1,720,975 research outputs found
Human CYP11A1 4.4kb promoter drives Cre recombinase expression in the mouse brain
No full text類固醇荷爾蒙主要於腎上腺、性腺與胎盤產生，近年已有研究發現腦部也能自行合成神經性類固醇，影響腦內的功能。在類固醇合成過程的第一步也是速率決定的步驟，是由P450膽固醇側鏈截切酶(P450scc)所催化。雖然前人利用RT-PCR技術測得此酵素的基因CYP11A1能在腦內表現，證明腦部具有新生類固醇的能力，但CYP11A1基因在腦內的表現量卻遠遠低於在腎上腺內的表現量，這使得P450scc在腦內的分佈區域和生理作用難以被確切描述。
本實驗室利用長度為4.4kb的人類CYP11A1啟動子控制Cre重組酶，產生了SCC-Cre的基因轉殖小鼠，目的是將來對類固醇生成組織內的基因做功能性的研究。我們發現Cre重組基因除了專一性表現在腎上腺與性腺，腦組織也有很好的Cre重組酶表現。在本篇研究中，我們分析Cre重組酶在腦內的活性與表現分布，結果顯示其主要分布在間腦區域的上丘腦與丘腦前端，以及中腦背部的上丘結構與頂蓋前區；在海馬迴結構中則有較弱的表現。我們進一步觀察到Cre重組基因在胚胎發育第10天的腦部開始有表現，並一直持續至出生前，其分布位置與成鼠的腦部一致。另外我們還觀察到在胚胎鼠的嗅覺上皮組織與視網膜內層有Cre表現。這些結果皆顯示轉殖的CYP11A1啟動子能驅動Cre重組酶在鼠腦內表現，且分布位置能反映目前已知的腦內內生性Cyp11a1基因的表現。鼠腦內生性Cyp11a1因表現量太低，難以被明確且直接的偵測，因此SCC-Cre小鼠提供了一個有價值的動物模式助於我們了解Cyp11a1在腦內可能的分布情形。另外， CYP11A1基因上游的4.4kb序列也是第一次被證實具有足以調控基因在腦部表現的元素。Steroid hormones are mainly synthesized in adrenals, gonads and placenta. Recent studies have found that steroids can be de novo synthesized in brain, termed neurosteroid, to affect brain functions. The cholesterol side-chain cleavage enzyme (P450scc), encoded by CYP11A1 gene, catalyzes the first and rate-limiting step in steroid synthetic pathway. The expression of P450scc in the CNS has been detected by RT-PCR to demonstrate the steroidogenic capacity in the brain. However, the levels of CYP11A1 expression are much lower than that in adrenal glands. It is therefore difficult to identify the exact expressional pattern and also brings challenges to elucidate the physiological function of P450scc in brain.
We generated a SCC-Cre transgenic mouse, in which Cre recombinase expression is under the control of the human CYP11A1 promoter. It has been shown that Cre recombinanse was specifically expressd in the adrenals and gonads. In addition, we found that the brain tissues also express Cre protein in the SCC-Cre mice. By RT-PCR analysis, the expression of Cre was identified in all regions of brain except cerebellum. High levels of Cre expression was detected in the epithalamus and anterior thalamus of the diencephalons, and superior colliculus and pretectum of the midbrain. Weak expression was also found in the hippocampal formation. The Cre recombinase activity was first present in the embryonic brain at 10.5 days postcoitum in a pattern similar to that of adult brain. The Cre expression was further observed in the olfactory epithelium and the inner layer of retina. In conclusion, the 4.4 kb of 5’flanking region of the human CYP11A1 genes contains efficient regulatory elements to drive transgene expression in the mouse brain. Our SCC-Cre transgenic mice provide a valuable animal model to understand the possible expressional pattern of CYP11A1 in the brain.表次 ……………………………………………………………………….. IV
