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The author (van Setten) thanks the Karin Sandqvists Foundation (Karin Sandqvists Stiftelse) Stockholm, Sweden, the Eye Foundation (Ögonfonden), Stockholm, Sweden and the Crown Princess Margaretas Foundation Working committee for the visually impaired KMA (Stiftelsen Kronprinsessan Margaretas Arbetsnämnd för synskadade KMA) Stockholm, Sweden, for the funding received forming the base for the presented model of dry eye disease.

We present ALMA deep spectroscopy for a lensed galaxy at $z_{\rm spec}=8.496$ with $\log(M_{\rm star}/M_{\odot})\sim7.8$ whose optical nebular lines and stellar continuum are detected by JWST/NIRSpec and NIRCam Early Release Observations in SMACS0723. Our ALMA spectrum shows [OIII]88$\mu$m and [CII]158$\mu$m line detections at $4.0\sigma$ and $4.5\sigma$, respectively. The redshift and position of the [OIII] line coincide with those of the JWST source, while the [CII] line is blue-shifted by 90 km s$^{-1}$ with a spatial offset of $0.''5$ ($\approx0.5$ kpc in source plane) from the JWST source. The NIRCam F444W image, including [OIII]$\lambda$5007 and H$\beta$ line emission, spatially extends beyond the stellar components by a factor of $>8$. This indicates that the $z=8.5$ galaxy has already experienced strong outflows whose oxygen and carbon produce the extended [OIII]$\lambda$5007 and the offset [CII] emission, which would promote ionizing photon escape and facilitate reionization. With careful slit-loss corrections and removals of emission spatially outside the galaxy, we evaluate the [OIII]88$\mu$m/$\lambda$5007 line ratio, and derive the electron density $n_{\rm e}$ by photoionization modeling to be $220^{+170}_{-100}$ cm$^{-3}$, which is comparable with those of $z\sim2-3$ galaxies. We estimate an [OIII]88$\mu$m/[CII]158$\mu$m line ratio in the galaxy of $>4$, as high as those of known $z\sim6-9$ galaxies. This high [OIII]88$\mu$m/[CII]158$\mu$m line ratio is generally explained by the high $n_{\rm e}$ as well as the low metallicity ($Z_{\rm gas}/Z_{\odot}=0.04^{+0.02}_{-0.02}$), high ionization parameter ($\log U > -2.27$), and low carbon-to-oxygen abundance ratio ($\log$(C/O) $=[-0.52:-0.24]$) obtained from the JWST/NIRSpec data; further [CII] follow-up observations will constrain the covering fraction of photodissociation regions., Comment: 27 pages, 11 figures, 5 tables. Submitted to ApJ

IRSA 2017 : Tagungsband, Proceedings : 1st International Railway Symposium Aachen, Aachen, Germany, 28-30 November 2017 / Herausgeber Univ.-Prof. Dr. ir. Dr. h. c. De Doncker, Rik W. (Institut für Stromrichtertechnik und elektrische Antriebe (ISEA), Aachen), Univ.-Prof. Dr.-Ing. Nießen, Nils (Verkehrswissenschaftliches Institut (VIA), Aachen), Univ.-Prof. Dr.-Ing. Schindler, Christian (Institut für Schienenfahrzeuge und Transportsysteme (IFS)/Institute of Rail Vehicles and Transport Systems 1st International Railway Symposium Aachen, IRSA 2017, Aachen, Germany, 28 Nov 2017 - 30 Nov 2017; Aachen : [RWTH Aachen] 647-659 (2018)., Published by [RWTH Aachen], Aachen

Supplemental material, sj-docx-1-tam-10.1177_17588359211009143 for Efficacy and safety of trifluridine/tipiracil plus bevacizumab and trifluridine/tipiracil or regorafenib monotherapy for chemorefractory metastatic colorectal cancer: a retrospective study by Keigo Chida, Daisuke Kotani, Yoshiaki Nakamura, Akihito Kawazoe, Yasutoshi Kuboki, Kohei Shitara, Takashi Kojima, Hiroya Taniguchi, Jun Watanabe, Itaru Endo and Takayuki Yoshino in Therapeutic Advances in Medical Oncology

