The quantity of the long lived (half-life 15.7 million years) radioactive isotope 129I in the pre-nuclear age ocean was approximately 100 kg. Various nuclear related activities, including weapons testing, nuclear fuel reprocessing, Chernobyl and other authorized or non-authorized dumping of radioactive waste have increased the ocean inventory of 129I by more than one order of magnitude. The most important of these sources are the direct marine discharges from the commercial reprocessing facilities at La Hague (France) and Sellafield (UK) which have discharged approximately 1640 kg in the English Channel, and approximately 720 kg in the Irish Sea, respectively. We discuss how this 129I can be used as both a 'pathway' and 'transit time' tracer in the North Atlantic and Arctic oceans, as well as a parameter for distinguishing between reprocessed and non-reprocessed nuclear waste in the ocean, and as a proxy for the transport and dilution of other soluble pollutants input to the North Sea.
BACKGROUND: The Two-Pool Glucose (TPG) model has an important role to play in diabetes research since it enables analysis of data obtained from the frequently sampled labeled (hot) glucose tolerance test (FSHGT). TPG modeling allows determination of the separate effects of insulin on the disposal of glucose and on the hepatic production of glucose. It therefore provides a basis for the accurate estimation of glucose effectiveness, insulin sensitivity, and the profile of the rate of endogenous glucose production. Until now, there has been no program available dedicated to the TPG model, and a number of technical reasons have deterred researchers from performing TPG analysis. METHODS AND RESULTS: In this paper, we describe AKA-TPG, a new program that combines automatic kinetic analysis of the TPG model data with database technologies. AKA-TPG enables researchers who have no expertise in modeling to quickly fit the TPG model to individual FSHGT data sets consisting of plasma concentrations of unlabeled glucose, labeled glucose, and insulin. Most importantly, because the entire process is automated, parameters are almost always identified, and parameter estimates are accurate and reproducible. AKA-TPG enables the demographic data of hundreds of individual subjects, their individual unlabeled and labeled glucose and insulin data, and each subject's parameters and indices derived from AKA-TPG to be securely stored in, and retrieved from, a database. We describe how the stratification and population analysis tools in AKA-TPG are used and present population estimates of TPG model parameters for young, healthy (without diabetes) Nordic men. CONCLUSION: Researchers now have a practical tool to enable kinetic and epidemiological analysis of TPG data sets.
Protein kinase ASK1 (Apoptosis signal-regulating kinase 1) plays a key role in cell differentiation, aging and apoptosis. High activity of the kinase is associated with several pathologies. The ASK1 inhibitors might be therapeutic for patients with neurodegenerative, cardiovascular diseases and fibrous histiocytoma. In this work the identification of ASK1 inhibitors was performed by the methods of computer modeling and biochemical testing in vitro. The virtual screening experiments were carried out targeting the ATP binding site of ASK1 by browsing the database which contained 164 840 compounds of diverse chemical classes. The best-scored 300 ligands have been taken for the kinase assay analysis. In vitro tests revealed that derivatives of 2-thioxo-thiazolidin-4-one exhibited inhibitory activity against ASK1. The most active compound was 5-bromo-3-(4-oxo-2-thioxo-thiazolidin-5-ylidene)-1,3-dihydro-indol-2-one (IC50 = 2 microM). Binding mode for inhibitors of this class with ASK1 ATP-binding site was proposed. Our results can be used for further optimization and developing more potent and selective inhibitors of ASK1.
Quantitative soil ingestion studies employing a mass balance tracer approach have been used to provide a defensible means to estimate soil ingestion for human health risk assessments. Past studies have focused on soil ingestion in populations living in urban/suburban environments. There is a paucity of reliable quantitative soil ingestion data to support human health risk assessments of other lifestyles that may be predisposed to ingesting soil, such as agricultural workers or indigenous populations following traditional lifestyles. The results of a preliminary analysis of sampling and analytical variability that would result from assessing activities typical of populations in rural or wilderness areas and conducted over wide areas show that approximately 225 subject days would be required to detect a difference of 20mg/d in soil ingestion. Given the typically small populations in these areas, future soil ingestion studies should be focused on specific activities with a high potential for soil ingestion.