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We measured the vibration of a prototype superconducting magnetic bearing (SMB) operating at liquid nitrogen temperature. This prototype system was designed as a breadboard model for LiteBIRD low-frequency telescope (LFT) polarization modulator unit. We set an upper limit of the vibration amplitude at $36~\mathrm{\mu m}$ at the rotational synchronous frequency. During the rotation, the amplitude of the magnetic field produced varies. From this setup, we compute the static and AC amplitude of the magnetic fields produced by the SMB magnet at the location of the LFT focal plane as $0.24~\mathrm{G}$ and $3\times10^{-5}$$~\mathrm{G}$, respectively. From the AC amplitude, we compute TES critical temperature variation of $7\times10^{-8}$$~\mathrm{K}$ and fractional change of the SQUID flux is $\delta \Phi/\Phi_0|_{ac}=3.1\times10^{-5}$. The mechanical vibration can be also estimated to be $3.6\times 10^{-2}$$~\mathrm{N}$ at the rotation mechanism location., Comment: 7 pages, 5 figures, accepted for publication in Journal of Low Temperature Physics

STUDY QUESTION Is there a relation between specific Na+/K+ ATPase isoform expression and localization in human blastocysts and the developmental behavior of the embryo? SUMMARY ANSWER Na+/K+ ATPase α1, β1 and β3 are the main isoforms expressed in human blastocysts and no association was found between the expression level of their respective mRNAs and the rate of blastocyst expansion. WHAT IS KNOWN ALREADY In mouse embryos, Na+/K+ ATPase α1 and β1 are expressed in the basolateral membrane of trophectoderm (TE) cells and are believed to be involved in blastocoel formation (cavitation). STUDY DESIGN, SIZE, DURATION A total of 20 surplus embryos from 11 patients who underwent IVF and embryo transfer at a university hospital between 2009 and 2018 were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS After freezing and thawing Day 5 human blastocysts, their developmental behavior was observed for 24 h using time-lapse imaging, and the expression of Na+/K+ ATPase isoforms was examined using quantitative RT-PCR (RT-qPCR). The expressed isoforms were then localized in blastocysts using fluorescent immunostaining. MAIN RESULTS AND THE ROLE OF CHANCE RT-qPCR results demonstrated the expression of Na+/K+ ATPase α1, β1 and β3 isoforms in human blastocysts. Isoforms α1 and β3 were localized to the basolateral membrane of TE cells, and β1 was localized between TE cells. A high level of β3 mRNA expression correlated with easier hatching (P = 0.0261). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The expression of mRNA and the localization of proteins of interest were verified, but we have not been able to perform functional analysis. WIDER IMPLICATIONS OF THE FINDINGS Of the various Na+/K+ ATPase isoforms, expression levels of the α1, β1 and β3 mRNAs were clearly higher than other isoforms in human blastocysts. Since α1 and β3 were localized to the basolateral membrane via fluorescent immunostaining, we believe that these subunits contribute to the dilation of the blastocoel. The β1 isoform is localized between TE cells and may be involved in tight junction formation, as previously reported in mouse embryos. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the JSPS KAKENHI (https://www.jsps.go.jp/english/index.html), grant number 17K11215. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicts of interest.

Study question What was the impact on treatment age in Japan after a subsidy policy change that set age limits for assisted reproductive technology (ART) treatment? Summary answer The national policy introducing age limits in the subsidy may have promoted ART treatment among younger women. What is known already Japan has provided partial subsidies for ART treatment since 2004. To promote treatment at a younger age, the government introduced a subsidy policy in 2016 that set age limits: up to six treatment cycles for women younger than 40 years of age; and up to three cycles for women between 40 and 42 years old. However, two out of 47 prefectures continued to provide subsidies to women aged 43 and older. Study design, size, duration We conducted a time series analysis of the utilisation of ART before and after the introduction of age limits, using data from the Japanese national ART registry from 2012 to 2016. Participants/materials, setting, methods We described the number of fresh and frozen treatment cycles, comparing the number between 45 prefectures that followed the national policy change (hereafter, prefectures with age limits) and two prefectures that did not (hereafter, prefectures without age limits). Ordinary least squares regression models were used to assess the impact of the policy change by prefecture on the number of ART cycles by women of different ages. Main results and the role of chance The overall number of fresh and frozen ART cycles continuously increased in all age groups from 2012 to 2016. Meanwhile, the number of fresh ART cycles among women aged ≤ 36 and 37-39 years in 2016 increased from the previous year by + 4.0% and +1.8% in prefectures with age limits, whereas it decreased in prefectures without age limits: -3.1% and -2.3%, respectively. The number of fresh ART cycles among women aged 40-42 and 43-45 years in prefectures with age limits in 2016 changed by + 1.5% and -0.1%, respectively, whereas it increased considerably in prefectures without age limits by + 9.6% and +65.4%, respectively. Similar changes were shown for the frozen cycles. After controlling for underlying time trends and prefectural characteristics, the policy change significantly increased the number of fresh and frozen ART treatment cycles among women aged ≤ 36 years and decreased the treatment cycles of women aged 40-42 years. Limitations, reasons for caution We evaluated the change observed in the year of the policy change and could not assess longer-term trends. Additionally, unobserved factors might have contributed to the change in treatment numbers. Wider implications of the findings The introduction of a policy to set an age limit for the partial ART subsidy resulted in a significant increase in treatment even among age groups younger than the boundary groups. The policy change might have conveyed educational messages regarding the benefits of early treatment. Trial registration number not applicable

