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Sample records for induces phosphatidylserine externalization

  1. MRP-1 and BCRP Promote the Externalization of Phosphatidylserine in Oxalate-treated Renal Epithelial Cells: Implications for Calcium Oxalate Urolithiasis.

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    Li, YiFu; Yu, ShiLiang; Gan, XiuGuo; Zhang, Ze; Wang, Yan; Wang, YingWei; An, RuiHua

    2017-09-01

    To investigate the possible involvement of multidrug resistance-associated protein 1 (MRP-1) and breast cancer resistance protein (BCRP) in the oxalate-induced redistribution of phosphatidylserine (PS) in renal epithelial cell membranes. A western blot analysis was used to examine the MRP-1 and BCRP expression levels. Surface-expressed PS was detected by the annexin V-binding assay. The cell-permeable fluorogenic probe 2,7-dichlorofluorescein diacetate was used to measure the intracellular reactive oxygen species (ROS) level. A rat model of hyperoxaluria was obtained using 0.5% ethylene glycol and 1.0% ammonium chloride. In addition, certain animals received verapamil (50 mg/kg body weight), which is a common inhibitor of MRP-1 and BCRP. The degree of nephrolithiasis was assessed histomorphometrically using sections stained by Pizzolato method and by measuring the calcium oxalate crystal content in the renal tissue. Oxalate produced a concentration-dependent increase in the synthesis of MRP-1 and BCRP. Treatment with MK571 and Ko143 (MRP-1- and BCRP-specific inhibitors, respectively) significantly attenuated the oxalate-induced PS externalization. Adding the antioxidant N-acetyl-l-cysteine significantly reduced MRP-1 and BCRP expression. In vivo, markedly decreased nephrocalcinosis was observed compared with that in the rat model of hyperoxaluria without verapamil treatment. Oxalate induces the upregulation of MRP-1 and BCRP, which act as phospholipid floppases causing PS externalization in the renal epithelial cell membrane. The process is mediated by intracellular ROS production. The ROS-mediated increase in the synthesis of MRP-1 and BCRP can play an important role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells.

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    Semeraro, F; Ammollo, C T; Esmon, N L; Esmon, C T

    2014-10-01

    Extracellular histones exert part of their prothrombotic activity through the stimulation of blood cells. Besides platelets, histones can bind to red blood cells (RBCs), which are important contributors to thrombogenesis, but little is known about the functional consequences of this interaction. To evaluate the effect of histones on the procoagulant potential of human RBCs with particular regard to the expression of surface phosphatidylserine (PS). PS exposure on human RBCs treated with a natural mixture of histones or recombinant individual histones was evaluated with fluorescein isothiocyanate-annexin-V binding and measured with flow cytometry. Calcium influx in RBCs loaded with the calcium-sensitive fluorophore Fluo-4 AM was assessed with flow cytometry. The procoagulant potential of histone-treated RBCs was evaluated with a purified prothrombinase assay and a one-stage plasma recalcification clotting test. Natural histones induced PS exposure on RBCs in a dose-dependent manner, and neutralization or cleavage of histones by heparin or activated protein C, respectively, abolished PS externalization. H4 was mainly responsible for the stimulating activity of histones, whereas the other subtypes were almost ineffective. Similarly, natural histones and H4 induced influx of calcium into RBCs, whereas the other individual histones did not. Histone-induced exposure of PS on RBCs translated into increased prothrombinase complex-mediated prothrombin activation and accelerated fibrin formation in plasma. Histones induce RBCs to express a procoagulant phenotype through the externalization of PS. This finding provides new insights into the prothrombotic activity of extracellular histones. © 2014 International Society on Thrombosis and Haemostasis.

  3. Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. I. Inhibition of de novo phosphatidylserine biosynthesis by exogenous phosphatidylserine and its efficient incorporation

    International Nuclear Information System (INIS)

    Nishijima, M.; Kuge, O.; Akamatsu, Y.

    1986-01-01

    The effect of phosphatidylserine exogenously added to the medium on de novo biosynthesis of phosphatidylserine was investigated in cultured Chinese hamster ovary cells. When cells were cultured for several generations in medium supplemented with phosphatidylserine and 32 Pi, the incorporation of 32 Pi into cellular phosphatidylserine was remarkably inhibited, the degree of inhibition being dependent upon the concentration of added phosphatidylserine. 32 Pi uptake into cellular phosphatidylethanolamine was also partly reduced by the addition of exogenous phosphatidylserine, consistent with the idea that phosphatidylethanolamine is biosynthesized via decarboxylation of phosphatidylserine. However, incorporation of 32 Pi into phosphatidylcholine, sphingomyelin, and phosphatidylinositol was not significantly affected. In contrast, the addition of either phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, or phosphatidylinositol to the medium did not inhibit endogenous biosynthesis of the corresponding phospholipid. Radiochemical and chemical analyses of the cellular phospholipid composition revealed that phosphatidylserine in cells grown with 80 microM phosphatidylserine was almost entirely derived from the added phospholipid. Phosphatidylserine uptake was also directly determined by using [ 3 H]serine-labeled phospholipid. Pulse and pulse-chase experiments with L-[U- 14 C] serine showed that when cells were cultured with 80 microM phosphatidylserine, the rate of synthesis of phosphatidylserine was reduced 3-5-fold. Enzyme assaying of extracts prepared from cells grown with and without phosphatidylserine indicated that the inhibition of de novo phosphatidylserine biosynthesis by the added phosphatidylserine appeared not to be caused by a reduction in the level of the enzyme involved in the base-exchange reaction between phospholipids and serine

  4. Sensing Phosphatidylserine in Cellular Membranes

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    Jason G. Kay

    2011-01-01

    Full Text Available Phosphatidylserine, a phospholipid with a negatively charged head-group, is an important constituent of eukaryotic cellular membranes. On the plasma membrane, rather than being evenly distributed, phosphatidylserine is found preferentially in the inner leaflet. Disruption of this asymmetry, leading to the appearance of phosphatidylserine on the surface of the cell, is known to play a central role in both apoptosis and blood clotting. Despite its importance, comparatively little is known about phosphatidylserine in cells: its precise subcellular localization, transmembrane topology and intracellular dynamics are poorly characterized. The recent development of new, genetically-encoded probes able to detect phosphatidylserine within live cells, however, is leading to a more in-depth understanding of the biology of this phospholipid. This review aims to give an overview of the current methods for phosphatidylserine detection within cells, and some of the recent realizations derived from their use.

  5. Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes.

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    Irma Pujol-Autonell

    Full Text Available The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes.To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes.A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides.We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion.We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for

  6. Mercury-Induced Externalization of Phosphatidylserine and Caspase 3 Activation in Human Liver Carcinoma (HepG2 Cells

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    Paul B. Tchounwou

    2006-03-01

    Full Text Available Apoptosis arises from the active initiation and propagation of a series of highly orchestrated specific biochemical events leading to the demise of the cell. It is a normal physiological process, which occurs during embryonic development as well as in the maintenance of tissue homeostasis. Diverse groups of molecules are involved in the apoptosis pathway and it functions as a mechanism to eliminate unwanted or irreparably damaged cells. However, inappropriate induction of apoptosis by environmental agents has broad ranging pathologic implications and has been associated with several diseases including cancer. The toxicity of several heavy metals such as mercury has been attributed to their high affinity to sulfhydryl groups of proteins and enzymes, and their ability to disrupt cell cycle progression and/or apoptosis in various tissues. The aim of this study was to assess the potential for mercury to induce early and late-stage apoptosis in human liver carcinoma (HepG2 cells. The Annexin-V and Caspase 3 assays were performed by flow cytometric analysis to determine the extent of phosphatidylserine externalization and Caspase 3 activation in mercury-treated HepG2 cells. Cells were exposed to mercury for 10 and 48 hours respectively at doses of 0, 1, 2, and 3 μg/mL based on previous cytotoxicity results in our laboratory indicating an LD50 of 3.5 ± 0.6 μg/mL for mercury in HepG2 cells. The study data indicated a dose response relationship between mercury exposure and the degree of early and late-stage apoptosis in HepG2 cells. The percentages of cells undergoing early apoptosis were 0.03 ± 0.03%, 5.19 ± 0.04%, 6.36 ± 0.04%, and 8.84 ± 0.02% for 0, 1, 2, and 3 μg/mL of mercury respectively, indicating a gradual increase in apoptotic cells with increasing doses of mercury. The percentages of Caspase 3 positive cells undergoing late apoptosis were 3.58 ± 0.03%, 17.06 ± 0

  7. Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. II. Isolation and characterization of phosphatidylserine auxotrophs

    International Nuclear Information System (INIS)

    Kuge, O.; Nishijima, M.; Akamatsu, Y.

    1986-01-01

    Chinese hamster ovary (CHO) cell mutants that required exogenously added phosphatidylserine for cell growth were isolated by using the replica technique with polyester cloth, and three such mutants were characterized. Labeling experiments on intact cells with 32 Pi and L-[U- 14 C]serine revealed that a phosphatidylserine auxotroph, designated as PSA-3, was strikingly defective in phosphatidylserine biosynthesis. When cells were grown for 2 days without phosphatidylserine, the phosphatidylserine content of PSA-3 was about one-third of that of the parent. In extracts of the mutant, the enzymatic activity of the base-exchange reaction of phospholipids with serine producing phosphatidylserine was reduced to 33% of that in the parent; in addition, the activities of base-exchange reactions of phospholipids with choline and ethanolamine in the mutant were also reduced to 1 and 45% of those in the parent, respectively. Furthermore, it was demonstrated that the serine-exchange activity in the parent was inhibited approximately 60% when choline was added to the reaction mixture whereas that in the mutant was not significantly affected. From the results presented here, we conclude the following. There are at least two kinds of serine-exchange enzymes in CHO cells; one (serine-exchange enzyme I) can catalyze the base-exchange reactions of phospholipids with serine, choline, and ethanolamine while the other (serine-exchange enzyme II) does not use the choline as a substrate. Serine-exchange enzyme I, in which mutant PSA-3 is defective, plays a major role in phosphatidylserine biosynthesis in CHO cells. Serine-exchange enzyme I is essential for the growth of CHO cells

  8. Fertilization Induces a Transient Exposure of Phosphatidylserine in Mouse Eggs

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    Curia, Claudio A.; Ernesto, Juan I.; Stein, Paula; Busso, Dolores; Schultz, Richard M.; Cuasnicu, Patricia S.; Cohen, Débora J.

    2013-01-01

    Phosphatidylserine (PS) is normally localized to the inner leaflet of the plasma membrane and the requirement of PS translocation to the outer leaflet in cellular processes other than apoptosis has been demonstrated recently. In this work we investigated the occurrence of PS mobilization in mouse eggs, which express flippase Atp8a1 and scramblases Plscr1 and 3, as determined by RT-PCR; these enzyme are responsible for PS distribution in cell membranes. We find a dramatic increase in binding of flouresceinated-Annexin-V, which specifically binds to PS, following fertilization or parthenogenetic activation induced by SrCl2 treatment. This increase was not observed when eggs were first treated with BAPTA-AM, indicating that an increase in intracellular Ca2+ concentration was required for PS exposure. Fluorescence was observed over the entire egg surface with the exception of the regions overlying the meiotic spindle and sperm entry site. PS exposure was also observed in activated eggs obtained from CaMKIIγ null females, which are unable to exit metaphase II arrest despite displaying Ca2+ spikes. In contrast, PS exposure was not observed in TPEN-activated eggs, which exit metaphase II arrest in the absence of Ca2+ release. PS exposure was also observed when eggs were activated with ethanol but not with a Ca2+ ionophore, suggesting that the Ca2+ source and concentration are relevant for PS exposure. Last, treatment with cytochalasin D, which disrupts microfilaments, or jasplakinolide, which stabilizes microfilaments, prior to egg activation showed that PS externalization is an actin-dependent process. Thus, the Ca2+ rise during egg activation results in a transient exposure of PS in fertilized eggs that is not associated with apoptosis. PMID:23951277

  9. Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy

    International Nuclear Information System (INIS)

    Ran, Sophia; Thorpe, Philip E.

    2002-01-01

    Purpose: (1) To determine whether exposure of phosphatidylserine (PS) occurs on vascular endothelium in solid tumors in mice. (2) To determine whether PS exposure can be induced on viable endothelial cells in tissue culture by conditions present in the tumor microenvironment. Methods and Materials: Externalized PS in vivo was detected by injecting mice with a monoclonal anti-PS antibody and examining frozen sections of tumors and normal tissues for anti-PS antibody bound to vascular endothelium. Apoptotic cells were identified by anti-active caspase-3 antibody or by TUNEL assay. PS exposure on cultured endothelial cells was determined by 125 I-annexin V binding. Results: Anti-PS antibody bound specifically to vascular endothelium in six tumor models. The percentage of PS-positive vessels ranged from 4% to 40% in different tumor types. Vascular endothelium in normal organs was unstained. Very few tumor vessels expressed apoptotic markers. Hypoxia/reoxygenation, acidity, inflammatory cytokines, thrombin, or hydrogen peroxide induced PS exposure on cultured endothelial cells without causing loss of viability. Conclusions: Vascular endothelial cells in tumors, but not in normal tissues, externalize PS. PS exposure might be induced by tumor-associated oxidative stress and activating cytokines. PS is an abundant and accessible marker of tumor vasculature and could be used for tumor imaging and therapy

  10. Glu- and Lys-forms of plasminogen differentially affect phosphatidylserine exposure on the platelet surface

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    D. D. Zhernossekov

    2017-04-01

    Full Text Available Plasminogen/plasmin system is known for its ability to support hemostatic balance of blood. However, plasminogen may be considered as an adhesive ligand and in this way could affect the functioning of blood cells. We showed that exogenous Lys-plasminogen, but not its Glu-form, inhibited platelet aggregation and suppressed platelet α-granule secretion. The aim of this work was to investigate the influence of Glu- and Lys-form of plasminogen on the formation of platelet procoagulant surface using phosphatidylserine exposure as a marker. Human platelets were obtained from human platelet-rich plasma (donors were healthy volunteers, men aged 30-40 years by gel-filtration on Sepharose 2B. Phosphatidylserine exposure on the platelet surface was evaluated by flow cytometry with FITC-conjugated annexin A5. Glu- and Lys-plasminogen have different impact on the platelet functioning. Exogenous Lys-plasminogen has no significant effect on phosphatidylserine exposure, while Glu-plasminogen increases phosphatidylserine exposure on the surface of thrombin- and collagen-activated human platelets. Glu-plasminogen can be considered as a co-stimulator of agonist-induced platelet secretion and procoagulant surface formation. Meanwhile effects of Lys-plasminogen are probably directed at platelet-platelet interactions and not related to agonist-stimulated pro-apoptotic changes. The observed different effects of Glu- and Lys-plasminogen on phosphatidylserine exposure can be explained by their structural peculiarities.

  11. Identification of phosphatidylserine as a ligand for the CD300a immunoreceptor

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    Nakahashi-Oda, Chigusa; Tahara-Hanaoka, Satoko; Honda, Shin-ichiro [Department of Immunology, Division of Biomedical Sciences, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Japan Science and Technology Agency, CREST, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Shibuya, Kazuko [Department of Immunology, Division of Biomedical Sciences, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Shibuya, Akira, E-mail: ashibuya@md.tsukuba.ac.jp [Department of Immunology, Division of Biomedical Sciences, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Japan Science and Technology Agency, CREST, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer CD300a is a new phosphatidylserine receptor expressed on myeloid cells. Black-Right-Pointing-Pointer Phosphatidylserine delivers a signal for recruitment of SHP-1 by CD300a in mast cells. Black-Right-Pointing-Pointer The CD300a/phosphatidylserine interaction is blocked by MFG-E8 or anti-CD300a antibody. -- Abstract: CD300a is a member of CD300 family molecules consisting of seven genes on human chromosome 17 and nine genes in mouse chromosome 11. CD300a has a long cytoplasmic region containing the consensus immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence. Upon crosslinking with antibodies against CD300a, CD300a mediates an inhibitory signal in myeloid cells. However, the ligand for CD300a has not been identified and the physiological role of CD300a remained unclear. Here, we demonstrate that the chimeric fusion protein of CD300a extracellular domain with the Fc portion of human IgG specifically bound phosphatidylserine (PS), which is exposed on the outer leaflet of the plasma membrane of apoptotic cells. PS binding to CD300a induced SHP-1 recruitment by CD300a in mast cells in response to LPS. These results indicated that CD300a is a new PS receptor.

  12. Temporal Changes in Phosphatidylserine Expression and Glucose Metabolism after Myocardial Infarction: An in Vivo Imaging Study in Mice

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    Sebastian Lehner

    2012-11-01

    Full Text Available Positron emission tomography (PET for in vivo monitoring of phosphatidylserine externalization and glucose metabolism can potentially provide early predictors of outcome of cardioprotective therapies after myocardial infarction. We performed serial [68Ga]annexin A5 PET (annexin-PET and [18F]fluorodeoxyglucose PET (FDG-PET after myocardial infarction to determine the time of peak phosphatidylserine externalization in relation to impaired glucose metabolism in infracted tissue. Annexin- and FDG-PET recordings were obtained in female (C57BL6/N mice on days 1 to 4 after ligation of the left anterior descending (LAD artery. [68Ga]annexin A5 uptake (%ID/g in the LAD artery territory increased from 1.7 ± 1.1 on day 1 to 5.0 ± 3.3 on day 2 and then declined to 2.0 ± 1.4 on day 3 (p = .047 vs day 2 and 1.6 ± 1.4 on day 4 (p = .014 vs day 2. These results matched apoptosis rates as estimated by autoradiography and fluorescein staining. FDG uptake (%ID/g declined from 28 ± 14 on day 1 to 14 ± 3.5 on day 4 (p < .0001 vs day 1. Whereas FDG-PET revealed continuous loss of cell viability after permanent LAD artery occlusion, annexin-PET indicated peak phosphatidylserine expression at day 2, which might be the optimal time point for therapy monitoring.

  13. Brain cortex phosphatidylserine inhibits phosphatidylinositol turnover in rat anterior pituitary glands

    International Nuclear Information System (INIS)

    Bonetti, A.C.; Canonico, P.L.; MacLeod, R.M.

    1985-01-01

    The in vitro effect of bovine brain cortex phosphatidylserine on 32 Pi incorporation into phosphatidylinositol, phosphatidylcholine, and phosphatidylethanolamine of rat anterior pituitary glands was studied. Phosphatidylserine (0.1 to 66.6 microM) decreased the incorporation of 32 Pi into phosphatidylinositol, but not phosphatidylcholine or phosphatidylethanolamine, in a concentration-related manner. The inhibitory effect of phosphatidylinositol was similar to that of dopamine in the same experimental conditions. The combined effects of submaximal concentrations of dopamine and phosphatidylserine elicited an apparently additive inhibitory effect on phosphatidylinositol synthesis. The inhibitory effect of phosphatidylserine was completely reversed by haloperidol and sulpiride and only partially by pimozide, antidopaminergic agents which per se do not affect phosphatidylinositol synthesis. The stimulatory effect of TRH to increase 32 Pi incorporation into phosphatidylinositol was decreased by phosphatidylserine. These observations suggest that the decrease in prolactin release in the presence of phosphatidylserine may be evoked through a dopaminergic mechanism

  14. Toxoplasma gondii exposes phosphatidylserine inducing a TGF-β1 autocrine effect orchestrating macrophage evasion

    International Nuclear Information System (INIS)

    Seabra, Sergio H.; Souza, Wanderley de; Matta, Renato A. da

    2004-01-01

    Toxoplasmosis is a worldwide disease caused by Toxoplasma gondii. Activated macrophages control T. gondii growth by nitric oxide (NO) production. However, T. gondii active invasion inhibits NO production, allowing parasite persistence. Here we show that the mechanism used by T. gondii to inhibit NO production persisting in activated macrophages depends on phosphatidylserine (PS) exposure. Masking PS with annexin-V on parasites or activated macrophages abolished NO production inhibition and parasite persistence. NO production inhibition depended on a transforming growth factor-β 1 (TGF-β 1 ) autocrine effect confirmed by the expression of Smad 2 and 3 in infected macrophages. TGF-β 1 led to inducible nitric oxide synthase (iNOS) degradation, actin filament (F-actin) depolymerization, and lack of nuclear factor-κB (NF-κB) in the nucleus. All these features were reverted by TGF-β 1 neutralizing antibody treatment. Thus, T. gondii mimics the evasion mechanism used by Leishmania amazonensis and also the anti-inflammatory response evoked by apoptotic cells

  15. Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages

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    Ji Wang

    2016-06-01

    Full Text Available Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%–8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions.

  16. Cryopreservation and xenografting of human ovarian fragments: medulla decreases the phosphatidylserine translocation rate

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    Vladimir Isachenko

    2016-11-01

    Full Text Available Abstract Background Phosphatidylserine is the phospholipid component which plays a key role in cell cycle signaling, specifically in regards to necrosis and apoptosis. When a cell affected by some negative factors, phosphatidylserine is no longer restricted to the intracellular side of membrane and can be translocated to the extracellular surface of the cell. Cryopreservation can induce translocation of phosphatidylserine in response to hypoxia, increasing intracellular Ca2+, osmotic disruption of cellular membranes, generation of reactive oxygen species and lipid peroxidation. As such the aim of this study was to test the level of phosphatidylserine translocation in frozen human medulla-contained and medulla-free ovarian tissue fragments. Methods Ovarian fragments from twelve patients were divided into small pieces of two types, medulla-free cortex (Group 1, n = 42, 1.5–3.0 × 1.5–3.0 × 0.5–0.8 mm and cortex with medulla (Group 2, n = 42, 1.5–3.0 × 1.5–3.0 × 1.5–2.0 mm, pre-cooled after operative removal to 5 °C for 24 h and then conventionally frozen with 6 % dimethyl sulfoxide, 6 % ethylene glycol and 0.15 M sucrose in standard 5-ml cryo-vials. After thawing at +100 °C and step-wise removal of cryoprotectants in 0.5 M sucrose, ovarian pieces were xenografted to SCID mice for 45 days. The efficacy of tissues cryopreservation, taking into account the presence or absence of medulla, was evaluated by the development of follicles (histology with hematoxylin-eosin and through the intensity of translocation of phosphatidylserine (FACS with FITC-Annexin V and Propidium Iodide. Results For Groups 1 and 2, the mean densities of follicles per 1 mm3 were 9.8, and 9.0, respectively. In these groups, 90 and 90 % preantral follicles appeared morphologically normal. However, FACS analysis showed a significantly decreased intensity of translocation of phosphatidylserine (FITC-Annexin V positive after

  17. Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome.

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    Sousa, Sérgio B; Jenkins, Dagan; Chanudet, Estelle; Tasseva, Guergana; Ishida, Miho; Anderson, Glenn; Docker, James; Ryten, Mina; Sa, Joaquim; Saraiva, Jorge M; Barnicoat, Angela; Scott, Richard; Calder, Alistair; Wattanasirichaigoon, Duangrurdee; Chrzanowska, Krystyna; Simandlová, Martina; Van Maldergem, Lionel; Stanier, Philip; Beales, Philip L; Vance, Jean E; Moore, Gudrun E

    2014-01-01

    Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism.

  18. Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. III. Genetic evidence for utilization of phosphatidylcholine and phosphatidylethanolamine as precursors

    International Nuclear Information System (INIS)

    Kuge, O.; Nishijima, M.; Akamatsu, Y.

