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Saiki, Masaro, e Toshihiko Yano. "Oceanographic Research Vessel Keifn Marn". Marine Technology Society Journal 35, n.º 3 (1 de setembro de 2001): 59–63. http://dx.doi.org/10.4031/002533201788057846.
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The Japan Meteorological Agency (JMA) built a new oceanographic research vessel Keifu Maru in order to enhance the monitoring activities related to global environmental issues including climate change and global warming. Particular attention is focused on the role of the ocean in the climate change. The RIV Keifu Maru is specially equipped with the towed CTD system, which allows making measurements of upper ocean temperature and salinity underway, and the measuring system of carbon dioxide concentrations in the air and the sea surface water.
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Seo, Bo-Kyung. "The family of Wani and Ojinni Viewed through the Changes of Common Ancestry Keifu". Korea-Japan Historical Review 53 (30 de abril de 2016): 65. http://dx.doi.org/10.18496/kjhr.2016.04.53.65.
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Mori, Kazumasa. "Equatorial Convection Observed by the Research Vessel Keifu Maru during the TOGA COARE IOP, November 1992". Journal of the Meteorological Society of Japan. Ser. II 73, n.º 2B (1995): 491–508. http://dx.doi.org/10.2151/jmsj1965.73.2b_491.
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Rambing, Juergen Geovane, Rianna Sumampouw e Yenni Wahani. "ANALISIS YOKAI DALAM ANIME GEGEGE NO KITARO". KOMPETENSI 2, n.º 9 (23 de dezembro de 2022): 1612–23. http://dx.doi.org/10.53682/kompetensi.v2i9.5316.
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Tujuan penelitian ini untuk mendeskripsikan Yokai menurut pandangan orang Jepang dalam Anime Gegege no Kitaro. Anime Gegege no Kitaro merupakan Anime pertama yang menggambarkan ciri fisik Yokai itu. Menurut Kawase Shobo Shinsa dalam bukunya "Zusetsu Yokai-ga No Keifu" (2009) menerangkan bahwa karya yang mengisahkan Yokai Anime pertama oleh Mizuki Shigeru ini melahirkan sebuah genre baru yaitu genre Yokai dalam industri Anime. Gegege no Kitaro dengan pemeran utamanya Yokai itu sendiri, memperkenalkan mengenai asal usul dan petualangan di dunia Yokai disetiap episodenya. Anime Gegege no Kitaro sebagai salah satu cermin untuk mempelajari seperti apa ciri fisik Yokai itu. Mizuki Shigeru dan buku berjilidnya yang kembali memperkenalkan Yokai dari masa lalu ke Jepang modern, dimana Yokai terus menjadi aspek penting dari budaya populer Jepang. Pengaruh Yokai dapat dirasakan, dinikmati maupun dipelajari melalui buku, film, animasi, desain produk, video game Jepang dan lainnya. Pada zaman modern ini, budaya Jepang yang populer secara mendunia membawa Yokai semakin dikenal di seluruh dunia sebagai salah satu budaya populer Jepang.
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Mori, Kazumasa. "Internal Structure and Time Evolution of a Cloud Cluster in the Western Tropical Pacific Region Observed by Keifu Maru". Journal of the Meteorological Society of Japan. Ser. II 70, n.º 6 (1992): 1111–23. http://dx.doi.org/10.2151/jmsj1965.70.6_1111.
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Mori, Kazumasa, Syuji Ishigaki, Takao Maehira, Masakatsu Ohya e Hitoshi Takeuchi. "Structure and Evolution of Convection within Typhoon Yancy (T9313) in the Early Developing Stage Observed by the Keifu Maru Radar". Journal of the Meteorological Society of Japan. Ser. II 77, n.º 2 (1999): 459–82. http://dx.doi.org/10.2151/jmsj1965.77.2_459.
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Fujisawa, Taro. "Book Review: Chyuugoku Gendai Bungaku no Keifu: Kakumei to Tsuuzoku wo Megutte (The genealogy of modern Chinese literature: revolution and popularity)". China Information 19, n.º 2 (julho de 2005): 356–57. http://dx.doi.org/10.1177/0920203x0501900220.
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Murakami, Masako, Yorimi Mizushima e Chikako Irisawa. "Successful Handling of a Patient in Advanced Age in the National Lep-rosarium Kikuchi Keifu-En with a Case of Delusion of being robbed". Japanese journal of leprosy 61, n.º 2 (1992): 104–6. http://dx.doi.org/10.5025/hansen1977.61.104.
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Jephthah, Stéphanie, Linda K. Månsson, Domagoj Belić, Jens Preben Morth e Marie Skepö. "Physicochemical Characterisation of KEIF—The Intrinsically Disordered N-Terminal Region of Magnesium Transporter A". Biomolecules 10, n.º 4 (17 de abril de 2020): 623. http://dx.doi.org/10.3390/biom10040623.
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Magnesium transporter A (MgtA) is an active transporter responsible for importing magnesium ions into the cytoplasm of prokaryotic cells. This study focuses on the peptide corresponding to the intrinsically disordered N-terminal region of MgtA, referred to as KEIF. Primary-structure and bioinformatic analyses were performed, followed by studies of the undisturbed single chain using a combination of techniques including small-angle X-ray scattering, circular dichroism spectroscopy, and atomistic molecular-dynamics simulations. Moreover, interactions with large unilamellar vesicles were investigated by using dynamic light scattering, laser Doppler velocimetry, cryogenic transmission electron microscopy, and circular dichroism spectroscopy. KEIF was confirmed to be intrinsically disordered in aqueous solution, although extended and containing little β-structure and possibly PPII structure. An increase of helical content was observed in organic solvent, and a similar effect was also seen in aqueous solution containing anionic vesicles. Interactions of cationic KEIF with anionic vesicles led to the hypothesis that KEIF adsorbs to the vesicle surface through electrostatic and entropic driving forces. Considering this, there is a possibility that the biological role of KEIF is to anchor MgtA in the cell membrane, although further investigation is needed to confirm this hypothesis.
