significant art significant aspect significant aspects significant asset significant assets significant assistance significant association significant associations significant at p significant attention significant audit significant barrier significant barriers significant bearing significant benefit significant benefits significant biological significant bit significant bits significant bleeding significant blood significant blow significant body significant book significant boost significant brain significant breakthrough significant building significant buildings significant burden significant business significant byte significant canadian significant capacity significant capital significant carbon significant career significant case significant cases significant cash significant casualties significant cause significant causes significant cell significant challenge significant challenges significant challenges remain significant change significant changes significant changes have significant changes have taken significant changes were made significant character significant characteristics significant chemical significant chunk significant climate significant clinical significant collection significant commercial significant commitment significant commitments significant community significant competition significant competitive significant competitive advantage significant complications significant component significant components significant concentration significant concentrations significant concern significant concerns significant conflict significant connection significant consequences significant constraint significant constraints significant content significant contribution significant contribution to the development significant contributions significant contributor significant contributors significant control significant controversy significant correlation significant correlations significant cost significant cost reduction significant cost savings significant costs significant credit significant criticism significant cultural significant current significant customer significant cuts significant cytotoxicity