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https://w.atwiki.jp/hajimaruatrain/pages/111.html
武ノ沢広域鉄道の開発記になるはずだったページです。 ほんものはこちら https //w.atwiki.jp/hajimaruatrain/sp/pages/110.html
https://w.atwiki.jp/taitoku/pages/105.html
HTML HTML HEAD TITLE HTMLについて /TITLE HEAD BODY b ホームページ /b を作る際習得しなければならない言語。 br といっても簡単。 br 全て覚えようとするから難しいのであって、理解するだけなら十分もあれば足りる。 br /BODY /HTML 入門サイト やさしいホームページ入門 関連項目 CSS JavaScript* PHP*
https://w.atwiki.jp/economicsln/pages/16.html
マクロ URLを適当に並べていく money, banking financial market mishkin papers mishkin syllabus Bundesbank Mini-Course on Monetary Economics Topics in monetary theory (Tronto) カリブレーション Northwestern matsuyama http //faculty.wcas.northwestern.edu/~kmatsu/index.html Albany masters http //www.albany.edu/~am755146/teaching.htm 早稲田 yano https //sites.google.com/site/macroeconometrics2011/ 神戸 nakatani 上級マクロ http //www.econ.kobe-u.ac.jp/~nakatani/lecture-note.htm bernenke and mishkin http //www.aeaweb.org/articles.php?doi=10.1257/jep.11.2.97 貨幣と信用の理論 kiyotaki http //www.imes.boj.or.jp/japanese/kinyu/kinyu93.html 一橋 shioji matlab http //www.econ.hit-u.ac.jp/~shioji/kinkei2012.htm intermediate macro http //www.econ.hit-u.ac.jp/~shioji/chukyumacro2011.htm 一橋 abe http //www.ier.hit-u.ac.jp/~nabe/ LSE wouterdenhaan http //www.wouterdenhaan.com/summercourse_material.html
https://w.atwiki.jp/koa_times/pages/38.html
wiki編集時に利用可能なHTMLタグ一部抜粋 brタグ fontタグ brタグ 改行は複数個以上試用することで反映するが、brタグを使うことでの無駄な空白なく改行が可能。 サンプル文章 br / サンプル文章 brタグなし サンプル文章 サンプル文章 brタグあり サンプル文章 サンプル文章 fontタグ 文字サイズ・色が変更可能。 size="XX" XX部分に任意の数字 color="XXXXX" XXXXX部分に任意のカラーコードもしくは色名を指定(red、green、white等) font="XXXXX" XXXXX部分に任意のフォント名 font size= 5 color= #ff0000 face= Impact TESTテスト /font font size= 4 color= green face= HG行書体 TESTテスト /font font size= 6 color= blue face= MingLiU TESTテスト /font TESTテスト TESTテスト TESTテスト imgタグ 画像埋め込みが可能。Markdownでも可能だがサイズ指定などができる。 width="XXX" XXX部分に任意の数字 height="XXX" XXX部分に任意の数字 img src= https //img.atwiki.jp/koa_times/attach/38/12/up0.jpg width= 300 height= 200 サイズ指定300*200 サイズ指定150*100 aタグ(バナー作成) バナー(リンクが埋め込まれた画像)が可能。 バナーの作成方法は下記参照。画像をクリックすると別のページに飛びます。 バナー作成例 a href= https //w.atwiki.jp/koa_times/pages/21.html target= _blank img src= https //img.atwiki.jp/koa_times/attach/38/12/up0.jpg border= 0 width= 300 height= 200 /a 作成されたバナー aタグ(リンク作成) リンクについてはMarkdownでは別タブ指定の記載方法がなぜかアットwiki上で無効のため、外部リンクはaタグ推奨気味。 下記の例をクリックして試してください。 リンク作成例 #Markdown [リンク](https //w.atwiki.jp/koa_times/pages/21.html) #aタグ a href= https //w.atwiki.jp/koa_times/pages/21.html target= _blank リンク /a Markdownで作成したリンク リンク aタグで作成したリンク リンク 管理者追記:こちらもご参照ください
https://w.atwiki.jp/hitkik/pages/23.html
Windows で、HTTPでのやり取りを眺めるツール。 HTTP debug tool IE ---- Fiddler2 http //www.fiddler2.com/Fiddler2/firstrun.asp extension http //www.fiddler2.com/fiddler2/extensions.asp Firefox ---- Firebug 文字コード明示 html lang="ja" まず、 html の中で使用言語を示します。ja は日本語を示します。 日本語以外では en (英語)、fr (フランス語)、de (ドイツ語)、zh (中国語) などがあります。 meta http-equiv="Content-Type" content="text/html; charset=Shift_JIS" METAタグのContent-typeを明示すると同時に文字コードも明示します。 Shift_JIS 以外は EUC-JP, iso-2022-jp (JIS), UTF-8(Unicode) などがあります。 Shift_JIS はアンダーバー。EUC-JP と iso-2022-jp, UTF-8はハイフンです。 × content="text/html;" charset="Shift_JIS" ○ content="text/html; charset=Shift_JIS" 行間を広げる BODY STYLE="line-height 150%" line-heightの活用 div style="font 900 46pt;line-height 6pt;" div style="color #404040;text-indent 50px;" abc /div div style="color #808080;text-indent 100px;" def /div div style="color red;text-indent 150px;" ghi /div /div スタイルシートを使ったテキストフィルタ http //www.tohoho-web.com/css/filter.htm スタイルシートクイックレファレンス http //www.htmq.com/style/index.shtml 以下広告