Summary Background Satralizumab, a humanised monoclonal antibody targeting the interleukin-6 receptor, reduced the risk of relapse in patients with neuromyelitis optica spectrum disorder (NMOSD) when added to immunosuppressant therapy. This study assessed the safety and efficacy of satralizumab monotherapy in patients with the disorder. Methods In this phase 3, double-blind, placebo-controlled, parallel-group trial, we enrolled adults aged 18–74 years with aquaporin-4 antibody seropositive or seronegative NMOSD at 44 investigational sites in 13 countries. Eligible participants had experienced at least one documented NMOSD attack or relapse in the past 12 months and had a score of 6·5 or less on the Expanded Disability Status Scale. Exclusion criteria included clinical relapse 30 days or fewer before baseline. Participants were randomly assigned (2:1) to receive satralizumab 120 mg or visually matched placebo subcutaneously at weeks 0, 2, 4, and every 4 weeks thereafter. Taking immunosuppressants concomitantly was prohibited. The primary endpoint was time to the first protocol-defined relapse, based on the intention-to-treat population and analysed with stratification for two randomisation factors (previous therapy for prevention of attacks and nature of the most recent attack). Safety was assessed in all participants who received at least one dose of satralizumab or placebo. The double-blind phase was due to last until 44 protocol-defined relapses occurred or 1·5 years after random assignment of the last patient enrolled, whichever occurred first; participants could enter an open-label phase after the occurrence of a protocol-defined relapse or at the end of the double-blind phase. The study is registered with ClinicalTrials.gov , NCT02073279 . Findings 95 (57%) of 168 screened participants were randomly assigned to treatment (63 to satralizumab; 32 to placebo) between Aug 5, 2014, and April 2, 2017. Protocol-defined relapses occurred in 19 (30%) patients receiving satralizumab and 16 (50%) receiving placebo (hazard ratio 0·45, 95% CI 0·23–0·89; p=0·018). 473·9 adverse events per 100 patient-years occurred in the satralizumab group, as did 495·2 per 100 patient-years in the placebo group; the incidence of serious adverse events and adverse events leading to withdrawal was similar between groups. Interpretation Satralizumab monotherapy reduced the rate of NMOSD relapse compared with placebo in the overall trial population, with a favourable safety profile. The patient population included a ratio of aquaporin-4 antibody seropositive and seronegative patients that was reflective of clinical practice. Satralizumab has the potential to become a valuable treatment option for patients with NMOSD. Funding Chugai Pharmaceutical (Roche).

We present the catalog of Interplanetary Network (IPN) localizations for 199 short-duration gamma-ray bursts (sGRBs) detected by the Konus-Wind (KW) experiment between 2011 January 1 and 2021 August 31, which extends the initial sample of IPN localized KW sGRBs (arXiv:1301.3740) to 495 events. We present the most comprehensive IPN localization data on these events, including probability sky maps in HEALPix format., Published in ApJS

Full list of authors: Kawauchi, K.; Murgas, F.; Palle, E.; Narita, N.; Fukui, A.; Hirano, T.; Parviainen, H.; Ishikawa, H. T.; Watanabe, N.; Esparaza-Borges, E.; Kuzuhara, M.; Orell-Miquel, J.; Krishnamurthy, V; Mori, M.; Kagetani, T.; Zou, Y.; Isogai, K.; Livingston, J. H.; Howell, S. B.; Crouzet, N.; de Leon, J. P.; Kimura, T.; Kodama, T.; Korth, J.; Kurita, S.; Laza-Ramos, A.; Luque, R.; Madrigal-Aguado, A.; Miyakawa, K.; Morello, G.; Nishiumi, T.; Rodriguez, G. E. F.; Sanchez-Benavente, M.; Stangret, M.; Teng, H.; Terada, Y.; Gnilka, C. L.; Guerrero, N.; Harakawa, H.; Hodapp, K.; Hori, Y.; Ikoma, M.; Jacobson, S.; Konishi, M.; Kotani, T.; Kudo, T.; Kurokowa, T.; Kusakabe, N.; Nishikawa, J.; Omiya, M.; Serizawa, T.; Tamura, M.; Ueda, A.; Vievard, S.--This is an Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., Context. The NASA space telescope TESS is currently in the extended mission of its all-sky search for new transiting planets. Of the thousands of candidates that TESS is expected to deliver, transiting planets orbiting nearby M dwarfs are particularly interesting targets since they provide a great opportunity to characterize their atmospheres by transmission spectroscopy. Aims. We aim to validate and characterize the new sub-Neptune-sized planet candidate TOI-2136.01 orbiting a nearby M dwarf (d = 33.36 ± 0.02pc, Teff = 3373 ± 108 K) with an orbital period of 7.852 days. Methods. We use TESS data, ground-based multicolor photometry, and radial velocity measurements with the InfraRed Doppler (IRD) instrument on the Subaru Telescope to validate the planetary nature of TOI-2136.01, and estimate the stellar and planetary parameters. We also conduct high-resolution transmission spectroscopy to search for helium in its atmosphere. Results. We confirm that TOI-2136.01 (now named TOI-2136b) is a bona fide planet with a planetary radius of Rp = 2.20 ± 0.07R⊕ and a mass of Mp = 4.7−2.6+3.1 M⊕. We also search for helium 10830 Å absorption lines and place an upper limit on the equivalent width of, The MEarth Project acknowledges funding from the David and Lucile Packard Fellowship for Science and Engineering, the National Science Foundation under grants AST-0807690, AST-1109468, AST-1616624 and AST-1004488 (Alan T. Waterman Award), the National Aeronautics and Space Administration under Grant No. 80NSSC18K0476 issued through the XRP Program, and the John Templeton Foundation. Based on observations obtained with the Samuel Oschin 48-inch Telescope at the Palomar Observatory as part of the Zwicky Transient Facility project. Z.T.F. is supported by the National Science Foundation under Grant No. AST-1440341 and a collaboration including Caltech, IPAC, the Weizmann Institute for Science, the Oskar Klein Center at Stockholm University, the University of Maryland, the University of Washington, Deutsches Elektronen-Synchrotron and Humboldt University, Los Alamos National Laboratories, the TANGO Consortium of Taiwan, the University of Wisconsin at Milwaukee, and Lawrence Berkeley National Laboratories. Operations are conducted by COO, IPAC, and UW. Our data reductions benefited from PyRAF and PyFITS that are the products of the Space Telescope Science Institute, which is operated by AURA for NASA. G.M. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 895525. R.L. acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación, through project PID2019-109522GB-C52, and the Centre of Excellence “Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). J.K. gratefully acknowledge the support of the Swedish National Space Agency (SNSA; DNR 2020-00104). This work is partly supported by JSPS KAKENHI Grant Numbers JP21K20376, JP21K13975, JP21H00035, JP21K20388, JP20K14518, JP20K14521, JP19K14783, JP18H05439, JP17H04574, by Grant-in-Aid for JSPS Fellows Grant Number JP20J21872, by JST CREST Grant Number JPMJCR1761, by Astrobiology Center PROJECT Research AB031014, by Astrobiology Center SATELLITE Research project AB022006, and the Astrobiology Center of National Institutes of Natural Sciences (NINS) (Grant Number AB031010). M.T. is supported by MEXT/JSPS KAKENHI grant Nos. 18H05442, 15H02063, and 22000005. Some of the observations in the paper made use of the High-Resolution Imaging instrument Alopeke obtained under Gemini LLP Proposal Number: GN/S-2021A-LP-105. Alopeke was funded by the NASA Exoplanet Exploration Program and built at the NASA Ames Research Center by Steve B. Howell, Nic Scott, Elliott P. Horch, and Emmett Quigley. Alopeke was mounted on the Gemini North (and/or South) telescope of the international Gemini Observatory, a program of NSF’s OIR Lab, which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation, on behalf of the Gemini partnership: the National Science Foundation (United States), National Research Council (Canada), Agencia Nacional de Investigación y Desarrollo (Chile), Mnisterio de Ciencia, Tecnología e Innovación (Argentina), Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brazil), and Korea Astronomy and Space Science Institute (Republic of Korea).

