The bovine corpus luteum as an modell for Angiogenesis, Anti-Angiogenesis and vascular regression

Deckblatt-Impressum persönlicher Dank Inhaltsverzeichnis Abkürzungen Einleitung Literaturübersicht Material und Methoden Eigene Untersuchungen Diskussion Zusammenfassung Summary Literaturverzeichnis Danksagung SelbständigkeitserklärungDas bovine Corpus luteum stellt ein hervorragendes Modell zur Untersuchung der kontrollierten An- und Rückbildung von Blutgefäßen dar. Ziel dieser Dissertationsarbeit war die morphometrische Untersuchung eines spezifischen vaskulären Anbildungs- und Rückbildungsmusters während der Entwicklung und Rückbildung des Gelbkörpers. Ein möglicher Zusammenhang zwischen den morphometrischen Ergebnissen und dem Auftreten bestimmter, die Angiogenese beeinflussender Faktoren, nämlich VEGF, VEGF-R2 und Ang-2, sollte dargestellt werden. Außerdem sollten die einzelnen Phasen der Angiogenese und insbesondere die der Anti-Angiogenese im Hinblick auf Gefäßdichte und Apoptosen dokumentiert werden. Als Organproben dienten 47 bovine Corpora lutea verschiedener Zyklusstadien. Dabei kamen neben licht- und elektronenmikroskopischen Untersuchungen auch lektinhistochemische und immunhistochemische Methoden sowie Apoptosetests zur Anwendung. Ein wichtiges Ergebnis dieser Studie war, dass sich das Corpus hämorrhagicum in drei Zonen gliedert. Das Zentrum des sich entwickelnden Gelbkörpers, Zone 1, besteht aus Erythrozyten und Fibrin. Die sich nach außen anschließende Zone 2 ist durch VEGF-positive Makrophagen, die durch Freisetzung von VEGF die Migration und Proliferation von Endothelzellen während der frühen lutealen Angiogenese fördern, Erythrozyten und Bindegewebe charakterisiert. Im frühen und späten Residualgelbkörper kommt es zu einer massiven Einwanderung von Makrophagen, die den programmierten Zelltod lutealer Endothelzellen vermitteln können. Das wichtigste Ergebnis dieser Studie war, dass im Corpus luteum in Rückbildung eine neue Angiogenesewelle auftritt, wie der Anstieg der kapillären Dichte und die gleichzeitige Vergrößerung der Anzahl VEGF-positiver Zellen belegen. Die erneute Angiogenesewelle während des Abbaus des Gelbkörpers könnte gleichzeitig den Aufbau des Gelbkörpers des nachfolgenden Zyklus vermitteln. Die Ergebnisse der Untersuchung des Corpus albicans ergaben gleichfalls einen erneuten Anstieg der Kapillarenanzahl und des prozentualen Flächenanteils der Gefäßlumina in Stadium 10 des Corpus albicans. Es ist anzunehmen, dass das Corpus albicans von außen nach innen organisiert wird. Erstmalig gelang die immunhistochemische Darstellung von VEGF-R2 und Ang-2 in vaskulären glatten Muskelzellen aus dem bovinen Corpus luteum. Es ist anzunehmen, dass VEGF und Ang-2 Mitogene für vaskuläre glatte Muskelzellen im bovinen Ovar darstellen. Die ultrastrukturellen Untersuchungen ergaben, dass die durch den Verschluss größerer Blutgefäße durch abgeschwemmte Zellen bedingte Mangeldurchblutung den auslösenden Faktor für den programmierten Zelltod von lutealen Endothelzellen darstellen könnte. Ein weiteres wichtiges Ergebnis dieser Studie war, dass Hochleistungskühe im Vergleich zu Kühen, die zu Zweinutzungsrassen zu zählen sind, eine intensivere luteale Angiogenese zeigen und die bei Hochleistungsmilchkühen auftretenden Störungen der ovariellen Funktionen möglicherweise durch eine Hochregulierung angiogener Prozesse oder einen Defekt der Gegenregulation der Angiogenese (Anti-Angiogenese) bedingt sein könnten.The bovine corpus luteum is an excellent model for controlled vascular development and regression. The aim of this study was to examine the pattern of blood vessel growth and regression during the development and luteolysis of the corpus luteum. A potential coherence between the morphometric results and factors involved in angiogenesis, namely VEGF, VEGF-R2 and Ang-2 should be pointed out. Each step of angiogenesis and particulary anti-angiogenesis should be documented with regard to vascular density and apoptosis. 47 bovine corpora lutea from different stages of the oestrous cycle were examined by light- and electron-microscopy, lectinhistochemistry, immunohistochemistry and TUNEL-Test. An important result of this study was that the corpus hämorrhagicum could be divided into three zones: the central zone of the developing corpus luteum consisting of erythrocyts and fibrin; the outer zone characterized by erythrocyts, connective tissue and VEGF-positive macrophages which might stimulate migration and proliferation of endothelial cells during early luteal angiogenesis. In the early and late regressing corpus luteum many macrophages could be observed which might be responsible for the programmed cell death of endothelial cells. The most important result of the present study was that during late luteal regression a new angiogenic phase sets in. A moderate increase of capillaries becomes obvious and the VEGF-immunolabelling is high during late regression. It is possible that the new angiogenic phase in the regressing corpus luteum is not only important for regression of the corpus luteum but also for the development of the corpus luteum of the following cycle. The results of this study show further more an increase of capillaries and blood vessel lumina in stadium 10 of the corpus albicans. Therefore it may be that the corpus albicans is organized from the outer to the inner zone. For the first time VEGF-R2 and Ang-2 could be shown in vascular smooth muscle cells of the bovine corpus luteum indicating that these two factors are important mitogens for vascular smooth muscle cells in the bovine ovary. Ultrastructural analysis shows that the obliteration of blood vessels by cells causes a reduction of blood flow which might trigger programmed cell death of luteal endothelial cells. Another important result of this study was that high-performance cows show a more intensive luteal angiogenesis than other cows. This may indicate that ovarial dysfunctions in these animals are the result of an increased angiogenesis or an defect of anti-angiogenesis

