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What would be the point of running in it in a vm with the same system? Use a different system.
Also what are you doing in calibre to cause the memory to increase? For instance if I start calibre memory usage is ~ 100MB then I use the edit metadata dialog for many books, memory usage climbs to 200MB and stays constant there no matter how many books I edit the metadata for. Since most tasks in calibre happen in short lived worker processes, I dont see how they could be leaking memory.
The only other things I can think of that happen in the same process are running the calibre content server and connecting to a device.
Two things you can do to decrease coupling to the system is use the binary calibre install and in Preferences->Look & Feel change the theme from system default to calibre.
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