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Takahashi, Toshiaki. "Keiu Nakamura's Search for English Dictionaries". Historical English Studies in Japan, n.º 24 (1992): 33–42. http://dx.doi.org/10.5024/jeigakushi.1992.33.
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IOH, Hideyuki. "Review of Arabu keihu taikei no tanjō to hatten by Daisuke Takano". Bulletin of the Society for Near Eastern Studies in Japan 52, n.º 2 (2010): 172–78. http://dx.doi.org/10.5356/jorient.52.172.
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Knox, John. "Qiu v. Secretary-General of the United Nations". American Journal of International Law 85, n.º 4 (outubro de 1991): 686–89. http://dx.doi.org/10.2307/2203275.
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In September 1984, the UN Secretary-General (Respondent) offered five-year fixed-term contracts as interpreters to Rong Qiu, Kefu Zhou, and Jiping Yao (Applicants), who had just completed the UN training course for interpreters at the Beijing Institute of Foreign Languages. The letters of appointment accepted by the Applicants stated that they were “on secondment from the Government of China.” They received very good performance ratings, and in the spring of 1989 their department recommended that they be offered probationary, career-track appointments when their contracts expired.
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Wu, Mei. "Mathematical Model and Algorithm Design of PDCA Cyclic Block Control Based on Digital Sensor". Applied Mechanics and Materials 543-547 (março de 2014): 585–88. http://dx.doi.org/10.4028/www.scientific.net/amm.543-547.585.
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In this paper we introduce the PDCA theory into the computer communication, realize the computer cyclic block control, and get the overall arrangement network of computer sensor. In the first part we introduce the application of PDCA in computer, the second part we establish of the mathematical model of computer block cyclic control theory. In order to verify the availability of mathematical model, we designed the computer control experiment of digital sensor. After the temperature calibration of DHT11 sensor in temperature check box, the calibration data is stored in the OTP memory in the form of a program. And we use Keilu Vision2 compiler to realize the LED display of detected temperature. It provides the technical reference for the application of computer control technology.
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Kalberg, T., J. Kask, K. Schwarzer, A. Talpas e C. Wegner. "Sea floor deposits in Keibu Bay and Nõva Bay (northwestern Estonia) and the adjacent offshore area". Proceedings of the Estonian Academy of Sciences. Geology 52, n.º 1 (2003): 42. http://dx.doi.org/10.3176/geol.2003.1.03.
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Erwiyani, Yera. "Pelaksanaan Kegiatan Keagamaan di Mesjid Miftahul Jannah Kenagarian Koto Padang Kabupaten Dharmasraya". Jurnal Impresi Indonesia 1, n.º 2 (15 de março de 2022): 135–42. http://dx.doi.org/10.36418/jii.v1i2.13.
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Latar belakang peneliti membuat skripsi ini adalah ketika penulis melakukan observasi terlihat minat masyarakat yang tidak andil ke masjid untuk melaksanakan shalat dan imamnya orang-orang keitu saja dalam melaksanakan shalat sehingga imam di masjid tersebut tidak baik dalam dari segi bacaannya. Dan imam tersebut selalu ingin menjadi imam di masjid tersebut tanpa menghiraukan bacaannya. Sedangkan jama’ah nya sudah belajar tentang bagaimana menjadi imam yang baik dalam melaksanakan shalat. Sering terjadi dalam melaksanakan ibadah shalat shaf shalat perempuan dan laki-laki kurang terisi, Majelis taklim yang tidak berjalan rutin. Penelitian ini bertujuan untuk mengetahui bagaimana Bentuk Proses Pelaksanaan Kegiatan Keagamaan Di Masjid Miftahul Jannah Di Kenagarian Koto Padang Kecamatan Koto Baru Kabupaten Dharmasraya.
Pendekatan yang digunakan dalam penelitian ini adalah pendekatan kualitatif, artinya peneliti akan melihat langsung fenomena yang terjadi di masyarakat. Daalam penelitian ini, peneliti menggunakan bentuk penelitian deskriptif kualitatif. Informan kunci dalam penelitian ini adalah pengurus masjid miftahul jannah, sedangkan informan pendukung adalah masyarakat. Peneliti menggunakan teknik wawancara dan didukung dengan dokumentasi, Data yang terkumpul kemudian dianalisis dengan menggunakan teknik analisis dekskriptif.
Dari penelitian yang penulis lakukan dapat ditarik kesimpulan bahwa bentuk proses pelaksanaan kegiatan keagamaan di masjid miftahul jannah yaitu: Pelaksanaan shalat berjamaah, Majelis taklim,Taman pendidikan Al-Qur’an (TPA), Bimbingan Zikir, Pelaksanaan Ceramah dan Pelaksanaan Shalat Jumat.
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Erwiyani, Yera. "Pelaksanaan Kegiatan Keagamaan di Mesjid Miftahul Jannah Kenagarian Koto Padang Kabupaten Dharmasraya". Jurnal Impresi Indonesia 1, n.º 2 (15 de março de 2022): 135–42. http://dx.doi.org/10.58344/jii.v1i2.13.
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Latar belakang peneliti membuat skripsi ini adalah ketika penulis melakukan observasi terlihat minat masyarakat yang tidak andil ke masjid untuk melaksanakan shalat dan imamnya orang-orang keitu saja dalam melaksanakan shalat sehingga imam di masjid tersebut tidak baik dalam dari segi bacaannya. Dan imam tersebut selalu ingin menjadi imam di masjid tersebut tanpa menghiraukan bacaannya. Sedangkan jama’ah nya sudah belajar tentang bagaimana menjadi imam yang baik dalam melaksanakan shalat. Sering terjadi dalam melaksanakan ibadah shalat shaf shalat perempuan dan laki-laki kurang terisi, Majelis taklim yang tidak berjalan rutin. Penelitian ini bertujuan untuk mengetahui bagaimana Bentuk Proses Pelaksanaan Kegiatan Keagamaan Di Masjid Miftahul Jannah Di Kenagarian Koto Padang Kecamatan Koto Baru Kabupaten Dharmasraya.