    1986-01-01

    We reported that Chinese hamster ovary (CHO) cells contain two different serine-exchange enzymes (I and II) which catalyze the base-exchange reaction of phospholipid(s) with serine and that a phosphatidylserine-requiring mutant (strain PSA-3) of CHO cells is defective in serine-exchange enzyme I and lacks the ability to synthesize phosphatidylserine. In this study, we examined precursor phospholipids for phosphatidylserine biosynthesis in CHO cells. When mutant PSA-3 and parent (CHO-K1) cells were cultured with [ 32 P]phosphatidylcholine, phosphatidylserine in the parent accumulated radioactivity while that in the mutant was not labeled significantly. On the contrary, when cultured with [ 32 P]phosphatidylethanolamine, the mutant incorporated the label into phosphatidylserine more efficiently than the parent. Furthermore, we found that mutant PSA-3 grew normally in growth medium supplemented with 30 microM phosphatidylethanolamine as well as phosphatidylserine and that the biosynthesis of phosphatidylserine in the mutant was normal when cells were cultured in the presence of exogenous phosphatidylethanolamine. The simplest interpretation of these findings is that phosphatidylserine in CHO cells is biosynthesized through the following sequential reactions: phosphatidylcholine----phosphatidylserine----phosphatidylethanolamine--- - phosphatidylserine. The three reactions are catalyzed by serine-exchange enzyme I, phosphatidylserine decarboxylase, and serine-exchange enzyme II, respectively

  19. Specific membrane binding of factor VIII is mediated by O-phospho-L-serine, a moiety of phosphatidylserine.

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    Gilbert, G E; Drinkwater, D

    1993-09-21

    Phosphatidylserine, a negatively charged lipid, is exposed on the platelet membrane following cell stimulation, correlating with the expression of factor VIII receptors. We have explored the importance of the negative electrostatic potential of phosphatidylserine vs chemical moieties of phosphatidylserine for specific membrane binding of factor VIII. Fluorescein-labeled factor VIII bound to membranes containing 15% phosphatidic acid, a negatively charged phospholipid, with low affinity compared to phosphatidylserine-containing membranes. Binding was not specific as it was inhibited by other proteins in plasma. Factor VIII bound to membranes containing 10% phosphatidylserine in spite of a varying net charge provided by 0-15% stearylamine, a positively charged lipid. The soluble phosphatidylserine moiety, O-phospho-L-serine, inhibited factor VIII binding to phosphatidylserine-containing membranes with a Ki of 20 mM, but the stereoisomer, O-phospho-D-serine, was 5-fold less effective. Furthermore, binding of factor VIII to membranes containing synthetic phosphatidyl-D-serine was 5-fold less than binding to membranes containing phosphatidyl-L-serine. Membranes containing synthetic phosphatidyl-L-homoserine, differing from phosphatidylserine by a single methylene, supported high-affinity binding, but it was not specific as factor VIII was displaced by other plasma proteins. O-Phospho-L-serine also inhibited the binding of factor VIII to platelet-derived microparticles with a Ki of 20 mM, and the stereoisomer was 4-fold less effective. These results indicate that membrane binding of factor VIII is mediated by a stereoselective recognition O-phospho-L-serine of phosphatidylserine and that negative electrostatic potential is of lesser importance.

  20. Stimulation of erythrocyte phosphatidylserine exposure by mercury ions

    International Nuclear Information System (INIS)

    Eisele, Kerstin; Lang, Philipp A.; Kempe, Daniela S.; Klarl, Barbara A.; Niemoeller, Olivier; Wieder, Thomas; Huber, Stephan M.; Duranton, Christophe; Lang, Florian

    2006-01-01

    The sequelae of mercury intoxication include induction of apoptosis. In nucleated cells, Hg 2+ -induced apoptosis involves mitochondrial damage. The present study has been performed to elucidate effects of Hg 2+ in erythrocytes which lack mitochondria but are able to undergo apoptosis-like alterations of the cell membrane. Previous studies have documented that activation of a Ca 2+ -sensitive erythrocyte scramblase leads to exposure of phosphatidylserine at the erythrocyte surface, a typical feature of apoptotic cells. The erythrocyte scramblase is activated by osmotic shock, oxidative stress and/or energy depletion which increase cytosolic Ca 2+ activity and/or activate a sphingomyelinase leading to formation of ceramide. Ceramide sensitizes the scramblase to Ca 2+ . The present experiments explored the effect of Hg 2+ ions on erythrocytes. Phosphatidylserine exposure after mercury treatment was estimated from annexin binding as determined in FACS analysis. Exposure to Hg 2+ (1 μM) indeed significantly increased annexin binding from 2.3 ± 0.5% (control condition) to 23 ± 6% (n = 6). This effect was paralleled by activation of a clotrimazole-sensitive K + -selective conductance as measured by patch-clamp recordings and by transient cell shrinkage. Further experiments revealed also an increase of ceramide formation by ∼66% (n = 7) after challenge with mercury (1 μM). In conclusion, mercury ions activate a clotrimazole-sensitive K + -selective conductance leading to transient cell shrinkage. Moreover, Hg 2+ increases ceramide formation. The observed mechanisms could similarly participate in the triggering of apoptosis in nucleated cells by Hg 2+

  1. Isolation and characterization of a Chinese hamster ovary cell mutant with altered regulation of phosphatidylserine biosynthesis

    International Nuclear Information System (INIS)

    Hasegawa, K.; Kuge, O.; Nishijima, M.; Akamatsu, Y.

    1989-01-01

    We have screened approximately 10,000 colonies of Chinese hamster ovary (CHO) cells immobilized on polyester cloth for mutants defective in [14C]ethanolamine incorporation into trichloroacetic acid-precipitable phospholipids. In mutant 29, discovered in this way, the activities of enzymes involved in the CDP-ethanolamine pathway were normal; however, the intracellular pool of phosphorylethanolamine was elevated, being more than 10-fold that in the parental CHO-K1 cells. These results suggested that the reduced incorporation of [14C]ethanolamine into phosphatidylethanolamine in mutant 29 was due to dilution of phosphoryl-[14C]ethanolamine with the increased amount of cellular phosphorylethanolamine. Interestingly, the rate of incorporation of serine into phosphatidylserine and the content of phosphatidylserine in mutant 29 cells were increased 3-fold and 1.5-fold, respectively, compared with the parent cells. The overproduction of phosphorylethanolamine in mutant 29 cells was ascribed to the elevated level of phosphatidylserine biosynthesis, because ethanolamine is produced as a reaction product on the conversion of phosphatidylethanolamine to phosphatidylserine, which is catalyzed by phospholipid-serine base-exchange enzymes. Using both intact cells and the particulate fraction of a cell extract, phosphatidylserine biosynthesis in CHO-K1 cells was shown to be inhibited by phosphatidylserine itself, whereas that in mutant 29 cells was greatly resistant to the inhibition, compared with the parental cells. As a conclusion, it may be assumed that mutant 29 cells have a lesion in the regulation of phosphatidylserine biosynthesis by serine-exchange enzyme activity, which results in the overproduction of phosphatidylserine and phosphorylethanolamine as well

  2. Phosphatidylserine and the human brain.

    Science.gov (United States)

    Glade, Michael J; Smith, Kyl

    2015-06-01

    The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function. A scientific literature search was conducted on MEDLINE for relevant articles regarding PS and the human brain published before June 2014. Additional publications were identified from references provided in original papers; 127 articles were selected for inclusion in this review. A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability. Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    International Nuclear Information System (INIS)

    Borborema, Samanta E.T.; Nascimento, Nanci do; Osso Junior, Joao A.

    2009-01-01

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, 122 Sb and 124 Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  4. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia], e-mail: samanta@usp.br, e-mail: nnascime@ipen.br; Andrade Junior, Heitor F. de [Instituto de Medicina Tropical de Sao Paulo (IMTSP), Sao Paulo, SP (Brazil)], e-mail: hfandrad@usp.br; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia], e-mail: jaosso@ipen.br

    2009-07-01

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, {sup 122}Sb and {sup 124}Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  5. 10 CFR 72.94 - Design basis external man-induced events.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Design basis external man-induced events. 72.94 Section 72... WASTE Siting Evaluation Factors § 72.94 Design basis external man-induced events. (a) The region must be examined for both past and present man-made facilities and activities that might endanger the proposed...

  6. Non-invasive in vivo imaging of arthritis in a collagen-induced murine model with phosphatidylserine-binding near-infrared (NIR) dye.

    Science.gov (United States)

    Chan, Marion M; Gray, Brian D; Pak, Koon Y; Fong, Dunne

    2015-03-09

    Development of non-invasive molecular imaging techniques that are based on cellular changes in inflammation has been of active interest for arthritis diagnosis. This technology will allow real-time detection of tissue damage and facilitate earlier treatment of the disease, thus representing an improvement over X-rays, which detect bone damage at the advanced stage. Tracing apoptosis, an event occurring in inflammation, has been a strategy used. PSVue 794 is a low-molecular-weight, near-infrared (NIR)-emitting complex of bis(zinc2+-dipicolylamine) (Zn-DPA) that binds to phosphatidylserine (PS), a plasma membrane anionic phospholipid that becomes flipped externally upon cell death by apoptosis. In this study, we evaluated the capacity of PSVue 794 to act as an in vivo probe for non-invasive molecular imaging assessment of rheumatoid arthritis (RA) via metabolic function in murine collagen-induced arthritis, a widely adopted animal model for RA. Male DBA/1 strain mice were treated twice with chicken collagen type II in Freund's adjuvant. Their arthritis development was determined by measuring footpad thickness and confirmed with X-ray analysis and histology. In vivo imaging was performed with the NIR dye and the LI-COR Odyssey Image System. The level of emission was compared among mice with different disease severity, non-arthritic mice and arthritic mice injected with a control dye without the Zn-DPA targeting moiety. Fluorescent emission correlated reliably with the degree of footpad swelling and the manifestation of arthritis. Ex vivo examination showed emission was from the joint. Specificity of binding was confirmed by the lack of emission when arthritic mice were given the control dye. Furthermore, the PS-binding protein annexin V displaced the NIR dye from binding, and the difference in emission was numerically measurable on a scale. This report introduces an economical alternative method for assessing arthritis non-invasively in murine models. Inflammation in

  7. Apoptosis-inducing factor (Aif1) mediates anacardic acid-induced apoptosis in Saccharomyces cerevisiae.

    Science.gov (United States)

    Muzaffar, Suhail; Chattoo, Bharat B

    2017-03-01

    Anacardic acid is a medicinal phytochemical that inhibits proliferation of fungal as well as several types of cancer cells. It induces apoptotic cell death in various cell types, but very little is known about the mechanism involved in the process. Here, we used budding yeast Saccharomyces cerevisiae as a model to study the involvement of some key elements of apoptosis in the anacardic acid-induced cell death. Plasma membrane constriction, chromatin condensation, DNA degradation, and externalization of phosphatidylserine (PS) indicated that anacardic acid induces apoptotic cell death in S. cerevisiae. However, the exogenous addition of broad-spectrum caspase inhibitor Z-VAD-FMK or deletion of the yeast caspase Yca1 showed that the anacardic acid-induced cell death is caspase independent. Apoptosis-inducing factor (AIF1) deletion mutant was resistant to the anacardic acid-induced cell death, suggesting a key role of Aif1. Overexpression of Aif1 made cells highly susceptible to anacardic acid, further confirming that Aif1 mediates anacardic acid-induced apoptosis. Interestingly, instead of the increase in the intracellular reactive oxygen species (ROS) normally observed during apoptosis, anacardic acid caused a decrease in the intracellular ROS levels. Quantitative real-time PCR analysis showed downregulation of the BIR1 survivin mRNA expression during the anacardic acid-induced apoptosis.

  8. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-12-01

    response. e. Correlate imaging findings with histological studies of vascular damage, tumor cell and endothelial cell apoptosis or necrosis and vascular ...phosphatidylserine (PS) is exposed exclusively on tumor vascular endothelium of brain metastases in mouse models. A novel PS-targeting antibody, PGN635... vascular endothelial cells in multi-focal brain metastases throughout the whole mouse brain. Vascular endothelium in normal brain tissues is negative

  9. Emulsified phosphatidylserine, simple and effective peptide carrier for induction of potent epitope-specific T cell responses.

    Science.gov (United States)

    Ichihashi, Toru; Satoh, Toshifumi; Sugimoto, Chihiro; Kajino, Kiichi

    2013-01-01

    To induce potent epitope-specific T cell immunity by a peptide-based vaccine, epitope peptides must be delivered efficiently to antigen-presenting cells (APCs) in vivo. Therefore, selecting an appropriate peptide carrier is crucial for the development of an effective peptide vaccine. In this study, we explored new peptide carriers which show enhancement in cytotoxic T lymphocyte (CTL) induction capability. Data from an epitope-specific in vivo CTL assay revealed that phosphatidylserine (PS) has a potent adjuvant effect among candidate materials tested. Further analyses showed that PS-conjugated antigens were preferentially and efficiently captured by professional APCs, in particular, by CD11c(+)CD11b(+)MHCII(+) conventional dendritic cells (cDCs) compared to multilamellar liposome-conjugates or unconjugated antigens. In addition, PS demonstrated the stimulatory capacity of peptide-specific helper T cells in vivo. This work indicates that PS is the easily preparable efficient carrier with a simple structure that delivers antigen to professional APCs effectively and induce both helper and cytotoxic T cell responses in vivo. Therefore, PS is a promising novel adjuvant for T cell-inducing peptide vaccines.

  10. Chronic Treatment with Squid Phosphatidylserine Activates Glucose Uptake and Ameliorates TMT-Induced Cognitive Deficit in Rats via Activation of Cholinergic Systems

    Directory of Open Access Journals (Sweden)

    Hyun-Jung Park

    2012-01-01

    Full Text Available The present study examined the effects of squid phosphatidylserine (Squid-PS on the learning and memory function and the neural activity in rats with TMT-induced memory deficits. The rats were administered saline or squid derived Squid-PS (Squid-PS 50 mg kg−1, p.o. daily for 21 days. The cognitive improving efficacy of Squid-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the passive avoidance task and by performing choline acetyltransferase (ChAT and acetylcholinesterase (AchE immunohistochemistry. 18F-Fluorodeoxyglucose and performed a positron emission tomography (PET scan was also performed. In the passive avoidance test, the control group which were injected with TMT showed a markedly lower latency time than the non-treated normal group (P<0.05. However, treatment of Squid-PS significantly recovered the impairment of memory compared to the control group (P<0.05. Consistent with the behavioral data, Squid-PS significantly alleviated the loss of ChAT immunoreactive neurons in the hippocampal CA3 compared to that of the control group (P<0.01. Also, Squid-PS significantly increased the AchE positive neurons in the hippocampal CA1 and CA3. In the PET analysis, Squid-PS treatment increased the glucose uptake more than twofold in the frontal lobe and the hippocampus (P<0.05, resp.. These results suggest that Squid-PS may be useful for improving the cognitive function via regulation of cholinergic enzyme activity and neural activity.

  11. The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal

    Directory of Open Access Journals (Sweden)

    Hafner Martin

    2004-08-01

    Full Text Available Abstract Background Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr on phagocytes has been implicated in the recognition and engulfment of apoptotic cells and in anti-inflammatory signaling. To determine the biological function of the phosphatidylserine receptor in vivo, we inactivated the Ptdsr gene in the mouse. Results Ablation of Ptdsr function in mice causes perinatal lethality, growth retardation and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. Ptdsr -/- mice with anophthalmia develop novel lesions, with induction of ectopic retinal-pigmented epithelium in nasal cavities. A comprehensive investigation of apoptotic cell clearance in vivo and in vitro demonstrated that engulfment of apoptotic cells was normal in Ptdsr knockout mice, but Ptdsr-deficient macrophages were impaired in pro- and anti-inflammatory cytokine signaling after stimulation with apoptotic cells or with lipopolysaccharide. Conclusion Ptdsr is essential for the development and differentiation of multiple organs during embryogenesis but not for apoptotic cell removal. Ptdsr may thus have a novel, unexpected developmental function as an important differentiation-promoting gene. Moreover, Ptdsr is not required for apoptotic cell clearance by macrophages but seems to be necessary for the regulation of macrophage cytokine responses. These results clearly contradict the current view that the phosphatidylserine receptor primarily functions in apoptotic cell clearance.

  12. A Model for Microcontroller Functionality Upset Induced by External Pulsed Electromagnetic Irradiation

    Science.gov (United States)

    2016-11-21

    AFRL-RD-PS- AFRL-RD-PS- TN-2016-0003 TN-2016-0003 A Model for Microcontroller Functionality Upset Induced by External Pulsed Electromagnetic...TYPE Technical Note 3. DATES COVERED (From - To) 22-11-2015 – 21-11-2016 4. TITLE AND SUBTITLE A Model for Microcontroller Functionality Upset Induced by... microcontroller (µC) subjected to external irradiation by a narrowband electromagnetic (EM) pulse. In our model, the state of a µC is completely specified by

  13. Emulsified phosphatidylserine, simple and effective peptide carrier for induction of potent epitope-specific T cell responses.

    Directory of Open Access Journals (Sweden)

    Toru Ichihashi

    Full Text Available BACKGROUND: To induce potent epitope-specific T cell immunity by a peptide-based vaccine, epitope peptides must be delivered efficiently to antigen-presenting cells (APCs in vivo. Therefore, selecting an appropriate peptide carrier is crucial for the development of an effective peptide vaccine. In this study, we explored new peptide carriers which show enhancement in cytotoxic T lymphocyte (CTL induction capability. METHODOLOGY/PRINCIPAL FINDINGS: Data from an epitope-specific in vivo CTL assay revealed that phosphatidylserine (PS has a potent adjuvant effect among candidate materials tested. Further analyses showed that PS-conjugated antigens were preferentially and efficiently captured by professional APCs, in particular, by CD11c(+CD11b(+MHCII(+ conventional dendritic cells (cDCs compared to multilamellar liposome-conjugates or unconjugated antigens. In addition, PS demonstrated the stimulatory capacity of peptide-specific helper T cells in vivo. CONCLUSIONS/SIGNIFICANCE: This work indicates that PS is the easily preparable efficient carrier with a simple structure that delivers antigen to professional APCs effectively and induce both helper and cytotoxic T cell responses in vivo. Therefore, PS is a promising novel adjuvant for T cell-inducing peptide vaccines.

  14. Antibody targeting of phosphatidylserine for the detection and immunotherapy of cancer

    Directory of Open Access Journals (Sweden)

    Belzile O

    2018-01-01

    Full Text Available Olivier Belzile,1 Xianming Huang,2,3 Jian Gong,2,3 Jay Carlson,2,3 Alan J Schroit,1 Rolf A Brekken,1 Bruce D Freimark2,3 1Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, 2Department of Preclinical Research, 3Department of Antibody Discovery, Peregrine Pharmaceuticals, Inc., Tustin, CA, USA Abstract: Phosphatidylserine (PS is a negatively charged phospholipid in all eukaryotic cells that is actively sequestered to the inner leaflet of the cell membrane. Exposure of PS on apoptotic cells is a normal physiological process that triggers their rapid removal by phagocytic engulfment under noninflammatory conditions via receptors primarily expressed on immune cells. PS is aberrantly exposed in the tumor microenvironment and contributes to the overall immunosuppressive signals that antagonize the development of local and systemic antitumor immune responses. PS-mediated immunosuppression in the tumor microenvironment is further exacerbated by chemotherapy and radiation treatments that result in increased levels of PS on dying cells and necrotic tissue. Antibodies targeting PS localize to tumors and block PS-mediated immunosuppression. Targeting exposed PS in the tumor microenvironment may be a novel approach to enhance immune responses to cancer. Keywords: immunosuppression, tumor microenvironment, immunotherapy, imaging, phosphatidylserine, bavituximab

  15. Floating and flying ferrofluid bridges induced by external magnetic fields

    Science.gov (United States)

    Ma, Rongchao; Zhou, Yixin; Liu, Jing

    2015-04-01

    A ferrofluid is a mixture that exhibits both magnetism and fluidity. This merit enables the ferrofluid to be used in a wide variety of areas. Here we show that a floating ferrofluid bridge can be induced between two separated boards under a balanced external magnetic field generated by two magnets, while a flying ferrofluid bridge can be induced under an unbalanced external magnetic field generated by only one magnet. The mechanisms of the ferrofluid bridges were discussed and the corresponding mathematical equations were also established to describe the interacting magnetic force between the ferro particles inside the ferrofluid. This work answered a basic question that, except for the well-known floating water bridges that are related to electricity, one can also build up a liquid bridge that is related to magnetism.

  16. Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus.

    Science.gov (United States)

    Adu-Gyamfi, Emmanuel; Johnson, Kristen A; Fraser, Mark E; Scott, Jordan L; Soni, Smita P; Jones, Keaton R; Digman, Michelle A; Gratton, Enrico; Tessier, Charles R; Stahelin, Robert V

    2015-09-01

    Lipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles. The lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry. Copyright © 2015, American

  17. Breakdown of Phosphatidylserine Asymmetry Following Treatment of Erythrocytes with Lumefantrine

    Directory of Open Access Journals (Sweden)

    Kousi Alzoubi

    2014-02-01

    Full Text Available Background: Lumefantrine, a commonly used antimalarial drug, inhibits hemozoin formation in parasites. Several other antimalarial substances counteract parasitemia by triggering suicidal death or eryptosis of infected erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i, formation of ceramide, oxidative stress and/or activation of p38 kinase, protein kinase C (PKC, or caspases. The present study explored, whether lumefantrine stimulates eryptosis. Methods: Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species from 2',7'-dichlorodihydrofluorescein-diacetate fluorescence, content of reduced glutathione (GSH from mercury orange fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 h exposure to lumefantrine (3 µg/mL was followed by a significant increase of annexin-V-binding without significantly altering forward scatter, [Ca2+]i, ROS formation, reduced GSH, or ceramide abundance. The annexin-V-binding following lumefantrine treatment was not significantly modified by p38 kinase inhibitors SB203580 (2 μM and p38 Inh III (1 μM, PKC inhibitor staurosporine (1 µM or pancaspase inhibitor zVAD (1 or 10 µM. Conclusions: Lumefantrine triggers cell membrane scrambling, an effect independent from entry of extracellular Ca2+, ceramide formation, ROS formation, glutathione content, p38 kinase, PKC or caspases.

  18. Effects of the number of inducer blades on the anti-cavitation characteristics and external performance of a centrifugal pump

    International Nuclear Information System (INIS)

    Guo, XiaoMei; Shi, GaoPing; Zhu, ZuChao; Cui, BaoLing

    2016-01-01

    Installing an inducer upstream of the main impeller is an effective approach for improving the anti-cavitation performance of a high speed centrifugal pump. For a high-speed centrifugal pump with an inducer, the number of inducer blades can affect its internal flow and external performance. We studied the manner in which the number of inducer blades can affect the anti-cavitation characteristics and external performance of a centrifugal pump. We first use the Rayleigh-Plesset equation and the mixture model to simulate the vapor liquid flow in a centrifugal pump with an inducer, and then predict its external performance. Finally, we tested the external performance of a centrifugal pump with 2-, 3- and 4-bladed inducers, respectively. The results show that the simulations of external performance in a centrifugal pump are in accordance with our experiments. Based on this, we obtained vapor volume fraction distributions for the inducer, the impeller, and in the corresponding whole flow parts. We discovered that the vapor volume fraction of a centrifugal pump with a 3- bladed inducer is less than that of a centrifugal pump with 2- or 4-bladed inducers, which means that a centrifugal pump with a 3-bladed inducer has a better external and anti-cavitation performance.

  19. Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine.

    Science.gov (United States)

    Riedl, Sabrina; Leber, Regina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar

    2015-11-01

    Host defense-derived peptides have emerged as a novel strategy for the development of alternative anticancer therapies. In this study we report on characteristic features of human lactoferricin (hLFcin) derivatives which facilitate specific killing of cancer cells of melanoma, glioblastoma and rhabdomyosarcoma compared with non-specific derivatives and the synthetic peptide RW-AH. Changes in amino acid sequence of hLFcin providing 9-11 amino acids stretched derivatives LF11-316, -318 and -322 only yielded low antitumor activity. However, the addition of the repeat (di-peptide) and the retro-repeat (di-retro-peptide) sequences highly improved cancer cell toxicity up to 100% at 20 μM peptide concentration. Compared to the complete parent sequence hLFcin the derivatives showed toxicity on the melanoma cell line A375 increased by 10-fold and on the glioblastoma cell line U-87mg by 2-3-fold. Reduced killing velocity, apoptotic blebbing, activation of caspase 3/7 and formation of apoptotic DNA fragments proved that the active and cancer selective peptides, e.g. R-DIM-P-LF11-322, trigger apoptosis, whereas highly active, though non-selective peptides, such as DIM-LF11-318 and RW-AH seem to kill rapidly via necrosis inducing membrane lyses. Structural studies revealed specific toxicity on cancer cells by peptide derivatives with loop structures, whereas non-specific peptides comprised α-helical structures without loop. Model studies with the cancer membrane mimic phosphatidylserine (PS) gave strong evidence that PS only exposed by cancer cells is an important target for specific hLFcin derivatives. Other negatively charged membrane exposed molecules as sialic acid, heparan and chondroitin sulfate were shown to have minor impact on peptide activity. Copyright © 2015. Published by Elsevier B.V.

  20. Inducing and destruction of chimeras and chimera-like states by an external harmonic force

    Science.gov (United States)

    Shepelev, I. A.; Vadivasova, T. E.

    2018-03-01

    We study the phenomena of chimera destruction and inducing of chimera-like states in an ensemble of nonlocally coupled chaotic Rössler oscillators under an external harmonic force. The localized harmonic influence can lead to both destruction and changing of the spatial topology of chimeras. At the same time this influence can cause the emergence of stable chimera-like states (induced chimeras) for the regime of partial coherent chaos. Induced chimeras are also observed for the global influence. We show the possibility of controlling the chimera-like state topology by varying the parameters of localized external harmonic influence.

  1. Dying a thousand death. Radionuclide imaging of apoptosis

    International Nuclear Information System (INIS)

    Blankenberg, F.; Ohtsuki, K.; Strauss, H.W.

