Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Phenotypic Variation Is Almost Entirely Independent of the Host-Pathogen Relationship in Clinical Isolates of S. aureus.

A key feature of Staphylococcus aureus biology is its ability to switch from an apparently benign colonizer of ~30% of the population to a cutaneous pathogen, to a deadly invasive pathogen. Little is known about the mechanisms driving this transition or the propensity of different S. aureus strains to engender different types of host-pathogen interactions. At the same time, significant weight has been given to the role of specific in vitro phenotypes in S. aureus virulence. Biofilm formation, hemolysis and pigment formation have all been associated with virulence in mice.To determine if there is a correlation between in vitro phenotype and the three types of host-pathogen relationships commonly exhibited by S. aureus in the context of its natural human host, we assayed 300 clinical isolates for phenotypes implicated in virulence including hemolysis, sensitivity to autolysis, and biofilm formation. For comparative purposes, we also assayed phenotype in 9 domesticated S. aureus strains routinely used for analysis of virulence determinants in laboratory settings.Strikingly, the clinical strains exhibited significant phenotypic uniformity in each of the assays evaluated in this study. One exception was a small, but significant, correlation between an increased propensity for biofilm formation and isolation from skin and soft tissue infections (SSTIs). In contrast, we observed a high degree of phenotypic variation between common laboratory strains that exhibit virulence in mouse models. These data suggest the existence of significant evolutionary pressure on the S. aureus genome and highlight a role for host factors as a strong determinant of the host-pathogen relationship. In addition, the high degree of variation between laboratory strains emphasizes the need for caution when applying data obtained in one lab strain to the analysis of another

Release and elementary mechanisms of nitric oxide in hair cells

The enzyme nitric oxide (NO) synthase, that produces the signaling molecule NO, has been identified in several cell types in the inner ear. However, it is unclear whether a measurable quantity of NO is released in the inner ear to confer specific functions. Indeed, the functional significance of NO and the elementary cellular mechanism thereof are most uncertain. Here, we demonstrate that the sensory epithelia of the frog saccule release NO and explore its release mechanisms by using self-referencing NO-selective electrodes. Additionally, we investigated the functional effects of NO on electrical properties of hair cells and determined their underlying cellular mechanism. We show detectable amounts of NO are released by hair cells (>50 nM). Furthermore, a hair-cell efferent modulator acetylcholine produces at least a threefold increase in NO release. NO not only attenuated the baseline membrane oscillations but it also increased the magnitude of current required to generate the characteristic membrane potential oscillations. This resulted in a rightward shift in the frequency-current relationship and altered the excitability of hair cells. Our data suggest that these effects ensue because NO reduces whole cell Ca(2+) current and drastically decreases the open probability of single-channel events of the L-type and non L-type Ca(2+) channels in hair cells, an effect that is mediated through direct nitrosylation of the channel and activation of protein kinase G. Finally, NO increases the magnitude of Ca(2+)-activated K(+) currents via direct NO nitrosylation. We conclude that NO-mediated inhibition serves as a component of efferent nerve modulation of hair cells

Summary of EzrA phenotypes.

<p>For comparative purposes we have summarized the phenotypes observed by each EzrA mutant used in this study. Cartoons depicting the localization of EzrA rings by fluorescence microscopy are shown in green and those depicting FtsZ rings are shown in red.</p

Schematic of EzrA deletion mutants employed in this study.

<p>The predicted coiled-coil structure of EzrA is drawn to scale. Numbers refer to amino acid positions. Coiled-coil regions are shaded blue. The QNR motif is shaded yellow and circled in the full-length protein. Lines indicate deleted regions. The QNR domain construct missing all four coiled-coils is just under the full-length protein. All constructs used for <i>in vivo</i> analysis were fused in-frame to a C-terminal GFP moiety (not shown) to simplify analysis. All constructs used for <i>in vitro</i> analysis were fused in-frame to a N-terminal Thio tag to enhance solubility and a N-terminal 6x-His tag for purification purposes (not shown).</p

The Frequency of EzrA CC deletion mutant cells with polar FtsZ rings.

<p>The Frequency of EzrA CC deletion mutant cells with polar FtsZ rings.</p

Coiled-coils 3 and 4 are required for interactions between EzrA and FtsZ <i>in vitro</i> in the context of the nearly full length EzrA (27–562).

<p>90° angle light scattering data from FtsZ assembly reactions conducted in the presence of wild type EzrA and various coiled-coil deletion mutants. Readings were taken four times per second at 30°C, and a baseline was gathered for 1 min before the addition of 1 mM GTP to the cuvette. Baseline values are subtracted for each sample. Bars represent the maximum scatter averaged across three independent experiments with standard deviation at the top. While CC1 and CC2 are dispensable for EzrA activity <i>in vitro</i>, the loss of either CC3 or CC4 completely abolished EzrA mediated inhibition of FtsZ assembly. FtsZ is at 5 µM, EzrAs are at 10 µM, and GTP is at 1 mM in all reactions.</p

Swapping EzrA's transmembrane helix with similar domains from other proteins does not impact EzrA localization or function.

<p>(A) Cartoon of proteins used to generate EzrA TM chimeras. The TM employed in the chimera is highlighted in red. (B) (Left) Immunofluorescence images of cells expressing wild type EzrA, an EzrA deletion mutant missing the entire transmembrane domain, as well as four EzrA chimeras in which the transmembrane domain has been substituted with the appropriately oriented TM from a heterologous protein. EzrA localization is wild type in all four chimeras. (Right) Localization of FtsZ-GFP in <i>ezrA</i>-TM chimera cells. FtsZ localization is wild type in all four chimeras. Thick arrows indicate medial EzrA and FtsZ localization. Thin arrows indicate EzrA localization at septa. Arrowheads indicate polar FtsZ rings. Exposure times are equivalent for each fluorophore. Bars  = 5 µm. (C) All four chimeras behave like wild type <i>ezrA</i> alleles with regard to their sensitivity to MinCD overexpression and heat sensitivity in an <i>ftsZts</i> background. Bars equal standard deviation from three repeated experiments. (D) A plot of cell length distributions between wild type and mutant strains indicates that cell length is not impacted by the TM swaps.</p

FtsZ is required for EzrA localization to the midcell.

<p>Strain PL851 encoding <i>ezrA</i>-gfp and an IPTG inducible <i>ftsZ</i> allele, <i>ftsZ</i>::P<i>_spac</i>-<i>ftsZ</i>, was grown in LB at 37°C for three generations in the presence (A) or absence of inducer (B). Depletion of FtsZ disrupts EzrA-GFP localization to midcell. Instead, EzrA-GFP appears diffusely distributed throughout the cell. Exposure times are the same in A and B, however brightness and contrast were increased in B to allow for better visualization of diffuse EzrA-GFP localization.</p