Taming tosyl azide: the development of a scalable continuous diazo transfer process

Heat and shock sensitive tosyl azide was generated and used on demand in a telescoped diazo transfer process. Small quantities of tosyl azide were accessed in a one pot batch procedure using shelf stable, readily available reagents. For large scale diazo transfer reactions tosyl azide was generated and used in a telescoped flow process, to mitigate the risks associated with handling potentially explosive reagents on scale. The in situ formed tosyl azide was used to rapidly perform diazo transfer to a range of acceptors, including β-ketoesters, β-ketoamides, malonate esters and β-ketosulfones. An effective in-line quench of sulfonyl azides was also developed, whereby a sacrificial acceptor molecule ensured complete consumption of any residual hazardous diazo transfer reagent. The telescoped diazo transfer process with in-line quenching was used to safely prepare over 21 g of an α-diazocarbonyl in >98% purity without any column chromatography

Photoactive organic-inorganic hybrid polymer waveguides for optical device technologies

© 2020 SPIE. Organic-inorganic hybrid polymers based on ureasils have found application as waveguides in luminescent solar concentrators and visible light communications. The mechanical properties, and thus processability of ureasils, has previously been qualitatively linked to the chemical structure, but has not yet been studied in detail. In this study, a series of low molecular weight ureasil polymers has been synthesised, and the correlation between the chemical structure and the optical and mechanical properties investigated. A wide-range of techniques are employed to investigate this relationship, including steady-state photoluminescence and Fourier-transform infrared spectroscopy, 4-point flexural testing, and uniaxial tensile testing.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 818762 - SPECTRACON). T. J. F. S. thanks the EPSRC (EP/N509620/1) for financial support

Biological impact assessment of nanomaterial used in nanomedicine. introduction to the NanoTEST project.

Therapeutic nanoparticles (NPs) are used in nanomedicine as drug carriers or imaging agents, providing increased selectivity/specificity for diseased tissues. The first NPs in nanomedicine were developed for increasing the efficacy of known drugs displaying dose-limiting toxicity and poor bioavailability and for enhancing disease detection. Nanotechnologies have gained much interest owing to their huge potential for applications in industry and medicine. It is necessary to ensure and control the biocompatibility of the components of therapeutic NPs to guarantee that intrinsic toxicity does not overtake the benefits. In addition to monitoring their toxicity in vitro, in vivo and in silico, it is also necessary to understand their distribution in the human body, their biodegradation and excretion routes and dispersion in the environment. Therefore, a deep understanding of their interactions with living tissues and of their possible effects in the human (and animal) body is required for the safe use of nanoparticulate formulations. Obtaining this information was the main aim of the NanoTEST project, and the goals of the reports collected together in this special issue are to summarise the observations and results obtained by the participating research teams and to provide methodological tools for evaluating the biological impact of NPs

The North Atlantic Oscillation and U.K. Butterfly Populations

The North Atlantic Oscillation (NAO) is a natural climate fluctuation that has a considerable influence on the weather in Scandinavia, western Europe and the Mediterranean. The NAO influences the direction of travel of autumn and winter storms and depressions across the North Atlantic and has been shown to have an effect on a range of species as diverse as Red Deer, Soay Sheep, Cod and marine Copepods. Here we consider whether the NAO can also control the population size of butterflies in the UK

Exposure to benzene at work and the risk of leukemia: a systematic review and meta-analysis

Background A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). Methods A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size). Results In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant. Conclusions Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML

Paleomagnetic evidence for a long-lived, potentially reversing martian dynamo at ~3.9 Ga

The 4.1-billion-year-old meteorite Allan Hills 84001 (ALH 84001) may preserve a magnetic record of the extinct martian dynamo. However, previous paleomagnetic studies have reported heterogeneous, nonunidirectional magnetization in the meteorite at submillimeter scales, calling into question whether it records a dynamo field. We use the quantum diamond microscope to analyze igneous Fe-sulfides in ALH 84001 that may carry remanence as old as 4.1 billion years (Ga). We find that individual, 100-μm-scale ferromagnetic mineral assemblages are strongly magnetized in two nearly antipodal directions. This suggests that the meteorite recorded strong fields following impact heating at 4.1 to 3.95 Ga, after which at least one further impact heterogeneously remagnetized the meteorite in a nearly antipodal local field. These observations are most simply explained by a reversing martian dynamo that was active until 3.9 Ga, thereby implying a late cessation for the martian dynamo and potentially documenting reversing behavior in a nonterrestrial planetary dynamo

Tidal dynamics and mangrove carbon sequestration during the Oligo–Miocene in the South China Sea

Modern mangroves are among the most carbon-rich biomes on Earth, but their long-term (≥106 yr) impact on the global carbon cycle is unknown. The extent, productivity and preservation of mangroves are controlled by the interplay of tectonics, global sea level and sedimentation, including tide, wave and fluvial processes. The impact of these processes on mangrove-bearing successions in the Oligo–Miocene of the South China Sea (SCS) is evaluated herein. Palaeogeographic reconstructions, palaeotidal modelling, and facies analysis suggest that elevated tidal range and bed shear stress optimised mangrove development along tide-influenced tropical coastlines. Preservation of mangrove organic carbon (OC) was promoted by high tectonic subsidence and fluvial sediment supply. Lithospheric storage of OC in peripheral SCS basins potentially exceeded 4000 Gt (equivalent to 2000 ppm of atmospheric CO2). These results highlight the crucial impact of tectonic and oceanographic processes on mangrove OC sequestration within the global carbon cycle on geological timescales

Flecainide reduces Ca2+ spark and wave frequency via inhibition of the sarcolemmal sodium current

AIMS: Ca(2+) waves are thought to be important in the aetiology of ventricular tachyarrhythmias. There have been conflicting results regarding whether flecainide reduces Ca(2+) waves in isolated cardiomyocytes. We sought to confirm whether flecainide inhibits waves in the intact cardiomyocyte and to elucidate the mechanism. METHODS AND RESULTS: We imaged spontaneous sarcoplasmic reticulum (SR) Ca(2+) release events in healthy adult rat cardiomyocytes. Variation in stimulation frequency was used to produce Ca(2+) sparks or waves. Spark frequency, wave frequency, and wave velocity were reduced by flecainide in the absence of a reduction of SR Ca(2+) content. Inhibition of I(Na) via alternative pharmacological agents (tetrodotoxin, propafenone, or lidocaine) produced similar changes. To assess the contribution of I(Na) to spark and wave production, voltage clamping was used to activate contraction from holding potentials of −80 or −40 mV. This confirmed that reducing Na(+) influx during myocyte stimulation is sufficient to reduce waves and that flecainide only causes Ca(2+) wave reduction when I(Na) is active. It was found that Na(+)/Ca(2+)-exchanger (NCX)-mediated Ca(2+) efflux was significantly enhanced by flecainide and that the effects of flecainide on wave frequency could be reversed by reducing [Na(+)](o), suggesting an important downstream role for NCX function. CONCLUSION: Flecainide reduces spark and wave frequency in the intact rat cardiomyocyte at therapeutically relevant concentrations but the mechanism involves I(Na) reduction rather than direct ryanodine receptor (RyR2) inhibition. Reduced I(Na) results in increased Ca(2+) efflux via NCX across the sarcolemma, reducing Ca(2+) concentration in the vicinity of the RyR2