Have the courage to pursue your highest goal

Have the courage to pursue your highest goal tài liệu, giáo án, bài giảng , luận văn, luận án, đồ án, bài tập lớn về tất...

Glycolipids with nonreducing end a-mannosyl residues that have the potential to activate invariant Va19 NKT cells Michio Shimamura 1 , Yi-Ying Huang 1 , Naoki Okamoto 1 , Yutaka Watanabe 2 , Yoshiko Murakami 3 , Taroh Kinoshita 3 , Yoshio Hirabayashi 4 , Chikara Murakata 4 , Yukishige Ito 4 and Tomoya Ogawa 4 1 Developmental Immunology Unit, Mitsubishi Kagaku Institute of Life Sciences, Machida, Japan 2 Faculty of Engineering, Ehime University, Matsuyama, Japan 3 Research Institute for Microbial Diseases, Osaka University, Suita, Japan 4 Riken (The Institute of Physical and Chemical Research), Wakou, Japan Natural killer T (NKT) cells are defined as lympho- cytes bearing both the common NK marker NK1.1, a product of a member of the NKR-P1 gene family, and T cell receptor (TCR)–CD3 complex [1]. Cells forming the major component of NKT cells [NK1.1 + Va14- Ja18 invariant TCR a + cells (Va14 NKT cells)] Keywords glycolipid; immune response; invariant TCR a; MHC class Ib; NKT cell Correspondence M. Shimamura, 11 Minamiooya, Machida, Tokyo 194-8511, Japan Fax: +81 42 724 6317 Tel: +81 42 724 6348 E-mail: michio@libra.ls.m-kagaku.co.jp (Received 26 January 2007, revised 4 April 2007, accepted 5 April 2007) doi:10.1111/j.1742-4658.2007.05826.x We have previously demonstrated that a-mannosyl ceramide and its deriva- tives promote immune responses of NK1.1 + invariant Va19-Ja33 T cell receptor (TCR) a + T cells (Va19 NKT cells). In this study, attempts were made to determine the structural requirements for natural ligands for Va19 NKT cells. Naturally occurring and synthetic glycolipids were analyzed for their ability to stimulate the cells prepared from invariant Va19-Ja33 TCR transgenic mice, in which development of Va19 NKT cells is facilitated. As a result, a-mannosyl phosphatidylinositols such as 2,6-di-a-mannosyl phos- phatidylinositol and a-mannosyl-4a-glucosaminyl-6-phosphatidylinositol (a-Man-GlcNH 2 -PtdIns) as well as a-mannosyl ceramide derivatives were found to activate the cells from the transgenic mouse liver, gut lamina pro- pria and spleen in vivo and in vitro. Thus, glycolipids with nonreducing end a-mannosyl residues are suggested to be potent antigens for Va19 NKT cells. Next, a series of invariant Va19-Ja33 TCR + hybridomas, each with variations in the sequence of the Va-Ja junction and the TCR b chain, were tested for responsiveness toward the a-mannosyl glycolipids. A loose correlation between the primary structure of the TCR and the reactive glycolipids was observed. For instance, hybridomas expressing TCRs consisting of an a chain with a variation in the Va19-Ja33 junction and a Vb6 + b chain showed affinity towards a-mannosyl ceramide and a-Man- GlcNH 2 -PtdIns, whereas those expressing TCRs with an invariant Va19-Ja33 a chain and a Vb8 + b chain responded to 2,6-di-a-mannosyl phosphatidylinositol. Thus, it is suggested that Va19 NKT cells with micro- heterogeneity in the TCR structure have been generated for defense against various antigens expressing a-mannosyl glycolipids. Abbreviations a-GalCer, a-galactosyl ceramide; a-ManCer, a-mannosyl ceramide; a-ManCer(Phe), N-[1-(a-mannosyloxymethyl)-3-(4-octylphenyl)propyl] hexadecanamide; a-Man-GlcNH 2 -PtdIns, a-mannosyl-4a-glucosamine-6-phosphatidylinositol; (a-Man) 2 -PtdIns, 2,6-di-a-mannosyl phosphatidylinositol; b2m, b 2 -microglobulin; GPI, glycosylphosphatidylinositol; IFN, interferon; IL, interleukin; LAM, lipoarabinomannan; LPL, lamina propria lymphocyte; MNC, mononuclear Have the courage to pursue your highest goal Have the courage to pursue your highest goal Bởi: Joe Tye “You connect with your highest goal when you awaken full of enthusiasm for the day and when you know you are making a contribution It is synonymous with being in the flow, periods in which you are so totally absorbed with what you are doing that time stops and fulfillment comes naturally It is making your life itself a work of art.” Michael Ray: The Highest Goal: The Secret that Sustains You in Every Moment The single most important class I’ve ever taken I wasn’t even registered for – I was a stowaway When I was at the Stanford Graduate School of Business in 1984, by far the most popular course was Michael Ray’s class on Creativity in Business (he was also author of the bestselling book of the same title) I didn’t even make the waiting list So I showed up anyway and sat on the floor at the back of the room While it was not policy to allow students to audit classes that had been fully subscribed, this being a course on creativity we came to an agreement on how I could participate, since I’d shown up (remember – Woody Allen says 90 percent of success is simply showing up) Twenty years later I was Michael’s guest speaker for his last class before he retired In the interim I’d founded (created) a nonprofit organization to fight the tobacco industry and the company that is now Values Coach Inc I know I never would have done either had it not been for what I learned – both about the world and about myself – by auditing Michael’s class The night before that class Michael and I went out for dinner I told him that in the years since school I’d come