LRP5 and LRP6 Are Not Required for Protective Antigen–Mediated Internalization or Lethality of Anthrax Lethal Toxin

Anthrax toxin (AnTx) plays a key role in the pathogenesis of anthrax. AnTx is composed of three proteins: protective antigen (PA), edema factor, and lethal factor (LF). PA is not toxic but serves to bind cells and translocate the toxic edema factor or LF moieties to the cytosol. Recently, the low-density lipoprotein receptor–related protein LRP6 has been reported to mediate internalization and lethality of AnTx. Based on its similarity to LRP6, we hypothesized that LRP5 may also play a role in cellular uptake of AnTx. We assayed PA-dependent uptake of anthrax LF or a cytotoxic LF fusion protein (FP59) in cells and mice harboring targeted deletions of Lrp5 or Lrp6. Unexpectedly, we observed that uptake was unaltered in the presence or absence of either Lrp5 or Lrp6 expression. Moreover, we observed efficient PA-mediated uptake into anthrax toxin receptor (ANTXR)–deficient Chinese hamster ovary cells (PR230) that had been stably engineered to express either human ANTXR1 or human ANTXR2 in the presence or absence of siRNA specific for LRP5 or LRP6. Our results demonstrate that neither LRP5 nor LRP6 is necessary for PA-mediated internalization or lethality of anthrax lethal toxin

Neutron time-of-flight measurements of charged-particle energy loss in inertial confinement fusion plasmas

Neutron spectra from secondary ^{3}H(d,n)α reactions produced by an implosion of a deuterium-gas capsule at the National Ignition Facility have been measured with order-of-magnitude improvements in statistics and resolution over past experiments. These new data and their sensitivity to the energy loss of fast tritons emitted from thermal ^{2}H(d,p)^{3}H reactions enable the first statistically significant investigation of charged-particle stopping via the emitted neutron spectrum. Radiation-hydrodynamic simulations, constrained to match a number of observables from the implosion, were used to predict the neutron spectra while employing two different energy loss models. This analysis represents the first test of stopping models under inertial confinement fusion conditions, covering plasma temperatures of k_{B}T≈1-4  keV and particle densities of n≈(12-2)×10^{24}  cm^{-3}. Under these conditions, we find significant deviations of our data from a theory employing classical collisions whereas the theory including quantum diffraction agrees with our data

Addressing data integration challenges to link ecological processes across scales

Data integration is a statistical modeling approach that incorporates multiple data sources within a unified analytical framework. Macrosystems ecology – the study of ecological phenomena at broad scales, including interactions across scales – increasingly employs data integration techniques to expand the spatiotemporal scope of research and inferences, increase the precision of parameter estimates, and account for multiple sources of uncertainty in estimates of multiscale processes. We highlight four common analytical challenges to data integration in macrosystems ecology research: data scale mismatches, unbalanced data, sampling biases, and model development and assessment. We explain each problem, discuss current approaches to address the issue, and describe potential areas of research to overcome these hurdles. Use of data integration techniques has increased rapidly in recent years, and given the inferential value of such approaches, we expect continued development and wider application across ecological disciplines, especially in macrosystems ecology

Assessment of ion kinetic effects in shock-driven inertial confinement fusion implosions using fusion burn imaging

The significance and nature of ion kinetic effects in D3He-filled, shock-driven inertial confinement fusion implosions are assessed through measurements of fusion burn profiles. Over this series of experiments, the ratio of ion-ion mean free path to minimum shell radius (the Knudsen number, NK) was varied from 0.3 to 9 in order to probe hydrodynamic-like to strongly kinetic plasma conditions; as the Knudsen number increased, hydrodynamic models increasingly failed to match measured yields, while an empirically-tuned, first-step model of ion kinetic effects better captured the observed yield trends [Rosenberg et al., Phys. Rev. Lett. 112, 185001 (2014)]. Here, spatially resolved measurements of the fusion burn are used to examine kinetic ion transport effects in greater detail, adding an additional dimension of understanding that goes beyond zero-dimensional integrated quantities to one-dimensional profiles. In agreement with the previous findings, a comparison of measured and simulated burn profiles shows that models including ion transport effects are able to better match the experimental results. In implosions characterized by large Knudsen numbers (NK3), the fusion burn profiles predicted by hydrodynamics simulations that exclude ion mean free path effects are peaked far from the origin, in stark disagreement with the experimentally observed profiles, which are centrally peaked. In contrast, a hydrodynamics simulation that includes a model of ion diffusion is able to qualitatively match the measured profile shapes. Therefore, ion diffusion or diffusion-like processes are identified as a plausible explanation of the observed trends, though further refinement of the models is needed for a more complete and quantitative understanding of ion kinetic effects

Measurement of Charged-Particle Stopping in Warm Dense Plasma

We measured the stopping of energetic protons in an isochorically heated solid-density Be plasma with an electron temperature of ~32  eV, corresponding to moderately coupled [(e[superscript 2]/a)/(k[subscript B]T[subscript e] + E[subscript F]) ~ 0.3] and moderately degenerate [k[subscript B]T[subscript e]/E[subscript F] ~ 2] “warm-dense matter” (WDM) conditions. We present the first high-accuracy measurements of charged-particle energy loss through dense plasma, which shows an increased loss relative to cold matter, consistent with a reduced mean ionization potential. The data agree with stopping models based on an ad hoc treatment of free and bound electrons, as well as the average-atom local-density approximation; this work is the first test of these theories in WDM plasma.United States. Dept. of Energy (Grant DE-NA0001857)United States. Dept. of Energy (Grant DE-FC52-08NA28752)Lawrence Livermore National Laboratory (Grant B597367)University of Rochester. Laboratory for Laser Energetics (Grant 415935-G)University of Rochester. Fusion Science Center (Grant 524431)National Laser User’s Facility (Grant DE-NA0002035)National Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374

