Monte Carlo N-Particle forward modeling for density reconstruction of double shell capsule radiographs.

In the Double Shell Inertial Confinement Fusion concept, characterizing the shape asymmetry of imploding metal shells is vital for understanding energy-efficient compression and radiative losses of the thermonuclear fuel. The Monte Carlo N-Particle MCNP® code forward models radiography of Double Shell capsule implosions using the Advanced Radiographic Capability at the National Ignition Facility. A procedure is developed for using MCNP to reconstruct density profiles from the radiograph image intensity. For a given Double Shell imploding target geometry, MCNP radiographs predict image contrast, which can help guide experimental design. In future work, the calculated MCNP synthetic radiographs will be compared with experimental radiographs to determine the radial and azimuthal density profiles of the Double Shell capsules.

Rainfall triggers more deep-seated landslides than Cascadia earthquakes in the Oregon Coast Range, USA.

The coastal Pacific Northwest USA hosts thousands of deep-seated landslides. Historic landslides have primarily been triggered by rainfall, but the region is also prone to large earthquakes on the 1100-km-long Cascadia Subduction Zone megathrust. Little is known about the number of landslides triggered by these earthquakes because the last magnitude 9 rupture occurred in 1700 CE. Here, we map 9938 deep-seated bedrock landslides in the Oregon Coast Range and use surface roughness dating to estimate that past earthquakes triggered fewer than half of the landslides in the past 1000 years. We find landslide frequency increases with mean annual precipitation but not with modeled peak ground acceleration or proximity to the megathrust. Our results agree with findings about other recent subduction zone earthquakes where relatively few deep-seated landslides were mapped and suggest that despite proximity to the megathrust, most deep-seated landslides in the Oregon Coast Range were triggered by rainfall.

Erratum: Measurement of Preheat Due to Nonlocal Electron Transport in Warm Dense Matter [Phys. Rev. Lett. 120, 025002 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.120.025002.

Assessment of the effects of immunogenicity on the pharmacokinetics, efficacy and safety of tildrakizumab.

BACKGROUND: We evaluated antidrug antibody (ADA) development in patients with chronic plaque psoriasis from three clinical trials of tildrakizumab, a humanized anti-interleukin-23p19 monoclonal antibody (P05495, reSURFACE 1 and reSURFACE 2). OBJECTIVES: To determine the effects of immunogenicity on the pharmacokinetics, efficacy and safety of tildrakizumab. METHODS: In 1400 (weeks 12-16) and 780 (weeks 52-64) evaluable patients randomized to tildrakizumab 100 or 200 mg, treatment-emergent ADA-positive (TE-POS) patients were identified and characterized for neutralizing antibodies (NAbs). Pharmacokinetics, safety and efficacy were evaluated by ADA status. RESULTS: In patients treated with tildrakizumab 100 or 200 mg continuously, < 7% were inconclusive at 52-64 weeks. In long-term data through 52-64 weeks, the incidence of TE-POS was 6·5% (100 mg) and 8·2% (200 mg) and the incidence of TE-POS NAb-POS was 2·5% (100 mg) and 3·2% (200 mg). TE-POS NAb-POS patients had modestly increased median tildrakizumab clearance (36·5%) compared with ADA-NEG patients. Percentage Psoriasis Area and Severity Index improvements in TE-POS NAb-POS vs. ADA-NEG patients on continuous treatment through week 52 were 76% (n = 10) vs. 91% (n = 342) for 100 mg and 77% (n = 12) vs. 87% (n = 299) for 200 mg. The incidence of potential immunogenicity-related adverse events did not indicate a clear trend in any positive ADA patient category compared with ADA-NEG patients through weeks 52-64. The effects of ADA on pharmacokinetics, efficacy and safety at 12-16 weeks were also summarized. CONCLUSIONS: ADA development with tildrakizumab treatment for 52-64 weeks was low; around 3% of patients developed TE-POS NAb-POS ADAs and showed lower serum concentrations and corresponding reduced efficacy. No relationship between ADAs and safety was observed. What's already known about this topic? Unwanted immune responses - for example immunogenicity and antidrug antibodies (ADAs) - have been observed with therapeutic monoclonal antibodies and can affect efficacy and safety. Tildrakizumab is a humanized monoclonal antibody targeting interleukin-23 and is currently approved for patients with plaque psoriasis. What does this study add? ADA development in tildrakizumab-treated patients with psoriasis over 52 weeks was low. The small proportion of patients who had treatment-emergent ADAs and had neutralizing antibodies experienced lower serum tildrakizumab concentrations and reduced efficacy. No relationship between ADAs and safety events was observed.

