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1. Risk Factors for Elevated D-Dimer Levels in Patients with Gastrointestinal Tumors Treated with Endoscopic Submucosal Dissection

Author

Shogo Komatsuda, Shinya Kodashima, Ken Ikusaka, Naoaki Aoki, Yuki Shimizu, Minoru Oda, Fumito Harada, Taku Honda, Shingo Komazaki, Miyoko Sakurai, Daisuke Yanagisawa, Kyohei Maruyama, Hitoshi Aoyagi, Akari Isono, Ryo Miura, Koichiro Abe, Toshihiko Arizumi, Yoshinari Asaoka, Takatsugu Yamamoto, and Atsushi Tanaka

Subjects
D-dimer, deep-vein thrombosis, endoscopic submucosal dissection, gastrointestinal tumor, sedative, Medicine
Abstract

Endoscopic submucosal dissection (ESD) is almost always performed with a sedative because of the longer procedure times involved. The risk of post-ESD deep vein thrombosis (DVT) has been reported as relatively high, and D-dimer levels are sometimes elevated after ESD. This retrospective study evaluated factors affecting changes in D-dimer levels from before to after ESD to identify causes of elevated D-dimer levels after ESD. This retrospective analysis included 117 patients with gastrointestinal tumors resected using ESD. After excluding eight patients with pre-ESD levels of D-dimer >1.5 μg/mL, factors correlating with changes in D-dimer from before to after ESD were analyzed using logistic regression analysis in 109 patients. Sedation was accomplished primarily using midazolam, but, because the sedative effect of midazolam shows marked inter-individual variability, a “corrected midazolam dose” was determined by dividing the total midazolam dose by the initial dose to correct for inter-individual differences in the sedative effect of midazolam. This value was used as one potential explanatory variable in the subgroup analysis of the 103 patients who received midazolam. In the subgroup analysis using the corrected midazolam dose as an explanatory variable, only the corrected midazolam dose correlated with a change in D-dimer ≥1.0 μg/mL in multivariate analysis (odds ratio (OR) = 1.5, 95% confidence interval (CI) 0.43–0.95; p = 0.030). The corrected midazolam dose correlated with increases in post-ESD D-dimer levels. This potential relationship indicates that patients undergoing ESD and requiring extended sedation may be at increased risk of DVT.

Published
2023
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3. Gastrointestinal Bleeding During Direct Oral Anticoagulant Therapy in Patients With Nonvalvular Atrial Fibrillation and Risk of Polypharmacy

Author

Taku, Honda, Koichiro, Abe, Minoru, Oda, Fumito, Harada, Kyohei, Maruyama, Hitoshi, Aoyagi, Ryo, Miura, Kumiko, Konno, Toshihiko, Arizumi, Yoshinari, Asaoka, Shinya, Kodashima, Ken, Kozuma, Takatsugu, Yamamoto, and Atsushi, Tanaka

Subjects
Stroke, Pharmacology, Atrial Fibrillation, Polypharmacy, Anti-Inflammatory Agents, Humans, Administration, Oral, Anticoagulants, Pharmacology (medical), Gastrointestinal Hemorrhage, Retrospective Studies
Abstract

Although concomitant medications have been raised as a factor affecting hemorrhage during direct oral anticoagulant (DOAC) therapy, details remain unelucidated. This study was conducted to clarify the relationship between concomitant medications with possible pharmacokinetic interactions and number of concomitant medications, and bleeding and embolism in patients with nonvalvular atrial fibrillation on DOACs. The subjects were 1010 patients prescribed DOACs from a single-center at the Teikyo University Hospital between April 2011 and June 2018. This study was an exploratory analysis and investigated their course between the first prescription and December 2018, including the presence or absence of clinically relevant bleeding, gastrointestinal bleeding, and major cardiovascular and cerebrovascular events. Impacts of medications were evaluated by the general linear model with inverse probability-weighted propensity score. The observation period was 2272 patient-years. The rate of bleeding was 4.7%/year, gastrointestinal bleeding was 2.8%/year, and major cardiovascular and cerebrovascular events were 2.0%/year. Taking 10 or more oral medications concurrently was a significant risk for gastrointestinal bleeding (hazard ratio, 2.046 [95%CI, 1.188-3.526]; P = .010). Nonsteroidal anti-inflammatory drugs were the only significant risk for gastrointestinal bleeding. Clinicians should be aware of gastrointestinal bleeding when using DOACs with patients taking more than 10 medications and/or nonsteroidal anti-inflammatory drugs.

