Still searching for environmental justice

Communities want improved environmental conditions, a goal that is bogged down by strong views on poverty, racism, and development.     

Carbocyclic analogues of the potent cytidine deaminase inhibitor 1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine)

Three carbocylic analogues of the potent cytidine deaminase inhibitor (CDA) zebularine [1-(beta-D-ribofuranosyl)-1, 2-dihydropyrimidin-2-one, 1a] were synthesized. The selected pseudosugar templates correspond, respectively, to the cyclopentenyl moiety of neplanocin A (compound 4), the cyclopentyl moiety of aristeromycin (compound 5), and a newly designed, rigid bicyclo[3.1. 0]hexane moiety (compound 6). These three carba-nucleoside versions of zebularine were fashioned to overcome the inherent instability of the parent drug. Each target compound was approached differently using either convergent or linear approaches. The immediate precursor to the cyclopentenyl analogue 4 was obtained by a Mitsunobu coupling of pseudosugar 7 with 2-hydroxypyrimidine. The cyclopentyl analogue 5 was linearly constructed from carbocyclic amine 17, and the final target 6 was similarly constructed from the carbobicyclic amine 27. Of the three target compounds, only 5 showed a significant level of inhibition against human CDA, but it was 16 times less potent than zebularine (Ki = 38 microM vs Ki(apparent) = 2.3 microM). Although these carbocyclic analogues appeared to be more stable than zebularine, replacement of the electronegative CO4' oxygen for the less electronegative carbon in 4-6 presumably reduces the capacity of the pyrimidin-2(1H)-one ring to form a covalent hydrate, a step considered crucial for the compound to function as a transition-state inhibitor of the enzyme.     

Managing data caches using selective cache line replacement

As processor performance continues to improve, more demands are being placed on the performance of the memory system. The caches employed in current processor designs are very similar to those described in early cache studies. In this paper, a detailed characterization of data cache behavior for individual load instructions is given. It will be shown that by selectively allocating cache lines according the characteristics of individual load instructions, overall performance can be improved for both the data cache and the memory system. This approach can improve some aspects of memory performance by as much as 60 percent on existing executables. This work was supported by National Science Foundation Grants CCR-94-03651, CCR-92-13651, CCR-92-13627, MIP-92-57259, and generous grants from the SUN Microsystems and Tektronix corporations.