Pendekatan yang digunakan dalam penelitian ini adalah pendekatan kualitatif, artinya peneliti akan melihat langsung fenomena yang terjadi di masyarakat. Daalam penelitian ini, peneliti menggunakan bentuk penelitian deskriptif kualitatif. Informan kunci dalam penelitian ini adalah pengurus masjid miftahul jannah, sedangkan informan pendukung adalah masyarakat. Peneliti menggunakan teknik wawancara dan didukung dengan dokumentasi, Data yang terkumpul kemudian dianalisis dengan menggunakan teknik analisis dekskriptif.
Dari penelitian yang penulis lakukan dapat ditarik kesimpulan bahwa bentuk proses pelaksanaan kegiatan keagamaan di masjid miftahul jannah yaitu: Pelaksanaan shalat berjamaah, Majelis taklim,Taman pendidikan Al-Qur’an (TPA), Bimbingan Zikir, Pelaksanaan Ceramah dan Pelaksanaan Shalat Jumat.
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Yamashita, Shigekazu. "On the first Japanese and Chinese translations of J. S. Mill's “On Liberty” by Keiu Nakamura and Yen Fu". Historical English Studies in Japan, n.º 33 (2000): 57–71. http://dx.doi.org/10.5024/jeigakushi.2001.57.
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Breen, J. L. "Shintoists in Restoration Japan (1868–1872): Towards a Reassessment". Modern Asian Studies 24, n.º 3 (julho de 1990): 579–602. http://dx.doi.org/10.1017/s0026749x00010477.
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In April of 1868, the Restoration government issued an anti-Christian proscription—‘a fixed law for all ages’ it was styled. Christianity was declared a pernicious sect; rewards were offered for information leading to the discovery of Christians. In the name of the proscription, the government carried out a persecution which, in the first four years of the new era, resulted in the deaths of as many as 500 native Christians. These men, women and children died from torture, starvation or from sickness induced by the conditions in which they were kept. The native Christians were, of course, from the recently discovered hidden Christian communities around Nagasaki. The Nagasaki Christian affair is a fascinating one to which I shall return, but I mention it at the outset since it serves usefully to stress the climate of the times as far as Christianity was concerned. Given this climate, it is remarkable that there emerged by 1871, or thereabouts, a small number of enlightened intellectuals who criticized government policy on Christianity and went so far as to advocate religious freedom. The most famous of the few were Mori Arinori, Nakamura Keiu, Fukuzawa Yukichi and Nishi Amane—names known to anyone familiar with early Meiji intellectual history. There is, however, one other name that needs to be added to this short list. That is Fukuba Bisei. The little known Fukuba Bisei was, perhaps, the most remarkable of these men since he was an early Meiji Shintoist.
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Imai, Y., H. Ikeuchi, J. Suwa, Y. Ohishi, M. Watanabe, M. Nakasatomi, H. Hamatani, T. Sakairi, Y. Kaneko e K. Hiromura. "SAT0177 MULTITARGET THERAPY WITH TACROLIMUS AND MYCOPHENOLATE MOFETIL FOR TREATMENT OF LUPUS NEPHRITIS PRESENTED WITH RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 1030.1–1030. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1775.
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Background:Although, most lupus nephritis patients present with chronic glomerulonephritis or nephrotic syndrome, some patients develop rapidly progressive glomerulonephritis (RPGN), which is a clinical syndrome characterized by rapid loss of renal function over a short period of time (days to months). Multitarget therapy using tacrolimus and mycophenolate mofetil (MMF) has been reported to be effective as induction therapy of Class III to Class V lupus nephritis1. However, its efficacy on lupus nephritis presented with RPGN has not been well reported.Objectives:We aimed to examine the efficacy of multitarget therapy on lupus nephritis presented with RPGN.Methods:We retrospectively analyzed patients with biopsy-proven lupus nephritis, who clinically showed RPGN, and were treated by multitarget therapy with tacrolimus and MMF in our department. Data were expressed as mean±SD.Results:Five lupus nephritis patients (3 female) with RPGN were treated by multitarget therapy as induction therapy. Mean age was 36.6±13.5 years old. Renal biopsy at treatment revealed Class IV(A) in 2, Class IV(A+C) in 1 and Class IV(A)+V in 2. The percentage of glomerular crescents was 23.1±25.4%. eGFR and proteinuria at the initiation of treatment were 46.8±11.5 mL/min/1.73m2and 7.7±3.4 g/gCr, respectively. Patients were initially treated with methylprednisolone pulse therapy followed by 0.8-1.0 mg/kg of prednisolone (PSL), 2-3 mg/day of tacrolimus and 1000 mg/day of MMF. At 6 months, eGFR and proteinuria improved to 72.9±11.3 mL/min/1.73m2and 0.19±0.13 g/gCr, respectively. At 12 months, eGFR and proteinuria further improved to 76.8±7.8 mL/min/1.73m2and 0.10±0.07 g/gCr, respectively and the dose of PSL was reduced to 6.6±1.5 mg/day. Three patients became positive for cytomegalovirus antigenemia and were successfully treated with antiviral therapy.Conclusion:Multitarget therapy is effective in lupus nephritis even in patients presented with RPGN.References:[1]Liu Z, Zhang H, Liu Z,et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial.Ann Int Med2015; 162: 18-26.Disclosure of Interests:Yoichi Imai: None declared, Hidekazu Ikeuchi Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Junya Suwa: None declared, Yuko Ohishi: None declared, Mitsuharu Watanabe: None declared, Masao Nakasatomi: None declared, Hiroko Hamatani: None declared, Toru Sakairi: None declared, Yoriaki Kaneko Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc. b, Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Keiju Hiromura Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.
