Although T cell-directed therapy in RA was questionable for a while, insight into T cell subclasses has grown and more subtle targeting of CTLA4 on T cell subsets looks promising.
Other companies say their experimental drugs are more subtle and targeted, but they may still affect the enzyme's other targets.
For example, it is common to detect subtle non-target activity in an untargeted liver lobe due to minor microsphere reflux or arterio-portal shunting, with no clinically relevant sequelae.
However, Caudill et al. (2001) found no significant decrease in global methylation in the treated compared with the control groups, suggesting more subtle or targeted effects.
The brightness difference was fairly subtle: 56.3 cd/m (target luminance) versus 48.5 cd/m (non-target luminance).
There is precedent for using subtle advertising to target certain groups that society might momentarily deem controversial, Stanton said.
Subtle differences in target sites or their own expression in tissues, and differential response to external signals may contribute to distinct functions, activating or repressing target gene expression – either basally or in response to growth factors – depending on a constellation of ETS factors that compete for binding to ETS binding elements [ 28- 38].
Exceptions are cases of visually subtle, trace non-target activity where the absorbed doses are unlikely to be clinically relevant.
We do not believe that these differences, or the subtle differences in target-intensity, can explain the discrepancy between previous and present results.
Furthermore, the violation paradigm used by Besson et al. [40] and Bonnel et al. [41], in which the last note of the sung phrase of the opera excerpt was not only unexpected in the context but also out-of-key, may have made wrong notes more salient for the listener than the more subtle different melody targets used in the present experiment.