Published
2022

4. Empagliflozin in Patients with Chronic Kidney Disease

Author

Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda Dugal, Terri Chant, Laura Jones, Emily Laity, Megan Miners, James Muir, Elizabeth Swanson, Andrew Frankel, James Tomlinson, Marlon Alegata, Rashid Almasarwah, Anthoula Apostolidi, Maria Vourvou, Thomas Walters, Maarten Taal, Hari Dukka, Nitin Kolhe, Carly McDonald, Kelly White, Shiva Ugni, Smita Gunda, Rotimi Oluyombo, Vicki Brindle, Ping Coutts, Tracy Fuller, Evelyn Nadar, Suresh Ramadoss, Nichola Motherwell, Susannah Pajak, Louise Tonks, Sunil Bhandari, Richard Bodington, Adil Hazara, Dominic Fellowes, Christopher Wong, Christopher Goldsmith, Sherald Barnes, Ann Bennett, Claire Burston, Samantha Hope, Nicola Hunt, Lini Kurian, Richard Fish, Daniela Farrugia, Judy Lee, Emma Sadler, Hannah Turner, Christopher Hill, Henry Brown, Agnes Masengu, Peter Maxwell, Nina Bleakley, Hugh Murtagh, William Petchey, Vivian Yiu, Joanne Kellett, Angharad Williams, Helen Clarke, Victoria Carnall, Sarah Benyon, Caroline Blake, Stephanie Estcourt, Jane Piper, Neal Morgan, Carolyn Hutchinson, Teresa McKinley, Alastair Woodman, Judi Graham, Niall Leonard, John Smyth, Vicki Adell, Samantha Hagan, Ben Caplin, Amin Oomatia, Eleanor Damian, Toluleyi Sobande, Tim Doulton, Michael Delaney, Mahmoud Montasser, Jenny Hansen, David Loader, Angela Moon, Frances Morris, Smeeta Sinha, Chukwuma Chukwu, Amy Hudson, Diane Campbell, Melanie Kershaw, Stephanie Whittaker, Ayesha Irtiza-Ali, Farid Ghalli, Heba Nosseir, Allison Leslie, Kate Trivedi, Donald Fraser, Mohammad Alhadj Ali, Sian Griffin, Farah Latif, Justyna Witczak, Alexa Wonnacott, Lynda Jeffers, Yvette Webley, Paul Phelan, Eve Miller-Hodges, Ailsa Geddes, Margaret Glenwright, Amy Hunter, Thomas Pickett, Jim Moriarty, Linda Hill, Amanda Tyler, Waqar Ayub, Gail Evans, Sue Hewins, Davina Hewitt, Kerry Read, Samira Bell, Leanne Cosgrove, Rachel Craik, Shona Murray, Nitin Bhandary, Holly Coles, Rashmi Easow, Maya Joseph, Arif Khwaja, Yvonne Jackson, Angeline Mbuyisa, Rachel Sellars, Nihil Chitalia, Cynthia Mohandas, Anca Gherman, Charlotte Kamundi, Olumide Olufuwa, Kieran McCafferty, Adedolapo Adeleke, Cara Healy, Damini Jeyarajah, Edward Kinsella-Perks, Richard Smith, Brian Camilleri, Carol Buckman, Jenny Finch, Vanessa Rivers, Andrew Connor, Sheila Carr, Lisa Shainberg, Andrew Lewington, Richard Baker, Suzannah Dorey, Kay Tobin, Rosalyn Wheatley, Debasish Banerjee, Richard Hull, Sharirose Abat, Riny Paul, Mahzuz Karim, Zay Htet, Saad Tufail, Ravi Varma, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Emily Tropman, Thahir Abdul-Samad, Anne Grace, Marie Phipps, Rebecca Suckling, Subash Somalanka, Bhrigu Sood, Pauline Swift, Sarah Acheampong, Kwame Ansu, Martia Augustin, Anna Sampson, Lynn Vinall, Kim Wren, Shamila Wanninayake, Nicholas Wooding, Heather Edwards, Lydia Owen, Stephanie Bolton, Marion Carson, Michael Matthews, Nigel Brunskill, Jorge Jesus-Silva, Alex Howson, Mary Quashie-Akponeware, Hilary Tindall, Chidambaram Nethaji, Helen Eldon, Rajan Patel, Patrick Mark, Alastair Rankin, Michael Sullivan, Kirsty Forsyth, Rowan McDougall, Tanaji Dasgupta, Louisa Davies, Maggie Ryder, Philip Grimmer, Clare Macdonald, Mary Webster, Newcastle Newcastle, Timothy Ellam, Edwin Wong, Christine Meshykhi, Andrea Webster, Peter Wilson, Enric Vilar, Jocelyn Berdeprado, Eunice Doctolero, Lily Wilkinson, Frank McCarroll, Hesham Ammar, Ying Kuan, Conor Moran, Girish Shivashankar, Ryan Campbell, Deborah Glowski, Paula McDermott, Amar Ali, Zuber Patel, Christine Bond, Gillian Whalley, Haitao Zhang, Liu Yang, Lihua Zhang, Tingting Kan, Ling Zhu, Jinghong Zhao, Weiping Hou, Jing Wu, Hong Cheng, Weijing Bian, Zhirui Zhao, Fengmin Shao, Huixia Cao, Xiaojing Jiao, Peiyuan Niu, Jianying Niu, Yu Chen, Lihong Zhang, Shenglang Zhu, Haiyan Lin, Shaopeng Yao, Jiehui Chen, Ying Jiang, Ying Hu, Huaying Xiao, Fuye Yang, Xinzhou Zhang, Baochun Guo, Qiu Jin, Lixia Liu, Xiangcheng Xiao, Yanyun Xie, Ting Meng, Chuanwen Xu, Jie Huang, Yanmei Xu, Weixin Kong, Xiaoliang Wang, Qianpan Liu, Xueying Wang, Ming Gao, Xiumei Hu, Ying Lu, Li Wang, Kun Peng, Wei Wang, Qiuhong Gong, Jianfang Cai, Xiaojue Li, Xuejiao Liu, Shuhan Zhou, Hong Liu, Yao Weng, Shuai Tang, Yao Yao, Shi Zhao, Chen Cheng, Wei Wei, Na Li, Sadanah Aqashiah Mazlan, Alia Zubaidah Bahtar, Elliyyin Katiman, Noraini Othman, Lily Mushahar, Nurdiana Mazlan, Nur Sharafina Safiee, Sarasa Ramasamy, Hin Seng Wong, Hajar Ahmad Rosdi, Esther Zhao Zhi Tan, Ju Fan Tay, Kok Seng Teng, Hasnah Yahaya, Wen Jiun Liu, Lik Wee Ee, Kenneth Kay Leong Khoo, Yuana Mohd Yusoff, Fariz Safhan Mohamad Nor, Mohd Kamil Ahmad, Mohd Ramli Seman, Clare Hui Hong Tan, Laura Lui Sian Ngu, Jaime Yoke May Chan, Javelin Peji, Chek Loong Loh, Yee Yan Lee, Sridhar Ramanaidu, Kah Mean Thong, Yik Hong Wong, Suria Junus, Chen Hua Ching, Mohammad Faisal Asmee, Ku Ruziana Ku Md Razi, Chun Leong Low, Christopher Sze Bing Sim, Zhang Duan Tham, Noor Kamila Abdullah, Tai Meng Chen, Yong Chieh Chan, Eason Chang, Huan Yean Kang, Kai Quan Lee, Sue Ann Lee, Aik Kheng Lee, Jeevika Vinathan, Rizna Abdul Cader, Ruslinda Mustafar, Lydia Kamaruzaman, Rozita Mohd, Rahimah Ismail, Chong Men Leong, Chee Koon Low, Liang Wei Wong, Norlezah Adnan, Sabariah Ibrahim, Mohamad Zaimi Abdul Wahab, Sunita Bavanandan, Yik Shen Lim, Wan Hazlina Wan Mohamad, Siti Munirah Jaafar, Nur Ashykeen Mohd Fauzi, Aziee Sudin, Soo Kun Lim, Chye Chung Gan, Albert Hing, Wan Ahmad Faizal Alaidin Razali, Yew Fong Liew, Chelsia Bao Tyng Chan, Mei Chih Cheng, Yu Chen Ong, Loke Meng Ong, Farah Amalina Mohamed Affandi, Korina Rahmat, Ban Chai Peng, Masayu Amat, Nuzaimin Hadafi Ahmad, Doo Yee Mah, Yi Loon Tye, Zaid Azhari, Siti Nabilah Mohamad Zaini, Mohd Aidil Musa, Norazinizah Ahmad Miswan, Rafizanur Ramli, Nor Aziah Ahmad, Bak Leong Goh, Nurul Izah Ahmad, Fairol Huda Ibrahim, Tze Jian Ng, Malini Shanmuganathan, Li Lian Tay, Zaiha Harun, Salmi Ramli, Nurul 'Ain Yusof, Rossenizal Abd Rahman, Muhammad Iqbal Abdul Hafidz, Nur Hidayati Mohd Sharif, Irda Yasmoon Awang, Eitaro Nakashima, Rui Imamine, Makiko Minatoguchi, Yukari Miura, Miduki Nakaoka, Yoshiki Suzuki, Hitomi Yoshikawa, Koki Shin, Kanae Fujita, Misuzu Iwasa, Haruka Sasajima, Airi Sato, Yoshiyuki Hamamoto, Yuki Fujita, Takuya Haraguchi, Takanori Hyo, Kiyohiro Izumi, Toshiyuki Komiya, Sodai Kubota, Takeshi Kurose, Hitoshi Kuwata, Susumu Nakatani, Kaori Oishi, Saki Okamoto, Kaori Okamura, Jun Takeoka, Nagaaki Tanaka, Katsuya Tanigaki, Naohiro Toda, Koin Watanabe, Hiromi Komori, Rika Kumuji, Asako Takesada, Aya Tanaka, Shoichi Maruyama, Tomonori Hasegawa, Akiko Ishiguro, Takuji Ishimoto, Kazuhiro Ito, Yutaka Kamimura, Noritoshi Kato, Sawako Kato, Hiroshi Kojima, Tomoki Kosugi, Kayaho Maeda, Masasi Mizuno, Shoji Saito, Hitomi Sato, Yuka Sato, Yasuhiro Suzuki, Akihito Tanaka, Yoshinari Yasuda, Fujiko Hasegawa, Maiko Hayashi, Shizuka Higashi, Kaho Shimamura, Momoko Sumi, Kazuki Tajima, Chimaki Unekawa, Kana Wakayama, Yukiko Wakita, Takatoshi Otani, Ayako Imai, Sayaka Kawashima, Eri Kogure, Tomoe Sato, Misato Takezawa, Shinya Yoshida, Hideo Araki, Yuko 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Reina Umeno, Yoshihisa Wada, Toshiya Yamamoto, Yu Yamanouchi, Masumi Abe, Yoko Inukai, Wataru Ogawa, Shunichiro Asahara, Hideki Fujii, Shunsuke Goto, Yushi Hirota, Tetsuya Hosooka, Keiji Kono, Shinichi Nishi, Yuko Okada, Kazuhiko Sakaguchi, Kenji Sugawara, Michiko Takahashi, Tomoko Takai, Yoshikazu Tamori, Kentaro Watanabe, Miyu Kitajima, Misaki Nishi, Junko Wada, Yasuhiko Ito, Hideki Kamiya, Akimasa Asai, Nao Asai, Saeko Asano, Shogo Banno, Yohei Ejima, Hanako Hase, Tomohide Hayami, Tatsuhito Himeno, Takahiro Ishikawa, Mayumi Ito, Shiho Iwagaitsu, Rina Kasagi, Yoshiro Kato, Makoto Kato, Koichi Kato, Takayuki Katsuno, Miyuka Kawai, Hiroshi Kinashi, Masaki Kondo, Masako Koshino, Naoya Matsuoka, Yoshiaki Morishita, Mikio Motegi, Jiro Nakamura, Hiromi Shimoda, Hirokazu Sugiyama, Shin Tsunekawa, Makoto Yamaguchi, Kazuyo Takahashi, Hirotaka Watada, Takashi Funayama, Yasuhiko Furukawa, Tomohito Gohda, Hiromasa Goto, Hideyoshi Kaga, Yasuhiko Kanaguchi, Akio Kanazawa, Kayo Kaneko, Toshiki 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Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative

Subjects
chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)

Published
2023

5. RESEARCH ON THE SEMI-RIGID COLUMN BASE OF REINFORCED CONCRETE

Author

Takumi Misaki, MInoru Oda, and Osamu Takahashi

Subjects
Geography, Planning and Development, Development
Abstract

The stress state of the structure from external force, mainly depends on the rigidity when the deformation is minimum and depends on the load capacity when it comes to large deformation. The joints of ordinary reinforced concrete buildings are rigid joints, and the bending stress is focused on the column base of the first-floor columns, therefore the cross section of the first-floor columns turn large. Along with this, various problems are considered, such as excessive areas of the cross-section on the upper floors, and complications of the reinforcement, due to disunity of the column cross-sections. Given these backgrounds, semi-rigid column bases were developed to control the bending stress distribution of the columns. In this study, bending shear experiments were conducted in order to understand the structural characteristics of the semi-rigid columns depending on cross-sectional shapes, and the behavior of the semi-rigid columns were confirmed. In addition, semi-rigid column analysis models with various cross-sectional shapes were proposed, and the effective usages of semi-rigid columns with types of cross-sectional shapes were proposed.

Published
2022

7. (Invited) Ge-on-Insulator MOSFETs for High-Performance and 3D-LSI Applications

Author

Yoshiki Kamata, Wipakorn Jevasuwan, Eiko Mieda, Tatsuro Maeda, Yoshihiko Moriyama, Toshifumi Irisawa, E. Kurosawa, Masahiro Koike, Mizuki Ono, Tsutomu Tezuka, Yuuichi Kamimuta, Minoru Oda, Koji Usuda, Yuichi Kurashima, Kiyoe Furuse, Hideki Takagi, and Keiji Ikeda

Subjects
Materials science, business.industry, Speech recognition, Optoelectronics, Insulator (electricity), business
Abstract

Germanium is recognized as new channel material to be introduced in near future CMOS technologies. The advantages are the high hole mobility, the high p-type dopant activation and the low contact resistivity, whereas the smaller band gap results in higher off state current than Si devices. Therefore, Ge-MOSFETs are considered to be most promising to use as a pMOS counterpart of III-V nMOSFETs for high-performance CMOS devices. In order to suppress the off leakage current, Ge-on-insulator (GeOI) substrates may be preferable than bulk substrates. On the other hand, the low thermal budget of the fabrication processes can provide another opportunity for Ge devices. Sequentially stackable COMS devices may be a possible application for 3D-LSIs instead of a TSV technology. Poly-Ge CMOS devices on insulating layers may be one of solutions for the 3D-LSIs. In this paper, electrical properties and processes of high performance strained Ge nanowire pMOSFETs and poly-Ge trigate pFETs both on buried oxide (SiO2) layers, which are dedicated for the former and the latter applications, respectively, are presented. The Ge nanowire devices were formed by a two-step Ge condensation technique for the channels and a self-aligned NiGe process for the source and drain [1]. A compressive strain of around 4% along the channel direction of was observed after the condensation process, suggesting that no relaxation of the misfit strain between Si and Ge was occurred. A significantly high-hole mobility of 1922 cm2/Vs has been achieved thanks to the high strain and the good interfacial quality between the gate insulator and the Ge channel. Ion/Ioff over 105 has also been attained for the Ge nanowire pMOSFET with a gate length (Lg ) of 45 nm. Poly-Ge junction-less (JL) pFETs with a Lg down to 40 nm were formed on a SiO2 layer on a Si substrate [2]. The poly-Ge channel was naturally p-type with a hole concentration around 5x1018 cm-3 presumably due to the crystalline defects. No additional doping has been done. A high Ion/Ioff of around 105 was observed for narrow fin (7 nm) devices, although wider devices (>11 nm) exhibited degraded cut-off characteristics. We also found that the current drivability was drastically improved by using a flash lamp annealing (FLA) method due to the high hole mobility in the poly-Ge channel. A drain current value of 280 μA/μm was achieved at Vd =-1 V for the Lg =80 nm device [3], which is comparable with that of a mono-crystalline Si-pMOSFET of 130-nm technology node. In summary, two types of GeOI pMOSFETs for near-future high-performance logic CMOS-ICs and low-cost stackable applications were demonstrated. In both types of devices, the GeOI platform and non-planar gate configurations are key technologies to achieve sufficiently high Ion/Ioff values, which is one of major concerns to implement Ge devices into markets. Acknowledgement This work was granted by JSPS through FIRST Program initiated by the Council for Science and Technology Policy (CSTP). References [1] K. Ikeda et al., Symp. VLSI Tech., (2013), T30 [2] Y. Kamata et al., Symp. VLSI Tech., (2013), T94 [3] K. Usuda, ISDRS 2013 WP3-04

Published
2014

8. Fabrication of bonded GeOI substrates with thin Al2O3/SiO2 buried oxide layers

Author

Minoru Oda, Yuuichi Kamimuta, Tsutomu Tezuka, Toshifumi Irisawa, Yoshihiko Moriyama, Yoshiaki Nakamura, Keiji Ikeda, and Akira Sakai

Subjects
Electron mobility, Materials science, Fabrication, Wafer bonding, chemistry.chemical_element, Polishing, Conductance, Germanium, Condensed Matter Physics, Electronic, Optical and Magnetic Materials, chemistry, Chemical-mechanical planarization, Materials Chemistry, Electronic engineering, Electrical and Electronic Engineering, Composite material, Order of magnitude
Abstract

Fabrication of bonded Germanium on insulator (GeOI) substrates with thin Al 2 O 3 /SiO 2 buried oxide layers was demonstrated for the first time. Thin Al 2 O 3 layers grown by an atomic-layer deposition method, which have hydroxyl groups on their surfaces, were inserted to Ge/SiO 2 interfaces to strengthen the adhesion between them. The interface bonded in the atmosphere at room temperature without post-anneal processes is flat and exhibits no additional interface. After the wafer bonding, thick GeOI layers were thinned by mechanical polishing, chemical mechanical polishing and O 3 water etching. The flatness of the surface is equivalent to that of commercially available Ge substrates. The interface state density ( D it ) of the Ge/Al 2 O 3 interface is estimated with low-temperature conductance technique and the D it of as low as 3.9 × 10 11 eV −1 cm −2 at the interface is obtained. This value is almost one order of magnitude lower than previously reported D it of Ge/SiO 2 interfaces. These results suggest that negligible negative impact on carrier mobility and sub-threshold characteristics is expected for the back-side interface in the GeOI substrate with thin Al 2 O 3 /SiO 2 BOX layers.

Published
2013

10. Understanding of carrier transport in high-performance solid phase crystallized poly-Si nano-wire transistors

Author

Masumi Saitoh, Minoru Oda, Kiwamu Sakuma, and Yuuichi Kamimuta

Subjects
Electron mobility, Materials science, Phonon scattering, Scattering, Annealing (metallurgy), business.industry, Nanowire, Induced high electron mobility transistor, 02 engineering and technology, 021001 nanoscience & nanotechnology, law.invention, law, Electronic engineering, Surface roughness, Optoelectronics, Crystallization, 0210 nano-technology, business
Abstract

High-performance poly-Si nano-wire transistors were fabricated by Advanced SPC process, that consists of optimized a-Si deposition, crystallization annealing and poly-Si thinning processes. In order to determine what the dominant factor of scattering mechanism is, carrier mobility behavior at each temperature and surface carrier density (Ns) are fully investigated. It reveals that the hole mobility is dominated by phonon scattering in wide Ns regime. On the other hand, it is suggested that the electron mobility is dominated by Coulomb scattering by defects inside grains at low N s and surface roughness scattering at high N s .