We present element abundance ratios and ionizing radiation of local young low-mass (~$10^{6}$ M_sun) extremely metal poor galaxies (EMPGs) with a 2% solar oxygen abundance (O/H)_sun and a high specific star-formation rate (sSFR~300 Gyr$^{-1}$), and other (extremely) metal poor galaxies, which are compiled from Extremely Metal-Poor Representatives Explored by the Subaru Survey (EMPRESS) and the literature. Weak emission lines such as [FeIII]4658 and HeII4686 are detected in very deep optical spectra of the EMPGs taken with 8m-class telescopes including Keck and Subaru (Kojima et al. 2019, Izotov et al. 2018), enabling us to derive element abundance ratios with photoionization models. We find that neon- and argon-to-oxygen ratios are comparable to those of known local dwarf galaxies, and that the nitrogen-to-oxygen abundance ratios (N/O) are lower than 20% (N/O)_sun consistent with the low oxygen abundance. However, the iron-to-oxygen abundance ratios (Fe/O) of the EMPGs are generally high; the EMPGs with the 2%-solar oxygen abundance show high Fe/O ratios of ~90-140% (Fe/O)_sun, which are unlikely explained by suggested scenarios of Type Ia supernova iron productions, iron's dust depletion, and metal-poor gas inflow onto previously metal-riched galaxies with solar abundances. Moreover, these EMPGs have very high HeII4686/H$��$ ratios of ~1/40, which are not reproduced by existing models of high-mass X-ray binaries whose progenitor stellar masses are less than 120 M_sun. Comparing stellar-nucleosynthesis and photoionization models with a comprehensive sample of EMPGs identified by this and previous EMPG studies, we propose that both the high Fe/O ratios and the high HeII4686/H$��$ ratios are explained by the past existence of super massive ($>$300 M_sun) stars, which may evolve into intermediate-mass black holes ($\gtrsim$100 M_sun)., ApJ in press. 23 pages, 7 Figures, 6 Tables

We present an IGM HI tomography map in a survey volume of $16 \times 19 \times 131 \ h^{-3} {\rm comoving \ Mpc}^{3}$ (cMpc$^3$) centered at MAMMOTH-1 nebula and three neighbouring quasars at $z=2.3$. MAMMOTH-1 nebula is an enormous Ly$��$ nebula (ELAN), hosted by a type-II quasar dubbed MAMMOTH1-QSO, that extends over $1\ h^{-1}$ cMpc with not fully clear physical origin. Here we investigate the HI-gas distribution around MAMMOTH1-QSO with the ELAN and three neighbouring type-I quasars, making the IGM HI tomography map with a spatial resolution of $2.6\ h^{-1}$ cMpc. Our HI tomography map is reconstructed with HI Ly$��$ forest absorption of bright background objects at $z=2.4-2.9$: one eBOSS quasar and 16 Keck/LRIS galaxy spectra. We estimate the radial profile of HI flux overdensity for MAMMOTH1-QSO, and find that MAMMOTH1-QSO resides in a volume with significantly weak HI absorption. This suggests that MAMMOTH1-QSO has a proximity zone where quasar illuminates and photo-ionizes the surrounding HI gas and suppresses HI absorption, and that the ELAN is probably a photo-ionized cloud embedded in the cosmic web. The HI radial profile of MAMMOTH1-QSO is very similar to those of three neighbouring type-I quasars at $z=2.3$, which is compatible with the AGN unification model. We compare the distributions of the HI absorption and star-forming galaxies in our survey volume, and identify a spatial offset between density peaks of star-forming galaxies and HI gas. This segregation may suggest anisotropic UV background radiation created by star-forming galaxy density fluctuations., 15 pages, 9 figures. Accepted for Publication in ApJ

Table S2. Patient characteristics. (DOCX 17 kb)

Table S6. Subgroup analysis of progression-free survival. (DOCX 16 kb)

Table S3. Clinicopathological features of responders to nivolumab in patients with MMR-P. (DOCX 16 kb)

Table S5. Characteristics of patients with MMR-D and EBV positive gastric cancer. (DOCX 18 kb)

Supplemental material, 2019-00123R1_Production_Supplemental_Figures_online_supp for Localization of Tricellular Tight Junction Molecule LSR at Midbody and Centrosome During Cytokinesis in Human Epithelial Cells by Takumi Konno, Takayuki Kohno, Shin Kikuchi, Hiroshi Shimada, Seiro Satohisa, Kenichi Takano, Tsuyoshi Saito and Takashi Kojima in Journal of Histochemistry & Cytochemistry

Table S1. Gene list of the Oncomineâ ˘ Comprehensive Assay version 3. (DOCX 15 kb)

We have initiated a new survey for local extremely metal-poor galaxies (EMPGs) with Subaru/Hyper Suprime-Cam (HSC) large-area (~500 deg^2) optical images reaching a 5 sigma limit of ~26 magnitude, about 100 times deeper than the Sloan Digital Sky Survey (SDSS). To select Z/Z_sun6 reported recently. We spectroscopically confirm that 3 out of 10 candidates are truly EMPGs with Z/Z_sun, 30 pages, 26 figures, and 8 tables; (Revision: metallicities changed due to the use of a more pricise dust correction method, but conclusion does not change, Minor: a table, some figures, and sentences are added for a clear explanation.)

