We report the first detection of C2 (0,0) and CN (0,0) absorption bands in the interstellar medium. The detection was made using the near-infrared (0.91-1.35 m) high-resolution (R = 20,000 and ...68,000) spectra of Cygnus OB2 No. 12 collected with the WINERED spectrograph mounted on the 1.3 m Araki telescope. The A-X (1,0) bands of C2 and CN were detected simultaneously. These near-infrared bands have larger oscillator strengths, compared with the A-X (2,0) bands of C2 and CN in the optical. In the spectrum of the C2 (0,0) band with R = 68,000, three velocity components in the line of sight could be resolved and the lines were detected up to high rotational levels (J″ ∼ 20). By analyzing the rotational distribution of C2, we could estimate the kinetic temperature and gas density of the clouds with high accuracy. Furthermore, we marginally detected weak lines of 12C13C for the first time in the interstellar medium. Assuming that the rotational distribution and the oscillator strengths of the relevant transitions of 12C2 and 12C13C are the same, the carbon isotope ratio was estimated to be 12C/13C = 50-100, which is consistent with the ratio in the local interstellar medium. We also constrained the oscillator strength ratio of the C2 (0,0) and (1,0) bands, for which there exists a discrepancy between theoretical calculations and experimental results. This unique constraint obtained from astronomical observation will contribute to improving the accuracy of the oscillator strength measurement, which will lead to further advancements of the C2 excitation model and allow the physical conditions of clouds to be derived.
The origin of the Galactic center diffuse X-ray emission (GCDX) is still under intense investigation. In particular, the interpretation of the hot (kT approximate 7 keV) component of the GCDX, ...characterized by the strong Fe 6.7 keV line emission, has been contentious. If the hot component originates from a truly diffuse interstellar plasma, not a collection of unresolved point sources, such plasma cannot be gravitationally bound, and its regeneration would require a huge amount of energy. Here, we show that the spatial distribution of the GCDX does not correlate with the number density distribution of an old stellar population traced by near-infrared light, strongly suggesting a significant contribution of the diffuse interstellar plasma. Contributions of the old stellar population to the GCDX are implied to be ~50% and ~20% in the nuclear stellar disk (NSD) and nuclear star cluster, respectively. For the NSD, a scale height of 0degrees.32 + or - 0degrees.02 is obtained for the first time from the stellar number density profiles. We also show the results of the extended near-infrared polarimetric observations in the central 3degrees x 2degrees region of our Galaxy, and confirm that the GCDX region is permeated by a large scale, toroidal magnetic field (MF) as previously claimed. Together with observed MF strengths close to energy equipartition, the hot plasma could be magnetically confined, reducing the amount of energy required to sustain it.
Context. Nuclear star clusters (NSCs) at the dynamical center of galaxies appear to have a complex star formation history. This suggests repeated star formation, even in the influence of the strong ...tidal field from supermassive black holes. Although the central region of our Galaxy is an ideal target for studies of the star formation history in the NSCs, most studies in the past have concentrated on a projected distance of RSgr A ∗ ~ 0.5 pc from the supermassive black hole Sgr A*. Aims. In our previous study, we detected 31 so far unknown early-type star candidates throughout the Galactic NSC (at RSgr A ∗ = 0.5–3 pc). They were found via near-infrared (NIR) imaging observations with narrow-band filters which are sensitive to CO absorption lines at ~2.3 μm, a prominent feature for old, late-type stars. The aim of this study is to confirm the spectral type for the early-type star candidates. Methods. We have carried out NIR spectroscopic observations of the early-type star candidates using Subaru/IRCS/AO188 and the laser guide star system. K-band spectra for 20 out of the 31 candidates and reference late-type stars were obtained. By determining an equivalent width, EW(CO), of the 12CO absorption feature at ≈2.294 μm, we have derived an effective temperature and a bolometric magnitude for each candidate and late-type star, and then constructed an HR diagram. Results. No young (~Myr) massive stars are included in the 20 candidates we observed; however, 13 candidates are most likely intermediate-age giants (50–500 Myr). Two other sources have ages of ~1 Gyr and the remaining five sources are old (>1 Gyr), late-type giants. Conclusions. Although none of the early-type star candidates from our previous narrow-band imaging observations can be confirmed as a young star, we find that the photometric technique can distinguish old, late-type giants from young and intermediate-age populations. From the 20 spectroscopically observed candidates, 65% of them are confirmed as being younger than 500 Myr. The intermediate-age stars could be as yet unknown members of a population formed in a starburst ~100 Myr ago. Finding no young (~a few Myr) stars at RSgr A ∗ = 0.5–3 pc favors the in situ formation scenario for the presence of the young stars at RSgr A ∗< 0.5 pc, although we do not completely exclude the possible existence of unknown young, massive stars in the region from our observations. Furthermore, the different spatial distributions of the young and the intermediate-age stars imply that the Galactic NSC is an aggregate of stars that were born in different places and under a variety of physical conditions.