Published
2016

12. Carrier transport analysis of high-performance poly-Si Nanowire transistor fabricated by advanced SPC with record-high electron mobility

Author

Yuuichi Kamimuta, Masumi Saitoh, Minoru Oda, and Kiwamu Sakuma

Subjects
Electron mobility, Materials science, Scattering, business.industry, Transistor, Nanowire, Nanotechnology, law.invention, law, Gate oxide, Thin-film transistor, Surface roughness, Optoelectronics, Grain boundary, business
Abstract

This paper presents the fundamental carrier transport analysis of high-mobility poly-Si nanowire transistors (NW Tr). By adopting advanced SPC (solid-phase crystallization) process, record-high electron mobility (192cm2/Vs) and Ion (200μA/μm) at If of 4nA/μm are achieved without using lasers or catalysts. Carrier density and temperature dependence of mobility, and also physical analysis of poly-Si crystallinity and the channel size, reveal that the origin of mobility degradation in conventional SPC poly-Si Tr. is Coulomb scattering due to defects inside grains as well as defects at grain boundaries and enhanced surface roughness scattering at poly-Si/gate oxide interface, all of which are weakened by advanced SPC process. At high carrier density, mobility of poly-Si nFETs and pFETs by advanced SPC process even exceeds bulk-Si (110) nFETs and (100) pFETs.

Published
2015

13. (Invited) Non-Planar Transistors with High-Mobility SiGe/Ge Channels for CMOS Applications

Author

Yoshihiko Moriyama, Keiji Ikeda, Toshifumi Irisawa, Tsutomu Tezuka, Masahiro Koike, Yuuichi Kamimuta, Minoru Oda, and Yoshiki Kamata

Subjects
Planar, Materials science, CMOS, law, business.industry, Transistor, Optoelectronics, business, law.invention
Abstract

Firstly, advantages and fabrication processes for strained SiGe fin- and wire-pMOSFETs are summarized. It is shown that strained SiGe-on-insulator channels formed by the Ge condensation process is effective to keep strain in the channel and hence to boost the current drivability of pMOSFETs. Secondly, our recent progress on a new gate-stack technology using SrGex interlayer and fabrication process of narrow Ge-fin structures using anisotropic wet etching were demonstrated for all-Ge CMOS applications. It is shown that these processes are beneficial for realizing non-planar Ge-CMOS devices in future technology nodes.

Published
2010

14. Individual analysis of inter and intragrain defects in electrically characterized polycrystalline silicon nanowire TFTs by multicomponent dark-field imaging based on nanobeam electron diffraction two-dimensional mapping

Author

Hiroki Tanaka, Riichiro Takaishi, Masumi Saitoh, Minoru Oda, Takanori Asano, and Kiwamu Sakuma

Subjects
010302 applied physics, Diffraction, Materials science, Physics and Astronomy (miscellaneous), business.industry, General Engineering, Nanowire, General Physics and Astronomy, 02 engineering and technology, engineering.material, 021001 nanoscience & nanotechnology, 01 natural sciences, Dark field microscopy, Crystal, Polycrystalline silicon, Electron diffraction, Thin-film transistor, 0103 physical sciences, engineering, Optoelectronics, Grain boundary, 0210 nano-technology, business
Abstract

We visualize the grain structures for individual nanosized thin film transistors (TFTs), which are electrically characterized, with an improved data processing technique for the dark-field image reconstruction of nanobeam electron diffraction maps. Our individual crystal analysis gives the one-to-one correspondence of TFTs with different grain boundary structures, such as random and coherent boundaries, to the characteristic degradations of ON-current and threshold voltage. Furthermore, the local crystalline uniformity inside a single grain is detected as the difference in diffraction intensity distribution.

Published
2018

15. Butyrylcholinesterase and Erythrocyte Sulfhydryl-dependent Enzyme Hydrolyze Gabexate in Human Blood

Author

Toshiyuki Kimura, Nobuhiro Fujiyama, Kenji Matsumura, Kazuhito Watanabe, Satoshi Yamaori, Minoru Oda, Tatsuya Funahashi, Ikuo Yamamoto, and Mika Kushihara

Subjects
Serine protease, biology, DTNB, Health, Toxicology and Mutagenesis, Albumin, Toxicology, Human serum albumin, Molecular biology, chemistry.chemical_compound, chemistry, Biochemistry, Gabexate, biology.protein, medicine, Diisopropyl fluorophosphate, Butyrylcholinesterase, medicine.drug, Phenylmethylsulfonyl Fluoride
Abstract

Gabexate (GB), a serine protease inhibitor that is widely used for the treatment of acute pancreatitis and disseminated intravascular coagulation, has been reported to be partly hydrolyzed by human serum albumin. However, other enzymes responsible for GB hydrolysis in human blood remain unclear. In this study, we examined in vitro metabolism of GB with human blood samples. The hydrolytic activities of the plasma and erythrocytes at 100µM of GB were 167 ± 26 and 151 ± 9n mol/min/ml blood fraction (mean ± S.D., n = 8), respectively. Kinetic analysis indicated that Vmax and Km values were 1.75µmol/min/ml blood fraction and 529µ Mf or the plasma and 10.6µmol/min/ml blood fraction and 7360µ Mf or the erythrocytes, respectively. The activity of human plasma wa si nhibited by ethopropazine, a butyrylcholinesterase inhibitor (27% inhibition at 100µM). Furthermore, the plasma activity was inhibited by 5,5 � -dithiobis(2-nitrobenzoic acid) (DTNB) (40% inhibition at 5000µM), suggesting the involvement of albumin in the plasma GB hydrolysis. The erythrocyte activity was also decreased by DTNB (56% inhibition at 5000µM), implying that this activity was dependent on the presence of sulfhydryl group(s), while little or no inhibition of the activity was seen with phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate, and BW284C51. Butyrylcholinesterase from human serum showed GB hydrolytic activity with Vmax of 363 nmol/min/m gp rotein and Km of 263µM. These results suggest that, in addition to albumin, butyrylcholinesterase and erythrocyte sulfhydryl-dependent enzyme are responsible for GB hydrolysis in human blood.

Published
2007

16. Involvement of Human Blood Arylesterases and Liver Microsomal Carboxylesterases in Nafamostat Hydrolysis

Author

Nobuhiro Fujiyama, Ikuo Yamamoto, Tomomichi Sone, Tatsuya Funahashi, Toshiyuki Kimura, Mika Kushihara, Masakazu Isobe, Minoru Oda, Kenji Matsumura, Kazuhito Watanabe, Tohru Ohshima, and Satoshi Yamaori

Subjects
Male, Erythrocytes, Serine Proteinase Inhibitors, Adolescent, Carboxylesterase 1, Pharmaceutical Science, In Vitro Techniques, Guanidines, Arylesterase, chemistry.chemical_compound, Carboxylesterase, Chlorocebus aethiops, medicine, Animals, Humans, Pharmacology (medical), Enzyme Inhibitors, Whole blood, Pharmacology, Hydrolysis, Middle Aged, Recombinant Proteins, Benzamidines, Nafamostat, chemistry, Biochemistry, COS Cells, Microsomes, Liver, Microsome, Diisopropyl fluorophosphate, Female, PMSF, Carboxylic Ester Hydrolases, Half-Life, medicine.drug
Abstract

Metabolism of nafamostat, a clinically used serine protease inhibitor, was investigated with human blood and liver enzyme sources. All the enzyme sources examined (whole blood, erythrocytes, plasma and liver microsomes) showed nafamostat hydrolytic activity. V(max) and K(m) values for the nafamostat hydrolysis in erythrocytes were 278 nmol/min/mL blood fraction and 628 microM; those in plasma were 160 nmol/min/mL blood fraction and 8890 microM, respectively. Human liver microsomes exhibited a V(max) value of 26.9 nmol/min/mg protein and a K(m) value of 1790 microM. Hydrolytic activity of the erythrocytes and plasma was inhibited by 5, 5'-dithiobis(2-nitrobenzoic acid), an arylesterase inhibitor, in a concentration-dependent manner. In contrast, little or no suppression of these activities was seen with phenylmethylsulfonyl fluoride (PMSF), diisopropyl fluorophosphate (DFP), bis(p-nitrophenyl)phosphate (BNPP), BW284C51 and ethopropazine. The liver microsomal activity was markedly inhibited by PMSF, DFP and BNPP, indicating that carboxylesterase was involved in the nafamostat hydrolysis. Human carboxylesterase 2 expressed in COS-1 cells was capable of hydrolyzing nafamostat at 10 and 100 microM, whereas recombinant carboxylesterase 1 showed significant activity only at a higher substrate concentration (100 microM). The nafamostat hydrolysis in 18 human liver microsomes correlated with aspirin hydrolytic activity specific for carboxylesterase 2 (r=0.815, p

