Quantitative structure-activity relationships have been found among macrolide antibacterial agents in their potencies against the bacterial pathogen Pasteurella multocida both in vitro and in mouse infections. To obtain these relationships we measured, among other things, the pK(a)'s and log P's of 15 known macrolides of diverse structures. Among these compounds, in vitro potency [log(1/MIC)] is a function of log P, log D, and CMR (R = 0.86). In vivo potency is a function of the higher pK(a), the HPLC chromatographic capacity factor log k', log(1/MIC) and pNF (R = 0.93). pNF is defined as the negative logarithm of the fraction of neutral drug molecules present in aqueous solution at pH 7.4. The same physical properties were determined for 14 macrolides not used in developing the original QSAR models. Using the in vivo model, we calculated the mouse protection potency ranges for these new compounds. Ten estimates agreed with those observed, three were lower by a half-order of magnitude, and one was calculated to be active in the range of 15-50 mg/kg, but in fact was not active at 50 mg/kg, the highest level tested. When these new compounds were combined with the original 15, and the QSAR's updated, the new equations for the in vitro and in vivo potencies were essentially the same as those originally found. Hence, the physical properties indicated above are major determinants of macrolide antibacterial potencies.
This study investigates the nature of price changes in a variety of major and minor foreign exchange markets. The results suggest that the log of price changes over one (trading) day intervals seems to follow a non-normal stable distribution function. Different measures of location (and to lesser extent scale) are present for different days of the week. Dollar denominated price changes are high on Mondays and Wednesdays and low on Thursdays and Fridays for all currencies. The Wednesday-Thursday result is consistent with the settlement procedures used in foreign exchange transactions in the dollar. The Friday-Monday result is consistent with an increase in demand for the dollar prior to the weekend.THIS STUDY OFFERS SOME previously unavailable results on the nature of price changes in a certain set of speculative markets. In particular, this is a study of the distributional characteristics of daily and weekly price changes for a number of major and minor foreign exchange markets. The results document the existence of non-normal stable distributions for price changes in foreign exchange markets. These price change distributions differ by day of the week in ways that are only partly attributable to the institutional structure of the market. The results of the study are interpreted within the context of understanding how foreign exchange markets operate, and within the context of prior studies of stock market data concerned with summarizing the probability distribution of price changes for different intervals, including days of the week.Since Bachelier's [1] original treatise that contained the proposition that speculative market prices follow a process that could be described by a normal distribution, there have been numerous alternative attempts to describe the stochastic processes which characterize speculative market prices. These studies have not resulted in any generalized description of the probability distribution of price changes in such markets. Indeed, the evidence suggests substantial differences in the process among various types of financial instruments. The failure to achieve consensus can be traced to the lack of robustness in the statistical procedures employed to estimate processes and to differences in the underlying institutional or economic arrangements which are unique to that market. The possibility of differences in the information set used to assess value or differences in technology for transmitting information makes it important to secure additional for their comments.
694The Journal of Finance knowledge of the pricing process in different speculative markets. Such knowledge is essential to the formation of estimates of risk and return for the construction of optimal investor portfolios, as well as for understanding how speculative markets operate.The implications of the results of this investigation for the nature of speculative markets are both general and specific. General implications are reached concerning the process by which foreign exchange markets adjust to either information flows...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.