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Sample records for cftr depletion results

  1. CFTR depletion results in changes in fatty acid composition and promotes lipogenesis in intestinal Caco 2/15 cells.

    Geneviève Mailhot

    2010-05-01

    .Collectively, our results indicate that CFTR depletion may disrupt FA homeostasis in intestinal cells through alterations in FA uptake and transport combined with stimulation of lipogenesis that occurs by an LXR/RXR-independent mechanism. These findings exclude a contributing role of CFTR in CF-associated fat malabsorption.

  2. Involvement of the Cdc42 pathway in CFTR post-translational turnover and in its plasma membrane stability in airway epithelial cells.

    Romain Ferru-Clément

    Full Text Available Cystic fibrosis transmembrane conductance regulator (CFTR is a chloride channel that is expressed on the apical plasma membrane (PM of epithelial cells. The most common deleterious allele encodes a trafficking-defective mutant protein undergoing endoplasmic reticulum-associated degradation (ERAD and presenting lower PM stability. In this study, we investigated the involvement of the Cdc42 pathway in CFTR turnover and trafficking in a human bronchiolar epithelial cell line (CFBE41o- expressing wild-type CFTR. Cdc42 is a small GTPase of the Rho family that fulfils numerous cell functions, one of which is endocytosis and recycling process via actin cytoskeleton remodelling. When we treated cells with chemical inhibitors such as ML141 against Cdc42 and wiskostatin against the downstream effector N-WASP, we observed that CFTR channel activity was inhibited, in correlation with a decrease in CFTR amount at the cell surface and an increase in dynamin-dependent CFTR endocytosis. Anchoring of CFTR to the cortical cytoskeleton was then presumably impaired by actin disorganization. When we performed siRNA-mediated depletion of Cdc42, actin polymerization was not impacted, but we observed actin-independent consequences upon CFTR. Total and PM CFTR amounts were increased, resulting in greater activation of CFTR. Pulse-chase experiments showed that while CFTR degradation was slowed, CFTR maturation through the Golgi apparatus remained unaffected. In addition, we observed increased stability of CFTR in PM and reduction of its endocytosis. This study highlights the involvement of the Cdc42 pathway at several levels of CFTR biogenesis and trafficking: (i Cdc42 is implicated in the first steps of CFTR biosynthesis and processing; (ii it contributes to the stability of CFTR in PM via its anchoring to cortical actin; (iii it promotes CFTR endocytosis and presumably its sorting toward lysosomal degradation.

  3. Cholesterol modulates CFTR confinement in the plasma membrane of primary epithelial cells.

    Abu-Arish, Asmahan; Pandzic, Elvis; Goepp, Julie; Matthes, Elizabeth; Hanrahan, John W; Wiseman, Paul W

    2015-07-07

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma-membrane anion channel that, when mutated, causes the disease cystic fibrosis. Although CFTR has been detected in a detergent-resistant membrane fraction prepared from airway epithelial cells, suggesting that it may partition into cholesterol-rich membrane microdomains (lipid rafts), its compartmentalization has not been demonstrated in intact cells and the influence of microdomains on CFTR lateral mobility is unknown. We used live-cell imaging, spatial image correlation spectroscopy, and k-space image correlation spectroscopy to examine the aggregation state of CFTR and its dynamics both within and outside microdomains in the plasma membrane of primary human bronchial epithelial cells. These studies were also performed during treatments that augment or deplete membrane cholesterol. We found two populations of CFTR molecules that were distinguishable based on their dynamics at the cell surface. One population showed confinement and had slow dynamics that were highly cholesterol dependent. The other, more abundant population was less confined and diffused more rapidly. Treatments that deplete the membrane of cholesterol caused the confined fraction and average number of CFTR molecules per cluster to decrease. Elevating cholesterol had the opposite effect, increasing channel aggregation and the fraction of channels displaying confinement, consistent with CFTR recruitment into cholesterol-rich microdomains with dimensions below the optical resolution limit. Viral infection caused the nanoscale microdomains to fuse into large platforms and reduced CFTR mobility. To our knowledge, these results provide the first biophysical evidence for multiple CFTR populations and have implications for regulation of their surface expression and channel function. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation.

    De Stefano, Daniela; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; De Gregorio, Fabiola; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; De Rosa, Giuseppe; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

    2014-01-01

    Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in Cftr(F508del) homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.

  5. First functional polymorphism in CFTR promoter that results in decreased transcriptional activity and Sp1/USF binding

    Taulan, M.; Lopez, E.; Guittard, C.; Rene, C.; Baux, D.; Altieri, J.P.; DesGeorges, M.; Claustres, M.; Romey, M.C.

    2007-01-01

    Growing evidences show that functionally relevant polymorphisms in various promoters alter both transcriptional activity and affinities of existing protein-DNA interactions, and thus influence disease progression in humans. We previously reported the -94G>T CFTR promoter variant in a female CF patient in whom any known disease-causing mutation has been detected. To investigate whether the -94G>T could be a regulatory variant, we have proceeded to in silico analyses and functional studies including EMSA and reporter gene assays. Our data indicate that the promoter variant decreases basal CFTR transcriptional activity in different epithelial cells and alters binding affinities of both Sp1 and USF nuclear proteins to the CFTR promoter. The present report provides evidence for the first functional polymorphism that negatively affects the CFTR transcriptional activity and demonstrates a cooperative role of Sp1 and USF transcription factors in transactivation of the CFTR gene promoter

  6. Diminished self-chaperoning activity of the DeltaF508 mutant of CFTR results in protein misfolding.

    Adrian W R Serohijos

    2008-02-01

    Full Text Available The absence of a functional ATP Binding Cassette (ABC protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR from apical membranes of epithelial cells is responsible for cystic fibrosis (CF. Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1. Biochemical and cell biological studies show that the DeltaF508 mutant exhibits inefficient biosynthetic maturation and susceptibility to degradation probably due to misfolding of NBD1 and the resultant misassembly of other domains. However, little is known about the direct effect of the Phe508 deletion on the NBD1 folding, which is essential for rational design strategies of cystic fibrosis treatment. Here we show that the deletion of Phe508 alters the folding dynamics and kinetics of NBD1, thus possibly affecting the assembly of the complete CFTR. Using molecular dynamics simulations, we find that meta-stable intermediate states appearing on wild type and mutant folding pathways are populated differently and that their kinetic accessibilities are distinct. The structural basis of the increased misfolding propensity of the DeltaF508 NBD1 mutant is the perturbation of interactions in residue pairs Q493/P574 and F575/F578 found in loop S7-H6. As a proof-of-principle that the S7-H6 loop conformation can modulate the folding kinetics of NBD1, we virtually design rescue mutations in the identified critical interactions to force the S7-H6 loop into the wild type conformation. Two redesigned NBD1-DeltaF508 variants exhibited significantly higher folding probabilities than the original NBD1-DeltaF508, thereby partially rescuing folding ability of the NBD1-DeltaF508 mutant. We propose that these observed defects in folding kinetics of mutant NBD1 may also be modulated by structures separate from the 508 site. The identified structural determinants of increased misfolding propensity of

  7. Characterization of nasal potential difference in cftr knockout and F508del-CFTR mice.

    Emilie Lyne Saussereau

    Full Text Available BACKGROUND: Treatments designed to correct cystic fibrosis transmembrane conductance regulator (CFTR defects must first be evaluated in preclinical experiments in the mouse model of cystic fibrosis (CF. Mice nasal mucosa mimics the bioelectric defect seen in humans. The use of nasal potential difference (V(TE to assess ionic transport is a powerful test evaluating the restoration of CFTR function. Nasal V(TE in CF mice must be well characterized for correct interpretation. METHODS: We performed V(TE measurements in large-scale studies of two mouse models of CF--B6;129 cftr knockout and FVB F508del-CFTR--and their respective wild-type (WT littermates. We assessed the repeatability of the test for cftr knockout mice and defined cutoff points distinguishing between WT and F508del-CFTR mice. RESULTS: We determined the typical V(TE values for CF and WT mice and demonstrated the existence of residual CFTR activity in F508del-CFTR mice. We characterized intra-animal variability in B6;129 mice and defined the cutoff points for F508del-CFTR chloride secretion rescue. Hyperpolarization of more than -2.15 mV after perfusion with a low-concentration Cl(- solution was considered to indicate a normal response. CONCLUSIONS: These data will make it possible to interpret changes in nasal V(TE in mouse models of CF, in future preclinical studies.

  8. The CFTR-Associated Ligand Arrests the Trafficking of the Mutant ΔF508 CFTR Channel in the ER Contributing to Cystic Fibrosis

    Emily Bergbower

    2018-01-01

    Full Text Available Background/Aims: The CFTR-Associated Ligand (CAL, a PDZ domain containing protein with two coiled-coil domains, reduces cell surface WT CFTR through degradation in the lysosome by a well-characterized mechanism. However, CAL’s regulatory effect on ΔF508 CFTR has remained almost entirely uninvestigated. Methods: In this study, we describe a previously unknown pathway for CAL by which it regulates the membrane expression of ΔF508 CFTR through arrest of ΔF508 CFTR trafficking in the endoplasmic reticulum (ER using a combination of cell biology, biochemistry and electrophysiology. Results: We demonstrate that CAL is an ER localized protein that binds to ΔF508 CFTR and is degraded in the 26S proteasome. When CAL is inhibited, ΔF508 CFTR retention in the ER decreases and cell surface expression of mature functional ΔF508 CFTR is observed alongside of enhanced expression of plasma membrane scaffolding protein NHERF1. Chaperone proteins regulate this novel process, and ΔF508 CFTR binding to HSP40, HSP90, HSP70, VCP, and Aha1 changes to improve ΔF508 CFTR cell surface trafficking. Conclusion: Our results reveal a pathway in which CAL regulates the cell surface availability and intracellular retention of ΔF508 CFTR.

  9. Leukocyte depletion results in improved lung function and reduced inflammatory response after cardiac surgery

    Gu, YJ; Boonstra, PW; vanOeveren, W

    Leukocyte depletion during cardiopulmonary bypass has been demonstrated in animal experiments to improve pulmonary function, Conflicting results have been reported, however, with clinical depletion by arterial line filter of leukocytes at the beginning of cardiopulmonary bypass. In this study, we

  10. Osteoblast CFTR inactivation reduces differentiation and osteoprotegerin expression in a mouse model of cystic fibrosis-related bone disease.

    Michael S Stalvey

    signaling was defective in Cftr-/- murine calvarial osteoblasts. These results support that genetic inactivation of CFTR in osteoblasts contributes to low bone mass and that targeting osteoblasts may represent an effective strategy to treat CFBD.

  11. Stimulation of Intestinal Cl- Secretion Through CFTR by Caffeine Intake in Salt-Sensitive Hypertensive Rats

    Xiao Wei

    2018-03-01

    Full Text Available Background/Aims: High salt consumption is a major risk factor for hypertension, and sodium homeostasis is regulated by both intestinal sodium absorption and urinary sodium excretion. Chronic caffeine intake has been reported to attenuate salt-sensitive hypertension by promoting urinary sodium excretion; however, its exact role in intestinal sodium absorption remains unknown. Here, we investigated whether and how chronic caffeine consumption antagonizes salt-sensitive hypertension by inhibiting intestinal sodium absorption. Methods: Dahl salt-sensitive rats were fed 8% NaCl chow and 0.1% caffeine in their drinking water for 15 days. The blood pressure and fecal sodium content were measured. The effect of caffeine on the movement of Cl- in enterocyte cells was determined with the Ussing chamber assay. Results: Rats that were treated with caffeine displayed significantly lower mean blood pressure and higher fecal sodium content than the controls. Consistent with these findings, caffeine intake decreased fluid absorption by the intestine in the fluid perfusion experiment. Further, the results from the Ussing chamber assay indicated that caffeine promoted Cl- secretion through enterocyte apical cystic fibrosis transmembrane conductance regulator (CFTR, and thus inhibited sodium absorption. Moreover, depletion of cAMP or inhibition of CFTR completely abolished the effect of caffeine on Cl- secretion. Conclusion: The results indicate that chronic caffeine consumption reduces sodium absorption by promoting CFTR-mediated Cl- secretion in the intestine, which contributes to the anti-hypertensive effect of caffeine in salt-sensitive rats.

  12. Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

    LaRusch, Jessica; Jung, Jinsei; General, Ignacio J.; Lewis, Michele D.; Park, Hyun Woo; Brand, Randall E.; Gelrud, Andres; Anderson, Michelle A.; Banks, Peter A.; Conwell, Darwin; Lawrence, Christopher; Romagnuolo, Joseph; Baillie, John; Alkaade, Samer; Cote, Gregory

    2014-01-01

    CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev ) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize tha...

  13. Targeting the intracellular environment in cystic fibrosis: restoring autophagy as a novel strategy to circumvent the CFTR defect

    Valeria Rachela Villella

    2013-01-01

    Full Text Available Cystic fibrosis (CF patients harboring the most common deletion mutation of the cystic fibrosis transmembrane conductance regulator (CFTR, F508del, are poor responders to potentiators of CFTR channel activity which can be used to treat a small subset of CF patients who genetically carry plasma membrane-resident CFTR mutants. The misfolded F508del-CFTR protein is unstable in the plasma membrane even if rescued by pharmacological agents that prevent its intracellular retention and degradation. CF is a conformational disease in which defective CFTR induces an impressive derangement of general proteostasis resulting from disabled autophagy. In this review, we discuss how rescuing Beclin 1 (BECN1, a major player of autophagosome formation, either by means of direct gene transfer or indirectly by administration of proteostasis regulators, could stabilize F508del-CFTR at the plasma membrane. We focus on the relationship between the improvement of peripheral proteostasis and CFTR plasma membrane stability in F508del-CFTR homozygous bronchial epithelia or mouse lungs. Moreover, this article reviews recent preclinical evidence indicating that targeting the intracellular environment surrounding the misfolded mutant CFTR instead of protein itself could constitute an attractive therapeutic option to sensitize patients carrying the F508del-CFTR mutation to the beneficial action of CFTR potentiators on lung inflammation.

  14. Targeting the Intracellular Environment in Cystic Fibrosis: Restoring Autophagy as a Novel Strategy to Circumvent the CFTR Defect

    Villella, Valeria Rachela; Esposito, Speranza; Bruscia, Emanuela M.; Maiuri, Maria Chiara; Raia, Valeria; Kroemer, Guido; Maiuri, Luigi

    2013-01-01

    Cystic fibrosis (CF) patients harboring the most common deletion mutation of the CF transmembrane conductance regulator (CFTR), F508del, are poor responders to potentiators of CFTR channel activity which can be used to treat a small subset of CF patients who genetically carry plasma membrane (PM)-resident CFTR mutants. The misfolded F508del-CFTR protein is unstable in the PM even if rescued by pharmacological agents that prevent its intracellular retention and degradation. CF is a conformational disease in which defective CFTR induces an impressive derangement of general proteostasis resulting from disabled autophagy. In this review, we discuss how rescuing Beclin 1 (BECN1), a major player of autophagosome formation, either by means of direct gene transfer or indirectly by administration of proteostasis regulators, could stabilize F508del-CFTR at the PM. We focus on the relationship between the improvement of peripheral proteostasis and CFTR PM stability in F508del-CFTR homozygous bronchial epithelia or mouse lungs. Moreover, this article reviews recent pre-clinical evidence indicating that targeting the intracellular environment surrounding the misfolded mutant CFTR instead of protein itself could constitute an attractive therapeutic option to sensitize patients carrying the F508del-CFTR mutation to the beneficial action of CFTR potentiators on lung inflammation. PMID:23346057

  15. Determination of CFTR densities in erythrocyte plasma membranes using recognition imaging

    Ebner, Andreas; Hinterdorfer, Peter [Institute for Biophysics, University of Linz, A-4040 Linz (Austria); Nikova, Dessy; Lange, Tobias; Bruns, Reimer; Oberleithner, Hans; Schillers, Hermann [Institute of Physiology II, University of Muenster, D-48149 Muenster (Germany); Haeberle, Johannes; Falk, Sabine; Duebbers, Angelika [Department of Pediatrics, University Hospitals of Muenster, D-48149 Muenster (Germany)], E-mail: schille@uni-muenster.de

    2008-09-24

    CFTR (cystic fibrosis transmembrane conductance regulator) is a cAMP-regulated chloride (Cl{sup -}) channel that plays an important role in salt and fluid movement across epithelia. Cystic fibrosis (CF), the most common genetic disease among Caucasians, is caused by mutations in the gene encoding CFTR. The most predominant mutation, F508del, disturbs CFTR protein trafficking, resulting in a reduced number of CFTR in the plasma membrane. Recent studies indicate that CFTR is not only found in epithelia but also in human erythrocytes. Although considerable attempts have been made to quantify CFTR in cells, conclusions on numbers of CFTR molecules localized in the plasma membrane have been drawn indirectly. AFM has the power to provide the needed information, since both sub-molecular spatial resolution and direct protein recognition via antibody-antigen interaction can be observed. We performed a quantification study of the CFTR copies in erythrocyte membranes at the single molecule level, and compared the difference between healthy donors and CF patients. We detected that the number of CFTR molecules is reduced by 70% in erythrocytes of cystic fibrosis patients.

  16. Determination of CFTR densities in erythrocyte plasma membranes using recognition imaging

    Ebner, Andreas; Hinterdorfer, Peter; Nikova, Dessy; Lange, Tobias; Bruns, Reimer; Oberleithner, Hans; Schillers, Hermann; Haeberle, Johannes; Falk, Sabine; Duebbers, Angelika

    2008-01-01

    CFTR (cystic fibrosis transmembrane conductance regulator) is a cAMP-regulated chloride (Cl - ) channel that plays an important role in salt and fluid movement across epithelia. Cystic fibrosis (CF), the most common genetic disease among Caucasians, is caused by mutations in the gene encoding CFTR. The most predominant mutation, F508del, disturbs CFTR protein trafficking, resulting in a reduced number of CFTR in the plasma membrane. Recent studies indicate that CFTR is not only found in epithelia but also in human erythrocytes. Although considerable attempts have been made to quantify CFTR in cells, conclusions on numbers of CFTR molecules localized in the plasma membrane have been drawn indirectly. AFM has the power to provide the needed information, since both sub-molecular spatial resolution and direct protein recognition via antibody-antigen interaction can be observed. We performed a quantification study of the CFTR copies in erythrocyte membranes at the single molecule level, and compared the difference between healthy donors and CF patients. We detected that the number of CFTR molecules is reduced by 70% in erythrocytes of cystic fibrosis patients

  17. Investigating CFTR and KCa3.1 Protein/Protein Interactions.

    Hélène Klein

    Full Text Available In epithelia, Cl- channels play a prominent role in fluid and electrolyte transport. Of particular importance is the cAMP-dependent cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR with mutations of the CFTR encoding gene causing cystic fibrosis. The bulk transepithelial transport of Cl- ions and electrolytes needs however to be coupled to an increase in K+ conductance in order to recycle K+ and maintain an electrical driving force for anion exit across the apical membrane. In several epithelia, this K+ efflux is ensured by K+ channels, including KCa3.1, which is expressed at both the apical and basolateral membranes. We show here for the first time that CFTR and KCa3.1 can physically interact. We first performed a two-hybrid screen to identify which KCa3.1 cytosolic domains might mediate an interaction with CFTR. Our results showed that both the N-terminal fragment M1-M40 of KCa3.1 and part of the KCa3.1 calmodulin binding domain (residues L345-A400 interact with the NBD2 segment (G1237-Y1420 and C- region of CFTR (residues T1387-L1480, respectively. An association of CFTR and F508del-CFTR with KCa3.1 was further confirmed in co-immunoprecipitation experiments demonstrating the formation of immunoprecipitable CFTR/KCa3.1 complexes in CFBE cells. Co-expression of KCa3.1 and CFTR in HEK cells did not impact CFTR expression at the cell surface, and KCa3.1 trafficking appeared independent of CFTR stimulation. Finally, evidence is presented through cross-correlation spectroscopy measurements that KCa3.1 and CFTR colocalize at the plasma membrane and that KCa3.1 channels tend to aggregate consequent to an enhanced interaction with CFTR channels at the plasma membrane following an increase in intracellular Ca2+ concentration. Altogether, these results suggest 1 that the physical interaction KCa3.1/CFTR can occur early during the biogenesis of both proteins and 2 that KCa3.1 and CFTR form a dynamic complex, the formation of which

  18. Biophysical characterisation of calumenin as a charged F508del-CFTR folding modulator.

    Rashmi Tripathi

    Full Text Available The cystic fibrosis transmembrane regulator (CFTR is a cyclic-AMP dependent chloride channel expressed at the apical surface of epithelial cells lining various organs such as the respiratory tract. Defective processing and functioning of this protein caused by mutations in the CFTR gene results in loss of ionic balance, defective mucus clearance, increased proliferation of biofilms and inflammation of human airways observed in cystic fibrosis (CF patients. The process by which CFTR folds and matures under the influence of various chaperones in the secretory pathway remains incompletely understood. Recently, calumenin, a secretory protein, belonging to the CREC family of low affinity calcium binding proteins has been identified as a putative CFTR chaperone whose biophysical properties and functions remain uncharacterized. We compared hydropathy, instability, charge, unfoldability, disorder and aggregation propensity of calumenin and other CREC family members with CFTR associated chaperones and calcium binding proteins, wild-type and mutant CFTR proteins and intrinsically disordered proteins (IDPs. We observed that calumenin, along with other CREC proteins, was significantly more charged and less folded compared to CFTR associated chaperones. Moreover like IDPs, calumenin and other CREC proteins were found to be less hydrophobic and aggregation prone. Phylogenetic analysis revealed a close link between calumenin and other CREC proteins indicating how evolution might have shaped their similar biophysical properties. Experimentally, calumenin was observed to significantly reduce F508del-CFTR aggregation in a manner similar to AavLEA1, a well-characterized IDP. Fluorescence microscopy based imaging analysis also revealed altered trafficking of calumenin in bronchial cells expressing F508del-CFTR, indicating its direct role in the pathophysiology of CF. In conclusion, calumenin is characterized as a charged protein exhibiting close similarity with

  19. Transmembrane helical interactions in the CFTR channel pore.

    Jhuma Das

    2017-06-01

    Full Text Available Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR gene affect CFTR protein biogenesis or its function as a chloride channel, resulting in dysregulation of epithelial fluid transport in the lung, pancreas and other organs in cystic fibrosis (CF. Development of pharmaceutical strategies to treat CF requires understanding of the mechanisms underlying channel function. However, incomplete 3D structural information on the unique ABC ion channel, CFTR, hinders elucidation of its functional mechanism and correction of cystic fibrosis causing mutants. Several CFTR homology models have been developed using bacterial ABC transporters as templates but these have low sequence similarity to CFTR and are not ion channels. Here, we refine an earlier model in an outward (OWF and develop an inward (IWF facing model employing an integrated experimental-molecular dynamics simulation (200 ns approach. Our IWF structure agrees well with a recently solved cryo-EM structure of a CFTR IWF state. We utilize cysteine cross-linking to verify positions and orientations of residues within trans-membrane helices (TMHs of the OWF conformation and to reconstruct a physiologically relevant pore structure. Comparison of pore profiles of the two conformations reveal a radius sufficient to permit passage of hydrated Cl- ions in the OWF but not the IWF model. To identify structural determinants that distinguish the two conformations and possible rearrangements of TMHs within them responsible for channel gating, we perform cross-linking by bifunctional reagents of multiple predicted pairs of cysteines in TMH 6 and 12 and 6 and 9. To determine whether the effects of cross-linking on gating observed are the result of switching of the channel from open to close state, we also treat the same residue pairs with monofunctional reagents in separate experiments. Both types of reagents prevent ion currents indicating that pore blockage is primarily responsible.

  20. CFTR, Mucins, and Mucus Obstruction in Cystic Fibrosis

    Kreda, Silvia M.; Davis, C. William; Rose, Mary Callaghan

    2012-01-01

    Mucus pathology in cystic fibrosis (CF) has been known for as long as the disease has been recognized and is sometimes called mucoviscidosis. The disease is marked by mucus hyperproduction and plugging in many organs, which are usually most fatal in the airways of CF patients, once the problem of meconium ileus at birth is resolved. After the CF gene, CFTR, was cloned and its protein product identified as a cAMP-regulated Cl− channel, causal mechanisms underlying the strong mucus phenotype of the disease became obscure. Here we focus on mucin genes and polymeric mucin glycoproteins, examining their regulation and potential relationships to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR). Detailed examination of CFTR expression in organs and different cell types indicates that changes in CFTR expression do not always correlate with the severity of CF disease or mucus accumulation. Thus, the mucus hyperproduction that typifies CF does not appear to be a direct cause of a defective CFTR but, rather, to be a downstream consequence. In organs like the lung, up-regulation of mucin gene expression by inflammation results from chronic infection; however, in other instances and organs, the inflammation may have a non-infectious origin. The mucus plugging phenotype of the β-subunit of the epithelial Na+ channel (βENaC)-overexpressing mouse is proving to be an archetypal example of this kind of inflammation, with a dehydrated airway surface/concentrated mucus gel apparently providing the inflammatory stimulus. Data indicate that the luminal HCO3 − deficiency recently described for CF epithelia may also provide such a stimulus, perhaps by causing a mal-maturation of mucins as they are released onto luminal surfaces. In any event, the path between CFTR dysfunction and mucus hyperproduction has proven tortuous, and its unraveling continues to offer its own twists and turns, along with fascinating glimpses into biology. PMID:22951447

  1. Predominant constitutive CFTR conductance in small airways

    Lytle Christian

    2005-01-01

    Full Text Available Abstract Background The pathological hallmarks of chronic obstructive pulmonary disease (COPD are inflammation of the small airways (bronchiolitis and destruction of lung parenchyma (emphysema. These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter. Methods We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. Results In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25, but when gluconate replaced luminal Cl-, the bionic Cl- diffusion potentials (-58 ± 3 mV; n = 25 were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl- permeability was at least 5 times greater than Na+ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM+IBMX (100 μM, ATP (100 μM, or adenosine (100 μM, but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM, GlyH-101* (5–50 μM, and CFTRInh-172* (5 μM. RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. Conclusion These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR.

  2. Early results of studies on the levels of depleted uranium excreted by Balkan residents

    Priest, N.D.; Thirlwell, M.

    2002-01-01

    Urine samples collected from residents of Bosnia and Herzegovina and Kosovo were analysed to determine their natural and depleted uranium content using MC-ICP-MS. All may have been exposed to depleted uranium released as a consequence of the deployment of armour-piercing rounds by the US Air Force. A 236 U tracer was employed to determine chemical recovery. Early results suggest that the levels of natural and depleted uranium excretion by the subjects, which ranged in age from 1 to 71 years, ranged from 2.8 - 58.2 ng d -1 and 1.3 - 46.3 ng d -1 , respectively. The results suggest accumulated body burdens of depleted uranium ranging from close to zero to 46 μg. All the body burdens predicted are lower than published values for the uranium content of the body (90μg) and health effects are not predicted. Further studies are underway to check the provenance of the results. (author)

  3. Toxicity of Depleted Uranium Dust Particles: Results of a New Model

    Zucchetti, M.

    2013-01-01

    Depleted uranium (DU) is mostly composed of U-238, a naturally radioactive isotope. Concerning chemical toxicity, uranium, being a heavy metal, is known to have toxic effects on specific organs in the body, the kidneys in particular. Its effects are similar to those of other heavy metals, such as lead and cadmium. Scientific evidence resulting both from in vitro and in vivo analyses shows that current models of the mechanisms of toxicity of uranium dust are not fully satisfactory. They should be refined in order to obtain more effective responses and predictions regarding health effects. In particular, radiotoxicity potential of Depleted Uranium dust originated by military use of this material for ammunition must be re-evaluated taking into account the bystander effect, the dose enhancing effect and other minor phenomena. Uranium dust has both chemical and radiological toxicity: the synergistic aspect of the two effects has to be accounted for, in order to arrive to a complete description of the phenomenon. The combination of the two different toxicities (chemical and radiological) of depleted uranium is attempted here for the first time, approaching the long-term effects of Depleted Uranium, and in particular the carcinogenetic effects. A case study (Balkan war, 1999) is discussed. (Author)

  4. Advancing clinical development pathways for new CFTR modulators in cystic fibrosis.

    Mayer-Hamblett, Nicole; Boyle, Michael; VanDevanter, Donald

    2016-05-01

    Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70,000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Evidence that CFTR is expressed in rat tracheal smooth muscle cells and contributes to bronchodilation

    Mettey Yvette

    2006-08-01

    Full Text Available Abstract Background The airway functions are profoundly affected in many diseases including asthma, chronic obstructive pulmonary disease (COPD and cystic fibrosis (CF. CF the most common lethal autosomal recessive genetic disease is caused by mutations of the CFTR gene, which normally encodes a multifunctional and integral membrane protein, the CF transmembrane conductance regulator (CFTR expressed in airway epithelial cells. Methods To demonstrate that CFTR is also expressed in tracheal smooth muscle cells (TSMC, we used iodide efflux assay to analyse the chloride transports in organ culture of rat TSMC, immunofluorescence study to localize CFTR proteins and isometric contraction measurement on isolated tracheal rings to observe the implication of CFTR in the bronchodilation. Results We characterized three different pathways stimulated by the cAMP agonist forskolin and the isoflavone agent genistein, by the calcium ionophore A23187 and by hypo-osmotic challenge. The pharmacology of the cAMP-dependent iodide efflux was investigated in detail. We demonstrated in rat TSMC that it is remarkably similar to that of the epithelial CFTR, both for activation (using three benzo [c]quinolizinium derivatives and for inhibition (glibenclamide, DPC and CFTRinh-172. Using rat tracheal rings, we observed that the activation of CFTR by benzoquinolizinium derivatives in TSMC leads to CFTRinh-172-sensitive bronchodilation after constriction with carbachol. An immunolocalisation study confirmed expression of CFTR in tracheal myocytes. Conclusion Altogether, these observations revealed that CFTR in the airways of rat is expressed not only in the epithelial cells but also in tracheal smooth muscle cells leading to the hypothesis that this ionic channel could contribute to bronchodilation.

  6. Micelle-induced depletion interaction and resultant structure in charged colloidal nanoparticle system

    Ray, D.; Aswal, V. K., E-mail: vkaswal@barc.gov.in [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Kohlbrecher, J. [Laboratory for Neutron Scattering, Paul Scherrer Institut, CH-5232 PSI Villigen (Switzerland)

    2015-04-28

    The evolution of the interaction and the resultant structure in the mixed system of anionic silica nanoparticles (Ludox LS30) and non-ionic surfactant decaethylene glycol monododecylether (C12E10), undergoing phase separation, have been studied using small-angle neutron scattering and dynamic light scattering. The measurements have been carried out for a fixed concentration of nanoparticle (1 wt. %) with varying concentration of surfactant (0 to 1 wt. %), in the absence and presence of an electrolyte. It is found that the micelles of non-ionic surfactant adsorb on the nanoparticle in the absence of electrolyte (form stable system), whereas these micelles become non-adsorbing in the presence of electrolyte (show phase separation). The phase separation arises because of C12E10 micelles, causing depletion interaction between nanoparticles and leading to their aggregation. The interaction is modeled by double Yukawa potential accounting for attractive depletion as well as repulsive electrostatic forces. Both the interactions (attraction and repulsion) are found to be of long-range. The nanoparticle aggregation (phase separation) is governed by the increase in the magnitude and the range of the depletion attraction with the increase in the surfactant concentration. The nanoparticle aggregates formed are quite large in size (order of micron) and are characterized by the surface fractal having simple cubic packing of nanoparticles within the aggregates.

  7. The hypertonic environment differentially regulates wild-type CFTR and TNR-CFTR chloride channels.

    Lassance-Soares, Roberta M; Cheng, Jie; Krasnov, Kristina; Cebotaru, Liudmila; Cutting, Garry R; Souza-Menezes, Jackson; Morales, Marcelo M; Guggino, William B

    2010-01-01

    This study tested the hypotheses that the hypertonic environment of the renal medulla regulates the expression of cystic fibrosis transmembrane conductance regulator protein (CFTR) and its natural splice variant, TNR-CFTR. To accomplish this, Madin-Darby canine kidney (MDCK) stable cell lines expressing TNR-CFTR or CFTR were used. The cells were treated with hypertonic medium made with either NaCl or urea or sucrose (480 mOsm/kg or 560 mOsm/kg) to mimic the tonicity of the renal medulla environment. Western blot data showed that CFTR and TNR-CFTR total cell protein is increased by hypertonic medium, but using the surface biotinylation technique, only CFTR was found to be increased in cell plasma membrane. Confocal microscopy showed TNR-CFTR localization primarily at the endoplasmic reticulum and plasma membrane. In conclusion, CFTR and TNR-CFTR have different patterns of distribution in MDCK cells and they are modulated by a hypertonic environment, suggesting their physiological importance in renal medulla. Copyright © 2010 S. Karger AG, Basel.

  8. Side chain and backbone contributions of Phe508 to CFTR folding

    Thibodeau, Patrick H.; Brautigam, Chad A.; Machius, Mischa; Thomas, Philip J. (U. of Texas-SMED)

    2010-12-07

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an integral membrane protein, cause cystic fibrosis (CF). The most common CF-causing mutant, deletion of Phe508, fails to properly fold. To elucidate the role Phe508 plays in the folding of CFTR, missense mutations at this position were generated. Only one missense mutation had a pronounced effect on the stability and folding of the isolated domain in vitro. In contrast, many substitutions, including those of charged and bulky residues, disrupted folding of full-length CFTR in cells. Structures of two mutant nucleotide-binding domains (NBDs) reveal only local alterations of the surface near position 508. These results suggest that the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR.

  9. Contamination with radionuclides and depleted uranium as a result of NATO aggression against Yugoslavia

    Veselinovic, D.; Kopecni, M.M.

    2001-01-01

    It appears that the amount of depleted uranium (DU) is approaching 10 6 tons at world level. Depleted uranium is a by-product in uranium enrichment process. As such, and at the same time being low radioactive, DU has legal status of low-level radioactive waste. On the other hand, DU is natural present in nature. This is the reason why many claim that it cannot produce major damage if discharged in the environment and that it can be used for ammunition construction material. To regret, DU due to its remarkable physical and mechanical properties has been widely used for the military purposes only. Nowadays many armies have it as a part of standard ammunition stock. To much less extend, it has been used as a shield for various types of armored vehicles. So far, DU has been extensively used on a large scale at several locations on the globe. The most important ones are the test area in Mohave Desert, USA, Gulf War, Iraq, Bosnia and Herzegovina and most recently NATO aggression on Yugoslavia. As a result of extensive DU use, there are many pro and contras regarding DU harmful effects on the environment and life in general. On the subject expert opinion strongly disagree, while public opinion is very much against its use, in particular for military purpose.From the existing experience on the DU impact on the life and environment it is evident that DU can create harmful effects. So far, humans were of prime importance and most of the observations, results and discussions refer to humans, but also there is a growing concern for the biota in general. This paper summarizes some of the known facts regarding depleted uranium, its use as a material for ammunition manufacturing and possible harmful affects in connection with it. Paper also suggests some of the measures that could be considered to follow and remedy the current DU contamination of Kosovo and Metohija, and some other spots in FR Yugoslavia. (author)

  10. CFTR chloride channel as a molecular target of anthraquinone compounds in herbal laxatives

    Yang, Hong; Xu, Li-na; He, Cheng-yan; Liu, Xin; Fang, Rou-yu; Ma, Tong-hui

    2011-01-01

    Aim: To clarify whether CFTR is a molecular target of intestinal fluid secretion caused by the anthraquinone compounds from laxative herbal plants. Methods: A cell-based fluorescent assay to measure I− influx through CFTR chloride channel. A short-circuit current assay to measure transcellular Cl− current across single layer FRT cells and freshly isolated colon mucosa. A closed loop experiment to measure colon fluid secretion in vivo. Results: Anthraquinone compounds rhein, aloe-emodin and 1,8-dihydroxyanthraquinone (DHAN) stimulated I− influx through CFTR chloride channel in a dose-dependent manner in the presence of physiological concentration of cAMP. In the short-circuit current assay, the three compound enhanced Cl− currents in epithelia formed by CFTR-expressing FRT cells with EC50 values of 73±1.4, 56±1.7, and 50±0.5μmol/L, respectively, and Rhein also enhanced Cl− current in freshly isolated rat colonic mucosa with a similar potency. These effects were completely reversed by the CFTR selective blocker CFTRinh-172. In in vivo closed loop experiments, rhein 2 mmol/L stimulated colonic fluid accumulation that was largely blocked by CFTRinh-172. The anthraquinone compounds did not elevate cAMP level in cultured FRT cells and rat colonic mucosa, suggesting a direct effect on CFTR activity. Conclusion: Natural anthraquinone compounds in vegetable laxative drugs are CFTR potentiators that stimulated colonic chloride and fluid secretion. Thus CFTR chloride channel is a molecular target of vegetable laxative drugs. PMID:21602836

  11. A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

    Chen Xie

    Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

  12. Important role of platelets in modulating endotoxin-induced lung inflammation in CFTR-deficient mice.

    Caiqi Zhao

    Full Text Available Mutation of CFTR (cystic fibrosis transmembrane conductance regulator leads to cystic fibrosis (CF. Patients with CF develop abnormalities of blood platelets and recurrent lung inflammation. However, whether CFTR-mutated platelets play a role in the development of lung inflammation is elusive. Therefore, we intratracheally challenged wildtype and F508del (a common type of CFTR mutation mice with LPS to observe changes of F508del platelets in the peripheral blood and indexes of lung inflammation (BAL neutrophils and protein levels. Furthermore, we investigated whether or not and how F508del platelets modulate the LPS-induced acute lung inflammation by targeting anti-platelet aggregation, depletion of neutrophils, reconstitution of bone marrow or neutrophils, blockade of P-selectin glycoprotein ligand-1 (PSGL-1, platelet activating factor (PAF, and correction of mutated CFTR trafficking. We found that LPS-challenged F508del mice developed severe thrombocytopenia and had higher levels of plasma TXB2 coincided with neutrophilic lung inflammation relative to wildtype control. Inhibition of F508del platelet aggregation or depletion of F508del neutrophils diminished the LPS-induced lung inflammation in the F508del mice. Moreover, wildtype mice reconstituted with either F508del bone marrow or neutrophils developed worse thrombocytopenia. Blocking PSGL-1, platelet activating factor (PAF, or rectifying trafficking of mutated CFTR in F508del mice diminished and alveolar neutrophil transmigration in the LPS-challenged F508del mice. These findings suggest that F508del platelets and their interaction with neutrophils are requisite for the development of LPS-induced lung inflammation and injury. As such, targeting platelets might be an emerging strategy for dampening recurrent lung inflammation in cystic fibrosis patients.

  13. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis.

    LaRusch, Jessica; Jung, Jinsei; General, Ignacio J; Lewis, Michele D; Park, Hyun Woo; Brand, Randall E; Gelrud, Andres; Anderson, Michelle A; Banks, Peter A; Conwell, Darwin; Lawrence, Christopher; Romagnuolo, Joseph; Baillie, John; Alkaade, Samer; Cote, Gregory; Gardner, Timothy B; Amann, Stephen T; Slivka, Adam; Sandhu, Bimaljit; Aloe, Amy; Kienholz, Michelle L; Yadav, Dhiraj; Barmada, M Michael; Bahar, Ivet; Lee, Min Goo; Whitcomb, David C

    2014-07-01

    CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<0.0001). WNK1-SPAK pathway-activated increases in CFTR

  14. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis.

    Jessica LaRusch

    2014-07-01

    Full Text Available CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev cause complete loss of CFTR function and result in cystic fibrosis (CF, a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002. Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005 and male infertility (OR 395, p<<0.0001. WNK1-SPAK pathway-activated increases in

  15. CFTR mediates noradrenaline-induced ATP efflux from DRG neurons.

    Kanno, Takeshi; Nishizaki, Tomoyuki

    2011-09-24

    In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via β(3) adrenoceptors linked to G(s) protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG neurons. In an outside-out patch-clamp configuration from acutely dissociated rat DRG neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS, were evoked by approaching the patch-electrode tip close to a neuron, indicating that ATP is released from DRG neurons, to activate P2X receptor. NA increased the frequency of the single-channel events, but such NA effect was not found for DRG neurons transfected with the siRNA to silence the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the immunocytochemical study using acutely dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite cells, fibroblasts, or Schwann cells. It is concluded from these results that CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel.

  16. Analysis of Y chromosome microdeletions and CFTR gene mutations as genetic markers of infertility in Serbian men

    Dinić Jelena

    2007-01-01

    Full Text Available Background/Aim. Impaired fertility of a male partner is the main cause of infertility in up to one half of all infertile couples. At the genetic level, male infertility can be caused by chromosome aberrations or gene mutations. The presence and types of Y chromosome microdeletions and cystic fybrosis transmembrane conductance regulator (CFTR gene mutations as genetic cause of male infertility was tested in Serbian men. The aim of this study was to analyze CFTR gene mutations and Y chromosome microdelations as potential causes of male infertility in Serbian patients, as well as to test the hypothesis that CFTR mutations in infertile men are predominantly located in the several last exons of the gene. Methods. This study has encompassed 33 men with oligo- or azoospermia. The screening for Y chromosome microdeletions in the azoospermia factor (AZF region was performed by multiplex PCR analysis. The screening of the CFTR gene was performed by denaturing gradient gel electrophoresis (DGGE method. Results. Deletions on Y chromosome were detected in four patients, predominantly in AZFc region (four of total six deletions. Mutations in the CFTR gene were detected on eight out of 66 analyzed chromosomes of infertile men. The most common mutation was F508del (six of total eight mutations. Conclusion. This study confirmed that both Y chromosome microdeletions and CFTR gene mutations played important role in etiology of male infertility in Serbian infertile men. Genetic testing for Y chromosome microdeletions and CFTR gene mutations has been introduced in routine diagnostics and offered to couples undergoing assisted reproduction techniques. Considering that both the type of Y chromosome microdeletion and the type of CFTR mutation have a prognostic value, it is recommended that AZF and CFTR genotyping should not only be performed in patients with reduced sperm quality before undergoing assisted reproduction, but also for the purpose of preimplantation and

  17. Results of the analysis of the intercomparison samples of the depleted uranium dioxide SR-20

    Aigner, H.; Deron, S.; Kuhn, E.; Ronesch, K.; Zoigner, A.

    Samples of a homogeneous powder of depleted uranium dioxide, SR-20, were distributed to 32 laboratories in January 1980 for intercomparison of the precisions and accuracies of wet chemical assay. 11 laboratories reported their results (ANNEX 1). 5 laboratories applied titration procedures, 4 of them applied methods derived from the Davies and Gray procedure (1), 2 laboratories used controlled potential coulometry, 2 laboratories used precipitation procedures, 1 laboratory used fluorimetry and 1 laboratory used activation analysis. An analysis of variance yields for each laboratory the estimates of the measurement errors, the dissolution or treatment errors and the random calibration errors. The measurement errors vary between 0.01% and 1.7% relative. The differences to the reference value vary between -9.1% and +0.92% uranium, but 9 laboratories agree within +-1%U with the reference value. The mean bias of these 9 laboratories is equal to +0.04%U. The standard deviation of the biases of these 9 laboratories is equal to 0.36%.U

  18. Results of the analysis of the intercomparison samples of the depleted uranium dioxide SR-10

    Aigner, H.; Deron, S.; Kuhn, E.; Zoigner, A.

    1981-01-01

    Samples of a homogeneous powder of depleted uranium dioxide, SR-10, were distributed to 27 laboratories in February 1979 for intercomparison of the precisions and accuracies of wet chemical assay. 7 laboratories reported their results. 6 laboratories applied titration procedures, 4 of them applied methods derived from the Davies and Gray procedure (1), and one laboratory used controlled potential coulometry. An analysis of variance yields for each laboratory the estimates of the measurement errors, the dissolution or treatment errors and the random calibration errors. The measurement errors vary between 0.01% and 0.10% relative. The differences to the reference value vary between -0.48% and +0.87% uranium, but 5 laboratories agree within +-0.25% U with the reference value. The biases of 5 laboratories are greater than expected from their random errors. The mean bias of the 7 laboratories is equal to +0.03% U. The standard deviation of the laboratory biases is equal to 0.43% U. (author)

  19. Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles.

    Terlizzi, Vito; Castaldo, Giuseppe; Salvatore, Donatello; Lucarelli, Marco; Raia, Valeria; Angioni, Adriano; Carnovale, Vincenzo; Cirilli, Natalia; Casciaro, Rosaria; Colombo, Carla; Di Lullo, Antonella Miriam; Elce, Ausilia; Iacotucci, Paola; Comegna, Marika; Scorza, Manuela; Lucidi, Vincenzina; Perfetti, Anna; Cimino, Roberta; Quattrucci, Serena; Seia, Manuela; Sofia, Valentina Maria; Zarrilli, Federica; Amato, Felice

    2017-04-01

    The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator ( CFTR ) complex alleles. We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans , or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (pT] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). The effect of complex alleles partially depends on the mutation in trans . Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Methods and results for stress analyses on 14-ton, thin-wall depleted UF6 cylinders

    Kirkpatrick, J.R.; Chung, C.K.; Frazier, J.L.; Kelley, D.K.

    1996-10-01

    Uranium enrichment operations at the three US gaseous diffusion plants produce depleted uranium hexafluoride (DUF 6 ) as a residential product. At the present time, the inventory of DUF 6 in this country is more than half a million tons. The inventory of DUF 6 is contained in metal storage cylinders, most of which are located at the gaseous diffusion plants. The principal objective of the project is to ensure the integrity of the cylinders to prevent causing an environmental hazard by releasing the contents of the cylinders into the atmosphere. Another objective is to maintain the cylinders in such a manner that the DUF 6 may eventually be converted to a less hazardous material for final disposition. An important task in the DUF 6 cylinders management project is determining how much corrosion of the walls can be tolerated before the cylinders are in danger of being damaged during routine handling and shipping operations. Another task is determining how to handle cylinders that have already been damaged in a manner that will minimize the chance that a breach will occur or that the size of an existing breach will be significantly increased. A number of finite element stress analysis (FESA) calculations have been done to analyze the stresses for three conditions: (1) while the cylinder is being lifted, (2) when a cylinder is resting on two cylinders under it in the customary two-tier stacking array, and (3) when a cylinder is resting on tis chocks on the ground. Various documents describe some of the results and discuss some of the methods whereby they have been obtained. The objective of the present report is to document as many of the FESA cases done at Oak Ridge for 14-ton thin-wall cylinders as possible, giving results and a description of the calculations in some detail

  1. Depleted Monolithic Pixels (DMAPS) in a 150 nm technology: lab and beam results

    Obermann, T.; Hemperek, T.; Hügging, F.; Krüger, H.; Pohl, D.-L.; Wermes, N.; Schwenker, B.

    2017-01-01

    The fully depleted monolithic active pixel sensor (DMAPS) is a new concept integrating full CMOS circuitry onto a fully depletable silicon substrate wafer. The realization of prototypes of the DMAPS concept relies on the availability of multiple well CMOS processes and high resistive substrates. The CMOS foundry ESPROS Photonics offers both and was chosen for prototyping. Two prototypes, EPCB01 and EPCB02, were developed in a 150 nm process on a high resistive n-type wafer of 50 μm thickness. The prototypes have 352 square pixels of 40 μm pitch and small n-well charge collection node with very low capacitance (n + -implantation size: 5 μm by 5 μm) and about 150 transistors per pixel (CSA and discriminator plus a small digital part).

  2. Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect.

    Guido Veit

    2016-05-01

    Full Text Available The most common cystic fibrosis (CF causing mutation, deletion of phenylalanine 508 (ΔF508 or Phe508del, results in functional expression defect of the CF transmembrane conductance regulator (CFTR at the apical plasma membrane (PM of secretory epithelia, which is attributed to the degradation of the misfolded channel at the endoplasmic reticulum (ER. Deletion of phenylalanine 670 (ΔF670 in the yeast oligomycin resistance 1 gene (YOR1, an ABC transporter of Saccharomyces cerevisiae phenocopies the ΔF508-CFTR folding and trafficking defects. Genome-wide phenotypic (phenomic analysis of the Yor1-ΔF670 biogenesis identified several modifier genes of mRNA processing and translation, which conferred oligomycin resistance to yeast. Silencing of orthologues of these candidate genes enhanced the ΔF508-CFTR functional expression at the apical PM in human CF bronchial epithelia. Although knockdown of RPL12, a component of the ribosomal stalk, attenuated the translational elongation rate, it increased the folding efficiency as well as the conformational stability of the ΔF508-CFTR, manifesting in 3-fold augmented PM density and function of the mutant. Combination of RPL12 knockdown with the corrector drug, VX-809 (lumacaftor restored the mutant function to ~50% of the wild-type channel in primary CFTRΔF508/ΔF508 human bronchial epithelia. These results and the observation that silencing of other ribosomal stalk proteins partially rescue the loss-of-function phenotype of ΔF508-CFTR suggest that the ribosomal stalk modulates the folding efficiency of the mutant and is a potential therapeutic target for correction of the ΔF508-CFTR folding defect.

  3. Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice.

    Haiya Wu

    Full Text Available CFTR (cystic fibrosis transmembrane conductance regulator is expressed by both neutrophils and platelets. Lack of functional CFTR could lead to severe lung infection and inflammation. Here, we found that mutation of CFTR (F508del or inhibition of CFTR in mice led to more severe thrombocytopenia, alveolar neutrocytosis and bacteriosis, and lower lipoxin A4/MIP-2 (macrophage inhibitory protein-2 or lipoxin A4/neutrophil ratios in the BAL (bronchoalveolar lavage during acute E. coli pneumonia. In vitro, inhibition of CFTR promotes MIP-2 production in LPS-stimulated neutrophils; however, lipoxin A4 could dose-dependently suppress this effect. In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1 or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice. Concurrently, F508del mice had higher plasma platelet activating factor (PAF levels and PAF-AH activity compared to wildtype under LPS challenge. Inhibiting hydrolysis of PAF by a specific PAF-AH (PAF-acetylhydrolase inhibitor, MAFP, could worsen LPS-induced lung inflammation in F508del mice compared to vehicle treated F508del group. Particularly, depletion of platelets in F508del mice could significantly decrease plasma lipoxin A4 and PAF-AH activity and deteriorate LPS-induced lung inflammation compared to control F508del mice. Taken together, lipoxin A4 and PAF are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice, suggesting that lipoxin A4 and PAF might be therapeutic targets for ameliorating CFTR-deficiency deteriorated lung inflammation.

  4. Les vésicules extracellulaires comme vecteurs de macromolécules bioactives : modèle du transporteur ABCC7 (CFTR) et application à la biothérapie de la mucoviscidose

    Vituret , Cyrielle

    2015-01-01

    Cystic fibrosis is a genetic disease in which its prognosis depends on the lung damage. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), resulting in a dysfunctional CFTR protein normally located at the plasma membrane of epithelial cells. This thesis is a study of a novel therapeutic approach to use extracellular vesicles (EVs), microvesicles and exosomes, as transfer vectors for CFTR mRNA and protein to target cells. The proof of concept for ...

  5. Analysis of cystic fibrosis gener product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis.

    Gelrud, Andres; Sheth, Sunil; Banerjee, Subhas; Weed, Deborah; Shea, Julie; Chuttani, Ram; Howell, Douglas A; Telford, Jennifer J; Carr-Locke, David L; Regan, Meredith M; Ellis, Lynda; Durie, Peter R; Freedman, Steven D

    2004-08-01

    The mechanism by which pancreas divisum may lead to recurrent episodes of acute pancreatitis in a subset of individuals is unknown. Abnormalities of the cystic fibrosis gene product (CFTR) have been implicated in the genesis of idiopathic chronic pancreatitis. The aim of this study was to determine if CFTR function is abnormal in patients with pancreas divisum and recurrent acute pancreatitis (PD/RAP). A total of 69 healthy control subjects, 12 patients with PD/RAP, 16 obligate heterozygotes with a single CFTR mutation, and 95 patients with cystic fibrosis were enrolled. CFTR function was analyzed by nasal transepithelial potential difference testing in vivo. The outcomes of the PD/RAP patients following endoscopic and surgical treatments were concomitantly analyzed. Direct measurement of CFTR function in nasal epithelium in response to isoproterenol demonstrated that the values for PD/RAP were intermediate between those observed for healthy controls and cystic fibrosis patients. The median value was 13 mV for PD/RAP subjects, which was statistically different from healthy controls (22 mV, p= 0.001) and cystic fibrosis pancreatic sufficient (-1 mV, p < 0.0001) and pancreatic insufficient (-3 mV, p < 0.0001) patients. These results suggest a link between CFTR dysfunction and recurrent acute pancreatitis in patients with pancreas divisum and may explain why a subset of patients with pancreas divisum develops recurrent acute pancreatitis. Copyright 2004 American College of Gastroenterology

  6. CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants.

    Claustres, Mireille; Thèze, Corinne; des Georges, Marie; Baux, David; Girodon, Emmanuelle; Bienvenu, Thierry; Audrezet, Marie-Pierre; Dugueperoux, Ingrid; Férec, Claude; Lalau, Guy; Pagin, Adrien; Kitzis, Alain; Thoreau, Vincent; Gaston, Véronique; Bieth, Eric; Malinge, Marie-Claire; Reboul, Marie-Pierre; Fergelot, Patricia; Lemonnier, Lydie; Mekki, Chadia; Fanen, Pascale; Bergougnoux, Anne; Sasorith, Souphatta; Raynal, Caroline; Bareil, Corinne

    2017-10-01

    Most of the 2,000 variants identified in the CFTR (cystic fibrosis transmembrane regulator) gene are rare or private. Their interpretation is hampered by the lack of available data and resources, making patient care and genetic counseling challenging. We developed a patient-based database dedicated to the annotations of rare CFTR variants in the context of their cis- and trans-allelic combinations. Based on almost 30 years of experience of CFTR testing, CFTR-France (https://cftr.iurc.montp.inserm.fr/cftr) currently compiles 16,819 variant records from 4,615 individuals with cystic fibrosis (CF) or CFTR-RD (related disorders), fetuses with ultrasound bowel anomalies, newborns awaiting clinical diagnosis, and asymptomatic compound heterozygotes. For each of the 736 different variants reported in the database, patient characteristics and genetic information (other variations in cis or in trans) have been thoroughly checked by a dedicated curator. Combining updated clinical, epidemiological, in silico, or in vitro functional data helps to the interpretation of unclassified and the reassessment of misclassified variants. This comprehensive CFTR database is now an invaluable tool for diagnostic laboratories gathering information on rare variants, especially in the context of genetic counseling, prenatal and preimplantation genetic diagnosis. CFTR-France is thus highly complementary to the international database CFTR2 focused so far on the most common CF-causing alleles. © 2017 Wiley Periodicals, Inc.

  7. Depleted uranium

    Huffer, E.; Nifenecker, H.

    2001-02-01

    This document deals with the physical, chemical and radiological properties of the depleted uranium. What is the depleted uranium? Why do the military use depleted uranium and what are the risk for the health? (A.L.B.)

  8. The U.S. Department of Veterans' Affairs depleted uranium exposed cohort at 25 Years: Longitudinal surveillance results

    McDiarmid, Melissa A.; Gaitens, Joanna M.; Hines, Stella; Condon, Marian; Roth, Tracy; Oliver, Marc; Gucer, Patricia; Brown, Lawrence; Centeno, Jose A.; Dux, Moira; Squibb, Katherine S.

    2017-01-01

    Background: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. Methods: During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. Results: On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations. The DU isotopic signature is observed principally in participants possessing embedded fragments. Those with only an inhalation exposure have lower urine U concentration and a natural isotopic signature. Conclusions: At 25 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As U body burden continues to accrue from in-situ mobilization from metal fragment depots, and increases with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort. - Highlights: • Gulf War I veterans wounded with depleted uranium are monitored for health changes. • In 2015 in-patient clinical surveillance was performed on 36 members of the cohort. • Mobilization of U from embedded fragments is evidenced by elevated U in urine. • This cohort of continues to show no U-related health effects.

  9. The U.S. Department of Veterans' Affairs depleted uranium exposed cohort at 25 Years: Longitudinal surveillance results

    McDiarmid, Melissa A.; Gaitens, Joanna M.; Hines, Stella [Department of Veterans Affairs Medical Center Baltimore, Maryland, 10 N. Greene St., Baltimore, MD 21201 (United States); Department of Medicine, University of Maryland School of Medicine, 655 W Baltimore S, Baltimore, MD 21201 (United States); Condon, Marian, E-mail: mcondon@medicine.umaryland.edu [Department of Veterans Affairs Medical Center Baltimore, Maryland, 10 N. Greene St., Baltimore, MD 21201 (United States); Roth, Tracy; Oliver, Marc; Gucer, Patricia [Department of Veterans Affairs Medical Center Baltimore, Maryland, 10 N. Greene St., Baltimore, MD 21201 (United States); Department of Medicine, University of Maryland School of Medicine, 655 W Baltimore S, Baltimore, MD 21201 (United States); Brown, Lawrence [Department of Veterans Affairs Medical Center Baltimore, Maryland, 10 N. Greene St., Baltimore, MD 21201 (United States); Department of Pathology, University of Maryland School of Medicine, 655 W Baltimore S, Baltimore, MD 21201 (United States); Centeno, Jose A. [US Food and Drug Administration, Center for Devices and Radiological Health Office of Science and Engineering Laboratories, Silver Spring, MD 20993 (United States); Dux, Moira [Department of Veterans Affairs Medical Center Baltimore, Maryland, 10 N. Greene St., Baltimore, MD 21201 (United States); Squibb, Katherine S. [Department of Veterans Affairs Medical Center Baltimore, Maryland, 10 N. Greene St., Baltimore, MD 21201 (United States); Department of Medicine, University of Maryland School of Medicine, 655 W Baltimore S, Baltimore, MD 21201 (United States)

    2017-01-15

    Background: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. Methods: During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. Results: On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations. The DU isotopic signature is observed principally in participants possessing embedded fragments. Those with only an inhalation exposure have lower urine U concentration and a natural isotopic signature. Conclusions: At 25 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As U body burden continues to accrue from in-situ mobilization from metal fragment depots, and increases with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort. - Highlights: • Gulf War I veterans wounded with depleted uranium are monitored for health changes. • In 2015 in-patient clinical surveillance was performed on 36 members of the cohort. • Mobilization of U from embedded fragments is evidenced by elevated U in urine. • This cohort of continues to show no U-related health effects.

  10. Paranodal reorganization results in the depletion of transverse bands in the aged central nervous system

    Shepherd, Mark N.; Pomicter, Anthony D.; Velazco, Cristine S.; Henderson, Scott C.; Dupree, Jeffrey L.

    2012-01-01

    Paranodal axo-glial junctional complexes anchor the myelin sheath to the axon and breakdown of these complexes presumably facilitates demyelination. Myelin deterioration is also prominent in the aging central nervous system (CNS); however, the stability of the paranodal complexes in the aged CNS has not been examined. Here, we show that transverse bands, prominent components of paranodal junctions, are significantly reduced in the aged CNS; however, the number of paired clusters of both myelin and axonal paranodal proteins is not altered. Ultrastructural analyses also reveal that thicker myelin sheaths display a “piling” of paranodal loops, the cytoplasm-containing sacs that demarcate the paranode. Loops involved in piling are observed throughout the paranode and are not limited to loops positioned in either the nodal- or juxtanodal-most regions. Here, we propose that as myelination continues, previously anchored loops lose their transverse bands and recede away from the axolemma. Newly juxtaposed loops then lose their transverse bands, move laterally to fill in the gap left by the receded loops and finally reform their transverse bands. This paranodal reorganization results in conservation of paranodal length, which may be important in maintaining ion channel spacing and axonal function. Furthermore, we propose that transverse band reformation is less efficient in the aged CNS, resulting in the significant reduction of these junctional components. Although demyelination was not observed, we propose that loss of transverse bands facilitates myelin degeneration and may predispose the aged CNS to a poorer prognosis following a secondary insult. PMID:20888080

  11. Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o- Cells

    Annalucia Carbone

    2018-01-01

    Full Text Available We previously found that human amniotic mesenchymal stem cells (hAMSCs in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ- mediated intercellular communication (GJIC in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43, a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C, and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells.

  12. Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o- Cells.

    Carbone, Annalucia; Zefferino, Roberto; Beccia, Elisa; Casavola, Valeria; Castellani, Stefano; Di Gioia, Sante; Giannone, Valentina; Seia, Manuela; Angiolillo, Antonella; Colombo, Carla; Favia, Maria; Conese, Massimo

    2018-01-01

    We previously found that human amniotic mesenchymal stem cells (hAMSCs) in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE) on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ-) mediated intercellular communication (GJIC) in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio) were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43), a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C), and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells.

  13. Test beam results of a depleted monolithic active pixel sensor (DMAPS) prototype

    Obermann, Theresa; Hemperek, Tomasz; Huegging, Fabian; Krueger, Hans; Wermes, Norbert [Bonn Univ. (Germany); Schwenker, Benjamin [Goettingen Univ. (Germany); Collaboration: ATLAS Pixel-Collaboration

    2016-07-01

    New monolithic detector concepts are currently being explored for future particle physics experiments, in particular for the upgrade of the ATLAS detector. Common to monolithic pixel detectors is the integration of the front-end circuitry and the sensor on the same silicon substrate. The DMAPS concept makes use of high resistive silicon as substrate. It enables the application of a high bias voltage to create a drift field for the charge collection in the sensor part as well as the full usage of CMOS logic in the same piece of silicon. DMAPS prototypes from several foundries are available since three years and have been extensively characterized in the lab. In this talk, results of test beam campaigns, with neutron irradiated prototypes implemented in the ESPROS process, are presented.

  14. Combined Bicarbonate Conductance-Impairing Variants in CFTR and SPINK1 Are Associated with Chronic Pancreatitis in Patients without Cystic Fibrosis

    Schneider, Alexander; LaRusch, Jessica; Sun, Xiumei; Aloe, Amy; Lamb, Janette; Hawes, Robert; Cotton, Peter; Brand, Randall E.; Anderson, Michelle A.; Money, Mary E.; Banks, Peter A.; Lewis, Michele D.; Baillie, John; Sherman, Stuart; DiSario, James; Burton, Frank R.; Gardner, Timothy B.; Amann, Stephen T.; Gelrud, Andres; George, Ryan; Kassabian, Sirvart; Martinson, Jeremy; Slivka, Adam; Yadav, Dhiraj; Oruc, Nevin; Barmada, M. Michael; Frizzell, Raymond; Whitcomb, David C.

    2010-01-01

    Background & Aims Idiopathic chronic pancreatitis (ICP) is a complex inflammatory disorder associated with multiple genetic and environmental factors. In individuals without cystic fibrosis (CF), variants of CFTR that inhibit bicarbonate conductance but maintain chloride conductance might selectively impair secretion of pancreatic juice, leading to trypsin activation and pancreatitis. We investigated whether sequence variants in the gene encoding the pancreatic secretory trypsin inhibitor, SPINK1, further increase the risk of pancreatitis in these patients. Methods We screened patients with ICP (sporadic or familial) and controls for variants in SPINK1 associated with chronic pancreatitis (CP) risk (in exon 3) and in all 27 exons of CFTR. The final study group included 53 patients with sporadic ICP, 27 probands with familial ICP, and 150 unrelated controls, plus 503 controls for limited genotyping. CFTR wild-type (wt) and p.R75Q were cloned and expressed in HEK293 cells and relative conductances of HCO3− and Cl− were measured. Results SPINK1 variants were identified in 36% of subjects and 3% controls (odds ratio [OR]=16.5). One variant of CFTR that has not been associated with CF, p.R75Q, was found in 16% of subjects and 5.4% controls (OR=3.4). Co-inheritance of CFTR p.R75Q and SPINK1 variants occurred in 8.75% of patients and 0.15% controls (OR=62.5). Patch-clamp recordings of cells that expressed CFTR p.R75Q demonstrated normal chloride currents but significantly reduced bicarbonate currents (P=0.0001). Conclusions The CFTR variant p.R75Q causes a selective defect in bicarbonate conductance and increases risk for pancreatitis. Co-inheritance of CF-associated, and some not associated, CFTR variants with SPINK1 variants significantly increase risk of ICP. PMID:20977904

  15. S737F is a new CFTR mutation typical of patients originally from the Tuscany region in Italy.

    Terlizzi, Vito; Di Lullo, Antonella Miriam; Comegna, Marika; Centrone, Claudia; Pelo, Elisabetta; Castaldo, Giuseppe; Raia, Valeria; Braggion, Cesare

    2018-01-03

    An increasing number of patients have been described as having a number of Cystic Fibrosis Transmembrane conductance Regulator (CFTR) variants for which it lacks a clear genotype-phenotype correlation. We assesses the clinical features of patients bearing the S737F (p.Ser737Phe) CFTR missense variant and evaluated the residual function of CFTR protein on nasal epithelial cells (NEC). A retrospective database was performed from individuals homozygous or compound heterozygous for the S737F variant followed in the Cystic Fibrosis (CF) Centre of Florence. We performed a nasal brushing in cooperating patients and compared the results with those of patients followed in the pediatric CF Centre of Naples. 9/295 (3%) subjects carrying at least S737F CFTR variant on one allele were identified. Patients were diagnosed in 7/9 cases by newborn screening and in two cases for dehydration with hypochloremic metabolic alkalosis; at diagnosis sweat chloride levels (SCL) were in the pathological range in only one case. After a mean follow up of 8,6 years (range 0,5-15,8), SCL were in the pathological range in 8/9 cases (mean age at CF diagnosis: 1,5 years), all patients were pancreatic sufficiency and respiratory function was normal. The gating activity on NEC was 15.6% and 12.7% in two patients compound heterozygous for W1282X and DelE22_24, while it was ranged between 6,2% and 9,8% in CF patients. S737F is a CFTR mutation associated to hypochloremic alkalosis in childhood, mild CF phenotype in teenage years and a residual function of CFTR protein.

