94 research outputs found

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

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    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

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

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    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

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    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

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    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

    Get PDF
    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

    Culturally Relevant Science Teaching in Middle School

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    To respond to calls for more research on culturally relevant science teaching, we present findings from one middle school science teacher’s practices in an effort to contribute to this research. We describe how a discussion lab centered on Derrick Bell’s (1992) short story The Space Traders was purposively included in a lesson on scientific bias to engage middle school students in thinking about bias in larger societal contexts and in their own lives. We review literature in the growing field of culturally relevant science teaching as building on Ladson-Billings’s (1995a, 1995b, 2006) conception of culturally relevant pedagogy. We then describe the context and method of our study and present findings drawn from multiple data sources. We close with a discussion aimed at both practicing teachers and teacher educators. </jats:p

    Discussion of “Some Swelling Characteristics of Compacted Clays”

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