Published
2006

17. Effect of β2-microglobulin adsorption column on dialysis-related amyloidosis

Author

Suhail Ahmad, Minoru Oda, Hirotsugu Kobata, Masami Shimazaki, Takaya Abe, Hirohito Hasegawa, Kazuhiro Uchita, Motohiro Kamimura, Masaaki Fukunishi, Tomiya Abe, Tadao Akizawa, and Hikari Orita

Subjects
Adult, Male, medicine.medical_specialty, motor terminal latency, medicine.medical_treatment, Urology, Dialysis patients, dialysis-related amyloidosis, Adsorption, Dialysis related amyloidosis, Renal Dialysis, medicine, Humans, Dialysis, Aged, Chemistry, Beta-2 microglobulin, Amyloidosis, β2-microglobulin adsorption column, Equipment Design, Middle Aged, medicine.disease, Surgery, Treatment Outcome, Motor terminal latency, Nephrology, Blood Component Removal, pinch strength, Female, Hemodialysis, beta 2-Microglobulin
Abstract

Effect of β2-microglobulin adsorption column on dialysis-related amyloidosis.Backgroundβ2-microglobulin (β2-m) is considered a major pathogenic factor in dialysis-related amyloidosis (DRA), often seen in long-term dialysis patients. No effective therapy for this severely debilitating disease is currently available. Lixelle™, an adsorption column, has been developed for the elimination of β2-m; the efficacy of this column has been evaluated in this study.MethodsSeventeen hemodialysis patients with DRA were first treated with high-flux dialysis for a minimum of 1 year. This was followed by 1-year treatment with Lixelle™ column connected in series to the high-flux dialyzer. Treatments were used three times a week for both phases of this study. During the study period, β2-m, pinch strength, motor terminal latency, and activities of daily living were evaluated.ResultsAfter 1-year treatment with high-flux dialysis the β2-m level remained unchanged; however, after 1-year treatment with the addition of the Lixelle™ column, β2-m level decreased significantly from 34.5 ± 8.4mg/L to 28.8 ± 7.3mg/L (P < 0.05). After 1 year of Lixelle™ column use, the pinch strength increased from 6.8 ± 4.7 pounds to 9.1 ± 5.5 pounds (P < 0.01), and the median motor terminal latency was significantly reduced from 5.1 ± 1.0 mseconds to 4.5 ± 1.1 mseconds. A significant improvement was also observed in the activities of daily living score of the upper extremities.ConclusionThese results suggest that the addition of Lixelle™ to the high-flux dialyzer is associated with a significant clinical improvement in DRA patients.

Published
2003

19. Demonstration of ultimate CMOS based on 3D stacked InGaAs-OI/SGOI wire channel MOSFETs with independent back gate

Author

Tatsuro Maeda, Toshifumi Irisawa, Tsutomu Tezuka, Eiko Mieda, Keiji Ikeda, Yoshihiko Moriyama, and Minoru Oda

Subjects
Materials science, CMOS, business.industry, Optoelectronics, Ring oscillator, business, Communication channel
Abstract

An ultimate CMOS structure composed of high mobility wire channel InGaAs-OI nMOSFETs and SGOI pMOSFETs has been successfully fabricated by means of sequential 3D integration. Well behaved CMOS inverters and first demonstration of InGaAs/SiGe (Ge) dual channel CMOS ring oscillators are reported. The 21-stage CMOS ring oscillator operation was achieved at V dd as low as 0.37 V with the help of adaptive back gate bias, V BG control.

Published
2014

20. Strained germanium nanowire MOSFETs

Author

Toshifumi Irisawa, Yoshihiko Moriyama, Mizuki Ono, Tsutomu Tezuka, Keiji Ikeda, Yuuichi Kamimuta, and Minoru Oda

Subjects
Electron mobility, Materials science, Strain (chemistry), business.industry, Strain measurement, Nanowire, chemistry.chemical_element, Germanium, chemistry, Logic gate, MOSFET, Electronic engineering, Optoelectronics, business, Aluminum oxide
Published
2014

21. Growth process for high performance of InGaAs MOSFETs

Author

Tsutomu Tezuka, Yasuyuki Miyamoto, Kazuto Ohsawa, Minoru Oda, Toshifumi Irisawa, Y. Mishima, Toru Kanazawa, and Yoshiharu Yonai

Subjects
Imagination, Chemical substance, Materials science, business.industry, media_common.quotation_subject, Doping, Process (computing), Epitaxy, Semiconductor, Ion implantation, Optoelectronics, business, Science, technology and society, media_common
Abstract

To obtain high performance in nMOSFETs, the introduction of high-mobility channel material such as InGaAs is a promising approach. However, the required source doping concentration for a high driving current cannot be obtained by ion implantation in InGaAs. One method of achieving a heavily doped source in III-V semiconductor MOSFETs is by growing an epitaxial source/drain structure. 1 For realizing such a source, we used a regrown InGaAs source 2,3 and an InP source. 4 The regrown sources are also important for high current drivability of 3D or multi-gate devices. The other advantage of regrowth in multi-gate devices is a smooth surface for high electron mobility. 5 In this report, we describe the growth process for high-performance InGaAs MOSFETs.

Published
2014

22. High electron mobility triangular InGaAs-OI nMOSFETs with (111)B side surfaces formed by MOVPE growth on narrow fin structures

Author

Osamu Ichikawa, Yasuyuki Miyamoto, Yoshihiko Moriyama, Tatsuro Maeda, T. Osada, Keiji Ikeda, Toshifumi Irisawa, Tsutomu Tezuka, Wipakorn Jevasuwan, M. Hata, Eiko Mieda, and Minoru Oda

Subjects
Electron mobility, Materials science, business.industry, Electrical engineering, Trapping, Ion, Gallium arsenide, chemistry.chemical_compound, Hysteresis, chemistry, MOSFET, Optoelectronics, Metalorganic vapour phase epitaxy, business, Noise (radio)
Abstract

Triangular In0.53Ga0.47As-OI nMOSFETs with smooth (111)B side surfaces on Si have been successfully fabricated. Triangular shaped channels with bottom width down to 30 nm were formed by MOVPE growth on narrow InGaAs-OI fins. The formed (111)B surface was demonstrated to provide higher mobility compared with reference InGaAs-OI tri-gate (1.9×) as well as bulk (100) InGaAs nMOSFETs (1.6×), which is possibly due to reduced Dit in conduction band and resultant suppressed carrier trapping at the MOS interface. Lower noise and hysteresis in triangular device supported this model. High Ion value of 930 μA/μm at Lg = 300 nm indicates the potential of the triangular InGaAs-OI nMOSFETs for ultra-low power and high performance CMOS applications.

Published
2013

23. Advantage of (001)/<100> oriented channels in biaxially- and uniaxially strained-Ge-on-insulator pMOSFETs with NiGe metal source/drain

Author

Mizuki Ono, Yuuichi Kamimuta, Minoru Oda, Yoshihiko Moriyama, Keiji Ikeda, Tsutomu Tezuka, E. Kurosawa, and Toshifumi Irisawa

Subjects
Materials science, business.industry, Transconductance, Contact resistance, chemistry.chemical_element, Germanium, Insulator (electricity), Metal, Effective mass (solid-state physics), chemistry, visual_art, Parasitic element, MOSFET, Electronic engineering, visual_art.visual_art_medium, Optoelectronics, business
Abstract

We compared current drivability between (001)/ and (001)/ strained Ge-on-insulator pMOSFETs under biaxial and uniaxial stress. Higher intrinsic transconductance (gm, int) was experimentally demonstrated for the first time in the (001)/ devices with a gate length (Lg) less than 100 nm under the both strain conditions, although this is not the case for the long-channel devices. This is possibly attributable to more significant non-parabolicity of the valence band (VB) dispersion, i.e., heavier effective mass at energy apart from the VB minimum, along than along . It is also found that the parasitic resistance (RSD) governed by the contact resistance between the NiGe-source and the strained-Ge channel is lower along direction than the counterpart. As a result, higher drive current was observed for a device with Lg of 55 nm under both the biaxial-(644 μA/μm) and uniaxial stress (536 μA/μm) at Vd = -0.5 V than for counterpart, although mobility was highest in the channel under the uniaxial stress.