圖次 ………………………………………………………………………... IV
腦解剖構造中英文名稱對照表 …………………………………………... V
中文摘要 …………………………………………………………………… VIII
英文摘要 …………………………………………………………………... IX
第一章 前言 ………………………………………………………………. 1
一、類固醇的生成途徑 …………………………………………….. 1
二、神經性類固醇的生成及其功能 ………………………………… 2
1、 神經性類固醇的生成途徑 ………………………………... 2
2、 神經性類固醇的功能 …………………………………….. 3
三、腦內細胞色素P450膽固醇側鏈截切酶 (Cyp11a1)的研究 …... 4
1、 Cyp11a1在腦內的表現量 ……………………………….. 4
2、 Cyp11a1在腦內的分布 …………………………………… 5
3、 Cyp11a1在腦內的活性與生理意義 ……………………... 6
4、 研究腦內Cyp11a1功能與基因調控的困難 …………….. 7
四、Cre/loxP系統於組織專一性的基因剔除之應用 ………………. 8
1、 建立方式與基因功能研究的應用 ………………………. 8
2、 Cre重組酶表現位置與活性的檢測 …………………….. 9
五、人類CYP11A1啟動子於生物體內的研究 ……………………. 9
1、 細胞株實驗模式 ………………………………………… 9
2、 基因轉殖動物模式 ………………………………………. 10
3、 本實驗室建立的SCC-Cre動物模式 …………………… 11
六、研究動機與目的 ………………………………………………… 12
第二章 材料與方法 …………………………………………………….. 12
一、轉殖基因的建構 ………………………………………………… 12
二、SCC-Cre基因轉殖小鼠的產生 ………………………………… 12
三、SCC-Cre/R26R小鼠之交配與鑑定 ……………………………. 12
四、小鼠基因型檢測 (Genotyping) ………………………………… 13
五、小鼠不同胚胎時期的判定 ……………………………………... 13
六、灌流 ……………………………………………………………... 14
七、取腦 ……………………………………………………………. 14
八、冷凍組織切片 …………………………………………………... 15
九、X-gal酵素活性染色 …………………………………………… 15
十、反轉錄-聚合酵素連鎖反應 (RT-PCR) ………………………… 15
1. 組織準備 ……………………………………………………. 15
2. 抽取RNA …………………………………………………… 16
3. DNase處理 …………………………………………………... 16
4. 反轉錄作用 ………………………………………………….. 17
5. 聚合酵素鏈鎖反應 (PCR) …………………………………. 17
第三章 結果 ………………………………………………………………. 19
一、Cre重組酶在成鼠腦內的表現分布 …………………………… 19
二、Cre重組酶在胚胎鼠腦內之表現 ……………………………… 22
三、內生性Cyp11a1與轉殖基因在小鼠腦內表現之比較 ………. 24
第四章 討論 ……………………………………………………………… 26
一、人類CYP11A1基因上游的4.4kb片段足以調控轉殖基因在腦
組織表現 ...................................................................................... 26
二、以Cre重組酶在SCC-Cre小鼠的表現預測內生性Cyp11a1在
腦內表現布 ................................................................................... 28
三、人類CYP11A1基因5’端4.4kb可以調控胚胎時期腦內內源基
因的表現 ……………………………………………………….. 29
四、由Cre重組酶在腦內表現之特徵探討Cyp11a1可能的神經功
能 ………………………………………………………………… 30
參考文獻 ……………………………………………………………… 33
表 ……………………………………………………………………… 43
圖 ……………………………………………………………………… 4
Impedance Spectroscopy of Organic Light-Emitting Devices
No full text近年來，有機發光元件已經快速發展成一具有潛力的平面顯示技術，為了滿足高效率、低操作電壓、長壽命的元件特性要求，必須設法了解元件材料、介面與整體特性。然而，這些有機發光元件中重要的現象與機制一般並不易從最典型的 I-V-L 量測中獲得明確的相關資訊，因此希望能藉由對於材料本身及介面特性相當靈敏的阻抗分析技術之輔助，深入研究有機發光元件，改善並提升元件特性。
在本論文的第一部份中，我們針對單層有機元件之阻抗頻譜做深入探討，接著利用Fluxim有機元件模擬程式，模擬單層有機電洞材料(HI010)元件內部載子濃度隨位置分布情形，並配合電路模型，推測造成元件阻抗頻譜在等效電路中分層的原因之一為電性不同，即不同的時間常數。
在本論文的第二部份中，我們針對單載子有機電洞材料層元件之阻抗頻譜做深入探討。我們分別使用「電洞注入材料(HI008)/電洞注入材料(HI010)」與「電洞注入材料(HI008)/電洞注入材料(HI010)/電洞傳輸材料(HT006)」製作雙層及三層電洞材料元件，改變兩種結構中某一層的材料厚度，探討不同厚度下，元件在阻抗頻譜上的變化。