  16. CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients.

    Ewa Ziętkiewicz

    Full Text Available Cystic fibrosis (CF is caused by mutations in the cystic fibrosis transmembrane regulator gene (CFTR. In light of the strong allelic heterogeneity and regional specificity of the mutation spectrum, the strategy of molecular diagnostics and counseling in CF requires genetic tests to reflect the frequency profile characteristic for a given population. The goal of the study was to provide an updated comprehensive estimation of the distribution of CFTR mutations in Polish CF patients and to assess the effectiveness of INNOLiPA_CFTR tests in Polish population. The analyzed cohort consisted of 738 patients with the clinically confirmed CF diagnosis, prescreened for molecular defects using INNOLiPA_CFTR panels from Innogenetics. A combined efficiency of INNOLiPA CFTR_19 and CFTR_17_TnUpdate tests was 75.5%; both mutations were detected in 68.2%, and one mutation in 14.8% of the affected individuals. The group composed of all the patients with only one or with no mutation detected (109 and 126 individuals, respectively was analyzed further using a mutation screening approach, i.e. SSCP/HD (single strand conformational polymorphism/heteroduplex analysis of PCR products followed by sequencing of the coding sequence. As a result, 53 more mutations were found in 97 patients. The overall efficiency of the CF allele detection was 82.5% (7.0% increase compared to INNOLiPA tests alone. The distribution of the most frequent mutations in Poland was assessed. Most of the mutations repetitively found in Polish patients had been previously described in other European populations. The most frequent mutated allele, F508del, represented 54.5% of Polish CF chromosomes. Another eight mutations had frequencies over 1%, 24 had frequencies between 1 and 0.1%; c.2052-2053insA and c.3468+2_3468+3insT were the most frequent non-INNOLiPA mutations. Mutation distribution described herein is also relevant to the Polish diaspora. Our study also demonstrates that the reported

  17. Regulatory crosstalk by protein kinases on CFTR trafficking and activity

    Farinha, Carlos Miguel; Swiatecka-Urban, Agnieszka; Brautigan, David; Jordan, Peter

    2016-01-01

    Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride ion channel in fluid-transporting epithelia. There is abundant evidence that CFTR activity (i.e. channel opening and closing) is regulated by protein kinases and phosphatases via phosphorylation and dephosphorylation. Here, we review recent evidence for the role of protein kinases in regulation of CFTR delivery to and retention in the plasma membrane. We review this information in a broader context of regulation of other transporters by protein kinases because the overall functional output of transporters involves the integrated control of both their number at the plasma membrane and their specific activity. While many details of the regulation of intracellular distribution of CFTR and other transporters remain to be elucidated, we hope that this review will motivate research providing new insights into how protein kinases control membrane transport to impact health and disease.

  18. Longevity and plasticity of CFTR provide an argument for noncanonical SNP organization in hominid DNA.

    Aubrey E Hill

    Full Text Available Like many other ancient genes, the cystic fibrosis transmembrane conductance regulator (CFTR has survived for hundreds of millions of years. In this report, we consider whether such prodigious longevity of an individual gene--as opposed to an entire genome or species--should be considered surprising in the face of eons of relentless DNA replication errors, mutagenesis, and other causes of sequence polymorphism. The conventions that modern human SNP patterns result either from purifying selection or random (neutral drift were not well supported, since extant models account rather poorly for the known plasticity and function (or the established SNP distributions found in a multitude of genes such as CFTR. Instead, our analysis can be taken as a polemic indicating that SNPs in CFTR and many other mammalian genes may have been generated--and continue to accrue--in a fundamentally more organized manner than would otherwise have been expected. The resulting viewpoint contradicts earlier claims of 'directional' or 'intelligent design-type' SNP formation, and has important implications regarding the pace of DNA adaptation, the genesis of conserved non-coding DNA, and the extent to which eukaryotic SNP formation should be viewed as adaptive.

  19. Development of allele-specific multiplex PCR to determine the length of poly-T in intron 8 of CFTR

    Neng Chen

    2014-07-01

    Full Text Available Cystic fibrosis transmembrane conductance regulator (CFTR gene mutation analysis has been implemented for Cystic Fibrosis (CF carrier screening, and molecular diagnosis of CF and congenital bilateral absence of the vas deferens (CBAVD. Although poly-T allele analysis in intron 8 of CFTR is required when a patient is positive for R117H, it is not recommended for routine carrier screening. Therefore, commercial kits for CFTR mutation analysis were designed either to mask the poly-T allele results, unless a patient is R117H positive, or to have the poly-T analysis as a standalone reflex test using the same commercial platform. There are other standalone assays developed to detect poly-T alleles, such as heteroduplex analysis, High Resolution Melting (HRM curve analysis, allele-specific PCR (AS-PCR and Sanger sequencing. In this report, we developed a simple and easy-to-implement multiplex AS-PCR assay using unlabeled standard length primers, which can be used as a reflex or standalone test for CFTR poly-T track analysis. Out of 115 human gDNA samples tested, results from our new AS-PCR matched to the previous known poly-T results or results from Sanger sequencing.

  20. F508del-CFTR rescue: a matter of cell stress response.

    Nieddu, Erika; Pollarolo, Benedetta; Merello, Luisa; Schenone, Silvia; Mazzei, Mauro

    2013-01-01

    Cystic fibrosis (CF) is a common inherited fatal disease affecting 70,000 people worldwide, with a median predicted age of survival of approximately 38 years. The deletion of Phenylalanine in position 508 of the Cystic Fibrosis Transmembrane conductance Regulator (F508del-CFTR) is the most common mutation in CF patients: the deleted protein, not properly folded, is degraded. To date no commercial drugs are available. Low temperature, some osmolytes and conditions able to induce heat shock protein 70 (Hsp70) expression and heat shock cognate 70 (Hsc70) inhibition result in F508del-CFTR rescue, hence restoring its physiological function: this review sheds light on the correlation between these several evidences. Interestingly, all these approaches have a role in the cell stress response (CSR), a set of cell reactions to stress. In addition, unpredictably, F508del-CFTR rescue has to be considered in the frame of CSR: entities that induce - or are induced during - the CSR are, in general, also able to correct trafficking defect of CFTR. Specifically, the low temperature induces, by definition, a CSR; osmolytes, such as glycerol and trimethylamine N-oxide (TMAO), are products of the CSR; pharmacological correctors, such as Matrine and 4-phenylbutirric acid (4PBA), down-regulate the constitutive Hsc70 in favor of an up-regulation of the inducible chaperone Hsp70, another component of the CSR. The identification of a common mechanism of action for different types of correctors could drive the discovery of new active molecules in CF, overcoming methods clinically inapplicable, such as the low temperature.

  1. Antibodies to the CFTR modulate the turgor pressure of guard cell protoplasts via slow anion channels.

    Leonhardt, N; Bazin, I; Richaud, P; Marin, E; Vavasseur, A; Forestier, C

    2001-04-06

    The plasma membrane guard cell slow anion channel is a key element at the basis of water loss control in plants allowing prolonged osmolite efflux necessary for stomatal closure. This channel has been extensively studied by electrophysiological approaches but its molecular identification is still lacking. Recently, we described that this channel was sharing some similarities with the mammalian ATP-binding cassette protein, cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel [Leonhardt, N. et al. (1999) Plant Cell 11, 1141-1151]. Here, using the patch-clamp technique and a bioassay, consisting in the observation of the change in guard cell protoplasts volume, we demonstrated that a functional antibody raised against the mammalian CFTR prevented ABA-induced guard cell protoplasts shrinking and partially inhibited the slow anion current. Moreover, this antibody immunoprecipitated a polypeptide from guard cell protein extracts and immunolabeled stomata in Vicia faba leaf sections. These results indicate that the guard cell slow anion channel is, or is closely controlled by a polypeptide, exhibiting one epitope shared with the mammalian CFTR.

  2. Interaction between a novel TGFB1 haplotype and CFTR genotype is associated with improved lung function in cystic fibrosis.

    Bremer, Lindsay A; Blackman, Scott M; Vanscoy, Lori L; McDougal, Kathryn E; Bowers, Amanda; Naughton, Kathleen M; Cutler, David J; Cutting, Garry R

    2008-07-15

    Cystic fibrosis (CF), the most common lethal single gene disorder in Caucasians, is due to mutations in the CFTR gene. Twin and sibling analysis indicates that modifier genes, rather than allelic variation in CFTR, are responsible for most of the variability in severity of lung disease, the major cause of mortality in CF patients. We used a family-based approach to test for association between lung function and two functional SNPs (rs1800469, '-509' and rs1982073, 'codon 10') in the 5' region of transforming growth factor-beta1 (TGFB1), a putative CF modifier gene. Quantitative transmission disequilibrium testing of 472 CF patient-parent-parent trios revealed that both TGFB1 SNPs showed significant transmission distortion when patients were stratified by CFTR genotype. Although lung function and nutritional status are correlated in CF patients, there was no evidence of association between the TGFB1 SNPs and variation in nutritional status. Additional tagging SNPs (rs8179181, rs2278422, rs8110090, rs4803455 and rs1982072) that capture most of the diversity in TGFB1 were also typed but none showed association with variation in lung function. However, a haplotype composed of the -509 C and codon 10 T alleles along with the C allele of the 3' SNP rs8179181 was highly associated with increased lung function in patients grouped by CFTR genotype. These results demonstrate that TGFB1 is a modifier of CF lung disease and reveal a previously unrecognized beneficial effect of TGFB1 variants upon the pulmonary phenotype.

  3. Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation.

    Chaowalit Yuajit

    Full Text Available Cyst enlargement in polycystic kidney disease (PKD involves cAMP-activated proliferation of cyst-lining epithelial cells and transepithelial fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR chloride channel. This study aimed to investigate an inhibitory effect and detailed mechanisms of steviol and its derivatives on cyst growth using a cyst model in Madin-Darby canine kidney (MDCK cells. Among 4 steviol-related compounds tested, steviol was found to be the most potent at inhibiting MDCK cyst growth. Steviol inhibition of cyst growth was dose-dependent; steviol (100 microM reversibly inhibited cyst formation and cyst growth by 72.53.6% and 38.2±8.5%, respectively. Steviol at doses up to 200 microM had no effect on MDCK cell viability, proliferation and apoptosis. However, steviol acutely inhibited forskolin-stimulated apical chloride current in MDCK epithelia, measured with the Ussing chamber technique, in a dose-dependent manner. Prolonged treatment (24 h with steviol (100 microM also strongly inhibited forskolin-stimulated apical chloride current, in part by reducing CFTR protein expression in MDCK cells. Interestingly, proteasome inhibitor, MG-132, abolished the effect of steviol on CFTR protein expression. Immunofluorescence studies demonstrated that prolonged treatment (24 h with steviol (100 microM markedly reduced CFTR expression at the plasma membrane. Taken together, the data suggest that steviol retards MDCK cyst progression in two ways: first by directly inhibiting CFTR chloride channel activity and second by reducing CFTR expression, in part, by promoting proteasomal degradation of CFTR. Steviol and related compounds therefore represent drug candidates for treatment of polycystic kidney disease.

  4. 21 CFR 866.5900 - Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system.

    2010-04-01

    ... regulator (CFTR) gene mutation detection system. 866.5900 Section 866.5900 Food and Drugs FOOD AND DRUG...) gene mutation detection system. (a) Identification. The CFTR gene mutation detection system is a device... Guidance Document: CFTR Gene Mutation Detection System.” See § 866.1(e) for the availability of this...

  5. CFTR is a tumor suppressor gene in murine and human intestinal cancer

    Than, B. L. N.; Linnekamp, J. F.; Starr, T. K.; Largaespada, D. A.; Rod, A.; Zhang, Y.; Bruner, V.; Abrahante, J.; Schumann, A.; Luczak, T.; Niemczyk, A.; O'Sullivan, M. G.; Medema, J. P.; Fijneman, R. J. A.; Meijer, G. A.; van den Broek, E.; Hodges, C. A.; Scott, P. M.; Vermeulen, L.; Cormier, R. T.

    2016-01-01

    CFTR, the cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regulation and tissue homeostasis of various epithelia. In the gastrointestinal (GI) tract CFTR promotes chloride and bicarbonate secretion, playing an essential role in ion and acid-base

  6. CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis

    Lopes-Pacheco, Miquéias

    2016-01-01

    Cystic fibrosis (CF) is the most common life-threatening monogenic disease afflicting Caucasian people. It affects the respiratory, gastrointestinal, glandular and reproductive systems. The major cause of morbidity and mortality in CF is the respiratory disorder caused by a vicious cycle of obstruction of the airways, inflammation and infection that leads to epithelial damage, tissue remodeling and end-stage lung disease. Over the past decades, life expectancy of CF patients has increased due to early diagnosis and improved treatments; however, these patients still present limited quality of life. Many attempts have been made to rescue CF transmembrane conductance regulator (CFTR) expression, function and stability, thereby overcoming the molecular basis of CF. Gene and protein variances caused by CFTR mutants lead to different CF phenotypes, which then require different treatments to quell the patients’ debilitating symptoms. In order to seek better approaches to treat CF patients and maximize therapeutic effects, CFTR mutants have been stratified into six groups (although several of these mutations present pleiotropic defects). The research with CFTR modulators (read-through agents, correctors, potentiators, stabilizers and amplifiers) has achieved remarkable progress, and these drugs are translating into pharmaceuticals and personalized treatments for CF patients. This review summarizes the main molecular and clinical features of CF, emphasizes the latest clinical trials using CFTR modulators, sheds light on the molecular mechanisms underlying these new and emerging treatments, and discusses the major breakthroughs and challenges to treating all CF patients. PMID:27656143

  7. Incidence and Carrier Frequency of CFTR Gene Mutations in Pregnancies With Echogenic Bowel in Nova Scotia and Prince Edward Island.

    Miller, Michelle E; Allen, Victoria M; Brock, Jo-Ann K

    2018-03-01

    Fetal echogenic bowel (echogenic bowel) is associated with cystic fibrosis (CF), with a reported incidence ranging from 1% to 13%. Prenatal testing for CF in the setting of echogenic bowel can be done by screening parental or fetal samples for pathogenic CFTR variants. If only one pathogenic variant is identified, sequencing of the CFTR gene can be undertaken, to identify a second pathogenic variant not covered in the standard screening panel. Full gene sequencing, however, also introduces the potential to identify variants of uncertain significance (VUSs) that can create counselling challenges and cause parental anxiety. To provide accurate counselling for families in the study population, the incidence of CF associated with echogenic bowel and the carrier frequency of CFTR variants were investigated. All pregnancies for which CF testing was undertaken for the indication of echogenic bowel (from Nova Scotia and Prince Edward Island) were identified (January 2007-July 2017). The CFTR screening and sequencing results were reviewed, and fetal outcomes related to CF were assessed. A total of 463 pregnancies with echogenic bowel were tested. Four were confirmed to be affected with CF, giving an incidence of 0.9% in this cohort. The carrier frequency of CF among all parents in the cohort was 5.0% (1 in 20); however, when excluding parents of affected fetuses, the carrier frequency for the population was estimated at 4.1% (1 in 25). CFTR gene sequencing identified an additional VUS in two samples. The incidence of CF in pregnancies with echogenic bowel in Nova Scotia and Prince Edward Island is 0.9%, with an estimated population carrier frequency of 4.1%. These results provide the basis for improved counselling to assess the risk of CF in the pregnancy, after parental carrier screening, using Bayesian probability. Counselling regarding VUSs should be undertaken before gene sequencing. Copyright © 2017 Society of Obstetricians and Gynaecologists of Canada. Published by

  8. Management of depleted uranium

    2001-01-01

    Large stocks of depleted uranium have arisen as a result of enrichment operations, especially in the United States and the Russian Federation. Countries with depleted uranium stocks are interested in assessing strategies for the use and management of depleted uranium. The choice of strategy depends on several factors, including government and business policy, alternative uses available, the economic value of the material, regulatory aspects and disposal options, and international market developments in the nuclear fuel cycle. This report presents the results of a depleted uranium study conducted by an expert group organised jointly by the OECD Nuclear Energy Agency and the International Atomic Energy Agency. It contains information on current inventories of depleted uranium, potential future arisings, long term management alternatives, peaceful use options and country programmes. In addition, it explores ideas for international collaboration and identifies key issues for governments and policy makers to consider. (authors)

  9. Cystic fibrosis transmembrane conductance regulator (CFTR allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients.

    Serena Schippa

    Full Text Available INTRODUCTION: In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF. CFTR mutations (F508del is the most common lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. METHODS: Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. RESULTS: Patients were classified by two different criteria: 1 presence/absence of F508del mutation; 2 disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum were reduced. CONCLUSIONS: This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.

  10. Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells.

    Gaëlle Gonzalez

    Full Text Available Cell microparticles (MPs released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5, and serotype 35 (HAdV35, respectively. We found that MPs derived from CHO cells (MP-donor cells constitutively expressing CAR (MP-CAR or CD46 (MP-CD46 were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins.

  11. Activation of CFTR by ASBT-mediated bile salt absorption

    Bijvelds, MJC; Jorna, H; Verkade, HJ; Bot, AGM; Hofmann, F; Agellon, LB; Sinaasappel, M; de Jonge, HR

    2005-01-01

    In cholangiocytes, bile salt (BS) uptake via the apical sodium-dependent bile acid transporter (ASBT) may evoke ductular flow by enhancing cAMP-mediated signaling to the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. We considered that ASBT-mediated BS uptake in the distal

  12. Insulin-like growth factor 1 (IGF-1 enhances the protein expression of CFTR.

    Ha Won Lee

    Full Text Available Low levels of insulin-like growth factor 1 (IGF-1 have been observed in the serum of cystic fibrosis (CF patients. However, the effects of low serum IGF-1 on the cystic fibrosis transmembrane conductance regulator (CFTR, whose defective function is the primary cause of cystic fibrosis, have not been studied. Here, we show in human cells that IGF-1 increases the steady-state levels of mature wildtype CFTR in a CFTR-associated ligand (CAL- and TC10-dependent manner; moreover, IGF-1 increases CFTR-mediated chloride transport. Using an acceptor photobleaching fluorescence resonance energy transfer (FRET assay, we have confirmed the binding of CAL and CFTR in the Golgi. We also show that CAL overexpression inhibits forskolin-induced increases in the cell-surface expression of CFTR. We found that IGF-1 activates TC10, and active TC10 alters the functional association between CAL and CFTR. Furthermore, IGF-1 and active TC10 can reverse the CAL-mediated reduction in the cell-surface expression of CFTR. IGF-1 does not increase the expression of ΔF508 CFTR, whose processing is arrested in the ER. This finding is consistent with our observation that IGF-1 alters the functional interaction of CAL and CFTR in the Golgi. However, when ΔF508 CFTR is rescued with low temperature or the corrector VRT-325 and proceeds to the Golgi, IGF-1 can increase the expression of the rescued ΔF508 CFTR. Our data support a model indicating that CAL-CFTR binding in the Golgi inhibits CFTR trafficking to the cell surface, leading CFTR to the degradation pathway instead. IGF-1-activated TC10 changes the interaction of CFTR and CAL, allowing CFTR to progress to the plasma membrane. These findings offer a potential strategy using a combinational treatment of IGF-1 and correctors to increase the post-Golgi expression of CFTR in cystic fibrosis patients bearing the ΔF508 mutation.

  13. Synchrotron x-ray fluorescence analyses of stratospheric cosmic dust: New results for chondritic and nickel-depleted particles

    Flynn, G.J.; Sutton, S.R.

    1989-06-01

    Trace element abundance determinations were performed using synchrotron x-ray fluorescence on nine particles collected from the stratosphere and classified as ''cosmic''. Improvements to the Synchrotron Light Source allowed the detection of all elements between Cr and Mo, with the exceptions of Co and As, in our largest particle. The minor and trace element abundance patterns of three Ni-depleted particles were remarkably similar to those of extraterrestrial igneous rocks. Fe/Ni and Fe/Mn ratios suggest that one of these may be of lunar origin. All nine particles exhibited an enrichment in Br, ranging form 1.3 to 38 times the Cl concentration. Br concentrations were uncorrelated with particle size, as would be expected for a surface correlated component acquires from the stratosphere. 27 refs., 4 figs., 2 tabs

  14. Serotonin depletion results in a decrease of the neuronal activation caused by rivastigmine in the rat hippocampus

    Kornum, Birgitte R; Weikop, Pia; Moller, Arne

    2006-01-01

    nicotinic receptors located at nerve terminals. The aim of the present study was to determine in which areas and to what extent 5-HT mediates the neuronal response to ACh release. For this purpose, neuronal activity was measured in rats with rivastigmine-induced elevated ACh levels after a 95% 5-HT...... depletion obtained by dosing p-chlorophenylalanine followed by D,L-fenfluramine. Neuronal activation was quantified by stereological measurements of c-Fos immunoreactivity. The brain areas examined were medial prefrontal cortex, septum, dorsal hippocampus, and dorsal raphe nucleus. Rivastigmine...... brain areas examined. It is concluded that 5-HT mediates part of the ACh-induced hippocampal neuronal activation, possibly mediated via locally released 5-HT....

  15. Sphingosine-1-Phosphate Is a Novel Regulator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR Activity.

    Firhan A Malik

    Full Text Available The cystic fibrosis transmembrane conductance regulator (CFTR attenuates sphingosine-1-phosphate (S1P signaling in resistance arteries and has emerged as a prominent regulator of myogenic vasoconstriction. This investigation demonstrates that S1P inhibits CFTR activity via adenosine monophosphate-activated kinase (AMPK, establishing a potential feedback link. In Baby Hamster Kidney (BHK cells expressing wild-type human CFTR, S1P (1μmol/L attenuates forskolin-stimulated, CFTR-dependent iodide efflux. S1P's inhibitory effect is rapid (within 30 seconds, transient and correlates with CFTR serine residue 737 (S737 phosphorylation. Both S1P receptor antagonism (4μmol/L VPC 23019 and AMPK inhibition (80μmol/L Compound C or AMPK siRNA attenuate S1P-stimluated (i AMPK phosphorylation, (ii CFTR S737 phosphorylation and (iii CFTR activity inhibition. In BHK cells expressing the ΔF508 CFTR mutant (CFTRΔF508, the most common mutation causing cystic fibrosis, both S1P receptor antagonism and AMPK inhibition enhance CFTR activity, without instigating discernable correction. In summary, we demonstrate that S1P/AMPK signaling transiently attenuates CFTR activity. Since our previous work positions CFTR as a negative S1P signaling regulator, this signaling link may positively reinforce S1P signals. This discovery has clinical ramifications for the treatment of disease states associated with enhanced S1P signaling and/or deficient CFTR activity (e.g. cystic fibrosis, heart failure. S1P receptor/AMPK inhibition could synergistically enhance the efficacy of therapeutic strategies aiming to correct aberrant CFTR trafficking.

  16. Halo Star Lithium Depletion

    Pinsonneault, M. H.; Walker, T. P.; Steigman, G.; Narayanan, Vijay K.

    1999-01-01

    The depletion of lithium during the pre-main-sequence and main-sequence phases of stellar evolution plays a crucial role in the comparison of the predictions of big bang nucleosynthesis with the abundances observed in halo stars. Previous work has indicated a wide range of possible depletion factors, ranging from minimal in standard (nonrotating) stellar models to as much as an order of magnitude in models that include rotational mixing. Recent progress in the study of the angular momentum evolution of low-mass stars permits the construction of theoretical models capable of reproducing the angular momentum evolution of low-mass open cluster stars. The distribution of initial angular momenta can be inferred from stellar rotation data in young open clusters. In this paper we report on the application of these models to the study of lithium depletion in main-sequence halo stars. A range of initial angular momenta produces a range of lithium depletion factors on the main sequence. Using the distribution of initial conditions inferred from young open clusters leads to a well-defined halo lithium plateau with modest scatter and a small population of outliers. The mass-dependent angular momentum loss law inferred from open cluster studies produces a nearly flat plateau, unlike previous models that exhibited a downward curvature for hotter temperatures in the 7Li-Teff plane. The overall depletion factor for the plateau stars is sensitive primarily to the solar initial angular momentum used in the calibration for the mixing diffusion coefficients. Uncertainties remain in the treatment of the internal angular momentum transport in the models, and the potential impact of these uncertainties on our results is discussed. The 6Li/7Li depletion ratio is also examined. We find that the dispersion in the plateau and the 6Li/7Li depletion ratio scale with the absolute 7Li depletion in the plateau, and we use observational data to set bounds on the 7Li depletion in main-sequence halo

  17. An immortal cell line to study the role of endogenous CFTR in electrolyte absorption.

    Bell, C L; Quinton, P M

    1995-01-01

    The intact human reabsorptive sweat duct (RD) has been a reliable model for investigations of the functional role of "endogenous" CFTR (cystic fibrosis transmembrane conductance regulator) in normal and abnormal electrolyte absorptive function. But to overcome the limitations imposed by the use of fresh, intact tissue, we transformed cultured RD cells using the chimeric virus Ad5/SV40 1613 ori-. The resultant cell line, RD2(NL), has remained differentiated forming a polarized epithelium that expressed two fundamental components of absorption, a cAMP activated Cl- conductance (GCl) and an amiloride-sensitive Na+ conductance (GNa). In the unstimulated state, there was a low level of transport activity; however, addition of forskolin (10(-5) M) significantly increased the Cl- diffusion potential (Vt) generated by a luminally directed Cl- gradient from -15.3 +/- 0.7 mV to -23.9 +/- 1.1 mV, n = 39; and decreased the transepithelial resistance (Rt) from 814.8 +/- 56.3 omega.cm2 to 750.5 +/- 47.5 omega.cm2, n = 39, (n = number of cultures). cAMP activation, anion selectivity (Cl- > I- > gluconate), and a dependence upon metabolic energy (metabolic poisoning inhibited GCl), all indicate that the GCl expressed in RD2(NL) is in fact CFTR-GCl. The presence of an apical amiloride-sensitive GNa was shown by the amiloride (10(-5) M) inhibition of GNa as indicated by a reduction of Vt and equivalent short circuit current by 78.0 +/- 3.1% and 77.9 +/- 2.6%, respectively, and an increase in Rt by 7.2 +/- 0.8%, n = 36. In conclusion, the RD2(NL) cell line presents the first model system in which CFTR-GCl is expressed in a purely absorptive tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Association between F508 deletion in CFTR and chronic pancreatitis risk.

    Zhao, Dong; Xu, Yanzhen; Li, Jiatong; Fu, Shien; Xiao, Feifan; Song, Xiaowei; Xie, Zhibin; Jiang, Min; He, Yan; Liu, Chengwu; Wen, Qiongxian; Yang, Xiaoli

    2017-09-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) has been reported to influence individual susceptibility to chronic pancreatitis (CP), but the results of previous studies are controversial. We performed a study to demonstrate the relationship between CFTR and CP. We searched PubMed, Scopus, and Embase for studies of patients with CP. Seven studies from 1995 to 2016 were identified, and included 64,832 patients. Pooled prevalence and 95% confidence intervals (CIs) were calculated. F508 deletion in CFTR was significantly positively associated with CP risk in the overall analysis (odds ratio [OR]=3.20, 95% CI: 2.30-4.44, I 2 =31.7%). In subgroup analysis stratified by ethnicity, F508 deletion was significantly associated with CP risk in Indian populations, using a fixed effects model (ORs=5.45, 95% CI: 2.52-11.79, I 2 =0.0%), and in non-Indian populations, using a random effects model (ORs=3.59, 95% CI: 1.73-7.48, I 2 =60.9%). At the same time, we found that Indians with F508 deletion had much higher CP prevalence than non-Indians. Interestingly, F508 deletion was also associated with CP and idiopathic CP risk in subgroup analysis stratified by aeitiology, using the fixed effects model. Based on current evidence, F508 deletion is a risk factor for CP, and Indians with F508 deletion have much higher CP morbidity. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  19. Dendrimer-based selective autophagy-induction rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection in cystic fibrosis.

    Scott Mackenzie Brockman

    Full Text Available Cystic Fibrosis (CF is a genetic disorder caused by mutation(s in the CF-transmembrane conductance regulator (Cftr gene. The most common mutation, ΔF508, leads to accumulation of defective-CFTR protein in aggresome-bodies. Additionally, Pseudomonas aeruginosa (Pa, a common CF pathogen, exacerbates obstructive CF lung pathology. In the present study, we aimed to develop and test a novel strategy to improve the bioavailability and potentially achieve targeted drug delivery of cysteamine, a potent autophagy-inducing drug with anti-bacterial properties, by developing a dendrimer (PAMAM-DEN-based cysteamine analogue.We first evaluated the effect of dendrimer-based cysteamine analogue (PAMAM-DENCYS on the intrinsic autophagy response in IB3-1 cells and observed a significant reduction in Ub-RFP and LC3-GFP co-localization (aggresome-bodies by PAMAM-DENCYS treatment as compared to plain dendrimer (PAMAM-DEN control. Next, we observed that PAMAM-DENCYS treatment shows a modest rescue of ΔF508-CFTR as the C-form. Moreover, immunofluorescence microscopy of HEK-293 cells transfected with ΔF508-CFTR-GFP showed that PAMAM-DENCYS is able to rescue the misfolded-ΔF508-CFTR from aggresome-bodies by inducing its trafficking to the plasma membrane. We further verified these results by flow cytometry and observed significant (p<0.05; PAMAM-DEN vs. PAMAM-DENCYS rescue of membrane-ΔF508-CFTR with PAMAM-DENCYS treatment using non-permeabilized IB3-1 cells immunostained for CFTR. Finally, we assessed the autophagy-mediated bacterial clearance potential of PAMAM-DENCYS by treating IB3-1 cells infected with PA01-GFP, and observed a significant (p<0.01; PAMAM-DEN vs. PAMAM-DENCYS decrease in intracellular bacterial counts by immunofluorescence microscopy and flow cytometry. Also, PAMAM-DENCYS treatment significantly inhibits the growth of PA01-GFP bacteria and demonstrates potent mucolytic properties.We demonstrate here the efficacy of dendrimer-based autophagy

  20. Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data.

    Accurso, Frank J; Van Goor, Fredrick; Zha, Jiuhong; Stone, Anne J; Dong, Qunming; Ordonez, Claudia L; Rowe, Steven M; Clancy, John Paul; Konstan, Michael W; Hoch, Heather E; Heltshe, Sonya L; Ramsey, Bonnie W; Campbell, Preston W; Ashlock, Melissa A

    2014-03-01

    We examined data from a Phase 2 trial {NCT00457821} of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with aG551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity. Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing,and analysis was employed for the first time. Sweat chloride and chloride ion transport (NPD) were integrated into a model of CFTR activity. Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40% of normal. Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators.

  1. Effects of ageing conditions on the precipitates evolution, chromium depletion and intergranular corrosion susceptibility of AISI 316L: experimental and modeling results

    Sahlaoui, H.; Makhlouf, K.; Sidhom, H.; Philibert, J

    2004-05-15

    Chromium carbides and intermetallic phases which form in industrial AISI 316L stainless steel during ageing for up to 80 000 h between 550 and 650 deg. C were identified by combining transmission electron microscopy (TEM) thin foil imaging and electron diffraction and used to establish the time-temperature-precipitation (TTP) diagram. Following the precipitation phenomena, the chemical changes in the grain boundary region were determined by energy-dispersive X-ray microprobe analysis using a scanning transmission electron microscope (STEM). From the experimentally determined chromium profiles the chromium depleted zones were quantified. The interactions between carbide precipitation involving chromium depletion and intergranular corrosion (IGC) were clearly visible from superposition of TTP diagrams and time-temperature-sensitization (TTS) diagrams obtained from ASTM standardized tests. In addition, an experimental criterion to sensitization-desensitization phenomenon was established. Moreover, an analytical model has been developed in this study and successfully validated to predict the profiles of chromium depleted zones. This model coupled with the previously described criterion provides TTS diagrams in good agreement with experimental results.

  2. Frequency of common CFTR gene mutations in Venezuelan patients with cystic fibrosis

    Sánchez, Karen; Arcia, Orlando; Matute, Xiorama; Mindiola, Luz; Chaustre, Ismenia; Takiff, Howard

    2014-01-01

    Mutations in the CFTR gene in Cystic Fibrosis (CF) patients have geographic differences and there is scant data on their prevalence in Venezuelan patients. This study determined the frequency of common CFTR gene mutations in these patients. We amplified and sequenced exons 7, 10, 11, 19, 20 and 21, which contain the most common CFTR mutations, from 105 Venezuelan patients in the National CF Program. Eleven different mutations were identified, four with frequencies greater than 1%: p.Phe508del...

  3. Intra-individual biological variation in sweat chloride concentrations in CF, CFTR dysfunction, and healthy pediatric subjects.

    Cirilli, Natalia; Raia, Valeria; Rocco, Ilaria; De Gregorio, Fabiola; Tosco, Antonella; Salvadori, Laura; Sepe, Angela Ornella; Buzzetti, Roberto; Minicuci, Nadia; Castaldo, Giuseppe

    2018-04-02

    The sweat test is one of the main diagnostic tools used in newborn screening programs and as a confirmatory test, in case of suspect of Cystic Fibrosis (CF). Since sweat chloride (Cl) concentration is also considered an appropriate parameter to explore the efficacy of CFTR modulators in clinical trials, it is crucial to evaluate the biological variability of this test in healthy and pathological conditions. The aim of this pilot study was to determine the intra-individual biological variability of sweat Cl, both in healthy individuals and CF patients and to assess its correlation with diet, season, and menstrual cycle. Thirty-five out of 36 selected subjects (6-18 years) were enrolled by 2 CF care centers and assigned to 3 cohorts: CF, CFTR-related disorder (CFTR-RD) and healthy volunteers. Each participant was subjected to eight sweat tests in different conditions and time of the year. Data were analyzed using linear mixed effects models for repeated measures, taking also into account intra-individual correlations. We observed a high intra-individual variability of sweat Cl, with the lowest mean CV% values among CF patients (20.21 in CF, 29.74 in CFTR-RD, and 31.15 in healthy subjects). Gender and diet had no influence on sweat Cl variability, nor had pubertal age and menstrual phase. Results of this pilot study confirmed that sweat Cl variability is high in CF patients, although non-CF individuals displayed even higher mean CV% values. Season significantly influenced sweat test values only in CF patients, likely due to changes in their hydration status. © 2018 Wiley Periodicals, Inc.

  4. CFTR mutation analysis and haplotype associations in CF patients☆

    Cordovado, S.K.; Hendrix, M.; Greene, C.N.; Mochal, S.; Earley, M.C.; Farrell, P.M.; Kharrazi, M.; Hannon, W.H.; Mueller, P.W.

    2011-01-01

    Most newborn screening (NBS) laboratories use second-tier molecular tests for cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease Control and Prevention’s NBS Quality Assurance Program offers proficiency testing (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation detection. Extensive molecular characterization on 76 CF patients, family members or screen positive newborns was performed for quality assurance. The coding, regulatory regions and por...

  5. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

    Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

    2015-05-29

    The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Cysteamine re-establishes the clearance of Pseudomonas aeruginosa by macrophages bearing the cystic fibrosis-relevant F508del-CFTR mutation.

    Ferrari, Eleonora; Monzani, Romina; Villella, Valeria R; Esposito, Speranza; Saluzzo, Francesca; Rossin, Federica; D'Eletto, Manuela; Tosco, Antonella; De Gregorio, Fabiola; Izzo, Valentina; Maiuri, Maria C; Kroemer, Guido; Raia, Valeria; Maiuri, Luigi

    2017-01-12

    Cystic fibrosis (CF), the most common lethal monogenic disease in Caucasians, is characterized by recurrent bacterial infections and colonization, mainly by Pseudomonas aeruginosa, resulting in unresolved airway inflammation. CF is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which functions as a chloride channel in epithelial cells, macrophages, and other cell types. Impaired bacterial handling by macrophages is a feature of CF airways, although it is still debated how defective CFTR impairs bacterial killing. Recent evidence indicates that a defective autophagy in CF macrophages leads to alterations of bacterial clearance upon infection. Here we use bone marrow-derived macrophages from transgenic mice to provide the genetic proof that defective CFTR compromises both uptake and clearance of internalized Pseudomonas aeruginosa. We demonstrate that the proteostasis regulator cysteamine, which rescues the function of the most common F508del-CFTR mutant and hence reduces lung inflammation in CF patients, can also repair the defects of CF macrophages, thus restoring both bacterial internalization and clearance through a process that involves upregulation of the pro-autophagic protein Beclin 1 and re-establishment of the autophagic pathway. Altogether these results indicate that cysteamine restores the function of several distinct cell types, including that of macrophages, which might contribute to its beneficial effects on CF.

  7. Cftr Modulates Wnt/β-Catenin Signaling and Stem Cell Proliferation in Murine Intestine

    Ashlee M. Strubberg

    2018-01-01

    Conclusions: CF intestine shows increased ISC proliferation and Wnt/β-catenin signaling. Loss of Cftr increases pHi in ISCs, which stabilizes the plasma membrane association of the Wnt transducer Dvl, likely facilitating Wnt/β-catenin signaling. Absence of Cftr-dependent suppression of ISC proliferation in the CF intestine may contribute to increased risk for intestinal tumors.

  8. Rescuing mutant CFTR: a multi-task approach to a better outcome in treating cystic fibrosis.

    Amaral, Margarida D; Farinha, Carlos M

    2013-01-01

    Correcting multiple defects of mutant CFTR with small molecule compounds has been the goal of an increasing number of recent Cystic Fibrosis (CF) drug discovery programmes. However, the mechanism of action (MoA) by which these molecules restore mutant CFTR is still poorly understood, in particular of CFTR correctors, i.e., compounds rescuing to the cells surface the most prevalent mutant in CF patients--F508del-CFTR. However, there is increasing evidence that to fully restore the multiple defects associated with F508del-CFTR, different small molecules with distinct corrective properties may be required. Towards this goal, a better insight into MoA of correctors is needed and several constraints should be addressed. The methodological approaches to achieve this include: 1) testing the combined effect of compounds with that of other (non-pharmacological) rescuing strategies (e.g., revertants or low temperature); 2) assessing effects in multiple cellular models (non-epithelial vs epithelial, non-human vs human, immortalized vs primary cultures, polarized vs non polarized, cells vs tissues); 3) assessing compound effects on isolated CFTR domains (e.g., compound binding by surface plasmon resonance, assessing effects on domain folding and aggregation); and finally 4) assessing compounds specificity in rescuing different CFTR mutants and other mutant proteins. These topics are reviewed and discussed here so as to provide a state-of-the art review on how to combine multiple ways of rescuing mutant CFTR to the ultimate benefit of CF patients.

  9. From the endoplasmic reticulum to the plasma membrane: mechanisms of CFTR folding and trafficking.

    Farinha, Carlos M; Canato, Sara

    2017-01-01

    CFTR biogenesis starts with its co-translational insertion into the membrane of endoplasmic reticulum and folding of the cytosolic domains, towards the acquisition of a fully folded compact native structure. Efficiency of this process is assessed by the ER quality control system that allows the exit of folded proteins but targets unfolded/misfolded CFTR to degradation. If allowed to leave the ER, CFTR is modified at the Golgi and reaches the post-Golgi compartments to be delivered to the plasma membrane where it functions as a cAMP- and phosphorylation-regulated chloride/bicarbonate channel. CFTR residence at the membrane is a balance of membrane delivery, endocytosis, and recycling. Several adaptors, motor, and scaffold proteins contribute to the regulation of CFTR stability and are involved in continuously assessing its structure through peripheral quality control systems. Regulation of CFTR biogenesis and traffic (and its dysregulation by mutations, such as the most common F508del) determine its overall activity and thus contribute to the fine modulation of chloride secretion and hydration of epithelial surfaces. This review covers old and recent knowledge on CFTR folding and trafficking from its synthesis to the regulation of its stability at the plasma membrane and highlights how several of these steps can be modulated to promote the rescue of mutant CFTR.

  10. Evaluation of potential regulatory elements identified as DNase I hypersensitive sites in the CFTR gene

    Phylactides, M.; Rowntree, R.; Nuthall, H.

    2002-01-01

    hypersensitive sites (DHS) within the locus. We previously identified at least 12 clusters of DHS across the CFTR gene and here further evaluate DHS in introns 2,3,10,16,17a, 18, 20 and 21 to assess their functional importance in regulation of CFTR gene expression. Transient transfections of enhancer/reporter...

  11. Compounds that correct F508del-CFTR trafficking can also correct other protein trafficking diseases: an in vitro study using cell lines

    Sampson Heidi M

    2013-01-01

    Full Text Available Abstract Background Many genetic diseases are due to defects in protein trafficking where the mutant protein is recognized by the quality control systems, retained in the endoplasmic reticulum (ER, and degraded by the proteasome. In many cases, the mutant protein retains function if it can be trafficked to its proper cellular location. We have identified structurally diverse correctors that restore the trafficking and function of the most common mutation causing cystic fibrosis, F508del-CFTR. Most of these correctors do not act directly as ligands of CFTR, but indirectly on other pathways to promote folding and correction. We hypothesize that these proteostasis regulators may also correct other protein trafficking diseases. Methods To test our hypothesis, we used stable cell lines or transient transfection to express 2 well-studied trafficking disease mutations in each of 3 different proteins: the arginine-vasopressin receptor 2 (AVPR2, also known as V2R, the human ether-a-go-go-related gene (KCNH2, also known as hERG, and finally the sulfonylurea receptor 1 (ABCC8, also known as SUR1. We treated cells expressing these mutant proteins with 9 structurally diverse F508del-CFTR correctors that function through different cellular mechanisms and assessed whether correction occurred via immunoblotting and functional assays. Results were deemed significantly different from controls by a one-way ANOVA (p  Results Here we show that F508del-CFTR correctors RDR1, KM60 and KM57 also correct some mutant alleles of other protein trafficking diseases. We also show that one corrector, the cardiac glycoside ouabain, was found to alter the glycosylation of all mutant alleles tested. Conclusions Correctors of F508del-CFTR trafficking might have broader applications to other protein trafficking diseases.

  12. Novel CFTR missense mutations in Brazilian patients with congenital absence of vas deferens: counseling issues Mutações novas no gene CFTR de pacientes brasileiros portadores de agenesia dos vasos deferentes: dificuldades no aconselhamento

    Patricia de Campos Pieri

    2007-01-01

    Full Text Available PURPOSE: Screening for mutations in the entire Cystic Fibrosis gene (CFTR of Brazilian infertile men with congenital absence of vas deferens, in order to prevent transmission of CFTR mutations to offspring with the use of assisted reproductive technologies. METHOD: Specific polymerase chain reaction (PCR primers were designed to each of the 27 exons and splicing sites of interest followed by single strand conformational polymorphism and Heteroduplex Analysis (SSCP-HA in precast 12.5% polyacrylamide gels at 7ºC and 20ºC. Fragments with abnormal SSCP migration pattern were sequenced. RESULTS: Two novel missense mutations (S753R and G149W were found in three patients (two brothers together with the IVS8-5T allele in hetrozygosis. CONCLUSION: The available screenings for CF mutations do not include the atypical mutations associated to absence of vas deferens and thus, when these tests fail to find mutations, there is still a genetic risk of affected children with the help of assisted reproduction. We recommend the screening of the whole CFTR gene for these infertile couples, as part of the work-up before assisted reproduction.OBJETIVO: Pesquisar mutações em toda a extensão do gene que causa a Fibrose Cística (CFTR de homens brasileiros inférteis por agenesia congênita dos vasos deferentes, com a finalidade de prevenir a transmissão de mutações em CFTR à prole com o uso das tecnologias de reprodução assistida. MÉTODOS: Foram desenhados oligonucleotídeos específicos para realização de reação de polimerização em cadeia (PCR para cada um dos 27 exons e sítios de processamento de interesse no gene CFTR. O PCR foi seguido pela técnica de SSCP-HA (polimorfismos de conformação no DNA de fita simples e na formação de heteroduplexes em géis pré-fabricados de poliacrilamida a 12,5% em duas temperaturas, 7ºC e 20ºC. Os fragmentos com padrão alterado na migração do SSCP foram submetidos a seqüenciamento automatizado

  13. Manipulating proteostasis to repair the F508del-CFTR defect in cystic fibrosis.

    Esposito, Speranza; Tosco, Antonella; Villella, Valeria R; Raia, Valeria; Kroemer, Guido; Maiuri, Luigi

    2016-12-01

    Cystic fibrosis (CF) is a lethal monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that entails the (diagnostic) increase in sweat electrolyte concentrations, progressive lung disease with chronic inflammation and recurrent bacterial infections, pancreatic insufficiency, and male infertility. Therapies aimed at restoring the CFTR defect have emerged. Thus, a small molecule which facilitates chloride channel opening, the potentiator Ivacaftor, has been approved for the treatment of CF patients bearing a particular class of rare CFTR mutations. However, small molecules that directly target the most common misfolded CFTR mutant, F508del, and improve its intracellular trafficking in vitro, have been less effective than expected when tested in CF patients, even in combination with Ivacaftor. Thus, new strategies are required to circumvent the F508del-CFTR defect. Airway and intestinal epithelial cells from CF patients bearing the F508del-CFTR mutation exhibit an impressive derangement of cellular proteostasis, with oxidative stress, overactivation of the tissue transglutaminase (TG2), and disabled autophagy. Proteostasis regulators such as cysteamine can rescue and stabilize a functional F508del-CFTR protein through suppressing TG2 activation and restoring autophagy in vivo in F508del-CFTR homozygous mice, in vitro in CF patient-derived cell lines, ex vivo in freshly collected primary patient's nasal cells, as well as in a pilot clinical trial involving homozygous F508del-CFTR patients. Here, we discuss how the therapeutic normalization of defective proteostasis can be harnessed for the treatment of CF patients with the F508del-CFTR mutation.

  14. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium

    Walker, Nancy M.; Liu, Jinghua; Stein, Sydney R.; Stefanski, Casey D.; Strubberg, Ashlee M.

    2015-01-01

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl− and HCO3− efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3−)-loading proteins and upregulation of the basolateral membrane HCO3−-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl−/HCO3− exchange with maximized gradients, it also had increased intracellular Cl− concentration relative to wild-type. Pharmacological reduction of intracellular Cl− concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl− and HCO3− efflux, which impairs pHi regulation by Ae2. Retention of Cl− and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. PMID:26542396

  15. Rab4GTPase modulates CFTR function by impairing channel expression at plasma membrane

    Saxena, Sunil K.; Kaur, Simarna; George, Constantine

    2006-01-01

    Cystic fibrosis (CF), an autosomal recessive disorder, is caused by the disruption of biosynthesis or the function of a membrane cAMP-activated chloride channel, CFTR. CFTR regulatory mechanisms include recruitment of channel proteins to the cell surface from intracellular pools and by protein-protein interactions. Rab proteins are small GTPases involved in regulated trafficking controlling vesicle docking and fusion. Rab4 controls recycling events from endosome to the plasma membrane, fusion, and degradation. The colorectal cell line HT-29 natively expresses CFTR and responds to cAMP stimulation with an increase in CFTR-mediated currents. Rab4 over-expression in HT-29 cells inhibits both basal and cAMP-stimulated CFTR-mediated currents. GTPase-deficient Rab4Q67L and GDP locked Rab4S22N both inhibit channel activity, which appears characteristically different. Active status of Rab4 was confirmed by GTP overlay assay, while its expression was verified by Western blotting. The pull-down and immunoprecipitation experiments suggest that Rab4 physically interacts with CFTR through protein-protein interaction. Biotinylation with cell impermeant NHS-Sulfo-SS-Biotin implies that Rab4 impairs CFTR expression at cell surface. The enhanced cytosolic CFTR indicates that Rab4 expression restrains CFTR appearance at the cell membrane. The study suggests that Rab4 regulates the channel through multiple mechanisms that include protein-protein interaction, GTP/GDP exchange, and channel protein trafficking. We propose that Rab4 is a dynamic molecule with a significant role in CFTR function

  16. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.

    Walker, Nancy M; Liu, Jinghua; Stein, Sydney R; Stefanski, Casey D; Strubberg, Ashlee M; Clarke, Lane L

    2016-01-15

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. Copyright © 2016 the American Physiological Society.

  17. Intestinal epithelial cell-specific RARα depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system.

    Jijon, H B; Suarez-Lopez, L; Diaz, O E; Das, S; De Calisto, J; Yaffe, M B; Pittet, M J; Mora, J R; Belkaid, Y; Xavier, R J; Villablanca, E J

    2018-05-01

    Retinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined. Here we demonstrate that lack of RA receptor α (RARα) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells. Mechanistically, lack of RARα resulted in increased KLF4 + goblet cell precursors in the distal bowel, whereas RA treatment inhibited klf4 expression and goblet cell differentiation in zebrafish. These changes in secretory cells are associated with increased Reg3g, reduced luminal bacterial detection, and an underdeveloped intestinal immune system, as evidenced by an almost complete absence of lymphoid follicles and gut resident mononuclear phagocytes. This underdeveloped intestinal immune system shows a decreased ability to clear infection with Citrobacter rodentium. Collectively, our findings indicate that epithelial cell-intrinsic RARα signaling is critical to the global development of the intestinal immune system.

  18. Revisiting Antarctic Ozone Depletion

    Grooß, Jens-Uwe; Tritscher, Ines; Müller, Rolf

    2015-04-01

    Antarctic ozone depletion is known for almost three decades and it has been well settled that it is caused by chlorine catalysed ozone depletion inside the polar vortex. However, there are still some details, which need to be clarified. In particular, there is a current debate on the relative importance of liquid aerosol and crystalline NAT and ice particles for chlorine activation. Particles have a threefold impact on polar chlorine chemistry, temporary removal of HNO3 from the gas-phase (uptake), permanent removal of HNO3 from the atmosphere (denitrification), and chlorine activation through heterogeneous reactions. We have performed simulations with the Chemical Lagrangian Model of the Stratosphere (CLaMS) employing a recently developed algorithm for saturation-dependent NAT nucleation for the Antarctic winters 2011 and 2012. The simulation results are compared with different satellite observations. With the help of these simulations, we investigate the role of the different processes responsible for chlorine activation and ozone depletion. Especially the sensitivity with respect to the particle type has been investigated. If temperatures are artificially forced to only allow cold binary liquid aerosol, the simulation still shows significant chlorine activation and ozone depletion. The results of the 3-D Chemical Transport Model CLaMS simulations differ from purely Lagrangian longtime trajectory box model simulations which indicates the importance of mixing processes.

  19. Environmental Pollution in five floors (5th to 9th) Resulting from the use of Depleted Uranium Weaponry in the Al-Tahreer Tower Building

    Ameen, N.H; Al-ghirrawy, M.A; Kadhim, H.H

    2014-01-01

    The goals of this study include measuring the increase in radioactivity and removal the contamination regions to protect the population and the environment resulting from bombing the Al-Tahreer Tower Building (the Turkish restaurant previously) by the depleted uranium bullets through direct measurement and sampling of soil from five floors (Fifth,Sixth,Seventh,Eighth,and Ninth) of the building, which contains fourteen floors in addition to basement by using different types of portable monitoring equipment s.The results of radiological surveys by using the portable monitor (CAB) indicated the presence of contaminated soil reached to 55 c/sec, and small particles of depleted uranium shells has very high levels of contamination reached to 70 c /sec ,while the background level is (0.5 c/sec) ,and the higher exposure rates is 55 μR/hr when the portable monitor (Ludlum) put on the contaminated regions approximately on distance 0.5 cm), where the natural background level is 9 μR/hr in the floors of the building.The radiological analyses of the collected soil samples were done in the laboratory of the center of Radiological Researches in the Ministry of sciences and Technology by using gamma spectrometry (which contains High- purity Germanium Detector) with a efficiency of 40% and resolution 2 keV for Energy, 1.33Mev, collection, preparations and tests of soil samples were all done according to IAEA.The laboratory results indicated the presence of high concentrations of the isotopes Th-234 (1550.1) Bq/kg, and Pa-234 m (1394.8) in the soil samples taken from the floors while the concentrations of Th-234 and Pa-234 m in natural background levels are (nearly 40, nil) Bq/Kg respectively which is a clear indication of the presence of high concentrations an isotope of uranium - 238 as they are supposed to be in equilibrium radiation.

  20. Ego depletion impairs implicit learning.

    Thompson, Kelsey R; Sanchez, Daniel J; Wesley, Abigail H; Reber, Paul J

    2014-01-01

    Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

  1. Thermodynamic study of the native and phosphorylated regulatory domain of the CFTR

    Marasini, Carlotta, E-mail: marasini@ge.ibf.cnr.it [Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via De Marini 6, 16149 Genova (Italy); Galeno, Lauretta; Moran, Oscar [Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via De Marini 6, 16149 Genova (Italy)

    2012-07-06

    Highlights: Black-Right-Pointing-Pointer CFTR mutations produce cystic fibrosis. Black-Right-Pointing-Pointer Chloride transport depends on the regulatory domain phosphorylation. Black-Right-Pointing-Pointer Regulatory domain is intrinsically disordered. Black-Right-Pointing-Pointer Secondary structure and protein stability change upon phosphorylation. -- Abstract: The regulatory domain (RD) of the cystic fibrosis transmembrane conductance regulator (CFTR), the defective protein in cystic fibrosis, is the region of the channel that regulates the CFTR activity with multiple phosphorylation sites. This domain is an intrinsically disordered protein, characterized by lack of stable or unique tertiary structure. The disordered character of a protein is directly correlated with its function. The flexibility of RD may be important for its regulatory role: the continuous conformational change may be necessary for the progressive phosphorylation, and thus activation, of the channel. However, the lack of a defined and stable structure results in a considerable limitation when trying to in build a unique molecular model for the RD. Moreover, several evidences indicate significant structural differences between the native, non-phosphorylated state, and the multiple phosphorylated state of the protein. The aim of our work is to provide data to describe the conformations and the thermodynamic properties in these two functional states of RD. We have done the circular dichroism (CD) spectra in samples with a different degree of phosphorylation, from the non-phosphorylated state to a bona fide completely phosphorylated state. Analysis of CD spectra showed that the random coil and {beta}-sheets secondary structure decreased with the polypeptide phosphorylation, at expenses of an increase of {alpha}-helix. This observation lead to interpret phosphorylation as a mechanism favoring a more structured state. We also studied the thermal denaturation curves of the protein in the two

  2. Thermodynamic study of the native and phosphorylated regulatory domain of the CFTR

    Marasini, Carlotta; Galeno, Lauretta; Moran, Oscar

    2012-01-01

    Highlights: ► CFTR mutations produce cystic fibrosis. ► Chloride transport depends on the regulatory domain phosphorylation. ► Regulatory domain is intrinsically disordered. ► Secondary structure and protein stability change upon phosphorylation. -- Abstract: The regulatory domain (RD) of the cystic fibrosis transmembrane conductance regulator (CFTR), the defective protein in cystic fibrosis, is the region of the channel that regulates the CFTR activity with multiple phosphorylation sites. This domain is an intrinsically disordered protein, characterized by lack of stable or unique tertiary structure. The disordered character of a protein is directly correlated with its function. The flexibility of RD may be important for its regulatory role: the continuous conformational change may be necessary for the progressive phosphorylation, and thus activation, of the channel. However, the lack of a defined and stable structure results in a considerable limitation when trying to in build a unique molecular model for the RD. Moreover, several evidences indicate significant structural differences between the native, non-phosphorylated state, and the multiple phosphorylated state of the protein. The aim of our work is to provide data to describe the conformations and the thermodynamic properties in these two functional states of RD. We have done the circular dichroism (CD) spectra in samples with a different degree of phosphorylation, from the non-phosphorylated state to a bona fide completely phosphorylated state. Analysis of CD spectra showed that the random coil and β-sheets secondary structure decreased with the polypeptide phosphorylation, at expenses of an increase of α-helix. This observation lead to interpret phosphorylation as a mechanism favoring a more structured state. We also studied the thermal denaturation curves of the protein in the two conditions, monitoring the changes of the mean residue ellipticity measured at 222 nm as a function of temperature

  3. Functional cure of SIVagm infection in rhesus macaques results in complete recovery of CD4+ T cells and is reverted by CD8+ cell depletion.

    Ivona Pandrea

    2011-08-01

    Full Text Available Understanding the mechanism of infection control in elite controllers (EC may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly selected late time points in infection, after control is achieved, and the access to tissues is limited. We report that SIVagm infection is elite-controlled in rhesus macaques (RMs and therefore can be used as an animal model for EC HIV infection. A robust acute infection, with high levels of viral replication and dramatic mucosal CD4(+ T cell depletion, similar to pathogenic HIV-1/SIV infections of humans and RMs, was followed by complete and durable control of SIVagm replication, defined as: undetectable VLs in blood and tissues beginning 72 to 90 days postinoculation (pi and continuing at least 4 years; seroreversion; progressive recovery of mucosal CD4(+ T cells, with complete recovery by 4 years pi; normal levels of T cell immune activation, proliferation, and apoptosis; and no disease progression. This "functional cure" of SIVagm infection in RMs could be reverted after 4 years of control of infection by depleting CD8 cells, which resulted in transient rebounds of VLs, thus suggesting that control may be at least in part immune mediated. Viral control was independent of MHC, partial APOBEC restriction was not involved in SIVagm control in RMs and Trim5 genotypes did not impact viral replication. This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status.

  4. The HDAC inhibitor SAHA does not rescue CFTR membrane expression in Cystic Fibrosis.

    Bergougnoux, Anne; Petit, Aurélie; Knabe, Lucie; Bribes, Estelle; Chiron, Raphaël; De Sario, Albertina; Claustres, Mireille; Molinari, Nicolas; Vachier, Isabelle; Taulan-Cadars, Magali; Bourdin, Arnaud

    2017-07-01

    The development of suitable Cystic Fibrosis (CF) models for preclinical bench tests of therapeutic candidates is challenging. Indeed, the validation of molecules to rescue the p.Phe508del-CFTR channel (encoded by the Cystic Fibrosis Transmembrane conductance Regulator gene carrying the p.Phe508del mutation) requires taking into account their overall effects on the epithelium. Suberoylanilide Hydroxamic Acid (SAHA), a histone deacetylase inhibitor (HDACi), was previously shown to be a CFTR corrector via proteostasis modulation in CFTR-deficient immortalized cells. Here, we tested SAHA effects on goblet cell metaplasia using an ex vivo model based on the air-liquid interface (ALI) culture of differentiated airway epithelial cells obtained by nasal scraping from CF patients and healthy controls. Ex vivo epithelium grew successfully in ALI cultures with significant rise in the expression of CFTR and of markers of airway epithelial differentiation compared to monolayer cell culture. SAHA decreased CFTR transcript and protein levels in CF and non-CF epithelia. Whereas SAHA induced lysine hyperacetylation, it did not change histone modifications at the CFTR promoter. SAHA reduced MUC5AC and MUC5B expression and inhibited goblet epithelial cell differentiation. Similar effects were obtained in CF and non-CF epithelia. All the effects were fully reversible within five days from SAHA withdrawal. We conclude that, ex vivo, SAHA modulate the structure of airway epithelia without specific effect on CFTR gene and protein suggesting that HDACi cannot be useful for CF treatment. Copyright © 2017. Published by Elsevier Ltd.

  5. The cystic fibrosis transmembrane recruiter the alter ego of CFTR as a multi-kinase anchor.

    Mehta, Anil

    2007-11-01

    This review focuses on a newly discovered interaction between protein kinases involved in cellular energetics, a process that may be disturbed in cystic fibrosis for unknown reasons. I propose a new model where kinase-mediated cellular transmission of energy provides mechanistic insight to a latent role of the cystic fibrosis transmembrane conductance regulator (CFTR). I suggest that CFTR acts as a multi-kinase recruiter to the apical epithelial membrane. My group finds that, in the cytosol, two protein kinases involved in cell energy homeostasis, nucleoside diphosphate kinase (NDPK) and AMP-activated kinase (AMPK), bind one another. Preliminary data suggest that both can also bind CFTR (function unclear). The disrupted role of this CFTR-kinase complex as 'membrane transmitter to the cell' is proposed as an alternative paradigm to the conventional ion transport mediated and CFTR/chloride-centric view of cystic fibrosis pathogenesis. Chloride remains important, but instead, chloride-induced control of the phosphohistidine content of one kinase component (NDPK, via a multi-kinase complex that also includes a third kinase, CK2; formerly casein kinase 2). I suggest that this complex provides the necessary near-equilibrium conditions needed for efficient transmission of phosphate energy to proteins controlling cellular energetics. Crucially, a new role for CFTR as a kinase controller is proposed with ionic concentration acting as a signal. The model posits a regulatory control relay for energy sensing involving a cascade of protein kinases bound to CFTR.

  6. Optimizing nasal potential difference analysis for CFTR modulator development: assessment of ivacaftor in CF subjects with the G551D-CFTR mutation.

    Steven M Rowe

    Full Text Available Nasal potential difference (NPD is used as a biomarker of the cystic fibrosis transmembrane conductance regulator (CFTR and epithelial sodium channel (ENaC activity. We evaluated methods to detect changes in chloride and sodium transport by NPD based on a secondary analysis of a Phase II CFTR-modulator study. Thirty-nine subjects with CF who also had the G551D-CFTR mutation were randomized to receive ivacaftor (Kalydeco™; also known as VX-770 in four doses or placebo twice daily for at least 14 days. All data were analyzed by a single investigator who was blinded to treatment assignment. We compared three analysis methods to determine the best approach to quantify changes in chloride and sodium transport: (1 the average of both nostrils; (2 the most-polarized nostril at each visit; and (3 the most-polarized nostril at screening carried forward. Parameters of ion transport included the PD change with zero chloride plus isoproterenol (CFTR activity, the basal PD, Ringer's PD, and change in PD with amiloride (measurements of ENaC activity, and the delta NPD (measuring CFTR and ENaC activity. The average and most-polarized nostril at each visit were most sensitive to changes in chloride and sodium transport, whereas the most-polarized nostril at screening carried forward was less discriminatory. Based on our findings, NPD studies should assess both nostrils rather than a single nostril. We also found that changes in CFTR activity were more readily detected than changes in ENaC activity, and that rigorous standardization was associated with relatively good within-subject reproducibility in placebo-treated subjects (± 2.8 mV. Therefore, we have confirmed an assay of reasonable reproducibility for detecting chloride-transport improvements in response to CFTR modulation.

  7. NM23 proteins: innocent bystanders or local energy boosters for CFTR?

    Muimo, Richmond; Alothaid, Hani Mm; Mehta, Anil

    2018-03-01

    NM23 proteins NDPK-A and -B bind to the cystic fibrosis (CF) protein CFTR in different ways from kinases such as PKA, CK2 and AMPK or linkers to cell calcium such as calmodulin and annexins. NDPK-A (not -B) interacts with CFTR through reciprocal AMPK binding/control, whereas NDPK-B (not -A) binds directly to CFTR. NDPK-B can activate G proteins without ligand-receptor coupling, so perhaps NDPK-B's binding influences energy supply local to a nucleotide-binding site (NBD1) needed for CFTR to function. Curiously, CFTR (ABC-C7) is a member of the ATP-binding cassette (ABC) protein family that does not obey 'clan rules'; CFTR channels anions and is not a pump, regulates disparate processes, is itself regulated by multiple means and is so pleiotropic that it acts as a hub that orchestrates calcium signaling through its consorts such as calmodulin/annexins. Furthermore, its multiple partners make CFTR dance to different tunes in different cellular and subcellular locations as it recycles from the plasma membrane to endosomes. CFTR function in airway apical membranes is inhibited by smoking which has been dubbed 'acquired CF'. CFTR alone among family members possesses a trap for other proteins that it unfurls as a 'fish-net' and which bears consensus phosphorylation sites for many protein kinases, with PKA being the most canonical. Recently, the site of CFTR's commonest mutation has been proposed as a knock-in mutant that alters allosteric control of kinase CK2 by log orders of activity towards calmodulin and other substrates after CFTR fragmentation. This link from CK2 to calmodulin that binds the R region invokes molecular paths that control lumen formation, which is incomplete in the tracheas of some CF-affected babies. Thus, we are poised to understand the many roles of NDPK-A and -B in CFTR function and, especially lumen formation, which is defective in the gut and lungs of many CF babies.

  8. CFTR Genotype and Maximal Exercise Capacity in Cystic Fibrosis: A Cross-sectional Study.

    Radtke, Thomas; Hebestreit, Helge; Gallati, Sabina; Schneiderman, Jane E; Braun, Julia; Stevens, Daniel; Hulzebos, Erik Hj; Takken, Tim; Boas, Steven R; Urquhart, Don S; Lands, Larry C; Tejero, Sergio; Sovtic, Aleksandar; Dwyer, Tiffany; Petrovic, Milos; Harris, Ryan A; Karila, Chantal; Savi, Daniela; Usemann, Jakob; Mei-Zahav, Meir; Hatziagorou, Elpis; Ratjen, Felix; Kriemler, Susi

    2018-02-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with cystic fibrosis may be an important determinant of maximal exercise capacity in cystic fibrosis. Previous studies on the relationship between CFTR genotype and maximal exercise capacity are scarce and contradictory. This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (V.O2peak), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. In an international, multicenter, cross-sectional study, we collected data on CFTR genotype and cardiopulmonary exercise tests in patients with cystic fibrosis who were ages 8 years and older. CFTR mutations were classified into functional classes I–V. The final analysis included 726 patients (45% females; age range, 8–61 yr; forced expiratory volume in 1 s, 16 to 123% predicted) from 17 cystic fibrosis centers in North America, Europe, Australia, and Asia, all of whom had both valid maximal cardiopulmonary exercise tests and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (V.O2peak, 77.3 ± 19.1% predicted), but values were comparable among different CFTR classes. We did not detect an association between CFTR genotype functional classes I–III and either V.O2peak (percent predicted) (adjusted β = −0.95; 95% CI, −4.18 to 2.29; P = 0.57) or maximum work rate (Wattmax) (adjusted β = −1.38; 95% CI, −5.04 to 2.27; P = 0.46) compared with classes IV–V. Those with at least one copy of a F508del-CFTR mutation and one copy of a class V mutation had a significantly lower V.O2peak (β = −8.24%; 95% CI, −14.53 to −2.99; P = 0.003) and lower Wattmax (adjusted β = −7.59%; 95% CI, −14.21 to −0.95; P = 0.025) than those with two copies of a class II mutation. On the basis of linear regression analysis adjusted for

  9. A survey of detergents for the purification of stable, active human cystic fibrosis transmembrane conductance regulator (CFTR).

