172 research outputs found

    Business Models and Programming Choice: Digital Video Recorders Shaping the TV Industry

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    This paper focuses on the influence that Digital Video Recorders (DVRs) are expected to have on the business models and in particular the programming choice of TV stations and cable / satellite TV service providers. After presenting the theoretical underpinnings with respect to programming choice modeling for the TV industry, this work examines DVRs in detail covering their main product features, impacts on viewer behavior, and the current roll-out status. This paper then investigates how these DVR features impact earlier insights from programming choice modeling and how they lead to changed business models for TV stations. The paper concludes with a brief summary and a critical outlook for a TV industry business model

    Development of an in vitro read out system to analyze the differentiation potential of human hematopoietic stem and progenitor cells

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    Hämatopoetische Stammzellen (HSZ) stellen das derzeit bestuntersuchte Stammzellsystem im Menschen dar. Dennoch sind die hierarchische Organisation der Stamm- und Vorläuferzellen sowie die genauen Linienverwandtschaft reifer Blutzellen noch immer nicht vollständig aufgeklärt. Nach dem klassischen Modell der Hämatopoese bringen HSZ multipotente Progenitoren hervor (MPP), die im weiteren Verlauf der Differenzierung entweder lymphatisch oder myeloisch spezifiziert werden. Durch die Beschreibung von Vorläuferzellen, die lymphatisches sowie partielles myeloisches aber kein erythrozytäres und megakaryozytäres Differenzierungspotential aufweisen, wurde das klassische Modell mit der Aufspaltung in den lymphatischen und myeloischen Zweig von mehreren Arbeitsgruppen falsifiziert. Das Ziel dieser Arbeit war folglich die Entwicklung einer in vitro Analysemethode, die eine Beschreibung der genauen Abstammungsverhältnisse in der humanen Hämatopoese sowie die Detektion primitiver hämatopoetischer Stamm- und Vorläuferzellen (HSVZ) auf Einzelzellebene ermöglicht. Als Grundlage hierzu wurde der klassische ML-IC (myeloid-lymphoid initiating cell) Ansatz verwendet, der eine retrospektive Analyse von Zellen mit lympho-myeloischem Differenzierungspotential ermöglicht. Zu untersuchende Einzelzellen werden hierzu in Kokultur mit murinen Stromazellen expandiert und das myeloische (LTC-IC) und lymphatische (NK-IC) Differenzierungspotential der Nachkommenschaft analysiert. Eine wesentliche Voraussetzung für den erweiterten ML-IC Ansatz stellen somit Kulturbedingungen dar, die eine Expansion von Einzelzellen ohne den Verlust des initialen Differenzierungspotentials in der neu entstehenden Nachkommenschaft ermöglichen. Weiterhin werden für die Analyse des Differenzierungspotentials der Nachkommenschaft funktionelle in vitro Differenzierungsansätze für den Nachweis aller hämatopoetischen Linien benötigt. Zu Beginn der Arbeit wurde das Entwicklungspotential expandierter HSVZ in der Suspensionskultur genauer analysiert. Primitive HSVZ mit LTC-IC, NK-IC, SRC sowie myeloischem Koloniebildungspotential konnten in der CD133+CD34+ Fraktion erhalten werden, wohingegen CD133+CD34+ HSVZ mit erythrozytärem innerhalb von 6 Tagen vollständig verloren gingen. Zellen mit erythrozytärem Differenzierungspotential wurden exklusiv in der neu entstehenden CD133lowCD34+ Fraktion detektiert. Diese Beobachtung gemeinsam mit weiteren Ergebnissen aus der Arbeitsgruppe führte zur Beschreibung neuer Linienverwandtschaften und eine alternativen Modellvorstellung der humanen Hämatopoese. Demnach findet eine frühe Aufspaltung in den lympho-myeloischen (CD133+CD34+) und erythro-myeloischen (CD133lowCD34+) Zweig statt, wobei Eosinophile und Basophile von CD133low erythro-myeloischen Progenitoren (EMP) und Neutrophile von CD133+ lymphatisch-spezifizierten multipotenten Progenitoren (LMPP) gebildet werden. Da insbesondere das erythrozytäre Differenzierungspotential in der Suspensionskultur verloren ging, wurden der Erhalt multipotenter HSVZ in Kokultur mit Zellen muriner Stromazelllinien sowie primären humanen mesenchymalen und endothelialen Stromazellen analysiert, die laut der Literatur eine Expansion multipotenter HSVZ ermöglichen. Überraschenderweise ermöglichten weder die murinen noch die humanen Stromazellen einen reproduzierbaren und zuverlässigen Erhalt multipotenter CD133+CD34+ HSVZ. In allen getesteten Bedingungen ging das erythrozytäre Differenzierungspotential in der CD133+CD34+ Fraktion über die Zeit nahezu vollständig verloren. Ein Erhalt aller initialen Differenzierungspotentiale in der gesamten Nachkommenschaft wurde hingegen von einzelnen mesenchymalen sowie endothelialen Stromazellen unterstützt. Derzeitige in vitro Kulturbedingungen ermöglichen keine unlimitierte Expansion primärer humaner Stromazellen. Um humane Primärzellen, die einen Erhalt aller initialen Differenzierungspotentiale ermöglichen, für die weiterführende Analysen sowie die initiale Expansionsphase im erweiterten ML-IC Ansatz zu konservieren, wurden ein System zur konditionellen Immortalisierung selektionierter Stromazellen etabliert. Von den immortalisierten humanen Primärzellen unterstützten insbesondere Zellen der mesenchymalen Stromazelllinie KM MNZ B Klon 2 einen reproduzierbaren Erhalt von HSVZ mit T-Zell, NK-Zell, Makrophagen/Monozyten, Granulozyten (Neutrophile, Basophile, Eosinophile), Megakaryozyten sowie Erythrozyten Potential. Diese Stromazellen ermöglichen folglich geeignete Kulturbedingungen für die initiale Expansionsphase im erweiterten ML-IC Ansatz. Auch wenn der erweiterte ML-IC Ansatz bislang nicht vollständig etabliert ist, konnte diese Arbeit wesentliche Ergebnisse zur Beschreibung neuer Linienverwandtschaften sowie einer alternativen Modellvorstellung der humanen Hämatopoese beitragen. Der Befund, dass multipotente HSVZ die einzigen CD133+CD34+ Zellen mit erythrozytärem Differenzierungspotential darstellen, ermöglicht zudem eine einfache Detektion und Quantifizierung multipotenter HSZ/MPP in weiterführenden Versuchen. Weiterhin wurden im Rahmen dieser Arbeit zusätzliche linienspezifische in vitro Differenzierungsansätze zur Detektion von Zellen mit CFC, T-Zell, Erythrozyten sowie Megakaryozyten Potential erfolgreich etabliert. Gemeinsam mit der Qualifizierung einer humanen mesenchymalen Stromazelllinie, die den Erhalt aller getesteten Linienpotentiale in der hämatopoetischen Nachkommenschaft ermöglicht, stellen diese Vorarbeiten eine wichtige Grundlage für die zukünftige Analyse einzelner HSVZ im erweiterten ML-IC Ansatz dar.Hematopoietic stem cells (HSCs) represent the best studied somatic stem cell entity in humans so far. Nevertheless, there are many unresolved questions regarding the hierarchical organization within the stem and progenitor cell compartment as well as the precise lineage relationships of mature blood cells. According to the classical model of human hematopoiesis, HSC give rise to multipotent hematopoietic progenitor cells (HPCs) and become restricted either to the lymphoid or myeloid lineage. Recent discoveries of lymphoid progenitors which retain partial myeloid but lack erythroid potential, e.g. the lymphoid primed multipotent progenitor cells (LMPP), have challenged this model. Consequently, the major aim of this thesis was to develop a read out system allowing the unravelling of the precise