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Overview Find Happy Eggs Tame the Fatal Bugs Help Festival Decoration Happy Pet Vending Machine Overview Juno 市民はあらゆる動物実験を快く思わず、実験用だった全ての動物達をペットとして放出する事にした 訳注 ： 各街に２人ずついる Festival Guide と話すと、Happy Three Leaf Clover １個と引き換えに Juno へ転送してくれるただ、各クエストの必要 Base レベルは20だが Juno から出られるフィールドはレベル80前後の狩り場なので注意 Find Happy Eggs 必要条件 Base Lv 20 狩り対象 Happy Egg 10体 報酬 アイテム Clover Ticket ３個 このクエスト若しくはインスタンスは反復可能(*1) 1. Member of Happy Egg Festival (/navi yuno 175/162) と話して、Happy Egg を10体退治して欲しいという彼女の要請を受ける 2. 退治を完了して彼女の所へ戻ると、報酬として Clover Ticket を３個もらえる Tame the Fatal Bugs 必要条件 Base Lv 20 アイテム Something Fatal 狩り対象 Strange Egg(*2) 報酬 アイテム Clover Ticket ３個 このクエスト若しくはインスタンスは反復可能 1. Festival Guide (/navi yuno 142/55) と話して、Strange Egg から出て来るヤバい虫の捕獲 (つまりは退治) を引き受ける 2. アイテム D. Burger を使いヤバい虫を誘き寄せて10匹分 Something Fatal に変え、彼の所へ戻ると Clover Ticket を３個もらえる 彼に虫を30匹取り戻してやる(*3)と、お礼に Costume Egg Crispinette がもらえる Note D. Burger は Festival Guide に Something Fatal を10個引き渡すまで無くなる(*4)事は無い その後の進行を楽にしたいのであれば Something Fatal の在庫を更に増やしておくといいだろう Something Fatal はアイテム説明の中身と違ってキャラクター固定ではない Help Festival Decoration 必要条件 Base Lv 20 アイテム Happy Three Leaf Clover 10個 狩り対象 Clover Poporing Clover Lunatic 報酬 アイテム Clover Ticket ３個 このクエスト若しくはインスタンスは反復可能 1. Festival Deco Expert (/navi yuno 165/153) と話して Happy Three Leaf Clover を10個持って来る事を引き受ける 2. Clover Poporing や Clover Lunatic からブツを10個狩り集めて(*5)Festival Deco Expert に渡すと、報酬として Clover Ticket を３個もらえる Note Happy Three Leaf Clover はアイテム説明とは違ってキャラクター固定ではない Happy Pet Vending Machine 1. Happy Pet Vending Machine (/navi yuno 176/152) をクリックすると Clover Ticket １個につき Lovely Egg Box １個と交換される Box の中から出る物は下記の通り(*6) Small Doll Needle (Teddy Bear 捕獲用) Costume Green Clover Hat Chocolate Egg (HP 回復アイテム)(*7) Tasty Cookie Egg (SP 回復アイテム)(*8) Holy Egg Contract in Shadow - Deviruchi Deadly Noxious Herb - Poison Spore Delicious Shaved Ice - Marionette Dew Laden Moss - Spore Earthworm the Dude - Picky Fatty Chubby Earthworm - Peco Peco Girl Doll - Miyabi Doll Girl s Naivety - Incubus Her Heart - Bongun No Recipient - Munak Old Broom - Dokebi Orange Juice - Drops Rainbow Carrot - Lunatic Soft Apron - Alice Sweet Milk - Savage Bebe Sweet Potato - Smokie Tantan Noodle - Green Maiden Tropical Banana - Yoyo Very Red Juice - Loli Ruri Well-Dried Bone - Baby Desert Wolf Categories Repeatable Quests | Quest Window Quests
