Centralization of workers (via ASICs)
Trust of discovery nodes
Trust of supernodes
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I'm starting off with the last, because they seem to be the easiest to solve.
Rather than storing the entire block chain as individual nodes, it really should be distributed and trusted. While the public ledger makes a ton of sense, and maintaining an entire copy of the ledger locally seems like a good idea, trying to make it all fit on one single node will be tricky. Not everyone's a sysadmin, with the ability to make a 10 PB block storage device.
I feel as though a modified torrent could easily solve this issue.
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This is tricky. I don't really don't have a peer to peer resolution service idea... any solutions? Maybe like addresses resolve addresses and genius block is your *discovery* node... that'd be vulnerability to availability. What's your solution?
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ASICs are tricky. Ideally, we don't want a single hardware manufacture to control the rules. There's a few other alogirthms, but ASICs are purpose built for mining... so how to do design a problem that can't be solved better by wiring up chips. I guess hardware miners already lost when they should have forked against ASICs.
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Scaling is the behemoth problem. Honestly, I think if we can trust super nodes more often, this really is a non-issue though, so let's just hit the low hanging fruit?