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Because of the imbalance in the supply and demand of red blood cells (RBCs), especially for alloimmunized patients or patients with rare blood phenotypes, extensive research has been done to generate therapeutic quantities of mature RBCs from hematopoietic stem cells of various sources, such as bone marrow, peripheral blood, and cord blood. Since human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can be maintained indefinitely in vitro, they represent potentially inexhaustible sources of donor-free RBCs. In contrast to other ex vivo stem-cell-derived cellular therapeutics, tumorigenesis is not a concern, as RBCs can be irradiated without marked adverse effects on in vivo function. Here, we provide a comprehensive review of the recent publications relevant to the generation and characterization of hESC- and iPSC-derived erythroid cells and discuss challenges to be met before the eventual realization of clinical usage of these cells.
Adipose tissue as a stem cell source is ubiquitously available and has several advantages compared to other sources. It is easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose-derived mesenchymal stromal/stem cells (ASCs) yields a high amount of stem cells, which is essential for stem-cell-based therapies and tissue engineering. Several studies have provided evidence that ASCs in situ reside in a perivascular niche, whereas the exact localization of ASCs in native adipose tissue is still under debate. ASCs are isolated by their capacity to adhere to plastic. Nevertheless, recent isolation and culture techniques lack standardization. Cultured cells are characterized by their expression of characteristic markers and their capacity to differentiate into cells from meso-, ecto-, and entodermal lineages. ASCs possess a high plasticity and differentiate into various cell types, including adipocytes, osteoblasts, chondrocytes, myocytes, hepatocytes, neural cells, and endothelial and epithelial cells. Nevertheless, recent studies suggest that ASCs are a heterogeneous mixture of cells containing subpopulations of stem and more committed progenitor cells. This paper summarizes and discusses the current knowledge of the tissue localization of ASCs in situ, their characterization and heterogeneity in vitro, and the lack of standardization in isolation and culture methods.
Within the last twenty years, the contraction method has turned out to be a fruitful approach to distributional convergence of sequences of random variables which obey additive recurrences. It was mainly invented for applications in the real-valued framework; however, in recent years, more complex state spaces such as Hilbert spaces have been under consideration. Based upon the family of Zolotarev metrics which were introduced in the late seventies, we develop the method in the context of Banach spaces and work it out in detail in the case of continuous resp. cadlag functions on the unit interval. We formulate sufficient conditions for both the sequence under consideration and its possible limit which satisfies a stochastic fixed-point equation, that allow to deduce functional limit theorems in applications. As a first application we present a new and considerably short proof of the classical invariance principle due to Donsker. It is based on a recursive decomposition. Moreover, we apply the method in the analysis of the complexity of partial match queries in two-dimensional search trees such as quadtrees and 2-d trees. These important data structures have been under heavy investigation since their invention in the seventies. Our results give answers to problems that have been left open in the pioneering work of Flajolet et al. in the eighties and nineties. We expect that the functional contraction method will significantly contribute to solutions for similar problems involving additive recursions in the following years.
European pea crabs - taxonomy, morphology, and host-ecology (Crustacea: Brachyura: Pinnotheridae)
(2010)
Pinnotherids are small crabs symbiotic to a variety of invertebrates. The European species infest bivalves and sea squirts. Their way of life is parasitic and poses a threat to commercially exploited bivalves. While juveniles of both sexes still look very similar - being agile swimmers and partially free living - a metamorphosis takes place in the female after mating and results in a conspicuous sexual dimorphism. Thereafter, the female settles in its host definitely and is morphologically strongly adapted to the parasitic life phase. A very high reproductive output was demonstrated among several pea crab species infesting bivalves. Despite from that, hardly any information is present in the literature on the pinnotherids’ reproductive biology and the underlying morphology.
Due to their cryptic way of life, the sexual dimorphism, and the different morphotypes of the female, the taxonomy of the Pinnotheridae is a serious challenge. Two widely accepted species are recognized on European coasts: Pinnotheres pisum and Nepinnotheres pinnotheres. Pinnotheres pectunculi was so far only known from the bivalve Glycymeris glycymeris in its type locality Roscoff (France), while Pinnotheres ascidicola and Pinnotheres marioni were described as living exclusively in ascidians without careful comparison with the previously described species. In order to produce standardized comparative descriptions, pea crabs were collected and studied from different hosts and localities in the Northeast Atlantic and in the Mediterranean. Nepinnotheres pinnotheres and Pinnotheres pisum were redescribed with consideration to characters of female and male. According to our morphological analysis, Pinnotheres ascidicola and Pinnotheres marioni are junior synonyms of Nepinnotheres pinnotheres, whereas the status of Pinnotheres pectunculi as a valid species was ascertained. Important characters are the mouthparts, the male gonopods, and especially chelipeds that showed consistent characteristics among different crab stages of both sexes.