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Happy New Genesis Happy New Genesis アーティスト ティクニウトリ・ショロトル 発売日 2019年8月28日 レーベル アニプレックス CDデイリー最高順位 3位(2019年8月29日) 週間最高順位 3位(2019年9月3日) 月間最高順位 13位(2019年8月) 年間最高順位 108位(2019年) 初動総合売上 14453 累計総合売上 21489 収録内容 曲名 タイアップ 視聴 1 Happy New Genesis GRANBLUE FANTASY キャラソン CD/総合ランキング 週 月日 CDシングル 総合シングル 順位 週/月間枚数 累計枚数 順位 週/月間枚数 累計枚数 1 9/3 3 14169 14169 3 14453 14453 2019年8月 7 14169 14169 13 14453 14453 2 9/10 8 2416 16585 16 2465 16918 3 9/17 8 1204 17789 20 1204 18073 4 9/24 10 756 18545 19 756 18829 5 10/1 17 547 19092 28 547 19376 2019年9月 14 4923 19092 29 4923 19376 6 10/8 341 19433 341 19717 7 10/15 215 19648 215 19932 8 10/22 254 19902 254 20186 9 10/29 219 20121 219 20405 10 11/5 171 20292 171 20576 2019年10月 1200 20292 72 1200 20576 10 12/24 154 20446 154 20730 11 12/31 133 20579 133 20863 12 20/1/7 114 20693 114 20977 13 1/14 148 20841 148 21125 14 1/21 137 20978 137 21262 15 4/14 97 21075 97 21359 16 4/21 59 21134 59 21418 17 5/5 71 21205 71 21489 関連CD Never Ending Fantasy
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Happy Summer Days 原題：Happy Summer Days 発売：1992年6月19日 概要 アウトドアをテーマとした作品を収録したビデオソフト。『Walt Disney Cartoon Classics』として発売された。日本未発売。 北米では『Fun on the Job!』『The Goofy World of Sports』とセットでLD化されている。 収録内容 グーフィーのライオン狩り ドナルドとアリの王国 ミッキーの魚釣り グーフィーのバケーション
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Happy Morning 歌詞：りこぴん氏 対応曲：3-419氏type1.mp3 a 00 15 毎朝わたしはジョギングしてるの 筋肉（まっする♪）がないから a 00 26 いつでも同じ道を 走っているから いつでも会う人は同じ b 00 37 でも今日は違う人が一人で走ってたよ 素敵なその子にひとめぼれしちゃうの c 00 49 それから毎朝走るのが楽しみ 「おはよう」って声かけるだけだけれど c 1 00 だんだん体力とかもついてきたかなぁ 明日も早起きをして走りたいな
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タグ 明るい 曲名H 歌 榊原ゆい 作詞 wight 作曲 mo2 作品 HAPPY WARDROBEイメージソング Happy Wardrobe ORIGINAL SOUND TRACK
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Risk Management 101 Loss FinancingInsurance Self-Insurance / Non-Insurance Retention / Deductibles Contractual Transfer / Hold Harmless Indemnification Loss ControlLoss PreventionSafety Committee Risk Evaluation / Analysis Loss ReductionSubrogation Claim Administration Negotiations with the Insurer Household Finance and Financial Literacy-Related Organization National Council on Economic EducationNECC Survey US Financial Literacy and Education Commission Survey of Consumer Finances Federal Reserve Bank Consumer Information Pages National Association of Economic Educators Statistical Abstract of the United States Financial Literacy Legislation Paper Papers by Annamaria Lusardi Douglas Bernheim et. al(2001). "Education and Saving The Long-Term Effects of High School Financial Curriculum Mandates", Journal of Public Economics Other Fiscal Year 2001-2009 State Tables for the U.S. Department of Education Education Statistics Bankruptcy StatisticsBankruptcy Abuse Prevention and Consumer Protection Act of 2005 (BAPCPA) 日本における消費者教育 Other Study Guides