e17567 Background: Platinum-taxane chemotherapy and surgical debulking are the optimal treatment for patients with advanced ovarian cancer. While initial response rates are above 80%, tumor recurrence occurs in about 70 to 80% of patients. Cells with defects in homologous recombination repair (HRR) are susceptible to cell death induced by Poly (ADP-ribose) polymerase inhibitors (PARPi). These drugs are used to treat recurrent neoplasms that have BRCA1 or BRCA2 mutations or homologous recombination deficiency (HRD). Low tumor percentage in test samples, which is common in clinical practice, is often overlooked when addressing HRD tests. The goal of this study was to determine the optimal tumor content rate needed to detect HRD changes. Methods: A total of sixteen ovarian neoplasms were studied. These samples were sequenced using Illumina TSO500 NGS and interpreted using NxClinical software 6.1. In all cases, HRD scores were evaluated. A score of ≥42 was determined to be HR-deficient and a score < 42 was considered HR-proficient. We aimed to identify the optimal tumor percentage needed for detection of HRD alterations. HRD scores were calculated with tumor percentages of 70%, 60%, 40%, and 20%. Additionally, chemotherapy response scores (CRS) were available in 8 of 16 cases. We correlated the CRS with HRD scores. Results: In this project, visualization of a 523-gene cancer exome panel was shown to be 66.7% sensitive and 100% specific for detecting genomic scars (HRD score). 68.75% of cases showed low HRD score and 31.25% of cases showed a high HRD score. Next generation sequencing (NGS) results for most specimens are adequate with a tumor content rate of 70%. CRS1 cases were HR-proficient. For CRS2 and CRS3 we had mixed results. Conclusions: HRD correlates with platinum sensitivity in epithelial ovarian tumors, which has clinical significance as a predictor of sensitivity to PARPi. During treatment, tissue samples are obtained at different times points and sources, some at diagnosis/surgical debulking and some after neoadjuvant therapy. After neoadjuvant treatment, tumor volume is reduced. Cytology specimens are convenient for obtaining tumoral cells, but tumor volumes are usually small. Profiling tumors of low volume decrease the chances of detecting a patient’s eligibility for targeted maintenance. Our next steps will evaluate the performance of tissue microarrays using the Infinium CytoSNP-850K array compared to NGC cytogenomics at low tumor volumes.

BackgroundMPO-ANCA-associated vasculitis (MPO-AAV) is a systemic small vessel vasculitis with the production of MPO-ANCA in the serum. This disease develops necrotizing and crescent glomerulonephritis (NCGN) and peritubular capillaritis-mediated interstitial damages in the kidneys, and pulmonary hemorrhage due to capillaritis in the lungs. Recent studies have revealed that neutrophil extracellular traps (NETs) induced by MPO-ANCA are critically involved in its pathogenesis,1 and neutrophil elastase (NE) plays an essential role in the formation of NETs.2 Cathepsin C (CatC) functions as a key enzyme in the activation process of several neutrophil serine proteases (NSPs) such as NE, proteinase 3 and cathepthin G by converting the inactive forms of the NSPs to the active forms by digesting dipeptides at the N-terminus of the enzymes.3ObjectivesAlthough glucocorticoids and immunosuppressive drugs used as the standard of cares can lead remission in MPO-AAV patients, there are remaining unmet medical needs such as severe side effects, resistance to the treatment and relapse. Therefore, development of new therapeutic strategies is awaited. The aim of this study is to demonstrate the efficacy of MOD06051, a novel CatC inhibitor, against MPO-AAV, using an MPO-AAV rat model established previously.4MethodsIn vitro studies: Cathpsins and NE inhibitory activity was measured using recombinant enzymes and fluorescent substrates. Cellular NE activity in the granulocytes differentiated from the primary human bone marrow-derived hematopietic stem cells under the presence or absence of MOD06051 was determined using fluorescent substrates.In vivo studies: 4-week-old Wistar Kyoto (WKY) rats were immunized with human MPO according to Little’s protocol.4 The rats were divided into three groups (n=8 in each group), and vehicle (0.5% methylcellulose) or MOD06051 (0.3 or 3 mg/kg bid) was orally administered every day for 42 days. All rats were euthanized at the end of the study for serological and histological evaluations.ResultsIn vitro studies: MOD06051 inhibited the enzymatic activity of human recombinant CatC with an IC50 value of 1.5 nM, and no other cathepsins nor NE inhibition was observed at 10 μM. The NE activity in primary human granulocytes was suppressed by MOD06051 with an IC50 value of 18 nM.In vivo studies: MPO-ANCA was induced in all groups at the same level. The percentage of affected glomeruli including those with NCGN, NET-forming neutrophils in the peripheral blood and glomeruli, and glomerular neutrophil counts were significantly suppressed by MOD06051 treatment in a dose-dependent manner. Furthermore, hematuria score, urinary NGAL (Neutrophil Gelatinase-Associated Lipocalin), tubular erythrocyte cast counts, and pulmonary hemorrhage foci were significantly decreased in the 3 mg/kg of MOD06051 treated group with the similar trends in 0.3 mg/kg group.ConclusionMOD06051 showed sepcific inhibition of CatC activity. This compound suppressed the serine proteases activation in primary human neutrophils and NET formation in the MPO-AAV model rats, resulting in amelioration of MPO-ANCA-induced tissue destruction, including NCGN and tubular interstitial damages in the kidneys, and disorder of alveolar septal capillaries in the lungs. MOD06051 appears to be a promising agent for treatment of MPO-AAV patients.References[1]Nakazawa D, et al. Nat Rev Rheumatol 15: 91-101, 2019.[2]Papayannopoulos V, et al. J Cell Biol 191: 677-691, 2010.[3]Korkmaz B, et al. Pharmacol Ther 190: 202-236, 2018.[4]Little MA, et al. Am J Pathol 174: 1212-1220, 2009.Disclosure of InterestsAkihiro Ishizu Grant/research support from: Modulus Discovery, Inc., Mai Taniguchi: None declared, Suishin Arai: None declared, Yuka Nishibata Grant/research support from: Modulus Discovery, Inc., Sakiko Masuda Grant/research support from: Modulus Discovery, Inc., Utano Tomaru: None declared, Takafumi Shimizu Shareholder of: Modulus Discovery, Inc., Employee of: Modulus Discovery, Inc., William Sinko Shareholder of: Modulus Discovery, Inc., Employee of: Modulus Discovery, Inc., Tadashi Nagakura Shareholder of: Modulus Discovery, Inc., Employee of: Modulus Discovery, Inc., Yoh Terada Shareholder of: Modulus Discovery, Inc., Employee of: Modulus Discovery, Inc.

