We introduce the antibody landscape, a method for the quantitative analysis of antibodymediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among ...pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
A study of the transition from collisional to collisionless plasma flows has been carried out at the National Ignition Facility using high Mach number (M>4) counterstreaming plasmas. In these ...experiments, CD-CD and CD-CH planar foils separated by 6-10 mm are irradiated with laser energies of 250 kJ per foil, generating ∼1000 km/s plasma flows. Varying the foil separation distance scales the ion density and average bulk velocity and, therefore, the ion-ion Coulomb mean free path, at the interaction region at the midplane. The characteristics of the flow interaction have been inferred from the neutrons and protons generated by deuteron-deuteron interactions and by x-ray emission from the hot, interpenetrating, and interacting plasmas. A localized burst of neutrons and bright x-ray emission near the midpoint of the counterstreaming flows was observed, suggesting strong heating and the initial stages of shock formation. As the separation of the CD-CH foils increases we observe enhanced neutron production compared to particle-in-cell simulations that include Coulomb collisions, but do not include collective collisionless plasma instabilities. The observed plasma heating and enhanced neutron production is consistent with the initial stages of collisionless shock formation, mediated by the Weibel filamentation instability.
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.
The structure of a strong collisional shock front forming in a plasma is directly probed for the first time in laser-driven gas-jet experiments. Thomson scattering of a 526.5 nm probe beam was used ...to diagnose temperature and ion velocity distribution in a strong shock (M∼11) propagating through a low-density (ρ∼0.01 mg/cc) plasma composed of hydrogen. A forward-streaming population of ions traveling in excess of the shock velocity was observed to heat and slow down on an unmoving, unshocked population of cold protons, until ultimately the populations merge and begin to thermalize. Instabilities are observed during the merging, indicating a uniquely plasma-phase process in shock front formation.
Multiple non-animal-based test methods have never been formally validated. In order to use such new approach methods (NAMs) in a regulatory context, criteria to define their readiness are necessary. ...The field of developmental neurotoxicity (DNT) testing is used to exemplify the application of readiness criteria. The costs and number of untested chemicals are overwhelming for in vivo DNT testing. Thus, there is a need for inexpensive, high-throughput NAMs, to obtain initial information on potential hazards, and to allow prioritization for further testing. A background on the regulatory and scientific status of DNT testing is provided showing different types of test readiness levels, depending on the intended use of data from NAMs. Readiness criteria, compiled during a stakeholder workshop, uniting scientists from academia, industry and regulatory authorities are presented. An important step beyond the listing of criteria, was the suggestion for a preliminary scoring scheme. On this basis a (semi)-quantitative analysis process was assembled on test readiness of 17 NAMs with respect to various uses (e.g. prioritization/screening, risk assessment). The scoring results suggest that several assays are currently at high readiness levels. Therefore, suggestions are made on how DNT NAMs may be assembled into an integrated approach to testing and assessment (IATA). In parallel, the testing state in these assays was compiled for more than 1000 compounds. Finally, a vision is presented on how further NAM development may be guided by knowledge of signaling pathways necessary for brain development, DNT pathophysiology, and relevant adverse outcome pathways (AOP).
Monoenergetic-proton radiographs of laser-generated, high-Mach-number plasma jets colliding at various angles shed light on the structures and dynamics of these collisions. The observations compare ...favorably with results from 2D hydrodynamic simulations of multistream plasma jets, and also with results from an analytic treatment of electron flow and magnetic field advection. In collisions of two noncollinear jets, the observed flow structure is similar to the analytic model's prediction of a characteristic feature with a narrow structure pointing in one direction and a much thicker one pointing in the opposite direction. Spontaneous magnetic fields, largely azimuthal around the colliding jets and generated by the well-known ∇T(e)×∇n(e) Biermann battery effect near the periphery of the laser spots, are demonstrated to be "frozen in" the plasma (due to high magnetic Reynolds number Re(M)∼5×10(4)) and advected along the jet streamlines of the electron flow. These studies provide novel insight into the interactions and dynamics of colliding plasma jets.
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