The species-specific effects of guinea pig adaptive mutations in Marburg virus VP40 and L on the protein’s functions and viral fitness

Marburg virus (MARV) is a highly pathogenic virus that causes severe, often lethal diseases specifically in humans and non-human primates. In rodents MARV is non-pathogenic. However, sequential passaging of MARV in rodents results in selection of a rodent-lethal virus. Lofts et al. established a guinea pig-lethal MARV containing only four non-silent amino acid changes in viral genome (Lofts et al., 2007). One amino acid substitution (D184N) was detected in the viral matrix protein VP40 and three amino acid substitutions were detected in the RNA-dependent RNA polymerase L (S741C, D758A and A759D). We analyzed the effects of the guinea pig-adaptive mutations on the functions of VP40 and L in a comparative study including human and guinea pig cells. Functional analyses were performed with ectopically expressed VP40D184N and L mutants by using different assays. The influence of the D184N mutation in VP40 on the replicative capacities of MARV in guinea pig cells was analyzed by infection of cells with recombinant MARV containing the D184N mutation in VP40. The first part of the study demonstrated that a recombinant rMARV containing only the D184N amino acid substitution in VP40 displayed a higher level of viral fitness specifically in guinea pig, but not in human cells. The mutant virus showed higher replicative capacities, enlarged inclusion bodies and enhanced infectivity only in guinea pig cells. Detailed comparative analysis of VP40 functions, in human and guinea pig cells, indicated that the membrane binding capabilities and the interferon antagonistic function were not altered by the D184N amino acid substitution. However, presence of the D184N mutation in VP40 enhanced the production of VP40-induced virus-like particles (VLPs) specifically in guinea pig cells. In addition, the amount of NP in infectious virus-like particles (iVLPs) and virus preparations was enhanced in presence of the D184N mutation in VP40 specifically in guinea pig cells. These data might partially explain the higher infectivity of VP40D184N containing iVLPs compared to wildtype VP40 containing iVLPs. Most importantly, the inhibitory capacity of VP40 on replication and transcription was species-specifically lowered by the D184N mutation in VP40, allowing significantly higher levels of replication and transcription in guinea pig cells. The second part of the study focused on the importance of the mutations in the L protein observed in the guinea pig-lethal MARV. Interestingly, only the S714C substitution increased replication in both species while the other mutations, D758A and A759D severely impaired the polymerase function. All L mutant proteins displayed proper expression and were able to localize into inclusion bodies which represent the sites of viral transcription/replication. Finally, co-expression of plasmids encoding L with the S741C amino acid substitution and VP40D184N in guinea pig cells resulted in eight fold higher levels of replication and transcription in comparison to human cells. This suggested that the D184N mutation in VP40 and the S741C mutation in L together significantly improve replication of MARV in guinea pig cells. Altogether these data suggests that the D184N substitution in VP40 and the S714C substitution in L can contribute to the increased pathogenicity of guinea pig-lethal MARV

Finite-Temperature Dynamics and Thermal Intraband Magnon Scattering in Haldane Spin-One Chains

The antiferromagnetic spin-one chain is considerably one of the most fundamental quantum many-body systems, with symmetry protected topological order in the ground state. Here, we present results for its dynamical spin structure factor at finite temperatures, based on a combination of exact numerical diagonalization, matrix-product-state calculations and quantum Monte Carlo simulations. Open finite chains exhibit a sub-gap band in the thermal spectral functions, indicative of localized edge-states. Moreover, we observe the thermal activation of a distinct low-energy continuum contribution to the spin spectral function with an enhanced spectral weight at low momenta and its upper threshold. This emerging thermal spectral feature of the Haldane spin-one chain is shown to result from intra-band magnon scattering due to the thermal population of the single-magnon branch, which features a large bandwidth-to-gap ratio. These findings are discussed with respect to possible future studies on spin-one chain compounds based on inelastic neutron scattering.Comment: 10 pages with 11 figures total (including Supplemental Material); changes in v2: new Figs. S1 and S5, Fig. S3 expanded + related discussion + many smaller modifications to match published versio

Detecting instruction effects. Deciding between covariance analytical and change-score approach

The article focuses on estimating effects in nonrandomized studies with two outcome measurement occasions and one predictor variable. Given such a design, the analysis approach can be to include the measurement at the previous time point as a predictor in the regression model (ANCOVA), or to predict the change-score of the outcome variable (CHANGE). Researchers demonstrated that both approaches can result in different conclusions regarding the reported effect. Current recommendations on when to apply which approach are, in part, contradictory. In addition, they lack direct reference to the educational and instructional research contexts, since they do not consider latent variable models in which variables are measured without measurement error. This contribution assists researchers in making decisions regarding their analysis model. Using an underlying hypothetical data-generating model, we identify for which kind of data-generating scenario (i.e., under which assumptions) the defined true effect equals the estimated regression coefficients of the ANCOVA and the CHANGE approach. We give empirical examples from instructional research and discuss which approach is more appropriate, respectively. (DIPF/Orig.

