1,720,961 research outputs found
De moleculaire pathogenese van late-onset Fuchs’ endotheeldystrofie van de cornea
No full textIn this doctoral thesis, we have investigated the pathogenesis of late-onset Fuchs’ endothelial corneal dystrophy (FECD).
FECD is a degenerative disorder of the corneal endothelium (CE). The CE is the inner layer of the cornea (the cornea is the transparent front part of the eye). The cornea does not contain blood vessels, but receives water and nutrients from the anterior eye chamber fluid (a.k.a. aqueous humor) and the tear film. To prevent the cornea from swelling (edema), the CE constantly pumps out excess fluid and waste products, safeguarding the normal corneal thickness and transparency.
FECD is characterized by a loss of CE cells (CECs), resulting in clouded vision, painful ulcerations and even blindness. Usually both eyes are affected. The prevalence of FECD is estimated at 4% of people older than 40. The only curative treatment consists of replacing the diseased CE layer with a healthy donor layer. FECD is currently the most common indication for this kind of surgery in the Western world. However, as an estimated 10 million people worldwide suffer from corneal blindness (awaiting corneal transplantation), and the prevalence of FECD is expected to rise with aging of the population, there is a need to develop alternative therapies. Therefore, we need a better understanding of the underlying molecular mechanisms of FECD. Significant efforts have been made to improve our understanding of the pathophysiology of FECD, but a unifying theory and tangible drug targets are lacking.
This doctoral thesis aimed to gain new insights into the molecular pathogenesis of FECD, and to differentiate between processes that are specific for FECD (primary, causative factors) and processes that are nonspecific (e.g., secondary to corneal edema), to direct the future development of targeted drug therapy.
To this end, we have analyzed the gene expression profile in CECs from patients with late-onset FECD, in comparison with normal controls (normal corneas from donors and eyes with malignant melanoma), and non-FECD edematous (NFE) corneas (including pseudophakic bullous keratopathy and decompensated corneal grafts). To study these gene expression profiles, we used microarray expression analysis, reverse transcriptase quantitative polymerase chain reaction, and RNA-sequencing technology. Subsequently, we have examined interesting findings at the protein level, using immunohistochemistry (IHC) and immunofluorescence on CE whole mount specimens and cross-sections of full-thickness corneas. Finally, we have measured the concentration of molecules of interest in the aqueous humor.
Novel methodological elements in this project are: 1) the use of RNA-sequencing to study the gene expression profile of CECs with FECD, 2) the comparison with a third group of NFE corneas to differentiate between specific and nonspecific findings in FECD, 3) the development of a semi-automated computer algorithm to analyze IHC staining.
The main achievement of this work is the identification of circulating fibrocytes and dendritic derivatives as a consistent finding in CE layers of patients with symptomatic late-onset FECD. This is novel, because, formerly, it was thought that the CE layer from patients with FECD contained only CECs. Circulating fibrocytes are bone marrow-derived, and play a role in normal wound healing, but also in pathogenic fibrosis.
Furthermore, our data indicate that oxidative phosphorylation, mitochondrial dysfunction, decreased unfolded protein response, inhibition of the oxidative stress response, and downregulation of complement system genes play a specific role in the pathogenesis of FECD, whereas other processes, such as premature cellular senescence, extracellular matrix deposition, epithelial-mesenchymal transition, and the newly identified circulating fibrocytes are nonspecific elements (which also play a role in NFE corneas).
Moreover, we have selected a set of 20 genes that are specifically differentially expressed in FECD versus normal and FECD versus NFE, including cochlin (COCH), olfactomedin like 1 (OLFML1) and scm-like with four mbt domains 2 (SFMBT2).
These results will impact the research field, as they lay the foundations for a novel branch of research into the role of circulating fibrocytes in FECD and other CE disorders. Further research is needed to characterize the recruitment, differentiation, and function of circulating fibrocytes in FECD.
Furthermore, patients with FECD might benefit from antifibrotic treatments that are being developed to treat fibrosing disorders of other organs, in which circulating fibrocytes are involved.
Moreover, the new insights into primary and secondary processes in the pathogenesis of FECD, will help direct the future development of non-surgical therapies (for prevention, treatment, and prevention of progression of FECD). In the long run, this should alleviate the burden that FECD imposes on corneal tissue banks, and help reduce corneal blindness worldwide.status: Publishe
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
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