    1999-01-01

    Programmed cell death, apoptosis, in an inducible, organized, energy requiring form of demise that results in the disappearance of a cell without the induction of an inflammatory response. Apoptotic cell death is strikingly different than necrotic death, which is disorderly, does not require energy and results in local inflammation, usually secondary to sudden release of intercellular contents. Apoptosis is induced when cells undergo severe injury to their nucleus, as occurs following exposure to gamma or X-radiation, or mitochondria, as as occurs in variety of viral illnesses. Apoptosis can also be induced by externals signals, such as interaction of 'fas' ligand with 'fas' receptors. Once the cell is committed to apoptosis, the caspase enzyme cascade is activate. An early effect of caspase activation is the rapid expression of phosphatidylserine on the external leaflet of the cell membrane. Membrane bound phosphatidylserine expression serves as a signal to surrounding cells, identifying the expressing cell as undergoing apoptosis. A deficiency or an excess of programmed cell death is an integral component of autoimmune disorders, transplant rejection and cancer. A technique to image programmed cell death would be used to assist in the development of drugs, designed to treat these diseases, and to monitor the effectiveness of therapy The sudden expression of phosphatidylserine on the cell membrane is target that could be used for this purpose. A 35 kD physiologic protein, Annexin V lipocortin, binds with nanomolar affinity to membrane bound phosphatidylserine. Annexin V has been radiolabeled with Technetium-99m by direct coupling to free sulfhydryl groups, and through the hydrazinonicatinamide and N2S2 linking agents. The biodistribution of the agents labeled with each of the methods is slightly different. In all cases the radiopharmaceutical binds to cell undergoing apoptosis 'in vitro', and permits imaging of the process in experimental animals

  2. Comparison of molecular species of various transphosphatidylated phosphatidylserine (PS) with bovine cortex PS by mass spectrometry

    NARCIS (Netherlands)

    Chen, S.; Li, K.W.

    2008-01-01

    The exogenous introduction of a molecular species mixture of bovine cortex phosphatidylserine (BC-PS) has been claimed to improve memory function in subjects suffering from age-associated memory impairment and dementia. However, it has been also reported that oral administration of another molecular

  3. New parameterization of external and induced fields in geomagnetic field modeling, and a candidate model for IGRF 2005

    DEFF Research Database (Denmark)

    Olsen, Nils; Sabaka, T.J.; Lowes, F.

    2005-01-01

    When deriving spherical harmonic models of the Earth's magnetic field, low-degree external field contributions are traditionally considered by assuming that their expansion coefficient q(1)(0) varies linearly with the D-st-index, while induced contributions are considered assuming a constant ratio...... Q(1) of induced to external coefficients. A value of Q(1) = 0.27 was found from Magsat data and has been used by several authors when deriving recent field models from Orsted and CHAMP data. We describe a new approach that considers external and induced field based on a separation of D-st = E-st + I......-st into external (E-st) and induced (I-st) parts using a 1D model of mantle conductivity. The temporal behavior of q(1)(0) and of the corresponding induced coefficient are parameterized by E-st and I-st, respectively. In addition, we account for baseline-instabilities of D-st by estimating a value of q(1...

  4. External field induced switching of tunneling current in the coupled quantum dots

    OpenAIRE

    Mantsevich, V. N.; Maslova, N. S.; Arseyev, P. I.

    2014-01-01

    We investigated the tunneling current peculiarities in the system of two coupled by means of the external field quantum dots (QDs) weakly connected to the electrodes in the presence of Coulomb correlations. It was found that tuning of the external field frequency induces fast multiple tunneling current switching and leads to the negative tunneling conductivity. Special role of multi-electrons states was demonstrated. Moreover we revealed conditions for bistable behavior of the tunneling curre...

  5. Targeting Phosphatidylserine with a 64Cu-Labeled Peptide for Molecular Imaging of Apoptosis.

    Science.gov (United States)

    Perreault, Amanda; Richter, Susan; Bergman, Cody; Wuest, Melinda; Wuest, Frank

    2016-10-03

    Molecular imaging of programmed cell death (apoptosis) in vivo is an innovative strategy for early assessment of treatment response and treatment efficacy in cancer patients. Externalization of phosphatidylserine (PS) to the cell membrane surface of dying cells makes this phospholipid an attractive molecular target for the development of apoptosis imaging probes. In this study, we have radiolabeled PS-binding 14-mer peptide FNFRLKAGAKIRFG (PSBP-6) with positron-emitter copper-64 ( 64 Cu) for PET imaging of apoptosis. Peptide PSBP-6 was conjugated with radiometal chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through an aminovaleric acid (Ava) linker for subsequent radiolabeling with 64 Cu to prepare radiotracer 64 Cu-NOTA-Ava-PSBP-6. PS-binding potencies of PSBP-6, NOTA-Ava-PSBP-6, and nat Cu-NOTA-Ava-PSBP-6 were determined in a competitive radiometric PS-binding assay. Radiotracer 64 Cu-NOTA-Ava-PSBP-6 was studied in camptothecin-induced apoptotic EL4 mouse lymphoma cells and in a murine EL4 tumor model of apoptosis using dynamic PET imaging. Peptide PSBP-6 was also conjugated via an Ava linker with fluorescein isothiocyanate (FITC). FITC-Ava-PSBP-6 was evaluated in flow cytometry and fluorescence confocal microscopy experiments. Radiopeptide 64 Cu-NOTA-Ava-PSBP-6 was synthesized in high radiochemical yields of >95%. The IC 50 values for PS-binding potency of PSBP-6, NOTA-Ava-PSBP-6, and nat Cu-NOTA-PSBP-6 were 600 μM, 30 μM, and 23 μM, respectively. A competitive radiometric cell binding assay confirmed binding of 64 Cu-NOTA-Ava-PSBP-6 to camptothecin-induced apoptotic EL4 cells in a Ca 2+ -independent manner. PET imaging studies demonstrated significantly higher uptake of 64 Cu-NOTA-Ava-PSBP-6 in apoptotic EL4 tumors (SUV 5min 0.95 ± 0.04) compared to control tumors (SUV 5min 0.74 ± 0.03). Flow cytometry studies showed significantly higher binding of FITC-Ava-PSBP-6 to EL4 cells treated with camptothecin compared to untreated cells

  6. Molecular mechanism of action of oxazolinoanthracyclines in cells derived from human solid tumors. Part 2.

    Science.gov (United States)

    Denel-Bobrowska, Marta; Łukawska, Małgorzata; Bukowska, Barbara; Gajek, Arkadiusz; Oszczapowicz, Irena; Marczak, Agnieszka

    2018-02-01

    Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are derivatives of anthracyclines (DOX and DAU) with a modified daunosamine moiety. We aimed to clarify their mechanisms of action by investigating intracellular accumulation and effects on the cell cycle, phosphatidylserine externalization, and proteasome 20S activity. Experimental model consisted of SKOV-3, A549 and HepG2 cells. Compounds were used at the concentration of 80nM. Intracellular accumulation, drug uptake, and proteasome 20S activity were evaluated by fluorimetric methods. The effects on the cell cycle and phosphatidylserine externalization were measured by flow cytometry. O-DOX was equivalent to DOX in terms of inducing G2/M arrest, but O-DAU was less potent in SKOV-3, HepG2, and A549 cells. O-DOX had the greatest effect on initiating apoptosis in all tested cells. Externalization of phosphatidylserine was significantly higher following O-DOX treatment compared with control cells and cells incubated with DOX. The intracellular accumulation and uptake of the derivatives were similar to those of the reference drugs. Tested compounds are able to activate proteasome 20S activity. Our results extended the understanding of the toxicity, mechanism of action, and biochemical properties of oxazoline derivatives of doxorubicin and daunorubicin, including their effects on cell cycle, apoptosis and DNA degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Combined effects of external electric and magnetic fields on electromagnetically induced transparency of a two-dimensional quantum dot

    International Nuclear Information System (INIS)

    Rezaei, Gh.; Shojaeian Kish, S.; Avazpour, A.

    2012-01-01

    In this article effects of external electric and magnetic fields on the electromagnetically induced transparency of a hydrogenic impurity confined in a two-dimensional quantum dot are investigated. To do this the probe absorption, group velocity and refractive index of the medium in the presence of external electric and magnetic fields are discussed. It is found that, electromagnetically induced transparency occurs in the system and its frequency, transparency window and group velocity of the probe field strongly depend on the external fields. In comparison with atomic system, one may control the electromagnetically induced transparency and the group velocity of light in nano structures with the dot size and confinement potential.

  8. Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells.

    Science.gov (United States)

    Qin, Guiqi; Zhao, ChuBiao; Zhang, Lili; Liu, Hongyu; Quan, Yingyao; Chai, Liuying; Wu, Shengnan; Wang, Xiaoping; Chen, Tongsheng

    2015-08-01

    This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.

  9. Lysosomal ceramide generated by acid sphingomyelinase triggers cytosolic cathepsin B-mediated degradation of X-linked inhibitor of apoptosis protein in natural killer/T lymphoma cell apoptosis

    OpenAIRE

    Taniguchi, M; Ogiso, H; Takeuchi, T; Kitatani, K; Umehara, H; Okazaki, T

    2015-01-01

    We previously reported that IL-2 deprivation induced acid sphingomyelinase-mediated (ASM-mediated) ceramide elevation and apoptosis in an NK/T lymphoma cell line KHYG-1. However, the molecular mechanism of ASM?ceramide-mediated apoptosis during IL-2 deprivation is poorly understood. Here, we showed that IL-2 deprivation induces caspase-dependent apoptosis characterized by phosphatidylserine externalization, caspase-8, -9, and -3 cleavage, and degradation of X-linked inhibitor of apoptosis pro...

  10. Movement Induces the Use of External Spatial Coordinates for Tactile Localization in Congenitally Blind Humans.

    Science.gov (United States)

    Heed, Tobias; Möller, Johanna; Röder, Brigitte

    2015-01-01

    To localize touch, the brain integrates spatial information coded in anatomically based and external spatial reference frames. Sighted humans, by default, use both reference frames in tactile localization. In contrast, congenitally blind individuals have been reported to rely exclusively on anatomical coordinates, suggesting a crucial role of the visual system for tactile spatial processing. We tested whether the use of external spatial information in touch can, alternatively, be induced by a movement context. Sighted and congenitally blind humans performed a tactile temporal order judgment task that indexes the use of external coordinates for tactile localization, while they executed bimanual arm movements with uncrossed and crossed start and end postures. In the sighted, start posture and planned end posture of the arm movement modulated tactile localization for stimuli presented before and during movement, indicating automatic, external recoding of touch. Contrary to previous findings, tactile localization of congenitally blind participants, too, was affected by external coordinates, though only for stimuli presented before movement start. Furthermore, only the movement's start posture, but not the planned end posture affected blind individuals' tactile performance. Thus, integration of external coordinates in touch is established without vision, though more selectively than when vision has developed normally, and possibly restricted to movement contexts. The lack of modulation by the planned posture in congenitally blind participants suggests that external coordinates in this group are not mediated by motor efference copy. Instead the task-related frequent posture changes, that is, movement consequences rather than planning, appear to have induced their use of external coordinates.

  11. Dielectric-spectroscopy approach to ferrofluid nanoparticle clustering induced by an external electric field.

    Science.gov (United States)

    Rajnak, Michal; Kurimsky, Juraj; Dolnik, Bystrik; Kopcansky, Peter; Tomasovicova, Natalia; Taculescu-Moaca, Elena Alina; Timko, Milan

    2014-09-01

    An experimental study of magnetic colloidal particles cluster formation induced by an external electric field in a ferrofluid based on transformer oil is presented. Using frequency domain isothermal dielectric spectroscopy, we study the influence of a test cell electrode separation distance on a low-frequency relaxation process. We consider the relaxation process to be associated with an electric double layer polarization taking place on the particle surface. It has been found that the relaxation maximum considerably shifts towards lower frequencies when conducting the measurements in the test cells with greater electrode separation distances. As the electric field intensity was always kept at a constant value, we propose that the particle cluster formation induced by the external ac electric field accounts for that phenomenon. The increase in the relaxation time is in accordance with the Schwarz theory of electric double layer polarization. In addition, we analyze the influence of a static electric field generated by dc bias voltage on a similar shift in the relaxation maximum position. The variation of the dc electric field for the hysteresis measurements purpose provides understanding of the development of the particle clusters and their decay. Following our results, we emphasize the utility of dielectric spectroscopy as a simple, complementary method for detection and study of clusters of colloidal particles induced by external electric field.

  12. Recombinant Vaccinia Viruses Coding Transgenes of Apoptosis-Inducing Proteins Enhance Apoptosis But Not Immunogenicity of Infected Tumor Cells

    Science.gov (United States)

    Tkachenko, Anastasiya; Richter, Vladimir

    2017-01-01

    Genetic modifications of the oncolytic vaccinia virus (VV) improve selective tumor cell infection and death, as well as activation of antitumor immunity. We have engineered a double recombinant VV, coding human GM-CSF, and apoptosis-inducing protein apoptin (VV-GMCSF-Apo) for comparing with the earlier constructed double recombinant VV-GMCSF-Lact, coding another apoptosis-inducing protein, lactaptin, which activated different cell death pathways than apoptin. We showed that both these recombinant VVs more considerably activated a set of critical apoptosis markers in infected cells than the recombinant VV coding GM-CSF alone (VV-GMCSF-dGF): these were phosphatidylserine externalization, caspase-3 and caspase-7 activation, DNA fragmentation, and upregulation of proapoptotic protein BAX. However, only VV-GMCSF-Lact efficiently decreased the mitochondrial membrane potential of infected cancer cells. Investigating immunogenic cell death markers in cancer cells infected with recombinant VVs, we demonstrated that all tested recombinant VVs were efficient in calreticulin and HSP70 externalization, decrease of cellular HMGB1, and ATP secretion. The comparison of antitumor activity against advanced MDA-MB-231 tumor revealed that both recombinants VV-GMCSF-Lact and VV-GMCSF-Apo efficiently delay tumor growth. Our results demonstrate that the composition of GM-CSF and apoptosis-inducing proteins in the VV genome is very efficient tool for specific killing of cancer cells and for activation of antitumor immunity. PMID:28951871

  13. The effects of phosphatidylserine on endocrine response to moderate intensity exercise

    Directory of Open Access Journals (Sweden)

    Purpura Martin

    2008-07-01

    Full Text Available Abstract Background Previous research has indicated that phosphatidylserine (PS supplementation has the potential to attenuate the serum cortisol response to acute exercise stress. Equivocal findings suggest that this effect might be dose dependent. This study aimed to examine the influence of short-term supplementation with a moderate dose of PS (600 mg per day on plasma concentrations of cortisol, lactate, growth hormone and testosterone before, during, and following moderate intensity exercise in healthy males. Methods 10 healthy male subjects participated in the study. Each subject was assigned to ingest 600 mg PS or placebo per day for 10 days using a double-blind, placebo-controlled, crossover design. Serial venous blood samples were taken at rest, after a 15 minute moderate intensity exercise protocol on a cycle ergometer that consisted of five 3-minute incremental stages beginning at 65% and ending at 85% VO2 max, and during a 65 minute passive recovery. Plasma samples were assessed for cortisol, growth hormone, testosterone, lactate and testosterone to cortisol ratio for treatment (PS or placebo. Results Mean peak cortisol concentrations and area under the curve (AUC were lower following PS (39 ± 1% and 35 ± 0%, respectively when compared to placebo (p Conclusion The findings suggest that PS is an effective supplement for combating exercise-induced stress and preventing the physiological deterioration that can accompany too much exercise. PS supplementation promotes a desired hormonal status for athletes by blunting increases in cortisol levels.

  14. Transcriptional response to deletion of the phosphatidylserine decarboxylase Psd1p in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Gsell, Martina; Mascher, Gerald; Schuiki, Irmgard; Ploier, Birgit; Hrastnik, Claudia; Daum, Günther

    2013-01-01

    In the yeast, Saccharomyces cerevisiae, the synthesis of the essential phospholipid phosphatidylethanolamine (PE) is accomplished by a network of reactions which comprises four different pathways. The enzyme contributing most to PE formation is the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) which catalyzes conversion of phosphatidylserine (PS) to PE. To study the genome wide effect of an unbalanced cellular and mitochondrial PE level and in particular the contribution of Psd1p to this depletion we performed a DNA microarray analysis with a ∆psd1 deletion mutant. This approach revealed that 54 yeast genes were significantly up-regulated in the absence of PSD1 compared to wild type. Surprisingly, marked down-regulation of genes was not observed. A number of different cellular processes in different subcellular compartments were affected in a ∆psd1 mutant. Deletion mutants bearing defects in all 54 candidate genes, respectively, were analyzed for their growth phenotype and their phospholipid profile. Only three mutants, namely ∆gpm2, ∆gph1 and ∆rsb1, were affected in one of these parameters. The possible link of these mutations to PE deficiency and PSD1 deletion is discussed.

  15. H2O2 INDUCES APOPTOSIS OF RABBIT CHONDROCYTES VIA BOTH THE EXTRINSIC AND THE CASPASE-INDEPENDENT INTRINSIC PATHWAYS

    Directory of Open Access Journals (Sweden)

    CAIPING ZHUANG

    2013-07-01

    Full Text Available Osteoarthritis (OA, one of the most common joint diseases with unknown etiology, is characterized by the progressive destruction of articular cartilage and the apoptosis of chondrocytes. The purpose of this study is to elucidate the molecular mechanisms of H2O2-mediated rabbit chondrocytes apoptosis. CCK-8 assay showed that H2O2 treatment induced a remarkable reduction of cell viability, which was further verified by the remarkable phosphatidylserine externalization after H2O2 treatment for 1 h, the typical characteristics of apoptosis. H2O2 treatment induced a significant dysfunction of mitochondrial membrane potential (ΔΨm, but did not induce casapse-9 activation, indicating that H2O2 treatment induced caspase-independent intrinsic apoptosis that was further verified by the fact that silencing of AIF but not inhibiting caspase-9 potently prevented H2O2-induced apoptosis. H2O2 treatment induced a significant increase of caspase-8 and -3 activation, and inhibition of caspase-8 or -3 significantly prevented H2O2-induced apoptosis, suggesting that the extrinsic pathway played an important role. Collectively, our findings demonstrate that H2O2 induces apoptosis via both the casapse-8-mediated extrinsic and the caspase-independent intrinsic apoptosis pathways in rabbit chondrocytes.

  16. Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody Fragment

    Directory of Open Access Journals (Sweden)

    Jian Gong

    2013-06-01

    Full Text Available Imaging tumors and their response to treatment could be a valuable biomarker toward early assessment of therapy in patients with cancer. Phosphatidylserine (PS is confined to the inner leaflet of the plasma membrane in normal cells but is externalized on tumor vascular endothelial cells (ECs and tumor cells, and PS exposure is further enhanced in response to radiation and chemotherapy. In the present study, we evaluated the potential of a PS-targeting human F(ab'2 antibody fragment, PGN650, to detect exposure of PS in tumor-bearing mice. Tumor uptake of PGN650 was measured by near-infrared optical imaging in human tumor xenografts in immunodeficient mice. PGN650 specifically targeted tumors and was shown to target CD31-positive ECs and tumor cells. Tumor uptake of PGN650 was significantly higher in animals pretreated with docetaxel. The peak tumor to normal tissue (T/N ratio of probe was observed at 24 hours postinjection of probe, and tumor binding was detected for at least 120 hours. In repeat dose studies, PGN650 uptake in tumors was significantly higher following pretreatment with docetaxel compared to baseline uptake prior to treatment. PGN650 may be a useful probe to detect PS exposed in tumors and to monitor enhanced PS exposure to optimize therapeutic agents to treat tumors.

  17. Effect of phosphatidylserine on free radical susceptibility in human diploid fibroblasts.

    Science.gov (United States)

    Latorraca, S; Piersanti, P; Tesco, G; Piacentini, S; Amaducci, L; Sorbi, S

    1993-01-01

    We studied the effect of phosphatidylserine (PdtSER) on oxygen metabolite toxicity in skin fibroblast cell lines from apparently normal subjects. Fibroblast damage was produced by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by xanthine-oxidase (Xo). In order to quantify cell damage, we measured lactate dehydrogenase (LDH) activity in culture medium and cell viability in fibroblast cultures, with and without preincubation for 4 days with PdtSER 13 microM, after Xo incubation. We found a significant increase of LDH activity in culture medium of cells without preincubation with PdtSER. No significant increase of LDH activity was observed in the same cell lines after preincubation with PdtSER.

  18. Involvement of a putative substrate binding site in the biogenesis and assembly of phosphatidylserine decarboxylase 1 from Saccharomyces cerevisiae.

    Science.gov (United States)

    Di Bartolomeo, Francesca; Doan, Kim Nguyen; Athenstaedt, Karin; Becker, Thomas; Daum, Günther

    2017-07-01

    In the yeast Saccharomyces cerevisiae, the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) produces the largest amount of cellular phosphatidylethanolamine (PE). Psd1p is synthesized as a larger precursor on cytosolic ribosomes and then imported into mitochondria in a three-step processing event leading to the formation of an α-subunit and a β-subunit. The α-subunit harbors a highly conserved motif, which was proposed to be involved in phosphatidylserine (PS) binding. Here, we present a molecular analysis of this consensus motif for the function of Psd1p by using Psd1p variants bearing either deletions or point mutations in this region. Our data show that mutations in this motif affect processing and stability of Psd1p, and consequently the enzyme's activity. Thus, we conclude that this consensus motif is essential for structural integrity and processing of Psd1p. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. N-Acetyl-L-cysteine protects thyroid cells against DNA damage induced by external and internal irradiation.

    Science.gov (United States)

    Kurashige, Tomomi; Shimamura, Mika; Nagayama, Yuji

    2017-11-01

    We evaluated the effect of the antioxidant N-acetyl-L-cysteine (NAC) on the levels of reactive oxygen species (ROS), DNA double strand breaks (DSB) and micronuclei (MN) induced by internal and external irradiation using a rat thyroid cell line PCCL3. In internal irradiation experiments, ROS and DSB levels increased immediately after 131 I addition and then gradually declined, resulting in very high levels of MN at 24 and 48 h. NAC administration both pre- and also post- 131 I addition suppressed ROS, DSB and MN. In external irradiation experiments with a low dose (0.5 Gy), ROS and DSB increased shortly and could be prevented by NAC administration pre-, but not post-irradiation. In contrast, external irradiation with a high dose (5 Gy) increased ROS and DSB in a bimodal way: ROS and DSB levels increased immediately after irradiation, quickly returned to the basal levels and gradually rose again after >24 h. The second phase was in parallel with an increase in 4-hydroxy-2-nonenal. The number of MN induced by the second wave of ROS/DSB elevations was much higher than that by the first peak. In this situation, NAC administered pre- and post-irradiation comparably suppressed MN induced by a delayed ROS elevation. In conclusion, a prolonged ROS increase during internal irradiation and a delayed ROS increase after external irradiation with a high dose caused serious DNA damage, which were efficiently prevented by NAC. Thus, NAC administration even both after internal or external irradiation prevents ROS increase and eventual DNA damage.

  20. Microangiopathic antiphospholipid antibody syndrome due to anti-phosphatidylserine/prothrombin complex IgM antibody.

    Science.gov (United States)

    Senda, Yumi; Ohta, Kazuhide; Yokoyama, Tadafumi; Shimizu, Masaki; Furuichi, Kengo; Wada, Takashi; Yachie, Akihiro

    2017-03-01

    Herein we describe a case of microangiopathic antiphospholipid syndrome (MAPS) due to anti-phosphatidylserine/prothrombin complex (aPS/PT) IgM antibody successfully treated with rituximab. A significant correlation was observed between the clinical course and the aPS/PT IgM antibody titer, which can rise earlier before the appearance of clinical symptoms. Rituximab can be safely and effectively used for MAPS. Although detection of only aPS/PT IgM antibody is rare, aPS/PT IgM antibody might be associated with the pathogenesis of MAPS and might be a useful marker of disease activity. © 2017 Japan Pediatric Society.

  1. Basic Safety Considerations for Nuclear Power Plant Dealing with External Human Induced Events

    Energy Technology Data Exchange (ETDEWEB)

    Salem, W., E-mail: wafaasalem21@yahoo.com [Nuclear and Radiological Regulatory Authority (Egypt)

    2014-10-15

    Facilities and human activities in the region in which a nuclear power plant is located may under some conditions affect its safety. The potential sources of human induced events external to the plant should be identified and the severity of the possible resulting hazard phenomena should be evaluated to derive the appropriate design bases for the plant. They should also be monitored and periodically assessed over the lifetime of the plant to ensure that consistency with the design assumptions is maintained. External human induced events that could affect safety should be investigated in the site evaluation stage for every nuclear power plant site. The region is required to be examined for facilities and human activities that have the potential, under certain conditions, to endanger the nuclear power plant over its entire lifetime. Each relevant potential source is required to be identified and assessed to determine the potential interactions with personnel and plant items important to safety. (author)

  2. Comorbidity in illness-induced posttraumatic stress disorder versus posttraumatic stress disorder due to external events in a nationally representative study.