Tuning the structural instability of SrTiO_3 by Eu doping: The phase diagram of Sr_1-xEu_xTiO_3

The phase diagram of Sr_1-xEu_xTiO_3 is determined experimentally by electron paramagnetic resonance and resistivity measurements and analyzed theoretically within the self-consistent phonon approximation as a function of x ([0.03-1.0]). The transition temperature of the structural instability of the system increases nonlinearly to higher temperatures with increasing x. This is interpreted theoretically by a substantial alteration in the dynamics caused by a change in the double-well potential from broad and shallow to narrow and deep.Comment: 15 pages, 5 figure

Ullutsinni Kalaallit Nunaanni piniariaatsit aalisariaatsillu

Die vorliegende Diplomarbeit befasst sich mit gegenwärtigen Navigationsmethoden und Techniken der Jagd und des Fischfangs an der zentralen Westküste Grönlands. Sie baut auf den Einsichten einer 6-monatigen Feldforschung, die an den Orten Ilulissat, Ataa, Uummannaq und Saqqaq durchgeführt wurde. Die Untersuchung umfasst sowohl den Bereich der Objekte als auch die Bereiche praktischen und verbalisierten Wissens, die ich durch einen praxistheoretischen Zugang zu verbinden versuche. Dabei liegt die Betonung auf menschlichem Handeln in einer materiellen Umwelt – einer Umwelt, die zunehmend durch die Präsenz globaler Waren verändert wird. Globale Waren haben ihren Platz im Komplex der Subsistenzjagd gefunden und zu Veränderungen in der materiellen Umgebung grönländischer Jäger geführt. Die Konsequenzen der Inkludierung neuer Materialien äußern sich nicht allein in der Substitution traditioneller Materialien. Dies wird in den veränderten Arten der Produktion und des Gebrauchs von Ausrüstungsgegenständen ersichtlich, die zur Jagd und zum Fischfang eingesetzt werden. Die Verbreitung von High-Tech Ausrüstung hat gegenwärtige Jäger in Bedrängnis gebracht. Insbesondere die Zukunft des „Hunting way of life“ steht vor einer großen Herausforderung angesichts der leichteren Erhältlichkeit effektiver Jagdausrüstung. Denn Waren sind prinzipiell jedem zugänglich, der über das nötige Kapital verfügt. Auf diese Weise treten technische Fertigkeiten, die zuvor für die Herstellung von Jagdbehelfen notwendig waren, in den Hintergrund. In vielen Fällen ist der Verlust dieser Fertigkeiten gleichbedeutend mit dem Verlust von Wissen über den Umgang mit der Ausrüstung. Ein weiterer Risikofaktor liegt in der Komplexität moderner Apparate, die Potential zur Umstrukturierung besitzen. Ein Beispiel hierfür wäre der Jagdkarabiner, der, durch sein Potential auf weite Entfernung zu töten, den Jagdablauf bei der Robbenjagd am offenen Wasser nachhaltig verändert hat. Durch die zunehmende Vorherrschaft von Waren in den Haushalten von Jägern sind neue Abhängigkeitsverhältnisse zu Händlern und folglich zu Quellen finanziellen Einkommens entstanden. Das Resultat ist eine schleichenden Ökonomisierung des „Hunting way of life“, die Anlass zur Diskussion gegeben hat, ob es sich bei der heutigen Subsistenzjagd um einen Teil eines marktwirtschaftlichen Systems handelt oder das marktwirtschaftliche System in die Subsistenzjagd integriert wird. Trotz der Tatsache, dass globale Waren ihren Platz im Alltag der Jäger erlangt haben, vermochten sie das vorhandene Repertoire an Routine-Skills in der Herstellung und im Gebrauch von Jagdausrüstung kaum zu ersetzen. Dies bezeugt die detaillierte Beschreibung von Jagd- und Fischfangbehelfen, die ich im Zuge meiner Feldforschung gesammelt habe. Gleichzeitig zeigt ein genauer Blick auf das Inventar der Sammlung, dass es zu einer beinahe vollständigen Substitution traditioneller Materialien durch industriell gefertigte Materialien gekommen ist. 180 Die Objektbeschreibungen sind nicht auf die Besprechung der materiellen Komponenten und deren Eigenschaften beschränkt, sondern geben ein Verständnis für den kulturellen Kontext, in dem die Gegenstände Anwendung finden, wobei die praktische Anwendung der Behelfe besondere Aufmerksamkeit erfährt.This master thesis is concerned with an exploration of contemporary hunting and fishing techniques and methods of navigation, as practised on the central west coast of Greenland. It draws on 6-months of fieldwork, conducted in various places such as Ilulissat, Ataa, Uummannaq and Saqqaq. The exploration comprises the realm of objects as well as the realms of practical and verbalized knowledge. I seek to link these domains by a practice theoretical approach to human action in a material environment – an environment, which increasingly is altered by the presence of global commodities. Global goods have found their way into the complex of subsistence hunting and have provoked alterations within the hunters‟ material surroundings. The consequences of the inclusion of new materials are more than mere substitution of traditional materials. This is exemplified in the changing ways of producing and using equipment designed for hunting and fishing purposes. Furthermore, the introduction of high-tech equipment is causing serious hardship for contemporary hunters, and challenges the future of the „Hunting way of life“. Commodities are quite open in their accessibility and can be bought by anyone who possesses enough money to do so. Thus, the ability to gather money has superseded the technical skills, formerly necessary to produce hunting gear. In many cases, this loss of skill means a loss of knowledge in handling the equipment. Another risk factor lies in the complexity of modern apparatus and their restructuring power. An example would be the rifle, which, due to its ability to kill at long distance, has changed the sequence of the seal hunt on open water. The increasing presence of commodities in the hunters‟ households has created dependency on suppliers and therefore also on sources of financial income. This has led to a latent commodification of the “Hunting way of life” and giving rise to the question of whether substistence hunting nowadays represents a part of a marked economy or the other way around. Even though global goods have become present in the hunters‟ daily routine, they have not been able to replace a pre-existing inventory of basic skills, particular to the profession. The detailed description of equipment, which I have collected in the course of my fieldwork, bears witness to this fact. At the same time, a closer look at the inventory shows how complete the transition is from traditional materials to industrially produced ones. The descriptions of the objects are not limited to the material properties of the respective artefact but give an understanding of its cultural context, particularly with regard to the practical use of the object