Table S4. Molecular features of responders to nivolumab in patients with MMR-P. (DOCX 16 kb)

Supplemental material, DS_10.1369_0022155419841013 for Rho-kinase and PKCα Inhibition Induces Primary Cilia Elongation and Alters the Behavior of Undifferentiated and Differentiated Temperature-sensitive Mouse Cochlear Cells by Akito Kakiuchi, Takayuki Kohno, Takuya Kakuki, Yakuto Kaneko, Takumi Konno, Yukino Hosaka, Tomohiro Hata, Shin Kikuchi, Takafumi Ninomiya, Tetsuo Himi, Kenichi Takano and Takashi Kojima in Journal of Histochemistry & Cytochemistry

Figure S1. Response to nivolumab by tumor mutation burden. (DOCX 22 kb)

We present our new ALMA observations targeting [OIII]88um, [CII]158um, [NII]122um, and dust continuum emission for three Lyman break galaxies at z=6.0293-6.2037 identified in the Subaru/Hyper Suprime-Cam survey. We clearly detect [OIII] and [CII] lines from all of the galaxies at 4.3-11.8sigma levels, and identify multi-band dust continuum emission in two of the three galaxies, allowing us to estimate infrared luminosities and dust temperatures simultaneously. In conjunction with previous ALMA observations for six galaxies at z>6, we confirm that all the nine z=6-9 galaxies have high [OIII]/[CII] ratios of L[OIII]/L[CII]~3-20, ~10 times higher than z~0 galaxies. We also find a positive correlation between the [OIII]/[CII] ratio and the Lya equivalent width (EW) at the ~90% confidence level. We carefully investigate physical origins of the high [OIII]/[CII] ratios at z=6-9 using Cloudy, and find that high density of the interstellar medium, low C/O abundance ratio, and the cosmic microwave background attenuation are responsible to only a part of the z=6-9 galaxies. Instead, the observed high [OIII]/[CII] ratios are explained by 10-100 times higher ionization parameters or low photodissociation region (PDR) covering fractions of 0-10%, both of which are consistent with our [NII] observations. The latter scenario can be reproduced with a density bounded nebula with PDR deficit, which would enhance the Lya, Lyman continuum, and C+ ionizing photons escape from galaxies, consistent with the [OIII]/[CII]-Lya EW correlation we find., 20 pages, 18 figures, Accepted for publication in ApJ

We present Lyα and UV-nebular emission line properties of bright Lyα emitters (LAEs) at z = 6-7 with a luminosity of log LLyα/[erg s-1] = 43-44 identified in the 21 deg2 area of the SILVERRUSH early sample developed with the Subaru Hyper Suprime-Cam survey data. Our optical spectroscopy newly confirms 21 bright LAEs with clear Lyα emission, and contributes to making a spectroscopic sample of 96 LAEs at z = 6-7 in SILVERRUSH. From the spectroscopic sample, we select seven remarkable LAEs as bright as Himiko and CR7 objects, and perform deep Keck/MOSFIRE and Subaru/nuMOIRCS near-infrared spectroscopy reaching the 3 σ flux limit of ∼2 × 10-18 erg s-1 for the UV-nebular emission lines of He II λ1640, CIV λλ1548,1550, and OIII]λλ1661,1666. Except for one tentative detection of C IV, we find no strong UV-nebular lines down to the flux limit, placing the upper limits of the rest-frame equivalent widths (EW0) of ∼2-4 A for CIV, He II, and OIII] lines. We also investigate the VLT/X-SHOOTER spectrum of CR7 whose 6 σ detection of He II is claimed by Sobral et al. Although two individuals and the ESO archive service carefully reanalyzed the X-SHOOTER data that are used in the study of Sobral et al., no He II signal of CR7 is detected, supportive of weak UV-nebular lines of the bright LAEs even for CR7. The spectral properties of these bright LAEs are thus clearly different from those of faint dropouts at z ∼ 7 that have strong UV-nebular lines shown in the various studies. Comparing these bright LAEs and the faint dropouts, we find anti-correlations between the UV-nebular line EW0 and the UV-continuum luminosity, which are similar to those found at z ∼ 2-3.

