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Using galaxies as background light sources to map intervening Lya absorption is a novel approach to study the interplay among galaxies, the circum-galactic medium (CGM), and the intergalactic medium (IGM). Introducing a new measure of z = 3.1$ HI Lya absorption relative to the cosmic mean, Delta_NB497, estimated from photometric data of star-forming galaxies at 3.3 < z < 3.5, we have made two-dimensional Delta_NB497 maps in the z = 3.1 SSA22 proto-cluster region and two control fields (SXDS and GOODS-N fields) with a spatial resolution of ~ 5 comoving Mpc. The Delta_NB497 measurements in the SSA22 field are systematically larger than those in the control fields, and this HI absorption enhancement extends more than 50 comoving Mpc. The field-averaged (i.e., ~50 comoving Mpc scale) Delta_NB497 and the overdensity of Lya emitters (LAEs) seem to be correlated, while there is no clear dependency of the Delta_NB497 on the local LAE overdensity in a few comoving Mpc scale. These results suggest that diffuse HI gas spreads out in/around the SSA22 proto-cluster. We have also found an enhancement of Delta_NB497 at a projected distance < 100 physical kpc from the nearest z = 3.1 galaxies at least in the SSA22 field, which is probably due to HI gas associated with the CGM of individual galaxies. The HI absorption enhancement in the CGM-scale tends to be weaker around galaxies with stronger Lya emission, which suggests that the Lya escape fraction from galaxies depends on hydrogen neutrality in the CGM., 13 pages, 11 figures, 1 table, accepted to MNRAS

井上雅夫先生 退職記念論文集

Supplemental Digital Content is available in the text, Rapid response system (RRS) efficacy and national early warning score (NEWS) performances have largely been reported in inpatient settings, with few such reports undertaken in outpatient settings. This study aimed to investigate NEWS validity in predicting poor clinical outcomes among outpatients who had activated the RRS using single-parameter criteria. A single-center retrospective cohort study From April 1, 2014 to November 30, 2017 in an urban 350-bed referral hospital in Japan We collected patient characteristics such as activation triggers, interventions, arrival times, dispositions, final diagnoses, and patient outcomes. Poor clinical outcomes were defined as unplanned intensive care unit transfers or deaths within 24 hours. Correlations between the NEWS and clinical outcomes at the time of deterioration and disposition were analyzed. Among 31 outpatients, the NEWS value decreased significantly after a medical emergency team intervention (median, 8 vs 4, P

Background Although R0 surgery is recommended for stage IV colorectal cancer, the degree of required lymphadenectomy has not been established. The aim of this study was to investigate the prognostic impact of high ligation (HL) of the feeding artery and the number of retrieved lymph nodes after R0 surgery for colorectal cancer and synchronous colorectal cancer liver metastasis (CRLM). Methods This was a multi‐institutional retrospective analysis of patients with colorectal cancer and synchronous CRLM who had R0 surgery between January 1997 and December 2007. Clinical and pathological features were compared in patients who underwent HL and those who had a low ligation (LL). Kaplan–Meier analysis was performed to estimate the effect of HL on overall survival (OS). The impact of several risk factors on survival was analysed using the Cox proportional hazards model. Results Of 549 patients, 409 (74·5 per cent) had HL. Median follow‐up was 51·4 months. HL significantly improved the 5‐year OS rate (58·2 per cent versus 49·3 per cent for LL; P = 0·017). Multivariable analysis revealed HL to be a significant prognostic factor compared with LL (5‐year mortality: hazard ratio (HR) 0·68, 95 per cent c.i. 0·51 to 0·90; P = 0·007). In subgroup analysis, the positive effect of HL on OS was greatest in patients with lymph node metastasis. Conclusion HL of the feeding artery was associated with improved OS in patients with colorectal cancer and synchronous CRLM after R0 surgery., Although R0 surgery is recommended for stage IV colorectal cancer, the degree of lymphadenectomy required has not been established. A multi‐institutional retrospective analysis was done of patients with colorectal cancer and synchronous hepatic metastases who were treated with R0 surgery. More aggressive lymphadenectomy could improve the overall survival of these patients. High ligation improves survival.

著者人数: 40名 (所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 山田, 亨), Number of authors: 40 (Affiliation. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS): Yamada, Toru), Accepted: 2019-09-03, 資料番号: SA1190163000

We report a case of a staghorn stone containing ammonium acid urate that was effectively treated with drug therapy alone. A 46-year-old man had recurring urinary tract stones. He had no previous episode of urinary tract stones that required hospitalization and operation. He received only drug therapy for hyperuricemia in another hospital. Ultrasonography and computed tomography revealed a left staghorn stone measuring 37×34 mm. The kidney-ureter-bladder radiograph did not show any stones. His urine was acidic, and we estimated that the left staghorn stone consisted of urate. Oral administration of sodium hydrogen carbonate was initiated to alkalize the urine, and treatment with transurethral lithotripsy (TUL) was scheduled. Before the TUL, analysis of an excreted stone sample revealed that it consisted of ammonium acid urate. The staghorn stone was completely removed in 10 months after the first medical examination. At present, the patient is free of urinary tract stones.