Transverse electron beam dynamics in the beam loading regime

GeV electron bunches accelerated on a centimeter scale device exemplify the extraordinary advances of laser-plasma acceleration. The combination of high charges from optimized injection schemes and intrinsic femtosecond short bunch duration yields kiloampere peak currents. Further enhancing the current while reducing the energy spread will pave the way for future application, e.g. the driver for compact secondary radiation sources such as high-field THz, high-brightness x-ray or gamma-ray sources. One essential key for beam transport to a specific application is an electron bunch with high quality beam parameters such as low energy spread as well as small divergence and spot size. The inherent micrometer size at the plasma exit is typically sufficient for an efficient coupling into a conventional beamline. However, energy spread and beam divergence require optimization before the beam can be transported efficiently. Induced by the high peak current, the beam loading regime can be used in order to achieve optimized beam parameters for beam transport.In this thesis, the impact of beam loading on the transverse electron dynamic is systematically studied by investigating betatron radiation and electron beam divergence. For this reason, the bubble regime with self-truncated ionization injection (STII) is applied to set up a nanocoulomb-class laser wakefield accelerator. The accelerator is driven by 150TW laser pulses from the DRACO high power laser system. A supersonic gas jet provides a 3mm long acceleration medium with electron densities from 3 × 10^18 cm^−3 to 5 × 10^18 cm^−3. The STII scheme together with the employed setup yields highly reproducible injections with bunch charges of up to 0.5 nC. The recorded betatron radius at the accelerator exit is about one micron and reveals that the beam size stays at the same value. The optimal beam loading, which is observed at around 250 pC to 300 pC, leads to the minimum energy spread of ~40MeV and a 20% smaller divergence. It is demonstrated that an incomplete betatron phase mixing due to the small energy spread can explain the experimentally observed minimum beam divergence

Characterization of fuel segregation in a fluidized bed by magnetic particle tracking

A Magnetic Particle Tracking (MPT) system is used to experimentally characterize the vertical distribution of fuel particles in a fluidized bed. The measurements are carried out in a fluid-dynamically down-scaled cold unit resembling a 1×1 m2 boiler operating at 850 °C. The MPT system yields spatial and temporal information of the tracer particle with accuracies in the order of 10-3 m and 10-3 s, respectively. The MPT system is used to study how fuel segregation is influenced by physical properties of the fuel (sizes and densities representing different fuel types) and operational conditions, such as fluidization velocity, bed height and pressure drop across the gas distributor. For the range of fluidization velocities investigated, the results show two fuel segregation regimes: 1) a low-velocity mixing-regime, for which the presence of fuel particles at the dense bed surface and splash zone decreases strongly with increased fluidization velocity, and 2) a high-velocity mixing-regime where the presence of fuel at the bed surface and the splash zone increases with fluidization velocity, but with a weaker dependence than in the low-velocity regime. The fluidization velocity separating the two regimes depends on bed height and fuel properties