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MIZUTA, Susumu. "AN ARCHITECTURAL & TECHNOLOGICAL STUDY ON THE SUGAR CANE MILL IN KEIOU PERIOD COMPARING WITH THE SUGAR CANE INDUSTRY OF AMAMI-OSHIMA ISLAND : Studies on the SYUSEIKAN projects from the view of the British merchants (3)". Journal of Architecture and Planning (Transactions of AIJ) 71, n.º 610 (2006): 177–84. http://dx.doi.org/10.3130/aija.71.177.
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Imai, Y., H. Ikeuchi, J. Suwa, Y. Ohishi, M. Watanabe, M. Nakasatomi, H. Hamatani, T. Sakairi, Y. Kaneko e K. Hiromura. "AB0443 LONG-TERM OUTCOMES OF MULTITARGET THERAPY OF MYCOPHENOLATE MOFETIL AND TACROLIMUS IN LUPUS NEPHRITIS: A SINGLE CENTER RETROSPECTIVE ANALYSIS". Annals of the Rheumatic Diseases 81, Suppl 1 (23 de maio de 2022): 1350.1–1350. http://dx.doi.org/10.1136/annrheumdis-2022-eular.4154.
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BackgroundRecent studies showed the efficacy of multitarget therapy with mycophenolate mofetil (MMF) and calcineurin inhibitor for induction therapy for lupus nephritis (LN)1. However, long-term outcomes have not been well elucidated.ObjectivesWe retrospectively analyzed the long-term outcomes of multitarget therapy of MMF and tacrolimus.MethodsWe examined 27 LN patients (4 male, 23 female) treated with multitarget therapy for induction therapy between Oct. 2009 and Nov. 2018 in our department. Complete remission (CR) was defined as 1) UPCR<0.5 g/gCr, and 2) serum creatinine (S-Cr) normal or if abnormal, within 15% of baseline; 1) and 2) were observed in 2 consecutive visits. Relapse was defined as UPCR>1.0 g/gCr or intensification of immunosuppressive treatment after achievement of CR.ResultsThe mean age was 38.6±11．6 years old. 17 patients were new-onset LN, and 10 patients were relapse LN. UPCR and eGFR before treatment were 4.42±2.98 g/gCr and 71.5±32.9 mL/min/1.73m2, respectively. Renal histology was Class III in 1, III+V in ４, IV in 12. IV+V in 9 and V in 1 by ISN/RPS 2003 classification. CR at 6 and 12 months were 59% and 74%, respectively. Patients were treated by multitarget therapy for median of 25 months (IQR, 5.5-37). Finally, 26 (96%) patients achieved CR. During multitarget therapy, there were 15 serious adverse events: deep vein thrombosis in 2, myocardial infarctions in 2, cervical intraepithelial neoplasia in 2, heart failure in 1, herpes zoster in 1, viral myocarditis in 1, cytomegalovirus gastroenteritis in 1, cholecystitis in 1, pyelonephritis in 1, bacterial enteritis in 1, sepsis in 1, and breast cancer in 1. During the median observation period of 94 months (IQR, 63-111.5) after the initiation of multitarget therapy, 1 patient died due to sudden death. No patient reached end-stage kidney disease or doubling S-Cr. 16 patients relapsed at median of 32 months (IQR,13.8-64.5) after CR; 8 patients relapsed on multitarget therapy, and 8 patients relapsed after cessation of multitarget therapy. Relapse was associated with chronic lesions in renal biopsy and normal or higher C4 levels at treatment initiation by Kaplan Meier analysis (Log-rank, P=0.006, P<0.001, respectively).ConclusionMultitarget therapy effectively induced CR and maintained renal function in long-term period. However, relapse was often observed during or after withdrawal of multitarget therapy.References[1]Liu Z, Zhang H, Liu Z, et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Int Med 2015; 162: 18-26.Disclosure of InterestsYoichi Imai: None declared, Hidekazu Ikeuchi: None declared, Junya Suwa: None declared, Yuko Ohishi: None declared, Mitsuharu Watanabe: None declared, Masao Nakasatomi: None declared, Hiroko Hamatani: None declared, Toru Sakairi: None declared, Yoriaki Kaneko: None declared, Keiju Hiromura Speakers bureau: Chugai, Astellas., Grant/research support from: Chugai, Astellas.
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CHIAVACCI, David. "Wakamono to Shigoto: ‘Gakkō Keiyu no Shūshoku’ o Koete (Young People and Employment in Japan: Beyond the ‘School-Mediated Job Search’), by Yuki Honda. Tokyo: Tōkyō Daigaku Shuppankai, 2005, vi + 224 pp., ¥3,800 (hardcover ISBN 4-13-051311-7)". Social Science Japan Journal 9, n.º 2 (20 de julho de 2006): 322–25. http://dx.doi.org/10.1093/ssjj/jyl015.
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Nomura, Kotaro, Shogo Kumagai, Shohei Koyama, Keiju Aokage, Yoshihisa Shimada, Kiyotaka Yoh, Masashi Wakabayashi et al. "Abstract 1211: Biomarker analysis of pembrolizumab and ramucirumab neoadjuvant therapy for PD-L1-positive stage IB-IIIA lung cancer: EAST ENERGY trial". Cancer Research 84, n.º 6_Supplement (22 de março de 2024): 1211. http://dx.doi.org/10.1158/1538-7445.am2024-1211.
