Methanethiol-dependent dimethylsulfide production in soil environments

Dimethylsulfide (DMS) is an environmentally important trace gas with roles in sulfur cycling, signalling to higher organisms and in atmospheric chemistry. DMS is believed to be predominantly produced in marine environments via microbial degradation of the osmolyte dimethylsulfoniopropionate (DMSP). However, significant amounts of DMS are also generated from terrestrial environments, for example, peat bogs can emit ~6 μmol DMS m−2 per day, likely via the methylation of methanethiol (MeSH). A methyltransferase enzyme termed ‘MddA’, which catalyses the methylation of MeSH, generating DMS, in a wide range of bacteria and some cyanobacteria, may mediate this process, as the mddA gene is abundant in terrestrial metagenomes. This is the first study investigating the functionality of MeSH-dependent DMS production (Mdd) in a wide range of aerobic environments. All soils and marine sediment samples tested produced DMS when incubated with MeSH. Cultivation-dependent and cultivation-independent methods were used to assess microbial community changes in response to MeSH addition in a grassland soil where 35.9% of the bacteria were predicted to contain mddA. Bacteria of the genus Methylotenera were enriched in the presence of MeSH. Furthermore, many novel Mdd+ bacterial strains were isolated. Despite the abundance of mddA in the grassland soil, the Mdd pathway may not be a significant source of DMS in this environment as MeSH addition was required to detect DMS at only very low conversion rates

Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures

Laser-wakefield accelerators (LWFAs) are high acceleration-gradient plasma-based particle accelerators capable of producing ultra-relativistic electron beams. Within the strong focusing fields of the wakefield, accelerated electrons undergo betatron oscillations, emitting a bright pulse of X-rays with a micrometer-scale source size that may be used for imaging applications. Non-destructive X-ray phase contrast imaging and tomography of heterogeneous materials can provide insight into their processing, structure, and performance. To demonstrate the imaging capability of X-rays from an LWFA, we have examined an irregular eutectic in the aluminum-silicon (Al-Si) system. The lamellar spacing of the Al-Si eutectic microstructure is on the order of a few micrometers, thus requiring high spatial resolution. We present comparisons between the sharpness and spatial resolution in phase contrast images of this eutectic alloy obtained via X-ray phase contrast imaging at the Swiss Light Source (SLS) synchrotron and X-ray projection microscopy via an LWFA source. An upper bound on the resolving power of 2.7 ± 0.3 µm of the LWFA source in this experiment was measured. These results indicate that betatron X-rays from LWFA can provide an alternative to conventional synchrotron sources for high resolution imaging of eutectics and, more broadly, complex microstructures

Fragmented Regionalism? Delivering Integrated Regional Strategies in Yorkshire and the Humber

