871 research outputs found

    A new ion beam cooler and buncher for ISOLTRAP and mass measurements of radioactive argon isotopes

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    A new ion beam cooler and buncher for ISOLTRAP and mass measurements of radioactive argon isotopes - ISOLTRAP is a Penning trap mass spectrometer installed at ISOLDE/CERN. It is set up to measure the mass of short-lived nuclides with a relative accuracy delta m / m of typically 1* 10^-7. In this work an ion beam cooler and buncher based on a linear radio frequency quadrupole trap has been installed and characterized. By this the overall efficiency of the ISOLTRAP spectrometer was increased by three orders of magnitude. This allows for measuring nuclides that are only produced in minute quantities as for instance 33Ar. In this work the mass of 33,34,42,43Ar has been measured with a relative accuracy of about 1* 10^-7. 33Ar with its half-live of only 174 ms is the shortest-lived nuclide ever investigated in a Penning trap. The high accuracy of the mass measurement of 33Ar made a stringent IMME test for the A=33, T=3/2 isospin quartets possible

    Tracking the evolution of the norm of refugee protection

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    Includes abstract.The Convention Relating to the Status of Refugees not only, it is argued in this paper, established the international refugee regime with a strong relation to human rights, but also laid the groundwork for the establishment of a norm of refugee protection as a standard of appropriate behaviour toward refugees. The paper aims to prove this first assertion by employing the Constructivist-based norm life-cycle theoretical framework advanced by Martha Finnemore and Kathryn Sikkink. This paper will show that a norm of refugee protection was established over time but that its tenets have increasingly been ignored by states thereby eroding the initial norm of refugee protection. ... The second assertion with which this paper is faced therefore is that the intensity of the erosion of this norm of refugee protection is such that its continued existence is questionable

    The co-design of organizational artifacts and their role in articulating the aesthetics of organizational culture

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    The purpose of this paper is to contribute to the field of organisational aesthetics from a design management perspective. To do this, this paper will provide rich insights into the role design plays in understanding, shaping, and reinforcing organisational culture, in a way that helps organisations build and sustain their innovative capacity. By describing a range of case studies, which form part of a 3-year research project entitled “Creating Cultures of Innovation”, this paper will i) outline “formally designed” organisational artefacts, which could be viewed as an expression of the formal culture of an organisation; ii) describe how co-designed organisational artefacts developed during this innovation research project can be seen to uncover and shape a changing organisational culture that encourages an innovative mindset pertaining to the company’s organisational development; and iii) how recognizing this activity as design could help organisations capitalize on design’s role in innovation. For example, from this study, the formally-designed artefacts that currently exist in the organisation (e.g. organisational charts, business cards, job descriptions), and the co-designed artefacts which were formed as a result of collaborative design interventions (e.g. the Yarn Journey , collage, learning spaces) give management and staff the ability to better understand current culture, develop strategies for innovation, and embed an innovative culture in their organisation, moving forward. In addition, if designers and managers are able to better articulate design’s value, this could help designers better bring this benefit to businesses, and help businesses “ripple out” this behavior so that it permeates the organisation and gains support

    Estimating affinities of calcium ions to proteins

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    Ca2+-ions have a range of affinities to different proteins, depending on the various functions of these proteins. This makes the determination of Ca2+-protein affinities an interesting subject for functional studies. We have investigated the performance of two methods – Fold-X and AutoDock vina – in the prediction of Ca2+-protein affinities. Both methods, although based on different energy functions, showed virtually the same correlation with experimental affinities. Guided by insight from experiment, we further derived a simple linear model based on the solvent accessible surface of Ca2+ that had practically the same performance in terms of absolute errors as the more complex docking methods

    New approach for the induced charge calculation for cylindrical electrodes

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    Charge transfer in collisions between highly charged Xe ions and Mg atom

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    Simulation of Resistive Cooling in cylindrical Penning Traps

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    Studies about Cecropin P1 - an antimicrobial peptide