Published
2013

24. 3D integration of high mobility InGaAs nFETs and Ge pFETs for ultra low power and high performance CMOS

Author

Toshifumi Irisawa, Yuuichi Kamimuta, Takenori Osada, Tsutomu Tezuka, Wipakorn Jevasuwan, Minoru Oda, Keiji Ikeda, Yoshihiko Moriyama, Osamu Ichikawa, Tatsuro Maeda, M. Hata, and Eiko Mieda

Subjects
Materials science, business.industry, chemistry.chemical_element, Germanium, Gallium arsenide, chemistry.chemical_compound, Integrated injection logic, CMOS, chemistry, Low-power electronics, Logic gate, MOSFET, Optoelectronics, business, Degradation (telecommunications)
Abstract

InGaAs/Ge stacked 3D CMOS inverters have been successfully demonstrated down to Vdd = 0.2 V. The negligible degradation of the top and the bottom device characteristics indicates high technical feasibility of the InGaAs/Ge stacked 3D integration for ultra low-power and high performance CMOS.

Published
2013

27. Adhesive and sealing effects of TO-193 on tissues and organs in various experimental models

Author

Katsuhide Kariya, Goro Ito, Hiroyuki Uchiyama, Tadashi Muto, Tomoo Kojima, Yuriko Maekawa, Sanae Kashiwabara, Satoshi Kanno, Minoru Oda, Hiroshi Yamazaki, Masateru Kurumi, and Yoshiko Koshiyama

Subjects
Male, Fibrin adhesive, Guinea Pigs, Fibrinogen, Fibrin, Rats, Sprague-Dawley, Aprotinin, Dogs, Thrombin, Suture (anatomy), medicine, Animals, Femur, Rats, Wistar, Lung, Skin, Pharmacology, Factor XIII, biology, Chemistry, Stomach, Rats, Drug Combinations, Liver, Collagen sponge, Evaluation Studies as Topic, biology.protein, Biophysics, Female, Tissue Adhesives, Adhesive, medicine.drug
Abstract

We studied the adhesive and sealing effects of sheet style fibrin adhesive, TO-193 (TachoComb), on some tissues and organs, comparing them with those of sheet style collagen agent, collagen sponge, Novacol, and Avitene and liquid fibrin adhesive agent, Beriplast P. TO-193 showed more a potent adhesive effect on liver than the sheet style collagen agents and was more potent on bone and skin than the liquid fibrin adhesive agent. Furthermore, TO-193 had a potent sealing effect at the site of incomplete suture immediately after application on a motile organ such as lung and stomach. These effects may be partly attributable to rapid expression of the effect due to the presence of a high concentration of fibrinogen on coverage. Enhancement of fibrin penetrability to the tissues by compression and inhibition of cleavage of coverage by the collagen sponge also may be participating in the effects of TO-193. These results suggest that TO-193 will be a valuable adhesive and sealing agent.

Published
1999

30. The mechanism of action of KBT-3022, a new antiplatelet agent

Author

Akira Yamashita, Konomi Matsuo, Koichi Yokota, and Minoru Oda

Subjects
Blood Platelets, Male, medicine.medical_specialty, Thromboxane, Metabolite, Guinea Pigs, Phosphatidic Acids, In Vitro Techniques, Thromboxane A2, chemistry.chemical_compound, Cytochrome P-450 Enzyme System, Internal medicine, medicine, Animals, Cyclooxygenase Inhibitors, Pyrroles, Platelet, Platelet activation, Isomerases, Pharmacology, Arachidonic Acid, biology, Thrombin, Phosphatidic acid, Epoprostenol, Prostaglandin Endoperoxides, Synthetic, Intramolecular Oxidoreductases, Thiazoles, Endocrinology, chemistry, Mechanism of action, 3',5'-Cyclic-AMP Phosphodiesterases, Prostaglandin-Endoperoxide Synthases, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, biology.protein, Rabbits, Thromboxane-A Synthase, Cyclooxygenase, medicine.symptom, Platelet Aggregation Inhibitors
Abstract

1. 1. The mechanism of action of a new antiplatelet agent, KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) and its active main metabolite, desethyl KBT-3022, was investigated. 2. 2. KBT-3022 and desethyl KBT-3022 inhibited cyclooxygenase from ovine seminal gland with IC 50 values of 0.69 and 0.43 μM, respectively. 3. 3. At concentrations higher than those required for cyclooxygenase inhibition, desethyl KBT-3022 inhibited cAMP-phosphodiesterase, specific binding of U46619, and release of phosphatidic acid from thrombin-stimulated platelets. 4. 4. Oral administration of KBT-3022 inhibited the production of thromboxane B 2 during blood coagulation more potently than the production of 6-keto-prostaglandin F 1α from aortic strips in guinea pigs. 5. 5. These findings suggest that KBT-3022 may inhibit platelet activation principally via the inhibition of cyclooxygenase by desethyl KBT-3022.

Published
1997

34. Effect of KBT-3022, a new cyclooxygenase inhibitor, on experimental brain edema in vitro and in vivo

Author

Noriko Yamamoto, Koichi Yokota, Minoru Oda, and Akira Yamashita

Subjects
Male, Guinea Pigs, Indomethacin, Brain Edema, In Vitro Techniques, Pharmacology, Gerbil, Brain Ischemia, Cerebral edema, Guinea pig, Brain ischemia, Lipid peroxidation, chemistry.chemical_compound, In vivo, medicine, Animals, Cyclooxygenase Inhibitors, Pyrroles, Arachidonic Acid, Aspirin, biology, business.industry, Brain, medicine.disease, Thiazoles, chemistry, Anesthesia, biology.protein, Arachidonic acid, Lipid Peroxidation, Cyclooxygenase, Gerbillinae, business
Abstract

The effect of KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate), a new cyclooxygenase inhibitor, on experimental brain edema was studied. In vitro, KBT-3022 (100 microM) and its metabolite desethyl KBT-3022 (10 and 100 microM), but neither acetylsalicylic acid nor indomethacin, inhibited arachidonic acid-induced swelling of guinea pig cortical slices. KBT-3022 (3-100 microM) and desethyl KBT-3022 (3-30 microM), but neither acetylsalicylic acid nor indomethacin, inhibited lipid peroxidation in guinea pig brain homogenate. In vivo, oral administration of KBT-3022 (1, 3 and 10 mg/kg) and indomethacin (10 and 30 mg/kg), but not acetylsalicylic acid, prevented brain edema induced by bilateral carotid occlusion and recirculation in gerbils. Indomethacin then prevented postischemic hyperthermia, but not KBT-3022. KBT-3022 (10 mg/kg) and indomethacin (30 mg/kg) inhibited lactate accumulation in gerbil brain after ischemia and recirculation. These results suggest that KBT-3022 prevents development of both cytotoxic edema in vitro and vasogenic edema in vivo.