https://w.atwiki.jp/vocaloidenglishlyric/pages/897.html
【Tags Jesus-P Rin Wonderful ☆ Opportunity tM M】 Original Music title マイレイン English music title My Rain Romaji music title Mai Rein Music Lyrics written, Voice edited by じーざすP (Jesus-P) / ワンダフル☆オポチュニティ! (Wonderful ☆ Opportunity) Music arranged by じーざすP (Jesus-P) / ワンダフル☆オポチュニティ! (Wonderful ☆ Opportunity) Singer(s) 鏡音リン (Kagamine Rin) Click here for the original Japanese Lyrics Romaji lyrics (transliterated by motokokusanagi2009): ano hi watashi tachi wa waratte bakari de otona ni naru koto ga yume mitai datta itsumo itsu no toki demo hanashi tai no wa riyū gaaru hoshigatteru nowa itsumo watashi bakari ne moshi mada wagamama kīte kureru no naraba watashi o samashi te yasashī ame no yōni sotto ureshī koto kanashī koto setsunai koto rakkī na koto ame nochi hare ni naru yōni zenbu mune ni tsume kon de namida no ame yama nai toki wa kimi no sono yasashi kute tsuyoi kasa de mamotte hoshī yo mata waraeru kara sunao tsukamu yōna munashī mainichi motto saki no saki no saki made miyō ame agari no kira kira ni chīsa na me ga tobi dashi te sōzō shite mite hoshī no sukoshi hora karuku naru yo moshi mada wagamama kīte kureru no naraba watashi o samashi te moshi mada wagamama kīte kureru no naraba watashi o mitome te todoi teru? watashi no kimochi todoi teru no? henji ga hoshī yo kokoro o hirai te mite yo nē ureshī koto kanashī koto setsunai koto rakkī nakoto ame nochi hare ni naru yōni zenbu mune ni tsume kon de namida no ame yama nai kara kimi no sono yasashi kute tsuyoi kasa de mamotte hoshī yo dakara hayaku kite [Jesus-P, JesusP, Jiizasu-P, JiizasuP, Wonderful ☆ Opportunity]
https://w.atwiki.jp/goemode/pages/31.html
HTML5とFlashの機能比較 http //clockmaker.jp/blog/2010/02/flash-vs-html5/ --- Apple HTML5デモサイト http //www.apple.com/html5/ (Safariから閲覧可能) --- Icon Generator http //icon-generator.net/ --- beautifl http //beautifl.net/
https://w.atwiki.jp/mrfrtech/pages/11.html
Market Scenario The global Security Analytics Market is expected to expand at a strong 27% CAGR over the forecast period from 2017 to 2023. According to the latest research report from Market Research Future (MRFR). The global security analytics market is expected to reach a valuation of approximately USD 15 billion by 2023, according to the MRFR report. The report profiles the global security analytics market in detail and presents a comprehensive overview of the market for readers. The report presents a detailed analysis of the major drivers and restraints affecting the global security analytics market, including projections of how these key factors are expected to affect the market soon. Request a Free Sample @ https //www.marketresearchfuture.com/sample_request/4211 Competitive Outlook Leading players in the global security analytics market include Alien Vault Inc., Blue Coat Systems Inc., Alert Logic Inc. (Click Security), LogRhythm