The objective of this study is to assess the response of telemetered common marmosets to multiple cardiac ion channel inhibitors and to clarify the usefulness of this animal model in evaluating the effects of drug candidates on electrocardiogram (ECG). Six multiple cardiac ion channel inhibitors (sotalol, astemizole, flecainide, quinidine, verapamil and terfenadine) were orally administered to telemetered common marmosets and changes in QTc, PR interval and QRS duration were evaluated. Drugs plasma levels were determined to compare the sensitivity in common marmosets to that in humans. QTc prolongation was observed in the marmosets dosed with sotalol, astemizole, flecainide, quinidine, verapamil and terfenadine. PR prolongation was noted after flecainide and verapamil administration, and QRS widening occurred following treatment with flecainide and quinidine. Drugs plasma levels associated with ECG changes in marmosets were similar to those in humans, except for verapamil-induced QTc prolongation. Verapamil-induced change is suggested due to body temperature decrease. These results indicate that telemetered common marmoset is a useful animal for evaluation of the ECG effects of multiple cardiac ion channel inhibitors and the influence of body temperature change should be considered in the assessment.

We investigate the stellar population of star-forming galaxies at $z \sim 4$ by focusing on their slope of rest-frame ultraviolet (UV) continuum, $\beta$ where $f_{\lambda} \propto \lambda^{\beta}$. We investigate the sample of bright Lyman Break Galaxies (LBGs) with $i' \leq 26.0$ in the Subaru/XMM-Newton Deep Survey field by using the SED fitting analysis. We find that the apparently redder ($\beta_{\mathrm{obs}} > -1.73$) LBGs tend to be dusty ($\mathrm{Av} > 1.0$), have the young stellar population ($\beta_{\mathrm{int}} < -2.42$), and the intrinsically active star-forming galaxies (SFR $\gtrsim$ a few $\times 10^{2}$ $\mathrm{M_{\odot}} \mathrm{yr^{-1}}$). It means that a significant fraction of the UV-selected LBGs at $z \sim 4$ is on-going active and dust obscured star-forming galaxies. We compare the IR to UV luminosity ratio assuming the dust attenuation laws with the sub-millimeter observations from previous works. The result suggests that the Calzetti-like dust attenuation law is preferable for the active and dusty star-forming LBGs at $z = 4$. We also find that an extrapolation of the $\beta_{\mathrm{int}}$-$M_{\mathrm{UV,int}}$ relation toward the fainter magnitude range below our sample magnitude limit intersects the $\beta_{\mathrm{obs}}$-$M_{\mathrm{UV,obs}}$ relation previously obtained in the deeper narrow-area observations at $M_{\mathrm{UV}} = -18.9$ and $\beta = -1.94$, which coincides with the break point of $\beta_{\mathrm{obs}}$-$M_{\mathrm{UV,obs}}$ relation observed so far. The coincidence suggest that we see the almost dust-free population at $M_{\mathrm{UV,obs}} \gtrsim -18.9$., Comment: 20 pages, 20 figures

Monitoring dramatic changes in intracellular calcium ion levels during cardiac contraction and relaxation, known as calcium transient, in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) would be an attractive strategy for assessing compounds on cardiac contractility. In addition, as arrhythmogenic compounds are known to induce characteristic waveform changes in hiPSC-CMs, it is expected that calcium transient would allow evaluation of not only compound-induced effects on cardiac contractility, but also compound arrhythmogenic potential. Using a combination of calcium transient in hiPSC-CMs and a fast kinetic fluorescence imaging detection system, we examined in this study changes in calcium transient waveforms induced by a series of 17 compounds that include positive/negative inotropic agents as well as cardiac ion channel activators/inhibitors. We found that all positive inotropic compounds induced an increase in peak frequency and/or peak amplitude. The effects of a negative inotropic compound could clearly be detected in the presence of a β-adrenergic receptor agonist. Furthermore, most arrhythmogenic compounds raised the ratio of peak decay time to peak rise time (D/R ratio) in calcium transient waveforms. Compound concentrations at which these parameters exceeded cutoff values correlated well with systemic exposure levels at which arrhythmias were reported to be evoked. In conclusion, we believe that peak analysis of calcium transient and determination of D/R ratio are reliable methods for assessing compounds' cardiac contractility and arrhythmogenic potential, respectively. Using these approaches would allow selection of compounds with low cardiotoxic potential at the early stage of drug discovery.

To evaluate the suitability of the rat Pig-a assay on reticulocytes (PIGRET assay) as a short-term test, red blood cell (RBC) Pig-a and PIGRET assays after single doses with hydroxyurea (HU) and melphalan (L-PAM) were conducted and the results of both assays were compared. HU was administered once orally to male SD rats at 250, 500 and 1000 mg/kg, and both assays were conducted using peripheral blood withdrawn from the jugular vein at 1, 2 and 4 weeks after dosing. L-PAM was administered at 1.25, 2.5 and 5 mg/kg in the same manner. L-PAM produced significant dose-dependent increases in mutant frequencies in the PIGRET assay after single oral doses, but did not produce dose-dependent increases in mutant frequencies in the RBC Pig-a assay. These results suggest that the PIGRET assay is more sensitive for the evaluation of the mutagenic potential of L-PAM than the RBC Pig-a assay. In contrast, HU, a clastogenic but not DNA-reactive compound, gave negative results in both assays. The results with these 2 chemicals indicate that the single-dose PIGRET assay in rats has the potential to properly detect DNA-reactive compounds that directly cause DNA damage in a short-term assay.

