163 research outputs found
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Low temperature setting iron phosphate ceramics as a stabilization and solidification agent for incinerator ash contaminated with transuranic and RCRA metals
Incineration of combustible Mixed Transuranic Waste yields an ash residue that contains oxides of Resource Conservation and Recovery Act (RCRA) and transuranic metals. In order to dispose of this ash safely, it has to be solidified and stabilized to satisfy appropriate requirements for repository disposal. This paper describes a new method for solidification of incinerator ash, using room temperature setting iron phosphate ceramics, and includes fabrication procedures for these waste forms as well as results of the MCC-1 static leach test, XRD analysis, scanning electron microscopy studies and density measurements of the solidified waste form produced
Recommendations for accurate genotyping of SARS-CoV-2 using amplicon-based sequencing of clinical samples.
Genotyping of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in monitoring viral evolution and transmission during the pandemic. The quality of the sequence data obtained from these genotyping efforts depends on several factors, including the quantity/integrity of the input material, the technology, and laboratory-specific implementation. The current lack of guidelines for SARS-CoV-2 genotyping leads to inclusion of error-containing genome sequences in genomic epidemiology studies. We aimed to establish clear and broadly applicable recommendations for reliable virus genotyping.
We established and used a sequencing data analysis workflow that reliably identifies and removes technical artefacts; such artefacts can result in miscalls when using alternative pipelines to process clinical samples and synthetic viral genomes with an amplicon-based genotyping approach. We evaluated the impact of experimental factors, including viral load and sequencing depth, on correct sequence determination.
We found that at least 1000 viral genomes are necessary to confidently detect variants in the SARS-CoV-2 genome at frequencies of ≥10%. The broad applicability of our recommendations was validated in over 200 clinical samples from six independent laboratories. The genotypes we determined for clinical isolates with sufficient quality cluster by sampling location and period. Our analysis also supports the rise in frequencies of 20A.EU1 and 20A.EU2, two recently reported European strains whose dissemination was facilitated by travel during the summer of 2020.
We present much-needed recommendations for the reliable determination of SARS-CoV-2 genome sequences and demonstrate their broad applicability in a large cohort of clinical samples
Modeling double strand break susceptibility to interrogate structural variation in cancer
Abstract Background Structural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. Many SVs are thought to emerge from errors in the repair processes following DNA double strand breaks (DSBs). Results We used experimentally quantified DSB frequencies in cell lines with matched chromatin and sequence features to derive the first quantitative genome-wide models of DSB susceptibility. These models are accurate and provide novel insights into the mutational mechanisms generating DSBs. Models trained in one cell type can be successfully applied to others, but a substantial proportion of DSBs appear to reflect cell type-specific processes. Using model predictions as a proxy for susceptibility to DSBs in tumors, many SV-enriched regions appear to be poorly explained by selectively neutral mutational bias alone. A substantial number of these regions show unexpectedly high SV breakpoint frequencies given their predicted susceptibility to mutation and are therefore credible targets of positive selection in tumors. These putatively positively selected SV hotspots are enriched for genes previously shown to be oncogenic. In contrast, several hundred regions across the genome show unexpectedly low levels of SVs, given their relatively high susceptibility to mutation. These novel coldspot regions appear to be subject to purifying selection in tumors and are enriched for active promoters and enhancers. Conclusions We conclude that models of DSB susceptibility offer a rigorous approach to the inference of SVs putatively subject to selection in tumors
State of the art of immunoassay methods for B-type natriuretic peptides: An update
The aim of this review article is to give an update on the state of the art of the immunoassay
methods for the measurement of B-type natriuretic peptide (BNP) and its related peptides.
Using chromatographic procedures, several studies reported an increasing number of
circulating peptides related to BNP in human plasma of patients with heart failure. These
peptides may have reduced or even no biological activity. Furthermore, other studies have
suggested that, using immunoassays that are considered specific for BNP, the precursor of the
peptide hormone, proBNP, constitutes a major portion of the peptide measured in plasma of
patients with heart failure. Because BNP immunoassay methods show large (up to 50%)
systematic differences in values, the use of identical decision values for all immunoassay
methods, as suggested by the most recent international guidelines, seems unreasonable. Since
proBNP significantly cross-reacts with all commercial immunoassay methods considered
specific for BNP, manufacturers should test and clearly declare the degree of cross-reactivity of
glycosylated and non-glycosylated proBNP in their BNP immunoassay methods. Clinicians
should take into account that there are large systematic differences between methods when
they compare results from different laboratories that use different BNP immunoassays. On the
other hand, clinical laboratories should take part in external quality assessment (EQA) programs
to evaluate the bias of their method in comparison to other BNP methods. Finally, the authors
believe that the development of more specific methods for the active peptide, BNP1–32, should
reduce the systematic differences between methods and result in better harmonization of
results
The ice-free topography of Svalbard
We present a first version of the Svalbard ice-free topography (SVIFT1.0) using a mass-conserving approach for mapping glacier ice thickness. SVIFT1.0 is informed by more than 900’000 point-measurements of glacier thickness, totalling almost 8’300 km of thickness profiles. It is publicly available for download. Our estimate for the total ice volume is 6’253km3, equivalent to 1.6cm sea-level rise. The thickness map suggests that 13% of the glacierised area is grounded below sea-level. Thickness values are provided together with a map of error estimates that comprise uncertainties in the thickness surveys as well as in other input variables. Aggregated error estimates are used to define a likely ice-volume range of 5’200-7’400km3. The ice-front thickness of marine-terminating glaciers is a key quantity for ice-loss attribution because it controls the potential ice discharge by iceberg calving into the ocean. We find a mean ice-front thickness of 133m for the archipelago
Neuronal enhancers are hotspots for DNA single-strand break repair
Defects in DNA repair frequently lead to neurodevelopmental and neurodegenerative diseases, underscoring the particular importance of DNA repair in long-lived post-mitotic neurons1,2. The cellular genome is subjected to a constant barrage of endogenous DNA damage, but surprisingly little is known about the identity of the lesion(s) that accumulate in neurons and whether they accrue throughout the genome or at specific loci. Here we show that post-mitotic neurons accumulate unexpectedly high levels of DNA single-strand breaks (SSBs) at specific sites within the genome. Genome-wide mapping reveals that SSBs are located within enhancers at or near CpG dinucleotides and sites of DNA demethylation. These SSBs are repaired by PARP1 and XRCC1-dependent mechanisms. Notably, deficiencies in XRCC1-dependent short-patch repair increase DNA repair synthesis at neuronal enhancers, whereas defects in long-patch repair reduce synthesis. The high levels of SSB repair in neuronal enhancers are therefore likely to be sustained by both short-patch and long-patch processes. These data provide the first evidence of site- and cell-type-specific SSB repair, revealing unexpected levels of localized and continuous DNA breakage in neurons. In addition, they suggest an explanation for the neurodegenerative phenotypes that occur in patients with defective SSB repair
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