Inc., Arbor Networks Inc., FireEye Inc., EMC RSA, HP Enterprise, IBM Corporation, and Cisco Systems Inc. Major tech giants such as Cisco, IBM, and HP are making significant investments in the security analytics sector due to the growing use of mobile devices for communication and data sharing. The growing demand for cloud computing and the Internet of Things is also likely to be a major driver for investment in the security analytics sector over the forecast period. Segmentation By application, the global security analytics market is segmented into web security analytics, network security analytics, end point security analytics, application security analytics, and others. The network security analytics segment holds the largest share in the global security analytics market. By service, the global security analytics market is segmented into professional services, consulting, training and education, support and maintenance, and managed services. By organization size, the global security analytics market is segmented into SMEs and large enterprises. By deployment, the global security analytics market is segmented into cloud and on-premise. By end use vertical, the market is segmented into BFSI, healthcare, manufacturing, retail, education, IT and telecommunication, transportation, government and defense, and others. Regional Analysis North America holds the largest share in the global security analytics market. Asia Pacific is expected to exhibit the highest growth rate over the forecast period. Browse Full Report Details @ https //www.marketresearchfuture.com/reports/security-analytics-market-4211 Table of Contents 1Executive Summary 2Scope of the Report 2.1Market Definition 2.2Scope of the Study 2.2.1Research objectives 2.2.2Assumptions Limitations 2.3Markets Structure Continued…. View Similar Report** Internet of Things (IoT) Market By Software (Data Management, Network Management), By Hardware(Sensors, camera), By Services (Manage Services, Professional Services), By Organization Type (Small and Medium Scale Business, Large Scale Business) https //ictmrfr.blogspot.com/2022/03/blockchain-as-service-market-share.html https //ictmrfr.blogspot.com/2022/03/digital-payment-in-healthcare-market.html Rugged Handheld Electronic Devices Market https //www.marketresearchfuture.com/reports/rugged-handheld-devices-market-8047 Industry News The global Security Analytics market Share Report Market Trends has been affected due to the lockdown across the regions. This pandemic situation has hampered the Security Analytics market Share Report Market Growth as well as its productivity, supply chain, and others. Moreover, the global market has lost its investors due to the increasing loss for the products, supply, transportation, workforce, and others. However, in the meantime, the key market players have implied various strategic techniques to boost global market growth. Thus, to meet the global market demands, the global market increased its speed in producing more valuable products for its intended customers. Recently, the global market has stabilized its position in the global market and is expected to register a higher Security Analytics market Share Report Market Size for the forecast period. About Market Research