Nuclear magnetic resonance (NMR) spectroscopy provides detailed information about dynamic processes through line-shape changes, which are traditionally limited to equilibrium conditions. However, a ...wealth of information is available by studying chemical reactions under off-equilibrium conditions-e.g., in states that arise upon mixing reactants that subsequently undergo chemical changes-and in monitoring the reactants and products in real time. Herein, we propose and demonstrate a time-resolved kinetic NMR experiment that combines rapid mixing techniques, continuous flow, and single-scan spectroscopic imaging methods, leading in unison to a 2D spectrotemporal NMR correlation that provides high-quality kinetic information of off-equilibrium chemical reactions. These kinetic 2D NMR spectra possess a high-resolution spectral dimension revealing the individual chemical sites, correlated with a time-independent, steady-state spatial axis that delivers information concerning temporal changes along the reaction coordinate. A comprehensive description of the kinetic, spectroscopic, and experimental features associated with these spectrotemporal NMR analyses is presented. Experimental demonstrations are carried out using an enzymatically catalyzed reaction leading to site- and time-resolved kinetic NMR data, that are in excellent agreement with control experiments and literature values.
Hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. HBcrAg combines the antigenic reactivity resulting from denatured hepatitis ...B e antigen (HBeAg), HBV core antigen and an artificial core-related protein (p22cr). In Asian patients, high levels of HBcrAg have been suggested to be an independent risk factor for hepatocellular carcinoma, while low levels could guide safe cessation of treatment with nucleos(t)ide analogues. We here studied HBcrAg levels in different phases of HBV infection in a large European cohort predominantly infected with genotypes A and D: HBeAg-positive immune tolerance (n = 30), HBeAg-positive immune clearance (IC) (n = 60), HBeAg-negative hepatitis (ENH) (n = 50), HBeAg-negative inactive/quiescent carrier phase (c) (n = 109) and acute hepatitis B (n = 8). Median HBcrAg levels were high in the immune tolerance and immune clearance phases (8.41 and 8.11 log U/mL, respectively), lower in ENH subjects (4.82 log U/mL) but only 2.00 log U/mL in ENQ subjects. Correlation between HBcrAg and HBV DNA varied among the different phases of HBV infection, while HBcrAg moderately correlated with hepatitis B surface antigen in all phases. ENQ patients had HBcrAg levels <3 log U/mL in 79%, in contrast to only 12% in the ENH group. HBcrAg levels vary significantly during the different phases of HBV infection. HBcrAg may serve as valuable marker for virus replication and reflect the transcriptional activity of intrahepatic cccDNA. In HBeAg-negative patients, HBcrAg may help to distinguish between inactive carriers (ENQ) and those with active disease (ENH).
Thermally sprayed coatings are one of the potential ways to increase corrosion performance of Mg alloys dedicated for aircraft applications. In our research, a novel thermal spray process called Warm ...Spraying (WS) was used to deposit Ti coatings onto AZ91E magnesium alloy. WS gives us the possibility to control the temperature of the sprayed particles by changing the nitrogen flow rate (NFR) what as a result determine the porosity of WS coatings. The microstructure, porosity and oxygen content of coatings deposited under three different NFR was determined. A relation between porosity, oxygen content and NFR was revealed. The corrosion testing in 3.5% NaCl solution of as-sprayed coatings revealed their poor corrosion resistance that led to fast degradation of the substrate. The following post-treatment with epoxy-based polymer resulted in a significant improvement of the corrosion performance of Ti warm sprayed coatings.