Gene Gauntier

During the years 1907-1912, Gene Gauntier, the first “Kalem Girl,” was the preeminent figure at the Kalem Film Manufacturing Company. She played key roles in the events that comprise established film history. She wrote the scenario for Ben Hur (1907), the work involved in the controversy that established the first copyright laws covering motion pictures, and wrote and acted in key films. In addition, she acted in the Nan, the Confederate Spy series: The Girl Spy (1909), The Girl Spy Before Vicksburg (1910), The Further Adventures of the Girl Spy (1910), cross-dressing forerunners of the serial action queens. She appeared in The Lad From Old Ireland (1910), the first film shot on location outside of the United States, and in From the Manger to the Cross (1912), the first feature-length treatment of the life of Christ. The Kalem Company was the first to make fiction motion pictures on location around the world, which has meant that 35mm film prints and other documents may have been deposited in archives outside the United States, the best example of which is the Irish Film Archives in Dublin, where one extant Gene Gauntier Feature Players title and five Kalem titles are archived (Condon 2008)

Opening Remarks

You are all extended the very warmest welcome to the University of Missouri-Rolla. This four day conference on energy, the second of its kind, is filled with papers and activities that should find some interest for almost everyone involved in energy activities. All of us on this campus want you to have a rewarding four days and to enjoy yourselves as well. It goes without saying that we stand ready to aid you in every way that is possible. I want to commend the organizers, particularly Dr. Derald Morgan, for his hard and dedicated work in putting the conference together

A comparative assessment of vibration control capabilities of a L-shaped Gurney flap

This work presents the capabilities of a novel L-shaped trailing-edge Gurney flap as a device for vibration reduction. The primary effect of this L-tab is represented by a modification of the reference aerofoil mean line shape through by two counter-rotating vortical structures created at the trailing edge. The comparison of the aerodynamic loads generated by the novel L-tab Gurney flap and a classical trailing-edge flap allows to estimate the ranges of reduced frequency where the L-tab is expected to perform better than a trailing edge flap and vice versa. Linear aerostructural models for a typical section representative of a helicopter blade equipped with a partial-span L-tab or a trailing-edge flap are built, and a higher harmonic control algorithm is applied. Performance are compared between the two devices to reduce separately the N/rev harmonics of the blade root rotating frame vertical force, flapping and feathering moments. The attainment of similar results with classical trailing-edge device is a further confirmation of the potential feasibility of this novel L-tab as an effective alternative means for vibration reduction on rotor blades

Flutter and forced response of mistuned rotors using standing wave analysis

A standing wave approach is applied to the analysis of the flutter and forced response of tuned and mistuned rotors. The traditional traveling wave cascade airforces are recast into standing wave arbitrary motion form using Pade approximants, and the resulting equations of motion are written in the matrix form. Applications for vibration modes, flutter, and forced response are discussed. It is noted that the standing wave methods may prove to be more versatile for dealing with certain applications, such as coupling flutter with forced response and dynamic shaft problems, transient impulses on the rotor, low-order engine excitation, bearing motion, and mistuning effects in rotors

Three-dimensional Aeroelastic and Aerothermoelastic Behavior in Hypersonic Flow

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76667/1/AIAA-2005-2175-915.pd

Wall effects on pressure fluctuations in turbulent channel flow

The purpose of the present paper is to study the influence of wall-echo on pressure fluctuations $p'$, and on statistical correlations containing $p'$, {\em viz} redistribution $\phi_{ij}$, pressure diffusion $d_{ij}^{(p)}$, and velocity/pressure-gradient $\Pi_{ij}$. We extend the usual analysis of turbulent correlations containing pressure fluctuations in wall-bounded \tsc{dns} computations [Kim J.: {\em J. Fluid Mech.} {\bf 205} (1989) 421--451], separating $p'$ not only into rapid $p_{(\mathrm{r})}'$ and slow $p_{(\mathrm{s})}'$ parts [Chou P.Y.: {\em Quart. Appl. Math.} {\bf 3} (1945) 38--54], but further into volume ($p'_{(\mathrm{r};\mathfrak{V})}$ and $p'_{(\mathrm{s};\mathfrak{V})}$) and surface (wall-echo; $p'_{(\mathrm{r};w)}$ and $p'_{(\mathrm{s};w)}$) terms. An algorithm, based on a Green's function approach, is developed to compute the above splittings for various correlations containing pressure fluctuations (redistribution, pressure diffusion, velocity/pressure-gradient), in fully developed turbulent plane channel flow. This exact analysis confirms previous results based on a method-of-images approximation [Manceau R., Wang M., Laurence D.: {\em J. Fluid Mech.} {\bf 438} (2001) 307--338] showing that, at the wall, $p'_{(\mathfrak{V})}$ and $p'_{(w)}$ are usually of the same sign and approximately equal. The above results are then used to study the contribution of each mechanism on the pressure correlations in low Reynolds-number plane channel flow, and to discuss standard second-moment-closure modelling practices

Geometrically Nonlinear Aeroelastic Scaling for Very Flexible Aircraft

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106446/1/AIAA2013-1894.pd