Expression kinetics and innate immune response after electroporation and LNP-mediated delivery of a self-amplifying mRNA in the skin

In this work, we studied the expression kinetics and innate immune response of a self-amplifying mRNA (sa-RNA) after electroporation and lipid-nanoparticle (LNP)-mediated delivery in the skin of mice. Intradermal electroporation of the sa-RNA resulted in a plateau-shaped expression, with the plateau between day 3 and day 10. The overall protein expression of sa-RNA was significantly higher than that obtained after electroporation of plasmid DNA (pDNA) or non-replication mRNAs. Moreover, using IFN-beta reporter mice, we elucidated that intradermal electroporation of sa-RNA induced a short-lived moderate innate immune response, which did not affect the expression of the sa-RNA. A completely different expression profile and innate immune response were observed when LNPs were used. The expression peaked 24 h after intradermal injection of sa-RNA-LNPs and subsequently showed a sharp drop. This drop might be explained by a translational blockage caused by the strong innate immune response that we observed in IFN-beta reporter mice shortly (4 h) after intradermal injection of sa-RNA-LNPs. A final interesting observation was the capacity of sa-RNA-LNPs to transfect the draining lymph nodes after intradermal injection

Dust remobilization in fusion plasmas under steady state conditions

The first combined experimental and theoretical studies of dust remobilization by plasma forces are reported. The main theoretical aspects of remobilization in fusion devices under steady state conditions are analyzed. In particular, the dominant role of adhesive forces is highlighted and generic remobilization conditions - direct lift-up, sliding, rolling - are formulated. A novel experimental technique is proposed, based on controlled adhesion of dust grains on tungsten samples combined with detailed mapping of the dust deposition profile prior and post plasma exposure. Proof-of-principle experiments in the TEXTOR tokamak and the EXTRAP-T2R reversed-field pinch are presented. The versatile environment of the linear device Pilot-PSI allowed for experiments with different magnetic field topologies and varying plasma conditions that were complemented with camera observations.Comment: 16 pages, 11 figures, 3 table

Erosion yields of carbon under various plasma conditions in Pilot-PSI

Fine-grain graphite targets have been exposed to ITER divertor relevant plasmas in Pilot-PSI to address material migration issues in fusion devices. Optical emission spectroscopy and mass loss measurements have been employed to quantify gross chemical erosion and net erosion yields, respectively. Effects of the ion impact energy and target geometry on carbon erosion yields have been studied. It is concluded that temporal evolution of gross chemical erosion is strongly connected with changes in morphology of plasma exposed surfaces. The net carbon erosion yield is increased when the targets are partly covered by insulating boron-nitride rings.Comment: 14 pages, 4 figures, Contribution to the 19th International Conference on Plasma Surface Interaction

Density functional study of the actinide nitrides

The full potential all electron linearized augmented plane wave plus local orbitals (FP-LAPW + lo) method, as implemented in the suite of software WIEN2K, has been used to systematically investigate the structural, electronic, and magnetic properties of the actinide compounds AnN (An = Ac, Th, Pa, U, Np, Pu, Am). The theoretical formalism used is the generalized gradient approximation to density functional theory (GGA-DFT) with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional. Each compound has been studied at six levels of theory: non-magnetic (NM), non-magnetic with spin-orbit coupling (NM+SOC), ferromagnetic (FM), ferromagnetic with spin-orbit coupling (FM+SOC), anti-ferromagnetic (AFM), and anti-ferromagnetic with spin-orbit coupling (AFM+SOC). The structural parameters, bulk moduli, densities of states, and charge distributions have been computed and compared to available experimental data and other theoretical calculations published in the literature. The total energy calculations indicate that the lowest energy structures of AcN, ThN, and PaN are degenerate at the NM+SOC, FM+SOC, and AFM+SOC levels of theory with vanishing total magnetic moments in the FM+SOC and AFM+SOC cases, making the ground states essentially non-magnetic with spin-orbit interaction. The ground states of UN, NpN, PuN, and AmN are found to be FM+SOC at the level of theory used in the present computations. The nature of the interactions between the actinide metals and nitrogen atom, and the implications on 5f electron delocalization and localization are discussed in detail.Comment: 5 tables, 12 figure

Characterizing the recovery of a solid surface after tungsten nano-tendril formation

Recovery of a flat tungsten surface from a nano-tendril surface is attempted through three techniques; a mechanical wipe, a 1673&nbsp;K annealing, and laser-induced thermal transients. Results were determined through SEM imaging and elastic recoil detection to assess the helium content in the surface. The mechanical wipe leaves a ∼0.5&nbsp;μm deep layer of nano-tendrils on the surface post-wipe regardless of the initial nano-tendril layer depth. Laser-induced thermal transients only significantly impact the surface morphology at heat loads of 35.2&nbsp;MJ/m2&nbsp;s1/2 or above, however a fully flat or recovered surface was not achieved for 100 transients at this heat load despite reducing the helium content by a factor of ∼7. A 1673&nbsp;K annealing removes all detectable levels of helium but sub-surface voids/bubbles remain intact. The surface is recovered to a nearly flat state with only some remnants of nano-tendrils re-integrating into the surface remaining.</p

Comparison of pap smear, visual inspection with acetic acid, human papillomavirus DNA-PCR testing and cervicography

Objective: To assess the test qualities of four screening methods to detect cervical intra-epithelial neoplasia in an urban African setting. Method: Six hundred fiftythree women, attending a family planning clinic in Nairobi (Kenya), underwent four concurrent screening methods: pap smear, visual inspection with acetic acid (VIA), PCR for high risk human papillomavirus (HR HPV) and cervicography. The presence of cervical intra-epithelial neoplasia (CIN) was verified by colposcopy or biopsy. Result: Sensitivity (for CIN2 or higher) and specificity (to exclude any CIN or cancer) were 83.3% (95% CI [73.6, 93.0]) and 94.6% (95% CI [92.6, 96.5]), respectively, for pap smear; 73.3% (95% CI [61.8, 84.9]) and 80.0% (95% CI [76.6, 83.4]) for VIA; 94.4% (95% CI [84.6, 98.8]) and 73.9% (95% CI [69.7, 78.2]) for HR HPV; and 72.3% (95% CI [59.1, 85.6]) and 93.2% (95% CI [90.8, 95.7]) for cervicography. Conclusion: The pap smear had the highest specificity (94.6%) and HPV testing the highest sensitivity (94.4%). The visual methods, VIA and cervicography, were similar and showed an accuracy in between the former two tests