152 research outputs found

    Measurements on NASA Langley Durable Combustor Rig by TDLAT: Preliminary Results

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    Detailed knowledge of the internal structure of high-enthalpy flows can provide valuable insight to the performance of scramjet combustors. Tunable Diode Laser Absorption Spectroscopy (TDLAS) is often employed to measure temperature and species concentration. However, TDLAS is a path-integrated line-of-sight (LOS) measurement, and thus does not produce spatially resolved distributions. Tunable Diode Laser Absorption Tomography (TDLAT) is a non-intrusive measurement technique for determining two-dimensional spatially resolved distributions of temperature and species concentration in high enthalpy flows. TDLAT combines TDLAS with tomographic image reconstruction. Several separate line-of-sight TDLAS measurements are analyzed in order to produce highly resolved temperature and species concentration distributions. Measurements have been collected at the University of Virginia's Supersonic Combustion Facility (UVaSCF) as well as at the NASA Langley Direct-Connect Supersonic Combustion Test Facility (DCSCTF). Measurements collected at the DCSCTF required significant modifications to system hardware and software designs due to its larger measurement area and shorter test duration. Initial LOS measurements from the NASA Langley DCSCTF operating at an equivalence ratio of 0.5 are presented. Results show the capability of TDLAT to adapt to several experimental setups and test parameters

    Geophysical investigation of the neolithic Calanais landscape

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    YesThe northern and western isles of Scotland have proved fertile ground for archaeological investigation over the last 100 years. However, the nature of the landscape with its rugged coastlines and irregular topography, together with rapid peat growth rates, make for challenging surveying. Commonly, an archaeological monument or series of monuments is identified but little is known about the surrounding areas and, in particular, the palaeo-landscapes within which the monuments are located. This situation is exemplified by the standing stones of Calanais in Lewis. Here, surrounding peat bogs have buried a significant portion of the landscape around which the stones were first erected. This project identifies remote sensing geophysical techniques that are effective in mapping the buried (lost) landscape and thus aid better contextualisation of the stone monuments within it. Further, the project demonstrates the most appropriate techniques for prospecting across these buried landscapes for as yet unidentified stone features associated with the lives of the people who constructed the monuments.Scottish EnterpriseResearch Development Fund Publication Prize Award winner, December 2019

    Theoretical and experimental investigation of the equation of state of boron plasmas

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    We report a theoretical equation of state (EOS) table for boron across a wide range of temperatures (5.1×\times104^4-5.2×\times108^8 K) and densities (0.25-49 g/cm3^3), and experimental shock Hugoniot data at unprecedented high pressures (5608±\pm118 GPa). The calculations are performed with full, first-principles methods combining path integral Monte Carlo (PIMC) at high temperatures and density functional theory molecular dynamics (DFT-MD) methods at lower temperatures. PIMC and DFT-MD cross-validate each other by providing coherent EOS (difference <<1.5 Hartree/boron in energy and <<5% in pressure) at 5.1×\times105^5 K. The Hugoniot measurement is conducted at the National Ignition Facility using a planar shock platform. The pressure-density relation found in our shock experiment is on top of the shock Hugoniot profile predicted with our first-principles EOS and a semi-empirical EOS table (LEOS 50). We investigate the self diffusivity and the effect of thermal and pressure-driven ionization on the EOS and shock compression behavior in high pressure and temperature conditions We study the performance sensitivity of a polar direct-drive exploding pusher platform to pressure variations based on comparison of the first-principles calculations with LEOS 50 via 1D hydrodynamic simulations. The results are valuable for future theoretical and experimental studies and engineering design in high energy density research. (LLNL-JRNL-748227)Comment: 12 pages, 9 figures, 2 table

    N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells

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    © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. R-loops are nucleic acid structures formed by an RNA:DNA hybrid and unpaired single-stranded DNA that represent a source of genomic instability in mammalian cells1–4. Here we show that N6-methyladenosine (m6A) modification, contributing to different aspects of messenger RNA metabolism5,6, is detectable on the majority of RNA:DNA hybrids in human pluripotent stem cells. We demonstrate that m6A-containing R-loops accumulate during G2/M and are depleted at G0/G1 phases of the cell cycle, and that the m6A reader promoting mRNA degradation, YTHDF2 (ref. 7), interacts with R-loop-enriched loci in dividing cells. Consequently, YTHDF2 knockout leads to increased R-loop levels, cell growth retardation and accumulation of γH2AX, a marker for DNA double-strand breaks, in mammalian cells. Our results suggest that m6A regulates accumulation of R-loops, implying a role for this modification in safeguarding genomic stability

    Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

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    Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months
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