Postsurgical oral administration of uracil and tegafur inhibits progression of micrometastasis of human breast cancer cells in nude mice

We recently established a metastasis model in nude mice using the MKL-4 cell line, a contransfectant of the MCF-7 human breast cancer cell line with fgf-4 and lacZ in which micrometastases in several organs can be quantitatively observed. First, to develop a new postsurgical metastasis model, we investigated the timing of occurrence of micrometastasis and the influence of tumor removal on the progression of micrometastasis in this model. Micrometastases into lymph nodes and lungs were detected 3 weeks after the cell injections. Tumor removal 3 weeks after the injections significantly enhanced the progression of micrometastasis into lymph nodes and bone. Second, to study the effect of a mixed compound, UFT (a molar ratio of uracil:tegafur of 4:1), which has been widely used in the postsurgical adjuvant setting in Japan, 15 or 20 mg/kg UFT were administered p.o. for 4 weeks to tumor-bearing mice or to mice in which transplanted tumors were resected 3 weeks after the injections. Either dose of UFT significantly inhibited the tumor growth as well as the progression of micrometastasis into lymph nodes, lungs, liver, and brain. In addition, enhanced progression of micrometastasis in all explored organs by the tumor removal was significantly inhibited by the administration of either dose of UFT. In conclusion, this new postsurgical metastasis model may be useful for evaluating the efficacy of agents used in the postoperative adjuvant setting. UFT may be an effective drug for inhibiting the progression of micrometastasis after surgery.     

LQ optimal control for a class of pulse width modulated systems

We consider linear quadratic optimal control for a class of pulse width modulated systems. The problem is motivated from a practical application—digital control of switching power converters. The control synthesis problem is posed based on a sampled data model of the original switching dynamics and a linear quadratic criterion that takes the intersampling behavior into account.     

A study of an automated porphyria diagnosis system using urinary porphyrin profile analysis

Porphyrins are essential substances for the biosynthesis of heme. Porphyria results from a disorder in the metabolism of porphyrin. Patients suffering from Porphyria exhibit changes in their porphyrin profiles as measured in excretia and organs. A highly sensitive and simple analytical method using high-performance liquid chromatography (HPLC) for all porphyrin metabolites in urine was established. This method is able to separate porphyrins such as uroporphyrin, carboxylic acid porphyrins of hepta-, hexa-, penta-, and coproporphyrin isomers of I and III in a sample of human urine. In this study, the combination of HPLC with a computer system for automated porphyria diagnosis was investigated. The profile of all urinary porphyrins from patients with various Porphyria were measured by HPLC and diagnosed by the computer diagnostic system. This system enabled the estimation of 5 types of porphyrias with a high accuracy of diagnosis.     

A low-power four-transistor SRAM cell with a stacked vertical poly-silicon PMOS and a dual-word-voltage scheme

To realize high-density SRAMs, we developed a four-transistor SRAM cell with a newly developed stacked vertical poly-silicon PMOS. The vertical poly-silicon PMOS has a gate surrounding a body that forms a channel and yields a drive current of 20 /spl mu/A at 25/spl deg/C. Vertical poly-silicon PMOSs are used as transfer MOSs and are stacked over the bulk NMOSs, used as driver MOSs, to reduce the size of a four-transistor SRAM cell. As a result, the size of the proposed four-transistor SRAM cell was 38% of that of a six-transistor SRAM cell. We also developed an electric-field-relaxation scheme to reduce cell leakage and a dual-word-voltage scheme to improve cell stability. By applying these two schemes to the proposed four-transistor SRAM cell, we achieved a 90% reduction in cell leakage and an improvement in cell stability.     

Effect of a combination of hexamethylphosphoramide and alkyl alcohol on the stereospecificity of radical polymerization of N-isopropylacrylamide

Radical polymerization of N-isopropylacrylamide (NIPAAm) was investigated at low temperatures in the presence of both hexamethylphosphoramide (HMPA) and alkyl alcohols. Although HMPA and alkyl alcohols separately induced syndiotactic specificity in NIPAAm polymerization in toluene at low temperatures, a combination of HMPA and less bulky alkyl alcohols, such as methanol and ethanol, was found to induce isotactic specificity at −80 °C. NMR analysis of mixtures of NIPAAm, ethanol and HMPA suggested the formation of a 1:1:1 complex through O-H•••O=C and N-H•••O=P hydrogen bonding. It is believed that the steric effect of HMPA enhanced by cooperative hydrogen bonding was responsible for the combined effect of HMPA and alkyl alcohols in inducing isotactic specificity.     

Synthesis and biological activities of optically active 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinone (OPC-18790)

The enantiomers of 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinon e (OPC-18790), a novel cardiotonic agent, were synthesized and evaluated for positive inotropic activity. The key intermediates, 2,3-epoxypropoxy derivatives, were obtained by the alkylation of 6-hydroxy-2(1H)-quinolinone with optically active epichlorohydrin and subsequent ring closure. In an in vitro study, the (R)-(+)-isomer was about 10-fold more potent than the (S)-(-)-isomer.     

A 256-Mb SDRAM using a register-controlled digital DLL

This paper describes the key technologies used in a 256-Mb synchronous DRAM with a clock access time of 1 ns. This DRAM is stable against temperature, voltage, and process variation through the use of a register-controlled digital delay-locked loop (RDLL). The total timing error of the RDLL is about 0.4 ns, sufficient for high frequency operation at 150 to 200 MHz. Unlike most conventional high-density DRAMs, the bit lines are placed above the storage capacitors in this DRAM to relax the design rules of the core area. The noise issues were analyzed and resolved to help implement the technology for mass production of 0.28- to 0.24-μm 200-MHz DRAMs     

Theoretical simulation of electron-beam-excited xenon-chloride (XeCl) lasers

By developing a comprehensive computer code fore-beam excited XeCl lasers, we studied mainly the effect of Ar and Ne diluents on the performance characteristics of XeCl lasers. According to the analysis of the XeCl* formation process, the XeCl* relaxation process, and the 308 nm absorption process, it is found that the XeCl* formation efficiency is determined mainly by the rate of the charge transfer process (from Ar+ and Ne+ diluent ions to Xe+); in other words, by the difference between ionic potentials of Xe and the diluent gas used. The extraction efficiency is found to be decided mainly by the quenching rate of a three-body reaction for a short-pulse (55 ns) and a high-excitation-rate (∼ 3 MW/cm³) pumping, and by the absorption process for a long-pulse (500 ns) and a low-excitation-rate (∼ 0.2 MW/cm³) pumping. However, note that no appreciable difference in the intrinsic efficiency is found between the Ar/Xe/HCl and Ne/Xe/HCl mixtures. We also analyzed the dependence of the intrinsic XeCl laser efficiency on the pumping pulse width and excitation rate for Ar/Xe/HCl and Ne/Xe/HCl mixtures. As a result, the same intrinsic efficiencies are obtainable for both Ar- and Ne-based mixtures although the optimum operating conditions are slightly different. The maximum intrinsic efficiency of 5 percent is obtainable both for the Ar/Xe/HCl mixture at 3 atm and with 1.5 MW/cm³, 200 ns (FWHM) pumping and for the Ne/Xe/HCl mixture at 4 atm and with 2 MW/cm³, 200 ns (FWHM) pumping.