Deep mixed ocean volume in the Labrador Sea in HighResMIP models

Simulations from seven global coupled climate models performed at high and standard resolution as part of the high resolution model intercomparison project (HighResMIP) are analyzed to study deep ocean mixing in the Labrador Sea and the impact of increased horizontal resolution. The representation of convection varies strongly among models. Compared to observations from ARGO-floats and the EN4 data set, most models substantially overestimate deep convection in the Labrador Sea. In four out of five models, all four using the NEMO-ocean model, increasing the ocean resolution from 1° to 1/4° leads to increased deep mixing in the Labrador Sea. Increasing the atmospheric resolution has a smaller effect than increasing the ocean resolution. Simulated convection in the Labrador Sea is mainly governed by the release of heat from the ocean to the atmosphere and by the vertical stratification of the water masses in the Labrador Sea in late autumn. Models with stronger sub-polar gyre circulation have generally higher surface salinity in the Labrador Sea and a deeper convection. While the high-resolution models show more realistic ocean stratification in the Labrador Sea than the standard resolution models, they generally overestimate the convection. The results indicate that the representation of sub-grid scale mixing processes might be imperfect in the models and contribute to the biases in deep convection. Since in more than half of the models, the Labrador Sea convection is important for the Atlantic Meridional Overturning Circulation (AMOC), this raises questions about the future behavior of the AMOC in the models

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

A regime view of future atmospheric circulation changes in northern mid-latitudes

Future wintertime atmospheric circulation changes in the Euro–Atlantic (EAT) and Pacific–North American (PAC) sectors are studied from a weather regimes perspective. The Coupled Model Intercomparison Project phases 5 and 6 (CMIP5 and CMIP6) historical simulation performance in reproducing the observed regimes is first evaluated, showing a general improvement in the CMIP6 models, which is more evident for EAT. The circulation changes projected by CMIP5 and CMIP6 scenario simulations are analysed in terms of the change in the frequency and persistence of the regimes. In the EAT sector, significant positive trends are found for the frequency and persistence of NAO+ (North Atlantic Oscillation) for SSP2–4.5, SSP3–7.0 and SSP5–8.5 scenarios with a concomitant decrease in the frequency of the Scandinavian blocking and Atlantic Ridge regimes. For PAC, the Pacific Trough regime shows a significant increase, while the Bering Ridge is predicted to decrease in all scenarios analysed. The spread among the model responses is linked to different levels of warming in the polar stratosphere, the tropical upper troposphere, the North Atlantic and the Arctic.</p

Recent advances in the knowledge of the Río de la Plata estuary circulation, forcings and variability

The Río de la Plata, located in the eastern coast of Southern South America, approximately at 35\ub0 S, is one of the largest estuaries of the world. With an estuarine area of 35000 Km2, a drainage area of 3.5&#61620;106 Km2 and a mean discharge of 25000 m3s-1, it ranks 4th and 5th worldwide in fresh water discharge and drainage area, respectively. Besides its geographical extension, the estuary is of great social and economical importance for the countries on its shores. The capital cities of both countries and a number of harbors, resorts and industrial centers are located there. The estuary constitutes the main source of drinking water for the millions of inhabitants in the region, for whom it is also an important amusement zone. The estuary has important fisheries and possesses the unusual feature of being a spawning and nursery area for several coastal species. Because of these reasons the estuary is being impacted by anthropogenic actions, which consequences have not been completely evaluated yet. Due to the intense discharge, when the fresh river water meets the open ocean, an intense and active salinity front followed by a fresh water plume, which influence can be tracked up to 23\ub0 S, is formed. This front is important not only for fisheries, but also modifies the coastal circulation and the mixing and convection conditions with important oceanographic implications. Despite of its social and oceanographic importance, not much was known about the Río de la Plata circulation, its variability and forcings a few years ago. Recently, in the context of National and International Projects -as UNDP/GEF Project Environmental Protection of the Río de la Plata and its Maritime Front (FREPLATA), and Estudio de la dinámica oceánica y atmosférica del Estuario del Río de la Plata mediante un sistema de modelado numérico integral (PROPLATA) founded by the Agencia Nacional de Promoción Científica of Argentina- important advances in our understanding of the physical oceanography of this system were done. This improvement is in a large extent the result of the collection, by the first time, of long term ADCP current data that allowed the study of current variability from very high frequencies to intra-seasonal time scales, and its connection to wind variability. Also, the application of numerical models contributed to the understanding of the mechanisms that control estuarine motions and the effect of their variability. As a result, our view of the behavior of this system has essentially enhanced and in many aspects has changed. In this sense, the aim of this presentation will be to discuss what we learned during the last few years and the main gaps that must be fulfilled in order to allow for an adequate representation of the system to permit its forecasting, management and control will be pointed out.Pages: 1393-141

