People have remarkable difficulty generating two responses that must follow different temporal sequences, unless the temporal patterns are simply related (e.g., periods in 2:1, 3:1 relation). For example, it is hard to tap to two conflicting rhythms presented concurrently (i.e., a polyrhythm) using the right and left hands (Klapp, 1979), or to tap while articulating a conflicting speech utterance (Klapp, 1981). The present experiments indicate that difficulties in processing conflicting rhythms occur even when people must (a) merely monitor the stimuli and indicate the termination of one rhythmic sequence or (b) tap with a single hand. Responding to polyrhythms is thus difficult even without multiple limb coordination. Furthermore, the difficulty of two-handed tapping to polyrhythms that involve two different tones was found to decrease as the pitch difference between the tones was decreased. This result indicates that the difficulty of rhythmic coordination can be perceptually manipulated in a striking fashion. Polyrhythmic performance thus provides an excellent opportunity for examining possible interactions of perceptual and motor organizations.

Maternal and fetal plasma differ in their concentrations of the important drug binding plasma proteins, albumin and alpha 1-acid glycoprotein, with albumin being slightly more concentrated in fetal plasma, and alpha 1-acid glycoprotein being only 37% of the maternal concentration at term. In general, these differences relate linearly to the bound to free concentration ratio of drugs associated with these proteins. Although only the free concentration is generally considered to be the pharmacologically active form, these differences can dramatically affect the total concentration and relative distribution of drugs between maternal and fetal plasma. In order to test our hypothesis that plasma protein binding is the major determinant of fetal/maternal drug distribution at steady-state, we examined whether fetal binding could be predicted from adult binding information. Data from studies of maternal plasma protein binding were used to predict fetal plasma protein binding based solely on the differences in protein concentrations. These predictions were compared with observed fetal binding data. This analysis showed a slope near unity and a high correlation (r2 = 0.900) which implies that there are no significant differences between the binding affinities of these proteins. A similar analysis performed using data on drug binding in non-pregnant adults gave an r2 or 0.971. Having established that fetal plasma proteins bind drugs similarly to their maternal counterparts, fetal/maternal plasma drug concentration ratios (F/M) were predicted for various drugs using information from literature on the drug's adult plasma protein binding, the protein to which it binds, and the fetal and maternal plasma concentrations of that binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA sequences and three distinct in vitro functions of Nef were evaluated in a group of seven perinatally infected children. nef gene sequences obtained before and after virus culture showed that one of the five non-/slow progressors harbored a virus with large deletions. nef genes from the remaining four children were full length but contained discrete changes at a higher frequency than the rapid progressors. In functional studies, 40 of 44 Nef proteins derived from the whole study group were capable of binding the cellular serine kinase p62, indicating that this function is well conserved among naturally occurring viruses. In contrast, representative Nef proteins derived from the long-term non-/slow progressors were found to be defective or far less capable of enhancing viral replication and/or viral infectivity in herpesvirus saimiri-transformed human T cells and peripheral blood mononuclear cells. On reversion of highly prevalent point mutations in the defective proteins, viral replication could be restored to wild-type levels. Our results suggest that nef genes derived from pediatric long-term nonprogressors have gross deletions in isolated cases but a higher prevalence of discrete changes that may impair Nef function in primary T cell assays, but not all functions reported for Nef.

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This study examined whether positive and negative social ties moderate the effects of negative daily events on psychological distress of 110 community-dwelling elders age 60-89. In accord with the stress-buffering hypothesis, the effect of negative daily events on psychological distress significantly (p less than .05) decreased as positive social ties increased. Contrary to the stress-amplifying hypothesis, negative social ties did not interact with negative daily events to influence psychological distress, but instead, had a significant (p less than .01) additive effect on it.