Aim We conducted a retrospective study to investigate the frequency of appetite loss during treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in elderly patients, aged 75 years or older, with non-small cell lung cancer harboring EGFR gene mutations. Patients and methods Data of a total of 64 patients, including 39 relatively young (hereinafter, younger) patients and 25 elderly patients were analyzed. Results Appetite loss of all grades (p=0.074) and of grade 3 or greater (p=0.030) was more frequently observed in elderly patients. Diarrhea and oral mucositis were also more frequent in elderly patients, although they did not reach statistical significance. No apparent differences were observed in the frequency of aspartate aminotransferase/ alanine aminotransferase elevation, skin rash or fatigue between the two patient groups. The median (95% confidence interval) progression-free survival times were 10.8 (6.6-16.4) months and 11.8 (4.4-20.3) months in the younger and elderly patient groups, respectively. Conclusion Our findings suggest that appetite loss is a major adverse effect in elderly patients with non-small cell lung cancer receiving treatment with EGFR-TKIs.

MicroRNA (miRNA) is a class of small non-coding RNAs containing approximately 20 nucleotides that negatively regulate target gene expression. Little is known about the role of individual miRNAs and their targets in immune- and inflammation-related responses in drug-induced liver injury. In the present study, involvement of miRNAs in the T helper (Th) 2-type immune response was investigated using a methimazole (MTZ)-induced liver injury mouse model. Co-administration of L-buthionine-S,R-sulfoximine and MTZ induced acute hepatocellular necrosis and elevated plasma levels of alanine aminotransferase (ALT) from 4h onward in female Balb/c mice. The hepatic mRNA expression of Th2 promotive factors was significantly increased concomitantly with plasma ALT levels. In contrast, the hepatic mRNA expression of Th2 suppressive factors was significantly decreased during the early phase of liver injury. Comprehensive profiling of hepatic miRNA expression was analyzed before the onset of MTZ-induced liver injury. Using in silico prediction of miRNAs that possibly regulate Th2-related genes and subsequent quantification, we identified up-regulation of expression of miR-29b-1-5p and miR-449a-5p. Among targets of these miRNAs, down-regulation of Th2 suppressive transcription factors, such as SRY-related HMG-box 4 (SOX4) and lymphoid enhancer factor-1 (LEF1), were observed from the early phase of liver injury. In conclusion, negative regulation of the expression of SOX4 by miR-29b-1-5p and that of LEF1 by miR-449a-5p is suggested to play an important role in the development of Th2 bias in MTZ-induced liver injury.

The effects of temperature-dependent thermophysical properties on droplet flow characteristics in a parallel-plate channel at submicron scale are investigated. The dissipative particle dynamics method with many-body (MDPD) and energy conservation (DPDe) configurations (MDPDe) was used. Droplet flows were simulated to study the effects of the temperature difference between top and bottom walls, body force on MDPDe particles, and wall-wetting conditions. The effects on the droplet flow were discussed. Droplet flows with a subzero wall temperature were simulated. An ice layer was formed on the wall. Its thickness and shape changed depending on surface wetting, temperature gradient, and body force.

The Mach number and pressure at the outlet plane of a straight micro-tube were investigated numerically for both laminar and turbulent flow cases. The numerical methodology is based on the arbitrary Lagrangian-Eulerian method. The LB1 turbulence model was used for the turbulent flow case. The compressible momentum and energy equations with the assumption of the ideal gas were solved. The computational domain is extended to the downstream region from the micro-tube outlet. The back pressure was given to the outside of the downstream region. The computations were performed for a tube whose diameter ranges from 50 to 500 μm. The average Mach number at the outlet plane of the choked flow depends on the tube diameter and ranges from 1.16 to 1.25. The flow characteristics of the under-expanded gas flow in a straight micro-tube were revealed.

Kubota and colleagues show that neurons sequester VEGF to prune blood vessels during eye development., Vascular development involves not only vascular growth, but also regression of transient or unnecessary vessels. Hyaloid vasculature is the temporary circulatory system in fetal eyes, which spontaneously degenerates when the retinal blood vessels start to grow. Failure of the hyaloid vessels to regress leads to disease in humans, persistent hyperplastic primary vitreous, which causes severe intraocular hemorrhage and impairs visual function. However, the mechanism underlying the endogenous program that mediates spontaneous regression of the hyaloid vessels is not well understood. In this study, we identify a robust switch triggering this program directed by neurons in mice. Marked up-regulation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) occurs in retinal neurons just after birth via distal-multipotent-mesodermal enhancer, a hemangioblast-specific enhancer of VEGFR2. Genetic deletion of neuronal VEGFR2 interrupts this program, resulting in massive hyaloid vessels that persist even during late postnatal days. This abnormality is caused by excessive VEGF proteins in the vitreous cavity as a result of impairment in the neuronal sequestration of VEGF. Collectively, our data indicate that neurons trigger transition from the fetal to the postnatal circulatory systems in the retina.

