Imbalanced land-surface water budgets in a numerical weather prediction system

There has been a significant increase in the skill and resolution of numerical weather prediction models (NWPs) in recent decades, extending the time scales of useful weather predictions. The land-surface models (LSMs) of NWPs are often employed in hydrological applications, which raises the question of how hydrologically representative LSMs really are. In this paper, precipitation (P), evaporation (E) and runoff (R) from the European Centre for Medium-Range Weather Forecasts (ECMWF) global models were evaluated against observational products. The forecasts differ substantially from observed data for key hydrological variables. In addition, imbalanced surface water budgets, mostly caused by data assimilation, were found on both global (P-E) and basin scales (P-E-R), with the latter being more important. Modeled surface fluxes should be used with care in hydrological applications and further improvement in LSMs in terms of process descriptions, resolution and estimation of uncertainties is needed to accurately describe the land-surface water budgets

Hyperresolution information and hyperresolution ignorance in modelling the hydrology of the land surface

There is a strong drive towards hyperresolution earth system models in order to resolve finer scales of motion in the atmosphere. The problem of obtaining more realistic representation of terrestrial fluxes of heat and water, however, is not just a problem of moving to hyperresolution grid scales. It is much more a question of a lack of knowledge about the parameterisation of processes at whatever grid scale is being used for a wider modelling problem. Hyperresolution grid scales cannot alone solve the problem of this hyperresolution ignorance. This paper discusses these issues in more detail with specific reference to land surface parameterisations and flood inundation models. The importance of making local hyperresolution model predictions available for evaluation by local stakeholders is stressed. It is expected that this will be a major driving force for improving model performance in the future. Keith BEVEN, Hannah CLOKE, Florian PAPPENBERGER, Rob LAMB, Neil HUNTE

Disinformative data in large-scale hydrological modelling

Large-scale hydrological modelling has become an important tool for the study of global and regional water resources, climate impacts, and water-resources management. However, modelling efforts over large spatial domains are fraught with problems of data scarcity, uncertainties and inconsistencies between model forcing and evaluation data. Model-independent methods to screen and analyse data for such problems are needed. This study aimed at identifying data inconsistencies in global datasets using a pre-modelling analysis, inconsistencies that can be disinformative for subsequent modelling. The consistency between (i) basin areas for different hydrographic datasets, and (ii) between climate data (precipitation and potential evaporation) and discharge data, was examined in terms of how well basin areas were represented in the flow networks and the possibility of water-balance closure. It was found that (i) most basins could be well represented in both gridded basin delineations and polygon-based ones, but some basins exhibited large area discrepancies between flow-network datasets and archived basin areas, (ii) basins exhibiting too-high runoff coefficients were abundant in areas where precipitation data were likely affected by snow undercatch, and (iii) the occurrence of basins exhibiting losses exceeding the potential-evaporation limit was strongly dependent on the potential-evaporation data, both in terms of numbers and geographical distribution. Some inconsistencies may be resolved by considering sub-grid variability in climate data, surface-dependent potential-evaporation estimates, etc., but further studies are needed to determine the reasons for the inconsistencies found. Our results emphasise the need for pre-modelling data analysis to identify dataset inconsistencies as an important first step in any large-scale study. Applying data-screening methods before modelling should also increase our chances to draw robust conclusions from subsequent model simulations

Sub-daily runoff predictions using parameters calibrated on the basis of data with a daily temporal resolution

Concentration times in small and medium-sized basins (∼10–1000 km2) are commonly less than 24 h. Flood-forecasting models are thus required to provide simulations at high temporal resolutions (1 h–6 h), although time-series of input and runoff data with sufficient lengths are often only available at the daily temporal resolution, especially in developing countries. This has led to study the relationships of estimated parameter values at the temporal resolutions where they are needed from the temporal resolutions where they are available. This study presents a methodology to treat empirically model-parameter dependencies on the temporal resolution of data in two small basins using a bucket-type hydrological model, HBV-light, and the generalised likelihood uncertainty estimation approach for selecting its parameters. To avoid artefacts due to the numerical resolution or numerical method of the differential equations within the model, the model was consistently run using modelling time-steps of one-hour regardless of the temporal resolution of the rainfall-runoff data. The distribution of the parameters calibrated at several temporal resolutions in the two basins did not show model-parameter dependencies on the temporal resolution of data and the direct transferability of calibrated parameter sets (e.g., daily) for runoff simulations at other temporal resolutions for which they were not calibrated (e.g., 3 h or 6 h) resulted in a moderate (if any) decrease in model performance, in terms of Nash-Sutcliffe and volume-error efficiencies. The results of this study indicate that if sub-daily forcing data can be secured, flood forecasting in basins with sub-daily concentration times may be possible with model-parameter values calibrated from long time series of daily data. Further studies using more models and basins are required to test the generality of these results