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Abstract Background: Neoadjuvant treatments with novel combination immunotherapies for resectable non-small cell lung cancer (NSCLC) are being developed. Combination therapy with antiangiogenic agents and anti-PD-1/PD-L1 antibody has shown enhanced antitumor effects. EAST ENERGY is a single-arm multicenter phase 2 trial of neoadjuvant pembrolizumab and ramucirumab in patients with PD-L1-positive stage IB-IIIA NSCLC (NCT04040361). In this study, we aimed to identify biomarkers that predicts the efficacy of the neoadjuvant therapy. Furthermore, we aimed to elucidate the effect of the neoadjuvant therapy on the tumor microenvironment (TME). Methods: Patients enrolled in the EAST ENERGY trial (n=24) for whom pre- and post-treatment specimens were available (n=20) were included in this study. RNA-sequencing and multiplex immunohistochemistry (mIHC) were used to examine the association between the immunological phenotype of the TME and major pathological response (MPR), and changes in the TME before and after treatment. Results: MPR was achieved in 50.0% (12/24) of patients. Biomarker analyses with RNA-sequencing revealed that high expression of cancer-associated genes, and upregulation of interferon-gamma and interferon-alpha response in pre-treatment tumor were associated with MPR (q value<0.001). mIHC in pre-treatment samples revealed that abundance of CD8+ T cells in the pre-treatment TME was associated with MPR (p=0.039). On the other hand, infiltration of immunosuppressive cells such as Treg or M2-macrophages were not associated with resistance for the treatment (p=0.836, 0.639, respectively). Next, to clarify the effect of the neoadjuvant therapy on the TME, comparative analyses of pre- and post-treatment samples was performed. In gene set enrichment analysis, the neoadjuvant therapy enhanced gene set associated with interferon-gamma response (q value=0.051). Furthermore, angiogenesis-related gene set were downregulated after the treatment (q value=0.090). mIHC analyses revealed that the number of CD8+ T cells in the TME was significantly increased after the neoadjuvant therapy (p<0.001). Notably, Tregs/CD8+ T cells ratio and the number of M2-macrophage in the TME were significantly decreased after the neoadjuvant therapy (p=0.032, 0.003, respectively). Conclusion: In the neoadjuvant therapy with pembrolizumab and ramucirumab, immune-activated status before treatment serves as a potential biomarker for predicting treatment response. Moreover, combining ramucirumab with pembrolizumab reduced immunosuppressive cells in the TME and inhibited tumor angiogenesis. These results suggest that this combination therapy modifies the TME and augments antitumor immunity. Larger clinical trial is warranted to assess the efficacy of neoadjuvant therapy with ramucirumab and pembrolizumab in patients with PD-L1-positive NSCLC. Citation Format: Kotaro Nomura, Shogo Kumagai, Shohei Koyama, Keiju Aokage, Yoshihisa Shimada, Kiyotaka Yoh, Masashi Wakabayashi, Miki Fukutani, Hideki Furuya, Tomohiro Miyoshi, Kenta Tane, Joji Samejima, Tetsuro Taki, Takuo Hayashi, Jun Matsubayashi, Genichiro Ishii, Norihiko Ikeda, Hiroyoshi Nishikawa, Masahiro Tsuboi. Biomarker analysis of pembrolizumab and ramucirumab neoadjuvant therapy for PD-L1-positive stage IB-IIIA lung cancer: EAST ENERGY trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1211.
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Kinoshita, M., Y. Kaneko, M. Watanabe, Y. Imai, S. Shrestha, J. Suwa, Y. Ohishi et al. "OP0306 CD11C-SPECIFIC ABLATION OF SHP1 INDUCES AUTOIMMUNE SIALADENITIS SIMILAR TO SJÖGREN’S SYNDROME". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 189.1–190. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1044.
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Background:Dendritic cells (DCs) play important roles in inducing immune response as well as maintaining immune tolerance. Src homology 2 domain-containing protein tyrosine phosphatase-1 (Shp1) is a negative regulator of signaling in hematopoietic cells and is expressed in a variety of immune cells including DCs. Shp1 homozygous mutant mice (motheaten mice) develop multiple immunological abnormalities and they die around four weeks after birth because of severe pneumonitis. Motheaten mice produce large amounts of autoantibodies, and besides, B-1a cells, a distinct B cell subset, which are an important source of autoantibodies increase in these mice. The functional abnormality of DCs in motheaten mice has not been characterized, but DCs and macrophages increase in various organs of motheaten mice.To analyze the function of Shp1 in DCs, we generated Shp1 conditional knockout mice (Shp1 CKO) in whichShp1gene is specifically depleted in CD11c+cells. We found that aged shp1 CKO developed autoimmune glomerulonephritis. We also found that they developed severe tubulointerstitial nephritis (TIN) at the age of 40 weeks, which is characterized by the infiltration of CD11c+and F4/80+cells. CD4+T cells from Shp1 CKO produce much more amount of IFNγ. Collectively, Shp1 in DCs acts as a key regulatory molecule to protect against autoimmunity.Objectives:We analyzed salivary glands of CKO to confirm whether they have autoimmune sialadenitis because TIN is known to be the most common renal manifestations of Sjögren’s syndrome in human.Methods:Shp1 CKO are generated by crossing a mouse line carrying floxedShp1allele to mice expressing Cre recombinase under the control of the CD11c promoter. Sex- and age-matchedPtpn6fl/fllittermates withoutCregene were studied as controls. We analyzed secretory function of the salivary glands in response to pilocarpine stimulation in Shp1 CKO at the age of 40 weeks or older. We then performed histological examination of salivary glands (submandibular glands and sublingual glands) with light-microscopy and immunohistochemical staining. The mononuclear cells prepared from the salivary glands were analyzed by flow cytometry (FCM). We also quantified anti-SSA/Ro60 antibodies and anti-SSB/LA antibodies by ELISA.Results:Shp1 CKO secreted less saliva flow compared to control mice by pilocarpine stimulation. Histological study showed Shp1 CKO exhibited massive infiltration of inflammatory cells in salivary glands associated with periductal foci and periductal fibrosis. Most of infiltrated cells were stained by anti- CD4 or B220 mAbs. FCM revealed that B cells increased in the salivary glands of Shp1 CKO. In addition, B-1a cells also increased in the salivary glands of the mice. The levels of anti-SSA/Ro60 antibodies and anti-SSB/LA antibodies were increased in Shp1 CKO.Conclusion:CD11c-specific ablation of Shp1 induces the ectopic generation of lymphoid structure in salivary glands and impairment of salivary secretion. Autoantibody profile in Shp1 CKO resembled that in human Sjögren’s syndrome. Our findings suggest that aged Shp1 CKO have the potential to become a new mouse model for the analysis of Sjögren’s syndrome.References:[1]Green C. M. et al. J Heredity. 1975; 250-258.[2]Kaneko T. et al. J Immunology. 2012; 5397-540.[3]Watanabe M. et al. Biochem Biophys Rep. in press.Disclosure of Interests:Masato Kinoshita: None declared, Yoriaki Kaneko Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.b, Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Mitsuharu Watanabe: None declared, Yoichi Imai: None declared, Shreya Shrestha: None declared, Junya Suwa: None declared, Yuko Ohishi: None declared, Hiroko Hamatani: None declared, Masao Nakasatomi: None declared, Toru Sakairi: None declared, Hidekazu Ikeuchi Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Yoshihisa Nojima: None declared, Keiju Hiromura Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.
