End-to-End Joint Target and Non-Target Speakers ASR

This paper proposes a novel automatic speech recognition (ASR) system that can transcribe individual speaker's speech while identifying whether they are target or non-target speakers from multi-talker overlapped speech. Target-speaker ASR systems are a promising way to only transcribe a target speaker's speech by enrolling the target speaker's information. However, in conversational ASR applications, transcribing both the target speaker's speech and non-target speakers' ones is often required to understand interactive information. To naturally consider both target and non-target speakers in a single ASR model, our idea is to extend autoregressive modeling-based multi-talker ASR systems to utilize the enrollment speech of the target speaker. Our proposed ASR is performed by recursively generating both textual tokens and tokens that represent target or non-target speakers. Our experiments demonstrate the effectiveness of our proposed method.Comment: Accepted at Interspeech 202

Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study

Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The present structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects

Deficiency of calcium/calmodulin-dependent serine protein kinase disrupts the excitatory-inhibitory balance of synapses by down-regulating GluN2B

Calcium/calmodulin-dependent serine protein kinase (CASK) is a membrane-associated guanylate kinase (MAGUK) protein that is associated with neurodevelopmental disorders. CASK is thought to have both pre- and postsynaptic functions, but the mechanism and consequences of its functions in the brain have yet to be elucidated, because homozygous CASK-knockout (CASK-KO) mice die before brain maturation. Taking advantage of the X-chromosome inactivation (XCI) mechanism, here we examined the synaptic functions of CASK-KO neurons in acute brain slices of heterozygous CASK-KO female mice. We also analyzed CASK-knockdown (KD) neurons in acute brain slices generated by in utero electroporation. Both CASK-KO and CASK-KD neurons showed a disruption of the excitatory and inhibitory (E/I) balance. We further found that the expression level of the N-methyl-d-aspartate receptor subunit GluN2B was decreased in CASK-KD neurons and that overexpressing GluN2B rescued the disrupted E/I balance in CASK-KD neurons. These results suggest that the down-regulation of GluN2B may be involved in the mechanism of the disruption of synaptic E/I balance in CASK-deficient neurons

Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice

Background. Although numerous reports addressing pathological involvements of diabetic polyneuropathy have been conducted, a universally effective treatment of diabetic polyneuropathy has not yet been established. Recently, regenerative medicine studies in diabetic polyneuropathy using somatic stem/progenitor cell have been reported. However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects. Here, we investigated the efficacy of treatment for diabetic polyneuropathy using angioblast-like cells derived from mouse embryonic stem cells. Methods and Results. Angioblast-like cells were obtained from mouse embryonic stem cells and transplantation of these cells improved several physiological impairments in diabetic polyneuropathy: hypoalgesia, delayed nerve conduction velocities, and reduced blood flow in sciatic nerve and plantar skin. Furthermore, pathologically, the capillary number to muscle fiber ratios were increased in skeletal muscles of transplanted hindlimbs, and intraepidermal nerve fiber densities were ameliorated in transplanted plantar skin. Transplanted cells maintained their viabilities and differentiated to endothelial cells and smooth muscle cells around the injection sites. Moreover, several transplanted cells constructed chimeric blood vessels with recipient cells. Conclusions. These results suggest that transplantation of angioblast like cells induced from embryonic stem cells appears to be a novel therapeutic strategy for diabetic polyneuropathy

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

MOA-2020-BLG-135Lb: A New Neptune-class Planet for the Extended MOA-II Exoplanet Microlens Statistical Analysis

