Autoimmunity Is a Significant Feature of Idiopathic Pulmonary Arterial Hypertension.

Rationale: Autoimmunity is believed to play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear whether this is causative or a bystander of disease and if it carries any prognostic or treatment significance. Objectives: To study autoimmunity in IPAH using a large cross-sectional cohort. Methods: Assessment of the circulating immune cell phenotype was undertaken using flow cytometry, and the profile of serum immunoglobulins was generated using a standardized multiplex array of 19 clinically validated autoantibodies in 473 cases and 946 control subjects. Additional glutathione S-transferase fusion array and ELISA data were used to identify a serum autoantibody to BMPR2 (bone morphogenetic protein receptor type 2). Clustering analyses and clinical correlations were used to determine associations between immunogenicity and clinical outcomes. Measurements and Main Results: Flow cytometric immune profiling demonstrates that IPAH is associated with an altered humoral immune response in addition to raised IgG3. Multiplexed autoantibodies were significantly raised in IPAH, and clustering demonstrated three distinct clusters: "high autoantibody," "low autoantibody," and a small "intermediate" cluster exhibiting high concentrations of ribonucleic protein complex. The high-autoantibody cluster had worse hemodynamics but improved survival. A small subset of patients demonstrated immunoglobulin reactivity to BMPR2. Conclusions: This study establishes aberrant immune regulation and presence of autoantibodies as key features in the profile of a significant proportion of patients with IPAH and is associated with clinical outcomes.

Observation of Hydrodynamic Flows in Imploding Fusion Plasmas on the National Ignition Facility.

Inertial confinement fusion implosions designed to have minimal fluid motion at peak compression often show significant linear flows in the laboratory, attributable per simulations to percent-level imbalances in the laser drive illumination symmetry. We present experimental results which intentionally varied the mode 1 drive imbalance by up to 4% to test hydrodynamic predictions of flows and the resultant imploded core asymmetries and performance, as measured by a combination of DT neutron spectroscopy and high-resolution x-ray core imaging. Neutron yields decrease by up to 50%, and anisotropic neutron Doppler broadening increases by 20%, in agreement with simulations. Furthermore, a tracer jet from the capsule fill-tube perturbation that is entrained by the hot-spot flow confirms the average flow speeds deduced from neutron spectroscopy.

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.

Energy calibration of high-resolution X-Ray TES microcalorimeters with 3 eV optical photons.

With the improving energy resolution of transitionedge sensor (TES) based microcalorimeters, performance verification and calibration of these detectors has become increasingly challenging, especially in the energy range below 1 keV where fluorescent atomic X-ray lines have linewidths that are wider than the detector energy resolution and require impractically high statistics to determine the gain and deconvolve the instrumental profile. Better behaved calibration sources such as grating monochromators are too cumbersome for space missions and are difficult to use in the lab. As an alternative, we are exploring the use of pulses of 3 eV optical photons delivered by an optical fiber to generate combs of known energies with known arrival times. Here, we discuss initial results of this technique obtained with 2 eV and 0.7 eV resolution X-ray microcalorimeters. With the 2 eV detector, we have achieved photon number resolution for pulses with mean photon number up to 133 (corresponding to 0.4 keV).

Fabrication of X-ray Microcalorimeter Focal Planes Composed of Two Distinct Pixel Types.

We are developing superconducting transition-edge sensor (TES) microcalorimeter focal planes for versatility in meeting specifications of X-ray imaging spectrometers including high count-rate, high energy resolution, and large field-of-view. In particular, a focal plane composed of two sub-arrays: one of fine-pitch, high count-rate devices and the other of slower, larger pixels with similar energy resolution, offers promise for the next generation of astrophysics instruments, such as the X-ray Integral Field Unit (X-IFU) instrument on the European Space Agency's Athena mission. We have based the sub-arrays of our current design on successful pixel designs that have been demonstrated separately. Pixels with an all gold X-ray absorber on 50 and 75 micron scales where the Mo/Au TES sits atop a thick metal heatsinking layer have shown high resolution and can accommodate high count-rates. The demonstrated larger pixels use a silicon nitride membrane for thermal isolation, thinner Au and an added bismuth layer in a 250 micron square absorber. To tune the parameters of each sub-array requires merging the fabrication processes of the two detector types. We present the fabrication process for dual production of different X-ray absorbers on the same substrate, thick Au on the small pixels and thinner Au with a Bi capping layer on the larger pixels to tune their heat capacities. The process requires multiple electroplating and etching steps, but the absorbers are defined in a single ion milling step. We demonstrate methods for integrating heatsinking of the two types of pixel into the same focal plane consistent with the requirements for each sub-array, including the limiting of thermal crosstalk. We also discuss fabrication process modifications for tuning the intrinsic transition temperature (Tc) of the bilayers for the different device types through variation of the bilayer thicknesses. The latest results on these "hybrid" arrays will be presented.