Chemogenetic profiling reveals PP2A-independent cytotoxicity of proposed PP2A activators iHAP1 and DT-061

Protein phosphatase 2A (PP2A) is an abundant phosphoprotein phosphatase that acts as a tumor suppressor. For this reason, compounds able to activate PP2A are attractive anticancer agents. The compounds iHAP1 and DT‐061 have recently been reported to selectively stabilize specific PP2A‐B56 complexes to mediate cell killing. We were unable to detect direct effects of iHAP1 and DT‐061 on PP2A‐B56 activity in biochemical assays and composition of holoenzymes. Therefore, we undertook genome‐wide CRISPR‐Cas9 synthetic lethality screens to uncover biological pathways affected by these compounds. We found that knockout of mitotic regulators is synthetic lethal with iHAP1 while knockout of endoplasmic reticulum (ER) and Golgi components is synthetic lethal with DT‐061. Indeed we showed that iHAP1 directly blocks microtubule assembly both in vitro and in vivo and thus acts as a microtubule poison. In contrast, DT‐061 disrupts both the Golgi apparatus and the ER and lipid synthesis associated with these structures. Our work provides insight into the biological pathways perturbed by iHAP1 and DT‐061 causing cellular toxicity and argues that these compounds cannot be used for dissecting PP2A‐B56 biology

Clinical Manifestations and Modes of Death among Patients with Ebola Virus Disease, Monrovia, Liberia, 2014

Although the high case fatality rate (CFR) associated with Ebola virus disease (EVD) is well documented, there are limited data on the actual modes of death. We conducted a retrospective, observational cohort study among patients with laboratory-confirmed EVD. The patients were all seen at the Eternal Love Winning Africa Ebola Treatment Unit in Monrovia, Liberia, from June to August 2014. Our primary objective was to describe the modes of death of our patients and to determine predictors of mortality. Data were available for 53 patients with laboratory-confirmed EVD, with a median age of 35 years. The most frequent presenting symptoms were weakness (91%), fever (81%), and diarrhea (78%). Visible hemorrhage was noted in 25% of the cases. The CFR was 79%. Odds of death were higher in patients with diarrhea (odds ratio = 26.1, P &lt; 0.01). All patients with hemorrhagic signs died (P &lt; 0.01). Among the 18 fatal cases for which clinical information was available, three distinct modes of death were observed: Sudden death after a moderate disease process (44%), profuse hemorrhage (33%), and encephalopathy (22%). We found that these modes of death varied by age (P = 0.04), maximum temperature (P = 0.43), heart rate on admission (P = 0.04), time to death from symptom onset (P = 0.13), and duration of hospitalization (P = 0.04). Although further study is required, our findings provide a foundation for developing treatment strategies that factor in patients with specific disease phenotypes (which often require the use of aggressive hydration). These findings provide insights into underlying pathogenic mechanisms resulting in severe EVD and suggest direction for future research and development of effective treatment options.</p

Magneto-optic probe measurements in low density-supersonic jets

A magneto-optic probe was used to make time-resolved measurements of the magnetic field in both a single supersonic jet and in a collision between two supersonic turbulent jets, with an electron density ⇡ 1018 cm3 and electron temperature ⇡ 4 eV. The magneto-optic data indicated the magnetic field reaches B ⇡ 200 G. The measured values are compared against those obtained with a magnetic induction probe. Good agreement of the time-dependent magnetic field measured using the two techniques is found