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Appearance — defines the appearance of the application, for example here is a part of the same dialog when the Cleanlooks appearance has been applied:
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Window Layout — this option allows to control the behavior of windows, multiple or tabs.
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Open last project at startup — if the option is checked, the last project is opened when UGENE is started. Also you can choose default settings for saving project.
Path to downloaded data — specifies the path where files downloaded from the remote databases will be stored.
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Path for temporary files — the path where will be stored temporary files.
File storage — the path where will be stored UGENE files.
Default settings — this option resets the default settings.