Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats

The RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral–CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function

Astrometric VLBI observations of H2_2O masers in an extreme OH/IR star candidate NSV17351

Results of astrometric very long baseline interferometry (VLBI) observations towards an extreme OH/IR star candidate NSV17351 are presented. We used the VERA (VLBI Exploration of Radio Astrometry) VLBI array to observe 22\,GHz H$_2$O masers of NSV17351. We derived an annual parallax of 0.247$\pm$0.035 mas which corresponds to a distance of 4.05$\pm$0.59 kpc. By averaging the proper motions of 15 maser spots, we obtained the systemic proper motion of NSV17351 to be ($\mu_{\alpha}\cos{\delta}, \mu_{\delta}$)$^{\mathrm{avg}}$ $=$ ($-$1.19 $\pm$ 0.11, 1.30 $\pm$ 0.19) mas\,yr$^{-1}$. The maser spots spread out over a region of 20 mas $\times$ 30 mas, which can be converted to a spatial distribution of $\sim$80 au $\times$ $\sim$120 au at the source distance. Internal motions of the maser spots suggest an outward moving maser region with respect to the estimated position of the central star. From single dish monitoring of the H$_2$O maser emission, we estimate the pulsation period of NSV17351 to be 1122$\pm$24 days. This is the first report of the periodic activity of NSV17351, indicating that NSV17351 could have a mass of $\sim$4\,M$_{\odot}$. We confirmed that the time variation of H$_2$O masers can be used as a period estimator of variable OH/IR stars. Furthermore, by inspecting dozens of double-peaked H$_2$O maser spectra from the last 40 years, we detected a long-term acceleration in the radial velocity of the circumstellar matter to be $0.17\pm0.03$ km\,s$^{-1}$\,yr$^{-1}$ Finally, we determined the position and kinematics of NSV17351 in the Milky Way Galaxy and found that NSV17351 is located in an interarm region between the Outer and Perseus arms. We note that astrometric VLBI observations towards extreme OH/IR stars are useful samples for studies of the Galactic dynamics.Comment: Published in the Publications of the Astronomical Society of Japa

Current status of Japanese detectors

Current status of TAMA and CLIO detectors in Japan is reported in this article. These two interferometric gravitational-wave detectors are being developed for the large cryogenic gravitational wave telescope (LCGT) which is a future plan for detecting gravitational wave signals at least once per year. TAMA300 is being upgraded to improve the sensitivity in low frequency region after the last observation experiment in 2004. To reduce the seismic noises, we are installing new seismic isolation system, which is called TAMA Seismic Attenuation System, for the four test masses. We confirmed stable mass locks of a cavity and improvements of length and angular fluctuations by using two SASs. We are currently optimizing the performance of the third and fourth SASs. We continue TAMA300 operation and R&D studies for LCGT. Next data taking in the summer of 2007 is planned. CLIO is a 100-m baseline length prototype detector for LCGT to investigate interferometer performance in cryogenic condition. The key features of CLIO are that it locates Kamioka underground site for low seismic noise level, and adopts cryogenic Sapphire mirrors for low thermal noise level. The first operation of the cryogenic interferometer was successfully demonstrated in February of 2006. Current sensitivity at room temperature is close to the target sensitivity within a factor of 4. Several observation experiments at room temperature have been done. Once the displacement noise reaches at thermal noise level of room temperature, its improvement by cooling test mass mirrors should be demonstrated.Comment: 6 pages, 5 figures, Proceedings of GWDAW-1

Identification of a Small Molecule that Increases Hemoglobin Oxygen Affinity and Reduces SS Erythrocyte Sickling

