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    Sense of Self in Adolescents at Risk of Schizophrenia

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    自我的崩解、毀壞是精神分裂症的核心基礎,並且在疾病的前驅期即會出現一些因自我感改變所造成的異常自我經驗。本研究之目的在探索自我感困擾在不同罹病風險程度族群中的差別,及個體於疾病演進歷程中自我感的變化趨勢,以擴充對精神分裂症自我感困擾的認識。此外,本研究試圖了解風險族群中,自我感困擾對於日後精神分裂症是否發病的預測力,以期能提昇早期篩檢之精確度以利早期介入,進而降低精神分裂症對個體造成的影響。本研究藉由學校、醫院轉介系統以及大眾傳播媒體募集324位較具罹患精神分裂症風險之參與者。藉由臨床專業評估,依其風險程度分為:極高風險組(52人)、中度風險組(41人)與邊緣風險組(44人);亦包48位精神分裂症初次發病患者,以及139位健康正常參與者,以玆對照。使用工具為自填式問卷,包括:基本資料、前驅症狀量表、自我感量表以及身材外貌及自信評估。本研究採前瞻式研究方法,除了基礎線期的測量外,初次發病組及極高風險組每半年追蹤一次,其餘風險組及正常對照組則一年追蹤一次,追蹤為期兩年。研究結果顯示自我感困擾與正負性及解構症狀之相關未達顯著,然而與部分一般症狀達顯著相關(如睡眠障礙、不悅情緒)。不同風險組間的自我感困擾無顯著差異;然而風險組及初次發病組的自我感困擾則均與正常對照組有顯著差異,顯示自我感困擾可區辨正常組及臨床組。自我感困擾嚴重度有隨著精神分裂症風險程度的升高而升高的趨勢。然而發病之後,其自我感困擾卻明顯下降。「自我認同遲鈍不確定」及「身材外貌現在相對於過去的差異」對於個體是否會轉變發病為精神分裂症最具預測力。本研究據以進行理論及臨床應用上之討論。Self-disturbance is a disturbance caused by the alteration of the basic sense of self. It may be the core feature of schizophrenia and its prodrome. The purpose of the study was to explore the details of self-disturbance in individuals of different risk levels of schizophrenia, and to examine whether self-disturbance can be predictive to psychosis. A prospective study was designed on participants recruited by referrals from a community-based population. Through clinical interviews by experienced psychiatrists, three pre-psychotic risk groups were established: an ultra-high risk group (UHR; n = 52), an intermediate-risk group (IRG; n = 41), and a marginal-risk group (MRG; n = 44). Also 48 participants with first-episode psychosis (FEP) and 139 healthy controls (NC group) were recruited as comparison. All participants were examine with Sense of Self Scale (SOS) to assess the severity of their self-disturbance, and the scale of appraisal of appearance and self-confidence to assess their subjective appraisal of the past, present and ideal appearance and self-confidence. In the two-year follow-up, the FEP and UHR were followed twice a year, and the rest once a year. Results revealed that self-disturbance could discriminate the healthy control and clinical groups (i.e. risk groups and first-episode group). And no matter observed within or between groups, the trend of alteration in self-disturbance existed as that its severity increased as risk level increased; however, when participants converted to psychosis, the severity of self-disturbance decreased. Besides, one subscale of sense of self and discrepancy between appraisal of present and past appearance were predictive to the full-blown of psychosis

