1,720,960 research outputs found
Infection of ENU Mutant Mice With Human Herpes Simplex Virus-1 (HSV-1) to Probe Immune Deviations in the Host Predominantly Expressing IL-15 Splice Variants
No full text介白質-15 (interlukine-15, IL-15) 是細胞激素的一種。除了參與重要的免疫反應之外，同時也涉及了宿主體內其他的生理反應，諸如:骨骼肌的代謝亦或是角質細胞的增生。基於作用的多效性以及分佈的廣泛性，IL-15生物活性的調控就顯得相當的重要。近幾年來，科學界在自然情況下發現人體內的許多細胞激素選擇性剪接異構體，並且藉用體外實驗的方式觀察到這些異構蛋白對於原型細胞激素的生物活性扮演了抑制調控的角色。然而，這些細胞激素剪接異構體的免疫生物活性尚未在體內實驗裡得到進一步的証實。本論文利用由國家型基因突變鼠核心實驗室以ENU誘導突變所建立的突變鼠品系191(P191)，經過人類疱疹一型病毒(Human Herpes Simplex Virus-1，HSV-1)的感染模式，希望能進一步地了解IL-15選擇性剪接異構體對原型IL-15調控下的免疫機制的影響。 我們將小鼠皮膚經過HSV-1感染後，藉由組織切片染色的方法比較突變鼠與正常鼠對病毒感染的反應結果發現:P191小鼠比野生型小鼠(C57BL/6，B6)能更快地產生病毒感染所引起的典型皮層細胞的病理變化並且顯示較嚴重程度的細胞破壞。經由免疫組織化學染色的結果得知這些皮膚組織的破壞程度和病毒蛋白表現的豐富程度相關。此外，從免疫組織螢光染色的結果觀察到，B6小鼠經過HSV-1 病毒感染後雖然能在皮膚組織誘發表現IL-15及IL-15Rα，但是這些因子在P191小鼠的皮膚表現卻相對地降低。雖然小鼠的皮膚經過病毒的感染會發生皮層細胞的壞死，正常鼠卻能在感染後七天內開始出現皮膚修復的現象，同時伴隨表現Gr-1抗原的細胞的浸潤與聚集。不過，這些表現Gr1抗原的細胞卻無法在病毒感染後各個時間點所收集的P191小鼠皮膚中觀察到，同時P191小鼠需要經過較長的時間才能修復受到病毒感染而破壞的皮膚組織。雖然不論是正常鼠或是突變鼠的皮膚在病毒感染後都能觀察到CD3+ T 細胞的浸潤，它們對於二種品系的小鼠在控制病毒感染的作用與角色還需要進一步地研究與探討。總之，本實驗結果發現，在基因轉錄水平上表現較高程度IL-15異構體的P191小鼠經過HSV-1的表皮感染後，不但比正常鼠容易產生病毒的複製並且造成較嚴重的組織破壞，對於控制病毒感染與進行組織修復的時間與機智也與正常鼠有許多的差異。究竟這些差異如何由IL-15異構體轉錄本所造成以及該異構體轉錄本是否能在體內轉譯為蛋白質後並且進一步地影響原型IL-15的生物活性,或是同時能影響其它多項控制疱疹病毒感染的免疫機制，仍有待未來更進一步的實驗證明與探討。Interlukine-15 (IL-15) is one of important cytokines and exhibits a high degree of pleiotropy, controlling a wide range of functions including immune responses, metabolism of skeletal muscle and proliferation of keratinocytes. However, very little is known about the mechanisms by which the expression and bioactivity of IL-15 are controlled. Whereas several forms of IL-15 alternative splice variants are identified in normal mice, their roles in the control of IL-15 expression remain unclear. In this study, we used an ENU mutant mouse model generated by the MMPCF (Mouse Mutagenesis Program Core Facility) to investigate how the immune responses against virus infection are affected when the host predominantly expresses IL-15 splice variants. Normal C57BL/6 (B6) and mutant pedigree 191 (P191) were infected with Human Herpes Simplex Virus-1 (HSV-1) via epicutanous route. Skin samples with lesional areas were collected and sectioned for further analysis. Results from H & E stain showed that HSV-1 induced typical pathological changes in skin tissues of both types of mice including cell ballooning, vesicular degeneration and epidermal cytolysis. However, these changes appeared earlier and more severe in P191 than in wild type B6 skin. Expression of HSV-1 proteins was also more abundant in P191 than in B6 skin by immunohistochemical stain. Whereas expressions of IL-15 and IL-15R were induced in the subdermal area of B6 skin after HSV-1 