Based on our sampling, we estimated the host-range of the European species. Nepinnotheres pinnotheres lives in ascidians and in the pen shell Pinna nobilis. Pinnotheres pisum infests numerous bivalve species - Pinna nobilis included. For Pinnotheres pectunculi novel host records are presented, all from the bivalve family Veneridae. Furthermore, feeding of the Pinnotheres-species was observed. They use a setae comb ventrally on the claw to brush mucus (and the accumulated food particles) from the bivalve gills. Feeding strategies and host-ecology will be thoroughly discussed in consideration to other Pinnotheridae.
We investigated the reproductive systems of European pinnotherids by histological methods, scanning and transmission electron microscopy, and confocal laser scanning microscopy.
The Eubrachyura have internal fertilization: paired vaginas enlarge into storage structures, the spermathecae, which are connected to the ovaries by oviducts. Sperm is stored until the oocytes are mature and transported into the spermathecae, where fertilization takes place. In the investigated pinnotherids, the vagina is of the ‘concave pattern’. Musculature is attached alongside flexible parts of the vagina-wall to control the dimension of its lumen. The genital opening is closed by a muscular mobile operculum.
The spermatheca can be divided into two distinct regions by function and morphology. The ventral part includes the connection with vagina and oviduct and is regarded as the zone where fertilization takes place. It is lined with cuticle except where the oviduct enters the spermatheca by the ‘holocrine transfer tissue’. At ovulation, the oocytes have to pass through this multi-layered glandular epithelium, which has a holocrine mode secretion. The dorsal part of the spermatheca is lined by a highly secretory apocrine glandular epithelium, which was to date only found in fiddler crabs of the genus Uca.
The male internal reproductive system consists of paired testes and corresponding vasa deferentia. The sperm morphology of pinnotherids conforms to other thoracotremes, with slight differences between Nepinnotheres pinnotheres and Pinnotheres pisum. Spermatozoa become enveloped into spermatophores in the secretory proximal vas deferens. The medial vas deferens is strongly enlarged and stores spermatophores embedded in seminal plasma. The distal vas deferens holds tubular appendices, which extend into the ventral cephalothorax and slightly into the pleon. These appendices produce and store vast quantities of seminal plasma. The copulatory system of the Brachyura is formed by paired penes and two pairs of gonopods, which function in sperm transfer. In pinnotherids, the long first gonopods transfers the sperm mass to the female. It holds the ejaculatory canal inside, which opens proximally and distally. The second gonopod is solid, short and conical. During copulation, the penis and the second gonopod are inserted into the base of the tubular first gonopod. The second gonopod functions in the transport of the sperm mass inside the ejaculatory canal towards its distal opening. The specific shape of the second gonopod is strongly adapted for a sealing of the tubular first gonopod with longitudinal cuticle foldings that interlock inside the first gonopod. The presented results are discussed concerning their function in reproduction and in respect of the systematic account.
The role of secretion in sperm transfer, storage and fertilization among the Brachyura is still under debate. It is notable that structure and function of secretion are more complex in pinnotherids and probably more efficient than in other brachyuran crabs, which will be discussed, in view of the parasitic way of life and the high fecundity of pinnotherids.
Das geographische Verbreitungsgebiet von Arten ist ein fundamentales Struktur gebendes Merkmal der biologischen Welt. Warum Arten so verteilt sind, wie sie sind ist seit langem eine der zentralen Fragen in Ökologie, Biogeographie und Evolution. Gegenwärtig verändern sich, im Wesentlichen als unbeabsichtigtes Nebenprodukt menschlicher ökonomischen Aktivitäten und Populationsdynamik, die geographischen Verbreitungsgebiete von Arten mit entscheidender Bedeutung für Land- und Forstwirtschaft, als Krankheitsvektoren oder als Teil der biologischen Systeme, die Ökosystemfunktionen bereitstellen. Daher ist es dringend notwendig, dass wir unser Verständnis über die Dynamiken, aus denen die geographische Verbreitung von Arten erwachsen, verbessern. Mit dieser Doktorarbeit versuche ich, in drei Untersuchungen zur Dynamik der Verbreitungsgebiete von Singvögeln einen Beitrag zu unserem in Entwicklung begriffenen Verständnis der multiplen Faktoren die Artverbreitungsgebiete beeinflussen, zu leisten.
