Astrometry of Galactic Star Forming Region Sharpless 269 with VERA : Parallax Measurements and Constraint on Outer Rotation Curve

We have performed high-precision astrometry of H2O maser sources in Galactic star forming region Sharpless 269 (S269) with VERA. We have successfully detected a trigonometric parallax of 189+/-8 micro-arcsec, corresponding to the source distance of 5.28 +0.24/-0.22 kpc. This is the smallest parallax ever measured, and the first one detected beyond 5 kpc. The source distance as well as proper motions are used to constrain the outer rotation curve of the Galaxy, demonstrating that the difference of rotation velocities at the Sun and at S269 (which is 13.1 kpc away from the Galaxy's center) is less than 3%. This gives the strongest constraint on the flatness of the outer rotation curve and provides a direct confirmation on the existence of large amount of dark matter in the Galaxy's outer disk.Comment: 7 pages and 4 figures, Accepted by PASJ (Vol. 59, No. 5, October 25, 2007 issue

Distance to Orion KL Measured with VERA

We present the initial results of multi-epoch VLBI observations of the 22 GHz H2O masers in the Orion KL region with VERA (VLBI Exploration of Radio Astrometry). With the VERA dual-beam receiving system, we have carried out phase-referencing VLBI astrometry and successfully detected an annual parallax of Orion KL to be 2.29+/-0.10 mas, corresponding to the distance of 437+/-19 pc from the Sun. The distance to Orion KL is determined for the first time with the annual parallax method in these observations. Although this value is consistent with that of the previously reported, 480+/-80 pc, which is estimated from the statistical parallax method using proper motions and radial velocities of the H2O maser features, our new results provide the much more accurate value with an uncertainty of only 4%. In addition to the annual parallax, we have detected an absolute proper motion of the maser feature, suggesting an outflow motion powered by the radio source I along with the systematic motion of source I itself.Comment: 7 pages, 3 figures. PASJ, in press (Vol. 59, No. 5, October 25, 2007 issue

Absolute Proper Motions of H2O Masers Away from the Galactic Plane Measured with VERA in the "Superbubble" Region NGC 281

We report on absolute proper-motion measurements of an H2O maser source in the NGC 281 West molecular cloud, which is located ~320 pc above the Galactic plane and is associated with an HI loop extending from the Galactic plane. We have conducted multi-epoch phase-referencing observations of the maser source with VERA (VLBI Exploration of Radio Astrometry) over a monitoring period of 6 months since May 2006. We find that the H2O maser features in NGC 281 West are systematically moving toward the southwest and further away from the Galactic plane with a vertical velocity of ~20-30 km/s at its estimated distance of 2.2-3.5 kpc. Our new results provide the most direct evidence that the gas in the NGC 281 region on the HI loop was blown out from the Galactic plane, most likely in a superbubble driven by multiple or sequential supernova explosions in the Galactic plane.Comment: 10 pages, 5 figures, PASJ in press (Vol. 59, No. 4; August 25, 2007 issue

VLBI Astrometry of AGB Variables with VERA -- A Semiregular Variable S Crateris --

We present a distance measurement for the semiregular variable S Crateris (S Crt) based on its annual parallax. With the unique dual beam system of the VLBI Exploration for Radio Astrometry (VERA) telescopes, we measured the absolute proper motion of a water maser spot associated with S Crt, referred to the quasar J1147-0724 located at an angular separation of 1.23$^{\circ}$. In observations spanning nearly two years, we have detected the maser spot at the LSR velocity of 34.7 km s$^{-1}$, for which we measured the annual parallax of 2.33$\pm$0.13 mas corresponding to a distance of 430$^{+25}_{-23}$ pc. This measurement has an accuracy one order of magnitude better than the parallax measurements of HIPPARCOS. The angular distribution and three-dimensional velocity field of maser spots indicate a bipolar outflow with the flow axis along northeast-southwest direction. Using the distance and photospheric temperature, we estimate the stellar radius of S Crt and compare it with those of Mira variables.Comment: 9 pages, 4 figures, accepted for publication in PASJ (Vol.60, No.5, October 25, VERA special issue

Sr Isotopic Composition of NIES Certified Reference Material No. 28 Urban Aerosols

An interlaboratory study of the National Institute for Environmental Studies (NIES) certified reference material (CRM) No. 28 Urban Aerosols collected from the filters of a central ventilating system in a building in the Beijing city center from 1996 to 2005 was performed to obtain an information value of the Sr isotopic composition. The Sr isotopic composition was measured using multi-collector-inductively coupled plasma-mass spectrometry (MC-ICP-MS) to confirm the CRM’s within- and between-bottle homogeneity, and the results showed a 87Sr/86Sr ratio of 0.710227 ± 0.000019 (2SD, n = 18). The Sr isotopic compositions were intercompared using thermal ionization mass spectrometry (TIMS), which showed good agreement with values obtained at NIES. Subsequently, a consistent 87Sr/86Sr ratio was observed between two dissolution (hotplate vs. high-pressure bomb) and Sr separation (Sr spec resin vs. cation exchange resin) methods. To validate and reproduce the accuracy of our analytical methods, the Sr isotopic compositions of secondary reference materials, JB-1b and JA-2, were also measured. Our results showed that NIES CRM No. 28 is appropriate for the quality control of Sr isotope measurements of particulate matter analyses for environmental and geochemical studies