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Oshida, Keiyu, Mikito Hirakata, Emi Tomikawa, Chizuka Sakai, Masashi Uchida, Rieko Shimozono, Akiko Izawa et al. "Abstract 679: TXB-001 is an upgraded conjugated anthracycline that targets tumors with reduced risk of cardiotoxicity, hand-foot syndrome and alopecia". Cancer Research 84, n.º 6_Supplement (22 de março de 2024): 679. http://dx.doi.org/10.1158/1538-7445.am2024-679.
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Abstract TXB-001 is a well-optimized N-(2-hydroxypropyl)methacrylamide copolymer-based conjugated pirarubicin (THP) and a novel candidate for developing anticancer drugs. It exhibits tumor-specific accumulation due to the enhanced permeability and retention effects and prolonged circulation time compared with free THP. Its hydrazone bond is dissociated under lower pH conditions, providing selective and rapid release of THP in acidic tumor environments. Therefore, TXB-001 is expected to have high efficacy and low toxicity. Anthracycline anticancer drugs have been widely used for the treatment of several cancers, but their use is limited by several adverse effects (AEs), including cardiotoxicity, which is a life-threatening AE. Furthermore, the maximum lifetime cumulative dose is decided for each anthracycline in clinical use, which leads to discontinuation of the medication. Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL®, a liposomal formulation of doxorubicin (DOX), and although it is not a life-threatening condition, it significantly deteriorates quality of life (QOL). Alopecia is another common AE, which is relatively noninvasive but adversely affects mental health and reduces QOL. In this study, we confirmed the efficacy of TXB-001 in a mice triple-negative breast cancer (TNBC) model and evaluated the cardiotoxicity-, HFS- and alopecia-inducing effects of TXB-001 in mice and rats to compare the severity with existing anthracycline anticancer drugs, including DOXIL®. The pharmacokinetic (PK) analysis in several tissues, including plasma, tumor, heart, skin of the chest, and palmar and plantar areas, was also performed after a single intravenous administration in rodents. As a result, TXB-001 showed an equivalent or greater antitumor effects than other anthracyclines in the TNBC model, and the AEs were scarcely observed. TXB-001 did not decrease left ventricular ejection fraction, with no or little HFS-like changes compared with DOXIL®, which showed significant histopathological changes. TXB-001 also showed weaker alopecia-inducing effects than DOX, DOXIL®, and THP. In the PK analysis, TXB-001 was distributed in the tumor at a higher concentration than in other tissues, except for plasma. Hence, most of the THP, the active ingredient, was released in the tumor. The exposure of the heart in the TXB-001-treated group was one-tenth of that in the DOXIL®-treated group. Moreover, accumulation in the skin, especially in palmar and plantar areas, was observed for DOXIL®, but no accumulation in the skin was observed for TXB-001. This PK profile consistently demonstrated the antitumor activity of TXB-001, without AEs. TXB-001 reduces the chance of dose-limiting and QOL-threatening AEs, and thus, cancer patients can continue treatment, making it a more convenient anticancer drug in clinical use with a wide safety margin. Citation Format: Keiyu Oshida, Mikito Hirakata, Emi Tomikawa, Chizuka Sakai, Masashi Uchida, Rieko Shimozono, Akiko Izawa, Yoko Koga, Tsubasa Okano, Hideki Narumi, Lisa Munakata, Ryo Suzuki, Miki Nonaka, Yasuhito Uezono. TXB-001 is an upgraded conjugated anthracycline that targets tumors with reduced risk of cardiotoxicity, hand-foot syndrome and alopecia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 679.
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Abe, Yoshiaki, Yamashita Takeshi, Ueda Mikio, Kazutaka Sunami, Kentaro Narita, Hiroki Kobayashi, Hiroyuki Takamatsu, Akihiro Kitadate, Masami Takeuchi e Kosei Matsue. "Evaluation of the Revised International Staging System in 400 Patients with Symptomatic Myeloma in a Japanese Clinical Setting". Blood 132, Supplement 1 (29 de novembro de 2018): 4477. http://dx.doi.org/10.1182/blood-2018-99-109934.
