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Polyaniline-based atomic switches are material building blocks whose nanoscale structure and resultant neuromorphic character provide a new physical substrate for the development next-generation, nanoarchitectonic-enabled computing systems. Metal ion-doped devices consisting of a Ag/metal ion doped polyaniline/Pt sandwich structure were fabricated using an in situ wet process. The devices exhibited repeatable resistive switching between high (ON) and low (OFF) conductance states in both Ag+ and Cu2+ ion-doped devices. The threshold voltage for switching was>0.8 V and average ON/OFF conductance ratios (30 cycles for 3 samples) were 13 and 16 for Ag+ and Cu2+ devices, respectively. The ON state duration was determined by the decay to an OFF state after pulsed voltages of differing amplitude and frequency. The switching behaviour is analagous to short-term (STM) and long-term (LTM) memories of biological synapses. Memristive behaviour and evidence of quantized conductance were also observed and interpreted in terms of metal filament formation bridging the metal doped polymer layer. The successful realization of these properties within physical material systems indicate polyaniline frameworks as suitable neuromorphic substrates for in materia computing.

Hiromi Asada,1 Yoshimitsu Takahashi,1 Yuka Ono,2 Noriko Kishi,2 Yukinori Matsuo,2 Takashi Mizowaki,2 Takeo Nakayama1 1Department of Health Informatics, Kyoto University School of Public Health, Kyoto, 606-8501, Japan; 2Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, JapanCorrespondence: Hiromi Asada, Department of Health Informatics, Kyoto University School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan, Tel/Fax +81-75-753-9479, Email asada.hiromi.62a@st.kyoto-u.ac.jpPurpose: Patients undergoing radiotherapy often have their skin marked. Previous studies on skin markings examined the durability and physical effects of the markings, but no study has focused on patients’ emotional experiences toward the markings. This study aimed to clarify how patients undergoing radiotherapy feel about skin markings, as well as factors that affect patients’ emotional experiences.Patients and Methods: We conducted a cross-sectional study using a self-administered questionnaire and medical records. Participants were patients aged ≥ 20 years undergoing cancer radiotherapy at a designated cancer care hospital. The primary outcome was the level of uncomfortable emotions toward skin markings, and the secondary outcome was the level of favorable ratings on skin markings. To examine factors related to uncomfortable emotions, ordinal logistic regression analysis was performed.Results: Questionnaire forms were distributed to 153 patients, and responses were collected from 132 (86%). Among 108 patients included in the analysis, 56% (59/105, excluding 3 who did not answer this question) responded that they were uncomfortable with skin markings. The proportion of patients who favorably rated skin markings was 63% (59/93, excluding 15 who did not answer this question). No factors were significantly associated with the primary outcome.Conclusion: Many patients accepted skin markings with resignation, as they understood the necessity of the markings in their treatment. Medical staff should understand the emotional experiences of patients toward skin markings and take sufficient care to ensure that they are provided with explanations, including the impact of skin markings on their daily lives, as well as a sense of security that treatment is being performed in a precise manner.Keywords: radiotherapy, marking, emotional experiences, questionnaire survey