Future At Market Research Future (MRFR), we enable our customers to unravel the complexity of various industries through our Cooked Research Report (CRR), Half-Cooked Research Reports (HCRR), Raw Research Reports (3R), Continuous-Feed Research (CFR), and Market Research Consulting Services. Contact Market Research Future (Part of Wantstats Research and Media Private Limited) 99 Hudson Street, 5Th Floor New York, NY 10013 United States of America 1 628 258 0071 (US) 44 2035 002 764 (UK) Email sales@marketresearchfuture.com Website https //www.marketresearchfuture.com
https://w.atwiki.jp/biones/pages/14.html
参考書 物理数学 物理のための数学 物理入門コース (10) 理工系学生ならほとんど知っているだろう超有名本。 サッサと読める。偏微分方程式の章はふーん、程度に読んでおけばおk。 物理の数学 (岩波基礎物理シリーズ (10) 岩波の新しいシリーズで、上と双璧をなす本?かと思いきや、ベクトル解析の各種定理の証明が2次元だったり、いい加減。 範囲はものすごく広く、関数、1変数の微分積分から複素関数、偏微分方程式まで載ってる。説明は丁寧なところと激しく不親切なところがはっきりしてる。 上の2冊は手っ取り早く数学の知識をつける時と、個別の分野を読んだあとに辞書代わりに使うのに役立つかと。 物理のための応用数学 基本的に初学者を念頭においていない1ステップ上の本。 特殊関数に関してはこれが多分一番わかりやすい本。直行関数系の話から始まる。超幾何合流型微分方程式まで載っているが、全然使わないのですぐ忘れる。グリーン関数も一応載っている。 1章の微分、2章の変分法も応用が載っていて(・∀・)イイ!! 微分積分 (理工系の数学入門コース) 僕は最初新しいシリーズの薩摩さんの方を読んでいたが、どうも問題数が少ないので、こっちを買ってみた(マーケットプレイスで300円くらいだった)。しかも4年の時に・・・・。薩摩さんより範囲は狭いが、多分こっちの方がいいと思う。演習書も買う必要ないし・・・・。 他の分野でも、迷ったらこのシリーズを買っておけばとりあえず大ハズレは無い・・・・と思う。 キーポイント線形代数 (理工系数学のキーポイント) キーポイント行列と変換群 理工系数学のキーポイント (8) 両方ともとにかく読みやすい。一応それなりに範囲はカバーしてる。が、問題が無いので、試験には不向きかと。 下の方もあわせて読むと、よりいいと思う。理論系に行きたい人は早めに読んでおいて損は無いと思う。 なっとくする複素関数 タイトルで馬鹿にしちゃいけません! 留数定理、解析接続、リーマン面までものすごく丁寧に説明してあります。 演習問題も豊富。 図書館で借りただけで持ってないが、岩波のシリーズより、矢野基礎解析より断然よかった。 理工系の基礎数学 (9) あんまり読めてません・・・。日本語の本で、絶版になってない物理向けの群論の本ではベターだと思いました。 微分・位相幾何 理工系の基礎数学 微分形式の計算法はすぐに身につく。序章もわかりやすい。 ベクトル空間がしっかりわかっていればそんなに難しくないはず。 力学・解析力学 力学・解析力学 岩波基礎物理シリーズ (1) 割と早い段階で解析力学を使う。 コンパクトでくどくなく、わかりやすいと思う。 ところどころ難しい箇所があるので飛ばしておk。 正準変換、ハミルトン・ヤコビの偏微分方程式は載ってない。 物理入門コース 1 力学(1) 物理入門コース 2 解析力学(2) 上はものすごく丁寧。ラグランジュ方程式は載ってないので、下の本が必読。 下は、最初はニュートンの方程式からラグランジュ方程式を導く。 変分原理の後はイマイチ。 量子力学を学ぶための解析力学入門 名著。超おススメ。具体的な力学の問題は解けるようにはならない。将来場の理論をやりたい人に特に向いてると思う。 電磁気学 電磁気学の考え方 (物理の考え方) 初学者向けだが個人的にはゲージ変換まで載っているので、これだけで十分。 このシリーズの中では戦闘力がこの本だけインフレしてる。 下の本より新しいせいか、説明もすっきりしてる気がする。 電磁気学 (物理テキストシリーズ) 上との違いは、具体的な問題が多いこと。マクスウエルの応力テンソルとか読んだだけで忘れまくり・・・・・・。最初っから、直線電流をδ関数使ってで計算してる。 熱・統計力学 この分野は苦手極まりないんで・・・・・・・・。 熱力学(三宅) どの本読んでもカルノーサイクルの後あたりでだるくなる・・・・・・。 統計力学 (岩波基礎物理シリーズ) カノニカル分布の議論を古典論で始める教科書は大抵死亡。 この本は離散系(量子論)で議論して、4章で古典論に対応させてるので、わかりやすい。 統計はこれ以外まともに読めた本はなかった。 相対性理論 時空と重力 (物理学の廻廊) タイトルのとおり、一般相対論を見据えてリーマン幾何の解説をしつこいくらい丁寧にしてある。最初のローレンツ変換はダランベルシャンの不変性から導く。 入門書に最適。 相対性理論 岩波基礎物理シリーズ (9)(佐藤勝彦) わかりやすいが、計算が丁寧なところはめちゃ丁寧だけど、省くとこはめっさ省く。変分原理のあたりや、シュバルツシルト解のあたりとか省略が激しい。が、全部無理にトレースする必要もないので、おk。後半は著者の専門の宇宙論。 テンソル形式のマクスウエル方程式もちゃんと書いてある。 量子力学 量子論の基礎―その本質のやさしい理解のために (新物理学ライブラリ) 21世紀の名著の1つ。量子論入門講義の記事のネタにしてる(というかほとんどインスパイア) 大学でやる量子力学の講義とは、だいぶ違います。一般論から話が進むので、面食らう人も多いと思います。量子論一般の教科書ですが、初心者からプロまで使えるらしいです。物理の心得がなくても十分読めると思います。 普通の教科書は 量子力学〈1〉 (猪木・河合、講談社) 学部生の量子力学の教科書の定番の一つになってます。 程度は若干高めで、7章(角運動量)は挫折率が高い事で有名です。ちなみに2巻は基本的に素粒子をやりたい人向けの内容になっています。 この本の6章までの内容と、角運動量、近似法(摂動論、変分法、WKB)を学ぶと、大体量子力学を学んだといって良いと思う。 もっと易しい本になると 初等量子力学 (原島 しょうかぼう) 易しいですが、基本は大体網羅しています。特殊関数の計算も丁寧です。僕が最初の1冊を勧めるとしたらこれでしょう。 場の量子論 Quantum Field Theoryr 易しい・・・と評判。 が、途中でイミフになった。 An Introduction to Quantum Field Theory (Frontiers in Physics) 大学院のM1のゼミの超定番本。 計算はしょりすぎwwwwww 一人じゃ絶対よめねぇwwww 演習場の量子論―基礎から学びたい人のために (SGC Books) (柏) 一番まともに読めた。 つかかってるのは、グリーン関数の知識が必要っぽいとこと、経路積分に出てくるグラスマン数のあたり。 もう少し解説が多ければ神本になるかも・・・・・。 量子場を学ぶための場の解析力学入門 量子力学は粒子を基本変数に取るのに対し、場の量子論は場を基本変数に取る。スピノルや、Noetherの定理、その他もろもろ量子力学と場の量子論のギャップを埋めるための知識が書いてある。 多分、一番重要なのはNoetherの定理で、場の量子論の最初に大抵書いてあるので、理解できれば読む必要は無い・・・・・・とどっかに書いてあった。 新しい版で、最後に経路積分を使った場の量子化が追加されてるが、わからなかった。