•Titanium warm sprayed coatings for corrosion protection•Improvement of corrosion resistance with post-treatment•Over 1000 h protection of Mg based substrate provided by Ti warm sprayed coating combined with epoxy-based sealing
Efficient acquisition of high-quality ultra-wideline (UW) solid-state NMR powder patterns in short experimental time frames is challenging. UW NMR powder patterns often possess inherently low ...signal-to-noise (S/N) and usually overlap for samples containing two or more magnetically distinct nuclides, which obscures spectral features and drastically lowers the spectral resolution. Currently, there is no reliable method for resolving overlapping powder patterns originating from unreceptive nuclei affected by large anisotropic NMR interactions. Herein, we discuss new methods for resolving individual UW NMR spectra associated with magnetically distinct nuclei by exploiting their different relaxation characteristics using 2D relaxation-assisted separation (RAS) experiments. These experiments use a non-negative Tikhonov fitting (NNTF) routine to process high-quality T 1 and T 2 eff relaxation data sets to produce high-resolution, 2D spin-relaxation correlation spectra for both spin-1/2 and quadrupolar nuclei in organic and organometallic solids under static (i.e., stationary) conditions. It is found that (i) T 2 eff RAS data sets can be acquired in a fraction of the time required for analogous T 1 RAS data sets, because a time-incremented 2D data set is not required for the former, and (ii) Tikhonov regularization is superior to conventional non-negative least-squares fitting, as it more reliably and robustly results in cleaner separation of patterns based on relaxation time constants.
The effect of annealing on the mechanical and corrosion response of 316L stainless steel produced using laser powder bed fusion (LPBF) was investigated. The as-printed materials were subjected to ...annealing at a temperature of 1000 °C for 2 h. Microstructural observations revealed that after annealing the cellular network inside the grains disappeared, and a slight increase in grain size and the proportion of low-angle grain boundaries (LAGBs) occurred. The most significant microstructural changes occurred with the nano-inclusions, as the annealing resulted in change in their chemical composition, a decrease in their density (number per unit volume), while simultaneously their size increased. All these changes caused a decline in the mechanical properties of the steel and an increase in its susceptibility to localized corrosion.
A free vibration analysis of homogeneous and isotropic circular thin plates with nonlinear thickness variation and clamped edges is considered. The limited independent solutions of differential Euler ...equation were expanded in the power series based on the properties of integral equations. The analytical frequency equations as power series were obtained using the method of successive approximations.
Summary
Background
Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates ...and good tolerability in most patient populations in pre‐registration studies.
Aim
To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real‐world conditions.
Methods
Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT.
Results
A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b‐infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti‐viral therapies and 84 (40.2%) were null‐responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child–Pugh B and post‐orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On‐treatment decompensation was experienced by seven (3.3%) patients.
Conclusions
The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1‐infected patients treated in the real‐world setting.
Nuclear magnetic resonance (NMR) is a well-established technique, to study crystalline and amorphous solids, that provides rich structural and dynamical insights. Many solids NMR experiments, ...however, are challenged by sensitivity considerations, which demand the use of optimized data acquisition protocols. When inhomogeneous broadenings dominate the lineshapes, as is often the case when dealing with quadrupolar nuclei, the application of multiple echoes by means of Carr-Purcell Meiboom-Gill (CPMG) sequence variants can considerably facilitate the acquisition of solid-state NMR data. This study explores the use of steady-state free precession (SSFP) experiments, another proposal derived from Carr’s early work. SSFP sequences are commonly utilized in magnetic resonance imaging acquisitions, which are also dominated by (gradient-imposed) inhomogeneous broadenings, where they are well-known to provide the highest sensitivity per unit time. SSFP sequences are also common in nuclear quadrupole resonanceyet to our knowledge they have been less explored within the realm of high-field solids NMR on static and spinning samples. The present study examines the application of SSFP to these scenarios, in particular, in what concerns its ability to enhance the sensitivity of wide-line spectra. The regimes when SSFP could be advantageous compared to CPMG acquisitions are examined, and sensitivity enhancements of between 1 and 2 orders of magnitude per unit time are theoretically predicted and experimentally demonstrated in certain instances. Aspects in need of improvement to enable a wider use of SSFP-based approaches, particularly to wide-line quadrupolar studies, are also examined.
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