We report the light-curve analysis for the event MOA-2020-BLG-135, which leads to the discovery of a new Neptune-class planet, MOA-2020-BLG-135Lb. With a derived mass ratio of $q=1.52_{-0.31}^{+0.39} \times 10^{-4}$ and separation $s\approx1$, the planet lies exactly at the break and likely peak of the exoplanet mass-ratio function derived by the MOA collaboration (Suzuki et al. 2016). We estimate the properties of the lens system based on a Galactic model and considering two different Bayesian priors: one assuming that all stars have an equal planet-hosting probability and the other that planets are more likely to orbit more massive stars. With a uniform host mass prior, we predict that the lens system is likely to be a planet of mass $m_\mathrm{planet}=11.3_{-6.9}^{+19.2} M_\oplus$ and a host star of mass $M_\mathrm{host}=0.23_{-0.14}^{+0.39} M_\odot$, located at a distance $D_L=7.9_{-1.0}^{+1.0}\;\mathrm{kpc}$. With a prior that holds that planet occurrence scales in proportion to the host star mass, the estimated lens system properties are $m_\mathrm{planet}=25_{-15}^{+22} M_\oplus$, $M_\mathrm{host}=0.53_{-0.32}^{+0.42} M_\odot$, and $D_L=8.3_{-1.0}^{+0.9}\; \mathrm{kpc}$. This planet qualifies for inclusion in the extended MOA-II exoplanet microlens sample.Comment: 22 pages, 6 figures, 4 tables, submitted to the AAS Journal

Exportin 4 Interacts with Sox9 through the HMG Box and Inhibits the DNA Binding of Sox9

Sox9 is a transcription factor that is required for tissue development in mammals. In general, such transcription factors require co-regulators for precise temporal and spatial control of the activation and inactivation of the numerous genes necessary for precise development during embryogenesis. Here we identify a new Sox9 co-regulator: Using affinity chromatography with immobilized Sox9 protein, we identified exportin 4 (Exp4) as an interacting protein of Sox9 in human cultured cells. Interaction between endogenous Exp4 and Sox9 proteins was confirmed in the human osteosarcoma U2OS cells by immunoprecipitation experiments using anti-Sox9 antibody. siRNA depletion of Exp4 enhanced transcription of Sox9 target genes in U2OS cells, but did not affect nuclear localization of Sox9. These results suggest that Exp4 regulates Sox9 activity in the nucleus. Furthermore we found that the HMG box of Sox9 was responsible for binding to Exp4, and the HMG box was required for suppression of Sox9-mediated transcription. This contrasts with the known Sox9 co-regulators which bind to its transcriptional activation domain. Chromatin immunoprecipitation analyses revealed that Exp4 prevents Sox9 binding to the enhancers of its target genes. These results demonstrate that Exp4 acts as a Sox9 co-regulator that directly regulates binding of Sox9 to its target genes

Functional analysis of RRAS2 pathogenic variants with a Noonan-like phenotype

Introduction: RRAS2, a member of the R-Ras subfamily of Ras-like low-molecular-weight GTPases, is considered to regulate cell proliferation and differentiation via the RAS/MAPK signaling pathway. Seven RRAS2 pathogenic variants have been reported in patients with Noonan syndrome; however, few functional analyses have been conducted. Herein, we report two patients who presented with a Noonan-like phenotype with recurrent and novel RRAS2 pathogenic variants (p.Gly23Val and p.Gly24Glu, respectively) and the results of their functional analysis.Materials and methods: Wild-type (WT) and mutant RRAS2 genes were transiently expressed in Human Embryonic Kidney293 cells. Expression of RRAS2 and phosphorylation of ERK1/2 were confirmed by Western blotting, and the RAS signaling pathway activity was measured using a reporter assay system with the serum response element-luciferase construct. WT and p.Gly23Val RRAS2 were expressed in Drosophila eye using the glass multiple reporter-Gal4 driver. Mutant mRNA microinjection into zebrafish embryos was performed, and the embryo jaws were observed.Results: No obvious differences in the expression of proteins WT, p.Gly23Val, and p.Gly24Glu were observed. The luciferase reporter assay showed that the activity of p.Gly23Val was 2.45 ± 0.95-fold higher than WT, and p.Gly24Glu was 3.06 ± 1.35-fold higher than WT. For transgenic flies, the p.Gly23Val expression resulted in no adults flies emerging, indicating lethality. For mutant mRNA-injected zebrafish embryos, an oval shape and delayed jaw development were observed compared with WT mRNA-injected embryos. These indicated hyperactivity of the RAS signaling pathway.Discussion: Recurrent and novel RRAS2 variants that we reported showed increased in vitro or in vivo RAS signaling pathway activity because of gain-of-function RRAS2 variants. Clinical features are similar to those previously reported, suggesting that RRAS2 gain-of-function variants cause this disease in patients

