Bile Acid–Drug Interaction via Organic Anion-Transporting Polypeptide 4C1 Is a Potential Mechanism of Altered Pharmacokinetics of Renally Excreted Drugs

Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC₅₀, K_i values, and bile acid–drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics.     

Characterizing landscape changes in central Rondonia using Landsat TM imagery

An analysis of landscape changes in a region of pioneer settlements in central Rondonia, western Brazilian Amazon, was derived from Landsat TM data. Total deforested area increased from 206 x 103 ha in 1977, to 565 x 103 ha in 1985 and to 1210 x 103 ha, or 35.5% of the region, in 1995. Eighty-one per cent of the total 1995 deforestation had occurred in regions within 12.5km from areas of pioneer colonization deforested by 1977. Deforested area exceeded 79% in regions within 12.5km from the region's first road.     

Highly reliable 200 mW AlGaAs laser diode with fundamental transverse mode

A highly reliable 200 mW AlGaAs laser diode with a fundamental transverse mode has been developed, by optimising its structure with a 0.8 mu m thick p-cladding layer, a 1200 mu m long cavity length, and a front facet coating with a low reflectivity of 2%. The maximum output power was 500 mW, and stable fundamental transverse mode operation was obtained up to 350 mW. Stable operation under 200 mW and 50 degrees C was confirmed for more than 1200 h. Optical feedback noise was below 3*10/sup -14/ Hz/sup -1/.<>     

Process and device characterization for a 30-GHz fT submicrometer double poly-Si bipolar technology using BF2-implanted base with rapid thermal process

Process and device parameters are characterized in detail for a 30-GHz f_T submicrometer double poly-Si bipolar technology using a BF₂-implanted base with a rapid thermal annealing (RTA) process. Temperature ramping during the emitter poly-Si film deposition process minimizes interfacial oxide film growth. An emitter RTA process at 1050°C for 30 s is required to achieve an acceptable emitter-base junction leakage current with an emitter resistance of 6.7×10^-7 Ω-cm², while achieving an emitter junction depth of 50 nm with a base width of 82 nm. The primary transistor parameters and the tradeoffs between cutoff frequency and collector-to-emitter breakdown voltage are characterized as functions of base implant dose, pedestal collector implant dose, link-base implant dose, and epitaxial-layer thickness. Transistor geometry dependences of device characteristics are also studied. Based on the characterization results for poly-Si resistors, boron-doped p-type poly-Si resistors show significantly better performance in temperature coefficient and linearity than arsenic-doped n-type poly-Si resistors     

25 Gbit/s selector module using 0.2 mu m GaAs MESFET technology

A high-speed selector module has been developed. It is constructed from a selector IC mounted in a ceramic package, a power supply unit, phase shifters, and coaxial cables. The IC was designed using LSCFL and fabricated with 0.2 mu m gate length GaAs MESFETs. The selector module operated above 25 Gbit/s. It is expected to be applied to high-speed IC measurements.<>     

A 0.65-ns, 72-kb ECL-CMOS RAM macro for a 1-Mb SRAM

An ultrahigh-speed 72-kb ECL-CMOS RAM macro for a 1-Mb SRAM with 0.65-ns address-access time, 0.80-ns write-pulse width, and 30.24-μm ² memory cells has been developed using 0.3-μm BiCMOS technology. Two key techniques for achieving ultrahigh speed are an ECL decoder/driver circuit with a BiCMOS inverter and a write-pulse generator with a replica memory cell. These circuit techniques can reduce access time and write-pulse width of the 72-kb RAM macro to 71% and 58% of those of RAM macros with conventional circuits. In order to reduce crosstalk noise for CMOS memory-cell arrays driven at extremely high speeds, a twisted bit-line structure with a normally on MOS equalizer is proposed. These techniques are especially useful for realizing ultrahigh-speed, high-density SRAM's, which have been used as cache and control storages in mainframe computers     

Human body detection in wet snowpack by an FM-CW radar

An FM-CW radar system was applied to detect a human body buried in a very wet snowpack. This radar uses the L-band microwave frequency with a maximum output power of 100 mW, and utilizes digital signal processing techniques. Field experiments were carried out to detect and map a human body embedded at a depth of 125 cm in a natural snowpack. The radar is shown to have a potential ability to detect avalanche victims, indicating that it may become a tool for snow rescuer operations     

Self-aligned silicide technology for ultra-thin SIMOX MOSFETs

The salicide technology using rapid thermal annealing was applied to MOSFETs on thin-film SOI. Since the SOI film was limited to a thickness of less than 100 nm, the silicidation reaction between Ti and Si atoms on the SOI surface exhibited new features that depended on the initial thickness of the deposited Ti. There was an optimum thickness of as-deposited Ti on silicidation due to the restricted thickness of the Si layer. Beyond the optimum point, the region adjacent to the silicided Si layer works as a Si source to assure stoichiometric TiSi₂. The subthreshold slopes and carrier mobilities were not changed by the salicide process. Junction leakage characteristics were slightly degraded; however, the change was small enough for device application. The influence on AC characteristics was well demonstrated for a high-speed CMOS ring oscillator with a gate length of 0.7 μm. The minimum delay time/stage was 46 ps/stage at 5 V. This gives 1.8 times higher speed operation than the controlled bulk CMOS ring oscillators with the same design rule     

Modal dispersion control and distortion suppression of picosecondpulses in suspended coplanar waveguides

The propagation and dispersion characteristics of picosecond electrical pulses in a suspended coplanar waveguide (SCPW) are investigated, and it is shown that the SCPW is a very promising transmission structure for ultrashort pulses. Numerical results for the modal dispersion of the SCPW are presented and compared to those of the conventional CPW, and a field-coupling theory is used to explain the evolution in the dispersion behavior. An evaluation based on the numerical analysis shows that a SCPW with properly controlled dispersion can exhibit a five times improvement in pulse transmission capability compared to the conventional CPW. Both computer simulations and experimental measurements show a substantial suppression in pulse distortion as well, compared to conventional CPWs     

Dependence of the frequency shift of the optical-microwave doubleresonance signal in the Cs D2 line on the pumpingfrequency and power of a GaAs semiconductor laser

The OMDR (optical-microwave double resonance) effect in the Cs D₂ line was studied for realizing a gas-cell-type Cs atomic frequency standard. A glass cell containing Cs with buffer gases (Ar/N₂=1.26, total pressure=39 torr) was placed in a TE₀₁₂ mode microwave cavity at a temperature of 45°C and was pumped using a GaAs semiconductor laser frequency locked to an external interferometer tuned to the 6P_3/2 (F=2,3,4)←6 S_1/2(F=3) transition. The OMDR signal appearing at the resonance to the F=4←3 hyperfine transition of the 6S_1/2 state shifted with detuning of the laser frequency and with change of the laser and microwave powers. The dependence of the shift on these variables around an optimum operating condition was obtained as, Δν_MW[Hz]=-(0.31±0.02) {1+(0.44±0.15) (ΔP_L/P_L)} Δν_L [MHz]-10(ΔV_MW/V _MW)