The question of whether red is a more activating colour than blue is discussed by reference to two opposing schools of thought.
The target is shift-up if there are more activating factors, and vice versa [12], [13].
Some studies have reported significantly more activating mutations in codon 12/13 of Kirsten rat sarcoma viral oncogene homolog (KRAS) in RSCCs than in LSCRCs [ 14, 15].
These findings indicate that interacting with a partner who shows little positive emotion and who is unresponsive to emotional cues is more physiologically activating than interacting with a partner who shows greater positive emotion and responsiveness [ 75].
A potential solution to this problem is to add a step in the network expansion procedure: after introducing complementary nodes for all nodes with direct inhibitory effects, we enumerate all activating input-output paths with inhibitory edges separated by more than one activating edge and introduce the complementary nodes necessary for the maintenance of these paths in the extended network.
The signalling networks evaluated in this study have no, one and two instances, respectively, of a pair of inhibitory edges separated by more than one activating edge, and applying the solution described above has negligibly minor effects on the results.
It is apparent from our B-SIFT analysis that the systematic prediction of activating mutations is more complex than the analogous prediction of deleterious mutations.
Based on the same screening strategy, researchers in Sirtris Pharmaceuticals found more than 5,000 SIRT1-activating compounds (STACs).
The average Tanimoto similarity of a 1 vs all comparison using our in house atom centred fingerprint (Figure 17) gives a value of 0.164 for the training data and 0.137 for the extracted ACTIVATING features, the activating features are therefore more diverse than the training set as a whole.
As dimeric SMAC-mimetics have been shown to be more potent than their monomeric counterparts in activating apoptosis (Li et al, 2004), we synthesised three homodimeric compounds by coupling two SMAC067 units with different linkers (Supplementary Figure S2).