    Science.gov (United States)

    Sommer, Jordana L; Mota, Natalie; Edmondson, Donald; El-Gabalawy, Renée

    2018-05-10

    The current study compared physical and mental health characteristics and quality of life of illness-induced posttraumatic stress disorder (PTSD) versus those with PTSD due to external traumatic events in a population-based sample. PTSD was assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-5) using DSM-5 criteria in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions. Participants with past-year PTSD (n = 1779) were categorized into two groups: illness-induced (6.5%) and other trauma-induced PTSD (92.9%) based on index trauma. Group differences in physical health, mental health, and quality of life were estimated using multiple logistic and linear regressions with adjustment for demographics and medical morbidity. Compared to PTSD due to external events, illness-induced PTSD had higher rates of life-threatening illness in the past year. Illness-induced PTSD compared to PTSD due to external events was associated with reduced odds of depressive/bipolar disorders and antisocial personality disorder, but increased odds of cannabis use disorder. The groups did not differ on quality of life after accounting for medical morbidity. Illness-induced PTSD is common among American adults and has a similar impact on quality of life as PTSD due to external events, but may have distinct mental health correlates. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Eryptosis in lead-exposed workers

    International Nuclear Information System (INIS)

    Aguilar-Dorado, Itzel-Citlalli; Hernández, Gerardo; Quintanar-Escorza, Martha-Angelica; Maldonado-Vega, María; Rosas-Flores, Margarita; Calderón-Salinas, José-Víctor

    2014-01-01

    Eryptosis is a physiological phenomenon in which old and damaged erythrocytes are removed from circulation. Erythrocytes incubated with lead have exhibited major eryptosis. In the present work we found evidence of high levels of eryptosis in lead exposed workers possibly via oxidation. Blood samples were taken from 40 male workers exposed to lead (mean blood lead concentration 64.8 μg/dl) and non-exposed workers (4.2 μg/dl). The exposure to lead produced an intoxication characterized by 88.3% less δ-aminolevulinic acid dehydratase (δALAD) activity in lead exposed workers with respect to non-lead exposed workers. An increment of oxidation in lead exposed workers was characterized by 2.4 times higher thiobarbituric acid-reactive substance (TBARS) concentration and 32.8% lower reduced/oxidized glutathione (GSH/GSSG) ratio. Oxidative stress in erythrocytes of lead exposed workers is expressed in 192% higher free calcium concentration [Ca 2+ ] i and 1.6 times higher μ-calpain activity with respect to non-lead exposed workers. The adenosine triphosphate (ATP) concentration was not significantly different between the two worker groups. No externalization of phosphatidylserine (PS) was found in non-lead exposed workers (< 0.1%), but lead exposed workers showed 2.82% externalization. Lead intoxication induces eryptosis possibly through a molecular pathway that includes oxidation, depletion of reduced glutathione (GSH), increment of [Ca 2+ ], μ-calpain activation and externalization of PS in erythrocytes. Identifying molecular signals that induce eryptosis in lead intoxication is necessary to understand its physiopathology and chronic complications. - Graphical abstract: Fig. 1. (A) Blood lead concentration (PbB) and (B) phosphatidylserine externalization on erythrocyte membranes of non-lead exposed (□) and lead exposed workers (■). Values are mean ± SD. *Significantly different (P < 0.001). - Highlights: • Erythrocytes of lead exposed workers showed higher PS

  4. Eryptosis in lead-exposed workers

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar-Dorado, Itzel-Citlalli [Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico); Hernández, Gerardo [Section of Methodology of Science, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico); Quintanar-Escorza, Martha-Angelica [Faculty of Medicine, UJED, Durango, DGO (Mexico); Maldonado-Vega, María [CIATEC, León, GTO (Mexico); Rosas-Flores, Margarita [Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico); Calderón-Salinas, José-Víctor, E-mail: jcalder@cinvestav.mx [Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico)

    2014-12-01

    Eryptosis is a physiological phenomenon in which old and damaged erythrocytes are removed from circulation. Erythrocytes incubated with lead have exhibited major eryptosis. In the present work we found evidence of high levels of eryptosis in lead exposed workers possibly via oxidation. Blood samples were taken from 40 male workers exposed to lead (mean blood lead concentration 64.8 μg/dl) and non-exposed workers (4.2 μg/dl). The exposure to lead produced an intoxication characterized by 88.3% less δ-aminolevulinic acid dehydratase (δALAD) activity in lead exposed workers with respect to non-lead exposed workers. An increment of oxidation in lead exposed workers was characterized by 2.4 times higher thiobarbituric acid-reactive substance (TBARS) concentration and 32.8% lower reduced/oxidized glutathione (GSH/GSSG) ratio. Oxidative stress in erythrocytes of lead exposed workers is expressed in 192% higher free calcium concentration [Ca{sup 2+}]{sub i} and 1.6 times higher μ-calpain activity with respect to non-lead exposed workers. The adenosine triphosphate (ATP) concentration was not significantly different between the two worker groups. No externalization of phosphatidylserine (PS) was found in non-lead exposed workers (< 0.1%), but lead exposed workers showed 2.82% externalization. Lead intoxication induces eryptosis possibly through a molecular pathway that includes oxidation, depletion of reduced glutathione (GSH), increment of [Ca{sup 2+}], μ-calpain activation and externalization of PS in erythrocytes. Identifying molecular signals that induce eryptosis in lead intoxication is necessary to understand its physiopathology and chronic complications. - Graphical abstract: Fig. 1. (A) Blood lead concentration (PbB) and (B) phosphatidylserine externalization on erythrocyte membranes of non-lead exposed (□) and lead exposed workers (■). Values are mean ± SD. *Significantly different (P < 0.001). - Highlights: • Erythrocytes of lead exposed workers

  5. Large-scale, near-Earth, magnetic fields from external sources and the corresponding induced internal field

    Science.gov (United States)

    Langel, R. A.; Estes, R. H.

    1983-01-01

    Data from MAGSAT analyzed as a function of the Dst index to determine the first degree/order spherical harmonic description of the near-Earth external field and its corresponding induced field. The analysis was done separately for data from dawn and dusk. The MAGSAT data was compared with POGO data. A local time variation of the external field persists even during very quiet magnetic conditions; both a diurnal and 8-hour period are present. A crude estimate of Sq current in the 45 deg geomagnetic latitude range is obtained for 1966 to 1970. The current strength, located in the ionosphere and induced in the Earth, is typical of earlier determinations from surface data, although its maximum is displaced in local time from previous results.

  6. Influence of external magnetic field on laser-induced gold nanoparticles fragmentation

    International Nuclear Information System (INIS)

    Serkov, A. A.; Rakov, I. I.; Simakin, A. V.; Kuzmin, P. G.; Shafeev, G. A.; Mikhailova, G. N.; Antonova, L. Kh.; Troitskii, A. V.; Kuzmin, G. P.

    2016-01-01

    Laser-assisted fragmentation is an efficient method of the nanoparticles size and morphology control. However, its exact mechanisms are still under consideration. One of the remaining problems is the plasma formation, inevitably occurring upon the high intensity laser irradiation. In this Letter, the role of the laser-induced plasma is studied via introduction of high-intensity external magnetic field (up to 7.5 T). Its presence is found to cause the plasma emission to start earlier regarding to a laser pulse, also increasing the plume luminosity. Under these conditions, the acceleration of nanoparticles fragmentation down to a few nanometers is observed. Laser-induced plasma interaction with magnetic field and consequent energy transfer from plasma to nanoparticles are discussed.

  7. Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6

    Directory of Open Access Journals (Sweden)

    Ke Geng

    2017-11-01

    Full Text Available The Tyro3, Axl, and Mertk (TAM receptors are homologous type I receptor tyrosine kinases that have critical functions in the clearance of apoptotic cells in multicellular organisms. TAMs are activated by their endogenous ligands, growth arrest-specific 6 (Gas6, and protein S (Pros1, that function as bridging molecules between externalized phosphatidylserine (PS on apoptotic cells and the TAM ectodomains. However, the molecular mechanisms by which Gas6/Pros1 promote TAM activation remains elusive. Using TAM/IFNγR1 reporter cell lines to monitor functional TAM activity, we found that Gas6 activity was exquisitely dependent on vitamin K-mediated γ-carboxylation, whereby replacing vitamin K with anticoagulant warfarin, or by substituting glutamic acid residues involved in PS binding, completely abrogated Gas6 activity as a TAM ligand. Furthermore, using domain and point mutagenesis, Gas6 activity also required both an intact Gla domain and intact EGF-like domains, suggesting these domains function cooperatively in order to achieve TAM activation. Despite the requirement of γ-carboxylation and the functional Gla domain, non-γ-carboxylated Gas6 and Gla deletion/EGF-like domain deletion mutants still retained their ability to bind TAMs and acted as blocking decoy ligands. Finally, we found that distinct sources of PS-positive cells/vesicles (including apoptotic cells, calcium-induced stressed cells, and exosomes bound Gas6 and acted as cell-derived or exosome-derived ligands to activate TAMs. Taken together, our findings indicate that PS is indispensable for TAM activation by Gas6, and by inference, provides new perspectives on how PS, regulates TAM receptors and efferocytosis.

  8. Snake cytotoxins bind to membranes via interactions with phosphatidylserine head groups of lipids.

    Directory of Open Access Journals (Sweden)

    Anastasia G Konshina

    Full Text Available The major representatives of Elapidae snake venom, cytotoxins (CTs, share similar three-fingered fold and exert diverse range of biological activities against various cell types. CT-induced cell death starts from the membrane recognition process, whose molecular details remain unclear. It is known, however, that the presence of anionic lipids in cell membranes is one of the important factors determining CT-membrane binding. In this work, we therefore investigated specific interactions between one of the most abundant of such lipids, phosphatidylserine (PS, and CT 4 of Naja kaouthia using a combined, experimental and modeling, approach. It was shown that incorporation of PS into zwitterionic liposomes greatly increased the membrane-damaging activity of CT 4 measured by the release of the liposome-entrapped calcein fluorescent dye. The CT-induced leakage rate depends on the PS concentration with a maximum at approximately 20% PS. Interestingly, the effects observed for PS were much more pronounced than those measured for another anionic lipid, sulfatide. To delineate the potential PS binding sites on CT 4 and estimate their relative affinities, a series of computer simulations was performed for the systems containing the head group of PS and different spatial models of CT 4 in aqueous solution and in an implicit membrane. This was done using an original hybrid computational protocol implementing docking, Monte Carlo and molecular dynamics simulations. As a result, at least three putative PS-binding sites with different affinities to PS molecule were delineated. Being located in different parts of the CT molecule, these anion-binding sites can potentially facilitate and modulate the multi-step process of the toxin insertion into lipid bilayers. This feature together with the diverse binding affinities of the sites to a wide variety of anionic targets on the membrane surface appears to be functionally meaningful and may adjust CT action against

  9. Vacuum energy induced by an external magnetic field in a curved space

    International Nuclear Information System (INIS)

    Sitenko, Yu.A.; Rakityansky, D.G.

    1998-01-01

    The asymptotic expansion of the product of an operator raised to an arbitrary power and an exponential function of this operator is obtained. With the aid of this expansion, the density of vacuum energy induced by a static external magnetic field of an Abelian or a non-Abelian nature is expressed in terms of the DeWitt-Seeley-Gilkey coefficients

  10. Phosphatidylserine and caffeine attenuate postexercise mood disturbance and perception of fatigue in humans.

    Science.gov (United States)

    Wells, Adam J; Hoffman, Jay R; Gonzalez, Adam M; Stout, Jeffrey R; Fragala, Maren S; Mangine, Gerald T; McCormack, William P; Jajtner, Adam R; Townsend, Jeremy R; Robinson, Edward H

    2013-06-01

    Phosphatidylserine (PS) may attenuate the adverse effects of physical fatigue. Therefore, we investigated the effects of a multi-ingredient supplement containing 400 mg/d PS and 100 mg/d caffeine (supplement [SUP]) for 2 weeks on measures of cognitive function (CF), reaction time (RT), and mood (MD) following an acute exercise stress. It is hypothesized that PS will maintain preexercise CF and RT scores, while attenuating postexercise fatigue. Participants completed 2 acute bouts of resistance exercise (T1 and T2) separated by 2-week ingestion of SUP or control (CON). Outcome measures were assessed pre- and postexercise. When collapsed across groups, a significant decrease in RT performance was seen in the 60-second reaction drill from pre- to postexercise at T1. All other RT tests were similar from pre- to postexercise at T1. Reaction time was not significantly changed by PS. When collapsed across groups, a significant increase in performance of the serial subtraction test was seen. A significant increase (8.9% and 7.1%) in the number of correct answers and a significant decrease (8.0% and 7.5%) in time to answer were seen from pre- to postworkout at T1 and T2, respectively. A significant increase in total MD score from pre- to postworkout was observed for CON but not for PS at T2. Phosphatidylserine significantly attenuated pre- to postexercise perception of fatigue compared to CON. Ingestion of SUP for 14 days appears to attenuate postexercise MD scores and perception of fatigue, but does not affect CF or RT, in recreationally trained individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling.

    Science.gov (United States)

    Huang, Xiaohong; Huang, Youhua; Ouyang, Zhengliang; Xu, Lixiao; Yan, Yang; Cui, Huachun; Han, Xin; Qin, Qiwei

    2011-08-01

    Virus induced cell death, including apoptosis and nonapoptotic cell death, plays a critical role in the pathogenesis of viral diseases. Singapore grouper iridovirus (SGIV), a novel iridovirus of genus Ranavirus, causes high mortality and heavy economic losses in grouper aquaculture. Here, using fluorescence microscopy, electron microscopy and biochemical assays, we found that SGIV infection in host (grouper spleen, EAGS) cells evoked nonapoptotic programmed cell death (PCD), characterized by appearance of cytoplasmic vacuoles and distended endoplasmic reticulum, in the absence of DNA fragmentation, apoptotic bodies and caspase activation. In contrast, SGIV induced typical apoptosis in non-host (fathead minnow, FHM) cells, as evidenced by caspase activation and DNA fragmentation, suggesting that SGIV infection induced nonapoptotic cell death by a cell type dependent fashion. Furthermore, viral replication was essential for SGIV induced nonapoptotic cell death, but not for apoptosis. Notably, the disruption of mitochondrial transmembrane potential (ΔΨm) and externalization of phosphatidylserine (PS) were not detected in EAGS cells but in FHM cells after SGIV infection. Moreover, the extracellular signal-regulated kinase (ERK) signaling was involved in SGIV infection induced nonapoptotic cell death and viral replication. This is a first demonstration of ERK-mediated nonapoptotic cell death induced by a DNA virus. These findings contribute to understanding the mechanisms of iridovirus pathogenesis.

  12. External field-induced chaos in classical and quantum Hamiltonian systems

    International Nuclear Information System (INIS)

    Lin, W.C.

    1986-01-01

    Classical nonlinear nonintegrable systems exhibit dense sets of resonance zones in phase space. Global chaotic motion appears when neighboring resonance zones overlap. The chaotic motion signifies the destruction of a quasi constant of motion. The motion of a particle, trapped in one of the wells of a sinusoidal, potential driven by a monochromatic external field was studied. Global chaotic behavior sets in when the amplitude of the external field reaches a critical value. The particle then escapes the well. The critical values are found to be in good agreement with a resonance overlap criterion rather than a renormalization-group scheme. A similar system was then studied, but with the particle being confined in an infinite square well potential instead. A stochastic layer is found in the low-energy part of the phase space. The resonance zone structure is found to be in excellent agreement with predictions. The critical values for the onset of global chaotic behavior are found to be in excellent agreement with the renormalization group scheme. The quantum version of the second model above was then considered. In a similar fashion, the external field induces quantum resonance zones. The spectral statistics were computed, and a transition of statistics from Poissonian to Wigner-like was found as overlap of quantum resonances occurs. This also signifies the destruction of a quasi-constant of motion

  13. Vitamin D fails to prevent serum starvation- or staurosporine-induced apoptosis in human and rat osteosarcoma-derived cell lines

    International Nuclear Information System (INIS)

    Witasp, Erika; Gustafsson, Ann-Catrin; Cotgreave, Ian; Lind, Monica; Fadeel, Bengt

    2005-01-01

    Previous studies have suggested that 1,25(OH) 2 D 3 , the active form of vitamin D 3 , may increase the survival of bone-forming osteoblasts through an inhibition of apoptosis. On the other hand, vitamin D 3 has also been shown to trigger apoptosis in human cancer cells, including osteosarcoma-derived cell lines. In the present study, we show that 1,25(OH) 2 D 3 induces a time- and dose-dependent loss of cell viability in the rat osteosarcoma cell line, UMR-106, and the human osteosarcoma cell line, TE-85. We were unable, however, to detect nuclear condensation, phosphatidylserine externalization, or other typical signs of apoptosis in this model. Moreover, 1,25(OH) 2 D 3 failed to protect against apoptosis induced by serum starvation or incubation with the protein kinase inhibitor, staurosporine. These in vitro findings are thus at variance with several previous reports in the literature and suggest that induction of or protection against apoptosis of bone-derived cells may not be a primary function of vitamin D 3

  14. Subversion of Immunity by Leishmania amazonensis Parasites: Possible Role of Phosphatidylserine as a Main Regulator

    Directory of Open Access Journals (Sweden)

    Joao Luiz Mendes Wanderley

    2012-01-01

    Full Text Available Leishmania amazonensis parasites cause progressive disease in most inbred mouse strains and are associated with the development of diffuse cutaneous leishmaniasis in humans. The poor activation of an effective cellular response is correlated with the ability of these parasites to infect mononuclear phagocytic cells without triggering their activation or actively suppressing innate responses of these cells. Here we discuss the possible role of phosphatidylserine exposure by these parasites as a main regulator of the mechanism underlying subversion of the immune system at different steps during the infection.

  15. The effect of internal and external fields of view on visually induced motion sickness

    NARCIS (Netherlands)

    Bos, J.E.; Vries, S.C. de; Emmerik, M.L. van; Groen, E.L.

    2010-01-01

    Field of view (FOV) is said to affect visually induced motion sickness. FOV, however, is characterized by an internal setting used by the graphics generator (iFOV) and an external factor determined by screen size and viewing distance (eFOV). We hypothesized that especially the incongruence between

  16. Elevated levels of antibodies against phosphatidylserine/prothrombin complex and/or cardiolipin associated with infection and recurrent purpura in a child: a forme fruste of antiphospholipid syndrome?

    Science.gov (United States)

    Kinoshita, Yuri; Mayumi, Nobuko; Inaba, Motoyuki; Igarashi, Touru; Katagiri, Ichigen; Kawana, Seiji

    2015-07-15

    Antiphospholipid syndrome is an autoimmune disorder characterized by the occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy, in the presence of anti-phospholipid antibodies. The diagnosis of antiphospholipid syndrome is usually established based on clinical and laboratory findings by strictly following the 2006 Sapporo classification. However, the diagnosis remains challenging owing to the ongoing debates on the serological criteria. We report a case we describe as forme fruste antiphospholipid syndrome in which these criteria were not fulfilled. Purpura appeared repeatedly in a female infant starting from the age of 6 months and following episodes of upper respiratory infections and vaccinations. The levels of anti-cardiolipin IgG antibodies and anti-phosphatidylserine/prothrombin complex antibodies were elevated in accordance with these events. Histopathological evaluation revealed multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection has long been associated with antiphospholipid syndrome, and anti-phosphatidylserine/prothrombin antibodies are considered a new marker for the diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome should be considered even if the antiphospholipid syndrome diagnostic criteria are not completely fulfilled, especially in the presence of elevated levels of anti-phosphatidylserine/prothrombin antibodies and known preceding infections.

  17. External main-induced events in relation to nuclear power plant siting

    International Nuclear Information System (INIS)

    1981-01-01

    This safety Guide recomments procedures and provides information for use in implementing that part of the code of safety in Nuclear Power Plant Siting (IAEA Safety Series No. 50-C-S) which concerns man-induced events external to the plant, up to the evaluation of corresponding design basis parameters. Like the code, the Guide forms part of the IAEA's programme, referred to as the NUSS programme, for establishing codes of practice and safety Guides relating to land-based stationary thermal neutron power plants

  18. Efficient identification of phosphatidylserine-binding proteins by ORF phage display

    International Nuclear Information System (INIS)

    Caberoy, Nora B.; Zhou, Yixiong; Alvarado, Gabriela; Fan, Xianqun; Li, Wei

    2009-01-01

    To efficiently elucidate the biological roles of phosphatidylserine (PS), we developed open-reading-frame (ORF) phage display to identify PS-binding proteins. The procedure of phage panning was optimized with a phage clone expressing MFG-E8, a well-known PS-binding protein. Three rounds of phage panning with ORF phage display cDNA library resulted in ∼300-fold enrichment in PS-binding activity. A total of 17 PS-binding phage clones were identified. Unlike phage display with conventional cDNA libraries, all 17 PS-binding clones were ORFs encoding 13 real proteins. Sequence analysis revealed that all identified PS-specific phage clones had dimeric basic amino acid residues. GST fusion proteins were expressed for 3 PS-binding proteins and verified for their binding activity to PS liposomes, but not phosphatidylcholine liposomes. These results elucidated previously unknown PS-binding proteins and demonstrated that ORF phage display is a versatile technology capable of efficiently identifying binding proteins for non-protein molecules like PS.

  19. The cytotoxic effect of oxybuprocaine on human corneal epithelial cells by inducing cell cycle arrest and mitochondria-dependent apoptosis.

    Science.gov (United States)

    Fan, W-Y; Wang, D-P; Wen, Q; Fan, T-J

    2017-08-01

    Oxybuprocaine (OBPC) is a widely used topical anesthetic in eye clinic, and prolonged and repeated usage of OBPC might be cytotoxic to the cornea, especially to the outmost corneal epithelium. In this study, we characterized the cytotoxic effect of OBPC on human corneal epithelial (HCEP) cells and investigated its possible cellular and molecular mechanisms using an in vitro model of non-transfected HCEP cells. Our results showed that OBPC at concentrations ranging from 0.025% to 0.4% had a dose- and time-dependent cytotoxicity to HCEP cells. Moreover, OBPC arrested the cells at S phase and induced apoptosis of these cells by inducing plasma membrane permeability, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation. Furthermore, OBPC could trigger the activation of caspase-2, -3, and -9, downregulate the expression of Bcl-xL, upregulate the expression of Bax along with the cytoplasmic amount of mitochondria-released apoptosis-inducing factor, and disrupt mitochondrial transmembrane potential. Our results suggest that OBPC has a dose- and time-dependent cytotoxicity to HCEP cells by inducing cell cycle arrest and cell apoptosis via a death receptor-mediated mitochondria-dependent proapoptotic pathway, and this novel finding provides new insights into the acute cytotoxicity and its toxic mechanisms of OBPC on HCEP cells.

  20. Quasi-static electric field in a cylindrical volume conductor induced by external coils.

    Science.gov (United States)

    Esselle, K P; Stuchly, M A

    1994-02-01

    An expansion technique based on modified Bessel functions is used to obtain an analytical solution for the electric field induced in a homogeneous cylindrical volume conductor by an external coil. The current in the coil is assumed to be changing slowly so that quasi-static conditions can be justified. Valid for any coil type, this solution is ideal for fast computation of the induced electric field at a large number of points. Efficient implementation of this method in a computer code is described and numerical results are presented for a perpendicular circular coil and a tangential double-square coil.

  1. Propagation of the state change induced by external forces in local interactions

    Science.gov (United States)

    Lu, Jianjun; Tokinaga, Shozo

    2016-10-01

    This paper analyses the propagation of the state changes of agents that are induced by external forces applied to a plane. In addition, we propose two models for the behavior of the agents placed on a lattice plane, both of which are affected by local interactions. We first assume that agents are allowed to move to another site to maximise their satisfaction. Second, we utilise a model in which the agents choose activities on each site. The results show that the migration (activity) patterns of agents in both models achieve stability without any external forces. However, when we apply an impulsive external force to the state of the agents, we then observe the propagation of the changes in the agents' states. Using simulation studies, we show the conditions for the propagation of the state changes of the agents. We also show the propagation of the state changes of the agents allocated in scale-free networks and discuss the estimation of the agents' decisions in real state changes. Finally, we discuss the estimation of the agents' decisions in real state temporal changes using economic and social data from Japan and the United States.

  2. Antibodies to phosphatidylserine/prothrombin complex as an additional diagnostic marker of APS?

    Science.gov (United States)

    Žigon, P; Čučnik, S; Ambrožič, A; Sodin Šemrl, S; Kveder, T; Božič, B

    2012-06-01

    Antiprothrombin antibodies can be measured by ELISA using either a prothrombin/phosphatidylserine complex (aPS/PT) or prothrombin alone (aPT) as antigen. We aimed to compare the clinical features of autoimmune patients with avidity of aPS/PT and determine the diagnostic efficiency of aPS/PT and aPT for assessing antiphospholipid syndrome (APS). aPS/PT were of low (n = 9), heterogeneous (n = 31) and high (n = 8) avidity out of 48 cases. None of the samples with low avidity were positive in aPT ELISA. Among patients with heterogeneous or high avidity aPS/PT, there was a significantly greater number of patients with APS as compared to patients with low avidity (38/39 vs. 7/9; p < 0.05). No SLE patients had high avidity antiprothrombin antibodies.

