Background In our previous study about 75% of children with cow's milk allergy tolerated baked milk products, which improved their prognosis and quality of life. Objective We sought to identify ...biomarkers of varying degrees of clinical tolerance among a cohort of children with cow's milk allergy. Methods One hundred thirty-two subjects were initially classified as baked milk–reactive, baked milk–tolerant, or having “outgrown milk allergy” based on the results of oral food challenges. The baked milk–tolerant group was then divided into 3 groups based on the amount and degree of heat-denatured milk protein that they could tolerate. Serum was analyzed for allergen-specific IgE and IgG4 levels, basophil reactivity was assessed in whole blood stimulated with serial 10-fold dilutions of milk protein, and skin prick tests (SPTs) were performed to commercial milk extract. Activated basophils were defined by using flow cytometry as CD63bright CD203c+ CD123+ HLA-DRdim/− CD41a− lineage− . Data were analyzed by using the Jonckheere-Terpstra test. Results Significant differences across the 5 clinical groups were seen for median casein- and milk-specific IgE levels, casein-specific IgG4 levels, and casein IgE/IgG4 ratios; milk-specific to nonspecific basophil activation ratio, median basophil reactivity, and spontaneous basophil activation (CD203c expression after stimulation with RPMI); and milk SPT wheal diameters. Casein- and milk-specific IgE level, milk-specific basophil reactivity, and milk SPT wheal diameter are all significantly greater among patients with milk allergy who react to baked milk than among those who tolerate it. Conclusions The majority of patients with milk allergy are able to tolerate some forms of baked milk in their diets. Different phenotypes of children with cow's milk allergy can be distinguished by casein- and milk-specific IgE levels, milk-specific basophil reactivity, and milk SPT mean wheal diameters. Spontaneous basophil activation is greater among patients with more severe clinical milk reactivity.
EAACI Molecular Allergology User's Guide Matricardi, P. M.; Kleine-Tebbe, J.; Hoffmann, H. J. ...
Pediatric allergy and immunology,
20/May , Letnik:
27, Številka:
S23
Journal Article
Recenzirano
Odprti dostop
The availability of allergen molecules (‘components’) from several protein families has advanced our understanding of immunoglobulin E (IgE)‐mediated responses and enabled ‘component‐resolved ...diagnosis’ (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low‐abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross‐reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE‐mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross‐reactive panallergens from plant (lipid transfer proteins, polcalcins, PR‐10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE‐mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.
Anion redox in lithium transition-metal oxides such as Li2RuO3 and Li2MnO3 has catalyzed intensive research efforts to find transition-metal oxides with anion redox that may boost the energy density ...of lithium-ion batteries. The physical origin of the observed anion redox remains debatable, and more direct experimental evidence is needed. In this work, we have shown electronic signatures of oxygen–oxygen coupling, direct evidence central to lattice oxygen redox (O2–/(O2) n−), in charged Li2–x RuO3 after Ru oxidation (Ru4+/Ru5+) upon first electron removal with lithium deintercalation. Experimental Ru L3-edge high-energy-resolution fluorescence-detected X-ray absorption spectra (HERFD-XAS), supported by ab initio simulations, revealed that the increased intensity in the high-energy shoulder upon lithium deintercalation resulted from increased O–O coupling, inducing (O–O) σ*-like states with π overlap with Ru d-manifolds, in agreement with O K-edge XAS spectra. Experimental and simulated O K-edge X-ray emission spectra further supported this observation with the broadening of the oxygen nonbonding feature upon charging, also originated from (O–O) σ* states. This lattice oxygen redox of Li2–x RuO3 was accompanied by a small amount of O2 evolution in the first charge from differential electrochemistry mass spectrometry but diminished in the subsequent cycles, in agreement with the more reduced states of Ru in later cycles from Ru L3-edge HERFD-XAS. These observations indicated that Ru redox contributed more to discharge capacities after the first cycle. This study has pinpointed the key spectral fingerprints related to lattice oxygen redox from a molecular level and constructed a transferrable framework to rationally interpret the spectroscopic features by combining advanced experiments and theoretical calculations to design materials for Li-ion batteries and electrocatalysis applications.
To limit further rising levels in methane emissions from stationary and mobile sources and to enable promising technologies based on methane, the development of efficient combustion catalysts that ...completely oxidize CH4 to CO2 and H2O at low temperatures in the presence of high steam concentrations is required. Palladium is widely considered as one of the most promising materials for this reaction, and a better understanding of the factors affecting its activity and stability is crucial to design even more improved catalysts that efficiently utilize this precious metal. Here we report a study of the effect of three important variables (particle size, support, and reaction conditions including water) on the activity of supported Pd catalysts. We use uniform palladium nanocrystals as catalyst precursors to prepare a library of well-defined catalysts to systematically describe structure–property relationships with help from theory and in situ X-ray absorption spectroscopy. With this approach, we confirm that PdO is the most active phase and that small differences in reaction rates as a function of size are likely due to variations in the surface crystal structure. We further demonstrate that the support exerts a limited influence on the PdO activity, with inert (SiO2), acidic (Al2O3), and redox-active (Ce0.8Zr0.2O2) supports providing similar rates, while basic (MgO) supports show remarkably lower activity. Finally, we show that the introduction of steam leads to a considerable decrease in rates that is due to coverage effects, rather than structural and/or phase changes. Altogether, the data suggest that to further increase the activity and stability of Pd-based catalysts for methane combustion, increasing the surface area of supported PdO phases while avoiding strong adsorption of water on the catalytic surfaces is required. This study clarifies contrasting reports in the literature about the active phase and stability of Pd-based materials for methane combustion.