First high-convergence cryogenic implosion in a near-vacuum hohlraum.

Recent experiments on the National Ignition Facility [M. J. Edwards et al., Phys. Plasmas 20, 070501 (2013)] demonstrate that utilizing a near-vacuum hohlraum (low pressure gas-filled) is a viable option for high convergence cryogenic deuterium-tritium (DT) layered capsule implosions. This is made possible by using a dense ablator (high-density carbon), which shortens the drive duration needed to achieve high convergence: a measured 40% higher hohlraum efficiency than typical gas-filled hohlraums, which requires less laser energy going into the hohlraum, and an observed better symmetry control than anticipated by standard hydrodynamics simulations. The first series of near-vacuum hohlraum experiments culminated in a 6.8 ns, 1.2 MJ laser pulse driving a 2-shock, high adiabat (α∼3.5) cryogenic DT layered high density carbon capsule. This resulted in one of the best performances so far on the NIF relative to laser energy, with a measured primary neutron yield of 1.8×10(15) neutrons, with 20% calculated alpha heating at convergence ∼27×.

Measurement of the T + T neutron spectrum using the national ignition facility.

Neutron time-of-flight spectra from inertial confinement fusion experiments with tritium-filled targets have been measured at the National Ignition Facility. These spectra represent a significant improvement in energy resolution and statistics over previous measurements, and afford the first definitive observation of a peak resulting from sequential decay through the ground state of (5)He at low reaction energies E(c.m.) 100

Neutron time of flight (nToF) detectors for inertial fusion experiments.

Neutrons generated in Inertial Confinement Fusion (ICF) experiments provide valuable information to interpret the conditions reached in the plasma. The neutron time-of-flight (nToF) technique is well suited for measuring the neutron energy spectrum due to the short time (100 ps) over which neutrons are typically emitted in ICF experiments. By locating detectors 10s of meters from the source, the neutron energy spectrum can be measured to high precision. We present a contextual review of the current state of the art in nToF detectors at ICF facilities in the United States, outlining the physics that can be measured, the detector technologies currently deployed and analysis techniques used.

Dorsal hippocampal lesions boost performance in the rat sequential reaction time task.

It is commonly accepted that the hippocampus plays a major role in declarative memory across species and that it is of particular relevance for spatial memory in rodents. However, the interplay between hippocampal function and nondeclarative memory systems, such as procedural stimulus-response (S-R) or sequential learning, is less clear: depending on task requirements, an interaction, dissociation or interference between hippocampal function and other memory systems may occur. This study was conducted to investigate the influence of dorsal ibotenic hippocampal lesions on learning and performance of sequential behavior in a rat version of the serial reaction time task (SRTT). Magnetic resonance imaging (MRI) analyses of the lesions revealed a bilateral volume reduction of ≈ 46% (histological analyses: ≈ 59%) of the total hippocampus. They were largely confined to its dorsal part and led to an expected spatial memory deficits in an object place recognition test as compared to healthy controls, even though sham lesions had the same effect. Our earlier studies on sequential learning had revealed substantial impairments in case of dorsal striatal dopaminergic lesions. In the present study, however, hippocampal lesioned animals unexpectedly showed superior performance throughout SRTT testing and training as compared to controls, which resulted in a higher degree of subsequent automated sequential behavior. Thus, our data reveal the infrequent case where hippocampal lesions lead to long-term improvements in test performance of a type of rather complex procedural behavior. One possible explanation for this effect is that hippocampal activity in rodents can interfere with other memory systems during the acquisition of procedural tasks with very low spatial requirements, as used here. Alternative explanations for the observed superior SRTT performance in lesioned animals, such as hyperactivity or increased exploratory drive are also topic of the discussion.

Construction and study of instrument response functions for analysis of the National Ignition Facility (NIF) neutron time-of-flight detectors.