Published
1996

35. Inhibitory Effects of the New Anti-platelet Agent KBT-3022 and Its Metabolite on Rabbit Neutrophil Function In Vitro

Author

Koichi Yokota, Minoru Oda, Noriko Yamamoto, and Yuji Obata

Subjects
Male, Ticlopidine, Neutrophils, Leukotriene B4, Metabolite, Indomethacin, Tetrazoles, Complement C5a, Complement C3-C5 Convertases, Pharmacology, Ticlopidine Hydrochloride, Structure-Activity Relationship, chemistry.chemical_compound, Superoxides, Cell Adhesion, Animals, Cyclooxygenase Inhibitors, Pyrroles, Platelet Activating Factor, IC50, Binding Sites, Aspirin, Chemistry, Superoxide, Anti-Inflammatory Agents, Non-Steroidal, In vitro, Cilostazol, N-Formylmethionine Leucyl-Phenylalanine, Thiazoles, Biochemistry, Phorbol, Tetradecanoylphorbol Acetate, Calcium, Rabbits, Platelet Aggregation Inhibitors, Intracellular
Abstract

The effects of the new anti-platelet agent KBT-3022, ethyl 2-[4,5-bis(4-methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate, and its metabolite desethyl KBT-3022 on rabbit neutrophil function were investigated in comparison with the effects of acetylsalicylic acid (ASA), ticlopidine hydrochloride (TP), cilostazol (CIL) and indomethacin (IM). The adhesion and migration of neutrophils induced by formyl-methionyl-leucyl-phenylalanine (fMLP) were inhibited by all the compounds tested, their rank order of potency being KBT-3022 = desethyl KBT-3022 > TP = CIL = IM > ASA. KBT-3022, desethyl KBT-3022, CIL and IM all suppressed fMLP-induced increases in the intracellular free Ca2+ concentration ([Ca2+]i) in neutrophils, their potencies correlating with their inhibitory effects on fMLP-induced adhesion and migration. KBT-3022 (1 microM), desethyl KBT-3022 (1-10 microM) and CIL (10 microM) but not IM significantly inhibited both neutrophil migration and the increase in [Ca2+]i induced by leukotriene B4 (LTB4). KBT-3022 (1 microM) and desethyl KBT-3022 (1 microM) suppressed the increase in [Ca2+]i induced by complement C5a. Although KBT-3022 and desethyl KBT-3022 did not influence [3H]LTB4 and [125I]C5a specific binding, [3H]fMLP specific binding was inhibited by desethyl KBT-3022 (IC50: 1.9 microM). Neutrophil adhesion and superoxide anion production stimulated by phorbol 12-myristate 13-acetate were partially inhibited by KBT-3022 (1 microM) and desethyl KBT-3022 (1-10 microM). These results suggest that KBT-3022 and desethyl KBT-3022 have a wider spectrum of action and are more potent inhibitors of neutrophil activation than ASA, TP, CIL and IM.

Published
1996

36. High mobility p-n junction-less InGaAs-OI tri-gate nMOSFETs with metal source/drain for ultra-low-power CMOS applications

Author

Yoshihiko Moriyama, Wipakorn Jevasuwan, Toshifumi Irisawa, Toshio Ishihara, Tsutomu Tezuka, Keiji Ikeda, M. Hata, Tatsuro Maeda, Minoru Oda, Osamu Ichikawa, and Eiko Mieda

Subjects
Electron mobility, Ultra low power, Materials science, business.industry, Electrical engineering, Gallium arsenide, Metal, chemistry.chemical_compound, CMOS, chemistry, visual_art, Low-power electronics, MOSFET, visual_art.visual_art_medium, Optoelectronics, business, p–n junction
Abstract

We have successfully fabricated InGaAs-OI tri-gate nMOSFETs, for the first time. The devices were depletion-type (p-n junction-less) nFETs with Fin-channel width (W fin ) down to 20 nm and had metal source/drain structures. It was experimentally demonstrated that W fin scaling effectively improved cut-off properties at N d up to 5 × 1018 cm−3 and the electron mobility in the narrowest channel (W fin = 20 nm) was about 3x higher than that of the inversion layer. It was also demonstrated that enhancement of In content from 53% to 70% leaded to 30% I on enhancement without I off degradation.

Published
2012

37. Effect of KBT-3022, a New Diphenylthiazole Derivative, on Platelet Functions

Author

Koichi Yokota, Noriko Yamamoto, Akira Yamashita, Minoru Oda, and Yasuo Morimoto

Subjects
Blood Platelets, Serotonin, Ultraviolet Rays, Metabolite, Guinea Pigs, Administration, Oral, Pharmaceutical Science, Biology, Pharmacology, Ticlopidine Hydrochloride, Mice, chemistry.chemical_compound, Thrombin, Species Specificity, medicine, Animals, Edema, Humans, Pyrroles, Platelet, Platelet activation, Arachidonic Acid, Aspirin, Biological activity, Rats, Adenosine Diphosphate, Thiazoles, Adenosine diphosphate, chemistry, Biochemistry, Erythema, Gastric Mucosa, Arachidonic acid, Collagen, Rabbits, Platelet Aggregation Inhibitors, medicine.drug
Abstract

The effects of KBT-3022 and its metabolite desethyl KBT-3022 on platelet aggregation were determined in rat, guinea-pig, rabbit and human platelets in-vitro and ex-vivo. KBT-3022 and desethyl KBT-3022 inhibited platelet aggregation induced by arachidonic acid and collagen in-vitro more potently than aggregation induced by adenosine diphosphate, platelet-activating factor or thrombin, as well as by acetylsalicylic acid, and their effects were approximately 100 times more potent than those of acetylsalicylic acid. Desethyl KBT-3022, but not KBT-3022 or acetylsalicylic acid, inhibited thrombin-induced aggregation and 5-hydroxytryptamine release from platelets more potently than ticlopidine hydrochloride at higher concentrations. Oral administration of KBT-3022 inhibited both arachidonic acid- and collagen-induced platelet aggregation and reduced platelet retention in a glass-bead column approx. 100 times more potently than acetylsalicylic acid. KBT-3022 showed little or no anti-inflammatory effect on either ultraviolet-induced erythema or arachidonic acid induced ear oedema, and had lower gastro-ulcerogenicity than acetylsalicylic acid. These results suggest that KBT-3022 is a potent inhibitor of platelet activation with weak side-effects.

Published
1995

38. The Effects of KBT-3022, a New Anti-platelet Agent, on Hemorheological Properties in Guinea Pigs

Author

Koichi Yokota, Noriko Yamamoto, Minoru Oda, and Akira Yamashita

Subjects
medicine.medical_specialty, Ticlopidine, medicine.drug_class, Guinea Pigs, Blood viscosity, Drug Evaluation, Preclinical, Hematocrit, Fibrinogen, Guinea pig, Plasma, Adenosine Triphosphate, Oral administration, Erythrocyte Deformability, Internal medicine, Animals, Medicine, Pyrroles, Pentoxifylline, 2,3-Diphosphoglycerate, Aspirin, medicine.diagnostic_test, business.industry, Vascular disease, Anticoagulant, Hematology, Blood Viscosity, Diphosphoglyceric Acids, medicine.disease, Thiazoles, Red blood cell, Endocrinology, medicine.anatomical_structure, Hemorheology, Immunology, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

SummaryUsing guinea pigs, a study was conducted on the effects of KBT-3022, a new anti-platelet agent, on hemorheological properties in various tests including blood filterability, blood viscosity, shear stress-induced red blood cell (RBC) deformability and contents of ATP and 2,3-diphosphoglycerate (2,3-DPG). Oral administration of KBT-3022 at 1 and 10 mg/kg significantly increased blood filterability, and significantly reduced blood viscosity at 10 mg/kg without changing the hematocrit, plasma fibrinogen concentration or plasma viscosity. KBT-3022 (10 mg/kg, p.o.) improved RBC deformability in response to shear stress, which was evoked by passing the blood through a thin tube. This dose of KBT-3022 also increased the contents of ATP and 2,3-DPG in RBC. These findings indicate that KBT-3022 may reduce blood viscosity as a sequel to improvement of RBC deformability through direct action on RBC. The increase in the intracellular levels of ATP and 2,3-DPG was considered to be involved in this improvement of hemorheological properties. These hemorheological effects of KBT-3022 appear to be promising for the treatment of patients with ischemic vascular disease.

