Stainless steels are contaminated with a wide range of radionuclides over time when exposed to the harsh acidic environments in nuclear reprocessing facilities. Existing research into the ...contamination of stainless steel with problematic radionuclides has predominantly focused on single-contaminant systems. Hence a more comprehensive understanding is a necessity for the development and optimisation of decontamination and decommissioning strategies, thus minimising waste volumes and associated costs. This work aims to understand contaminant uptake behaviour on AISI 304 stainless steel in a mixed element system (Cs, Sr) over extended time periods (up to 420 days) and the effects of temperature and surface finish on contaminant uptake over shorter time periods (up to 28 days). Steel coupons were immersed in 12 M HNO3 to accelerate corrosion with both caesium and strontium ions (1 mM) and maintained at 50 °C. The extent of uptake was assessed through solution analysis using ICP-OES, identifying that strontium uptake exceeded caesium's in all tested scenarios, with maximum uptake values of 0.208 g m−2 and 0.170 g m−2 obtained at 50 °C for strontium and caesium, respectively. Kinetic modelling confirmed that uptake followed pseudo-second order behaviour. Stainless steel coupons were characterised after exposure, which found grain dropping and bulk dissolution had occurred after 420 days, leading to reduced levels of surface uptake. X-ray Photoelectron Spectroscopy found evidence of caesium and strontium chromates formed via co-precipitation with chromium corrosion products, confirming observations by previous studies. Furthermore, depth profiling with LA-ICP-MS found evidence of contaminants diffusing into the bulk substrate (by 30 - 40 nm), which has significant implications for the development and optimisation of decontamination approaches which can minimise excess waste generation.
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AISI Type 304 stainless steel coupons have been exposed to a simulant aqueous environment representative of the Magnox Reprocessing Plant (MRP) at Sellafield, UK. The experiments were performed for ...extended time periods (up to 420 days) at elevated temperatures to develop a comprehensive understanding of the extent, nature, and depth of contamination for pipework and vessels in Magnox spent nuclear fuel reprocessing environments. This will inform upcoming decommissioning work which represents a major post-operational challenge. Previous relevant literature has focused on developing fundamental understanding of contamination mechanisms of stainless steels in simplistic, single-element systems, which lack elements of industrial relevance. Contamination behavior is expected to be drastically different in these more complex environments. A characterization portfolio has been developed to enable detailed assessment of corrosion and contamination behavior in acidic reprocessing environments. Solution, surface, and depth analysis determined that uptake was dominated by the elements present in highest concentrations within the environment, namely, Mg, Nd, and Cs. Most contaminants were incorporated into a relatively thin surface oxide layer (<100 nm) in metal oxide form, although there were some exceptions (Cs and Sr). Grain boundary etching was present despite very low corrosion rates (3 μm year
). As a result of this lack of corrosion, diffusion of contaminants beyond the immediate surface (10-20 nm) did not occur, evidenced through depth profiling. As a result of these findings, surface-based decontamination techniques minimizing excess secondary waste generation can be further developed in order to reduce the environmental and economic burden associated with decommissioning activities.
Metallic plant infrastructure (e.g. pipework, vessels and structural materials) is often subjected to extreme environments within nuclear facilities such as acidic spent fuel reprocessing and fuel ...storage ponds. Exposed surfaces can become contaminated with a wide range of radioactive contaminants, including high yield fission products and actinides. Identification of the mechanisms by which radionuclides interact with metallic surfaces, such as stainless steel, is a crucial factor during decontamination strategy development. Once contamination mechanisms are fully understood, careful selection of tailored decontamination approaches will lead to both primary and secondary waste volume reduction, subsequently reducing the economic and environmental burdens associated with disposal, allowing for recycling or re-use of the material. This review of the literature provides a summary of work accumulated in the field of radionuclide contamination of stainless steel surfaces. Trends with respect to contamination mechanisms, as well as the factors contributing to contamination such as surface chemistry and corrosion, are presented. The outstanding research needs to further develop our understanding of contamination mechanisms have been identified, including the advanced materials characterisation techniques likely to play a significant role in contaminant identification.
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•Understanding how metal surfaces are contaminated is essential to decommissioning.•Contamination influenced significantly by solution and material properties.•Mechanisms include electrostatic interactions, co-precipitation and bulk diffusion.•Tailored decontamination approaches can subsequently be developed.
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•Weak-base polyamine resins have demonstrated very large iodide uptake capacities.•Dubinin–Radushkevich isotherm-fitting confirms an anion-exchange mechanism is ...prevalent.•Breakthrough behaviour is well-described by the Dose-Response model.•Co-existing anions molybdate and nitrate suppressed uptake, but not completely.•Addition of diiodine increased uptake, seemingly due to charge-transfer complex formation with the resin matrix.
Two weak base anion exchange resins, Lewatit A365 and Purolite MTS9850, have been tested for the removal of aqueous iodide from conditions simulating nuclear waste reprocessing streams. pH variation and relevant co-contaminant addition (nitrate, molybdate and iodine) allowed for assessment of iodide extraction behaviour of each resin. Isotherm experiments were performed and maximum uptake capacities obtained exceed current industrial adsorbents, such as silver-impregnated zeolites. Maximum loading capacities, determined by Dubinin–Radushkevich isotherm, were 761±14mg g−1 for MTS9850 and 589±15mg g−1 for A365. Uptake for both resins was significantly suppressed by nitrate and molybdate ions. The presence of dissolved iodine in the raffinate however, was found to increase iodide uptake. This was explained by characterisation of the spent resin surface by infrared and Raman spectroscopy, which determined the presence of triiodide, indicating charge-transfer complex formation on the surface. Dynamic studies assessed the effect of co-contaminants on iodide uptake in a column environment. Data was fitted to three dynamic models, with the Dose-Response model providing the best description of breakthrough. In all cases iodide breakthrough was accelerated, indicating suppression of uptake, but capacity was still significant.
The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral ...species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease.
COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).
Truncations of Titin Causing Dilated Cardiomyopathy Herman, Daniel S; Lam, Lien; Taylor, Matthew R.G ...
New England journal of medicine/The New England journal of medicine,
02/2012, Volume:
366, Issue:
7
Journal Article
Peer reviewed
Open access
Titin, an important protein in the sarcomere, is the largest human protein. This study identified mutations in the titin gene that result in a truncated protein as important causes of dilated ...cardiomyopathy.
Gene mutation is an important cause of cardiomyopathy. Mutations in eight sarcomere-protein genes cause hypertrophic cardiomyopathy, detected in 40 to 70% of patients.
1
,
2
Variations in more than 40 genes, most of which encode components of the sarcomere, the cytoskeleton, or the nuclear lamina, have been shown or posited to cause dilated cardiomyopathy.
3
,
4
Clinical evaluation identifies 30 to 50% of patients with dilated cardiomyopathy as having a relative who is affected or likely to be affected,
5
–
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implicating a genetic cause. However, pathogenic mutations have been found in only 20 to 30% of patients.
8
TTN,
the gene encoding titin, . . .
After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid-2021, it remains a significant threat ...globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2:
, a species closely related to SARS-CoV-2 that emerged in 2002, and
, which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease.
The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.
Summary Background Patients with metastatic castration-resistant prostate cancer have few treatment options. We investigated the safety and efficacy of lenalidomide, an immunomodulatory agent with ...anti-angiogenic properties, in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. Methods In this randomised, double-blind, placebo-controlled, phase 3 study, we randomly assigned chemotherapy-naive patients with progressive metastatic castration-resistant prostate cancer in a 1:1 ratio to receive docetaxel (75 mg/m2 ) on day 1 and prednisone (5 mg twice daily) on days 1–21 and either lenalidomide (25 mg) or placebo once daily on days 1–14 of each 21 day treatment cycle. Permuted block randomisation was done with an interactive voice response system and stratified by Eastern Cooperative Oncology Group performance status, geographic region, and type of disease progression. Clinicians, patients, and investigators were masked to treatment allocation. The primary endpoint was overall survival. Efficacy analysis was by intention to treat. Patients who received at least one dose of study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov , number NCT00988208. Findings 1059 patients were enrolled and randomly assigned between Nov 11, 2009, and Nov 23, 2011 (533 to the lenalidomide group and 526 to the control group), and 1046 patients received study treatment (525 in the lenalidomide group and 521 in the placebo group). At data cutoff (Jan 13, 2012) after a median follow-up of 8 months (IQR 5–12), 221 patients had died: 129 in the lenalidomide group and 92 in the placebo group. Median overall survival was 17·7 months (95% CI 14·8–18·8) in the lenalidomide group and not reached in the placebo group (hazard ratio HR 1·53, 95% CI 1·17–2·00, p=0·0017). The trial was subsequently closed early due to futility. The number of deaths that occurred during treatment or less than 28 days since the last dose were similar in both groups (18 3% of 525 patients in the lenalidomide group vs 13 2% of 521 patients). 109 (21%) patients in the lenalidomide group and 78 (15%) in the placebo group died more than 28 days from last dose, mainly due to disease progression. At least one grade 3 or higher adverse event was reported in 381 (73%) of 525 patients receiving lenalidomide and 303 (58%) of 521 patients receiving placebo. Grade 3–4 neutropenia (114 22% for lenalidomide vs 85 16% for placebo), febrile neutropenia (62 12% vs 23 4%), diarrhoea (37 7% vs 12 2%), pneumonia (24 5% vs five 1%), dyspnoea (22 4% vs nine 2%), asthenia (27 5% vs 17 3%), and pulmonary embolism (32 6% vs seven 1%) occurred more frequently in the lenalidomide group than in the placebo group. Interpretation Overall survival with the combination of lenalidomide, docetaxel, and prednisone was significantly worse than with docetaxel and prednisone for chemotherapy-naive men with metastatic, castration-resistant prostate cancer. Further research with this treatment combination is not warranted. Funding Celgene Corporation.
Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase ...A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5, and a designed variant with escape mutations, PMS20. Adjuvant studies demonstrate variant neutralization titers are highest with 3M-052-aqueous formulation (AF). Immunization twice with RBD-scNPs protect NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protect mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect animals from multiple different SARS-related viruses. Such a vaccine could provide broad immunity to SARS-CoV-2 variants.
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•ExoMol provides comprehensive spectroscopic data for key molecules.•The ExoMol data structure is defined.•A summary of present and future contents of the database is given.
The ...ExoMol database (www.exomol.com) provides extensive line lists of molecular transitions which are valid over extended temperature ranges. The status of the current release of the database is reviewed and a new data structure is specified. This structure augments the provision of energy levels (and hence transition frequencies) and Einstein A coefficients with other key properties, including lifetimes of individual states, temperature-dependent cooling functions, Landé g-factors, partition functions, cross sections, k-coefficients and transition dipoles with phase relations. Particular attention is paid to the treatment of pressure broadening parameters. The new data structure includes a definition file which provides the necessary information for utilities accessing ExoMol through its application programming interface (API). Prospects for the inclusion of new species into the database are discussed.
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