1) Zu einem mechanistischeren Verständnis von Artmerkmalen und Verbreitungsgebietsgrößen: Ein wichtiger, ungelöster Fragenkomplex in der Makroökologie ist, die immense interspezifische Variation in der Größe geographischer Verbreitungsgebiete zu verstehen. Während man davon ausgeht, dass Artmerkmale wie Fekundität und Körpergröße einen Effekt auf Verbreitungsgebietsgrößen haben, fehlt ein allgemeines Verständnis davon, wie Verbreitungsgebietsgrößen von mehreren Merkmalen gemeinsam beeinflusst werden. Hier beurteilen wir den Effekt von Lebensgeschichtsmerkmalen (Fekundität, Ausbreitungsfähigkeit), ökologischen Merkmalen (Habitatnische, Nahrungsnische, Zugverhalten, Flexibilität im Zugverhalten) und morphologischen Merkmalen (Körpergröße) auf die globale Verbreitungsgebietsgröße von 165 europäischen Singvögeln. Wir identifizieren Hypothesen zur Beziehung von Artmerkmalen und Verbreitungsgebietsgrößen aus der Literatur und verwenden die Methodik der Pfadanalyse, um sie zu testen. Die Größe der globalen geographischen Verbreitungsgebiete europäischer Singvögel wurde von Lebensgeschichtsmerkmalen (Fekundidtät und Ausbreitungsfähigkeit), ökologischen Merkmalen (Habitatnischenbreite, Nahrungsnischenposition und Zugverhalten) und von Körpergröße beeinflusst. Artmerkmale beeinflussten Verbreitungsgebietsgrößen auf direktem und indirektem Weg. Insbesondere der Einfluss von Körpergröße war komplex mit positiven und negativen Effekten über verschiedene Pfade. Die Größe von Verbreitungsgebieten ist sehr wahrscheinlich auch von anderen Faktoren als von Artmerkmalen abhängig. Wir zeigen, dass es notwendig ist, den direkten und indirekten Einfluss einer Vielzahl von Merkmalen zu entwirren, um die Mechanismen, die makroökologische Beziehungen generieren, aufzuklären.
2) Konkurrenz und Ausbreitungsfähigkeit interagieren bei der Bestimmung der geographischen Verbreitung von Vögeln: Es ist weiterhin eine Herausforderung für Ökologie und Evolutionsbiologie, die Faktoren zu verstehen , die die geographische Verbreitung von Arten beeinflussen. Wir untersuchen wie Konkurrenz, Ausbreitungsfähigkeit, das Alter eines Taxons und Habitatverschiebungen seit dem letzten glazialen Maximum das Ausmaß beeinflussen, in dem Arten der Vogelgattung Sylvia in allen Gegenden mit geeigneten Umweltbedingungen vorkommen (d.h. range filling).
Wir haben range filling in der Vogelgattung Sylvia (Grasmücken) unter Verwendung von Boosted Regression Trees und Ridge-Regression quantifiziert. Mittels multipler Regression haben wir für die Effekte von intragenerischer Konkurrenz, Ausbreitungfähigkeit, Alter des Taxons und Habitatverschiebung seit dem letzten glazialen Maximum auf range filling getestet.
Grasmücken mit hoher Ausbreitungsfähigkeit zeigten höheres range filling, aber nur wenn Konkurrenz in Gebieten mit weniger geeignetem Habitat innerhalb ihres potentiellen Verbreitungsgebietes niedrig war. Das Alter eines Taxon und Habitatverschiebung seit dem letzten glazialen Maximum hatten keinen konsistenten Effekt. Wir zeigen, dass die Verbreitungsgebiete von Grasmücken mit hoher Wahrscheinlichkeit durch den simultanen, interaktiven Effekt von Konkurrenz und Ausbreitungsfähigkeit geformt werden. Wenn biotische Interaktionen wie Konkurrenz generell die Fähigkeit von Arten beeinflussen auf der kontinentalen Skala neue Gebiete zu kolonisieren, wird es eine Herausforderung sein, den Effekt von Klimawandel auf Biodiversität vorherzusagen.
