Derivatisable Cyanobactin Analogues: A Semisynthetic Approach

Many natural cyclic peptides have potent and potentially useful biological activities. Their use as therapeutic starting points is often limited by the quantities available, the lack of known biological targets and the practical limits on diversification to fine-tune their properties. We report the use of enzymes from the cyanobactin family to heterocyclise and macrocyclise chemically synthesised substrates so as to allow larger-scale syntheses and better control over derivatisation. We have made cyclic peptides containing orthogonal reactive groups, azide or dehydroalanine, that allow chemical diversification, including the use of fluorescent labels that can help in target identification. We show that the enzymes are compatible and efficient with such unnatural substrates. The combination of chemical synthesis and enzymatic transformation could help renew interest in investigating natural cyclic peptides with biological activity, as well as their unnatural analogues, as therapeutics.

Synthesis of novel pyrophosphorothiolate-linked dinucleoside cap analogues in a ball mill

Michaelis–Arbuzov reactions of S-aryl disulfide derivatives of 3′-thiothymidine or 5′-thioadenosine with tris(trimethylsilyl) phosphite proceeded in high yields to the corresponding phosphorothiolate monoesters. Subsequent hydrolytic desilylation and phosphate coupling were effected in one-pot using liquid-assisted grinding in a vibration ball mill. Novel 3′,5′- and 5′,5′-pyrophosphorothiolate-linked dinucleoside cap analogues were thereby prepared.

Good Laboratory Practice for optimization research

Good Laboratory Practice has been a part of non-clinical research for over 40 years. Optimization Research, despite having many papers discussing standards being published over the same period of time, has yet to embrace standards that underpin its research. In this paper we argue the need to adopt standards in optimization research. Building on previous papers, many of which have suggested that the optimization research community should adopt certain standards, we suggest a concrete set of recommendations that the community should adopt. We also discuss how the proposals in this paper could be progressed.

The generation and amplification of intergalactic magnetic fields in analogue laboratory experiments with high power lasers

The advent of high-power laser facilities has, in the past two decades, opened a new field of research where astrophysical environments can be scaled down to laboratory dimensions, while preserving the essential physics. This is due to the invariance of the equations of magneto-hydrodynamics to a class of similarity transformations. Here we review the relevant scaling relations and their application in laboratory astrophysics experiments with a focus on the generation and amplification of magnetic fields in cosmic environment. The standard model for the origin of magnetic fields is a multi stage process whereby a vanishing magnetic seed is first generated by a rotational electric field and is then amplified by turbulent dynamo action to the characteristic values observed in astronomical bodies. We thus discuss the relevant seed generation mechanisms in cosmic environment including resistive mechanism, collision-less and fluid instabilities, as well as novel laboratory experiments using high power laser systems aimed at investigating the amplification of magnetic energy by magneto-hydrodynamic (MHD) turbulence. Future directions, including efforts to model in the laboratory the process of diffusive shock acceleration are also discussed, with an emphasis on the potential of laboratory experiments to further our understanding of plasma physics on cosmic scales.

Laboratory measurements of resistivity in warm dense plasmas relevant to the microphysics of brown dwarfs

Since the observation of the first brown dwarf in 1995, numerous studies have led to a better understanding of the structures of these objects. Here we present a method for studying material resistivity in warm dense plasmas in the laboratory, which we relate to the microphysics of brown dwarfs through viscosity and electron collisions. Here we use X-ray polarimetry to determine the resistivity of a sulphur-doped plastic target heated to Brown Dwarf conditions by an ultra-intense laser. The resistivity is determined by matching the plasma physics model to the atomic physics calculations of the measured large, positive, polarization. The inferred resistivity is larger than predicted using standard resistivity models, suggesting that these commonly used models will not adequately describe the resistivity of warm dense plasma related to the viscosity of brown dwarfs.

 Graphitization of Small Carbonate Samples for Paleoceanographic Research at the Godwin Radiocarbon Laboratory, University of Cambridge

A new radiocarbon preparation facility was set up in 2010 at the Godwin Laboratory for Palaeoclimate Research, at the University of Cambridge. Samples are graphitized via hydrogen reduction on an iron powder catalyst before being sent to the Chrono Centre, Belfast, or the Australian National University for accelerator mass spectrometry (AMS) analysis. The experimental setup and procedure have recently been developed to investigate the potential for running small samples of foraminiferal carbonate. By analyzing background values of samples ranging from 0.04 to 0.6 mg C along with similar sized secondary standards, the setup and experimental procedures were optimized for small samples. “Background” modern 14C contamination has been minimized through careful selection of iron powder, and graphitization has been optimized through the use of “small volume” reactors, allowing samples containing as little as 0.08 mg C to be graphitized and accurately dated. Graphitization efficiency/fractionation is found not to be the main limitation on the analysis of samples smaller than 0.07 mg C, which rather depends primarily on AMS ion beam optics, suggesting further improvements in small sample analysis might yet be achieved with our methodology.