Purpose: Heat shock protein 105 (HSP105) is overexpressed in a variety of human cancers, including colorectal cancer (CRC) and esophageal cancer (EC). We identified HLA-A24 or A2-restricted HSP105 peptides that can induce HSP105 peptide-specific cytotoxic T lymphocytes (CTLs) (EP1536006, JP5112615, JP5291641, US9,404,925) and curried out a phase I clinical trial of HLA-A24 or A2-restricted HSP105 peptide vaccine in patients with CRC or EC (UMIN ID000017809). In this study, we aimed to demonstrate the immunological efficacy of the novel vaccine. Experimental design: 30 patients (HLA-A24 group; 15 patients, HLA-A2 group; 15 patients) with advanced CRC or EC were enrolled. Two types of vaccine (A24-1 and A24-7 or A2-7 and A2-12) were administered into the patients, matching HLA-types. Immunological responses were analyzed by ex vivo and in vitro IFN-γ ELISPOT assay using peripheral blood mononuclear cells before and after vaccination, and cytokines produced by HSP105-specific CTLs were measured by Cytometric Bead Array assay. We also analyzed the correlation between immunological responses and prognosis. Result: HSP105 peptide vaccines induced HSP105 peptide-specific CTLs in 15 of 30 patients. In HLA-A24 group, there were 7 patients with the induction only in ex vivo and almost all patients (n=13) showed skin reactions of vaccine sites. By contrast, in HLA-A2 group, there were 4 patients with the induction in ex vivo and 6 patients in in vitro, respectively, and only 6 patients with skin reactions of vaccine sites. In all patients, the existence of skin reaction correlated with the induction in ex vivo (p Citation Format: Yasuhiro Shimizu, Toshiaki Yoshikawa, Kojima Takashi, Kayoko Shoda, Kazuto Nosaka, Shoichi Mizuno, Satoshi Wada, Yuki Fujimoto, Tetsuro Sasada, Kenichi Kohashi, Hideaki Bando, Itaru Endo, Tetsuya Nakatsura. Immunologic efficacy of heat shock protein 105 peptide vaccine in patients with advanced colorectal and esophageal cancer [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A017.

We conduct a systematic search for galaxies at $z=0.1-1.5$ with [OII]$\lambda3727$, [OIII]$\lambda5007$, or H$��\lambda6563$ emission lines extended over at least 30 kpc by using deep narrowband and broadband imaging in Subaru-XMM Deep Survey (SXDS) field. These extended emission-line galaxies are dubbed [OII], [OIII], or H$��$ blobs. Based on a new selection method that securely selects extended emission-line galaxies, we find 77 blobs at $z=0.40-1.46$ with the isophotal area of emission lines down to $1.2\times10^{-18}$ erg s$^{-1}$ cm$^{-2}$ kpc$^{-2}$. Four of them are spectroscopically confirmed to be [OIII] blobs at $z=0.83$. We identify AGN activities in 8 blobs with X-ray and radio data and find that the fraction of AGN contribution increases with increasing isophotal area of the extended emission. With the Kolmogorov-Smirnov (KS) and Anderson-Darling tests, we confirm that the stellar-mass distributions of H$��$ and [OII] blobs are not drawn from those of the emitters at the $>90$% confidence level in that H$��$ and [OII] blobs are located at the massive end of the distributions, but cannot reject null hypothesis of being the same distributions in terms of the specific star formation rates. It is suggested that galactic-scale outflows tend to be more prominent in more massive star-forming galaxies. Exploiting our sample homogeneously selected over the large area, we derive the number densities of blobs at each epoch. The number densities of blobs decrease drastically with redshifts at the rate that is larger than that of the decrease of cosmic star formation densities., 17 pages, 16 figures, Accepted for Publication in ApJ

Circadian rhythms are a fundamental property of most organisms, from cyanobacteria to humans. In the unicellular obligately photoautotrophic cyanobacterium Synechococcus elongatus PCC 7942, essentially all promoter activities are controlled by the KaiABC-based clock under continuous light conditions. When Synechococcus cells are transferred from the light to continuous dark (DD) conditions, the expression of most genes, including the clock genes kaiA and kaiBC , is rapidly down-regulated, whereas the KaiC phosphorylation cycle persists. Therefore, we speculated that the posttranslational oscillator might not drive the transcriptional circadian output without de novo expression of the kai genes. Here we show that the cyanobacterial clock regulates the transcriptional output even in the dark. The expression of a subset of genes in the genomes of cells grown in the dark was dramatically affected by kaiABC nullification, and the magnitude of dark induction was dependent on the time at which the cells were transferred from the light to the dark. Moreover, under DD conditions, the expression of some dark-induced gene transcripts exhibited temperature-compensated damped oscillations, which were nullified in kaiABC -null strains and were affected by a kaiC period mutation. These results indicate that the Kai protein-based posttranslational oscillator can drive the circadian transcriptional output even without the de novo expression of the clock genes.