Dissipative particle dynamics with energy conversion (DPDe) is a simulation technique that has been used to model thermal transport characteristics and heat transfer at mesoscale. This study shows further development of the DPDe method capturing solid/liquid phase-change phenomena and its application to water freezing in a parallel-plate straight channel. In this work, the weighting functions of the random and dissipative forces are modeled as functions of temperature in order to correctly predict the temperature dependent properties of the fluid in a two-dimensional domain. An equation of state is incorporated in the model in order to model the solidification of water. Careful consideration is taken to couple the latent heat of the system to real world units, and the solidification predicted using this model is compared to a well known analytical solution. The developed model is employed to simulate the thermally developing flow in a parallel-plate channel with constant wall temperatures below the freezing point. A liquid pump is introduced along with a region initiating the liquid temperature in order to create the thermally developing flow. The investigations show that the fluid velocity has a small effect on the time it takes for the channel to freeze completely. The dominating factor will be the temperature of the solid walls in the domain. The simulations also show that when a higher wall temperature is applied, the solid/liquid interface will be rougher due to mesoscopic fluctuations of heat and momentum. (C) 2015 Elsevier Masson SAS. All rights reserved. (Less)

Validation of the anatomically complex configurations of the Lumbar Puncture Simulator II (KYOTO KAGAKU CO., LTD., 15 Kitanekoya-cho Fushimi-ku Kyoto, Japan 612-8388) have not been reported. Previous validation of the normal anatomic configuration has been reported. This study aims to evaluate evidence for construct and content validity of 4 interchangeable lumbar puncture (LP) complex anatomic configurations of this simulator.We performed a cross-sectional study between April 2018 and May 2019. Novice volunteer medical students and expert physicians who had performed over 30 LP procedures performed sequential LP procedures on each of 4 simulated interchangeable anatomic LP puncture blocks (normal, obesity, geriatric, combined geriatric/obesity). Primary outcome measures compared between groups for each LP procedure were return of cerebrospinal fluid within 5 minutes and a calculated performance score. Subjective face validity and content validity 5-point Likert questionnaires were completed by participants.35 novice (n = 19) and expert (n = 16) subjects completed 140 procedures. Significant differences were found between novice and expert groups for both cerebrospinal fluid success rates and performance scores for normal (P = .001/P = .001) geriatric (P = .005/P = .002) and obesity (P = .003/P = < .001) configurations. There were no differences for the geriatric/obesity configuration. Expert median score of simulator realism (face validity) was 4 (range 3-4); median score of utility as a training tool (content validity) was 4 (range 4-5).We provide evidence for construct validity for each of the complex LP configurations, except combined geriatric/obesity. Expert physicians found the simulator sufficiently realistic to effectively teach LP skills.

Shear-thickening and thinning behaviors are often observed in the rheological measurements of dilute surfactant solutions with drag-reducing ability in wall-bounded turbulent flows. This study proposes a simple rheological modeling method based on combining constitutive equations, such as Giesekus and FENE-P models, with a fluidity equation to determine both thickening and thinning behaviors in simple shear flows simultaneously. The Giesekus and FENE-P models, which are typically used in numerical studies on turbulent drag reduction, cannot capture such complex behaviors. However, the proposed models, called f-Giesekus and f-FENE-P models, can predict the shear-thickening properties. The developed models are inspired by the Bautista–Manero–Puig model, where the Oldroyd-B model (upper-convected Maxwell model) is coupled with the fluidity equation. Parametric studies prove that the proposed models can accurately predict both the shear-thickening and shear-thinning properties. Notably, the f-FENE-P model shows prominent flexibility to determine the plateau region of the shear viscosity as a function of the shear rate. We verify that the analytical solutions of the f-FENE-P model agree with the experimental data of the shear viscosity in dilute drag-reducing surfactant solutions, except for the remarkable steep increase in the shear viscosity. The start-up shear flow is also studied to confirm various transitions accompanied by the overshoot and undershoot of the f-FENE-P model.

We study variability of active galactic nuclei (AGNs) by using the deep optical multiband photometry data obtained from the Hyper Suprime-Cam Subaru Strategic Program (HSC SSP) survey in the COSMOS field. The images analyzed here were taken with 8, 10, 13, and 15 epochs over three years in the $g$, $r$, $i$, and $z$ bands, respectively. We identified 491 robust variable AGN candidates, down to $i=25$ mag and with redshift up to $4.26$. Ninety percent of the variability-selected AGNs are individually identified with the X-ray sources detected in the Chandra COSMOS Legacy survey. We investigate their properties in variability by using structure function analysis and find that the structure function for low-luminosity AGNs ($L_{\mathrm{bol}}\lesssim10^{45}$ erg s$^{-1}$) shows a positive correlation with luminosity, which is the opposite trend for the luminous quasars. This trend is likely to be caused by larger contribution of the host galaxy light for lower-luminosity AGNs. Using the model templates of galaxy spectra, we evaluate the amount of host galaxy contribution to the structure function analysis and find that dominance of the young stellar population is needed to explain the observed luminosity dependence. This suggests that low-luminosity AGNs at $0.8\lesssim z\lesssim1.8$ are predominantly hosted in star-forming galaxies. The X-ray stacking analysis reveals the significant emission from the individually X-ray undetected AGNs in our variability-selected sample. The stacked samples show very large hardness ratios in their stacked X-ray spectrum, which suggests that these optically variable sources have large soft X-ray absorption by dust-free gas., 27 pages, 22 figures. Accepted for publication in ApJ

