Exceptional Retreat of Kangerlussuaq Glacier, East Greenland, Between 2016 and 2018

Kangerlussuaq Glacier is one of Greenland’s largest tidewater outlet glaciers, accounting for approximately 5% of all ice discharge from the Greenland ice sheet. In 2018 the Kangerlussuaq ice front reached its most retreated position since observations began in 1932. We determine the relationship between retreat and: (i) ice velocity; and (ii) surface elevation change, to assess the impact of the retreat on the glacier trunk. Between 2016 and 2018 the glacier retreated ∼5 km and brought the Kangerlussuaq ice front into a major (∼15 km long) overdeepening. Coincident with this retreat, the glacier thinned as a result of near-terminus acceleration in ice flow. The subglacial topography means that 2016–2018 terminus recession is likely to trigger a series of feedbacks between retreat, thinning, and glacier acceleration, leading to a rapid and high-magnitude increase in discharge and sea level rise contribution. Dynamic thinning may continue until the glacier reaches the upward sloping bed ∼10 km inland of its current position. Incorporating these non-linear processes into prognostic models of the ice sheet to 2100 and beyond will be critical for accurate forecasting of the ice sheet’s contribution to sea level rise

On the annual variability of Antarctic aerosol size distributions at Halley Research Station

The Southern Ocean and Antarctic region currently best represent one of the few places left on our planet with conditions similar to the preindustrial age. Currently, climate models have a low ability to simulate conditions forming the aerosol baseline; a major uncertainty comes from the lack of understanding of aerosol size distributions and their dynamics. Contrasting studies stress that primary sea salt aerosol can contribute significantly to the aerosol population, challenging the concept of climate biogenic regulation by new particle formation (NPF) from dimethyl sulfide marine emissions. We present a statistical cluster analysis of the physical characteristics of particle size distributions (PSDs) collected at Halley (Antarctica) for the year 2015 (89 % data coverage; 6-209 nm size range; daily size resolution). By applying the Hartigan-Wong k-mean method we find eight clusters describing the entire aerosol population. Three clusters show pristine average low particle number concentrations (<121-179 cm(-3)) with three main modes (30, 75-95 and 135-160 nm) and represent 57 % of the annual PSD (up to 89 %-100 % during winter and 34 %-65 % during summer based on monthly averages). Nucleation and Aitken mode PSD clusters dominate summer months (SeptemberJanuary, 59 %-90 %), whereas a clear bimodal distribution (43 and 134 nm, respectively; Hoppel minimum at mode 75 nm) is seen only during the December-April period (6%-21 %). Major findings of the current work include: (1) NPF and growth events originate from both the sea ice marginal zone and the Antarctic plateau, strongly suggesting multiple vertical origins, including the marine boundary layer and free troposphere; (2) very low particle number concentrations are detected for a substantial part of the year (57 %), including summer (34 %-65 %), suggesting that the strong annual aerosol concentration cycle is driven by a short temporal interval of strong NPF events; (3) a unique pristine aerosol cluster is seen with a bimodal size distribution (75 and 160 nm, respectively), strongly associated with high wind speed and possibly associated with blowing snow and sea spray sea salt, dominating the winter aerosol population (34 %-54 %). A brief comparison with two other stations (Dome C - Concordia- and King Sejong Station) during the year 2015 (240 d overlap) shows that the dynamics of aerosol number concentrations and distributions are more complex than the simple sulfate-sea-spray binary combination, and it is likely that an array of additional chemical components and processes drive the aerosol population. A conceptual illustration is proposed indicating the various atmospheric processes related to the Antarctic aerosols, with particular emphasis on the origin of new particle formation and growth.Peer reviewe

Influence of sea‐ice‐derived halogens on atmospheric HOx as observed in springtime coastal Antarctica