The analysis of the National Ignition Facility (NIF) neutron time-of-flight (nToF) detectors uses a forward-fit routine that depends critically on the instrument response functions (IRFs) of the diagnostics. The details of the IRFs used can have large impacts on measurements such as ion temperature and down-scattered ratio (DSR). Here, we report on the recent steps taken to construct and validate nToF IRFs at the NIF to an increased degree of accuracy, as well as remove the need for fixed DSR baseline offsets. The IRF is treated in two parts: a "core," measured experimentally with an x-ray impulse source, and a "tail" that occurs later in time and has limited experimental data. The tail region is calibrated with the data from indirect drive exploding pusher shots, which have little neutron scattering and are traditionally assumed to have zero DSR. Using analytic modeling estimates, the non-zero DSR for these shots is estimated. The impact of varying IRF tail components on DSR is investigated with a systematic parameter study, and good agreement is found with the non-zero DSR estimates. These approaches will be used to improve the precision and uncertainty of NIF nToF DSR measurements.

Design of a multi-detector, single line-of-sight, time-of-flight system to measure time-resolved neutron energy spectra.

In the dynamic environment of burning, thermonuclear deuterium-tritium plasmas, diagnosing the time-resolved neutron energy spectrum is of critical importance. Strategies exist for this diagnosis in magnetic confinement fusion plasmas, which presently have a lifetime of ∼1012 longer than inertial confinement fusion (ICF) plasmas. Here, we present a novel concept for a simple, precise, and scale-able diagnostic to measure time-resolved neutron spectra in ICF plasmas. The concept leverages general tomographic reconstruction techniques adapted to time-of-flight parameter space, and then employs an updated Monte Carlo algorithm and National Ignition Facility-relevant constraints to reconstruct the time-evolving neutron energy spectrum. Reconstructed spectra of the primary 14.028 MeV nDT peak are in good agreement with the exact synthetic spectra. The technique is also used to reconstruct the time-evolving downscattered spectrum, although the present implementation shows significantly more error.

Constraining time-dependent ion temperature measurements in inertial confinement fusion (ICF) implosions with an intermediate distance neutron time-of-flight (nToF) detector.

A concept for using an intermediate distance (0.3-3.0 m) neutron time-of-flight (nToF) to provide a constraint on the measurement of the time-dependence of ion temperature in inertial confinement fusion implosions is presented. Simulated nToF signals at different distances are generated and, with a priori knowledge of the burn-averaged quantities and burn history, analyzed to determine requirements for a future detector. Results indicate a signal-to-noise ratio >50 and time resolution <20 ps to constrain the ion temperature gradient to ∼±25% (0.5 keV/100 ps).

The Vacuum Cherenkov Detector (VCD) for γ-ray measurements in inertial confinement fusion experiments.

Inertial confinement fusion experiments at both the National Ignition Facility (NIF) and the Laboratory for Laser Energetics OMEGA laser facility currently utilize Cherenkov detectors, with fused silica as the Cherenkov medium. At the NIF, the Quartz Cherenkov Detectors improve the precision of neutron time-of-flight measurements; and at OMEGA, the Diagnostic for Areal Density provides measurements of capsule shell areal densities. An inherent property of fused silica is the radiator's relatively low energy threshold for Cherenkov photon production (Ethreshold < 1 MeV), making it advantageous over gas-based Cherenkov detectors for experiments requiring low-energy γ detection. The Vacuum Cherenkov Detector (VCD) has been specifically designed for efficient detection of low energy γ's. Its primary use is in implosion experiments, which will study reactions relevant to stellar and big-bang nucleosynthesis, such as T(4He,γ)7Li, 4He(3He,γ)7Be, and 12C(p,γ)13N. The VCD is compatible with LLE's standard Ten-Inch Manipulator diagnostic insertion module. This work will outline the design and characterization of the VCD as well as provide results from recent experiments conducted at the OMEGA laser facility.

Proof-of-concept of a neutron time-of-flight ellipsoidal detector.

The time-resolved measurement of neutrons emitted from nuclear implosions at inertial confinement fusion facilities is used to characterize the fusing plasma. Several significant quantities are routinely measured by neutron time-of-flight (nToF) detectors in these experiments. Current nToF detectors use scintillators as well as solid-state Cherenkov radiators. The latter has an inherently faster time response and can provide a co-registered γ-ray measurement as well as improved precision in the bulk hot-spot velocity. This work discusses a nToF ellipsoidal detector that also utilizes a solid-state Cherenkov radiator. The detector has the potential to achieve a fast instrument response function allowing for characterization of the γ-ray burn history as well as the ability to field the detector closer to the fusion source. Proof-of-concept testing of the nToF ellipsoidal detector has been conducted at the National Ignition Facility using commercial optics. A time-resolved neutron signal has been measured from the diagnostic. Preliminary simulations corroborate the results.

The five line-of-sight neutron time-of-flight (nToF) suite on the National Ignition Facility (NIF).