hierarchical relationships and the detection of the most primitive human hematopoietic stem and progenitor cells (HSPCs) at a single cell level. To this end, we decided to extend the clonal myeloid/lymphoid-initiating cell (ML-IC) assay in which individual hematopoietic cells are expanded on murine stromal cells before progeny is transferred into myeloid (LTC-IC) and lymphoid (NK-IC) read-outs. By combining the results of the different lineage read outs, the developmental potential of the initially deposited cell can be determined retrospectively. A major prerequisite for the extended ML-IC (eML-IC) assay are in vitro culture conditions allowing the expansion of single cells while maintaining all initial lineage potentials within the arising daughter cell fraction. Furthermore, functional lineage read-outs to detect and analyze all hematopoietic cell fates are required. Monoculture of human HSPCs in suspension resulted in the maintenance of cells with LTC-IC, NK-IC, SRC and myeloid colony-formation potential in the CD133+CD34+ cell fractions. HSPCs with erythroid potentials were rapidly lost from this fraction and were exclusively found within the newly arising CD133lowCD34+ population. These observations and further results of our group led to a revision of the current model of hematopoiesis. The new model predicts a very first segregation of lympho-myeloid (CD133+CD34+) and erythro-myeloid (CD133lowCD34+) potentials, with eosinophils and basophils developing from CD133low erythro-myeloid progenitors (EMPs), while neutrophils develop from CD133+ lymphoid-primed multipotent progenitors (LMPPs). Due to the loss of erythroid potentials in suspension culture we studied the ability of established murine stromal cell line cells as well as primary human mesenchymal and endothelial stromal cells to maintain multipotent CD133+CD34+ HSPCs with erythroid potential. None of the tested cells allowed a consistent maintenance of multipotent CD133+CD34+ cells. In all conditions CD133+CD34+ HSPC with erythroid potentials were lost over time. However, on certain mesenchymal and endothelial stromal cells, all initial lineage potentials could be maintained in the entire offspring. In order to conserve human stromal cells supporting the maintenance of all initial lineage potentials, we established a strategy to conditionally immortalize these cells. Within co-culture experiments, cells of the mesenchymal cell line KM MNZ B Clone 2 supported the maintenance of cells with T cell, NK cell, macrophage, granulocyte (neutrophil, basophil and eosinophil), megakaryocyte and erythrocyte potential displaying a promising candidate for the initial expansion of single cells in the enhanced ML-IC assay. Although the enhanced ML-IC assay could not completely be established, this thesis helped to unravel new hematopoietic lineage relationships which led to a new model of human hematopoiesis providing a simple possibility to detect multipotent stem and progenitor cells. According to the new model, multipotent HSPCs are the only human hematopoietic cells that express CD133 and reveal erythroid potentials which can easily be detected and enumerated within conventional colony-forming cell (CFC) assays. Additionally, various lineage read outs allowing the detection of cells with CFC, T cell, erythrocyte and megakaryocyte potential as well as a human mesenchymal stroma cell line supporting the expansion and maintenance of various hematopoietic lineage potential have successfully been established. Taken together, these tools provide the basic requirements to further establish the enhanced ML-IC assay and analyze the developmental potential of human hematopoietic stem and progenitor cells at a single cell level