著者人数: 13名, Accepted: 2019-01-09, 資料番号: SA1180257000

The SR24 multi-star system hosts both circumprimary and circumsecondary disks, which are strongly misaligned from each other. The circumsecondary disk is circumbinary in nature. Interestingly, both disks are interacting, and they possibly rotate in opposite directions. To investigate the nature of this unique twin disk system, we present 0.''1 resolution near-infrared polarized intensity images of the circumstellar structures around SR24, obtained with HiCIAO mounted on the Subaru 8.2 m telescope. Both the circumprimary disk and the circumsecondary disk are resolved and have elongated features. While the position angle of the major axis and radius of the NIR polarization disk around SR24S are 55$^{\circ}$ and 137 au, respectively, those around SR24N are 110$^{\circ}$ and 34 au, respectively. With regard to overall morphology, the circumprimary disk around SR24S shows strong asymmetry, whereas the circumsecondary disk around SR24N shows relatively strong symmetry. Our NIR observations confirm the previous claim that the circumprimary and circumsecondary disks are misaligned from each other. Both the circumprimary and circumsecondary disks show similar structures in $^{12}$CO observations in terms of its size and elongation direction. This consistency is because both NIR and $^{12}$CO are tracing surface layers of the flared disks. As the radius of the polarization disk around SR24N is roughly consistent with the size of the outer Roche lobe, it is natural to interpret the polarization disk around SR24N as a circumbinary disk surrounding the SR24Nb-Nc system., Comment: 14 pages, 5 figures, accepted for publication in AJ

The hepatitis C virus (HCV) causes acute hepatitis C and is commonly detected via HCV antibody testing. However, delayed seroconversion of HCV antibodies and non-specific symptoms may hinder the diagnosis of this disease. A 71-year-old woman developed acute hepatitis while hospitalised for back pain. An HCV antibody test was negative, and she had no risk factors for hepatitis C. She was referred to our hospital for further evaluation. The HCV antibody test was repeated 16 days after the initial test; owing to a positive result, she was diagnosed with acute hepatitis C. Several months thereafter, the HCV spontaneously cleared. When diagnosing an HCV infection, the time at which the testing is performed needs to coincide with the time at which HCV antibody seroconversion occurs. Timely diagnosis of an HCV infection allows appropriate treatment during the acute phase which may prevent disease progression to the chronic phase.

著者人数: 59名（所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 權, 靜美), Accepted: 2018-06-08, 資料番号: SA1180097000

Measurements in the infrared wavelength domain allow us to assess directly the physical state and energy balance of cool matter in space, thus enabling the detailed study of the various processes that govern the formation and early evolution of stars and planetary systems in the Milky Way and of galaxies over cosmic time. Previous infrared missions, from IRAS to Herschel, have revealed a great deal about the obscured Universe, but sensitivity has been limited because up to now it has not been possible to fly a telescope that is both large and cold. Such a facility is essential to address key astrophysical questions, especially concerning galaxy evolution and the development of planetary systems. SPICA is a mission concept aimed at taking the next step in mid- and far-infrared observational capability by combining a large and cold telescope with instruments employing state-of-the-art ultra-sensitive detectors. The mission concept foresees a 2.5-meter diameter telescope cooled to below 8 K. Rather than using liquid cryogen, a combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With cooling not dependent on a limited cryogen supply, the mission lifetime can extend significantly beyond the required three years. The combination of low telescope background and instruments with state-of-the-art detectors means that SPICA can provide a huge advance on the capabilities of previous missions. The SPICA instrument complement offers spectral resolving power ranging from ~50 through 11000 in the 17-230 µm domain as well as ~28.000 spectroscopy between 12 and 18 µm. Additionally, SPICA will be capable of efficient 30-37 µm broad band mapping, and small field spectroscopic and polarimetric imaging in the 100-350 µm range. SPICA will enable far infrared spectroscopy with an unprecedented sensitivity of ~5x10-20 W/m2 (5σ/1hr) - at least two orders of magnitude improvement over what has been attained to date. With this exceptional leap in performance, new domains in infrared astronomy will become accessible, allowing us, for example, to unravel definitively galaxy evolution and metal production over cosmic time, to study dust formation and evolution from very early epochs onwards, and to trace the formation history of planetary systems.

This study was focused on improving the numerical accuracy of the dissipative particle dynamics simulation via modifying its numerical time integration scheme. Despite the integration of the pairwise Langevin part dealt with by most of the previous studies, we paid attention to the improvement of the standard Liouville part. The numerical accuracy was measured by the configurational temperature in this study. Employing a fourth order symplectic scheme showed a significant improvement of the numerical accuracy for the simulations especially with a large time increment when comparing it with existing schemes, which indicates that enough resolution in time was attained when our modified scheme was employed. In addition, a set of simulations was performed for a wider range of time increments than previous studies. The results showed that the computational error demonstrated different orders of accuracy for different time increment ranges, which led to the fact that the dominant effect on the error is conservative and random forces for the large and small increment ranges.This study was focused on improving the numerical accuracy of the dissipative particle dynamics simulation via modifying its numerical time integration scheme. Despite the integration of the pairwise Langevin part dealt with by most of the previous studies, we paid attention to the improvement of the standard Liouville part. The numerical accuracy was measured by the configurational temperature in this study. Employing a fourth order symplectic scheme showed a significant improvement of the numerical accuracy for the simulations especially with a large time increment when comparing it with existing schemes, which indicates that enough resolution in time was attained when our modified scheme was employed. In addition, a set of simulations was performed for a wider range of time increments than previous studies. The results showed that the computational error demonstrated different orders of accuracy for different time increment ranges, which led to the fact that the dominant effect on the error is conserva...

