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Abstract. Multi-meter sea level rise (SLR) is thought to be possible within the next few centuries, with most of the uncertainty originating from the Antarctic land ice contribution. One source of uncertainty relates to the ice sheet model initialization. Since ice sheets have a long response time (compared to other Earth system components such as the atmosphere), ice sheet model initialization methods can have significant impacts on how the ice sheet responds to future forcings. To assess this, we generated 25 different ice sheet spin-ups, using the Community Ice Sheet Model (CISM) at a 4 km resolution. During each spin-up, we varied two key parameters known to impact the sensitivity of the ice sheet to future forcing: one related to the sensitivity of the ice shelf melt rate to ocean thermal forcing (TF) and the other related to the basal friction. The spin-ups all nudge toward observed thickness and enforce a no-advance calving criterion, such that all final spin-up states resemble observations but differ in their melt and friction parameter settings. Each spin-up was then forced with future ocean thermal forcings from 13 different CMIP6 models under the Shared Socioeconomic Pathway (SSP)5-8.5 emissions scenarioand modern climatological surface mass balance data. Our results show that the effects of the ice sheet and ocean parameter settings used during the spin-up are capable of impacting multi-century future SLR predictions by as much as 2 m. By the end of this century, the effects of these choices are more modest, but still significant, with differences of up to 0.2 m of SLR. We have identified a combined ocean and ice parameter space that leads to widespread mass loss within 500 years (low friction and high melt rate sensitivity). To explore temperature thresholds, we also ran a synthetically forced CISM ensemble that is focused on the Amundsen region only. Given certain ocean and ice parameter choices, Amundsen mass loss can be triggered with thermal forcing anomalies between 1.5 and 2 ∘C relative to the spin-up.Our results emphasize the critical importance of considering ice sheet and ocean parameter choices during spin-up for SLR predictions and suggest the importance of including glacial isostatic adjustment in ice sheet simulations. 

HS3ST1is a genetic risk gene associated with Alzheimer’s disease (AD) and overexpressed in patients, but how it contributes to the disease progression is unknown. We report the analysis of brain heparan sulfate (HS) from AD and other tauopathies using a LC-MS/MS method. A specific 3-O-sulfated HS displayed sevenfold increase in the AD group (n= 14,P< 0.0005). Analysis of the HS modified by recombinant sulfotransferases and HS from genetic knockout mice revealed that the specific 3-O-sulfated HS is made by 3-O-sulfotransferase isoform 1 (3-OST-1), which is encoded by theHS3ST1gene. A synthetic tetradecasaccharide (14-mer) carrying the specific 3-O-sulfated domain displayed stronger inhibition for tau internalization than a 14-mer without the domain, suggesting that the 3-O-sulfated HS is used in tau cellular uptake. Our findings suggest that the overexpression ofHS3ST1gene may enhance the spread of tau pathology, uncovering a previously unidentified therapeutic target for AD. 

Modelling of cardiac electrical behaviour has led to important mechanistic insights, but important challenges, including uncertainty in model formulations and parameter values, make it difficult to obtain quantitatively accurate results. An alternative approach is combining models with observations from experiments to produce a data-informed reconstruction of system states over time. Here, we extend our earlier data-assimilation studies using an ensemble Kalman filter to reconstruct a three-dimensional time series of states with complex spatio-temporal dynamics using only surface observations of voltage. We consider the effects of several algorithmic and model parameters on the accuracy of reconstructions of known scroll-wave truth states using synthetic observations. In particular, we study the algorithm’s sensitivity to parameters governing different parts of the process and its robustness to several model-error conditions. We find that the algorithm can achieve an acceptable level of error in many cases, with the weakest performance occurring for model-error cases and more extreme parameter regimes with more complex dynamics. Analysis of the poorest-performing cases indicates an initial decrease in error followed by an increase when the ensemble spread is reduced. Our results suggest avenues for further improvement through increasing ensemble spread by incorporating additive inflation or using a parameter or multi-model ensemble. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’. 

Abstract Glaciers of the McMurdo dry valleys (MDVs) Antarctica are the main source of streamflow in this polar desert. Because summer air temperatures hover near 0°C small changes in the energy balance strongly affect meltwater generation. Here we demonstrate that increased surface roughness, which alters the turbulent transfer of energy between the ice surface and atmosphere, yields a detectable increase in meltwater runoff. At low elevations on the glaciers, basin‐like topography became significantly rougher over 13 years between repeat lidar surveys, yielding greater melt. In contrast, the smoother ice at higher elevation exhibited no detectable change in roughness. We pose a conceptual model of the cycle of glacier surface change as a result of climate forcing whereby glacier surfaces transition from being dominated by sublimation to becoming increasingly melt‐dominated, which is reversible under prolonged cool periods. This research advances our understanding of warm season effects on polar glaciers. 

The Southern Ocean overturning circulation is driven by winds, heat fluxes, and freshwater sources. Among these sources of freshwater, Antarctic sea-ice formation and melting play the dominant role. Even though ice-shelf melt is relatively small in magnitude, it is located close to regions of convection, where it may influence dense water formation. Here, we explore the impacts of ice-shelf melting on Southern Ocean water mass transformation (WMT) using simulations from the Energy Exascale Earth System Model (E3SM) both with and without the explicit representation of melt fluxes from beneath Antarctic ice shelves. We find that ice-shelf melting enhances transformation of Upper Circumpolar Deep Water (UCDW), converting it to lower density values. While the overall differences in Southern Ocean WMT between the two simulations are moderate, freshwater fluxes produced by ice-shelf melting have a further, indirect impact on the Southern Ocean overturning circulation through their interaction with sea-ice formation and melting, which also cause considerable upwelling. We further find that surface freshening and cooling by ice-shelf melting causes increased Antarctic sea-ice production and stronger density stratification near the Antarctic coast. In addition, ice-shelf melting causes decreasing air temperature, which may be directly related to sea-ice expansion. The increased stratification reduces vertical heat transport from the deeper ocean. Although the addition of ice-shelf melting processes leads to no significant changes in Southern Ocean WMT, the simulations and analysis conducted here point to a relationship between increased Antarctic ice-shelf melting and the increased role of sea ice in Southern Ocean overturning.