Prebiosignature Molecules Can Be Detected in Temperate Exoplanet Atmospheres with JWST

The search for biosignatures on exoplanets connects the fields of biology and biochemistry to astronomical observation, with the hope that we might detect evidence of active biological processes on worlds outside the solar system. Here we focus on a complementary aspect of exoplanet characterisation connecting astronomy to prebiotic chemistry: the search for molecules associated with the origin of life, prebiosignatures. Prebiosignature surveys in planetary atmospheres offer the potential to both constrain the ubiquity of life in the galaxy and provide important tests of current prebiotic syntheses outside of the laboratory setting. Here, we quantify the minimum abundance of identified prebiosignature molecules that would be required for detection by transmission spectroscopy using JWST. We consider prebiosignatures on five classes of terrestrial planet: an ocean planet, a volcanic planet, a post-impact planet, a super-Earth, and an early Earth analogue. Using a novel modelling and detection test pipeline, with simulated JWST noise, we find the detection thresholds of hydrogen cyanide (HCN), hydrogen sulfide (H2S), cyanoacetylene (HC3N), ammonia (NH3), methane (CH4), acetylene (C2H2), sulfur dioxide (SO2), nitric oxide (NO), formaldehyde (CH2O), and carbon monoxide (CO) in a variety of low mean molecular weight (<5) atmospheres. We test the dependence of these detection thresholds on M dwarf target star and the number of observed transits, finding that a modest number of transits (1-10) are required to detect prebiosignatures in numerous candidate planets, including TRAPPIST-1e with a high mean molecular weight atmosphere. We find that the NIRSpec G395M/H instrument is best suited for detecting most prebiosignatures.Comment: 28 pages, 12 figures, accepted for publication in A

Sequence-defined phosphoestamers for selective inhibition of the KRASG12D/RAF1 interaction

RAS proteins are the most frequently mutated in cancer, yet they have proved extremely difficult to target in drug discovery, largely because interfering with the interaction of RAS with its downstream effectors comes up against the challenge of protein-protein interactions (PPIs). Sequence-defined synthetic oligomers could combine the precision and customisability of synthetic molecules with the size required to address entire PPI surfaces. We have adapted the phosphoramidite chemistry of oligonucleotide synthesis to produce a library of nearly one million non-nucleosidic oligophosphoester sequences (phosphoestamers) composed of units taken from synthetic supramolecular chemistry, and used a fluorescent-activated bead sorting (FABS) process to select those that inhibit the interaction between KRASG12D (the most prevalent, and undrugged, RAS mutant) and RAF, a downstream effector of RAS that drives cell proliferation. Hits were identified using tandem mass spectrometry, and orthogonal validation showed effective inhibition of KRASG12D with IC50 values as low as 25 nM, and excellent selectivity over the wild type form. These findings have the potential to lead to new drugs that target mutant RAS-driven cancers, and provide proof-of-principle for the phosphoestamer chemical platform against PPIs in general - opening up new possibilities in neurodegenerative disease, viral infection, and many more conditions

Climate Scenario analysis for pension schemes:a UK case study

This paper demonstrates how climate scenario analysis can be used for forward-looking assessment of the risks and opportunities for financial institutions, using a case study for a UK defined benefit pension scheme. It uses a top-down modelling tool developed by Ortec Finance in partnership with Cambridge Econometrics to explore the possible impacts of three plausible (not extreme) climate pathways of the scheme’s assets and liabilities. It finds that the funding risks are greater under all three climate pathways than under the climate-uninformed base scenario. In the absence of changes to the investment strategy or recovery plan, the time taken to reach full funding is increased by three to nine years. Given that most models currently used by actuaries do not make explicit adjustments for climate change, these modelled results suggest it is quite likely that pension schemes are systematically underestimating the funding risks they face

Climate scenario analysis:An illustration of potential long-term economic &amp; financial market impacts

This paper illustrates the potential impacts of climate change on financial markets, focusing on their long-term significance. It uses a top-down modelling tool developed by Ortec Finance in partnership with Cambridge Econometrics that combines climate science with macro-economic and financial effects to examine the possible impacts of three plausible (not extreme) climate pathways. The paper first considers the impact on gross domestic product (GDP), finding that GDP is lower in all three pathways, with the most severe reduction in the Failed Transition Pathway where the Paris Agreement climate targets are not met. The model then translates these GDP impacts into financial market effects. In the Failed Transition Pathway, cumulative global equity returns are approximately 50% lower over the period 2020–2060 than in the climate-uninformed base case. For the other two pathways where the Paris Agreement targets are met, the corresponding figures are 15% and 25% lower returns than in the base case. Results are provided for other asset classes too. These demonstrate that climate change represents a significant market risk, with implications for financial planning, modelling and regulation