PEROXIREDOXIN Q stimulates the activity of the chloroplast 16:1Δ3trans FATTY ACID DESATURASE4.

Thylakoid membrane lipids, comprised of glycolipids and the phospholipid phosphatidylglycerol (PG), are essential for normal plant growth and development. Unlike other lipid classes, chloroplast PG in nearly all plants contains a substantial fraction of the unusual trans fatty acid 16:1Δ3trans or 16:1t. We determined that, in Arabidopsis thaliana, 16:1t biosynthesis requires both FATTY ACID DESATURASE4 (FAD4) and a thylakoid-associated redox protein, PEROXIREDOXIN Q (PRXQ), to produce wild-type levels of 16:1t. The FAD4-PRXQ biochemical relationship appears to be very specific in planta, as other fatty acids (FA) desaturases do not require peroxiredoxins for their activity, nor does FAD4 require other chloroplast peroxiredoxins under standard growth conditions. Although most of chloroplast PG assembly occurs at the inner envelope membrane, FAD4 was primarily associated with the thylakoid membranes facing the stroma. Furthermore, co-production of PRXQ with FAD4 was required to produce Δ3-desaturated FAs in yeast. Alteration of the redox state of FAD4 or PRXQ through site-directed mutagenesis of conserved cysteine residues impaired Δ3 FA production. However, these mutations did not appear to directly alter disulfide status of FAD4. These results collectively demonstrate that the production of 16:1t is linked to the redox status of the chloroplast through PRXQ associated with the thylakoids.

Results of a pilot study of isoniazid in patients with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP), the most common porphyria of childhood and the third most common porphyria of adulthood, is characterized clinically by painful, non-blistering cutaneous photosensitivity. Two distinct inheritance patterns involving mutations affecting genes that encode enzymes of the heme biosynthetic pathway underlie the clinical phenotype. Aminolevulinic acid synthase 2 (ALAS2), the rate limiting enzyme of the heme pathway in the erythron, is a therapeutic target in EPP because inhibiting enzyme function would reduce downstream production of protoporphyrin IX (PPIX), preventing accumulation of the toxic molecule and thereby ameliorating symptoms. Isoniazid (INH) is widely used for treatment of latent and active M. tuberculosis (TB). Sideroblastic anemia is observed in some patients taking INH, and studies have shown that this process is a consequence of inhibition of ALAS2 by INH. Based on these observations, we postulated that INH might have therapeutic activity in patients with EPP. We challenged this hypothesis in a murine model of EPP and showed that, after 4 weeks of treatment with INH, both plasma PPIX and hepatic PPIX were significantly reduced. Next, we tested the effect of INH on patients with EPP. After eight weeks, no significant difference in plasma or red cell PPIX was observed among the 15 patients enrolled in the study. These results demonstrate that while INH can lower PPIX in an animal model of EPP, the standard dose used to treat TB is insufficient to affect levels in humans.

Direct-drive double-shell implosion: A platform for burning-plasma physics studies.

Double-shell ignition designs have been studied with the indirect-drive inertial confinement fusion (ICF) scheme in both simulations and experiments in which the inner-shell kinetic energy was limited to ∼10-15 kJ, even driven by megajoule-class lasers such as the National Ignition Facility. Since direct-drive ICF can couple more energy to the imploding shells, we have performed a detailed study on direct-drive double-shell (D^{3}S) implosions with state-of-the-art physics models implemented in radiation-hydrodynamic codes (lilac and draco), including nonlocal thermal transport, cross-beam energy transfer (CBET), and first-principles-based material properties. To mitigate classical unstable interfaces, we have proposed the use of a tungsten-beryllium-mixed inner shell with gradient-density layers that can be made by magnetron sputtering. In our D^{3}S designs, a 70-µm-thick beryllium outer shell is driven symmetrically by a high-adiabat (α≥10), 1.9-MJ laser pulse to a peak velocity of ∼240 km/s. Upon spherical impact, the outer shell transfers ∼30-40 kJ of kinetic energy to the inner shell filled with deuterium-tritium gas or liquid, giving neutron-yield energies of ∼6 MJ in one-dimensional simulations. Two-dimensional high-mode draco simulations indicated that such high-adiabat D^{3}S implosions are not susceptible to laser imprint, but the long-wavelength perturbations from the laser port configuration along with CBET can be detrimental to the target performance. Nevertheless, neutron yields of ∼0.3-1.0-MJ energies can still be obtained from our high-mode draco simulations. The robust α-particle bootstrap is readily reached, which could provide a viable platform for burning-plasma physics studies. Once CBET mitigation and/or more laser energy becomes available, we anticipate that break-even or moderate energy gain might be feasible with the proposed D^{3}S scheme.

