Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa), the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgE-binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein's digestibility is not affected by such processing

Intersecting single-cell transcriptomics and genome-wide association studies identifies crucial cell populations and candidate genes for atherosclerosis

Genome-wide association studies (GWASs) have discovered hundreds of common genetic variants for atherosclerotic disease and cardiovascular risk factors. The translation of susceptibility loci into biological mechanisms and targets for drug discovery remains challenging. Intersecting genetic and gene expression data has led to the identification of candidate genes. However, previously studied tissues are often non-diseased and heterogeneous in cell composition, hindering accurate candidate prioritization. Therefore, we analysed single-cell transcriptomics from atherosclerotic plaques for cell-type-specific expression to identify atherosclerosis-associated candidate gene-cell pairs.\nWe applied gene-based analyses using GWAS summary statistics from 46 atherosclerotic and cardiovascular disease, risk factors, and other traits. We then intersected these candidates with single-cell RNA sequencing (scRNA-seq) data to identify genes specific for individual cell (sub)populations in atherosclerotic plaques. The coronary artery disease (CAD) loci demonstrated a prominent signal in plaque smooth muscle cells (SMCs) (SKI, KANK2, and SORT1) P-adj. = 0.0012, and endothelial cells (ECs) (SLC44A1, ATP2B1) P-adj. = 0.0011. Finally, we used liver-derived scRNA-seq data and showed hepatocyte-specific enrichment of genes involved in serum lipid levels.\nWe discovered novel and known gene-cell pairs pointing to new biological mechanisms of atherosclerotic disease. We highlight that loci associated with CAD reveal prominent association levels in mainly plaque SMC and EC populations. We present an intuitive single-cell transcriptomics-driven workflow rooted in human large-scale genetic studies to identify putative candidate genes and affected cells associated with cardiovascular traits. Collectively, our workflow allows for the identification of cell-specific targets relevant for atherosclerosis and can be universally applied to other complex genetic diseases and traits.Biopharmaceutic

Description of processes for the immobilization of selected transuranic wastes

Processed sludge and incinerator-ash wastes contaminated with transuranic (TRU) elements may require immobilization to prevent the release of these elements to the environment. As part of the TRU Waste Immobilization Program sponsored by the Department of Energy (DOE), the Pacific Northwest Laboratory is developing applicable waste-form and processing technology that may meet this need. This report defines and describes processes that are capable of immobilizing a selected TRU waste-stream consisting of a blend of three parts process sludge and one part incinerator ash. These selected waste streams are based on the compositions and generation rates of the waste processing and incineration facility at the Rocky Flats Plant. The specific waste forms that could be produced by the described processes include: in-can melted borosilicate-glass monolith; joule-heated melter borosilicate-glass monolith or marble; joule-heated melter aluminosilicate-glass monolith or marble; joule-heated melter basaltic-glass monolith or marble; joule-heated melter glass-ceramic monolith; cast-cement monolith; pressed-cement pellet; and cold-pressed sintered-ceramic pellet

Isotopic safeguards techniques

Information is presented to explain and illustrate the idea and uses of isotopic safeguards techniques. A generalized, simple approach is maintained to facilitate understanding of the techniques. Once understood, the application, demonstration, and implementation of isotopic safeguards techniques becomes much easier

In situ vitrification pilot-scale radioactive test

Pacific Northwest Laboratory (PNL) is developing in situ vitrification (ISV) as an in-place stabilization technique for selected liquid radioactive waste disposal sites. The process melts the wastes and surrounding soil to produce a durable glass and crystalline waste form. These ISV process development testing and evaluation studies are being conducted for the US Department of Energy. The results of an ISV pilot-scale test conducted in June of 1983 in which soils contaminated with actual radioactive transuranic and mixed fission product elements were vitrified are discussed. The primary objectives of the radioactive test were to: demonstrate containment and confinement of the radioactive material; verify equipment performance of the power and off-gas systems; identify losses to the off-gas system; and characterize the behavior of the radioactive material in the vitrified soil. The test successfully demonstrated the processing containment of radionuclides both within the vitrified mass and in the off-gas system. No environmental release of radioactive material was measured during testing operations. The vitrified soil had a greater than 99% retention of all radionuclides. Losses to the off-gas system varied from less than or equal to 0.03% for particulate materials (plutonium and strontium) to 0.8% for cesium which is a more volatile element. The off-gas system effectively contained both volatile and entrained radioactive materials. Analysis of the vitrified soil revealed that all radionuclides were distributed throughout the vitrified zone, some more uniformly than others. No migration of radionuclides outside the vitrification zone occurred, as indicated by analysis of soil samples from around the block. Previous waste form leaching studies indicate an acceptable durability of the ISV product. 8 references, 34 figures, 8 tables

