High-performance Ge/Si electro-absorption optical modulator up to 85°C and its highly efficient photodetector operation

We studied a high-speed Ge/Si electro-absorption optical modulator (EAM) evanescently coupled with a Si waveguide of a lateral p–n junction for a high-bandwidth optical interconnect over a wide range of temperatures from 25 °C to 85 °C. We demonstrated 56 Gbps high-speed operation at temperatures up to 85 °C. From the photoluminescence spectra, we confirmed that the bandgap energy dependence on temperature is relatively small, which is consistent with the shift in the operation wavelengths with increasing temperature for a Ge/Si EAM. We also demonstrated that the same device operates as a high-speed and high-efficiency Ge photodetector with the Franz-Keldysh (F-K) and avalanche-multiplication effects. These results demonstrate that the Ge/Si stacked structure is promising for both high-performance optical modulators and photodetectors integrated on Si platforms

Modulation bandwidth improvement of III-V/Si hybrid MOS optical modulator by reducing parasitic capacitance

In this work, we numerically and experimentally examined the impact of parasitic capacitance on the modulation bandwidth of a III-V/Si hybrid metal-oxide-semiconductor (MOS) optical modulator. The numerical analysis revealed that the parasitic capacitance between the III-V membrane and the Si slab should be considered to achieve high-speed modulation, particularly in the case of a thick gate oxide. We also fabricated a high-speed InGaAsP/Si hybrid MOS optical modulator with a low capacitance using a SiO2-embedded Si waveguide. The fabricated device exhibited a modulation efficiency of 0.245 Vcm and a 3 dB bandwidth of up to 10 GHz. Clear eye patterns with 25 Gbps non-return-to-zero (NRZ) modulation and 40 Gbps 4-level pulse amplitude modulation (PAM-4) were obtained without pre-emphasis

Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor blocker, losartan, on murine pancreatic tumor growth via anti-angiogenic activities.

Pancreatic cancer is one of the leading causes of cancer death, and represents a challenging chemotherapeutic problem. The crucial role of angiogenesis in tumor growth has been widely recognized, and several reports have revealed that the combination treatment of the conventional chemotherapeutic drugs and anti-angiogenic agents exerted synergistic anti-cancerous effects. It has been reported that the clinically used angiotensin type-1 receptor blocker (ARB) exerted potent anti-angiogenic activity. The aim of our current study was to examine the combination effect of gemcitabine (GEM), a widely used conventional chemotherapeutic drug against pancreas cancer, and losartan (Lo), an ARB, on murine pancreatic tumor growth, especially in conjunction with angiogenesis. When used individually, GEM and Lo at clinically comparable low doses moderately suppressed pancreatic tumor development. The combination treatment with GEM and Lo exerted a marked inhibitory effect as compared with single agent treatments even after the tumor was fully established. Neovascularization and the expression of the vascular endothelial growth factor (VEGF), a central angiogenic factor, in the tumor were both markedly suppressed in a magnitude similar to the inhibitory effects against the tumor growth. Since both agents are widely used in the clinical practice, the combination regimen of GEM and Lo may represent a potential new therapeutic strategy for pancreatic cancer in the future

The intriguing giant bow shocks near HH 131

Using the High Dispersion Spectrograph at the Subaru Telescope, echelle spectra of two giant arcs, i.e. nebulosities Cw and L associated with HH 131 in Orion are presented. Typical emission lines of Herbig-Haro objects have been detected towards Cw. With the 2.16 m telescope of National Astronomical Observatories, spectra of Nebu. C, L and K are obtained, which also show strong [SII]6717/6731, H$\alpha$ and [NII]6583 emission lines. Position-velocity distributions of Cw and L are analyzed. The fastest radial velocity of Cw is V_r ~ -18.0 km/s. When the flow at L goes to the south, it slows down. The fastest radial velocity of L has been observed of -45.0 km/s and the slowest value is about -18.3 km/s. The similarity of the velocities and their positional connection indicate that Cw and L are physically associated. The entire flow tends to become less excited and less ionized when going further to the south (i.e., from Nebu. K, L to C). The electron densities of all the observed nebulosities are low (n_e ~ 10^2 cm^-3). Double kinematic signatures have been found in Cw from its [NII]6583 profiles while the observed H$\alpha$ profiles of Cw are almost symmetric. Bow shock models appear to agree with the observed position-velocity diagrams of the [NII spectra better than H$\alpha$ spectra. With the suggestion that these arcs are HH shocks possibly ejected out of the Orion A molecular cloud by an uncertain source, their spectra show low to intermediate excitation from their diagnostic line ratios.Comment: 27 pages, 10 figures, accepted for publiscation in A

Different tumoricidal effects of interferon subclasses and p53 status on hepatocellular carcinoma development and neovascularization.