    Hildebrandt, Ellen; Zhang, Qinghai; Cant, Natasha; Ding, Haitao; Dai, Qun; Peng, Lingling; Fu, Yu; DeLucas, Lawrence J; Ford, Robert; Kappes, John C; Urbatsch, Ina L

    2014-11-01

    Structural knowledge of the cystic fibrosis transmembrane conductance regulator (CFTR) requires developing methods to purify and stabilize this aggregation-prone membrane protein above 1mg/ml. Starting with green fluorescent protein- and epitope-tagged human CFTR produced in mammalian cells known to properly fold and process CFTR, we devised a rapid tandem affinity purification scheme to minimize CFTR exposure to detergent in order to preserve its ATPase function. We compared a panel of detergents, including widely used detergents (maltosides, neopentyl glycols (MNG), C12E8, lysolipids, Chaps) and innovative detergents (branched alkylmaltosides, facial amphiphiles) for CFTR purification, function, monodispersity and stability. ATPase activity after reconstitution into proteoliposomes was 2-3 times higher when CFTR was purified using facial amphiphiles. ATPase activity was also demonstrated in purified CFTR samples without detergent removal using a novel lipid supplementation assay. By electron microscopy, negatively stained CFTR samples were monodisperse at low concentration, and size exclusion chromatography showed a predominance of monomer even after CFTR concentration above 1mg/ml. Rates of CFTR aggregation quantified in an electrophoretic mobility shift assay showed that detergents which best preserved reconstituted ATPase activity also supported the greatest stability, with CFTR monomer half-lives of 6-9days in MNG or Chaps, and 12-17days in facial amphiphile. Cryoelectron microscopy of concentrated CFTR in MNG or facial amphiphile confirmed mostly monomeric protein, producing low resolution reconstructions in conformity with similar proteins. These protocols can be used to generate samples of pure, functional, stable CFTR at concentrations amenable to biophysical characterization. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Comparison of depletion results for a boiling water reactor fuel element with CASMO and SCALE 6.1 (TRITON/NEWT)

    Mesado, C.; Morera, D.; Miro, R.; Barrachina, T.; Verdu, G.; Soler, Amparo; Melara, Jose

    2013-01-01

    In this work, the results of depletion calculations with CASMO and SCALE 6.1 (TRITON) are compared. To achieve it, a region of a Boiling Water Reactor (BWR) fuel element is modeled, using both codes. To take into account different operating conditions, the simulations are repeated with different void fraction, ranging from null void fraction to a void fraction closed to one. Special care was used to keep in mind that the homogenization of the materials and the two group approach was the same in both codes. Additionally, KENO-VI and MCDANCOFF modules are used. The k-effective calculated by KENO-VI is used to ensure that the starting point was correct and MCDANCOFF module is used to calculate the Dancoff factors in order to improve the model accuracy. To validate the whole process, a comparison of k eff , and cross-sections collapsed and homogenized is shown. The results show a very good agreement, with an average error around the 1.75%. Furthermore, an automatic process for translating CASMO data to SCALE input decks was developed. The reason for the translation is the fact that SCALE's TRITON module is a new code very powerful and continuously being developed. Thus, great advantage can be taken from the current and future SCALE features. This is hoped to produce more realistic models, and hence, increase the accuracy of neutronic libraries. (author)

  11. Comparative Analysis of VERA Depletion Problems

    Park, Jinsu; Kim, Wonkyeong; Choi, Sooyoung; Lee, Hyunsuk; Lee, Deokjung

    2016-01-01

    Each code has its own solver for depletion, which can produce different depletion calculation results. In order to produce reference solutions for depletion calculation comparison, sensitivity studies should be preceded for each depletion solver. The sensitivity tests for burnup interval, number of depletion zones, and recoverable energy per fission (Q-value) were performed in this paper. For the comparison of depletion calculation results, usually the multiplication factors are compared as a function of burnup. In this study, new comparison methods have been introduced by using the number density of isotope or element, and a cumulative flux instead of burnup. In this paper, optimum depletion calculation options are determined through the sensitivity study of the burnup intervals and the number of depletion intrazones. Because the depletion using CRAM solver performs well for large burnup intervals, smaller number of burnup steps can be used to produce converged solutions. It was noted that the depletion intra-zone sensitivity is only pin-type dependent. The 1 and 10 depletion intra-zones for the normal UO2 pin and gadolinia rod, respectively, are required to obtain the reference solutions. When the optimized depletion calculation options are used, the differences of Q-values are found to be a main cause of the differences of solutions. In this paper, new comparison methods were introduced for consistent code-to-code comparisons even when different kappa libraries were used in the depletion calculations

  12. Ozone-Depleting Gases in the Atmosphere: Results From 28 Years of Measurements by the NOAA Climate Monitoring and Diagnostics Laboratory (CMDL)

    Hurst, D. F.; Elkins, J. W.; Montzka, S. A.; Butler, J. H.; Dutton, G. S.; Hall, B. D.; Mondeel, D. J.; Moore, F. L.; Nance, J. D.; Romashkin, P. A.; Thompson, T. M.

    2005-12-01

    Back in 1978, NOAA/CMDL initiated the weekly filling of flasks at CMDL observatories in Alaska, Hawaii, American Samoa, and Antarctica for analyses of CFC-11, CFC-12 and N2O in the home laboratory. A decade later, each observatory was outfitted with an automated gas chromatograph to make routine, in situ measurements of these three source gases plus methyl chloroform and carbon tetrachloride. Both measurement programs are ongoing, having expanded over the years to include methyl halides and substitutes for regulated halocarbons, to presently account for 95% of the total burden of long-lived Cl and Br believed to enter the stratosphere. These long-term monitoring data have been assimilated into temporal records of the global tropospheric burdens of ozone-depleting chlorine and bromine which are critical input to models that predict future trends in stratospheric ozone. Other information pivotal to ozone projections, such as the atmospheric lifetimes of source gases, stratospheric entry values for total chlorine and total bromine, and identification of the stratospheric sink regions for long-lived source gases, has been gained from in situ measurements by NOAA/CMDL instruments aboard NASA high-altitude aircraft (ER-2 and WB-57) and balloons since 1991. Though CMDL's routine monitoring activities provide important historical records of halogenated source gases in the atmosphere, significant inaccuracies in ozone projections may propagate from the uncertain estimates of impending emissions of ozone-depleting gases. Scenarios of future halocarbon emissions require substantial assumptions about past and pending compliance with the Montreal Protocol, and the sizes and release rates of existing global reservoirs (banks) of halocarbons. Recent work by CMDL has focused on quantifying halocarbon bank emission rates in Russia, the USA, and Canada through geographically extensive measurements aboard trains and low-altitude aircraft. The USA and Canada results indicate that

  13. Purification and crystallization of the cystic fibrosis transmembrane conductance regulator (CFTR).

    Rosenberg, Mark F; Kamis, Alhaji Bukar; Aleksandrov, Luba A; Ford, Robert C; Riordan, John R

    2004-09-10

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein that is mutated in patients suffering from cystic fibrosis. Here we report the purification and first crystallization of wild-type human CFTR. Functional characterization of the material showed it to be highly active. Electron crystallography of negatively stained two-dimensional crystals of CFTR has revealed the overall architecture of this channel for two different conformational states. These show a strong structural homology to two conformational states of another eukaryotic ATP-binding cassette transporter, P-glycoprotein. In contrast to P-glycoprotein, however, both conformational states can be observed in the presence of a nucleotide, which may be related to the role of CFTR as an ion channel rather than a transporter. The hypothesis that the two conformations could represent the "open" and "closed" states of the channel is considered.

  14. Computational design of a PDZ domain peptide inhibitor that rescues CFTR activity.

    Kyle E Roberts

    Full Text Available The cystic fibrosis transmembrane conductance regulator (CFTR is an epithelial chloride channel mutated in patients with cystic fibrosis (CF. The most prevalent CFTR mutation, ΔF508, blocks folding in the endoplasmic reticulum. Recent work has shown that some ΔF508-CFTR channel activity can be recovered by pharmaceutical modulators ("potentiators" and "correctors", but ΔF508-CFTR can still be rapidly degraded via a lysosomal pathway involving the CFTR-associated ligand (CAL, which binds CFTR via a PDZ interaction domain. We present a study that goes from theory, to new structure-based computational design algorithms, to computational predictions, to biochemical testing and ultimately to epithelial-cell validation of novel, effective CAL PDZ inhibitors (called "stabilizers" that rescue ΔF508-CFTR activity. To design the "stabilizers", we extended our structural ensemble-based computational protein redesign algorithm K* to encompass protein-protein and protein-peptide interactions. The computational predictions achieved high accuracy: all of the top-predicted peptide inhibitors bound well to CAL. Furthermore, when compared to state-of-the-art CAL inhibitors, our design methodology achieved higher affinity and increased binding efficiency. The designed inhibitor with the highest affinity for CAL (kCAL01 binds six-fold more tightly than the previous best hexamer (iCAL35, and 170-fold more tightly than the CFTR C-terminus. We show that kCAL01 has physiological activity and can rescue chloride efflux in CF patient-derived airway epithelial cells. Since stabilizers address a different cellular CF defect from potentiators and correctors, our inhibitors provide an additional therapeutic pathway that can be used in conjunction with current methods.

  15. Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations.

    Pompei, Fiorenza; Ciminelli, Bianca Maria; Bombieri, Cristina; Ciccacci, Cinzia; Koudova, Monika; Giorgi, Silvia; Belpinati, Francesca; Begnini, Angela; Cerny, Milos; Des Georges, Marie; Claustres, Mireille; Ferec, Claude; Macek, Milan; Modiano, Guido; Pignatti, Pier Franco

    2006-01-01

    An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed.

  16. Depletion of regulatory T cells in a hapten-induced inflammation model results in prolonged and increased inflammation driven by T cells

    Christensen, A. D.; Skov, Søren; Kvist, P. H.

    2015-01-01

    Regulatory T cells (Tregs ) are known to play an immunosuppressive role in the response of contact hypersensitivity (CHS), but neither the dynamics of Tregs during the CHS response nor the exaggerated inflammatory response after depletion of Tregs has been characterized in detail. In this study we...... show that the number of Tregs in the challenged tissue peak at the same time as the ear-swelling reaches its maximum on day 1 after challenge, whereas the number of Tregs in the draining lymph nodes peaks at day 2. As expected, depletion of Tregs by injection of a monoclonal antibody to CD25 prior...

  17. Genomic sequencing in cystic fibrosis newborn screening: what works best, two-tier predefined CFTR mutation panels or second-tier CFTR panel followed by third-tier sequencing?

    Currier, Robert J; Sciortino, Stan; Liu, Ruiling; Bishop, Tracey; Alikhani Koupaei, Rasoul; Feuchtbaum, Lisa

    2017-10-01

    PurposeThe purpose of this study was to model the performance of several known two-tier, predefined mutation panels and three-tier algorithms for cystic fibrosis (CF) screening utilizing the ethnically diverse California population.MethodsThe cystic fibrosis transmembrane conductance regulator (CFTR) mutations identified among the 317 CF cases in California screened between 12 August 2008 and 18 December 2012 were used to compare the expected CF detection rates for several two- and three-tier screening approaches, including the current California approach, which consists of a population-specific 40-mutation panel followed by third-tier sequencing when indicated.ResultsThe data show that the strategy of using third-tier sequencing improves CF detection following an initial elevated immunoreactive trypsinogen and detection of only one mutation on a second-tier panel.ConclusionIn a diverse population, the use of a second-tier panel followed by third-tier CFTR gene sequencing provides a better detection rate for CF, compared with the use of a second-tier approach alone, and is an effective way to minimize the referrals of CF carriers for sweat testing. Restricting screening to a second-tier testing to predefined mutation panels, even broad ones, results in some missed CF cases and demonstrates the limited utility of this approach in states that have diverse multiethnic populations.

  18. Ego Depletion Impairs Implicit Learning

    Thompson, Kelsey R.; Sanchez, Daniel J.; Wesley, Abigail H.; Reber, Paul J.

    2014-01-01

    Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent. PMID:25275517

  19. Ego depletion impairs implicit learning.

    Kelsey R Thompson

    Full Text Available Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

  20. Leukocyte-depletion of blood components does not significantly reduce the risk of infectious complications. Results of a double-blinded, randomized study

    Titlestad, I. L.; Ebbesen, L. S.; Ainsworth, A. P.

    2001-01-01

    Allogeneic blood transfusions are claimed to be an independent risk factor for postoperative infections in open colorectal surgery due to immunomodulation. Leukocyte-depletion of erythrocyte suspensions has been shown in some open randomized studies to reduce the rate of postoperative infection t...

  1. EG-VEGF, BV8, and their receptor expression in human bronchi and their modification in cystic fibrosis: Impact of CFTR mutation (delF508).

    Chauvet, Sylvain; Traboulsi, Wael; Thevenon, Laura; Kouadri, Amal; Feige, Jean-Jacques; Camara, Boubou; Alfaidy, Nadia; Benharouga, Mohamed

    2015-08-01

    Enhanced lung angiogenesis has been reported in cystic fibrosis (CF). Recently, two highly homologous ligands, endocrine gland vascular endothelial growth factor (EG-VEGF) and mammalian Bv8, have been described as new angiogenic factors. Both ligands bind and activate two closely related G protein-coupled receptors, the prokineticin receptor (PROKR) 1 and 2. Yet, the expression, regulation, and potential role of EG-VEGF, BV8, and their receptors in normal and CF lung are still unknown. The expression of the receptors and their ligands was examined using molecular, biochemical, and immunocytochemistry analyses in lungs obtained from CF patients vs. control and in normal and CF bronchial epithelial cells. Cystic fibrosis transmembrane conductance regulator (CFTR) activity was evaluated in relation to both ligands, and concentrations of EG-VEGF were measured by ELISA. At the mRNA level, EG-VEGF, BV8, and PROKR2 gene expression was, respectively, approximately five, four, and two times higher in CF lungs compared with the controls. At the cellular level, both the ligands and their receptors showed elevated expressions in the CF condition. Similar results were observed at the protein level. The EG-VEGF secretion was apical and was approximately two times higher in CF compared with the normal epithelial cells. This secretion was increased following the inhibition of CFTR chloride channel activity. More importantly, EG-VEGF and BV8 increased the intracellular concentration of Ca(2+) and cAMP and stimulated CFTR-chloride channel activity. Altogether, these data suggest local roles for epithelial BV8 and EG-VEGF in the CF airway peribronchial vascular remodeling and highlighted the role of CFTR activity in both ligand biosynthesis and secretion. Copyright © 2015 the American Physiological Society.

  2. Depleted uranium management alternatives

    Hertzler, T.J.; Nishimoto, D.D.

    1994-08-01

    This report evaluates two management alternatives for Department of Energy depleted uranium: continued storage as uranium hexafluoride, and conversion to uranium metal and fabrication to shielding for spent nuclear fuel containers. The results will be used to compare the costs with other alternatives, such as disposal. Cost estimates for the continued storage alternative are based on a life-cycle of 27 years through the year 2020. Cost estimates for the recycle alternative are based on existing conversion process costs and Capital costs for fabricating the containers. Additionally, the recycle alternative accounts for costs associated with intermediate product resale and secondary waste disposal for materials generated during the conversion process.

  3. Consequences of biome depletion

    Salvucci, Emiliano

    2013-01-01

    The human microbiome is an integral part of the superorganism together with their host and they have co-evolved since the early days of the existence of the human species. The modification of the microbiome as a result changes in food and social habits of human beings throughout their life history has led to the emergence of many diseases. In contrast with the Darwinian view of nature of selfishness and competence, new holistic approaches are rising. Under these views, the reconstitution of the microbiome comes out as a fundamental therapy for emerging diseases related to biome depletion.

  4. Depleted uranium management alternatives

    Hertzler, T.J.; Nishimoto, D.D.

    1994-08-01

    This report evaluates two management alternatives for Department of Energy depleted uranium: continued storage as uranium hexafluoride, and conversion to uranium metal and fabrication to shielding for spent nuclear fuel containers. The results will be used to compare the costs with other alternatives, such as disposal. Cost estimates for the continued storage alternative are based on a life-cycle of 27 years through the year 2020. Cost estimates for the recycle alternative are based on existing conversion process costs and Capital costs for fabricating the containers. Additionally, the recycle alternative accounts for costs associated with intermediate product resale and secondary waste disposal for materials generated during the conversion process

  5. Two Salt Bridges Differentially Contribute to the Maintenance of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channel Function*

    Cui, Guiying; Freeman, Cody S.; Knotts, Taylor; Prince, Chengyu Z.; Kuang, Christopher; McCarty, Nael A.

    2013-01-01

    Previous studies have identified two salt bridges in human CFTR chloride ion channels, Arg352-Asp993 and Arg347-Asp924, that are required for normal channel function. In the present study, we determined how the two salt bridges cooperate to maintain the open pore architecture of CFTR. Our data suggest that Arg347 not only interacts with Asp924 but also interacts with Asp993. The tripartite interaction Arg347-Asp924-Asp993 mainly contributes to maintaining a stable s2 open subconductance state. The Arg352-Asp993 salt bridge, in contrast, is involved in stabilizing both the s2 and full (f) open conductance states, with the main contribution being to the f state. The s1 subconductance state does not require either salt bridge. In confirmation of the role of Arg352 and Asp993, channels bearing cysteines at these sites could be latched into a full open state using the bifunctional cross-linker 1,2-ethanediyl bismethanethiosulfonate, but only when applied in the open state. Channels remained latched open even after washout of ATP. The results suggest that these interacting residues contribute differently to stabilizing the open pore in different phases of the gating cycle. PMID:23709221

  6. A little CFTR goes a long way: CFTR-dependent sweat secretion from G551D and R117H-5T cystic fibrosis subjects taking ivacaftor.

    Jessica E Char

    Full Text Available To determine if oral dosing with the CFTR-potentiator ivacaftor (VX-770, Kalydeco improves CFTR-dependent sweating in CF subjects carrying G551D or R117H-5T mutations, we optically measured sweat secretion from 32-143 individually identified glands in each of 8 CF subjects; 6 F508del/G551D, one G551D/R117H-5T, and one I507del/R117H-5T. Two subjects were tested only (- ivacaftor, 3 only (+ ivacaftor and 3 (+/- ivacaftor (1-5 tests per condition. The total number of gland measurements was 852 (- ivacaftor and 906 (+ ivacaftor. A healthy control was tested 4 times (51 glands. For each gland we measured both CFTR-independent (M-sweat and CFTR-dependent (C-sweat; C-sweat was stimulated with a β-adrenergic cocktail that elevated [cAMP]i while blocking muscarinic receptors. Absent ivacaftor, almost all CF glands produced M-sweat on all tests, but only 1/593 glands produced C-sweat (10 tests, 5 subjects. By contrast, 6/6 subjects (113/342 glands produced C-sweat in the (+ ivacaftor condition, but with large inter-subject differences; 3-74% of glands responded with C/M sweat ratios 0.04%-2.57% of the average WT ratio of 0.265. Sweat volume losses cause proportionally larger underestimates of CFTR function at lower sweat rates. The losses were reduced by measuring C/M ratios in 12 glands from each subject that had the highest M-sweat rates. Remaining losses were estimated from single channel data and used to correct the C/M ratios, giving estimates of CFTR function (+ ivacaftor  = 1.6%-7.7% of the WT average. These estimates are in accord with single channel data and transcript analysis, and suggest that significant clinical benefit can be produced by low levels of CFTR function.

  7. Curcumin/poly(2-methyl-2-oxazoline-b-tetrahydrofuran-b-2-methyl-2-oxazoline) formulation: An improved penetration and biological effect of curcumin in F508del-CFTR cell lines.

    Gonçalves, Cristine; Gomez, Jean-Pierre; Même, William; Rasolonjatovo, Bazoly; Gosset, David; Nedellec, Steven; Hulin, Philippe; Huin, Cécile; Le Gall, Tony; Montier, Tristan; Lehn, Pierre; Pichon, Chantal; Guégan, Philippe; Cheradame, Hervé; Midoux, Patrick

    2017-08-01

    Neutral amphiphilic triblock ABA copolymers are of great interest to solubilize hydrophobic drugs. We reported that a triblock ABA copolymer consisting of methyl-2-oxazoline (MeOx) and tetrahydrofuran (THF) (MeOx 6 -THF 19 -MeOx 6 ) (TBCP2) can solubilize curcumin (Cur) a very hydrophobic molecule exhibiting multiple therapeutic effects but whose insolubility and low stability in water is a major drawback for clinical applications. Here, we provide evidences by flow cytometry and confocal microscopy that Cur penetration in normal and ΔF508-CFTR human airway epithelial cell lines is facilitated by TBCP2. When used on ΔF508-CFTR cell lines, the Cur/TBCP2 formulation promotes the restoration of the expression of the CFTR protein in the plasma membrane. Furthermore, patch-clamp and MQAE fluorescence experiments show that this effect is associated with a correction of a Cl - selective current at the membrane surface of F508del-CFTR cells. The results show the great potential of the neutral amphiphilic triblock copolymer MeOx 6 -THF 19 -MeOx 6 as carrier for curcumin in a Cystic Fibrosis context. We anticipate that other MeOx n -THF m -MeOx n copolymers could have similar behaviours for other highly insoluble therapeutic drugs or cosmetic active ingredients. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Combinatorial effects of genistein and sex-steroids on the level of cystic fibrosis transmembrane regulator (CFTR), adenylate cyclase (AC) and cAMP in the cervix of ovariectomised rats.

    Salleh, Naguib; Ismail, Nurain; Muniandy, Sekaran; Korla, Praveen Kumar; Giribabu, Nelli

    2015-12-01

    The combinatorial effects of genistein and estrogen (E) or estrogen plus progesterone (E+P) on CFTR, AC and cAMP levels in cervix were investigated. Ovariectomised adult female rats received 50 or 100mg/kg/day genistein with E or E followed by E+P [E+(E+P)] for seven consecutive days. Cervixes were harvested and analyzed for CFTR mRNA levels by Real-time PCR. Distribution of AC and CFTR proteins in endocervix were observed by immunohistochemistry. Levels of cAMP were measured by enzyme-immunoassay. Molecular docking predicted interaction between genistein and AC. Our results indicate that levels of CFTR, AC and cAMP in cervix of rats receiving genistein plus E were higher than E-only treatment (pcervix of E and E+(E+P)-treated rats by genistein could affect the cervical secretory function which could influence the female reproductive processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr-/-) mouse model with hepato-biliary pathology.

    Bodewes, Frank A J A; van der Wulp, Mariëtte Y M; Beharry, Satti; Doktorova, Marcela; Havinga, Rick; Boverhof, Renze; James Phillips, M; Durie, Peter R; Verkade, Henkjan J

    2015-07-01

    Cftr(-/-tm1Unc) mice develop progressive hepato-biliary pathology. We hypothesize that this liver pathology is related to alterations in biliary bile hydrophobicity and bile salt metabolism in Cftr(-/-tm1Unc) mice. We determined bile production, biliary and fecal bile salt- and lipid compositions and fecal bacterial composition of C57BL/6J Cftr(-/-tm1Unc) and control mice. We found no differences between the total biliary bile salt or lipid concentrations of Cftr(-/-) and controls. Compared to controls, Cftr(-/-) mice had a ~30% higher bile production and a low bile hydrophobicity, related to a ~7 fold higher concentration of the choleretic and hydrophilic bile salt ursocholate. These findings coexisted with a significantly smaller quantity of fecal Bacteroides bacteria. Liver pathology in Cftr(-/-tm1Unc) is not related to increased bile hydrophobicity. Cftr(-/-) mice do however display a biliary phenotype characterized by increased bile production and decreased biliary hydrophobicity. Our findings suggest Cftr dependent, alterations in intestinal bacterial biotransformation of bile salts. Copyright © 2014. Published by Elsevier B.V.

  10. Deuterium-depleted water

    Stefanescu, Ion; Steflea, Dumitru; Saros-Rogobete, Irina; Titescu, Gheorghe; Tamaian, Radu

    2001-01-01

    Deuterium-depleted water represents water that has an isotopic content smaller than 145 ppm D/(D+H) which is the natural isotopic content of water. Deuterium depleted water is produced by vacuum distillation in columns equipped with structured packing made from phosphor bronze or stainless steel. Deuterium-depleted water, the production technique and structured packing are patents of National Institute of Research - Development for Cryogenics and Isotopic Technologies at Rm. Valcea. Researches made in the last few years showed the deuterium-depleted water is a biological active product that could have many applications in medicine and agriculture. (authors)

  11. Resveratrol increases F508del-CFTR dependent salivary secretion in cystic fibrosis mice

    Barbara Dhooghe

    2015-07-01

    Full Text Available Cystic fibrosis (CF is a fatal genetic disease associated with widespread exocrine gland dysfunction. Studies have suggested activating effects of resveratrol, a naturally-occurring polyphenol compound with antioxidant and anti-inflammatory properties, on CF transmembrane conductance regulator (CFTR protein function. We assayed, in F508del-CFTR homozygous (CF and in wild-type mice, the effect of resveratrol on salivary secretion in basal conditions, in response to inhibition by atropine (basal β-adrenergic-dependent component and to stimulation by isoprenaline (CFTR-dependent component. Both components of the salivary secretion were smaller in CF mice than in controls. Two hours after intraperitoneal administration of resveratrol (50 mg/kg dissolved in DMSO, the compound was detected in salivary glands. As in both CF and in wild-type mice, DMSO alone increased the response to isoprenaline in males but not in females, the effect of resveratrol was only measured in females. In wild-type mice, isoprenaline increased secretion by more than half. In CF mice, resveratrol rescued the response to isoprenaline, eliciting a 2.5-fold increase of β-adrenergic-stimulated secretion. We conclude that the salivary secretion assay is suitable to test DMSO-soluble CFTR modulators in female mice. We show that resveratrol applied in vivo to mice reaches salivary glands and increases β-adrenergic secretion. Immunolabelling of CFTR in human bronchial epithelial cells suggests that the effect is associated with increased CFTR protein expression. Our data support the view that resveratrol is beneficial for treating CF. The salivary secretion assay has a potential application to test efficacy of novel CF therapies.

  12. Riddle of depleted uranium

    Hussein, A.S.

    2005-01-01

    Depleted Uranium (DU) is the waste product of uranium enrichment from the manufacturing of fuel rods for nuclear reactors in nuclear power plants and nuclear power ships. DU may also results from the reprocessing of spent nuclear reactor fuel. Potentially DU has both chemical and radiological toxicity with two important targets organs being the kidney and the lungs. DU is made into a metal and, due to its availability, low price, high specific weight, density and melting point as well as its pyrophoricity; it has a wide range of civilian and military applications. Due to the use of DU over the recent years, there appeared in some press on health hazards that are alleged to be due to DU. In these paper properties, applications, potential environmental and health effects of DU are briefly reviewed

  13. Kinetics of depletion interactions

    Vliegenthart, G.A.; Schoot, van der P.P.A.M.

    2003-01-01

    Depletion interactions between colloidal particles dispersed in a fluid medium are effective interactions induced by the presence of other types of colloid. They are not instantaneous but built up in time. We show by means of Brownian dynamics simulations that the static (mean-field) depletion force

  14. Statistical implications in Monte Carlo depletions - 051

    Zhiwen, Xu; Rhodes, J.; Smith, K.

    2010-01-01

    As a result of steady advances of computer power, continuous-energy Monte Carlo depletion analysis is attracting considerable attention for reactor burnup calculations. The typical Monte Carlo analysis is set up as a combination of a Monte Carlo neutron transport solver and a fuel burnup solver. Note that the burnup solver is a deterministic module. The statistical errors in Monte Carlo solutions are introduced into nuclide number densities and propagated along fuel burnup. This paper is towards the understanding of the statistical implications in Monte Carlo depletions, including both statistical bias and statistical variations in depleted fuel number densities. The deterministic Studsvik lattice physics code, CASMO-5, is modified to model the Monte Carlo depletion. The statistical bias in depleted number densities is found to be negligible compared to its statistical variations, which, in turn, demonstrates the correctness of the Monte Carlo depletion method. Meanwhile, the statistical variation in number densities generally increases with burnup. Several possible ways of reducing the statistical errors are discussed: 1) to increase the number of individual Monte Carlo histories; 2) to increase the number of time steps; 3) to run additional independent Monte Carlo depletion cases. Finally, a new Monte Carlo depletion methodology, called the batch depletion method, is proposed, which consists of performing a set of independent Monte Carlo depletions and is thus capable of estimating the overall statistical errors including both the local statistical error and the propagated statistical error. (authors)

  15. MOx Depletion Calculation Benchmark

    San Felice, Laurence; Eschbach, Romain; Dewi Syarifah, Ratna; Maryam, Seif-Eddine; Hesketh, Kevin

    2016-01-01

    Under the auspices of the NEA Nuclear Science Committee (NSC), the Working Party on Scientific Issues of Reactor Systems (WPRS) has been established to study the reactor physics, fuel performance, radiation transport and shielding, and the uncertainties associated with modelling of these phenomena in present and future nuclear power systems. The WPRS has different expert groups to cover a wide range of scientific issues in these fields. The Expert Group on Reactor Physics and Advanced Nuclear Systems (EGRPANS) was created in 2011 to perform specific tasks associated with reactor physics aspects of present and future nuclear power systems. EGRPANS provides expert advice to the WPRS and the nuclear community on the development needs (data and methods, validation experiments, scenario studies) for different reactor systems and also provides specific technical information regarding: core reactivity characteristics, including fuel depletion effects; core power/flux distributions; Core dynamics and reactivity control. In 2013 EGRPANS published a report that investigated fuel depletion effects in a Pressurised Water Reactor (PWR). This was entitled 'International Comparison of a Depletion Calculation Benchmark on Fuel Cycle Issues' NEA/NSC/DOC(2013) that documented a benchmark exercise for UO 2 fuel rods. This report documents a complementary benchmark exercise that focused on PuO 2 /UO 2 Mixed Oxide (MOX) fuel rods. The results are especially relevant to the back-end of the fuel cycle, including irradiated fuel transport, reprocessing, interim storage and waste repository. Saint-Laurent B1 (SLB1) was the first French reactor to use MOx assemblies. SLB1 is a 900 MWe PWR, with 30% MOx fuel loading. The standard MOx assemblies, used in Saint-Laurent B1 reactor, include three zones with different plutonium enrichments, high Pu content (5.64%) in the center zone, medium Pu content (4.42%) in the intermediate zone and low Pu content (2.91%) in the peripheral zone

  16. Clinical expression of patients with the D1152H CFTR mutation.

    Terlizzi, Vito; Carnovale, Vincenzo; Castaldo, Giuseppe; Castellani, Carlo; Cirilli, Natalia; Colombo, Carla; Corti, Fabiola; Cresta, Federico; D'Adda, Alice; Lucarelli, Marco; Lucidi, Vincenzina; Macchiaroli, Annamaria; Madarena, Elisa; Padoan, Rita; Quattrucci, Serena; Salvatore, Donatello; Zarrilli, Federica; Raia, Valeria

    2015-07-01

    Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and hemoptysis). However, their clinical expression was less severe as compared to a group of CF patients homozygous for the F508del mutation. Finally, 8 subjects compound heterozygous for D1152H and a IV-V class mutation showed very mild disease. The natural history of subjects bearing the D1152H mutation is widely heterogeneous and is influenced by the mutation in trans. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  17. Structure and Dynamics of NBD1 from CFTR Characterized Using Crystallography and Hydrogen/Deuterium Exchange Mass Spectrometry

    Lewis, H.A.; Wang, C.; Zhao, X.; Hamuro, Y.; Conners, K.; Kearins, M.C.; Lu, F.; Sauder, J.M.; Molnar, K.S.; Coales, S.J.; Maloney, P.C.; Guggino, W.B.; Wetmore, D.R.; Weber, P.C.; Hunt, J.F. (SGX); (ExSAR); (Cystic); (JHU-MED); (Columbia)

    2012-04-30

    The {Delta}F508 mutation in nucleotide-binding domain 1 (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) is the predominant cause of cystic fibrosis. Previous biophysical studies on human F508 and {Delta}F508 domains showed only local structural changes restricted to residues 509-511 and only minor differences in folding rate and stability. These results were remarkable because {Delta}F508 was widely assumed to perturb domain folding based on the fact that it prevents trafficking of CFTR out of the endoplasmic reticulum. However, the previously reported crystal structures did not come from matched F508 and {Delta}F508 constructs, and the {Delta}F508 structure contained additional mutations that were required to obtain sufficient protein solubility. In this article, we present additional biophysical studies of NBD1 designed to address these ambiguities. Mass spectral measurements of backbone amide {sup 1}H/{sup 2}H exchange rates in matched F508 and {Delta}F508 constructs reveal that {Delta}F508 increases backbone dynamics at residues 509-511 and the adjacent protein segments but not elsewhere in NBD1. These measurements also confirm a high level of flexibility in the protein segments exhibiting variable conformations in the crystal structures. We additionally present crystal structures of a broader set of human NBD1 constructs, including one harboring the native F508 residue and others harboring the {Delta}F508 mutation in the presence of fewer and different solubilizing mutations. The only consistent conformational difference is observed at residues 509-511. The side chain of residue V510 in this loop is mostly buried in all non-{Delta}F508 structures but completely solvent exposed in all {Delta}F508 structures. These results reinforce the importance of the perturbation {Delta}F508 causes in the surface topography of NBD1 in a region likely to mediate contact with the transmembrane domains of CFTR. However, they also suggest that increased

  18. Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.

    Naziha Bakouh

    Full Text Available A growing number of proteins, including ion transporters, have been shown to interact with Cystic Fibrosis Transmembrane conductance Regulator (CFTR. CFTR is an epithelial chloride channel that is involved in Cystic Fibrosis (CF when mutated; thus a better knowledge of its functional interactome may help to understand the pathophysiology of this complex disease. In the present study, we investigated if CFTR and the sodium-phosphate co-transporter type 2a (NPT2a functionally interact after heterologous expression of both proteins in Xenopus laevis oocytes.NPT2a was expressed alone or in combination with CFTR in X. laevis oocytes. Using the two-electrode voltage-clamp technique, the inorganic phosphate-induced current (IPi was measured and taken as an index of NPT2a activity. The maximal IPi for NPT2a substrates was reduced when CFTR was co-expressed with NPT2a, suggesting a decrease in its expression at the oolemna. This was consistent with Western blot analysis showing reduced NPT2a plasma membrane expression in oocytes co-expressing both proteins, whereas NPT2a protein level in total cell lysate was the same in NPT2a- and NPT2a+CFTR-oocytes. In NPT2a+CFTR- but not in NPT2a-oocytes, IPi and NPT2a surface expression were increased upon PKA stimulation, whereas stimulation of Exchange Protein directly Activated by cAMP (EPAC had no effect. When NPT2a-oocytes were injected with NEG2, a short amino-acid sequence from the CFTR regulatory domain that regulates PKA-dependent CFTR trafficking to the plasma membrane, IPi values and NPT2a membrane expression were diminished, and could be enhanced by PKA stimulation, thereby mimicking the effects of CFTR co-expression.We conclude that when both CFTR and NPT2a are expressed in X. laevis oocytes, CFTR confers to NPT2a a cAMPi-dependent trafficking to the membrane. This functional interaction raises the hypothesis that CFTR may play a role in phosphate homeostasis.

  19. Are relative depletions altered inside diffuse clouds?

    Joseph, C.L.

    1988-01-01

    The data of Jenkins, Savage, and Spitzer (1986) were used to analyze interstellar abundances and depletions of Fe, P, Mg, and Mn toward 37 stars, spanning nearly 1.0 (dex) in mean line-of-sight depletion. It was found that the depletions of these elements are linearly correlated and do not show evidence of differences in the rates of depletion or sputtering from one element to another. For a given level of overall depletion, the sightline-to-sightline rms variance in the depletion for each of these elements was less than 0.16 (dex), which is significantly smaller than is the element-to-element variance. The results suggest that, for most diffuse lines of sight, the relative abundances of these elements are set early in the lifetime of the grains and are not altered significantly thereafter. 53 references

  20. The human CFTR protein expressed in CHO cells activates aquaporin-3 in a cAMP-dependent pathway: study by digital holographic microscopy

    Jourdain, P.

    2013-12-11

    The transmembrane water movements during cellular processes and their relationship to ionic channel activity remain largely unknown. As an example, in epithelial cells it was proposed that the movement of water could be directly linked to cystic fibrosis transmembrane conductance regulator (CFTR) protein activity through a cAMP-stimulated aqueous pore, or be dependent on aquaporin. Here, we used digital holographic microscopy (DHM) an interferometric technique to quantify in situ the transmembrane water fluxes during the activity of the epithelial chloride channel, CFTR, measured by patch-clamp and iodide efflux techniques. We showed that the water transport measured by DHM is fully inhibited by the selective CFTR blocker CFTRinh172 and is absent in cells lacking CFTR. Of note, in cells expressing the mutated version of CFTR (F508del-CFTR), which mimics the most common genetic alteration encountered in cystic fibrosis, we also show that the water movement is profoundly altered but restored by pharmacological manipulation of F508del-CFTR-defective trafficking. Importantly, whereas activation of this endogenous water channel required a cAMP-dependent stimulation of CFTR, activation of CFTR or F508del-CFTR by two cAMP-independent CFTR activators, genistein and MPB91, failed to trigger water movements. Finally, using a specific small-interfering RNA against the endogenous aquaporin AQP3, the water transport accompanying CFTR activity decreased. We conclude that water fluxes accompanying CFTR activity are linked to AQP3 but not to a cAMP-stimulated aqueous pore in the CFTR protein.

  1. A large-scale study of the random variability of a coding sequence: a study on the CFTR gene.

    Modiano, Guido; Bombieri, Cristina; Ciminelli, Bianca Maria; Belpinati, Francesca; Giorgi, Silvia; Georges, Marie des; Scotet, Virginie; Pompei, Fiorenza; Ciccacci, Cinzia; Guittard, Caroline; Audrézet, Marie Pierre; Begnini, Angela; Toepfer, Michael; Macek, Milan; Ferec, Claude; Claustres, Mireille; Pignatti, Pier Franco

    2005-02-01

    Coding single nucleotide substitutions (cSNSs) have been studied on hundreds of genes using small samples (n(g) approximately 100-150 genes). In the present investigation, a large random European population sample (average n(g) approximately 1500) was studied for a single gene, the CFTR (Cystic Fibrosis Transmembrane conductance Regulator). The nonsynonymous (NS) substitutions exhibited, in accordance with previous reports, a mean probability of being polymorphic (q > 0.005), much lower than that of the synonymous (S) substitutions, but they showed a similar rate of subpolymorphic (q < 0.005) variability. This indicates that, in autosomal genes that may have harmful recessive alleles (nonduplicated genes with important functions), genetic drift overwhelms selection in the subpolymorphic range of variability, making disadvantageous alleles behave as neutral. These results imply that the majority of the subpolymorphic nonsynonymous alleles of these genes are selectively negative or even pathogenic.

  2. A New Targeted CFTR Mutation Panel Based on Next-Generation Sequencing Technology.

    Lucarelli, Marco; Porcaro, Luigi; Biffignandi, Alice; Costantino, Lucy; Giannone, Valentina; Alberti, Luisella; Bruno, Sabina Maria; Corbetta, Carlo; Torresani, Erminio; Colombo, Carla; Seia, Manuela

    2017-09-01

    Searching for mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) is a key step in the diagnosis of and neonatal and carrier screening for cystic fibrosis (CF), and it has implications for prognosis and personalized therapy. The large number of mutations and genetic and phenotypic variability make this search a complex task. Herein, we developed, validated, and tested a laboratory assay for an extended search for mutations in CFTR using a next-generation sequencing-based method, with a panel of 188 CFTR mutations customized for the Italian population. Overall, 1426 dried blood spots from neonatal screening, 402 genomic DNA samples from various origins, and 1138 genomic DNA samples from patients with CF were analyzed. The assay showed excellent analytical and diagnostic operative characteristics. We identified and experimentally validated 159 (of 188) CFTR mutations. The assay achieved detection rates of 95.0% and 95.6% in two large-scale case series of CF patients from central and northern Italy, respectively. These detection rates are among the highest reported so far with a genetic test for CF based on a mutation panel. This assay appears to be well suited for diagnostics, neonatal and carrier screening, and assisted reproduction, and it represents a considerable advantage in CF genetic counseling. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  3. Addressing Ozone Layer Depletion

    Access information on EPA's efforts to address ozone layer depletion through regulations, collaborations with stakeholders, international treaties, partnerships with the private sector, and enforcement actions under Title VI of the Clean Air Act.

  4. Applicability and Efficiency of NGS in Routine Diagnosis: In-Depth Performance Analysis of a Complete Workflow for CFTR Mutation Analysis.

    Adrien Pagin

    Full Text Available Actually, about 2000 sequence variations have been documented in the CFTR gene requiring extensive and multi-step genetic testing in the diagnosis of cystic fibrosis and CFTR-related disorders. We present a two phases study, with validation and performance monitoring, of a single experiment methodology based on multiplex PCR and high throughput sequencing that allows detection of all variants, including large rearrangements, affecting the coding regions plus three deep intronic loci.A total of 340 samples, including 257 patients and 83 previously characterized control samples, were sequenced in 17 MiSeq runs and analyzed with two bioinformatic pipelines in routine diagnostic conditions. We obtained 100% coverage for all the target regions in every tested sample.We correctly identified all the 87 known variants in the control samples and successfully confirmed the 62 variants identified among the patients without observing false positive results. Large rearrangements were identified in 18/18 control samples. Only 17 patient samples showed false positive signals (6.6%, 12 of which showed a borderline result for a single amplicon. We also demonstrated the ability of the assay to detect allele specific dropout of amplicons when a sequence variation occurs at a primer binding site thus limiting the risk for false negative results.We described here the first NGS workflow for CFTR routine analysis that demonstrated equivalent diagnostic performances compared to Sanger sequencing and multiplex ligation-dependent probe amplification. This study illustrates the advantages of NGS in term of scalability, workload reduction and cost-effectiveness in combination with an improvement of the overall data quality due to the simultaneous detection of SNVs and large rearrangements.

  5. The molecular analysis of mutations in exons 4, 11 and 21 of the cystic fibrosis transmembrane conductance regulator (CFTR gene in cystic fibrosis patients in Kermanshah, Iran

    Nasibe Karimi

    2017-03-01

    Full Text Available Introduction: Cystic fibrosis (CF is a common genetic disorder in white populations with an autosomal recessive pattern, caused by mutations in the CFTR gene. The frequency of more than 1950 various mutations reported in the CFTR gene significantly varies in different populations. ∆F508 is a common mutation in exon 10, which is first addressed in the molecular analysis of the disease. Other exons are required to be investigated owing to failing to identify mutations in the patients. The present study was conducted to investigate mutations in exons 4, 11 and 21 of the CFTR gene using the sequencing method in CF patients in Kermanshah province, Iran. Methods: The present descriptive study was conducted on all patients with CF presenting to the medical genetics center in Kermanshah in 2010-2011. After taking blood samples and extracting DNA using saturated NaCl solution, sequences of exons were amplified using PCR and sequenced for identifying mutations. Results: The frequency of mutations was found to be respectively 0, 0 and 5.5% in exon 11, 21 and 4. The D110H mutation was found to be homozygous in one subject and heterozygous in another. Moreover, the 4029A>G polymorphism (12.9% was found to be homozygous in two subjects and heterozygous in three others. Conclusion: The D110H mutation is recommended to be included in the screening programs of the study population. The results obtained support the effects of ethnic and geographical factors on the distribution of CF mutations.

  6. CD4 Depletion or CD40L Blockade Results in Antigen-Specific Tolerance in a Red Blood Cell Alloimmunization Model

    Prabitha Natarajan

    2017-08-01

    Full Text Available Approximately 3–10% of human red blood cell (RBC transfusion recipients form alloantibodies to non-self, non-ABO blood group antigens expressed on donor RBCs, with these alloantibodies having the potential to be clinically significant in transfusion and pregnancy settings. However, the majority of transfused individuals never form detectable alloantibodies. Expanding upon observations that children initially transfused with RBCs at a young age are less likely to form alloantibodies throughout their lives, we hypothesized that “non-responders” may not only be ignorant of antigens on RBCs but instead tolerized. We investigated this question in a reductionist murine model, in which transgenic donors express the human glycophorin A (hGPA antigen in an RBC-specific manner. Although wild-type mice treated with poly IC and transfused with hGPA RBCs generated robust anti-hGPA IgG alloantibodies that led to rapid clearance of incompatible RBCs, those transfused in the absence of an adjuvant failed to become alloimmunized. Animals depleted of CD4+ cells or treated with CD40L blockade prior to initial hGPA RBC exposure, in the presence of poly IC, failed to generate detectable anti-hGPA IgG alloantibodies. These non-responders to a primary transfusion remained unable to generate anti-hGPA IgG alloantibodies upon secondary hGPA exposure and did not prematurely clear transfused hGPA RBCs even after their CD4 cells had returned or their CD40L blockade had resolved. This observed tolerance was antigen (hGPA specific, as robust IgG responses to transfused RBCs expressing a third-party antigen occurred in all studied groups. Experiments completed in an RBC alloimmunization model that allowed evaluation of antigen-specific CD4+ T-cells (HOD (hen egg lysozyme, ovalbumin, and human duffyb demonstrated that CD40L blockade prevented the expansion of ovalbumin 323-339 specific T-cells after HOD RBC transfusion and also prevented germinal center formation. Taken

  7. The Chemistry and Toxicology of Depleted Uranium

    Sidney A. Katz

    2014-03-01

    Full Text Available Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U down to reactor grade uranium (~5% 235U, and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles. Such weapons were used by the military in the Persian Gulf, the Balkans and elsewhere. The testing of depleted uranium weapons and their use in combat has resulted in environmental contamination and human exposure. Although the chemical and the toxicological behaviors of depleted uranium are essentially the same as those of natural uranium, the respective chemical forms and isotopic compositions in which they usually occur are different. The chemical and radiological toxicity of depleted uranium can injure biological systems. Normal functioning of the kidney, liver, lung, and heart can be adversely affected by depleted uranium intoxication. The focus of this review is on the chemical and toxicological properties of depleted and natural uranium and some of the possible consequences from long term, low dose exposure to depleted uranium in the environment.

  8. Current insights into the role of PKA phosphorylation in CFTR channel activity and the pharmacological rescue of cystic fibrosis disease-causing mutants.

    Chin, Stephanie; Hung, Maurita; Bear, Christine E

    2017-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) channel gating is predominantly regulated by protein kinase A (PKA)-dependent phosphorylation. In addition to regulating CFTR channel activity, PKA phosphorylation is also involved in enhancing CFTR trafficking and mediating conformational changes at the interdomain interfaces of the protein. The major cystic fibrosis (CF)-causing mutation is the deletion of phenylalanine at position 508 (F508del); it causes many defects that affect CFTR trafficking, stability, and gating at the cell surface. Due to the multiple roles of PKA phosphorylation, there is growing interest in targeting PKA-dependent signaling for rescuing the trafficking and functional defects of F508del-CFTR. This review will discuss the effects of PKA phosphorylation on wild-type CFTR, the consequences of CF mutations on PKA phosphorylation, and the development of therapies that target PKA-mediated signaling.

  9. Deuterium - depleted water. Achievements and perspectives

    Titescu, Gh.; Stefanescu, I.; Saros-Rogobete, I.

    2001-01-01

    reproduction of fish with deuterium - depleted water fecundated solutions confirmed favourable influence in embryo growth stage and resistance in next growth stages; 5. it was studied germination, growth and quantitative character's variability in plants; one can remark the favourable influence of deuterium - depleted water on biological process in plants in various ontogenetic stages; 6. the deuterium depletion in seawater produces the diminution of the water spectral energy related to an increased metabolism of Tetraselmis suecica. Although the results obtained in Romania have a special scientific value, the application of these researches is in progress. We have to mention that at present all the amount of deuterium - depleted water produced at Rm. Valcea is exported to Hungary were it is used to produce drugs for the prevention and the treatment of cancer. (authors)

  10. Physics of fully depleted CCDs

    Holland, S E; Bebek, C J; Kolbe, W F; Lee, J S

    2014-01-01

    In this work we present simple, physics-based models for two effects that have been noted in the fully depleted CCDs that are presently used in the Dark Energy Survey Camera. The first effect is the observation that the point-spread function increases slightly with the signal level. This is explained by considering the effect on charge-carrier diffusion due to the reduction in the magnitude of the channel potential as collected signal charge acts to partially neutralize the fixed charge in the depleted channel. The resulting reduced voltage drop across the carrier drift region decreases the vertical electric field and increases the carrier transit time. The second effect is the observation of low-level, concentric ring patterns seen in uniformly illuminated images. This effect is shown to be most likely due to lateral deflection of charge during the transit of the photo-generated carriers to the potential wells as a result of lateral electric fields. The lateral fields are a result of space charge in the fully depleted substrates arising from resistivity variations inherent to the growth of the high-resistivity silicon used to fabricate the CCDs

  11. CFTR-dependent chloride efflux in cystic fibrosis mononuclear cells is increased by ivacaftor therapy.

    Guerra, Lorenzo; D'Oria, Susanna; Favia, Maria; Castellani, Stefano; Santostasi, Teresa; Polizzi, Angela M; Mariggiò, Maria A; Gallo, Crescenzio; Casavola, Valeria; Montemurro, Pasqualina; Leonetti, Giuseppina; Manca, Antonio; Conese, Massimo

    2017-07-01

    The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) potentiator ivacaftor (Kalydeco®) improves clinical outcome in G551D cystic fibrosis (CF) patients. Here, we have investigated whether ivacaftor has a clinical impact on non-G551D gating mutations and function of circulating leukocytes as well. Seven patients were treated with ivacaftor and evaluated at baseline, and at 1-3 and 6 months. Besides clinical and systemic inflammatory parameters, circulating mononuclear cells (MNC) were evaluated for CFTR-dependent chloride efflux by spectrofluorimetry, neutrophils for oxidative burst by cytofluorimetry and HVCN1 mRNA expression by real time PCR. Ivacaftor determined a significant decrease in sweat chloride concentrations at all time points during treatment. Body mass index (BMI), FEV 1 , and FVC showed an increasing trend. While C-reactive protein decreased significantly at 2 months, the opposite behavior was noticed for circulating monocytes. CFTR activity in MNC was found to increase significantly at 3 and 6 months. Neutrophil oxidative burst peaked at 2 months and then decreased to baseline. HVCN1 mRNA expression was significantly higher than baseline at 1-3 months and decreased after 6 months of treatment. The chloride efflux in MNC correlated positively with both FEV 1 and FVC. On the other hand, sweat chloride correlated positively with CRP and WBC, and negatively with both respiratory function tests. A cluster analysis confirmed that sweat chloride, FEV 1 , FVC, BMI, and MNC chloride efflux behaved as a single entity over time. In patients with non-G551D mutations, ivacaftor improved both chloride transport in sweat ducts and chloride efflux in MNC, that is, functions directly imputed to CFTR. © 2017 Wiley Periodicals, Inc.

  12. CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis.

    Tarique, Abdullah A; Sly, Peter D; Holt, Patrick G; Bosco, Anthony; Ware, Robert S; Logan, Jayden; Bell, Scott C; Wainwright, Claire E; Fantino, Emmanuelle

    2017-07-01

    The role of the macrophages in cystic fibrosis (CF) lung disease has been poorly studied. We hypothesized that alternatively activated M2 macrophages are abnormal in CF lung disease. Blood samples were collected from adults (n=13) children (n=27) with CF on admission for acute pulmonary exacerbation and when clinically stable. Monocytes were differentiated into macrophages and polarized into classical (M1) and alternatively-activated (M2) phenotypes, function determined ex-vivo and compared with healthy controls. In the absence of functional cystic fibrosis trans-membrane conductance regulator (CFTR), either naturally in patients with CF or induced with CFTR inhibitors, monocyte-derived macrophages do not respond to IL-13/IL-4, fail to polarize into M2s associated with a post-transcriptional failure to produce and express IL-13Rα1 on the macrophage surface Polarization to the M1 phenotype was unaffected. CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  13. A new compound heterozygous CFTR mutation in a Chinese family with cystic fibrosis.

    Xie, Yingjun; Huang, Xueqiong; Liang, Yujian; Xu, Lingling; Pei, Yuxin; Cheng, Yucai; Zhang, Lidan; Tang, Wen

    2017-11-01

    Cystic fibrosis (CF) is the most common autosomal recessive disease among Caucasians but is rarer in the Chinese population, because mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To elucidate the causative role of a novel compound heterozygous mutation of CF. In this study, clinical samples were obtained from two siblings with recurrent airway infections, clubbed fingers, salt-sweat and failure to gain weight in a non-consanguineous Chinese family. Next-generation sequencing was performed on the 27 coding exons of CFTR in both children, with confirmation by Sanger sequencing. Next-generation sequencing showed the same compound heterozygous CFTR mutation (c.865A>T p.Arg289X and c.3651_3652insAAAT p.Tyr1219X) in both children. As this mutation is consistent with the clinical manifestations of CF and no other mutations were detected after scanning the gene sequence, we suggest that the CF phenotype is caused by compound heterozygosity for c.865A>T and c.3651_3652insAAAT. As c865A>T is not currently listed in the "Cystic Fibrosis Mutation Database", this information about CF in a Chinese population is of interest. © 2015 John Wiley & Sons Ltd.

  14. Evaluation 2 of B10 depletion in the WH PWR

    Park, Sang Won; Woo, Hae Suk; Kim, Sun Doo; Chae, Hee Dong; Myung, Sun Yup; Jang, Ju Kyung

    2001-01-01

    This paper presents the methodology to evaluate the B 10 depletion behavior in the pressurized water reactor. And B 10 depletion evaluation is performed based on the prediction program and the measured data of B 10 . The result shows that B 10 depletion during normal operation is not negligible. Therefore, adjustments for this depletion effect should be made to calculate the estimated critical postion(ECP) and determine the boron concentration required to maintain the specified shutdown margin

  15. Capital expenditure and depletion

    Rech, O.; Saniere, A.

    2003-01-01

    In the future, the increase in oil demand will be covered for the most part by non conventional oils, but conventional sources will continue to represent a preponderant share of the world oil supply. Their depletion represents a complex challenge involving technological, economic and political factors. At the same time, there is reason for concern about the decrease in exploration budgets at the major oil companies. (author)

  16. Capital expenditure and depletion

    Rech, O.; Saniere, A

    2003-07-01

    In the future, the increase in oil demand will be covered for the most part by non conventional oils, but conventional sources will continue to represent a preponderant share of the world oil supply. Their depletion represents a complex challenge involving technological, economic and political factors. At the same time, there is reason for concern about the decrease in exploration budgets at the major oil companies. (author)

  17. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1.

    Andreucci, M.; Michael, A.; Kramers, C.; Park, K.M.; Chen, A.; Matthaeus, T.; Alessandrini, A.; Haq, S.; Force, T.; Bonventre, J.V.

    2003-01-01

    BACKGROUND: Cell death and survival pathways are critical determinants of epithelial cell fate after ischemia. Forkhead proteins have been implicated in the regulation of cellular survival. METHODS and RESULTS: We have found that none of the forkhead family of proteins, FKHR, is phosphorylated after

  18. Ecological considerations of natural and depleted uranium

    Hanson, W.C.

    1980-01-01

    Depleted 238 U is a major by-product of the nuclear fuel cycle for which increasing use is being made in counterweights, radiation shielding, and ordnance applications. This paper (1) summarizes the pertinent literature on natural and depleted uranium in the environment, (2) integrates results of a series of ecological studies conducted at Los Alamos Scientific Laboratory (LASL) in New Mexico where 70,000 kg of depleted and natural uranium has been expended to the environment over the past 34 years, and (3) synthesizes the information into an assessment of the ecological consequences of natural and depleted uranium released to the environment by various means. Results of studies of soil, plant, and animal communities exposed to this radiation and chemical environment over a third of a century provide a means of evaluating the behavior and effects of uranium in many contexts

  19. Stimulation of wild-type, F508del- and G551D-CFTR chloride channels by non toxic modified pyrrolo[2,3-b]pyrazine derivatives

    Luc eDannhoffer

    2011-08-01

    Full Text Available Cystic Fibrosis is a major inherited disorder involving abnormalities of fluid and electrolyte transport in a number of different organs due to abnormal function of Cystic Fibrosis Transmembrane conductance Regulator (CFTR protein. We recently identified a family of CFTR activators, which contains the hit: RP107 [7-n-butyl-6-(4-hydroxyphenyl[5H]-pyrrolo[2,3-b]pyrazine]. Here, we further evaluated the effect of the chemical modifications of the RP107-OH radical on CFTR activation. The replacement of the OH radical by a fluorine atom at position 2 (RP193 or 4 (RP185 significantly decreased the toxicity of the compounds without altering the ability to activate CFTR, especially for RP193. The non-toxic compound RP193 has no effect on cAMP production but stimulates the channel activity of wild-type CFTR in stably transfected CHO cells, in human bronchial epithelial NuLi-1 cells and in primary culture of human bronchial epithelial cells. Whole cell and single patch clamp recordings showed that RP193 induced a linear, time and voltage-independent current, which was fully inhibited by two different and selective CFTR inhibitors (CFTRinh-172 and GPinh-5a. Moreover, RP193 stimulates CFTR in temperature-rescued CuFi-1 (F508del/F508del human bronchial epithelial cells and in CHO cells stably expressing G551D-CFTR. This study shows that it is feasible to reduce cytotoxicity of chemical compounds without affecting their potency to activate CFTR and to rescue the class 2 F508del-CFTR and class 3 G551D-CFTR CF mutant activities.

  20. Ozone-depleting Substances (ODS)

    U.S. Environmental Protection Agency — This site includes all of the ozone-depleting substances (ODS) recognized by the Montreal Protocol. The data include ozone depletion potentials (ODP), global warming...

  1. Sensibility analysis of fuel depletion using different nuclear fuel depletion codes

    Martins, F.; Velasquez, C.E.; Castro, V.F.; Pereira, C.; Silva, C. A. Mello da

    2017-01-01

    Nowadays, the utilization of different nuclear codes to perform the depletion and criticality calculations has been used to simulated nuclear reactors problems. Therefore, the goal is to analyze the sensibility of the fuel depletion of a PWR assembly using three different nuclear fuel depletion codes. The burnup calculations are performed using the codes MCNP5/ORIGEN2.1 (MONTEBURNS), KENO-VI/ORIGEN-S (TRITONSCALE6.0) and MCNPX (MCNPX/CINDER90). Each nuclear code performs the burnup using different depletion codes. Each depletion code works with collapsed energies from a master library in 1, 3 and 63 groups, respectively. Besides, each code uses different ways to obtain neutron flux that influences the depletions calculation. The results present a comparison of the neutronic parameters and isotopes composition such as criticality and nuclides build-up, the deviation in results are going to be assigned to features of the depletion code in use, such as the different radioactive decay internal libraries and the numerical method involved in solving the coupled differential depletion equations. It is also seen that the longer the period is and the more time steps are chosen, the larger the deviation become. (author)

  2. Sensibility analysis of fuel depletion using different nuclear fuel depletion codes

    Martins, F.; Velasquez, C.E.; Castro, V.F.; Pereira, C.; Silva, C. A. Mello da, E-mail: felipmartins94@gmail.com, E-mail: carlosvelcab@hotmail.com, E-mail: victorfariascastro@gmail.com, E-mail: claubia@nuclear.ufmg.br, E-mail: clarysson@nuclear.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear

    2017-07-01

    Nowadays, the utilization of different nuclear codes to perform the depletion and criticality calculations has been used to simulated nuclear reactors problems. Therefore, the goal is to analyze the sensibility of the fuel depletion of a PWR assembly using three different nuclear fuel depletion codes. The burnup calculations are performed using the codes MCNP5/ORIGEN2.1 (MONTEBURNS), KENO-VI/ORIGEN-S (TRITONSCALE6.0) and MCNPX (MCNPX/CINDER90). Each nuclear code performs the burnup using different depletion codes. Each depletion code works with collapsed energies from a master library in 1, 3 and 63 groups, respectively. Besides, each code uses different ways to obtain neutron flux that influences the depletions calculation. The results present a comparison of the neutronic parameters and isotopes composition such as criticality and nuclides build-up, the deviation in results are going to be assigned to features of the depletion code in use, such as the different radioactive decay internal libraries and the numerical method involved in solving the coupled differential depletion equations. It is also seen that the longer the period is and the more time steps are chosen, the larger the deviation become. (author)

  3. Depletion of 4-hydroxynonenal in hGSTA4-transfected HLE B-3 cells results in profound changes in gene expression

    Patrick, Brad; Li Jie; Jeyabal, Prince V.S.; Reddy, Prasada M.R.V.; Yang Yusong; Sharma, Rajendra; Sinha, Mala; Luxon, Bruce; Zimniak, Piotr; Awasthi, Sanjay; Awasthi, Yogesh C.

    2005-01-01

    Previously, we have shown that overexpression of 4-hydroxy-2-nonenal (HNE)-detoxifying enzyme glutathione S-transferase A4-4 (hGSTA4-4) in human lens epithelial cells (HLE B-3) leads to pro-carcinogenic phenotypic transformation of these cells [R. Sharma, et al. Eur. J. Biochem. 271 (2004) 1960-1701]. We now demonstrate that hGSTA4-transfection also causes a profound change in the expression of genes involved in cell adhesion, cell cycle control, proliferation, cell growth, and apoptosis, which is consistent with phenotypic changes of the transformed cells. The expression of p53, p21, p16, fibronectin 1, laminin γ1, connexin 43, Fas, integrin α6, TGFα, and c-jun was down-regulated, while the expression of protein kinase C beta II (PKCβII), c-myc, cyclin-dependent kinase 2 (CDK2), and TGFβ was up-regulated in transfected cells. These results demonstrate that HNE serves as a crucial signaling molecule and, by modulating the expression of genes, can influence cellular functions

  4. Issues in Stratospheric Ozone Depletion.

    Lloyd, Steven Andrew

    measurements. Therefore a laboratory prototype of an instrument to measure ClONO _2 concentrations in situ was developed, adapting techniques recently developed in this research group to measure ClO concentrations at the part-per-trillion level. The detection scheme involves heating a flowing air sample to almost 500K, thermally dissociating ClONO _2 into ClO and NO_2 , and measuring the resulting ClO concentration by titrating with NO to produce Cl atoms, which are detected by resonance fluoresence. The calibration of this technique is very sensitive to flow parameters (temperature, pressure, flow velocity, added NO concentration, and homogeneity of flow). The issues developed in this thesis contribute to our understanding of the mechanisms of stratospheric ozone depletion and its potential global impact. It is becoming increasingly apparent that our ability to predict the future course of global ozone depletion is critically dependent on our ability to reproduce in situ and remote measurements with numerical models.

  5. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  6. Crystallographic and single-particle analyses of native- and nucleotide-bound forms of the cystic fibrosis transmembrane conductance regulator (CFTR) protein.

    Awayn, N H; Rosenberg, M F; Kamis, A B; Aleksandrov, L A; Riordan, J R; Ford, R C

    2005-11-01

    Cystic fibrosis, one of the major human inherited diseases, is caused by defects in the CFTR (cystic fibrosis transmembrane conductance regulator), a cell-membrane protein. CFTR acts as a chloride channel which can be opened by ATP. Low-resolution structural studies of purified recombinant human CFTR are described in the present paper. Localization of the C-terminal decahistidine tag in CFTR was achieved by Ni2+-nitriloacetate nanogold labelling, followed by electron microscopy and single-particle analysis. The presence of the gold label appears to improve the single-particle-alignment procedure. Projection structures of CFTR from two-dimensional crystals analysed by electron crystallography displayed two alternative conformational states in the presence of nucleotide and nanogold, but only one form of the protein was observed in the quiescent (nucleotide-free) state.

  7. Distribution of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR Mutations in a Cohort of Patients Residing in Palestine.

    Issa Siryani

    Full Text Available Cystic fibrosis (CF is an autosomal recessive inherited life-threatening disorder that causes severe damage to the lungs and the digestive system. In Palestine, mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR that contributes to the clinical presentation of CF are ill defined. A cohort of thirty three clinically diagnosed CF patients from twenty one different Palestinian families residing in the central and southern part of Palestine were incorporated in this study. Sweat chloride testing was performed using the Sweat Chek Conductivity Analyzer (ELITECH Group, France to confirm the clinical diagnosis of CF. In addition, nucleic acid from the patients' blood samples was extracted and the CFTR mutation profiles were assessed by direct sequencing of the CFTR 27 exons and the intron-exon boundaries. For patient's DNA samples where no homozygous or two heterozygous CFTR mutations were identified by exon sequencing, DNA samples were tested for deletions or duplications using SALSA MLPA probemix P091-D1 CFTR assay. Sweat chloride testing confirmed the clinical diagnosis of CF in those patients. All patients had NaCl conductivity >60 mmol/l. In addition, nine different CFTR mutations were identified in all 21 different families evaluated. These mutations were c.1393-1G>A, F508del, W1282X, G85E, c.313delA, N1303K, deletion exons 17a-17b-18, deletion exons 17a-17b and Q1100P. c.1393-1G>A was shown to be the most frequent occurring mutation among tested families. We have profiled the underling mutations in the CFTR gene of a cohort of 21 different families affected by CF. Unlike other studies from the Arab countries where F508del was reported to be the most common mutation, in southern/central Palestine, the c.1393-1G>A appeared to be the most common. Further studies are needed per sample size and geographic distribution to account for other possible CFTR genetic alterations and their frequencies. Genotype

  8. A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

    Ponzano, Stefano; Nigrelli, Giulia; Fregonese, Laura; Eichler, Irmgard; Bertozzi, Fabio; Bandiera, Tiziano; Galietta, Luis J V; Papaluca, Marisa

    2018-06-30

    In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended. Copyright ©ERS 2018.

  9. CO Depletion: A Microscopic Perspective

    Cazaux, S. [Faculty of Aerospace Engineering, Delft University of Technology, Delft (Netherlands); Martín-Doménech, R.; Caro, G. M. Muñoz; Díaz, C. González [Centro de Astrobiología (INTA-CSIC), Ctra. de Ajalvir, km 4, Torrejón de Ardoz, E-28850 Madrid (Spain); Chen, Y. J. [Department of Physics, National Central University, Jhongli City, 32054, Taoyuan County, Taiwan (China)

    2017-11-10

    In regions where stars form, variations in density and temperature can cause gas to freeze out onto dust grains forming ice mantles, which influences the chemical composition of a cloud. The aim of this paper is to understand in detail the depletion (and desorption) of CO on (from) interstellar dust grains. Experimental simulations were performed under two different (astrophysically relevant) conditions. In parallel, Kinetic Monte Carlo simulations were used to mimic the experimental conditions. In our experiments, CO molecules accrete onto water ice at temperatures below 27 K, with a deposition rate that does not depend on the substrate temperature. During the warm-up phase, the desorption processes do exhibit subtle differences, indicating the presence of weakly bound CO molecules, therefore highlighting a low diffusion efficiency. IR measurements following the ice thickness during the TPD confirm that diffusion occurs at temperatures close to the desorption. Applied to astrophysical conditions, in a pre-stellar core, the binding energies of CO molecules, ranging between 300 and 850 K, depend on the conditions at which CO has been deposited. Because of this wide range of binding energies, the depletion of CO as a function of A{sub V} is much less important than initially thought. The weakly bound molecules, easily released into the gas phase through evaporation, change the balance between accretion and desorption, which result in a larger abundance of CO at high extinctions. In addition, weakly bound CO molecules are also more mobile, and this could increase the reactivity within interstellar ices.

