Pre-DECIGO can get the smoking gun to decide the astrophysical or cosmological origin of GW150914-like binary black holes

Pre-DECIGO consists of three spacecraft arranged in an equilateral triangle with 100km arm lengths orbiting 2000km above the surface of the earth. It is hoped that the launch date will be in the late 2020s. Pre-DECIGO has one clear target: binary black holes (BBHs) like GW150914 and GW151226. Pre-DECIGO can detect $\sim 30M_\odot-30M_\odot$ BBH mergers up to redshift $z\sim 30$. The cumulative event rate is $\sim 1.8\times 10^{5}\,{\rm events~yr^{-1}}$ in the Pop III origin model of BBHs like GW150914, and it saturates at $z\sim 10$, while in the primordial BBH (PBBH) model, the cumulative event rate is $\sim 3\times 10^{4}\,{\rm events~ yr^{-1}}$ at $z=30$ even if only $0.1\%$ of the dark matter consists of PBHs, and it is still increasing at $z=30$. In the Pop I/II model of BBHs, the cumulative event rate is $(3-10)\times10^{5}\,{\rm events~ yr^{-1}}$ and it saturates at $z \sim 6$. We present the requirements on orbit accuracy, drag free techniques, laser power, frequency stability, and interferometer test mass. For BBHs like GW150914 at 1Gpc, SNR$\sim 90$ is achieved with the definition of Pre-DECIGO in the $0.01-100$Hz band. Pre-DECIGO can measure the mass spectrum and the $z$-dependence of the merger rate to distinguish various models of BBHs like GW150914. Pre-DECIGO can also predict the direction of BBHs at $z=0.1$ with an accuracy of $\sim 0.3\,{\rm deg}^2$ and a merging time accuracy of $\sim 1$s at about a day before the merger so that ground-based GW detectors further developed at that time as well as electromagnetic follow-up observations can prepare for the detection of merger in advance. For intermediate mass BBHs at a large redshift $z > 10$, the QNM frequency after the merger can be within the Pre-DECIGO band so that the ringing tail can also be detectable to confirm the Einstein theory of general relativity with SNR$\sim 35$. [abridged]Comment: 17 pages, 10 figures, added some references, modifications to match the published version in PTE

BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System

Elucidating fine architectures and functions of cellular and synaptic connections requires development of new flexible methods. Here, we created a concept called the “battle of transgenes,” based on which we generated strategies using genetically engineered battles of multiple recombinases. The strategies enabled split-tunable allocation of multiple transgenes. We demonstrated the versatility of these strategies and technologies in inducing strong and multi-sparse allocations of multiple transgenes. Furthermore, the combination of our transgenic strategy and expansion microscopy enabled three-dimensional high-resolution imaging of whole synaptic structures in the hippocampus with simultaneous visualizations of endogenous synaptic proteins. These strategies and technologies based on the battle of genes may accelerate the analysis of whole synaptic and cellular connections in diverse life science fields

BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System

Elucidating fine architectures and functions of cellular and synaptic connections requires development of new flexible methods. Here, we created a concept called the “battle of transgenes,” based on which we generated strategies using genetically engineered battles of multiple recombinases. The strategies enabled split-tunable allocation of multiple transgenes. We demonstrated the versatility of these strategies and technologies in inducing strong and multi-sparse allocations of multiple transgenes. Furthermore, the combination of our transgenic strategy and expansion microscopy enabled three-dimensional high-resolution imaging of whole synaptic structures in the hippocampus with simultaneous visualizations of endogenous synaptic proteins. These strategies and technologies based on the battle of genes may accelerate the analysis of whole synaptic and cellular connections in diverse life science fields

CCR7 Signals Are Essential for Cortex–Medulla Migration of Developing Thymocytes

Upon TCR-mediated positive selection, developing thymocytes relocate within the thymus from the cortex to the medulla for further differentiation and selection. However, it is unknown how this cortex–medulla migration of thymocytes is controlled and how it controls T cell development. Here we show that in mice deficient for CCR7 or its ligands mature single-positive thymocytes are arrested in the cortex and do not accumulate in the medulla. These mutant mice are defective in forming the medullary region of the thymus. Thymic export of T cells in these mice is compromised during the neonatal period but not in adulthood. Thymocytes in these mice show no defects in maturation, survival, and negative selection to ubiquitous antigens. TCR engagement of immature cortical thymocytes elevates the cell surface expression of CCR7. These results indicate that CCR7 signals are essential for the migration of positively selected thymocytes from the cortex to the medulla. CCR7-dependent cortex–medulla migration of thymocytes plays a crucial role in medulla formation and neonatal T cell export but is not essential for maturation, survival, negative selection, and adult export of thymocytes

Angiotensin II inhibits insulin-induced actin stress fiber formation and glucose uptake via ERK1/2

There is crosstalk in intracellular signaling between Angiotensin II (Ang II) and insulin. We hypothesized that the underlying mechanism might be related to changes in cytoskeleton. In the presence of 100 nM of Ang II, insulin-induced glucose uptake was decreased and insulin-induced actin filament organization was inhibited. PKC inhibitors, including GF 109203x and p38 MAPK inhibitor (SB 203580) neither improved insulin-induced actin reorganization nor glucose uptake. In contrast, the Ang II-induced inhibition of glucose uptake and actin filament disorganization was reversed by 10 μmol ERK 1/2 MAPK inhibitor (PD 98059). Pretreatment of Ang II increased ERK1/2 phosphorylation and inhibited insulin-induced Akt phosphorylation. The effect of Ang II on ERK 1/2 phosphorylation was blocked by Ang II type 1 receptor antagonists, RNH 6270 and PD 98059 but not by SB 203580 or Guanosine-5’-O-(2-ThioDiphosphate), a G-protein inhibitor. We next tested the effect of broad-spectrum matrix metalloproteinase (MMP) inhibitor (GM 6001) on Ang II-inhibition of insulin signaling pathway. GM 6001 did not improve Ang II-induced actin filament disorganization and did not inhibit ERK1/2 phosphorylation. From these data in L6 myotube, we conclude that Ang II negatively regulates the insulin signal not through MMP signaling pathway but specifically through MMP-independent ERK 1/2 activation pathway, providing an alternative molecular mechanism for angiotensin-induced insulin resistance

Essential role of CCL21 in establishment of central self-tolerance in T cells.

The chemokine receptor CCR7 directs T cell relocation into and within lymphoid organs, including the migration of developing thymocytes into the thymic medulla. However, how three functional CCR7 ligands in mouse, CCL19, CCL21Ser, and CCL21Leu, divide their roles in immune organs is unclear. By producing mice specifically deficient in CCL21Ser, we show that CCL21Ser is essential for the accumulation of positively selected thymocytes in the thymic medulla. CCL21Ser-deficient mice were impaired in the medullary deletion of self-reactive thymocytes and developed autoimmune dacryoadenitis. T cell accumulation in the lymph nodes was also defective. These results indicate a nonredundant role of CCL21Ser in the establishment of self-tolerance in T cells in the thymic medulla, and reveal a functional inequality among CCR7 ligands in vivo

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