Measurement of the neutron spectrum from inertial confinement fusion implosions is one of the primary diagnostics of implosion performance. Analysis of the spectrum gives access to quantities such as neutron yield, hot-spot velocity, apparent ion temperature, and compressed fuel ρr through measurement of the down-scatter ratio. On the National Ignition Facility, the neutron time-of-flight suite has been upgraded to include five independent, collimated lines of sight, each comprising a high dynamic range bibenzyl/diphenylacetylene-stilbene scintillator [R. Hatarik et al., Plasma Fusion Res. 9, 4404104 (2014)] and high-speed fused silica Cherenkov detectors [A. S. Moore et al., Rev. Sci. Instrum. 89, 10I120 (2018)].

Three-dimensional diagnostics and measurements of inertial confinement fusion plasmas.

Recent inertial confinement fusion measurements have highlighted the importance of 3D asymmetry effects on implosion performance. One prominent example is the bulk drift velocity of the deuterium-tritium plasma undergoing fusion ("hotspot"), vHS. Upgrades to the National Ignition Facility neutron time-of-flight diagnostics now provide vHS to better than 1 part in 104 and enable cross correlations with other measurements. This work presents the impact of vHS on the neutron yield, downscatter ratio, apparent ion temperature, electron temperature, and 2D x-ray emission. The necessary improvements to diagnostic suites to take these measurements are also detailed. The benefits of using cross-diagnostic analysis to test hotspot models and theory are discussed, and cross-shot trends are shown.

Interpolating individual line-of-sight neutron spectrometer measurements onto the "sky" at the National Ignition Facility (NIF).

Nuclear diagnostics provide measurements of inertial confinement fusion implosions used as metrics of performance for the shot. The interpretation of these measurements for shots with low mode asymmetries requires a way of combining the data to produce a "sky map" where the individual line-of-sight values are used to interpolate to other positions in the sky. These interpolations can provide information regarding the orientation of the low mode asymmetries. We describe the interpolation method, associated uncertainties, and correlations between different metrics, e.g., Tion, down scatter ratio, and hot-spot velocity direction. This work is also related to recently reported studies [H. G. Rinderknecht et al., Phys. Rev. Lett. 124, 145002 (2020) and K. M. Woo et al., Phys. Plasmas 27, 062702 (2020)] of low mode asymmetries. We report an analysis that makes use of a newly commissioned line of sight, a scheme for incorporating multiple neutron spectrum measurement types, and recent work on the sources of implosion asymmetry to provide a more complete picture of implosion performance.

Microcalorimeter measurement of x-ray spectra from a high-temperature magnetically confined plasma.

A NASA-built x-ray microcalorimeter spectrometer has been installed on the MST facility at the Wisconsin Plasma Physics Laboratory and has recorded x-ray photons emitted by impurity ions of aluminum in a majority deuterium plasma. Much of the x-ray microcalorimeter development has been driven by the needs of astrophysics missions, where imaging arrays with few-eV spectral resolution are required. The goal of our project is to adapt these single-photon-counting microcalorimeters for magnetic fusion energy research and demonstrate the value of such measurements for fusion science. Microcalorimeter spectrometers combine the best characteristics of the x-ray instrumentation currently available on fusion devices: high spectral resolution similar to an x-ray crystal spectrometer and the broadband coverage of an x-ray pulse height analysis system. Fusion experiments are increasingly employing high-Z plasma-facing components and require measurement of the concentration of all impurity ion species in the plasma. This diagnostic has the capability to satisfy this need for multi-species impurity ion data and will also contribute to measurements of impurity ion temperature and flow velocity, Zeff, and electron density. Here, we introduce x-ray microcalorimeter detectors and discuss the diagnostic capability for magnetic fusion energy experiments. We describe our experimental setup and spectrometer operation approach at MST, and we present the results from an initial measurement campaign.

Optimal choice of multiple line-of-sight measurements determining plasma hotspot velocity at the National Ignition Facility.

The measurement of plasma hotspot velocity provides an important diagnostic of implosion performance for inertial confinement fusion experiments at the National Ignition Facility. The shift of the fusion product neutron mean kinetic energy as measured along multiple line-of-sight time-of-flight spectrometers provides velocity vector components from which the hotspot velocity is inferred. Multiple measurements improve the hotspot velocity inference; however, practical considerations of available space, operational overhead, and instrumentation costs limit the number of possible line-of-sight measurements. We propose a solution to this classical "experiment design" problem that optimizes the precision of the velocity inference for a limited number of measurements.