Support for the in situ vitrification treatability study at the Idaho National Engineering Laboratory: FY 1988 summary

The objective of this project is to determine if in situ vitrification (ISV) is a viable, long-term confinement technology for previously buried solid transuranic and mixed waste at the Radioactive Waste Management Complex (RWMC). The RWMC is located at the Idaho National Engineering Laboratory (INEL). In situ vitrification is a thermal treatment process that converts contaminated soils and wastes into a durable glass and crystalline form. During processing, heavy metals or other inorganic constituents are retained and immobilized in the glass structure, and organic constituents are typically destroyed or removed for capture by an off-gas treatment system. The primary FY 1988 activities included engineering-scale feasibility tests on INEL soils containing a high metals loading. Results of engineering-scale testing indicate that wastes with a high metals content can be successfully processed by ISV. The process successfully vitrified soils containing localized metal concentrations as high as 42 wt % without requiring special methods to prevent electrical shorting within the melt zone. Vitrification of this localized concentration resulted in a 15.9 wt % metals content in the entire ISV test block. This ISV metals limit is related to the quantity of metal that accumulates at the bottom of the molten glass zone. Intermediate pilot-scale testing is recommended to determine metals content scale-up parameters in order to project metals content limits for large-scale ISV operation at INEL

Engineering-scale in situ vitrification of simulated Oak Ridge National Laboratory liquid waste seepage trenches

An engineering-scale test of in situ vitrification (ISV) was successfully completed in January 1990 using Oak Ridge National Laboratory (ORNL) nonradioactive cesium (CS)-spiked soils. The objectives of this engineering-scale ISV test were to: (1) assess the application of electrode feeding to ORNL soils; (2) evaluate several real-time temperature monitoring methods for the melt; (3) evaluate Cs retention in the glass; and (4) determine the effectiveness of a pretreatment filter for removal of Cs from the off-gas stream. The test was part of a larger program to determine the applicability of the ISV process as a remedial action technique for the treatment of ORNL liquid waste seepage trenches

Selected transuranic waste immobilization systems

Waste contaminated with transuranic (TRU) elements may require treatment prior to final disposal. Pacific Northwest Laboratory has conducted research and development to identify and characterize the wastes; to evaluate the possible immobilization requirements and treatment alternatives; and to develop immobilization process technologies. This paper describes systems that are anticipated to be capable of immobilizing a selected TRU waste stream consisting of a blend of process sludge and incinerator ash. The selected waste streams are based on the waste compositions generated at the Rocky Flats Plant, Golden, Colorado. The specific process and waste forms are: in-can glass melting, borosilicate glass monolith; joule-heated glass melting, borosilicate/aluminosilicate glass monolith; glass marble, borosilicate/aluminosilicate glass marble; basalt glass-ceramic, basalt glass-ceramic monolith; cast cement, cast cement monolith; pressed cement, pressed cement pellet; and cold-pressed sintered ceramic, pressed ceramic pellet

In-situ vitrification of transuranic wastes: systems evaluation and applications assessment

Major advantages of in-situ vitrification (ISV) as a means of stabilizing radioactive waste are: long term durability of the waste form; cost effectiveness; safety in terms of minimizing worker and public exposure; and applicability to different kinds of soils and buried wastes. This document describes ISV technology that is available as another viable tool for in place stabilization of waste sites. The following sections correspond to the chapters in the body of this document: description of the ISV process; analysis of the performane of the ISV tests conducted thus far; parameters of the ISV process; cost analysis for the ISV process; analysis of occupational and public exposure; and assessment of waste site applications