We report on an experimental investigation of the dual (index and surface-relief) grating formation in methacrylate photopolymers in the green. It is found that the dynamics of the diffracted signal from high spatial frequency dual gratings recorded in a thin film sample is mainly determined by the evolution of the volume index grating and is strongly dependent on writing intensities. Low spatial frequency dual gratings recorded in a bulk sample are also investigated. Depth profile and magnitude of the index grating are estimated quantitatively from the diffraction efficiency as a function of polish depth from the bulk sample’s surface. It is confirmed that the surface-relief grating is dominant in the light diffraction from the bulk sample.

The effect of chemical composition and firing conditions on the core loss characteristics of MnZn ferrite has been studied with special reference to the factors of core loss. It was found that hysteresis and eddy current losses comprise most of the core loss for MnZn ferrite used at 100kHz. Especially, the eddy current loss remarkably increased with increasing the frequency in comparison with hysteresis loss. On the basis of the fact that the eddy current loss bears a linear relationship to the electrical resistivity, an experimented addition of SnO2 to MnZn ferrite has been tried to improve the electrical resistivity. As a result, MnZn ferrite with low power loss has been successfully developed.

Effects of hydrostatic pressure on the Raman spectra have been investigated for four kinds of 1,3‐diketone crystals with hydrogen‐bonded molecular chains. In all the crystals we studied, intense CO stretching Raman mode shows pressure‐induced softening reflecting compression of the hydrogen bonds. Furthermore, application of pressure broadens the both C=O and C–O stretching modes and intensifies several specific vibrational bands. We ascribed these spectral changes to formation or growth of the kink‐type defects of the hydrogen‐bonded sequence.

We demonstrate permanent holographic storage in the green with high diffraction efficiency and recording sensitivity in TiO2 nanoparticle-dispersed methacrylate photopolymer films. It is shown that the diffraction efficiency as well as the recording sensitivity significantly increase with an increase of nanoparticle concentration. It is also found that volumetric shrinkage during holographic exposure is noticeably suppressed by inclusion of the nanoparticles.

Infrared absorbance (IR) spectra and Raman scattering spectra were measured as a function of pressure for molecular crystals of several 1,3-diketones, which are composed of hydrogen-bonded π -molecular chains. An unconventional proton-related band is commonly observed in the IR spectra around 1800-2000cm−1 in these compounds. We ascribed the observed band to proton vibration localized around kink-(or antikink-) solitons. The intensity of the band rapidly increases with application of hydrostatic pressure, suggesting increase in number of the solitons-like defects of the molecular chains via deformation of the double-well type proton potential.

This paper studies a class of social welfare relations (SWRs) on the set of infinite utility streams. In particular, we examine the SWRs satisfying Q-Anonymity, an impartiality axiom stronger than Finite Anonymity, as well as Strong Pareto and a certain equity axiom. First, we characterize the extension of the generalized Lorenz SWR by combining Q-Anonymity with Strong Pareto and Pigou-Dalton Equity. Second, we replace Pigou-Dalton Equity with Hammond Equity for characterizing the extended leximin SWR. Third, we give an alternative characterization of the extended utilitarian SWR by substituting Incremental Equity for Pigou-Dalton Equity.

We investigate the dynamics ofholographic grating formation in methacrylate photopolymer films. Dual gratings consisting of surface relief and volume holograms are observed. The influence of such grating formation on temporal behavior of the diffiacted signal is discussed.

Infrared (IR) and visible absorbance spectra were measured as a function of hydrostatic pressure for five kinds of organic crystals composed of hydrogen‐bonded molecular chains. An unconventional vibrational band is observed in the IR spectra around 1800 cm− 1 commonly in these compounds and its intensity rapidly increases with pressure. We have ascribed the observed band to a proton vibration localized around kink‐type defects or solitons in the hydrogen‐bonded molecular chains. In accordance with the pressure‐induced growth of the IR band, a new electronic absorption band appears in the visible region below the ordinary molecular excitation, suggesting a change in the electronic structures within the molecules around the soliton.