Quasi‐periodic variations of a few to several days are observed in the energetic plasma and magnetic dipolarization in Jupiter's magnetosphere. Variation in the plasma mass flux related to Io's ...volcanic activity is proposed as a candidate for the variety of the period. Using a long‐term monitoring of Jupiter's northern aurora by the Earth‐orbiting planetary space telescope Hisaki, we analyzed the quasi‐periodic variation seen in the auroral power integrated over the northern pole for 2014–2016, which included monitoring Io's volcanically active period in 2015 and the solar wind near Jupiter during Juno's approach phase in 2016. Quasi‐periodic variation with periods of 0.8–8 days was detected. The difference between the periodicities during volcanically active and quiet periods is not significant. Our data set suggests that the difference of period between volcanically active and quiet conditions is below 1.25 days. This is consistent with the expected difference estimated from a proposed relationship based on a theoretical model applied to the plasma variation of this volcanic event. The periodicity does not show a clear correlation with the auroral power, central meridional longitude, nor Io phase angle. The periodic variation is continuously observed in addition to the auroral modulation due to solar wind variation. Furthermore, Hisaki auroral data sometimes shows particularly intense auroral bursts of emissions lasting <10 h. We find that these bursts coincide with peaks of the periodic variations. Moreover, the occurrence of these bursts increases during the volcanically active period. This auroral observation links parts of previous observations to give a global view of Jupiter's magnetospheric dynamics.
Key Points
Quasi‐periodic variations of a few to several days seen in Jupiter's polar‐integrated northern aurora observed by Hisaki
Auroral bursts <10 h sometimes seen at peak of periodic variation, whose occurrence increases with Io's volcanic activity
This periodic variation additionally seen in aurora intensity enhancements associated with solar wind variations
Currently, only limited knowledge is available regarding the phenotypic association between fibroblast growth factor receptor 3 (FGFR3) alterations and the tumor microenvironment (TME) in bladder ...cancer (BLCA).
A multi-omics analysis on 389 BLCA and 35 adjacent normal tissues from a cohort of OMPU-NCC Consortium Japan was retrospectively performed by integrating the whole-exome and RNA-sequence dataset and clinicopathological record. A median follow-up duration of all BLCA cohort was 31 months.
FGFR3 alterations (aFGFR3), including recurrent mutations and fusions, accounted for 44% of non-muscle invasive bladder cancer (NMIBC) and 15% of muscle-invasive bladder cancer (MIBC). Within MIBC, the consensus subtypes LumP was significantly more prevalent in aFGFR3, whereas the Ba/Sq subtype exhibited similarity between intact FGFR3 (iFGFR3) and aFGFR3 cases. We revealed that basal markers were significantly increased in MIBC/aFGFR3 compared to MIBC/iFGFR3. Transcriptome analysis highlighted TIM3 as the most upregulated immune-related gene in iFGFR3, with differential immune cell compositions observed between iFGFR3 and aFGFR3. Using EcoTyper, TME heterogeneity was discerned even within aFGFR cases, suggesting potential variations in the response to checkpoint inhibitors (CPIs). Among 72 patients treated with CPIs, the objective response rate (ORR) was comparable between iFGFR3 and aFGFR3 (20% vs 31%; p = 0.467). Strikingly, a significantly higher ORR was noted in LumP/aFGFR3 compared to LumP/iFGFR3 (50% vs 5%; p = 0.022). This trend was validated using data from the IMvigor210 trial. Additionally, several immune-related genes, including IDO1, CCL24, IL1RL1, LGALS4, and NCAM (CD56) were upregulated in LumP/iFGFR3 compared to LumP/aFGFR3 cases.
Differential pathways influenced by aFGFR3 were observed between NMIBC and MIBC, highlighting the upregulation of both luminal and basal markers in MIBC/aFGFR3. Heterogeneous TME was identified within MIBC/aFGFR3, leading to differential outcomes for CPIs. Specifically, a favorable ORR in LumP/aFGFR3 and a poor ORR in LumP/iFGFR3 were observed. We propose TIM3 as a potential target for iFGFR3 (ORR: 20%) and several immune checkpoint genes, including IDO1 and CCL24, for LumP/iFGFR3 (ORR: 5%), indicating promising avenues for precision immunotherapy for BLCA.
The pristine sample from the near-Earth carbonaceous asteroid (162173) Ryugu collected by the Hayabusa2 spacecraft enabled us to analyze the pristine extraterrestrial material without uncontrolled ...exposure to the Earth's atmosphere and biosphere. The initial analysis team for the soluble organic matter reported the detection of wide variety of organic molecules including racemic amino acids in the Ryugu samples. Here we report the detection of uracil, one of the four nucleobases in ribonucleic acid, in aqueous extracts from Ryugu samples. In addition, nicotinic acid (niacin, a B
vitamer), its derivatives, and imidazoles were detected in search for nitrogen heterocyclic molecules. The observed difference in the concentration of uracil between A0106 and C0107 may be related to the possible differences in the degree of alteration induced by energetic particles such as ultraviolet photons and cosmic rays. The present study strongly suggests that such molecules of prebiotic interest commonly formed in carbonaceous asteroids including Ryugu and were delivered to the early Earth.
