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.     

Fibre Bragg grating compression-tuned over 110 nm

A fibre Bragg grating with a tuning range covering beyond the C- and L-bands has been realised, which represents the broadest tuning range reported of any Bragg grating. The device exhibits constant spectral response and polarisation mode dispersion within these bands.     

The effects of a detuned optical input on bistable laser diodeswith inhomogeneous current injection

The effects of an external optical input on a bistable laser diode (BLD) with inhomogeneous current injection are discussed. The bistable behavior of optical output versus injection current is shown to be variously modified, depending on the wavelength and power of the optical input. Optical set and reset operations and optical logic achieved by optical input pulses can be explained by these characteristics of a BLD modified by an external optical signal. Analysis using rate equations is also offered to help interpretation of experimental results, as well as the optical output and the bias current injected into the BLD     

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     

A design technique for a high-gain, 10-GHz class-bandwidth GaAsMESFET amplifier IC module

A design procedure is proposed for a high-gain and wideband IC module, using stability analysis and a unified design methodology for ICs and packages. A multichip structure is developed using stability analysis and the requirements for stable operation are determined for each IC chip, package, and interface condition between them. Furthermore, to reduce the parasitic influences, several improvements in the interface and package design are clarified, such as wideband matching and LC resonance damping. IC design using effective feedback techniques for enlarging the bandwidth are also presented. The ICs are fabricated using 0.2-μm GaAs MESFET IC technology. To verify the validity of these techniques, an equalizer IC module for 10-Gb/s optical communication systems was fabricated, achieving a gain of 36 dB and a bandwidth of 9 GHz     

Chaos control and noise suppression in external-cavitysemiconductor lasers

Feedback-induced chaos and intensity noise enhancement in a laser diode with external optical feedback are studied by computer simulations. The enhancement of relative intensity noise (RIN) that is often observed in experiments is considered as a result of the feedback-induced deterministic chaos and the intensity noise suppression is treated from the viewpoint of chaos control. Especially, the conventional noise suppressing technique known as a high-frequency injection modulation is turned into a problem of stabilizing chaos through parameter modulations. We developed an analytical method which allows to optimize the modulation frequency from the linear stability analysis of the dynamical model that describes the laser diode with external feedback. The robustness of the modulation with respect to the modulation frequency and depth is verified and the results suggest the feasibility of applying our method to actual noise suppression. The RIN in the low-frequency region (up to 100 MHz) is shown to be reduced to the solitary laser level when the feedback-induced chaos is effectively controlled with the optimized modulation frequency     

Performance analysis of variable optical delay circuit using highly nonlinear fiber parametric wavelength converters

The performance of a variable optical delay circuit that employs a fiber loop with highly nonlinear fiber parametric wavelength converters is discussed using both experiments and simulations. In our optical delay circuit, the delay time is determined from the number of circulations, which is controlled by the initially selected wavelength of the optical signal. We discuss the factors that limit the number of circulations described in our previous paper, derive the parameters that provide good performance levels, and confirm the performance by simulation. The simulated results indicate that 100 wavelength conversions can be achieved, namely, 100 different delay times can be given to optical packets.     

Transmission of 2-ps optical pulses at 1550 nm over 40-km standardfiber using midspan optical phase conjugation in semiconductor opticalamplifiers

We demonstrate transmission of 2-ps optical pulses at 1550 nm over 40 km of standard fiber by employing midspan optical phase conjugation in semiconductor optical amplifiers (SOAs). The second-order group-velocity dispersion of the fiber is completely compensated and the third-order dispersion becomes a major transmission limitation. This experiment shows that the midspan optical phase conjugation system using SOAs is applicable to ultrahigh bit rates greater than 100 Gb/s     

A novel ferromagnetic thermo-stent for plaque stabilization that self-regulates the temperature

The purpose of this study is to investigate the vascular wall with a thermally self-regulating, cylindrical stent made of a low Curie temperature ferromagnetic alloy. Physiologic saline was circulated in the silicone model vessel implanted with the stent. The stent-temperature remained nearly constant for variable saline flows, saline temperatures, and magnetic flux densities. Stent implants of this type in human blood vessels could potentially enable thermotherapy and temperature determination without catheterization.