Counsell D., Hart T., Jonas A. E. G. and Kettle J. (2007) Fragmented regionalism? Delivering integrated regional strategies in Yorkshire and the Humber, Regional Studies 41, -. The paper draws upon research conducted in Yorkshire and the Humber to explore the issues and tensions surrounding the integration of regional strategy processes (planning, economic development, housing, sustainable development) across an English region in the context of wider processes of regional devolution. Whilst normative in intent, the research nonetheless speaks to wider academic debates relating to the new forms of governance surrounding regional devolution in the UK and to what extent the 'government of governance' at the regional scale requires new modes of regional strategy coordination. Counsell D., Hart T., Jonas A. E. G. et Kettle J. (2007) Une decentralisation morcelee? Tenir ses engagements quant aux strategies regionales integrees dans le Yorkshire et Humberside, Regional Studies 41, -. Cet article puise dans des recherches conduites dans le Yorkshire et Humberside afin d'examiner les questions et les tensions qui entourent l'integration des processus necessaires aux strategies regionales (a savoir, la planification, le developpement economique, le logement, le developpement durable) a travers une region d'Angleterre et dans le cadre plus general de la decentralisation. Alors que le but en est normatif, toujours est-il que la recherche cherche a aborder des debats academiques plus generaux qui se rapportent aux nouvelles formes de gouvernance qui entourent la decentralisation au Royaume-Uni et considere dans quelle mesure 'le gouvernement de la gouvernance' necessite sur le plan regional de nouvelles facons de coordonner la strategie regionale. Integration de politique Strategies regionales Planification regionale Logement regional Counsell D., Hart T., Jonas A. E. G. und Kettle J. (2007) Fragmentierter Regionalismus? Die Umsetzung integrierter Regionalstrategien fur die Region Yorkshire and the Humber, Regional Studies 41, -. In diesem Beitrag werden anhand von Studien, die in der Region Yorkshire and the Humber durchgefuhrt wurden, die Probleme und Spannungen untersucht, die in einer englischen Region bei der Integration regionaler Strategieprozesse (Planung, Wirtschaftsentwicklung, Wohnungswesen, nachhaltige Entwicklung) innerhalb des Kontextes der weitlaufigeren regionalen Dezentralisierungsprozesse entstehen. Obwohl unsere Forschung eine normative Absicht verfolgt, richtet sie sich gleichwohl an die breitere akademische Debatte uber neue Regierungsformen nach der britischen Dezentralisierung und uber die Frage, in welchem Ausmass das “Government of Governance” auf regionaler Ebene neue Arten der regionalen Strategiekoordinierung erforderlich macht. Politikintegration Regionalstrategien Regionalplanung Regionales Wohnungswesen Counsell D., Hart T., Jonas A. E. G. y Kettle J. (2007) ¿Regionalismo fragmentado? Estrategias regionales integradas en Yorkshire y Humber, Regional Studies 41, -. Las conclusiones de este ensayo se han extraido a partir de la investigacion llevada a cabo en la region inglesa de Yorkshire y Humber analizando los escollos y las tensiones que ha suscitado la integracion de los procesos de la estrategia regional (planificacion, desarrollo economico, vivienda, desarrollo sostenible) en un contexto mas amplio de la transferencia regional de competencias. Aunque la intencion sea normativa, en nuestro estudio tratamos debates academicos mas desarrollados con respecto a las nuevas formas de gobierno sobre la transferencia regional de competencias en el Reino Unido y estudiamos en que medida el 'Gobierno de gobernanza' a escala regional requiere nuevos modelos para coordinar la estrategia regional. Integracion politica Estrategias regionales Planificacion regional Vivienda regionalPolicy integration, Regional strategies, Regional planning, Regional housing,

Pentavalent rhenium-188 dimercaptosuccinic acid for targeted radiotherapy: synthesis and preliminary animal and human studies

Pentavalent rhenium-188 dimercaptosuccinic acid [Re-188(V)DMSA] is a beta-emitting analogue of Tc-99m(V)DMSA, a tracer that is taken up in a variety of tumours and bone metastases. The aim of this study was to develop the kit-based synthesis of the agent on a therapeutic scale, to assess its stability in vivo, and to obtain preliminary biodistribution and dosimetry estimates, prior to evaluation of its potential as a targeted radiotherapy agent. The organ distribution of Re-188 in mice was determined 2 h after injection of 3 MBq Re-188(V)DMSA prepared from eluate from a W-188/Re-188 generator. Three patients with cancer of the prostate and three with cancer of the bronchus, all with bone metastases confirmed with a standard Tc-99m-hydroxymethylene diphosphonate (Tc-99m-HDP) scan, were given 370 MBq Re-188(V)DMSA and imaged at 3 h and 24 h using the 155-keV gamma-photon (15%). Blood and urine samples were collected to determine clearance and to analyse the speciation of Re-188. Organ residence times were estimated from the scans, and used to estimate radiation doses using MIRDOSE 3. In mice,Re-188(V)DMSA was selective for bone and kidney. In patients, it showed selectivity for bone metastases (particularly those from prostate carcinoma) and kidney, but uptake in normal bone was not significantly greater than in surrounding soft tissues. Of the normal tissues the kidneys received the highest radiation dose (0.5-1.3 mGy/MBq). The images were strongly reminiscent of 99mTc(V)DMSA scans in similar patients. High-performance liquid chromatography analysis of blood and urine showed no evidence of Re-188 in any chemical form other than Re-188(V)DMSA up to 24 h. In conclusion, Re-188(V)DMSA and its Re-186 analogue warrant further clinical assessment as generator/kit-derived agents for treatment of painful bone metastases. These agents should also be assessed in medullary thyroid carcinoma and other soft tissue tumours which have been shown to accumulate Tc-99m(`V)DMSA