  10. The Toxicity of Depleted Uranium

    Briner, Wayne

    2010-01-01

    Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a c...

  11. EPRI depletion benchmark calculations using PARAGON

    Kucukboyaci, Vefa N.

    2015-01-01

    Highlights: • PARAGON depletion calculations are benchmarked against the EPRI reactivity decrement experiments. • Benchmarks cover a wide range of enrichments, burnups, cooling times, and burnable absorbers, and different depletion and storage conditions. • Results from PARAGON-SCALE scheme are more conservative relative to the benchmark data. • ENDF/B-VII based data reduces the excess conservatism and brings the predictions closer to benchmark reactivity decrement values. - Abstract: In order to conservatively apply burnup credit in spent fuel pool criticality analyses, code validation for both fresh and used fuel is required. Fresh fuel validation is typically done by modeling experiments from the “International Handbook.” A depletion validation can determine a bias and bias uncertainty for the worth of the isotopes not found in the fresh fuel critical experiments. Westinghouse’s burnup credit methodology uses PARAGON™ (Westinghouse 2-D lattice physics code) and its 70-group cross-section library, which have been benchmarked, qualified, and licensed both as a standalone transport code and as a nuclear data source for core design simulations. A bias and bias uncertainty for the worth of depletion isotopes, however, are not available for PARAGON. Instead, the 5% decrement approach for depletion uncertainty is used, as set forth in the Kopp memo. Recently, EPRI developed a set of benchmarks based on a large set of power distribution measurements to ascertain reactivity biases. The depletion reactivity has been used to create 11 benchmark cases for 10, 20, 30, 40, 50, and 60 GWd/MTU and 3 cooling times 100 h, 5 years, and 15 years. These benchmark cases are analyzed with PARAGON and the SCALE package and sensitivity studies are performed using different cross-section libraries based on ENDF/B-VI.3 and ENDF/B-VII data to assess that the 5% decrement approach is conservative for determining depletion uncertainty

  12. Is congenital bilateral absence of vas deferens a primary form of cystic fibrosis? Analyses of the CFTR gene in 67 patients

    Mercier, B.; Verlingue, C.; Audrezet, M.P.; Ferec, C. [Centre de Biogenetique C.D.T.S., Brest (France); Lissens, W.; Bonduelle, M. [University Hospital VUB, Brussels (United Kingdom); Silber, S.J. [St. Luke`s Hospital, St. Louis, MO (United States); Novelli, G. [Catholic Univ. of Rome (Italy)

    1995-01-01

    Congenital bilateral absence of the vas deferens (CBAVD) is an important cause of sterility in men. Although the genetic basis of this condition is still unclear, it has been shown recently that some of these patients carry mutations in their cystic fibrosis transmembrane conductance regulator (CFTR) genes. To extend this observation, we have analyzed the entire coding sequence of the CFTR gene in a cohort of 67 men with CBAVD, who are otherwise healthy. We have identified four novel missense mutations (A800G, G149R, R258G, and E193K). We have shown that 42% of subjects were carriers of one CFTR allele and that 24% are compound heterozygous for CFTR alleles. Thus, we have been unable to identify 76% of these patients as carrying two CFTR mutations. Furthermore, we have described the segregation of CFTR haplotypes in the family of one CBAVD male; in this family are two male siblings, with identical CFTR loci but displaying different phenotypes, one of them being fertile and the other sterile. The data presented in this family, indicating a discordance between the CBAVD phenotype and a marked carrier ({delta}F508) chromosome, support the involvement of another gene(s), in the etiology of CBAVD. 35 refs., 2 figs., 1 tab.

  13. Monoamine depletion by reuptake inhibitors

    Hinz M

    2011-10-01

    Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics Inc, Cape Coral, FL; 2Stein Orthopedic Associates, Plantation, FL; 3DBS Labs Inc, Duluth, MN, USABackground: Disagreement exists regarding the etiology of cessation of the observed clinical results with administration of reuptake inhibitors. Traditionally, when drug effects wane, it is known as tachyphylaxis. With reuptake inhibitors, the placebo effect is significantly greater than the drug effect in the treatment of depression and attention deficit hyperactivity disorder, leading some to assert that waning of drug effects is placebo relapse, not tachyphylaxis.Methods: Two groups were retrospectively evaluated. Group 1 was composed of subjects with depression and Group 2 was composed of bariatric subjects treated with reuptake inhibitors for appetite suppression.Results: In Group 1, 200 subjects with depression were treated with citalopram 20 mg per day. A total of 46.5% (n = 93 achieved relief of symptoms (Hamilton-D rating score ≤ 7, of whom 37 (39.8% of whom experienced recurrence of depression symptoms, at which point an amino acid precursor formula was started. Within 1–5 days, 97.3% (n = 36 experienced relief of depression symptoms. In Group 2, 220 subjects were treated with phentermine 30 mg in the morning and citalopram 20 mg at 4 pm. In this group, 90.0% (n = 198 achieved adequate appetite suppression. The appetite suppression ceased in all 198 subjects within 4–48 days. Administration of an amino acid precursor formula restored appetite suppression in 98.5% (n = 195 of subjects within 1–5 days.Conclusion: Reuptake inhibitors do not increase the total number of monoamine molecules in the central nervous system. Their mechanism of action facilitates redistribution of monoamines from one place to another. In the process, conditions are induced that facilitate depletion of monoamines. The "reuptake inhibitor monoamine depletion theory" of this paper

  14. Restoration of CFTR Activity in Ducts Rescues Acinar Cell Function and Reduces Inflammation in Pancreatic and Salivary Glands of Mice.

    Zeng, Mei; Szymczak, Mitchell; Ahuja, Malini; Zheng, Changyu; Yin, Hongen; Swaim, William; Chiorini, John A; Bridges, Robert J; Muallem, Shmuel

    2017-10-01

    Sjögren's syndrome and autoimmune pancreatitis are disorders with decreased function of salivary, lacrimal glands, and the exocrine pancreas. Nonobese diabetic/ShiLTJ mice and mice transduced with the cytokine BMP6 develop Sjögren's syndrome and chronic pancreatitis and MRL/Mp mice are models of autoimmune pancreatitis. Cystic fibrosis transmembrane conductance regulator (CFTR) is a ductal Cl -  channel essential for ductal fluid and HCO 3 - secretion. We used these models to ask the following questions: is CFTR expression altered in these diseases, does correction of CFTR correct gland function, and most notably, does correcting ductal function correct acinar function? We treated the mice models with the CFTR corrector C18 and the potentiator VX770. Glandular, ductal, and acinar cells damage, infiltration, immune cells and function were measured in vivo and in isolated duct/acini. In the disease models, CFTR expression is markedly reduced. The salivary glands and pancreas are inflamed with increased fibrosis and tissue damage. Treatment with VX770 and, in particular, C18 restored salivation, rescued CFTR expression and localization, and nearly eliminated the inflammation and tissue damage. Transgenic overexpression of CFTR exclusively in the duct had similar effects. Most notably, the markedly reduced acinar cell Ca 2+ signaling, Orai1, inositol triphosphate receptors, Aquaporin 5 expression, and fluid secretion were restored by rescuing ductal CFTR. Our findings reveal that correcting ductal function is sufficient to rescue acinar cell function and suggests that CFTR correctors are strong candidates for the treatment of Sjögren's syndrome and pancreatitis. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Groundwater Depletion Embedded in International Food Trade

    Dalin, Carole; Wada, Yoshihide; Kastner, Thomas; Puma, Michael J.

    2017-01-01

    Recent hydrological modeling and Earth observations have located and quantified alarming rates of groundwater depletion worldwide. This depletion is primarily due to water withdrawals for irrigation, but its connection with the main driver of irrigation, global food consumption, has not yet been explored. Here we show that approximately eleven per cent of non-renewable groundwater use for irrigation is embedded in international food trade, of which two-thirds are exported by Pakistan, the USA and India alone. Our quantification of groundwater depletion embedded in the world's food trade is based on a combination of global, crop-specific estimates of non-renewable groundwater abstraction and international food trade data. A vast majority of the world's population lives in countries sourcing nearly all their staple crop imports from partners who deplete groundwater to produce these crops, highlighting risks for global food and water security. Some countries, such as the USA, Mexico, Iran and China, are particularly exposed to these risks because they both produce and import food irrigated from rapidly depleting aquifers. Our results could help to improve the sustainability of global food production and groundwater resource management by identifying priority regions and agricultural products at risk as well as the end consumers of these products.

  16. Depletion sensitivity predicts unhealthy snack purchases.

    Salmon, Stefanie J; Adriaanse, Marieke A; Fennis, Bob M; De Vet, Emely; De Ridder, Denise T D

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose weight on snack purchase behavior were explored. Participants included in the study were instructed to report every snack they bought over the course of one week. The dependent variables were the number of healthy and unhealthy snacks purchased. The results of the present study demonstrate that depletion sensitivity predicts the amount of unhealthy (but not healthy) snacks bought. The more sensitive people are to depletion, the more unhealthy snacks they buy. Moreover, there was some tentative evidence that this relation is more pronounced for people with a weak as opposed to a strong goal to lose weight, suggesting that a strong goal to lose weight may function as a motivational buffer against self-control failures. All in all, these findings provide evidence for the external validity of depletion sensitivity and the relevance of this construct in the domain of eating behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Groundwater depletion embedded in international food trade

    Dalin, Carole; Wada, Yoshihide; Kastner, Thomas; Puma, Michael J.

    2017-03-01

    Recent hydrological modelling and Earth observations have located and quantified alarming rates of groundwater depletion worldwide. This depletion is primarily due to water withdrawals for irrigation, but its connection with the main driver of irrigation, global food consumption, has not yet been explored. Here we show that approximately eleven per cent of non-renewable groundwater use for irrigation is embedded in international food trade, of which two-thirds are exported by Pakistan, the USA and India alone. Our quantification of groundwater depletion embedded in the world’s food trade is based on a combination of global, crop-specific estimates of non-renewable groundwater abstraction and international food trade data. A vast majority of the world’s population lives in countries sourcing nearly all their staple crop imports from partners who deplete groundwater to produce these crops, highlighting risks for global food and water security. Some countries, such as the USA, Mexico, Iran and China, are particularly exposed to these risks because they both produce and import food irrigated from rapidly depleting aquifers. Our results could help to improve the sustainability of global food production and groundwater resource management by identifying priority regions and agricultural products at risk as well as the end consumers of these products.

  18. The new MCNP6 depletion capability

    Fensin, M. L.; James, M. R.; Hendricks, J. S.; Goorley, J. T.

    2012-01-01

    The first MCNP based in-line Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology. (authors)

  19. The New MCNP6 Depletion Capability

    Fensin, Michael Lorne; James, Michael R.; Hendricks, John S.; Goorley, John T.

    2012-01-01

    The first MCNP based inline Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology.

  20. High order depletion sensitivity analysis

    Naguib, K.; Adib, M.; Morcos, H.N.

    2002-01-01

    A high order depletion sensitivity method was applied to calculate the sensitivities of build-up of actinides in the irradiated fuel due to cross-section uncertainties. An iteration method based on Taylor series expansion was applied to construct stationary principle, from which all orders of perturbations were calculated. The irradiated EK-10 and MTR-20 fuels at their maximum burn-up of 25% and 65% respectively were considered for sensitivity analysis. The results of calculation show that, in case of EK-10 fuel (low burn-up), the first order sensitivity was found to be enough to perform an accuracy of 1%. While in case of MTR-20 (high burn-up) the fifth order was found to provide 3% accuracy. A computer code SENS was developed to provide the required calculations

  1. Gq activity- and β-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility

    Lin, Hui; Li, Rui-Rui; Liang, Zong-Lai; Gao, Yuan; Yang, Zhao; He, Dong-Fang; Lin, Amy; Mo, Hui; Lu, Yu-Jing; Li, Meng-Jing; Kong, Wei; Chung, Ka Young; Yi, Fan; Li, Jian-Yuan; Qin, Ying-Ying; Li, Jingxin; Thomsen, Alex R B; Kahsai, Alem W; Chen, Zi-Jiang; Xu, Zhi-Gang; Liu, Mingyao

    2018-01-01

    Luminal fluid reabsorption plays a fundamental role in male fertility. We demonstrated that the ubiquitous GPCR signaling proteins Gq and β-arrestin-1 are essential for fluid reabsorption because they mediate coupling between an orphan receptor ADGRG2 (GPR64) and the ion channel CFTR. A reduction in protein level or deficiency of ADGRG2, Gq or β-arrestin-1 in a mouse model led to an imbalance in pH homeostasis in the efferent ductules due to decreased constitutive CFTR currents. Efferent ductule dysfunction was rescued by the specific activation of another GPCR, AGTR2. Further mechanistic analysis revealed that β-arrestin-1 acts as a scaffold for ADGRG2/CFTR complex formation in apical membranes, whereas specific residues of ADGRG2 confer coupling specificity for different G protein subtypes, this specificity is critical for male fertility. Therefore, manipulation of the signaling components of the ADGRG2-Gq/β-arrestin-1/CFTR complex by small molecules may be an effective therapeutic strategy for male infertility. PMID:29393851

  2. The Toxicity of Depleted Uranium

    Wayne Briner

    2010-01-01

    Full Text Available Depleted uranium (DU is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed.

  3. Depleted uranium and the Gulf War syndrome

    1999-01-01

    Some military personnel involved in the 1991Gulf War have complained of continuing stress-like symptoms for which no obvious cause has been found. These symptoms have at times been attributed to the use of depleted uranium (DU) in shell casings which are believed to have caused toxic effects. Depleted uranium is natural uranium which is depleted in the rarer U-235 isotope. It is a heavy metal and in common with other heavy metals is chemically toxic. It is also slightly radioactive and could give rise to a radiological hazard if dispersed in finely divided form so that it was inhaled. In response to concerns, the possible effects of DU have been extensively studied along with other possible contributors to G ulf War sickness . This article looks at the results of some of the research that has been done on DU. (author)

  4. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients.

    Schippa, Serena; Iebba, Valerio; Santangelo, Floriana; Gagliardi, Antonella; De Biase, Riccardo Valerio; Stamato, Antonella; Bertasi, Serenella; Lucarelli, Marco; Conte, Maria Pia; Quattrucci, Serena

    2013-01-01

    In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF). CFTR mutations (F508del is the most common) lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. Patients were classified by two different criteria: 1) presence/absence of F508del mutation; 2) disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme) were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum) were reduced. This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.

  5. Is Ego Depletion Real? An Analysis of Arguments.

    Friese, Malte; Loschelder, David D; Gieseler, Karolin; Frankenbach, Julius; Inzlicht, Michael

    2018-03-01

    An influential line of research suggests that initial bouts of self-control increase the susceptibility to self-control failure (ego depletion effect). Despite seemingly abundant evidence, some researchers have suggested that evidence for ego depletion was the sole result of publication bias and p-hacking, with the true effect being indistinguishable from zero. Here, we examine (a) whether the evidence brought forward against ego depletion will convince a proponent that ego depletion does not exist and (b) whether arguments that could be brought forward in defense of ego depletion will convince a skeptic that ego depletion does exist. We conclude that despite several hundred published studies, the available evidence is inconclusive. Both additional empirical and theoretical works are needed to make a compelling case for either side of the debate. We discuss necessary steps for future work toward this aim.

  6. Poroelasticity of high porosity chalk under depletion

    Andreassen, Katrine Alling; Fabricius, Ida Lykke

    2013-01-01

    on mechanical test results is found to be low-er than the pretest dynamic Biot coefficient determined from elastic wave propagation for the loading path and with less deviation under depletion. The calculated lateral stress is lower than the experimentally measured lateral stress depending on loading path...

  7. Depletion mode pumping of solid state lasers

    Mundinger, D.; Solarz, R.; Beach, R.; Albrecht, G.; Krupke, W.

    1990-01-01

    Depletion mode pumping of solid state lasers is a new concept which offers features that are of interest for many practical applications. In this paper the authors discuss the physical properties and mechanisms that set the design requirements, present model calculations for a practical laser design, and discuss the results of recent experiments

  8. Glutathione depletion in tissues after administration of buthionine sulphoximine

    Minchinton, A.I.; Rojas, A.; Smith, A.; Soranson, J.A.; Shrieve, D.C.; Jones, N.R.; Bremner, J.C.

    1984-01-01

    Buthionine sulphoximine (BSO) an inhibitor of glutathione (GSH) biosynthesis, was administered to mice in single and repeated doses. The resultant pattern of GSH depletion was studied in liver, kidney, skeletal muscle and three types of murine tumor. Liver and kidney exhibited a rapid depletion of GSH. Muscle was depleted to a similar level, but at a slower rate after a single dose. All three tumors required repeated administration of BSO over several days to obtain a similar degree of depletion to that shown in the other tissues

  9. The importance of functional tests to assess the effect of a new CFTR variant when genotype-phenotype correlation is not possible.

    Hinzpeter, Alexandre; Reboul, Marie-Pierre; Callebaut, Isabelle; Zordan, Cécile; Costes, Bruno; Guichoux, Julie; Iron, Albert; Lacombe, Didier; Martin, Natacha; Arveiler, Benoit; Fanen, Pascale; Fergelot, Patricia; Girodon, Emmanuelle

    2017-05-01

    In vitro functional tests aimed to investigate CFTR dysfunction appear critical to help elucidate the functional impact of new variants of uncertain clinical significance and solve inconclusive cases, especially in early deceased newborns.

  10. Ozone depleting substances management inventory system

    Felix Ivan Romero Rodríguez

    2018-02-01

    Full Text Available Context: The care of the ozone layer is an activity that contributes to the planet's environmental stability. For this reason, the Montreal Protocol is created to control the emission of substances that deplete the ozone layer and reduce its production from an organizational point of view. However, it is also necessary to have control of those that are already circulating and those present in the equipment that cannot be replaced yet because of the context of the companies that keep it. Generally, the control mechanisms for classifying the type of substances, equipment and companies that own them, are carried in physical files, spreadsheets and text documents, which makes it difficult to control and manage the data stored in them. Method: The objective of this research is to computerize the process of control of substances that deplete the ozone layer. An evaluation and description of all process to manage Ozone-Depleting Substances (ODS, and its alternatives, is done. For computerization, the agile development methodology SCRUM is used, and for the technological solution tools and free open source technologies are used. Result: As a result of the research, a computer tool was developed that automates the process of control and management of substances that exhaust the ozone layer and its alternatives. Conclusions: The developed computer tool allows to control and manage the ozone-depleting substances and the equipment that use them. It also manages the substances that arise as alternatives to be used for the protection of the ozone layer.

  11. Hsp90 depletion goes wild

    Siegal, Mark L; Masel, Joanna

    2012-01-01

    Abstract Hsp90 reveals phenotypic variation in the laboratory, but is Hsp90 depletion important in the wild? Recent work from Chen and Wagner in BMC Evolutionary Biology has discovered a naturally occurring Drosophila allele that downregulates Hsp90, creating sensitivity to cryptic genetic variation. Laboratory studies suggest that the exact magnitude of Hsp90 downregulation is important. Extreme Hsp90 depletion might reactivate transposable elements and/or induce aneuploidy, in addition to r...

  12. "When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect.

    Salmon, Stefanie J; Adriaanse, Marieke A; De Vet, Emely; Fennis, Bob M; De Ridder, Denise T D

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion.

  13. Too Depleted to Try? Testing the Process Model of Ego Depletion in the Context of Unhealthy Snack Consumption.

    Haynes, Ashleigh; Kemps, Eva; Moffitt, Robyn

    2016-11-01

    The process model proposes that the ego depletion effect is due to (a) an increase in motivation toward indulgence, and (b) a decrease in motivation to control behaviour following an initial act of self-control. In contrast, the reflective-impulsive model predicts that ego depletion results in behaviour that is more consistent with desires, and less consistent with motivations, rather than influencing the strength of desires and motivations. The current study sought to test these alternative accounts of the relationships between ego depletion, motivation, desire, and self-control. One hundred and fifty-six undergraduate women were randomised to complete a depleting e-crossing task or a non-depleting task, followed by a lab-based measure of snack intake, and self-report measures of motivation and desire strength. In partial support of the process model, ego depletion was related to higher intake, but only indirectly via the influence of lowered motivation. Motivation was more strongly predictive of intake for those in the non-depletion condition, providing partial support for the reflective-impulsive model. Ego depletion did not affect desire, nor did depletion moderate the effect of desire on intake, indicating that desire may be an appropriate target for reducing unhealthy behaviour across situations where self-control resources vary. © 2016 The International Association of Applied Psychology.

  14. Podocyte Depletion in Thin GBM and Alport Syndrome.

    Wickman, Larysa; Hodgin, Jeffrey B; Wang, Su Q; Afshinnia, Farsad; Kershaw, David; Wiggins, Roger C

    2016-01-01

    The proximate genetic cause of both Thin GBM and Alport Syndrome (AS) is abnormal α3, 4 and 5 collagen IV chains resulting in abnormal glomerular basement membrane (GBM) structure/function. We previously reported that podocyte detachment rate measured in urine is increased in AS, suggesting that podocyte depletion could play a role in causing progressive loss of kidney function. To test this hypothesis podometric parameters were measured in 26 kidney biopsies from 21 patients aged 2-17 years with a clinic-pathologic diagnosis including both classic Alport Syndrome with thin and thick GBM segments and lamellated lamina densa [n = 15] and Thin GBM cases [n = 6]. Protocol biopsies from deceased donor kidneys were used as age-matched controls. Podocyte depletion was present in AS biopsies prior to detectable histologic abnormalities. No abnormality was detected by light microscopy at 70% podocyte depletion. Low level proteinuria was an early event at about 25% podocyte depletion and increased in proportion to podocyte depletion. These quantitative data parallel those from model systems where podocyte depletion is the causative event. This result supports a hypothesis that in AS podocyte adherence to the GBM is defective resulting in accelerated podocyte detachment causing progressive podocyte depletion leading to FSGS-like pathologic changes and eventual End Stage Kidney Disease. Early intervention to reduce podocyte depletion is projected to prolong kidney survival in AS.

  15. Analysis and Application of Whey Protein Depleted Skim Milk Systems

    Sørensen, Hanne

    homogenisation (UHPH). The microfiltration will result in a milk fraction more or less depleted from whey protein, and could probably in combination with UHPH treatment contribute to milk fractions and cheeses with novel micro and macrostructures. These novel fractions could be used as new ingredients to improve......-destructive methods for this purpose. A significant changed structure was observed in skim milk depleted or partly depleted for whey protein, acidified and UHPH treated. Some of the properties of the UHPH treated skim milk depleted from whey protein observed in this study support the idea, that UHPH treatment has...... this. LF-NMR relaxation were utilised to obtain information about the water mobility (relaxation time), in diluted skim milk systems depleted from whey protein. Obtained results indicate that measuring relaxation times with LF-NMR could be difficult to utilize, since no clear relationship between...

  16. Transient Treg depletion enhances therapeutic anti‐cancer vaccination

    Aston, Wayne J.; Chee, Jonathan; Khong, Andrea; Cleaver, Amanda L.; Solin, Jessica N.; Ma, Shaokang; Lesterhuis, W. Joost; Dick, Ian; Holt, Robert A.; Creaney, Jenette; Boon, Louis; Robinson, Bruce; Lake, Richard A.

    2016-01-01

    Abstract Introduction Regulatory T cells (Treg) play an important role in suppressing anti‐ immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti‐cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. Methods Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored. Results DTX specifically depleted Treg in a transient, dose‐dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor‐peptide vaccination. Conclusions BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti‐tumor immunity. DTX‐mediated Treg depletion is transient, dose‐dependent, and leads to strong anti‐tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor‐specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies. PMID:28250921

  17. NOMAD: a nodal microscopic analysis method for nuclear fuel depletion

    Rajic, H.L.; Ougouag, A.M.

    1987-01-01

    Recently developed assembly homogenization techniques made possible very efficient global burnup calculations based on modern nodal methods. There are two possible ways of modeling the global depletion process: macroscopic and microscopic depletion models. Using a microscopic global depletion approach NOMAD (NOdal Microscopic Analysis Method for Nuclear Fuel Depletion), a multigroup, two- and three-dimensional, multicycle depletion code was devised. The code uses the ILLICO nodal diffusion model. The formalism of the ILLICO methodology is extended to treat changes in the macroscopic cross sections during a depletion cycle without recomputing the coupling coefficients. This results in a computationally very efficient method. The code was tested against a well-known depletion benchmark problem. In this problem a two-dimensional pressurized water reactor is depleted through two cycles. Both cycles were run with 1 x 1 and 2 x 2 nodes per assembly. It is obvious that the one node per assembly solution gives unacceptable results while the 2 x 2 solution gives relative power errors consistently below 2%

  18. Sweat chloride and immunoreactive trypsinogen in infants carrying two CFTR mutations and not affected by cystic fibrosis.

    Castellani, Carlo; Tridello, Gloria; Tamanini, Anna; Assael, Baroukh M

    2017-07-01

    Newborns with raised immunotrypsinogen levels who have non-pathological sweat chloride values and carry two cystic fibrosis transmembrane regulator ( CFTR ) mutations of which at least one is not acknowledged to be cystic fibrosis (CF)-causing are at risk of developing clinical manifestations consistent with CFTR-related disorders or even CF. It is not known whether newborns with similar genotypes and normal immunoreactive trypsinogen (IRT) may share the same risk. This study found that newborns with these characteristics and normal IRT have lower sweat chloride values than those with raised IRT (p=0.007). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Analysis of the CFTR gene in Venezuelan cystic fibrosis patients, identification of six novel cystic fibrosis-causing genetic variants

    Sánchez, Karen; De Mendonca,Elizabeth; Matute,Xiorama; Chaustre,Ismenia; Villalon,Marlene; Takiff,Howard

    2016-01-01

    Karen Sánchez,1 Elizabeth de Mendonca,1 Xiorama Matute,2 Ismenia Chaustre,2 Marlene Villalón,3 Howard Takiff4 1Unit of Genetic and Forensic Studies, Venezuelan Institute for Scientific Research (IVIC), 2Hospital JM de los Ríos, 3Hospital José Ignacio Baldo, Algodonal, National Reference Unit, 4Laboratory of Molecular Genetics, Venezuelan Institute for Scientific Research (IVIC), Caracas, Venezuela. Abstract: The mutations in the CFTR gene found in ...

  20. Isotopic depletion with Monte Carlo

    Martin, W.R.; Rathkopf, J.A.

    1996-06-01

    This work considers a method to deplete isotopes during a time- dependent Monte Carlo simulation of an evolving system. The method is based on explicitly combining a conventional estimator for the scalar flux with the analytical solutions to the isotopic depletion equations. There are no auxiliary calculations; the method is an integral part of the Monte Carlo calculation. The method eliminates negative densities and reduces the variance in the estimates for the isotope densities, compared to existing methods. Moreover, existing methods are shown to be special cases of the general method described in this work, as they can be derived by combining a high variance estimator for the scalar flux with a low-order approximation to the analytical solution to the depletion equation

  1. Barium depletion study on impregnated cathodes and lifetime prediction

    Roquais, J.M.; Poret, F.; Doze, R. le; Ricaud, J.L.; Monterrin, A.; Steinbrunn, A.

    2003-01-01

    In the thermionic cathodes used in cathode ray-tubes (CRTs), barium is the key element for the electronic emission. In the case of the dispenser cathodes made of a porous tungsten pellet impregnated with Ba, Ca aluminates, the evaporation of Ba determines the cathode lifetime with respect to emission performance in the CRT. The Ba evaporation results in progressive depletion of the impregnating material inside the pellet. In the present work, the Ba depletion with time has been extensively characterized over a large range of cathode temperature. Calculations using the depletion data allowed modeling of the depletion as a function of key parameters. The link between measured depletion and emission in tubes has been established, from which an end-of-life criterion was deduced. Taking modeling into account, predicting accelerated life-tests were performed using high-density maximum emission current (MIK)

  2. Gulf war depleted uranium risks.

    Marshall, Albert C

    2008-01-01

    US and British forces used depleted uranium (DU) in armor-piercing rounds to disable enemy tanks during the Gulf and Balkan Wars. Uranium particulate is generated by DU shell impact and particulate entrained in air may be inhaled or ingested by troops and nearby civilian populations. As uranium is slightly radioactive and chemically toxic, a number of critics have asserted that DU exposure has resulted in a variety of adverse health effects for exposed veterans and nearby civilian populations. The study described in this paper used mathematical modeling to estimate health risks from exposure to DU during the 1991 Gulf War for both US troops and nearby Iraqi civilians. The analysis found that the risks of DU-induced leukemia or birth defects are far too small to result in an observable increase in these health effects among exposed veterans or Iraqi civilians. The analysis indicated that only a few ( approximately 5) US veterans in vehicles accidentally targeted by US tanks received significant exposure levels, resulting in about a 1.4% lifetime risk of DU radiation-induced fatal cancer (compared with about a 24% risk of a fatal cancer from all other causes). These veterans may have also experienced temporary kidney damage. Iraqi children playing for 500 h in DU-destroyed vehicles are predicted to incur a cancer risk of about 0.4%. In vitro and animal tests suggest the possibility of chemically induced health effects from DU internalization, such as immune system impairment. Further study is needed to determine the applicability of these findings for Gulf War exposure to DU. Veterans and civilians who did not occupy DU-contaminated vehicles are unlikely to have internalized quantities of DU significantly in excess of normal internalization of natural uranium from the environment.

  3. Analysis of the CFTR gene in Venezuelan cystic fibrosis patients, identification of six novel cystic fibrosis-causing genetic variants.

    Sánchez, Karen; de Mendonca, Elizabeth; Matute, Xiorama; Chaustre, Ismenia; Villalón, Marlene; Takiff, Howard

    2016-01-01

    The mutations in the CFTR gene found in patients with cystic fibrosis (CF) have geographic differences, but there are scant data on their prevalence in Venezuelan patients. This study determined the frequency of common CFTR gene mutations in a group of Venezuelan patients with CF. The 27 exons of the CFTR gene from 110 Venezuelan patients in the National CF Program were amplified and sequenced. A total of 36 different mutations were identified, seven with frequencies greater than 1%: p.Phe508del (27.27%), p.Gly542* (3.18%), c.2988+1G>A (3.18%), p.Arg334Trp (1.36%), p.Arg1162* (1.36%), c.1-8G>C (1.36%), and p.[Gly628Arg;Ser1235Arg](1.36). In 40% of patients, all with a clinical diagnosis of CF, no mutations were found. This report represents the largest cohort of Venezuelan patients with CF ever examined, and includes a wider mutation panel than has been previously studied in this population. Mutations common in Southern European populations predominate, and several new mutations were discovered, but no mutations were found in 40% of the cohort.

  4. Hsp90 depletion goes wild

    Siegal Mark L

    2012-02-01

    Full Text Available Abstract Hsp90 reveals phenotypic variation in the laboratory, but is Hsp90 depletion important in the wild? Recent work from Chen and Wagner in BMC Evolutionary Biology has discovered a naturally occurring Drosophila allele that downregulates Hsp90, creating sensitivity to cryptic genetic variation. Laboratory studies suggest that the exact magnitude of Hsp90 downregulation is important. Extreme Hsp90 depletion might reactivate transposable elements and/or induce aneuploidy, in addition to revealing cryptic genetic variation. See research article http://wwww.biomedcentral.com/1471-2148/12/25

  5. Reactor fuel depletion benchmark of TINDER

    Martin, W.J.; Oliveira, C.R.E. de; Hecht, A.A.

    2014-01-01

    Highlights: • A reactor burnup benchmark of TINDER, coupling MCNP6 to CINDER2008, was performed. • TINDER is a poor candidate for fuel depletion calculations using its current libraries. • Data library modification is necessary if fuel depletion is desired from TINDER. - Abstract: Accurate burnup calculations are key to proper nuclear reactor design, fuel cycle modeling, and disposal estimations. The TINDER code, originally designed for activation analyses, has been modified to handle full burnup calculations, including the widely used predictor–corrector feature. In order to properly characterize the performance of TINDER for this application, a benchmark calculation was performed. Although the results followed the trends of past benchmarked codes for a UO 2 PWR fuel sample from the Takahama-3 reactor, there were obvious deficiencies in the final result, likely in the nuclear data library that was used. Isotopic comparisons versus experiment and past code benchmarks are given, as well as hypothesized areas of deficiency and future work

  6. Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps.

    Wei, Shipeng; Roessler, Bryan C; Chauvet, Sylvain; Guo, Jingyu; Hartman, John L; Kirk, Kevin L

    2014-07-18

    ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares gating principles with conventional ligand-gated ion channels, but the allosteric network that couples ATP binding at its nucleotide binding domains (NBDs) with conformational changes in its transmembrane helices (TMs) is poorly defined. It is also unclear whether the mechanisms that govern CFTR gating are conserved with the thermodynamically distinct MRPs. Here we report a new class of gain of function (GOF) mutation of a conserved proline at the base of the pore-lining TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP). TM6 proline mutations exhibited additive GOF effects when combined with a previously reported GOF mutation located in an outer collar of TMs that surrounds the pore-lining TMs. Each TM substitution allosterically rescued the ATP sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP binding. Both classes of GOF mutations also rescued defective drug export by a yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the conserved TM6 proline helps set the energy barrier to both CFTR channel opening and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar allosteric mechanisms for coupling conformational changes in their translocation pathways to ATP binding at their NBDs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Health and environmental impact of depleted uranium

    Furitsu, Katsumi

    2010-01-01

    Depleted Uranium (DU) is 'nuclear waste' produced from the enrichment process and is mostly made up of 238 U and is depleted in the fissionable isotope 235 U compared to natural uranium (NU). Depleted uranium has about 60% of the radioactivity of natural uranium. Depleted uranium and natural uranium are identical in terms of the chemical toxicity. Uranium's high density gives depleted uranium shells increased range and penetrative power. This density, combined with uranium's pyrophoric nature, results in a high-energy kinetic weapon that can punch and burn through armour plating. Striking a hard target, depleted uranium munitions create extremely high temperatures. The uranium immediately burns and vaporizes into an aerosol, which is easily diffused in the environment. People can inhale the micro-particles of uranium oxide in an aerosol and absorb them mainly from lung. Depleted uranium has both aspects of radiological toxicity and chemical toxicity. The possible synergistic effect of both kinds of toxicities is also pointed out. Animal and cellular studies have been reported the carcinogenic, neurotoxic, immuno-toxic and some other effects of depleted uranium including the damage on reproductive system and foetus. In addition, the health effects of micro/ nano-particles, similar in size of depleted uranium aerosols produced by uranium weapons, have been reported. Aerosolized DU dust can easily spread over the battlefield spreading over civilian areas, sometimes even crossing international borders. Therefore, not only the military personnel but also the civilians can be exposed. The contamination continues after the cessation of hostilities. Taking these aspects into account, DU weapon is illegal under international humanitarian laws and is considered as one of the inhumane weapons of 'indiscriminate destruction'. The international society is now discussing the prohibition of DU weapons based on 'precautionary principle'. The 1991 Gulf War is reportedly the first

  8. Funciones de los canales iónicos CFTR y ENAC en la fibrosis quística

    Alejandra G. Palma

    2014-04-01

    Full Text Available La fibrosis quística se debe a la ausencia o defecto del canal transmembrana regulador de la fibrosis quística (CFTR, un canal de cloruro codificado en el gen cftr que juega un papel clave en la homeostasis del agua e iones. El CFTR es activado por el AMPc y se localiza en las membranas apicales y basolaterales de las vías aéreas, intestino y glándulas exocrinas. Una de sus funciones primarias en los pulmones es mantener la capa de líquido superficial a través de su función de canal y regular el canal epitelial de sodio sensible al amiloride (ENaC. Se han identificado más de 1900 mutaciones en el gen cftr. La enfermedad se caracteriza por secreciones viscosas en las glándulas exocrinas y por niveles elevados de cloruro de sodio en el sudor. En la fibrosis quística el CFTR no funciona y el ENaC está desregulado; el resultado es un aumento en la reabsorción de sodio y agua con la formación de un líquido viscoso. En las glándulas sudoríparas tanto el Na+ como el Cl- se retienen en el lumen causando una pérdida de electrolitos durante la sudoración y el NaCl se elimina al sudor. Así, los niveles elevados de NaCl son la base del test del sudor inducido por pilocarpina, un método de diagnóstico para la enfermedad. En esta revisión se discuten los movimientos de Cl- y Na+ en las glándulas sudoríparas y pulmón así como el papel del ENaC en la patogénesis de la enfermedad.

  9. Depletion field focusing in semiconductors

    Prins, M.W.J.; Gelder, Van A.P.

    1996-01-01

    We calculate the three-dimensional depletion field profile in a semiconductor, for a planar semiconductor material with a spatially varying potential upon the surface, and for a tip-shaped semiconductor with a constant surface potential. The nonuniform electric field gives rise to focusing or

  10. Depletion interactions in lyotropic nematics

    Schoot, van der P.P.A.M.

    2000-01-01

    A theoretical study of depletion interactions between pairs of small, globular colloids dispersed in a lyotropic nematic of hard, rodlike particles is presented. We find that both the strength and range of the interaction crucially depends on the configuration of the spheres relative to the nematic

  11. Depleted uranium: an explosive dossier

    Barrillot, B.

    2001-01-01

    This book relates the history of depleted uranium, contemporaneous with the nuclear bomb history. Initially used in nuclear weapons and in experiments linked with nuclear weapons development, this material has been used also in civil industry, in particular in aeronautics. However, its properties made it interesting for military applications all along the 'cold war'. (J.S.)

  12. Global depletion of groundwater resources

    Wada, Y.; Beek, L.P.H. van; van Kempen, C.M.; Reckman, J.W.T.M.; Vasak, S.; Bierkens, M.F.P.

    2010-01-01

    In regions with frequent water stress and large aquifer systems groundwater is often used as an additional water source. If groundwater abstraction exceeds the natural groundwater recharge for extensive areas and long times, overexploitation or persistent groundwater depletion occurs. Here we

  13. Impact of mineral resource depletion

    Brent, AC

    2006-09-01

    Full Text Available In a letter to the editor, the authors comment on BA Steen's article on "Abiotic Resource Depletion: different perceptions of the problem with mineral deposits" published in the special issue of the International Journal of Life Cycle Assessment...

  14. Depleted uranium plasma reduction system study

    Rekemeyer, P.; Feizollahi, F.; Quapp, W.J.; Brown, B.W.

    1994-12-01

    A system life-cycle cost study was conducted of a preliminary design concept for a plasma reduction process for converting depleted uranium to uranium metal and anhydrous HF. The plasma-based process is expected to offer significant economic and environmental advantages over present technology. Depleted Uranium is currently stored in the form of solid UF 6 , of which approximately 575,000 metric tons is stored at three locations in the U.S. The proposed system is preconceptual in nature, but includes all necessary processing equipment and facilities to perform the process. The study has identified total processing cost of approximately $3.00/kg of UF 6 processed. Based on the results of this study, the development of a laboratory-scale system (1 kg/h throughput of UF6) is warranted. Further scaling of the process to pilot scale will be determined after laboratory testing is complete

  15. Improvements in EBR-2 core depletion calculations

    Finck, P.J.; Hill, R.N.; Sakamoto, S.

    1991-01-01

    The need for accurate core depletion calculations in Experimental Breeder Reactor No. 2 (EBR-2) is discussed. Because of the unique physics characteristics of EBR-2, it is difficult to obtain accurate and computationally efficient multigroup flux predictions. This paper describes the effect of various conventional and higher order schemes for group constant generation and for flux computations; results indicate that higher-order methods are required, particularly in the outer regions (i.e. the radial blanket). A methodology based on Nodal Equivalence Theory (N.E.T.) is developed which allows retention of the accuracy of a higher order solution with the computational efficiency of a few group nodal diffusion solution. The application of this methodology to three-dimensional EBR-2 flux predictions is demonstrated; this improved methodology allows accurate core depletion calculations at reasonable cost. 13 refs., 4 figs., 3 tabs

  16. Depleted depletion drives polymer swelling in poor solvent mixtures.

    Mukherji, Debashish; Marques, Carlos M; Stuehn, Torsten; Kremer, Kurt

    2017-11-09

    Establishing a link between macromolecular conformation and microscopic interaction is a key to understand properties of polymer solutions and for designing technologically relevant "smart" polymers. Here, polymer solvation in solvent mixtures strike as paradoxical phenomena. For example, when adding polymers to a solvent, such that all particle interactions are repulsive, polymer chains can collapse due to increased monomer-solvent repulsion. This depletion induced monomer-monomer attraction is well known from colloidal stability. A typical example is poly(methyl methacrylate) (PMMA) in water or small alcohols. While polymer collapse in a single poor solvent is well understood, the observed polymer swelling in mixtures of two repulsive solvents is surprising. By combining simulations and theoretical concepts known from polymer physics and colloidal science, we unveil the microscopic, generic origin of this collapse-swelling-collapse behavior. We show that this phenomenon naturally emerges at constant pressure when an appropriate balance of entropically driven depletion interactions is achieved.

  17. Lagopedo: two F-region ionospheric depletion experiments

    Pongratz, M.B.; Smith, G.M.; Sutherland, C.D.; Zinn, J.

    1977-01-01

    A significant depletion of ionospheric plasma was produced by a chemical release experiment in the F-layer ionosphere over Hawaii. The results of measurements of the hole produced in the ionospheric plasma are reported

  18. Ly6G-mediated depletion of neutrophils is dependent on macrophages.

    Bruhn, Kevin W; Dekitani, Ken; Nielsen, Travis B; Pantapalangkoor, Paul; Spellberg, Brad

    2016-01-01

    Antibody-mediated depletion of neutrophils is commonly used to study neutropenia. However, the mechanisms by which antibodies deplete neutrophils have not been well defined. We noticed that mice deficient in complement and macrophages had blunted neutrophil depletion in response to anti-Ly6G monoclonal antibody (MAb) treatment. In vitro, exposure of murine neutrophils to anti-Ly6G MAb in the presence of plasma did not result in significant depletion of cells, either in the presence or absence of complement. In vivo, anti-Ly6G-mediated neutrophil depletion was abrogated following macrophage depletion, but not complement depletion, indicating a requirement for macrophages to induce neutropenia by this method. These results inform the use and limitations of anti-Ly6G antibody as an experimental tool for depleting neutrophils in various immunological settings.

  19. The ichthyotoxic alga Chattonella marina induces Na+, K+-ATPase, and CFTR proteins expression in fish gill chloride cells in vivo

    Tang, Janet Y.M.; Wong, Chris K.C.; Au, Doris W.T.

    2007-01-01

    Our previous studies demonstrated that the ichthyotoxic Chattonella marina stimulated proliferation of branchial chloride cell (CC) and induced osmotic distress akin to hyperactive elimination of ions in fish (Rhabdosargus sarba). To ascertain the in vivo effects of C. marina on key CC ion transporters, the localization and expression of Na + , K + -ATPase (NKA) and cystic fibrosis transmembrane conductance regulator (CFTR) proteins in response to C. marina exposure were investigated, using a quantitative immunocytochemical approach. The polarized distributions of NKA (α subunit) and CFTR proteins in branchial CCs of R. sarba remained unchanged under C. marina exposure. However, significant inductions of these two ion-transporters were detected in CCs of fish after 6 h exposure. By real-time PCR, no significant changes in gill NKA and CFTR mRNA expressions were detected, suggesting a post-transcriptional pathway is likely involved in regulating the ion transporters abundance. This study is the first to demonstrate the in vivo effects of harmful algal toxin on NKA and CFTR protein expressions in gill transepithelial cells. Taken together, an augmentation of branchial CCs together with hyper-stimulation of NKA and CFTR in CCs attribute to the rapid development of osmotic distress in C. marina susceptible fish

  20. The ultimate disposition of depleted uranium

    1990-12-01

    Significant amounts of the depleted uranium (DU) created by past uranium enrichment activities have been sold, disposed of commercially, or utilized by defense programs. In recent years, however, the demand for DU has become quite small compared to quantities available, and within the US Department of Energy (DOE) there is concern for any risks and/or cost liabilities that might be associated with the ever-growing inventory of this material. As a result, Martin Marietta Energy Systems, Inc. (Energy Systems), was asked to review options and to develop a comprehensive plan for inventory management and the ultimate disposition of DU accumulated at the gaseous diffusion plants (GDPs). An Energy Systems task team, under the chairmanship of T. R. Lemons, was formed in late 1989 to provide advice and guidance for this task. This report reviews options and recommends actions and objectives in the management of working inventories of partially depleted feed (PDF) materials and for the ultimate disposition of fully depleted uranium (FDU). Actions that should be considered are as follows. (1) Inspect UF{sub 6} cylinders on a semiannual basis. (2) Upgrade cylinder maintenance and storage yards. (3) Convert FDU to U{sub 3}O{sub 8} for long-term storage or disposal. This will include provisions for partial recovery of costs to offset those associated with DU inventory management and the ultimate disposal of FDU. Another recommendation is to drop the term tails'' in favor of depleted uranium'' or DU'' because the tails'' label implies that it is waste.'' 13 refs.

  1. Implantation of a new calculation method of fuel depletion in the CITHAM code

    Alvarenga, M.A.B.

    1985-01-01

    It is evaluated the accuracy of the linear aproximation method used in the CITHAN code to obtain the solution of depletion equations. Results are compared with the Benchmark problem. The convenience of depletion chain before criticality calculations is analysed. The depletion calculation was modified using linear combination technic of linear chains. (M.C.K.) [pt

  2. Associative Interactions in Crowded Solutions of Biopolymers Counteract Depletion Effects.

    Groen, Joost; Foschepoth, David; te Brinke, Esra; Boersma, Arnold J; Imamura, Hiromi; Rivas, Germán; Heus, Hans A; Huck, Wilhelm T S

    2015-10-14

    The cytosol of Escherichia coli is an extremely crowded environment, containing high concentrations of biopolymers which occupy 20-30% of the available volume. Such conditions are expected to yield depletion forces, which strongly promote macromolecular complexation. However, crowded macromolecule solutions, like the cytosol, are very prone to nonspecific associative interactions that can potentially counteract depletion. It remains unclear how the cytosol balances these opposing interactions. We used a FRET-based probe to systematically study depletion in vitro in different crowded environments, including a cytosolic mimic, E. coli lysate. We also studied bundle formation of FtsZ protofilaments under identical crowded conditions as a probe for depletion interactions at much larger overlap volumes of the probe molecule. The FRET probe showed a more compact conformation in synthetic crowding agents, suggesting strong depletion interactions. However, depletion was completely negated in cell lysate and other protein crowding agents, where the FRET probe even occupied slightly more volume. In contrast, bundle formation of FtsZ protofilaments proceeded as readily in E. coli lysate and other protein solutions as in synthetic crowding agents. Our experimental results and model suggest that, in crowded biopolymer solutions, associative interactions counterbalance depletion forces for small macromolecules. Furthermore, the net effects of macromolecular crowding will be dependent on both the size of the macromolecule and its associative interactions with the crowded background.

  3. The enhancements and testing for the MCNPX depletion capability

    Fensin, M. L.; Hendricks, J. S.; Anghaie, S.

    2008-01-01

    Monte Carlo-linked depletion methods have gained recent interest due to the ability to more accurately model true system physics and better track the evolution of temporal nuclide inventory by simulating the actual physical process. The integration of INDER90 into the MCNPX Monte Carlo radiation transport code provides a completely self-contained Monte- Carlo-linked depletion capability in a single Monte Carlo code that is compatible with most nuclear criticality (KCODE) particle tracking features in MCNPX. MCNPX depletion tracks all necessary reaction rates and follows as many isotopes as cross section data permits in order to achieve a highly accurate temporal nuclide inventory solution. We describe here the depletion methodology dating from the original linking of MONTEBURNS and MCNP to the first public release of the integrated capability (MCNPX 2. 6.B, June, 2006) that has been reported previously. Then we further detail the many new depletion capability enhancements since then leading to the present capability. The H.B. Robinson benchmark calculation results are also reported. The new MCNPX depletion capability enhancements include: (1) allowing the modeling of as large a system as computer memory capacity permits; (2) tracking every fission product available in ENDF/B VII. 0; (3) enabling depletion in repeated structures geometries such as repeated arrays of fuel pins; (4) including metastable isotopes in burnup; and (5) manually changing the concentrations of key isotopes during different time steps to simulate changing reactor control conditions such as dilution of poisons to maintain criticality during burnup. These enhancements allow better detail to model the true system physics and also improve the robustness of the capability. The H.B. Robinson benchmark calculation was completed in order to determine the accuracy of the depletion solution. Temporal nuclide computations of key actinide and fission products are compared to the results of other

  4. The study of necessity of verification-methods for Depleted Uranium

    Park, J. B.; Ahn, S. H.; Ahn, G. H.; Chung, S. T.; Shin, J. S.

    2006-01-01

    ROK has tried to establish management system for depleted uranium from 2004, and ROK achieved some results in this field including management software, management skill, and the list of company using the nuclear material. But, the studies for the depleted uranium are insufficient exclude the studies of KAERI. In terms of SSAC, we have to study more about whether the depleted uranium is really dangerous material or not and how is the depleted uranium diverted to the nuclear weapon. The depleted uranium was controlled by the item counting in the national system for the small quantity nuclear material. We don't have unique technical methods to clarify the depleted uranium on-the-spot inspection not laboratory scale. Therefore, I would like to suggest of the necessity of the verification methods for depleted uranium. Furthermore, I would like to show you the methods of the verification of the depleted uranium in national system up to now

  5. T-cell-depleted haploidentical stem cell transplantation results improve with time in adults with acute leukemia: A study from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT).

    Sestili, Simona; Labopin, Myriam; Ruggeri, Annalisa; Velardi, Andrea; Ciceri, Fabio; Maertens, Johan; Kanz, Lothar; Aversa, Franco; Lewalle, Philippe; Bunjes, Donald; Mohty, Mohamad; Nagler, Arnon

    2018-05-15

    T-cell-depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high-risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full-matched donor. To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T-cell-depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005-2011 [n = 191] and 2012-2015 [n = 117]). The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft-versus-host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2-year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced-intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2-year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival

  6. Challenges dealing with depleted uranium in Germany - Reuse or disposal

    Moeller, Kai D.

    2007-01-01

    During enrichment large amounts of depleted Uranium are produced. In Germany every year 2.800 tons of depleted uranium are generated. In Germany depleted uranium is not classified as radioactive waste but a resource for further enrichment. Therefore since 1996 depleted Uranium is sent to ROSATOM in Russia. However it still has to be dealt with the second generation of depleted Uranium. To evaluate the alternative actions in case a solution has to be found in Germany, several studies have been initiated by the Federal Ministry of the Environment. The work that has been carried out evaluated various possibilities to deal with depleted uranium. The international studies on this field and the situation in Germany have been analyzed. In case no further enrichment is planned the depleted uranium has to be stored. In the enrichment process UF 6 is generated. It is an international consensus that for storage it should be converted to U 3 O 8 . The necessary technique is well established. If the depleted Uranium would have to be characterized as radioactive waste, a final disposal would become necessary. For the planned Konrad repository - a repository for non heat generating radioactive waste - the amount of Uranium is limited by the licensing authority. The existing license would not allow the final disposal of large amounts of depleted Uranium in the Konrad repository. The potential effect on the safety case has not been roughly analyzed. As a result it may be necessary to think about alternatives. Several possibilities for the use of depleted uranium in the industry have been identified. Studies indicate that the properties of Uranium would make it useful in some industrial fields. Nevertheless many practical and legal questions are open. One further option may be the use as shielding e.g. in casks for transport or disposal. Possible techniques for using depleted Uranium as shielding are the use of the metallic Uranium as well as the inclusion in concrete. Another

  7. Study and application of microscopic depletion model in core simulator of COSINE project

    Hu Xiaoyu; Wang Su; Yan Yuhang; Liu Zhanquan; Chen Yixue; Huang Kai

    2013-01-01

    Microscopic depletion correction is one of the commonly used techniques that could improve the historical effect and attain higher precision of diffusion calculation and alleviate the inaccuracy caused by historical effect. Core simulator of COSINE project (core and system integrated engine for design and analysis) has developed a hybrid macroscopic-microscopic depletion model to track important isotopes during each depletion history and correct the macro cross sections. The basic theory was discussed in this paper. The effect and results of microscopic depletion correction were also analyzed. The preliminary test results demonstrate that the microscopic depletion model is effective and practicable for improving the precision of core calculation. (authors)

  8. Mercury toxicity in the shark (Squalus acanthias) rectal gland: apical CFTR chloride channels are inhibited by mercuric chloride.

    Ratner, Martha A; Decker, Sarah E; Aller, Stephen G; Weber, Gerhard; Forrest, John N

    2006-03-01

    In the shark rectal gland, basolateral membrane proteins have been suggested as targets for mercury. To examine the membrane polarity of mercury toxicity, we performed experiments in three preparations: isolated perfused rectal glands, primary monolayer cultures of rectal gland epithelial cells, and Xenopus oocytes expressing the shark cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. In perfused rectal glands we observed: (1) a dose-dependent inhibition by mercury of forskolin/3-isobutyl-1-methylxanthine (IBMX)-stimulated chloride secretion; (2) inhibition was maximal when mercury was added before stimulation with forskolin/IBMX; (3) dithiothrietol (DTT) and glutathione (GSH) completely prevented inhibition of chloride secretion. Short-circuit current (Isc) measurements in monolayers of rectal gland epithelial cells were performed to examine the membrane polarity of this effect. Mercuric chloride inhibited Isc more potently when applied to the solution bathing the apical vs. the basolateral membrane (23 +/- 5% and 68 +/- 5% inhibition at 1 and 10 microM HgCl2 in the apical solution vs. 2 +/- 0.9% and 14 +/- 5% in the basolateral solution). This inhibition was prevented by pre-treatment with apical DTT or GSH; however, only the permeant reducing agent DTT reversed mercury inhibition when added after exposure. When the shark rectal gland CFTR channel was expressed in Xenopus oocytes and chloride conductance was measured by two-electrode voltage clamping, we found that 1 microM HgCl2 inhibited forskolin/IBMX conductance by 69.2 +/- 2.0%. We conclude that in the shark rectal gland, mercury inhibits chloride secretion by interacting with the apical membrane and that CFTR is the likely site of this action. Copyright 2006 Wiley-Liss, Inc.

  9. Assessment Of Depleted Uranium Contamination In Selective IRAQI Soils

    Mohammed, A.A.; Hussien, A.Sh.M.; Tawfiq, N.F.

    2008-01-01

    The aim of this research was to measure the radiation exposure rates in three selected Locations in southren part of Iraq (two in Nassireya, and one in Amara) resulted from the existence of depleted uranium in soil and metal pieces have been taken from destroyed tank and study mathmatically the concentration of Depleted Uranium by its dispersion from soil surface by winds and rains from 2003 to 2007. The exposure rates were measured using inspector device, while depleted uranium concentration in soil samples and tank's matal pieces were detected with Solid State Nuclear Track Detectors(SSNTDs). The wind and rain effects were considered in the calculation of dispersion effect on depleted uranium concentration in soil, where the wind effect were calculated with respect to the sites nature and soil conditions, and rain effect with respect to dispersive-convective equation for radionuclide in soil. The results obtained for the exposure rates were high near the penetrated surfac, moderate and low in soil and metal pices. The Depleted Uranium concentration in soil and metal pieces have the highest value in Nassireya. The results from dispersion calculation (wind & rain) showed that the depleted uranium concentration in 2008 will be less than the danger level and in allowable contamination range

  10. Exposure to nature counteracts aggression after depletion.

    Wang, Yan; She, Yihan; Colarelli, Stephen M; Fang, Yuan; Meng, Hui; Chen, Qiuju; Zhang, Xin; Zhu, Hongwei

    2018-01-01

    Acts of self-control are more likely to fail after previous exertion of self-control, known as the ego depletion effect. Research has shown that depleted participants behave more aggressively than non-depleted participants, especially after being provoked. Although exposure to nature (e.g., a walk in the park) has been predicted to replenish resources common to executive functioning and self-control, the extent to which exposure to nature may counteract the depletion effect on aggression has yet to be determined. The present study investigated the effects of exposure to nature on aggression following depletion. Aggression was measured by the intensity of noise blasts participants delivered to an ostensible opponent in a competition reaction-time task. As predicted, an interaction occurred between depletion and environmental manipulations for provoked aggression. Specifically, depleted participants behaved more aggressively in response to provocation than non-depleted participants in the urban condition. However, provoked aggression did not differ between depleted and non-depleted participants in the natural condition. Moreover, within the depletion condition, participants in the natural condition had lower levels of provoked aggression than participants in the urban condition. This study suggests that a brief period of nature exposure may restore self-control and help depleted people regain control over aggressive urges. © 2017 Wiley Periodicals, Inc.

  11. Importance of energetic solar protons in ozone depletion

    Stephenson, J A.E.; Scourfield, M W.J. [Natal Univ., Durban (South Africa). Space Physics Research Inst.

    1991-07-11

    CHLORINE-catalysed depletion of the stratospheric ozone layer has commanded considerable attention since 1985, when Farman et al. observed a decrease of 50% in the total column ozone over Antarctica in the austral spring. Here we examine the depletion of stratospheric ozone caused by the reaction of ozone with nitric oxide generated by energetic solar protons, associated with solar flares. During large solar flares in March 1989, satellite observations indicated that total column ozone was depleted by {approx} 9% over {approx} 20% of the total area between the South Pole and latitude 70{sup o}S. Chlorine-catalysed ozone depletion takes place over a much larger area, but our results indicate that the influence of solar protons on atmospheric ozone concentrations should not be ignored. (author).

  12. Importance of energetic solar protons in ozone depletion

    Stephenson, J.A.E.; Scourfield, M.W.J.

    1991-01-01

    CHLORINE-catalysed depletion of the stratospheric ozone layer has commanded considerable attention since 1985, when Farman et al. observed a decrease of 50% in the total column ozone over Antarctica in the austral spring. Here we examine the depletion of stratospheric ozone caused by the reaction of ozone with nitric oxide generated by energetic solar protons, associated with solar flares. During large solar flares in March 1989, satellite observations indicated that total column ozone was depleted by ∼ 9% over ∼ 20% of the total area between the South Pole and latitude 70 o S. Chlorine-catalysed ozone depletion takes place over a much larger area, but our results indicate that the influence of solar protons on atmospheric ozone concentrations should not be ignored. (author)

  13. Comparative evaluation of seven commercial products for human serum enrichment/depletion by shotgun proteomics.

    Pisanu, Salvatore; Biosa, Grazia; Carcangiu, Laura; Uzzau, Sergio; Pagnozzi, Daniela

    2018-08-01

    Seven commercial products for human serum depletion/enrichment were tested and compared by shotgun proteomics. Methods were based on four different capturing agents: antibodies (Qproteome Albumin/IgG Depletion kit, ProteoPrep Immunoaffinity Albumin and IgG Depletion Kit, Top 2 Abundant Protein Depletion Spin Columns, and Top 12 Abundant Protein Depletion Spin Columns), specific ligands (Albumin/IgG Removal), mixture of antibodies and ligands (Albumin and IgG Depletion SpinTrap), and combinatorial peptide ligand libraries (ProteoMiner beads), respectively. All procedures, to a greater or lesser extent, allowed an increase of identified proteins. ProteoMiner beads provided the highest number of proteins; Albumin and IgG Depletion SpinTrap and ProteoPrep Immunoaffinity Albumin and IgG Depletion Kit resulted the most efficient in albumin removal; Top 2 and Top 12 Abundant Protein Depletion Spin Columns decreased the overall immunoglobulin levels more than other procedures, whereas specifically gamma immunoglobulins were mostly removed by Albumin and IgG Depletion SpinTrap, ProteoPrep Immunoaffinity Albumin and IgG Depletion Kit, and Top 2 Abundant Protein Depletion Spin Columns. Albumin/IgG Removal, a resin bound to a mixture of protein A and Cibacron Blue, behaved less efficiently than the other products. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Capstone Depleted Uranium Aerosols: Generation and Characterization

    Parkhurst, MaryAnn; Szrom, Fran; Guilmette, Ray; Holmes, Tom; Cheng, Yung-Sung; Kenoyer, Judson L.; Collins, John W.; Sanderson, T. Ellory; Fliszar, Richard W.; Gold, Kenneth; Beckman, John C.; Long, Julie

    2004-10-19

    In a study designed to provide an improved scientific basis for assessing possible health effects from inhaling depleted uranium (DU) aerosols, a series of DU penetrators was fired at an Abrams tank and a Bradley fighting vehicle. A robust sampling system was designed to collect aerosols in this difficult environment and continuously monitor the sampler flow rates. Aerosols collected were analyzed for uranium concentration and particle size distribution as a function of time. They were also analyzed for uranium oxide phases, particle morphology, and dissolution in vitro. The resulting data provide input useful in human health risk assessments.

  15. Uranium, depleted uranium, biological effects

    2001-01-01

    Physicists, chemists and biologists at the CEA are developing scientific programs on the properties and uses of ionizing radiation. Since the CEA was created in 1945, a great deal of research has been carried out on the properties of natural, enriched and depleted uranium in cooperation with university laboratories and CNRS. There is a great deal of available data about uranium; thousands of analyses have been published in international reviews over more than 40 years. This presentation on uranium is a very brief summary of all these studies. (author)

  16. A modern depleted uranium manufacturing facility

    Zagula, T.A.

    1995-07-01

    The Specific Manufacturing Capabilities (SMC) Project located at the Idaho National Engineering Laboratory (INEL) and operated by Lockheed Martin Idaho Technologies Co. (LMIT) for the Department of Energy (DOE) manufactures depleted uranium for use in the U.S. Army MIA2 Abrams Heavy Tank Armor Program. Since 1986, SMC has fabricated more than 12 million pounds of depleted uranium (DU) products in a multitude of shapes and sizes with varying metallurgical properties while maintaining security, environmental, health and safety requirements. During initial facility design in the early 1980's, emphasis on employee safety, radiation control and environmental consciousness was gaining momentum throughout the DOE complex. This fact coupled with security and production requirements forced design efforts to focus on incorporating automation, local containment and computerized material accountability at all work stations. The result was a fully automated production facility engineered to manufacture DU armor packages with virtually no human contact while maintaining security, traceability and quality requirements. This hands off approach to handling depleted uranium resulted in minimal radiation exposures and employee injuries. Construction of the manufacturing facility was complete in early 1986 with the first armor package certified in October 1986. Rolling facility construction was completed in 1987 with the first certified plate produced in the fall of 1988. Since 1988 the rolling and manufacturing facilities have delivered more than 2600 armor packages on schedule with 100% final product quality acceptance. During this period there was an annual average of only 2.2 lost time incidents and a single individual maximum radiation exposure of 150 mrem. SMC is an example of designing and operating a facility that meets regulatory requirements with respect to national security, radiation control and personnel safety while achieving production schedules and product quality

  17. "When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T D

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In

  18. "When the going gets tough, who keeps going?" : Depletion sensitivity moderates the ego-depletion effect

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In

  19. When the Going Gets Tough, Who Keeps Going? Depletion Sensitivity Moderates the Ego-Depletion Effect

    Stefanie J. Salmon

    2014-06-01

    Full Text Available Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion.

  20. Potential For Stratospheric Ozone Depletion During Carboniferous

    Bill, M.; Goldstein, A. H.

    Methyl bromide (CH3Br) constitutes the largest source of bromine atoms to the strato- sphere whereas methyl chloride (CH3Cl) is the most abundant halocarbon in the tro- posphere. Both gases play an important role in stratospheric ozone depletion. For in- stance, Br coupled reactions are responsible for 30 to 50 % of total ozone loss in the polar vortex. Currently, the largest natural sources of CH3Br and CH3Cl appear to be biological production in the oceans, inorganic production during biomass burning and plant production in salt marsh ecosystems. Variations of paleofluxes of CH3Br and CH3Cl can be estimated by analyses of oceanic paleoproductivity, stratigraphic analyses of frequency and distribution of fossil charcoal indicating the occurrence of wildfires, and/or by paleoreconstruction indicating the extent of salt marshes. Dur- ing the lower Carboniferous time (Tournaisian-Visean), the southern margin of the Laurasian continent was characterized by charcoal deposits. Estimation on frequency of charcoal layers indicates that wildfires occur in a range of 3-35 years (Falcon-Lang 2000). This suggests that biomass burning could be an important source of CH3Br and CH3Cl during Tournaisian-Viesan time. During Tounaisian and until Merame- cian carbon and oxygen isotope records have short term oscillations (Bruckschen et al. 1999, Mii et al. 1999). Chesterian time (mid- Carboniferous) is marked by an in- crease in delta18O values ( ~ 2 permil) and an increase of glacial deposit frequency suggesting lower temperatures. The occurrence of glacial deposits over the paleopole suggests polar conditions and the associated special features of polar mete- orology such as strong circumpolar wind in the stratosphere (polar vortex) and polar stratospheric clouds. Thus, conditions leading to polar statospheric ozone depletion can be found. Simultaneously an increase in delta13C values is documented. We interpret the positive shift in delta13C as a result of higher bioproductivity

  1. Muscle glycogen depletion patterns during draught work in Standardbred horses.

    Gottlieb, M

    1989-03-01

    Muscle fibre recruitment was investigated during draught loaded exercise by studying glycogen depletion patterns from histochemical stains of muscle biopsies from the gluteus and semitendinosus muscles. Three Standardbred trotters performed several intervals of draught loaded exercise on a treadmill with 34 kp at a trot (7 m/sec) and with 34 and 80 kp, respectively at a walk (2m/sec). Exercise was continued until the horses were unwilling to continue. Glycogen depletion was seen in all three fibre types when trotting with 34 kp for 5 or 10 mins. When an equal weight resistance was pulled at a walk, glycogen depletion was first seen in type I fibres only, then followed by a small percentage of type IIA fibres after at least 1 h. When 80 kp was pulled at a walk both type I and IIA fibres showed glycogen depletion, and after at least 30 mins exercise a small percentage of type IIB fibres was also depleted. These results indicate that the muscle fibres are depleted, in order, from type I through IIA to IIB as the intensity or duration of draught work increases.