Observation of strong electromagnetic fields around laser-entrance holes of ignition-scale hohlraums in inertial-confinement fusion experiments at the National Ignition Facility

Energy spectra and spectrally resolved one-dimensional fluence images of self-emitted charged-fusion products (14.7 MeV D[superscript 3]He protons) are routinely measured from indirectly driven inertial-confinement fusion (ICF) experiments utilizing ignition-scaled hohlraums at the National Ignition Facility (NIF). A striking and consistent feature of these images is that the fluence of protons leaving the ICF target in the direction of the hohlraum's laser entrance holes (LEHs) is very nonuniform spatially, in contrast to the very uniform fluence of protons leaving through the hohlraum equator. In addition, the measured nonuniformities are unpredictable, and vary greatly from shot to shot. These observations were made separately at the times of shock flash and of compression burn, indicating that the asymmetry persists even at ~0.5–2.5 ns after the laser has turned off. These phenomena have also been observed in experiments on the OMEGA laser facility with energy-scaled hohlraums, suggesting that the underlying physics is similar. Comprehensive data sets provide compelling evidence that the nonuniformities result from proton deflections due to strong spontaneous electromagnetic fields around the hohlraum LEHs. Although it has not yet been possible to uniquely determine whether the fields are magnetic (B) or electric (E), preliminary analysis indicates that the strength is ~1 MG if B fields or ~10[superscript 9] V cm[superscript −1] if E fields. These measurements provide important physics insight into the ongoing ignition experiments at the NIF. Understanding the generation, evolution, interaction and dissipation of the self-generated fields may help to answer many physics questions, such as why the electron temperatures measured in the LEH region are anomalously large, and may help to validate hydrodynamic models of plasma dynamics prior to plasma stagnation in the center of the hohlraum.United States. Dept. of Energy (DE-FG52-07 NA280 59)United States. Dept. of Energy (DE-FG03-03SF22691)Lawrence Livermore National Laboratory (B543881)Lawrence Livermore National Laboratory (LD RD-08-ER-062)University of Rochester. Fusion Science Center (412761-G)General Atomics (DE-AC52-06NA 27279)Stewardship Science Graduate Fellowship (DE-FC52-08NA28752

Observation of a Reflected Shock in an Indirectly Driven Spherical Implosion at the National Ignition Facility

A 200  μm radius hot spot at more than 2 keV temperature, 1  g/cm[superscript 3] density has been achieved on the National Ignition Facility using a near vacuum hohlraum. The implosion exhibits ideal one-dimensional behavior and 99% laser-to-hohlraum coupling. The low opacity of the remaining shell at bang time allows for a measurement of the x-ray emission of the reflected central shock in a deuterium plasma. Comparison with 1D hydrodynamic simulations puts constraints on electron-ion collisions and heat conduction. Results are consistent with classical (Spitzer-Harm) heat flux.United States. Dept. of Energy (Contract DE-AC52-07NA27344)Brookhaven National Laboratory (Laboratory Directed Research and Development Grant 11-ERD-050

Scaled laboratory experiments explain the kink behaviour of the Crab Nebula jet

The remarkable discovery by the Chandra X-ray observatory that the Crab nebula's jet periodically changes direction provides a challenge to our understanding of astrophysical jet dynamics. It has been suggested that this phenomenon may be the consequence of magnetic fields and magnetohydrodynamic instabilities, but experimental demonstration in a controlled laboratory environment has remained elusive. Here we report experiments that use high-power lasers to create a plasma jet that can be directly compared with the Crab jet through well-defined physical scaling laws. The jet generates its own embedded toroidal magnetic fields; as it moves, plasma instabilities result in multiple deflections of the propagation direction, mimicking the kink behaviour of the Crab jet. The experiment is modelled with three-dimensional numerical simulations that show exactly how the instability develops and results in changes of direction of the jet

Ion Thermal Decoupling and Species Separation in Shock-Driven Implosions

Anomalous reduction of the fusion yields by 50% and anomalous scaling of the burn-averaged ion temperatures with the ion-species fraction has been observed for the first time in D[superscript 3]He-filled shock-driven inertial confinement fusion implosions. Two ion kinetic mechanisms are used to explain the anomalous observations: thermal decoupling of the D and [superscript 3]He populations and diffusive species separation. The observed insensitivity of ion temperature to a varying deuterium fraction is shown to be a signature of ion thermal decoupling in shock-heated plasmas. The burn-averaged deuterium fraction calculated from the experimental data demonstrates a reduction in the average core deuterium density, as predicted by simulations that use a diffusion model. Accounting for each of these effects in simulations reproduces the observed yield trends.United States. National Nuclear Security Administration (Grant DE-NA0001857)University of Rochester. Fusion Science Center (Grant 415023-G)National Laser User’s Facility (Grant DE-NA0002035)University of Rochester. Laboratory for Laser Energetics (Grant 415935-G)Lawrence Livermore National Laboratory (Grant B600100