RNA Interference Analysis of Legionella in Drosophila Cells: Exploitation of Early Secretory Apparatus Dynamics

Legionella pneumophila translocates multiple bacterial effector proteins into host cells to direct formation of a replication vacuole for the bacterium. The emerging consensus is that formation of this compartment involves recruitment of membrane material that traffics between the endoplasmic reticulum (ER) and Golgi. To investigate this model, a targeted approach was used to knock down expression of proteins involved in membrane trafficking, using RNA interference in Drosophila cells. Surprisingly, few single knockdowns of ER–Golgi transport proteins decreased L. pneumophila replication. By analyzing double-stranded RNAs in pairs, combinations were identified that together caused defects in intracellular replication, consistent with the model that membrane traffic funnels into the replication vacuole from multiple sources. In particular, simultaneous depletion of the intermediate compartment and Golgi-tethering factor transport protein particle together with the ER SNARE protein Sec22 reduced replication efficiency, indicating that introduction of lesions at distinct sites in the secretory system reduces replication efficiency. In contrast to knockdowns in secretory traffic, which required multiple simultaneous hits, knockdown of single cytosolic components of ER-associated degradation, including Cdc48/p97 and associated cofactors, was sufficient to inhibit intracellular replication. The requirement for the Cdc48/p97 complex was conserved in mammalian cells, in which replication vacuoles showed intense recruitment of ubiquitinated proteins, the preferred substrates of Cdc48/p97. This complex promoted dislocation of both ubiquitinated proteins and bacterial effectors from the replication vacuole, consistent with the model that maintenance of high-level replication requires surveillance of the vacuole surface. This work demonstrates that L. pneumophila has the ability to gain access to multiple sites in the secretory system and provides the first evidence for a role of the Cdc48/p97 complex in promoting intracellular replication of pathogens and maintenance of replication vacuoles

Energy-scaling of the product state distribution for three-body recombination of ultracold atoms

Three-body recombination is a chemical reaction where the collision of three atoms leads to the formation of a diatomic molecule. In the ultracold regime it is expected that the production rate of a molecule generally decreases with its binding energy $E_b$, however, its precise dependence and the physics governing it have been left unclear so far. Here, we present a comprehensive experimental and theoretical study of the energy dependency for three-body recombination of ultracold Rb. For this, we determine production rates for molecules in a state-to-state resolved manner, with the binding energies $E_b$ ranging from 0.02 to 77 GHz$\times h$. We find that the formation rate approximately scales as $E_b^{-\alpha}$, where $\alpha$ is in the vicinity of 1. The formation rate typically varies only within a factor of two for different rotational angular momenta of the molecular product, apart from a possible centrifugal barrier suppression for low binding energies. In addition to numerical three-body calculations we present a perturbative model which reveals the physical origin of the energy scaling of the formation rate. Furthermore, we show that the scaling law potentially holds universally for a broad range of interaction potentials.Comment: 15 pages, 13 figure

Kondo-like transport and magnetic field effect of charge carrier fluctuations in granular aluminum oxide thin films

Granular aluminum oxide is an attractive material for superconducting quantum electronics. However, its low-temperature normal state transport properties are still not fully understood, while they could be related to the unconventional phenomenon of the superconductivity in this material. In order to obtain useful information on this aspect, a detailed study of charge carrier fluctuations has been performed in granular aluminum oxide films. The results of electric noise measurements indicate the presence of a Kondo-type spin-flip scattering mechanism for the conducting electrons in the normal state, at low temperatures. Moreover, the magnetic field dependence of the noise amplitude suggests that interface magnetic moments are the main source of fluctuations. The identification of the nature of fluctuation processes is a mandatory requirement for the improvement of quality and performance of quantum devices

Radiation pressure instability driven variability in the accreting black holes

The time dependent evolution of the accretion disk around black hole is computed. The classical description of the $\alpha$-viscosity is adopted so the evolution is driven by the instability operating in the innermost radiation-pressure dominated part of the accretion disk. We assume that the optically thick disk always extends down to the marginally stable orbit so it is never evacuated completely. We include the effect of the advection, coronal dissipation and vertical outflow. We show that the presence of the corona and/or the outflow reduce the amplitude of the outburst. If only about half of the energy is dissipated in the disk (with the other half dissipated in the corona and carried away by the outflow) the outburst amplitude and duration are consistent with observations of the microquasar GRS 1915+105. Viscous evolution explains in a natural way the lack of direct transitions from the state C to the state B in color-color diagram of this source. Further reduction of the fraction of energy dissipated in the optically thick disk switches off the outbursts which may explain why they are not seen in all high accretion rate sources being in the Very High State.Comment: 31 pages, 14 figures; accepted to Ap