https://w.atwiki.jp/tiger/pages/7.html
SOS1-/- mice impair Cdc42 activation in PC12 cells. SOS-/- fly impair the development of eyes. Overexpression of GAB1 exhibit neurite outgrowth, DNA synthesis and survival in PC12 cells. SHCB-deficient animals exhibit a loss of peptidergic and nonpeptidergic nociceptive sensory neurons, Hippocampal long-term potentiation in ShcC mutant mice is significantly enhanced. SHCA controls the size of brain. Cbl-b null mice exhibit the enhancement of long-term memory. SOS1-/- mice impair Cdc42 activation in PC12 cells. 1 Mol Biol Cell. 2005 May;16(5) 2207-17. Epub 2005 Feb 23. Local phosphatidylinositol 3,4,5-trisphosphate accumulation recruits Vav2 and Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth factor-stimulated PC12 cells. Aoki K, Nakamura T, Fujikawa K, Matsuda M. Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. Neurite outgrowth is an important process in the formation of neuronal networks. Rac1 and Cdc42, members of the Rho-family GTPases, positively regulate neurite extension through reorganization of the actin cytoskeleton. Here, we examine the dynamic linkage between Rac1/Cdc42 and phosphatidylinositol 3-kinase (PI3-kinase) during nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Activity imaging using fluorescence resonance energy transfer probes showed that PI3-kinase as well as Rac1/Cdc42 was transiently activated in broad areas of the cell periphery immediately after NGF addition. Subsequently, local and repetitive activation of PI3-kinase and Rac1/Cdc42 was observed at the protruding sites. Depletion of Vav2 and Vav3 by RNA interference significantly inhibited both Rac1/Cdc42 activation and the formation of short processes leading to neurite outgrowth. At the NGF-induced protrusions, local phosphatidylinositol 3,4,5-trisphosphate accumulation recruited Vav2 and Vav3 to activate Rac1 and Cdc42, and conversely, Vav2 and Vav3 were required for the local activation of PI3-kinase. These observations demonstrated for the first time that Vav2 and Vav3 are essential constituents of the positive feedback loop that is comprised of PI3-kinase and Rac1/Cdc42 and cycles locally with morphological changes. Publication Types Research Support, Non-U.S. Gov t PMID 15728722 [PubMed - indexed for MEDLINE] SOS-/- fly impair the development of eyes. 1 Cell. 1991 Jan 11;64(1) 39-48. Genetic dissection of a neurodevelopmental pathway Son of sevenless functions downstream of the sevenless and EGF receptor tyrosine kinases. Rogge RD, Karlovich CA, Banerjee U. Department of Biology, University of California, Los Angeles 90024. We have isolated a dominant mutation in a gene called Son of sevenless (Sos) that is an allele-specific suppressor of the sevenless phenotype. This suppressor function is autonomously required in R7 and is sensitive to the dosage of the Sos and bride of sevenless genes. Loss-of-function alleles of Sos are