Before revision:  The proposed analysis framework provided a natural link between global and local ultrasensitivity descriptors and was particularly well-suited to study the ultrasensitivity in MAP kinase cascades. We used our methodology to revisit O'Shaughnessy et al.  tunable synthetic MAPK cascade, in which they claim to have found a new source of ultrasensitivity: ultrasensitivity generated de novo, which arises due to cascade structure itself.
After revision:  The proposed analysis framework provided a natural link between global and local ultrasensitivity descriptors and was particularly well-suited to characterize and better understand mathematical models used to study real biological systems. As a case study we considered three mathematical models introduced by O'Shaughnessy et al. tunable synthetic MAPK cascade, in which they claim to have found a new source of ultrasensitivity: ultrasensitivity generated de novo, which arises due to cascade structure itself.