We report current status of developing Soft X-ray Imager (SXI), the X-ray CCD camera onboard X-Ray Imaging and Spectroscopy Mission (XRISM). Four flight model (FM) CCDs have been selected considering several items including energy resolution at 5.9keV, CTI, dark current, etc. We have also completed calibration campaign for all the FM CCDs. Initial analyses show that the response function for monochromatic X-rays is basically the same as that of Hitomi CCDs. The focal plane including the single-stage Stirling cooler has been assembled. Production of key parts in SXI sensor body such as contamination blocking filter and onboard calibration source has been finished and they are waiting for assemble. The digitized signals of the CCD are corrected step by step before conversion to X-ray energy. We are preparing calibration database for the correction such as CTI, gain, and line redistribution function.

Over four thousands of exoplanets have been found to date. To understand the formation mechanisms of these diverse exoplanets, it is essential to unveil the detailed physical properties of these exoplanets by various methods, including high-precision transit photometry from the ground. So far two observing techniques have succeeded in achieving high-precision photometry from the ground; one is defocusing and the other is using optical diffusers. Diffusers spread light from stars over many pixels and stabilize the top-hat like point spread function (PSF), reducing systematic noises in photometric observations. In addition to it, diffusers enable us to use longer exposure times, which reduces atmospheric scintillation noises. We have developed diffuser units and installed them to the optical three-band imager MuSCAT. Each diffuser unit can store two types of diffusers with different opening angles, which allows us to change the strength of scatter of light from stars. We installed the diffuser units to MuSCAT in July 2019 and carried out on-sky examination. We observed out of transit (oot) phase of 11 planet-hosting stars alternatively with the following three configurations: with diffusers, without diffusers and with onfocus, and without diffusers and with defocus. From these observations, we confirmed that diffusers stabilized PSF and peak counts of stars. Throughput of the diffusers are measured to be about 93%. In addition, with diffusers, we succeeded in observing 55 Cnc, which is too bright (V=5.4) to observe without diffusers. We achieved the photometric precisions of 426, 641, and 783 ppm per 1 minute, or 188, 221, and 196 ppm per 5 minutes, in g', r', and zs-band, respectively.

We present experimental studies on the charge transfer inefficiency (CTI) of charge-coupled device (CCD) developed for the soft X-ray imaging telescope, Xtend, aboard the XRISM satellite. The CCD is equipped with a charge injection (CI) capability, in which sacrificial charge is periodically injected to fill the charge traps. By evaluating the re-emission of the trapped charge observed behind the CI rows, we find that there are at least three trap populations with different time constants. The traps with the shortest time constant, which is equivalent to a transfer time of approximately one pixel, are mainly responsible for the trailing charge of an X-ray event seen in the following pixel. A comparison of the trailing charge in two clocking modes reveals that the CTI depends not only on the transfer time but also on the area, namely the imaging or storage area. We construct a new CTI model with taking into account with both transfer-time and area dependence. This model reproduces the data obtained in both clocking modes consistently. We also examine apparent flux dependence of the CTI observed without the CI technique. The higher incident X-ray flux is, the lower the CTI value becomes. It is due to a sacrificial charge effect by another X-ray photon. This effect is found to be negligible when the CI technique is used., 8 pages, 8 figures, accepted for publication in NIMA, proceedings of the 12th International "Hiroshima" Symposium on the Development and Application of Semiconductor Tracking Detector (HSTD12)

We have been developing P-channel Charge-Coupled Devices (CCDs) for the upcoming X-ray Astronomy Satellite XRISM, planned to be launched in 2021. While the basic design of the CCD camera (Soft X-ray Imager: SXI) is almost the same as that of the lost Hitomi (ASTRO-H) observatory, we are planning to reduce the "light leakages" that is one of the largest problems recognized in Hitomi data. We adopted a double-layer optical blocking layer on the XRISM CCDs and also added an extra aluminum layer on the backside of them. We develop a newly designed test sample CCD and irradiate it with optical light to evaluate the optical blocking performance. As a result, light leakages are effectively reduced compared with that of the Hitomi CCDs. We thus conclude that the issue is solved by the new design and that the XRISM CCDs satisfy the mission requirement for the SXI., 6 pages, 4 figures, accepted for publication in NIMA, proceedings of the 12th International "Hiroshima" Symposium on the Development and Application of Semiconductor Tracking Detector (HSTD12)

Balanced rates of mitochondrial division and fusion are required to maintain mitochondrial function, as well as cellular and organismal homeostasis. In mammals, the cellular machines that mediate these processes are dynamin-related GTPases; the cytosolic DRP1 mediates division, while the outer membrane MFN1/2 and inner membrane OPA1 mediate fusion. Unbalanced mitochondrial dynamics are linked to varied pathologies, including cell death and neurodegeneration, raising the possibility that small molecules that target the division and fusion machines to restore balance may have therapeutic potential. Here we describe the discovery of novel small molecules that directly and selectively inhibit assembly-stimulated GTPase activity of the division dynamin, DRP1. In addition, these small molecules restore wild type mtDNA copy number in MFN1 knockout mouse embryonic fibroblast cells, a phenotype linked to deficient mitochondrial fusion activity. Thus, these compounds are unique tools to explore the roles of mitochondrial division in cells, and to assess the potential therapeutic efficacy of rebalancing mitochondrial dynamics in pathologies associated with excessive mitochondrial division.

