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    False memory in patient with temporal lobe epilepsy

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    文獻指出錯誤記憶的產生與過度依賴要旨記憶及監控功能受損有關。Schacter、Verfaellie、及Pradere(1996)認為失憶症者與阿茲海默型失智症者之要旨記憶保留困難可能與內側顳葉結構損毀有關。然而,神經影像顯示,要旨記憶與內側顳葉有關,監控功能與額葉有關。因此,對於額葉亦受損的失憶症者與阿茲海默型失智症者來說,錯誤記憶表現可能無法排除監控能力受損的影響。基於上述,本研究欲透過腦部受損部位侷限於內側顳葉之顳葉癲癇病患,探討要旨記憶保留困難與內側顳葉結構受損的問題。並同時建立國內顳葉癲癇患者之神經認知功能的資料。 共有45位顳葉癲癇患者(左側16位、右側15位、及雙側14位),與22位正常人參與本研究。患者需符合:(1)EEG顯示顳葉異常放電;(2)MRI顯示內側顳葉硬化;(3)未曾接受過腦部手術;(4)未曾有影響認知功能的病史。正常人則需符合未曾有影響認知功能的病史。每位受試者需接受神經認知功能檢查與錯誤記憶作業。 研究結果發現:學習記憶方面,無論語文或視覺材料,左側及雙側患者均顯著低於正常人;語意記憶方面,左側、右側、及雙側患者均明顯低於正常人。錯誤記憶表現上,僅發現雙側患者顯著低於正常人。進一步資料分析顯示,雙側患者錯誤記憶少可能與旨記憶保留困難有關。 本研究結果顯示,雙內側顳葉結構在要旨記憶表現上扮演重要的角色,支持過去文獻(Schacter, Verfaellie et al., 1996)的看法。然而,本研究在判斷內側顳葉顳葉受損部位時,部分雙側患者僅依據MRI的發現,並非同時考慮EEG與MRI的結果,因此,本研究在結果的解釋上仍有其限制。關於顳葉以外區域異常放電是否影響錯誤記憶表現,需進一步研究。Literature shows that false memory manifestation results from an overdependence on semantic gist and/or impaired ability to monitor information. Schacter and co-workers claimed that the retention deficit of semantic gist information in amnesic and demented patients with Alzheimer’s disease (AD) is presumably due to lesions of mesial temporal lobe structures. Accordingly, the underlying neural substrates involving gist memory have been suggested to be associated with mesial temporal regions, while source monitoring function has been proposed to be related to frontal lobe function. However, neuropathological involvement of frontal regions in these amnesic and AD patients might confound the results of these false memory studies. Using patients with temporal lobe epilepsy (TLE) due to unilateral or bilateral mesial temporal sclerosis bearing brain-damaged locations restricted to medial portions of temporal areas, the present study was thus to examine the issue of whether the impaired retention of semantic gist materials is associated with mesial temporal dysfunction. Meanwhile, this study made an attempt to document neurocognitive functions in our Taiwan patients with TLE. Forty-five patients with TLE (16 left, 15 right, and 14 bilateral) and 22 healthy controls participated in the study. The inclusion criteria for patients with TLE consisted of: (1) EEG abnormalities restricted to the temporal lobes; (2) no lesion other than mesial temporal lobe sclerosis on brain MRI; (3) no history of brain surgery; and (4) no physical and psychiatric illness. Normal control subjects were also free of neurological and psychiatric disorders. All subjects were given the false memory task and a battery of neurocognitive tests. The results revealed that left and bilateral TLE patients evidenced a significant deficit of delayed verbal and visual episodic and semantic memory function compared to their normal control counterparts, even after controlling for VIQ while only defective semantic memory manifested in right TLE patients. However, only bilateral TLE patients evidenced a low level of false memory functioning. Further data analysis revealed that a low level of false memory manifestation in bilateral TLE patient seemed to be related to a failure to retain gist information. Based on the present results, it appeared that bilateral mesial temporal structures might play an important role in gist memory functioning. These findings thus seemed further corroborate Schacter and colleagues’ claim. However, a caveat should be taken with care for interpreting the present results because only half of bilateral TLE patients did evidence lesions of mesial temporal lobes merely based on MRI rather than on both EEG and MRI findings. Thus, the issue of whether abnormal EEG sites other than temporal areas might affect false memory functioning remains unclear and awaits further investigation.第一章 緒論..............................................................................................................1 第一節 錯誤記憶........................................................................................3 第二節 顳葉癲癇症……………………………………………………..19 第三節 本研究目的……………………………………………………..28 第二章 研究方法…………………...……………………..……………………..30 第一節 受試者…………………………………………………………..30 第二節 研究工具………………………………………………………..32 第三節 研究程序………………………………………………………..35 第三章 研究結果……………………..……………………...…………………..36 第一節 神經認知測驗之結果…………………………………………..37 第二節 錯誤記憶作業之結果…………………………………………..41 第三節 以神經認知功能預測錯誤記憶表現…………………………..45 第四節 總結……………………………………………………………..51 第四章 討論………..……………………………………………………………..54 第一節 顳葉癲癇患者的神經認知功能………………………………..54 第二節 顳葉癲癇患者的錯誤記憶表現………………………………..58 第三節 本研究之限制…………………………………………………..63 第四節 本研究之貢獻與未來研究方向………………………………..63 參考文獻……………….…………………………………………………………..65 附錄………………...………………………………………………………………..75 附錄一 錯誤記憶作業之字詞……………..……………………………75 附錄二 研究同意書………………………..……………………………7

    Molecular regulatory mechanism ofIGFBP-3 expression in ovarian endometrioid carcinoma

