A Sub-1-µs Start-Up Time, Fully-Integrated 32-MHz Relaxation Oscillator for Low-Power Intermittent Systems

This paper presents a fully integrated 32-MHz relaxation oscillator (ROSC) capable of sub-1-µs start-up time operation for low-power intermittent VLSI systems. The proposed ROSC employs current mode architecture that is different from conventional voltage mode architecture. This enables compact and fast switching speed to be achieved. By designing transistor sizes equally between one in a bias circuit and another in a voltage to current converter, the effect of process variation can be minimized. A prototype chip in a 0.18-µm CMOS demonstrated that the ROSC generates a stable clock frequency of 32.6 MHz within 1-µs start-up time. Measured line regulation and temperature coefficient were ±0.69% and ±0.38%, respectively

Effect of Dehydroaltenusin-C12 Derivative, a Selective DNA Polymerase α Inhibitor, on DNA Replication in Cultured Cells

Dehydroaltenusin is a selective inhibitor of mammalian DNA polymerase α (pol α) from a fungus (Alternaria tennuis). We have designed, synthesized, and characterized a derivative of dehydroaltenusin conjugated with a C12-alkyl side chain (dehydroaltenusin-C12 [C12]). C12 was the strongest pol α inhibitor in vitro. We introduced C12 into NIH3T3 cells with the help of a hypotonic shift, that is, a transient exposure of cultured cells in hypotonic buffer with small molecules which can not penetrate cells. The cells that took in C12 by hypotonic shift showed cell growth inhibition. At a low concentration (5 μM), DNA replication was inhibited and several large replication protein A (RPA) foci, which is different from dUTP foci. Furthermore, when C12 was incubated with aphidicolin, RPA foci were not observed in cells. Finally, these findings suggest that C12 inhibited DNA replication through pol α inhibition, and generated single-stranded DNA, resulted in uncoupling of the leading strand and lagging strand synthesis. These findings suggest that C12 could be more interesting as a molecule probe or anticancer agent than aphidicolin. C12 might provide novel markers for the development of antiproliferative drugs