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Abstract Background:In 2015, the International Myeloma Working Group (IMWG) developed the Revised International Staging System (R-ISS), which combined the ISS with the status of high-risk cytogenetic abnormalities (CAs) and serum levels of lactate dehydrogenase to identify three multiple myeloma (MM) entities with clearly different outcomes. However, although MM tends to affect older adults, the original and validation studies of the R-ISS included relatively younger patients. Furthermore, although studies report that bortezomib-containing therapies can reverse the unfavorable prognostic impact of the t(4;14) CA,most original and validation studies of the R-ISS included few patients who had been treated with bortezomib. Therefore, the results of these studies are less applicable to patients in the era of novel targeted agents. Methods: This study retrospectively analyzed the data of 400 consecutive patients who were newly diagnosed with MM and treated with chemotherapy between January 2006 and December 2017 at Kameda Medical Center, Kamogowa-shi, Japan; Keiju Kanazawa Hospital, Ishikawa, Japan and National Hospital Organization Okayama Medical Center, Okayama, Japan. We included only patients who had been treated with novel agents (e.g., immunomodulatory agents or proteasome inhibitors) to reduce the prognostic impact of heterogeneity in chemotherapy. Results: The 400 included patients had a median age of 72 years (interquartile range [IQR]: 64-79 years). The median observation period was 37.9 months (IQR: 16.4-67.9 months). Ninety-eight (24.5%), 121 (30.2%) and 181 (45.2%) patients were classified as ISS stages I, II, and III, respectively, while 66 (16.5%), 243 (60.8%), and 91 (22.8%) patients were classified as R-ISS stages I, II, and III, respectively. Additionally, 384 (96.0%) patients were treated with bortezomib. R-ISS stages II and III differed significantly in terms of age, with the former including significantly older patients than the latter (median age: 74 and 70 years, respectively; P=0.001). The Kaplan-Meier overall survival (OS) curves according to the ISS and R-ISS stages are shown in Figure 1A and 1B, respectively. The three groups of patients categorized by ISS stage differed significantly in terms of survival duration. By contrast, no significant differences in OS were observed between R-ISS stages II and III (median OS: 63.4 and 54.7 months, respectively; P=0.32).Furthermore, receiver operating characteristic (ROC) curves were developed tocompare the prognostic performances of the ISS and R-ISS. Notably, the area under curve (AUC) was significantly greater for the ISS than for the R-ISS (0.659 vs. 0.608, respectively; P=0.029, Figure 2A). ISS stage III patients recategorized to R-ISS stage III were significantly younger than those recategorized to R-ISS stage II (median age, 70 vs. 77 years; P<0.001) and had a relatively more favorable OS (Figure 3). Patients with high-risk cytogenetic abnormality t(4;14) were significantly younger than the others and also had an improved OS (Figure 4), which was attributed to young age and bortezomib therapy.We again divided the patients into three groups using a modified R-ISS (mR-ISS) categorization in which only t(14;16) and del(17p) were included as high-risk CAs.The three groups categorized by mR-ISS stage exhibited significant differences in survival (Figure 1C).We additionally developed a ROC curve for the mR-ISS, and the resulting AUC value was significantly greater than that obtained for the R-ISS (0.657 vs. 0.608, respectively; P=0.001, Figure 2B). Conclusions: Our study is the first to suggest that the performance of the R-ISS may be somewhat limited when applied to patients with MM who are treated with novel agents in ageing societies. Furthermore, we suggest that this limitation may be attributed to the inclusion of t(4;14) as a high-risk CA in the R-ISS categorization strategy. This potential limitation suggests that the R-ISS should be carefully interpreted on an individual basis when applied to patients in a real-world setting. Our findings are of particular interest because many developed countries, including Western countries, are approaching a period of super-ageing such as that observed currently in Japan. Disclosures Sunami: Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Merck Sharp and Dohme: Research Funding; Takeda: Research Funding; AbbVie: Research Funding; Sanofi: Research Funding. Takamatsu:Janssen: Honoraria; Bristol-Myers Squibb: Research Funding; Ono: Research Funding; Celgene: Honoraria, Research Funding.
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Goldston, Daniel, Apoorva Panidapu e Jordan Schettler. "Explicit calculations for Sono’s multidimensional sieve of 𝐸₂-numbers". Mathematics of Computation, 23 de janeiro de 2024. http://dx.doi.org/10.1090/mcom/3938.
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We derive explicit formulas for integrals of certain symmetric polynomials used in Keiju Sono’s multidimensional sieve of E 2 E_2 -numbers, i.e., integers which are products of two distinct primes. We use these computations to produce the currently best-known bounds for gaps between multiple E 2 E_2 -numbers. For example, we show there are infinitely many occurrences of four E 2 E_2 -numbers within a gap size of 94 94 unconditionally and within a gap size of 32 32 assuming the Elliott-Halberstam conjecture for primes and E 2 E_2 -numbers.
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Ibarra, Irune, e Bittor Hidalgo Eizagirre. "Mikoleta eta Sainthillen eskuizkribuen azterketa konparatua". Anuario del Seminario de Filología Vasca "Julio de Urquijo", 17 de dezembro de 2021. http://dx.doi.org/10.1387/asju.23299.
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Artikulu honetan, 1653. urteko Modo Breve izeneko dokumentua nork eskuizkribatu zuen argitu nahi da. Orain arte Rafael Mikoletaren eskuz eginikoa dela pentsatu izan da. Berriki, ordea, Samuel Sainthill Ingalaterrako jaunaren eskuizkribu bat eskuratu ahal izan dugu, eta zalantza areagotu Modo Breve bera noren eskutik egina den. Auzia argitzeko, azterketa konparatu bat egiten da, grafoskopian erabiltzen den metodo grafonomikoaren bidez; hau da, letren forma, idatziaren ezaugarri orokorrak eta keinu-tipoak aztertu dira. Ondorio nagusi bezala, baiezta daiteke 1653. urteko eskuizkribuaren ezaugarriak Sainthillen idatziaren antzekoak direla, eta ez Mikoletarenaren antzekoak. Azkenik, baieztapen hau ikertzen jarraitzeko bideak proposatzen dira.
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Lagman, Jasmin G., Jacqueline Tucker, Connie Koons, Kenny Hirschi e Daisy V. Shirk. "A Case of Psychosis in an Adolescent Male Using CBD Keif Nugs". Primary Care Companion For CNS Disorders 24, n.º 1 (30 de dezembro de 2021). http://dx.doi.org/10.4088/pcc.21cr02947.
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Mikhalev, Alexey. "Empires’ Keif, or Opium Trade on the Tea Route in the Era of Late Empires". Quaestio Rossica 12, n.º 1 (29 de março de 2024). http://dx.doi.org/10.15826/qr.2024.1.878.