Fishes in a changing world: learning from the past to promote sustainability of fish populations.

Populations of fishes provide valuable services for billions of people, but face diverse and interacting threats that jeopardize their sustainability. Human population growth and intensifying resource use for food, water, energy and goods are compromising fish populations through a variety of mechanisms, including overfishing, habitat degradation and declines in water quality. The important challenges raised by these issues have been recognized and have led to considerable advances over past decades in managing and mitigating threats to fishes worldwide. In this review, we identify the major threats faced by fish populations alongside recent advances that are helping to address these issues. There are very significant efforts worldwide directed towards ensuring a sustainable future for the world's fishes and fisheries and those who rely on them. Although considerable challenges remain, by drawing attention to successful mitigation of threats to fish and fisheries we hope to provide the encouragement and direction that will allow these challenges to be overcome in the future.

Measurement of Preheat Due to Nonlocal Electron Transport in Warm Dense Matter.

This Letter presents a novel approach to study electron transport in warm dense matter. It also includes the first x-ray Thomson scattering (XRTS) measurement from low-density CH foams compressed by a strong laser-driven shock at the OMEGA laser facility. The XRTS measurement is combined with velocity interferometry (VISAR) and optical pyrometry (SOP) providing a robust measurement of thermodynamic conditions in the shock. Evidence of significant preheat contributing to elevated temperatures reaching 17.5-35 eV in shocked CH foam is measured by XRTS. These measurements are complemented by abnormally high shock velocities observed by VISAR and early emission seen by SOP. These results are compared to radiation hydrodynamics simulations that include first-principles treatment of nonlocal electron transport in warm dense matter with excellent agreement. Additional simulations confirm that the x-ray contribution to this preheat is negligible.

The influence of citrate and oxalate on 99TcVII, Cs, NpV and UVI sorption to a Savannah River Site soil.

Batch sorption experiments were conducted with 0.5-50 ppb 99Tc, 133Cs, 237Np and U in the presence and absence of citrate and/or oxalate in a 25 g/L Savannah River Site (SRS) soil suspension. Citrate and oxalate were the ligands of choice due to their relevancy to plant exudates, the nuclides were selected for their wide range of biogeochemical behavior, and the soil from SRS was selected as a model Department of Energy (DOE) site soil. Batch samples were continually mixed on a rotary shaker and maintained at a pH of approximately 5. Analysis via ICP-MS indicated that sorption of 237Np increased with ligand concentration compared to baseline studies, as did sorption of 99Tc although to a lesser extent. The increased sorption of 237Np is proposed to be due to a combination of factors that are dependent on the ligand(s) present in the specific system including, ligand dissolution of the soil by citrate and formation of tertiary soil-oxalate-Np complexes. The increased 99Tc sorption is attributed to the dissolution of the soil by the ligands, leading to an increase in the number of available sorption sites for 99Tc. Uranium sorption decreased and dissolution of native uranium was also observed with increasing ligand concentration, thought to be a result of the formation of strong U-ligand complexes remaining in the aqueous phase. The majority of these effects were observed at the highest ligand concentrations of 50 mgC/L. No notable changes were observed for the 133Cs system which is ascribed to the minimal interaction of Cs+ with these organic ligands.

Gully evolution and geomorphic adjustments of badlands to reforestation.