  3. Bimodal cell death induced by high radiation doses in the radioresistant sf9 insect cell line

    International Nuclear Information System (INIS)

    Chandna, S.

    2003-01-01

    Full text: This study was conducted to investigate the mode(s) of cell death induced by high radiation doses in the highly radioresistant Sf9 insect ovarian cell line. Methods: Cells were exposed to γ-radiation doses 200Gy and 500Gy, harvested at various time intervals (6h-72h) following irradiation, and subjected to cell morphology assay, DNA agarose gel electrophoresis, single cell gel electrophoresis (SCGE; comet assay) and Annexin-V labeling for the detection of membrane phosphatidylserine externalization. Cell morphology was assessed in cells entrapped and fixed in agarose gel directly from the cell suspension, thus preventing the possible loss of fragments/ apoptotic bodies. Surviving fraction of Sf9 cells was 0.01 at 200Gy and 98%) undergoing extensive DNA fragmentation at 500Gy, whereas the frequency of cells with DNA fragmentation was considerably less (∼12%) at 200Gy. Conclusions: While the mode of cell death at 200Gy seems to be different from typical apoptosis, a dose of 500Gy induced bimodal cell death, with typical apoptotic as well as the atypical cell death observed at 200Gy

  4. Hsp105 family proteins suppress staurosporine-induced apoptosis by inhibiting the translocation of Bax to mitochondria in HeLa cells

    International Nuclear Information System (INIS)

    Yamagishi, Nobuyuki; Ishihara, Keiichi; Saito, Youhei; Hatayama, Takumi

    2006-01-01

    Hsp105 (Hsp105α and Hsp105β), major heat shock proteins in mammalian cells, belong to a subgroup of the HSP70 family, HSP105/110. Previously, we have shown that Hsp105α has completely different effects on stress-induced apoptosis depending on cell type. However, the molecular mechanisms by which Hsp105α regulates stress-induced apoptosis are not fully understood. Here, we established HeLa cells that overexpress either Hsp105α or Hsp105β by removing doxycycline and examined how Hsp105 modifies staurosporine (STS)-induced apoptosis in HeLa cells. Apoptotic features such as the externalization of phosphatidylserine on the plasma membrane and nuclear morphological changes were induced by the treatment with STS, and the STS-induced apoptosis was suppressed by overexpression of Hsp105α or Hsp105β. In addition, we found that overexpression of Hsp105α or Hsp105β suppressed the activation of caspase-3 and caspase-9 by preventing the release of cytochrome c from mitochondria. Furthermore, the translocation of Bax to mitochondria, which results in the release of cytochrome c from the mitochondria, was also suppressed by the overexpression of Hsp105α or Hsp105β. Thus, it is suggested that Hsp105 suppresses the stress-induced apoptosis at its initial step, the translocation of Bax to mitochondria in HeLa cells

  5. Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation.

    Science.gov (United States)

    Mallik, Suman; Prasad, Ramesh; Bhattacharya, Anindita; Sen, Prosenjit

    2018-05-10

    Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.

  6. External human induced events in site evaluation for nuclear power plants. Safety guide

    International Nuclear Information System (INIS)

    2004-01-01

    The purpose of the present Safety Guide is to provide recommendations and guidance for the examination of the region considered for site evaluation for a plant in order to identity hazardous phenomena associated with human induced events initiated by sources external to the plant. In some cases it also presents preliminary guidance for deriving values of relevant parameters for the design basis. This Safety Guide is also applicable for periodic site evaluation and site evaluation following a major human induced event, and for the design and operation of the site's environmental monitoring system. Site evaluation includes site characterization. Consideration of external events that could lead to a degradation of the safety features of the plant and cause a release of radioactive material from the plant and/or affect the dispersion of such material in the environment. And consideration of population issues and access issues significant to safety (such as the feasibility of evacuation, the population distribution and the location of resources). The process of site evaluation continues throughout the lifetime of the facility, from siting to design, construction, operation and decommissioning. The external human induced events considered in this Safety Guide are all of accidental origin. Considerations relating to the physical protection of the plant against wilful actions by third parties are outside its scope. However, the methods described herein may also have some application for the purposes of such physical protection. The present Safety Guide may also be used for events that may originate within the boundaries of the site, but from sources which are not directly involved in the operational states of the nuclear power plant units, such as fuel depots or areas for the storage of hazardous materials for the construction of other facilities at the same site. Special consideration should be given to the hazardous material handled during the construction, operation and

  7. Leishmania promastigotes lack phosphatidylserine but bind annexin V upon permeabilization or miltefosine treatment.

    Directory of Open Access Journals (Sweden)

    Adrien Weingärtner

    Full Text Available The protozoan parasite Leishmania is an intracellular pathogen infecting and replicating inside vertebrate host macrophages. A recent model suggests that promastigote and amastigote forms of the parasite mimic mammalian apoptotic cells by exposing phosphatidylserine (PS at the cell surface to trigger their phagocytic uptake into host macrophages. PS presentation at the cell surface is typically analyzed using fluorescence-labeled annexin V. Here we show that Leishmania promastigotes can be stained by fluorescence-labeled annexin V upon permeabilization or miltefosine treatment. However, combined lipid analysis by thin-layer chromatography, mass spectrometry and (31P nuclear magnetic resonance (NMR spectroscopy revealed that Leishmania promastigotes lack any detectable amount of PS. Instead, we identified several other phospholipid classes such phosphatidic acid, phosphatidylethanolamine; phosphatidylglycerol and phosphatidylinositol as candidate lipids enabling annexin V staining.

  8. The external cruising costs of parking

    NARCIS (Netherlands)

    Inci, E.; van Ommeren, J.N.; Kobus, Martijn

    2017-01-01

    Existing work emphasizes the importance of traffic congestion externalities, but typically ignores cruising-for-parking externalities. We estimate the marginal external cruising costs of parking—that is, the time costs that an additional parked car imposes on drivers by inducing them to cruise for

  9. LABCG2, a New ABC Transporter Implicated in Phosphatidylserine Exposure, Is Involved in the Infectivity and Pathogenicity of Leishmania

    Science.gov (United States)

    González-Rey, Elena; Delgado, Mario; Castanys, Santiago; Pérez-Victoria, José M.; Gamarro, Francisco

    2013-01-01

    Leishmaniasis is a neglected disease produced by the intracellular protozoan parasite Leishmania. In the present study, we show that LABCG2, a new ATP-binding cassette half-transporter (ABCG subfamily) from Leishmania, is involved in parasite virulence. Down-regulation of LABCG2 function upon expression of an inactive mutant version of this half-transporter (LABCG2K/M) is shown to reduce the translocation of short-chain analogues of phosphatidylserine (PS). This dominant-negative phenotype is specific for the headgroup of the phospholipid, as the movement of phospholipid analogues of phosphatidylcholine, phosphatidylethanolamine or sphingomyelin is not affected. In addition, promastigotes expressing LABCG2K/M expose less endogenous PS in the stationary phase than control parasites. Transient exposure of PS at the outer leaflet of the plasma membrane is known to be one of the mechanisms used by Leishmania to infect macrophages and to silence their immune response. Stationary phase/metacyclic promastigotes expressing LABCG2K/M are less infective for macrophages and show decreased pathogenesis in a mouse model of cutaneous leishmaniasis. Thus, mice infected with parasites expressing LABCG2K/M did not develop any lesion and showed significantly lower inflammation and parasite burden than mice infected with control parasites. Our results indicate that LABCG2 function is required for the externalization of PS in Leishmania promastigotes, a process that is involved in the virulence of the parasite. PMID:23638200

  10. Binding of Thrombin-Activated Platelets to a Fibrin Scaffold through ?IIb?3 Evokes Phosphatidylserine Exposure on Their Cell Surface

    OpenAIRE

    Brzoska, Tomasz; Suzuki, Yuko; Mogami, Hideo; Sano, Hideto; Urano, Tetsumei

    2013-01-01

    Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS) and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyz...

  11. Development and pharmacokinetic of antimony encapsulated in liposomes of phosphatidylserine using radioisotopes in experimental leishmaniasis

    International Nuclear Information System (INIS)

    Borborema, Samanta Etel Treiger

    2010-01-01

    Leishmaniasis are a complex of parasitic diseases caused by intra macrophage protozoa of the genus Leishmania, and is fatal if left untreated. Pentavalent antimonials, though toxic and their mechanism of action being unclear, remain the first-line drugs for treatment. Effective therapy could be achieved by delivering antileishmanial drugs to these sites of infection. Liposomes are phospholipid vesicles that promote improvement in the efficacy and action of drugs in target cell. Liposomes are taken up by the cells of mononuclear phagocytic system (MPS). The purpose of this study was to develop a preparation of meglumine antimonate encapsulated in liposomes of phosphatidylserine and to study its pharmacokinetic in healthy mice to establish its metabolism and distribution. Quantitative analysis of antimony from liposomes demonstrated that Neutron Activation Analysis was the most sensitive technique with almost 100 % of accuracy. All liposome formulations presented a mean diameter size of 150 nm. The determination of IC 50 in infected macrophage showed that liposome formulations were between 10 - 63 fold more effective than the free drug, indicating higher selectivity index. By fluorescence microscopy, an increased uptake of fluorescent-liposomes was seen in infected macrophages during short times of incubation compared with non-infected macrophages. Biodistribution studies showed that meglumine antimonate irradiated encapsulated in liposomes of phosphatidylserine promoted a targeting of antimony for MPS tissues and maintained high doses in organs for a prolonged period. In conclusion, these data suggest that meglumine antimonate encapsulated in liposomes showed higher effectiveness than the non-liposomal drug against Leishmania infection. The development of liposome formulations should be a new alternative for the chemotherapy of infection diseases, especially Leishmaniasis, as they are used to sustain and target pharmaceuticals to the local of infection. (author)

  12. Analysis of external events - Nuclear Power Plant Dukovany

    International Nuclear Information System (INIS)

    Hladky, Milan

    2000-01-01

    PSA of external events at level 1 covers internal events, floods, fires, other external events are not included yet. Shutdown PSA takes into account internal events, floods, fires, heavy load drop, other external events are not included yet. Final safety analysis report was conducted after 10 years of operation for all Dukovany operational units. Probabilistic approach was used for analysis of aircraft drop and external man-induced events. The risk caused by man-induced events was found to be negligible and was accepted by State Office for Nuclear Safety (SONS)

  13. Trifluoperazine-Induced Suicidal Erythrocyte Death and S-Nitrosylation Inhibition, Reversed by the Nitric Oxide Donor Sodium Nitroprusside

    Directory of Open Access Journals (Sweden)

    Mehrdad Ghashghaeinia

    2017-08-01

    Full Text Available Background and Purpose: The high potency antipsychotic drug trifluoperazine (10-[3-(4-methyl-1-piperazinyl-propyl]-2-(trifluoromethyl-(10H-phenothiazine dihydrochloride; TFP may either counteract or promote suicidal cell death or apoptosis. Similar to apoptosis, erythrocytes may enter eryptosis, characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis can be stimulated by an increase in cytoplasmic Ca2+ concentration ([Ca2+]i and inhibited by nitric oxide (NO. We explored whether TFP treatment of erythrocytes induces phosphatidylserine exposure, cell shrinkage, and calcium influx, whether it impairs S-nitrosylation and whether these effects are inhibited by NO. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and protein nitrosylation from fluorescence switch of the Bodipy-TMR/Sypro Ruby signal. Results: Exposure of human erythrocytes to TFP significantly enhanced the percentage of annexin-V-binding cells, raised [Ca2+]i, and decreased S-nitrosylation. The effect of TFP on annexin-V-binding was not affected by removal of extracellular Ca2+ alone, but was significantly inhibited by pre-treatment with sodium nitroprusside (SNP, an effect significantly augmented by additional removal of extracellular Ca2+. A 3 hours treatment with 0.1 µM Ca2+ ionophore ionomycin triggered annexin-V-binding and cell shrinkage, effects fully reversed by removal of extracellular Ca2+. Conclusions: TFP induces eryptosis and decreases protein S-nitrosylation, effects blunted by nitroprusside. The effect of nitroprusside is attenuated in the presence of extracellular Ca2+.

  14. The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry.

    Science.gov (United States)

    Meertens, Laurent; Carnec, Xavier; Lecoin, Manuel Perera; Ramdasi, Rasika; Guivel-Benhassine, Florence; Lew, Erin; Lemke, Greg; Schwartz, Olivier; Amara, Ali

    2012-10-18

    Dengue viruses (DVs) are responsible for the most medically relevant arboviral diseases. However, the molecular interactions mediating DV entry are poorly understood. We determined that TIM and TAM proteins, two receptor families that mediate the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, serve as DV entry factors. Cells poorly susceptible to DV are robustly infected after ectopic expression of TIM or TAM receptors. Conversely, DV infection of susceptible cells is inhibited by anti-TIM or anti-TAM antibodies or knockdown of TIM and TAM expression. TIM receptors facilitate DV entry by directly interacting with virion-associated PtdSer. TAM-mediated infection relies on indirect DV recognition, in which the TAM ligand Gas6 acts as a bridging molecule by binding to PtdSer within the virion. This dual mode of virus recognition by TIM and TAM receptors reveals how DVs usurp the apoptotic cell clearance pathway for infectious entry. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Phosphatidylserine transport by Ups2-Mdm35 in respiration-active mitochondria.

    Science.gov (United States)

    Miyata, Non; Watanabe, Yasunori; Tamura, Yasushi; Endo, Toshiya; Kuge, Osamu

    2016-07-04

    Phosphatidylethanolamine (PE) is an essential phospholipid for mitochondrial functions and is synthesized mainly by phosphatidylserine (PS) decarboxylase at the mitochondrial inner membrane. In Saccharomyces cerevisiae, PS is synthesized in the endoplasmic reticulum (ER), such that mitochondrial PE synthesis requires PS transport from the ER to the mitochondrial inner membrane. Here, we provide evidence that Ups2-Mdm35, a protein complex localized at the mitochondrial intermembrane space, mediates PS transport for PE synthesis in respiration-active mitochondria. UPS2- and MDM35-null mutations greatly attenuated conversion of PS to PE in yeast cells growing logarithmically under nonfermentable conditions, but not fermentable conditions. A recombinant Ups2-Mdm35 fusion protein exhibited phospholipid-transfer activity between liposomes in vitro. Furthermore, UPS2 expression was elevated under nonfermentable conditions and at the diauxic shift, the metabolic transition from glycolysis to oxidative phosphorylation. These results demonstrate that Ups2-Mdm35 functions as a PS transfer protein and enhances mitochondrial PE synthesis in response to the cellular metabolic state. © 2016 Miyata et al.

  16. Micafungin induced apoptosis in Candida parapsilosis independent of its susceptibility to micafungin

    Directory of Open Access Journals (Sweden)

    Fazal Shirazi

    2015-10-01

    Full Text Available We hypothesized that the cell wall inhibitor micafungin (MICA induces apoptosis in both MICA-susceptible (MICA-S and MICA–non-susceptible (MICA-NS Candida parapsilosis. Antifungal activity and apoptosis were analyzed in MICA-S and MICA-NS C. parapsilosis strains following exposure to micafungin for 3 h at 37°C in RPMI 1640 medium. Apoptosis was characterized by detecting phosphatidylserine externalization (PS, plasma membrane integrity, reactive oxygen species (ROS generation, mitochondrial membrane potential changes, adenosine triphosphate (ATP release, and caspase-like activity. Apoptosis was detected in MICA exposed (0.25 to 1 mg/L susceptible C. parapsilosis strains and was associated with apoptosis of 20-52% of analyzed cells versus only 5-30% of apoptosis in MICA-NS cells exposed to micafungin (0.5 to 2 mg/L; P = 0.001. The MICA antifungal activity was correlated with apoptotic cells showing increased dihydrorhodamine-123 staining (indicating ROS production, Rh-123 staining (decreased mitochondrial membrane potential, elevated ATP, and increased metacaspase activity. In conclusion, MICA is pro-apoptotic in MICA-S cells, but still exerts apoptotic effects in MICA –NS C. parapsilosis.

  17. The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues Rosa Laura López-Marqués1, Lisbeth Rosager Poulsen1, Katharina Meffert2, Thomas Pomorski2, Michael Gjedde Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation...... physiological function.   1 Poulsen, L.R; López-Marqués, R.L et al. (2008) The Arabidopsis P4-ATPase ALA3 localizes to the Golgi and requires a ß-subunit to function in lipid translocation and secretory vesicle formation. The Plant Cell, vol. 20, 658-676. 2 Gomès, E. et al. (2000) Chilling tolerance...... in Arabidopsis involves ALA1, a member of a new family of putative aminophospholipid translocases. The Plant Cell, vol. 12, 2441-2453....

  18. The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues

    DEFF Research Database (Denmark)

    Poulsen, Lisbeth Rosager

      The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues Rosa Laura López-Marqués1, Lisbeth Rosager Poulsen1, Katharina Meffert2, Thomas Pomorski2, Michael Gjedde Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation...... physiological function.   1 Poulsen, L.R; López-Marqués, R.L et al. (2008) The Arabidopsis P4-ATPase ALA3 localizes to the Golgi and requires a ß-subunit to function in lipid translocation and secretory vesicle formation. The Plant Cell, vol. 20, 658-676. 2 Gomès, E. et al. (2000) Chilling tolerance...... in Arabidopsis involves ALA1, a member of a new family of putative aminophospholipid translocases. The Plant Cell, vol. 12, 2441-2453....

  19. The effect of the external medium on the gravity-induced polarity of cytoplasmic streaming in Chara corallina (Characeae)

    Science.gov (United States)

    Staves, M. P.; Wayne, R.; Leopold, A. C.

    1997-01-01

    Gravity induces a polarity of cytoplasmic streaming in vertical internodal cells of Chara such that the downwardly directed stream moves faster than the upwardly directed stream. In order to determine whether the statolith theory (in which intracellular sedimenting particles are responsible for gravity sensing) or the gravitational pressure theory (in which the entire protoplast acts as the gravity sensor) best explain the gravity response in Chara internodal cells, we controlled the physical properties of the external medium, including density and osmolarity, with impermeant solutes and examined the effect on the polarity of cytoplasmic streaming. As the density of the external medium is increased, the polarity of cytoplasmic streaming decreases and finally disappears when the density of the external medium is equal to that of the cell (1015 kg/m3). A further increase in the density of the external medium causes a reversal of the gravity response. These results are consistent with the gravitational pressure theory of gravity sensing since the buoyancy of the protoplast is dependent on the difference between the density of the protoplast and the external medium, and are inconsistent with the statolith theory since the buoyancy of intracellular particles are unaffected by changes in the external medium.

  20. Propensity of red blood cells to undergo P2X7 receptor-mediated phosphatidylserine exposure does not alter during in vivo or ex vivo aging.

    Science.gov (United States)

    Sophocleous, Reece A; Mullany, Phillip R F; Winter, Kelly M; Marks, Denese C; Sluyter, Ronald

    2015-08-01

    Phosphatidylserine (PS) exposure facilitates the removal of red blood cells (RBCs) from the circulation, potentially contributing to the loss of stored RBCs after transfusion, as well as senescent RBCs. Activation of the P2X7 receptor by extracellular adenosine 5'-triphosphate (ATP) can induce PS exposure on freshly isolated human RBCs, but whether this process occurs in stored RBCs or changes during RBC aging is unknown. RBCs were processed and stored according to Australian blood banking guidelines. PS exposure was determined by annexin V binding and flow cytometry. Efficacy of P2X antagonists was assessed by flow cytometric measurements of ATP-induced ethidium+ uptake in RPMI 8226 cells. Osmotic fragility was assessed by lysis in hypotonic saline. RBCs were fractionated by discontinuous density centrifugation. ATP (1 mmol/L) induced PS exposure on RBCs stored for less than 1 week. This process was near-completely inhibited by the P2X7 antagonists A438079 and AZ10606120 and the P2X1/P2X7 antagonist MRS2159 but not the P2X1 antagonist NF499. ATP-induced PS exposure on RBCs was not dependent on K+, Na+, or Cl- fluxes. ATP did not alter the osmotic fragility of stored RBCs. ATP-induced PS exposure was similar between RBCs of different densities. ATP-induced PS exposure was also similar between RBCs stored for less than 1 week or for 6 weeks. The propensity of RBCs to undergo P2X7-mediated PS exposure does not alter during in vivo and ex vivo aging. Thus, P2X7 activation is unlikely to be involved in the removal of senescent RBCs or stored RBCs after transfusion. © 2015 AABB.

  1. Lack of HXK2 Induces Localization of Active Ras in Mitochondria and Triggers Apoptosis in the Yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Loredana Amigoni

    2013-01-01

    Full Text Available We recently showed that activated Ras proteins are localized to the plasma membrane and in the nucleus in wild-type cells growing exponentially on glucose, while in the hxk2Δ strain they accumulated mainly in mitochondria. An aberrant accumulation of activated Ras in these organelles was previously reported and correlated to mitochondrial dysfunction, accumulation of ROS, and cell death. Here we show that addition of acetic acid to wild-type cells results in a rapid recruitment of Ras-GTP from the nucleus and the plasma membrane to the mitochondria, providing a further proof that Ras proteins might be involved in programmed cell death. Moreover, we show that Hxk2 protects against apoptosis in S. cerevisiae. In particular, cells lacking HXK2 and showing a constitutive accumulation of activated Ras at the mitochondria are more sensitive to acetic-acid-induced programmed cell death compared to the wild type strain. Indeed, deletion of HXK2 causes an increase of apoptotic cells with several morphological and biochemical changes that are typical of apoptosis, including DNA fragmentation, externalization of phosphatidylserine, and ROS production. Finally, our results suggest that apoptosis induced by lack of Hxk2 may not require the activation of Yca1, the metacaspase homologue identified in yeast.

  2. Lack of HXK2 induces localization of active Ras in mitochondria and triggers apoptosis in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Amigoni, Loredana; Martegani, Enzo; Colombo, Sonia

    2013-01-01

    We recently showed that activated Ras proteins are localized to the plasma membrane and in the nucleus in wild-type cells growing exponentially on glucose, while in the hxk2Δ strain they accumulated mainly in mitochondria. An aberrant accumulation of activated Ras in these organelles was previously reported and correlated to mitochondrial dysfunction, accumulation of ROS, and cell death. Here we show that addition of acetic acid to wild-type cells results in a rapid recruitment of Ras-GTP from the nucleus and the plasma membrane to the mitochondria, providing a further proof that Ras proteins might be involved in programmed cell death. Moreover, we show that Hxk2 protects against apoptosis in S. cerevisiae. In particular, cells lacking HXK2 and showing a constitutive accumulation of activated Ras at the mitochondria are more sensitive to acetic-acid-induced programmed cell death compared to the wild type strain. Indeed, deletion of HXK2 causes an increase of apoptotic cells with several morphological and biochemical changes that are typical of apoptosis, including DNA fragmentation, externalization of phosphatidylserine, and ROS production. Finally, our results suggest that apoptosis induced by lack of Hxk2 may not require the activation of Yca1, the metacaspase homologue identified in yeast.

  3. External man-induced events in relation to nuclear power plant design

    International Nuclear Information System (INIS)

    1982-01-01

    This Guide deals with the basic design requirements for nuclear power plants, and presents a general design approach for protection against the effects of man-induced events. Section 2 discusses the general design approach. Section 3 outlines the development of the basic information necessary for an evaluation of the adequacy of a design against the effects of aircraft crashes, fires, explosions, and the release of toxic gases or corrosive substances. Section 4 outlines the design logic for protection against external man-induced events. It indicates possible methods of ensuring overall plant safety, including protection against possible secondary effects. Included for each event are: a methodology for calculating the design input parameters from the data generated in the siting study, system protection considerations from the effects of this man-induced event, and criteria for judging the adequacy of the protection provided. Specific design guidance related to acts of sabotage is not provided in this Guide. It should be recognized, however, that for certain situations such acts can be important to safety and could constitute the controlling postulated initiating event for design. The list of events covered is not necessarily complete. However, important events on which enough work has already been done in various Member States to enable their effects to be converted into generally accepted design parameters are included. In addition, other man-induced events such as dam ruptures, ship collisions, construction accidents and the like are identified but no general guidelines for design can be specified for these at present. These events need to be considered on an ad hoc basis, in order to arrive at design input parameters for them

  4. Roles of effective helical ripple rates in nonlinear stability of externally induced magnetic islands

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Seiya, E-mail: n-seiya@kobe-kosen.ac.jp [Kobe City College of Technology, Kobe, Hyogo 651-2194 (Japan)

    2015-02-15

    Magnetic islands are externally produced by resonant magnetic perturbations (RMPs) in toroidal plasmas. Spontaneous annihilation of RMP-induced magnetic islands called self-healing has been observed in helical systems. A possible mechanism of the self-healing is shielding of RMP penetration by helical ripple-induced neoclassical flows, which give rise to neoclassical viscous torques. In this study, effective helical ripple rates in multi-helicity helical systems are revisited, and a multi-helicity effect on the self-healing is investigated, based on a theoretical model of rotating magnetic islands. It is confirmed that effective helical ripple rates are sensitive to magnetic axis positions. It is newly found that self-healing thresholds also strongly depend on magnetic axis positions, which is due to dependence of neoclassical viscous torques on effective helical ripple rates.

