In this context, if you are up to something it simply means that you are doing something... you could also be scheming (secret plan).
1. - Hey Frank what are you up to?
- Nothing much... I'm just surfing the internet.
2. - What have you been up to these days?
- I'm on vacation so I've been watching a lot of my favorite TV series.
3. I wonder (I'm curious about) what Steven is up to these days. I haven't heard from him in a while (long time).
4. I don't know what you're up to, but you've got some explaining to do.
Another meaning (it doesn't apply to this comic strip) is if you are up to something then you feel like doing something... it expresses that you want to do something.
- What are you doing this weekend? Are you up to having a barbeque?
- I'm definitely up to it!
Sly means to be intelligent or smart, but usually in a manipulative way.
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