Epitaxially regrown quantum dot photonic crystal surface emitting lasers

Quantum dot-based epitaxially regrown photonic crystal surface emitting lasers are demonstrated at room temperature. The GaAs-based devices, which are monolithically integrated on the same wafer, exhibit ground state lasing at ∼1230 nm and excited state lasing at ∼1140 nm with threshold current densities of 0.69 and 1.05 kA/cm2, respectively

IFN-β-inducing, unusual viral RNA species produced by paramyxovirus infection accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner

The interferon (IFN) system is one of the most important defensive responses of mammals against viruses, and is rapidly evoked when the pathogen-associated molecular patterns (PAMPs) of viruses are sensed. Non-self, virus-derived RNA species have been identified as the PAMPs of RNA viruses. In the present study, we compared different types of IFN-β-inducing and -non-inducing viruses in the context of Sendai virus infection. We found that some types of unusual viral RNA species were produced by infections with IFN-β-inducing viruses and accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner. One of these structures was similar to the so-called antiviral stress granules (avSGs) formed by an infection with IFN-inducing viruses whose C proteins were knocked-out or mutated. Non-encapsidated, unusual viral RNA harboring the 5'-terminal region of the viral genome as well as RIG-I and typical SG markers accumulated in these granules. Another was a non-SG-like inclusion formed by an infection with the Cantell strain; a copyback-type DI genome, but not an authentic viral genome, specifically accumulated in the inclusion, whereas RIG-I and SG markers did not. The induction of IFN-β was closely associated with the production of these unusual RNAs as well as the formation of the cytoplasmic structures

Systematic study of external optical feedback tolerance in 1300 nm quantum dot lasers

Resilience of 1300nm In(Ga)As/GaAs quantum dot lasers to external optical feedback is systematically investigated from − 10°C to 85 °C. The high-resolution spectral and current-dependent linewidth enhancement factor is measured for all modes in the positive net modal gain region. Complimentary to that, analysis of the free-running and under deployment specific feedback relative intensity noise is discussed in the context of compliance against the IEEE 802.3ah specifications at the full range of temperatures

Proposal for common active 1.3-μm quantum dot electroabsorption modulated DFB laser

Opportunities for the monolithic integration of a novel common quantum dot (QD)-active electroabsorption modulated laser are explored. An electric-field and temperature-dependent spectroscopic study of optical absorption and gain are presented in the state-of-the-art 1.3-μm In(Ga)As/GaAs QD active material. The unique gain/absorption spectral shape, attributed to the QD's density of states, allows for a number of possible modulation schemes dependent upon the selected laser wavelength detuning from the gain peak. Intensity modulation and change in absorption, leading to negative chirp operation, are demonstrated via absorption spectroscopy and gain measurement of eight-layer-stack QD-active material. Such a device would be able to provide positive or negative chirp dependent upon modulation scheme and gain/Bragg wavelength detuning

Coherent power scaling in photonic crystal surface emitting laser arrays

A key benefit of photonic crystal surface emitting lasers (PCSELs) is the ability to increase output power through scaling the emission area while maintaining high quality single mode emission, allowing them to close the brightness gap which exists between semiconductor lasers and gas and fiber lasers. However, there are practical limits to the size, and hence power, of an individual PCSEL device, and there are trade-offs between single-mode stability and parasitic in-plane losses with increasing device size. In this paper, we discuss 2D coherent arrays as an approach to area and coherent power scaling of PCSELs. We demonstrate in two and three element PCSEL arrays an increase in the differential efficiency of the system due to a reduction in in-plane loss

Cell Cycle-Dependent Rho GTPase Activity Dynamically Regulates Cancer Cell Motility and Invasion <i>In Vivo</i>

<div><p>The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. <i>In vivo</i> inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that <i>Arhgap11a</i>, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and <i>in vivo</i> expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of <i>Arhgap11a</i> in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.</p></div

Visualization of cell cycle-dependent cancer cell mobilization and invasion.

<p>(A) Establishment and analyses of HCT116 colon cancer cells stably expressing Fucci. (<i>Upper</i>) The Fucci system enables monitoring of the cell cycle in live cells in real time. The nuclei of cells in the G1/G0, early S, and S/G2/M phases are labeled red, yellow, and green, respectively. (<i>Lower</i>) Snapshots of Fucci-expressing HCT116 cells. Scale bars represent 20 μm. (B) Intravital multiphoton imaging of Fucci-positive HCT116 cells inoculated into NOD/SCID mice. (<i>Left</i>) A representative image of Fucci-expressing HCT116 cells implanted in the cecum (green: Fucci-green (mAG), S/G2/M; red: Fucci-red (mKO2), G1; blue: collagen fibers (second harmonic generation (SHG) imaging)). Scale bars represent 75 μm. (<i>Right</i>) Quantification of the numbers of Fucci-green and -red HCT116 cells in different areas of inoculated tumors. Central and marginal zones were defined as areas further or closer than 75 μm from the border between the tumor and normal tissues, respectively. (C) Representative image at the edge of a Fucci-expressing HCT116 tumor mass. The entire area (<i>left</i>) and a time series (<i>right</i>) of magnified images (one per 400 s) of cancer cells invading the interstitium (green: Fucci-green (mAG), S/G2/M; red: Fucci-red (mKO2), G1; blue: collagen fibers (SHG imaging) (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083629#pone.0083629.s015" target="_blank">Movie S1</a>). Actual images (<i>upper</i> panels) and cell trajectories (<i>lower</i> panels) are shown. Scale bars represent 100 μm (<i>left</i>) and 10 μm (<i>right</i>). (D) Representative image of extravasating Fucci-expressing HeLa cells. The entire area (<i>left</i>) and a time series (<i>right</i>) of magnified images of cancer cells extravasating from blood vessels (one per 12 min) (green: Fucci-green (mAG), S/G2/M; red: Fucci-red (mKO2), G1; blue: collagen fibers (SHG imaging) (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083629#pone.0083629.s016" target="_blank">Movie S2</a>). Actual images (<i>upper</i> panels) and cell trajectories (<i>lower</i> panels) are shown. Scale bars represent 100 μm (<i>left</i>) and 10 μm (<i>right</i>). (E) Cellular motility in Fucci-green- and -red-positive cells was measured for 4 h (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083629#pone.0083629.s017" target="_blank">Movie S3</a>). (<i>Left</i>) Green and red spheres represent Fucci-green- and -red-positive cells, respectively, and yellow lines show the associated trajectories. Scale bars represent 100 μm. (<i>Right</i>) Mean tracking velocities of Fucci-green- and -red-positive cells. Data (n = 379 for Fucci green and n = 259 for Fucci red) were obtained from individual cells in three independent experiments. The velocities of the two groups were compared by Mann-Whitney <i>U</i>-test (p = 0.0191). The median and interquartile ranges for each group are overlaid on the dot plots.</p