  5. Clofazimine Induced Suicidal Death of Human Erythrocytes

    Directory of Open Access Journals (Sweden)

    Arbace Officioso

    2015-08-01

    Full Text Available Background/Aims: The antimycobacterial riminophenazine clofazimine has previously been shown to up-regulate cellular phospholipase A2 and to induce apoptosis. In erythrocytes phospholipase A2 stimulates eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Phospholipase A2 is in part effective by fostering formation of prostaglandin E2, which triggers Ca2+ entry. Stimulators of Ca2+ entry and eryptosis further include oxidative stress and energy depletion. The present study tested, whether and how clofazimine induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, cytosolic Ca2+ activity ([Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS from 2′, 7′-dichlorodihydrofluorescein diacetate (DCFDA fluorescence, and cytosolic ATP level utilizing a luciferin-luciferase assay kit. Results: A 24-48 hours exposure of human erythrocytes to clofazimine (≥1.5 µg/ml significantly increased the percentage of annexin-V-binding cells without appreciably modifying forward scatter. Clofazimine significantly increased [Ca2+]i, significantly decreased cytosolic ATP, but did not significantly modify ROS. The effect of clofazimine on annexin-V-binding was significantly blunted, but not fully abolished by removal of extracellular Ca2+, and by phospholipase A2 inhibitor quinacrine (25 µM. Clofazimine further augmented the effect of Ca2+ ionophore ionomycin (0.1 µM on eryptosis. The clofazimine induced annexin-V-binding was, however, completely abrogated by combined Ca2+ removal and addition of quinacrine. Conclusion: Clofazimine stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect in part dependent on entry of extracellular Ca2+, paralleled by cellular energy depletion and sensitive to

  6. Quercus Suber L. Cork Extracts Induce Apoptosis in Human Myeloid Leukaemia HL-60 Cells.

    Science.gov (United States)

    Bejarano, Ignacio; Godoy-Cancho, Belén; Franco, Lourdes; Martínez-Cañas, Manuel A; Tormo, María A

    2015-08-01

    Quercus suber L. cork contains a diversity of phenolic compounds, mostly low molecular weight phenols. A rising number of reports support with convergent findings that polyphenols evoke pro-apoptotic events in cancerous cells. However, the literature related to the anti-cancer bioactivity of Q. suber L. cork extractives (QSE) is still limited. Herein, we aim to describe the antitumor potential displayed by cork extractives obtained by different extraction methods in the human promyelocytic leukaemia cells. In order to quantify the effects of QSE on cancer cells viability, phosphatidylserine exposure, caspase-3 activity, mitochondrial membrane potential and cell cycle were evaluated. The results indicated that the QSE present a time-dependent and dose-dependent cytotoxicity in the human promyelocytic leukaemia cells. Such a noxious effect leads these leukaemia cells to their death through apoptotic processes by altering the mitochondrial outer membrane potential, activating caspase-3 and externalizing phosphatidylserine. However, cells cycle progression was not affected by the treatments. This study contributes to open a new way to use this natural resource by exploiting its anti-cancer properties. Moreover, it opens new possibilities of application of cork by-products, being more efficient in the sector of cork-based agriculture. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  7. New tests to detect antiphospholipid antibodies: antiprothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies.

    Science.gov (United States)

    Sciascia, Savino; Khamashta, Munther A; Bertolaccini, Maria Laura

    2014-05-01

    Antiprothrombin antibodies have been proposed as potential new biomarkers for thrombosis and/or pregnancy morbidity in the setting of the antiphospholipid syndrome (APS). Antiprothrombin antibodies are commonly detected by ELISA, using prothrombin coated onto irradiated plates (aPT), or prothrombin in complex with phosphatidylserine (aPS/PT), as antigen. Although these antibodies can co-exist in the same patient, aPT and aPS/PT seem to belong to different populations of autoantibodies. Early research explored the role of antibodies to prothrombin as potential antigenic targets for the lupus anticoagulant (LA). To date their clinical significance is being investigated and their potential role in identifying patients at higher risk of developing thrombotic events or pregnancy morbidity is being probed.

  8. ISS External Contamination Environment for Space Science Utilization

    Science.gov (United States)

    Soares, Carlos; Mikatarian, Ron; Steagall, Courtney; Huang, Alvin; Koontz, Steven; Worthy, Erica

    2014-01-01

    (1) The International Space Station is the largest and most complex on-orbit platform for space science utilization in low Earth orbit, (2) Multiple sites for external payloads, with exposure to the associated natural and induced environments, are available to support a variety of space science utilization objectives, (3) Contamination is one of the induced environments that can impact performance, mission success and science utilization on the vehicle, and (4)The ISS has been designed, built and integrated with strict contamination requirements to provide low levels of induced contamination on external payload assets.

  9. Flow-induced vibration of steam generator helical tubes subjected to external liquid cross flow and internal two-phase flow

    International Nuclear Information System (INIS)

    Jong Chull Jo; Myung Jo Jhung; Woong Sik Kim; Hho Jung Kim

    2005-01-01

    Full text of publication follows: This paper addresses the potential flow-induced vibration problems in a helically-coiled tube steam generator of integral-type nuclear reactor, of which the tubes are subjected to liquid cross flow externally and multi-phase flow externally. The thermal-hydraulic conditions of both tube side and shell side flow fields are predicted using a general purpose computational fluid dynamics code employing the finite volume element modeling. To get the natural frequency and corresponding mode shape of the helical type tubes with various conditions, a finite element analysis code is used. Based on the results of both helical coiled tube steam generator thermal-hydraulic and coiled tube modal analyses, turbulence-induced vibration and fluid-elastic instability analyses are performed. And then the potential for damages on the tubes due to either turbulence-induced vibration or fluid-elastic instability is assessed. In the assessment, special emphases are put on the detailed investigation for the effects of support conditions, coil diameter, and helix pitch on the modal, vibration amplitude and instability characteristics of tubes, from which a technical information and basis needed for designers and regulatory reviewers can be derived. (authors)

  10. Expressing air pollution-induced health-related externalities in physical terms with the help of DALYs.

    Science.gov (United States)

    Bachmann, Till M; van der Kamp, Jonathan

    2017-06-01

    The unintended impacts of industrial activity on human health and the environment have regularly been assessed and monetised (referred to as "external costs"). External costs are, however, a rather abstract aggregate so that decision makers cannot easily relate them to tangible impacts. At the same time, physical health impact indicators have different units that cannot readily be compared and communicated in a joint way. To support better informed decisions at policy or company level, we propose and demonstrate a way to facilitate communication on non-monetized, that is, physical health indicators quantified in studies. The concept Disability-Adjusted Life Year (DALY) is chosen as metric due to its widespread use. We establish a comprehensive and consistent set of six health endpoints caused by particles and ozone, and derive related up-to-date DALYs. Further we apply the DALY values to a French smart grid demonstration project. Owing to its size, the gains in terms of reduced DALYs are however small. In contrast to external cost assessments, in the frame of which morbidity endpoints usually contribute to around 10-15%, they are found to be insubstantial in the overall DALY score (i.e. below 1%). This is because DALYs only consider time losses weighted by severity while external costs also factor in further welfare effects, i.e. combining resource, disutility and opportunity costs of illness. As a result, methodological limitations, mainly existing for the morbidity-related DALY values, appear to be less of concern. Overall, using the DALYs with and without morbidity impacts is justifiable. Either choice in the communication of health-related physical externalities induces the need to explain the limitations in terms of the treatment of morbidity endpoints (notably their definition and the disability weights used) or their complete disregard. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs.

    Science.gov (United States)

    Muñoz-Islas, Enriqueta; González-Hernández, Abimael; Lozano-Cuenca, Jair; Ramírez-Rosas, Martha Beatríz; Medina-Santillán, Roberto; Centurión, David; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

    2015-10-01

    During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1-C3) for infusions of 5-HT. The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action. © International Headache Society 2015.

  12. Saponin B, a novel cytostatic compound purified from Anemone taipaiensis, induces apoptosis in a human glioblastoma cell line.

    Science.gov (United States)

    Wang, Yuangang; Tang, Haifeng; Zhang, Yun; Li, Juan; Li, Bo; Gao, Zhenhui; Wang, Xiaoyang; Cheng, Guang; Fei, Zhou

    2013-11-01

    Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors. Saponin B, a novel compound isolated from the medicinal plant, Anemone taipaiensis, has been found to have a strong time- and dose-dependent cytostatic effect on human glioma cells and to suppress the growth of U87MG GBM cells. In this study, we investigated whether saponin B induces the apoptosis of glioblastoma cells and examined the underlying mechanism(s) of action of saponin B. Saponin B significantly suppressed U87MG cell proliferation. Flow cytometric analysis of DNA in the U87MG cells confirmed that saponin B blocked the cell cycle at the S phase. Furthermore, treatment of the U87MG cells with saponin B induced chromatin condensation and led to the formation of apoptotic bodies, as observed under a fluorescence microscope, and Annexin V/PI assay further suggested that phosphatidylserine (PS) externalization was apparent at higher drug concentrations. Treatment with saponin B activated the receptor-mediated pathway of apoptosis, as western blot analysis revealed the activation of Fas-l. Saponin B increased the Bax and caspase-3 ratio and decreased the protein expression of Bcl-2. The results from the present study demonstrate that the novel compound, saponin B, effectively induces the apoptosis of GBM cells and inhibits glioma cell growth and survival. Therefore, saponin B may be a potential candidate for the development of novel cancer therapeutics with antitumor activity against gliomas.

  13. Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives.

    Science.gov (United States)

    Peterson, Lisa K; Willis, Rohan; Harris, E Nigel; Branch, Ware D; Tebo, Anne E

    2016-01-01

    Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy-related morbidity accompanied by persistently positive antiphospholipid antibodies (aPL). Current laboratory criteria for APS classification recommend testing for lupus anticoagulant as well as IgG and IgM anticardiolipin, and beta-2 glycoprotein I (anti-β2GPI) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative for the recommended criteria aPL tests. While acknowledging that such patients may have clinical features that are not of an autoimmune etiology, experts also speculate that these "seronegative" patients may test negative for relevant autoantibodies as a result of a lack of harmonization and/or standardization. Alternatively, they may have aPL that target other antigens involved in the pathogenesis of APS. In the latter, autoantibodies that recognize a phosphatidylserine/prothrombin (PS/PT) complex have been reported to be associated with APS and may have diagnostic relevance. This review highlights analytical and clinical attributes associated with PS/PT antibodies, taking into consideration the performance characteristics of criteria aPL tests in APS with specific recommendations for harmonization and standardization efforts. © 2016 Elsevier Inc. All rights reserved.

  14. Fucoxanthin Induced Suicidal Death of Human Erythrocytes

    Directory of Open Access Journals (Sweden)

    Marilena Briglia

    2015-12-01

    Full Text Available Background/Aims: Fucoxanthin, a carotenoid isolated from brown seaweeds, induces suicidal death or apoptosis of tumor cells and is thus considered for the treatment or prevention of malignancy. In analogy to apoptosis of nucleated cell, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i, oxidative stress and activation of p38 kinase or protein kinase C. The present study explored, whether and how fucoxanthin induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and abundance of reactive oxygen species (ROS from DCFDA dependent fluorescence and lipid peroxidation using BODIPY fluoresence. Results: A 48 hours exposure of human erythrocytes to fucoxanthin significantly increased the percentage of annexin-V-binding cells (≥ 50 µM, significantly decreased average forward scatter (≥ 25 µM, significantly increased hemolysis (≥ 25 µM, significantly increased Fluo3-fluorescence (≥ 50 µM, significantly increased lipid peroxidation, but did not significantly modify DCFDA fluorescence. The effect of fucoxanthin on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+, and was insensitive to p38 kinase inhibitor skepinone (2 µM and to protein kinase C inhibitor calphostin (100 nM. Conclusion: Fucoxanthin triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of Ca2+ entry.

  15. International Space Station External Contamination Environment for Space Science Utilization

    Science.gov (United States)

    Soares, Carlos E.; Mikatarian, Ronald R.; Steagall, Courtney A.; Huang, Alvin Y.; Koontz, Steven; Worthy, Erica

    2014-01-01

    The International Space Station (ISS) is the largest and most complex on-orbit platform for space science utilization in low Earth orbit. Multiple sites for external payloads, with exposure to the associated natural and induced environments, are available to support a variety of space science utilization objectives. Contamination is one of the induced environments that can impact performance, mission success and science utilization on the vehicle. The ISS has been designed, built and integrated with strict contamination requirements to provide low levels of induced contamination on external payload assets. This paper addresses the ISS induced contamination environment at attached payload sites, both at the requirements level as well as measurements made on returned hardware, and contamination forecasting maps being generated to support external payload topology studies and science utilization.

  16. Radiation-induced external ear canal cholesteatoma-like disease

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, Akiko; Okuno, Hideji; Noguchi, Keisuke; Komatsuzaki, Atsushi [Tokyo Medical and Dental Univ. (Japan). School of Medicine

    1999-06-01

    Three cases of cholesteatoma-like disease in the ear canals after radiation therapy for head and neck tumor were reported. Effect of irradiation on bone and soft tissue including skin brings about pathological reaction to the external ear canal as well. Two types of disease resembling cholesteatomas have been recognized: keratosis obturans (KO) and external auditory canal cholesteatoma (EACC). KO appears to be derived from disease of canal skin involved with keratinization, creating a widning of the canal. EACC, on the other hand, seems to develop in the disease of bony canal where a localized absorption of its bone with invasion of squamous epithelium takes place. (author)

  17. Inducing and manipulating magnetization in 2D zinc–oxide by strain and external voltage

    Science.gov (United States)

    Taivansaikhan, P.; Tsevelmaa, T.; Rhim, S. H.; Hong, S. C.; Odkhuu, D.

    2018-04-01

    Two-dimensional (2D) structures that exhibit intriguing magnetic phenomena such as perpendicular magnetic anisotropy and its switchable feature are of great interests in spintronics research. Herein, the density functional theory studies reveal the critical impacts of strain and external gating on vacancy-induced magnetism and its spin direction in a graphene-like single layer of zinc oxide (ZnO). In contrast to the pristine and defective ZnO with an O-vacancy, the presence of a Zn-vacancy induces significant magnetic moments to its first neighboring O and Zn atoms due to the charge deficit. We further predict that the direction of magnetization easy axis reverses from an in-plane to perpendicular orientation under a practically achievable biaxial compressive strain of only ~1–2% or applying an electric field by means of the charge density modulation. This magnetization reversal is mainly driven by the strain- and electric-field-induced changes in the spin–orbit coupled d states of the first-neighbor Zn atom to a Zn-vacancy. These findings open interesting prospects for exploiting strain and electric field engineering to manipulate magnetism and magnetization orientation of 2D materials.

  18. Gain with and without population inversion via vacuum-induced coherence in a V-type atom without external coherent driving

    International Nuclear Information System (INIS)

    Xu Weihua; Wu Jinhui; Gao Jinyue

    2006-01-01

    In a three-level V-type atomic system without any external coherent driving, owing to the coherence that results from the vacuum of the radiation field, both the probe gain with and without population inversion can be achieved with very weak incoherent pumping. The gain is achieved in the absence of any external coherent driving field, so it is different from the gain without inversion in ordinary laser-driven schemes where a coherent driving field is necessary to create the coherence. The gain is also different from the conventional lasing gain because the population inversion is achieved via vacuum-induced coherence, which is dependent on the atomic coherence

  19. N-Acetylcysteine Amide Protects Against Oxidative Stress–Induced Microparticle Release From Human Retinal Pigment Epithelial Cells

    Science.gov (United States)

    Carver, Kyle A.; Yang, Dongli

    2016-01-01

    Purpose Oxidative stress is a major factor involved in retinal pigment epithelium (RPE) apoptosis that underlies AMD. Drusen, extracellular lipid- and protein-containing deposits, are strongly associated with the development of AMD. Cell-derived microparticles (MPs) are small membrane-bound vesicles shed from cells. The purpose of this study was to determine if oxidative stress drives MP release from RPE cells, to assess whether these MPs carry membrane complement regulatory proteins (mCRPs: CD46, CD55, and CD59), and to evaluate the effects of a thiol antioxidant on oxidative stress–induced MP release. Methods Retinal pigment epithelium cells isolated from human donor eyes were cultured and treated with hydrogen peroxide (H2O2) to induce oxidative stress. Isolated MPs were fixed for transmission electron microscopy or processed for component analysis by flow cytometry, Western blot analysis, and confocal microscopy. Results Transmission electron microscopy showed that MPs ranged in diameter from 100 to 1000 nm. H2O2 treatment led to time- and dose-dependent elevations in MPs with externalized phosphatidylserine and phosphatidylethanolamine, known markers of MPs. These increases were strongly correlated to RPE apoptosis. Oxidative stress significantly increased the release of mCRP-positive MPs, which were prevented by a thiol antioxidant, N-acetylcysteine amide (NACA). Conclusions This is the first evidence that oxidative stress induces cultured human RPE cells to release MPs that carry mCRPs on their surface. The levels of released MPs are strongly correlated with RPE apoptosis. N-acetylcysteine amide prevents oxidative stress–induced effects. Our findings indicate that oxidative stress reduces mCRPs on the RPE surface through releasing MPs. PMID:26842754

  20. Methanolic Extracts from Brown Seaweeds Dictyota cilliolata and Dictyota menstrualis Induce Apoptosis in Human Cervical Adenocarcinoma HeLa Cells

    Directory of Open Access Journals (Sweden)

    Dayanne Lopes Gomes

    2015-04-01

    Full Text Available Carcinoma of the uterine cervix is the second most common female tumor worldwide, surpassed only by breast cancer. Natural products from seaweeds evidencing apoptotic activity have attracted a great deal of attention as new leads for alternative and complementary preventive or therapeutic anticancer agents. Here, methanol extracts from 13 species of tropical seaweeds (Rhodophytas, Phaeophyta and Chlorophyta collected from the Northeast of Brazil were assessed as apoptosis-inducing agents on human cervical adenocarcinoma (HeLa. All extracts showed different levels of cytotoxicity against HeLa cells; the most potent were obtained from the brown alga Dictyota cilliolata (MEDC and Dictyota menstrualis (MEDM. In addition, MEDC and MEDM also inhibits SiHa (cervix carcinoma cell proliferation. Studies with these two extracts using flow cytometry and fluorescence microscopy showed that HeLa cells exposed to MEDM and MEDC exhibit morphological and biochemical changes that characterize apoptosis as shown by loss of cell viability, chromatin condensation, phosphatidylserine externalization, and sub-G1 cell cycle phase accumulation, also MEDC induces cell cycle arrest in cell cycle phase S. Moreover, the activation of caspases 3 and 9 by these extracts suggests a mitochondria-dependent apoptosis route. However, other routes cannot be ruled out. Together, these results point out the methanol extracts of the brown algae D. mentrualis and D. cilliolata as potential sources of molecules with antitumor activity.

  1. Evaluation of the Induced Activity in Air by the External Proton Beam in the Target Room of the Proton Accelerator Facility of Proton Engineering Frontier Project

    International Nuclear Information System (INIS)

    Lee, Cheol Woo; Lee, Young Ouk; Cho, Young Sik; Ahn, So Hyun

    2007-01-01

    One of the radiological concerns is the worker's exposure level and the concentration of the radionuclides in the air after shutdown, for the safety analysis on the proton accelerator facility. Although, the primary radiation source is the protons accelerated up to design value, all of the radio-nuclide is produced from the secondary neutron and photon induced reaction in air. Because, the protons don't penetrate the acceleration equipment like the DTL tank wall or BTL wall, secondary neutrons or photons are only in the air in the accelerator tunnel building because of the short range of the proton in the materials. But, for the case of the target rooms, external proton beams are occasionally used in the various experiments. When these external proton beams travel through air from the end of the beam transport line to the target, they interact directly with air and produce activation products from the proton induced reaction. The external proton beam will be used in the target rooms in the accelerator facility of the Proton Accelerator Frontier Project (PEFP). In this study, interaction characteristics of the external proton beam with air and induced activity in air from the direct interaction of the proton beam were evaluated

  2. External Events PSA for the Paks NPP

    International Nuclear Information System (INIS)

    Bareith, Attila; Karsa, Zoltan; Siklossy, Tamas; Vida, Zoltan

    2014-01-01

    quantification and interpretation of results. The risk of core damage induced by natural external hazards was quantified to the extent seen feasible. In addition to risk quantification, unresolved issues and necessary follow-on analyses were identified and proposed. At present an action plan is being developed for these analyses. Core damage risk has been assessed quantitatively for wind, snow and frost hazards. Detailed importance, sensitivity and uncertainty analyses were conducted. Moreover the main risk contributors induced by these external events were also identified. Additional follow-on analyses were proposed to enable an improved risk quantification by means of reducing uncertainties, establishing a better technical basis for the applied analytical assumptions, or decreasing unnecessarily high conservatism. Based on the findings of hazard assessment and plant response analysis, the core damage risk induced by extreme rainfall and lightning was found to be insignificant. However, some follow-on analyses were proposed and safety enhancement measures were conceptualised to fully underpin this conclusion. Due to lack of appropriate data and supporting analysis on the capacity of plant systems and components no PSA model has been developed yet for extreme temperatures. Follow-on analyses necessary for quantifying the risk of core damage induced by extreme temperatures have been identified. (authors)

  3. Aqueous Fraction of Nephelium ramboutan-ake Rind Induces Mitochondrial-Mediated Apoptosis in HT-29 Human Colorectal Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Muhamad Noor Alfarizal Kamarudin

    2012-05-01

    Full Text Available The aim of this study was to investigate the cytotoxic and apoptotic effects of Nephelium ramboutan-ake (pulasan rind in selected human cancer cell lines. The crude ethanol extract and fractions (ethyl acetate and aqueous of N. ramboutan-ake inhibited the growth of HT-29, HCT-116, MDA-MB-231, Ca Ski cells according to MTT assays. The N. ramboutan-ake aqueous fraction (NRAF was found to exert the greatest cytotoxic effect against HT-29 in a dose-dependent manner. Evidence of apoptotic cell death was revealed by features such as chromatin condensation, nuclear fragmentation and apoptotic body formation. The result from a TUNEL assay strongly suggested that NRAF brings about DNA fragmentation in HT-29 cells. Phosphatidylserine (PS externalization on the outer leaflet of plasma membranes was detected with annexin V-FITC/PI binding, confirming the early stage of apoptosis. The mitochondrial permeability transition is an important step in the induction of cellular apoptosis, and the results clearly suggested that NRAF led to collapse of mitochondrial transmembrane potential in HT-29 cells. This attenuation of mitochondrial membrane potential (Δψm was accompanied by increased production of ROS and depletion of GSH, an increase of Bax protein expression, and induced-activation of caspase-3/7 and caspase-9. These combined results suggest that NRAF induces mitochondrial-mediated apoptosis.

  4. Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry

    Science.gov (United States)

    Moller-Tank, Sven; Kondratowicz, Andrew S.; Davey, Robert A.; Rennert, Paul D.

    2013-01-01

    The cell surface receptor T cell immunoglobulin mucin domain 1 (TIM-1) dramatically enhances filovirus infection of epithelial cells. Here, we showed that key phosphatidylserine (PtdSer) binding residues of the TIM-1 IgV domain are critical for Ebola virus (EBOV) entry through direct interaction with PtdSer on the viral envelope. PtdSer liposomes but not phosphatidylcholine liposomes competed with TIM-1 for EBOV pseudovirion binding and transduction. Further, annexin V (AnxV) substituted for the TIM-1 IgV domain, supporting a PtdSer-dependent mechanism. Our findings suggest that TIM-1-dependent uptake of EBOV occurs by apoptotic mimicry. Additionally, TIM-1 enhanced infection of a wide range of enveloped viruses, including alphaviruses and a baculovirus. As further evidence of the critical role of enveloped-virion-associated PtdSer in TIM-1-mediated uptake, TIM-1 enhanced internalization of pseudovirions and virus-like proteins (VLPs) lacking a glycoprotein, providing evidence that TIM-1 and PtdSer-binding receptors can mediate virus uptake independent of a glycoprotein. These results provide evidence for a broad role of TIM-1 as a PtdSer-binding receptor that mediates enveloped-virus uptake. Utilization of PtdSer-binding receptors may explain the wide tropism of many of these viruses and provide new avenues for controlling their virulence. PMID:23698310

  5. Health-related external cost assessment in Europe: methodological developments from ExternE to the 2013 Clean Air Policy Package.

