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The role of endothelial proteoglycans and extracellular matrix for the flow- dependent dilatation of isolated normal and atherosclerotic human coronary arteries
No full text0 Titelblatt, Inhaltsverzeichnis, Abkürzungen
1 Einleitung 7
1.1 Geschichte 8
1.2 Fluß und Scherkraft - Begriffsbestimmung und Meßbereiche 9
1.2.1 Laminare Scherkraft 10
1.2.2 Turbulente Scherkraft 10
1.3 Wandaufbau humaner Koronararterien 11
1.3.1 Endothel 11
1.3.2 Extrazelluläre Matrix 13
1.3.3 Endotheliale Proteoglycane als Fluß-Sensoren 15
1.4 Mechanismen der Vasomotorik 16
1.4.1 Vasokonstriktion 16
1.4.2 Flußabhängige Vasodilatation 17
1.5 Desiderate 21
1.6 Ziel der Arbeit 22
2 Methoden 23
2.1 Präparation 23
2.1.1 Explantation 23
2.1.2 Feinpräparation und Äquilibrierung 23
2.1.3 Lösungen und Substanzen 23
2.2 Messung der Flußrate 25
2.3 Messung der Kraftentwicklung 25
2.4 Messung des Membranpotentials 25
2.4.1 Mikroelektroden 25
2.4.2 Meßverstärker und Datenaufnahme 26
2.4.3 Einstiche 26
2.5 Versuchsdurchführung 27
2.6 Korrektur der 'stress relaxation' 27
2.7 Auswertung 28
2.7.1 Auswertungsmodell 28
2.7.2 Statistische Methoden 29
3 Ergebnisse 30
3.1 Kraft- und Potentialentwicklung von unbehandelten normalen Gefäßen 30
3.2 Kraft- und Potentialentwicklung von deendothelialisierten normalen
Gefäßen 30
3.3 Kraft- und Potentialentwicklung von trypsinisierten normalen Gefäßen 33
3.4 Kraft- und Potentialentwicklung von unbehandelten arteriosklerotischen
Gefäßen 33
3.5 Kraft- und Potentialentwicklung von deendothelialisierten
arteriosklerotischen Gefäßen 36
3.6 Kraft- und Potentialentwicklung von trypsinisierten arteriosklerotischen
Gefäßen 36
3.7 Kraftentwicklung in Abhängigkeit vom Sensor in normalen Gefäßen 38
3.8 Kraftentwicklung in Abhängigkeit von der Matrix in normalen Gefäßen 40
3.9 Kraftentwicklung in Abhängigkeit vom Sensor in arteriosklerotischen
Gefäßen 40
3.10 Kraftentwicklung in Abhängigkeit von der Matrix in arteriosklerotischen
Gefäßen 42
4 Diskussion 43
4.1 Elektromechanische Kopplung in humanen Koronararterien 43
4.2 Trypsinisierung 45
4.2.1 Auswirkung in normalen Gefäßen 46
4.2.2 Auswirkung in arteriosklerotischen Gefäßen 47
4.3 Deendothelialisierung 47
4.4 Mechanosensorik und Mechanotransduktion in normalen Gefäßen 47
4.4.1 Anforderungen 48
4.4.2 Kandidaten 48
4.5 Mechanosensorik und -transduktion bei Arteriosklerose 51
4.5.1 Endotheliale Dysfunktion 52
4.5.2 Matrixveränderungen bei Arteriosklerose 53
4.6 Einfluß von endothelständigem Sensor und subendothelialer Matrix auf die
Kraftentwicklung bei verschiedenen Flußraten in normalen Gefäßen 54
4.7 Einfluß von endothelständigem Sensor und subendothelialer Matrix auf die
Kraftentwicklung bei verschiedenen Flußraten in arteriosklerotischen Gefäßen
55
5 Literatur 56
6 Zusammenfassung, Danksagung, Lebenslauf 71
Danksagung 73Die Bedeutung eines intakten Endothels für die flußabhängige Dilatation
arterieller Gefäße ist unbestritten und methodologisch befriedigend
untersucht. Weniger Aufmerksamkeit wurde der Rolle der extrazellulären Matrix
bei der Vermittlung des Flussreizes gewidmet sowie dem Anteil, den beide,
Endothel und Matrix, an Membranpotential und Gefäßtonus arteriosklerotischer
Gefäße haben. Diese Arbeit stellt eine erste systematische vergleichende
Untersuchung des Beitrags von Endothel und Matrix zu Membranpotential- und
Tonusentwicklung in Abhängigkeit von systematisch variierten Flußraten in
normalen und arteriosklerotischen Gefäßen unter jeweils identischen
Versuchsbedingungen dar. Hierzu wurden unbehandelte, intakte humane Koronar-
Präparate wurden mit mechanisch deendothelialisierten Präparaten verglichen
sowie mit Präparaten, die zuvor mit einer niedrig-konzentrierten Trypsinlösung
inkubiert worden waren. Die Trypsinbehandlung führte zur Lösung der Ektodomäne
des endothelialen transmembranalen Proteoglykans Syndecan sowie zur
Desintegration von Teilen der subendothelialen Matrix. Das Membranpotential
wurde intrazellulär mit Glaskapillar-Mikroelektroden, die Kraftentwicklung mit
einem induktiven Kraftaufnehmer gemessen. Mit zunehmender Flußrate von 3
ml/min auf 100 ml/min hyperpolarisierte die glattmuskuläre Zellmembran
unbehandelten nicht-arteriosklerotischen Präparate. Hiermit ging eine
Tonusabnahme in Höhe von 0,512 g einher. Die deendothelialisierten nicht-
arteriosklerotischen Präparate wiesen eine deutlich geringfügigere
Hyperpolarisation und eine Relaxation um lediglich 0,280 g auf. Trypsinisierte
nicht-arteriosklerotische Gefäße zeigten eine Depolarisation sowie eine
Kontraktion von 0,391 g. Unbehandelte arteriosklerotische Präparate wiesen
gegenüber unbehandelten nicht-arteriosklerotischen Präparaten eine
Hyperpolarisation und eine signifikant geringfügigere Abnahme der Wandspannung
