In an effort to enhance dFdC cytotoxicity and help normalize response rates, we created a bifunctional fusion enzyme that combines the enzymatic activities of deoxycytidine kinase (dCK) and uridine/cytidine monophosphate kinase (UCMK) in a single polypeptide.
Tamoxifen was used as the control to normalize response unless otherwise noted.
Monitored response was a composite quality response (Q*) which balanced conflicting normalized responses, such as resolution and migration time.
For all measurements, the averaged, normalized response to the stimulant vs the averaged, normalized response to control solvent was compared using a Student's t-test for equal or unequal variances (Vassar Stats).
Application of 200 n m PMA to α4S443Aβ2δ GABAARs resulted in a progressive decline in GABA-evoked noise, similar to that seen with wild-type GABAARs (Fig. 8E: normalized response, 196.1 ± 11.9% at 5 min after PMA application, 165.0 ± 12.5% at 20 min after PMA application, n = 7, P = 0.01).
Applying PMA to α4β2S410Aδ GABAARs failed to affect the current noise evoked by 300 n m GABA (Fig. 8D: normalized response, 294.4 ± 29.0% at 5 min after PMA application, 300.7 ± 8.5% at 15 min after PMA application, n = 7, P = 0.4).
However, the potential for psychotherapy to normalize neurobiological responses to pleasant stimuli has not been evaluated.
Therefore, approaches that control steady state H2O2 levels, a key contributor to excessive cytokine prodcution, would be expected to normalize inflammatory responses in CF epithelial cells.
In order to normalize the response range across subjects, average initial response and final response points were calculated (as detailed above) and each subject's phase code was linearly transformed to range between them.