Gary Becker's Price Theory/ゲイリー・ベッカー流価格理論 Health Risk Decision Analysis/健康リスク意思決定分析 Health Economics in the U.S and Europe/アメリカとヨーロッパの医療経済学 Health Economics in Japan and Asian Countries/日本とアジアの医療経済学 Demography/人口学 Global Health/グローバル・ヘルス Environmental Economics/アメリカの環境経済学 Law and Economics/法と経済学 Global and Domestic Health Law/グローバル・国内医療法 Empirical Microeconomics/実証ミクロ経済学 Social Insurance/社会保険
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乗り物 アクセサリ アバター 傭兵 乗り物 画像 アイテム名 グロ鯖 日本鯖 #ref error ：ご指定のファイルが見つかりません。ファイル名を確認して、再度指定してください。 (cow.jpg) タウルス4種Wild Taurus ○ ○ ルドルフ- - ○ TATSUMAKI- - ○ ウルスUrus ○ ○ -Ent ○ ○期間限定イベント褒章 -Ghoul Bear ○ - コロッサスColossus ○ ○期間限定イベント褒章 ゴーレムGolem ○ ○ マンティコアManticore ○ ○ MVPカー- - ○期間限定イベント褒章 ハンタークルーザーChopper ○ ○ 手裏剣Ninja Star ○ ○ セイバートゥースSabretooth ○ ○ APUAPU ○ ○ 魔法のほうき（永久）- - ○ ヒドラHydra ○ ○ マルスMars Rider ○ ○ ユニコーンUnicorn ○ ○ ヘリウスのグリフォンHelios Griffin ○ ○ 白虎Snow Tiger ○ ○ マーキュリーMercury Rider ○ ○ 戦闘型 白虎Armed Snow Tiger ○ ○ 戦闘型火山ラプトルArmed Volcanic Raptor ○ ○ 火山ラプトルVolcanic Raptor ○ ○ 戦闘型ビザンティンエレファントArmed Byzantine Elephant ○ ○ ビザンティンエレファントByzantine Elephant ○ ○ 地獄馬Hell Horse ○ ○ 天馬Heavenly Horse ○ ○ シャイアShire ○ ○ ハクニーHackney ○ ○ サラブレッドThroughbred ○ ○ アクセサリ 画像 アイテム名 グロ鯖 日本鯖 -Blue Dragon Wings ○ - もふもふりゅっく- - ○ -Swordmaster s Wings ○ ○ -Lilith s Wings ○ - -Arms of Blight ○ - 白龍の翼White Dragon Wings ○ ○ 白虎カバンTiger Cub Bag ○ ○ アレスの翼Ares Wings ○ ○ メフィストの十字架Mephisto s Cross ○ ○ 手裏剣の飾りNinja Blades ○ ○ 子犬バッグPuppy Bag ○ ○ ヒドラの翼Hydra s Wings ○ ○ アルゴスの翼Argo s Wings ○ ○ ミカエルの翼Michael s Wings ○ ○ ネコバッグKitty Bag ○ ○ ルシファーの翼Lucifer s Wings ○ ○ 光の翼Wings of Light ○ ○ 漆黒の翼Wings of DarknessUnicorn ○ ○ アバター 女性 男性 アイテム名 グロ鯖 日本鯖 黒ミサドレス ○ ○ Detective outfit ○ ○ 聖獣の神秘装飾衣- - ○ 特撮ヒーロースーツ- - ○ クーロンウェア- - ○ 海賊ロックウェア- - ○ マリーンズユニフォーム- - ○ 夏の思い出- - ○ 忍装束- - ○ アメフトユニフォーム- - ○ -Detective Outfit ○ - もSanta Costume ○ ○クリスマス限定 アニマルコスチュームAnimal Outfit ○ ○ -Festive Swimsuit ○ - ホワイトゴシックドレスWhite Gothic Outfit ○ ○ハンドブック特典 帝国軍礼式軍服もOfficer Uniform ○ ○ -Trojan Outfit ○ ○トロイイベント特典 -Zorro Outfit ○ -Coming soon バウンティハンターウェアOutlaw Costume ○ ○ 銃士隊衣装Musketeer Outfit ○ ○ 学生服School Uniform ○ ○ ゾンビ衣装Zombie Outfit ○ ○イベント限定 忍者服Ninja Outfit ○ ○ キュートなウサギ服Cute Bunny Costume ○ ○ 保安官衣装Sheriff Outfit ○ ○ 海賊服Pirate Costume ○ ○ グレースのドレスGrace Costume ○ ○ -Shogun Outfit ○ - アパッチドレスNative American Costume ○ ○ チャイナドレスChangshan Costume ○ ○ メイド服Maid Uniform ○ ○ ゴシックドレスGothic Outfit ○ ○ 深紅の夜会服Scarlet Costume ○ ○ 優雅な貴族服Elegant Victorian Costume ○ ○ ディーラースーツCasino Outfit ○ ○ キョンシー服Jiangshi Outfit ○ ○ 水着Swimsuit ○ ○ 傭兵 Copyright © 2008 NEXON Co., Ltd. All Rights Reserved. Copyright © 2008 NDOORS Corporation. All Rights Reserved.