Full list of authors: Fukui, A.; Korth, J.; Livingston, J. H.; Twicken, J. D.; Osorio, M. R. Zapatero; Jenkins, J. M.; Mori, M.; Murgas, F.; Ogihara, M.; Narita, N.; Pallé, E.; Stassun, K. G.; Nowak, G.; Ciardi, D. R.; Alvarez-Hernandez, L.; Béjar, V. J. S.; Casasayas-Barris, N.; Crouzet, N.; de Leon, J. P.; Esparza-Borges, E.; Soto, D. Hidalgo; Isogai, K.; Kawauchi, K.; Klagyivik, P.; Kodama, T.; Kurita, S.; Kusakabe, N.; Luque, R.; Madrigal-Aguado, A.; Rodriguez, P. Montanes; Morello, G.; Nishiumi, T.; Orell-Miquel, J.; Oshagh, M.; Parviainen, H.; Sánchez-Benavente, M.; Stangret, M.; Terada, Y.; Watanabe, N.; Chen, G.; Tamura, M.; Bosch-Cabot, P.; Bowen, M.; Eastridge, K.; Freour, L.; Gonzales, E.; Guerra, P.; Jundiyeh, Y.; Kim, T. K.; Kroer, L. V.; Levine, A. M.; Morgan, E. H.; Reefe, M.; Tronsgaard, R.; Wedderkopp, C. K.; Wittrock, J.; Collins, K. A.; Hesse, K.; Latham, D. W.; Ricker, G. R.; Seager, S.; Vanderspek, R.; Winn, J.; Bachelet, E.; Bowman, M.; McCully, C.; Daily, M.; Harbeck, D.; Volgenau, N. H., We report the discovery of one super-Earth- (TOI-1749b) and two sub-Neptune-sized planets (TOI-1749c and TOI-1749d) transiting an early M dwarf at a distance of 100 pc, which were first identified as planetary candidates using data from the TESS photometric survey. We have followed up this system from the ground by means of multiband transit photometry, adaptive optics imaging, and low-resolution spectroscopy, from which we have validated the planetary nature of the candidates. We find that TOI-1749b, c, and d have orbital periods of 2.39, 4.49, and 9.05 days, and radii of 1.4, 2.1, and 2.5 R ⊕, respectively. We also place 95% confidence upper limits on the masses of 57, 14, and 15 M ⊕ for TOI-1749b, c, and d, respectively, from transit timing variations. The periods, sizes, and tentative masses of these planets are in line with a scenario in which all three planets initially had a hydrogen envelope on top of a rocky core, and only the envelope of the innermost planet has been stripped away by photoevaporation and/or core-powered mass-loss mechanisms. These planets are similar to other planetary trios found around M dwarfs, such as TOI-175b,c,d and TOI-270b,c,d, in the sense that the outer pair has a period ratio within 1% of 2. Such a characteristic orbital configuration, in which an additional planet is located interior to a near 2:1 period-ratio pair, is relatively rare around FGK dwarfs. © 2021. The American Astronomical Society. All rights reserved., Funding for the TESS mission is provided by NASA's Science Mission Directorate. We acknowledge the use of public TESS data from pipelines at the TESS Science Office and at the TESS Science Processing Operations Center (SPOC). Resources supporting this work were provided by the NASA High-End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center for the production of the SPOC data products. This research has made use of the Exoplanet Follow-up Observation Program website, which is operated by the California Institute of Technology, under contract with the National Aeronautics and Space Administration under the Exoplanet Exploration Program. This paper includes data collected by the TESS mission that are publicly available from the Mikulski Archive for Space Telescopes (MAST). This paper is based on observations made with the MuSCAT3 instrument, developed by the Astrobiology Center and under financial supports by JSPS KAKENHI (JP18H05439) and JST PRESTO (JPMJPR1775), at Faulkes Telescope North on Maui, HI, operated by the Las Cumbres Observatory. Based on observations obtained with the Samuel Oschin 48 inch Telescope at the Palomar Observatory as part of the Zwicky Transient Facility project. Z.T.F. is supported by the National Science Foundation under grant No. AST-1440341 and a collaboration including Caltech, IPAC, the Weizmann Institute for Science, the Oskar Klein Center at Stockholm University, the University of Maryland, the University of Washington, Deutsches Elektronen-Synchrotron and Humboldt University, Los Alamos National Laboratories, the TANGO Consortium of Taiwan, the University of Wisconsin at Milwaukee, and Lawrence Berkeley National Laboratories. Operations are conducted by COO, IPAC, and UW. This work is partly supported by JSPS KAKENHI grant Nos. JP17H04574, JP18H01265, and JP18H05439, Grant-in-Aid for JSPS Fellows grant No. JP20J21872, JST PRESTO grant No. JPMJPR1775, and a University Research Support Grant from the National Astronomical Observatory of Japan (NAOJ). This work is also partly financed by the Spanish Ministry of Economics and Competitiveness through grants PGC2018-098153-B-C31 and PID2019-109522GB-C53. J.K. gratefully acknowledges the support of the Swedish National Space Agency (DNR 2020-00104). G.M. has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant agreement No. 895525. M.T. is supported by JSPS KAKENHI grant Nos.18H05442, 15H02063, and 22000005., With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709.

We present observations of two bright M dwarfs (TOI-1634 and TOI-1685: $J=9.5-9.6$) hosting ultra-short period (USP) planets, identified by the TESS mission. The two stars are similar in temperature, mass, and radius ($T_\mathrm{eff}\,\approx\,3500$ K, $M_\star\,\approx\,0.45-0.46\,M_\odot$, and $R_\star\approx 0.45-0.46\,R_\odot$), and the planets are both super-Earth-sized ($1.25\,R_\oplus, Comment: 29 pages, 21 figures, 4 tables; AJ in press

Patients diagnosed with an endometrial cancer precursor lesion on biopsy may be found to have endometrial cancer at the time of subsequent surgery. The current study seeks to identify patients with endometrial intraepithelial neoplasia (EIN) on biopsy that may be harboring an occult carcinoma. Immunohistochemical stains for gene loss of expression (LOE) for 6 genes, PTEN, ARID1A, MSH6, MSH2, MLH1, and PMS2, were performed on 113 biopsy specimens with EIN. For the 95 patients with follow-up histology, 40 patients had cancer, 41 had EIN, and 14 had normal endometrium. PTEN LOE was found frequently in both EIN and endometrial cancer, and therefore had low positive predictive value. All specimens with ARID1A, MSH6, MSH2, MLH1, or PMS2 LOE on biopsy were subsequently found to have cancer. LOE of any gene was associated with modest sensitivity (0.78) in identifying patients with endometrial cancer who had EIN on biopsy. Further investigation is warranted to determine if gene LOE is a useful clinical tool when evaluating patients with EIN on biopsy., Highlights • PTEN, ARID1A, MSH6, MSH2, MLH1, and PMS2 were analyzed on patients with EIN. • Loss of expression was associated with the subsequent finding of endometrial cancer. • Sensitivity was 0.78 for loss of expression of any gene and the finding of cancer.