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This paper offers an analysis of the process by which new borders appeared in Inner Asia during the late imperial period. The research focuses on the borders of Russia, Qing, and Mongolia at the time of the collapse of the Qing Empire and political crisis in Russia, which led to its demise in 1917. The author aims to reveal the influence of these processes on the region referring to transborder smuggling via the transformation of the control and power of central governments. In the author’s opinion, two key factors defined the increase in opium smuggling at the Russo-Mongolian border in 1900–1917. First, political destabilization on the outskirts of the Qing Empire. Second, Cossack regiments were sent from the border to Europe to take part in World War I, thus border control was greatly reduced. The research for this study is based upon the materials of the Russian Imperial customs in the town of Kyakhta, the long-time center of Russo-Chinese trade. Based on archival data, one can trace the volumes and routes of opium smuggling from Iran to Mongolia. The area under consideration is well researched as a cross-border smuggling point; however, the problem of the illicit opium trade is still insufficiently analyzed. This is due to both political obstacles and access to sources. This article is the first attempt at a systematic study of opium trafficking through Kyakhta. The destination of the routes was the town of Maimaicheng, located near Kyakhta and inhabited by Chinese merchants. Opium was also bought by the honghuzi – armed robbers operating near the border. However, when the Civil War broke out in Russia (1917–1922), and the Far Eastern Republic was established, opium supply via the Trans-Siberian Railway declined as this route was no longer safe. Therefore, the notion of regional order and disorder is an important category for this research. This framework offers a way of better understanding Trans-Eurasian relations in the twentieth century.
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Koder Hamid, Mona, Linda K. Månsson, Viktoriia Meklesh, Per Persson e Marie Skepö. "Molecular dynamics simulations of the adsorption of an intrinsically disordered protein: Force field and water model evaluation in comparison with experiments". Frontiers in Molecular Biosciences 9 (26 de outubro de 2022). http://dx.doi.org/10.3389/fmolb.2022.958175.
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This study investigates possible structural changes of an intrinsically disordered protein (IDP) when it adsorbs to a solid surface. Experiments on IDPs primarily result in ensemble averages due to their high dynamics. Therefore, molecular dynamics (MD) simulations are crucial for obtaining more detailed information on the atomistic and molecular levels. An evaluation of seven different force field and water model combinations have been applied: (A) CHARMM36IDPSFF + CHARMM-modified TIP3P, (B) CHARMM36IDPSFF + TIP4P-D, (C) CHARMM36m + CHARMM-modified TIP3P, (D) AMBER99SB-ILDN + TIP3P, (E) AMBER99SB-ILDN + TIP4P-D, (F) AMBERff03ws + TIP4P/2005, and (G) AMBER99SB-disp + disp-water. The results have been qualitatively compared with those of small-angle X-ray scattering, synchrotron radiation circular dichroism spectroscopy, and attenuated total reflectance Fourier transform infrared spectroscopy. The model IDP corresponds to the first 33 amino acids of the N-terminal of the magnesium transporter A (MgtA) and is denoted as KEIF. With a net charge of +3, KEIF is found to adsorb to the anionic synthetic clay mineral Laponite® due to the increase in entropy from the concomitant release of counterions from the surface. The experimental results show that the peptide is largely disordered with a random coil conformation, whereas the helical content (α- and/or 310-helices) increased upon adsorption. MD simulations corroborate these findings and further reveal an increase in polyproline II helices and an extension of the peptide conformation in the adsorbed state. In addition, the simulations provided atomistic resolution of the adsorbed ensemble of structures, where the arginine residues had a high propensity to form hydrogen bonds with the surface. Simulations B, E, and G showed significantly better agreement with experiments than the other simulations. Particularly noteworthy is the discovery that B and E with TIP4P-D water had superior performance to their corresponding simulations A and D with TIP3P-type water. Thus, this study shows the importance of the water model when simulating IDPs and has also provided an insight into the structural changes of surface-active IDPs induced by adsorption, which may play an important role in their function.
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Sato, Maho, e Kotaro Suzuki. "Ocular Findings on Patients after Anti-PD-1/PD-L1 Antibodies Treatment: A Prospective Observation Report, A Pilot Study". Journal of Ophthalmology Research Reviews & Reports, 31 de março de 2024, 1–6. http://dx.doi.org/10.47363/jorrr/2024(5)167.
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Purpose: Immune checkpoint inhibitors (ICIs) cause ICI-related adverse events (irAEs) such as dry eye and uveitis, which can be severe, sometimes necessitating the suspension of ICI treatment. Retrospective studies have targeted ocular irAEs which can detect only moderate to severe symptomatic uveitis. To the best of our knowledge, this is the first prospective study on ocular irAEs. We aimed to investigate symptomatic and subclinical ocular changes in ICI-treated eyes, to identify early changes in ocular irAE and control conditions without suspending ICI treatment. Methods: 22 participants who began ICI treatment between July 2020 and July 2021 in Keiyu Hospital, Japan (3 women and 19 men; age, 69.1 ± 7.9 years, range, 53–83 years) were prospectively evaluated. The patients underwent ocular examinations before and 1, 3, and every 2 months after the initial dose of ICI. Examinations included measurement of best-corrected visual acuity, fundus biomicroscopy, spectral domain optical coherence tomography (OCT) and aqueous flare. Central choroidal thickness (CCT) was measured using OCT. Results: Among the 22 participants, 6 developed systemic irAEs. Of these 6 patients, one experienced ocular pain after ICI treatment, likely due to dry eye disease. We did not observe any change in CCT or aqueous flare, even in patients with systemic AEs. We were unable to ascertain whether CCT or aqueous flare are valuable clues for the early identification of ocular irAEs. We continue this prospective study with a larger sample size. Conclusions: Systemic irAEs are not necessarily accompanied by ophthalmological changes.