Quasi-continuous tuning of a 1.3-µm-wavelength superstructure grating distributed Bragg reflector laser by enhancing carrier-induced refractive index change.

To overcome the limitation of the small tuning range of 1.3-µm-wavelength distributed Bragg reflector (DBR) lasers using the carrier-plasma effect, we designed a DBR structure with InAlAs carrier confinement layers and an InGaAlAs core layer. We found that the enhanced carrier density and small effective mass of electrons in the core layer of the DBR regions resulted in a wide Bragg wavelength shift. The enhanced refractive-index change due to the new structure enabled us to fabricate the world's first 1.3-µm-wavelength superstructure-grating DBR laser with a quasi-continuous tuning range of over 30 nm.

Elevation of sensitivity to anticancer agents of human lung adenocarcinoma A549 cells by knockdown of claudin-2 expression in monolayer and spheroid culture models.

Claudins, tight junctional proteins, regulate the paracellular permeability of ions and small molecules. Claudin-2 is highly expressed in human lung adenocarcinoma cells and is involved in the up-regulation of cell proliferation. However, the effect of claudin-2 on cellular sensitivity to anticancer agents has not been clarified. The cytotoxicity of anticancer agents such as cisplatin, gefitinib and doxorubicin (DXR) was increased by claudin-2 knockdown in A549 cells. Claudin-2 knockdown also significantly decreased the expression level of multidrug resistance-associated protein/ABCC2. The expression levels of other drug efflux transporters were unchanged. The intracellular accumulation of 5-chloromethylfluorescein diacetate (CMFDA) and DXR, substrates of ABCC2, was increased by claudin-2 knockdown, whereas the efflux was decreased. MK-571, an inhibitor of ABCC2, enhanced the cytotoxicity of anticancer agents. Claudin-2 knockdown decreased the levels of p-c-Jun and nuclear Sp1. SP600125, an inhibitor of c-Jun, and mithramycin, an inhibitor of Sp1, decreased the level of ABCC2. The promoter activity of ABCC2 was decreased by claudin-2 knockdown, SP600125 and mithramycin treatments, suggesting that claudin-2 is involved in the up-regulation of ABCC2 expression at the transcriptional level. Claudin-2 knockdown increased the paracellular permeability of DXR in a 2D monolayer culture model. In addition, the accumulation of DXR into spheroids was enhanced by claudin-2 knockdown, resulting in a reduction in cell viability. We suggest that claudin-2 may be a novel therapeutic target in lung adenocarcinoma, because claudin-2 knockdown increased the accumulation of anticancer agents in cancer cells and spheroids.

Clathrin-dependent endocytosis of claudin-2 by DFYSP peptide causes lysosomal damage in lung adenocarcinoma A549 cells.

Claudins are tight junctional proteins and comprise a family of over 20 members. Abnormal expression of claudins is reported to be involved in tumor progression. Claudin-2 is highly expressed in lung adenocarcinoma tissues and increases cell proliferation, whereas it is not expressed in normal tissues. Claudin-2-targeting molecules such as peptides and small molecules may be novel anti-cancer drugs. The short peptide with the sequence DFYSP, which mimics the second extracellular loop of claudin-2, decreased claudin-2 content in the cytoplasmic fraction of A549 cells. In contrast, it did not affect the content in the nuclear fraction. The decrease in claudin-2 content was inhibited by chloroquine (CQ), a lysosomal inhibitor, but not by MG-132, a proteasome inhibitor. In the presence of DFYSP peptide and CQ, claudin-2 was co-localized with LAMP-1, a lysosomal marker. The DFYSP peptide-induced decrease in claudin-2 content was inhibited by monodancylcadaverine (MDC), an inhibitor of clathrin-dependent endocytosis. DFYSP peptide increased lysosome content and cathepsin B release, and induced cellular injury, which were inhibited by MDC. Cellular injury induced by DFYSP peptide was inhibited by necrostatin-1, an inhibitor of necrotic cell death, but not by Z-VAD-FMK, an inhibitor of apoptotic cell death. Our data indicate that DFYSP peptide increases the accumulation of the peptide and claudin-2 into the lysosome, resulting in lysosomal damage. Claudin-2 may be a new target for lung cancer therapy.

Systematic study of thresholdless oscillation in high-ß buried multiple-quantum-well photonic crystal nanocavity lasers.