    Flip Graph Connectivity for Arrangements of Pseudolines and Pseudocircles

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    Flip graphs of combinatorial and geometric objects are at the heart of many deep structural insights and connections between different branches of discrete mathematics and computer science. They also provide a natural framework for the study of reconfiguration problems. We study flip graphs of arrangements of pseudolines and of arrangements of pseudocircles, which are combinatorial generalizations of lines and circles, respectively. In both cases we consider triangle flips as local transformation and prove conjectures regarding their connectivity. In the case of nn pseudolines we show that the connectivity of the flip graph equals its minimum degree, which is exactly n2n-2. For the proof we introduce the class of shellable line arrangements, which serve as reference objects for the construction of disjoint paths. In fact, shellable arrangements are elements of a flip graph of line arrangements which are vertices of a polytope (Felsner and Ziegler; DM 241 (2001), 301--312). This polytope forms a cluster of good connectivity in the flip graph of pseudolines. In the case of pseudocircles we show that triangle flips induce a connected flip graph on \emph{intersecting} arrangements and also on cylindrical intersecting arrangements. The result for cylindrical arrangements is used in the proof for intersecting arrangements. We also show that in both settings the diameter of the flip graph is in Θ(n3)\Theta(n^3). Our constructions make essential use of variants of the sweeping lemma for pseudocircle arrangements (Snoeyink and Hershberger; Proc.\ SoCG 1989: 354--363). We finally study cylindrical arrangements in their own right and provide new combinatorial characterizations of this class

    An EigenValue Stabilization Technique for Immersed Boundary Finite Element Methods in Explicit Dynamics

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    The application of immersed boundary methods in static analyses is often impeded by poorly cut elements (small cut elements problem), leading to ill-conditioned linear systems of equations and stability problems. While these concerns may not be paramount in explicit dynamics, a substantial reduction in the critical time step size based on the smallest volume fraction χ\chi of a cut element is observed. This reduction can be so drastic that it renders explicit time integration schemes impractical. To tackle this challenge, we propose the use of a dedicated eigenvalue stabilization (EVS) technique. The EVS-technique serves a dual purpose. Beyond merely improving the condition number of system matrices, it plays a pivotal role in extending the critical time increment, effectively broadening the stability region in explicit dynamics. As a result, our approach enables robust and efficient analyses of high-frequency transient problems using immersed boundary methods. A key advantage of the stabilization method lies in the fact that only element-level operations are required. This is accomplished by computing all eigenvalues of the element matrices and subsequently introducing a stabilization term that mitigates the adverse effects of cutting. Notably, the stabilization of the mass matrix Mc\mathbf{M}_\mathrm{c} of cut elements -- especially for high polynomial orders pp of the shape functions -- leads to a significant raise in the critical time step size Δtcr\Delta t_\mathrm{cr}. To demonstrate the efficacy of our technique, we present two specifically selected dynamic benchmark examples related to wave propagation analysis, where an explicit time integration scheme must be employed to leverage the increase in the critical time step size.Comment: 45 pages, 25 figure

    Micro-SR-XRF and micro-PIXE studies for archaeological gold identification – The case of Carpathian (Transylvanian) gold and of Dacian bracelets

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    Abstract Trace-elements are more significant for provenancing archaeological metallic artifacts than the main components. For gold, the most promising elements are platinum group elements (PGE), Sn, Te, Sb, Hg and Pb. Several small fragments of natural Transylvanian gold – placer and primary – were studied by using micro-PIXE technique at the Legnaro National Laboratory AN2000 microbeam facility, Italy and at the AGLAE accelerator, C2RMF, Paris, France and by using micro synchrotron radiation X-ray fluorescence (micro-SR-XRF) at BESSY synchrotron, Berlin, Germany. The goal of the study was to identify the trace-elements, especially Sn, Sb and Te. A spectacular application to five Dacian gold bracelets authentication is presented (Sn and Sb traces)

    Toward wafer-scale diamond nano- and quantum technologies

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    We investigate native nitrogen vacancy (NV) and silicon vacancy (SiV) color centers in a commercially available, heteroepitaxial, wafer-sized, mm thick, single-crystal diamond. We observe single, native NV centers with a density of roughly 1 NV per µm3 and moderate coherence time (T2 = 5 µs) embedded in an ensemble of SiV centers. Using low temperature luminescence of SiV centers as a probe, we prove the high crystalline quality of the diamond especially close to the growth surface, consistent with a reduced dislocation density. Using ion implantation and plasma etching, we verify the possibility to fabricate nanostructures with shallow color centers rendering our material promising for fabrication of nanoscale sensing devices. As this diamond is available in wafer-sizes up to 100 mm, it offers the opportunity to up-scale diamond-based device fabrication
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