Safeguard Application Options for the Laser-Based Item Monitoring System (LBIMS)

Researchers at Oak Ridge National Laboratory (ORNL) are developing a Laser-Based Item Monitoring System (LBIMS) for advanced safeguards at nuclear facilities. LBIMS uses a low-power laser transceiver to monitor the presence and position of items with retroreflective tags. The primary advantages of LBIMS are its scalability to continuously monitor a wide range of items, its ability to operate unattended, its low cost of implementation, and its inherent information security due to its line-of-sight and non-broadcasting operation. The primary proposed safeguard application of LBIMS is described in its name: item monitoring. LBIMS could be implemented in a storage area to continuously monitor containers of nuclear material and the area in which they are stored. The system could be configured to provide off-site notification if any of the containers are moved or removed or if the area is accessed. Individual tags would be used to monitor storage containers, and additional tags could be used to record information regarding secondary storage units and room access. The capability to register small changes in tag position opens up the possibility of several other uses. These include continuously monitoring piping arrangements for design information verification or recording equipment positions for other safeguards systems, such as tracking the opening and closing of autoclaves as part of a cylinder tracking system or opening and closing valves on a sample or product take-off line. Combined with attribute tags, which transmit information from any kind of sensor by modulating the laser signal, LBIMS provides the capability to wirelessly and securely collect safeguards data, even in areas where radio-frequency or other wireless communication methods are not practicable. Four application types are described in this report: static item monitoring, in-process item monitoring with trigger tags, multi-layered integration with trigger tags, and line-of-sight data transfer with attribute tags. Field trials for each of these applications are described

Profile of World Uranium Enrichment Programs - 2007

It is generally agreed that the most difficult step in building a nuclear weapon is acquiring weapons grade fissile material, either plutonium or highly enriched uranium (HEU). Plutonium is produced in a nuclear reactor, while HEU is produced using a uranium enrichment process. Enrichment is also an important step in the civil nuclear fuel cycle, in producing low enriched uranium (LEU) for use in fuel for nuclear reactors. However, the same equipment used to produce LEU for nuclear fuel can also be used to produce HEU for weapons. Safeguards at an enrichment plant are the array of assurances and verification techniques that ensure uranium is only enriched to LEU, no undeclared LEU is produced, and no uranium is enriched to HEU or secretly diverted. There are several techniques for enriching uranium. The two most prevalent are gaseous diffusion, which uses older technology and requires a lot of energy, and gas centrifuge separation, which uses more advanced technology and is more energy efficient. Gaseous diffusion plants (GDPs) provide about 40% of current world enrichment capacity, but are being phased out as newer gas centrifuge enrichment plants (GCEPs) are constructed. Estimates of current and future enrichment capacity are always approximate, due to the constant upgrades, expansions, and shutdowns occurring at enrichment plants, largely determined by economic interests. Currently, the world enrichment capacity is approximately 53 million kg-separative work units (SWU) per year, with 22 million in gaseous diffusion and 31 million in gas centrifuge plants. Another 23 million SWU/year of capacity are under construction or planned for the near future, almost entirely using gas centrifuge separation. Other less-efficient techniques have also been used in the past, including electromagnetic and aerodynamic separations, but these are considered obsolete, at least from a commercial perspective. Laser isotope separation shows promise as a possible enrichment technique of the future, but has yet to be demonstrated commercially. In the early 1980s, six countries developing gas centrifuge technology (United States, United Kingdom, Germany, the Netherlands, Japan, and Australia) along with the International Atomic Energy Agency (IAEA) and the European Atomic Energy Community (EURATOM) began developing effective safeguards techniques for GCEPs. This effort was known as the Hexapartite Safeguards Project (HSP). The HSP had the goal of maximizing safeguards effectiveness while minimizing the cost to the operator and inspectorate, and adopted several recommendations, such as the acceptance of limited-frequency unannounced access (LFUA) inspections in cascade halls, and the use of nondestructive assay (NDA) measurements and tamper-indicating seals. While only the HSP participants initially committed to implementing all the measures of the approach, it has been used as a model for the safeguards applied to GCEPs in additional states. This report provides a snapshot overview of world enrichment capacity in 2007, including profiles of the uranium enrichment programs of individual states. It is based on open-source information, which is dependent on unclassified sources and may therefore not reflect the most recent developments. In addition, it briefly describes some of the safeguards techniques being used at various enrichment plants, including implementation of HSP recommendations

The Role of TSLP in IL-13-Induced Atopic March

Although atopic dermatitis (AD) is the initial step of the “atopic march”, a progression from AD to asthma, the underlying mechanism remains unknown. Selective expression of IL-13 in the skin of mice caused an AD phenotype resembling human AD, and the disorder was associated with enhanced production of thymic stromal lymphopoietin (TSLP) in the AD skin with a systemic Th2 immunity. Here we show that IL-13 transgenic mice with AD had significantly enhanced lung inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR) when sensitized and challenged by allergen. In addition, the level of TSLP was significantly higher in acute AD than in chronic AD. Furthermore, elimination of TSLP signaling significantly diminished the allergic asthma responses, immune cell production of Th2 cytokines (IL-4, IL-13), and serum IgE. These studies indicate that IL-13 induces AD and atopic march via a TSLP dependent mechanism

