Oligomerization and Nitration of the Grass Pollen Allergen Phl p 5 by Ozone,Nitrogen Dioxide,and Peroxynitrite: Reaction Products,Kinetics, and Health Effects

The allergenic and inflammatory potential of proteins can be enhanced by chemical modification upon exposure to atmospheric or physiological oxidants. The molecular mechanisms and kinetics of such modifications, however, have not yet been fully resolved. We investigated the oligomerization and nitration of the grass pollen allergen Phl p 5 by ozone (O₃), nitrogen dioxide (NO₂), and peroxynitrite (ONOO^–). Within several hours of exposure to atmospherically relevant concentration levels of O₃ and NO₂, up to 50% of Phl p 5 were converted into protein oligomers, likely by formation of dityrosine cross-links. Assuming that tyrosine residues are the preferential site of nitration, up to 10% of the 12 tyrosine residues per protein monomer were nitrated. For the reaction with peroxynitrite, the largest oligomer mass fractions (up to 50%) were found for equimolar concentrations of peroxynitrite over tyrosine residues. With excess peroxynitrite, the nitration degrees increased up to 40% whereas the oligomer mass fractions decreased to 20%. Our results suggest that protein oligomerization and nitration are competing processes, which is consistent with a two-step mechanism involving a reactive oxygen intermediate (ROI), as observed for other proteins. The modified proteins can promote pro-inflammatory cellular signaling that may contribute to chronic inflammation and allergies in response to air pollution.     

Improved error bound for multivariate Chebyshev polynomial interpolation

ABSTRACT

Chebyshev interpolation is a highly effective, intensively studied method and enjoys excellent numerical properties which provides tremendous application potential in mathematical finance. The interpolation nodes are known beforehand, implementation is straightforward and the method is numerically stable. For efficiency, a sharp error bound is essential, in particular for high-dimensional applications. For tensorized Chebyshev interpolation, we present an error bound that improves existing results significantly.     

Case‐based decision support for fault diagnosis: Do salient ratings discourage situation analysis?

In the processing industry, frequent faults call for assistance in diagnosis, and case‐based reasoning (CBR) can provide solutions applied by other operators in the past. This study investigated whether salient case ratings promote an uncritical acceptance of solutions. In 2 experiments, subjects diagnosed faults with a simulated CBR system, and ratings were presented in graphical or verbal format. In most trials, the case with the highest rating provided the correct solution, while in catch‐trials, it did not. Graphical ratings were hypothesized to speed up solutions but discourage cross‐checking and lead to errors in catch‐trials. These hypotheses were not confirmed, even though Experiment 2 maximized the incentive of relying on case ratings. While graphical ratings led subjects to start with the most highly rated case, they did not impair situation analysis and accuracy. The results suggest that during fault diagnosis people are not easily misled into overtrusting a CBR system.     

Effect of alternating postures on cognitive performance for healthy people performing sedentary work

Prolonged sitting is a risk factor for several diseases and the prevalence of worksite-based interventions such as sit-to-stand workstations is increasing. Although their impact on sedentary behaviour has been regularly investigated, the effect of working in alternating body postures on cognitive performance is unclear. To address this uncertainty, 45 students participated in a two-arm, randomised controlled cross-over trial under laboratory conditions. Subjects executed validated cognitive tests (working speed, reaction time, concentration performance) either in sitting or alternating working postures on two separate days (ClinicalTrials.gov Identifier: NCT02863731). MANOVA results showed no significant difference in cognitive performance between trials executed in alternating, standing or sitting postures. Perceived workload did not differ between sitting and alternating days. Repeated measures ANOVA revealed significant learning effects regarding concentration performance and working speed for both days. These results suggest that working posture did not affect cognitive performance in the short term.

Practitioner Summary: Prior reports indicated health-related benefits based on alternated (sit/stand) body postures. Nevertheless, their effect on cognitive performance is unknown. This randomised controlled trial showed that working in alternating body postures did not influence reaction time, concentration performance, working speed or workload perception in the short term.     

Randomized residual-based error estimators for the proper generalized decomposition approximation of parametrized problems

This article introduces a novel error estimator for the proper generalized decomposition (PGD) approximation of parametrized equations. The estimator is intrinsically random: it builds on concentration inequalities of Gaussian maps and an adjoint problem with random right-hand side, which we approximate using the PGD. The effectivity of this randomized error estimator can be arbitrarily close to unity with high probability, allowing the estimation of the error with respect to any user-defined norm as well as the error in some quantity of interest. The performance of the error estimator is demonstrated and compared with some existing error estimators for the PGD for a parametrized time-harmonic elastodynamics problem and the parametrized equations of linear elasticity with a high-dimensional parameter space.     

Computer-aided B-mode ultrasound diagnosis of hepatic steatosis: a feasibility study

Fatty liver (steatosis) occurs in obese patients, among others, and is related to the development of diabetes type-2. Timely diagnosis of steatosis is therefore of great importance. Steatosis is also the most common liver disease of high-yielding dairy cattle during early lactation. This makes it a suitable animal model for studying liver steatosis. Furthermore, reference of derived ultrasound parameters against a "gold standard" is possible in cattle by taking a liver biopsy for the assessment of fat concentration. The authors undertook this pilot study to investigate the hypothesis that quantitative, computer-aided B-mode ultrasound enables the noninvasive detection of hepatic steatosis. Echographic images were obtained postpartum from dairy cows (n = 12) in transcutaneous and direct (intraoperative) applications using a convex array transducer at 4.2 MHz. During surgery, a biopsy was taken from the caudate lobe to assess the liver fat content (fat score). A custom-designed software package for computer-aided ultrasound diagnosis (CAUS) was developed. After linearizing the post-processing look-up-table (LUT), the image gray levels were transferred into echo levels in decibels relative to the mean echo level in a tissue-mimicking phantom. The quantitative comparison of transcutaneous and intraoperative images enabled the correction for the attenuation effect of skin and subcutaneous fat layer on the mean echo level in the liver, as well as for the effects of the beam formation and attenuation of liver tissue on the echo level vs. depth. The residual attenuation coefficient (dB/cm) in fatty liver vs. normal liver was estimated and compensated for. Finally, echo level was estimated relative to the phantom used for calibration, and echo texture was characterized by the mean axial and lateral speckle size within the regions of interest. In the no fat/low fat group (n = 5) skin plus fat layer attenuation was 3.4 dB/cm. A correlation of skin layer thickness vs. fat score of r = 0.48 was found. The mean transcutaneous liver tissue echo level correlated well with fat score: r = 0.80. A residual liver attenuation coefficient of 0.76 dB/cm and 1.19 dB/cm was found in medium and high fat liver, respectively. In transcutaneous images, correlation of residual attenuation coefficient with fat score was r = 0.69. Axial and lateral speckle sizes were on the order of 0.2 and 1.0 cm, respectively, and no correlation was found with liver fat content. Results for transcutaneous and intraoperative images were similar. The authors conclude that this pilot study shows the feasibility of calibrated, computer-aided ultrasound for noninvasively diagnosing, possibly even screening, steatosis of the liver.