著者人数: 55名(所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 中川, 貴雄; 權, 靜美), Accepted: 2018-05-18, 資料番号: SA1180099000

In this article, the authors find that most alternative beta strategies have a characteristic in common: exposure to the lowcorrelation factor. This factor measures the distance between an alternative beta portfolio and the market-capitalization portfolio via a correlation coefficient. They empirically find that over the long term, strategies exhibiting “lower” correlation against the market-cap index tend to deliver higher risk-adjusted returns. This phenomenon is persistent across various stock markets, including U.S., developed, and emerging markets. The low-correlation factor can also be employed to increase the explanatory power of a standard Fama–French analysis, reducing the “residual/unexplained alpha” of the model. Finally, they show that by increasing exposure to the low-correlation factor during the portfolio construction of an equity strategy, it is possible to enhance its return–risk profile. Again, the results are consistent and robustly tested over long time periods, proving how the low-correlation enhancement can add significant value to the most common alternative beta strategies, such as minimum variance, risk parity, and even equal weighting.

Purpose – The purpose of this paper is to find out the applicability of the many-body dissipative particle dynamics (MDPD) method for various real fluids by specifically focusing on the effects of the MDPD parameters on the MDPD fluid properties. Design/methodology/approach – In this study, the MDPD method based on van der Waals (vdw) equation of state is employed. The simulations are conducted by using LAMMPS with some modifications of the original package to include the many-body features in the simulation. The simulations are investigated in a three-dimensional Cartesian box solution domain in which MDPD particles are distributed. In order to evaluate the MDPD liquid characteristics for a stationary liquid film, self-diffusivity, viscosity, Schmidt number (Sc) and surface tension, are estimated for different MDPD parameters. The parameters are carefully selected based on previous studies. A set of single-droplet simulations is also performed to analyze the droplet characteristics and its behavior on a solid-wall. Besides, the relationship between the characteristic length in the DPD simulations and scaling parameters for the stationary liquid-film case is discussed by employing the Ohnesorge number. Findings – The results show that the liquid properties in the MDPD simulations can be widely ranged by varying the MDPD parameters. The values are highly influenced by the many-body feature in the conservative force which is not included in the original DPD method. It is also found that the wetting ability of the MDPD fluid on solid walls can be easily controlled by changing a many-body parameter. The characteristic length between the MDPD reduced unit and real unit is related for the stationary liquid-film case by employing the Ohnesorge number. Originality/value – The present parametric study shows that the liquid properties in the MDPD method can vary by carefully controlling the MDPD parameters, which demonstrates the high-potential applicability of the method for various real fluids. This will contribute to research areas in multi-phase transport phenomena at nano and sub-micron scales in, for example, fuel cells, batteries and other engineering devices involving porous media.

Background & Aims Biliary tract cancers (BTCs) are clinically and pathologically heterogeneous and respond poorly to treatment. Genomic profiling can offer a clearer understanding of their carcinogenesis, classification and treatment strategy. We performed large-scale genome sequencing analyses on BTCs to investigate their somatic and germline driver events and characterize their genomic landscape. Methods We analyzed 412 BTC samples from Japanese and Italian populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing (WGS), and a further 266 samples by targeted sequencing. The subtypes were 136 intrahepatic cholangiocarcinomas (ICCs), 101 distal cholangiocarcinomas (DCCs), 109 peri-hilar type cholangiocarcinomas (PHCs), and 66 gallbladder or cystic duct cancers (GBCs/CDCs). We identified somatic alterations and searched for driver genes in BTCs, finding pathogenic germline variants of cancer-predisposing genes. We predicted cell-of-origin for BTCs by combining somatic mutation patterns and epigenetic features. Results We identified 32 significantly and commonly mutated genes including TP53 , KRAS , SMAD4 , NF1 , ARID1A , PBRM1 , and ATR , some of which negatively affected patient prognosis. A novel deletion of MUC17 at 7q22.1 affected patient prognosis. Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes such as BRCA1 , BRCA2 , RAD51D , MLH1 , or MSH2 were detected in 11% (16/146) of BTC patients. Conclusions BTCs have distinct genetic features including somatic events and germline predisposition. These findings could be useful to establish treatment and diagnostic strategies for BTCs based on genetic information. Lay summary We here analyzed genomic features of 412 BTC samples from Japanese and Italian populations. A total of 32 significantly and commonly mutated genes were identified, some of which negatively affected patient prognosis, including a novel deletion of MUC17 at 7q22.1 . Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes were detected in 11% of patients with BTC. BTCs have distinct genetic features including somatic events and germline predisposition.

The membrane is often considered as the heart of the proton exchange membrane fuel cell (PEMFC), and it is of pivotal importance for the involved transport phenomena and performance of the entire PEMFC. The Nafion(R) membrane is the most commonly used type of membrane in PEMFCs. In this paper, the nano-scale structure of the Nafion(R) membrane is reconstructed using dissipative particle dynamics. The average water pore sizes of the equilibrated membranes are estimated by employing the radial distribution function, and the reconstructed nano-scale membranes are then used to evaluate water diffusion within the membrane by calculating the mean square displacement. The tortuosity of the membrane is evaluated by comparing the diffusivity of the membrane to that of a limiting case of cylindrical channels. Important findings from this study are presented by the membrane structures, water diffusivity at different water saturations, and calculations of the tortuosity within the membrane. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved. (Less)