    The Immune Regulatory Role of Interleukin-10 In Murine Lupus

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    介白質-10 (IL-10)是一種具有免疫抑制性的細胞激素,能夠抑制T細胞的活化及其功能,而對於調節性T細胞的分化也具有重要功能。介白質-10在許多自體免疫疾病之致病機轉中扮演的角色也益趨重要,例如全身性紅斑性狼瘡。若在週邊引起發炎反應的組織中給予介白質-10,可以降低發炎反應,並增強調節性T細胞之功能,則能預期對疾病症狀之舒緩,而作為細胞激素療法發展的學理根據。本論文著重於探討介白質-10的免疫調節功能對於抑制T細胞活化功能之機轉,我們觀察到給予介白質-10之T細胞株,會減少其IL-2之分泌量。我們也進一步研究介白質-10下游訊息的傳遞,並發現PPARγ的表現量在介白質-10刺激之下有明顯增加,同時,加入PPARγ的抑制劑會使介白質-10抑制T細胞IL-2分泌的情形獲得恢復。這些研究結果顯示,介白質-10對於T細胞的功能抑制可能是透過下游PPARγ的訊息傳遞,因此與PPARγ有關的訊息傳導路徑可能在自體免疫疾病中扮演著重要角色。為了進一步研究局部大量表現介白質-10與紅斑性狼瘡疾病舒緩之關聯,我們使用靈芝多醣體PSG,此成分能使樹突細胞與T細胞產生大量介白質-10,利用腹腔注射PSG的方式來治療狼瘡小鼠,治療結果發現小鼠周邊血中調節性T細胞之比例較高,腎絲球腎炎的情形較輕微,並有較長的壽命,說明了介白質-10在紅斑性狼瘡可能的療效。The immunosuppressive cytokine, interleukin-10, can inhibit the activation and effector functions of T cells. It also plays a key role in differentiation and function of a regulatory T cell subset. The role that IL-10 plays in the pathogenesis of many autoimmune diseases is striking, including systemic lupus erythematosus. Delivery of IL-10 cytokine alone in the inflammatory region to alleviate the severity of this disease, or enhance the function of regulatory T cells induced by the cytokine is the principle of tissue-specific cytokine treatment. In this study, we focused on the immune-modulatory effect of IL-10 in the activation of T cells. Decreased production of IL-2 was observed in different T cell lines when cultured with IL-10. To further study the inhibitory mechanisms of IL-10 on T cells, we examined the signaling pathways downstream of IL-10 and found the increased PPARγ expression was induced by IL-10 treatment. In addition, the inhibition of IL-2 secretion by IL-10 could be partially restored by PPARγ antagonist, GW9662. Our results suggest the inhibitory effect on T cells by interleukin-10 is partly through their downstream PPARγ. This molecule and its associated signal pathways should be taken into consideration for its potential of being new target in the development of immunotherapy against SLE. To further understand the effects of IL-10 on the disease development of SLE in vivo, we intraperitoneally injected PSG to NZB/W F1 mice to induce IL-10 production. After treatment, the mice have higher percentage of Treg population, lower glomerulonephritis, and greater survival tendencies. This suggests the potential role of IL-10 in the treatment of murine lupus.謝誌…i 英文摘要…iii 中文摘要…v Chapter I. General Introducion 1.1 Background…2 1.1.1 Systemic lupus erythematosus…2 1.1.2 Murine model of lupus: NZB/W F1 mice…7 1.1.3 Interleukin-10…8 1.1.4 The role of interleukin-10 in SLE…9 1.1.5 The relationship of interleukin-10 and regulatory T cell function…10 1.1.6 Lentiviral vector…11 1.1.7 Peroxisome proliferator-activated receptor-gamma (PPARγ) …12 1.1.8 Polysaccharide components of Ganoderma lucidum (PSG) …14 1.2 Specific aims…15 Chapter II. Materials and Methods 2.1 Reagents…17 2.2 Cell lines…20 2.3 Plasmid construction…21 2.4 Transfection of COS-1 cells…22 2.5 Preparation of lentiviruses…22 2.6 Detection of cytokine expression by ELISA…23 2.7 Separation of splenic T cells by nylon wool…24 2.8 Stimulation of T cells…24 2.9 Letivirus transduction of splenic T cells…25 2.10 Detection of protein levels 2.10.1 SDS-PAGE…25 2.10.2 Western blot…26 2.11 Mice…27 2.12 In vivo treatment of PSG in NZB/W F1 mice…27 2.13 Examination of immunopathology 2.13.1 Detection of autoantibodies…28 2.13.2 Determination of renal pathology…29 2.14 Statistical analysis…30 Chapter III. Results 3.1 The inhibitory effect of IL-10 on T cell lines…32 3.2 Construction of pTYlinker-mIL10 plasmid for lentiviral delivery of mouse IL-10 gene 3.2.1 Construction of pTYlinker-mIL10 plasmid…32 3.2.2 IL-10-secreting capability of pTYlinker-mIL10 transfected cells…33 3.2.3 IL-10 production by lenti-mIL10 virus tranduced cells…33 3.2.4 Lenti-mIL10 virus-tranduction in mouse splenic T cells…34 3.3 The role of PPARγ in the inhibitory effect of IL-10 3.3.1 Ligand induced PPARγ expression in Jurkat cells…35 3.3.2 IL-10 induced PPARγ expression in human and mouse T cell lines…35 3.3.3 PPARγ antagonist reversed the inhibitory effect of IL-10 in human and mouse T cell lines…36 3.4 Application of PSG as an alternative way of local IL-10 induction for lupus treatment 3.4.1 PSG induced IL-10 production by dendritic cells of NZB/W F1 mice in vitro…36 3.4.2 PSG induced maturation of BMDC by enhancing the expression of DC surface markers and costimulatory molecules in vitro…37 3.5 PSG-treated lupus mice 3.5.1 Peripheral CD4+CD25+FoxP3+ regulatory T cells were increased after PSG treatment…38 3.5.2 Levels of autoantibodies in sera were no difference under PSG treatment…38 3.5.3 Clinical course and pathological changes of kidney…39 3.5.4 Prolonged survival of PSG-treated mice…40 Chapter IV. Discussion and perspectives…41 Figures…47 References…7

    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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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
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