recessive lethals, but in the eye Sos has a role in R cell development. Mutations in Sos also interact with the Ellipse allele of the Drosophila EGF receptor. We propose a model suggesting that the Sos product is downstream of sevenless and the EGF receptor, and that the dominant suppression results from the overexpression or increased activity of the gene product. Publication Types Research Support, Non-U.S. Gov t Research Support, U.S. Gov t, P.H.S. PMID 1846090 [PubMed - indexed for MEDLINE] Overexpression of GAB1 exhibit neurite outgrowth, DNA synthesis and survival in PC12 cells. 1 J Biol Chem. 1999 Dec 24;274(52) 37307-14. Gab1 mediates neurite outgrowth, DNA synthesis, and survival in PC12 cells. Korhonen JM, Said FA, Wong AJ, Kaplan DR. Montreal Neurological Institute, Brain Tumor Research Centre, Montreal, Quebec H3A 2B4, Canada. The Gab1-docking protein has been shown to regulate phosphatidylinositol 3-kinase PI3K activity and potentiate nerve growth factor (NGF)-induced survival in PC12 cells. Here, we investigated the potential of Gab1 to induce neurite outgrowth and DNA synthesis, two other important aspects of NGF-induced neuronal differentiation of PC12 cells and NGF-independent survival. We generated a recombinant adenovirus encoding hemagglutinin (HA)-epitope-tagged Gab1 and expressed this protein in PC12 cells. HA-Gab1 was constitutively tyrosine-phosphorylated in PC12 cells and induced the phosphorylation of Akt/protein kinase B and p44/42 mitogen-activated protein kinase. HA-Gab1-stimulated a 10-fold increase in neurite outgrowth in the absence of NGF and a 5-fold increase in NGF-induced neurite outgrowth. HA-Gab1 also stimulated DNA synthesis and caused NGF-independent survival in PC12 cells. Finally, we found that HA-Gab1-induced neuritogenesis was completely suppressed by pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) activity and 50% suppressed by inhibition of PI3K activity. In contrast, HA-Gab1-stimulated cell survival was efficiently suppressed only by inhibition of both PI3K and MEK activities. These results indicate that Gab1 is capable of mediating differentiation, DNA synthesis, and cell survival and uses both PI3K and MEK signaling pathways to achieve its effects. Publication Types Research Support, Non-U.S. Gov t PMID 10601297 [PubMed - indexed for MEDLINE] SHCB-deficient animals exhibit a loss of peptidergic and nonpeptidergic nociceptive sensory neurons, 1 Neuron. 2000 Dec;28(3) 819-33. The mammalian ShcB and ShcC phosphotyrosine docking proteins function in the maturation of sensory and sympathetic neurons. Sakai R, Henderson JT, O Bryan JP, Elia AJ, Saxton TM, Pawson T. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, Ontario, Canada. Shc proteins possess SH2 and PTB domains and serve a scaffolding function in signaling by a variety of receptor tyrosine kinases. There are three known mammalian Shc genes, of which ShcB and ShcC are primarily expressed in the nervous system. We have generated null mutations in ShcB and ShcC and have obtained mice lacking either ShcB or ShcC or both gene products. ShcB-deficient animals exhibit a loss of peptidergic and nonpeptidergic nociceptive sensory neurons, which is not enhanced by additional loss of ShcC. Mice lacking both ShcB and ShcC exhibit a significant loss of neurons within the superior cervical ganglia, which is not observed in either mutant alone. The results indicate that these Shc family members possess both unique and overlapping functions in regulating neural development and suggest physiological roles for ShcB/ShcC in TrkA signaling. PMID 11163269 [PubMed - indexed for MEDLINE] Hippocampal long-term potentiation in ShcC mutant mice is significantly enhanced. 