Explore the vast range of titles available.

Previously observed twice-Clausius–Clapeyron (2CC) scaling for extreme precipitation at hourly time scales has led to discussions about its origin. The robustness of this scaling is assessed by analyzing a subhourly dataset of 10-min resolution over the Netherlands. The results confirm the validity of the previously found 2CC scaling for extreme convective precipitation. Using a simple entraining plume model, an idealized deep convective environmental temperature profile is perturbed to analyze extreme precipitation scaling from a frequently used relation based on the column condensation rate. The plume model simulates a steady precipitation increase that is greater than Clausius–Clapeyron scaling (super-CC scaling). Precipitation intensity increase is shown to be controlled by a flux of moisture through the cloud base and in-cloud lateral moisture convergence. Decomposition of this scaling relation into a dominant thermodynamic and additional dynamic component allows for better understanding of the scaling and demonstrates the importance of vertical velocity in both dynamic and thermodynamic scaling. Furthermore, systematically increasing the environmental stability by adjusting the temperature perturbations from constant to moist adiabatic increase reveals a dependence of the scaling on the change in environmental stability. As the perturbations become increasingly close to moist adiabatic, the scaling found by the entraining plume model decreases to CC scaling. Thus, atmospheric stability changes, which are expected to be dependent on the latitude, may well play a key role in the behavior of precipitation extremes in the future climate.

Large-eddy simulations with strong lateral forcing representative of precipitation over the Netherlands are performed to investigate the influence of stability, relative humidity (RH), and moisture convergence on precipitation. Furthermore, a simple climate perturbation is applied to analyze the precipitation response to increasing temperatures. Precipitation is decomposed to distinguish between processes affecting the precipitating area and the precipitation intensity. It is shown that amplification of the moisture convergence and destabilization of the atmosphere both lead to an increase in precipitation, but on account of different effects: atmospheric stability mainly influences the precipitation intensity, whereas the moisture convergence mainly controls the precipitation area fraction. Extreme precipitation intensities show qualitatively similar sensitivities to atmospheric stability and moisture convergence. Precipitation increases with RH due to an increase in area fraction, despite a decrease in intensity. The precipitation response to the climate perturbation shows a stronger response for the precipitation intensity than the overall precipitation, with no clear dependency on changes in atmospheric stability, moisture covergence, and relative humidity.

Observations of extreme (sub-)hourly precipitation at mid-latitudes show a large dependency on the dew point temperature often close to 14% per degree-2 times the dependency of the specific humidity on dew point temperature which is given by the Clausius-Clapeyron (CC) relation. By simulating a selection of 11 cases over the Netherlands characterized by intense showers, we investigate this behavior in the non-hydrostatic weather prediction model Harmonie at a resolution of 2.5 km. These experiments are repeated using perturbations of the atmospheric profiles of temperature and humidity: (i) using an idealized approach with a 2° warmer (colder) atmosphere assuming constant relative humidity, and (ii) using changes in temperature and humidity derived from a long climate change simulation at 2° global warming. All perturbations have a difference in the local dew point temperature compared to the reference of approximately 2°. Differences are considerable between the cases, with dependencies ranging from almost zero to an increase of 18% per degree rise of the dew point temperature. On average however, we find an increase of extreme precipitation intensity of 11% per degree for the idealized perturbation, and 9% per degree for the climate change perturbation. For the most extreme events these dependencies appear to approach a rate of 11-14% per degree, in closer agreement with the observed relation.

The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset—accessible through the Beat AML data viewer (Vizome)—that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML. Analyses of samples from patients with acute myeloid leukaemia reveal that drug response is associated with mutational status and gene expression; the generated dataset provides a basis for future clinical and functional studies of this disease.