Distance to VY Canis Majoris with VERA

We report astrometric observations of H2O masers around the red supergiant VY Canis Majoris (VY CMa) carried out with VLBI Exploration of Radio Astrometry (VERA). Based on astrometric monitoring for 13 months, we successfully measured a trigonometric parallax of 0.88 +/- 0.08 mas, corresponding to a distance of 1.14 +0.11/-0.09 kpc. This is the most accurate distance to VY CMa and the first one based on an annual parallax measurement. The luminosity of VY CMa has been overestimated due to a previously accepted distance. With our result, we re-estimate the luminosity of VY CMa to be (3 +/- 0.5) x 10^5 L_sun using the bolometric flux integrated over optical and IR wavelengths. This improved luminosity value makes location of VY CMa on the Hertzsprung-Russel (HR) diagram much closer to the theoretically allowable zone (i.e. the left side of the Hayashi track) than previous ones, though uncertainty in the effective temperature of the stellar surface still does not permit us to make a final conclusion.Comment: 7 pages, 4 figures, accepted for publication in PASJ, VERA special issu

Beneficial Effects of Estrogen in a Mouse Model of Cerebrovascular Insufficiency

BACKGROUND: The M(5) muscarinic acetylcholine receptor is known to play a crucial role in mediating acetylcholine dependent dilation of cerebral blood vessels. Previously, we reported that male M(5) muscarinic acetylcholine knockout mice (M5R(-/-) mice) suffer from a constitutive constriction of cerebral arteries, reduced cerebral blood flow, dendritic atrophy, and short-term memory loss, without necrosis and/or inflammation in the brain. METHODOLOGY/PRINCIPAL FINDINGS: We employed the Magnetic Resonance Angiography to study the area of the basilar artery in male and female M5R(-/-) mice. Here we show that female M5R(-/-) mice did not show the reduction in vascular area observed in male M5R(-/-) mice. However, ovariectomized female M5R(-/-) mice displayed phenotypic changes similar to male M5R(-/-) mice, strongly suggesting that estrogen plays a key role in the observed gender differences. We found that 17beta-estradiol (E2) induced nitric oxide release and ERK activation in a conditional immortalized mouse brain cerebrovascular endothelial cell line. Agonists of ERalpha, ERbeta, and GPR30 promoted ERK activation in this cell line. Moreover, in vivo magnetic resonance imaging studies showed that the cross section of the basilar artery was restored to normal in male M5R(-/-) mice treated with E2. Treatment with E2 also improved the performance of male M5R(-/-) mice in a cognitive test and reduced the atrophy of neural dendrites in the cerebral cortex and hippocampus. M5R(-/-) mice also showed astrocyte swelling in cortex and hippocampus using the three-dimensional reconstruction of electron microscope images. This phenotype was reversed by E2 treatment, similar to the observed deficits in dendrite morphology and the number of synapses. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that M5R(-/-) mice represent an excellent novel model system to study the beneficial effects of estrogen on cerebrovascular function and cognition. E2 may offer new therapeutic perspectives for the treatment of cerebrovascular insufficiency related memory dysfunction

Protein Crosslinking by Transglutaminase Controls Cuticle Morphogenesis in Drosophila

Transglutaminase (TG) plays important and diverse roles in mammals, such as blood coagulation and formation of the skin barrier, by catalyzing protein crosslinking. In invertebrates, TG is known to be involved in immobilization of invading pathogens at sites of injury. Here we demonstrate that Drosophila TG is an important enzyme for cuticle morphogenesis. Although TG activity was undetectable before the second instar larval stage, it dramatically increased in the third instar larval stage. RNA interference (RNAi) of the TG gene caused a pupal semi-lethal phenotype and abnormal morphology. Furthermore, TG-RNAi flies showed a significantly shorter life span than their counterparts, and approximately 90% of flies died within 30 days after eclosion. Stage-specific TG-RNAi before the third instar larval stage resulted in cuticle abnormality, but the TG-RNAi after the late pupal stage did not, indicating that TG plays a key role at or before the early pupal stage. Immediately following eclosion, acid-extractable protein from wild-type wings was nearly all converted to non-extractable protein due to wing maturation, whereas several proteins remained acid-extractable in the mature wings of TG-RNAi flies. We identified four proteins—two cuticular chitin-binding proteins, larval serum protein 2, and a putative C-type lectin—as TG substrates. RNAi of their corresponding genes caused a lethal phenotype or cuticle abnormality. Our results indicate that TG-dependent protein crosslinking in Drosophila plays a key role in cuticle morphogenesis and sclerotization

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049