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

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

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Replication and Virus-Induced Transcriptome of HAdV-5 in Normal Host Cells versus Cancer Cells - Differences of Relevance for Adenoviral Oncolysis

Adenoviruses (Ads), especially HAdV-5, have been genetically equipped with tumor-restricted replication potential to enable applications in oncolytic cancer therapy. Such oncolytic adenoviruses have been well tolerated in cancer patients, but their anti-tumor efficacy needs to be enhanced. In this regard, it should be considered that cancer cells, dependent on their tissue of origin, can differ substantially from the normal host cells to which Ads are adapted by complex virus-host interactions. Consequently, viral replication efficiency, a key determinant of oncolytic activity, might be suboptimal in cancer cells. Therefore, we have analyzed both the replication kinetics of HAdV-5 and the virus-induced transcriptome in human bronchial epithelial cells (HBEC) in comparison to cancer cells. This is the first report on genome-wide expression profiling of Ads in their native host cells. We found that E1A expression and onset of viral genome replication are most rapid in HBEC and considerably delayed in melanoma cells. In squamous cell lung carcinoma cells, we observed intermediate HAdV-5 replication kinetics. Infectious particle production, viral spread and lytic activity of HAdV-5 were attenuated in melanoma cells versus HBEC. Expression profiling at the onset of viral genome replication revealed that HAdV-5 induced the strongest changes in the cellular transcriptome in HBEC, followed by lung cancer and melanoma cells. We identified prominent regulation of genes involved in cell cycle and DNA metabolism, replication and packaging in HBEC, which is in accord with the necessity to induce S phase for viral replication. Strikingly, in melanoma cells HAdV-5 triggered opposing regulation of said genes and, in contrast to lung cancer cells, no weak S phase induction was detected when using the E2F promoter as reporter. Our results provide a rationale for improving oncolytic adenoviruses either by adaptation of viral infection to target tumor cells or by modulating tumor cell functions to better support viral replication

Exosomes Derived from M. Bovis BCG Infected Macrophages Activate Antigen-Specific CD4+ and CD8+ T Cells In Vitro and In Vivo

Activation of both CD4+ and CD8+ T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma. Our previous studies showed that infected macrophages release from cells small membrane-bound vesicles called exosomes which contain mycobacterial lipid components and showed that these exosomes could stimulate a pro-inflammatory response in naïve macrophages. In the present study we demonstrate that exosomes stimulate both CD4+ and CD8+ splenic T cells isolated from mycobacteria-sensitized mice. Although the exosomes contain MHC I and II as well as costimulatory molecules, maximum stimulation of T cells required prior incubation of exosomes with antigen presenting cells. Exosomes isolated from M. bovis and M. tuberculosis infected macrophages also stimulated activation and maturation of mouse bone marrow-derived dendritic cells. Interestingly, intranasal administration of mice with exosomes isolated from M. bovis BCG infected macrophages induce the generation of memory CD4+ and CD8+ T cells. The isolated T cells also produced IFN-γ upon restimulation with BCG antigens. The release of exosomes from infected macrophages may overcome some of the defects in antigen presentation associated with mycobacterial infections and we suggest that exosomes may be a promising M. tuberculosis vaccine candidate

Rapid dissection and model-based optimization of inducible enhancers in human cells using a massively parallel reporter assay

Learning to read and write the transcriptional regulatory code is of central importance to progress in genetic analysis and engineering. Here we describe a massively parallel reporter assay (MPRA) that facilitates the systematic dissection of transcriptional regulatory elements. In MPRA, microarray-synthesized DNA regulatory elements and unique sequence tags are cloned into plasmids to generate a library of reporter constructs. These constructs are transfected into cells and tag expression is assayed by high-throughput sequencing. We apply MPRA to compare >27,000 variants of two inducible enhancers in human cells: a synthetic cAMP-regulated enhancer and the virus-inducible interferon-β enhancer. We first show that the resulting data define accurate maps of functional transcription factor binding sites in both enhancers at single-nucleotide resolution. We then use the data to train quantitative sequence-activity models (QSAMs) of the two enhancers. We show that QSAMs from two cellular states can be combined to design enhancer variants that optimize potentially conflicting objectives, such as maximizing induced activity while minimizing basal activity.National Human Genome Research Institute (U.S.) (grant R01HG004037)National Science Foundation (U.S.) ((NSF) grant PHY-0957573)National Science Foundation (U.S.) (NSF grant PHY-1022140)Broad Institut

Observation of a nuclear recoil peak at the 100 eV scale induced by neutron capture

Coherent elastic neutrino-nucleus scattering and low-mass Dark Matter detectors rely crucially on the understanding of their response to nuclear recoils. We report the first observation of a nuclear recoil peak at around 112 eV induced by neutron capture. The measurement was performed with a CaWO$_4$ cryogenic detector from the NUCLEUS experiment exposed to a $^{252}$Cf source placed in a compact moderator. The measured spectrum is found in agreement with simulations and the expected peak structure from the single-$\gamma$ de-excitation of $^{183}$W is identified with 3 $\sigma$ significance. This result demonstrates a new method for precise, in-situ, and non-intrusive calibration of low-threshold experiments