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    胰島素生長因子結合蛋白-3(IGFBP-3)藉由和胰島素生長因子之結合,在體內執行抑制細胞生長的功能.在本實驗室之前的研究中,我們利用卵巢癌侵襲模型(Ovarial cancer invasion model)來建立卵巢類子宮內膜腺癌細胞株(ovarian endometrioid carcinoma) OVTW59的分株(P0~P4)。藉著互補去氧核糖核酸微矩陣(cDNA microarray)和及時定量聚合酶鍊反應(Real-time RT PCR),我們發現由P0到P4其細胞株之IGFBP-3的基因表現由高到低有顯著差異。在一系列體外(in vitro)及動物實驗的功能性分析顯示,IGFBP-3能夠抑制卵巢類子宮內膜腺癌細胞的移動、侵襲以及轉移的能力,並可誘發癌細胞的凋亡,證明IGFBP-3有抑癌基因的特色。在本實驗中,我們利用卵巢類子宮內膜腺癌細胞株P0以及P4作為模型,去探討IGFBP-3 的表現是否受到其基因啟動區(promoter region)的甲基化(methylation)而抑制其基因的表現。經過去甲基化藥物5’-aza-dC的處理過後,P4的mRNA以及蛋白的表現量有顯著回升的情形。同時,我們利用亞硫酸定序及專一性甲基化聚合酶鍊反應來分析卵巢類子宮內膜腺癌細胞株以及60個臨床檢體的IGFBP-3基因啟動區(promoter region)之甲基化情形。發現在卵巢類子宮內膜腺癌中, 40.43% 病人IGFBP-3基因啟動區(promoter region)有過度甲基化的情形;並且在細胞模型中,我們發現IGFBP-3甲基化靜默的現象是透過IGFBP-3基因啟動區上p53轉錄因子(transcription factor)結合位置的過度甲基化,進而影響了p53 調控IGFBP-3的轉錄活性所導致。以上研究顯示, IGFBP-3基因啟動區(promoter region)過度甲基化為影響其基因表達的一個調控機制。Insulin growth factor binding protein-3 (IGFBP-3) functions as a carrier of insulin-like growth factors (IGFs) in vascular circulation and has been postulated to be a mediator of growth suppression signal in cells. In our previously study, IGFBP-3 was selected from the cDNA microarray analysis of the progressive increase in invasion capability of ovarian endometrioid carcinoma cancer cell line OVTW59 sublines P0 to P4, its expression is very low in the advanced cancer cells such as P4 cell line. It has been proved as a tumor suppressor to inhibit tumor cell migration, invasion and metastasis and induce apoptosis in ovarian cancer pathogenesis. Since promoter CpG island hypermethylation can silence gene expression, we investigated whether hypermethylation of the IGFBP-3 promoter is involved in loss of IGFBP-3 expression in ovarian endometrioid carcinoma. After treatment with DNA methyltransferase inhibitor 5’-aza-2-deoxycytidine for eight days, restored expression of IGFBP-3 mRNA transcript was found in ovarian cancer cell line P4. In addition, we examined the methylation status of IGFBP-3 by methylation-specific PCR (MSP) assay and bisulfite genomic DNA sequencing, The methylation status correlated with IGFBP-3 mRNA and protein expression levels in endometrioid carcinoma cell lines. Furthermore, we analyzed 60 clinical samples and found that IGFBP-3 promoter was hypermethylated in 40.43% of ovarian endometrioid carcinoma surgical specimens. Moreover, we also found the hyprermethylated CpG sites of -210,-206,-183 and -179 in p53 consensus binding region in IGFBP-3 promoter may play a critical role in the effect of its promoter activity, These findings indicate that the silenced IGFBP-3 expression in advanced P4 line and patients is primarily regulated IGFBP-3 promoter region by hypermethylation in the p53 binding region.中文摘要1 Abstract 2 Introduction3 Materials and Methods9 Results 19 Discussions 25 Tables 31 Figures 36 References 5

    Boundary Element Analysis of a Laminated Composite Plate Containing Holes

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    本文使用Wu and Hsiao(2015)所提之邊界積分方程式,分析含孔洞之有限複合材料層板受力矩的力學反應,尤其是孔洞的應力放大現象。Wu and Hsiao(2015)所提之邊界積分方程式是以曲率為幾何參數,對於自由板的問題可得相當準確的數值結果,但對於一般邊界條件則不完全適用,因此本文另改以轉角為幾何參數,提出一個新的邊界積分方程式以補原積分方程式之不足。該邊界積分方程式是以柯西積分式為核心並使用古典層板理論和類似異向彈性力學中的史磋法理論作為推導的基礎。本文算例有自由板或懸臂板受彎矩作用的問題,考慮的層板則有正交性、單層異向性、雙層異向性三種。運用邊界積分方程式所得的數值均與有限元素法結果比對,以評估兩種數值方法的優缺點及適用的狀況。This thesis uses the boundary integral equations proposed in Wu and Hsiao(2015) to analyze finite laminated plates with holes subjected to moments. Although the integral equations, which contain curvatures as geometric parameters, work well for free plates, they do not all apply to all boundary conditions. A new boundary integral formulation with rotations as parameters is proposed to remedy the issue. The formulation is based on a Stroh-Like formalism developed for the lamination theory with Cauchy integral formula. The numerical examples are a free plate or cantilever plate subjected to bending moments. The plates considered include homogeneous orthotropic, homogeneous anisotropic and two-layered anisotropic plates. The numerical results from boundary integral formulation are compared with those using finite element method to assess the advantages and disadvantages of two numerical methods

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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
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