Buried multiple-quantum-well (MQW) 2D photonic crystal cavities (PhC) achieve low non-radiative recombination and high carrier confinement thus making them highly efficient emitters. In this study, we have investigated the lasing characteristics of high-ß(spontaneous emission coupling factor) buried MQW photonic crystal nanocavity lasers to clarify the theoretically-predicted thresholdless operation in high-ß nanolasers. The strong light and carrier confinement and low non-radiative recombination in our nanolasers have enabled us to clearly demonstrate very smooth lasing transition in terms of the light-in vs light-out curve and cavity linewidth. To clarify the thresholdless lasing behavior, we carried out a lifetime measurement and a photon correlation measurement, which also confirmed the predicted behavior. In addition, we systematically investigated the dependence of ß on the detuning frequency, which was in good agreement with a numerical simulation based on the finite-difference time-domain method. This is the first convincing systematic study of nanolasers based on an MQW close to the thresholdless regime.

Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells.

Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines, although it is absent in normal lung tissue. However, the role of claudin-2 in cell proliferation and the regulatory mechanism of intracellular distribution remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells. This knockdown decreased the expression levels of ZONAB and cell cycle regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma tissues and proliferating A549 cells. The nuclear distribution of ZONAB and percentage of S phase cells were higher in cells exogenously expressing claudin-2 with a nuclear localization signal than in cells expressing claudin-2 with a nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of claudin-2, was higher than that of wild type. We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells.

All-optical switching for 10-Gb/s packet data by using an ultralow-power optical bistability of photonic-crystal nanocavities.

An all-optical packet switching using bistable photonic crystal nanocavity memories was demonstrated for the first time. Nanocavity-waveguide coupling systems were configured for 1 × 1, 1 × 2, and 1 × 3 switches for 10-Gb/s optical packet, and they were all operated with an optical bias power of only a few µW. The power is several magnitudes lower than that of previously reported all-optical packet switches incorporating all-optical memories. A theoretical investigation indicated the optimum design for reducing the power consumption even further, and for realizing a higher data-rate capability and higher extinction. A small footprint and integrability are also features of our switches, which make them attractive for constructing an all-optical packet switching subsystem with a view to realizing optical routing on a chip.

Heterogeneously integrated photonic-crystal lasers on silicon for on/off chip optical interconnects.

We demonstrate the continuous-wave operation of lambda-scale embedded active-region photonic-crystal (LEAP) lasers at room temperature, which we fabricated on a Si wafer. The on-Si LEAP lasers exhibit a threshold current of 31 µA, which is the lowest reported value for any type of semiconductor laser on Si. This reveals the great potential of LEAP lasers as light sources for on- or off-chip optical interconnects with ultra-low power consumption in future information communication technology devices including CMOS processors.

Novel approach for chirp and output power compensation applied to a 40-Gbit/s EADFB laser integrated with a short SOA.

We propose a novel approach for simultaneously controlling the chirp and increasing the output power of an EADFB laser by monolithically integrating a short-cavity SOA. We achieved a 40-Gbit/s 5-km SMF transmission at a wavelength of 1.55 µm by using an EADFB SOA with a lower power consumption than a stand-alone EADFB laser.

Directly modulated buried heterostructure DFB laser on SiO2/Si substrate fabricated by regrowth of InP using bonded active layer.

We describe the growth of InP layer using an ultrathin III-V active layer that is directly bonded to SiO2/Si substrate to fabricate a buried heterostructure (BH) laser. Using a 250-nm-thick bonded active layer, we succeeded in fabricating a BH distributed feedback (DFB) laser on SiO2/Si substrate. The use of a lateral current injection structure is important for forming a p-i-n junction using bonded thin film. The fabricated DFB laser is directly modulated by a 25.8-Gbit/s NRZ signal at 50°C. These results indicate that our fabrication method is a promising way to fabricate high-efficiency lasers at a low cost.

Increase in claudin-2 expression by an EGFR/MEK/ERK/c-Fos pathway in lung adenocarcinoma A549 cells.

In human adenocarcinoma, claudin-2 expression is higher than that in normal lung tissue, but the regulatory mechanism of its expression has not been clarified. In human adenocarcinoma A549 cells, claudin-2 level time-dependently increased under the control conditions. In contrast, claudin-1 expression remained constant for 24h. The concentration of epidermal growth factor (EGF) in medium time-dependently increased, which was inhibited by matrix metalloproteinase (MMP) inhibitor II, an inhibitor of MMP-1, 3, 7, and 9. MMP inhibitor II decreased claudin-2 and phosphorylated ERK1/2 (p-ERK1/2) levels, which were recovered by EGF. Both claudin-2 and p-ERK1/2 levels were decreased by EGF neutralizing antibody, EGF receptor (EGFR) siRNA, AG1478, an inhibitor of EGFR, U0126, an inhibitor of MEK, and the exogenous expression of dominant negative-MEK. These results suggest that EGF is secreted from A549 cells by MMP and increases claudin-2 expression mediated via the activation of an EGFR/MEK/ERK pathway. The inhibition of the signaling pathway decreased phosphorylated c-Fos and nuclear c-Fos levels. The introduction of c-Fos siRNA decreased claudin-2 level without affecting claudin-1. The promoter activity of human claudin-2 was decreased by AG1478 and U0126. Furthermore, the activity was decreased by the deletion or mutation of the AP-1 binding site of claudin-2 promoter. Chromatin immunoprecipitation and avidin-biotin conjugated DNA assays showed that c-Fos binds to the AP-1 binding site. We suggest that a secreted EGF up-regulates the transcriptional activity of claudin-2 mediated by the activation of an EGFR/MEK/ERK/c-Fos pathway in A549 cells.