Interferon (IFN) is known as a multifunctional cytokine. The aim of this study was to examine the different effects of IFN subclass; namely, IFN-α and IFN-β, on hepatocellular carcinoma (HCC) growth especially in conjunction with angiogenesis that is known to play a pivotal role in the tumor growth. Furthermore, we also examined whether the p53 status in the tumor would alter the anti-tumoral effect of IFN against HCC growth since the p53 status reportedly affected the therapeutic effect of anti-angiogenic agents against cancer. When compared with IFN-α, IFN-β exerted a more potent inhibitory effect on HCC growth, even after the tumor was established, along with suppression of neovascularization in the tumor. A single treatment with clinically comparable low doses of IFN-β significantly inhibited HCC growth whereas the same dose of IFN-α did not. IFN-β also significantly suppressed the tumor growth both in the p53-wild and p53-mutant HCC cells. Our in vitro study revealed that IFN-β showed a more potent inhibitory effect on the endothelial cell proliferation than IFN-α as in the in vivo study. Collectively, IFN may be an alternative anti-angiogenic agent against HCC since it exerted a significant tumoricidal effect regardless of the host p53 status even at a low dose. A cautious approach may be also required in the clinical practice since even in a same IFN subclass (class-I), IFN-α and IFN-β exert tumoricidal effects of different magnitudes on HCC

The vascular endothelial growth factor (VEGF) receptor-2 is a major regulator of VEGF-mediated salvage effect in murine acute hepatic failure

Although administration of the vascular endothelial growth factor (VEGF), a potent angiogenic factor, could improve the overall survival of destroyed sinusoidal endothelial cells (SEC) in chemically induced murine acute hepatic failure (AHF), the mechanistic roles of the VEGF receptors have not been elucidated yet. The respective roles of VEGF receptors; namely, Flt-1 (VEGFR-1: R1) and KDR/Flk-1 (VEGFR-2: R2), in the D-galactosamine (Gal-N) and lipopolysaccharide (LPS)-induced AHF were elucidated with specific neutralizing monoclonal antibody against R1 and R2 (R1-mAb and R2-mAb, respectively). The serum ALT elevation, with a peak at 24 h after Gal-N+LPS intoxication, was markedly augmented by means of the R1-mAb and R2-mAb. The aggregative effect of R2-mAb was more potent than that of R1-mAb, and the survival rate was 70% in the R2-mAb-treated group and 100% in the other groups. The results of SEC destruction were almost parallel to those of the ALT changes. Our in-vitro study showed that R1-mAb and R2-mAb significantly worsened the Gal-N+LPS-induced cytotoxicity and apoptosis of SEC mediated by caspase-3, which were almost of similar magnitude to those in the in-vivo study. In conclusion, these results indicated that R2 is a major regulator of the salvage effect of VEGF on the maintenance of SEC architecture and the anti-apoptotic effects against chemically-induced murine AHF

Selective aldosterone blocker ameliorates the progression of non-alcoholic steatohepatitis in rats.

Although non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma (HCC), no effective therapeutic modalities have been fully established yet. Recent studies have shown that the renin-angiotensin-aldosterone-system plays an important role in NASH. The aim of our current study was to elucidate the effects of aldosterone (Ald) inhibition on the progression of NASH. In the choline-deficient L-amino acid-defined diet-induced rat NASH model, the effects of a clinically used selective Ald blocker (SAB) were elucidated in conjunction with the activated hepatic stellate cells (HSC) and neovascularization, which are both known to play important roles in liver fibrosis development and hepatocarcinogenesis, respectively. Liver fibrosis development and the glutathione-S-transferase placental form-positive pre-neoplastic lesions were both markedly attenuated by SAB along with the suppression of the activated HSC and neovascularization. SAB inhibited the hepatic expression of transforming growth factor-β 1 and also that of the vascular endothelial growth factor. Our in vitro study showed that SAB also inhibited the Ald-induced HSC proliferation and in vitro angiogenesis in a dose-dependent manner. These results indicated that Ald plays a pivotal role in the progression of NASH. Considering that SAB is already widely used in clinical practice, this drug could represent a potential new strategy against NASH in the future

Losartan, an angiotensin-II type 1 receptor blocker, attenuates the liver fibrosis development of non-alcoholic steatohepatitis in the rat

<p>Abstract</p> <p>Background</p> <p>Apart from simple steatosis, the non-alcoholic steatohepatitis (NASH) can progress into liver fibrosis and cirrhosis. To date, however, no widely accepted therapeutic modalities have been established against NASH in the clinical practice. To find out promising new therapeutic agents, it is important to employ an appropriate experimental model of NASH, such as association with insulin resistance.</p> <p>Findings</p> <p>In the current study, we found that losartan, a clinically used angiotensin-II type 1 receptor blocker, significantly attenuated a choline-deficient L-amino acid-defined (CDAA) diet-induced steatohepatitis in obese diabetic- and insulin resistance-associated Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The transforming growth factor-beta, a well-known major fibrogenic cytokine, was also suppressed in a similar magnitude to that of the fibrosis area. Noteworthy was the finding that these inhibitory effects were achieved even at a clinically comparable low dose.</p> <p>Conclusion</p> <p>Since losartan is widely used without serious side effects in the clinical practice, this agent may be an effective new therapeutic strategy against NASH.</p

A 0.3-V operating, Vth-variation-tolerant SRAM under DVS environment for memory-rich SoC in 90-nm technology era and beyond

元・大学院自然科学研究科　　現・神戸大学大学院自然科学研究科We propose a voltage control scheme for 6T SRAM cells that makes a minimum operation voltage down to 0.3 V under DVS environment. A supply voltage to the memory cells and wordline drivers, bitline voltage, and body bias voltage of load pMOSFETs are controlled according to read and write operations, which secures operation margins even at a low operation voltage. A self-aligned timing control with a dummy wordline and its feedback is also introduced to guarantee stable operation in a wide range of the supply voltage. A measurement result of a 64-kb SRAM in a 90-nm process technology shows that a power reduction of 30 can be achieved at 100 MHz. In a 65-nm 64-Mb SRAM, a 74 power saving is expected at 1/6 of the maximum operating frequency. The performance penalty by the proposed scheme is less than 1, and area overhead is 5.6. Copyright © 2006 The Institute of Electronics, Information and Communication Engineers