Impact of ocean resolution and mean state on the rate of AMOC weakening

We examine the weakening of the Atlantic Meridional Overturning Circulation (AMOC) in response to increasing CO2 at different horizontal resolutions in a state-of-the-art climate model and in a small ensemble of models with differing resolutions. There is a strong influence of the ocean mean state on the AMOC weakening: models with a more saline western subpolar gyre have a greater formation of deep water there. This makes the AMOC more susceptible to weakening from an increase in CO2 since weakening ocean heat transports weaken the contrast between ocean and atmospheric temperatures and hence weaken the buoyancy loss. In models with a greater proportion of deep water formation further north (in the Greenland-Iceland-Norwegian basin), deep-water formation can be maintained by shifting further north to where there is a greater ocean-atmosphere temperature contrast. We show that ocean horizontal resolution can have an impact on the mean state, and hence AMOC weakening. In the models examined, those with higher resolutions tend to have a more westerly location of the North Atlantic Current and stronger subpolar gyre. This likely leads to a greater impact of the warm, saline subtropical Atlantic waters on the western subpolar gyre resulting in greater dense water formation there. Although there is some improvement of the higher resolution models over the lower resolution models in terms of the mean state, both still have biases and it is not clear which biases are the most important for influencing the AMOC strength and response to increasing CO2.LJ, MR, DI, TK, VM, CR, YR-R were funded by the PRIMAVERA project, funded by the European Union’s Horizon 2020 programme under grant agreement 641727. LJ, HH, MR, RW were supported by the Met Office Hadley Centre Climate Programme funded by BEIS and Defra (GA01101). We wish to thank two anonymous reviewers for their comments which improved this manuscript.Peer ReviewedPostprint (published version

A Novel Initialization Technique for Decadal Climate Predictions

International audienceModel initialization is a matter of transferring the observed information available at the start of a forecast to the model. An optimal initialization is generally recognized to be able to improve climate predictions up to a few years ahead. However, systematic errors in models make the initialization process challenging. When the observed information is transferred to the model at the initialization time, the discrepancy between the observed and model mean climate causes the drift of the prediction toward the model-biased attractor. Although such drifts can be generally accounted for with a posteriori bias correction techniques, the bias evolving along the prediction might affect the variability that we aim at predicting, and disentangling the small magnitude of the climate signal from the initial drift to be removed represents a challenge. In this study, we present an innovative initialization technique that aims at reducing the initial drift by performing a quantile matching between the observed state at the initialization time and the model state distribution. The adjusted initial state belongs to the model attractor and the observed variability amplitude is scaled toward the model one. Multi-annual climate predictions integrated for 5 years and run with the EC-Earth3 Global Coupled Model have been initialized with this novel methodology, and their prediction skill has been compared with the non-initialized historical simulations from CMIP6 and with the same decadal prediction system but based on full-field initialization. We perform a skill assessment of the surface temperature, the heat content in the ocean upper layers, the sea level pressure, and the barotropic ocean circulation. The added value of the quantile matching initialization is shown in the North Atlantic subpolar region and over the North Pacific surface temperature as well as for the ocean heat content up to 5 years. Improvements are also found in the predictive skill of the Atlantic Meridional Overturning Circulation and the barotropic stream function in the Labrador Sea throughout the 5 forecast years when compared to the full field method

Duration of response after DEB-TACE compared to lipiodol-TACE in HCC-naïve patients: a propensity score matching analysis

Objectives: To retrospectively compare long-term outcomes of first-line drug-eluting particle (DEB)- transarterial chemoembolization (TACE) and lipiodol-TACE, in patients with unresectable hepatocellular (HCC). Methods: We retrospectively reviewed our database to identify adult patients with treatment-naïve unresectable HCC, who underwent TACE from 2006 to 2013. Patients were excluded in the absence of complete medical records relative to first TACE, 1-month follow-up, and/or sufficient follow-up data. Periprocedural complications, duration of hospitalization, 1-month tumor response by mRECIST, time to tumor progression (TTP) and target tumor progression (TTTP), and overall survival (OS) were evaluated. Results: Out of an initial series of 656 patients, 329 patients were excluded for unavailability of sufficient baseline and/or follow-up data. The remaining 327 patients underwent either lipiodol-TACE (n = 160) or DEB-TACE (n = 167). Patients treated with lipiodol-TACE had a significantly higher tumor burden. By propensity score, patients were matched according to baseline differences (BCLC stage, uninodular or multinodular HCC, and unilobar or bilobar HCC), resulting in 101 patients in each treatment group. Lipiodol-TACE was associated with a significantly higher incidence of adverse events (p = 0.03), and longer hospitalization (mean, 2.5 days vs 1.9 days; p = 0.03), while tumor response, TTP, and OS were comparable. In patients achieving 1-month complete response (CR) of target tumor, TTTP was significantly (p = 0.009) longer after DEB-TACE compared to lipiodol-TACE (median, 835 vs 353 days), resulting in a lower number of re-treatments during the entire follow-up (0.75 vs 1.6, p = 0.01). Conclusion: Compared to lipiodol-TACE, DEB-TACE offers higher tolerability, reduced hospitalization, and more durable target tumor response after CR. Key Points: • Compared to lipiodol-TACE, DEB-TACE is better tolerated and has reduced side effects, which translates into shorter hospitalization. • When complete radiological response according to the mRECIST is obtained 1 month after the procedure, DEB-TACE offers a more durable local tumor control compared to lipiodol-TACE. • In these patients, the longer duration of response after DEB-TACE translates into a lower number of re-interventions