1,720,960 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
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
Functional and morphological adaptations in tafazzin-deficient pancreatic islets in the context of Barth syndrome
Das Barth Syndrom (BTHS) ist eine X-chromosomale Multisystem Erkrankung, die durch Mutationen in dem Gen verursacht wird, das für das mitochondriale Enzym Tafazzin (Taz) kodiert. Die Transacylase Tafazzin katalysiert den finalen Schritt in der Biosynthese von Cardiolipin (CL) und beeinflusst dadurch entscheidend die Phospholipid-Zusammensetzung in der inneren Mitochondrienmembran. BTHS-Patienten leiden unter einer Vielzahl schwer-wiegender Symptome, darunter Herzversagen, Muskelschwäche und systemischer Stoffwechselstörungen, einschließlich Hypoglykämie. Die Rolle von dysfunktionaler CL-Zusammensetzung in pankreatischen Inseln ist bisher weitgehend unerforscht.
Im Rahmen dieser Arbeit wurde ein shRNA-basiertes, Doxycyclin-induzierbares Tafazzin-Knockdown (Taz-KD) Maus Modell, bekannt als shTaz, verwendet, um die Eigenschaften und Funktionalität von Pankreasinseln im Zusammenhang mit BTHS zu untersuchen. Nach einer anfänglichen Charakterisierung des Taz-KD Modells mittels qPCR-Messung des Taz Gens und Lipidomik-Analyse bei Taz-KD Pankreasinseln, wurden die 20 Wochen alten Taz-KD Mäuse systemisch über das Körpergewicht und mithilfe eines Glukose-Toleranz-Tests mit Wildtyp (WT) Wurfgeschwister Mäusen verglichen. Anschließend wurden Pankreasschnitte mittels Immunfärbung zunächst nach der zellulären Zusammensetzung der Pankreasinseln (α-, β- oder δ-Zellen) und dann nach Apoptose- oder Proliferation-Markern untersucht. Danach wurde eine umfassende biochemische und funktionelle Analyse der isolierten Taz-KD Pankreasinseln durchgeführt. Außerdem wurde der Einfluss von Redox Veränderungen über Redox-Histologie und Western Blot bei Taz-KD Pankreasinseln analysiert. Da BTHS primär eine Schädigung der Mitochondrien verursacht, wurde die Funktion und Morphologie der Mitochondrien über einen Seahorse XFe96 Analysator und über konfokale Mikroskopie bei isolierten intakten und vereinzelten Taz-KD pankreatischen Inseln untersucht. Des Weiteren wurde die Zusammensetzung des RNA- und Lipid-Profils mittels RNA-Sequenzierung und Lipidomik-Analyse von WT und Taz-KD Pankreasinseln verglichen. Abschließend wurden ein neues Taz-KD in vitro Modell mit einer Woche Doxycyclin Gabe im Kulturmedium etabliert und mechanistisch untersucht. Diese Ergebnisse wurden mit den zuvor gewonnenen Daten der funktionellen Analyse von Taz-KD Pankreasinseln bei lebenslanger Doxycyclin Gabe im Futter verglichen, was ein umfassendes Verständnis der Biologie der Pankreasinseln bei der BTHS-Entwicklung ermöglicht.
In den Ergebnissen wurde zunächst die Effizienz des Taz-KD mit ca. 65% für Pankreasinseln und ca. 85% bei Herzen festgestellt. Trotz abgeschwächter Effizienz des Taz-KD bei Pankreasinseln kam es zu einer Abnahme der CL-Konzentration sowie einer geänderten CL-Spezies-Zusammensetzung. Zusätzlich, wurden ebenfalls andere Phospholipidklassen, insbesondere Phosphatidyl-ethanolamin, -cholin, -glycerol durch den Taz-KD signifikant beeinflusst. Die Taz-KD Mäuse zeigten ein verringertes Körpergewicht und eine verbesserte Glukose-Toleranz mit unveränderten Insulin- und Glukagon-Plasma-Werten gegenüber den WT-Kontrollen. Taz-KD Pankreasinseln zeigten eine vermehrte Anzahl an α-Zellen verbunden mit einer erhöhten Glukagon-Sekretion und unveränderter Insulin-Sekretion. Weitere funktionelle Experimente ergaben einen beschleunigten, zytosolischen Ca2+-Einstrom, eine unveränderte ATP-Produktion und eine erhöhte Glukose-Aufnahme der Taz-KD Pankreasinseln. Eine mitochondriale Redox-Analyse ergab einen leicht reduzierten in vivo sowie einen geringfügig oxidierten ex vivo Redox-Status, verbunden mit einer gesteigerten NOX4 Aktivität und einer erhöhten Menge an Prx3 bei Taz-KD Pankreasinseln. Die Mitochondrien von Taz-KD Pankreasinseln hatten ein vergrößertes Volumen und einen leicht erhöhten Sauerstoffverbrauch bei niedrigen Glukosemengen. Des Weiteren ergab eine Reactome Analyse der RNA-Sequenzierungsdaten, dass mehrere Gene die an der post-translationalen Modifikation der O-Glykosylierung beteiligt sind, in den Taz-KD Pankreas-inseln erhöht waren. Dieser Anstieg konnte auf Proteinebene durch Western Blot und Immunfärbung bestätigt werden. Abschließend wurde beim Taz-KD in vitro Modell im Vergleich zu gleich behandelten Kontrollen ebenfalls eine Abnahme um 65% der Taz RNA und ein geändertes CL-Profil beobachtet. Außerdem konnte eine verminderte ATP-Menge und Insulin Sekretion beim in vitro Taz-KD Modell gemessen werden.