3) Nischenverfügbarkeit in Zeit und Raum: Vogelzug der Grasmücken: Im Kontext neuer Fortschritte in der ökologischen Nischenmodellierung sind sowohl die Umwelt als auch die ökologische Nische einer Art als statische Entitäten behandelt und quantifiziert worden. In der Realität sind aber die Umwelt und die Nischenanforderungen einer Art auf einer Vielzahl von Skalen dynamisch. Wir schlagen ein konzeptionelles System vor das berücksichtigt, wie die realisierte Nische und geographische Verbreitung von Arten durch die entkoppelte raumzeitliche Verfügbarkeit unterschiedlicher Umweltbedingungen und durch Veränderungen der Nischenanforderungen über die Lebenszeit eines Organismus geformt werden. Das Testen von aus dem konzeptionellen System abgeleiteten Vorhersagen am Beispiel des Vogelzugs der Grasmücken ergab neue Erkenntnisse: Das Verfolgen der Klimanische im geographischen Raum war höchstwahrscheinlich nicht die treibende Kraft für Migration in der Gattung und steht potentiell im Konflikt mit dem Verfolgen der Landnutzungsnische. Die Nischen der Grasmücken waren während der Brutsaison schmaler, was zeigt, dass Nischenanforderungen zeitlich dynamisch sein können. Wir legen nahe, dass die Berücksichtigung dynamischer Umwelten und Nischenanforderungen zu einer entscheidenden Verbessserung unseres Verständnisses der treibenden Faktoren hinter der Bewegung von Organismen im Raum und der Dynamik ihrer Nischen und Verbreitungsgebiete führt.
The subject of this thesis aimed at a better understanding of the spectacular X-ray burst. The most likely astrophysical site is a very dense neutron star, which accretes H/He-rich matter from a close companion. While falling towards the neutron star, the matter is heated up and a thermonuclear runaway is ignited. The exact description of this process is dominated by the properties of a few proton-rich radioactive isotopes, which have a low interaction probability, hence a high abundance.
The topic of this thesis was therefore an investigation of the short-lived, proton-rich isotopes 31Cl and 32Ar. The Coulomb dissociation method is the modern technique of choice. Excitations with energies up to 20 MeV can be induced by the Lorentz contracted Coulomb field of a lead target. At the GSI Helmholtzzentrum für Schwerionenforschung GmbH in Darmstadt, Germany, a Ar beam was accelerated to an energy of 825 AMeV and fragmented in a beryllium target. The fragment separator was used to select the desired isotopes with a remaining energy of 650 AMeV. They were subsequently directed onto a 208 Pb target in the ALAND/LAND setup. The measurement was performed in inverse kinematics. All reaction products were detected and inclusive and exclusive measurements of the respective Coulomb dissociation cross sections were possible.
During the analysis of the experiment, it was possible to extract the energy-differential excitation spectrum of 31Cl, and to constrain astrophysically important parameters for the time-reversed 30S(p,γ)31Cl reaction. A single resonance at 0.443(37) MeV dominates the stellar reaction rate, which was also deduced and compared to previous calculations.
The integrated Coulomb dissociation cross section of this resonance was determined to 15(6) mb. The astrophysically important one- and two-proton emission channels were analyzed for 32Ar and energy-differential excitation spectra could be derived. The integrated Coulomb dissociation cross section for two proton emission were determined with two different techniques. The inclusive measurement yields a cross section of 214(29stat)(20sys) mb, whereas the exclusive reconstruction results in a cross section of 226(14stat)(23sys) mb. Both results are in very good agreement. The Coulomb dissociation cross section for the one-proton emission channel is extracted solely from the exclusive measurement and is 54(8stat)(6sys) mb.
Furthermore, the development of the Low Energy Neutron detector Array (LENA) for the upcoming R3B setup is described. The detector will be utilized in charge-exchange reactions to detect the low-energy recoil neutrons from (p,n)-type reactions. These reaction studies are of particular importance in the astrophysical context and can be used to constrain half lifes under stellar conditions. In the frame of this work, prototypes of the detector were built and successfully commissioned in several international laboratories.
The analysis was supported by detailed simulations of the detection characteristics.