of original research results on the design, analysis and implementation of these methods.

Dissipation of shear-free turbulence near boundaries

The rapid-distortion model of Hunt & Graham (1978) for the initial distortion of turbulence by a flat boundary is extended to account fully for viscous processes. Two types of boundary are considered: a solid wall and a free surface. The model is shown to be formally valid provided two conditions are satisfied. The first condition is that time is short compared with the decorrelation time of the energy-containing eddies, so that nonlinear processes can be neglected. The second condition is that the viscous layer near the boundary, where tangential motions adjust to the boundary condition, is thin compared with the scales of the smallest eddies. The viscous layer can then be treated using thin-boundary-layer methods. Given these conditions, the distorted turbulence near the boundary is related to the undistorted turbulence, and thence profiles of turbulence dissipation rate near the two types of boundary are calculated and shown to agree extremely well with profiles obtained by Perot & Moin (1993) by direct numerical simulation. The dissipation rates are higher near a solid wall than in the bulk of the flow because the no-slip boundary condition leads to large velocity gradients across the viscous layer. In contrast, the weaker constraint of no stress at a free surface leads to the dissipation rate close to a free surface actually being smaller than in the bulk of the flow. This explains why tangential velocity fluctuations parallel to a free surface are so large. In addition we show that it is the adjustment of the large energy-containing eddies across the viscous layer that controls the dissipation rate, which explains why rapid-distortion theory can give quantitatively accurate values for the dissipation rate. We also find that the dissipation rate obtained from the model evaluated at the time when the model is expected to fail actually yields useful estimates of the dissipation obtained from the direct numerical simulation at times when the nonlinear processes are significant. We conclude that the main role of nonlinear processes is to arrest growth by linear processes of the viscous layer after about one large-eddy turnover time.

Adeno-associated virus-8-Mediated intravenous transfer of myostatin propeptide leads to systemic functional improvements of slow but not fast muscle

Myostatin is a member of the transformating growth factor-_ (TGF-_) superfamily of proteins and is produced almost exclusively in skeletal muscle tissue, where it is secreted and circulates as a serum protein. Myostatin acts as a negative regulator of muscle mass through the canonical SMAD2/3/4 signaling pathway. Naturally occurring myostatin mutants exhibit a ‘double muscling’ phenotype in which muscle mass is dramatically increased as a result of both hypertrophy and hyperplasia. Myostatin is naturally inhibited by its own propeptide; therefore, we assessed the impact of adeno associated virus-8 (AAV8) myostatin propeptide vectors when systemically introduced in MF-1 mice. We noted a significant systemic increase in muscle mass in both slow and fast muscle phenotypes, with no evidence of hyperplasia; however, the nuclei-to- cytoplasm ratio in all myofiber types was significantly reduced. An increase in muscle mass in slow (soleus) muscle led to an increase in force output; however, an increase in fast (extensor digitorum longus [EDL]) muscle mass did not increase force output. These results suggest that the use of gene therapeutic regimens of myostatin inhibition for age-related or disease-related muscle loss may have muscle-specific effects.

Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx Mice

The administration of antisense oligonucleotides (AOs) to skip one or more exons in mutated forms of the DMD gene and so restore the reading frame of the transcript is one of the most promising approaches to treat Duchenne muscular dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and safety of long-term AO administration have not been conducted. Furthermore, it is essential to determine the minimal effective dose and frequency of administration. In this study, two different low doses (LDs) of phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23 in the mdx dystrophic mouse were administered for up to 12 months. Mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, particularly in the diaphragm. Moreover, the generalized physical activity was profoundly enhanced compared to untreated mdx mice showing that widespread, albeit partial, dystrophin expression restores the normal activity in mdx mice. Our results show for the first time that a chronic long-term administration of LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe, significantly ameliorates the muscular dystrophic phenotype and improves the activity of dystrophin-deficient mice, thus encouraging the further clinical translation of this approach in humans.

Support for global climate reorganization during the "Medieval Climate Anomaly"

Widely distributed proxy records indicate that the Medieval Climate Anomaly (MCA; *900–1350 AD) was characterized by coherent shifts in large-scale Northern Hemisphere atmospheric circulation patterns. Although cooler sea surface temperatures in the central and eastern equatorial Pacific can explain some aspects of medieval circulation changes, they are not sufficient to account for other notable features, including widespread aridity through the Eurasian sub-tropics, stronger winter westerlies across the North Atlantic and Western Europe, and shifts in monsoon rainfall patterns across Africa and South Asia. We present results from a full-physics coupled climate model showing that a slight warming of the tropical Indian and western Pacific Oceans relative to the other tropical ocean basins can induce a broad range of the medieval circulation and climate changes indicated by proxy data, including many of those not explained by a cooler tropical Pacific alone. Important aspects of the results resemble those from previous simulations examining the climatic response to the rapid Indian Ocean warming during the late twentieth century, and to results from climate warming simulations—especially in indicating an expansion of the Northern Hemisphere Hadley circulation. Notably, the pattern of tropical Indo-Pacific sea surface temperature (SST) change responsible for producing the proxy-model similarity in our results agrees well with MCA-LIA SST differences obtained in a recent proxy-based climate field reconstruction. Though much remains unclear, our results indicate that the MCA was characterized by an enhanced zonal Indo-Pacific SST gradient with resulting changes in Northern Hemisphere tropical and extra-tropical circulation patterns and hydroclimate regimes, linkages that may explain the coherent regional climate shifts indicated by proxy records from across the planet. The findings provide new perspectives on the nature and possible causes of the MCA—a remarkable, yet incompletely understood episode of Late Holocene climatic change.