在本論文的第三部份中，我們針對單載子有機電子材料層元件之阻抗頻譜做深入探討。我們分別使用「單層n型摻雜電子傳輸材料(n-ET011)」與「n型摻雜電子傳輸材料(n-ET011)/電子傳輸材料(ET010)」製作單層及雙層電子材料元件，並對n-ET011和ET010之材料厚度對於阻抗頻譜的影響做一探討，依序改變兩種結構中某一層的材料厚度比較其阻抗頻譜差異。Organic light-emitting devices (OLEDs) have been demonstrated as a potential display technology. In order to achieve high efficiency, low operating voltage and long operating lifetime, we should understand the characteristics of the materials and interfaces. However, typical I-V-L characteristics cannot reveal these important mechanisms of OLEDs. Impedance spectroscopy (IS) is a powerful method for characterizing many of the electrical properties of materials and their interfaces. With the aid of impedance spectroscopy, we can obtain more insights about the operation of OLEDs.
In the first part of the thesis, we investigated impedance spectroscopy of organic single-layer devices. Then, we adopted Fluxim simulation tool to obtain the distance-dependent carrier concentrations in the single-layer device (HI010). Besides, we constructed the equivalent circuits of the devices to demonstrate that one possible reason of different regions occurring in equivalent circuits may be associated with different electrical properties, that is, different time constants.
In the second part of the thesis, we adopted impedance spectroscopy to measure hole-only devices. We fabricated two different device structures – “hole-injection material (HI008)/ hole-injection material (HI010)” and “hole-injection material (HI008)/ hole-injection material (HI010)/hole-transport material (HT006)”. We systematically varied the material thickness of the HI008, HI010 and HT006 to investigate their effects on devices.
In the third part of the thesis, we performed comparative studies of the impedance spectroscopy of two different structures of electron–only devices– “n-doped electron-transport material (n-ET011) and n-doped electron-transport material (n-ET011)/ electron-transport material (ET010)”. To verify the effects of n-ET011 and ET010 on devices, we systematically varied their material thickness.致謝 I
摘要 III
Abstract IV
目次 VI
圖目次 VIII
表目次 XI
第一章 緒論 1
1.1 有機發光元件之簡介 1
1.2 阻抗頻譜原理與有機發光元件分析應用 2
1.3 研究動機與論文架構 3
第一章圖表 5
第二章 單層有機元件之阻抗頻譜與理論模擬分析 10
2.1 前言 10
2.2 研究方法 10
2.2.1 樣品來源 10
2.2.2 量測儀器與方法 10
2.2.3 數據分析方法 11
2.3 阻抗頻譜結果與討論 11
2.4 總結 14
第二章圖表 15
第三章 單載子有機電洞材料層元件之阻抗頻譜分析 29
3.1 前言 29
3.2 研究方法 29
3.2.1 樣品來源 29
3.2.2 量測儀器與方法 29
3.2.3 數據分析方法 30
3.3 阻抗頻譜結果與討論 30
3.3.1 雙層電洞材料元件 30
3.3.2 三層電洞材料元件 31
3.4 總結 32
第三章圖表 34
第四章 單載子有機電子材料層元件之阻抗頻譜分析 47
4.1 前言 47
4.2 研究方法 47
4.2.1 樣品來源 47
4.2.2 量測儀器與方法 47
4.2.3 數據分析方法 48
4.3 阻抗頻譜結果與討論 48
4.3.1 單層n型摻雜電子傳輸材料元件 48
4.3.2 雙層電子材料元件 49
第四章圖表 52
第五章 總結與未來展望 65
5.1 總結 65
5.2 未來展望 67
參考資料 6
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