Highlights • Endometrial and cervical adenocarcinomas may demonstrate morphologic overlap. • Distinction between these is important as it dictates treatment and prognosis. • This diagnostic dilemma can be approached with a panel of stains., In a biopsy specimen, adenocarcinomas of the endometrium and uterine cervix may demonstrate significant morphologic overlap. The distinction between these two entities prior to surgical resection is clinically significant as assigning the primary site dictates treatment and prognosis. This diagnostic dilemma is approached by the application of a panel of immunohistochemical stains, traditionally composed of CEA, vimentin, p16, ER, and PR. Most cases are successfully managed with this panel; however, in difficult cases additional tools are needed to suggest a more definitive diagnosis. In this study, we reviewed the efficacy of the customary panel of stains, as well as the added value of new stains in the diagnosis of endocervical adenocarcinoma. Our cohort included biopsy samples of 90 patients (81 endometrial and 9 endocervical adenocarcinomas) with a subsequent hysterectomy for confirmation of diagnosis. This study validated the customary panel of stains and suggests additional markers to aid in the differential diagnosis (PAX8 and CAIX). The addition of PAX8 to the traditional panel increases PPV from 85.71% to 100%. A PPV of 100% may also be attained with fewer stains (five total), with the application of a proposed new panel, which includes PAX8, CAIX, CEA, p16 and ER. This is the first-time differential expression of CAIX has been suggested in the distinction between endocervical and endometrial adenocarcinomas.

Periodontitis is a multifactorial disease in which bacterial, lifestyle, and genetic factors are involved. Although previous genetic association studies identified several susceptibility genes for periodontitis in European populations, there is little information for Asian populations. Here, we conducted a genome-wide association study and a replication study consisting of 2,760 Japanese periodontitis patients and 15,158 Japanese controls. Although single-nucleotide polymorphisms that surpassed a stringent genome-wide significance threshold ( P < 5 × 10−8) were not identified, we found 2 suggestive loci for periodontitis: KCNQ5 on chromosome 6q13 (rs9446777, P = 4.83 × 10−6, odds ratio = 0.82) and GPR141-NME8 at chromosome 7p14.1 (rs2392510, P = 4.17 × 10−6, odds ratio = 0.87). A stratified analysis indicated that the GPR141-NME8 locus had a strong genetic effect on the susceptibility to generalized periodontitis in Japanese individuals with a history of smoking. In conclusion, this study identified 2 suggestive loci for periodontitis in a Japanese population. This study should contribute to a further understanding of genetic factors for enhanced susceptibility to periodontitis.

ObjectiveThe aim of this study was to determine the histopathologic characteristics of patients with endometrial carcinoma with low-volume metastases (micrometastases and isolated tumor cells) compared with macrometastases.MethodsWe performed a retrospective review of patients with endometrial carcinoma.ResultsAmong 350 robotic-assisted hysterectomies for endometrial cancer, 187 (53%) underwent attempted sentinel lymph node (SLN) biopsy. At least 1 SLN was detected in 185, a 99% overall detection rate; 108 (58%) also had non-SLNs removed. Among 91 patients with SLNs and non-SLNs from the ipsilateral hemipelvis, both were negative in 74 (81%) and positive in 7 (8%), and 10 (11%) had a positive SLN with negative non-SLNs. Among 17 patients with SLNs and non-SLNs from the contralateral hemipelvis, both were negative in 12 (71%), both were positive in 3 (18%), and 2 patients (12%) had negative SLNs with contralateral positive non-SLNs. Among 79 patients with only a SLN dissection, 4 (5%) were positive; among 69 patients with only a non-SLN dissection, 14 (20%) had positive lymph nodes. Among 24 patients with metastatic SLNs, 9 (38%) had isolated tumor cells, 3 (13%) had micrometastases, and 12 (50%) had macrometastases. Among the 40 total patients with metastatic lymph nodes, low-volume metastases represented the largest metastatic deposit in one third of patients, all of which had SLN dissection. All 12 with low-volume metastases had endometrioid histology compared with less than half (46%) of those with macrometastases (P < 0.01). Grade 1 carcinoma was present in 7 (58%) of the patients with low-volume metastases compared with 4 (14%) of those with macrometastases (P < 0.01) Furthermore, significantly more patients with low-volume metastases versus macrometastases had less than 50% myometrial invasion (67% vs 4%, P < 0.001).ConclusionsLow-volume disease was present in one third of patients with nodal metastases, the largest metastatic deposit only in patients who had SLN dissection; these patients were significantly more likely to have grade 1 endometrioid carcinoma with less than 50% myometrial invasion, traditional “low-risk” features.

Background Relapsing polychondritis (RP) is a rare systemic inflammatory disorder and might often be refractory. Therefore, the discover of imaging modality would be required on diagnosis and treatment of RP. Objectives To assess the clinical implications of ultrasonography (US) in monitoring disease activity of relapsing polychondritis (RP). Methods Three cases of a 78-year-old man with RP, a 74-year-old woman with RP associated with optic perineuritis and a 42-year-old woman with RP associated with uveitis were assessed by US before and after treatments. Results Ultrasonography (US) of the auricle before treatment showed low-echoic swollen auricular cartilage with increased power Doppler signals (PDS) in all cases. US findings corresponded to the above-mentioned biopsy findings. After treatment with prednisolone combined with methotrexate, the auricular swelling completely resolved in all cases. Then, US findings also showed dramatic reductions in swelling of cartilage with the decrease in PDS. Conclusions US imaging can be used to differentiate between inflammation, vascular lesions, and tumors in the ear pinna. RP could be differentiated from the damage of repeated trauma (i.e. rugby) with producing subperichondrial serous effusion. As in the present cases, US imaging of the external ear and auricular cartilage in RP also facilitates evaluation of auricular lesions and monitoring of disease activity, especially when we consider the treatment response and the timing of drug tapering. Disclosure of Interest None declared

InterPlanetary Network (IPN) data are presented for the gamma-ray bursts in the second Fermi Gamma-Ray Burst Monitor (GBM) catalog. Of the 462 bursts in that catalog between 2010 July 12 and 2012 July 11, 428, or 93%, were observed by at least 1 other instrument in the 9-spacecraft IPN. Of the 428, the localizations of 165 could be improved by triangulation. For these bursts, triangulation gives one or more annuli whose half-widths vary between about 2.′3° and 16°, depending on the peak flux, fluence, time history, arrival direction, and the distance between the spacecraft. We compare the IPN localizations with the GBM 1σ, 2σ, and 3σ error contours and find good agreement between them. The IPN 3σ error boxes have areas between about 8 square arcminutes and 380 square degrees, and are an average of 2500 times smaller than the corresponding GBM 3σ localizations. We identify four bursts in the IPN/GBM sample whose origins were given as “uncertain,” but may in fact be cosmic. This leads to an estimate of over 99% completeness for the GBM catalog.