Retinoic acid-inducible gene (RIG)-I is an essential innate immune sensor that recognises pathogen RNAs and induces interferon (IFN) production. However, little is known about how host proteins ...regulate RIG-I activation. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine and ligand of the MET receptor tyrosine kinase is an antiviral regulator that promotes the RIG-I-mediated innate immune response. Upon binding to MET, LECT2 induces the recruitment of the phosphatase PTP4A1 to MET and facilitates the dissociation and dephosphorylation of phosphorylated SHP2 from MET, thereby protecting RIG-I from SHP2/c-Cbl-mediated degradation. In vivo, LECT2 overexpression enhances RIG-I-dependent IFN production and inhibits lymphocytic choriomeningitis virus (LCMV) replication in the liver, whereas these changes are reversed in LECT2 knockout mice. Forced suppression of MET abolishes IFN production and antiviral activity in vitro and in vivo. Interestingly, hepatocyte growth factor (HGF), an original MET ligand, inhibits LECT2-mediated anti-viral signalling; conversely, LECT2-MET signalling competes with HGF-MET signalling. Our findings reveal previously unrecognized crosstalk between MET-mediated proliferation and innate immunity and suggest that targeting LECT2 may have therapeutic value in infectious diseases and cancer.
The Japanese government began a human papillomavirus (HPV) vaccination program for girls aged 12‐16 years in 2010 but withdrew its recommendation in 2013 because of potential adverse effects, leading ...to drastically reduced vaccination uptake. To evaluate population‐level effects of HPV vaccination, women younger than 40 years of age newly diagnosed with cervical intraepithelial neoplasia grade 1‐3 (CIN1‐3), adenocarcinoma in situ (AIS), or invasive cervical cancer (ICC) have been registered at 21 participating institutes each year since 2012. A total of 7709 women were registered during 2012‐2017, of which 5045 were HPV genotyped. Declining trends in prevalence of vaccine types HPV16 and HPV18 during a 6‐year period were observed in CIN1 (50.0% to 0.0%, Ptrend < .0001) and CIN2‐3/AIS (83.3% to 45.0%, Ptrend = .07) only among women younger than 25 years of age. Overall, HPV vaccination reduced the proportion of HPV16/18‐attributable CIN2‐3/AIS from 47.7% to 33.0% (P = .003): from 43.5% to 12.5% as routine vaccination (P = .08) and from 47.8% to 36.7% as catch‐up vaccination (P = .04). The HPV16/18 prevalence in CIN2‐3/AIS cases was significantly reduced among female individuals who received their first vaccination at age 20 years or younger (P = .02). We could not evaluate vaccination effects on ICC owing to low incidence of ICC among women aged less than 25 years. We found HPV vaccination to be effective in protecting against HPV16/18‐positive CIN/AIS in Japan; however, our data did not support catch‐up vaccination for women older than 20 years. Older adolescents who skipped routine vaccination due to the government’s suspension of its vaccine recommendation could benefit from receiving catch‐up vaccination before age 20 years.
We found human papillomavirus (HPV) vaccination to be effective in protecting against HPV16/18‐positive cervical intraepithelial neoplasia (CIN)/adenocarcinoma in situ (AIS) in Japan. Over the 6‐year period of analysis, we found declining prevalence among women aged less than 25 years of HPV16 and HPV18 in CIN1 and CIN2‐3/AIS. The prevalence of HPV/16/18 in CIN2‐3/AIS was also lower overall for both national and catch‐up vaccination, and this was significant in women who were first vaccinated at age 20 years or younger. Our data did not support the effectiveness of catch‐up vaccination in women over age 20 years.
Early intervention is effective for developing motor ability and preventing contractures and deformities in patients with cerebral palsy (CP). Gait training using the newly developed Hybrid Assistive ...Limb (HAL) shows promise as an intervention to prevent deterioration in walking ability and deformities in pediatric CP patients. The purpose of this pilot study was to examine the safety and immediate effects on walking ability after gait training using the HAL in pediatric CP patients.
Nineteen patients (six females, 13 males; mean age 8.5 years; mean height 120.5 cm; mean weight 23.2 kg) were enrolled. The Gross Motor Functional Classification Scale level was I in two patients, II in two, III in eight, and IV in seven. The HAL was used for a single session of gait training. The primary outcome was safety of the HAL for use in pediatric CP patients. The secondary outcome was the immediate effect after gait training with HAL, evaluated by passive range of motion (ROM) and gait parameters, including gait speed (m/s), step length (cm), and cadence (step/min).
All 19 patients were able to carry out the gait training without any severe adverse events. Significant improvements were observed for mean internal/external rotation and abduction angles of the hip joint, and ankle dorsiflexion angles (n = 19). Significant improvements were observed for mean gait speed and step length based on expansion of the hip flexion-extension range (n = 11).
Gait training using the HAL is safe and can produce immediate improvements in ROM and walking ability in pediatric patients with CP.
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