  2. Self-Regulatory Capacities Are Depleted in a Domain-Specific Manner.

    Zhang, Rui; Stock, Ann-Kathrin; Rzepus, Anneka; Beste, Christian

    2017-01-01

    Performing an act of self-regulation such as making decisions has been suggested to deplete a common limited resource, which impairs all subsequent self-regulatory actions (ego depletion theory). It has however remained unclear whether self-referred decisions truly impair behavioral control even in seemingly unrelated cognitive domains, and which neurophysiological mechanisms are affected by these potential depletion effects. In the current study, we therefore used an inter-individual design to compare two kinds of depletion, namely a self-referred choice-based depletion and a categorization-based switching depletion, to a non-depleted control group. We used a backward inhibition (BI) paradigm to assess the effects of depletion on task switching and associated inhibition processes. It was combined with EEG and source localization techniques to assess both behavioral and neurophysiological depletion effects. The results challenge the ego depletion theory in its current form: Opposing the theory's prediction of a general limited resource, which should have yielded comparable effects in both depletion groups, or maybe even a larger depletion in the self-referred choice group, there were stronger performance impairments following a task domain-specific depletion (i.e., the switching-based depletion) than following a depletion based on self-referred choices. This suggests at least partly separate and independent resources for various cognitive control processes rather than just one joint resource for all self-regulation activities. The implications are crucial to consider for people making frequent far-reaching decisions e.g., in law or economy.

  3. Regret causes ego-depletion and finding benefits in the regrettable events alleviates ego-depletion.

    Gao, Hongmei; Zhang, Yan; Wang, Fang; Xu, Yan; Hong, Ying-Yi; Jiang, Jiang

    2014-01-01

    This study tested the hypotheses that experiencing regret would result in ego-depletion, while finding benefits (i.e., "silver linings") in the regret-eliciting events counteracted the ego-depletion effect. Using a modified gambling paradigm (Experiments 1, 2, and 4) and a retrospective method (Experiments 3 and 5), five experiments were conducted to induce regret. Results revealed that experiencing regret undermined performance on subsequent tasks, including a paper-and-pencil calculation task (Experiment 1), a Stroop task (Experiment 2), and a mental arithmetic task (Experiment 3). Furthermore, finding benefits in the regret-eliciting events improved subsequent performance (Experiments 4 and 5), and this improvement was mediated by participants' perceived vitality (Experiment 4). This study extended the depletion model of self-regulation by considering emotions with self-conscious components (in our case, regret). Moreover, it provided a comprehensive understanding of how people felt and performed after experiencing regret and after finding benefits in the events that caused the regret.

  4. How Ego Depletion Affects Sexual Self-Regulation: Is It More Than Resource Depletion?

    Nolet, Kevin; Rouleau, Joanne-Lucine; Benbouriche, Massil; Carrier Emond, Fannie; Renaud, Patrice

    2015-12-21

    Rational thinking and decision making are impacted when in a state of sexual arousal. The inability to self-regulate arousal can be linked to numerous problems, like sexual risk taking, infidelity, and sexual coercion. Studies have shown that most men are able to exert voluntary control over their sexual excitation with various levels of success. Both situational and dispositional factors can influence self-regulation achievement. The goal of this research was to investigate how ego depletion, a state of low self-control capacity, interacts with personality traits-propensities for sexual excitation and inhibition-and cognitive absorption, to cause sexual self-regulation failure. The sexual responses of 36 heterosexual males were assessed using penile plethysmography. They were asked to control their sexual arousal in two conditions, with and without ego depletion. Results suggest that ego depletion has opposite effects based on the trait sexual inhibition, as individuals moderately inhibited showed an increase in performance while highly inhibited ones showed a decrease. These results challenge the limited resource model of self-regulation and point to the importance of considering how people adapt to acute and high challenging conditions.

  5. Clusters of Cl- channels in CFTR-expressing em>Sf>9 cells switch spontaneously between slow and fast gating modes

    Larsen, Erik Hviid; Price, E. M.; Gabriel, S. E.

    1996-01-01

    channel. Excised outside-out patches of CFTR-infected and forskolin-stimulated cells exhibited wave-like gating kinetics of well-resolved current transitions. All-point Gaussian distributions revealed contributions from several (five to nine) identical channels. Such channels, in excised outside...

  6. Lumacaftor/ivacaftor, a novel agent for the treatment of cystic fibrosis patients who are homozygous for the F580del CFTR mutation.

    Bulloch, Marilyn N; Hanna, Cameron; Giovane, Richard

    2017-10-01

    Cystic Fibrosis (CF) is an autosomal recessive disease affecting up to 90,000 people worldwide. Approximately 73% of patients are homozygous for the F508del cystic fibrosis transmembrane conductance regulator [CFTR] mutation. Traditionally treatment has only included supportive care. Therefore, there is a need for safe and effective novel therapies targeting the underlying molecular defects seen with CF. Areas covered: In 2016, the Food and Drug Administration and the European Commission approved LUM/IVA (Orkambi), a CFTR modulator that includes both a CFTR corrector and potentiator, for CF patients homozygous for the F508del CFTR mutation. This article reviews the pharmacologic features, clinical efficacy, and safety of LUM/IVA and summarize the available pre-clinical and clinical data of LUM/IVA use. Expert commentary: LUM/IVA showed modest, but significant improvements from baseline in percent predicted FEV 1 (ppFEV 1 ) as well as a reduction in pulmonary exacerbations by 35% It was shown to be safe for short- and long-term use. Currently, LUM/IVA is the only oral agent in its class available and represents a milestone the development of therapies for the management of CF. Nonetheless, pharmacoeconomic data are necessary to justify its high cost before is use becomes standard of care.

  7. Structures of a minimal human CFTR first nucleotide-binding domain as a monomer, head-to-tail homodimer, and pathogenic mutant

    Atwell, Shane; Brouillette, Christie G.; Conners, Kris; Emtage, Spencer; Gheyi, Tarun; Guggino, William B.; Hendle, Jorg; Hunt, John F.; Lewis, Hal A.; Lu, Frances; Protasevich, Irina I.; Rodgers, Logan A.; Romero, Rich; Wasserman, Stephen R.; Weber, Patricia C.; Wetmore, Diana; Zhang, Feiyu F.; Zhao, Xun (Cystic); (UAB); (JHU); (Columbia); (Lilly)

    2010-04-26

    Upon removal of the regulatory insert (RI), the first nucleotide binding domain (NBD1) of human cystic fibrosis transmembrane conductance regulator (CFTR) can be heterologously expressed and purified in a form that remains stable without solubilizing mutations, stabilizing agents or the regulatory extension (RE). This protein, NBD1 387-646({Delta}405-436), crystallizes as a homodimer with a head-to-tail association equivalent to the active conformation observed for NBDs from symmetric ATP transporters. The 1.7-{angstrom} resolution X-ray structure shows how ATP occupies the signature LSGGQ half-site in CFTR NBD1. The {Delta}F508 version of this protein also crystallizes as a homodimer and differs from the wild-type structure only in the vicinity of the disease-causing F508 deletion. A slightly longer construct crystallizes as a monomer. Comparisons of the homodimer structure with this and previously published monomeric structures show that the main effect of ATP binding at the signature site is to order the residues immediately preceding the signature sequence, residues 542-547, in a conformation compatible with nucleotide binding. These residues likely interact with a transmembrane domain intracellular loop in the full-length CFTR channel. The experiments described here show that removing the RI from NBD1 converts it into a well-behaved protein amenable to biophysical studies yielding deeper insights into CFTR function.

  8. Purinergic regulation of CFTR and Ca2+ -activated Cl- channels and K+ channels in human pancreatic duct epithelium

    Wang, Jing; Haanes, Kristian A; Novak, Ivana

    2013-01-01

    mutated CFTR, basolateral ATP and UTP had negligible effects. In addition to Cl(-) transport in Capan-1 cells, the effects of 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DC-EBIO) and clotrimazole indicated functional expression of the intermediate conductance K(+) channels (IK, KCa3...

  9. Depleted uranium disposal options evaluation

    Hertzler, T.J.; Nishimoto, D.D.; Otis, M.D.

    1994-05-01

    The Department of Energy (DOE), Office of Environmental Restoration and Waste Management, has chartered a study to evaluate alternative management strategies for depleted uranium (DU) currently stored throughout the DOE complex. Historically, DU has been maintained as a strategic resource because of uses for DU metal and potential uses for further enrichment or for uranium oxide as breeder reactor blanket fuel. This study has focused on evaluating the disposal options for DU if it were considered a waste. This report is in no way declaring these DU reserves a ''waste,'' but is intended to provide baseline data for comparison with other management options for use of DU. To PICS considered in this report include: Retrievable disposal; permanent disposal; health hazards; radiation toxicity and chemical toxicity

  10. Uranium under its depleted state

    2001-01-01

    This day organised by the SFRP, with the help of the Army Health service, the service of radiation protection of Army and IPSN is an information day to inform the public about the real toxicity of uranium, and its becoming in man and environment, about the risks during the use of depleted uranium and eventual consequences of its dispersion after a conflict, to give information on how is managed the protection of workers (civil or military ones) and what is really the situation of French military personnel in these conflicts. The news have brought to the shore cases of leukemia it is necessary to bring some information to the origin of this disease. (N.C.)

  11. The Influence of Chronic Ego Depletion on Goal Adherence: An Experience Sampling Study.

    Wang, Ligang; Tao, Ting; Fan, Chunlei; Gao, Wenbin; Wei, Chuguang

    2015-01-01

    Although ego depletion effects have been widely observed in experiments in which participants perform consecutive self-control tasks, the process of ego depletion remains poorly understood. Using the strength model of self-control, we hypothesized that chronic ego depletion adversely affects goal adherence and that mental effort and motivation are involved in the process of ego depletion. In this study, 203 students reported their daily performance, mental effort, and motivation with respect to goal directed behavior across a 3-week time period. People with high levels of chronic ego depletion were less successful in goal adherence than those with less chronic ego depletion. Although daily effort devoted to goal adherence increased with chronic ego depletion, motivation to adhere to goals was not affected. Participants with high levels of chronic ego depletion showed a stronger positive association between mental effort and performance, but chronic ego depletion did not play a regulatory role in the effect of motivation on performance. Chronic ego depletion increased the likelihood of behavior regulation failure, suggesting that it is difficult for people in an ego-depletion state to adhere to goals. We integrate our results with the findings of previous studies and discuss possible theoretical implications.

  12. Functional classification of mitochondrion-rich cells in euryhaline Mozambique tilapia (Oreochromis mossambicus) embryos, by means of triple immunofluorescence staining for Na+/K+-ATPase, Na +/K+/2Cl- cotransporter and CFTR anion channel

    Hiroi, J.; McCormick, S.D.; Ohtani-Kaneko, R.; Kaneko, T.

    2005-01-01

    Mozambique tilapia Oreochromis mossambicus embryos were transferred from freshwater to seawater and vice versa, and short-term changes in the localization of three major ion transport proteins, Na+/K +-ATPase, Na+/K+/2Cl- cotransporter (NKCC) and cystic fibrosis transmembrane conductance regulator (CFTR) were examined within mitochondrion-rich cells (MRCs) in the embryonic yolk-sac membrane. Triple-color immunofluorescence staining allowed us to classify MRCs into four types: type I, showing only basolateral Na+/K +-ATPase staining; type II, basolateral Na+/K +-ATPase and apical NKCC; type III, basolateral Na+/K +-ATPase and basolateral NKCC; type IV, basolateral Na +/K+-ATPase, basolateral NKCC and apical CFTR. In freshwater, type-I, type-II and type-III cells were observed. Following transfer from freshwater to seawater, type-IV cells appeared at 12 h and showed a remarkable increase in number between 24 h and 48 h, whereas type-III cells disappeared. When transferred from seawater back to freshwater, type-IV cells decreased and disappeared at 48 h, type-III cells increased, and type-II cells, which were not found in seawater, appeared at 12 h and increased in number thereafter. Type-I cells existed consistently irrespective of salinity changes. These results suggest that type I is an immature MRC, type II is a freshwater-type ion absorptive cell, type III is a dormant type-IV cell and/or an ion absorptive cell (with a different mechanism from type II), and type IV is a seawater-type ion secretory cell. The intracellular localization of the three ion transport proteins in type-IV cells is completely consistent with a widely accepted model for ion secretion by MRCs. A new model for ion absorption is proposed based on type-II cells possessing apical NKCC.

  13. Is gas in the Orion nebula depleted

    Aiello, S.; Guidi, I.

    1978-01-01

    Depletion of heavy elements has been recognized to be important in the understanding of the chemical composition of the interstellar medium. This problem is also relevant to the study of H II regions. In this paper the gaseous depletion in the physical conditions of the Orion nebula is investigated. The authors reach the conclusion that very probably no depletion of heavy elements, due to sticking on dust grains, took place during the lifetime of the Orion nebula. (Auth.)

  14. Tryptophan depletion affects compulsive behaviour in rats

    Merchán, A; Navarro, S V; Klein, A B

    2017-01-01

    investigated whether 5-HT manipulation, through a tryptophan (TRP) depletion by diet in Wistar and Lister Hooded rats, modulates compulsive drinking in schedule-induced polydipsia (SIP) and locomotor activity in the open-field test. The levels of dopamine, noradrenaline, serotonin and its metabolite were......-depleted HD Wistar rats, while the LD Wistar and the Lister Hooded rats did not exhibit differences in SIP. In contrast, the TRP-depleted Lister Hooded rats increased locomotor activity compared to the non-depleted rats, while no differences were found in the Wistar rats. Serotonin 2A receptor binding...

  15. Ego depletion decreases trust in economic decision making

    Ainsworth, Sarah E.; Baumeister, Roy F.; Vohs, Kathleen D.; Ariely, Dan

    2014-01-01

    Three experiments tested the effects of ego depletion on economic decision making. Participants completed a task either requiring self-control or not. Then participants learned about the trust game, in which senders are given an initial allocation of $10 to split between themselves and another person, the receiver. The receiver receives triple the amount given and can send any, all, or none of the tripled money back to the sender. Participants were assigned the role of the sender and decided how to split the initial allocation. Giving less money, and therefore not trusting the receiver, is the safe, less risky response. Participants who had exerted self-control and were depleted gave the receiver less money than those in the non-depletion condition (Experiment 1). This effect was replicated and moderated in two additional experiments. Depletion again led to lower amounts given (less trust), but primarily among participants who were told they would never meet the receiver (Experiment 2) or who were given no information about how similar they were to the receiver (Experiment 3). Amounts given did not differ for depleted and non-depleted participants who either expected to meet the receiver (Experiment 2) or were led to believe that they were very similar to the receiver (Experiment 3). Decreased trust among depleted participants was strongest among neurotics. These results imply that self-control facilitates behavioral trust, especially when no other cues signal decreased social risk in trusting, such as if an actual or possible relationship with the receiver were suggested. PMID:25013237

  16. The depletion of aqueous nitrous acid in packed towers

    Counce, R.M.; Crawford, D.B.

    1987-01-01

    The depletion of aqueous nitrous acid was studied at 298 0 K and at slightly greater than atmospheric pressure. Solutions containing nitrous and nitric acids were contacted with nitrogen in towers packed with 6- and 13-mm Intalox saddles. The results indicate the existence of two depletion mechanisms for the conditions studied - liquid-phase decomposition and direct desorption of nitrous acid. Models based on mass-transfer and chemical-kinetic information are presented to explain the experimental results. 24 refs., 8 figs., 3 tabs

  17. results

    Salabura Piotr

    2017-01-01

    Full Text Available HADES experiment at GSI is the only high precision experiment probing nuclear matter in the beam energy range of a few AGeV. Pion, proton and ion beams are used to study rare dielectron and strangeness probes to diagnose properties of strongly interacting matter in this energy regime. Selected results from p + A and A + A collisions are presented and discussed.

  18. Depleted Uranium and Human Health.

    Faa, Armando; Gerosa, Clara; Fanni, Daniela; Floris, Giuseppe; Eyken, Peter V; Lachowicz, Joanna I; Nurchi, Valeria M

    2018-01-01

    Depleted uranium (DU) is generally considered an emerging pollutant, first extensively introduced into environment in the early nineties in Iraq, during the military operation called "Desert Storm". DU has been hypothesized to represent a hazardous element both for soldiers exposed as well as for the inhabitants of the polluted areas in the war zones. In this review, the possible consequences on human health of DU released in the environment are critically analyzed. In the first part, the chemical properties of DU and the principal civil and military uses are summarized. A concise analysis of the mechanisms underlying absorption, blood transport, tissue distribution and excretion of DU in the human body is the subject of the second part of this article. The following sections deal with pathological condition putatively associated with overexposure to DU. Developmental and birth defects, the Persian Gulf syndrome, and kidney diseases that have been associated to DU are the arguments treated in the third section. Finally, data regarding DU exposure and cancer insurgence will be critically analyzed, including leukemia/lymphoma, lung cancer, uterine cervix cancer, breast cancer, bladder cancer and testicular cancer. The aim of the authors is to give a contribution to the debate on DU and its effects on human health and disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Ozone depletion potentials of halocarbons

    Karol, I.L.; Kiselev, A.A.

    1992-01-01

    The concept of ozone depletion potential (ODP) is widely used in the evaluation of numerous halocarbons and of their replacements for effects on ozone, but the methods, model assumptions and conditions of ODP calculation have not been analyzed adequately. In this paper, a model study of effects on ozone after the instantaneous releases of various amounts of CH 3 CCl 3 and of CHF 2 Cl(HCFC-22) in the several conditions of the background atmosphere are presented, aimed to understand the main connections of ODP values with the methods of their calculations. To facilitate the ODP computation in numerous versions for long after the releases, the above rather short-lived gases have been used. The variation of released gas global mass from 1 Mt to 1 Gt leads to ODP value increase atmosphere. The same variations are analyzed for the CFC-free atmosphere of 1960s conditions for the anthropogenically loaded atmosphere in the 21st century according to the known IPCC- A scenario (business as usual). Recommendations of proper ways of ODP calculations are proposed for practically important cases

  20. Plutonium in depleted uranium penetrators

    McLaughlin, J.P.; Leon-Vintro, L.; Smith, K.; Mitchell, P.I.; Zunic, Z.S.

    2002-01-01

    Depleted Uranium (DU) penetrators used in the recent Balkan conflicts have been found to be contaminated with trace amounts of transuranic materials such as plutonium. This contamination is usually a consequence of DU fabrication being carried out in facilities also using uranium recycled from spent military and civilian nuclear reactor fuel. Specific activities of 239+240 Plutonium generally in the range 1 to 12 Bq/kg have been found to be present in DU penetrators recovered from the attack sites of the 1999 NATO bombardment of Kosovo. A DU penetrator recovered from a May 1999 attack site at Bratoselce in southern Serbia and analysed by University College Dublin was found to contain 43.7 +/- 1.9 Bq/kg of 239+240 Plutonium. This analysis is described. An account is also given of the general population radiation dose implications arising from both the DU itself and from the presence of plutonium in the penetrators. According to current dosimetric models, in all scenarios considered likely ,the dose from the plutonium is estimated to be much smaller than that due to the uranium isotopes present in the penetrators. (author)

  1. Pathogenic lysosomal depletion in Parkinson's disease.

    Dehay, Benjamin; Bové, Jordi; Rodríguez-Muela, Natalia; Perier, Celine; Recasens, Ariadna; Boya, Patricia; Vila, Miquel

    2010-09-15

    Mounting evidence suggests a role for autophagy dysregulation in Parkinson's disease (PD). The bulk degradation of cytoplasmic proteins (including α-synuclein) and organelles (such as mitochondria) is mediated by macroautophagy, which involves the sequestration of cytosolic components into autophagosomes (AP) and its delivery to lysosomes. Accumulation of AP occurs in postmortem brain samples from PD patients, which has been widely attributed to an induction of autophagy. However, the cause and pathogenic significance of these changes remain unknown. Here we found in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of PD that AP accumulation and dopaminergic cell death are preceded by a marked decrease in the amount of lysosomes within dopaminergic neurons. Lysosomal depletion was secondary to the abnormal permeabilization of lysosomal membranes induced by increased mitochondrial-derived reactive oxygen species. Lysosomal permeabilization resulted in a defective clearance and subsequent accumulation of undegraded AP and contributed directly to neurodegeneration by the ectopic release of lysosomal proteases into the cytosol. Lysosomal breakdown and AP accumulation also occurred in PD brain samples, where Lewy bodies were strongly immunoreactive for AP markers. Induction of lysosomal biogenesis by genetic or pharmacological activation of lysosomal transcription factor EB restored lysosomal levels, increased AP clearance and attenuated 1-methyl-4-phenylpyridinium-induced cell death. Similarly, the autophagy-enhancer compound rapamycin attenuated PD-related dopaminergic neurodegeneration, both in vitro and in vivo, by restoring lysosomal levels. Our results indicate that AP accumulation in PD results from defective lysosomal-mediated AP clearance secondary to lysosomal depletion. Restoration of lysosomal levels and function may thus represent a novel neuroprotective strategy in PD.

  2. OZONE DEPLETING SUBSTANCES ELIMINATION MANAGEMENT: THE SUCCESS STORY OF MACEDONIA

    Margarita Matlievska

    2013-04-01

    Full Text Available Man, with its activities, produces and uses substances that have negative impact on the environment and the human health, and can cause an economic damage. Consequently, they have a great impact on quality of life. Among the most harmful chemicals are Ozone Depleting Substances that are subject of regulation with international conventions. This Paper supports the fact that each country has to undertake national efforts for ozone depleting substances reduction and elimination. In that respect, the general objective of the Paper is to present the Macedonian unique experience regarding its efforts to reduce or eliminate these substances. The following two aspects were subject to the research: national legislation which regulates the Ozone Depleting Substances import and export as well as the implementation of the projects that resulted with the elimination of Ozone Depleting Substances quantities in the period 1995 – 2010. The research outcomes confirm the starting research hypothesis i.e. that with adequately created and implemented national action, the amount of Ozone Depleting Substances consumption can dramatically fall.

  3. Examining depletion theories under conditions of within-task transfer.

    Brewer, Gene A; Lau, Kevin K H; Wingert, Kimberly M; Ball, B Hunter; Blais, Chris

    2017-07-01

    In everyday life, mental fatigue can be detrimental across many domains including driving, learning, and working. Given the importance of understanding and accounting for the deleterious effects of mental fatigue on behavior, a growing body of literature has studied the role of motivational and executive control processes in mental fatigue. In typical laboratory paradigms, participants complete a task that places demand on these self-control processes and are later given a subsequent task. Generally speaking, decrements to subsequent task performance are taken as evidence that the initial task created mental fatigue through the continued engagement of motivational and executive functions. Several models have been developed to account for negative transfer resulting from this "ego depletion." In the current study, we provide a brief literature review, specify current theoretical approaches to ego-depletion, and report an empirical test of current models of depletion. Across 4 experiments we found minimal evidence for executive control depletion along with strong evidence for motivation mediated ego depletion. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  4. The Physical Origin of Long Gas Depletion Times in Galaxies

    Semenov, Vadim A.; Kravtsov, Andrey V.; Gnedin, Nickolay Y.

    2017-08-18

    We present a model that elucidates why gas depletion times in galaxies are long compared to the time scales of the processes driving the evolution of the interstellar medium. We show that global depletion times are not set by any "bottleneck" in the process of gas evolution towards the star-forming state. Instead, depletion times are long because star-forming gas converts only a small fraction of its mass into stars before it is dispersed by dynamical and feedback processes. Thus, complete depletion requires that gas transitions between star-forming and non-star-forming states multiple times. Our model does not rely on the assumption of equilibrium and can be used to interpret trends of depletion times with the properties of observed galaxies and the parameters of star formation and feedback recipes in galaxy simulations. In particular, the model explains the mechanism by which feedback self-regulates star formation rate in simulations and makes it insensitive to the local star formation efficiency. We illustrate our model using the results of an isolated $L_*$-sized disk galaxy simulation that reproduces the observed Kennicutt-Schmidt relation for both molecular and atomic gas. Interestingly, the relation for molecular gas is close to linear on kiloparsec scales, even though a non-linear relation is adopted in simulation cells. This difference is due to stellar feedback, which breaks the self-similar scaling of the gas density PDF with the average gas surface density.

  5. Bond rupture between colloidal particles with a depletion interaction

    Whitaker, Kathryn A.; Furst, Eric M., E-mail: furst@udel.edu [Department of Chemical and Biomolecular Engineering and Center for Molecular and Engineering Thermodynamics, University of Delaware, Newark, Delaware 19716 (United States)

    2016-05-15

    The force required to break the bonds of a depletion gel is measured by dynamically loading pairs of colloidal particles suspended in a solution of a nonadsorbing polymer. Sterically stabilized poly(methyl methacrylate) colloids that are 2.7 μm diameter are brought into contact in a solvent mixture of cyclohexane-cyclohexyl bromide and polystyrene polymer depletant. The particle pairs are subject to a tensile load at a constant loading rate over many approach-retraction cycles. The stochastic nature of the thermal rupture events results in a distribution of bond rupture forces with an average magnitude and variance that increases with increasing depletant concentration. The measured force distribution is described by the flux of particle pairs sampling the energy barrier of the bond interaction potential based on the Asakura–Oosawa depletion model. A transition state model demonstrates the significance of lubrication hydrodynamic interactions and the effect of the applied loading rate on the rupture force of bonds in a depletion gel.

  6. Ozone depletion following future volcanic eruptions

    Eric Klobas, J.; Wilmouth, David M.; Weisenstein, Debra K.; Anderson, James G.; Salawitch, Ross J.

    2017-07-01

    While explosive volcanic eruptions cause ozone loss in the current atmosphere due to an enhancement in the availability of reactive chlorine following the stratospheric injection of sulfur, future eruptions are expected to increase total column ozone as halogen loading approaches preindustrial levels. The timing of this shift in the impact of major volcanic eruptions on the thickness of the ozone layer is poorly known. Modeling four possible climate futures, we show that scenarios with the smallest increase in greenhouse gas concentrations lead to the greatest risk to ozone from heterogeneous chemical processing following future eruptions. We also show that the presence in the stratosphere of bromine from natural, very short-lived biogenic compounds is critically important for determining whether future eruptions will lead to ozone depletion. If volcanic eruptions inject hydrogen halides into the stratosphere, an effect not considered in current ozone assessments, potentially profound reductions in column ozone would result.

  7. Depletion sensitivity predicts unhealthy snack purchases

    Salmon, Stefanie J.; Adriaanse, Marieke A.; Fennis, Bob M.; De Vet, Emely; De Ridder, Denise T D

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  8. The Effect of Implicit Preferences on Food Consumption: Moderating Role of Ego Depletion and Impulsivity

    Wang, Yan; Zhu, Jinglei; Hu, Yi; Fang, Yuan; Wang, Guosen; Cui, Xianghua; Wang, Lei

    2016-01-01

    Ego depletion has been found to moderate the effect of implicit preferences on food consumption, such that implicit preferences predict consumption only under a depleted state. The present study tested how trait impulsivity impacts the effect of implicit preferences on food consumption in a depleted condition. Trait impulsivity was measured by means of self-report and a stop signal task. Results showed that both self-reported impulsivity and behavioral impulsivity moderated the ‘depletion and then eating according to implicit preferences’ effect, albeit in different ways. Participants high in self-reported impulsivity and low in behavioral impulsivity were more vulnerable to the effect of depletion on eating. The implications of these results for extant theories are discussed. Future research is needed to verify whether or not trait impulsivity is associated with vulnerability to depletion across different self-control domains. PMID:27881966

  9. Coupling effects of depletion interactions in a three-sphere colloidal system

    Chen Ze-Shun; Dai Gang; Gao Hai-Xia; Xiao Chang-Ming

    2013-01-01

    In a three-sphere system, the middle sphere is acted upon by two opposite depletion forces from the other two spheres. It is found that, in this system, the two depletion forces are coupled with each other and result in a strengthened depletion force. So the difference of the depletion forces of the three-sphere system and its corresponding two two-sphere systems is introduced to describe the coupling effect of the depletion interactions. The numerical results obtained by Monte-Carlo simulations show that this coupling effect is affected by both the concentration of small spheres and the geometrical confinement. Meanwhile, it is also found that the mechanisms of the coupling effect and the effect on the depletion force from the geometry factor are the same. (interdisciplinary physics and related areas of science and technology)

  10. Interstellar depletion anomalies and ionization potentials

    Tabak, R.G.

    1979-01-01

    Satellite observations indicate that (1) most elements are depleted from the gas phase when compared to cosmic abundances, (2) some elements are several orders of magnitude more depleted than others, and (3) these depletions vary from cloud to cloud. Since the most likely possibility is that the 'missing' atoms are locked into grains, depletions occur either by accretion onto core particles in interstellar clouds or earlier, during the period of primary grain formation. If the latter mechanism is dominant, then the most important depletion parameter is the condensation temperature of the elements and their various compounds. However, this alone is not sufficient to explain all the observed anomalies. It is shown that electrostatic effects - under a wide variety of conditions- can enormously enhance the capture cross-section of the grain. It is suggested that this mechanism can also account for such anomalies as the apparent 'overabundance' of the alkali metals in the gas phase. (orig.)

  11. Specification for the VERA Depletion Benchmark Suite

    Kim, Kang Seog [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-12-17

    CASL-X-2015-1014-000 iii Consortium for Advanced Simulation of LWRs EXECUTIVE SUMMARY The CASL neutronics simulator MPACT is under development for the neutronics and T-H coupled simulation for the pressurized water reactor. MPACT includes the ORIGEN-API and internal depletion module to perform depletion calculations based upon neutron-material reaction and radioactive decay. It is a challenge to validate the depletion capability because of the insufficient measured data. One of the detoured methods to validate it is to perform a code-to-code comparison for benchmark problems. In this study a depletion benchmark suite has been developed and a detailed guideline has been provided to obtain meaningful computational outcomes which can be used in the validation of the MPACT depletion capability.

  12. Resource depletion promotes automatic processing: implications for distribution of practice.

    Scheel, Matthew H

    2010-12-01

    Recent models of cognition include two processing systems: an automatic system that relies on associative learning, intuition, and heuristics, and a controlled system that relies on deliberate consideration. Automatic processing requires fewer resources and is more likely when resources are depleted. This study showed that prolonged practice on a resource-depleting mental arithmetic task promoted automatic processing on a subsequent problem-solving task, as evidenced by faster responding and more errors. Distribution of practice effects (0, 60, 120, or 180 sec. between problems) on rigidity also disappeared when groups had equal time on resource-depleting tasks. These results suggest that distribution of practice effects is reducible to resource availability. The discussion includes implications for interpreting discrepancies in the traditional distribution of practice effect.

  13. Electrophoretic analysis of cyanide depletion by Pseudomonas alcaligenes.

    Zaugg, S E; Davidson, R A; Walker, J C; Walker, E B

    1997-02-01

    Bacterial-facilitated depletion of cyanide is under development for remediation of heap leach operations in the gold mining industry. Capillary electrophoresis was found to be a powerful tool for quantifying cyanide depletion. Changes in cyanide concentration in aqueous suspensions of Pseudomonas alcaligenes bacteria and cyanide at elevated pH were easily monitored by capillary electrophoresis. The resulting data can be used to study rates of cyanide depletion by this strain of bacteria. Concentrations of these bacteria at 10(5) cells/mL were found to reduce cyanide from 100 ppm to less than 8 ppm in four days. In addition, other ions of interest in cyanide metabolism, such as formate, can be simultaneously analyzed. Direct UV detection of cyanide at 192 nm further simplifies the analytical method for these ions.

  14. Emittance increase caused by core depletion in collisions

    Bruce, R

    2009-01-01

    A new effect is presented, which changes the emittance during colliding-beam operation in circular colliders. If the initial transverse distribution is Gaussian, the collision probability is much higher for particles in the core of the beam than in the tails. When small-amplitude particles are removed, the remaining ones therefore have a larger transverse emittance. This effect, called core depletion, may cause a decrease in luminosity. An approximate analytic model is developed to study the effect and benchmarked against a multiparticle tracking simulation. Finally, the time evolution of the intensity and emittances of a Pb bunch in the Large Hadron Collider (LHC) at CERN is calculated, taking into account also other processes than collisions. The results show that integrated luminosity drops by 3--4% if core depletion is taken into account. It is also found that core depletion causes the transverse emittance to be larger when more experiments are active. This observation could be checked against experimenta...

  15. Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a G551D mutation.

    Cédric Bernarde

    Full Text Available Airway microbiota composition has been clearly correlated with many pulmonary diseases, and notably with cystic fibrosis (CF, an autosomal genetic disorder caused by mutation in the CF transmembrane conductance regulator (CFTR. Recently, a new molecule, ivacaftor, has been shown to re-establish the functionality of the G551D-mutated CFTR, allowing significant improvement in lung function.The purpose of this study was to follow the evolution of the airway microbiota in CF patients treated with ivacaftor, using quantitative PCR and pyrosequencing of 16S rRNA amplicons, in order to identify quantitative and qualitative changes in bacterial communities. Three G551D children were followed up longitudinally over a mean period of more than one year covering several months before and after initiation of ivacaftor treatment.129 operational taxonomy units (OTUs, representing 64 genera, were identified. There was no significant difference in total bacterial load before and after treatment. Comparison of global community composition found no significant changes in microbiota. Two OTUs, however, showed contrasting dynamics: after initiation of ivacaftor, the relative abundance of the anaerobe Porphyromonas 1 increased (p<0.01 and that of Streptococcus 1 (S. mitis group decreased (p<0.05, possibly in relation to the anti-Gram-positive properties of ivacaftor. The anaerobe Prevotella 2 correlated positively with the pulmonary function test FEV-1 (r=0.73, p<0.05. The study confirmed the presumed positive role of anaerobes in lung function.Several airway microbiota components, notably anaerobes (obligate or facultative anaerobes, could be valuable biomarkers of lung function improvement under ivacaftor, and could shed light on the pathophysiology of lung disease in CF patients.

  16. The CFTR Met 470 allele is associated with lower birth rates in fertile men from a population isolate.

    Gülüm Kosova

    2010-06-01

    Full Text Available Although little is known about the role of the cystic fibrosis transmembrane regulator (CFTR gene in reproductive physiology, numerous variants in this gene have been implicated in etiology of male infertility due to congenital bilateral absence of the vas deferens (CBAVD. Here, we studied the fertility effects of three CBAVD-associated CFTR polymorphisms, the (TGm and polyT repeat polymorphisms in intron 8 and Met470Val in exon 10, in healthy men of European descent. Homozygosity for the Met470 allele was associated with lower birth rates, defined as the number of births per year of marriage (P = 0.0029. The Met470Val locus explained 4.36% of the phenotypic variance in birth rate, and men homozygous for the Met470 allele had 0.56 fewer children on average compared to Val470 carrier men. The derived Val470 allele occurs at high frequencies in non-African populations (allele frequency = 0.51 in HapMap CEU, whereas it is very rare in African population (Fst = 0.43 between HapMap CEU and YRI. In addition, haplotypes bearing Val470 show a lack of genetic diversity and are thus longer than haplotypes bearing Met470 (measured by an integrated haplotype score [iHS] of -1.93 in HapMap CEU. The fraction of SNPs in the HapMap Phase2 data set with more extreme Fst and iHS measures is 0.003, consistent with a selective sweep outside of Africa. The fertility advantage conferred by Val470 relative to Met470 may provide a selective mechanism for these population genetic observations.

  17. Invariant TAD Boundaries Constrain Cell-Type-Specific Looping Interactions between Promoters and Distal Elements around the CFTR Locus.

    Smith, Emily M; Lajoie, Bryan R; Jain, Gaurav; Dekker, Job

    2016-01-07

    Three-dimensional genome structure plays an important role in gene regulation. Globally, chromosomes are organized into active and inactive compartments while, at the gene level, looping interactions connect promoters to regulatory elements. Topologically associating domains (TADs), typically several hundred kilobases in size, form an intermediate level of organization. Major questions include how TADs are formed and how they are related to looping interactions between genes and regulatory elements. Here we performed a focused 5C analysis of a 2.8 Mb chromosome 7 region surrounding CFTR in a panel of cell types. We find that the same TAD boundaries are present in all cell types, indicating that TADs represent a universal chromosome architecture. Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them. In contrast, looping interactions between promoters and regulatory elements are cell-type specific and occur mostly within TADs. This is exemplified by the CFTR promoter that in different cell types interacts with distinct sets of distal cell-type-specific regulatory elements that are all located within the same TAD. Finally, we find that long-range associations between loci located in different TADs are also detected, but these display much lower interaction frequencies than looping interactions within TADs. Interestingly, interactions between TADs are also highly cell-type-specific and often involve loci clustered around TAD boundaries. These data point to key roles of invariant TAD boundaries in constraining as well as mediating cell-type-specific long-range interactions and gene regulation. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Choice and ego-depletion: the moderating role of autonomy.

    Moller, Arlen C; Deci, Edward L; Ryan, Richard M

    2006-08-01

    The self-regulatory strength model maintains that all acts of self-regulation, self-control, and choice result in a state of fatigue called ego-depletion. Self-determination theory differentiates between autonomous regulation and controlled regulation. Because making decisions represents one instance of self-regulation, the authors also differentiate between autonomous choice and controlled choice. Three experiments support the hypothesis that whereas conditions representing controlled choice would be egodepleting, conditions that represented autonomous choice would not. In Experiment 3, the authors found significant mediation by perceived self-determination of the relation between the choice condition (autonomous vs. controlled) and ego-depletion as measured by performance.

  19. Depleted uranium determination at the Novi Sad low level facility

    Bikit, I.; Slivka, J.; Krmar, M.; Veskovic, M.; Conkic, Lj.; Varga, E.

    2002-01-01

    Natural uranium determination in environmental samples at the low-level gamma-spectroscopy laboratory of the Faculty of Science in Novi Sad has more than 20 years long tradition. When the issue of depleted uranium emerged the experimental advantages of the measuring equipment (GMX type of HPGe detector with enhanced efficiency below 100 keV, and iron low level shielding) where fully exploited. A detection technique selective for depleted uranium was developed. The details of this method together with the results for about 100 samples (soil, plants, water, food) are presented, and discussed. (author)

  20. Long-term management and use of depleted uranium

    Max, A.

    2001-01-01

    The products resulting from the process of enrichment of natural uranium, or reprocessed uranium, are enriched uranium products as the light fraction and depleted uranium (uranium tails) as the heavy fraction. If the source material is natural uranium, the mass ratios of uranium products and uranium tails can be derived relatively easily from the required enrichment level of the uranium product (product assay (% of U-235)) and the selected depletion level of the uranium tails (tails assay (% of U-235)). The paper discusses among other aspects the dependence of the tails mass on the required enrichment level of the relevant uranium product, for various tails assays. (orig./CB) [de

  1. Monte carlo depletion analysis of SMART core by MCNAP code

    Jung, Jong Sung; Sim, Hyung Jin; Kim, Chang Hyo; Lee, Jung Chan; Ji, Sung Kyun

    2001-01-01

    Depletion an analysis of SMART, a small-sized advanced integral PWR under development by KAERI, is conducted using the Monte Carlo (MC) depletion analysis program, MCNAP. The results are compared with those of the CASMO-3/ MASTER nuclear analysis. The difference between MASTER and MCNAP on k eff prediction is observed about 600pcm at BOC, and becomes smaller as the core burnup increases. The maximum difference bet ween two predict ions on fuel assembly (FA) normalized power distribution is about 6.6% radially , and 14.5% axially but the differences are observed to lie within standard deviation of MC estimations

  2. A new memory effect (MSD) in fully depleted SOI MOSFETs

    Bawedin, M.; Cristoloveanu, S.; Yun, J. G.; Flandre, D.

    2005-09-01

    We demonstrate that the transconductance and drain current of fully depleted MOSFETs can display an interesting time-dependent hysteresis. This new memory effect, called meta-stable dip (MSD), is mainly due to the long carrier generation lifetime in the silicon film. Our parametric analysis shows that the memory window can be adjusted in view of practical applications. Various measurement conditions and devices with different doping, front oxide and silicon film thicknesses are systematically explored. The MSD effect can be generalized to several fully depleted CMOS technologies. The MSD mechanism is discussed and validated by two-dimensional simulations results.

  3. Identification of the CFTR c.1666A>G Mutation in Hereditary Inclusion Body Myopathy Using Next-Generation Sequencing Analysis

    Yan Lu

    2018-05-01

    Full Text Available Hereditary inclusion body myopathy (HIBM is a rare autosomal recessive adult onset muscle disease which affects one to three individuals per million worldwide. This disease is autosomal dominant and occurs in adulthood. Our previous study reported a new subtype of HIBM linked to the susceptibility locus at 7q22.1-31.1. The present study is aimed to identify the candidate gene responsible for the phenotype in HIBM pedigree. After multipoint linkage analysis, we performed targeted capture sequencing on 16 members and whole-exome sequencing (WES on 5 members. Bioinformatics filtering was performed to prioritize the candidate pathogenic gene variants, which were further genotyped by Sanger sequencing. Our results showed that the highest peak of LOD score (4.70 was on chromosome 7q22.1-31.1.We identified 2 and 22 candidates using targeted capture sequencing and WES respectively, only one of which as CFTRc.1666A>G mutation was well cosegregated with the HIBM phenotype. Using transcriptome analysis, we did not detect the differences of CFTR's mRNA expression in the proband compared with healthy members. Due to low incidence of HIBM and there is no other pedigree to assess, mutation was detected in three patients with duchenne muscular dystrophyn (DMD and five patients with limb-girdle muscular dystrophy (LGMD. And we found that the frequency of mutation detected in DMD and LGMD patients was higher than that of being expected in normal population. We suggested that the CFTRc.1666A>G may be a candidate marker which has strong genetic linkage with the causative gene in the HIBM family.

  4. Depletion of interstellar elements and the interaction between gas and dust in space

    Snow, T.P. Jr.

    1975-01-01

    Recent data obtained with Copernicus, combined with new results from the literature, indicate that the depletions of interstellar elements may depend on cloud density in a simple way. This is expected if the depletions are due to accretion of gas particles onto grains under presently existing conditions, but is not expected if the depletions take place during the grain formation process, before mixing into the interstellar medium. The suggestion that depletion occurs via accretion may be supported by the existence of a good correlation between depletions and first ionization potentials of the elements, since the latter quantity determines to a great extent the chemical and physical properties, and hence possibly the sticking coefficient, of each species. If the grains do not carry large positive charges, then ion-grain encounters may be important not only in creating the depletions, but also in determining ionization equilibrium, particularly if a large population of very small grains is present

  5. Depletion interactions in two-dimensional colloid-polymer mixtures: molecular dynamics simulations

    Kim, Soon-Chul; Seong, Baek-Seok; Suh, Soong-Hyuck

    2009-01-01

    The depletion interactions acting between two hard colloids immersed in a bath of polymers, in which the interaction potentials include the soft repulsion/attraction, are extensively studied by using the molecular dynamics simulations. The collision frequencies and collision angle distributions for both incidental and reflection conditions are computed to study the dynamic properties of the colloidal mixtures. The depletion effect induced by the polymer-polymer and colloid-polymer interactions are investigated as well as the size ratio of the colloid and polymer. The simulated results show that the strong depletion interaction between two hard colloids appears for the highly asymmetric hard-disc mixtures. The attractive depletion force at contact becomes deeper and the repulsive barrier becomes wider as the asymmetry in size ratio increases. The strong polymer-polymer attraction leads to the purely attractive depletion interaction between two hard colloids, whereas the purely repulsive depletion interaction is induced by the strong colloid-polymer attraction.

  6. Depletion of heterogeneous source species pools predicts future invasion rates

    Andrew M. Liebhold; Eckehard G. Brockerhoff; Mark Kimberley; Jacqueline Beggs

    2017-01-01

    Predicting how increasing rates of global trade will result in new establishments of potentially damaging invasive species is a question of critical importance to the development of national and international policies aimed at minimizing future invasions. Centuries of historical movement and establishment of invading species may have depleted the supply of species...

  7. ISODEP, A Fuel Depletion Analysis Code for Predicting Isotopic ...

    The trend of results was found to be consistent with those obtained by analytical and other numerical methods. Discovery and Innovation Vol. 13 no. 3/4 December (2001) pp. 184-195. KEY WORDS: depletion analysis, code, research reactor, simultaneous equations, decay of nuclides, radionuclitides, isotope. Résumé

  8. Depletion length and space charge layer capacitance in doped semiconductor nanoshpere

    Nersesyan, S R; Petrosyan, S G

    2012-01-01

    The depletion length in a semiconductor nanosphere depends not only on the material parameters but on the nanosphere radius as well. For this reason, the depletion length does not present a universal characteristic length for all spherical interfaces. The difference from the standard flat model caused by the surface curvature is significant for a structure with the depletion length comparable to the radius of a nanosphere. We show that the depletion layer capacitance in a nanosphere becomes quite sensitive to the light intensity when, as a result of increasing optical generation rate, the surface potential barrier height is decreased and becomes very small. (paper)

  9. Effect of intratracheally instilled depleted uranium on immunological function of rats

    You Hanhu; Yang Zhihua; Cao Zhenshan; Zhu Maoxiang; Liu Xingrong

    2004-01-01

    Objective: To study immunological effects of depleted uranium in rats. Methods: Wistar rats were exposed to depleted uranium by single intratracheal instillation. Body weight and peripheral blood cells were measured weekly and immunological functions were evaluated by weight coefficient of immune organs, plague forming cells of splenocytes, total and subpopulation counts of lymphocytes in thymus. Results: Early after administration, body weight decreased and red blood cells as well as platelets reduced while white blood cells increased, which returned to normal within 1 or 2 months. Immunological functions of splenocytes and thymocytes were affected dose-dependently by depleted uranium. Conclusion: Depleted uranium induces immunological dysfunction in rats. (authors)

  10. Radiosensitization of CHO cells by the combination of glutathione depletion and low concentrations of oxygen: The effect of different levels of GSH depletion

    Clark, E.P.; Epp, E.R.; Zachgo, E.A.; Biaglow, J.E.

    1984-01-01

    Recently, the authors have examined the effect of GSH depletion by BSO on CHO cells equilibrated with oxygen at various concentrations (0.05-4.0%) and irradiated with 50 kVp x-rays. This is of interest because of the uncertain radiosensitizing effect GSH depletion may have on cells equilibrated with low oxygen concentrations. GSH depletion (0.1 mM BSO/24 hrs reduced [GSH] ≅ 10% of control) enhanced the radiosensitizing action of moderate (0.4-4.0%) concentrations of oxygen, i.e., GSH depletion reduced the [O/sub 2/] necessary to achieve an equivalent ER by ≅ 2-3 fold. However, GSH depletion was much more effective as a rediosensitizer when cells were equilibrated with low (<0.4%) concentrations of oxygen, i.e., GSH depletion reduced the [O/sub 2/] necessary to achieve an equivalent ER by 8-10 fold. Furthermore, while the addition of exogenous 5 mM GSH restored the ER to that observed when GSH was not depleted, the intracellular [GSH] was not increased. The results of these studies carried out at different levels of GSH depletion are presented

  11. Maximizing percentage depletion in solid minerals

    Tripp, J.; Grove, H.D.; McGrath, M.

    1982-01-01

    This article develops a strategy for maximizing percentage depletion deductions when extracting uranium or other solid minerals. The goal is to avoid losing percentage depletion deductions by staying below the 50% limitation on taxable income from the property. The article is divided into two major sections. The first section is comprised of depletion calculations that illustrate the problem and corresponding solutions. The last section deals with the feasibility of applying the strategy and complying with the Internal Revenue Code and appropriate regulations. Three separate strategies or appropriate situations are developed and illustrated. 13 references, 3 figures, 7 tables

  12. Compounds that correct F508del-CFTR trafficking can also correct other protein trafficking diseases: an in vitro study using cell lines

    Sampson Heidi M; Lam Hung; Chen Pei-Chun; Zhang Donglei; Mottillo Cristina; Mirza Myriam; Qasim Karim; Shrier Alvin; Shyng Show-Ling; Hanrahan John W; Thomas David Y

    2013-01-01

    Abstract Background Many genetic diseases are due to defects in protein trafficking where the mutant protein is recognized by the quality control systems, retained in the endoplasmic reticulum (ER), and degraded by the proteasome. In many cases, the mutant protein retains function if it can be trafficked to its proper cellular location. We have identified structurally diverse correctors that restore the trafficking and function of the most common mutation causing cystic fibrosis, F508del-CFTR...

  13. Fully Depleted Charge-Coupled Devices

    Holland, Stephen E.

    2006-01-01

    We have developed fully depleted, back-illuminated CCDs that build upon earlier research and development efforts directed towards technology development of silicon-strip detectors used in high-energy-physics experiments. The CCDs are fabricated on the same type of high-resistivity, float-zone-refined silicon that is used for strip detectors. The use of high-resistivity substrates allows for thick depletion regions, on the order of 200-300 um, with corresponding high detection efficiency for near-infrared and soft x-ray photons. We compare the fully depleted CCD to the p-i-n diode upon which it is based, and describe the use of fully depleted CCDs in astronomical and x-ray imaging applications

  14. Plasmonic Nanoprobes for Stimulated Emission Depletion Nanoscopy.

    Cortés, Emiliano; Huidobro, Paloma A; Sinclair, Hugo G; Guldbrand, Stina; Peveler, William J; Davies, Timothy; Parrinello, Simona; Görlitz, Frederik; Dunsby, Chris; Neil, Mark A A; Sivan, Yonatan; Parkin, Ivan P; French, Paul M W; Maier, Stefan A

    2016-11-22

    Plasmonic nanoparticles influence the absorption and emission processes of nearby emitters due to local enhancements of the illuminating radiation and the photonic density of states. Here, we use the plasmon resonance of metal nanoparticles in order to enhance the stimulated depletion of excited molecules for super-resolved nanoscopy. We demonstrate stimulated emission depletion (STED) nanoscopy with gold nanorods with a long axis of only 26 nm and a width of 8 nm. These particles provide an enhancement of up to 50% of the resolution compared to fluorescent-only probes without plasmonic components irradiated with the same depletion power. The nanoparticle-assisted STED probes reported here represent a ∼2 × 10 3 reduction in probe volume compared to previously used nanoparticles. Finally, we demonstrate their application toward plasmon-assisted STED cellular imaging at low-depletion powers, and we also discuss their current limitations.

  15. Real depletion in nodal diffusion codes

    Petkov, P.T.

    2002-01-01

    The fuel depletion is described by more than one hundred fuel isotopes in the advanced lattice codes like HELIOS, but only a few fuel isotopes are accounted for even in the advanced steady-state diffusion codes. The general assumption that the number densities of the majority of the fuel isotopes depend only on the fuel burnup is seriously in error if high burnup is considered. The real depletion conditions in the reactor core differ from the asymptotic ones at the stage of lattice depletion calculations. This study reveals which fuel isotopes should be explicitly accounted for in the diffusion codes in order to predict adequately the real depletion effects in the core. A somewhat strange conclusion is that if the real number densities of the main fissionable isotopes are not explicitly accounted for in the diffusion code, then Sm-149 should not be accounted for either, because the net error in k-inf is smaller (Authors)

  16. Depleted UF6 programmatic environmental impact statement

    1997-01-01

    The US Department of Energy has developed a program for long-term management and use of depleted uranium hexafluoride, a product of the uranium enrichment process. As part of this effort, DOE is preparing a Programmatic Environmental Impact Statement (PEIS) for the depleted UF 6 management program. This report duplicates the information available at the web site (http://www.ead.anl.gov/web/newduf6) set up as a repository for the PEIS. Options for the web site include: reviewing recent additions or changes to the web site; learning more about depleted UF 6 and the PEIS; browsing the PEIS and related documents, or submitting official comments on the PEIS; downloading all or part of the PEIS documents; and adding or deleting one's name from the depleted UF 6 mailing list

  17. Efficient characterization of fuel depletion in boiling water reactor

    Kim, S.H.

    1980-01-01

    An efficient fuel depletion method for boiling water reactor (BWR) fuel assemblies has been developed for fuel cycle analysis. A computer program HISTORY based on this method was designed to carry out accurate and rapid fuel burnup calculation for the fuel assembly. It has been usefully employed to study the depletion characteristics of the fuel assemblies for the preparation of nodal code input data and the fuel management study. The adequacy and the effectiveness of the assessment of this method used in HISTORY were demonstrated by comparing HISTORY results with more detailed CASMO results. The computing cost of HISTORY typically has been less than one dollar for the fuel assembly-level depletion calculations over the full life of the assembly, in contrast to more than $1000 for CASMO. By combining CASMO and HISTORY, a large number of expensive CASMO calculations can be replaced by inexpensive HISTORY. For the depletion calculations via CASMO/HISTORY, CASMO calculations are required only for the reference conditions and just at the beginning of life for other cases such as changes in void fraction, control rod condition and temperature. The simple and inexpensive HISTORY is sufficienty accurate and fast to be used in conjunction with CASMO for fuel cycle analysis and some BWR design calculations

  18. Stimulated emission depletion following two photon excitation

    Marsh, R. J.; Armoogum, D. A.; Bain, A. J.

    2002-01-01

    The technique of stimulated emission depletion of fluorescence (STED) from a two photon excited molecular population is demonstrated in the S, excited state of fluorescein in ethylene glycol and methanol. Two photon excitation (pump) is achieved using the partial output of a regeneratively amplified Ti:Sapphire laser in conjunction with an optical parametric amplifier whose tuneable output provides a synchronous depletion (dump) pulse. Time resolved fluorescence intensity and anisotropy measu...

  19. Depleted uranium: A DOE management guide

    1995-10-01

    The U.S. Department of Energy (DOE) has a management challenge and financial liability in the form of 50,000 cylinders containing 555,000 metric tons of depleted uranium hexafluoride (UF 6 ) that are stored at the gaseous diffusion plants. The annual storage and maintenance cost is approximately $10 million. This report summarizes several studies undertaken by the DOE Office of Technology Development (OTD) to evaluate options for long-term depleted uranium management. Based on studies conducted to date, the most likely use of the depleted uranium is for shielding of spent nuclear fuel (SNF) or vitrified high-level waste (HLW) containers. The alternative to finding a use for the depleted uranium is disposal as a radioactive waste. Estimated disposal costs, utilizing existing technologies, range between $3.8 and $11.3 billion, depending on factors such as applicability of the Resource Conservation and Recovery Act (RCRA) and the location of the disposal site. The cost of recycling the depleted uranium in a concrete based shielding in SNF/HLW containers, although substantial, is comparable to or less than the cost of disposal. Consequently, the case can be made that if DOE invests in developing depleted uranium shielded containers instead of disposal, a long-term solution to the UF 6 problem is attained at comparable or lower cost than disposal as a waste. Two concepts for depleted uranium storage casks were considered in these studies. The first is based on standard fabrication concepts previously developed for depleted uranium metal. The second converts the UF 6 to an oxide aggregate that is used in concrete to make dry storage casks

  20. Depleted Bulk Heterojunction Colloidal Quantum Dot Photovoltaics

    Barkhouse, D. Aaron R.

    2011-05-26

    The first solution-processed depleted bulk heterojunction colloidal quantum dot solar cells are presented. The architecture allows for high absorption with full depletion, thereby breaking the photon absorption/carrier extraction compromise inherent in planar devices. A record power conversion of 5.5% under simulated AM 1.5 illumination conditions is reported. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Spectrum of CFTR gene mutations in Ecuadorian cystic fibrosis patients: the second report of the p.H609R mutation.

    Ortiz, Sofía C; Aguirre, Santiago J; Flores, Sofía; Maldonado, Claudio; Mejía, Juan; Salinas, Lilian

    2017-11-01

    High heterogeneity in the CFTR gene mutations disturbs the molecular diagnosis of cystic fibrosis (CF). In order to improve the diagnosis of CF in our country, the present study aims to define a panel of common CFTR gene mutations by sequencing 27 exons of the gene in Ecuadorian Cystic Fibrosis patients. Forty-eight Ecuadorian individuals with suspected/confirmed CF diagnosis were included. Twenty-seven exons of CFTR gene were sequenced to find sequence variations. Prevalence of pathogenic variations were determined and compared with other countries' data. We found 70 sequence variations. Eight of these are CF-causing mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K. Also this study is the second report of p.H609R in Ecuadorian population. Mutation prevalence differences between Ecuadorian population and other Latin America countries were found. The panel of mutations suggested as an initial screening for the Ecuadorian population with cystic fibrosis should contain the mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X, R1162X, and N1303K. © 2017 NETLAB Laboratorios Especializados. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  2. [Frequency of the most common mutations of the CFTR gene in peruvian patients with cystic fibrosis using the ARMS-PCR technique].

    Aquino, Ruth; Protzel, Ana; Rivera, Juan; Abarca, Hugo; Dueñas, Milagros; Nestarez, Cecilia; Purizaga, Nestor; Diringer, Benoit

    2017-01-01

    To determine the frequency of the ten most common mutations of the CFTR gene reported in Latin Americausing amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) in patients with cystic fibrosis (CF) in two referral hospitals in Peru during the year 2014. The frequency of the ten most common mutations of the CFTR gene was assessed in patients of the Hospital Nacional Edgardo Rebagliati Martins and the Instituto Nacional de Salud del Niño, both located in Lima, Peru. Blood samples were collected from 36 patients with CF, and the ARMS-PCR technique was used to determine the presence of these mutations. The study group included 73.5% of patients with a known diagnosis of CF in the country when the study was carried out. ARMS-PCR allowed three of the mutations to be identified in a combined 30.6% of the alleles from patients with CF, and 64.9% of the mutated alleles were not identified. The mutations found were p.Phe508del (22,2%), p.Gly542* (6,9%), and p.Arg1162* (1,4%). There is significant variability in both the frequency and type of mutations present in our study population and in what has been reported in other Latin American countries. It is necessary to perform studies that use complete sequencing technology for the CFTR gene to identify other mutations present in our population.

  3. ANATOMY OF DEPLETED INTERPLANETARY CORONAL MASS EJECTIONS

    Kocher, M.; Lepri, S. T.; Landi, E.; Zhao, L.; Manchester, W. B. IV, E-mail: mkocher@umich.edu [Department of Climate and Space Sciences and Engineering, University of Michigan, 2455 Hayward Street, Ann Arbor, MI 48109-2143 (United States)

    2017-01-10

    We report a subset of interplanetary coronal mass ejections (ICMEs) containing distinct periods of anomalous heavy-ion charge state composition and peculiar ion thermal properties measured by ACE /SWICS from 1998 to 2011. We label them “depleted ICMEs,” identified by the presence of intervals where C{sup 6+}/C{sup 5+} and O{sup 7+}/O{sup 6+} depart from the direct correlation expected after their freeze-in heights. These anomalous intervals within the depleted ICMEs are referred to as “Depletion Regions.” We find that a depleted ICME would be indistinguishable from all other ICMEs in the absence of the Depletion Region, which has the defining property of significantly low abundances of fully charged species of helium, carbon, oxygen, and nitrogen. Similar anomalies in the slow solar wind were discussed by Zhao et al. We explore two possibilities for the source of the Depletion Region associated with magnetic reconnection in the tail of a CME, using CME simulations of the evolution of two Earth-bound CMEs described by Manchester et al.

  4. Unable to resist temptation : How self-control depletion promotes unethical behavior

    Gino, F.; Schweitzer, M.; Mead, N.L.; Ariely, D.

    2011-01-01

    Across four experimental studies, individuals who were depleted of their self-regulatory resources by an initial act of self-control were more likely to “impulsively cheat” than individuals whose self-regulatory resources were intact. Our results demonstrate that individuals depleted of self-control

  5. The interplay between SUCLA2, SUCLG2, and mitochondrial DNA depletion

    Miller, Chaya; Wang, Liya; Ostergaard, Elsebet

    2011-01-01

    SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome is a result of mutations in the β subunit of the ADP-dependent isoform of the Krebs cycle succinyl-CoA synthase (SCS). The mechanism of tissue specificity and mtDNA depletion is elusive but complementation by the GDP-dependent isoform en...

  6. Metallographic Characterization of Wrought Depleted Uranium

    Forsyth, Robert Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hill, Mary Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2018-02-14

    Metallographic characterization was performed on wrought depleted uranium (DU) samples taken from the longitudinal and transverse orientations from specific locations on two specimens. Characterization of the samples included general microstructure, inclusion analysis, grain size analysis, and microhardness testing. Comparisons of the characterization results were made to determine any differences based on specimen, sample orientation, or sample location. In addition, the characterization results for the wrought DU samples were also compared with data obtained from the metallographic characterization of cast DU samples previously characterized. No differences were observed in microstructure, inclusion size, morphology, and distribution, or grain size in regard to specimen, location, or orientation for the wrought depleted uranium samples. However, a small difference was observed in average hardness with regard to orientation at the same locations within the same specimen. The longitudinal samples were slightly harder than the transverse samples from the same location of the same specimen. This was true for both wrought DU specimens. Comparing the wrought DU sample data with the previously characterized cast DU sample data, distinct differences in microstructure, inclusion size, morphology and distribution, grain size, and microhardness were observed. As expected, the microstructure of the wrought DU samples consisted of small recrystallized grains which were uniform, randomly oriented, and equiaxed with minimal twinning observed in only a few grains. In contrast, the cast DU microstructure consisted of large irregularly shaped grains with extensive twinning observed in most grains. Inclusions in the wrought DU samples were elongated, broken and cracked and light and dark phases were observed in some inclusions. The mean inclusion area percentage for the wrought DU samples ranged from 0.08% to 0.34% and the average density from all wrought DU samples was 1.62E+04/cm

  7. Monte Carlo simulation in UWB1 depletion code

    Lovecky, M.; Prehradny, J.; Jirickova, J.; Skoda, R.

    2015-01-01

    U W B 1 depletion code is being developed as a fast computational tool for the study of burnable absorbers in the University of West Bohemia in Pilsen, Czech Republic. In order to achieve higher precision, the newly developed code was extended by adding a Monte Carlo solver. Research of fuel depletion aims at development and introduction of advanced types of burnable absorbers in nuclear fuel. Burnable absorbers (BA) allow the compensation of the initial reactivity excess of nuclear fuel and result in an increase of fuel cycles lengths with higher enriched fuels. The paper describes the depletion calculations of VVER nuclear fuel doped with rare earth oxides as burnable absorber based on performed depletion calculations, rare earth oxides are divided into two equally numerous groups, suitable burnable absorbers and poisoning absorbers. According to residual poisoning and BA reactivity worth, rare earth oxides marked as suitable burnable absorbers are Nd, Sm, Eu, Gd, Dy, Ho and Er, while poisoning absorbers include Sc, La, Lu, Y, Ce, Pr and Tb. The presentation slides have been added to the article

  8. Vitamin D depletion aggravates hypertension and target-organ damage

    Andersen, Louise Bjørkholt; Przybyl, Lukasz; Haase, Nadine

    2015-01-01

    BACKGROUND: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin. METHODS AND RESULTS: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (h......REN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P....6±3.3 versus 162.3±3.8 mm Hg, PVitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase-associated lipocalin, hREN, and r...

  9. Energetic magnetospheric protons in the plasma depletion layer

    Fuselier, S.A.

    1992-01-01

    Interplanetary magnetic field draping against the Earth's dayside subsolar magnetopause creates a region of reduced plasma density and increased magnetic field called the plasma depletion layer. In this region, leakage of energetic ions from the Earth's magnetosphere onto magnetic field lines in the plasma depletion layer can be studied without interference from ions accelerated at the Earth's quasi-parallel bow shock. Active Magnetospheric Particle Tracer Experiment/Charge Composition Explorer (AMPTE/CCE) observations for 13 plasma depletion layer events are used to determine the characteristics of energetic protons between a few keV/e and ∼100keV/e leaked from the magnetosphere. Results indicate that the leaked proton distributions resemble those in the magnetosphere except that they have lower densities and temperatures and much higher velocities parallel (or antiparallel) and perpendicular to the magnetic field. Compared to the low-energy magnetosheath proton distributions present in the depletion layer, the leaked energetic proton distributions typically have substantially higher flow velocities along the magnetic field indicate that the leaked energetic proton distributions to contribute to the energetic proton population seen upstream and downstream from the quasi-parallel bow shock. However, their contribution is small compared to the contribution from acceleration of protons at the bow shock because the leaked proton densities are on the order of 10 times smaller than the energetic proton densities typically observed in the vicinity of the quasi-parallel bow shock

  10. Energizing and depletion of neutrals by a collisional plasma

    Fruchtman, A

    2008-01-01

    Neutral depletion can significantly affect the steady state of low temperature plasmas. Recent theoretical analyses predicted previously unexpected effects of neutral depletion in both collisional and collisionless regimes. In this paper we address the effect of the energy deposited in the neutral gas by a collisional plasma. The fraction of power deposited in the neutrals is shown to be independent of the amount of power. The first case we address is of a thermalized neutral gas. It is shown that a low heat conductivity of the neutral gas is followed by a high neutral temperature that results in a high neutral depletion even if the plasma pressure is small. In the second case neutrals are accelerated through charge exchange with ions leading to what we call neutral pumping, which is equivalent to ion pumping in a collisionless plasma. Neutral depletion is found in the second case for both a closed system (no net mass flow) and an open system (a finite mass flow). A thruster that employs a collisional plasma and pumped neutrals is compared with the thruster analyzed before that employs collisionless plasma.