While sub-continuum heat conduction becomes more important as the size of micro/nanodevices keeps shrinking under the mean free path of heat carriers, its computation still remains challenging to the general engineering community due to the lack of easily accessible numerical simulation tools. To address this challenge, this article reports the finite element analysis (FEA) of transient ballistic-diffusive phonon heat transport in a two-dimensional domain using a commercial package (COMSOL Multiphysics). The Boltzmann transport equation under the gray relaxation-time approximation was numerically solved by discretizing the angular domain with the discrete ordinate method (DOM) and the spatial domain with the FEA. The DOM-FEA method was validated by comparing the results with different benchmark studies, such as the equation of phonon radiative transfer, the ballistic-diffusive equation, and the finite difference method of the phonon Boltzmann transport equation. The calculation of phonon heat transport for a 2-D square slab reveals that heat conduction becomes more ballistic with temperature jumps at boundaries as Knudsen number (Kn) increases. The ballistic nature also significantly affects transient thermal behaviors at high Kn numbers. The obtained results clearly demonstrate the capability of the DOM-FEA as a promising engineering tool for calculating sub-continuum phonon heat transport. (C) 2014 Elsevier Ltd. All rights reserved. (Less)

Lymph node metastasis is an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), but accurate preoperative diagnosis is difficult. The aim of this study was to measure the concentration of serum carbohydrate antigen 19-9 (s-CA19-9) as a preoperative predictor of lymph node metastasis.In our department, curative-intent hepatectomy for ICC has been performed only once the absence of metastases in para-aortic lymph nodes (PALN) has been confirmed from intraoperative frozen-section pathological examinations. The present study included 13 non-resected ICC patients with PALN metastasis (PALN group) and 44 resected ICC patients without PALN metastasis (non-PALN group). S-CA19-9 was examined to evaluate predictive performance for PALN metastasis and regional lymph node metastasis (pN1) from analysis of the receiver operating characteristic curve. In the non-PALN group, univariate and multivariate analyses for survival were performed on clinicopathological variables.From receiver operating characteristic curve analysis, s-CA19-9 showed good diagnostic accuracy for PALN metastasis (68%; cut-off, 200 U/mL) and pN1 (77%; cut-off, 100 U/mL). In univariate analysis, age (65 years), s-CA19-9 (≥100 U/mL), portal vein resection, pN1, and positive resection margin (R1) were all identified as significant negative prognostic factors. Five-year survival rates of patients with high s-CA19-9 and pN1 were 6.9% and 7.3%, respectively. In multivariate analysis, high s-CA19-9 and R1 represented independent predictors of poor prognosis.Preoperative s-CA19-9 appears useful as a biomarker in patients with ICC, for predicting not only lymph node metastasis but also prognosis after surgical resection with curative intent.

We report a case of ureteral carcinoma in which port site metastasis was found after a laparoscopic nephroureterectomy. The patient was a 77-year-old woman with a chiefcomplaint ofgross hematuria. A tumor was found in her left ureter by computed tomography (CT). The patient was diagnosed with a left ureter carcinoma with T2N0M0 or less. She underwent retroperitoneoscopic radical nephroureterectomy. The pathological diagnosis was an urothelial carcinoma, Grade 2, pT2Nx. She was carefully followed up without any adjuvant therapy. At 26 months postoperatively, a subcutaneous tumor was found at a port site without any disseminated disease or distant metastasis by CT and positron emission tomography-CT (PETCT). She underwent surgical resection ofthe subcutaneous tumor. Pathological diagnosis was port site metastatic urothelial carcinoma. She had no recurrence or metastasis at 24 months after the surgical resection without any adjuvant therapy.

Chihiro Taka, Ryuji Hayashi, Kazuki Shimokawa, Kotaro Tokui, Seisuke Okazawa, Kenta Kambara, Minehiko Inomata, Toru Yamada, Shoko Matsui, Kazuyuki Tobe First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Sugitani, Toyama, Toyama, Japan Background: Physical activity (PA) is considered as one of the most important prognostic predictors in chronic obstructive pulmonary disease (COPD) patients. Longevity gene, SIRT1, is reported to be involved in the pathogenesis of COPD by regulating the signaling pathways of oxidative stress, inflammation, and aging. We hypothesize that SIRT1 and related genes are also associated with the benefits of PA in COPD patients.Methods: Eighteen COPD outpatients were enrolled in this study, and their PA level was assessed with an accelerometer. We assessed the SIRT1 and related genes mRNA expression levels in the peripheral blood mononuclear cells (PBMCs) of the subjects. We carried out respiratory function testing, blood gas analysis, the 6-minute walk test, and measurement of the cross-sectional area of the erector spinae muscles (ESMCSA) by chest computed tomography. We analyzed the association of PA with the results of each of the examinations.Results: The mean age was 72±9 years, and the mean forced expiratory volume in 1 second was 1.4±0.56 L (52%±19% predicted). Our findings revealed a correlation between the daily PA and ESMCSA. The SIRT1 and Forkhead box O (FOXO)1 mRNA expression levels in PBMCs were positively correlated with moderate-PA time (r=0.60, p=0.008 for SIRT1 and r=0.59, p=0.01 for FOXO1). Keywords: COPD, accelerometer, mRNA, walking, sedentary, moderate

While systemic therapy is one of the therapeutic options available for post-operative recurrence of non-small cell lung cancer, efficacy of local therapy for locoregional recurrence or limited metastatic lesions has also been reported.We aimed to evaluate the clinical course of patients with post-operative recurrence(locoregional or limited metastatic lesion)after receiving local or systemic therapy.Clinical data were retrospectively analyzed and survival duration was compared using the logrank test.A total of 22 patients were included. Median progression-free survival in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies was 15.1 months, 6.3 months, and 13 months, respectively. Two patients receiving treatment with EGFR-TKI did not show disease progression at 41.3 months and 45.8 months(p=0.265). Median overall survivals in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies were 26.5 months, 20 months, and 37.9 months, respectively(p=0.510). After the treatment, 6 patients showed regrowth of the recurrent lesion, 8 patients showed remote metastases, and 2 patients showed both regrowth of the recurrent lesion and remote metastases.Patients who received treatment including local therapy showed longer survival duration, but statistical significance was not detected. Our study suggested that regrowth of the recurrent lesion and remote metastases can be equally observed after treatment.