Inhibitors of the tyrosine kinase EphB4.:part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines

Crystallographic studies of a range of 3-substituted anilinopyrimidine inhibitors of EphB4 have highlighted two alternative C-2 aniline conformations and this discovery has been exploited in the design of a highly potent series of 3,5-disubstituted anilinopyrimidines. The observed range of cellular activities has been rationalised on the basis of physicochemical and structural characteristics

Iodine-123 salmon calcitonin, an imaging agent for calcitonin receptors: synthesis, biodistribution, metabolism and dosimetry in humans

Calcitonin is used to reduce high serum calcium levels in patients with malignancy, and as therapy for osteoporosis and Paget's disease. Receptors for the peptide have been identified in some human cancer cells including those of lung, breast, bone, prostate, and medullary carcinoma of the thyroid, suggesting that an imaging agent for the receptors might be useful in nuclear oncology. A modified chloramine-T method was used to label a pharmaceutical form of salmon calcitonin (SCT) with iodine-123. Labelling can be performed within 5 min including purification, resulting in >95% radiochemical purity and 70% yield. Digestion analysis shows labelling with two iodine atoms on the tyrosine residue. A Chinese hamster ovary cell-based assay showed that the receptor binding and activation were not impaired by the labelling. Biodistribution in mice was similar to that of commercially available mono-iodinatd I-125-labelled SCT, kidney being the principal target organ. Evaluation in three patients previously diagnosed as having Pager's disease (injected with 37 MBq [I-123]diiodotyrosyl(22)-SCT, containing less than 4 IU hormone, imaged dynamically up to 0.5 h and at intervals up to 24 h) shows early uptake in liver, kidney and sites of known Paget's disease but not in normal bone, and later uptake in thyroid and stomach. Blood clearance was fitted to a biexponential with half-lives of 3.4-7.4 min and 3-34 h. Radiation dosimetry was estimated using MIRDOSE 3. The highest doses (mean mGy/MBq) were to thyroid (6.8x10(-1)) and kidney (6.0x10(-2)), with a whole-body dose 3.0x10(-2). High performance liquid chromatography analysis revealed that urinary radioactivity was mostly in the form of iodide and diiodotyrosine within minutes of injection, indicating rapid in vivo breakdown. In summary, [I-123]diiodotyrosyl(22)-SCT binds to calcitonin receptors and can image sites of Paget's disease but its imaging potential is not optimal because of rapid breakdown and clearance from target tissues, and an alternative radiolabelling approach is required

Effect of tether length on endo/exo stereoselectivity in alkene–arene meta‐photocycloaddition reactions towards the Aphidocolin/Stemodin scaffolds

Intramolecular alkene-arene meta-photocycloadditions are powerful transformations that use the enhanced reactivity of photoexcited benzene rings to facilitate addition of an alkene 1,3 across donor groups and form complex three-dimensional fused-ring systemsfrom readily accessible starting materials. Intramolecular examples havetraditionallybeen restricted to 3-memberedtethers, with cycloaddition resulting from exo-conformation. However, by judicious tether design we have demonstratedthat a 4-membered tether can also proceed in good yield; interestingly,viaan endo-exciplex(1.2:1) enabling access to both natural product skeletons and interesting scaffolds for medicinal chemistry research