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
Identifizierung von MECP2-Zielgenen und Proteinen verwandt mit MECP2
Cover
Table of Contents
page
1
Abbreviations
page
6
Abstract
page
8
1\. Introduction
page
10
2\. Materials and Methods
page
35
3\. Results
page
55
4\. Discussion
page
80
5\. German Summary
page
95
6\. Annex
page
97
7\. References
page
98
Acknowledgements
page
110
Curriculum Vitae and Publications
page
111Mutations in the gene coding for the methyl-CpG binding protein 2 (MECP2)
cause a severe form of mental retardation known as Rett syndrome. Almost
exclusively girls are affected by this disease. The first mutations in the
X-chromosomal gene MECP2 have been described in 1999, but the molecular
mechanisms underlying the disorder are still unknown. MECP2 can act as a
transcriptional repressor and only two neuronal target genes (Bdnf and Dlx5)
have been identified so far. While MECP2 is expressed ubiquitously, the
phenotype of the disease is primarily neuronal. This suggests that MECP2 has
an important function in the brain, whereas, in peripheral tissues, loss of
function of MECP2 might be compensated by functionally redundant proteins.
To find proteins that could potentially mediate such a compensation, two
strategies were applied. In a first project, a bioinformatics approach was
used to find additional polypeptides that contain an methyl-CpG binding domain
(MBD), the domain of MECP2 which binds to methylated CpGs. Six new such
proteins could be detected and were studied for their expression and domain
structure.
A second project aimed at identifying proteins with an overall amino acid
similarity to MECP2. Such proteins could point to additional, so far unknown
functions of MECP2. Two proteins were identified by database screens and their
properties are discussed in this thesis. The structure of one of them, the
neurofilament NEFH, suggests that MECP2 has an elongated shape.
To elucidate the target genes of MECP2 in the brain, chromatin
immunoprecipitation (ChIP) was established and combined with a cDNA microarray
approach. An animal model for Rett syndrome was used for this analysis. The
microarray experiment showed, that Mecp2-null animals differentially express
several genes that are induced during stress response by glucocorticoids.
Increased levels of mRNAs for plasma glucocorticoid-inducible kinase 1 (Sgk)
and FK506-binding protein 51 (Fkbp5) were observed. Immunohistochemistry
revealed, that in mouse brains Mecp2 and Fkbp5 as well as Sgk are expressed in
the same cells. These results suggests a modulating function of MECP2 in gene
expression regulation rather than a total repression since the transcriptional
repressor MECP2 and its target genes are expressed in the same cells.
In Fkbp5, three MECP2-binding regions could be determined by ChIP. One of the
regions is also a target site for the glucocorticoid receptor (GR). Therefore
a model can be proposed in which MECP2 and GR compete for a binding site in
Fkbp5 and regulate its transcription. In Rett patients this regulation would
be disturbed due to the loss of function of MECP2 leading to a constant
overexpression of glucocorticoid pathway downstream targets and potentially to
several features of the Rett syndrome phenotype.Rett Syndrom, eine schwere Form der geistigen Behinderung, wird durch
Mutationen in dem X-chromosomalen Gen des Methyl-CpG bindenden Proteins 2
(MECP2) verursacht und kommt fast ausschließlich bei Mädchen vor. Mutationen
in MECP2 wurden erstmals 1999 beschrieben, die molekularen Mechanismen, welche
der Krankheit zugrunde liegen, sind bisher aber unbekannt. Eine bekannte
Funktion von MECP2 ist die der Transkription-Repression.
Lediglich zwei neuronale Zielgene (Bdnf und Dlx5) wurden jedoch bisher
beschrieben. Obwohl MECP2 ubiquitär exprimiert ist, besteht bei Rett Syndrom
Patienten ein primär neuronaler Phänotyp. Diese Beobachtung lässt die
Vermutung zu, dass MECP2 im Gehirn eine wichtige Funktion erfüllt, während in
peripheren Geweben der Funktionsverlust von MECP2 durch ein funktionell
redundantes Protein kompensiert werden könnte.
Um Proteine zu finden, die eine solche kompensatorische Funktion übernehmen
könnten, wurden zwei Strategien angewandt. Im ersten Projekt wurde mit
bioinformatischen Mitteln nach Proteinen gesucht, die ebenso wie MECP2 eine
methyl-CpG bindende Domäne (MBD) besitzen. Sechs solcher Proteine wurden
gefunden und auf ihre Expression und Domänenstruktur hin untersucht.
Das zweite Projekt zielte darauf ab, Proteine zu identifizieren, die eine
globale Ähnlichkeit zu MECP2 aufweisen. Solche Proteine sollten Rückschlüsse
auf die Form und eventuell sogar auf bisher unbekannte Funktionen von MECP2
zulassen. Zwei solche paralogen Polypeptide wurden gefunden und die Struktur
eines dieser, NEFH, lässt vermuten, dass MECP2 eine längliche Form hat. Der
Sequenzvergleich zwischen NEFH und MECP2 deutet zudem auf eine potentielle
Phosphorylierungsstelle in MECP2 hin.
Um Zielgene von MECP2 im Gehirn zu finden, wurde die
Chromatinimmunpräzipitation (ChIP) etabliert und mit cDNS-Mikroarray
Untersuchungen eines Mausmodells für Rett Syndrom kombiniert. Die Auswertung
der Mikroarray-Daten zeigte, dass in diesen Tieren mehrere Gene differenziell
exprimiert sind, die normalerweise während der Stressanwort durch
Glukokortikoide reguliert werden. Erhöhte mRNS-Werte konnten für die "Plasma
Glukokortikoid-induzierbare Kinase 1" (Sgk) sowie für das "FK506-bindende
Protein 51" (Fkbp5) nachgewiesen werden. Durch Immunfärbung histologischer
Gehirnschnitte, konnte gezeigt werden, dass Mecp2 und Fkbp5 sowie Sgk in
denselben Zellen des Gehirns synthetisiert werden. Dies legt nahe, dass MECP2
eher eine Modulation der Expression bewirkt, als eine komplette Repression.
Mittels ChIP konnten drei Bindungsstellen von MECP2 in der genomischen Region
von Fkbp5 gefunden werden. Eine dieser Bindungsstellen kann zudem auch vom
Glukokortikoid-Rezeptor (GR) gebunden werden. Aufgrund dieser Ergebnisse wurde
eine Hypothese formuliert, nach der MECP2 und GR um die Bindung an eine Region
im Fkbp5 Gen konkurrieren und beide die Expression von FKBP5 regulieren. In
Rett Syndrom Patienten ist diese Regulation auf Grund des Funktionsverlusts
von MECP2 gestört. Dies würde zu einer Überexpression von Glukokortikoid-
regulierten Genen führen, wodurch mehrere Merkmale des Rett Syndrom-Phänotyps
erklärt werden könnten
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
- …
