779 research outputs found

    Exploring the Role of the PKHD1L1 Gene in Epithelial Cancer Cells

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    Bioterrorism Defense: Are State Mandated Compulsory Vaccination Programs an Infringement upon a Citizen\u27s Constitutional Rights

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    The agents of anthrax and smallpox threaten the health and welfare of the state citizenry and therefore the state can enact legislation appropriate to offset the possible harm. In order for the enacted legislation to withstand a constitutional challenge, the possible harm has to be a compelling governmental interest of public safety and welfare narrowly tailored to that goal. The purpose of this article is to demonstrate that the United States Department of Health and Human Services has the ability to recommend a compulsory vaccination program for citizens, and this program would not be in violation of a person\u27s constitutional right of liberty as guaranteed by the Fourteenth Amendment

    Public relations as visual meaning-making

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    This chapter explores the implications of the 'pictorial turn' for Public Relations and strategic communication, proposes a systematic framework for understanding how visual communication works, and concludes by considering future directions for conceptual engagement with visual meaning-making

    Essays on Energy Portfolio Management

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    Diese englischsprachige Dissertation behandelt ausgewählte Fragen zum Thema Portfoliomanagement in Energiemärkten. Im Kontext der modernen Portfoliotheorie werden theoretische Verteilungsannahmen untersucht, die einen optimalen Mittelwert-Varianz-Ansatz implizieren. Der Bereich zu Energiemärkten befasst sich einerseits mit Kurzfristprognosen von Day-Ahead-Preisen auf dem Strommarkt. Andererseits werden auf dem Erdgasmarkt die von komplexen Energiederivaten impliziten Volatilitäten analysiert. Einige interessante Beiträge, die diese Dissertation liefert, sind beispielsweise (i) die Erkenntnis, dass sich der Mittelwert-Varianz-Ansatz zur Bestimmung eines optimalen Portfolios von Vermögensgegenständen auch im Falle einer schiefen Renditeverteilung theoretisch rechtfertigen lässt, (ii) eine umfangreiche Vergleichsstudie mit verschiedenen Ansätzen zur Reduktion der Komplexität von multivariaten Strompreisprognosen und (iii) die Entwicklung eines theoretischen Rahmens und effizienten Algorithmus zur Übersetzung von Preisen für Swing-Optionen in implizite Volatilitäten

