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qooxdoo
[20 users on Ohloh]
qooxdoo is a comprehensive and innovative Ajax application framework. Leveraging object-oriented JavaScript allows developers to build impressive cross-browser applications. No HTML, CSS nor DOM knowledge is needed.

It includes a platform-independent development tool chain, a state-of-the-art GUI toolkit and an advanced client-server communication layer. It is Open Source under an LGPL/EPL dual license.