Limited visual control of the intelligibility of speech in face-to-face dialogue.

Speakers are thought to articulate individual words in running speech less carefully whenever additional nonacoustic information can help listeners recognize what is said (Fowler & Housum, 1987; Lieberman, 1963). Comparing single words excerpted from spontaneous dialogues and control tokens of the same words read by the same speakers in lists, Experiment 1 yielded a significant but general effect of visual context: Tokens introducing 71 new entities in dialogues in which participants could see one another's faces were more degraded (less intelligible to 54 naive listeners) than were tokens of the same words from dialogues with sight lines blocked. Loss of clarity was not keyed to moment-to-moment visual behavior. Subjects with clear sight lines looked at each other too rarely to account for the observed effect. Experiment 2 revealed that tokens of 60 words uttered while subjects were looking at each other were significantly less degraded (in length and in intelligibility to 72 subjects) vis-à-vis controls than were spontaneous tokens of the same words produced when subjects were looking elsewhere. Intelligibility loss was mitigated only when listeners looked at speakers. Two separate visual effects are discussed, one of the global availability and the other of the local use of the interlocutor's face.

Putative active site template model for cytochrome P4502C9 (tolbutamide hydroxylase).

Binding of substrates to the active site of cytochrome P450 enzymes largely relies on hydrophobic interactions. However, other binding interactions can take place giving the enzyme high regioselectivity and even stereoselectivity. For instance, within the major human cytochrome P450s involved in drug metabolism, cytochrome P4502D6 (CYP2D6) relies on an ion-pair interaction as a major binding factor. There are now a number of substrates reported that have routes of metabolism ascribed specifically to cytochrome P4502C9 (CYP2C9), the isoform mainly responsible for tolbutamide hydroxylation. Although chemically diverse, these substrates have the capability to be hydrogen bond donors (or acceptors). The substrate specificity has been rationalized in terms of a hydrogen bond donor/acceptor model and, by use of molecular modeling, an active site template model for CYP2C9 has been generated. The substrates modeled were phenytoin, warfarin, ibuprofen, naproxen, diclofenac, delta 1-tetrahydrocannabinol, 58C80, and tolbutamide. In addition to the substrates, the potent, selective inhibitor sulfaphenazole was also included in the modeling. An initial hydrogen bond donor site (N2) was identified on phenytoin, the most rigid of the substrates. Corresponding hydrogen bond donation sites were then identified on all of the molecules studied. Using molecular modeling, the site of metabolism and the hydrogen bond donation sites of the molecules were then overlaid on phenytoin to produce the putative active site model. The resultant model is described by a, the distance between the site of metabolism (Y), and the hydrogen bond donor heteroatom (X) and C, the angle between this and the hydrogen bond. The mean dimensions (+/- SD) for the nine substrates and one inhibitor (a = 6.7 +/- 1.0 A, C = 133 +/- 21 degrees) illustrate the degree of overlap achieved.