  11. Radiosensitization of mouse skin by oxygen and depletion of glutathione

    Stevens, Graham; Joiner, Michael; Joiner, Barbara; Johns, Helen; Denekamp, Juliana

    1995-01-01

    Purpose: To determine the oxygen enhancement ratio (OER) and shape of the oxygen sensitization curve of mouse foot skin, the extent to which glutathione (GSH) depletion radiosensitized skin, and the dependence of such sensitization on the ambient oxygen tension. Methods and Materials: The feet of WHT mice were irradiated with single doses of 240 kVp x-rays while mice were exposed to carbogen or gases with oxygen/nitrogen mixtures containing 8-100% O 2 . The anoxic response was obtained by occluding the blood supply to the leg of anesthetized mice with a tourniquet, surrounding the foot with nitrogen, and allowing the mice to breathe 10% O 2 . Further experiments were performed to assess the efficacy of this method to obtain an anoxic response. Radiosensitivity of skin was assessed using the acute skin-reaction assay. Glutathione levels were modified using two schedules of dl-buthionine sulphoximine (BSO) and diethylmaleate (DEM), which were considered to produce extensive and intermediate levels of GSH depletion in the skin of the foot during irradiation. Results: Carbogen caused the greatest radiosensitization of skin, with a reproducible enhancement of 2.2 relative to the anoxic response. The OER of 2.2 is lower than other reports for mouse skin. This may indicate that the extremes of oxygenation were not produced, although there was no direct evidence for this. When skin radiosensitivity was plotted against the logarithm of the oxygen tension in the ambient gas, a sigmoid curve with a K value of 17-21% O 2 in the ambient gas was obtained. Depletion of GSH caused minimal radiosensitization when skin was irradiated under anoxic or well-oxygenated conditions. Radiosensitization by GSH depletion was maximal at intermediate oxygen tensions of 10-21% O 2 in the ambient gas. Increasing the extent of GSH depletion led to increasing radiosensitization, with sensitization enhancement ratios of 1.2 and 1.1, respectively, for extensive and intermediate levels of GSH

  12. Evaluation of three high abundance protein depletion kits for umbilical cord serum proteomics

    Nie Jing

    2011-05-01

    Full Text Available Abstract Background High abundance protein depletion is a major challenge in the study of serum/plasma proteomics. Prior to this study, most commercially available kits for depletion of highly abundant proteins had only been tested and evaluated in adult serum/plasma, while the depletion efficiency on umbilical cord serum/plasma had not been clarified. Structural differences between some adult and fetal proteins (such as albumin make it likely that depletion approaches for adult and umbilical cord serum/plasma will be variable. Therefore, the primary purposes of the present study are to investigate the efficiencies of several commonly-used commercial kits during high abundance protein depletion from umbilical cord serum and to determine which kit yields the most effective and reproducible results for further proteomics research on umbilical cord serum. Results The immunoaffinity based kits (PROTIA-Sigma and 5185-Agilent displayed higher depletion efficiency than the immobilized dye based kit (PROTBA-Sigma in umbilical cord serum samples. Both the PROTIA-Sigma and 5185-Agilent kit maintained high depletion efficiency when used three consecutive times. Depletion by the PROTIA-Sigma Kit improved 2DE gel quality by reducing smeared bands produced by the presence of high abundance proteins and increasing the intensity of other protein spots. During image analysis using the identical detection parameters, 411 ± 18 spots were detected in crude serum gels, while 757 ± 43 spots were detected in depleted serum gels. Eight spots unique to depleted serum gels were identified by MALDI- TOF/TOF MS, seven of which were low abundance proteins. Conclusions The immunoaffinity based kits exceeded the immobilized dye based kit in high abundance protein depletion of umbilical cord serum samples and dramatically improved 2DE gel quality for detection of trace biomarkers.

  13. The health hazards of depleted uranium munitions. Part 1

    2001-01-01

    Depleted uranium is a toxic and weakly radioactive metal used for a variety of purposes. Perhaps its most controversial use is in battlefield munitions, where it can be widely dispersed in the form of fine particles and shrapnel that may enter the bodies of combatants and others through inhalation, ingestion or wounding. It is a matter of legitimate public concern whether the use of this material in this way could create unacceptable health hazards or damage to the environment. The objective of our study has been to provide the best scientific understanding of the ways in which the material may be distributed, how it may be taken up by humans, and the potential implications for health. For politicians, any hazards to health have to be balanced against the military advantages that the use of these munitions confers. We have not tried to reach a judgment on these political issues, but we believe that a better scientific understanding of the extent of the hazards will make it easier for these wider questions to be addressed in a more objective way. This report is the first of two, and addresses the likely levels of exposure to depleted uranium, the resulting radiological risks, and the lessons to be learned from epidemiological studies. Our second report will address toxicological risks and environmental issues. So far, we conclude that risks from radiation are low for most soldiers on the battlefield, and for civilians who later return to the area. However, there are uncertainties about the maximal levels of exposure to depleted uranium on the battlefield, and there may be circumstances in which a few soldiers are exposed to levels of depleted uranium that result in a significant risk to health. Further studies are needed to determine the levels of exposure to depleted uranium that might occur on the battlefield and to judge whether such higher risks are likely to occur in practice

  14. Enhanced Monte-Carlo-Linked Depletion Capabilities in MCNPX

    Fensin, Michael L.; Hendricks, John S.; Anghaie, Samim

    2006-01-01

    As advanced reactor concepts challenge the accuracy of current modeling technologies, a higher-fidelity depletion calculation is necessary to model time-dependent core reactivity properly for accurate cycle length and safety margin determinations. The recent integration of CINDER90 into the MCNPX Monte Carlo radiation transport code provides a completely self-contained Monte-Carlo-linked depletion capability. Two advances have been made in the latest MCNPX capability based on problems observed in pre-released versions: continuous energy collision density tracking and proper fission yield selection. Pre-released versions of the MCNPX depletion code calculated the reaction rates for (n,2n), (n,3n), (n,p), (n,a), and (n,?) by matching the MCNPX steady-state 63-group flux with 63-group cross sections inherent in the CINDER90 library and then collapsing to one-group collision densities for the depletion calculation. This procedure led to inaccuracies due to the miscalculation of the reaction rates resulting from the collapsed multi-group approach. The current version of MCNPX eliminates this problem by using collapsed one-group collision densities generated from continuous energy reaction rates determined during the MCNPX steady-state calculation. MCNPX also now explicitly determines the proper fission yield to be used by the CINDER90 code for the depletion calculation. The CINDER90 code offers a thermal, fast, and high-energy fission yield for each fissile isotope contained in the CINDER90 data file. MCNPX determines which fission yield to use for a specified problem by calculating the integral fission rate for the defined energy boundaries (thermal, fast, and high energy), determining which energy range contains the majority of fissions, and then selecting the appropriate fission yield for the energy range containing the majority of fissions. The MCNPX depletion capability enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code

  15. MCOR - Monte Carlo depletion code for reference LWR calculations

    Puente Espel, Federico, E-mail: fup104@psu.edu [Department of Mechanical and Nuclear Engineering, Pennsylvania State University (United States); Tippayakul, Chanatip, E-mail: cut110@psu.edu [Department of Mechanical and Nuclear Engineering, Pennsylvania State University (United States); Ivanov, Kostadin, E-mail: kni1@psu.edu [Department of Mechanical and Nuclear Engineering, Pennsylvania State University (United States); Misu, Stefan, E-mail: Stefan.Misu@areva.com [AREVA, AREVA NP GmbH, Erlangen (Germany)

    2011-04-15

    Research highlights: > Introduction of a reference Monte Carlo based depletion code with extended capabilities. > Verification and validation results for MCOR. > Utilization of MCOR for benchmarking deterministic lattice physics (spectral) codes. - Abstract: The MCOR (MCnp-kORigen) code system is a Monte Carlo based depletion system for reference fuel assembly and core calculations. The MCOR code is designed as an interfacing code that provides depletion capability to the LANL Monte Carlo code by coupling two codes: MCNP5 with the AREVA NP depletion code, KORIGEN. The physical quality of both codes is unchanged. The MCOR code system has been maintained and continuously enhanced since it was initially developed and validated. The verification of the coupling was made by evaluating the MCOR code against similar sophisticated code systems like MONTEBURNS, OCTOPUS and TRIPOLI-PEPIN. After its validation, the MCOR code has been further improved with important features. The MCOR code presents several valuable capabilities such as: (a) a predictor-corrector depletion algorithm, (b) utilization of KORIGEN as the depletion module, (c) individual depletion calculation of each burnup zone (no burnup zone grouping is required, which is particularly important for the modeling of gadolinium rings), and (d) on-line burnup cross-section generation by the Monte Carlo calculation for 88 isotopes and usage of the KORIGEN libraries for PWR and BWR typical spectra for the remaining isotopes. Besides the just mentioned capabilities, the MCOR code newest enhancements focus on the possibility of executing the MCNP5 calculation in sequential or parallel mode, a user-friendly automatic re-start capability, a modification of the burnup step size evaluation, and a post-processor and test-matrix, just to name the most important. The article describes the capabilities of the MCOR code system; from its design and development to its latest improvements and further ameliorations. Additionally

  16. MCOR - Monte Carlo depletion code for reference LWR calculations

    Puente Espel, Federico; Tippayakul, Chanatip; Ivanov, Kostadin; Misu, Stefan

    2011-01-01

    Research highlights: → Introduction of a reference Monte Carlo based depletion code with extended capabilities. → Verification and validation results for MCOR. → Utilization of MCOR for benchmarking deterministic lattice physics (spectral) codes. - Abstract: The MCOR (MCnp-kORigen) code system is a Monte Carlo based depletion system for reference fuel assembly and core calculations. The MCOR code is designed as an interfacing code that provides depletion capability to the LANL Monte Carlo code by coupling two codes: MCNP5 with the AREVA NP depletion code, KORIGEN. The physical quality of both codes is unchanged. The MCOR code system has been maintained and continuously enhanced since it was initially developed and validated. The verification of the coupling was made by evaluating the MCOR code against similar sophisticated code systems like MONTEBURNS, OCTOPUS and TRIPOLI-PEPIN. After its validation, the MCOR code has been further improved with important features. The MCOR code presents several valuable capabilities such as: (a) a predictor-corrector depletion algorithm, (b) utilization of KORIGEN as the depletion module, (c) individual depletion calculation of each burnup zone (no burnup zone grouping is required, which is particularly important for the modeling of gadolinium rings), and (d) on-line burnup cross-section generation by the Monte Carlo calculation for 88 isotopes and usage of the KORIGEN libraries for PWR and BWR typical spectra for the remaining isotopes. Besides the just mentioned capabilities, the MCOR code newest enhancements focus on the possibility of executing the MCNP5 calculation in sequential or parallel mode, a user-friendly automatic re-start capability, a modification of the burnup step size evaluation, and a post-processor and test-matrix, just to name the most important. The article describes the capabilities of the MCOR code system; from its design and development to its latest improvements and further ameliorations

  17. Development of an Application Programming Interface for Depletion Analysis (APIDA)

    Lago, Daniel; Rahnema, Farzad

    2017-01-01

    cell depletion problem. Results show APIDA to be effective and efficient in solving lattice depletion problems, in addition to being successful in terms of portability for users to implement via the API.

  18. Parametric investigations on the saturation intensity of Coumarin 102 for stimulated emission depletion application.

    Qin, H-Y; Zhao, W-X; Zhao, W; Zhang, C; Feng, X-Q; Liu, S-P; Wang, K-G

    2018-04-23

    Stimulated emission depletion (STED) microscopy performed using continuous-wave (CW) lasers has been investigated and developed by Willig et al. (Nature Methods, 2007, 4(11):915) for nearly a decade. Kuang et al. (Review of Scientific Instruments, 2010, 81:053709) developed the CW STED microscopy technique with 405 nm excitation and 532 nm depletion beams. In their research, Coumarin 102 dye was adopted and was found to be depletable. In this study, a parametric investigation of the depletion of Coumarin 102 dye is carried out experimentally. The influence of the excitation and depletion beam intensities and dye concentrations on the depletion efficiency are studied in detail. The results indicate the following: (1) The highest depletion occurs for the 100 μM Coumarin 102 solution, with a 1.4 μW excitation beam and a 115.3 mW depletion beam. (2) The minimum saturation intensity (Is) of STED, that is 13 MW cm -2 , is observed when the Coumarin 102 solution concentration is 10 μM. (3) Is values calculated directly from the depletion power derived with the cross-sectional area due to the full-width-at-half-maximum (FWHM) of the depletion beam show poor accuracy, where Is may be overestimated. Thus, a correction factor for the cross-sectional area is proposed. We also find that Is is not exactly constant for a fixed excitation beam power and dye concentration. This trend indicates that the conventional suppression function η(x)=e- ln (2)ISTED(x)/Is derived from picosecond STED may cause errors in evaluating the depletion process in CW STED microscopy. © 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

  19. Recirculating cooling water solute depletion models

    Price, W.T.

    1990-01-01

    Chromates have been used for years to inhibit copper corrosion in the plant Recirculating Cooling Water (RCW) system. However, chromates have become an environmental problem in recent years both in the chromate removal plant (X-616) operation and from cooling tower drift. In response to this concern, PORTS is replacing chromates with Betz Dianodic II, a combination of phosphates, BZT, and a dispersant. This changeover started with the X-326 system in 1989. In order to control chemical concentrations in X-326 and in systems linked to it, we needed to be able to predict solute concentrations in advance of the changeover. Failure to predict and control these concentrations can result in wasted chemicals, equipment fouling, or increased corrosion. Consequently, Systems Analysis developed two solute concentration models. The first simulation represents the X-326 RCW system by itself; and models the depletion of a solute once the feed has stopped. The second simulation represents the X-326, X-330, and the X-333 systems linked together by blowdown. This second simulation represents the concentration of a solute in all three systems simultaneously. 4 figs

  20. Depletion of compounds from thin oil films in seawater

    Brakstad, O.G.; Faksness, L.G.; Melbye, A.G.

    2002-01-01

    When oil is spilled on water, the oil compounds distribute between droplets and water-soluble phases in the water column. Some small organic acids, phenols, BTEX, and aromatic compounds will dissolve completely, but larger polycyclic aromatic hydrocarbons (PAH) and alkanes will remain in the droplet fraction. The biodegradation of droplets occurs at the oil-water interface. A method for immobilizing the oil films onto hydrophobic surfaces was developed in order to obtain a stable oil surface during the biodegradation period. A test system was also established to determine the depletion of oil compounds from the oil phase, including both abiotic and biotic processes. Three North Sea oils were used in the study. Two were paraffinic oils rich in n-alkanes and aromatic compounds, and one was asphalthenic which was richer in branched alkanes and PAH. The biodegradation period was 2 months at 13 degrees C. Samples from the water and thin film on the fabric was analyzed for carbon 10 and carbon 36 by gas chromatography-flame ionization detection. Semi-volatile organic compounds were analyzed using gas chromatography-mass spectrometry. Results indicated that the depletion process for alkanes was completely caused by biodegradation, while aromatic compounds were depleted by abiotic dissolution as well as by biodegradation. The system has potential for determining oil depletion processes under controlled surface-to-volume conditions, such as thin oil films and dispersed oil droplets. In addition, the system can be used to determine the depletion process in flow-through systems. 13 refs., 3 tabs., 9 figs

  1. Hybrid microscopic depletion model in nodal code DYN3D

    Bilodid, Y.; Kotlyar, D.; Shwageraus, E.; Fridman, E.; Kliem, S.

    2016-01-01

    Highlights: • A new hybrid method of accounting for spectral history effects is proposed. • Local concentrations of over 1000 nuclides are calculated using micro depletion. • The new method is implemented in nodal code DYN3D and verified. - Abstract: The paper presents a general hybrid method that combines the micro-depletion technique with correction of micro- and macro-diffusion parameters to account for the spectral history effects. The fuel in a core is subjected to time- and space-dependent operational conditions (e.g. coolant density), which cannot be predicted in advance. However, lattice codes assume some average conditions to generate cross sections (XS) for nodal diffusion codes such as DYN3D. Deviation of local operational history from average conditions leads to accumulation of errors in XS, which is referred as spectral history effects. Various methods to account for the spectral history effects, such as spectral index, burnup-averaged operational parameters and micro-depletion, were implemented in some nodal codes. Recently, an alternative method, which characterizes fuel depletion state by burnup and 239 Pu concentration (denoted as Pu-correction) was proposed, implemented in nodal code DYN3D and verified for a wide range of history effects. The method is computationally efficient, however, it has applicability limitations. The current study seeks to improve the accuracy and applicability range of Pu-correction method. The proposed hybrid method combines the micro-depletion method with a XS characterization technique similar to the Pu-correction method. The method was implemented in DYN3D and verified on multiple test cases. The results obtained with DYN3D were compared to those obtained with Monte Carlo code Serpent, which was also used to generate the XS. The observed differences are within the statistical uncertainties.

  2. Aqueous Colloid + Polymer Depletion System for Confocal Microscopy and Rheology

    Park, Nayoung; Umanzor, Esmeralda J.; Conrad, Jacinta C.

    2018-05-01

    We developed a model depletion system with colloidal particles that were refractive index- and density-matched to 80 (w/w)% glycerol in water, and characterized the effect of interparticle interactions on the structure and dynamics of non-equilibrium phases. 2,2,2-trifluoroethyl methacrylate-co-tert-butyl methacrylate copolymer particles were synthesized following Kodger et al. (Sci. Rep. 5, 14635 (2015)). Particles were dispersed in glycerol/water solutions to generate colloidal suspensions with good control over electrostatic interactions and a moderately high background viscosity of 55 mPa-s. To probe the effects of charge screening and depletion attractions on the suspension phase behavior, we added NaCl and polyacrylamide (M_w = 186 kDa) at various concentrations to particle suspensions formulated at volume fractions of phi = 0.05 and 0.3 and imaged the suspensions using confocal microscopy. The particles were nearly hard spheres at a NaCl concentration of 20 mM, but aggregated when the concentration of NaCl was further increased. Changes in the particle structure and dynamics with increasing concentration of the depletant polyacrylamide followed the trends expected from earlier experiments on depletion-driven gelation. Additionally, we measured the viscosity and corrected first normal stress difference of suspensions formulated at phi = 0.4 with and without added polymer. The solvent viscosity was suitable for rheology measurements without the onset of instabilities such as secondary flows or edge fracture. These results validate this system as an alternative to one common model system, suspensions of poly(methyl methacrylate) particles and polystyrene depletants in organic solvents, for investigating phase behavior and flow properties in attractive colloidal suspensions.

  3. A theoretical study on the effect of piezoelectric charges on the surface potential and surface depletion region of ZnO nanowires

    Purahmad, Mohsen; Stroscio, Michael A; Dutta, Mitra

    2013-01-01

    The electrostatic potential and depletion width in piezoelectric semiconductor nanowires are derived by considering a non-depleted region and a surface depleted region and solving the Poisson equation. By determining the piezoelectric-induced charge density, in terms of equivalent density of charges, the effect of piezoelectric charges on the surface depletion region and the distributed electric potential in nanowire have been investigated. The numerical results demonstrate that the ZnO NWs with a smaller radius have a larger surface depletion region which results in a stronger surface potential and depletion region perturbation by induced piezoelectric charges. (paper)

  4. Uncertainty Propagation in Monte Carlo Depletion Analysis

    Shim, Hyung Jin; Kim, Yeong-il; Park, Ho Jin; Joo, Han Gyu; Kim, Chang Hyo

    2008-01-01

    A new formulation aimed at quantifying uncertainties of Monte Carlo (MC) tallies such as k eff and the microscopic reaction rates of nuclides and nuclide number densities in MC depletion analysis and examining their propagation behaviour as a function of depletion time step (DTS) is presented. It is shown that the variance of a given MC tally used as a measure of its uncertainty in this formulation arises from four sources; the statistical uncertainty of the MC tally, uncertainties of microscopic cross sections and nuclide number densities, and the cross correlations between them and the contribution of the latter three sources can be determined by computing the correlation coefficients between the uncertain variables. It is also shown that the variance of any given nuclide number density at the end of each DTS stems from uncertainties of the nuclide number densities (NND) and microscopic reaction rates (MRR) of nuclides at the beginning of each DTS and they are determined by computing correlation coefficients between these two uncertain variables. To test the viability of the formulation, we conducted MC depletion analysis for two sample depletion problems involving a simplified 7x7 fuel assembly (FA) and a 17x17 PWR FA, determined number densities of uranium and plutonium isotopes and their variances as well as k ∞ and its variance as a function of DTS, and demonstrated the applicability of the new formulation for uncertainty propagation analysis that need be followed in MC depletion computations. (authors)

  5. Depletion of cellular poly (A) binding protein prevents protein synthesis and leads to apoptosis in HeLa cells

    Thangima Zannat, Mst.; Bhattacharjee, Rumpa B. [Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G2W1 (Canada); Bag, Jnanankur, E-mail: jbag@uoguelph.ca [Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G2W1 (Canada)

    2011-05-13

    Highlights: {yields} Depletion of cellular PABP level arrests mRNA translation in HeLa cells. {yields} PABP knock down leads to apoptotic cell death. {yields} PABP depletion does not affect transcription. {yields} PABP depletion does not lead to nuclear accumulation of mRNA. -- Abstract: The cytoplasmic poly (A) binding protein (PABP) is important in mRNA translation and stability. In yeast, depletion of PABP leads to translation arrest. Similarly, the PABP gene in Drosophila is important for proper development. It is however uncertain, whether mammalian PABP is essential for mRNA translation. Here we showed the effect of PABP depletion on mRNA metabolism in HeLa cells by using a small interfering RNA. Our results suggest that depletion of PABP prevents protein synthesis and consequently leads to cell death through apoptosis. Interestingly, no detectable effect of PABP depletion on transcription, transport and stability of mRNA was observed.

  6. Depletion of cellular poly (A) binding protein prevents protein synthesis and leads to apoptosis in HeLa cells

    Thangima Zannat, Mst.; Bhattacharjee, Rumpa B.; Bag, Jnanankur

    2011-01-01

    Highlights: → Depletion of cellular PABP level arrests mRNA translation in HeLa cells. → PABP knock down leads to apoptotic cell death. → PABP depletion does not affect transcription. → PABP depletion does not lead to nuclear accumulation of mRNA. -- Abstract: The cytoplasmic poly (A) binding protein (PABP) is important in mRNA translation and stability. In yeast, depletion of PABP leads to translation arrest. Similarly, the PABP gene in Drosophila is important for proper development. It is however uncertain, whether mammalian PABP is essential for mRNA translation. Here we showed the effect of PABP depletion on mRNA metabolism in HeLa cells by using a small interfering RNA. Our results suggest that depletion of PABP prevents protein synthesis and consequently leads to cell death through apoptosis. Interestingly, no detectable effect of PABP depletion on transcription, transport and stability of mRNA was observed.

  7. Ego depletion in visual perception: Ego-depleted viewers experience less ambiguous figure reversal.

    Wimmer, Marina C; Stirk, Steven; Hancock, Peter J B

    2017-10-01

    This study examined the effects of ego depletion on ambiguous figure perception. Adults (N = 315) received an ego depletion task and were subsequently tested on their inhibitory control abilities that were indexed by the Stroop task (Experiment 1) and their ability to perceive both interpretations of ambiguous figures that was indexed by reversal (Experiment 2). Ego depletion had a very small effect on reducing inhibitory control (Cohen's d = .15) (Experiment 1). Ego-depleted participants had a tendency to take longer to respond in Stroop trials. In Experiment 2, ego depletion had small to medium effects on the experience of reversal. Ego-depleted viewers tended to take longer to reverse ambiguous figures (duration to first reversal) when naïve of the ambiguity and experienced less reversal both when naïve and informed of the ambiguity. Together, findings suggest that ego depletion has small effects on inhibitory control and small to medium effects on bottom-up and top-down perceptual processes. The depletion of cognitive resources can reduce our visual perceptual experience.

  8. Self-regulation, ego depletion, and inhibition.

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Electrochemical corrosion behavior of MSIP Ni coating on depleted uranium surface

    Chen Lin; Li Kexue; Wang Qingfu; Wang Xiaohong; Guan Weijun

    2014-01-01

    The Ni film was prepared by magnetron sputtering ion plating to improve the corrosion resistance of depleted uranium. The corrosion resistance of the Ni film was examined by electrochemical corrosion station. The results show that the Ni film corrosion potential is -100.8 mV, whereas it is -641.2 mV for depleted uranium in 50 μg/g KCl solution. The Ni film is a barrier to protect the depleted uranium substrate avoiding the corrosive media attack. The Ni film polarization resistance and impedance are much higher, while the corrosion current density is much lower contrast with depleted uranium. None crack or flake is found through 70 h corrosion. The corrosion resistance and corrosion current keep stable. It is indicated that the corrosion resistance of depleted uranium is effectively improved after deposited Ni film by magnetron sputtering ion plating. (authors)

  10. Department of Energy depleted uranium recycle

    Kosinski, F.E.; Butturini, W.G.; Kurtz, J.J.

    1994-01-01

    With its strategic supply of depleted uranium, the Department of Energy is studying reuse of the material in nuclear radiation shields, military hardware, and commercial applications. the study is expected to warrant a more detailed uranium recycle plan which would include consideration of a demonstration program and a program implementation decision. Such a program, if implemented, would become the largest nuclear material recycle program in the history of the Department of Energy. The bulk of the current inventory of depleted uranium is stored in 14-ton cylinders in the form of solid uranium hexafluoride (UF 6 ). The radioactive 235 U content has been reduced to a concentration of 0.2% to 0.4%. Present estimates indicate there are about 55,000 UF 6 -filled cylinders in inventory and planned operations will provide another 2,500 cylinders of depleted uranium each year. The United States government, under the auspices of the Department of Energy, considers the depleted uranium a highly-refined strategic resource of significant value. A possible utilization of a large portion of the depleted uranium inventory is as radiation shielding for spent reactor fuels and high-level radioactive waste. To this end, the Department of Energy study to-date has included a preliminary technical review to ascertain DOE chemical forms useful for commercial products. The presentation summarized the information including preliminary cost estimates. The status of commercial uranium processing is discussed. With a shrinking market, the number of chemical conversion and fabrication plants is reduced; however, the commercial capability does exist for chemical conversion of the UF 6 to the metal form and for the fabrication of uranium radiation shields and other uranium products. Department of Energy facilities no longer possess a capability for depleted uranium chemical conversion

  11. Depleted uranium hexafluoride: Waste or resource?

    Schwertz, N.; Zoller, J.; Rosen, R.; Patton, S.; Bradley, C.; Murray, A.

    1995-07-01

    The US Department of Energy is evaluating technologies for the storage, disposal, or re-use of depleted uranium hexafluoride (UF 6 ). This paper discusses the following options, and provides a technology assessment for each one: (1) conversion to UO 2 for use as mixed oxide duel, (2) conversion to UO 2 to make DUCRETE for a multi-purpose storage container, (3) conversion to depleted uranium metal for use as shielding, (4) conversion to uranium carbide for use as high-temperature gas-cooled reactor (HTGR) fuel. In addition, conversion to U 3 O 8 as an option for long-term storage is discussed

  12. Depleted uranium processing and fluorine extraction

    Laflin, S.T.

    2010-01-01

    Since the beginning of the nuclear era, there has never been a commercial solution for the large quantities of depleted uranium hexafluoride generated from uranium enrichment. In the United States alone, there is already in excess of 1.6 billion pounds (730 million kilograms) of DUF_6 currently stored. INIS is constructing a commercial uranium processing and fluorine extraction facility. The INIS facility will convert depleted uranium hexafluoride and use it as feed material for the patented Fluorine Extraction Process to produce high purity fluoride gases and anhydrous hydrofluoric acid. The project will provide an environmentally friendly and commercially viable solution for DUF_6 tails management. (author)

  13. The Chemistry and Toxicology of Depleted Uranium

    Sidney A. Katz

    2014-01-01

    Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU) is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U) down to reactor grade uranium (~5% 235U), and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles....

  14. Muscle glycogen depletion and lactate concentration during downhill skiing.

    Tesch, P; Larsson, L; Eriksson, A; Karlsson, J

    1978-01-01

    Skilled and unskilled skiers were studied during downhill skiing. Muscle glycogen and muscle lactate concentrations in the vastus lateralis muscle were determined following different skiing conditions. Heavy glycogen utilization was found in the groups studied during a day of skiing. The skilled and unskilled skiers differed with respect to selective glycogen depletion pattern and the skilled subjects demonstrated greater depletion of slow twitch fibers than the unskilled subjects. Lactate concentrations ranged from approximately 5-26 mmoles x kg-1 wet muscle after approximately one minute of maximal skiing. This wide range was not found to be related to the level of skiing proficiency. However, skiing with varyingly angled boots, resulting in different knee angles, did affect lactate concentration. Lactate concentration was positively correlated to individual muscle fiber composition expressed as a percent of fast twitch fibers. The results suggest more pronounced involvement of aerobic energy metabolism in skilled skiers than in unskilled skiers.

  15. Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation.

    Someya, Masanori; Sakata, Koh-ichi; Matsumoto, Yoshihisa; Tauchi, Hiroshi; Kai, Masahiro; Hareyama, Masato; Fukushima, Masakazu

    2012-01-01

    Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothecin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mechanisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD depletion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization.

  16. VERA Pin and Fuel Assembly Depletion Benchmark Calculations by McCARD and DeCART

    Park, Ho Jin; Cho, Jin Young [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    Monte Carlo (MC) codes have been developed and used to simulate a neutron transport since MC method was devised in the Manhattan project. Solving the neutron transport problem with the MC method is simple and straightforward to understand. Because there are few essential approximations for the 6- dimension phase of a neutron such as the location, energy, and direction in MC calculations, highly accurate solutions can be obtained through such calculations. In this work, the VERA pin and fuel assembly (FA) depletion benchmark calculations are performed to examine the depletion capability of the newly generated DeCART multi-group cross section library. To obtain the reference solutions, MC depletion calculations are conducted using McCARD. Moreover, to scrutinize the effect by stochastic uncertainty propagation, uncertainty propagation analyses are performed using a sensitivity and uncertainty (S/U) analysis method and stochastic sampling (S.S) method. It is still expensive and challenging to perform a depletion analysis by a MC code. Nevertheless, many studies and works for a MC depletion analysis have been conducted to utilize the benefits of the MC method. In this study, McCARD MC and DeCART MOC transport calculations are performed for the VERA pin and FA depletion benchmarks. The DeCART depletion calculations are conducted to examine the depletion capability of the newly generated multi-group cross section library. The DeCART depletion calculations give excellent agreement with the McCARD reference one. From the McCARD results, it is observed that the MC depletion results depend on how to split the burnup interval. First, only to quantify the effect of the stochastic uncertainty propagation at 40 DTS, the uncertainty propagation analyses are performed using the S/U and S.S. method.

  17. Meta-analysis of depleted uranium levels in the Balkan region.

    Besic, Larisa; Muhovic, Imer; Asic, Adna; Kurtovic-Kozaric, Amina

    2017-06-01

    In recent years, contradicting data has been published on the connection between the presence of depleted uranium and an increased cancer incidence among military personnel deployed in the Balkans during the 1992-1999 wars. This has led to numerous research articles investigating possible depleted uranium contamination of the afflicted regions of the Balkan Peninsula, namely Bosnia & Herzegovina, Serbia, Kosovo and Montenegro. The aim of this study was to collect data from previously published reports investigating the levels of depleted uranium in the Balkans and to present the data in the form of a meta-analysis. This would provide a clear image of the extent of depleted uranium contamination after the Balkan conflict. In addition, we tested the hypothesis that there is a correlation between the levels of depleted uranium and the assumed depleted uranium-related health effects. Our results suggest that the majority of the examined sites contain natural uranium, while the area of Kosovo appears to be most heavily afflicted by depleted uranium pollution, followed by Bosnia & Herzegovina. Furthermore, the results indicate that it is not possible to make a valid correlation between the health effects and depleted uranium-contaminated areas. We therefore suggest a structured collaborative plan of action where long-term monitoring of the residents of depleted uranium-afflicted areas would be performed. In conclusion, while the possibility of depleted uranium toxicity in post-conflict regions appears to exist, there currently exists no definitive proof of such effects, due to insufficient studies of potentially afflicted populations, in addition to the lack of a common epidemiological approach in the reviewed literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Fully depleted back-illuminated p-channel CCD development

    Bebek, Chris J.; Bercovitz, John H.; Groom, Donald E.; Holland, Stephen E.; Kadel, Richard W.; Karcher, Armin; Kolbe, William F.; Oluseyi, Hakeem M.; Palaio, Nicholas P.; Prasad, Val; Turko, Bojan T.; Wang, Guobin

    2003-07-08

    An overview of CCD development efforts at Lawrence Berkeley National Laboratory is presented. Operation of fully-depleted, back-illuminated CCD's fabricated on high resistivity silicon is described, along with results on the use of such CCD's at ground-based observatories. Radiation damage and point-spread function measurements are described, as well as discussion of CCD fabrication technologies.

  19. Radiation survey and decontamination of cape Arza from depleted uranium

    Vukotić Perko

    2003-01-01

    Full Text Available In the action of NATO A-10 airplanes in 1999, the cape Arza, Serbia and Montenegro was contaminated by depleted uranium. The clean-up operations were undertaken at the site, and 242 uranium projectiles and their 49 larger fragments were removed from the cape. That is about 85% of the total number of projectiles by which Arza was contaminated. Here are described details of the applied procedures and results of the soil radioactivity measurements after decontamination.

  20. Deuterium depleted water. Romanian achievements and prospects

    Stefanescu, Ioan; Steflea, Dumitru; Titescu, Gheorghe; Tamaian, Radu

    2002-01-01

    The deuterium depleted water (DDW) is microbiologically pure distilled water with a deuterium content lower than that of natural waters which amounts to 140 - 150 ppm D/(D+H); variations depend on geographical zone and altitude. The procedure of obtaining DDW is based on isotopic separation of natural water by vacuum distillation. Isotope concentration can be chosen within 20 to 120 ppm D/(D+H). The ICSI at Rm. Valcea has patented the procedure and equipment for the production of DDW. According to the document SF-01-2002/INC-DTCI - ICSI Rm. Valcea, the product has a D/(D+H) isotope concentration of 25 ± 5. Studies and research for finding the effects and methods of application in different fields were initiated and developed in collaboration with different institutes in Romania. The following important results obtained so far could be mentioned: - absence of toxicity upon organisms; - activation of vascular reactivity; - enhancement of defence capacity of the organism through non-specific immunity activation; - increase of salmonid reproduction capacity and enhancement of the adaptability of alevins to the environmental conditions; - radioprotective effect to ionizing radiation; - maintaining meat freshness through osmotic shock; - stimulation of growth of aquatic macrophytes; - enhancement of culture plant development in certain ontogenetic stages. Mostly, the results and practical applications of the research were patented and awarded with gold medals at international invention fairs. At present, research-development programmes are undergoing to find active biological features of DDW in fighting cancer, on one hand, and its applicability as food additive of pets or performing animals, on the other hand

  1. Depleted uranium - 'the silver bullet'

    Munoz-Ferrada, C.; Wollongong University, NSW

    2001-01-01

    Article 35 of the Geneva protocols, signed by 150 countries in 1949 and an additional protocol signed from 1977 onwards prohibited the use of weapons that cause and inflict unnecessary injury and suffering. In the recent wars such as Bosnia, Kosovo and the Gulf War, more than 31,000 missiles were launched against enemy lines containing DU and more than 300 tonnes of DU during the Gulf War alone. DU is a radioactive and toxic element. In humans it can cause lung cancer, damage to the liver and kidney affecting the bone marrow and consequently destroying stem cells that form the white cells resulting in mutations and the long lasting effect of genetic damage

  2. “When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

    Salmon, S.J.; Adriaanse, M.A.; Vet, de E.W.M.L.; Fennis, B.M.; Ridder, de D.T.D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In

  3. “When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion. PMID:25009523

  4. Evolution of depleted mantle: The lead perspective

    Tilton, George R.

    1983-07-01

    Isotopic data have established that, compared to estimated bulk earth abundances, the sources of oceanic basaltic lavas have been depleted in large ion lithophile elements for at least several billions of years. Various data on the Tertiary-Mesozoic Gorgona komatiite and Cretaceous Oka carbonatite show that those rocks also sample depleted mantle sources. This information is used by analogy to compare Pb isotopic data from 2.6 billion year old komatiite and carbonatite from the Suomussalmi belt of eastern Finland and Munro Township, Ontario that are with associated granitic rocks and ores that should contain marked crustal components. Within experimental error no differences are detected in the isotopic composition of initial Pb in either of the rock suites. These observations agree closely with Sr and Nd data from other laboratories showing that depleted mantle could not have originated in those areas more than a few tenths of billions of years before the rocks were emplaced. On a world-wide basis the Pb isotope data are consistent with production of depleted mantle by continuous differentiation processes acting over approximately the past 3 billion years. The data show that Pb evolution is more complex than the simpler models derived from the Rb-Sr and Sm-Nd systems. The nature of the complexity is still poorly understood.

  5. Nitrogen depletion in field red giants

    Masseron, T.; Lagarde, N.; Miglio, A.

    2017-01-01

    , the behaviour of nitrogen data along the evolution confirms the existence of non-canonical extramixing on the red giant branch (RGB) for all low-mass stars in the field. But more surprisingly, the data indicate that nitrogen has been depleted between the RGB tip and the red clump. This may suggest that some...

  6. Elephant invasion and escalated depletion of environmental ...

    For decades, elephants' invasion is known to be associated with severe environmental consequences leading to escalated depletion o environmental resources (plants, water, wildlife and soil). This paper examined the effects of elephants' activity on the environmental resources inHong and Gombi Local Government areas ...

  7. Global Warming: Lessons from Ozone Depletion

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  8. Application of backtracking algorithm to depletion calculations

    Wu Mingyu; Wang Shixi; Yang Yong; Zhang Qiang; Yang Jiayin

    2013-01-01

    Based on the theory of linear chain method for analytical depletion calculations, the burnup matrix is decoupled by the divide and conquer strategy and the linear chain with Markov characteristic is formed. The density, activity and decay heat of every nuclide in the chain then can be calculated by analytical solutions. Every possible reaction path of the nuclide must be considered during the linear chain establishment process. To confirm the calculation precision and efficiency, the algorithm which can cover all the reaction paths and search the paths automatically according to the problem description and precision restrictions should be found. Through analysis and comparison of several kinds of searching algorithms, the backtracking algorithm was selected to establish and calculate the linear chains in searching process using depth first search (DFS) method, forming an algorithm which can solve the depletion problem adaptively and with high fidelity. The complexity of the solution space and time was analyzed by taking into account depletion process and the characteristics of the backtracking algorithm. The newly developed depletion program was coupled with Monte Carlo program MCMG-Ⅱ to calculate the benchmark burnup problem of the first core of China Experimental Fast Reactor (CEFR) and the preliminary verification and validation of the program were performed. (authors)

  9. Depletion of CpG Dinucleotides in Papillomaviruses and Polyomaviruses: A Role for Divergent Evolutionary Pressures.

    Upadhyay, Mohita; Vivekanandan, Perumal

    2015-01-01

    results highlight the existence of divergent evolutionary pressures leading to CpG dinucleotide depletion among small ds-DNA viruses infecting vertebrate hosts.

  10. CRDIAC: Coupled Reactor Depletion Instrument with Automated Control

    Logan, Steven K.

    2012-01-01

    When modeling the behavior of a nuclear reactor over time, it is important to understand how the isotopes in the reactor will change, or transmute, over that time. This is especially important in the reactor fuel itself. Many nuclear physics modeling codes model how particles interact in the system, but do not model this over time. Thus, another code is used in conjunction with the nuclear physics code to accomplish this. In our code, Monte Carlo N-Particle (MCNP) codes and the Multi Reactor Transmutation Analysis Utility (MRTAU) were chosen as the codes to use. In this way, MCNP would produce the reaction rates in the different isotopes present and MRTAU would use cross sections generated from these reaction rates to determine how the mass of each isotope is lost or gained. Between these two codes, the information must be altered and edited for use. For this, a Python 2.7 script was developed to aid the user in getting the information in the correct forms. This newly developed methodology was called the Coupled Reactor Depletion Instrument with Automated Controls (CRDIAC). As is the case in any newly developed methodology for modeling of physical phenomena, CRDIAC needed to be verified against similar methodology and validated against data taken from an experiment, in our case AFIP-3. AFIP-3 was a reduced enrichment plate type fuel tested in the ATR. We verified our methodology against the MCNP Coupled with ORIGEN2 (MCWO) method and validated our work against the Post Irradiation Examination (PIE) data. When compared to MCWO, the difference in concentration of U-235 throughout Cycle 144A was about 1%. When compared to the PIE data, the average bias for end of life U-235 concentration was about 2%. These results from CRDIAC therefore agree with the MCWO and PIE data, validating and verifying CRDIAC. CRDIAC provides an alternative to using ORIGEN-based methodology, which is useful because CRDIAC's depletion code, MRTAU, uses every available isotope in its depletion

  11. Performance Analysis of Depleted Oil Reservoirs for Underground Gas Storage

    Dr. C.I.C. Anyadiegwu

    2014-02-01

    Full Text Available The performance of underground gas storage in depleted oil reservoir was analysed with reservoir Y-19, a depleted oil reservoir in Southern region of the Niger Delta. Information on the geologic and production history of the reservoir were obtained from the available field data of the reservoir. The verification of inventory was done to establish the storage capacity of the reservoir. The plot of the well flowing pressure (Pwf against the flow rate (Q, gives the deliverability of the reservoir at various pressures. Results of the estimated properties signified that reservoir Y-19 is a good candidate due to its storage capacity and its flow rate (Q of 287.61 MMscf/d at a flowing pressure of 3900 psig

  12. Barium Depletion in Hollow Cathode Emitters

    Polk, James E.; Capece, Angela M.; Mikellides, Ioannis G.; Katz, Ira

    2009-01-01

    The effect of tungsten erosion, transport and redeposition on the operation of dispenser hollow cathodes was investigated in detailed examinations of the discharge cathode inserts from an 8200 hour and a 30,352 hour ion engine wear test. Erosion and subsequent re-deposition of tungsten in the electron emission zone at the downstream end of the insert reduces the porosity of the tungsten matrix, preventing the ow of barium from the interior. This inhibits the interfacial reactions of the barium-calcium-aluminate impregnant with the tungsten in the pores. A numerical model of barium transport in the internal xenon discharge plasma shows that the barium required to reduce the work function in the emission zone can be supplied from upstream through the gas phase. Barium that flows out of the pores of the tungsten insert is rapidly ionized in the xenon discharge and pushed back to the emitter surface by the electric field and drag from the xenon ion flow. This barium ion flux is sufficient to maintain a barium surface coverage at the downstream end greater than 0.6, even if local barium production at that point is inhibited by tungsten deposits. The model also shows that the neutral barium pressure exceeds the equilibrium vapor pressure of the impregnant decomposition reaction over much of the insert length, so the reactions are suppressed. Only a small region upstream of the zone blocked by tungsten deposits is active and supplies the required barium. These results indicate that hollow cathode failure models based on barium depletion rates in vacuum dispenser cathodes are very conservative.

  13. Biological effects of deuterium - depleted water

    Stefanescu, I.; Titescu, Gh.; Croitoru, Cornelia; Saros-Rogobete, Irina

    2000-01-01

    Deuterium-depleted water (DDW) is represented by water that has an isotopic content smaller than 145 ppm D/(D + H). DDW production technique consists in the separation of deuterium from water by a continuous distillation process under pressure of about 133.3 mbar. The water used as raw material has a isotopic content of 145 ppm D/(D + H) and can be demineralized water, distillated water or condensed-steam. DDW results as a distillate with an isotopic deuterium content of 15-80 ppm, depending on the level we want to achieve. Beginning with 1996 the Institute of Cryogenics and Isotopic Technologies, DDW producer, co-operated with Romanian specialized institutes for studying the biological effects of DDW. The role of naturally occurring D in living organisms was examined by using DDW instead of natural water. These investigations led to the following conclusions: - DDW caused a tendency towards the increase of the basal tone, accompanied by the intensification of the vasoconstrictor effects of phenylefrine, noradrenaline and angiotensin; the increase of the basal tone and vascular reactivity produced by the DDW persists after the removal of the vascular endothelium; - Animals treated with DDW showed an increase of the resistance both to sublethal and lethal gamma radiation doses, suggesting a radioprotective action by the stimulation of non-specific immune defense mechanisms; - DDW stimulates immuno-defense reactions represented by the opsonic, bactericidal and phagocyte capacity of the immune system together with an increase in the number of poly-morphonuclear neutrophils; - Investigations regarding artificial reproduction of fish with DDW fecundated solutions confirmed favorable influence in embryo growth stage and resistance and following growth stages; - It was studied germination, growth and quantitative character variability in plants; one can remark the favorable influence of DDW on biological processes in plants in various ontogenetic stages. (authors)

  14. Climate Change and Oil Depletion

    Rosa, Rui

    2002-01-01

    Primary energy sources have progressively displaced each other and shared the supply in terms that can historically be described by a model proposed by Cesare Marchetti as a generalization of the Fisher and Pry law. So wood, coal, oil and natural gas have displaced or are displacing each other, each one following a logistic evolution until a maximum share is attained, afterwards receding in a symmetrically similar way, provided there is no exhaustion of the respective resource base, each one completing its own life cycle. On the other hand, the persistent growth of the total energy demand implies that the total amount of each one of the successive primary energy sources, required to complete its life cycle, is growing as time lapses. So it is realized that coal resources are much larger than its total life cycle demand. The same is not the case of oil, whose resource base (estimate 2000 Gb) may be smaller than the integrated prospective demand unless this starts declining steadily in the near future. However, if the rate of growth of total energy demand is persists, the amount of natural gas required to complete a similar life cycle will likely exceed its actual resource base. One faces therefore two problems: the constraint on oil availability right now and a likely, even more severe, constraint on natural gas in about twenty years time. Combustion of fossil fuels always produces CO 2 emissions as well as nitrogen oxides. With the exception of natural gas, all other fuels also produce, to a variable extent, particulate matter (aerosols) and sulfur oxides. The permanent alteration of the chemical composition of the atmosphere as a result of all these emissions may affect the biogeochemical balance of the climate system. Such emissions produce recognized impacts of some sort at local and regional levels, either temporary or permanent. Whether actual impacts can be global and permanent is still under dispute; but the observed steady and simultaneous increase of the

  15. [Acute tryptophan depletion in eating disorders].

    Díaz-Marsa, M; Lozano, C; Herranz, A S; Asensio-Vegas, M J; Martín, O; Revert, L; Saiz-Ruiz, J; Carrasco, J L

    2006-01-01

    This work describes the rational bases justifying the use of acute tryptophan depletion technique in eating disorders (ED) and the methods and design used in our studies. Tryptophan depletion technique has been described and used in previous studies safely and makes it possible to evaluate the brain serotonin activity. Therefore it is used in the investigation of hypotheses on serotonergic deficiency in eating disorders. Furthermore, and given the relationship of the dysfunctions of serotonin activity with impulsive symptoms, the technique may be useful in biological differentiation of different subtypes, that is restrictive and bulimic, of ED. 57 female patients with DSM-IV eating disorders and 20 female controls were investigated with the tryptophan depletion test. A tryptophan-free amino acid solution was administered orally after a two-day low tryptophan diet to patients and controls. Free plasma tryptophan was measured at two and five hours following administration of the drink. Eating and emotional responses were measured with specific scales for five hours following the depletion. A study of the basic characteristics of the personality and impulsivity traits was also done. Relationship of the response to the test with the different clinical subtypes and with the temperamental and impulsive characteristics of the patients was studied. The test was effective in considerably reducing plasma tryptophan in five hours from baseline levels (76%) in the global sample. The test was well tolerated and no severe adverse effects were reported. Two patients withdrew from the test due to gastric intolerance. The tryptophan depletion test could be of value to study involvement of serotonin deficits in the symptomatology and pathophysiology of eating disorders.

  16. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

    McCarthy, John J.; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B.; Srikuea, Ratchakrit; Lawson, Benjamin A.; Grimes, Barry; Keller, Charles; Van Zant, Gary; Campbell, Kenneth S.; Esser, Karyn A.; Dupont-Versteegden, Esther E.; Peterson, Charlotte A.

    2011-01-01

    An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells. PMID:21828094

  17. Molecular mechanisms of reduced glutathione transport: role of the MRP/CFTR/ABCC and OATP/SLC21A families of membrane proteins

    Ballatori, Nazzareno; Hammond, Christine L.; Cunningham, Jennifer B.; Krance, Suzanne M.; Marchan, Rosemarie

    2005-01-01

    The initial step in reduced glutathione (GSH) turnover in all mammalian cells is its transport across the plasma membrane into the extracellular space; however, the mechanisms of GSH transport are not clearly defined. GSH export is required for the delivery of its constituent amino acids to other tissues, detoxification of drugs, metals, and other reactive compounds of both endogenous and exogenous origin, protection against oxidant stress, and secretion of hepatic bile. Recent studies indicate that some members of the multidrug resistance-associated protein (MRP/CFTR or ABCC) family of ATP-binding cassette (ABC) proteins, as well as some members of the organic anion transporting polypeptide (OATP or SLC21A) family of transporters contribute to this process. In particular, five of the 12 members of the MRP/CFTR family appear to mediate GSH export from cells namely, MRP1, MRP2, MRP4, MRP5, and CFTR. Additionally, two members of the OATP family, rat Oatp1 and Oatp2, have been identified as GSH transporters. For the Oatp1 transporter, efflux of GSH may provide the driving force for the uptake of extracellular substrates. In humans, OATP-B and OATP8 do not appear to transport GSH; however, other members of this family have yet to be characterized in regards to GSH transport. In yeast, the ABC proteins Ycf1p and Bpt1p transport GSH from the cytosol into the vacuole, whereas Hgt1p mediates GSH uptake across the plasma membrane. Because transport is a key step in GSH homeostasis and is intimately linked to its biological functions, GSH export proteins are likely to modulate essential cellular functions

  18. Frecuencia de las mutaciones más comunes del gen CFTR en pacientes peruanos con fibrosis quística mediante la técnica ARMS-PCR

    Aquino, Ruth; Protzel, Ana; Rivera, Juan; Abarca, Hugo; Dueñas, Milagros; Nestarez, Cecilia; Purizaga, Nestor; Diringer, Benoit

    2017-01-01

    Objetivos. Determinar la frecuencia de las diez mutaciones más comúnmente reportadas en América Latina del gen CFTR mediante Sistema de Mutación Refractario a la amplificación por PCR (ARMS-PCR) en los pacientes con fibrosis quística (FQ) de dos instituciones hospitalarias de referencia en el Perú durante el año 2014. Materiales y métodos. Se evaluó la frecuencia de las diez comúnmente reportadas más comúnmente reportadas del gen CFTR en los pacientes del Hospital Nacional Edgardo Rebagliati ...

  19. New Insights into Fully-Depleted SOI Transistor Response During Total Dose Irradiation

    Burns, J.A.; Dodd, P.E.; Keast, C.L.; Schwank, J.R.; Shaneyfelt, M.R.; Wyatt, P.W.

    1999-01-01

    Worst-case bias configuration for total-dose testing fully-depleted SOI transistors was found to be process dependent. No evidence was found for total-dose induced snap back. These results have implications for hardness assurance testing

  20. Depletion region surface effects in electron beam induced current measurements

    Haney, Paul M.; Zhitenev, Nikolai B. [Center for Nanoscale Science and Technology, National Institute of Standards and Technology, Gaithersburg, Maryland 20899 (United States); Yoon, Heayoung P. [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, Utah 84112 (United States); Gaury, Benoit [Center for Nanoscale Science and Technology, National Institute of Standards and Technology, Gaithersburg, Maryland 20899 (United States); Maryland NanoCenter, University of Maryland, College Park, Maryland 20742 (United States)

    2016-09-07

    Electron beam induced current (EBIC) is a powerful characterization technique which offers the high spatial resolution needed to study polycrystalline solar cells. Current models of EBIC assume that excitations in the p-n junction depletion region result in perfect charge collection efficiency. However, we find that in CdTe and Si samples prepared by focused ion beam (FIB) milling, there is a reduced and nonuniform EBIC lineshape for excitations in the depletion region. Motivated by this, we present a model of the EBIC response for excitations in the depletion region which includes the effects of surface recombination from both charge-neutral and charged surfaces. For neutral surfaces, we present a simple analytical formula which describes the numerical data well, while the charged surface response depends qualitatively on the location of the surface Fermi level relative to the bulk Fermi level. We find that the experimental data on FIB-prepared Si solar cells are most consistent with a charged surface and discuss the implications for EBIC experiments on polycrystalline materials.

  1. Feeling depleted and powerless: the construal-level mechanism.

    Kim, Junha; Lee, Sujin; Rua, Tuvana

    2015-04-01

    Individuals exercise self-control daily to achieve desired goals; at the same time, people engage in social interaction daily and influence (feel powerful) or are influenced (feel powerless) by others. Does controlling the self have an unforeseen consequence for people's perception of their capacity to control others? Five studies-one correlational and four experimental-demonstrate that ego depletion from prior self-control determines one's personal sense of power; low-level, concrete mental construals account for this relationship. Our results showed that people with higher trait self-control reported a greater sense of power (Study 1). People who had depleted their self-control-related regulatory resources (vs. those who had not) experienced a lower sense of power (Study 2). The relationship between ego depletion and low sense of power was mediated by construal level (Study 3) and observed only when low-level, concrete construals were present, but not under high-level, abstract construals (Studies 4 and 5). © 2015 by the Society for Personality and Social Psychology, Inc.

  2. ISOGEN: Interactive isotope generation and depletion code

    Venkata Subbaiah, Kamatam

    2016-01-01

    ISOGEN is an interactive code for solving first order coupled linear differential equations with constant coefficients for a large number of isotopes, which are produced or depleted by the processes of radioactive decay or through neutron transmutation or fission. These coupled equations can be written in a matrix notation involving radioactive decay constants and transmutation coefficients, and the eigenvalues of thus formed matrix vary widely (several tens of orders), and hence no single method of solution is suitable for obtaining precise estimate of concentrations of isotopes. Therefore, different methods of solutions are followed, namely, matrix exponential method, Bateman series method, and Gauss-Seidel iteration method, as was followed in the ORIGEN-2 code. ISOGEN code is written in a modern computer language, VB.NET version 2013 for Windows operating system version 7, which enables one to provide many interactive features between the user and the program. The output results depend on the input neutron database employed and the time step involved in the calculations. The present program can display the information about the database files, and the user has to select one which suits the current need. The program prints the 'WARNING' information if the time step is too large, which is decided based on the built-in convergence criterion. Other salient interactive features provided are (i) inspection of input data that goes into calculation, (ii) viewing of radioactive decay sequence of isotopes (daughters, precursors, photons emitted) in a graphical format, (iii) solution of parent and daughter products by direct Bateman series solution method, (iv) quick input method and context sensitive prompts for guiding the novice user, (v) view of output tables for any parameter of interest, and (vi) output file can be read to generate new information and can be viewed or printed since the program stores basic nuclide concentration unlike other batch jobs. The sample

  3. DUPoly process for treatment of depleted uranium and production of beneficial end products

    Kalb, P.D.; Adams, J.W.; Lageraaen, P.R.; Cooley, C.R.

    2000-01-01

    The present invention provides a process of encapsulating depleted uranium by forming a homogeneous mixture of depleted uranium and molten virgin or recycled thermoplastic polymer into desired shapes. Separate streams of depleted uranium and virgin or recycled thermoplastic polymer are simultaneously subjected to heating and mixing conditions. The heating and mixing conditions are provided by a thermokinetic mixer, continuous mixer or an extruder and preferably by a thermokinetic mixer or continuous mixer followed by an extruder. The resulting DUPoly shapes can be molded into radiation shielding material or can be used as counter weights for use in airplanes, helicopters, ships, missiles, armor or projectiles

  4. Radioactivity of drinking waters from regions exposed to depleted uranium ammunition bombing in 2003 end 2004

    Tanaskovic, I.; Pantelic, G.; Vuletic, V.; Eremic Savkovic, M.; Javorina, L.J.

    2006-01-01

    Due to the military application of the depleted uranium in our country, the problem of its radioactivity and hemo toxicity is actualized. The locations verified to be contaminated by depleted uranium ammunition were at the South part of Serbia (Pljackovica, Bratoselce, Borovac and Reljan). The soluble forms of uranium could translocated and dispersed from soils and sediments into surface waters and groundwater. The environmental presence of depleted uranium is considered as potential threat to human health. The study presents the results of radiological safety analysis of drinking water in 2003 and 2004. All samples were analyzed by gamma spectrometry and measurements of alpha and beta activity. (authors)

  5. Macroinvertebrate short-term responses to flow variation and oxygen depletion: A mesocosm approach.

    Calapez, Ana R; Branco, Paulo; Santos, José M; Ferreira, Teresa; Hein, Thomas; Brito, António G; Feio, Maria João

    2017-12-01

    In Mediterranean rivers, water scarcity is a key stressor with direct and indirect effects on other stressors, such as water quality decline and inherent oxygen depletion associated with pollutants inputs. Yet, predicting the responses of macroinvertebrates to these stressors combination is quite challenging due to the reduced available information, especially if biotic and abiotic seasonal variations are taken under consideration. This study focused on the response of macroinvertebrates by drift to single and combined effects of water scarcity and dissolved oxygen (DO) depletion over two seasons (winter and spring). A factorial design of two flow velocity levels - regular and low (vL) - with three levels of oxygen depletion - normoxia, medium depletion (dM) and higher depletion (dH) - was carried out in a 5-artificial channels system, in short-term experiments. Results showed that both stressors individually and together had a significant effect on macroinvertebrate drift ratio for both seasons. Single stressor effects showed that macroinvertebrate drift decreased with flow velocity reduction and increased with DO depletion, in both winter and spring experiments. Despite single stressors opposing effects in drift ratio, combined stressors interaction (vL×dM and vL×dH) induced a positive synergistic drift effect for both seasons, but only in winter the drift ratio was different between the levels of DO depletion. Stressors interaction in winter seemed to intensify drift response when reached lower oxygen saturation. Also, drift patterns were different between seasons for all treatments, which may depend on individual's life stage and seasonal behaviour. Water scarcity seems to exacerbate the oxygen depletion conditions resulting into a greater drifting of invertebrates. The potential effects of oxygen depletion should be evaluated when addressing the impacts of water scarcity on river ecosystems, since flow reductions will likely contribute to a higher oxygen

  6. Recurrence formulas for evaluating expansion series of depletion functions

    Vukadin, Z.

    1991-01-01

    A high-accuracy analytical method for solving the depletion equations for chains of radioactive nuclides is based on the formulation of depletion functions. When all the arguments of the depletion function are too close to each other, series expansions of the depletion function have to be used. However, the high-accuracy series expressions for the depletion functions of high index become too complicated. Recursion relations are derived which enable an efficient high-accuracy evaluation of the depletion functions with high indices. (orig.) [de

  7. Tuning Nanocrystal Surface Depletion by Controlling Dopant Distribution as a Route Toward Enhanced Film Conductivity

    Staller, Corey M.; Robinson, Zachary L.; Agrawal, Ankit; Gibbs, Stephen L.; Greenberg, Benjamin L.; Lounis, Sebastien D.; Kortshagen, Uwe R.; Milliron, Delia J.

    2018-05-01

    Electron conduction through bare metal oxide nanocrystal (NC) films is hindered by surface depletion regions resulting from the presence of surface states. We control the radial dopant distribution in tin-doped indium oxide (ITO) NCs as a means to manipulate the NC depletion width. We find in films of ITO NCs of equal overall dopant concentration that those with dopant-enriched surfaces show decreased depletion width and increased conductivity. Variable temperature conductivity data shows electron localization length increases and associated depletion width decreases monotonically with increased density of dopants near the NC surface. We calculate band profiles for NCs of differing radial dopant distributions and, in agreement with variable temperature conductivity fits, find NCs with dopant-enriched surfaces have narrower depletion widths and longer localization lengths than those with dopant-enriched cores. Following amelioration of NC surface depletion by atomic layer deposition of alumina, all films of equal overall dopant concentration have similar conductivity. Variable temperature conductivity measurements on alumina-capped films indicate all films behave as granular metals. Herein, we conclude that dopant-enriched surfaces decrease the near-surface depletion region, which directly increases the electron localization length and conductivity of NC films.

  8. Impact of Wildfire Emissions on Chloride and Bromide Depletion in Marine Aerosol Particles.

    Braun, Rachel A; Dadashazar, Hossein; MacDonald, Alexander B; Aldhaif, Abdulamonam M; Maudlin, Lindsay C; Crosbie, Ewan; Aghdam, Mojtaba Azadi; Hossein Mardi, Ali; Sorooshian, Armin

    2017-08-15

    This work examines particulate chloride (Cl - ) and bromide (Br - ) depletion in marine aerosol particles influenced by wildfires at a coastal California site in the summers of 2013 and 2016. Chloride exhibited a dominant coarse mode due to sea salt influence, with substantially diminished concentrations during fire periods as compared to nonfire periods. Bromide exhibited a peak in the submicrometer range during fire and nonfire periods, with an additional supermicrometer peak in the latter periods. Chloride and Br - depletions were enhanced during fire periods as compared to nonfire periods. The highest observed %Cl - depletion occurred in the submicrometer range, with maximum values of 98.9% (0.32-0.56 μm) and 85.6% (0.56-1 μm) during fire and nonfire periods, respectively. The highest %Br - depletion occurred in the supermicrometer range during fire and nonfire periods with peak depletion between 1.8-3.2 μm (78.8% and 58.6%, respectively). When accounting for the neutralization of sulfate by ammonium, organic acid particles showed the greatest influence on Cl - depletion in the submicrometer range. These results have implications for aerosol hygroscopicity and radiative forcing in areas with wildfire influence owing to depletion effects on composition.

  9. Depleted uranium hexafluoride: Waste or resource?

    Schwertz, N.; Zoller, J.; Rosen, R.; Patton, S. [Lawrence Livermore National Lab., CA (United States); Bradley, C. [USDOE Office of Nuclear Energy, Science, Technology, Washington, DC (United States); Murray, A. [SAIC (United States)

    1995-07-01

    the US Department of Energy is evaluating technologies for the storage, disposal, or re-use of depleted uranium hexafluoride (UF{sub 6}). This paper discusses the following options, and provides a technology assessment for each one: (1) conversion to UO{sub 2} for use as mixed oxide duel, (2) conversion to UO{sub 2} to make DUCRETE for a multi-purpose storage container, (3) conversion to depleted uranium metal for use as shielding, (4) conversion to uranium carbide for use as high-temperature gas-cooled reactor (HTGR) fuel. In addition, conversion to U{sub 3}O{sub 8} as an option for long-term storage is discussed.

  10. The depletion of the stratospheric ozone layer

    Sabogal Nelson

    2000-01-01

    The protection of the Earth's ozone layer is of the highest importance to mankind. The dangers of its destruction are by now well known. The depletion of that layer has reached record levels. The Antarctic ozone hole covered this year a record area. The ozone layer is predicted to begin recovery in the next one or two decades and should be restored to pre-1980 levels by 2050. This is the achievement of the regime established by the 1985 Vienna Convention for the Protection of the Ozone Layer and the 1987 Montreal Protocol on Substances that Deplete the Ozone Layer. The regime established by these two agreements has been revised, and made more effective in London (1990), Copenhagen (1992), Vienna (1995), and Beijing (1999)

  11. Optical assessment of phytoplankton nutrient depletion

    Heath, M.R.; Richardson, Katherine; Kiørboe, Thomas

    1990-01-01

    The ratio of light absorption at 480 and 665 nm by 90% acetone extracts of marine phytoplankton pigments has been examined as a potential indicator of phytoplankton nutritional status in both laboratory and field studies. The laboratory studies demonstrated a clear relationship between nutritiona......-replete and nutrient-depleted cells. The field data suggest that the absorption ratio may be a useful indicator of nutritional status of natural phytoplankton populations, and can be used to augment the interpretation of other data....

  12. Nuclear Fuel Depletion Analysis Using Matlab Software

    Faghihi, F.; Nematollahi, M. R.

    Coupled first order IVPs are frequently used in many parts of engineering and sciences. In this article, we presented a code including three computer programs which are joint with the Matlab software to solve and plot the solutions of the first order coupled stiff or non-stiff IVPs. Some engineering and scientific problems related to IVPs are given and fuel depletion (production of the 239Pu isotope) in a Pressurized Water Nuclear Reactor (PWR) are computed by the present code.

  13. Ozone depletion, greenhouse effect and atomic energy

    Adzersen, K.H.

    1991-01-01

    After describing the causes and effects of ozone depletion and the greenhouse effect, the author discusses the alternative offered by the nuclear industry. In his opinion, a worldwide energy strategy of risk minimisation will not be possible unless efficient energy use is introduced immediately, efficiently and on a reliable basis. Atomic energy is not viewed as an acceptable means of preventing the threatening climate change. (DG) [de

  14. The ultimate disposition of depleted uranium

    Lemons, T.R. [Uranium Enrichment Organization, Oak Ridge, TN (United States)

    1991-12-31

    Depleted uranium (DU) is produced as a by-product of the uranium enrichment process. Over 340,000 MTU of DU in the form of UF{sub 6} have been accumulated at the US government gaseous diffusion plants and the stockpile continues to grow. An overview of issues and objectives associated with the inventory management and the ultimate disposition of this material is presented.

  15. Carbon sequestration in depleted oil shale deposits

    Burnham, Alan K; Carroll, Susan A

    2014-12-02

    A method and apparatus are described for sequestering carbon dioxide underground by mineralizing the carbon dioxide with coinjected fluids and minerals remaining from the extraction shale oil. In one embodiment, the oil shale of an illite-rich oil shale is heated to pyrolyze the shale underground, and carbon dioxide is provided to the remaining depleted oil shale while at an elevated temperature. Conditions are sufficient to mineralize the carbon dioxide.

  16. Barium depletion in hollow cathode emitters

    Polk, James E.; Mikellides, Ioannis G.; Katz, Ira; Capece, Angela M.

    2016-01-01

    Dispenser hollow cathodes rely on a consumable supply of Ba released by BaO-CaO-Al 2 O 3 source material in the pores of a tungsten matrix to maintain a low work function surface. The examination of cathode emitters from long duration tests shows deposits of tungsten at the downstream end that appear to block the flow of Ba from the interior. In addition, a numerical model of Ba transport in the cathode plasma indicates that the Ba partial pressure in the insert may exceed the equilibrium vapor pressure of the dominant Ba-producing reaction, and it was postulated previously that this would suppress Ba loss in the upstream part of the emitter. New measurements of the Ba depletion depth from a cathode insert operated for 8200 h reveal that Ba loss is confined to a narrow region near the downstream end, confirming this hypothesis. The Ba transport model was modified to predict the depletion depth with time. A comparison of the calculated and measured depletion depths gives excellent qualitative agreement, and quantitative agreement was obtained assuming an insert temperature 70 °C lower than measured beginning-of-life values

  17. Verification of the cross-section and depletion chain processing module of DRAGON 3.06

    Chambon, R.; Marleau, G.; Zkiek, A.