Patients with Lynch Syndrome are at an increased risk for a variety of malignancies, including ovarian cancer. Ovarian cancers associated with Lynch Syndrome are predominantly clear cell or endometrioid in histology. Lynch Syndrome is characterized by germline mutations in mismatch repair (MMR) genes. The current study aims to assess the prevalence of loss of MMR expression in patients with endometrioid and clear cell ovarian carcinoma.A retrospective review identified 90 patients with endometrioid and/or clear cell carcinomas. Slides made from tumor tissue microarray blocks were evaluated using immunohistochemical stains with antibodies against MLH1, PMS2, MSH2, and MSH6. Statistical analysis was performed.Seven of the 90 cases (7.8%) had loss of MMR expression. The mean age of patients with loss of MMR expression (47 years) was significantly younger than those with retained MMR expression (p=0.014). Loss of MMR expression was present in 20% of patients under the age of 53 with clear cell or endometrioid cancers. Genetic studies found that 3 of the 5 patients with loss of MMR expression carried mutations consistent with Lynch Syndrome; acquired hypermethylation of MLH1 was noted in one patient. Six of 7 patients (86%) whose tumors lacked MMR expression had synchronous or metachronous primary malignancies, a significantly greater prevalence than those with retained MMR expression (p0.001).Patients under the age of 53 with clear cell or endometrioid ovarian carcinomas are at a clinically significant risk for loss of MMR expression and Lynch Syndrome; routine screening with immunohistochemical staining should be considered.

OBJECTIVE The benefit of evaluating the precursor of endometrial carcinoma, endometrial hyperplasia (intraepithelial neoplasia [EIN]), for loss of mismatch repair (MMR) protein expression and Lynch syndrome has yet to be determined. The present study aims to establish the incidence and type of loss of MMR protein expression in unselected premalignant lesions of endometrial adenocarcinoma, as well as the agreement of immunohistochemical staining in pretreatment endometrial biopsy (EMB) specimens with subsequent uterine resections. METHODS A retrospective review identified 112 endometrial biopsies meeting criteria for endometrial EIN. Slides made from tissue microarray blocks were evaluated using antibodies against MLH1, PMS2, MSH2, and MSH6. Cases with a deficit in MLH1 were evaluated for gene promoter hypermethylation by polymerase chain reaction analysis. Fifty-four subsequent hysterectomy specimens were retrieved and assessed for MMR protein expression. RESULTS Of the 112 endometrial biopsies with EIN, 4.5% (5/112) exhibited loss of MMR protein expression. The majority (4/5) demonstrated a deficit of MLH1, of which all exhibited inactivation via promoter hypermethylation. A single case displayed an absence of MSH6. Age was not significantly associated with MMR deficiency. There was no significant association between MMR status in the EMB and a subsequent diagnosis of cancer. Immunohistochemical staining in all successive hysterectomy cases was concordant with the pattern observed in the EMB specimen. CONCLUSIONS Sporadic hypermethylation of MLH1 seems to be the primary mechanism underlying defective MMR protein expression in EIN. Among our cohort, only 1 patient (

Background The aim of this study was to clarify the outcomes of lung resection for lung cancer in patients with cardiac disease, especially coronary artery disease, in a large-scale multi-institutional cohort. Methods We retrospectively analyzed the data on 1,254 patients who underwent major lung resection for lung cancer and had been diagnosed with coronary stenosis, atrial fibrillation, or both, in 58 institutions in Japan between January 2009 and December 2011. The primary outcome was 90-day postoperative mortality or in-hospital death. Results Among the 1,254 patients, 902 (71.9%) and 452 patients (36.0%) were preoperatively diagnosed with coronary stenosis and atrial fibrillation, respectively, and 951 patients (75.8%) received antiplatelet therapy. Among the patients with coronary stents (n = 532; 42.4%), 204 (16.3%) received drug-eluting stents. The 90-mortality or in-hospital death rate was 2.6% (n = 32), including stent thrombosis (n = 1), thromboembolic events without stent thrombosis (n = 2), and bleeding events (n = 2). In the multivariate analyses, blood transfusion, history of cerebrovascular disease, amount of bleeding, and history of congestive heart failure were associated with a higher independent risk of 90-day mortality or in-hospital death (odds ratio, 9.400, 3.574, 2.827, and 2.945, respectively). Preoperative discontinuation of antiplatelet therapy was not associated with an independent risk of 90-day mortality or in-hospital death on univariate analysis. Conclusions Major lung resection for lung cancer in patients with coronary artery disease is feasible. Our study suggests that discontinuation of antiplatelet therapy may not increase postoperative complications in patients with coronary artery disease.

Objective This study examines premenopausal and early menopause patients in a unique population with endometrial cancer and loss of mismatch repair (MMR) gene expression. The purpose is to compare clinical and pathologic differences in patients with loss of expression (LOE) to those with normal expression (NE). Methods Endometrial cancer patients under age 60 in-between 1998 and 2008 were identified from a single tumor registry. Clinical and pathologic data were abstracted from records. Staining for expression of MSH6, MSH2, MLH1, and PMS2 were performed on archived tissue blocks. Statistical analysis was performed. Results 158 patients were analyzed; 58% Asian, 34% Pacific Islander, and 8% Caucasian. 31 demonstrated LOE of at least one MMR gene; 127 retained NE. 50% Caucasian, 21.9% Asian, and 12.5% Pacific Island populations had LOE of one or more MMR genes. LOE was found to have a higher incidence of Grade III (p = 0.0013) and stage 3–4 tumors (p = 0.0079), mean depth of myometrial invasion (p = 0.0019), lymphovascular space invasion (p = 0.0020), nodal metastases (p = 0.0157), and a lower incidence of Grade I (p = 0.0020) and stage 1A tumors (p = 0.0085). LOE had a significantly lower mean BMI (p = 0.0001). 35% of patients in the NE vs zero in the LOE group had a BMI greater than 40. Conclusion Younger patients with LOE endometrial cancer appear to represent a clinically significant subgroup of patients without features characteristically found in classic type 1 endometrial cancer generally demonstrating lower BMI and tumors associated with poor prognostic characteristics. It is unclear if the distinctive ethnicity found in Hawaii has a significant impact on outcome. Further investigation is necessary to identify appropriate treatment strategies.