um 0,102 g auf. Deendothelialisierte arteriosklerotische Präparate zeigten
eine flußabhängige Hyperpolarisierung mit einer minimalen flußabhängigen
Relaxation um 0,070 g. Trypsinisierte arteriosklerotische Präparate zeigten
eine ausgeprägte flußabhängige Tonusabnahme von 0,612 g. Hieraus lässt sich
ableiten, dass bei physiologischen Flußraten zwischen 20 ml/min und 40 ml/min
das endotheliale Kompartiment normaler humaner Koronararterien zu etwa 65% an
der flußabhängigen Relaxation beteiligt ist, während bei Flußraten von 100
ml/min die flußabhängige Tonusabnahme zu 72% von der subendothelialen Matrix
getragen wird. In arteriosklerotisch veränderten Gefäßen kommt es zu einer
flußabhängigen Kontraktion, an der das endotheliale Kompartiment ab einer
Flußrate von 20 ml/min in zunehmendem Maß beteiligt ist. Bei Flußraten von 100
ml/min vermittelt das endotheliale Kompartiment eine Kontraktion in Höhe von
44% der maximalen Dilatation eines normalen Gefäßes; diese Kontraktion wird
zum größeren Teil von einer matrixvermittelten flußabhängigen Relaxation in
Höhe von 27% der maximalen Tonusabnahme eines normalen Gefäßes aufgehoben.
Diese Ergebnisse weisen auf das Ausmaß der durch Arteriosklerose induzierten
endothelialen Dysfunktion in den untersuchten Gefäßen hin und unterstreichen
die vitale Bedeutung einer intakten subendothelialen Matrix für die
Aufrechterhaltung physiologischer Flußmuster in arteriosklerotisch veränderten
Koronararterien.Despite its clinical importance and augmented research activity, the exact
mechanisms of mechanoperception at the luminal surface of the coronary artery
endothelium and of mechanotransduction on to the arterial smooth muscle cell
remain elusive. This research quantifies the impact of the luminal
proteoglycan syndecan as a potential mechanosensor, and the subendothelial
matrix as the site of mechanotransduction, in maintaining flow-dependent
vasodilatation in healthy and atherosclerotic human coronary arteries. We
measured the development of membrane potential and tension in non-
atherosclerotic and atherosclerotic segments of human coronary arteries under
flow rates of between 5 and 100 ml/min and compared these with the development
in de-endothelialised and trypsinised non-atherosclerotic and atherosclerotic
segments. Trypsinisation lead to the cleavage of the ectodomain of the luminal
proteoglycan syndecan as well as to the interruption of matrix integrity. The
membrane potential was measured intermittently with glass electrodes; vascular
wall tension was measured continuously by mounting the segment in the force
transduction unit of a flow chamber supplied with aerated, heated Krebs
solution at regularly increased flow rates. Untreated non-atherosclerotic
vessel segments showed a marked flow-dependent hyperpolarisation and a
relaxation of 0.512 g. In de-endothelialised non-atherosclerotic vessel
segments, membrane potential and tension were higher at baseline and decreased
less under flow, with a net relaxation of 0.280. Trypsinised non-
atherosclerotic vessel segments had still higher membrane potential and
tension at baseline and showed a marked flow-dependent depolarisation and
contraction of 0.391 g. In untreated atherosclerotic vessel segments, baseline
values for membrane potential and tension were higher than in healthy vessel
segments; under flow conditions, these segments exhibited a stunted
hyperpolarisation and relaxation at low flow rates, with subsequent
depolarisation and contraction under higher flow rates (net relaxation 0.102
g). De-endothelialised atherosclerotic vessel segments had higher baseline
values than de-endothelialised non-atherosclerotic vessel segments and showed
a minimal hyperpolarisation after initial depolarisation as well as a minimal
relaxation (0.070 g). Trypsinised atherosclerotic vessel segments had a
significantly lower baseline membrane potential and tension than untreated
atherosclerotic as well as trypsinised non-atherosclerotic vessel segments and
showed a marked flow-dependent relaxation (0.612). Based on these values, we
calculated the contribution of the luminal flow-sensor syndecan and the
subendothelial matrix to overall vasomotion to be 47% vs. 11% at flow rates of
5 ml/min, 65% vs. 25% at 20 ml/min, 65% vs. 38% at 40 ml/min, and 28% vs. 72%
at 100 ml/min in non-atherosclerotic vessels. In atherosclerotic vessels,
endothelium-induced contraction was 18% at 20 ml/min rising to 43,8% at 100
ml/min, with the matrix partly compensating this with a relaxation of 13% at 5
ml/min and 26% to 27% between 20 and 100 ml/min (100% = 0.461g, maximal net
relaxation of non-atherosclerotic, intact vessel segments)
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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