The pharmacological activity of DSP-6952, a novel compound was investigated, compared to that of clinically efficacious gastrointestinal (GI) prokinetic 5-hydroxytryptamine

We present the discovery of a substellar companion to the primary host lens in the microlensing event MOA-2012-BLG-006. The companion-to-host mass ratio is 0.016, corresponding to a companion mass of $\approx8~M_{\rm Jup} (M_*/0.5M_\odot)$. Thus, the companion is either a high-mass giant planet or a low-mass brown dwarf, depending on the mass of the primary $M_*$. The companion signal was separated from the peak of the primary event by a time that was as much as four times longer than the event timescale. We therefore infer a relatively large projected separation of the companion from its host of $\approx10~{\rm a.u.}(M_*/0.5M_\odot)^{1/2}$ for a wide range (3-7 kpc) of host star distances from the Earth. We also challenge a previous claim of a planetary companion to the lens star in microlensing event OGLE-2002-BLG-045., 16 pages, 5 figures

Scalp hemodynamics contaminates the signals from functional near-infrared spectroscopy (fNIRS). Numerous methods have been proposed to reduce this contamination, but no golden standard has yet been established. Here we constructed a multi-layered solid phantom to experimentally validate such methods. This phantom comprises four layers corresponding to epidermides, dermis/skull (upper dynamic layer), cerebrospinal fluid and brain (lower dynamic layer) and the thicknesses of these layers were 0.3, 10, 1, and 50 mm, respectively. The epidermides and cerebrospinal fluid layers were made of polystyrene and an acrylic board, respectively. Both of these dynamic layers were made of epoxy resin. An infrared dye and titanium dioxide were mixed to match their absorption and reduced scattering coefficients (μa and μs’, respectively) with those of biological tissues. The bases of both upper and lower dynamic layers have a slot for laterally sliding a bar that holds an absorber piece. This bar was laterally moved using a programmable stepping motor. The optical properties of dynamic layers were estimated based on the transmittance and reflectance using the Monte Carlo look-up table method. The estimated coefficients for lower and upper dynamic layers approximately coincided with those for biological tissues. We confirmed that the preliminary fNIRS measurement using the fabricated phantom showed that the signals from the brain layer were recovered if those from the dermis layer were completely removed from their mixture, indicating that the phantom is useful for evaluating methods for reducing the contamination of the signals from the scalp.

Functional near-infrared spectroscopy (fNIRS) is suitable for measuring brain functions during neurorehabilitation because of its portability and less motion restriction. However, it is not known whether neural reconstruction can be observed through changes in cerebral hemodynamics. In this study, we modified an fNIRS system for measuring the motor function of awake monkeys to study cerebral hemodynamics during neurorehabilitation. Computer simulation was performed to determine the optimal fNIRS source–detector interval for monkey motor cortex. Accurate digital phantoms were constructed based on anatomical magnetic resonance images. Light propagation based on the diffusion equation was numerically calculated using the finite element method. The source–detector pair was placed on the scalp above the primary motor cortex. Four different interval values (10, 15, 20, 25 mm) were examined. The results showed that the detected intensity decreased and the partial optical path length in gray matter increased with an increase in the source-detector interval. We found that 15 mm is the optimal interval for the fNIRS measurement of monkey motor cortex. The preliminary measurement was performed on a healthy female macaque monkey using fNIRS equipment and custom-made optodes and optode holder. The optodes were attached above bilateral primary motor cortices. Under the awaking condition, 10 to 20 trials of alternated single-sided hand movements for several seconds with intervals of 10 to 30 s were performed. Increases and decreases in oxy- and deoxyhemoglobin concentration were observed in a localized area in the hemisphere contralateral to the moved forelimb.

The difference in signal-to-noise ratio (SNR) within functional near-infrared spectroscopic (fNIRS)-measurement channels makes it difficult to compare the significance of the signal amplitude in an individual channel against the baseline or against signals in other channels. The difference in SNR mainly originates from the difference in light loss due to the hair coverage or the optode–scalp contact. During the initial calibration of most commercial fNIRS equipment, the detected signals in different channels are differently amplified such that the system effectively utilizes a dynamic range for measurement. While different amplification rates among the channels realize almost equal signal intensities, they also differently amplify the detection noises. This results in different apparent noises in the fNIRS signals between channels. In order to level the SNRs in all the measurement channels, the system needs to equalize the light intensities received by the detectors instead of changing the signal amplification rates. To realize this novel procedure for leveling the SNR among the channels, we developed an fNIRS system equipped with an optical attenuator at each source and detector. A systematic procedure for modulating the attenuators to level SNR over all channels was mathematically formulated, and the procedure was examined using an optical phantom with a surface covered with air.