    2008-01-01

    In this paper we present a verification of the module of the lattice code DRAGON 3.06 used for processing microscopic cross-section libraries, including their associated depletion chain. This verification is performed by reprogramming the capabilities of DRAGON in another language (MATLAB) and testing them on different problems typical of the CANDU reactor. The verification procedure consists in first programming MATLAB m-files to read the different cross section libraries in ASCII format and to compute the reference cross-sections and depletion chains. The same information is also recovered from the output files of DRAGON (using different m-files) and the resulting cross sections and depletion chain are compared with the reference library, the differences being evaluated and tabulated. The results show that the cross-section calculations and the depletion chains are correctly processed in version 3.06 of DRAGON. (author)

  18. Identification of eight novel mutations in a collaborative analysis of a part of the second transmembrane domain of the CFTR gene

    Mercier, B.; Audrezet, M.P.; Guillermit, H.; Quere, I.; Verlingue, C.; Ferec, C. (CDTS, Brest (France)); Lissens, W.; Bonduelle, M.; Liebaers, I. (University Hospital VUB, Brussels (Belgium)); Novelli, G.; Sangiuolo, F.; Dallapiccola, B. (IRCCS, Rotondo (Italy)); Kalaydjieva, L. (Inst. of Obstetrics, Sofia (Bulgaria)); Arce, M. De; Cashman, S. (Trinity College, Dublin (Ireland)); Kapranov, N. (NRC of medical Genetics, Moscow (Russian Federation)); Canki Klain, N. (Tozd Univerzitetna Ginekoloska Klinika, Ljubljana (Yugoslavia)); Lenoir, G. (Hopital des Enfants Malades Necker, Paris (France)); Chauveau, P. (Centre Hospitalier General, Le Havre (France)); Lanaerts, C. (Centre Hospitalier Regional et Universitaire, Amiens (France)); Rault, G. (Centre Helio-Marin, Roscoff (France))

    1993-04-01

    Cystic fibrosis transmembrane conductance regulator (CFTR), the gene responsible, when mutated, for cystic fibrosis (CF), spans over 230 kb on the long arm of chromosome 7 and is composed of 27 exons. The most common mutation responsible for CF worldwide is the deletion of a phenylalanine amino acid at codon 508 in the first nucleotide-binding fold and accounts for approximately 70% of CF chromosomes studied. More than 250 other mutations have been reported through the CF Genetic Analysis Consortium. The majority of the mutations previously described lie in the two nucleotide-binding folds. To explore exhaustively other regions of the gene, particularly exons coding for transmembrane domains, the authors have initiated a collaborative study between different laboratories to screen 369 non-[Delta]F508 CF chromosomes of seven ethnic European populations (Belgian, French, Breton, Irish, Italian, Yugoslavian, Russian). Among these chromosomes carrying an unidentified mutation, 63 were from Brittany, 50 of various French origin, 45 of Irish origin, 56 of Italian origin, 41 of Belgian origin, 2 of Turkish origin, 38 of Yugoslavian origin, 22 of Russian origin, and 52 of Bulgarian origin. Diagnostic criteria for CF included at least one positive sweat test and pulmonary disease with or without pancreatic disease. Using a denaturing gradient gel electrophoresis (DGGE) assay, they have identified eight novel mutations in exon 17b coding for part of the second transmembrane domain of the CFTR and they describe them in this report. 8 refs., 1 fig., 1 tab.

  19. Depletion interaction measured by colloidal probe atomic force microscopy

    Wijting, W.K.; Knoben, W.; Besseling, N.A.M.; Leermakers, F.A.M.; Cohen Stuart, M.A.

    2004-01-01

    We investigated the depletion interaction between stearylated silica surfaces in cyclohexane in the presence of dissolved polydimethylsiloxane by means of colloidal probe atomic force microscopy. We found that the range of the depletion interaction decreases with increasing concentration.

  20. Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

    Phadke, Manali; Krynetskaia, Natalia [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Mishra, Anurag [Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Krynetskiy, Evgeny, E-mail: ekrynets@temple.edu [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States)

    2011-07-29

    Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

  1. The depletion potential in one, two and three dimensions

    Abstract. We study the behavior of the depletion potential in binary mixtures of hard particles in one, two, and three dimensions within the framework of a general theory for depletion potential using density functional theory. By doing so we extend earlier studies of the depletion potential in three dimensions to the cases of d ...

  2. 26 CFR 1.642(e)-1 - Depreciation and depletion.

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Depreciation and depletion. 1.642(e)-1 Section 1... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(e)-1 Depreciation and depletion. An estate or trust is allowed the deductions for depreciation and depletion, but only to the extent the...

  3. 26 CFR 1.613-1 - Percentage depletion; general rule.

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Percentage depletion; general rule. 1.613-1... TAX (CONTINUED) INCOME TAXES (CONTINUED) Natural Resources § 1.613-1 Percentage depletion; general rule. (a) In general. In the case of a taxpayer computing the deduction for depletion under section 611...

  4. Effect of indomethacin and salt depletion on renal proton MR imaging

    Heyman, S.N.; Mammen, M.

    1991-01-01

    Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may effect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. (orig.)

  5. Effect of microstructure on radiation induced segregation and depletion in ion irradiated SS316 steel

    Jin, Hyung Ha; Kwon, Sang Chul; Kwon, Jun Hyun

    2011-01-01

    Irradiation assisted stress corrosion cracking (IASCC), void swelling and irradiation induced hardening are caused by change of characteristics of material by neutron irradiation, stress state of material and environmental situation. It has been known that chemical compositions varies at grain boundary (GB) significantly with fluence level and the depletion of Cr element at GB has been considered as one of important factors causing material degradation, especially, IASCC in austenitic stainless steel. However, experimental results of IASCC under PWR condition were directly not connected with Cr depletion phenomenon by neutron irradiation. Because the mechanism of IASCC under PWR has not yet been clearly understood in spite of many energetic researches, fundamental researches about radiation induced segregation and depletion in irradiated austenitic stainless steels have been attracted again. In this work, an effect of residual microstructure on radiation induced segregation and depletion of alloy elements at GB was investigated in ion irradiated SS316 steel using transmission electron microscope (TEM) with energy dispersive spectrometer (EDS)

  6. Reverse depletion effects and the determination of ligand density on some spherical bioparticles

    Wang, Chunxiang [Heilongjiang Bayi Agricultural University (China); Liu, Yanhui, E-mail: ionazati@itp.ac.cn; Fan, Yangtao; Liu, Yijun; Li, Qiancheng; Xu, Houqiang, E-mail: houqiangxu@yahoo.com [Guizhou University (China)

    2016-06-15

    In cell environments crowded with macromolecules, the depletion effects act and assist in the assembly of a wide range of cellular structures, from the cytoskeleton to the chromatin loop, which are well accepted. But a recent quantum dot experiment indicated that the dimensions of the receptor–ligand complex have strong effects on the size-dependent exclusion of proteins in cell environments. In this article, a continuum elastic model is constructed to resolve the competition between the dimension of the receptor–ligand complex and depletion effects in the endocytosis of a spherical virus-like bioparticle. Our results show that the depletion effects do not always assist endocytosis of a spherical virus-like bioparticle; while the dimension of the ligand–receptor complex is larger than the size of a small bioparticle in cell environments, the depletion effects do not work and reverse effects appear. The ligand density covered on the virus can be identified quantitatively.

  7. Microscale depletion of high abundance proteins in human biofluids using IgY14 immunoaffinity resin: analysis of human plasma and cerebrospinal fluid.

    Hyung, Seok-Won; Piehowski, Paul D; Moore, Ronald J; Orton, Daniel J; Schepmoes, Athena A; Clauss, Therese R; Chu, Rosalie K; Fillmore, Thomas L; Brewer, Heather; Liu, Tao; Zhao, Rui; Smith, Richard D

    2014-11-01

    Removal of highly abundant proteins in plasma is often carried out using immunoaffinity depletion to extend the dynamic range of measurements to lower abundance species. While commercial depletion columns are available for this purpose, they generally are not applicable to limited sample quantities (depletion media can be prohibitive for larger-scale studies. Modern LC-MS instrumentation provides the sensitivity necessary to scale-down depletion methods with minimal sacrifice to proteome coverage, which makes smaller volume depletion columns desirable for maximizing sample recovery when samples are limited, as well as for reducing the expense of large-scale studies. We characterized the performance of a 346 μL column volume microscale depletion system, using four different flow rates to determine the most effective depletion conditions for ∼6-μL injections of human plasma proteins and then evaluated depletion reproducibility at the optimum flow rate condition. Depletion of plasma using a commercial 10-mL depletion column served as the control. Results showed depletion efficiency of the microscale column increased as flow rate decreased, and that our microdepletion was reproducible. In an initial application, a 600-μL sample of human cerebrospinal fluid (CSF) pooled from multiple sclerosis patients was depleted and then analyzed using reversed phase liquid chromatography-mass spectrometry to demonstrate the utility of the system for this important biofluid where sample quantities are more commonly limited.

  8. Numerical Simulation of Ionospheric Electron Concentration Depletion by Rocket Exhaust

    Huang Yong; Shi Jiaming; Yuan Zhongcai

    2011-01-01

    In terms of the diffusive process of the gases injected from rocket exhaust into the ionosphere and the relevant chemical reactions between the gases and the composition of ionosphere, the modifications in ionosphere caused by the injected hydrogen and carbon dioxide gas from the rocket exhaust are investigated. The results show that the diffusive process of the injected gases at the ionospheric height is very fast, and the injected gases can lead to a local depletion of electron concentration in the F-region. Furthermore, the plasma 'hole' caused by carbon dioxide is larger, deeper and more durable than that by the hydrogen. (astrophysics and space plasma)

  9. Processing and Applications of Depleted Uranium Alloy Products

    1976-09-01

    ammunition, weapons, gyrorotors, and ballast. Depleted uranium used in fly- wheel devices, nuclear fuel casks, and ammunition could consume a significant...from straight in the range of 0,002 to 0.060-inch TIR (total indicated runout ) with an average of 0.025-inch TIR.* Solution heat treatment of the as-cast...an envelope thickness of 0.050 inch to allow for runout and to clean up surface imperfections. The runout resulting from heat treatment was in the

  10. Observations and Simulations of Formation of Broad Plasma Depletions Through Merging Process

    Huang, Chao-Song; Retterer, J. M.; Beaujardiere, O. De La; Roddy, P. A.; Hunton, D.E.; Ballenthin, J. O.; Pfaff, Robert F.

    2012-01-01

    Broad plasma depletions in the equatorial ionosphere near dawn are region in which the plasma density is reduced by 1-3 orders of magnitude over thousands of kilometers in longitude. This phenomenon is observed repeatedly by the Communication/Navigation Outage Forecasting System (C/NOFS) satellite during deep solar minimum. The plasma flow inside the depletion region can be strongly upward. The possible causal mechanism for the formation of broad plasma depletions is that the broad depletions result from merging of multiple equatorial plasma bubbles. The purpose of this study is to demonstrate the feasibility of the merging mechanism with new observations and simulations. We present C/NOFS observations for two cases. A series of plasma bubbles is first detected by C/NOFS over a longitudinal range of 3300-3800 km around midnight. Each of the individual bubbles has a typical width of approx 100 km in longitude, and the upward ion drift velocity inside the bubbles is 200-400 m/s. The plasma bubbles rotate with the Earth to the dawn sector and become broad plasma depletions. The observations clearly show the evolution from multiple plasma bubbles to broad depletions. Large upward plasma flow occurs inside the depletion region over 3800 km in longitude and exists for approx 5 h. We also present the numerical simulations of bubble merging with the physics-based low-latitude ionospheric model. It is found that two separate plasma bubbles join together and form a single, wider bubble. The simulations show that the merging process of plasma bubbles can indeed occur in incompressible ionospheric plasma. The simulation results support the merging mechanism for the formation of broad plasma depletions.

  11. Differential Membrane Dipolar Orientation Induced by Acute and Chronic Cholesterol Depletion.

    Sarkar, Parijat; Chakraborty, Hirak; Chattopadhyay, Amitabha

    2017-06-30

    Cholesterol plays a crucial role in cell membrane organization, dynamics and function. Depletion of cholesterol represents a popular approach to explore cholesterol-sensitivity of membrane proteins. An emerging body of literature shows that the consequence of membrane cholesterol depletion often depends on the actual process (acute or chronic), although the molecular mechanism underlying the difference is not clear. Acute depletion, using cyclodextrin-type carriers, is faster relative to chronic depletion, in which inhibitors of cholesterol biosynthesis are used. With the overall goal of addressing molecular differences underlying these processes, we monitored membrane dipole potential under conditions of acute and chronic cholesterol depletion in CHO-K1 cells, using a voltage-sensitive fluorescent dye in dual wavelength ratiometric mode. Our results show that the observed membrane dipole potential exhibits difference under acute and chronic cholesterol depletion conditions, even when cholesterol content was identical. To the best of our knowledge, these results provide, for the first time, molecular insight highlighting differences in dipolar reorganization in these processes. A comprehensive understanding of processes in which membrane cholesterol gets modulated would provide novel insight in its interaction with membrane proteins and receptors, thereby allowing us to understand the role of cholesterol in cellular physiology associated with health and disease.

  12. Substituting freshwater: Can ocean desalination and water recycling capacities substitute for groundwater depletion in California?

    Badiuzzaman, Pierre; McLaughlin, Eoin; McCauley, Darren

    2017-12-01

    While the sustainability of resource depletion is a longstanding environmental concern, wider attention has recently been given to growing water scarcity and groundwater depletion. This study seeks to test the substitutability assumption embedded in weak sustainability indicators using a case study of Californian water supply. The volume of groundwater depletion is used as a proxy for unsustainable water consumption, and defined by synthesising existing research estimates into low, medium and high depletion baselines. These are compared against projected water supply increases from ocean desalination and water recycling by 2035, to determine whether new, drought-proof water sources can substitute for currently unsustainable groundwater consumption. Results show that the maximum projected supply of new water, 2.47 million acre-feet per year (MAF/yr), is sufficient to meet low depletion estimates of 2.02 MAF/yr, but fails to come near the high depletion estimate of 3.44 MAF/yr. This does not necessarily indicate physical limitations of substitutability, but more so socio-economic limitations influenced by high comparative costs. By including capacities in demand-substitutability via urban water conservation, maximum predicted capacities reach 5.57 MAF/yr, indicating wide room for substitution. Based on these results, investment in social and institutional capital is an important factor to enhance demand-side substitutability of water and other natural resources, which has been somewhat neglected by the literature on the substitutability of natural resources. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The effect of motivation and positive affect on ego depletion: Replenishment versus release mechanism.

    Zhu, Ze; Li, Jian; Zhang, Bo; Li, Ye; Zhang, Houcan

    2017-12-01

    In this study, 2 experiments were conducted to investigate whether motivation and positive affect can alleviate ego depletion and to elucidate their possible mechanisms. In Experiment 1, a crossing-out-letter task was adapted to reach an ego depletion state for Chinese participants. Participants were then randomly assigned to the extrinsic motivation group, the positive affect group or the depletion control group. After the experimental treatment, a dumbbell task was used to measure participants' remaining self-regulatory resources. The results showed that participants in the motivation and positive affect groups performed better on the dumbbell task than participants in the depletion control group. Experiment 2 was similar to Experiment 1 except that participants were asked to perform an additional unexpected dumbbell task after a neutral video following the above procedure. The results of Experiment 1 were replicated; however, participants' performance on the additional dumbbell task differed. The positive affect group performed better than the depletion control group, indicating an increase in self-regulatory resources and thus supporting the replenishment effect of positive affect. No significant difference was found between the motivation group and the depletion control group. © 2015 International Union of Psychological Science.

  14. Effects of glutathione depletion by buthionine sulfoximine on radiosensitization by oxygen and misonidazole in vitro

    Shrieve, D.C.; Denekamp, J.; Minchinton, A.I.

    1985-01-01

    Buthionine sulfoximine (BSO) has been used to deplete glutathione (GSH) in V79-379A cells in vitro, and the effect on the efficiency of oxygen and misonidazole (MISO) as radiosensitizers has been determined. Treatment with 50 or 500 μM BSO caused a rapid decline in GSH content to less than 5% of control values after 10 hr of exposure. Removal of BSO resulted in a rapid regeneration of GSH after 50 μM BSO, but little regeneration was observed over the subsequent 10-hr period after 500 μM. Cells irradiated in monolayer on glass had an oxygen enhancement ratio (OER) of 3.1. After 10-14 hr pretreatment with 50 μM BSO, washed cells were radiosensitized by GSH depletion at all oxygen tensions tested. The OER was reduced to 2.6, due to greater radiosensitization of hypoxic cells than aerated ones by GSH depletion. In similar experiments performed with MISO, an enhancement ratio of 2.0 could be achieved with 0.2 mM MISO in anoxic BSO-pretreated cells, compared to 2.7 mM MISO in non-BSO-treated cells. These apparent increases in radiosensitizer efficiency in GSH-depleted cells could be explained on the basis of radiosensitization of hypoxic cells by GSH depletion alone. These results are consistent with hypoxic cell radiosensitization by GSH depletion and by MISO or oxygen acting by separate mechanisms

  15. Depleted uranium concrete container feasibility study

    Haelsig, R.T.

    1994-09-01

    The purpose of this report is to consider the feasibility of using containers constructed of depleted uranium aggregate concrete (DUCRETE) to store and transport radioactive materials. The method for this study was to review the advantages and disadvantages of DUCRETE containers considering design requirements for potential applications. The author found that DUCRETE is a promising material for onsite storage containers, provided DUCRETE vessels can be certified for one-way transport to disposal sites. The author also found that DUCRETE multipurpose spent nuclear fuel storage/transport packages are technically viable, provided altered temperature acceptance limits can be developed for DUCRETE

  16. B-cell-depleting Therapy in Systemic Lupus Erythematosus

    Ramos-Casals, Manuel; Sanz, Iñaki; Bosch, Xavier; Stone, John H.; Khamashta, Munther A.

    2014-01-01

    The emergence of a new class of agents (B-cell-depleting therapies) has opened a new era in the therapeutic approach to systemic lupus erythematosus, with belimumab being the first drug licensed for use in systemic lupus erythematosus in more than 50 years. Four agents deserve specific mention: rituximab, ocrelizumab, epratuzumab, and belimumab. Controlled trials have shown negative results for rituximab, promising results for epratuzumab, and positive results for belimumab. Despite these negative results, rituximab is the most-used agent in patients who do not respond or are intolerant to standard therapy and those with life-threatening presentations. B-cell-depleting agents should not be used in patients with mild disease and should be tailored according to individual patient characteristics, including ethnicity, organ involvement, and the immunological profile. Forthcoming studies of B-cell-directed strategies, particularly data from investigations of off-label rituximab use and postmarketing studies of belimumab, will provide new insights into the utility of these treatments in the routine management of patients with systemic lupus erythematosus. PMID:22444096

  17. Depletion of elements in shock-driven gas

    Gondhalekar, P.M.

    1985-01-01

    The depletion of elements in shocked gas in supernova remnants and in interstellar bubbles is examined. It is shown that elements are depleted in varying degrees in gas filaments shocked to velocities up to 200 km s -1 and that large differences in depletions are observed in gas filaments shocked to similar velocities. In the shocked gas the depletion of an element appears to be correlated with the electron density (or the neutral gas density) in the filaments. This correlation, if confirmed, is similar to the correlation between depletion and mean density of gas in the clouds in interstellar space. (author)

  18. Microscopic to macroscopic depletion model development for FORMOSA-P

    Noh, J.M.; Turinsky, P.J.; Sarsour, H.N.

    1996-01-01

    Microscopic depletion has been gaining popularity with regard to employment in reactor core nodal calculations, mainly attributed to the superiority of microscopic depletion in treating spectral history effects during depletion. Another trend is the employment of loading pattern optimization computer codes in support of reload core design. Use of such optimization codes has significantly reduced design efforts to optimize reload core loading patterns associated with increasingly complicated lattice designs. A microscopic depletion model has been developed for the FORMOSA-P pressurized water reactor (PWR) loading pattern optimization code. This was done for both fidelity improvements and to make FORMOSA-P compatible with microscopic-based nuclear design methods. Needless to say, microscopic depletion requires more computational effort compared with macroscopic depletion. This implies that microscopic depletion may be computationally restrictive if employed during the loading pattern optimization calculation because many loading patterns are examined during the course of an optimization search. Therefore, the microscopic depletion model developed here uses combined models of microscopic and macroscopic depletion. This is done by first performing microscopic depletions for a subset of possible loading patterns from which 'collapsed' macroscopic cross sections are obtained. The collapsed macroscopic cross sections inherently incorporate spectral history effects. Subsequently, the optimization calculations are done using the collapsed macroscopic cross sections. Using this approach allows maintenance of microscopic depletion level accuracy without substantial additional computing resources

  19. Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway.

    Saengjaroentham, Chonlawan; Supornsilpchai, Weera; Ji-Au, Wilawan; Srikiatkhachorn, Anan; Maneesri-le Grand, Supang

    2015-02-01

    Serotonin (5-HT) is an important neurotransmitter involved in the control of neural and vascular responses. 5-HT depletion can induce several neurological disorders, including migraines. Studies on a cortical spreading depression (CSD) migraine animal model showed that the cortical neurons sensitivity, vascular responses, and nitric oxide (NO) production were significantly increased in 5-HT depletion. However, the involvement of NO in the cerebrovascular responses in 5-HT depletion remains unclear. This study aimed to investigate the role of NO in the CSD-induced alterations of cerebral microvessels in 5-HT depletion. Rats were divided into four groups: control, control with L-NAME treatment, 5-HT depleted, and 5-HT depleted with L-NAME treatment. 5-HT depletion was induced by intraperitoneal injection with para-chlorophenylalanine (PCPA) 3 days before the experiment. The CSD was triggered by KCl application. After the second wave of CSD, N-nitro-l-arginine methyl ester (L-NAME) or saline was intravenously injected into the rats with or without L-NAME treatment groups, respectively. The intercellular adhesion molecules-1 (ICAM-1), cell adhesion molecules-1 (VCAM-1), and the ultrastructural changes of the cerebral microvessels were examined. The results showed that 5-HT depletion significantly increased ICAM-1 and VCAM-1 expressions in the cerebral cortex. The number of endothelial pinocytic vesicles and microvilli was higher in the 5-HT depleted group when compared to the control. Interestingly, L-NAME treatment significantly reduced the abnormalities observed in the 5-HT depleted group. The results of this study demonstrated that an increase of NO production is one of the mechanisms involved in the CSD-induced alterations of the cerebrovascular responses in 5-HT depletion.

  20. Deoxyribonucleoside kinases in mitochondrial DNA depletion.

    Saada-Reisch, Ann

    2004-10-01

    Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a heterogeneous group of mitochondrial disorders, manifested by a decreased mtDNA copy number and respiratory chain dysfunction. Primary MDS are inherited autosomally and may affect a single organ or multiple tissues. Mutated mitochondrial deoxyribonucleoside kinases; deoxyguanosine kinase (dGK) and thymidine kinase 2 (TK2), were associated with the hepatocerebral and myopathic forms of MDS respectively. dGK and TK2 are key enzymes in the mitochondrial nucleotide salvage pathway, providing the mitochondria with deoxyribonucleotides (dNP) essential for mtDNA synthesis. Although the mitochondrial dNP pool is physically separated from the cytosolic one, dNP's may still be imported through specific transport. Non-replicating tissues, where cytosolic dNP supply is down regulated, are thus particularly vulnerable to dGK and TK2 deficiency. The overlapping substrate specificity of deoxycytidine kinase (dCK) may explain the relative sparing of muscle in dGK deficiency, while low basal TK2 activity render this tissue susceptible to TK2 deficiency. The precise pathophysiological mechanisms of mtDNA depletion due to dGK and TK2 deficiencies remain to be determined, though recent findings confirm that it is attributed to imbalanced dNTP pools.

  1. Bone marrow scintigraphy in hemopoietic depletion states

    Fortynova, J.; Bakos, K.; Pradacova, J.

    1981-01-01

    Bone marrow scintigraphy was performed in 29 patients with hemopoietic depletion states of various etiology. Two tracers were used for visualization, viz., sup(99m)Tc-sulfur-colloid and 111 InCl 3 ;some patients were examined using both indicators. 111 InCl 3 is bound to transferrin and is adsorbed on the surface of reticulocytes and erythroblasts. A scintillation camera PHO GAMMA SEARLE IV fitted with a moving table and computer CLINCOM were used to obtain whole-body images. The comparison of all scans and marrow puncture smears was done. In patients with aplastic anemia with both hyperplastic or hypoplastic marrow good correlation of bone marrow scans and sternal puncture smears was found. In several cases the scintigraphic examination helped to establish the diagnosis of marrow depletion. A peculiar disadvantage of the imaging method with either sup(99m)Tc-sulfur-colloid or 111 InCl 3 is that it shows the disorders in erythropoietic and reticuloendothelial cells whereas the defects in myelopoietic cell series and platelet precursors are not provable. According to literature data, great attention is paid to the prognostic value of scintigraphic examination in aplastic anemia. (author)

  2. Bone marrow scintigraphy in hemopoietic depletion states

    Fortynova, J. (Ustav Hematologie a Krevni Transfuze, Prague (Czechoslovakia)); Bakos, K.; Pradacova, J. (Karlova Univ., Prague (Czechoslovakia). Biofyzikalni Ustav)

    1981-01-01

    Bone marrow scintigraphy was performed in 29 patients with hemopoietic depletion states of various etiology. Two tracers were used for visualization, viz., sup(99m)Tc-sulfur-colloid and /sup 111/InCl/sub 3/; some patients were examined using both indicators. /sup 111/InCl/sub 3/ is bound to transferrin and is adsorbed on the surface of reticulocytes and erythroblasts. A scintillation camera PHO GAMMA SEARLE IV fitted with a moving table and computer CLINCOM were used to obtain whole-body images. The comparison of all scans and marrow puncture smears was done. In patients with aplastic anemia with both hyperplastic or hypoplastic marrow good correlation of bone marrow scans and sternal puncture smears was found. In several cases the scintigraphic examination helped to establish the diagnosis of marrow depletion. A peculiar disadvantage of the imaging method with either sup(99m)Tc-sulfur-colloid or /sup 111/InCl/sub 3/ is that it shows the disorders in erythropoietic and reticuloendothelial cells whereas the defects in myelopoietic cell series and platelet precursors are not provable. According to literature data, great attention is paid to the prognostic value of scintigraphic examination in aplastic anemia.

  3. B cell depletion reduces T cell activation in pancreatic islets in a murine autoimmune diabetes model.

    Da Rosa, Larissa C; Boldison, Joanne; De Leenheer, Evy; Davies, Joanne; Wen, Li; Wong, F Susan

    2018-06-01

    Type 1 diabetes is a T cell-mediated autoimmune disease characterised by the destruction of beta cells in the islets of Langerhans, resulting in deficient insulin production. B cell depletion therapy has proved successful in preventing diabetes and restoring euglycaemia in animal models of diabetes, as well as in preserving beta cell function in clinical trials in the short term. We aimed to report a full characterisation of B cell kinetics post B cell depletion, with a focus on pancreatic islets. Transgenic NOD mice with a human CD20 transgene expressed on B cells were injected with an anti-CD20 depleting antibody. B cells were analysed using multivariable flow cytometry. There was a 10 week delay in the onset of diabetes when comparing control and experimental groups, although the final difference in the diabetes incidence, following prolonged observation, was not statistically significant (p = 0.07). The co-stimulatory molecules CD80 and CD86 were reduced on stimulation of B cells during B cell depletion and repopulation. IL-10-producing regulatory B cells were not induced in repopulated B cells in the periphery, post anti-CD20 depletion. However, the early depletion of B cells had a marked effect on T cells in the local islet infiltrate. We demonstrated a lack of T cell activation, specifically with reduced CD44 expression and effector function, including IFN-γ production from both CD4 + and CD8 + T cells. These CD8 + T cells remained altered in the pancreatic islets long after B cell depletion and repopulation. Our findings suggest that B cell depletion can have an impact on T cell regulation, inducing a durable effect that is present long after repopulation. We suggest that this local effect of reducing autoimmune T cell activity contributes to delay in the onset of autoimmune diabetes.

  4. Age-related mitochondrial DNA depletion and the impact on pancreatic Beta cell function.

    Nile, Donna L; Brown, Audrey E; Kumaheri, Meutia A; Blair, Helen R; Heggie, Alison; Miwa, Satomi; Cree, Lynsey M; Payne, Brendan; Chinnery, Patrick F; Brown, Louise; Gunn, David A; Walker, Mark

    2014-01-01

    Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% age-related decline in mitochondrial DNA (mtDNA) copy number in isolated human islets. The purpose of this study was to mimic this degree of mtDNA depletion in MIN6 cells to determine whether there is a direct impact on insulin secretion. Transcriptional silencing of mitochondrial transcription factor A, TFAM, decreased mtDNA levels by 40% in MIN6 cells. This level of mtDNA depletion significantly decreased mtDNA gene transcription and translation, resulting in reduced mitochondrial respiratory capacity and ATP production. Glucose-stimulated insulin secretion was impaired following partial mtDNA depletion, but was normalised following treatment with glibenclamide. This confirms that the deficit in the insulin secretory pathway precedes K+ channel closure, indicating that the impact of mtDNA depletion is at the level of mitochondrial respiration. In conclusion, partial mtDNA depletion to a degree comparable to that seen in aged human islets impaired mitochondrial function and directly decreased insulin secretion. Using our model of partial mtDNA depletion following targeted gene silencing of TFAM, we have managed to mimic the degree of mtDNA depletion observed in aged human islets, and have shown how this correlates with impaired insulin secretion. We therefore predict that the age-related mtDNA depletion in human islets is not simply a biomarker of the aging process, but will contribute to the age-related risk of type 2 diabetes.

  5. Effects of Acute Tryptophan Depletion on Three Different Types of Behavioral Impulsivity

    Donald M. Dougherty

    2010-01-01

    Full Text Available Introduction While central nervous system serotonin has been implicated in a variety of problematic impulsive behaviors, biological manipulation of brain serotonin using acute tryptophan depletion for studying changes in impulsive behavior has received little attention. Methods Using identical treatment conditions, we examined the effects of reduced serotonin synthesis for each of three matched groups using acute tryptophan depletion. Thirty healthy men and women (ages 18–45 were assigned to perform one of three tasks assessing different types of behavioral impulsivity: response initiation, response inhibition, and consequence sensitivity ( N = 90. Participants completed two experimental days during which each consumed either a tryptophan-depletion or balanced-placebo amino-acid formulation and completed 5 sessions of their respective tasks at 0.25 h before and 1.5, 4.0, 5.0, and 6.0 h after beverage consumption. Results During peak effectiveness (5.0 h to 6.0 h following amino-acid consumption, depletion produced selective differences dependent on the type of impulsivity being tested. Specifically, relative to baseline testing (pre-depletion, response initiation impulsivity was significantly increased during the peak effects of depletion. And, when compared to placebo control, both response initiation and consequence sensitivity impulsivity were increased during the peak effects of depletion. Conclusion Though response initiation and consequence sensitivity impulsivity were affected by tryptophan depletion, response inhibition impulsivity was not, suggesting that other biological processes may underlie this specific component of impulsivity. Future research in other populations or using different pharmacological agents is warranted to further examine the biological processes underlying these components of impulsivity.

  6. Effects of Acute Tryptophan Depletion on Three Different Types of Behavioral Impulsivity

    Donald M. Dougherty

    2010-06-01

    Full Text Available Introduction: While central nervous system serotonin has been implicated in a variety of problematic impulsive behaviors, biological manipulation of brain serotonin using acute tryptophan depletion for studying changes in impulsive behavior has received little attention. Methods: Using identical treatment conditions, we examined the effects of reduced serotonin synthesis for each of three matched groups using acute tryptophan depletion. Thirty healthy men and women (ages 18–45 were assigned to perform one of three tasks assessing different types of behavioral impulsivity: response initiation, response inhibition, and consequence sensitivity (N = 90. Participants completed two experimental days during which each consumed either a tryptophan-depletion or balanced-placebo amino-acid formulation and completed 5 sessions of their respective tasks at 0.25 h before and 1.5, 4.0, 5.0, and 6.0 h after beverage consumption. Results: During peak effectiveness (5.0 h to 6.0 h following amino-acid consumption, depletion produced selective differences dependent on the type of impulsivity being tested. Specifically, relative to baseline testing (pre-depletion, response initiation impulsivity was significantly increased during the peak effects of depletion. And, when compared to placebo control, both response initiation and consequence sensitivity impulsivity were increased during the peak effects of depletion. Conclusion: Though response initiation and consequence sensitivity impulsivity were affected by tryptophan depletion, response inhibition impulsivity was not, suggesting that other biological processes may underlie this specific component of impulsivity. Future research in other populations or using different pharmacological agents is warranted to further examine the biological processes underlying these components of impulsivity.

  7. Characteristics of Solar Wind Density Depletions During Solar Cycles 23 and 24

    Keunchan Park

    2017-06-01

    Full Text Available Solar wind density depletions are phenomena that solar wind density is rapidly decreased and keep the state. They are generally believed to be caused by the interplanetary (IP shocks. However, there are other cases that are hardly associated with IP shocks. We set up a hypothesis for this phenomenon and analyze this study. We have collected the solar wind parameters such as density, speed and interplanetary magnetic field (IMF data related to the solar wind density depletion events during the period from 1996 to 2013 that are obtained with the advanced composition explorer (ACE and the Wind satellite. We also calculate two pressures (magnetic, dynamic and analyze the relation with density depletion. As a result, we found total 53 events and the most these phenomena’s sources caused by IP shock are interplanetary coronal mass ejection (ICME. We also found that solar wind density depletions are scarcely related with IP shock’s parameters. The solar wind density is correlated with solar wind dynamic pressure within density depletion. However, the solar wind density has an little anti-correlation with IMF strength during all events of solar wind density depletion, regardless of the presence of IP shocks. Additionally, In 47 events of IP shocks, we find 6 events that show a feature of blast wave. The quantities of IP shocks are weaker than blast wave from the Sun, they are declined in a short time after increasing rapidly. We thus argue that IMF strength or dynamic pressure are an important factor in understanding the nature of solar wind density depletion. Since IMF strength and solar wind speed varies with solar cycle, we will also investigate the characteristics of solar wind density depletion events in different phases of solar cycle as an additional clue to their physical nature.

  8. Private sector embedded water risk: Merging the corn supply chain network and regional watershed depletion

    Kim, T.; Brauman, K. A.; Schmitt, J.; Goodkind, A. L.; Smith, T. M.

    2016-12-01

    Water scarcity in US corn farming regions is a significant risk consideration for the ethanol and meat production sectors, which comprise 80% of all US corn demand. Water supply risk can lead to effects across the supply chain, affecting annual corn yields. The purpose of our study is to assess the water risk to the US's most corn-intensive sectors and companies by linking watershed depletion estimates with corn production, linked to downstream companies through a corn transport model. We use a water depletion index as an improved metric for seasonal water scarcity and a corn sourcing supply chain model based on economic cost minimization. Water depletion was calculated as the fraction of renewable (ground and surface) water consumption, with estimates of more than 75% depletion on an annual average basis indicating a significant water risk. We estimated company water risk as the amount of embedded corn coming from three categories of water stressed counties. The ethanol sector had 3.1% of sourced corn grown from counties that were more than 75% depleted while the beef sector had 14.0%. From a firm perspective, Tyson, JBS, Cargill, the top three US corn demanding companies, had 4.5%, 9.6%, 12.8% of their sourced corn respectively, coming from watersheds that are more than 75% depleted. These numbers are significantly higher than the global average of 2.2% of watersheds being classified as more than 75% depleted. Our model enables corn using industries to evaluate their supply chain risk of water scarcity through modeling corn sourcing and watershed depletion, providing the private sector a new method for risk estimation. Our results suggest corn dependent industries are already linked to water scarcity risk in disproportionate amounts due to the spatial heterogeneity of corn sourcing and water scarcity.

  9. Use of 60 ppm deuterium depleted water in companionship animals

    Balint, Emilia; Manolescu, N.; Cranganu, D.; Militaru, Manuela; Pop, Aneta; Codreanu, M.; Panait, Marieta; Lastofka, D.

    2004-01-01

    There are presented the results of studies on the effects of deuterium depleted water in companionship animals. Based on these results, a new product was realized, 'Aqua Forte' that is a deuterium depleted potable water (60 ppm deuterium) with beneficial effects in animal's health maintaining. Aqua forte has prophylactic properties (in preventing diseases related to immune system) and therapeutic properties, as adjuvant in various therapeutic programs. The mechanism of action takes place at the cellular metabolism level by replacing the constitutional and free water of 150 ppm deuterium, this resulting in the stimulation of the immune cellular system and also of resistance at the onset of some pathological states. The non-specific stimulation implies performing both the humoral mediated immune reactions and of those cellularly mediated. Aqua forte is recommended in: - the feeding of the young weaned animals, the action being of growth stimulation, and increasing of the resistance against some diseases specific to the age; - as an adjuvant in some chronic diseases (hepatitis, pancreatitis, dermatological diseases, osteoarthropaties, hepato-renal syndrome, renal insufficiency, after surgical interventions, in antitumoral therapy); - in the feeding of the old animals for the quality of life improvement. (authors)

  10. Field ion microscopy study of depleted zones in tungsten after proton irradiation

    Farnum, D.J.; Sommer, W.F.; Inal, O.T.; Yu, J.

    1986-01-01

    Depleted zones in tungsten, that resulted from medium-energy proton irradiations, were studied using the Field Ion Microscope (FIM). The shapes and sizes of depleted zones is an important aspect of basic radiation damage. These data can be compared to models that have been suggested as well as aid development of new models. These depleted volumes are of interest not only for an understanding of basic radiation effects, but also because they affect material properties and can act as nucleation sites for voids or gas bubbles. Depleted zones were produced in annealed tungsten wires by irradiation with 600 to 800 MeV protons at the Los Alamos Meson Physics Facility. The defects observed in the irradiated samples included vacancies, depleted zones, grain boundaries, and dislocations. Single vacancies were the most commonly observed defect. Of the samples ''imaged,'' over 50 depleted zones were found within the area of high resolution in the area between the prominent [112] poles in a [110] oriented sample. The number of layers photographed in each sample was dependent upon the initial shape of the tip and ranged from 60 to 200 [110] sequential layers

  11. Rb-Sr And Sm-Nd Ages, and Petrogenesis of Depleted Shergottite Northwest Africa 5990

    Shih, C. Y.; Nyquist, L. E.; Reese, Y.; Irving, A. J.

    2011-01-01

    Northwest Africa (NWA) 5990 is a very fresh Martian meteorite recently found on Hamada du Draa, Morocco and was classified as an olivine-bearing diabasic igneous rock related to depleted shergottites [1]. The study of [1] also showed that NWA 5990 resembles QUE 94201 in chemical, textural and isotopic aspects, except QUE 94201 contains no olivine. The depleted shergottites are characterized by REE patterns that are highly depleted in LREE, older Sm-Nd ages of 327-575 Ma and highly LREE-depleted sources with Nd= +35+48 [2-7]. Age-dating these samples by Sm-Nd and Rb-Sr methods is very challenging because they have been strongly shocked and contain very low abundances of light rare earth elements (Sm and Nd), Rb and Sr. In addition, terrestrial contaminants which are commonly present in desert meteorites will compromise the equilibrium of isotopic systems. Since NWA 5990 is a very fresh meteorite, it probably has not been subject to significant desert weathering and thus is a good sample for isotopic studies. In this report, we present Rb-Sr and Sm-Nd isotopic results for NWA 5990, discuss the correlation of the determined ages with those of other depleted shergottites, especially QUE 94201, and discuss the petrogenesis of depleted shergottites.

  12. Self-Control Strength Depletion Reduces Self-Efficacy and Impairs Exercise Performance.

    Graham, Jeffrey D; Bray, Steven R

    2015-10-01

    The purpose of this study was to investigate the role of task self-efficacy as a psychological factor involved in the relationship between self-control depletion and physical endurance. Participants (N = 37) completed two isometric handgrip endurance trials, separated by a Stroop task, which was either congruent (control) or incongruent (causing depletion). Task self-efficacy for the second endurance trial was measured following the Stroop task. Participants in the depletion condition reported lower task self-efficacy and showed a greater reduction in performance on the second endurance trial when compared with controls. Task self-efficacy also mediated the relationship between self-control depletion and endurance performance. The results of this study provide evidence that task self-efficacy is negatively affected following self-control depletion. We recommend that task self-efficacy be further investigated as a psychological factor accounting for the negative change in self-control performance of physical endurance and sport tasks following self-control strength depletion.

  13. In vivo T cell depletion regulates resistance and morbidity in murine schistosomiasis

    Phillips, S.M.; Linette, G.P.; Doughty, B.L.; Byram, J.E.; Von Lichtenberg, F.

    1987-01-01

    These studies assessed the roles of subpopulations of T lymphocytes in inducing and modulating resistance to schistosomiasis and thereby influencing subsequent morbidity. C57BL/6 mice were depleted in vivo of Lyt-1+, Lyt-2+, and L3T4+ cells by the daily administration of monoclonal antibodies. The development of protective immunity, induced by exposure to irradiated Schistosoma mansoni cercariae as expressed in depleted animals, was compared to that demonstrated in undepleted, normal, and congenitally athymic C57BL/6 mice. The development of morbidity was determined by spleen weight, portal pressure and reticuloendothelial system activity. The results indicated that depletion of specific subpopulations of T lymphocytes minimally affected the primary development of parasites; however, depletion strongly influenced the development of resistance to the parasite and subsequent morbidity due to infection. Depletion of T lymphocytes by anti-Lyt-1+ or anti-L3T4+ antibody decreased the development of resistance, antibody and delayed-type hypersensitivity directed against schistosome antigens. Morbidity due to disease was increased. Depletion of Lyt-2+ cells produced opposite changes with augmented resistance and reduced morbidity. Congenitally athymic mice developed minimal resistance and morbidity. Moreover, resistance was inversely related to the morbidity shown by a given animal. These studies indicate that the development of protective immunity to S. mansoni cercariae is regulated by discrete subpopulations of T lymphocytes. The feasibility of decreasing morbidity by increasing specific immunologically mediated resistance is suggested

  14. Depleted-Heterojunction Colloidal Quantum Dot Solar Cells

    Pattantyus-Abraham, Andras G.

    2010-06-22

    Colloidal quantum dot (CQD) photovoltaics combine low-cost solution processability with quantum size-effect tunability to match absorption with the solar spectrum. Rapid recent advances in CQD photovoltaics have led to impressive 3.6% AM1.5 solar power conversion efficiencies. Two distinct device architectures and operating mechanisms have been advanced. The first-the Schottky device-was optimized and explained in terms of a depletion region driving electron-hole pair separation on the semiconductor side of a junction between an opaque low-work-function metal and a p-type CQD film. The second-the excitonic device-employed a CQD layer atop a transparent conductive oxide (TCO) and was explained in terms of diffusive exciton transport via energy transfer followed by exciton separation at the type-II heterointerface between the CQD film and the TCO. Here we fabricate CQD photovoltaic devices on TCOs and show that our devices rely on the establishment of a depletion region for field-driven charge transport and separation, and that they also exploit the large bandgap of the TCO to improve rectification and block undesired hole extraction. The resultant depletedheterojunction solar cells provide a 5.1% AM1.5 power conversion efficiency. The devices employ infrared-bandgap size-effect-tuned PbS CQDs, enabling broadband harvesting of the solar spectrum. We report the highest opencircuit voltages observed in solid-state CQD solar cells to date, as well as fill factors approaching 60%, through the combination of efficient hole blocking (heterojunction) and very small minority carrier density (depletion) in the large-bandgap moiety. © 2010 American Chemical Society.

  15. L-Tryptophan depletion bioreactor, a possible cancer therapy

    Rolf Bambauer

    2015-04-01

    Full Text Available The cancer therapeutic strategies knownto date are not adequate for all cancer patients. Most of them are followed by a high rate of side effects and complications. The L-tryptophan depletion bioreactor is described as a possible new method of cancer therapy. L-tryptophan is an essential amino acid which has been recognized as an important cancer nutrient and its removal can lead to destruction of the tumour. Normal human cells or tumor cells cannot synthesize L-tryptophan and therefore tumor resistance is unlikely to develop. L-tryptophan is also a constituent for different bio-molecules such as Serotonin, Melatonin, and is needed for other synthesis processes in the cell growth. L-tryptophan degrading enzymes with 3 iso-enzymes called tryptophan side chain oxydase (TSO I, II, III were isolated. The 3 iso-enzymes can be differentiated by tryptic digestion. They have different molecular weights with different effectivenesses. All the TSO enzymes have heme that can catalyze essentially similar reactions involving L-tryptophan as a substrate. The most effective TSO is the type TSO III. A column which contained TSO as a bioreactor was integrated in a plasmapheresis unit and tested it in different animals. In sheep and rabbits L-tryptophan depletion in plasma was shown at 95% and 100% rates respectively by a single pass through the bioreactor. The results in immune supprimized rats with tumors were impressive, too. In 20 different tumor cell lines there were different efficacies. Brest cancer and medulloblastoma showed the greatest efficacy of L-tryptophan degrading. The gene technology of TSO production from Pseudomonas is associated with formation of endotoxins. This disadvantage can be prevented by different washing procedures or by using fungal sources for the TSO production. TSO III is developed to treat cancer diseases successfully, and has low side effects. A combination of L-tryptophan depletion with all available cancer therapies is

  16. Depletion mapping and constrained optimization to support managing groundwater extraction

    Fienen, Michael N.; Bradbury, Kenneth R.; Kniffin, Maribeth; Barlow, Paul M.

    2018-01-01

    Groundwater models often serve as management tools to evaluate competing water uses including ecosystems, irrigated agriculture, industry, municipal supply, and others. Depletion potential mapping—showing the model-calculated potential impacts that wells have on stream baseflow—can form the basis for multiple potential management approaches in an oversubscribed basin. Specific management approaches can include scenarios proposed by stakeholders, systematic changes in well pumping based on depletion potential, and formal constrained optimization, which can be used to quantify the tradeoff between water use and stream baseflow. Variables such as the maximum amount of reduction allowed in each well and various groupings of wells using, for example, K-means clustering considering spatial proximity and depletion potential are considered. These approaches provide a potential starting point and guidance for resource managers and stakeholders to make decisions about groundwater management in a basin, spreading responsibility in different ways. We illustrate these approaches in the Little Plover River basin in central Wisconsin, United States—home to a rich agricultural tradition, with farmland and urban areas both in close proximity to a groundwater-dependent trout stream. Groundwater withdrawals have reduced baseflow supplying the Little Plover River below a legally established minimum. The techniques in this work were developed in response to engaged stakeholders with various interests and goals for the basin. They sought to develop a collaborative management plan at a watershed scale that restores the flow rate in the river in a manner that incorporates principles of shared governance and results in effective and minimally disruptive changes in groundwater extraction practices.

  17. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

    Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

    2015-09-01

    Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0.9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3.7%, 95% CI 0.1-7.3; p=0.046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in

  18. Mantle depletion and metasomatism recorded in orthopyroxene in highly depleted peridotites

    Scott, James; Liu, Jingao; Pearson, D. Graham

    2016-01-01

    Although trace element concentrations in clinopyroxene serve as a useful tool for assessing the depletion and enrichment history of mantle peridotites, this is not applicable for peridotites in which the clinopyroxene component has been consumed (~ 25% partial melting). Orthopyroxene persists in ...

  19. Including environmental concerns in management strategies for depleted uranium hexafluoride

    Goldberg, M.; Avci, H.I.; Bradley, C.E.

    1995-01-01

    One of the major programs within the Office of Nuclear Energy, Science, and Technology of the US Department of Energy (DOE) is the depleted uranium hexafluoride (DUF 6 ) management program. The program is intended to find a long-term management strategy for the DUF 6 that is currently stored in approximately 46,400 cylinders at Paducah, KY; Portsmouth, OH; and Oak Ridge, TN, USA. The program has four major components: technology assessment, engineering analysis, cost analysis, and the environmental impact statement (EIS). From the beginning of the program, the DOE has incorporated the environmental considerations into the process of strategy selection. Currently, the DOE has no preferred alternative. The results of the environmental impacts assessment from the EIS, as well as the results from the other components of the program, will be factored into the strategy selection process. In addition to the DOE's current management plan, other alternatives continued storage, reuse, or disposal of depleted uranium, will be considered in the EIS. The EIS is expected to be completed and issued in its final form in the fall of 1997

  20. Radiological air quality in a depleted uranium (DU) storage vault

    Robinson, T.; Cucchiara, A.L.

    1999-01-01

    The radiological air quality of two storage vaults, one with depleted uranium (DU) and one without, was evaluated and compared. The intent of the study was to determine if the presence of stored DU would significantly contribute to the gaseous/airborne radiation level compared to natural background. Both vaults are constructed out of concrete and are dimensionally similar. The vaults are located on the first floor of the same building. Neither vault has air supply or air exhaust. The doors to both vaults remained closed during the evaluation period, except for brief and infrequent access by the operational group. One vault contained 700 KG of depleted uranium, and the other vault contained documents inside of file cabinets. Radon detectors and giraffe air samplers were used to gather data on the quantity of gaseous/airborne radionuclides in both vaults. The results of this study indicated that there was no significant difference in the quantity of gaseous/airborne radionuclides in the two vaults. This paper gives a discussion of the effects of the stored DU on the air quality, and poses several theories supporting the results

  1. Deuterium-depleted water. Romanian achievements and perspective

    Stefanescu, Ion; Saros-Rogobete, Irina; Titescu, Gheorghe

    2001-01-01

    Deuterium-depleted water has an isotopic content smaller than 145 ppm D/(D+H) which is the natural isotopic content of water. Beginning with 1996 ICSI Rm. Valcea, deuterium-depleted water producer, co-operated with Romanian specialized institutes for biological effect's evaluation of deuterium-depleted water. These investigations lead to the following conclusions: - Deuterium-depleted water caused a tendency towards the increase of the basal tonus, accompanied by the intensification of the vasoconstrictor effects of phenylefrine, noradrenaline and angiotensin; the increase of the basal tonus and vascular reactivity produced by the deuterium-depleted water persist after the removal of the vascular endothelium; - Animals treated with deuterium-depleted water showed an increase of the resistance both to sublethal and to lethal gamma radiation doses, suggesting a radioprotective action; - Deuterium-depleted water stimulates immune defence reactions and increases the numbers of polymorphonuclear neutrophils; - Investigations regarding artificial reproduction of fish with deuterium-depleted water fecundated solutions confirmed favourable influence in embryo growth stage and resistance in subsequent growth stages; - It was studied germination, growth and quantitative character's variability in plants; one can remark the favourable influence of deuterium-depleted water on biological process in plants in various ontogenetic stages; - The deuterium depletion in seawater produces the diminution of the water spectral energy related to an increased metabolism of Tetraselmis Suecica. (authors)

  2. Groundwater depletion and sustainability of irrigation in the US High Plains and Central Valley

    Scanlon, Bridget R.; Faunt, Claudia C.; Longuevergne, Laurent; Reedy, Robert C.; Alley, William M.; McGuire, Virginia L.; McMahon, Peter B.

    2012-01-01

    Aquifer overexploitation could significantly impact crop production in the United States because 60% of irrigation relies on groundwater. Groundwater depletion in the irrigated High Plains and California Central Valley accounts for ∼50% of groundwater depletion in the United States since 1900. A newly developed High Plains recharge map shows that high recharge in the northern High Plains results in sustainable pumpage, whereas lower recharge in the central and southern High Plains has resulted in focused depletion of 330 km3 of fossil groundwater, mostly recharged during the past 13,000 y. Depletion is highly localized with about a third of depletion occurring in 4% of the High Plains land area. Extrapolation of the current depletion rate suggests that 35% of the southern High Plains will be unable to support irrigation within the next 30 y. Reducing irrigation withdrawals could extend the lifespan of the aquifer but would not result in sustainable management of this fossil groundwater. The Central Valley is a more dynamic, engineered system, with north/south diversions of surface water since the 1950s contributing to ∼7× higher recharge. However, these diversions are regulated because of impacts on endangered species. A newly developed Central Valley Hydrologic Model shows that groundwater depletion since the 1960s, totaling 80 km3, occurs mostly in the south (Tulare Basin) and primarily during droughts. Increasing water storage through artificial recharge of excess surface water in aquifers by up to 3 km3 shows promise for coping with droughts and improving sustainability of groundwater resources in the Central Valley. PMID:22645352

  3. TURTLE 24.0 diffusion depletion code

    Altomare, S.; Barry, R.F.

    1971-09-01

    TURTLE is a two-group, two-dimensional (x-y, x-z, r-z) neutron diffusion code featuring a direct treatment of the nonlinear effects of xenon, enthalpy, and Doppler. Fuel depletion is allowed. TURTLE was written for the study of azimuthal xenon oscillations, but the code is useful for general analysis. The input is simple, fuel management is handled directly, and a boron criticality search is allowed. Ten thousand space points are allowed (over 20,000 with diagonal symmetry). TURTLE is written in FORTRAN IV and is tailored for the present CDC-6600. The program is core-contained. Provision is made to save data on tape for future reference. (auth)

  4. Tylosin depletion from edible pig tissues.

    Prats, C; El Korchi, G; Francesch, R; Arboix, M; Pérez, B

    2002-12-01

    The depletion of tylosin from edible pig tissues was studied following 5 days of intramuscular (i.m.) administration of 10 mg/kg of tylosin to 16 crossbreed pigs. Animals were slaughtered at intervals after treatment and samples of muscle, kidney, liver, skin+fat, and injection site were collected and analysed by high-performance liquid chromatography (HPLC). Seven days after the completion of treatment, the concentration of tylosin in kidney, skin+fat, and at the injection site was higher than the European Union maximal residue limit (MRL) of 100 microg/kg. Tylosin residues in all tissues were below the quantification limit (50 microg/kg) at 10 and 14 days post-treatment.

  5. Depleted Reactor Analysis With MCNP-4B

    Caner, M.; Silverman, L.; Bettan, M.

    2004-01-01

    Monte Carlo neutronics calculations are mostly done for fresh reactor cores. There is today an ongoing activity in the development of Monte Carlo plus burnup code systems made possible by the fast gains in computer processor speeds. In this work we investigate the use of MCNP-4B for the calculation of a depleted core of the Soreq reactor (IRR-1). The number densities as function of burnup were taken from the WIMS-D/4 cell code calculations. This particular code coupling has been implemented before. The Monte Carlo code MCNP-4B calculates the coupled transport of neutrons and photons for complicated geometries. We have done neutronics calculations of the IRR-1 core with the WIMS and CITATION codes in the past Also, we have developed an MCNP model of the IRR-1 standard fuel for a criticality safety calculation of a spent fuel storage pool

  6. Kinetic depletion model for pellet ablation

    Kuteev, Boris V.

    2001-11-01

    A kinetic model for depletion effect, which determines pellet ablation when the pellet passes a rational magnetic surface, is formulated. The model predicts a moderate decrease of the ablation rate compared with the earlier considered monoenergy versions [1, 2]. For typical T-10 conditions the ablation rate reduces by a reactor of 2.5 when the 1-mm pellet penetrates through the plasma center. A substantial deceleration of pellets -about 15% per centimeter of low shire rational q region; is predicted. Penetration for Low Field Side and High Field Side injections is considered taking into account modification of the electron distribution function by toroidal magnetic field. It is shown that Shafranov shift and toroidal effects yield the penetration length for HFS injection higher by a factor of 1.5. This fact should be taken into account when plasma-shielding effects on penetration are considered. (author)

  7. Effects of drop testing on scale model shipping containers shielded with depleted uranium

    Butler, T.A.

    1980-02-01

    Three scale model shipping containers shielded with depleted uranium were dropped onto an essentially unyielding surface from various heights to determine their margins to failure. This report presents the results of a thorough posttest examination of the models to check for basic structural integrity, shielding integrity, and deformations. Because of unexpected behavior exhibited by the depleted uranium shielding, several tests were performed to further characterize its mechanical properties. Based on results of the investigations, recommendations are made for improved container design and for applying the results to full-scale containers. Even though the specimens incorporated specific design features, the results of this study are generally applicable to any container design using depleted uranium

  8. A three-dimensional model for lubricant depletion under sliding condition on bit patterned media of hard disk drives

    Wu, Lin

    2018-05-01

    In this paper, we model the depletion dynamics of the molecularly thin layer of lubricants on a bit patterned media disk of hard disk drives under a sliding air bearing head. The dominant physics and consequently, the lubricant depletion dynamics on a patterned disk are shown to be significantly different from the well-studied cases of a smooth disk. Our results indicate that the surface tension effect, which is negligible on a flat disk, apparently suppresses depletion by enforcing a bottleneck effect around the disk pattern peak regions to thwart the migration of lubricants. When the disjoining pressure is relatively small, it assists the depletion. But, when the disjoining pressure becomes dominant, the disjoining pressure resists depletion. Disk pattern orientation plays a critical role in the depletion process. The effect of disk pattern orientation on depletion originates from its complex interaction with other intermingled factors of external air shearing stress distribution and lubricant particle trajectory. Patterning a disk surface with nanostructures of high density, large height/pitch ratio, and particular orientation is demonstrated to be one efficient way to alleviate the formation of lubricant depletion tracks.

  9. Vitamin A depletion alters sensitivity of motor behavior to MK-801 in C57BL/6J mice

    Zhu Hui

    2010-01-01

    Full Text Available Abstract Background Vitamin A and its derivatives (retinoids are crucial for the development, maintenance and morphogenesis of the central nervous system (CNS. Although motor impairment has been reported in postnatal vitamin A depletion rodents, the effect of vitamin A depletion on homeostasis maintaining capability in response to external interference is not clear. Methods In the current study, we measured the effect of vitamin A depletion on motor ability and pain sensitivity under two different conditions: 1. prior to any injection and 2. after the injection of an N-methyl-D-aspartate (NMDA receptor antagonist (MK-801. Results Vitamin A depletion mice showed decreased body weight, enhanced locomotor activity, increased rearing and less tail flick latency. Vitamin A depletion also induced hypersensitivity of stereotypy, ataxia, rearing, and tail flick latency to MK-801, but hyposensitivity of locomotion to MK-801. Conclusions These findings suggest that vitamin A depletion affect broad basal behavior and disrupt homeostasis maintaining capability in response to glutamate perturbation. We provide a useful animal model for assessing the role of vitamin A depletion in regulating animal behavior, and for detecting how neurotransmitter pathways might be involved in vitamin A depletion related behavioral abnormalities.

  10. cGMP inhibition of type 3 phosphodiesterase is the major mechanism by which C-type natriuretic peptide activates CFTR in the shark rectal gland

    De Jonge, Hugo R.; Tilly, Ben C.; Hogema, Boris M.; Pfau, Daniel J.; Kelley, Catherine A.; Kelley, Megan H.; Melita, August M.; Morris, Montana T.; Viola, Ryan M.

    2013-01-01

    The in vitro perfused rectal gland of the dogfish shark (Squalus acanthias) and filter-grown monolayers of primary cultures of shark rectal gland (SRG) epithelial cells were used to analyze the signal transduction pathway by which C-type natriuretic peptide (CNP) stimulates chloride secretion. CNP binds to natriuretic receptors in the basolateral membrane, elevates cellular cGMP, and opens cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in the apical membrane. CNP-provoked chloride secretion was completely inhibitable by the nonspecific protein kinase inhibitor staurosporine and the PKA inhibitor H89 but insensitive to H8, an inhibitor of type I and II isoforms of cGMP-dependent protein kinase (cGKI and cGKII). CNP-induced secretion could not be mimicked by nonhydrolyzable cGMP analogs added alone or in combination with the protein kinase C activator phorbolester, arguing against a role for cGK or for cGMP-induced PKC signaling. We failed to detect a dogfish ortholog of cGKII by molecular cloning and affinity chromatography. However, inhibitors of the cGMP-inhibitable isoform of phosphodiesterase (PDE3) including milrinone, amrinone, and cilostamide but not inhibitors of other PDE isoenzymes mimicked the effect of CNP on chloride secretion in perfused glands and monolayers. CNP raised cGMP and cAMP levels in the SRG epithelial cells. This rise in cAMP as well as the CNP and amrinone-provoked chloride secretion, but not the rise in cGMP, was almost completely blocked by the Gαi-coupled adenylyl cyclase inhibitor somatostatin, arguing against a role for cGMP cross-activation of PKA in CNP action. These data provide molecular, functional, and pharmacological evidence for a CNP/cGMP/PDE3/cAMP/PKA signaling cascade coupled to CFTR in the SRG. PMID:24259420

  11. Temperature dependent simulation of diamond depleted Schottky PIN diodes

    Hathwar, Raghuraj; Dutta, Maitreya; Chowdhury, Srabanti; Goodnick, Stephen M.; Koeck, Franz A. M.; Nemanich, Robert J.

    2016-01-01

    Diamond is considered as an ideal material for high field and high power devices due to its high breakdown field, high lightly doped carrier mobility, and high thermal conductivity. The modeling and simulation of diamond devices are therefore important to predict the performances of diamond based devices. In this context, we use Silvaco ® Atlas, a drift-diffusion based commercial software, to model diamond based power devices. The models used in Atlas were modified to account for both variable range and nearest neighbor hopping transport in the impurity bands associated with high activation energies for boron doped and phosphorus doped diamond. The models were fit to experimentally reported resistivity data over a wide range of doping concentrations and temperatures. We compare to recent data on depleted diamond Schottky PIN diodes demonstrating low turn-on voltages and high reverse breakdown voltages, which could be useful for high power rectifying applications due to the low turn-on voltage enabling high forward current densities. Three dimensional simulations of the depleted Schottky PIN diamond devices were performed and the results are verified with experimental data at different operating temperatures

  12. Temperature dependent simulation of diamond depleted Schottky PIN diodes

    Hathwar, Raghuraj; Dutta, Maitreya; Koeck, Franz A. M.; Nemanich, Robert J.; Chowdhury, Srabanti; Goodnick, Stephen M.

    2016-06-01

    Diamond is considered as an ideal material for high field and high power devices due to its high breakdown field, high lightly doped carrier mobility, and high thermal conductivity. The modeling and simulation of diamond devices are therefore important to predict the performances of diamond based devices. In this context, we use Silvaco® Atlas, a drift-diffusion based commercial software, to model diamond based power devices. The models used in Atlas were modified to account for both variable range and nearest neighbor hopping transport in the impurity bands associated with high activation energies for boron doped and phosphorus doped diamond. The models were fit to experimentally reported resistivity data over a wide range of doping concentrations and temperatures. We compare to recent data on depleted diamond Schottky PIN diodes demonstrating low turn-on voltages and high reverse breakdown voltages, which could be useful for high power rectifying applications due to the low turn-on voltage enabling high forward current densities. Three dimensional simulations of the depleted Schottky PIN diamond devices were performed and the results are verified with experimental data at different operating temperatures

  13. Temperature dependent simulation of diamond depleted Schottky PIN diodes

    Hathwar, Raghuraj; Dutta, Maitreya; Chowdhury, Srabanti; Goodnick, Stephen M. [Department of Electrical Engineering, Arizona State University, Tempe, Arizona 85287-8806 (United States); Koeck, Franz A. M.; Nemanich, Robert J. [Department of Physics, Arizona State University, Tempe, Arizona 85287-8806 (United States)

    2016-06-14

    Diamond is considered as an ideal material for high field and high power devices due to its high breakdown field, high lightly doped carrier mobility, and high thermal conductivity. The modeling and simulation of diamond devices are therefore important to predict the performances of diamond based devices. In this context, we use Silvaco{sup ®} Atlas, a drift-diffusion based commercial software, to model diamond based power devices. The models used in Atlas were modified to account for both variable range and nearest neighbor hopping transport in the impurity bands associated with high activation energies for boron doped and phosphorus doped diamond. The models were fit to experimentally reported resistivity data over a wide range of doping concentrations and temperatures. We compare to recent data on depleted diamond Schottky PIN diodes demonstrating low turn-on voltages and high reverse breakdown voltages, which could be useful for high power rectifying applications due to the low turn-on voltage enabling high forward current densities. Three dimensional simulations of the depleted Schottky PIN diamond devices were performed and the results are verified with experimental data at different operating temperatures.

  14. Reverse depletion method for PWR core reload design

    Downar, T.J.; Kim, Y.J.

    1985-01-01

    Low-leakage fuel management is currently practiced in over half of all pressurized water reactor (PWR) cores. Prospects for even greater use of in-board fresh fuel loading are good as utilities seek to reduce core vessel fluence, mitigate pressurized thermal shock concerns, and extend vessel lifetime. Consequently, large numbers of burnable poison (BP) pins are being used to control the power peaking at the in-board fresh fuel positions. This has presented an additional complexity to the core reload design problem. In addition to determining the best location of each assembly in the core, the designer must concurrently determine the distribution of BP pins in the fresh fuel. A procedure was developed that utilizes the well-known Haling depletion to achieve an end-of-cycle (EOC) core state where the assembly pattern is configured in the absence of all control poison. This effectively separates the assembly assignment and BP distribution problems. Once an acceptable pattern at EOC is configured, the burnable and soluble poison required to control the power and core excess reactivity are solved for as unknown variables while depleting the cycle in reverse from the EOC exposure distribution to the beginning of cycle. The methods developed were implemented in an approved light water reactor licensing code to ensure the validity of the results obtained and provide for the maximum utility to PWR core reload design

  15. Depleted uranium instead of lead in munitions: the lesser evil.

    Jargin, Sergei V

    2014-03-01

    Uranium has many similarities to lead in its exposure mechanisms, metabolism and target organs. However, lead is more toxic, which is reflected in the threshold limit values. The main potential hazard associated with depleted uranium is inhalation of the aerosols created when a projectile hits an armoured target. A person can be exposed to lead in similar ways. Accidental dangerous exposures can result from contact with both substances. Encountering uranium fragments is of minor significance because of the low penetration depth of alpha particles emitted by uranium: they are unable to penetrate even the superficial keratin layer of human skin. An additional cancer risk attributable to the uranium exposure might be significant only in case of prolonged contact of the contaminant with susceptible tissues. Lead intoxication can be observed in the wounded, in workers manufacturing munitions etc; moreover, lead has been documented to have a negative impact on the intellectual function of children at very low blood concentrations. It is concluded on the basis of the literature overview that replacement of lead by depleted uranium in munitions would be environmentally beneficial or largely insignificant because both lead and uranium are present in the environment.