infection, they were much reduced in P191 lesional skin. In addition, the time for the skin to be healed after HSV-1 infection was longer for P191 than B6 mice. While significant numbers of Gr-1+ cells were detected on day 5 and peaked at day 10 in the dermis of infected B6 skin, they were nearly detected at all times in P191 skin after HSV-1 infection. Although CD3+ T cells were all detected in B6 and P191 skin after HSV-1 infection, their roles in the control of virus infection remain clarified. In summary, results from our study have shown that infection of P191 mice with HSV-1 resulted in altered immune responses as compared with wild type B6 mice. The differences at least but not limited include the susceptibility to HSV-1 infection, time for skin healing and recruitment of immune cells to lesional areas. How does the elevated level of IL-15 splice variants in P191 mice contribute to these deviations is not clear. More experiments will be done to understand whether IL-15 splice variants are expressed as variant proteins to antagonize prototype IL-15 and/or acquire novel functions in regulating host immune responses.誌謝 1文摘要 2文摘要 4一章 緒論 6一節 細胞激素與免疫反應 6. 調控細胞激素表達的機制 7. IL-2 cytokine family異構體的生物性特色 7IL-2 cytokine family 7IL-2 cytokine family與選擇性剪接異構體 8. 細胞激素異構體的應用發展性 10二節 動物模式在生物學研究上的重要性 10. ENU的致突變機轉 11. 從表型篩選到基因探索 13. ENU突變鼠在免疫學研究上的應用 13Pedigree 191 (P191) 14. P191 基因突變鼠免疫偏差(Immune Deviation)之探討 16三節 人類單純性疱疹一型病毒(Human Herpes Simplex Virus-1，HSV-1)的感染與免疫反應 16. HSV-1的特性與致病機轉 17. 宿主的防禦機制 18.1. 補體連鎖反應的活化 18.2. 免疫細胞與細胞激素的相互作用 19. 利用HSV-1病毒感染的模式探討P191小鼠的免疫偏差 20二章 材料與方法 22三章 實驗結果 34. 利用RT-PCR的方式確認Pedigree 191(P191)所表現的IL-15選擇性剪接異構體 34. 人類疱疹一型病毒感染小鼠上皮組織之感染動物模式的建立 35. 人類疱疹一型病毒感染小鼠上皮組織之病理現象 35. 人類疱疹一型病毒感染後，小鼠皮膚組織內病毒蛋白的偵測 36. 人類疱疹一型病毒感染皮膚後誘導的免疫反應 37.1. IL-15 與 IL-15Rα 37.2. Gr1+浸潤細胞 38.3. CD3+浸潤細胞 38. 總結 39四章 討論 41. 比較人類疱疹一型病毒感染野生型 B6 與 P191小鼠後皮膚組織病理變化差異之原因 41. 人類疱疹一型病毒的感染引誘皮膚組織CD3+ T 細胞的浸潤 42. HSV-1的清除和Gr-1+ 細胞的浸潤 43. IL-15的表達與Neutrophils的浸潤在抗HSV-1感染上的相關性 44五章 圖表 47六章 參考資料 60表目次. Detection of IL-15 mRNA splice variant in p191 by RT-PCR 47. Development of HSV-1 zosteriform model in B6 mice 49. HSV-1 induced cytopathological changes in mouse skin by H&E stain 50. Demonstration of expressions of HSV-1 proteins in skin by immunohistochemical staining 52. Expressions of IL-15 and IL-15 Rα in mouse skin after HSV-1 infection by immunofluorescence analysis 54. Detection of Gr-1 expressing cells within the cellular infiltration in HSV-1 infected skin by confocal microscopy 56. Detection of CD3 expressing cells within the cellular infiltration in HSV-1 infected skin by confocal microscopy 5
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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
- …