Published
1995

39. Protective Effect of KBT-3022, a New Cyclooxygenase Inhibitor, in Cerebral Hypoxia and Ischemia

Author

Noriko Yamamoto, Koichi Yokota, Akira Yamashita, Minoru Oda, and Mikio Yoshidomi

Subjects
Male, Cell Survival, Ischemia, Pharmacology, Hippocampal formation, Gerbil, Hippocampus, Brain Ischemia, Mice, Adenosine Triphosphate, Oral administration, medicine, Animals, Pyrroles, Enzyme Inhibitors, Hypoxia, Dose-Response Relationship, Drug, biology, business.industry, Cerebrovascular disorder, Cerebral hypoxia, Hypoxia (medical), medicine.disease, Thiazoles, Anesthesia, biology.protein, Cyclooxygenase, medicine.symptom, business
Abstract

The protective effect of KBT-3022 (ethyl 2-[4,5-bis-(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate), a new cyclooxygenase inhibitor, in cerebral hypoxia and ischemia was studied and compared with those of indomethacin and acetylsalicylic acid (ASA). Oral administration of KBT-3022 (3-100 mg/kg) and indomethacin (3 and 10 mg/kg) significantly prevented KCN-induced death in mice, while ASA (100mg/kg) had no effect. KBT-3022 (3 and 10 mg/kg, p.o.) and indomethacin (10 mg/kg, p.o.) significantly prolonged the survival time of mice subjected to normobaric hypoxia, while ASA (100 mg/kg, p.o.) had no effect. KBT-3022 (3-30 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.) significantly ameliorated delayed neuronal death in the gerbil hippocampal CA1 sector after occlusion of bilateral carotid arteries for 5 min, while ASA (300 mg/kg, p.o.) had no effect. KBT-3022 (10 mg/kg, p.o.) significantly inhibited ATP depletion in the gerbil hippocampus after a 1-min occlusion of bilateral carotid arteries, but had no effect on ATP depletion after a 5-min occlusion and the recovery during recirculation. These results show that KBT-3022 exerts protective effects against cerebral anoxia and hypoxia and ameliorates delayed neuronal death in the hippocampus. KBT-3022 may therefore be useful for prophylaxis of ischemic cerebrovascular disorders.

Published
1995

41. From Universe to Human Brain

Author

Minoru Oda

Subjects
Physics, medicine.anatomical_structure, media_common.quotation_subject, medicine, Microscopic imaging, General Physics and Astronomy, Astronomy, General Medicine, Astrophysics, Human brain, General Agricultural and Biological Sciences, Universe, media_common
Published
1995

42. Anti-thrombotic Activity of KBT-3022 in Experimental Models of Thrombosis

Author

Koichi Yokota, Minoru Oda, and Akira Yamashita

Subjects
Male, Extracorporeal Circulation, Ticlopidine, Guinea Pigs, Indomethacin, Mice, Inbred Strains, In Vitro Techniques, Pharmacology, Guinea pig, Ticlopidine Hydrochloride, Mice, Oral administration, medicine, Animals, Cyclooxygenase Inhibitors, Pyrroles, Thrombus, ED50, Arachidonic Acid, Aspirin, business.industry, Thrombosis, medicine.disease, Thiazoles, Venous thrombosis, Anesthesia, Silver Nitrate, Rabbits, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

In this study, we investigated the effects of KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate), a potent and long-lasting anti-platelet agent, in several experimental thrombosis models and compared them with those of other anti-platelet drugs. Oral administration of KBT-3022 prevented arachidonic acid-induced death due to pulmonary embolism in mice and rabbits with respective ED50 values of 0.29 and 0.12 mg/kg. The protective effect of acetylsalicylic acid (ASA) against mortality was weaker than that of KBT-3022, and ticlopidine hydrochloride (TP) showed no such effect in these models. In a guinea pig arterio-venous shunt model, the inhibition by KBT-3022 of thrombus formation on a silk thread inserted into the shunt was dose-dependent and 300 and 30 times more potent than the inhibition obtained with ASA and indomethacin, respectively. In a model of aortic thrombosis induced by perivascular application of 20% silver nitrate solution, KBT-3022 (1 mg/kg, p.o.) inhibited thrombus formation significantly, ASA (100 mg/kg, p.o.) tended to inhibit it, and TP had no effect. However, in a stasis-induced venous thrombosis model in guinea pigs, TP inhibited thrombus formation significantly, but KBT-3022 and ASA were ineffective. These results suggest that KBT-3022 may be a useful drug for the treatment and/or prophylaxis of thrombus formation in shunts and aortic thrombosis.

Published
1995

44. 0.8nm EOT and High Hole Mobility of Ge P-MISFETs Using HfAlO/GeOx/Ge Gate Stacks Formed by Plasma Oxidation and Atomic Layer Deposition

Author

Minoru Oda, Tsutomu Tezuka, Yuuichi Kamimuta, Yoshihiko Moriyama, and Keiji Ikeda

Subjects
Electron mobility, Materials science, Silicon, business.industry, Gate stack, chemistry.chemical_element, Plasma, Hafnium compounds, Atomic layer deposition, chemistry, Trap density, Electronic engineering, Optoelectronics, business, MISFET
Abstract

HfAlO/GeOx/Ge p-MISFETs with EOT of 0.84nm are demonstrated. Low interface trap density of GeOx/Ge interface enable us to high mobility. Careful control of high-k fixed charges will allow achieving low EOT and high mobility of Ge p-MISFETs.

Published
2012

45. Fabrication of Bonded GeOI Substrates with Thin Al2O3/SiO2 Buried Oxide Layers

Author

Akira Sakai, Minoru Oda, Tsutomu Tezuka, Keiji Ikeda, Toshifumi Irisawa, Yoshihiko Moriyama, Yoshiaki Nakamura, and Yuuichi Kamimuta

Subjects
Electron mobility, Fabrication, Materials science, Silicon, business.industry, chemistry.chemical_element, Polishing, Capacitance, Buried oxide, Atomic layer deposition, chemistry, Transmission electron microscopy, Electronic engineering, Optoelectronics, business
Abstract

Thin-body GeOI substrates with thin Al2O3/SiO2 BOX layers are successfully fabricated for the first time. It is found that the bonding interface was robust enough for Mechanical Polishing and CMP even after bonding at a room temperature in atmosphere. The GeOI surfaces etched with ozone water are atomically flat. Moreover, Dit of as low as 3.9e+11 eV-1cm-2 at the GeOI/BOX is obtained. These results suggest that negligible negative impact on carrier mobility and sub-threshold characteristics can be realized by using the GeOI substrates with thin Al2O3/SiO2 BOX layers.

Published
2012

46. Uniaxially Strained Ge-Rich SiGe Nanowire Channel Technology for High-Performance CMOS

Author

Minoru Oda, Tsutomu Tezuka, Yoshihiko Moriyama, Yuuichi Kamimuta, Keiji Ikeda, and Toshifumi Irisawa

Subjects
Electron mobility, Materials science, business.industry, Nanowire, Electrical engineering, Silicon on insulator, Silicon-germanium, chemistry.chemical_compound, chemistry, CMOS, Logic gate, Low-power electronics, Optoelectronics, business, Communication channel
Abstract

Hole-mobility and carrier-velocity characteristics of Ge-rich SGOI-nanowire were comprehensively investigated. The Ge-rich SGOI-nanowire channel devices were found to have higher hole-mobility and velocity than that of the unstrained-Ge and SOI devices. The ideal performance assessment revealed that a significant increase (over 2.6 times) in drive current is expected. These indicate that the Ge-rich uniaxially strained SGOI-nanowire channel device has potential to paves the way to future low-power consumption and high-performance CMOS technology.

Published
2012

47. High-mobility and low-parasitic resistance characteristics in strained Ge nanowire pMOSFETs with metal source/drain structure formed by doping-free processes

Author

Minoru Oda, Mizuki Ono, Daisuke Kosemura, Tsutomu Tezuka, Yoshihiko Moriyama, Atsushi Ogura, Koji Usuda, Toshifumi Irisawa, Yuuichi Kamimuta, and Keiji Ikeda

Subjects
Electron mobility, Materials science, Electrical resistivity and conductivity, Saturation current, business.industry, Schottky barrier, Parasitic element, MOSFET, Doping, Electronic engineering, Nanowire, Optoelectronics, business
Abstract

Metal source/drain (S/D) Ge nanowire MOSFETs with a compressive strain as high as 3.8% were fabricated by the 2-step Ge-condensation technique without intentional doping for the S/D. Record high inversion hole mobility (μ eff = 855 cm2/Vs @ N s = 5×1012cm−2) and saturation drain current 731µA/µm at V d =−1V were achieved among Ge nanowire pFETs ever reported. It is found that the extremely low contact resistivity ρ c ∼ 4×10−8O cm2 for the Schottky contact contributes to the high saturation current as well as the high mobility.

Published
2012

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