This forum post describes the procedure for getting HeatSignature to run in CrossOver.
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Install Steam in a new or existing bottle (I went with the bottle created when you ask CrossOver to install Steam)
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Install Heat Signature
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Install "Direct X for Modern Games"+
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Manually install the unlisted application CFF explorer from this link.
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Manually create a backup of the file C:\Program Files\Steam\steamapps\common\Heat Signature\Heat_Signature.exe
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Open CFF Explorer inside of the Steam bottle.
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Use the File-> Open menu in CFF Explorer to open the file C:\Program Files\Steam\steamapps\common\Heat Signature\Heat_Signature.exe
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Navigate to NT Header/File header - click the "click here" box in the "characteristics" row.
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Tick the box "App can handle >2gb address space".
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Save the updated file, overwriting the original (this is why you want to make a backup!).
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Launch Heat Signature normally.
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It is not clear that "DirectX for modern games" is required for this game.
The game runs pretty well at 2K resolution / 30FPS on a 2016 rMBP 15in under CrossOver 16.5.2 (16.2.5.30228), however I have noticed some slight graphical artifacting while zooming in and out, and the zoom/scrollwheel seems overly sensitive. That said however, the game is entirely playable. I do question the poor performance though (I could not push 60FPS@2k) - I can only assume that the game must either be badly optimized, or uses something that CrossOver doesn't have good hardware acceleration for yet, especially considering that my test system should be multiple times more powerful than the system requirements.