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High-performance scientific computing has recently seen a surge of interest in heterogeneous systems, with an emphasis on modern Graphics Processing Units (GPUs). These devices offer tremendous potential for performance and efficiency in important large-scale applications of computational science. However, exploiting this potential can be challenging, as one must adapt to the specialized and rapidly evolving computing environment currently exhibited by GPUs. One way of addressing this challenge is to embrace better techniques and develop tools tailored to their needs. This article presents one simple technique, GPU run-time code generation (RTCG), and PyCUDA, an open-source toolkit that supports this technique. In introducing PyCUDA, this article proposes the combination of a dynamic, high-level scripting language with the massive performance of a GPU as a compelling two-tiered computing …