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Epub is basically html in a zip file, so design it in an html editor. You need to design it like a 1990s website though, so that it will reflow to fit any device and work with any base font/size the reader has set. If you try to force a rigid structure like a magazine layout it won't work for everyone and will just annoy people.
If you have a Kindle, look at how the scifi and mystery magazines do it for their ebook editions. The free sample should give you enough of an idea of how to approach it.
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