Badlands and gullied areas are among those geomorphic environments with the highest erosion rates worldwide. Nevertheless, records of their evolution and their relations with anthropogenic land transformation are scarcer. Here we combine historical data with aerial photographs and tree-ring records to reconstruct the evolution of a badland in a Mediterranean environment of Central Spain. Historical sources suggest an anthropogenic origin of this badland landscape, caused by intense quarrying activities during the 18th century. Aerial photographs allowed detection of dramatic geomorphic changes and the evolution of an emerging vegetation cover since the 1960s, due to widespread reforestation. Finally, tree-ring analyses of exposed roots allowed quantification of recent channel incision of the main gully, and sheet erosion processes. Our results suggest that reforestation practices have influenced the initiation of an episode of incision in the main channel in the 1980s, through the hypothesized creation of disequilibrium in water-sediment balance following decoupling of hillslopes from channel processes. These findings imply an asymmetry in the geomorphic response of badlands to erosion such that in the early evolution stages, vegetation removal results in gullying, but that reforestation alone does not necessarily stabilize the landforms and may even promote renewed incision.

Free Energy Based Equation of State for Pentaerythritol Tetranitrate.

An equation of state for the energetic molecular crystal pentaerythritol tetranitrate (PETN) has been developed from a parametrized model for its Helmholtz free energy. The ion motion contribution to the free energy is represented by a sum of Debye models for the vibrational modes of mainly lattice phonon and intramolecular character. The dependence of the frequencies of the normal modes on density is captured using the quasi-harmonic approximation whereby the Debye temperatures for both populations of modes depend explicitly on specific volume. The dependence of the Debye temperatures on specific volume was parametrized to normal-mode frequencies computed from solid state dispersion-corrected density functional theory. The model provides a good description of the thermophysical properties of PETN. The equation of state has been applied to the calculation of thermodynamic states along the principal Hugoniot of single crystal PETN.

Simulated performance of the optical Thomson scattering diagnostic designed for the National Ignition Facility.

An optical Thomson scattering diagnostic has been designed for the National Ignition Facility to characterize under-dense plasmas. We report on the design of the system and the expected performance for different target configurations. The diagnostic is designed to spatially and temporally resolve the Thomson scattered light from laser driven targets. The diagnostic will collect scattered light from a 50 × 50 × 200 µm volume. The optical design allows operation with different probe laser wavelengths. A deep-UV probe beam (λ0 = 210 nm) will be used to Thomson scatter from electron plasma densities of ∼5 × 1020 cm-3 while a 3ω probe will be used for plasma densities of ∼1 × 1019 cm-3. The diagnostic package contains two spectrometers: the first to resolve Thomson scattering from ion acoustic wave fluctuations and the second to resolve scattering from electron plasma wave fluctuations. Expected signal levels relative to background will be presented for typical target configurations (hohlraums and a planar foil).

The design of the optical Thomson scattering diagnostic for the National Ignition Facility.

The National Ignition Facility (NIF) is a 192 laser beam facility designed to support the Stockpile Stewardship, High Energy Density and Inertial Confinement Fusion (ICF) programs. We report on the design of an Optical Thomson Scattering (OTS) diagnostic that has the potential to transform the community's understanding of NIF hohlraum physics by providing first principle, local, time-resolved measurements of under-dense plasma conditions. The system design allows operation with different probe laser wavelengths by manual selection of the appropriate beam splitter and gratings before the shot. A deep-UV probe beam (λ0-210 nm) will be used to optimize the scattered signal for plasma densities of 5 × 1020 electrons/cm3 while a 3ω probe will be used for experiments investigating lower density plasmas of 1 × 1019 electrons/cm3. We report the phase I design of a two phase design strategy. Phase I includes the OTS telescope, spectrometer, and streak camera; these will be used to assess the background levels at NIF. Phase II will include the design and installation of a probe laser.

Mapping Lysine Acetyltransferase-Ligand Interactions by Activity-Based Capture.

Changes in reversible protein acetylation mediate many key aspects of genomic regulation and enzyme function. The catalysts for this posttranslational modification, lysine acetyltransferases (KATs), have been difficult targets for characterization due to their complex architecture and challenging reconstitution. To address this challenge, here we describe methods to profile endogenous KAT activities using activity-based probes. This method facilitates the targeted analysis of several cellular KATs and can be used to study their interactions with many different types of ligands, including acyl-CoA metabolites. This competitive activity-based capture approach provides a method to assess the selectivity of ligands for different KAT families in complex proteomic settings, and thus has the potential to offer substantial insights into the regulation of cellular KAT function.