By monitoring the temperature inside cryogenic equipment such as superconducting magnet, we can detect the indication of failures and prevent the equipment suffered from damage. It is possible to measure the multipoint temperature by one optical fiber sensor. This sensor is suitable to measure the temperature at cryogenic temperatures because of low heat invasion and high voltage insulation. In this study, as for Fiber Bragg Grating as abbreviated FBG system of multipoint type, we investigated the reproducibility by measuring the temperature repeatedly, and multipoint measurement characteristics by measuring the temperature inside a cryogenic equipment with temperature gradient. We also investigated the improvement of the sensitivity for temperature at cryogenic temperatures by enhancing the thermal expansion coefficient using the coated optical fiber sensor.

e13516Background: Loss of expression of p53, ARID1a, MLH1, PMS2, MSH2, and MSH2 are commonly seen in endometrial adenocarcinomas. The objective of our study is to delineate the incidence of loss of...

著者人数: 12名, Accepted: 2007-09-04, 資料番号: SA1000314000

Suzaku launched in July 2005 is equipped with the wideband instruments covering 0.3–700 keV. In addition to these main instruments, active shield counters of the hard X-ray detector are designed to be a wideband all-sky monitor (WAM). The WAM is a powerful gamma-ray burst monitor with a wide energy range of 50–5000 keV and with a large effective area of 400 cm 2 even around 1 MeV. The paper describes the strategy for the prompt GRB observation with the WAM, and the follow-up observation of X-ray afterglows with the narrow field instruments. So far, the WAM has detected 53 GRBs and half of them were detected simultaneously with other satellites. In addition to that, from at least 8 GRBs, including a bright and hard GRB 051008, it is succeeded to observe significant gamma-ray emission up to 1 MeV. The X-ray afterglow observations were carried out on January 5 and on September 4, 2006. Their results are reported in separate paper.

Objective: To investigate the role of previous gynecologic surgery, hormone use, and use of non-steroidal anti-inflammatory drugs on the risk of type 1 and type 2 ovarian cancer. Methods: We utilized data collected for the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. All diagnosed ovarian cancers were divided into three groups: type 1, endometrioid, clear cell, mucinous, low grade serous, and low grade adenocarcinoma/not otherwise specified (NOS); type 2, high grade serous, undifferentiated, carcinosarcoma, and high grade adenocarcinoma/NOS; and other: adenocarcinoma with grade or histology not specified, borderline tumors, granulosa cell tumors. The odds ratios for type 1, type 2, and other ovarian cancers were assessed with regard to historical information for specific risk factors. Results: Ibuprofen use was associated with a decrease in risk for type 1 ovarian cancer. Tubal ligation and oral contraceptive use were associated with a decrease in risk for type 2 ovarian cancer. A history of ectopic pregnancy was associated with a decreased risk for all ovarian cancers by almost 70%. Conclusion: These findings support the hypothesis that carcinogenic pathways for type 1 and type 2 ovarian cancer are different and distinct. The marked reduction in all ovarian cancer risk noted with a history of ectopic pregnancy and salpingectomy implies that the fallopian tube plays a key role in carcinogenesis for both type 1 and type 2 ovarian cancer.

Objective Washing the hands using cleansers with antiseptic materials is the most popular method for hand hygiene and helps maintain health by preventing food poisoning and bacterial infections. However, repeated hand washing tends to induce eczema of the hand, such as dryness, cracking and erythema. Moreover, eczema on the hand leads to increased levels in Staphylococcus aureus (S. aureus) on the skin surface in contrast to expectations. Thus, mild hand cleansers which induce less eczema even with repeated washings are desired. Here, we evaluated the efficacy of a hand cleanser formulated with alkyl ether sulphate (AES), alkyl ether carboxylic acid (AEC) and alkyl glucoside (AG) that contains isopropyl methylphenol (IPMP) on skin symptoms and S. aureus levels. Methods Eczema of the hand and the presence of S. aureus on the skin surface were analysed prior to and following 4 weeks of usage of the hand cleanser. A soap-based hand cleanser with IPMP was used as a reference cleanser. Eczema and cutaneous conditions were evaluated by visual grading, transepidermal water loss (TEWL), stratum corneum moisture-retention ability (MRA) and skin surface pH. Results The repeated use of the soap-based hand cleanser significantly worsened the hand dryness, scaling and cracks on the tips of the fingers and significantly increased the TEWL and decreased the MRA. In contrast, usage of the test cleanser only induced a significant increase in skin dryness but did not induce skin scaling or cracking and did not increase TEWL or decrease the MRA. Corresponding to these changes in skin symptoms, the presence of S. aureus increased the following use of the reference cleanser but not the test cleanser. There was no significant difference in skin surface pH between the two cleansers. Moreover, the increase in S. aureus was significantly correlated to the worsening of skin dryness and scaling. Conclusion These results suggest that not only antimicrobial activity but also the mildness, which minimizes cutaneous effects, are important for hand cleansers to prevent the growth of S. aureus. The cleanser formulated with AES, AEC and AG containing IPMP is mild and is effective to promote hand hygiene.

Aiming at painless medical applications, a hollow microneedle imitating mosquito's proboscis is developed using three-dimensional laser lithography. Unlike other reported needles, presented microneedle is divided into two half parts, each is shaped like eaves-through and dependently moved. The tip of each part is three-dimensionally sharpened, and several jagged edges project to the outside. The combined halves act as one hollow microneedle, which can draw up human blood by capillary action. The microneedle can puncture an artificial skin without buckling. The resistive force during insertion can be reduced when the two halves are alternately advanced, which mimics the motion of mosquito's proboscis.

The outermost layer of skin, the epidermis, is cornified epithelial tissue composed of keratinocytes. To maintain the structure and function of the epidermis, the regulation of proliferation, differentiation, and cornification of keratinocytes is crucial, and various soluble factors secreted by keratinocytes are involved in these regulations. Previously, work has shown that keratinocytes secreted the protein Kdap (keratinocyte differentiation-associated protein) associated with the formation of cornified cell envelopes, a specialized protective barrier structure on the periphery of terminally differentiating keratinocytes. In the present report, the canine counterpart of human Kdap is identified and an attempt has been made to define its physiological role in canine keratinization. Canine Kdap (cKdap) showed structural features commonly observed in other counterparts and is secreted from transfected cells. The expression profile of cKdap mRNA, which was restrictively expressed in cornified epithelial tissues besides skin has also been determined. These findings indicate that there is a strong association between cKdap expression and cornification, which supports previous observations that Kdap is involved in the synthesis and/or degradation of cornified cell envelopes in humans and mice.