Soichiro Hozawa,1 Hiroyuki Ohbayashi,2 Michiko Tsuchiya,3 Yu Hara,4 Laurie A Lee,5 Takashi Nakayama,6 Jun Tamaoki,6 Andrew Fowler,7 Takanobu Nishi6 1Hiroshima Allergy and Respiratory Clinic, Hiroshima, Japan; 2Tohno Chuo Clinic, Gifu, Japan; 3Department of Respiratory Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan; 4Department of Pulmonology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan; 5GSK, Collegeville, PA, USA; 6GSK, Tokyo, Japan; 7GSK, Brentford, Middlesex, UKCorrespondence: Takanobu NishiGlaxoSmithKline K.K., 1-8-1 Akasaka, Minato-ku, Tokyo, 107-0052, JapanTel +81-70-4135-5303Fax +81-3-4231-5974Email takanobu.2.nishi@gsk.comPurpose: The pivotal CAPTAIN study reported a favorable safety profile with once-daily inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) triple combination of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in patients with inadequately controlled asthma, some of whom were Japanese. Here, we evaluate the long-term (52 weeks) safety of FF/UMEC/VI in Japanese patients with asthma.Patients and Methods: This was a Phase III, 52-week, multicenter, non-comparator, non-randomized, open-label study (NCT03184987) in Japanese adults receiving maintenance therapy with ICS/LABA, with or without LAMA. At enrollment, patients were allocated to either FF/UMEC/VI 100/62.5/25mcg (Group 1) or 200/62.5/25mcg (Group 2). Patients in Group 1 could have their treatment stepped up to 200/62.5/25mcg at Week 24 if their Asthma Control Questionnaire (ACQ)-7 score was > 0.75. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs). Secondary endpoints included vital signs, electrocardiogram measurements, and clinical laboratory tests (biochemistry, hematology, urinalysis). Efficacy was assessed as “other” endpoints.Results: A total of 111 Japanese patients were included in the intention-to-treat (ITT) population. Overall, 77 (69%) patients reported ≥ 1 AE (Group 1: n=30 [64%]; step-up group: n=7 [78%]; Group 2: n=40 [73%]). SAEs were reported for 1 (2.1%) and 2 (3.6%) patients in Groups 1 and 2, respectively. All SAEs were considered unrelated to study treatment. One AE and one SAE led to study withdrawal: oropharyngeal discomfort (Group 1); eosinophilic granulomatosis with polyangiitis (Group 2). No new safety concerns were identified throughout the 52-week treatment period.Conclusion: In this uncontrolled open-label study, no new safety concerns were observed with long-term (52 weeks) treatment with once-daily FF/UMEC/VI among 111 Japanese patients with asthma.Keywords: asthma, inhalers, Japan, safety, treatment outcome

Yosuke Kameoka,1 Fukuko Kishi,1 Minako Koura,2 Yoshio Yamakawa,1 Rora Nagasawa,1 Fuyu Ito,3 Junichiro Matsuda,2 Osamu Suzuki,2 Toshinori Nakayama,4 Kazuo Suzuki1,3–5 1Department of Research and Development, A-CLIP Institute, Ltd., Chiba, Japan; 2Laboratory of Animal Models for Human Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan; 3Asia International Institute of Infectious Disease Control, Teikyo University, Tokyo, Japan; 4Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan; 5Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan Background: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a pauci-immune disease with the inflammation of the small blood vessels. The efficacies of antibody drugs for induction therapies of vasculitis vary among cases. Here, we developed a novel clone of a single chain Fv region (ScFv) with vasculitis-specific therapeutic potential.Materials and methods: The clone, termed VasSF, was selected from our Escherichia coli expression library of recombinant human ScFv based on the therapeutic efficacy in an SCG/Kj mouse model of MPO-ANCA-associated vasculitis (MAAV), such as improvement of the urinary score and decreased crescent formation in glomeruli, granulomatous in lung, MPO-ANCA biomarkers, the anti-moesin antibody, and some cytokine levels.Results: We identified vasculitis-associated apolipoprotein A-II (VAP2) as a target molecule of the clone and confirmed the independently-established VAP2 antibodies were also therapeutic in SCG/Kj mice. In MAAV, MPO-ANCA and cytokines stimulate neutrophils by facilitating heterodimer formation of VAP2 with apolipoprotein A-I in HDL. Conclusion: VasSF would constitute a novel antibody drug for vasculitis by suppressing the heterodimer formation of the apolipoproteins. Keywords: VasSF, ANCA antibody drug, apolipoprotein, HDL, myeloperoxidase, MPO, SCG/Kj, vasculitis

Vertebrates have achieved great evolutionary success due in large part to the anatomical diversification of their jaw complex, which allows them to inhabit almost every ecological niche. While many studies have focused on mechanisms that pattern the jaw skeleton, much remains to be understood about the origins of novelty and diversity in the closely associated musculature. To address this issue, we focused on parrots, which have acquired two anatomically unique jaw muscles: the ethmomandibular and the pseudomasseter. In parrot embryos, we observe distinct and highly derived expression patterns for Scx, Bmp4, Tgfβ2 and Six2 in neural crest-derived mesenchyme destined to form jaw muscle connective tissues. Furthermore, immunohistochemical analysis reveals that cell proliferation is more active in the cells within the jaw muscle than in surrounding connective tissue cells. This biased and differentially regulated mode of cell proliferation in cranial musculoskeletal tissues may allow these unusual jaw muscles to extend towards their new attachment sites. We conclude that the alteration of neural crest-derived connective tissue distribution during development may underlie the spatial changes in jaw musculoskeletal architecture found only in parrots. Thus, parrots provide valuable insights into molecular and cellular mechanisms that may generate evolutionary novelties with functionally adaptive significance. © 2012 The Author(s) Published by the Royal Society. All rights reserved.