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    Antimikrobielle Peptide sind in allen Lebewesen verbreitete Peptide, welche ein breites Wirkspekt-rum gegen Bakterien, aber auch Pilze, Parasiten und Viren besitzen. Ihre Toxizität ist meist spezifisch und die Gefahr der Resistenzbildung im Vergleich zu medizinisch angewendeten Antibiotika gering. Dies macht sie für die medizinische Forschung und Anwendung sehr interessant. Um diese Peptide rational pharmakologisch zu optimieren ohne die Vorteile der AMPs gegenüber der Antibiotika ein-zubüßen, müssen der grundlegende Mechanismus der AMP-Bakterien-Interaktion entschlüsselt und die für die Toxizität nötigen Eigenschaften der Peptide identifiziert werden. Innerhalb dieser Arbeit wurde das Peptid Cecropin P1 aus dem Spulwurm des Schweins ausgewählt, welches spezifisch mit bakteriellen Membranen interagiert und Bakterien lysiert. Für die Charakteri-sierung der Struktur und Dynamik mittels NMR-Spektroskopie wurde das synthetische Cecro-pin P1-Gen in einen pET-SUMO-Vektor mit His-tag kloniert, in E. coli C43 15N-markiert exprimiert und das Peptid anschließende über eine His-tag-Affinitätschromatografie gereinigt. Die erstmals durchge-führte NMR-spektroskopische Analyse des Cecropin P1 in wässriger Umgebung ergab das Bild eines monomeren Peptides mit einer überwiegend α-helikalen amphipathischen N-terminalen Hälfte und einer im Vergleich dazu flexibleren unstrukturierten C-terminalen Hälfte mit einer hydrophoben Se-quenz. Auffällig ist dabei, dass der flexible Bereich nahe des Glycins an Position 21 beginnt, was da-rauf hindeutet, dass Cecropin P1 den Insektencecropinen mit ihrer α-Helix-„Gly-Pro-Gelenk“-α-Helix-Struktur in Membranumgebung ähnlicher ist als bisher angenommen. Weiterhin wurden Cecropin P1-Varianten entworfen um systematisch die Rolle der Hydrophobizität und Länge des hydrophoben Bereichs im C-terminalen Abschnitt von Cecropin P1 für die Toxizität in E. coli zu untersuchen. Die Toxizität der Cecropin P1 Varianten wurde dafür über die Ermittlung der minimalen inhibitorischen Konzentration (MIC) im laborintern etablierten Microplate Broth Dilution-Test abgeschätzt und zusätzlich mit einer Dreifach-Fluoreszenzfärbung näher charakterisiert. Diese Art der Charakterisierung lässt Aussagen über die totale Zellzahl, Viabilität und Membranintegrität der E. coli-Zellen nach Inkubation mit den Peptiden zu. Die größte Toxizität hatten hier Peptide mit einem 45 bis 55 % hydrophoben C-Terminus. Die Substitution der hydrophoben Aminosäuren an Position 22 bis 27 durch andere hydrophobe Aminosäuren ergab zwar eine identische MIC, veränder-te jedoch die Kinetik der Toxizität. Eine Verlängerung und Verkürzung der hydrophoben Sequenz im C-terminalen Bereich des Cecropin P1 um weitere hydrophobe Aminosäuren führte zu einer Vermin-derung der Toxizität. Dabei war eine Verkürzung um 2 Aminosäuren noch genauso toxisch wie das Wildtyp-Cecropin P1, die Verlängerung um 2 Aminosäuren verringerte die Toxizität signifikant. Die Arbeiten zeigen, dass weiterführende Studien zur Kinetik der Toxizitätswirkung der einzelnen Cecro-pin P1-Varianten und Visualisierung mit Hilfe der Fluoreszenzmikroskopie einen noch detaillierteren Einblick in den Toxizitätsmechanismus des Cecropin P1 geben könnten. Die erstmalige Expression von Isotopen-markiertem Cecropin P1 erlaubt zudem eine strukturelle und auch dynamische Analyse des Cecropin P1 mit Hilfe der NMR-Spektroskopie in verschiedenen Membransystemen und ermög-licht den Interaktionsmechanismus von Cecropin P1 mit Biomembranen detailliert zu untersuchen.Antimicrobial peptides are common in all living organisms. They have broad-spectrum activity against bacteria, fungi, parasites and viruses. Their toxicity is specific and the development of resistances less probable compared to conventional antibiotics. These characteristics make the medical use of anti-microbial peptides a matter of interest. For this reason the peptides have to be pharmacologically optimized without losing their benefits. Therefore it is reasonable to get insights into the molecular basis of peptide-membrane interaction mechanism and the determinants of the toxicity. Here Cecropin P1 from the porcine round worm Ascaris suum was chosen, which is known to interact with bacterial membranes and finally causes lysis of bacteria. To enable the structural and dynamical characterization of the peptide the synthetic gene encoding Cecropin P1 was cloned into a pET-SUMO vector with a His-tag, afterwards the 15N-labeled peptide was expressed in E. coli C43 and purified via immobilized metal ion affinity chromatography. First NMR-spectroscopy studies on Cecropin P1 in an aqueous environment indicate a monomeric peptide with an N-terminal α-helical structured part and a comparatively more flexible unstructured C-terminal half including a hydrophobic sequence. The enhanced flexibility starts around the con-served glycine at position 21, which is part of the flexible hinge in the helix-hinge-helix structure well known for the Cecropins of insects. This suggests a higher structural similarity of Cecropin P1 to the Cecropins of insects as expected. Furthermore Cecropin P1 variants were designed to analyze the relevance of hydrophobicity and length of the hydrophobic sequence of the C-terminal part of the peptide for the toxicity in E. coli. The toxicity of the variants was quantified with an established microplate broth dilution assay, which results in a minimal inhibitory concentration (MIC) of the peptide needed to completely kill the bac-teria. Additionally a triple fluorescence staining of bacteria incubated with peptide variants which gives information about total cell number, viability and membrane integrity was used to characterize the toxicity in detail. Cecropin P1 variants with 45-55 % hydrophobic C-terminus were most toxic, while the substitution of the hydrophobic amino acids 22-27 with different hydrophobic amino acids led to an identic MIC but altered kinetics of toxicity. Elongation with additional hydrophobic amino acids and shortening of the hydrophic C-terminal sequence of Cecropin P1 resulted in a decreased toxicity. These experiments indicate, that future studies on the kinetics of toxicity of the Cecropin P1 variants and visualization of bacteria threatened with peptide via fluorescence microscopy could give deeper insights into the mechanism of toxicity of Cecropin P1. For the first time 15N-labeled Cecropin P1 was produced and enables a structural and dynamical characterization of the peptide with different membrane models, which facilitates the detailed analysis of peptide-membrane interaction
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