Seasonal-to-decadal predictions with the ensemble Kalman filter and the Norwegian Earth System Model: a twin experiment

Here, we firstly demonstrate the potential of an advanced flow dependent data assimilation method for performing seasonal-to-decadal prediction and secondly, reassess the use of sea surface temperature (SST) for initialisation of these forecasts. We use the Norwegian Climate Prediction Model (NorCPM), which is based on the Norwegian Earth System Model (NorESM) and uses the deterministic ensemble Kalman filter to assimilate observations. NorESM is a fully coupled system based on the Community Earth System Model version 1, which includes an ocean, an atmosphere, a sea ice and a land model. A numerically efficient coarse resolution version of NorESM is used. We employ a twin experiment methodology to provide an upper estimate of predictability in our model framework (i.e. without considering model bias) of NorCPM that assimilates synthetic monthly SST data (EnKF-SST). The accuracy of EnKF-SST is compared to an unconstrained ensemble run (FREE) and ensemble predictions made with near perfect (i.e. microscopic SST perturbation) initial conditions (PERFECT). We perform 10 cycles, each consisting of a 10-yr assimilation phase, followed by a 10-yr prediction. The results indicate that EnKF-SST improves sea level, ice concentration, 2 m atmospheric temperature, precipitation and 3-D hydrography compared to FREE. Improvements for the hydrography are largest near the surface and are retained for longer periods at depth. Benefits in salinity are retained for longer periods compared to temperature. Near-surface improvements are largest in the tropics, while improvements at intermediate depths are found in regions of large-scale currents, regions of deep convection, and at the Mediterranean Sea outflow. However, the benefits are often small compared to PERFECT, in particular, at depth suggesting that more observations should be assimilated in addition to SST. The EnKF-SST system is also tested for standard ocean circulation indices and demonstrates decadal predictability for Atlantic overturning and sub-polar gyre circulations, and heat content in the Nordic Seas. The system beats persistence forecast and shows skill for heat content in the Nordic Seas that is close to PERFECT

Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation

Dimethyl fumarate (DMF) possesses anti-inflammatory properties and is approved for the treatment of psoriasis and multiple sclerosis. While clinically effective, its molecular target has remained elusive - although it is known to activate anti-oxidant pathways. We find that DMF inhibits pro-inflammatory cytokine production in response to TLR agonists independently of the Nrf2-Keap1 anti-oxidant pathway. Instead we show that DMF can inhibit the E2 conjugating enzymes involved in K63 and M1 polyubiquitin chain formation both in vitro and in cells. The formation of K63 and M1 chains is required to link TLR activation to downstream signaling, and consistent with the block in K63 and/or M1 chain formation, DMF inhibits NFκB and ERK1/2 activation, resulting in a loss of pro-inflammatory cytokine production. Together these results reveal a new molecular target for DMF and show that a clinically approved drug inhibits M1 and K63 chain formation in TLR induced signaling complexes. Selective targeting of E2s may therefore be a viable strategy for autoimmunity

Safety Standards of Flood Defenses

Hazard

Impact of including interdependencies between multiple riverine flood defences on the economically optimal flood safety levels

In risk analysis of riverine flood defence systems, sections of flood defences are often considered separately, herewith ignoring their interdependence, e.g. due to the hydraulic response following dike breaches in the system. In previous studies it has been found that such interdependence can have a significant influence on flood risk estimates and the spatial distribution. In this paper a method is proposed for the economic optimisation of riverine flood defence safety levels from a river system perspective. In order to deal with the computational challenge of integrating the hydraulic interactions in an economic optimisation, a surrogate model was developed. Despite the many simplifications, this model yields reasonably accurate results within acceptable time. The application of the model to a case study in the Netherlands has shown that taking into account interactions between flood defences has significant influence on optimal long term strategies for flood defences. The results suggest that accounting for interdependence in setting safety standards and reinforcement prioritisation yields a significant return on investment both in terms of lower investment cost and in terms of reduced risks.Accepted Author ManuscriptHydraulic Structures and Flood Ris