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Question What is the phosphatase of PTEN? What is the casein kinase activator or inhibitor? What is the proteins which bind to PTEN? Answer p53, Casein kinase 2, and so on. PTEN is dephospharylated by insulin-like growth factor and maybe activated. SHIPとの関係は？ 総説を読んで。 CSの共同体のCSの判断基準において、mental retardation はminor criteriaに入っている。ということは、それほどCSにおいて、mental retardationは重要なphenotypeではないらしい。これは、ちょっと残念。 結晶構造解析の結果から、C2ドメインとホスファターゼドメインはくっついている。 C2ドメインmutationも同様にCSで見られる。point mutation ではなくてnonsence mutation and deletion mutationである。おそらく、C2ドメインはPSなどにくっつくのではないかと推測されていて、膜に行くことができないために、CSになるのではないかと推測される。 ちなみに、ホスファターゼドメインはアルファへリックス。 C2ドメインはベータシートがメインだね。 PTENのタンパク質の安定性は、S380, 382,383のリン酸化による。 カゼインキナーゼが370, 380, 383, 385をリン酸化する。 366はGSK3bによってリン酸化される。 370, 380, 385はCK2によってリン酸化される。 Some author said that 380, 382, 383 and 385 is phosphorylation site. 383 is dephosphorylated by PTEN itself and regulates migration activity(science 2003). 1. History of PTEN PTEN is the acronym of phosphatase and tensin homologue on chromosome 10. PTEN was cloned from three groups in 1997 as a tumor suppressor for gliomas. rat PTEN homo sapiens PTEN 2. What is PTEN gonna cause? PTEN germline mutations are associated with Cowden disease, Bannayan-Zonana syndrome and Lhermitte Duclos disease which gives disorganized hamartomas in various organs. Cowden syndrome patients exist 1/200,000. Mutation of PTEN is a common event in diverse human cancers, occuring in about 50% of glioblastoma, endometrial, prostate carcinoma.Germline mutations in PTEN are associated with the dominantly inherited Cowden syndromes. Cowden syndrome is firstly described in 1963. CS is qutosomal dominant disorder. It was reported that the gene for this disease is in 10q22-q23 using linkage analysis of 12 families in 1996. Main features are macrocephaly and mental retardation. Approximately 80% of CS patients have PTEN mutations. cowden disease syndrome cowden2 PTEN null mice exhibit embryonic lethality. There are a bunch of conditional PTEN KO mice including astrocyte KO mice using GFAP-Cre and dividing neuronal cells KO mice using Nse-Cre. First paper shows LTP reduction and macrocephaly. Second paper indicates that this KO mice exhibit abnormal social interaction like autism and macrocephaly. 3. What is gonna happen when this protein is removed? PTEN KO mice show macrocephaly in organ and cell level as common feature. Morgan Sheng shows that knockdown of PTEN in CA1 pyramidal neuronal cells in hippocampus increases dendrite branching. 4. Molecular mechanism of PTEN The molecular weight of PTEN is 47kDa. The length of amino acids is 403. Domain structure PTEN s crystal structure has been decided. crystal structure of PTEN Starting from N-terminus, PTEN has catalytic domain, C2 domain and PDZ domain. In addition, PIP2 binding domain is there in N terminus. PTEN also has two PEST domain, which is important for PTEN stability. PTEN-PEST domain PTEN was initially believed to be a dual specificity phospho-tyrosine phosphatase (PTP). PTEN phosphorylates denature focal adhesion kinase (FAK) in vitro, and overexpression of PTEN in mammalian cells decreases FAK phosphorylation. In addition Shc has also been proposed as a substrate of PTEN. However PTEN is strikingly poor catalyst toward most artificial PTP substrates. PTEN prefers negatively charged substrates such as PIP3. In addition, it is reported that several frequently occurring missense mutations in Cowden disease (G129E) and in glioblastoma (R15S and R15I)result in a loss of lipid-specific phosphatase activity, whereas PTP activity is largely unaffected. In 2004, there was the paper in which PTEN downregulation causes decrease in expression level of NMDAR1 and NMDAR2B but not NMDAR2A. PTEN directly binds to NR1 and indirectly binds to NR2B. They found out LTP decrease is caused by PTEN RNAi through NR downregulation. Furthermore, they used C124A and G129E mutation of PTEN. C124A is deficient in phosphatase and PIP3 phosphatase activity. C129E is deficient in only PIP3 phosphatase activity. They found out G129E mutation increases LTP, but C124A decrease LTP with electrophysiology. Taken together, it seems that now PIP3 is preferential substrate for PTEN. Basically C2 domain is involved in Ca++-mediated membrane binding. However the C2 domain of PTEN is in a Ca++ independent manner. From this aspect, PTEN C2 domain is similar with one of novel PKC. PTEN C2 domain is known to bind to phospholipid, like PS. This indicates that mutations in C2 domain of PTEN, which leads to Cowden syndrome, causes deficient in PTEN binding to the plasma membrane, resulting in PIP3 increase. PDZ domain ligand gives binding with a bunch of proteins including NMDA receptor, SAP97 and Bazooka directly. About confomational change of PTEN 1. PIP2 binding. some papers shows that PIP2 activates the phosphatase domain via a conformational change. 2. phosphorylation 3. C2 domain 4. binding to other proteins 5. Localization of PTEN PTEN is expressed in cytosol and nuclear. One paper shows that GSK3beta and casein kinase lead to phosphorylation of PTEN, which leads to recruit PTEN and Myosin V complex to plasma membrane, resulting in PTEN activation. 6. post-translational modification It is reported that casein kinase phosphorylates PTEN, which leads to PTEN activation. ubiquitination oxidation 7. what is the effecter of PTEN? FAK and Shc as well as PIP3 have been reported. 8. what is the regulator of PTEN? It is known that GSK3beta and casein kinase regulate PTEN activity. How to answer for question as follows. It is known that protein tyrosine phosphatase is involved in tumore supressor. However, there is no example of PTPase that function as tumour suppressors. 1997, two groups reported PTEN is plausible candidate, which is located in 10p23. PTEN is mutated and deleted in a wide variety of tumours and tumours cell lines. Also germline transmission of mutations in PTEN were observed in Cowden disease. PTEN is dual phosphatase, which substrates is proteins and PIP3. However, PIP3 regulates Akt, which is related to tumour and survival signaling. So, PTEN s main role concerning to tumour suppressor is most likely PIP3 dephosphorylation. At least, it is reported that PTEN regulates Akt kinase activity in hippocampal neuron and increase sensitivity of apoptosis. You said that PIP3 is produced by mGluR pathway. However, restrict to glutamate uncaging, mGluR pathway seems not to relate to structual plasticity. So How is PIP3 produced? Answer Exactly one paper shows that mGluR is not related to structual plasticity using MCPG. However there are several pathway that regulates PIP3 dynamics. About PI3K, Ras binds to PI3K directly and regulates activity of PI3K. About PTEN, CK2 and GSK3b regulate PTEN activity, leading to reducing PIP3. So, PIP3 increase or decreases occurs using these pathway. I think. why PTEN causes something wrong? Because PI3K has a lot of splicing varients and homologue. However PTEN doesn t have. That is why PTEN cause some wrong.. How is PTEN activated? It remains unknow. One paper says that casein kinase phosphorylates PTEN and PTEN MyosinV complex moves to plasma membrane. casein kinase inhibitor is comercially available. I can examine whether PIP3 decrease abolished by casein kinase inhbitor. About SHIP SHIP is abbrebiation of SH2 domain-containing inositol polyphosphate 5-phosphatase. Findings so far published concerning the functional significance of SHIP are largely confined to the hemopoietic system. In brain, SHIP2 is not significantly expressed in hippocampus. SHIP2 And SHIP reduces the amount of PIP3 and Akt activity in glioblastoma cells. SHIP