CIRCE: Coordinated Ionospheric Reconstruction Cubesat Experiment

The Coordinated Ionospheric Reconstruction Cubesat Experiment (CIRCE) is a collaborative space mission between the UK Defence Science and Technology Laboratory (Dstl), and the US Naval Research Laboratory (NRL) in developing small satellite ionospheric physics capability. CIRCE will characterise space weather effects on a regional scale in the ionosphere/thermosphere system. Properly characterising the dynamic ionosphere is important for a wide range of both civil and defence applications such as GPS, communications, and sensing technology. Consisting of two near-identical 6U (2x3U) CubeSat buses, the CIRCE nanosatellites will fly in a lead-follow tandem configuration in co-planar near-polar orbits at 500km altitude. Provided by Blue Canyon Technologies (BCT), the two buses will use differential drag to achieve and maintain an in-track separation of between 250 and 500km, allowing short time-scale dynamics to be observed in-situ. These nanosatellites each carry a complement of 5 individual scientific instruments, contributed from academic, industrial, and government partners across the UK and US. Scheduled to launch in 2021 via the US Department of Defence Space Test Program, the two CIRCE satellites will provide observations to enable a greater understanding of the driving processes of geophysical phenomena in the ionosphere/thermosphere system, distributed across a wide range of latitudes, and altitudes, as the mission progresses

Aniline-Containing Derivatives of Parthenolide: Synthesis and Anti-Chronic Lymphocytic Leukaemia Activity

A protocol for squaric acid-catalysed 1,4-addition of aniline derivatives to parthenolide is identified, developed and disclosed.<br /

Boronic ester derivative-dependent activity of parthenolide analogues

Four parthenolide derived prodrugs, containing different boronic ester moieties, were synthesised, their drug-like properties were calculated and their activity against chronic lymphocytic leukaemia (CLL) MEC1 cells measured. Differences in the clogP, the propensity towards oxidation by hydrogen peroxide, the affinity of the associated diols to a model boronic acid and the biological activity against MEC1 cells were contrasted, and it was found that the propensity for oxidation correlated to biological activity

Coordinated Ionospheric Reconstruction CubeSat Experiment (CIRCE),

The UK’s Defence Science and Technology Laboratory (Dstl) is partnering with the US Naval Research Laboratory (NRL) on a joint mission to launch miniature sensors that will advance space weather measurement and modelling capabilities. The Coordinated Ionospheric Reconstruction Cubesat Experiment (CIRCE) comprises two 6U cube-satellites that will be launched into a near-polar low earth orbit (LEO), targeting 500 km altitude, in 2021. The UK contribution to CIRCE is the In situ and Remote Ionospheric Sensing (IRIS) suite, complementary to NRL sensors, and comprising three highly miniaturised payloads provided to Dstl by University College London (UCL), University of Bath, and University of Surrey/Surrey Satellite Technology Ltd (SSTL). One IRIS suite will be flown on each satellite, and incorporates an ion/neutral mass spectrometer, a tri-band global positioning system (GPS) receiver for ionospheric remote sensing, and a radiation environment monitor. From the US, NRL have provided two 1U Triple Tiny Ionospheric Photometers (Tri-TIPs) on each satellite (Nicholas et al., 201

Derivatisation of Parthenolide to Address Chemoresistant Chronic Lymphocytic Leukaemia

A protocol for growing, extracting and derivatising parthenolide obtained from feverfew varieties is reported. Aminated parthenolide derivatives were prepared via 1,4-addition of primary or secondary amines utilising established and modified methods. The parthenolide derivatives’ drug-likeness properties were computed and they were screened for anti-leukaemic activity against the TP53-mutant, chemo-refractory, MEC1 chronic lymphocytic leukaemia (CLL) cell line. A screening cascade identified a small number of the most active compounds and their properties, including in vivo pharmacokinetics and in vitro hERG liability, were compared against DMAPT. This cascade culminated in the identification of a new compound with good anti CLL activity, with fewer drawbacks than some headline compounds from the literature and with utility against drug-resistant disease. Literature precedent and molecular docking studies support a multi-target-driven mode of action

Derivatisation of Parthenolide to Address Chemoresistant Chronic Lymphocytic Leukaemia

A protocol for growing, extracting and derivatising parthenolide obtained from feverfew varieties is reported. Aminated parthenolide derivatives were prepared via 1,4-addition of primary or secondary amines utilising established and modified methods. The parthenolide derivatives’ drug-likeness properties were computed and they were screened for anti-leukaemic activity against the TP53-mutant, chemo-refractory, MEC1 chronic lymphocytic leukaemia (CLL) cell line. A screening cascade identified a small number of the most active compounds and their properties, including in vivo pharmacokinetics and in vitro hERG liability, were compared against DMAPT. This cascade culminated in the identification of a new compound with good anti CLL activity, with fewer drawbacks than some headline compounds from the literature and with utility against drug-resistant disease. Literature precedent and molecular docking studies support a multi-target-driven mode of action.<br /

Derivatisation of parthenolide to address chemoresistant chronic lymphocytic leukaemia

Parthenolide is a natural product that exhibits anti-leukaemic activity, however, its clinical use is limited by its poor bioavailability. It may be extracted from feverfew and protocols for growing, extracting and derivatising it are reported. A novel parthenolide derivative with good bioavailability and pharmacological properties was identified through a screening cascade based on in vitro anti-leukaemic activity and calculated “drug-likeness” properties, in vitro and in vivo pharmacokinetics studies and hERG liability testing. In vitro studies showed the most promising derivative to have comparable anti-leukaemic activity to DMAPT, a previously described parthenolide derivative. The newly identified compound was shown to have pro-oxidant activity and in silico molecular docking studies indicate a prodrug mode of action. A synthesis scheme is presented for the production of amine 7 used in the generation of 5f

The N-terminal RASSF family: a new group of Ras-association-domain-containing proteins, with emerging links to cancer formation

The RASSF (Ras-association domain family) has recently gained several new members and now contains ten proteins (RASSF1-10), several of which are potential tumour suppressors. The family can be split into two groups, the classical RASSF proteins (RASSF1-6) and the four recently added N-terminal RASSF proteins (RASSF7-10). The N-terminal RASSF proteins have a number of differences from the classical RASSF members and represent a newly defined set of potential Ras effectors. They have been linked to key biological processes, including cell death, proliferation, microtubule stability, promoter methylation, vesicle trafficking and response to hypoxia. Two members of the N-terminal RASSF family have also been highlighted as potential tumour suppressors. The present review will summarize what is known about the N-terminal RASSF proteins, addressing their function and possible links to cancer formation. It will also compare the N-terminal RASSF proteins with the classical RASSF proteins and ask whether the N-terminal RASSF proteins should be considered as genuine members or imposters in the RASSF family