1 J Neurosci. 2005 Feb 16;25(7) 1826-35. Hippocampal synaptic modulation by the phosphotyrosine adapter protein ShcC/N-Shc via interaction with the NMDA receptor. Miyamoto Y, Chen L, Sato M, Sokabe M, Nabeshima T, Pawson T, Sakai R, Mori N. Department of Molecular Genetics, National Institute for Longevity Sciences, Oobu 474-8522, Japan. N-Shc (neural Shc) (also ShcC), an adapter protein possessing two phosphotyrosine binding motifs [PTB (phosphotyrosine binding) and SH2 (Src homology 2) domains], is predominantly expressed in mature neurons of the CNS and transmits neurotrophin signals from the TrkB receptor to the Ras/mitogen-activated protein kinase (MAPK) pathway, leading to cellular growth, differentiation, or survival. Here, we demonstrate a novel role of ShcC, the modulation of NMDA receptor function in the hippocampus, using ShcC gene-deficient mice. In behavioral analyses such as the Morris water maze, contextual fear conditioning, and novel object recognition tasks, ShcC mutant mice exhibited superior ability in hippocampus-dependent spatial and nonspatial learning and memory. Consistent with this finding, electrophysiological analyses revealed that hippocampal long-term potentiation in ShcC mutant mice was significantly enhanced, with no alteration of presynaptic function, and the effect of an NMDA receptor antagonist on its expression in the mutant mice was notably attenuated. The tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B was also increased, suggesting that ShcC mutant mice have enhanced NMDA receptor function in the hippocampus. These results indicate that ShcC not only mediates TrkB-Ras/MAPK signaling but also is involved in the regulation of NMDA receptor function in the hippocampus via interaction with phosphotyrosine residues on the receptor subunits and serves as a modulator of hippocampal synaptic plasticity underlying learning and memory. PMID 15716419 [PubMed - indexed for MEDLINE] SHCA controls the size of brain. 1 J Neurosci. 2006 Jul 26;26(30) 7885-97. Neural-specific inactivation of ShcA results in increased embryonic neural progenitor apoptosis and microencephaly. McFarland KN, Wilkes SR, Koss SE, Ravichandran KS, Mandell JW. Department of Pathology (Neuropathology), Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA. Brain size is precisely regulated during development and involves coordination of neural progenitor cell proliferation, differentiation, and survival. The adapter protein ShcA transmits signals from receptor tyrosine kinases via MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) and PI3K (phosphatidylinositol 3-kinase)/Akt signaling pathways. In the CNS, ShcA expression is high during embryonic development but diminishes as cells differentiate and switches to ShcB/Sck/Sli and