The electronic structure and dynamics of ruthenium complexes are widely studied given their use in catalytic and light-harvesting materials. Here we investigate three model Ru complexes, ...RuIII(NH3)63+, RuII(bpy)32+, and RuII(CN)64–, with L3-edge 2p3d resonant inelastic X-ray scattering (RIXS) to probe unoccupied 4d valence orbitals and occupied 3d orbitals and to gain insight into the interactions between these levels. The 2p3d RIXS maps contain a higher level of spectral information than the L3 X-ray absorption near edge structure (XANES). This study provides a direct measure of the 3d spin–orbit splittings of 4.3, 4.0, and 4.1 eV between the 3d5/2 and 3d3/2 orbitals of the RuIII(NH3)63+, RuII(bpy)32+, and RuII(CN)64– complexes, respectively.
Multiplexed ion beam imaging by time-of-flight (MIBI-TOF) is a form of mass spectrometry imaging that uses metal labeled antibodies and secondary ion mass spectrometry to image dozens of proteins ...simultaneously in the same tissue section. Working with the National Cancer Institute's (NCI) Cancer Immune Monitoring and Analysis Centers (CIMAC), we undertook a validation study, assessing concordance across a dozen serial sections of a tissue microarray of 21 samples that were independently processed and imaged by MIBI-TOF or single-plex immunohistochemistry (IHC) over 12 days. Pixel-level features were highly concordant across all 16 targets assessed in both staining intensity (R
= 0.94 ± 0.04) and frequency (R
= 0.95 ± 0.04). Comparison to digitized, single-plex IHC on adjacent serial sections revealed similar concordance (R
= 0.85 ± 0.08) as well. Lastly, automated segmentation and clustering of eight cell populations found that cell frequencies between serial sections yielded an average correlation of R
= 0.94 ± 0.05. Taken together, we demonstrate that MIBI-TOF, with well-vetted reagents and automated analysis, can generate consistent and quantitative annotations of clinically relevant cell states in archival human tissue, and more broadly, present a scalable framework for benchmarking multiplexed IHC approaches.
The proposed International Linear Collider (ILC) is well-suited for discovering physics beyond the Standard Model and for precisely unraveling the structure of the underlying physics. The physics ...return can be maximized by the use of polarized beams. This report shows the paramount role of polarized beams and summarizes the benefits obtained from polarizing the positron beam, as well as the electron beam. The physics case for this option is illustrated explicitly by analyzing reference reactions in different physics scenarios. The results show that positron polarization, combined with the clean experimental environment provided by the linear collider, allows to improve strongly the potential of searches for new particles and the identification of their dynamics, which opens the road to resolve shortcomings of the Standard Model. The report also presents an overview of possible designs for polarizing both beams at the ILC, as well as for measuring their polarization.
In baked form, cow's milk and egg are less allergenic and are tolerated by most milk- and egg-allergic children. Not only may including baked milk and egg in the diets of children who are tolerant ...improve nutrition and promote more social inclusion but there is also evidence that inclusion may accelerate the resolution of unheated milk and egg allergy. Further research is needed on biomarkers that can predict baked milk or egg reactivity; however, data suggest casein- and ovomucoid-specific immunoglobulin E levels may be useful. Physician-supervised introduction of baked milk and egg is recommended because anaphylaxis has occurred.
Total reflection X‐ray fluorescence (TXRF) analysis is extensively used by the semiconductor industry for measuring trace metal contamination on silicon surfaces. In addition to determining the ...quantity of impurities on a surface, TXRF can reveal information about the vertical distribution of contaminants by measuring the fluorescence signal as a function of the angle of incidence. In this study, two samples were intentionally contaminated with copper in non‐deoxygenated and deoxygenated ultrapure water (UPW) resulting in impurity profiles that were either atomically dispersed in a thin film or particle‐like, respectively. The concentration profile of the samples immersed into deoxygenated UPW was calculated using a theoretical concentration profile representative of particles, yielding a mean particle height of 16.1 nm. However, the resulting theoretical profile suggested that a distribution of particle heights exists on the surface. The fit of the angular distribution data was further refined by minimizing the residual error of a least‐squares fit employing a model with a Gaussian distribution of particle heights about the mean height. The presence of a height distribution was also confirmed with atomic force microscopy measurements.
The angular distribution of the total reflection X‐ray fluorescence signal can suggest a distribution of particle heights deposited on a surface. This height distribution can be deduced by fitting theoretical concentration profiles representative of particles.
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