InGaAs nano-photodetectors based on photonic crystal waveguide including ultracompact buried heterostructure.

Ultrasmall InGaAs photodetectors based on a photonic crystal waveguide with a buried heterostructure (BH) were demonstrated for the first time. A sufficiently high DC responsivity of ~1 A/W was achieved for the 3.4-µm-long detector. The dynamic response revealed a 3-dB bandwidth of 6 GHz and a 10-Gb/s eye pattern. These results were thanks to the strong confinement of both photons and carriers in a small BH and will pave the way for unprecedented nano-photodetectors with a high quantum efficiency and small capacitance. Our device potentially has an ultrasmall junction capacitance of much less than 1 fF and may enable us to eliminate electrical amplifiers for future optical receivers and subsequent ultralow-power optical links on a chip.

Ultralow-energy and high-contrast all-optical switch involving Fano resonance based on coupled photonic crystal nanocavities.

We experimentally and theoretically clarified that a Fano resonant system based on a coupled optical cavity has better performance when used as an all-optical switch than a single cavity in terms of switching energy, contrast, and operation bandwidth. We successfully fabricated a Fano system consisting of doubly coupled photonic-crystal (PhC) nanocavities, and demonstrated all-optical switching for the first time. A steep asymmetric transmission spectrum was clearly observed, thereby enabling a low-energy and high-contrast switching operation. We achieved the switching with a pump energy of a few fJ, a contrast of more than 10 dB, and an 18 ps switching time window. These levels of performance are actually better than those for Lorentzian resonance in a single cavity. We also theoretically investigated the achievable performance in a well-designed Fano system, which suggested a high contrast for the switching of more than 20 dB in a fJ energy regime.

A flat-output widely tunable laser based on parallel-ring resonator integrated with electroabsorption modulator.

We present a novel parallel-ring-resonator tunable laser monolithically integrated with an InGaAlAs electroabsorption modulator. The fabricated tunable laser exhibits stable wavelength tuning with a step of 200 GHz over a wide tuning range of 35 nm, achieved with a single electrode control. The variation in the laser output power with wavelength tuning is less than 1 dB even at an injected tuning current of 20 mA. Clear eye openings at 25 Gbit/s with a dynamic extinction ratio of more than 10 dB are demonstrated over a wavelength range of 25.7 nm with a constant voltage swing of 2 V at 45 °C. Error-free operation is confirmed under the same operating conditions.

Room-temperature continuous-wave operation of lateral current injection wavelength-scale embedded active-region photonic-crystal laser.

We have developed a wavelength-scale embedded active-region photonic-crystal laser using lateral p-i-n structure. Zn diffusion and Si ion implantation are used for p- and n-type doping. Room-temperature continuous-wave lasing behavior is clearly observed from the injection current dependence of the output power, 3dB-bandwidth of the peak, and lasing wavelength. The threshold current is 390 µA and the estimated effective threshold current is 9.4 µA. The output power in output waveguide is 1.82 µW for a 2.0-mA current injection. These results indicate that the embedded active-region structure effectively reduce the thermal resistance. Ultrasmall electrically driven lasers are an important step towards on-chip photonic network applications.

Narrow linewidth operation of buried-heterostructure photonic crystal nanolaser.

We investigate the spectral linewidth of a monolithic photonic crystal nanocavity laser. The nanocavity laser is based on a buried heterostructure cavity in which an ultra-small InGaAsP active region is embedded in an InP photonic crystal. Although it was difficult to achieve narrow linewidth operation in previously reported photonic crystal nanocavity lasers, we have successfully demonstrated a linewidth of 143.5 MHz, which is far narrower than the cold cavity linewidth and the narrowest value yet reported for nanolasers and photonic crystal lasers. The narrow linewidth is accompanied by a low power consumption and an ultrasmall footprint, thus making this particular laser especially suitable for use as an integrated multi-purpose sensor.

Decrease in claudin-2 expression enhances cell migration in renal epithelial Madin-Darby canine kidney cells.