ShcC/N-Shc/Rai. To directly test ShcA function in brain development, we used Cre/lox technology to express a dominant-negative form of ShcA (ShcFFF) in nestin-expressing neural progenitors. ShcFFF-expressing mice display microencephaly with brain weights reduced to 50% of littermate controls throughout postnatal and adult life. The cerebrum appeared most severely affected, but the gross architecture of the brain is normal. Body weight was mildly affected with a delay in reaching mature weight. At a mechanistic level, the ShcFFF microencephaly phenotype appears to be primarily attributable to elevated apoptosis levels throughout the brain from embryonic day 10.5 (E10.5) to E12, which declined by E14.5. Apoptosis remained at normal basal levels throughout postnatal development. Proliferation indices were not significantly altered in the embryonic neuroepithelium or within the postnatal subventricular zone. In another approach with the same nestin-Cre transgene, conditional deletion of ShcA in mice with a homozygous floxed shc1 locus also showed a similar microencephaly phenotype. Together, these data suggest a critical role for ShcA in neural progenitor survival signaling and in regulating brain size. PMID 16870734 [PubMed - indexed for MEDLINE] Cbl-b null mice exhibit the enhancement of long-term memory. 1 Proc Natl Acad Sci U S A. 2006 Mar 28;103(13) 5125-30. Epub 2006 Mar 20. Enhancement of long-term memory retention and short-term synaptic plasticity in cbl-b null mice. Tan DP, Liu QY, Koshiya N, Gu H, Alkon D. Blanchette Rockefeller Neurosciences Institute, Rockville, MD 20850, USA. dptan@brni-jhu.org The cbl-b gene is a member of the cbl protooncogene family. It encodes a protein with multiple domains, which can interact with other proteins in a variety of signaling pathways. The functions of cbl family genes in the brain are unknown. In this report, we used genetic, immunohistochemical, behavioral, and electrophysiological approaches to study the role of cbl-b in learning and memory. Cbl-b null mice developed normally and had no abnormalities in their locomotor performance. In spatial learning and memory studies, cbl-b null and WT mice performed similarly during training. To test memory retention, two probe trials were used. cbl-b null mice performed slightly better 1 day after training. However, in the probe trial 45 days after training, the cbl-b null group showed significantly higher memory retention than WT mice, suggesting an enhancement of long-term memory. Using electrophysiological approaches, we found there was enhanced paired-pulse facilitation in the Schaffer Collateral-CA1 glutamatergic synapses of the cbl-b null mice. On the other hand, there was no difference in long-term potentiation between the two groups of mice. In summary, we provide evidence that (i) cbl-b protein is concentrated in the synaptic regions of CA1, CA3, and the dentate gyrus of the hippocampus; (ii) cbl-b null mice have enhanced long-term memory; and (iii) cbl-b null mice show an enhancement in short-term plasticity. These results indicate that cbl-b is a negative regulator of long-term memory, and its neuronal mechanism regulates synaptic transmission in the hippocampus. PMID 16549761 [PubMed - indexed for MEDLINE]