Efficient production of foot-and-mouth disease virus empty capsids in insect cells following down regulation of 3C protease activity

Foot-and-mouth disease virus (FMDV) is a significant economically and distributed globally pathogen of Artiodactyla. Current vaccines are chemically inactivated whole virus particles that require large-scale virus growth in strict bio-containment with the associated risks of accidental release or incomplete inactivation. Non-infectious empty capsids are structural mimics of authentic particles with no associated risk and constitute an alternate vaccine candidate. Capsids self-assemble from the processed virus structural proteins, VP0, VP3 and VP1, which are released from the structural protein precursor P1-2A by the action of the virus-encoded 3C protease. To date recombinant empty capsid assembly has been limited by poor expression levels, restricting the development of empty capsids as a viable vaccine. Here expression of the FMDV structural protein precursor P1-2A in insect cells is shown to be efficient but linkage of the cognate 3C protease to the C-terminus reduces expression significantly. Inactivation of the 3C enzyme in a P1-2A-3C cassette allows expression and intermediate levels of 3C activity resulted in efficient processing of the P1-2A precursor into the structural proteins which assembled into empty capsids. Expression was independent of the insect host cell background and leads to capsids that are recognised as authentic by a range of anti-FMDV bovine sera suggesting their feasibility as an alternate vaccine.

Assessment of potential climate change impacts on peatland dissolved organic carbon release and drinking water treatment from laboratory experiments

Catchments draining peat soils provide the majority of drinking water in the UK. Over the past decades, concentrations of dissolved organic carbon (DOC) have increased in surface waters. Residual DOC can cause harmful carcinogenic disinfection by-products to form during water treatment processes. Increased frequency and severity of droughts combined with and increased temperatures expected as the climate changes, have potentials to change water quality. We used a novel approach to investigate links between climate change, DOC release and subsequent effects on drinking water treatment. We designed a climate manipulation experiment to simulate projected climate changes and monitored releases from peat soil and litter, then simulated coagulation used in water treatment. We showed that the ‘drought’ simulation was the dominant factor altering DOC release and affected the ability to remove DOC. Our results imply that future short-term drought events could have a greater impact than increased temperature on DOC treatability.

Evidence for global climate reorganization during medieval times

A synthesis of global climate model results and inferences from proxy records suggests an increased sea surface temperature gradient between the tropical Indian and Pacific Oceans during medieval times.

'Thou glorious kingdome, thou chiefe of empires': Persia in seventeenth-century travel literature

This article discusses a series of texts by or about travellers to Safavid Persia in the early seventeenth century, and in particular the literature surrounding the Sherley brothers. It looks at the ways in which, in order to encourage support for the voyages they described, English travel writers emphasised the potential for closer Anglo-Persian relations. In doing so, such narratives took advantage of a developing awareness of sectarian division within Islam in order to differentiate Persia from the Ottoman Empire. The article then examines how The Travailes of the Three English Brothers (1607) by Day, Rowley and Wilkins, built on the possibilities suggested by the travel writings, and specifically their recognition of Islamic sectarian division, to develop an idealised model of how relations between Persia and England might function. More broadly, these texts demonstrate travellers’ interest in looking for potential correlation between Christian and Muslim identities during this period.

Prizes for modernity in the provinces: The Arts Council’s 1950-1951 regional playwriting competition

As part of its contribution to the 1951 Festival of Britain, the Arts Council ran what can be seen in retrospect to be an important playwriting competition. Disregarding the London stage entirely, it invited regional theatres throughout the UK to put forward nominations for new plays within their repertoire for 1950-1951. Each of the five winning plays would receive, what was then, the substantial sum of £100. Originality and innovation featured highly amongst the selection criteria, with 40 per cent of the judges’ marks being awarded for “interest of subject matter and inventiveness of treatment”. This article will assess some of the surprising outcomes of the competition and argue that it served as an important nexus point in British theatrical historiography between two key moments in post-war Britain: the first being the inauguration of the Festival of Britain in 1951, the other being the debut of John Osborne’s Look Back in Anger in May 1956. The article will also argue that the Arts Council’s play competition was significant for two other reasons. By circumventing the London stage, it provides a useful tool by which to reassess the state of new writing in regional theatre at the beginning of the 1950s and to question how far received views of parochialism and conservatism held true. The paper will also put forward a case for the competition significantly anticipating the work of George Devine at the English Stage Company, which during its early years established a reputation for itself by heavily exploiting the repertoire of new plays originally commissioned by regional theatres. This article forms part of a five year funded Arts and Humanities Research Council (AHRC) project, ‘Giving Voice to the Nation: The Arts Council of Great Britain and the Development of Theatre and Performance in Britain 1945-1994’. Details of the Arts Council’s archvie, which is housed at the Victoria & Albert Museum in London can be found at http://www.vam.ac.uk/vastatic/wid/ead/acgb/acgbf.html Keywords: Arts Council of Great Britain, regional theatre, playwriting, Festival of Britain, English Stage Company (Royal Court) , Yvonne Mitchell