Migration of renal epithelial cells increases after renal tubular damage, but its mechanism has not been clarified in detail. Hyperosmotic stress increased a cellular injury concomitant with a decrease in mRNA and protein expression of claudin-2 in renal tubular epithelial Madin-Darby canine kidney cells. We hypothesized that claudin-2 is involved in the regulation of cell migration. To knockdown claudin-2 expression, we made the cells expressing doxycycline-inducible claudin-2 shRNA vector. Claudin-2 knockdown affected neither the endogenous expression levels of claudin-1, -3, -4, and -7 nor the Triton X-100 solubility of these claudins. Transepithelial electrical resistance was increased by claudin-2 knockdown without affecting permeability to FITC-dextran (4,000 Da). BrdU incorporation assay and cell counting revealed that cell proliferation and viability are unaffected by claudin-2 knockdown. In the wound-healing assay, the recovery rate of wound area was increased by claudin-2 knockdown. The mRNA expression and activity of matrix metalloproteinase-9 (MMP-9) were increased by claudin-2 knockdown. A selective MMP-9 inhibitor suppressed cell migration in the claudin-2 knockdown cells. Hyperosmotic stress increased the expression and activity of MMP-9, which were inhibited by claudin-2 overexpression. These results suggest that the decrease in claudin-2 expression enhances cell migration mediated by the increase in the expression and activity of MMP-9.

20-Gbit/s directly modulated photonic crystal nanocavity laser with ultra-low power consumption.

We have demonstrated an ultracompact buried heterostructure photonic crystal (PhC) laser, consisting of an InGaAsP-based active region (5.0 x 0.3 x 0.15 µm3) buried in an InP layer. By employing a buried heterostructure with an InP layer, we can greatly improve thermal resistance and carrier confinement. We therefore achieved a low threshold input power of 6.8 µW and a maximum output power in the output waveguide of -10.3 dBm by optical pumping. The output light is effectively coupled to the output waveguide with a high external differential quantum efficiency of 53%. We observed a clear eye opening for a 20-Gbit/s NRZ signal modulation with an absorbed input power of 175.2 µW, resulting in an energy cost of 8.76 fJ/bit. This is the smallest reported energy cost for any type of semiconductor laser.

All-optical memory based on injection-locking bistability in photonic crystal lasers.

We have demonstrated an all-optical memory by using InGaAsP/InP buried heterostructure photonic crystal (BH-PhC) lasers. We achieved distinct optical injection locking bistability in an ultra-compact active region (4 × 0.3 × 0.16 µm3) with only 25 µW pump power in the PhC waveguide, which is two orders less than previously reported optical memories based on other bistable semiconductor lasers. Dynamic memory operations were achieved with pump power of 100 µW and switching power of 22 µW and 71 µW in the PhC waveguide. Fast switching times of about 60 ps were achieved. To the authors' best knowledge, this is the first demonstration of PhC laser-based all-optical memory.

40-Gb/s directly-modulated photonic crystal lasers under optical injection-locking.

CMOS integrated circuits (IC) usually requires high data bandwidth for off-chip input/output (I/O) data transport with sufficiently low power consumption in order to overcome pin-count limitation. In order to meet future requirements of photonic network interconnect, we propose an optical output device based on an optical injection-locked photonic crystal (PhC) laser to realize low-power and high-speed off-chip interconnects. This device enables ultralow-power operation and is suitable for highly integrated photonic circuits because of its strong light-matter interaction in the PhC nanocavity and ultra-compact size. High-speed operation is achieved by using the optical injection-locking (OIL) technique, which has been shown as an effective means to enhance modulation bandwidth beyond the relaxation resonance frequency limit. In this paper, we report experimental results of the OIL-PhC laser under various injection conditions and also demonstrate 40-Gb/s large-signal direct modulation with an ultralow energy consumption of 6.6 fJ/bit.

All-optical wavelength-routing switch with monolithically integrated filter-free tunable wavelength converters and an AWG.

We present a compact 4x8 wavelength-routing switch that monolithically integrates fast tunable wavelength converters (TWCs) and an arrayed-waveguide grating (AWG) for optical packet switching. The TWC consists of a double-ring-resonator-coupled tunable laser which allows rapid and stable switching, and an optical gate based on a parallel amplifier structure which prevents an input optical signal from being routed through the AWG (filter-free operation). A deep-ridge waveguide technology, employed for the AWG and ring resonators, facilitates the fabrication of the switch and makes the device compact. The filter-free TWCs achieve low crosstalk of the input optical signal of less than -22 dB. The wavelength routing operation of a non-return-to-zero (NRZ) signal at 10 Gbit/s is achieved with a switching time of less than 5 ns.