Tatsuya Nakayama,1,2 Yuko Kumeda,3 Ryuji Kawahara,4 Takahiro Yamaguchi,4,5 Yoshimasa Yamamoto5 1Center for Global Initiatives, Osaka University, Suita, Osaka, Japan; 2Division of Biomedical Food Research, National Institute of Health Science, Kawasaki, Kanagawa, Japan; 3Center for Microorganism Control, Osaka Prefecture University, Sakai, Osaka, Japan; 4Division of Microbiology, Osaka Institute of Public Health, Osaka, Japan; 5Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan Background: Due to increasing colistin usage, the dissemination of the colistin-resistant gene mcr-1 has been increasingly investigated. The aim of this study was to determine whether a traveler on a short-term international trip to a developing country could bring mcr-1 back to their home country. Materials and methods: Thirty-four travel events from Japan to Vietnam encompassing 19 travelers were assessed. A fecal specimen was collected from each traveler before and after each travel event and was inoculated on CHROMagar containing cefotaxime (CTX). Three to seven colonies exhibiting the characteristics of Escherichia coli were collected. Susceptibility to antibiotics and extended-spectrum β-lactamase (ESBL) production were determined by the disk diffusion method and the double-disk synergy test, respectively. ESBL-encoding genes were genotyped, and phylogenetic groupings were determined by multiplex polymerase chain reaction (PCR). The presence of mcr-1 was also confirmed by PCR and sequencing. Results: A total of 175 ESBL-producing E. coli isolated before and up to 2 weeks after traveling to Vietnam were analyzed. Genotyping of ESBL-producing isolates showed that blaCTX-M-1/blaTEM (27.7%) and blaCTX-M-9 (45.9%) were the most prevalent genotypes, while the most frequently detected phylogenetic group was D (41.9%) followed by B2 (23.0%). In a significant number of travel events, travelers brought ESBL-producing E. coli back to Japan and three events by three travelers carried mcr-1. ESBL-producing E. coli isolates harboring mcr-1 were identified as those carrying both blaCTX-M-14 or blaCTX-M-55 and mcr-1. Conclusion: Using Vietnam as an example, we have shown that even a short-term trip to some countries may result in ESBL-producing mcr-1-positive E. coli carriage by international travelers. Keywords: traveler, ESBL-producing E. coli, mcr-1, Vietnam, Japan

Yayoi Nishida,1 Yasuo Takahashi,1 Kotoe Tezuka,1 Keiko Yamazaki,1 Yoichi Yada,2 Tomohiro Nakayama,3,4 Satoshi Asai2 1Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, 2Division of Pharmacology, Department of Biomedical Sciences, 3Division of Companion Diagnostics, 4Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan Background: Multiple comorbidity is common and increases the complexity of the presentation of patients with COPD. This study was a comprehensive analysis of the relationship between a medical history of 22 disease categories and the presence of airflow limitation (AL) without any history of asthma or bronchiectasis, compatible with COPD. Methods: A total of 11,898 Japanese patients aged ≥40 years, who underwent spirometry tests, comprising patients with AL (n=2,309) or without AL (n=9,589), were evaluated. Generalized estimating equations were used to assess the relationship between the presence of AL and each disease. The model was adjusted for age, sex, body mass index (BMI) and pack-years of smoking. Results: In multivariate analysis, female sex (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.52–0.67), age (OR for 10-year age increase: 1.99; CI: 1.90–2.09), BMI (OR for 1 kg/m2 increase: 0.96; CI: 0.95–0.98) and smoking history (

This research presents a synthesis process of porous α-MoO3 wire from Mo wire and its application as an irradiation target used in the Dalat Nuclear Research Reactor (DNRR) for the first time. Water was used to extract 99Mo in the porous wire after irradiating, afterward, the result was compared with a previous experiment using α-MoO3 powder. In conclusion, combined with the Kyoto University Reactor (KUR) experiments, hot atoms ehnanced the extraction of 99Mo to water and the effectiveness in the porous wire was compared to that of commercial powder. [ABSTRACT FROM AUTHOR]