KMT-2021-BLG-1077L: The fifth confirmed multiplanetary system detected by microlensing

The high-magnification microlensing event KMT-2021-BLG-1077 exhibits a subtle and complex anomaly pattern in the region around the peak. We analyze the lensing light curve of the event with the aim of revealing the nature of the anomaly. We test various models in combination with several interpretations. We find that the anomaly cannot be explained by the usual three-body (2L1S and 1L2S) models. The 2L2S model improves the fit compared to the three-body models, but it still leaves noticeable residuals. On the other hand, the 3L1S interpretation yields a model explaining all the major anomalous features in the lensing light curve. According to the 3L1S interpretation, the estimated mass ratios of the lens companions to the primary are $\sim 1.56 \times 10^{-3}$ and $\sim 1.75 \times 10^{-3}$, which correspond to $\sim 1.6$ and $\sim 1.8$ times the Jupiter/Sun mass ratio, respectively, and therefore the lens is a multiplanetary system containing two giant planets. With the constraints of the event time-scale and angular Einstein radius, it is found that the host of the lens system is a low-mass star of mid-to-late M spectral type with a mass of $M_{\rm h} = 0.14^{+0.19}_{-0.07}~M_\odot$, and it hosts two gas giant planets with masses of $M_{\rm p_1}=0.22^{+0.31}_{-0.12}~M_{\rm J}$ and $M_{\rm p_2}=0.25^{+0.35}_{-0.13}~M_{\rm J}$. The planets lie beyond the snow line of the host with projected separations of $a_{\perp, {\rm p}_1}=1.26^{+1.41}_{-1.08}~{\rm AU}$ and $a_{\perp, {\rm p}_2}=0.93^{+1.05}_{-0.80}~{\rm AU}$. The planetary system resides in the Galactic bulge at a distance of $D_{\rm L}=8.24^{+1.02}_{-1.16}~{\rm kpc}$. The lens of the event is the fifth confirmed multiplanetary system detected by microlensing following OGLE-2006-BLG-109L, OGLE-2012-BLG-0026L, OGLE-2018-BLG-1011L, and OGLE-2019-BLG-0468L.Comment: 9 pages, 8 figure

KMT-2021-BLG-1150Lb: Microlensing planet detected through a densely covered planetary-caustic signal

Recently, there have been reports of various types of degeneracies in the interpretation of planetary signals induced by planetary caustics. In this work, we check whether such degeneracies persist in the case of well-covered signals by analyzing the lensing event KMT-2021-BLG-1150, for which the light curve exhibits a densely and continuously covered short-term anomaly. In order to identify degenerate solutions, we thoroughly investigate the parameter space by conducting dense grid searches for the lensing parameters. We then check the severity of the degeneracy among the identified solutions. We identify a pair of planetary solutions resulting from the well-known inner-outer degeneracy, and find that interpreting the anomaly is not subject to any degeneracy other than the inner-outer degeneracy. The measured parameters of the planet separation (normalized to the Einstein radius) and mass ratio between the lens components are $(s, q)_{\rm in}\sim (1.297, 1.10\times 10^{-3})$ for the inner solution and $(s, q)_{\rm out}\sim (1.242, 1.15\times 10^{-3})$ for the outer solution. According to a Bayesian estimation, the lens is a planetary system consisting of a planet with a mass $M_{\rm p}=0.88^{+0.38}_{-0.36}~M_{\rm J}$ and its host with a mass $M_{\rm h}=0.73^{+0.32}_{-0.30}~M_\odot$ lying toward the Galactic center at a distance $D_{\rm L} =3.8^{+1.3}_{-1.2}$~kpc. By conducting analyses using mock data sets prepared to mimic those obtained with data gaps and under various observational cadences, it is found that gaps in data can result in various degenerate solutions, while the observational cadence does not pose a serious degeneracy problem as long as the anomaly feature can be delineated.Comment: 9 pages, 8 figure