Small molecules that increase the oxygen affinity of human hemoglobin may reduce sickling of red blood cells in patients with sickle cell disease. We screened 38 700 compounds using small molecule microarrays and identified 427 molecules that bind to hemoglobin. We developed a high-throughput assay for evaluating the ability of the 427 small molecules to modulate the oxygen affinity of hemoglobin. We identified a novel allosteric effector of hemoglobin, di(5-(2,3-dihydro-1,4-benzodioxin-2-yl)-4H-1,2,4-triazol-3-yl)disulfide (TD-1). TD-1 induced a greater increase in oxygen affinity of human hemoglobin in solution and in red blood cells than did 5-hydroxymethyl-2-furfural (5-HMF), N-ethylmaleimide (NEM), or diformamidine disulfide. The three-dimensional structure of hemoglobin complexed with TD-1 revealed that monomeric units of TD-1 bound covalently to β-Cys93 and β-Cys112, as well as noncovalently to the central water cavity of the hemoglobin tetramer. The binding of TD-1 to hemoglobin stabilized the relaxed state (R3-state) of hemoglobin. TD-1 increased the oxygen affinity of sickle hemoglobin and inhibited in vitro hypoxia-induced sickling of red blood cells in patients with sickle cell disease without causing hemolysis. Our study indicates that TD-1 represents a novel lead molecule for the treatment of patients with sickle cell disease

Coincidence analysis to search for inspiraling compact binaries using TAMA300 and LISM data

Japanese laser interferometric gravitational wave detectors, TAMA300 and LISM, performed a coincident observation during 2001. We perform a coincidence analysis to search for inspiraling compact binaries. The length of data used for the coincidence analysis is 275 hours when both TAMA300 and LISM detectors are operated simultaneously. TAMA300 and LISM data are analyzed by matched filtering, and candidates for gravitational wave events are obtained. If there is a true gravitational wave signal, it should appear in both data of detectors with consistent waveforms characterized by masses of stars, amplitude of the signal, the coalescence time and so on. We introduce a set of coincidence conditions of the parameters, and search for coincident events. This procedure reduces the number of fake events considerably, by a factor $\sim 10^{-4}$ compared with the number of fake events in single detector analysis. We find that the number of events after imposing the coincidence conditions is consistent with the number of accidental coincidences produced purely by noise. We thus find no evidence of gravitational wave signals. We obtain an upper limit of 0.046 /hours (CL $= 90$) to the Galactic event rate within 1kpc from the Earth. The method used in this paper can be applied straightforwardly to the case of coincidence observations with more than two detectors with arbitrary arm directions.Comment: 28 pages, 17 figures, Replaced with the version to be published in Physical Review

Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004

We analyze the data of TAMA300 detector to search for gravitational waves from inspiraling compact star binaries with masses of the component stars in the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the years 2000-2004, are used for the event search. We combine the results of different observation runs, and obtained a single upper limit on the rate of the coalescence of compact binaries in our Galaxy of 20 per year at a 90% confidence level. In this upper limit, the effect of various systematic errors such like the uncertainty of the background estimation and the calibration of the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was correcte

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

Observation results by the TAMA300 detector on gravitational wave bursts from stellar-core collapses

We present data-analysis schemes and results of observations with the TAMA300 gravitational-wave detector, targeting burst signals from stellar-core collapse events. In analyses for burst gravitational waves, the detection and fake-reduction schemes are different from well-investigated ones for a chirp-wave analysis, because precise waveform templates are not available. We used an excess-power filter for the extraction of gravitational-wave candidates, and developed two methods for the reduction of fake events caused by non-stationary noises of the detector. These analysis schemes were applied to real data from the TAMA300 interferometric gravitational wave detector. As a result, fake events were reduced by a factor of about 1000 in the best cases. The resultant event candidates were interpreted from an astronomical viewpoint. We set an upper limit of 2.2x10^3 events/sec on the burst gravitational-wave event rate in our Galaxy with a confidence level of 90%. This work sets a milestone and prospects on the search for burst gravitational waves, by establishing an analysis scheme for the observation data from an interferometric gravitational wave detector

Stable Operation of a 300-m Laser Interferometer with Sufficient Sensitivity to Detect Gravitational-Wave Events within our Galaxy

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of $h\sim 5 \times 10^{-21} /\sqrt{\rm Hz}$, a signal-to-noise ratio (SNR) of 30 is expected for gravitational waves generated by a coalescence of 1.4 $M_\odot$-1.4 $M_\odot$ binary neutron stars at 10 kpc distance. %In addition, almost all noise sources which limit the sensitivity and which %disturb the stable operation have been identified. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.Comment: 5 pages, 4 figure