Autotuning of Exascale Applications With Anomalies Detection.

The execution of complex distributed applications in exascale systems faces many challenges, as it involves empirical evaluation of countless code variations and application runtime parameters over a heterogeneous set of resources. To mitigate these challenges, the research field of autotuning has gained momentum. The autotuning automates identifying the most desirable application implementation in terms of code variations and runtime parameters. However, the complexity and size of the exascale systems make the autotuning process very difficult, especially considering the number of parameter variations that have to be identified. Therefore, we introduce a novel approach for autotuning exascale applications based on a genetic multi-objective optimization algorithm integrated within the ASPIDE exascale computing framework. The approach considers multi-dimensional search space with support for pluggable objective functions, including execution time and energy requirements. Furthermore, the autotuner employs a machine learning-based event detection approach to detect events and anomalies during application execution, such as hardware failures or communication bottlenecks.

ERG induces taxane resistance in castration-resistant prostate cancer.

Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in in vitro and in vivo models of CRPC is associated with decreased sensitivity to taxanes. ERG affects several parameters of microtubule dynamics and inhibits effective drug-target engagement of docetaxel or cabazitaxel with tubulin. Finally, analysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ERG-overexpressing prostate cancers have twice the chance of docetaxel resistance than ERG-negative cancers. Our data suggest that ERG plays a role beyond regulating gene expression and functions outside the nucleus to cooperate with tubulin towards taxane insensitivity. Determining ERG rearrangement status may aid in patient selection for docetaxel or cabazitaxel therapy and/or influence co-targeting approaches.