Publisher's Note: Experimental investigation of stimulated Raman and Brillouin scattering instabilities driven by two successive collinear picosecond laser pulses [Phys. Rev. E 93, 043209 (2016)].

This corrects the article DOI: 10.1103/PhysRevE.93.043209.

Experimental investigation of stimulated Raman and Brillouin scattering instabilities driven by two successive collinear picosecond laser pulses.

Backward stimulated Raman and Brillouin scattering (SRS and SBS) are experimentally investigated by using two successive 1-µm, 1.5-ps FWHM laser pulses. The collinear pulses, separated by 3 or 6 ps and of moderate laser intensities (∼2×10^{16}Wcm^{-2}), are fired into a preionized He plasma of density ∼2.5-6×10^{19}cm^{-3}. The electron plasma waves and ion acoustic waves, respectively driven by SRS and SBS, are analyzed through space- and time-resolved Thomson scattering. Depending on the laser and plasma parameters, we observe the effect of the first pulse on the time-resolved SRS and SBS signals of the second pulse. The measurements are found to qualitatively agree with the results of a large-scale particle-in-cell simulation.

Tuberculosis screening at a diabetes clinic in the Republic of the Marshall Islands.

SETTING: Tuberculosis (TB) and diabetes mellitus (DM) are prominent public health problems in the Republic of the Marshall Islands, a small island nation with high rates of tuberculosis and diabetes. OBJECTIVE: Evaluate the rate of active and latent TB in a Pacific Island DM clinic. DESIGN: In one DM clinic on the island of Ebeye, 213 adult patients aged 27-86 years completed tuberculin skin testing and TB work-up between April 2010 and March 2012. RESULTS: Screening for TB led to the diagnosis of 77 patients with TB infection and 11 patients with TB disease. From these data, the prevalence of TB disease among DM patients in the clinic exceeded 5% (95% CI 2.2%-8.1%). All patients who completed TB screening were at high risk of TB disease, and those with DM aged  ≤ 50 years had a higher risk of TB disease than those with DM over age 50 (RR 3.1, C.I. 1.0-9.7, p = 0.05). CONCLUSION: The experience at the Ebeye Diabetes Clinic demonstrates that screening DM patients for TB can identify significant rates of TB infection and TB disease, and should be considered for other settings with a high background TB incidence. Further assessment of TB risks should explore age, gender, and level of diabetes control.

Demonstration of x-ray fluorescence imaging of a high-energy-density plasma.

Experiments at the Trident Laser Facility have successfully demonstrated the use of x-ray fluorescence imaging (XRFI) to diagnose shocked carbonized resorcinol formaldehyde (CRF) foams doped with Ti. One laser beam created a shock wave in the doped foam. A second laser beam produced a flux of vanadium He-α x-rays, which in turn induced Ti K-shell fluorescence within the foam. Spectrally resolved 1D imaging of the x-ray fluorescence provided shock location and compression measurements. Additionally, experiments using a collimator demonstrated that one can probe specific regions within a target. These results show that XRFI is a capable alternative to path-integrated measurements for diagnosing hydrodynamic experiments at high energy density.

Temperature measurements of shocked silica aerogel foam.

We present recent results of equation-of-state (EOS) measurements of shocked silica (SiO_{2}) aerogel foam at the OMEGA laser facility. Silica aerogel is an important low-density pressure standard used in many high energy density experiments, including the novel technique of shock and release. Due to its many applications, it has been a heavily studied material and has a well-known Hugoniot curve. This work then complements the velocity and pressure measurements with additional temperature data providing the full EOS information within the warm dense matter regime for the temperature interval of 1-15 eV and shock velocities between 10 and 40 km/s corresponding to shock pressures of 0.3-2 Mbar. The experimental results were compared with hydrodynamic simulations and EOS models. We found that the measured temperature was systematically lower than suggested by theoretical calculations. Simulations provide a possible explanation that the emission measured by optical pyrometry comes from a radiative precursor rather than from the shock front, which could have important implications for such measurements.