    Rab GTPases as mediators of neuronal robustness in Drosophila

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    One common feature of all eukaryotic cells is the presence of various specialized organelles, separated by membranes, which necessitates a coordinated trafficking of materials between these subcellular membrane-bound compartments. Especially neurons, with their long lifespan, polarized and often complex morphology, as well as their specialized functions, have particular requirements for membrane trafficking. Not surprisingly, membrane trafficking is involved in all aspects of neuronal development, function, and long-term maintenance. The evolutionary conserved family of small Rab GTPases functions as key regulator of coordinated vesicular trafficking in the endomembrane system. Expression profiling efforts revealed that in Drosophila half of all Rab GTPases are enriched in or specific to the nervous system, in humans it is one-third. However, the exact functions of the majority of nervous system-enriched Rab proteins are still unknown. Thus, studying the individual roles of those Rab GTPases more closely provides a great opportunity to gain more insight into the membrane trafficking networks in neurons. Ultimately, this will surely contribute to the understanding of what keeps neurons and in particular synapses healthy and functional over extended periods of time. In the nervous system, Rab GTPases and the membrane trafficking events these mediate have been widely associated with many neurodegenerative diseases. However, the established relations are often more correlatively than causatively linked, as discussed in Manuscript 1. Regarding the importance of an intact intracellular trafficking machinery for the development as well as neuronal function and maintenance, I primarily focused on the systematic functional analysis of nervous system-enriched Rab GTPases in Drosophila during my doctoral work. Previously, no systematic rab mutant characterization in any multicellular organism had been performed. The analysis, presented in Manuscript 2, revealed that the homozygous mutants of all nervous system-enriched Rab GTPases, raised under laboratory conditions, are viable and fertile, whereas, null mutants of ubiquitously expressed Rabs are all lethal under homozygosity. Thus, suggesting that Rab proteins, with high expression in the nervous system, serve more modulatory, specialized functions which are not essential for the survival of the organism. Further, we could show that all viable rab mutants differentially affect the development or neuronal function under variable, more challenging environmental conditions, such as temperature and light. This highlights the evolved robustness of developmental processes and nervous system function towards varying conditions. Additionally, during the in-depth functional analysis of nervous system-enriched Rab26, we revealed a stimulus-dependent role in the trafficking of the single acetylcholine receptor subunit Dα4 at cholinergic synapses of outer photoreceptors. However, we could not verify a role for Rab26 in the autophagic turnover of synaptic vesicles in neurons. Additional assays, such as the RUSH system, can be useful to support functional analyses. While this acute, synchronous release system could be established for Rabs in developing photoreceptors and salivary glands, wing imaginal discs proofed to be more sensitive and no working conditions could be established. Using the RUSH assay, different release dynamics with ‘fast’ as well as ‘slow’ releasing Rab GTPases could be identified as shown in Manuscript 3. Further, two nervous system-enriched Rab proteins, namely Rab23 and Rab26, show a clear re-localization from the cell body to the axon terminals, which is in agreement with their predominant synaptic neuropil localization revealed by expression profiling. In conclusion, the findings made during my doctoral work will contribute to a better understanding of the functional requirements of neurons regarding Rab-mediated membrane trafficking. The complete rab null mutant collection as well as the RUSH and LAMA transgenic toolbox provide a strong basis for further investigations of individual Rab functions during development and homeostasis

    SYNTHESIS AND CHARACTERIZATION OF BLUE LIGHT POLY(β-AMINO ESTER)S

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    Volumetric muscle loss (VML) is a debilitating injury which results in full or partial loss of function. Current clinical options utilize tissue grafts and bracing to restore function. Tissue graft implantation oftentimes leads to serious complications, some of which end in graft rejection and thereby necessitate further surgeries and procedures. Polymeric scaffolds show promise as scaffolding systems due to their mechanical properties and overall degradation profiles. Scaffolds need appropriate mechanical properties, 10-60 kPa modulus, and overall degradation times, five days to two weeks, to initiate tissue regeneration. Poly(β-amino ester)s (PBAE), a class of synthetic polymers, act as a safe biocompatible material with overall degradation times that are suitable for healing; however, due to harmful ultraviolet light (UV) irradiation from common crosslinking methods, these scaffold systems cannot be synthesized in vivo. This research presents the development and characterization of blue light (BL) crosslinked PBAEs. BL PBAEs showed vastly higher swelling ratios, 300-400% increase; decreased mechanical strength, an average decrease of 877 kPa in compressive modulus and 431 kPa in tensile modulus; and prolonged degradation patterns, 22% average mass retention. BL PBAEs show mechanical properties and degradation profiles that could be used as a skeletal muscle scaffolds

    Development and Characterization of a DEPFET Pixel Prototype System for the ILC Vertex Detector

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    For the future TeV-scale linear collider ILC (International Linear Collider) a vertex detector of unprecedented performance is needed to fully exploit its physics potential. By incorporating a field effect transistor into a fully depleted sensor substrate the DEPFET (Depleted Field Effect Transistor) sensor combines radiation detection and in-pixel amplification. For the operation at a linear collider the excellent noise performance of DEPFET pixels allows building very thin detectors with a high spatial resolution and a low power consumption. With this thesis a prototype system consisting of a 64×12864 \times 128 pixels sensor, dedicated steering and readout ASICs and a data acquisition board has been developed and successfully operated in the laboratory and under realistic conditions in beam test environments at DESY and CERN. A DEPFET matrix has been successfully read out using the on-chip zero-suppression of the readout chip CURO 2. The results of the system characterization and beam test results are presented
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