  16. Depleted uranium instead of lead in munitions: the lesser evil

    Jargin, Sergei V

    2014-01-01

    Uranium has many similarities to lead in its exposure mechanisms, metabolism and target organs. However, lead is more toxic, which is reflected in the threshold limit values. The main potential hazard associated with depleted uranium is inhalation of the aerosols created when a projectile hits an armoured target. A person can be exposed to lead in similar ways. Accidental dangerous exposures can result from contact with both substances. Encountering uranium fragments is of minor significance because of the low penetration depth of alpha particles emitted by uranium: they are unable to penetrate even the superficial keratin layer of human skin. An additional cancer risk attributable to the uranium exposure might be significant only in case of prolonged contact of the contaminant with susceptible tissues. Lead intoxication can be observed in the wounded, in workers manufacturing munitions etc; moreover, lead has been documented to have a negative impact on the intellectual function of children at very low blood concentrations. It is concluded on the basis of the literature overview that replacement of lead by depleted uranium in munitions would be environmentally beneficial or largely insignificant because both lead and uranium are present in the environment. (opinion)

  17. The effect of NO-donors on chloride efflux, intracellular Ca(2+) concentration and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells.

    Oliynyk, Igor; Hussain, Rashida; Amin, Ahmad; Johannesson, Marie; Roomans, Godfried M

    2013-06-01

    Since previous studies showed that the endogenous bronchodilator, S-nitrosglutathione (GSNO), caused a marked increase in CFTR-mediated chloride (Cl(-)) efflux and improved the trafficking of CFTR to the plasma membrane, and that also the nitric oxide (NO)-donor GEA3162 had a similar, but smaller, effect on Cl(-) efflux, it was investigated whether the NO-donor properties of GSNO were relevant for its effect on Cl(-) efflux from airway epithelial cells. Hence, the effect of a number of other NO-donors, sodium nitroprusside (SNP), S-nitroso-N-acetyl-DL-penicillamine (SNAP), diethylenetriamine/nitric oxide adduct (DETA-NO), and diethylenetriamine/nitric oxide adduct (DEA-NONOate) on Cl(-) efflux from CFBE (∆F508/∆F508-CFTR) airway epithelial cells was tested. Cl(-) efflux was determined using the fluorescent N-(ethoxycarbonylmethyl)-6-methoxyquinoliniu bromide (MQAE)-technique. Possible changes in the intracellular Ca(2+) concentration were tested by the fluorescent fluo-4 method in a confocal microscope system. Like previously with GSNO, after 4 h incubation with the NO-donor, an increased Cl(-) efflux was found (in the order SNAP>DETA-NO>SNP). The effect of DEA-NONOate on Cl(-) efflux was not significant, and the compound may have (unspecific) deleterious effects on the cells. Again, as with GSNO, after a short (5 min) incubation, SNP had no significant effect on Cl(-) efflux. None of the NO-donors that had a significant effect on Cl(-) efflux caused significant changes in the intracellular Ca(2+) concentration. After 4 h preincubation, SNP caused a significant increase in the mRNA expression of CFTR. SNAP and DEA-NONOate decreased the mRNA expression of all ENaC subunits significantly. DETA-NO caused a significant decrease only in α-ENaC expression. After a short preincubation, none of the NO-donors had a significant effect, neither on the expression of CFTR, nor on that of the ENaC subunits in the presence and absence of L-cysteine. It can be concluded that

  18. Depletion-induced biaxial nematic states of boardlike particles

    Belli, S; Van Roij, R; Dijkstra, M

    2012-01-01

    With the aim of investigating the stability conditions of biaxial nematic liquid crystals, we study the effect of adding a non-adsorbing ideal depletant on the phase behavior of colloidal hard boardlike particles. We take into account the presence of the depletant by introducing an effective depletion attraction between a pair of boardlike particles. At fixed depletant fugacity, the stable liquid-crystal phase is determined through a mean-field theory with restricted orientations. Interestingly, we predict that for slightly elongated boardlike particles a critical depletant density exists, where the system undergoes a direct transition from an isotropic liquid to a biaxial nematic phase. As a consequence, by tuning the depletant density, an easy experimental control parameter, one can stabilize states of high biaxial nematic order even when these states are unstable for pure systems of boardlike particles. (paper)

  19. Track Detection Technique Using CR-39 for Determining Depleted Uranium in Biological Specimens

    Murbat, S.M.

    2013-01-01

    Track detecting technique using CR-39 track detector has been implemented for determining depleted uranium concentration in biological specimens (tissues, bones, and blood) of patients infected with cancer diseases. Results were compared with specimens of patients infected with conventional diseases (noncancerous). Specimens were collected from middle and south of Iraq have been contaminated with depleted uranium in the Gulf war in 1991. Results show that this technique is efficient for determining depleted uranium concentration in biological specimens. It was found that all studies samples determine for patients infected with cancer diseases contain a high concentration of depleted uranium (more than the international standard) comparing with noncancerous diseases. Moreover, it was found that persons infected with Leukemia show more sensitive to uranium concentrations to induce the diseases (66-202 ppb), while (116- 1910 ppb) concentrations were needed for inducing cancer diseases in organs and tissues. Result confirmed the correlation between cancerous diseases and the munitions made of depleted uranium used in the Gulf war in 1991 leads to contaminate the Iraqi environment and causes a high risk against people in Iraq.

  20. Control of Single Molecule Fluorescence Dynamics by Stimulated Emission Depletion

    Marsh, R. J.; Osborne, M. A.; Bain, A. J.

    2003-01-01

    The feasibility of manipulating the single molecule absorption-emission cycle using picosecond stimulated emission depletion (STED) is investigated using a stochastic computer simulation. In the simulation the molecule is subjected to repeated excitation and depletion events using time delayed pairs of excitation (PUMP) and depletion (DUMP) pulses derived from a high repetition rate pulsed laser system. The model is used to demonstrate that a significant and even substantial reduction in the ...

  1. Research on using depleted uranium as nuclear fuel for HWR

    Zhang Jiahua; Chen Zhicheng; Bao Borong

    1999-01-01

    The purpose of our work is to find a way for application of depleted uranium in CANDU reactor by using MOX nuclear fuel of depleted U and Pu instead of natural uranium. From preliminary evaluation and calculation, it was shown that MOX nuclear fuel consisting of depleted uranium enrichment tailings (0.25% 235 U) and plutonium (their ratio 99.5%:0.5%) could replace natural uranium in CANDU reactor to sustain chain reaction. The prospects of application of depleted uranium in nuclear energy field are also discussed

  2. Producing, Importing, and Exporting Ozone-Depleting Substances

    Overview page provides links to information on producing, importing, and exporting ozone-depleting substances, including information about the HCFC allowance system, importing, labeling, recordkeeping and reporting.

  3. Gas generation matrix depletion quality assurance project plan

    1998-01-01

    The Los Alamos National Laboratory (LANL) is to provide the necessary expertise, experience, equipment and instrumentation, and management structure to: Conduct the matrix depletion experiments using simulated waste for quantifying matrix depletion effects; and Conduct experiments on 60 cylinders containing simulated TRU waste to determine the effects of matrix depletion on gas generation for transportation. All work for the Gas Generation Matrix Depletion (GGMD) experiment is performed according to the quality objectives established in the test plan and under this Quality Assurance Project Plan (QAPjP)

  4. A Critical Assessment of the Resource Depletion Potential of Current and Future Lithium-Ion Batteries

    Jens F. Peters

    2016-12-01

    Full Text Available Resource depletion aspects are repeatedly used as an argument for a shift towards new battery technologies. However, whether serious shortages due to the increased demand for traction and stationary batteries can actually be expected is subject to an ongoing discussion. In order to identify the principal drivers of resource depletion for battery production, we assess different lithium-ion battery types and a new lithium-free battery technology (sodium-ion under this aspect, applying different assessment methodologies. The findings show that very different results are obtained with existing impact assessment methodologies, which hinders clear interpretation. While cobalt, nickel and copper can generally be considered as critical metals, the magnitude of their depletion impacts in comparison with that of other battery materials like lithium, aluminum or manganese differs substantially. A high importance is also found for indirect resource depletion effects caused by the co-extraction of metals from mixed ores. Remarkably, the resource depletion potential per kg of produced battery is driven only partially by the electrode materials and thus depends comparably little on the battery chemistry itself. One of the key drivers for resource depletion seems to be the metals (and co-products in electronic parts required for the battery management system, a component rather independent from the actual battery chemistry. However, when assessing the batteries on a capacity basis (per kWh storage capacity, a high-energy density also turns out to be relevant, since it reduces the mass of battery required for providing one kWh, and thus the associated resource depletion impacts.

  5. Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats.

    Wang, Min; Li, Min; Geng, Xiwen; Song, Zhimin; Albers, H Elliott; Yang, Maoquan; Zhang, Xiao; Xie, Jinlu; Qu, Qingyang; He, Tingting

    2015-01-15

    The involvement of dopamine (DA) neuron loss in the etiology of Parkinson's disease has been well documented. The neural mechanisms underlying the effects of DA loss and the resultant motor dysfunction remain unknown. To gain insights into how loss of DA disrupts the electrical processes in the cortico-subcortical network, the present study explores the effects of DA neuron depletion on electrical activity in the primary motor cortex (M1), on the external and the internal segment of the globus pallidus (GPe and GPi respectively), and on their temporal relationships. Comparison of local field potentials (LFPs) in these brain regions from unilateral hemispheric DA neuron depleted rats and neurologically intact rats revealed that the spectrum power of LFPs in 12-70Hz (for M1, and GPe) and in 25-40Hz (for GPi) was significantly greater in the DA depleted rats than that in the control group. These changes were associated with a shortening of latency in LFP activities between M1 and GPe, from several hundred milliseconds in the intact animals to close to zero in the DA depleted animals. LFP oscillations in M1 were significantly more synchronized with those in GPe in the DA depleted rats compared with those in the control rats. By contrast, the synchronization of oscillation in LFP activities between M1 and GPi did not differ between the DA depleted and intact rats. Not surprisingly, rats that had DA neuron depletion spent more time along the ladder compared with the control rats. These data suggest that enhanced oscillatory activity and increased synchronization of LFPs may contribute to movement impairment in the rat model of Parkinson's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Depleting adult dentate gyrus neurogenesis increases cocaine-seeking behavior.

    Deroche-Gamonet, Véronique; Revest, Jean-Michel; Fiancette, Jean-François; Balado, Eric; Koehl, Muriel; Grosjean, Noëlle; Abrous, Djoher Nora; Piazza, Pier-Vincenzo

    2018-03-05

    The hippocampus is the main locus for adult dentate gyrus (DG) neurogenesis. A number of studies have shown that aberrant DG neurogenesis correlates with many neuropsychiatric disorders, including drug addiction. Although clear causal relationships have been established between DG neurogenesis and memory dysfunction or mood-related disorders, evidence of the causal role of DG neurogenesis in drug-seeking behaviors has not been established. Here we assessed the role of new DG neurons in cocaine self-administration using an inducible transgenic approach that selectively depletes adult DG neurogenesis. Our results show that transgenic mice with decreased adult DG neurogenesis exhibit increased motivation to self-administer cocaine and a higher seeking response to cocaine-related cues. These results identify adult hippocampal neurogenesis as a key factor in vulnerability to cocaine addiction.

  7. Active volume studies with depleted and enriched BEGe detectors

    Sturm, Katharina von [Eberhard Karls Universitaet Tuebingen (Germany); Universita degli Studi di Padova, Padua (Italy); Collaboration: GERDA-Collaboration

    2013-07-01

    The Gerda experiment is currently taking data for the search of the 0νββ decay in {sup 76}Ge. In 2013, 30 newly manufactured Broad Energy Germanium (BEGe) diodes will be deployed which will double the active mass within Gerda. These detectors were fabricated from high-purity germanium enriched in {sup 76}Ge and tested in the HADES underground laboratory, owned by SCK.CEN, in Mol, Belgium. As the BEGes are source and detector at the same time, one crucial parameter is their active volume which directly enters into the evaluation of the half-life. This talk illustrates the dead layer and active volume determination of prototype detectors from depleted germanium as well as the newly produced detectors from enriched material, using gamma spectroscopy methods and comparing experimental results to Monte-Carlo simulations. Recent measurements and their results are presented, and systematic effects are discussed.

  8. Alkali depletion and ion-beam mixing in glasses

    Arnold, G.W.

    1983-01-01

    Ion-implantation-induced alkali depletion in simple alkali-silicate glasses (12M 2 O.88SiO 2 ) has been studied for implantations at room temperature and near 77K. Results are consistent with a mechanism for alkali removal, by heavy ion bombardment, based on radiation-enhanced migration and preferential removal of alkali from the outermost layers. Similar results were obtained for mixed-alkali glasses ((12-x)Cs 2 .O.xM 2 O.88SiO 2 ) where, in addition, a mixed-alkali effect may also be operative. Some preliminary experiments with ion implantation through thin Al films on SiO 2 glass and on a phosphate glass show that inter-diffusion takes place and suggest that this ion-mixing technique may be a useful method for altering the physical properties of glass surfaces

  9. Images of the dark soliton in a depleted condensate

    Dziarmaga, Jacek; Karkuszewski, Zbyszek P; Sacha, Krzysztof

    2003-01-01

    The dark soliton created in a Bose-Einstein condensate becomes grey in the course of time evolution because its notch fills up with depleted atoms. This is the result of quantum mechanical calculations which describe the output of many experimental repetitions of creation of the stationary soliton, and its time evolution terminated by a destructive density measurement. However, such a description is not suitable to predict the outcome of a single realization of the experiment where two extreme scenarios and many combinations thereof are possible: one will see either (1) a displaced dark soliton without any atoms in the notch, but with a randomly displaced position, or (2) a grey soliton with a fixed position, but a random number of atoms filling its notch. In either case the average over many realizations will reproduce the mentioned quantum mechanical result. In this paper we use N-particle wavefunctions, which follow from the number-conserving Bogoliubov theory, to settle this issue

  10. Examination of disks from the IPNS depleted uranium target

    Strain, R.V.; Carpenter, J.M.

    1995-10-01

    This report describes the results of examining the Zircaloy-2 clad depleted uranium disks from the Intense Pulse Neutron Source (IPNS) Target. That target operated from August, 1981 to June, 1988 and from September, 1991 to September, 1992 at 450 MeV, pulsing at 30 Hz with a time average proton current of about 15 microA. The target was removed from service when the presence of fission products ( 135 Xe) in the coolant cover gas indicated a failure in the Zircaloy-2 cladding. Altogether, the target had absorbed about 240 mA hours of proton current, and endured between 50,000 and 100,000 thermal cycles. The purpose of the examination was to assess the condition of the disks and determine the cause of the cladding failure. The results of visual, gamma ray scanning, and destructive metallurgical examination of two disks are described

  11. MCNP evaluation of top node control rod depletion below the core in KKL

    Beran, Tâm; Seltborg, Per; Lindahl, Sten-Örjan; Bieli, Roger; Ledergerber, Guido

    2014-01-01

    In previous studies, there has been identified a significant discrepancy in the BWR control rod top node depletion between the two core simulator nodal codes POLCA7 and PRESTO-2, which indicates that there is a large general uncertainty in nodal codes in calculating the top node depletion of fully withdrawn control rods. In this study, the stochastic Monte Carlo code MCNP has been used to calculate the top node control rod depletion for benchmarking the nodal codes. By using the TIP signal obtained from an extended TIP campaign below the core performed in the KKL reactor, the MCNP model has been verified by comparing the axial profile between the TIP data and the gamma flux calculated by MCNP. The MCNP results have also been compared with calculations from POLCA7, which was found to yield slightly higher depletion rates than MCNP. It was also found that the 10 B depletion in the top node is very sensitive to the exact axial location of the control rod top when it is fully withdrawn. By using the MCNP results, the neutron flux model below the core in the nodal codes can be improved by implementing an exponential function for the neutron flux. (author)

  12. Kidney in potassium depletion. II. K+ handling by the isolated perfused rat kidney

    Hayashi, M.; Katz, A.I.

    1987-01-01

    In a companion paper the authors reported a large increment in Na + -K + -ATPase activity and [ 3 H]ouabain binding the inner stripe of outer medullary collecting tubules from K-depleted rats. To test the hypothesis that the increased number of Na + -K + pumps in these animals may be involved in potassium reabsorption they examined the effect of ouabain on K excretion by isolated, perfused kidneys from rats fed a K-free diet for 3 wk. Kidneys from K-depleted rats retain potassium avidly, both the fractional (FE/sub K/) and absolute K excretion being approximately fivefold lower than in control kidneys. Ouabain (5 mM) increased FE/sub K/ in kidneys from each K-depleted rat; similar results were obtained when kidneys were perfused with low and high potassium concentrations. In contrast, ouabain produced a variable effect in control kidneys, that depended on the perfusate potassium concentration. In K-depleted rats amiloride did not significantly alter K excretion and did not block the ouabain-induced kaliuresis, suggesting that the latter is not due to enhanced secretion secondary to increased distal fluid delivery. These results provide evidence for ouabain-sensitive potassium reabsorption in kidneys of chronically K-depleted rats, and suggest an explanation for the increased Na + -K + -ATPase observed in such animals

  13. Depletion of gamma-glutamylcyclotransferase in cancer cells induces autophagy followed by cellular senescence.

    Taniguchi, Keiko; Matsumura, Kengo; Ii, Hiromi; Kageyama, Susumu; Ashihara, Eishi; Chano, Tokuhiro; Kawauchi, Akihiro; Yoshiki, Tatsuhiro; Nakata, Susumu

    2018-01-01

    Gamma-glutamylcyclotransferase (GGCT) was originally identified as a protein highly expressed in bladder cancer tissues by proteomic analysis, and its higher expression in a variety of cancers compared to normal tissues have been shown. Depletion of GGCT in various cancer cells results in antiproliferative effects both in vitro and in vivo ; thus it is considered a promising therapeutic target. Although it has been shown that knockdown of GGCT induces cellular senescence and non-apoptotic cell death, associated with upregulation of cyclin-dependent kinase inhibitors (CDKIs) including p21 WAF1/CIP1 , the cellular events that follow GGCT depletion are not fully understood. Here, we show that GGCT depletion induced autophagy in MCF7 breast and PC3 prostate cancer cells. Conversely, overexpression of GGCT in NIH3T3 fibroblast under conditions of serum deprivation inhibited autophagy and increased proliferation. Simultaneous knockdown of autophagy related-protein 5, a critical effector of autophagy, along with GGCT in MCF7 and PC3 cells led to significant attenuation of the multiple cellular responses, including upregulation of CDKIs, increased numbers of senescence-associated β-galactosidase positive senescent cells, and growth inhibition. Furthermore, we show that autophagy-promoting signaling cascades including activation of the AMPK-ULK1 pathway and/or inactivation of the mTORC2-Akt pathway were triggered in GGCT-depleted cells. These results indicate that autophagy plays an important role in the growth inhibition of cancer cells caused by GGCT depletion.

  14. Role of batch depletion of broiler houses on the occurrence of Campylobacter spp. in chicken flocks

    Hald, Birthe; Rattenborg, Erik; Madsen, Mogens

    2001-01-01

    Aims: The effect of batch depletion of broiler houses for campylobacter occurrence in broiler flocks was estimated in 10 flocks, each comprising a separate female and male batch. Methods and Results: The chicks were sampled first bq; cloacal swabs in the broiler houses before the start...... that batch depletion of broiler houses increased the prevalence of Campylobacter spp.-infected broilers in the flocks, that the introduction occurred a hen catching the first batch, and that campylobacter spreads through the entire flock within a week. Significance and Impact of the Study: The results from...

  15. Determination of Mother Centriole Maturation in CPAP-Depleted Cells Using the Ninein Antibody

    Miseon Lee

    2015-03-01

    Full Text Available BackgroundMutations in centrosomal protein genes have been identified in a number of genetic diseases in brain development, including microcephaly. Centrosomal P4.1-associated protein (CPAP is one of the causal genes implicated in primary microcephaly. We previously proposed that CPAP is essential for mother centriole maturation during mitosis.MethodsWe immunostained CPAP-depleted cells using the ninein antibody, which selectively detects subdistal appendages in mature mother centrioles.ResultsNinein signals were significantly impaired in CPAP-depleted cells.ConclusionThe results suggest that CPAP is required for mother centriole maturation in mammalian cells. The selective absence of centriolar appendages in young mother centrioles may be responsible for asymmetric spindle pole formation in CPAP-depleted cells.

  16. Ferulic acid depletion by cultured soybean seedlings under action of glucose and methionine

    Herrig Vanessa

    2000-01-01

    Full Text Available Cultured soybean seedlings were used to investigate how glucose or methionine influenced depletion of ferulic acid. Three-day-old seedlings were grown in hydroponic solution containing ferulic acid plus glucose or methionine, and the level of the phenolic acid were monitored in the nutrient culture. The results showed that ferulic acid depletion was more rapid in the presence of those compounds. After 6 h, the increase caused by glucose (0.01 and 0.05 mM was more pronounced than methionine in the same concentrations. On the other hand, methionine (0.1 and 0.2 mM increased depletion more significantly than glucose. Results suggested that both compounds might to increase the allelopathic effects of ferulic acid in the seedlings.

  17. Molybdenum depletion around P-phases Ni-Cr-Mo-W weld metals

    Silva, Cleiton Carvalho; Miranda, Helio Cordeiro de; Farias, Jesualdo Pereira

    2010-01-01

    This work evaluated the local chemical composition in matrix/precipitate interface in a Ni-Cr-Mo-W alloy weld metals deposited on substrate of C-Mn steel. The microstructural characterization was carried out through optical microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). The results had shown that the presence of secondary phases precipitates in the interdendritic region. Through SEM analysis were observed indications of depletion of Mo around these phases. These precipitates were identified as P-phase by TEM analysis. The Mo depletion indications were confirmed through EDS. The Mo depletion was a result of a reheating due to several welding heat cycles deposited to promote the coating layer. (author)

  18. Simulations and observations of plasma depletion, ion composition, and airglow emissions in two auroral ionospheric depletion experiments

    Yau, A.W.; Whalen, B.A.; Harris, F.R.; Gattinger, R.L.; Pongratz, M.B.; Bernhardt, P.A.

    1985-01-01

    In an ionospheric depletion experiment where chemically reactive vapors such as H 2 O and CO 2 are injected into the O + dominant F region to accelerate the plasma recombination rate and to reduce the plasma density, the ion composition in the depleted region is modified, and photometric emissions are produced. We compare in situ ion composition, density, and photometric measurements from two ionospheric depletion experiments with predictions from chemical modeling. The two injections, Waterhole I and III, were part of an auroral perturbation experiment and occurred in different ambient conditions. In both injections a core region of greater than fivefold plasma depletion was observed over roughly-equal5-km diameter within seconds of the injection, surrounded by an outer region of less drastic and slower depletion. In Waterhole I the plasma density was depleted tenfold over a 30-km diamter region after 2 min. The ambient O + density was drastically reduced, and the molecular O + 2 abundance was enhanced fivehold in the depletion region. OH airglow emission associated with the depletion was observed with a peak emission intensity of roughly-equal1 kR. In Waterhole III the ambient density was a decade lower, and the plasma depletion was less drastic, being twofold over 30 km after 2 min. The airglow emissions were also much less intense and below measurement sensitivity (30 R for the OH 306.4-nm emission; 50 R for the 630.0-nm emission)

  19. Tylosin depletion in edible tissues of turkeys.

    Montesissa, C; De Liguoro, M; Santi, A; Capolongo, F; Biancotto, G

    1999-10-01

    The depletion of tylosin residues in edible turkey tissues was followed after 3 days of administration of tylosin tartrate at 500 mg l-1 in drinking water, to 30 turkeys. Immediately after the end of the treatment (day 0) and at day 1, 3, 5 and 10 of withdrawal, six turkeys (three males and three females) per time were sacrificed and samples of edible tissues were collected. Tissue homogenates were extracted, purified and analysed by HPLC according to a method previously published for the analysis of tylosin residues in pig tissues. In all tissues, tylosin residues were already below the detection limits of 50 micrograms kg-1 at time zero. However, in several samples of tissues (skin + fat, liver, kidney, muscle), from the six turkeys sacrificed at that time, one peak corresponding to an unknown tylosin equivalent was detected at measurable concentrations. The identification of this unknown compound was performed by LC-MS/MS analysis of the extracts from incurred samples. The mass fragmentation of the compound was consistent with the structure of tylosin D (the alcoholic derivative of tylosin A), the major metabolite of tylosin previously recovered and identified in tissues and/or excreta from treated chickens, cattle and pigs.

  20. Decommissioning plan depleted uranium manufacturing facility

    Bernhardt, D.E.; Pittman, J.D.; Prewett, S.V.

    1987-01-01

    Aerojet Ordnance Tennessee, Inc. (Aerojet) is decommissioning its California depleted uranium (DU) manufacturing facility. Aerojet has conducted manufacturing and research and development activities at the facility since 1977 under a State of California Source Materials License. The decontamination is being performed by a contractor selector for technical competence through competitive bid. Since the facility will be released for uncontrolled use it will be decontaminated to levels as low as reasonably achievable (ALARA). In order to fully apply the principles of ALARA, and ensure the decontamination is in full compliance with appropriate guides, Aerojet has retained Rogers and Associaties Engineering Corporation (RAE) to assist in the decommissioning. RAE has assisted in characterizing the facility and preparing contract bid documents and technical specifications to obtain a qualified decontamination contractor. RAE will monitor the decontamination work effort to assure the contractor's performance complies with the contract specifications and the decontamination plan. The specifications require a thorough cleaning and decontamination of the facility, not just sufficient cleaning to meet the numeric cleanup criteria

  1. Student Teacher Understanding of the Greenhouse Effect, Ozone Layer Depletion, and Acid Rain.

    Dove, Jane

    1996-01-01

    Describes the results of a survey designed to ascertain details of student teachers' knowledge and misconceptions about the greenhouse effect, acid rain, and ozone layer depletion. Results indicate familiarity with the issues but little understanding of the concepts involved and many commonly held misconceptions. (JRH)

  2. Stochastic interactions of two Brownian hard spheres in the presence of depletants

    Karzar-Jeddi, Mehdi; Fan, Tai-Hsi; Tuinier, Remco; Taniguchi, Takashi

    2014-01-01

    A quantitative analysis is presented for the stochastic interactions of a pair of Brownian hard spheres in non-adsorbing polymer solutions. The hard spheres are hypothetically trapped by optical tweezers and allowed for random motion near the trapped positions. The investigation focuses on the long-time correlated Brownian motion. The mobility tensor altered by the polymer depletion effect is computed by the boundary integral method, and the corresponding random displacement is determined by the fluctuation-dissipation theorem. From our computations it follows that the presence of depletion layers around the hard spheres has a significant effect on the hydrodynamic interactions and particle dynamics as compared to pure solvent and uniform polymer solution cases. The probability distribution functions of random walks of the two interacting hard spheres that are trapped clearly shift due to the polymer depletion effect. The results show that the reduction of the viscosity in the depletion layers around the spheres and the entropic force due to the overlapping of depletion zones have a significant influence on the correlated Brownian interactions

  3. Tuning of electrostatic vs. depletion interaction in deciding the phase behavior of nanoparticle-polymer system

    Kumar, Sugam, E-mail: sugam@barc.gov.in; Aswal, V. K. [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Kohlbrecher, J. [Laboratory for Neutron Scattering, Paul Scherrer Institut, H-5232 PSI Villigen (Switzerland)

    2015-06-24

    Nanoparticle-polymer system interestingly show a re-entrant phase behavior where charge stabilized silica nanoparticles (phase I) undergo particle clustering (phase II) and then back to individual particles (phase I) as a function of polymer concentration. Such phase behavior arises as a result of dominance of various interactions (i) nanoparticle-nanoparticle electrostatic repulsion (ii) polymer induced attractive depletion between nanoparticles and (iii) polymer-polymer repulsion, at different concentration regimes. Small-angle neutron scattering (SANS) has been used to study the evolution of interaction during this re-entrant phase behavior of nanoparticles by contrast-marching the polymer. The SANS data have been modeled using a two-Yukawa potential accounting for both attractive and repulsive parts of the interaction between nanoparticles. The degree of both of these parts has been separately tuned by varying the polymer concentration and ionic strength of the solution. Both of these parts are found to have long-range nature. At low polymer concentrations, the electrostatic repulsion dominates over the depletion attraction. The magnitude and the range of the depletion interaction increase with the polymer concentration leading to nanoparticle clustering. At higher polymer concentrations, the increased polymer-polymer repulsion reduces the strength of depletion leading to re-entrant phase behavior. The clusters formed under depletion attraction are found to have surface fractal morphology.

  4. Simulation of Halocarbon Production and Emissions and Effects on Ozone Depletion

    Holmes; Ellis

    1997-09-01

    / This paper describes an integrated model that simulates future halocarbon production/emissions and potential ozone depletion. Applications and historical production levels for various halocarbons are discussed first. A framework is then presented for modeling future halocarbon impacts incorporating differences in underlying demands, applications, regulatory mandates, and environmental characteristics. The model is used to simulate the potential impacts of several prominent issues relating to halocarbon production, regulation, and environmental interactions, notably: changes in agricultural methyl bromide use, increases in effectiveness of bromine for ozone depletion, modifications to the elimination schedule for HCFCs, short-term expansion of CFC demand in low use compliance countries, and delays in Russian Federation compliance. Individually, each issue does not unequivocally represent a significant likely increase in long-term atmospheric halogen loading and stratospheric ozone depletion. In combination, however, these impacts could increase peak halogen concentrations and long-term integral halogen loading, resulting in higher levels of stratospheric ozone depletion and longer exposure to increased levels of UV radiation.KEY WORDS: Halocarbons; Ozone depletion; Montreal Protocol; Integrated assessment

  5. Tuning of electrostatic vs. depletion interaction in deciding the phase behavior of nanoparticle-polymer system

    Kumar, Sugam; Aswal, V. K.; Kohlbrecher, J.

    2015-01-01

    Nanoparticle-polymer system interestingly show a re-entrant phase behavior where charge stabilized silica nanoparticles (phase I) undergo particle clustering (phase II) and then back to individual particles (phase I) as a function of polymer concentration. Such phase behavior arises as a result of dominance of various interactions (i) nanoparticle-nanoparticle electrostatic repulsion (ii) polymer induced attractive depletion between nanoparticles and (iii) polymer-polymer repulsion, at different concentration regimes. Small-angle neutron scattering (SANS) has been used to study the evolution of interaction during this re-entrant phase behavior of nanoparticles by contrast-marching the polymer. The SANS data have been modeled using a two-Yukawa potential accounting for both attractive and repulsive parts of the interaction between nanoparticles. The degree of both of these parts has been separately tuned by varying the polymer concentration and ionic strength of the solution. Both of these parts are found to have long-range nature. At low polymer concentrations, the electrostatic repulsion dominates over the depletion attraction. The magnitude and the range of the depletion interaction increase with the polymer concentration leading to nanoparticle clustering. At higher polymer concentrations, the increased polymer-polymer repulsion reduces the strength of depletion leading to re-entrant phase behavior. The clusters formed under depletion attraction are found to have surface fractal morphology

  6. Implications of stratospheric ozone depletion upon plant production

    Teramura, A.H.

    1990-01-01

    An increase in the amount of UV-B radiation reaching the earth's surface is identified as the major factor of concern to result from stratospheric ozone depletion. UV radiation is believed to have wide ranging effects on plant physiology and biochemistry. In screening studies of > 300 species and cultivars, > 50% have shown sensitivity to UV radiation. The most sensitive plant families appear to be Leguminosae, Cucurbitaceae and Cruciferae. The need for a better understanding of the effects of UV radiation on crop plant physiology and particularly of the repair and protective mechanisms developed by some species is stressed. This paper was presented at a colloquium on Implications of global climate changes on horticultural cropping practices and production in developing countries held at the 86th Annual Meeting of the American Society for Horticultural Science at Tulsa, Oklahoma, on 2 Aug. 1989

  7. Depleted uranium: Metabolic disruptor?; Uranium appauvri: perturbateur metabolique?

    Souidi, Maamar; Dublineau, Isabelle; Lestaevel, Philippe [Institut de Radioprotection et de Surete Nucleaire - IRSN, Direction de la radioprotection de l' homme, Laboratoire de radiotoxicologie experimentale, Service de radiobiologie et d' epidemiologie, BP 17, 92262 Fontenay-aux-Roses cedex (France)

    2011-11-15

    The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolizing vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions. (authors)

  8. Radon depletion in xenon boil-off gas

    Bruenner, S.; Cichon, D.; Lindemann, S.; Undagoitia, T.M.; Simgen, H. [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany)

    2017-03-15

    An important background in detectors using liquid xenon for rare event searches arises from the decays of radon and its daughters. We report for the first time a reduction of {sup 222}Rn in the gas phase above a liquid xenon reservoir. We show a reduction factor of >or similar 4 for the {sup 222}Rn concentration in boil-off xenon gas compared to the radon enriched liquid phase. A semiconductor-based α-detector and miniaturized proportional counters are used to detect the radon. As the radon depletion in the boil-off gas is understood as a single-stage distillation process, this result establishes the suitability of cryogenic distillation to separate radon from xenon down to the 10{sup -15} mol/mol level. (orig.)

  9. Climate variability, rice production and groundwater depletion in India

    Bhargava, Alok

    2018-03-01

    This paper modeled the proximate determinants of rice outputs and groundwater depths in 27 Indian states during 1980-2010. Dynamic random effects models were estimated by maximum likelihood at state and well levels. The main findings from models for rice outputs were that temperatures and rainfall levels were significant predictors, and the relationships were quadratic with respect to rainfall. Moreover, nonlinearities with respect to population changes indicated greater rice production with population increases. Second, groundwater depths were positively associated with temperatures and negatively with rainfall levels and there were nonlinear effects of population changes. Third, dynamic models for in situ groundwater depths in 11 795 wells in mainly unconfined aquifers, accounting for latitudes, longitudes and altitudes, showed steady depletion. Overall, the results indicated that population pressures on food production and environment need to be tackled via long-term healthcare, agricultural, and groundwater recharge policies in India.

  10. Depleted uranium and radiation - induced lung cancer and leukaemia

    Mould, R.F.

    2002-01-01

    Reports of leukaemias and other cancers among servicemen who took part in the 1991 Gulf war or in the more recent operations in the Balkans are of continuing interest, as is the possibility, however slight, that depleted uranium (DU) is one of the causative factors. This commentary includes the results of a UK epidemiological study on the mortality of Gulf war veterans and , although not containing information on DU exposure, gives data on overall levels of mortality and therefore carries more weight than anecdotal reports. Also included are brief summaries on radiation-induced lung cancer in uranium workers as well as radiation-induced leukaemia in Japanese atomic bomb survivors and patients ankylosing spondylitis treated using x-rays. This commentary concludes with a critique of Iraqi cancer statistics as well as giving information on environmental contamination in Kosovo and the use of DU ammunition. (author)

  11. The potentiality of depleted water to modify the tomatoes

    Butnaru, Gallia; Blidar, A.; Titescu, Gh.; Stefanescu, I.

    2004-01-01

    The possibility to improve the tomatoes bio-productivity parameters was tested using H 2 O-d and deuterium depleted water (DDW). There are presented the results obtained by seeds moisten before sowing. The plants vegetation until the first harvest and the fruits production and quality were studied. Making use of DDW has the following advantages: -accessibility, as the practical work is easy and economical; - nonpolluting, making use of the plants own bio-productive resources thus promoting the ecological agriculture. The effects registered during the experiments are: - seeds germination rhythm was faster in DDW conditions; - plants productivity was increased; - the capacity of light energetic convertibility was enhanced in the stress condition; - DDW seems to act as a 'helper' in the critical life cycle periods. (authors)

  12. PP005. Vitamin D depletion aggravates hypertension in transgenic rats

    Bjørkholt Andersen, Louise; Herse, Florian; Christesen, Henrik Thybo

    2013-01-01

    INTRODUCTION: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic pathways. OBJECTIVE: To investigate the impact of vitamin D in a transgenic rat model of angiotensin II-mediated hypertensive organ failure. METHODS: In 4-week-old age-matched rats overexpress......INTRODUCTION: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic pathways. OBJECTIVE: To investigate the impact of vitamin D in a transgenic rat model of angiotensin II-mediated hypertensive organ failure. METHODS: In 4-week-old age-matched rats...... determined once weekly. After three weeks, animals were sacrificed. Heart tissue was examined for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by RT-PCR. RESULTS: The vitamin D depleted group had higher blood pressure at week 1 (mean difference 23.4mmHg, 95% CI 9.1-37.7) and tended...

  13. Characterization of depleted uranium oxides fabricated using different processing methods

    Hastings, E.P.; Lewis, C.; FitzPatrick, J.; Rademacher, D.; Tandon, L.

    2008-01-01

    Identifying both physical and chemical characteristics of Special Nuclear Material (SNM) production processes is the corner stone of nuclear forensics. Typically, processing markers are based on measuring an interdicted sample's bulk chemical properties, such as the elemental or isotopic composition, or focusing on the chemical and physical morphology of only a few particles. Therefore, it is imperative that known SNM processes be fully characterized from bulk to trace level for each particle size range. This report outlines a series of particle size measurements and fractionation techniques that can be applied to a bulk SNM powders, categorizing both chemical and physical properties in discrete particle size fractions. This will be demonstrated by characterizing the process signatures of a series of different depleted uranium oxides prepared at increasing firing temperatures (350-1100 deg C). Results will demonstrate how each oxides' material density, particle size distribution, and morphology varies. (author)

  14. Electromagnetic ion cyclotron waves in the plasma depletion layer

    Denton, Richard E.; Hudson, Mary K.; Fuselier, Stephen A.; Anderson, Brian J.

    1993-01-01

    Results of a study of the theoretical properties of electromagnetic ion cyclotron (EMIC) waves which occur in the plasma depletion layer are presented. The analysis assumes a homogeneous plasma with the characteristics which were measured by the AMPTE/CCE satellite at 1450-1501 UT on October 5, 1984. Waves were observed in the Pc 1 frequency range below the hydrogen gyrofrequency, and these waves are identified as EMIC waves. The higher-frequency instability is driven by the temperature anisotropy of the H(+) ions, while the lower-frequency instability is driven by the temperature anisotropy of the He(2+) ions. It is argued that the higher-frequency waves will have k roughly parallel to B(0) and will be left-hand polarized, while the lower frequency wave band will have k oblique to B(0) and will be linearly polarized, in agreement with observations.

  15. Depleted CMOS pixels for LHC proton–proton experiments

    Wermes, N.

    2016-01-01

    While so far monolithic pixel detectors have remained in the realm of comparatively low rate and radiation applications outside LHC, new developments exploiting high resistivity substrates with three or four well CMOS process options allow reasonably large depletion depths and full CMOS circuitry in a monolithic structure. This opens up the possibility to target CMOS pixel detectors also for high radiation pp-experiments at the LHC upgrade, either in a hybrid-type fashion or even fully monolithic. Several pixel matrices have been prototyped with high ohmic substrates, high voltage options, and full CMOS electronics. They were characterized in the lab and in test beams. An overview of the necessary development steps and different approaches as well as prototype results are presented in this paper.

  16. Calculation of depletion with optimal distribution of initial control poison

    Castro Lobo, P.D. de.

    1978-03-01

    The spatial depletion equations are linearized within the time intervals and their solution is obtained by modal analysis. At the beginning of life an optimal poison distribution that maximizes neutron economy and the corresponding flux is determined. At the start of the subsequent time steps the flux distributions are obtained by pertubation method in relation to the start of the previous time steps. The problem was studied with constant poison distribution in order to evaluate the influence of the poison at the beginning of life. The results obtained by the modal expansion techniques are satisfactory. However, the optimization of the initial distribution of the control poison does not indicate any significant effect on the core life [pt

  17. Optimal Allocation of Sampling Effort in Depletion Surveys

    We consider the problem of designing a depletion or removal survey as part of estimating animal abundance for populations with imperfect capture or detection rates. In a depletion survey, animals are captured from a given area, counted, and withheld from the population. This proc...

  18. Effect of greenhouse gas emissions on stratospheric ozone depletion

    Velders GJM; LLO

    1997-01-01

    The depletion of the ozone layer is caused mainly by the increase in emissions of chlorine- and bromine-containing compounds like CFCs, halons, carbon tetrachloride, methyl chloroform and methyl bromide. Emissions of greenhouse gases can affect the depletion of the ozone layer through atmospheric

  19. Ego Depletion Does Not Interfere With Working Memory Performance.

    Singh, Ranjit K; Göritz, Anja S

    2018-01-01

    Ego depletion happens if exerting self-control reduces a person's capacity to subsequently control themselves. Previous research has suggested that ego depletion not only interferes with subsequent self-control but also with working memory. However, recent meta-analytical evidence casts doubt onto this. The present study tackles the question if ego depletion does interfere with working memory performance. We induced ego depletion in two ways: using an e-crossing task and using a Stroop task. We then measured working memory performance using the letter-number sequencing task. There was no evidence of ego depletion interfering with working memory performance. Several aspects of our study render this null finding highly robust. We had a large and heterogeneous sample of N = 1,385, which provided sufficient power. We deployed established depletion tasks from two task families (e-crossing task and Stroop), thus making it less likely that the null finding is due to a specific depletion paradigm. We derived several performance scores from the working memory task and ran different analyses to maximize the chances of finding an effect. Lastly, we controlled for two potential moderators, the implicit theories about willpower and dispositional self-control capacity, to ensure that a possible effect on working memory is not obscured by an interaction effect. In sum, this experiment strengthens the position that ego depletion works but does not affect working memory performance.

  20. Variation in RNA-Seq transcriptome profiles of peripheral whole blood from healthy individuals with and without globin depletion.

    Heesun Shin

    Full Text Available BACKGROUND: The molecular profile of circulating blood can reflect physiological and pathological events occurring in other tissues and organs of the body and delivers a comprehensive view of the status of the immune system. Blood has been useful in studying the pathobiology of many diseases. It is accessible and easily collected making it ideally suited to the development of diagnostic biomarker tests. The blood transcriptome has a high complement of globin RNA that could potentially saturate next-generation sequencing platforms, masking lower abundance transcripts. Methods to deplete globin mRNA are available, but their effect has not been comprehensively studied in peripheral whole blood RNA-Seq data. In this study we aimed to assess technical variability associated with globin depletion in addition to assessing general technical variability in RNA-Seq from whole blood derived samples. RESULTS: We compared technical and biological replicates having undergone globin depletion or not and found that the experimental globin depletion protocol employed removed approximately 80% of globin transcripts, improved the correlation of technical replicates, allowed for reliable detection of thousands of additional transcripts and generally increased transcript abundance measures. Differential expression analysis revealed thousands of genes significantly up-regulated as a result of globin depletion. In addition, globin depletion resulted in the down-regulation of genes involved in both iron and zinc metal ion bonding. CONCLUSIONS: Globin depletion appears to meaningfully improve the quality of peripheral whole blood RNA-Seq data, and may improve our ability to detect true biological variation. Some concerns remain, however. Key amongst them the significant reduction in RNA yields following globin depletion. More generally, our investigation of technical and biological variation with and without globin depletion finds that high-throughput sequencing by RNA

  1. Effects of tryptophan depletion on selective serotonin reuptake inhibitor-remitted patients with obsessive compulsive disorder.

    Hood, Sean D; Broyd, Annabel; Robinson, Hayley; Lee, Jessica; Hudaib, Abdul-Rahman; Hince, Dana A

    2017-12-01

    Serotonergic antidepressants are first-line medication therapies for obsessive-compulsive disorder, however it is not known if synaptic serotonin availability is important for selective serotonin reuptake inhibitor efficacy. The present study tested the hypothesis that temporary reduction in central serotonin transmission, through acute tryptophan depletion, would result in an increase in anxiety in selective serotonin reuptake inhibitor-remitted obsessive-compulsive disorder patients. Eight patients (four males) with obsessive-compulsive disorder who showed sustained clinical improvement with selective serotonin reuptake inhibitor treatment underwent acute tryptophan depletion in a randomized, double-blind, placebo-controlled, within-subjects design, over two days one week apart. Five hours after consumption of the depleting/sham drink the participants performed a personalized obsessive-compulsive disorder symptom exposure task. Psychological responses were measured using the Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and Visual Analogue Scales. Free plasma tryptophan to large neutral amino acid ratio decreased by 93% on the depletion day and decreased by 1% on the sham day, as anticipated. Psychological rating scores as measured by Visual Analogue Scale showed a significant decrease in perceived control and increase in interfering thoughts at the time of provocation on the depletion day but not on the sham day. A measure of convergent validity, namely Visual Analogue Scale Similar to past, was significantly higher at the time of provocation on both the depletion and sham days. Both the depletion and time of provocation scores for Visual Analogue Scale Anxiety, Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and blood pressure were not significant. Acute tryptophan depletion caused a significant decrease in perceived control and increase in interfering thoughts at the time of provocation. Acute tryptophan

  2. Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials.

    James F Curtin

    2008-04-01

    Full Text Available Regulatory T lymphocytes (Treg infiltrate human glioblastoma (GBM; are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61 has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients.Using a syngeneic intracrabial glioblastoma (GBM mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs present in tumors, draining lymph nodes and spleen and improved long-term survival (50% of mice survived >150 days. No improvement in survival was observed when Tregs were depleted 24 days after tumor implantation, suggesting that tumor burden is an important factor for determining efficacy of Treg depletion in clinical trials. In a T cell dependent model of brain tumor regression elicited by intratumoral delivery of adenoviral vectors (Ad expressing Fms-like Tyrosine Kinase 3 ligand (Flt3L and Herpes Simplex Type 1-Thymidine Kinase (TK with ganciclovir (GCV, we demonstrate that administration of PC61 24 days after tumor implantation (7 days after treatment inhibited T cell dependent tumor regression and long term survival. Further, depletion with PC61 completely inhibited clonal expansion of tumor antigen-specific T lymphocytes in response to the treatment.Our data demonstrate for the first time, that although Treg depletion inhibits the progression/eliminates GBM tumors, its efficacy is dependent on tumor burden. We conclude that this approach will be useful in a setting of minimal residual disease. Further, we also demonstrate that Treg depletion, using PC61 in combination with immunotherapy, inhibits clonal expansion of tumor antigen-specific T cells, suggesting that new, more

  3. Local depletion of glycogen with supramaximal exercise in human skeletal muscle fibres.

    Gejl, Kasper D; Ørtenblad, Niels; Andersson, Erik; Plomgaard, Peter; Holmberg, Hans-Christer; Nielsen, Joachim

    2017-05-01

    Glycogen is stored in local spatially distinct compartments within skeletal muscle fibres and is the main energy source during supramaximal exercise. Using quantitative electron microscopy, we show that supramaximal exercise induces a differential depletion of glycogen from these compartments and also demonstrate how this varies with fibre types. Repeated exercise alters this compartmentalized glycogen depletion. The results obtained in the present study help us understand the muscle metabolic dynamics of whole body repeated supramaximal exercise, and suggest that the muscle has a compartmentalized local adaptation to repeated exercise, which affects glycogen depletion. Skeletal muscle glycogen is heterogeneously distributed in three separated compartments (intramyofibrillar, intermyofibrillar and subsarcolemmal). Although only constituting 3-13% of the total glycogen volume, the availability of intramyofibrillar glycogen is of particular importance to muscle function. The present study aimed to investigate the depletion of these three subcellular glycogen compartments during repeated supramaximal exercise in elite athletes. Ten elite cross-country skiers (aged 25 ± 4 years, V̇O2 max : 65 ± 4 ml kg -1  min -1 ; mean ± SD) performed four ∼4 min supramaximal sprint time trials (STT 1-4) with 45 min of recovery. The subcellular glycogen volumes in musculus triceps brachii were quantified from electron microscopy images before and after both STT 1 and 4. During STT 1, the depletion of intramyofibrillar glycogen was higher in type 1 fibres [-52%; (-89:-15%)] than type 2 fibres [-15% (-52:22%)] (P = 0.02), whereas the depletion of intermyofibrillar glycogen [main effect: -19% (-33:0%), P = 0.006] and subsarcolemmal glycogen [main effect: -35% (-66:0%), P = 0.03] was similar between fibre types. By contrast, only intermyofibrillar glycogen volume was significantly reduced during STT 4, in both fibre types [main effect: -31% (-50:-11%), P = 0

  4. Influence of calcium depletion on iron-binding properties of milk.

    Mittal, V A; Ellis, A; Ye, A; Das, S; Singh, H

    2015-04-01

    We investigated the effects of calcium depletion on the binding of iron in milk. A weakly acidic cation-exchange resin was used to remove 3 different levels (18-22, 50-55, and 68-72%) of calcium from milk. Five levels of iron (5, 10, 15, 20, and 25 mM) were added to each of these calcium-depleted milks (CDM) and the resultant milks were analyzed for particle size, microstructure, and the distribution of protein and minerals between the colloidal and soluble phases. The depletion of calcium affected the distribution of protein and minerals in normal milk. Iron added to normal milk and low-CDM (~20% calcium depletion) bound mainly to the colloidal phase (material sedimented at 100,000 × g for 1 h at 20 °C), with little effect on the integrity of the casein micelles. Depletion of ~70% of the calcium from milk resulted in almost complete disintegration of the casein micelles, as indicated by all the protein remaining in the soluble phase upon ultracentrifugation. Addition of up to ~20 mM iron to high CDM resulted in the formation of small fibrous structures that remained in the soluble phase of milk. It appeared that the iron bound to soluble (nonsedimentable) caseins in high-CDM. We observed a decrease in the aqueous phosphorus content of all milks upon iron addition, irrespective of their calcium content. We considered the interaction between aqueous phosphorus and added iron to be responsible for the high iron-binding capacity of the proteins in milk. The soluble protein-iron complexes formed in high-CDM (~70% calcium depletion) could be used as an effective iron fortificant for a range of food products because of their good solubility characteristics. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. The Abiotic Depletion Potential: Background, Updates, and Future

    Lauran van Oers

    2016-03-01

    Full Text Available Depletion of abiotic resources is a much disputed impact category in life cycle assessment (LCA. The reason is that the problem can be defined in different ways. Furthermore, within a specified problem definition, many choices can still be made regarding which parameters to include in the characterization model and which data to use. This article gives an overview of the problem definition and the choices that have been made when defining the abiotic depletion potentials (ADPs for a characterization model for abiotic resource depletion in LCA. Updates of the ADPs since 2002 are also briefly discussed. Finally, some possible new developments of the impact category of abiotic resource depletion are suggested, such as redefining the depletion problem as a dilution problem. This means taking the reserves in the environment and the economy into account in the reserve parameter and using leakage from the economy, instead of extraction rate, as a dilution parameter.

  6. Aldosterone Response in Severe Hypokalemia and Volume Depletion: A Case Report and Review of the Recent Research

    Keiko Kai

    2016-01-01

    Full Text Available We report a case of severe hypokalemia and volume depletion complicated by chronic watery diarrhea resulting from chronic alcoholism in a 57-year-old man. Prompt replacement of normal saline with potassium chloride and cessation of alcohol intake resulted in a favorable outcome. We discuss the pathophysiology of the case, emphasizing the response of aldosterone in both hypokalemia and volume depletion, and provide a review of recent research.

  7. Depleted uranium hexafluoride management program : data compilation for the Paducah site

    Hartmann, H.

    2001-01-01

    This report is a compilation of data and analyses for the Paducah site, near Paducah, Kentucky. The data were collected and the analyses were done in support of the U.S. Department of Energy (DOE) 1999 Programmatic Environmental Impact Statement for Alternative Strategies for the Long-Term Management and Use of Depleted Uranium Hexafluoride (DOE/EIS-0269). The report describes the affected environment at the Paducah site and summarizes potential environmental impacts that could result from conducting the following depleted uranium hexafluoride (UF 6 ) activities at the site: continued cylinder storage, preparation of cylinders for shipment, conversion, and long-term storage. DOE's preferred alternative is to begin converting the depleted UF 6 inventory as soon as possible to either uranium oxide, uranium metal, or a combination of both, while allowing for use of as much of this inventory as possible

  8. Depleted uranium hexafluoride management program : data compilation for the Portsmouth site

    Hartmann, H. M.

    2001-01-01

    This report is a compilation of data and analyses for the Portsmouth site, near Portsmouth, Ohio. The data were collected and the analyses were done in support of the U.S. Department of Energy (DOE) 1999 Programmatic Environmental Impact Statement for Alternative Strategies for the Long-Term Management and Use of Depleted Uranium Hexafluoride (DOE/EIS-0269). The report describes the affected environment at the Portsmouth site and summarizes potential environmental impacts that could result from conducting the following depleted uranium hexafluoride (UF 6 ) management activities at the site: continued cylinder storage, preparation of cylinders for shipment, conversion, and long-term storage. DOE's preferred alternative is to begin converting the depleted UF 6 inventory as soon as possible to either uranium oxide, uranium metal, or a combination of both, while allowing for use of as much of this inventory as possible

  9. Depletion of selected polychlorodibenzodioxins and polychlorodibenzofurans in farmed trout exposed to contaminated feeds

    Brambilla, G.; Dellatte, E.; Fochi, I.; Iacovella, N.; Domenico, A. di [Dept. Food Safety and Animal Health, Ist. Superiore di Sanita, Rome (Italy)]|[Dept. Environment and Primary Health Care, Ist. Superiore di Sanita, Rome (Italy)

    2004-09-15

    Farmed fish can bioaccumulate persistent toxic substances when fed on animal-based fat feeds. This fact has recently prompted a re-evaluation of the overall toxicological risk associated with contamination levels recorded in farmed vs. wild salmons. The bioaccumulation of polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) in farmed trout has recently been described nevertheless, poor information is available about their depletion under controlled conditions. In this paper, the results of a 90-day depletion study in groups of trout exposed to three different levels of feed contamination for 30 days are reported. As a follow-up of a PCB depletion study the present paper aims at giving indications for risk management in fish farming practices, to prevent an unacceptable contamination of the produce intended for human consumption.

  10. Effect of polyamine depletion on DNA damage and repair following UV irradiation of HeLa cells

    Snyder, R.D.; Sunkara, P.S.

    1990-01-01

    Treatment of HeLa cells with the polyamine biosynthesis inhibitors, methylglyoxal bis(guanylhydrazone) (MGBG), difluoromethylornithine (DFMO) or a combination of the two, resulted in reduction in cellular polyamine levels. Analysis of UV light-induced DNA damage and repair in these polyamine depleted cells revealed distinct differences in the repair process relative to that seen in cells possessing a normal polyamine complement. Observed patterns of differential polyamine depletion by DFMO and MGBG, and partial reversal of repair inhibition by polyamine supplementation, suggest that polyamine depletion per se, rather than some secondary effect of inhibitor treatment, is responsible for the inhibition of repair. (author)

  11. Effect of polyamine depletion on DNA damage and repair following UV irradiation of HeLa cells

    Snyder, R.D.; Sunkara, P.S. (Merrell Dow Research Inst., Cincinnati, OH (USA))

    1990-09-01

    Treatment of HeLa cells with the polyamine biosynthesis inhibitors, methylglyoxal bis(guanylhydrazone) (MGBG), difluoromethylornithine (DFMO) or a combination of the two, resulted in reduction in cellular polyamine levels. Analysis of UV light-induced DNA damage and repair in these polyamine depleted cells revealed distinct differences in the repair process relative to that seen in cells possessing a normal polyamine complement. Observed patterns of differential polyamine depletion by DFMO and MGBG, and partial reversal of repair inhibition by polyamine supplementation, suggest that polyamine depletion per se, rather than some secondary effect of inhibitor treatment, is responsible for the inhibition of repair. (author).

  12. Formation of M23C6-type precipitates and chromium-depleted zones in austenite stainless steel

    Kaneko, Kenji; Fukunaga, Tatsuya; Yamada, Kazuhiro; Nakada, Nobuo; Kikuchi, Masao; Saghi, Zineb; Barnard, Jon S.; Midgley, Paul A.

    2011-01-01

    Graphical abstract: Precipitate formation during the in situ annealing experiment at 650 o C. -- Formation of M 23 C 6 carbides and chromium-depleted zones in commercially available type 304L stainless steel were investigated by in situ transmission electron microscopy and analytical transmission electron microscopy. It was found that each individual small M 23 C 6 carbide starts to grow with a clear orientation relationship with the matrix, and film-like carbide was subsequently observed at the interfaces with asymmetric Cr-depleted zones. From these experimental results, a model describing the precipitation of M 23 C 6 and the formation of the Cr-depleted zone was proposed.

  13. Human podocyte depletion in association with older age and hypertension.

    Puelles, Victor G; Cullen-McEwen, Luise A; Taylor, Georgina E; Li, Jinhua; Hughson, Michael D; Kerr, Peter G; Hoy, Wendy E; Bertram, John F

    2016-04-01

    Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease. Copyright © 2016 the American Physiological Society.

  14. Interstellar Silicon Depletion and the Ultraviolet Extinction

    Mishra, Ajay; Li, Aigen

    2018-01-01

    Spinning small silicate grains were recently invoked to account for the Galactic foreground anomalous microwave emission. These grains, if present, will absorb starlight in the far ultraviolet (UV). There is also renewed interest in attributing the enigmatic 2175 Å interstellar extinction bump to small silicates. To probe the role of silicon in the UV extinction, we explore the relations between the amount of silicon required to be locked up in silicates [Si/H]dust and the 2175 Å bump or the far-UV extinction rise, based on an analysis of the extinction curves along 46 Galactic sightlines for which the gas-phase silicon abundance [Si/H]gas is known. We derive [Si/H]dust either from [Si/H]ISM - [Si/H]gas or from the Kramers- Kronig relation which relates the wavelength-integrated extinction to the total dust volume, where [Si/H]ISM is the interstellar silicon reference abundance and taken to be that of proto-Sun or B stars. We also derive [Si/H]dust from fi�tting the observed extinction curves with a mixture of amorphous silicates and graphitic grains. We fi�nd that in all three cases [Si/H]dust shows no correlation with the 2175 Å bump, while the carbon depletion [C/H]dust tends to correlate with the 2175 Å bump. This supports carbon grains instead of silicates as the possible carrier of the 2175 Å bump. We also �find that neither [Si/H]dust nor [C/H]dust alone correlates with the far-UV extinction, suggesting that the far-UV extinction is a combined effect of small carbon grains and silicates.

  15. Clinical case of Mitochondrial DNA Depletion

    A. V. Degtyareva

    2017-01-01

    Full Text Available The article reports clinical case of early neonatal manifestation of a rare genetic disease – mitochondrial DNA depletion syndrome, confirmed in laboratory in Russia. Mutations of FBXL4, which encodes an orphan mitochondrial F-box protein, involved in the maintenance of mitochondrial DNA (mtDNA, ultimately leading to disruption of mtDNA replication and decreased activity of mitochondrial respiratory chain complexes. It’s a reason of abnormalities in clinically affected tissues, most of all the muscular system and the brain. In our case hydronephrosis on the right, subependimal cysts of the brain, partial intestinal obstruction accompanied by polyhydramnios were diagnosed antenatal. Baby’s condition at birth was satisfactory and worsened dramatically towards the end of the first day of life. Clinical presentation includes sepsis-like symptom complex, neonatal depression, muscular hypotonia, persistent decompensated lactic acidosis, increase in the concentration of mitochondrial markers in blood plasma and urine, and changes in the basal ganglia of the brain. Imaging of the brain by magnetic resonance imaging (MRI demonstrated global volume loss particularly the subcortical and periventricular white matter with significant abnormal signal in bilateral basal ganglia and brainstem with associated delayed myelination. Differential diagnosis was carried out with hereditary diseases that occur as a «sepsis-like» symptom complex, accompanied by lactic acidosis: a group of metabolic disorders of amino acids, organic acids, β-oxidation defects of fatty acids, respiratory mitochondrial chain disorders and glycogen storage disease. The diagnosis was confirmed after sequencing analysis of 62 mytochondrial genes by NGS (Next Generation Sequencing. Reported disease has an unfavorable prognosis, however, accurate diagnosis is very important for genetic counseling and helps prevent the re-birth of a sick child in the family.

  16. Depletion of the AP-1 repressor JDP2 induces cell death similar to apoptosis

    Lerdrup, Mads; Holmberg, Christian Henrik; Dietrich, Nikolaj

    2005-01-01

    JDP2 is a ubiquitously expressed nuclear protein that efficiently represses the activity of the transcription factor AP-1. Thus far, all studies of JDP2 function have relied on the ectopic expression of the protein. In this study, we use a different approach: depletion of JDP2 from cells. Specific...... depletion of JDP2 resulted in p53-independent cell death that resembles apoptosis and was evident at 72 h. The death mechanism was caspase dependent as the cells could be rescued by treatment with caspase inhibitor zVAD. Our studies suggest that JDP2 functions as a general survival protein, not only...

  17. Assessment of the environmental radioactive contamination levels by depleted uranium after NATO aggression on FR Yugoslavia

    Pavlovic, S.; Pavlovic, R.; Markovic, S; Plecas, I.

    2001-01-01

    During NATO aggression on FR Yugoslavia various ammunition have been used, some of them for the first time. Among others, 30 mm bullets with depleted uranium (DU) penetrators have been used. Radioactivity contamination surveys have started during the war due to indications that DU is used in cruise missiles. Besides that, there were a lot of radioactivity analysis of food, drinking water etc. Some of the obtained results are presented in this paper. Depleted uranium ammunition can permanently contaminate environment and so produce effects on population. Relation of the international radiation and environmental protection standards and contamination levels are discussed as well. (author)

  18. Interconnections between the depletion of minerals and fuels: The case of copper production in the United States

    Cleveland, C.J.; Ruth, M.

    1996-01-01

    Analyses of the relationship between natural resources and economic development frequently neglect the interdependency between the depletion of one resource and the depletion of other resources. Of particular interest is how energy resource extraction is affected by the depletion of nonfuel minerals due to the important role of energy in upgrading minerals to a useful state. Although this relationship has been described in theoretical terms, there is little detailed empirical support. To quantify the relationship between the depletion of mineral and fuel resources, the authors develop a dynamic model that is based on physical, technological, and economic data. The analysis quantifies the relationship between the depletion of copper in the US and the depletion of fossil fuel and uranium energy resources stimulated by the increase in demand for refined copper that is forecast for the next 50 years. The model calculates the increase in the energy cost of extracting energy due to the depletion of copper. The results of the model indicate that this feedback is significant. The energy cost of producing a refined ton of copper increases 23% over the 50-year simulation period due to the diminution in ore grade and diminishing returns to technical change. The increase in the energy cost for copper increases the production of fossil and uranium fuels, which diminishes their quality and increases their energy cost

  19. Dietary arginine depletion reduces depressive-like responses in male, but not female, mice.

    Workman, Joanna L; Weber, Michael D; Nelson, Randy J

    2011-09-30

    Previous behavioral studies have manipulated nitric oxide (NO) production either by pharmacological inhibition of its synthetic enzyme, nitric oxide synthase (NOS), or by deletion of the genes that code for NOS. However manipulation of dietary intake of the NO precursor, L-arginine, has been understudied in regard to behavioral regulation. L-Arginine is a common amino acid present in many mammalian diets and is essential during development. In the brain L-arginine is converted into NO and citrulline by the enzyme, neuronal NOS (nNOS). In Experiment 1, paired mice were fed a diet comprised either of an L-arginine-depleted, L-arginine-supplemented, or standard level of L-arginine during pregnancy. Offspring were continuously fed the same diets and were tested in adulthood in elevated plus maze, forced swim, and resident-intruder aggression tests. L-Arginine depletion reduced depressive-like responses in male, but not female, mice and failed to significantly alter anxiety-like or aggressive behaviors. Arginine depletion throughout life reduced body mass overall and eliminated the sex difference in body mass. Additionally, arginine depletion significantly increased corticosterone concentrations, which negatively correlated with time spent floating. In Experiment 2, adult mice were fed arginine-defined diets two weeks prior to and during behavioral testing, and again tested in the aforementioned tests. Arginine depletion reduced depressive-like responses in the forced swim test, but did not alter behavior in the elevated plus maze or the resident intruder aggression test. Corticosterone concentrations were not altered by arginine diet manipulation in adulthood. These results indicate that arginine depletion throughout development, as well as during a discrete period during adulthood ameliorates depressive-like responses. These results may yield new insights into the etiology and sex differences of depression. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Environmental fate of depleted uranium at three sites contaminated during the balkan conflict

    Radenkovic, M.; Joksic, J.; Todorovic, D.; Kovacevic, M.

    2006-01-01

    A study on depleted uranium fate in the sites contaminated during the 1999 war conflict in Serbia was conducted in phases until the clean up activities were completed. The ammunition remains found at the locations in the surface soil were collected in the first phase during the radiation survey of the affected areas. The most of depleted uranium penetrators left buried deep into the ground exposed to the weathering and corrosion processes. The contamination level in the air, water, soil and bio -indicators was controlled all the time by routine gamma and alpha spectrometry measurements. Depleted uranium migration was studied through the soil profile surrounding the penetrator during the 2001 at the Bratoselce location showing the contamination level fall to the 1% of its value at approximately 15 cm distance to the source. The samples taken from the soil layers at different distances in the profile are subjected to a modified Tessiers five-step sequential extraction procedure. The uranium and heavy metals contents were determined in the obtained fractions. Results have specified carbonates and iron hydrous-oxides as the most probable substrates for uranium physical/chemical associations formed in the soil for the time elapsed. A very strong dependence of substrate onto contamination level was found. The correlation of uranium and other heavy metals was obtained. The 234 U/ 238 U and 235 U/ 238 U ratios are determined in extracts by alpha spectrometry after appropriate radiochemical separation procedure and thin alpha sources electroplating. The analysis has shown the share of depleted in total uranium content in exchangeable, carbonate, hydrous or crystalline iron/manganese, organic and residue phases indicating the bioavailability of depleted uranium present in the soil. The results are discussed related to detailed geochemical analysis of the particular soil type common for this region. Depleted uranium content in soil samples taken at the locations after the