Survey of State-of-the-art NDA Methods Applicable to UF6 Cylinders - IAEA Task n 07/TAU-04

In the framework of a project aiming to establish an unattended measurement station at an isotope enrichment facility, IAEA required a study to describe the state of the art of NDA methods applicable to UF6 cylinders. The objective of the present work is to provide a feasibility assessment study of all known NDA techniques applicable to the quantitative verification of all uranium categories involved in an enrichment processing plant. The quantification of the UF6 cylinders covers: - the determination of the enrichment, - the confirmation the UF6 mass ( assumed to have been previously weighted by the plant operator and independently verified by inspectors), - the assay of the UF6 homogeneity. The different hypothesis and practical constraints to be taken into account for the study requirements are [1]: - the cylinders to be considered are either 30B type ( product) or 48Y type ( feed and tail), - the enriched uranium is either from natural origin or reprocessed uranium, - the cylinders must be assayed at various temperatures, - the distance between the cylinder and the detector must be at least 50 cm to allow for safe movements of the cylinders, - the UF6 mass determination would be accurate within 10% for low enriched uranium, 15% for natural uranium and 20% for depleted uranium, - the enrichment determination must be given with a total uncertainty which does not excess: ¿ 4.5% for low enriched uranium product, ¿ 9.5% for natural uranium, ¿ 18% for depleted uranium, - the measurements have to be performed in 5 minutes and in remote mode to minimize the intrusion on normal plant operator. With the objectives and assumptions as described above in mind, this document first gives an overview of the radiation properties of UF6 (chapter A) as well as some practical considerations regarding the 48Y and 30B cylinders (chapter B). The next part reviews the classical NDA methods applicable to UF6 and refers to intense measurement campaigns carried out in the years 70 -80 (chapter C), whereas the chapter D is dedicated to specific studies involving more recent techniques such as analysis of delayed neutrons and delayed photons. The most appropriate techniques will be then investigated in chapter E. The study will be based on our own results of previous measurement campaigns (235U determination with gamma detectors with germanium or LaBr3 detectors) and on MCNP simulations (passive and active neutron methods).JRC.G.8-Nuclear securit

Functional Consequences of Metabolic Zonation in Murine Livers: Insights for an Old Story

Background and Aims: Zone-dependent differences in expression of metabolic enzymes along the portocentral axis of the acinus are a long-known feature of liver metabolism. A prominent example is the preferential localization of the enzyme, glutamine synthetase, in pericentral hepatocytes, where it converts potentially toxic ammonia to the valuable amino acid, glutamine. However, with the exception of a few key regulatory enzymes, a comprehensive and quantitative assessment of zonal differences in the abundance of metabolic enzymes and, much more important, an estimation of the associated functional differences between portal and central hepatocytes is missing thus far. Approach and Results: We addressed this problem by establishing a method for the separation of periportal and pericentral hepatocytes that yields sufficiently pure fractions of both cell populations. Quantitative shotgun proteomics identified hundreds of differentially expressed enzymes in the two cell populations. We used zone-specific proteomics data for scaling of the maximal activities to generate portal and central instantiations of a comprehensive kinetic model of central hepatic metabolism (Hepatokin1). Conclusions: The model simulations revealed significant portal-to-central differences in almost all metabolic pathways involving carbohydrates, fatty acids, amino acids, and detoxification

Correction: Human and Drosophila Cryptochromes Are Light Activated by Flavin Photoreduction in Living Cells

Cryptochromes are a class of flavoprotein blue-light signaling receptors found in plants, animals, and humans that control plant development and the entrainment of circadian rhythms. In plant cryptochromes, light activation is proposed to result from photoreduction of a protein-bound flavin chromophore through intramolecular electron transfer. However, although similar in structure to plant cryptochromes, the light-response mechanism of animal cryptochromes remains entirely unknown. To complicate matters further, there is currently a debate on whether mammalian cryptochromes respond to light at all or are instead activated by non–light-dependent mechanisms. To resolve these questions, we have expressed both human and Drosophila cryptochrome proteins to high levels in living Sf21 insect cells using a baculovirus-derived expression system. Intact cells are irradiated with blue light, and the resulting cryptochrome photoconversion is monitored by fluorescence and electron paramagnetic resonance spectroscopic techniques. We demonstrate that light induces a change in the redox state of flavin bound to the receptor in both human and Drosophila cryptochromes. Photoreduction from oxidized flavin and subsequent accumulation of a semiquinone intermediate signaling state occurs by a conserved mechanism that has been previously identified for plant cryptochromes. These results provide the first evidence of how animal-type cryptochromes are activated by light in living cells. Furthermore, human cryptochrome is also shown to undergo this light response. Therefore, human cryptochromes in exposed peripheral and/or visual tissues may have novel light-sensing roles that remain to be elucidated

Impaired Meningeal Lymphatic Vessel Development Worsens Stroke Outcome

The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice. We also show that Vegfr3wt/mut mice develop significantly fewer meningeal LVs than Vegfr3wt/wt mice. Again, meningeal lymphangiogenesis occurs in the alymphatic zone lateral to the sagittal sinus only after PT-induced stroke in Vegfr3wt/wt mice. Interestingly, Vegfr3wt/mut mice develop larger stroke volumes than Vegfr3wt/wt mice after tMCAo, but not after PT. Our results reveal differences between PT and tMCAo models of stroke and underscore the need to consider method of stroke induction when investigating the role of meningeal lymphatics. Taken together, our data indicate that ischemic injury can induce the growth of meningeal LVs and that the absence of these LVs can impact post-stroke outcomes

Gait Characterization in Duchenne Muscular Dystrophy (DMD) Using a Single-Sensor Accelerometer: Classical Machine Learning and Deep Learning Approaches

Differences in gait patterns of children with Duchenne muscular dystrophy (DMD) and typically-developing (TD) peers are visible to the eye, but quantifications of those differences outside of the gait laboratory have been elusive. In this work, we measured vertical, mediolateral, and anteroposterior acceleration using a waist-worn iPhone accelerometer during ambulation across a typical range of velocities. Fifteen TD and fifteen DMD children from 3-16 years of age underwent eight walking/running activities, including five 25 meters walk/run speed-calibration tests at a slow walk to running speeds (SC-L1 to SC-L5), a 6-minute walk test (6MWT), a 100 meters fast-walk/jog/run (100MRW), and a free walk (FW). For clinical anchoring purposes, participants completed a Northstar Ambulatory Assessment (NSAA). We extracted temporospatial gait clinical features (CFs) and applied multiple machine learning (ML) approaches to differentiate between DMD and TD children using extracted temporospatial gait CFs and raw data. Extracted temporospatial gait CFs showed reduced step length and a greater mediolateral component of total power (TP) consistent with shorter strides and Trendelenberg-like gait commonly observed in DMD. ML approaches using temporospatial gait CFs and raw data varied in effectiveness at differentiating between DMD and TD controls at different speeds, with an accuracy of up to 100%. We demonstrate that by using ML with accelerometer data from a consumer-grade smartphone, we can capture DMD-associated gait characteristics in toddlers to teens

Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity

The cell's endogenous antioxidant system is vital to maintenance of redox homeostasis. Despite its central role in normal and pathophysiology, no non-invasive tools exist to measure this system in patients. The cystine/glutamate antiporter system xc- maintains the balance between intracellular reactive oxygen species and antioxidant production through the provision of cystine, a key precursor in glutathione biosynthesis. Here we show that tumor cell retention of a system xc--specific positron emission tomography radiotracer, (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG), decreases in proportion to levels of oxidative stress following treatment with a range of redox-active compounds. The decrease in [18F]FSPG retention correlated with a depletion of intracellular cystine resulting from increased de novo glutathione biosynthesis, shown through [U-13C6, U-15N2]cystine isotopic tracing. In vivo, treatment with the chemotherapeutic doxorubicin decreased [18F]FSPG tumor uptake in a mouse model of ovarian cancer, coinciding with markers of oxidative stress but preceding tumor shrinkage and decreased glucose utilization. Having already been used in pilot clinical trials, [18F]FSPG PET could be rapidly translated to the clinic as an early redox indicator of tumor response to treatment

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

The Electron Capture in 163^{163} Ho Experiment - a Short Update

The definition of the absolute neutrino mass scale is one of the main goals of the Particle Physics today. The study of the end-point regions of the β- and electron capture (EC) spectrum offers a possibility to determine the effective electron (anti-)neutrino mass in a completely model independent way, as it only relies on the energy and momentum conservation. The ECHo (Electron Capture in 163Ho) experiment has been designed in the attempt to measure the effective mass of the electron neutrino by performing high statistics and high energy resolution measurements of the 163 Ho electron capture spectrum. To achieve this goal, large arrays of low temperature metallic magnetic calorimeters (MMCs) implanted with with 163Ho are used. Here we report on the structure and the status of the experiment

Strategies for conducting situated studies of technology use in hospitals

Ethnographic methods are widely used for understanding situated practices with technology. When authors present their data gathering methods, they almost invariably focus on the bare essentials. These enable the reader to comprehend what was done, but leave the impression that setting up and conducting the study was straightforward. Text books present generic advice, but rarely focus on specific study contexts. In this paper, we focus on lessons learnt by non-clinical researchers studying technology use in hospitals: gaining access; developing good relations with clinicians and patients; being outsiders in healthcare settings; and managing the cultural divide between technology human factors and clinical practice. Drawing on case studies across various hospital settings, we present a repertoire of ways of working with people and technologies in these settings. These include engaging clinicians and patients effectively, taking an iterative approach to data gathering and being responsive to the demands and opportunities provided by the situation. The main contribution of this paper is to make visible many of the lessons we have learnt in conducting technology studies in healthcare, using these lessons to present strategies that other researchers can take up