Metabolic Network Topology Reveals Transcriptional Regulatory Signatures of Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a disorder characterized by both insulin resistance and impaired insulin secretion. Recent transcriptomics studies related to T2DM have revealed changes in expression of a large number of metabolic genes in a variety of tissues. Identification of the molecular mechanisms underlying these transcriptional changes and their impact on the cellular metabolic phenotype is a challenging task due to the complexity of transcriptional regulation and the highly interconnected nature of the metabolic network. In this study we integrate skeletal muscle gene expression datasets with human metabolic network reconstructions to identify key metabolic regulatory features of T2DM. These features include reporter metabolites—metabolites with significant collective transcriptional response in the associated enzyme-coding genes, and transcription factors with significant enrichment of binding sites in the promoter regions of these genes. In addition to metabolites from TCA cycle, oxidative phosphorylation, and lipid metabolism (known to be associated with T2DM), we identified several reporter metabolites representing novel biomarker candidates. For example, the highly connected metabolites NAD+/NADH and ATP/ADP were also identified as reporter metabolites that are potentially contributing to the widespread gene expression changes observed in T2DM. An algorithm based on the analysis of the promoter regions of the genes associated with reporter metabolites revealed a transcription factor regulatory network connecting several parts of metabolism. The identified transcription factors include members of the CREB, NRF1 and PPAR family, among others, and represent regulatory targets for further experimental analysis. Overall, our results provide a holistic picture of key metabolic and regulatory nodes potentially involved in the pathogenesis of T2DM

Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function

Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.1668F is a founder variant among Ashkenazi Jews (allele frequency of -.2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function.Genetics of disease, diagnosis and treatmen

Profile of World Uranium Enrichment Programs-2009

It is generally agreed that the most difficult step in building a nuclear weapon is acquiring fissile material, either plutonium or highly enriched uranium (HEU). Plutonium is produced in a nuclear reactor, whereas HEU is produced using a uranium enrichment process. Enrichment is also an important step in the civil nuclear fuel cycle, in producing low enriched uranium (LEU) for use as fuel for nuclear reactors to generate electricity. However, the same equipment used to produce LEU for nuclear reactor fuel can also be used to produce HEU for weapons. Safeguards at an enrichment plant are the array of assurances and verification techniques that ensure uranium is not diverted or enriched to HEU. There are several techniques for enriching uranium. The two most prevalent are gaseous diffusion, which uses older technology and requires a lot of energy, and gas centrifuge separation, which uses more advanced technology and is more energy efficient. Gaseous diffusion plants (GDPs) provide about 40% of current world enrichment capacity but are being phased out as newer gas centrifuge enrichment plants (GCEPs) are constructed. Estimates of current and future enrichment capacity are always approximate, due to the constant upgrades, expansions, and shutdowns occurring at enrichment plants, largely determined by economic interests. Currently, the world enrichment capacity is approximately 56 million kilogram separative work units (SWU) per year, with 22.5 million in gaseous diffusion and more than 33 million in gas centrifuge plants. Another 34 million SWU/year of capacity is under construction or planned for the near future, almost entirely using gas centrifuge separation. Other less-efficient techniques have also been used in the past, including electromagnetic and aerodynamic separations, but these are considered obsolete, at least from a commercial perspective. Laser isotope separation shows promise as a possible enrichment technique of the future but has yet to be demonstrated commercially. In the early 1980s, six countries developing gas centrifuge technology (United States, United Kingdom, Germany, the Netherlands, Japan, and Australia) along with the International Atomic Energy Agency and the European Atomic Energy Community began developing effective safeguards techniques for GCEPs. This effort was known as the Hexapartite Safeguards Project (HSP). The HSP had the goal of maximizing safeguards effectiveness while minimizing the cost to the operator and inspectorate, and adopted several recommendations, such as the acceptance of limited-frequency unannounced access inspections in cascade halls, and the use of nondestructive assay measurements and tamper-indicating seals. While only the HSP participants initially committed to implementing all the measures of the approach, it has been used as a model for the safeguards applied to GCEPs in additional states. Uranium enrichment capacity has continued to expand on all fronts in the last few years. GCEP capacity is expanding in anticipation of the eventual shutdown of the less-efficient GDPs, the termination of the U.S.-Russia HEU blend-down program slated for 2013, and the possible resurgence of nuclear reactor construction as part of an expected 'Nuclear Renaissance'. Overall, a clear trend in the world profile of uranium enrichment plant operation is the continued movement towards multinational projects driven by commercial and economic interests. Along this vein, the safeguards community is continuing to develop new safeguards techniques and technologies that are not overly burdensome to enrichment plant operators while delivering more effective and efficient results. This report provides a snapshot overview of world enrichment capacity in 2009, including profiles of the uranium enrichment programs of individual states. It is a revision of a 2007 report on the same topic; significant changes in world enrichment programs between the previous and current reports are emphasized. It is based entirely on open-source information, which is dependent on published sources and may therefore not be completely accurate or reflect the most recent developments. Consequently, readers should not assume that information cited here has the endorsement of either ORNL or the U.S. Department of Energy. We are merely reporting what's been reported. In addition, this report briefly describes some of the safeguards techniques being used at various enrichment plants, including implementation of HSP recommendations