to realize that his wasn’t really a class about creativity, it was a class about courage He gave me a conspiratorial wink and said, “Don’t tell anyone – they never would have let me teach a course about courage.” It’s too bad, really, that we don’t teach courses on courage and perseverance in school Nothing is more important – especially when your world is upside down For an eloquent poem about highest goals watch Taylor Mali perform What Teachers Make 1/1 TeAm YYePG Digitally signed by TeAm YYePG DN: cn=TeAm YYePG, c=US, o=TeAm YYePG, ou=TeAm YYePG, email=yyepg@msn.com Reason: I attest to the accuracy and integrity of this document Date: 2005.03.16 13:04:26 +08'00' How toGet Your Competition Fired (without Saying Anything Bad about Them) ffirs.qxd 11/30/04 10:03 PM Page i ffirs.qxd 11/30/04 10:03 PM Page ii How toGet Your Competition Fired (without Saying Anything Bad about Them) Using The Wedge ® to Increase Your Sales Randy Schwantz John Wiley & Sons, Inc. ffirs.qxd 11/30/04 10:03 PM Page iii Copyright © 2005 by Randy Schwantz. All rights reserved. Published by John Wiley & Sons, Inc., Hoboken, New Jersey. Published simultaneously in Canada. The Wedge ® , The Wedge ® logo, and Selling Is a Contact Sport ® are registered trademarks of Schwantz and Associates, Inc. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 646-8600, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008. 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HF5438.25.S3392 2005 658.85—dc22 2004017334 Printed in the United States of America. 10987654321 ffirs.qxd 11/30/04 10:03 PM Page iv To Lori, one of the world’s greatest jugglers, a champion of kids, horses, and basketball, my pillar, the apple of my eye, my one and [...]... examine the issue of trust When I talk to groups about the importance of being vulnerable, there’s always a flood of questions about the need for trust: How do I know if I can trust someone enough to be vulnerable? ” “I’ll only be vulnerable with someone if I’m sure they won’t turn on me.” How can you tell who’s got your back?” How do we build trust with people?” The good news is that the answers to these... from the data The bad news is that it’s a chicken-or -the- egg issue: We need to feel trust to be vulnerable and we need to be vulnerable in order to trust There is no trust test, no scoring system, no green light that tells us that it’s safe to let ourselves be seen The research participants described trust as a slow-building, layered process that happens over time In our family, we refer to trust as the. .. sense of the world I am only as good as the number of “likes” I get on Facebook or Instagram Because we are all vulnerable to the messaging that drives these behaviors, this new lens takes away the us-versus-those-damn-narcissists element I know the yearning to believe that what I’m doing matters and how easy it is to confuse that with the drive to be extraordinary I know how seductive it is to use the. .. worthy of love and belonging They don’t have better or easier lives, they don’t have fewer struggles with addiction or depression, and they haven’t survived fewer traumas or bankruptcies or divorces, but in the midst of all of these struggles, they have developed practices that enable them to hold on to the belief that they are worthy of love, belonging, and even joy 3 A strong belief in our worthiness... have to offer isn’t enough without the bells and whistles, without editing, and impressing I was afraid to walk on that stage and show the audience my kitchen-table self—these people were too important, too successful, too famous My kitchen-table self is too messy, too imperfect, too unpredictable Here’s the crux of the struggle: I want to experience your vulnerability but I don’t want to be vulnerable. .. inclination is to cure the narcissists” by cutting them down to size It doesn’t matter if I’m talking to teachers, parents, CEOs, or my neighbors, the response is the same: These egomaniacs need to know that they’re not special, they’re not that great, they’re not entitled to jack, and they need to get over themselves No one cares (This is the G-rated version.) Here’s where it gets tricky And frustrating... Wholehearted They attribute everything—from their professional success to their marriages to their proudest parenting moments to their ability to be vulnerable I had written about vulnerability in my earlier books; in fact, there’s even a chapter on it in my dissertation From the very beginning of my investigations, embracing vulnerability emerged as an important category I also understood the relationships between... excruciating to exquisite, but for me it’s been worth every step What we all share in common—what I’ve spent the past several years talking to leaders, parents, and educators about—is the truth that forms the very core of this book: What we know matters, but who we are matters more Being rather than knowing requires showing up and letting ourselves be seen It requires us to dare greatly, to be vulnerable The. . .THE phrase Daring Greatly is Making the Most Out of Seo to Achieve Your Content Goals #seoforcontent AT #confabEU BY @aleyda FROM @orainti hell0 #confabEU #seoforcontent AT #confabEU BY @aleyda FROM @orainti WHO’S THIS SEO AMONG SO MANY CONTENT SPECIALISTS? 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