We present first observations of OH and (HO2 + RO2) carried out in Antarctica outside the summer season. Measurements were made over 23 days in spring at the coastal Antarctic station Halley. Increases in concentrations were evident during the measurement period due to rapidly increasing solar irradiance, and clear diurnal cycles were present throughout. There were also notable differences in air mass composition depending on wind direction. Air masses that had traversed the sea‐ice‐zone had both higher concentrations of OH and a larger OH:(HO2 + RO2) ratio. We use steady‐state kinetic arguments and a 0‐D box model to probe the chemical drivers. We find that differences in bromine chemistry, previously measured at Halley, are sufficient to account for the observed differences in OH concentration as well as the ratio. There is some evidence also that chlorine chemistry is influencing concentrations of RO2

Measurement of gas-phase OH radical oxidation and film thickness of organic films at the air–water interface using material extracted from urban, remote and wood smoke aerosol

The presence of an organic film on a cloud droplet or aqueous aerosol particle has the potential to alter the chemical, optical and physical properties of the droplet or particle. In the study presented, water insoluble organic materials extracted from urban, remote (Antarctica) and wood burning atmospheric aerosol were found to have stable, compressible, films at the air–water interface that were typically ∼6–18 Å thick. These films are reactive towards gas-phase OH radicals and decay exponentially, with bimolecular rate constants for reaction with gas-phase OH radicals of typically 0.08–1.5 × 10−10 cm3 molecule−1 s−1. These bimolecular rate constants equate to initial OH radical uptake coefficients estimated to be ∼0.6–1 except woodsmoke (∼0.05). The film thickness and the neutron scattering length density of the extracted atmosphere aerosol material (from urban, remote and wood burning) were measured by neutron reflection as they were exposed to OH radicals. For the first time neutron reflection has been demonstrated as an excellent technique for studying the thin films formed at air–water interfaces from materials extracted from atmospheric aerosol samples. Additionally, the kinetics of gas-phase OH radicals with a proxy compound, the lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) was studied displaying significantly different behaviour, thus demonstrating it is not a good proxy for atmospheric materials that may form films at the air–water interface. The atmospheric lifetimes, with respect to OH radical oxidation, of the insoluble organic materials extracted from atmospheric aerosol at the air–water interface were a few hours. Relative to a possible physical atmospheric lifetime of 4 days, the oxidation of these films is important and needs inclusion in atmospheric models. The optical properties of these films were previously reported [Shepherd et al., Atmos. Chem. Phys., 2018, 18, 5235–5252] and there is a significant change in top of the atmosphere albedo for these thin films on core–shell atmospheric aerosol using the film thickness data and confirmation of stable film formation at the air–water interface presented here

Exploring the Trypanosoma brucei Hsp83 Potential as a Target for Structure Guided Drug Design

Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp), while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF). Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC) and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite

Psychological resilience in sport performers: a review of stressors and protective factors

Psychological resilience is important in sport because athletes must utilize and optimize a range of mental qualities to withstand the pressures that they experience. In this paper, we discuss psychological resilience in sport performers via a review of the stressors athletes encounter and the protective factors that help them withstand these demands. It is hoped that synthesizing what is known in these areas will help researchers gain a deeper profundity of resilience in sport, and also provide a rigorous and robust foundation for the development of a sport-specific measure of resilience. With these points in mind, we divided the narrative into two main sections. In the first section, we review the different types of stressors encountered by sport performers under three main categories: competitive, organizational, and personal. Based on our recent research examining psychological resilience in Olympics champions (Fletcher & Sarkar, 2012), in the second section we discuss the five main families of psychological factors (viz. positive personality, motivation, confidence, focus, perceived social support) that protect the best athletes from the potential negative effect of stressors. It is anticipated that this review will help sport psychology researchers examine the interplay between stressors and protective factors which will, in turn, focus the analytical lens on the processes underlying psychological resilience in athletes

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P &lt; 0.001) and PARP inhibitor therapy (P &lt; 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P &lt; 0.018) and WEE1 inhibitor (P &lt; 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P &lt; 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy