3,392 research outputs found

    Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene

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    G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH beta-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH beta-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH beta-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression

    Writing a History of Women's Writing from 700 to 1500

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    How can a history of British women’s writing be written? Such a project must necessarily be collaborative if it is to attempt to be comprehensive, but even then any claim to comprehensiveness has to be qualified: paradoxically the more expansive the history, the more partial it will be. The challenges of writing such a history are perhaps even greater for scholars working in the early periods because we are forced to confront and to rethink many deeply ingrained assumptions about women’s writing. This introductory essay focuses on a period of literary history that is often marginalized in accounts of women’s writing in English: the Middle Ages. It is a widely accepted view that there are only two women writers in English in the period before 1500, and therefore there is little to be said for an age (or ages) when women writers were so much an exception. Furthermore, the two medieval English women writers whose names are widely known, Julian of Norwich (1342/3-after 1416) and Margery Kempe (c.1373-after 1439), did not think of themselves as writers or authors. Nor were they responsible for literature as it is thought of today—they did not compose poetry, or romances, or fiction of any sort. Even these two ‘named’ women writers do not comfortably fit established evolutionary models of women’s literary history over the longue durée, with their emphases on the spread of literacy, the bias towards print culture, and the emergence of the woman poet, and ultimately of the professional author of drama or fiction. Yet the difficulty of locating how the medieval period fits in to literary history is not unique to women’s writing: medieval understandings of authorship, literature, and national identity, and the contexts and processes of writing and textual circulation were quite distinct from later periods and therefore deemed problematic more generally. This essay explores some of these issues and reflects on the difficulties we face writing a history of early women's writing

    Writing a History of Women's Writing from 700 to 1500

    No full text
    How can a history of British women’s writing be written? Such a project must necessarily be collaborative if it is to attempt to be comprehensive, but even then any claim to comprehensiveness has to be qualified: paradoxically the more expansive the history, the more partial it will be. The challenges of writing such a history are perhaps even greater for scholars working in the early periods because we are forced to confront and to rethink many deeply ingrained assumptions about women’s writing. This introductory essay focuses on a period of literary history that is often marginalized in accounts of women’s writing in English: the Middle Ages. It is a widely accepted view that there are only two women writers in English in the period before 1500, and therefore there is little to be said for an age (or ages) when women writers were so much an exception. Furthermore, the two medieval English women writers whose names are widely known, Julian of Norwich (1342/3-after 1416) and Margery Kempe (c.1373-after 1439), did not think of themselves as writers or authors. Nor were they responsible for literature as it is thought of today—they did not compose poetry, or romances, or fiction of any sort. Even these two ‘named’ women writers do not comfortably fit established evolutionary models of women’s literary history over the longue durée, with their emphases on the spread of literacy, the bias towards print culture, and the emergence of the woman poet, and ultimately of the professional author of drama or fiction. Yet the difficulty of locating how the medieval period fits in to literary history is not unique to women’s writing: medieval understandings of authorship, literature, and national identity, and the contexts and processes of writing and textual circulation were quite distinct from later periods and therefore deemed problematic more generally. This essay explores some of these issues and reflects on the difficulties we face writing a history of early women's writing

    Blowout of non-premixed turbulent jet flames with coflow under microgravity condition

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    The blowout behavior of non-premixed turbulent coflow jet flames under microgravity environment was studied experimentally by utilizing a 3.6 s drop tower. Variations of flames leading to liftoff as well as blowout were examined by varying the coflow velocity and compared with those obtained under the normal gravity condition. A modeling work was conducted to incorporate the effects of the gravity (buoyancy) and coflow velocity on blowout behavior. Major findings include: (1) the flame length in microgravity was longer than that in normal gravity and decreased with increasing coflow velocity. The flame in microgravity showed more intense yellow luminosity with larger sooting zone; (2) the flame liftoff height increased with increasing coflow velocity in both gravity levels. The flame base was closer to the burner in microgravity as compared with that in normal gravity; (3) the blowout velocity in microgravity was appreciably larger than that obtained in normal gravity; and (4) a physical model based on Damkohler number was developed by using similarity solutions to characterize the differences in the blowout limits considering both the coflow and gravity (buoyancy) effects. The proposed model can successfully predict the experimental data. This work provided new data and basic scaling analysis for blowout limit of non-premixed turbulent jet flames considering both the coflow and gravity (buoyancy) effects. (C) 2019 The Combustion Institute. Published by Elsevier Inc. All rights reserved

    Charles Berlitz, Author of "Doomsday," Takes Predictions

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    Charles Berlitz, author of "Doomsday," makes predictions that life will cease after 2000 A.D

    A study on the LH-moments for frequency analysis of extreme rainfall in climate change

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    碩士全球受氣候變遷之影響,極端水文事件發生之頻率加劇,無論是高強度之極端暴雨颱洪事件或低流量乾旱事件皆造成頻率分析上之困擾。以傳統之線性動差法(L-moments)進行高極端水文頻率分析時,容易對極端事件之重現期產生不合理之推估結果,因此發展高尾線性動差法(LH-moments)有其必要性,針對分布高尾端之部分加強其權重,使推估之參數更適用於極值部分。LH-moments方法結合三參數之通用極端值分布(Generalized Extreme Value, GEV)進行頻率分析,以提供洪水或暴雨等極端水文事件資料之應用。 本研究針對LH-moments方法結合GEV分布,應用於極端暴雨之頻率分析,加強權重 使高重現期之推測較為合理,並以資料之形狀參數作為判斷資料之指標,提出建議權重 以得到較為合理之重現期,並作為後續資料應用分析之參考。Under global climate change, the frequency of extreme hydrological events such as floods and droughts has increased, complicating frequency analyses. Reasonable estimates of return periods for extreme events cannot be obtained through the use of traditional L-moments method in frequency analyses. Instead, LH-moments method which assigns higher weights to data at extreme ends of the distribution should be applied for parameter estimations. In this research, the LH-moments method is applied in the frequency analysis of extreme rainfall events, in which rainfall data are fitted to 3-parameter generalized extreme value (GEV) distribution model. The weighing factor (m) for data at extreme ends of the distribution is raised in order to obtain better estimation of the return periods. The value of the shape parameter κ is used to determine the weighing factor m, so the most reasonable return period can be obtained. The value of the shape parameter κ would also serve as a reference for follow-up data analysis.謝誌 I 中文摘要 II 英文摘要 III 目錄 IV 表目錄 VI 圖目錄 VII 符號表 VIII 第1章 緒論 1 1-1研究動機與目的 1 1-2文獻回顧 2 第2章 理論基礎 4 2-1線性動差法(L-MOMENTS) 4 2-2高尾線性動差法(LH-MOMENTS) 8 2-3機率權重動差法(PROBABILITY WEIGHTED MOMENTS, PWMS) 9 2-4通用極端值分布(GENERALIZED EXTREME VALUE, GEV) 11 第3章 研究方法與實際案例 14 3-1通用極端值分布之特性 14 3-2設計流程圖 15 3-3合成資料探討分布之特性 16 3-3.1 LH-moments方法之 值探討 16 3-3.2合成資料之基本參數設定 17 3-3.3合成資料之條件設定 18 3-4計算步驟 18 3-4.1參數推求之前置步驟 18 3-4.2推求重現期之計算步驟 19 3-5實際案例之採用 19 第4章 結果與討論 21 4-1 EV1與EV2分布之參數特性 21 4-2 LH-MOMENTS方法之 值特性分析 23 4-3 合成資料之推測結果 24 4-3.1 重現期推測之探討 24 4-3.2 值之適用性探討 26 4-4 資料個數之探討 31 4-5 實際案例研究 32 4-5.1 實際案例之推估參數 32 4-5.2 實際案例三參數之探討 36 4-5.3 實際案例推測之重現期探討 40 4-5.4 實際案例之應用 42 第5章 結論與建議 45 5-1 結論 45 5-2 建議 46 參考文獻 47 附錄 49學號: 600480015, 學年度: 10

    Targeted Gene Disruption in Zebrafish Reveals Noncanonical Functions of LH Signaling in Reproduction

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    The pivotal role of gonadotropin signaling in regulating gonadal development and functions has attracted much research attention in the past 2 decades. However, the precise physiological role of gonadotropin signaling is still largely unknown in fish. In this study, we have established both LH beta-subunit (lhb) and LH receptor (lhr) knockout zebrafish lines by transcription activator-like effector nucleases. Intriguingly, both homozygous lhb and lhr mutant male fish are fertile. The fertilization rate, sperm motility, and histological structure of the testis were not affected in either lhb or lhr mutant males. On the contrary, homozygous lhb mutant females are infertile, whereas homozygous lhr mutant females are fertile. Folliculogenesis was not affected in either lhb or lhr mutants, but oocyte maturation and ovulation were disrupted in lhb mutant, whereas only ovulation was affected in lhr mutant. Differential expression of genes in the ovary involved in steroidogenesis, oocyte maturation, and ovulation was found between the lhb and lhr mutants. These data demonstrate the essential role of LH signaling in oocyte maturation and ovulation, and support the notion that LH acts through the FSH receptor in the absence of LH receptor. Moreover, the defects of lhb mutant could be partially restored by administration of human chorionic gonadotropin. This in vivo evidence in the present study demonstrates, for the first time in any vertebrate species, that LH signaling is indispensable in female reproduction but not in male reproduction. LH signaling is demonstrated to control oocyte maturation and ovulation in the ovary
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