    Science.gov (United States)

    van der Kamp, Jonathan; Bachmann, Till M

    2015-03-03

    "Getting the prices right" through internalizing external costs is a guiding principle of environmental policy making, one recent example being the EU Clean Air Policy Package released at the end of 2013. It is supported by impact assessments, including monetary valuation of environmental and health damages. For over 20 years, related methodologies have been developed in Europe in the Externalities of Energy (ExternE) project series and follow-up activities. In this study, we aim at analyzing the main methodological developments over time from the 1990s until today with a focus on classical air pollution-induced human health damage costs. An up-to-date assessment including the latest European recommendations is also applied. Using a case from the energy sector, we identify major influencing parameters: differences in exposure modeling and related data lead to variations in damage costs of up to 21%; concerning risk assessment and monetary valuation, differences in assessing long-term exposure mortality risks together with assumptions on particle toxicity explain most of the observed changes in damage costs. These still debated influencing parameters deserve particular attention when damage costs are used to support environmental policy making.

  6. External Contamination Control of Attached Payloads on the International Space Station

    Science.gov (United States)

    Soares, Carlos E.; Mikatarian, Ronald R.; Olsen, Randy L.; Huang, Alvin Y.; Steagall, Courtney A.; Schmidl, William D.; Wright, Bruce D.; Koontz, Steven

    2012-01-01

    The International Space Station (ISS) is an on-orbit platform for science utilization in low Earth orbit with multiple sites for external payloads with exposure to the natural and induced environments. Contamination is one of the induced environments that can impact performance, mission success and science utilization on the vehicle. This paper describes the external contamination control requirements and integration process for externally mounted payloads on the ISS. The external contamination control requirements are summarized and a description of the integration and verification process is detailed to guide payload developers in the certification process of attached payloads on the vehicle. A description of the required data certification deliverables covers the characterization of contamination sources. Such characterization includes identification, usage and operational data for each class of contamination source. Classes of external contamination sources covered are vacuum exposed materials, sources of leakage, vacuum venting and thrusters. ISS system level analyses are conducted by the ISS Space Environments Team to certify compliance with external contamination control requirements. This paper also addresses the ISS induced contamination environment at attached payload sites, both at the requirements level as well as measurements made on ISS.

  7. Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum

    International Nuclear Information System (INIS)

    Inouye, Minoru; Yamamura, Hideki; Nakano, Atsuhiro.

    1995-01-01

    Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 μmol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 μg/g at the time of irradiation and remaining at more than 40 μg/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositide-mediated signaling systems regulate radiation-induced apoptosis. (author)

  8. Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum.

    Science.gov (United States)

    Inouye, M; Yamamura, H; Nakano, A

    1995-09-01

    Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 mumol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 micrograms/g at the time of irradiation and remaining at more than 40 micrograms/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositidemediated signaling systems regulate radiation-induced apoptosis.

  9. Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Inouye, Minoru; Yamamura, Hideki [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine; Nakano, Atsuhiro

    1995-09-01

    Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 {mu}mol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 {mu}g/g at the time of irradiation and remaining at more than 40 {mu}g/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositide-mediated signaling systems regulate radiation-induced apoptosis. (author).

  10. Simple wealth distribution model causing inequality-induced crisis without external shocks

    Science.gov (United States)

    Benisty, Henri

    2017-05-01

    We address the issue of the dynamics of wealth accumulation and economic crisis triggered by extreme inequality, attempting to stick to most possibly intrinsic assumptions. Our general framework is that of pure or modified multiplicative processes, basically geometric Brownian motions. In contrast with the usual approach of injecting into such stochastic agent models either specific, idiosyncratic internal nonlinear interaction patterns or macroscopic disruptive features, we propose a dynamic inequality model where the attainment of a sizable fraction of the total wealth by very few agents induces a crisis regime with strong intermittency, the explicit coupling between the richest and the rest being a mere normalization mechanism, hence with minimal extrinsic assumptions. The model thus harnesses the recognized lack of ergodicity of geometric Brownian motions. It also provides a statistical intuition to the consequences of Thomas Piketty's recent "r >g " (return rate > growth rate) paradigmatic analysis of very-long-term wealth trends. We suggest that the "water-divide" of wealth flow may define effective classes, making an objective entry point to calibrate the model. Consistently, we check that a tax mechanism associated to a few percent relative bias on elementary daily transactions is able to slow or stop the build-up of large wealth. When extreme fluctuations are tamed down to a stationary regime with sizable but steadier inequalities, it should still offer opportunities to study the dynamics of crisis and the inner effective classes induced through external or internal factors.

  11. Phosphatidylserine-Liposomes Promote Tolerogenic Features on Dendritic Cells in Human Type 1 Diabetes by Apoptotic Mimicry

    Directory of Open Access Journals (Sweden)

    Silvia Rodriguez-Fernandez

    2018-02-01

    Full Text Available Type 1 diabetes (T1D is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow β-cell recovery has become vital. Relying on the inherent ability of apoptotic cells to induce immunological tolerance, we demonstrated that liposomes mimicking apoptotic β-cells arrested autoimmunity to β-cells and prevented experimental T1D through tolerogenic dendritic cell (DC generation. These liposomes contained phosphatidylserine (PS—the main signal of the apoptotic cell membrane—and β-cell autoantigens. To move toward a clinical application, PS-liposomes with optimum size and composition for phagocytosis were loaded with human insulin peptides and tested on DCs from patients with T1D and control age-related subjects. PS accelerated phagocytosis of liposomes with a dynamic typical of apoptotic cell clearance, preserving DCs viability. After PS-liposomes phagocytosis, the expression pattern of molecules involved in efferocytosis, antigen presentation, immunoregulation, and activation in DCs concurred with a tolerogenic functionality, both in patients and control subjects. Furthermore, DCs exposed to PS-liposomes displayed decreased ability to stimulate autologous T cell proliferation. Moreover, transcriptional changes in DCs from patients with T1D after PS-liposomes phagocytosis pointed to an immunoregulatory prolife. Bioinformatics analysis showed 233 differentially expressed genes. Genes involved in antigen presentation were downregulated, whereas genes pertaining to tolerogenic/anti-inflammatory pathways were mostly upregulated. In conclusion, PS-liposomes phagocytosis mimics efferocytosis and leads to phenotypic and functional changes in human DCs, which are accountable for tolerance induction. The herein reported results reinforce the potential of this novel immunotherapy to re-establish immunological

  12. Small--radiation-amplitude dynamical voltage model of an irradiated, externally unbiased Josephson tunnel junction

    International Nuclear Information System (INIS)

    McAdory, R.T. Jr.

    1988-01-01

    A theory is presented for the nonequilibrium voltage states of an irradiated Josephson junction shunted by an external resistor but with no external current or voltage biasing. This device, referred to as a free-running Josephson junction, is modeled in a small--radiation-amplitude, deterministic regime extending the previous work of Shenoy and Agarwal. The time-averaged induced voltage is treated as a dynamical variable, the external radiation is modeled as a current source, and the induced junction-radiation vector potential, with and without a mode structure, is treated to first order in the driving currents. A dynamical equation for the time-averaged induced voltage yields a (nonequilibrium) steady-state relation between the time-averaged induced voltage and the incident radiation amplitude valid for a wide range of voltages, including zero. Regions of bistability occur in the voltage--versus--incident-amplitude curves, some of which are dependent on the external resistor. The zero-voltage state breaks down, as the external radiation amplitude is increased, at a critical value of the incident-radiation amplitude inversely proportional to the external resistance

  13. The effect of internal and external fields of view on visually induced motion sickness.

    Science.gov (United States)

    Bos, Jelte E; de Vries, Sjoerd C; van Emmerik, Martijn L; Groen, Eric L

    2010-07-01

    Field of view (FOV) is said to affect visually induced motion sickness. FOV, however, is characterized by an internal setting used by the graphics generator (iFOV) and an external factor determined by screen size and viewing distance (eFOV). We hypothesized that especially the incongruence between iFOV and eFOV would lead to sickness. To that end we used a computer game environment with different iFOV and eFOV settings, and found the opposite effect. We speculate that the relative large differences between iFOV and eFOV used in this experiment caused the discrepancy, as may be explained by assuming an observer model controlling body motion. Copyright 2009 Elsevier Ltd. All rights reserved.

  14. Effect of External Use of Sesame Oil in the Prevention of Chemotherapy-Induced Phlebitis

    Science.gov (United States)

    Nekuzad, Nilufar; Ashke Torab, Tahereh; Mojab, Faraz; Alavi-Majd, Hamid; Azadeh, Payam; Ehtejab, Gholamreza

    2012-01-01

    Intravenous chemotherapy is an important mean for the treatment of cancers. Infusion phlebitis (Ph) is a common and acute complication of chemotherapy. The frequency of Ph is about 70% in patients undergoing chemotherapeutic management. It can induce the pain, increase the risk of thrombophlebitis, lead to incomplete follow-up, and thereby, affect the patient’s health status. Respecting the great importance of these issues, it is essential to prevent Ph. This study conducted to determine the effect of external use of Sesame Oil (SO) in the prevention of Ph. Sixty patients with colon or rectum cancer, who admitted for chemotherapeutic management, enrolled in clinical trial and were randomly divided into two equal groups: Control and Intervention. Ten drops of SO was applied twice a day for 14 days externally in intervention group, whereas the control group received nothing. Incidence and grade of Ph was measured in both groups. Data was analyzed through independent t-test, Χ2, Fisher’s exact test, Mann-Whitney, and Lagrange survival using SPSS 16. The incidence of Ph was 10% and 80% in intervention group and control group, respectively.There was a significant difference between two groups (p < 0.05). Ph was 8 times more frequent in control group (R R = 8; AR R = 70%). In addition, there was statistically significant difference between the grade and incidence of Ph with SO and control group (p < 0.05). According to these results, it seems that external use of SO is effective, safe and well-tolerated for prophylaxis from Ph. Therefore, it can be suggested as a selected prevention method for reducing the complication. PMID:24250538

  15. Phosphatidylserine Lateral Organization Influences the Interaction of Influenza Virus Matrix Protein 1 with Lipid Membranes.

    Science.gov (United States)

    Bobone, Sara; Hilsch, Malte; Storm, Julian; Dunsing, Valentin; Herrmann, Andreas; Chiantia, Salvatore

    2017-06-15

    Influenza A virus matrix protein 1 (M1) is an essential component involved in the structural stability of the virus and in the budding of new virions from infected cells. A deeper understanding of the molecular basis of virion formation and the budding process is required in order to devise new therapeutic approaches. We performed a detailed investigation of the interaction between M1 and phosphatidylserine (PS) (i.e., its main binding target at the plasma membrane [PM]), as well as the distribution of PS itself, both in model membranes and in living cells. To this end, we used a combination of techniques, including Förster resonance energy transfer (FRET), confocal microscopy imaging, raster image correlation spectroscopy, and number and brightness (N&B) analysis. Our results show that PS can cluster in segregated regions in the plane of the lipid bilayer, both in model bilayers constituted of PS and phosphatidylcholine and in living cells. The viral protein M1 interacts specifically with PS-enriched domains, and such interaction in turn affects its oligomerization process. Furthermore, M1 can stabilize PS domains, as observed in model membranes. For living cells, the presence of PS clusters is suggested by N&B experiments monitoring the clustering of the PS sensor lactadherin. Also, colocalization between M1 and a fluorescent PS probe suggest that, in infected cells, the matrix protein can specifically bind to the regions of PM in which PS is clustered. Taken together, our observations provide novel evidence regarding the role of PS-rich domains in tuning M1-lipid and M1-M1 interactions at the PM of infected cells. IMPORTANCE Influenza virus particles assemble at the plasma membranes (PM) of infected cells. This process is orchestrated by the matrix protein M1, which interacts with membrane lipids while binding to the other proteins and genetic material of the virus. Despite its importance, the initial step in virus assembly (i.e., M1-lipid interaction) is still

  16. Xylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells

    Directory of Open Access Journals (Sweden)

    Luciano de Souza Santos

    2017-01-01

    Full Text Available Xylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells. In this study, the underlying mechanism of xylopine cytotoxicity was assessed in human colon carcinoma HCT116 cells. Xylopine displayed potent cytotoxicity in different cancer cell lines in monolayer cultures and in a 3D model of cancer multicellular spheroids formed from HCT116 cells. Typical morphology of apoptosis, cell cycle arrest in the G2/M phase, increased internucleosomal DNA fragmentation, loss of the mitochondrial transmembrane potential, and increased phosphatidylserine externalization and caspase-3 activation were observed in xylopine-treated HCT116 cells. Moreover, pretreatment with a caspase-3 inhibitor (Z-DEVD-FMK, but not with a p53 inhibitor (cyclic pifithrin-α, reduced xylopine-induced apoptosis, indicating induction of caspase-mediated apoptosis by the p53-independent pathway. Treatment with xylopine also caused an increase in the production of reactive oxygen/nitrogen species (ROS/RNS, including hydrogen peroxide and nitric oxide, but not superoxide anion, and reduced glutathione levels were decreased in xylopine-treated HCT116 cells. Application of the antioxidant N-acetylcysteine reduced the ROS levels and xylopine-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. In conclusion, xylopine has potent cytotoxicity to different cancer cell lines and is able to induce oxidative stress and G2/M phase arrest, triggering caspase-mediated apoptosis by the p53-independent pathway in HCT116 cells.

  17. Controlled transport of solitons and bubbles using external perturbations

    International Nuclear Information System (INIS)

    Gonzalez, J.A.; Marcano, A.; Mello, B.A.; Trujillo, L.

    2006-01-01

    We investigate generalized soliton-bearing systems in the presence of external perturbations. We show the possibility of the transport of solitons using external waves, provided the waveform and its velocity satisfy certain conditions. We also investigate the stabilization and transport of bubbles using external perturbations in 3D-systems. We also present the results of real experiments with laser-induced vapor bubbles in liquids

  18. Neolignans from Nectandra megapotamica (Lauraceae Display in vitro Cytotoxic Activity and Induce Apoptosis in Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Vitor Ponci

    2015-07-01

    Full Text Available Nectandra megapotamica (Spreng. Mez. (Lauraceae is a well-known Brazilian medicinal plant that has been used in folk medicine to treat several diseases. In continuation of our ongoing efforts to discover new bioactive natural products from the Brazilian flora, this study describes the identification of cytotoxic compounds from the MeOH extract of N. megapotamica (Lauraceae leaves using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of eight tetrahydrofuran neolignans: calopeptin (1, machilin-G (2, machilin-I (3, aristolignin (4, nectandrin A (5, veraguensin (6, ganschisandrin (7, and galgravin (8. Different assays were conducted to evaluate their cytotoxic activities and to determine the possible mechanism(s related to the activity displayed against human leukemia cells. The most active compounds 4, 5 and 8 gave IC50 values of 14.2 ± 0.7, 16.9 ± 0.8 and 16.5 ± 0.8 µg/mL, respectively, against human leukemia (HL-60 tumor cells. Moreover, these compounds induced specific apoptotic hallmarks, such as plasma membrane bleb formation, nuclear DNA condensation, specific chromatin fragmentation, phosphatidyl-serine exposure on the external leaflet of the plasma membrane, cleavage of PARP as well as mitochondrial damage, which as a whole could be related to the intrinsic apoptotic pathway.

  19. Analysis of Amino Acid Residues of Potential Importance for Phosphati-dylserine Specificity of P4-type ATPase ATP8A2

    DEFF Research Database (Denmark)

    Mogensen, Louise; Vestergaard, Anna Lindeløv; Mikkelsen, Stine

    The asymmetric structure of the plasma membrane is maintained through internalization of phos-pholipids by the family of P4-ATPases by a poorly characterized mechanism. Studies in yeast point towards a non-classical pathway involving important residues of a two-gate mechanism [1]. Glycine-230...... 302 of ATP8A2 with alanine (N302A), tyrosine (N302Y) and serine (N302S). Furthermore, a triple mutant of ATP8A2 (Q95GQ96AN302S) was studied to reveal any cooperativity between the two gates, as observed in yeast [1]. The affinities of the mutants for phosphatidylserine and phosphatidylethanolamine...

  20. External gamma irradiation-induced effects in early-life stages of zebrafish, Danio rerio

    International Nuclear Information System (INIS)

    Gagnaire, B.; Cavalié, I.; Pereira, S.; Floriani, M.; Dubourg, N.; Camilleri, V.; Adam-Guillermin, C.

    2015-01-01

    Highlights: • The present study aimed to evaluate the effects of gamma rays on zebrafish larvae. • Different techniques were used: gene expression, biochemistry, microscopy and macroscopical observations. • The results showed that gamma irradiation can alter embryo-larval development at several levels of organization. - Abstract: In the general context of validation of tools useful for the characterization of ecological risk linked to ionizing radiation, the effects of an external gamma irradiation were studied in zebrafish larvae irradiated for 96 h with two dose rates: 0.8 mGy/d, which is close to the level recommended to protect ecosystems from adverse effects of ionizing radiation (0.24 mGy/d) and a higher dose rate of 570 mGy/d. Several endpoints were investigated, such as mortality, hatching, and some parameters of embryo-larval development, immunotoxicity, apoptosis, genotoxicity, neurotoxicity and histological alterations. Results showed that an exposure to gamma rays induced an acceleration of hatching for both doses and a decrease of yolk bag diameter for the highest dose, which could indicate an increase of global metabolism. AChE activity decreased with the low dose rate of gamma irradiation and alterations were also shown in muscles of irradiated larvae. These results suggest that gamma irradiation can induce damages on larval neurotransmission, which could have repercussions on locomotion. DNA damages, basal ROS production and apoptosis were also induced by irradiation, while ROS stimulation index and EROD biotransformation activity were decreased and gene expression of acetylcholinesterase, choline acetyltransferase, cytochrome p450 and myeloperoxidase increased. These results showed that ionizing radiation induced an oxidative stress conducting to DNA damages. This study characterized further the modes of action of ionizing radiation in fish.

  1. External gamma irradiation-induced effects in early-life stages of zebrafish, Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Gagnaire, B., E-mail: beatrice.gagnaire@irsn.fr [Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115 (France); Cavalié, I. [Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115 (France); Pereira, S. [Neolys Diagnostics, Lyon 69373 (France); Floriani, M.; Dubourg, N.; Camilleri, V.; Adam-Guillermin, C. [Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115 (France)

    2015-12-15

    Highlights: • The present study aimed to evaluate the effects of gamma rays on zebrafish larvae. • Different techniques were used: gene expression, biochemistry, microscopy and macroscopical observations. • The results showed that gamma irradiation can alter embryo-larval development at several levels of organization. - Abstract: In the general context of validation of tools useful for the characterization of ecological risk linked to ionizing radiation, the effects of an external gamma irradiation were studied in zebrafish larvae irradiated for 96 h with two dose rates: 0.8 mGy/d, which is close to the level recommended to protect ecosystems from adverse effects of ionizing radiation (0.24 mGy/d) and a higher dose rate of 570 mGy/d. Several endpoints were investigated, such as mortality, hatching, and some parameters of embryo-larval development, immunotoxicity, apoptosis, genotoxicity, neurotoxicity and histological alterations. Results showed that an exposure to gamma rays induced an acceleration of hatching for both doses and a decrease of yolk bag diameter for the highest dose, which could indicate an increase of global metabolism. AChE activity decreased with the low dose rate of gamma irradiation and alterations were also shown in muscles of irradiated larvae. These results suggest that gamma irradiation can induce damages on larval neurotransmission, which could have repercussions on locomotion. DNA damages, basal ROS production and apoptosis were also induced by irradiation, while ROS stimulation index and EROD biotransformation activity were decreased and gene expression of acetylcholinesterase, choline acetyltransferase, cytochrome p450 and myeloperoxidase increased. These results showed that ionizing radiation induced an oxidative stress conducting to DNA damages. This study characterized further the modes of action of ionizing radiation in fish.

  2. Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance.

    Science.gov (United States)

    Violante, Ines R; Li, Lucia M; Carmichael, David W; Lorenz, Romy; Leech, Robert; Hampshire, Adam; Rothwell, John C; Sharp, David J

    2017-03-14

    Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.

  3. PET imaging of apoptosis with 64Cu-labeled streptavidin following pretargeting of phosphatidylserine with biotinylated annexin-V

    International Nuclear Information System (INIS)

    Cauchon, Nicole; Langlois, Rejean; Rousseau, Jacques A.; Tessier, Guillaume; Cadorette, Jules; Lecomte, Roger; Hunting, Darel J.; Lier, Johan E. van; Pavan, Roberto A.; Zeisler, Stefan K.

    2007-01-01

    In vivo detection of apoptosis is a diagnostic tool with potential clinical applications in cardiology and oncology. Radiolabeled annexin-V (anxV) is an ideal probe for in vivo apoptosis detection owing to its strong affinity for phosphatidylserine (PS), the molecular flag on the surface of apoptotic cells. Most clinical studies performed to visualize apoptosis have used 99m Tc-anxV; however, its poor distribution profile often compromises image quality. In this study, tumor apoptosis after therapy was visualized by positron emission tomography (PET) using 64 Cu-labeled streptavidin (SAv), following pre-targeting of apoptotic cells with biotinylated anxV. Apoptosis was induced in tumor-bearing mice by photodynamic therapy (PDT) using phthalocyanine dyes as photosensitizers, and red light. After PDT, mice were injected i.v. with biotinylated anxV, followed 2 h later by an avidin chase, and after another 2 h with 64 Cu-DOTA-biotin-SAv. PET images were subsequently recorded up to 13 h after PDT. PET images delineated apoptosis in treated tumors as early as 30 min after 64 Cu-DOTA-biotin-SAv administration, with tumor-to-background ratios reaching a maximum at 3 h post-injection, i.e., 7 h post-PDT. Omitting the administration of biotinylated anxV or the avidin chase failed to provide a clear PET image, confirming that all three steps are essential for adequate visualization of apoptosis. Furthermore, differences in action mechanisms between photosensitizers that target tumor cells directly or via initial vascular stasis were clearly recognized through differences in tracer uptake patterns detecting early or delayed apoptosis. This study demonstrates the efficacy of a three-step 64 Cu pretargeting procedure for PET imaging of apoptosis. Our data also confirm the usefulness of small animal PET to evaluate cancer treatment protocols. (orig.)

  4. Pathological studies on carcinoma of the lung in rats induced by external x-ray irradiation

    International Nuclear Information System (INIS)

    Kodama, Tetsuro

    1978-01-01

    Lung tumors in Wistar rats were induced by administration of various doses of external irradiation through the anterior chest wall. Pulmonary fibrosis following external irradiation was observed in 13 of 17 rats (76.4%) in Group I (800R/day for 5 days), in 26 of 36 rats (78.8%) in Group II (800R/WK for 5 WKs), and in 6 of 18 rats (35.3%) in Group III (500R/WK for 4 WKs). The degree of pulmonary fibrosis was greater each time in the rats given 4,000R than in the rats given 2,000R. In Groups I and II 5 pulmonary tumors (2 squamous cell carcinomas, 1 adenocarcinoma, and 2 adenomas) were observed in 3 of 16 rats (17.6%), and 10 pulmonary tumors (4 squamous cell carcinomas, 1 adenocarcinoma, 4 adenomas, and 1 fibrosarcoma) were observed in 9 of 33 rats (24.2%), respectively. In Group III only 1 case of pulmonary adenoma was observed among 17 rats (6.8%). The first case of epithelial tumor of the lung was found in a rat in Group I. Histological findings during the course of the experiment revealed that the earliest changes following irradiation were those of radiation pneuminitis, characterized by engorged capillaries and edema in collapsed alveoli, with lymphocytic and plasma cell infiltrations. In addition, the nuclei of the lining cells of the alveoli and bronchioles were enlarged and atypical. From the 10th through the 20th experimental week, fibrosis of the alveolar septum and adenomatous hyperplasia of the alveolar lining became extensive, particularly in the bronchiolo-alveolar areas of the periphery of the lung. Atypical adenomatous hyperplasia occurred within the fibrotic lesion or in proximity to it. It was frequently followed by carcinoma, suggesting that carcinoma in the present experiment arose in atypical epithelium, induced by irradiation of the bronchiolo-alveolar epithelial lining

  5. Pathological studies on carcinoma of the lung in rats induced by external x-ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kodama, T [Hiroshima Univ. (Japan). School of Medicine

    1978-08-01

    Lung tumors in Wistar rats were induced by administration of various doses of external irradiation through the anterior chest wall. Pulmonary fibrosis following external irradiation was observed in 13 of 17 rats (76.4%) in Group I (800R/day for 5 days), in 26 of 36 rats (78.8%) in Group II (800R/WK for 5 WKs), and in 6 of 18 rats (35.3%) in Group III (500R/WK for 4 WKs). The degree of pulmonary fibrosis was greater each time in the rats given 4,000R than in the rats given 2,000R. In Groups I and II 5 pulmonary tumors (2 squamous cell carcinomas, 1 adenocarcinoma, and 2 adenomas) were observed in 3 of 16 rats (17.6%), and 10 pulmonary tumors (4 squamous cell carcinomas, 1 adenocarcinoma, 4 adenomas, and 1 fibrosarcoma) were observed in 9 of 33 rats (24.2%), respectively. In Group III only 1 case of pulmonary adenoma was observed among 17 rats (6.8%). The first case of epithelial tumor of the lung was found in a rat in Group I. Histological findings during the course of the experiment revealed that the earliest changes following irradiation were those of radiation pneuminitis, characterized by engorged capillaries and edema in collapsed alveoli, with lymphocytic and plasma cell infiltrations. In addition, the nuclei of the lining cells of the alveoli and bronchioles were enlarged and atypical. From the 10th through the 20th experimental week, fibrosis of the alveolar septum and adenomatous hyperplasia of the alveolar lining became extensive, particularly in the bronchiolo-alveolar areas of the periphery of the lung. Atypical adenomatous hyperplasia occurred within the fibrotic lesion or in proximity to it. It was frequently followed by carcinoma, suggesting that carcinoma in the present experiment arose in atypical epithelium, induced by irradiation of the bronchiolo-alveolar epithelial lining.