Die Ergebnisse dieser Arbeit zeigen, dass die Funktionalität der Taz-KD Pankreasinseln in vivo erhalten bleibt. Dies wird über verschiedene kompensatorische Wege einschließlich vergrößertes Mitochondrien-Volumen, erhöhter Glukoseaufnahme und amplifizierter O-Glykosylierung gewährleistet. Außerdem könnte die erhöhte Menge an α-Zellen und die gesteigerte Glukagon-Sekretion, die Insulin-Sekretion über parakrine Signalwirkung positiv beeinflussen. Diese adaptiven Mechanismen sind vielversprechende Ansatzpunkte für die Behandlung von Pankreasinseln bei metabolischen Defekten. Im Gegensatz dazu hat das Taz-KD in vitro Modell gezeigt, dass eine Reduktion der Taz RNA bei ausbleibenden adaptiven Mechanismen, eine direkte Störung der Pankreasinseln zur Folge hat. Dies verdeutlicht die wichtige Rolle von CL für die Funktion von Pankreasinseln.Barth syndrome (BTHS) is an X-linked multisystem disorder caused by mutations in the gene encoding the mitochondrial enzyme tafazzin (Taz). The transacylase tafazzin catalyses the final step in the biosynthesis of cardiolipin (CL), thereby decisively influencing the phospholipid composition in the inner mitochondrial membrane. BTHS patients suffer from a variety of severe symptoms, including heart failure, muscle weakness, and systemic metabolic disturbances, including hypoglycemia. The role of dysfunctional CL composition in pancreatic islets is mostly unexplored.
In this thesis, a shRNA-based doxycycline-inducible tafazzin knockdown (Taz-KD) mouse model, known as shTaz, was used to investigate the properties and functionality of pancreatic islets in the context of BTHS. After initial characterisation of the Taz-KD model using qPCR measurements of the Taz gene and lipidomics analysis of Taz-KD pancreatic islets, 20-week-old Taz-KD mice were compared systemically by body weight and using a glucose tolerance test with wildtype (WT) littermate mice. Subsequently, pancreas tissue slices were analysed, first for the cellular composition of the pancreatic islets (α-, β- or δ-cells) and then for apoptosis or proliferation markers. Subsequently, comprehensive biochemical and functional analyses of the isolated Taz-KD pancreatic islets were performed. In addition, the influence of redox changes on Taz-KD pancreatic islets was analysed using redox histology and western blotting. Since BTHS primarily causes mitochondrial damage, the function and morphology of mitochondria were examined using a Seahorse XFe96 analyser and confocal microscopy in isolated intact and dispersed Taz-KD pancreatic islets. Furthermore, the RNA and lipid profiles of WT and Taz-KD pancreatic islets were compared by RNA sequencing and lipidomics analysis. Finally, a new Taz-KD in vitro model with one week of doxycycline administration into the culture medium of isolated islets was established and mechanistically investigated. These results were compared with the earlier obtained data from the functional analyses of the Taz-KD pancreatic islets of mice receiving a lifelong doxycycline diet. Together these results provide a comprehensive understanding of pancreatic islet physiology during BTHS development.
The efficiency of doxycycline-induced Taz-KD was approximately 65% for pancreatic islets and 85% for hearts. Despite the attenuated efficiency of Taz-KD in pancreatic islets, it still resulted in a decreased concentration of CL and a significantly altered CL species composition. Taz-KD in pancreatic islets also significantly affected other phospholipid classes, specifically phosphatidyl-ethanolamine, -choline, and -glycerol. The Taz-KD mice displayed reduced body weight and improved glucose tolerance with unchanged plasma insulin and glucagon levels compared to WT controls. Taz-KD pancreatic islets had more α-cells, which was associated with enhanced glucagon but unchanged insulin secretion. Further functional experiments revealed a faster cytosolic Ca2+ influx upon glucose stimulation, an unchanged ATP production, and an increased glucose uptake of Taz-KD compared to WT pancreatic islets. Mitochondrial redox analysis revealed a slightly reduced in vivo and an oxidised ex vivo redox state, which was connected with increased NOX4 activity and a higher amount of Prx3 in Taz-KD compared to WT pancreatic islets. The mitochondria of Taz-KD pancreatic islets had a larger volume than control islets and a slightly increased oxygen consumption rate at low glucose levels. Moreover, Reactome analysis of RNA sequencing data revealed that several genes involved in the post-translational modification of O-glycosylation were increased in Taz-KD pancreatic islets. This increase was confirmed at the protein level by western blotting and immunostaining. Finally, using the Taz-KD in vitro model, a 65% decrease in Taz RNA and an altered CL profile were observed, when compared to doxycycline-cultured controls. Additionally, decreased ATP levels and impaired insulin secretion were measured in Taz-KD pancreatic islets from the in vitro model.
The results of this thesis show that the functionality of Taz-KD pancreatic islets is maintained in vivo. This is ensured via several compensatory mechanisms, including enhanced mitochondrial volume, increased glucose uptake, and amplified O-glycosylation. In addition, the increased number of α-cells and the higher glucagon secretion could positively influence insulin secretion via paracrine signalling. These adaptive mechanisms are promising targets for the treatment of pancreatic islets in metabolic disorders. On the other hand, the Taz-KD in vitro model has shown that a reduction of Taz RNA in the absence of compensatory mechanisms results in a direct defect of pancreatic islets. This highlights the vital role of CL remodelling in pancreatic islet functionality.SFB 89
Variations on the Author
“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
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
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
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
In 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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