it is the end or there is no hope for someone or something – informal
2002 - Guardian - The underlying problem is not the science itself, but the fact that the science is telling politicians something they are desperate not to hear that it's all up with our current model of gung-ho globalisation.
be up on
be well informed about a matter or subject
on the up and up
steadily improving – informal
honest or sincere, informal, chiefly - North American
something is up
something unusual or undesirable is afoot or happening – informal
1994 - Marianne Williamson – Illuminata - It feels as though something is up, as though something significant and big is about to happen.
up against it
facing some serious but unspecified difficulty – informal
up and about = up and doing
having risen from bed and active
up and running
taking place and active
1998 - New Scientist - The arms race may be up and running again.
up the ante
Increase what is at stake or under discussion, especially in a conflict or dispute
Ante comes from Latin, in which it means before. As an English noun it was originally (in the early 19th century) a term in poker and similar gambling games, meaning a stake put up by a player before drawing cards.
1998 - New Scientist - This report ups the ante on the pace at which these cases need to be identified and treated.
up for it
ready to take part in a particular activity – informal
2003 – Observer - If the chance ever arose to do my singing and play football for Southampton, I'd be well up for it.
up hill and down dale
all over the place
2001 - Observer - Why get ourselves bogged down with trials which may last many months and see our staff cross-examined up hill and down dale as defence counsel play the game of hunt the informant?
up in arms about
protesting angrily about something
1994 - Asian Times - A lack of checks and balances or legal redress for workers have trade unions up in arms.
up the spout
no longer working or likely to be useful or successful