A numerical study of the Southern Ocean including a thermodynamic active ice shelf - Part 1: Weddell Sea

There is a great amount of uncertainty regarding the understanding of the atmosphere-ocean-cryosphere interactions in the Southern Ocean despite the role that the region plays in our changing climate. With the aim of studying the relative importance of sea-ice and ice shelf processes in the Southern Ocean, a coupled ocean circulation sea-ice/ice shelf cavity model based on the Regional Ocean Model System (ROMS) is used in a periodic circumpolar domain with enhanced resolution in the Weddell Sea. A hierarchy of numerical experiments is performed where first a sea-ice model is used and then an ice shelf thermodynamic parameterization is included in order to evaluate the improvements resulting from each component. Results show that it is necessary to consider the formation and melting of sea-ice in order to adequately reproduce the observed hydrography and circulation. Inclusion of ice shelves cavities in the model only improves results if the ice shelf-ocean thermodynamic fluxes are active. Ice shelves and ocean interactions are an important process to be considered in order to obtain realistic hydrographic values under the ice shelf. The model framework presented in this work is a promising tool for analyzing the Southern Ocean response to future climate change scenarios

A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer.

8-Oxoguanine, a common mutagenic DNA lesion, generates G:C>T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this enzymatic function and are associated with colorectal cancer (CRC) in MUTYH-Associated Polyposis (MAP) syndrome. Here, we perform whole-exome sequencing that reveals a modest mutator phenotype in MAP CRCs compared to sporadic CRC stem cell lines or bulk tumours. The excess G:C>T:A transversion mutations in MAP CRCs exhibits a novel mutational signature, termed Signature 36, with a strong sequence dependence. The MUTYH mutational signature reflecting persistent 8-oxoG:A mismatches occurs frequently in the APC, KRAS, PIK3CA, FAT4, TP53, FAT1, AMER1, KDM6A, SMAD4 and SMAD2 genes that are associated with CRC. The occurrence of Signature 36 in other types of human cancer indicates that DNA 8-oxoguanine-related mutations might contribute to the development of cancer in other organs

HighResMIP versions of EC-Earth: EC-Earth3P and EC-Earth3P-HR - Description, model computational performance and basic validation

A new global high-resolution coupled climate model, EC-Earth3P-HR has been developed by the EC-Earth consortium, with a resolution of approximately 40 km for the atmosphere and 0.25° for the ocean, alongside with a standard-resolution version of the model, EC-Earth3P (80 km atmosphere, 1.0 ° ocean). The model forcing and simulations follow the High Resolution Model Intercomparison Project (HighResMIP) protocol. According to this protocol, all simulations are made with both high and standard resolutions. The model has been optimized with respect to scalability, performance, data storage and post-processing. In accordance with the HighResMIP protocol, no specific tuning for the high-resolution version has been applied. Increasing horizontal resolution does not result in a general reduction of biases and overall improvement of the variability, and deteriorating impacts can be detected for specific regions and phenomena such as some Euro-Atlantic weather regimes, whereas others such as the El Niño-Southern Oscillation show a clear improvement in their spatial structure. The omission of specific tuning might be responsible for this. The shortness of the spin-up, as prescribed by the HighResMIP protocol, prevented the model from reaching equilibrium. The trend in the control and historical simulations, however, appeared to be similar, resulting in a warming trend, obtained by subtracting the control from the historical simulation, close to the observational one

Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development while Allowing Accumulation of Myeloid Cells and LT-HSC Cells

Ying Yang 1 (YY1) is a multifunctional Polycomb Group (PcG) transcription factor that binds to multiple enhancer binding sites in the immunoglobulin (Ig) loci and plays vital roles in early B cell development. PcG proteins have important functions in hematopoietic stem cell renewal and YY1 is the only mammalian PcG protein with DNA binding specificity. Conditional knock-out of YY1 in the mouse B cell lineage results in arrest at the pro-B cell stage, and dosage effects have been observed at various YY1 expression levels. To investigate the impact of elevated YY1 expression on hematopoetic development, we utilized a mouse in vivo bone marrow reconstitution system. We found that mouse bone marrow cells expressing elevated levels of YY1 exhibited a selective disadvantage as they progressed from hematopoietic stem/progenitor cells to pro-B, pre-B, immature B and re-circulating B cell stages, but no disadvantage of YY1 over-expression was observed in myeloid lineage cells. Furthermore, mouse bone marrow cells expressing elevated levels of YY1 displayed enrichment for cells with surface markers characteristic of long-term hematopoietic stem cells (HSC). YY1 expression induced apoptosis in mouse B cell lines in vitro, and resulted in down-regulated expression of anti-apoptotic genes Bcl-xl and NFκB2, while no impact was observed in a mouse myeloid line. B cell apoptosis and LT-HSC enrichment induced by YY1 suggest that novel strategies to induce YY1 expression could have beneficial effects in the treatment of B lineage malignancies while preserving normal HSCs

Coupling a thermodynamically active ice shelf to a regional simulation of the Weddell Sea

A thermodynamically interactive ice shelf cavity parameterization is coupled to the Regional Ocean Model System (ROMS) and is applied to the Southern Ocean domain with enhanced resolution in the Weddell Sea. This implementation is tested in order to assess its degree of improvement to the hydrography (and circulation) of the Weddell Sea. Results show that the inclusion of ice shelf cavities in the model is feasible and somewhat realistic (considering the lack of under-ice observations for validation). Ice shelf–ocean interactions are an important process to be considered in order to obtain realistic hydrographic values under the ice shelf. The model framework presented in this work is a promising tool for analyzing the Southern Ocean's response to future climate change scenarios

Mechanical and microstructural characterisation of an aluminum friction stir-welded butt joint

The microstructure and the mechanical properties of a 6056 aluminium alloy Friction Stir-Welded (FSW) joint were investigated in the present study. The structure was analysed using light, scanning and transmission electron microscopy. The change in microstructure across the welded joint was found to correspond to significant variation in hardness. As in most FSW joints, the structure was characterised by the presence of a region of severely deformed grains in proximity of the weld nugget, i.e. of a region of fine recrystallised grains. Tensile tests showed that the joint material exhibited a rupture strength similar to the parent material, even though the former was significantly less ductile. This difference resulted in a reduction in ductility of the welded sheets. A T6 treatment increased tensile strength, but further reduced joint ductility. Nevertheless, the strength of the welded sheet was found to be very close (80-90%) to that of the base alloy