Functional analyses of ARHGAP11A in RhoA-mediated cellular reactions in HCT116 colon cancer cells.

<p>(A) Schematic illustration of RhoA-mediated cellular reactions. (B) Effect of overexpression of wild-type (WT) or constitutively active (Q63L) RhoA on the formation of F-actin stress fibers (visualized using Alexa 568-phalloidin) and focal adhesions (stained with anti-paxillin). GFP was co-transfected to identify the transfected cells. Scale bars represent 15 μm. (C) Effect of CT04, a potent RhoA inhibitor, on the formation of F-actin stress fibers (visualized using rhodamine-phalloidin) and focal adhesions (stained with anti-paxillin). Nuclei were stained with DAPI. Scale bars represent 15 μm. (D) Effect of overexpression of Halo-Tagged ARHGAP11A or its control on the formation of F-actin stress fibers (visualized using Alexa 568-phalloidin) and focal adhesions (stained with anti-paxillin) in HCT116 cells. Arrowheads identify Halo-Tag-expressing cells (labeled with Oregon green-conjugated Halo-Tag ligand). Scale bars represent 10 μm. (E) Quantification of mean intensities of F-actin in Halo-control (n = 80) and Halo-ARHGAP11A-expressing (n = 80) HCT116 cells. Data were compiled from three independent experiments. (F) Quantification of focal adhesions in Halo-control (n = 80) and Halo-ARHGAP11A-expressing (n = 80) HCT116 cells. Data were compiled from three independent experiments. (G) Effect of overexpression of Halo-Tagged ARHGAP11A or its control on the formation of F-actin stress fibers (visualized using Alexa 568-phalloidin) and focal adhesions (stained with anti-paxillin) in HeLa cells. Arrowheads identify Halo-Tag-expressing cells (labeled with Oregon green-conjugated Halo-Tag ligand). Scale bars represent 10 μm. (H) Quantification of mean intensities of F-actin in Halo-control (n = 80) and Halo-ARHGAP11A-expressing (n = 80) HeLa cells. Data were compiled from three independent experiments. (I) Quantification of the number of focal adhesions in Halo-control (n = 40) and Halo-ARHGAP11A-expressing (n = 46) HeLa cells. Data were compiled from three independent experiments.</p

Relative augmentation of Rac1 activity and increased invasive migration in ARHGAP11A-expressing cancer cells.

<p>(A) Schema representing the balance between RhoA and Rac1 for cell migration. (B) Analyses of Rac1 activity at the single-cell level in HCT116 cells expressing Halo-ARHGAP11A or its Halo control. Representative images of Raichu-Rac1-expressing HCT116 cells under Halo-control (<i>left</i>) or Halo-ARHGAP11A transfection (<i>right</i>) conditions. Rac1 activity was monitored by CFP/YFP FRET ratios derived from Raichu-Rac1. Expression of Halo-Tag was identified with TMR-conjugated Halo-Tag ligand. The scale bar represents 5 μm. (C) Quantification of FRET ratios in Halo-control (n = 30) and Halo-ARHGAP11A-expressing (n = 30) HCT116 cells. (D) Three-dimensional culture of HCT116 transfected with Halo-control or Halo-tagged ARHGAP11A, supplemented with Y27632 (for Halo-control only). The scale bar represents 50 μm. (E) Proportions of round-type HCT116 in 3D culture transfected with Halo-ARHGAP11A or Halo-control. Round-type cells were counted in three visual fields for each of three independent experiments. Columns represent the mean ± s.e.m. (F) <i>In vitro</i> invasion assay using 3D Matrigel plate. Migrated cells were visualized by staining culture membrane with Diff Quik stain (Dade Behring). HCT116 transfected with Halo-ARHGAP11A or Halo-control, and wild-type HCT116 treated with Y27632 were used in the assay. (G) Quantification of invasion indices from 3D Matrigel plate assays. Invasion indexes were calculated according to the equation shown in the Method section. Columns represent the means ± s.e.m.</p