Kondo-like transport and magnetic field effect of charge carrier fluctuations in granular aluminum oxide thin films

Granular aluminum oxide is an attractive material for superconducting quantum electronics. However, its low-temperature normal state transport properties are still not fully understood, while they could be related to the unconventional phenomenon of the superconductivity in this material. In order to obtain useful information on this aspect, a detailed study of charge carrier fluctuations has been performed in granular aluminum oxide films. The results of electric noise measurements indicate the presence of a Kondo-type spin-flip scattering mechanism for the conducting electrons in the normal state, at low temperatures. Moreover, the magnetic field dependence of the noise amplitude suggests that interface magnetic moments are the main source of fluctuations. The identification of the nature of fluctuation processes is a mandatory requirement for the improvement of quality and performance of quantum devices

Radiation pressure instability as a variability mechanism in the microquasar GRS 1915+105

Physical mechanism responsible for high viscosity in accretion disks is still under debate. Parameterization of the viscous stress as $\alpha P$ proved to be a successful representation of this mechanism in the outer parts of the disk, explaining the dwarf novae and X-ray novae outbursts as due to ionization instability. We show that this parameterization can be also adopted in the innermost part of the disk where the adoption of the $\alpha$-viscosity law implies the presence of the instability in the radiation pressure dominated region. We study the time evolution of such disks. We show that the time-dependent behavior of GRS 1915+105 can be well reproduced if $\alpha$-viscosity disk model is calculated accurately (with proper numerical coefficients in vertically averaged equations and with advection included), and if the model is supplemented with (i) moderate corona dissipating 50% of energy (ii) jet carrying luminosity-dependent fraction of energy. These necessary modifications in the form of the presence of a corona and a jet are well justified observationally. The model predicts outbursts at luminosity larger than 0.16$\dot M_{Edd}$, as required, correct outburst timescales and amplitudes, including the effect of increasing outburst timescale with mean luminosity. This result strongly suggests that the $\alpha$-viscosity law is a good description of the actual mechanism responsible for angular momentum transfer also in the innermost, radiation pressure dominated part of the disk around a black hole.Comment: 6 pages, 2 figures; accepted for publication in ApJ Letter

Emission and economic performance assessment of a solid oxide fuel cell micro-combined heat and power system in a domestic building

Combined heat and power (CHP) is a promising technological configuration for reducing energy consumption and increasing energy security in the domestic built environment. Fuel cells, on account of their: high electrical efficiency, low emissions and useful heat output have been identified as a key technological option for improving both building energy efficiency and reducing emissions in domestic CHP applications. The work presented in this paper builds upon results currently reported in the literature of fuel cells operating in domestic building applications, with an emission and economic performance assessment of a real, commercially available SOFC mCHP system operating in a real building; under a UK context. This paper aims to assess the emission and economic performance of a commercially available solid oxide fuel cell (SOFC) mCHP system, operating at The University of Nottingham's Creative Energy Homes. The performance assessment evaluates, over a one year period, the associated carbon (emission assessment) and operational costs (economic assessment) of the SOFC mCHP case compared to a ‘base case’ of grid electricity and a highly efficient gas boiler. Results from the annual assessment show that the SOFC mCHP system can generate annual emission reductions of up to 56% and cost reductions of 177% compared to the base case scenario. However support mechanisms such as; electrical export, feed in tariff and export tariff, are required in order to achieve this, the results are significantly less without. A net present value (NPV) analysis shows that the base case is still more profitable over a 15 year period, even though the SOFC mCHP system generates annual revenue; this is on account of the SOFC's high capital cost. In summary, grid interaction and incubator support is essential for significant annual emission and cost reductions compared to a grid electricity and gas boiler scenario. Currently capital cost is the greatest barrier to the economic viability of the system