Hi @yanhezhao,
Yes, this error is due to an insufficient amount of host (CPU) RAM to allocate space for the large box size. We have not closely profiled the memory usage of non-uniform refinement, so we can’t give a precise upper limit on the box size that is usable with a given amount of RAM. If you see this error it is still best to proceed by downsampling your particles to a smaller box size and repeating the refinement job. If the FSC resolution is not hitting the nyquist resolution, there is no degradation in result quality incurred by downsampling.
Best,
Michael