The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

The status of DECIGO

DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) is the planned Japanese space gravitational wave antenna, aiming to detect gravitational waves from astrophysically and cosmologically significant sources mainly between 0.1 Hz and 10 Hz and thus to open a new window for gravitational wave astronomy and for the universe. DECIGO will consists of three drag-free spacecraft arranged in an equilateral triangle with 1000 km arm lengths whose relative displacements are measured by a differential Fabry-Perot interferometer, and four units of triangular Fabry-Perot interferometers are arranged on heliocentric orbit around the sun. DECIGO is vary ambitious mission, we plan to launch DECIGO in era of 2030s after precursor satellite mission, B-DECIGO. B-DECIGO is essentially smaller version of DECIGO: B-DECIGO consists of three spacecraft arranged in an triangle with 100 km arm lengths orbiting 2000 km above the surface of the earth. It is hoped that the launch date will be late 2020s for the present

TGF-β1 Downregulates COX-2 Expression Leading to Decrease of PGE2 Production in Human Lung Cancer A549 Cells, Which Is Involved in Fibrotic Response to TGF-β1

<div><p>Transforming growth factor-ß1 (TGF-β1) is a multifunctional cytokine that is involved in various pathophysiological processes, including cancer progression and fibrotic disorders. Here, we show that treatment with TGF-β1 (5 ng/mL) induced downregulation of cyclooxygenase-2 (COX-2), leading to reduced synthesis of prostaglandin E2 (PGE2), in human lung cancer A549 cells. Treatment of cells with specific inhibitors of COX-2 or PGE2 receptor resulted in growth inhibition, indicating that the COX-2/PGE2 pathway contributes to proliferation in an autocrine manner. TGF-β1 treatment induced growth inhibition, which was attenuated by exogenous PGE2. TGF-β1 is also a potent inducer of epithelial mesenchymal transition (EMT), a phenotype change in which epithelial cells differentiate into fibroblastoid cells. Supplementation with PGE2 or PGE2 receptor EP4 agonist PGE1-alcohol, as compared with EP1/3 agonist sulprostone, inhibited TGF-β1-induced expression of fibronectin and collagen I (extracellular matrix components). Exogenous PGE2 or PGE2 receptor agonists also suppressed actin remodeling induced by TGF-β1. These results suggest that PGE2 has an anti-fibrotic effect. We conclude that TGF-β1-induced downregulation of COX-2/PGE2 signaling is involved in facilitation of fibrotic EMT response in A549 cells.</p> </div

Downregulation of COX-2 expression and PGE2 by TGF-β1 in A549 cells.

<p>(A) Expression of COX-2 protein was detected by immunoblotting as described in Materials and Methods. Treatment with TGF-β1 (5 ng/mL) suppressed expression of COX-2 but not COX-1 in A549 cells. HMGB1 was measured as a loading control. (B) Dose-dependent downregulation of COX-2 by TGF-β1. Twenty-four hours after TGF-β1 stimulation (1-10 ng/mL), expression of COX-2 and COX-1 was detected. (C) SB431542 (10 µM) or SIS3 (30 µM) blocked TGF-β1-induced COX-2 downregulation. Cells were pretreated for 60 min with the inhibitor, and then incubated with or without TGF-β1 (5 ng/mL) for 24 h. (D) TGF-β1 suppressed COX-2 production in A549 cells. Cells were treated with TGF-β1 (1-10 ng/mL) or NS-398 (50 µM) for 24 h, then the concentration of PGE2 in culture medium was measured by EIA as described in Materials and Methods. Each value represents the mean ± SE (n = 4). Significant differences between the indicated groups and control group are indicated by **(P < 0.01).</p

TGF-β1-induced suppression of COX-2 expression by transcriptional repression.

<p>(A) Time-dependent decrease of COX-2 mRNA expression by treatment with TGF-β1 (5 ng/mL). COX-2 mRNA level was measured by real-time RT-PCR as described in Materials and Methods. (B) Cells were pretreated with actinomycin D (5 µg/mL) for 1 h and incubated with or without TGF-β1 (5 ng/mL) for the indicated times. TGF-β1 did not affect decrease of COX-2 mRNA by actinomycin D. COX-2 expression levels were normalized for GAPDH expression levels and expressed as a percentage of that in non-treated cells (control). Each value represents the mean ± SE (n = 3). (C) Cells were incubated with CHX (50 µg/mL) or CHX plus TGF-β1 (5 ng/mL) for the indicated times and COX-2 protein expression was detected by immunoblotting. TGF-β1 did not affect decrease of COX-2 protein by CHX. The band intensities were quantified and COX-2/actin values were expressed as relative to those of control. Each value represents the mean ± SE (n = 4).</p

Involvement of COX-2/PGE2 signaling in proliferation of A549 cells.

<p>(A) A549 cells were incubated with NS-398 (50 µM) for 3 days and the cell cycle was analyzed as described in Materials and Methods. Treatment with NS-398 decreased the ratio of S phase cells. Each value represents the mean ± SE (n = 3). (B) Cells were treated with AH6809 (30 µM), L798106 (30 µM) or L161982 (30 µM) for 3 days, then the cell cycle was analyzed and the percentage of S phase was calculated. Each value represents the mean ± SE (n = 5-7) (C) Treatment with AH6809 (30 µM), L798106 (30 µM) or L161982 (30 µM) for 3 days suppressed proliferation of A549 cells. Cell proliferation was examined by BrdU assay as described in Materials and Methods. BrdU incorporation levels were expressed relative to that in non-treated cells (control). Each value represents the mean ± SE (n = 6). Significant differences between the indicated groups and control group are indicated by *(P < 0.05) and **(P < 0.01).</p