  6. Characterization of the apoptotic response induced by the cyanine dye D112: a potentially selective anti-cancer compound.

    Directory of Open Access Journals (Sweden)

    Ning Yang

    Full Text Available Chemotherapeutic drugs that are used in anti-cancer treatments often cause the death of both cancerous and noncancerous cells. This non-selective toxicity is the root cause of untoward side effects that limits the effectiveness of therapy. In order to improve chemotherapeutic options for cancer patients, there is a need to identify novel compounds with higher discrimination for cancer cells. In the past, methine dyes that increase the sensitivity of photographic emulsions have been investigated for anti-cancer properties. In the 1970's, Kodak Laboratories initiated a screen of approximately 7000 dye structural variants for selective toxicity. Among these, D112 was identified as a promising compound with elevated toxicity against a colon cancer cell line in comparison to a non-transformed cell line. Despite these results changing industry priorities led to a halt in further studies on D112. We decided to revive investigations on D112 and have further characterized D112-induced cellular toxicity. We identified that in response to D112 treatment, the T-cell leukemia cell line Jurkat showed caspase activation, mitochondrial depolarization, and phosphatidylserine externalization, all of which are hallmarks of apoptosis. Chemical inhibition of caspase enzymatic activity and blockade of the mitochondrial pathway through Bcl-2 expression inhibited D112-induced apoptosis. At lower concentrations, D112 induced growth arrest. To gain insight into the molecular mechanism of D112 induced mitochondrial dysfunction, we analyzed the intracellular localization of D112, and found that D112 associated with mitochondria. Interestingly, in the cell lines that we tested, D112 showed increased toxicity toward transformed versus non-transformed cells. Results from this work identify D112 as a potentially interesting molecule warranting further investigation.

  7. Protective Effects of Ferulic Acid on High Glucose-Induced Protein Glycation, Lipid Peroxidation, and Membrane Ion Pump Activity in Human Erythrocytes.

    Directory of Open Access Journals (Sweden)

    Weerachat Sompong

    Full Text Available Ferulic acid (FA is the ubiquitous phytochemical phenolic derivative of cinnamic acid. Experimental studies in diabetic models demonstrate that FA possesses multiple mechanisms of action associated with anti-hyperglycemic activity. The mechanism by which FA prevents diabetes-associated vascular damages remains unknown. The aim of study was to investigate the protective effects of FA on protein glycation, lipid peroxidation, membrane ion pump activity, and phosphatidylserine exposure in high glucose-exposed human erythrocytes. Our results demonstrated that FA (10-100 μM significantly reduced the levels of glycated hemoglobin (HbA1c whereas 0.1-100 μM concentrations inhibited lipid peroxidation in erythrocytes exposed to 45 mM glucose. This was associated with increased glucose consumption. High glucose treatment also caused a significant reduction in Na+/K+-ATPase activity in the erythrocyte plasma membrane which could be reversed by FA. Furthermore, we found that FA (0.1-100 μM prevented high glucose-induced phosphatidylserine exposure. These findings provide insights into a novel mechanism of FA for the prevention of vascular dysfunction associated with diabetes.

  8. Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

    Directory of Open Access Journals (Sweden)

    Misae Tsunaka

    2016-07-01

    Full Text Available Objectives: Combining vorinostat, L-asparaginase, and doxorubicin (Dox led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear. Methods: We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma, Molt4 (acute T-lymphoblastic leukemia, and Ramos (Burkitt lymphoma were employed to investigate these procoagulant effects. Results: Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase. Conclusion: These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs.

  9. Anti-phosphatidylserine/prothrombin antibodies: an additional diagnostic marker for APS?

    Science.gov (United States)

    Pregnolato, Francesca; Chighizola, Cecilia B; Encabo, Susan; Shums, Zakera; Norman, Gary L; Tripodi, Armando; Chantarangkul, Veena; Bertero, Tiziana; De Micheli, Valeria; Borghi, Maria Orietta; Meroni, Pier Luigi

    2013-07-01

    Among the diagnostic assays for anti-phospholipid syndrome (APS), lupus anticoagulant (LA) is the strongest predictor of thrombosis; however, it presents several limitations as interference with anticoagulant therapy and poor inter-laboratory agreement. Two-thirds of LA activity is apparently due to antibodies against prothrombin (PT), usually detectable by ELISA. Binding of PT to phosphatidylserine (PS) has been shown to enhance solid-phase anti-PT assay sensitivity. To determine the prevalence of antibodies against PS/PT (aPS/PT) in APS, we tested the semiquantitative QUANTA Lite(®) aPS/PT ELISA in a cohort of 80 APS patients. The prevalence of aPS/PT was 81.3%, rising to 87.6% when considering LA-positive subjects only. We observed a strong correlation between aPS/PT and LA (p = 0.006). To note, APS patients with thrombotic manifestations displayed significantly higher IgG aPS/PT titers compared to 20 aPL asymptomatic carriers (p = 0.012). To rule out a possible cross-reactivity of anti-β2 glycoprotein I antibodies (aβ2GPI) with PS/PT complex, we tested two monoclonal aβ2GPI antibodies and an affinity-purified (AP) polyclonal aβ2GPI IgG obtained from the serum of a patient reacting against both β2GPI and PS/PT. The two monoclonal antibodies did not show any reactivity against PS/PT complex, similarly the AP IgGs did not react toward PS/PT antigen while preserved their aβ2GPI activity. Our findings suggest that aPS/PT are a definite antibody population in APS. Moreover, the good correlation between aPS/PT ELISA and LA may support its use as a surrogate test for LA, particularly useful to overcome the technical limitations of the functional assay.

  10. Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

    Science.gov (United States)

    Kotb, Magd A.

    2012-01-01

    Ursodeoxycholic acid (UDCA) is a steroid bile acid approved for primary biliary cirrhosis (PBC). UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively). “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day) and toxic dose (28 mg/kg/day), and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified. PMID:22942741

  11. Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

    Directory of Open Access Journals (Sweden)

    Magd A. Kotb

    2012-07-01

    Full Text Available Ursodeoxycholic acid (UDCA is a steroid bile acid approved for primary biliary cirrhosis (PBC. UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively. “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day and toxic dose (28 mg/kg/day, and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.

  12. Phosphatidylserine and GTPase activation control Cdc42 nanoclustering to counter dissipative diffusion.

    Science.gov (United States)

    Sartorel, Elodie; Ünlü, Caner; Jose, Mini; Massoni-Laporte, Aurélie; Meca, Julien; Sibarita, Jean-Baptiste; McCusker, Derek

    2018-04-18

    The anisotropic organization of plasma membrane constituents is indicative of mechanisms that drive the membrane away from equilibrium. However, defining these mechanisms is challenging due to the short spatio-temporal scales at which diffusion operates. Here, we use high-density single protein tracking combined with photoactivation localization microscopy (sptPALM) to monitor Cdc42 in budding yeast, a system in which Cdc42 exhibits anisotropic organization. Cdc42 exhibited reduced mobility at the cell pole, where it was organized in nanoclusters. The Cdc42 nanoclusters were larger at the cell pole than those observed elsewhere in the cell. These features were exacerbated in cells expressing Cdc42-GTP, and were dependent on the scaffold Bem1, which contributed to the range of mobility and nanocluster size exhibited by Cdc42. The lipid environment, in particular phosphatidylserine levels, also played a role in regulating Cdc42 nanoclustering. These studies reveal how the mobility of a Rho GTPase is controlled to counter the depletive effects of diffusion, thus stabilizing Cdc42 on the plasma membrane and sustaining cell polarity. Movie S1 Movie S1 sptPALM imaging of live yeast expressing Pil1-mEOS expressed at the genomic locus. Pil1-mEOS was simultaneously photo-converted with a 405 nm laser and imaged with a 561 nm laser using HiLo illumination. Images were acquired at 20 ms intervals, of which 300 frames are shown at 7 frames per second.

  13. Salvinorin-A Induces Intense Dissociative Effects, Blocking External Sensory Perception and Modulating Interoception and Sense of Body Ownership in Humans.

    Science.gov (United States)

    Maqueda, Ana Elda; Valle, Marta; Addy, Peter H; Antonijoan, Rosa Maria; Puntes, Montserrat; Coimbra, Jimena; Ballester, Maria Rosa; Garrido, Maite; González, Mireia; Claramunt, Judit; Barker, Steven; Johnson, Matthew W; Griffiths, Roland R; Riba, Jordi

    2015-06-05

    Salvinorin-A is a terpene with agonist properties at the kappa-opioid receptor, the binding site of endogenous dynorphins. Salvinorin-A is found in Salvia divinorum, a psychoactive plant traditionally used by the Mazatec people of Oaxaca, Mexico, for medicinal and spiritual purposes. Previous studies with the plant and salvinorin-A have reported psychedelic-like changes in perception, but also unusual changes in body awareness and detachment from external reality. Here we comprehensively studied the profiles of subjective effects of increasing doses of salvinorin-A in healthy volunteers, with a special emphasis on interoception. A placebo and three increasing doses of vaporized salvinorin-A (0.25, 0.50, and 1mg) were administered to eight healthy volunteers with previous experience in the use of psychedelics. Drug effects were assessed using a battery of questionnaires that included, among others, the Hallucinogen Rating Scale, the Altered States of Consciousness, and a new instrument that evaluates different aspects of body awareness: the Multidimensional Assessment for Interoceptive Awareness. Salvinorin-A led to a disconnection from external reality, induced elaborate visions and auditory phenomena, and modified interoception. The lower doses increased somatic sensations, but the highest dose led to a sense of a complete loss of contact with the body. Salvinorin-A induced intense psychotropic effects characterized by a dose-dependent gating of external audio-visual information and an inverted-U dose-response effect on body awareness. These results suggest a prominent role for the kappa opioid receptor in the regulation of sensory perception, interoception, and the sense of body ownership in humans. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  14. TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine.

    Directory of Open Access Journals (Sweden)

    Stephanie Jemielity

    2013-03-01

    Full Text Available Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4 specifically bind phosphatidylserine (PS. TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies.

  15. Getting to the Outer Leaflet: Physiology of Phosphatidylserine Exposure at the Plasma Membrane.

    Science.gov (United States)

    Bevers, Edouard M; Williamson, Patrick L

    2016-04-01

    Phosphatidylserine (PS) is a major component of membrane bilayers whose change in distribution between inner and outer leaflets is an important physiological signal. Normally, members of the type IV P-type ATPases spend metabolic energy to create an asymmetric distribution of phospholipids between the two leaflets, with PS confined to the cytoplasmic membrane leaflet. On occasion, membrane enzymes, known as scramblases, are activated to facilitate transbilayer migration of lipids, including PS. Recently, two proteins required for such randomization have been identified: TMEM16F, a scramblase regulated by elevated intracellular Ca(2+), and XKR8, a caspase-sensitive protein required for PS exposure in apoptotic cells. Once exposed at the cell surface, PS regulates biochemical reactions involved in blood coagulation, and bone mineralization, and also regulates a variety of cell-cell interactions. Exposed on the surface of apoptotic cells, PS controls their recognition and engulfment by other cells. This process is exploited by parasites to invade their host, and in specialized form is used to maintain photoreceptors in the eye and modify synaptic connections in the brain. This review discusses what is known about the mechanism of PS exposure at the surface of the plasma membrane of cells, how actors in the extracellular milieu sense surface exposed PS, and how this recognition is translated to downstream consequences of PS exposure. Copyright © 2016 the American Physiological Society.

  16. Riboflavin acetate induces apoptosis in squamous carcinoma cells after photodynamic therapy.

    Science.gov (United States)

    Juarez, Andrea V; Sosa, Liliana Del V; De Paul, Ana L; Costa, Ana Paula; Farina, Marcelo; Leal, Rodrigo B; Torres, Alicia I; Pons, Patricia

    2015-12-01

    Several research efforts have been focused on finding newer and more efficient photosensitizers for photodynamic therapy (PDT). Although, it was demonstrated that riboflavin is an efficient photosensitizer for PDT, the effect of its ester derivate, riboflavin 2',3',4',5'-tetraacetate (RFTA), which has higher cellular uptake, has not been well defined. To evaluate the cell death generated by applying RFTA as the photosensitizer in PDT in a human cancer cell line of squamous carcinoma (SCC-13), these cells were incubated with riboflavin and its ester derivate, RFTA followed by irradiation with different blue light doses. Cell viability was evaluated using neutral red uptake assay and cell death was evaluated using transmission electron microscopy, TUNEL assay and annexin V-PE/7AAD double staining. The expression of caspase-3, Bax, Bcl-2, ERK 1/2 and p38(MAPK) was evaluated by Western blotting and generation of intracellular ROS and changes in anion superoxide levels were analyzed using 2',7'-dichlorofluorescein-diacetate and dihydroethidium dye, respectively. RFTA-PDT generated a decrease in cancer cell viability in a light dose-response. Treated SCC-13 cells exhibited chromatin condensation, formation of apoptotic bodies, increases in TUNEL-positive cells, phosphatidylserine externalization and decreased procaspase-3 and Bcl-2 protein expression and increment of ERK 1/2 phosphorylation. Moreover, trolox abolished the effect of PDT on cell viability linking the increase in intracellular ROS levels with the cell death observed, whereas that the pre-treatment with MEK inhibitor did not induce changes in SCC-13 cell survival. These findings demonstrate the effects of RFTA in triggering apoptosis induced by ROS (\\O2(-)) production after visible light irradiation of squamous carcinoma cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. ExternE transport methodology for external cost evaluation of air pollution

    DEFF Research Database (Denmark)

    Jensen, S. S.; Berkowicz, R.; Brandt, J.

    The report describes how the human exposure estimates based on NERI's human exposure modelling system (AirGIS) can improve the Danish data used for exposure factors in the ExternE Transport methodology. Initially, a brief description of the ExternE Tranport methodology is given and it is summarised...

  18. In Vivo and In Vitro Arsenic Exposition Induces Oxidative Stress in Anterior Pituitary Gland.

    Science.gov (United States)

    Ronchetti, Sonia A; Bianchi, María S; Duvilanski, Beatriz H; Cabilla, Jimena P

    2016-07-01

    Inorganic arsenic (iAs) is at the top of toxic metalloids. Inorganic arsenic-contaminated water consumption is one of the greatest environmental health threats worldwide. Human iAs exposure has been associated with cancers of several organs, neurological disorders, and reproductive problems. Nevertheless, there are no reports describing how iAs affects the anterior pituitary gland. The aim of this study was to investigate the mechanisms involved in iAs-mediated anterior pituitary toxicity both in vivo and in vitro. We showed that iAs administration (from 5 to 100 ppm) to male rats through drinking water increased messenger RNA expression of several oxidative stress-responsive genes in the anterior pituitary gland. Serum prolactin levels diminished, whereas luteinizing hormone (LH) levels were only affected at the higher dose tested. In anterior pituitary cells in culture, 25 µmol/L iAs significantly decreased prolactin release in a time-dependent fashion, whereas LH levels remained unaltered. Cell viability was significantly reduced mainly by apoptosis evidenced by morphological and phosphatidylserine externalization studies. This process is characterized by early depolarization of mitochondrial membrane potential and increased levels of reactive oxygen species. Expression of some key oxidative stress-responsive genes, such as heme oxygenase-1 and metallothionein-1, was also stimulated by iAs exposure. The antioxidant N-acetyl cysteine prevented iAs-induced effects on the expression of oxidative stress markers, prolactin release, and apoptosis. In summary, the present work demonstrates for the first time that iAs reduces prolactin release both in vivo and in vitro and induces apoptosis in anterior pituitary cells, possibly resulting from imbalanced cellular redox status. © The Author(s) 2016.

  19. Phosphatidylserine-exposing blood and endothelial cells contribute to the hypercoagulable state in essential thrombocythemia patients.

    Science.gov (United States)

    Tong, Dongxia; Yu, Muxin; Guo, Li; Li, Tao; Li, Jihe; Novakovic, Valerie A; Dong, Zengxiang; Tian, Ye; Kou, Junjie; Bi, Yayan; Wang, Jinghua; Zhou, Jin; Shi, Jialan

    2018-04-01

    The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P cells and serum-cultured ECs led to markedly shortened coagulation time and dramatically increased levels of FXa, thrombin, and fibrin production. This procoagulant activity could be largely blocked by addition of lactadherin (approx. 70% inhibition). Confocal microscopy showed that the FVa/FXa complex and fibrin fibrils colocalized with PS on ET serum-cultured ECs. Additionally, we found a relationship between D-dimer, prothrombin fragment F1 + 2, and PS exposure. Our study reveals a previously unrecognized link between hypercoagulability and exposed PS on cells, which might also be associated with distinct thrombotic risks among mutational subtypes in ET. Thus, blocking PS-binding sites may represent a new therapeutic target for preventing thrombosis in ET.

  20. External flood probabilistic safety analysis of a coastal NPP

    International Nuclear Information System (INIS)

    Pisharady, Ajai S.; Chakraborty, M.K.; Acharya, Sourav; Roshan, A.D.; Bishnoi, L.R.

    2015-01-01

    External events pose a definitive challenge to safety of NPP, solely due to their ability to induce common cause failures. Flooding incidents at Le Blayais NPP, France, Fort Calhoun NPP, USA and Fukushima Daiichi have pointed to the importance of external flooding as an important contributor to NPP risk. A methodology developed for external flood PSA of a coastal NPP vulnerable to flooding due to tsunami, cyclonic storm and intense local precipitation is presented in this paper. Different tasks for EFPSA has been identified along with general approach for completing each task

  1. Investigation of thermoelastic stresses induced at high altitudes on aircraft external fuel tanks

    Science.gov (United States)

    Mousseau, Stephanie Lynn Steber

    As composite technology has grown over the past several decades, the use of composite materials in military applications has become more feasible and widely accepted. Although composite materials provide many benefits, including strength optimization and reduced weight, damage and repair of these materials creates an additional challenge, especially when operating in a marine environment, such as on a carrier deck. This is evident within the Navy, as excessive damage often leads to the scrapping of F/A-18 External Fuel Tanks. This damage comes in many forms, the most elusive of which is delamination. Often the delamination found on the tanks is beyond repairable limits and the cause unknown, making it difficult to predict and prevent. The purpose of this investigation was to study the structure of the Navy's 330 gallon External Fuel Tanks and investigate one potential cause of delamination, stresses induced at high altitudes by cold temperatures. A stress analysis was completed using finite element software, and validation of the model was accomplished through testing of a scale model specimen. Due to the difficulties in modeling and predicting delamination, such as unknown presence of voids and understanding failure criteria, delamination was not modeled in Abaqus, rather stresses were observed and characteristics were studied to understand the potential for delamination within the layup. In addition, studies were performed to understand the effect of material properties and layup sequence on the stress distribution within the tank. Alternative design solutions are presented which could reduce the radial stresses within the tank, and recommendations are made for further study to understand the trade-offs between stress, cost, and manufacturability.

  2. Nonideal mixing of phosphatidylserine and phosphatidylcholine in the fluid lamellar phase.

    Science.gov (United States)

    Huang, J; Swanson, J E; Dibble, A R; Hinderliter, A K; Feigenson, G W

    1993-02-01

    The mixing of phosphatidylserine (PS) and phosphatidylcholine (PC) in fluid bilayer model membranes was studied by measuring binding of aqueous Ca2+ ions. The measured [Ca2+]aq was used to derive the activity coefficient for PS, gamma PS, in the lipid mixture. For (16:0, 18:1) PS in binary mixtures with either (16:0, 18:1)PC, (14:1, 14:1)PC, or (18:1, 18:1)PC, gamma PS > 1; i.e., mixing is nonideal, with PS and PC clustered rather than randomly distributed, despite the electrostatic repulsion between PS headgroups. To understand better this mixing behavior, Monte Carlo simulations of the PS/PC distributions were performed, using Kawasaki relaxation. The excess energy was divided into an electrostatic term Uel and one adjustable term including all other nonideal energy contributions, delta Em. Uel was calculated using a discrete charge theory. Kirkwood's coupling parameter method was used to calculate the excess free energy of mixing, delta GEmix, hence In gamma PS,calc. The values of In gamma PS,calc were equalized by adjusting delta Em in order to find the simulated PS/PC distribution that corresponded to the experimental results. We were thus able to compare the smeared charge calculation of [Ca2+]surf with a calculation ("masked evaluation method") that recognized clustering of the negatively charged PS: clustering was found to have a modest effect on [Ca2+]surf, relative to the smeared charge model. Even though both PS and PC tend to cluster, the long-range nature of the electrostatic repulsion reduces the extent of PS clustering at low PS mole fraction compared to PC clustering at an equivalent low PC mole fraction.

  3. Coherent polarization driven by external electromagnetic fields

    International Nuclear Information System (INIS)

    Apostol, M.; Ganciu, M.

    2010-01-01

    The coherent interaction of the electromagnetic radiation with an ensemble of polarizable, identical particles with two energy levels is investigated in the presence of external electromagnetic fields. The coupled non-linear equations of motion are solved in the stationary regime and in the limit of small coupling constants. It is shown that an external electromagnetic field may induce a macroscopic occupation of both the energy levels of the particles and the corresponding photon states, governed by a long-range order of the quantum phases of the internal motion (polarization) of the particles. A lasing effect is thereby obtained, controlled by the external field. Its main characteristics are estimated for typical atomic matter and atomic nuclei. For atomic matter the effect may be considerable (for usual external fields), while for atomic nuclei the effect is extremely small (practically insignificant), due to the great disparity in the coupling constants. In the absence of the external field, the solution, which is non-analytic in the coupling constant, corresponds to a second-order phase transition (super-radiance), which was previously investigated.

  4. Fast-ion losses induced by ELMs and externally applied magnetic perturbations in the ASDEX Upgrade tokamak

    International Nuclear Information System (INIS)

    Garcia-Munoz, M; Rodriguez-Ramos, M; Äkäslompolo, S; De Marne, P; Dunne, M G; Dux, R; Fietz, S; Fuchs, C; Geiger, B; Herrmann, A; Hoelzl, M; Kurzan, B; McDermott, R M; Strumberger, E; Evans, T E; Ferraro, N M; Pace, D C; Lazanyi, N; Nocente, M; Shinohara, K

    2013-01-01

    Phase-space time-resolved measurements of fast-ion losses induced by edge localized modes (ELMs) and ELM mitigation coils have been obtained in the ASDEX Upgrade tokamak by means of multiple fast-ion loss detectors (FILDs). Filament-like bursts of fast-ion losses are measured during ELMs by several FILDs at different toroidal and poloidal positions. Externally applied magnetic perturbations (MPs) have little effect on plasma profiles, including fast-ions, in high collisionality plasmas with mitigated ELMs. A strong impact on plasma density, rotation and fast-ions is observed, however, in low density/collisionality and q 95 plasmas with externally applied MPs. During the mitigation/suppression of type-I ELMs by externally applied MPs, the large fast-ion bursts observed during ELMs are replaced by a steady loss of fast-ions with a broad-band frequency and an amplitude of up to an order of magnitude higher than the neutral beam injection (NBI) prompt loss signal without MPs. Multiple FILD measurements at different positions, indicate that the fast-ion losses due to static 3D fields are localized on certain parts of the first wall rather than being toroidally/poloidally homogeneously distributed. Measured fast-ion losses show a broad energy and pitch-angle range and are typically on banana orbits that explore the entire pedestal/scrape-off-layer (SOL). Infra-red measurements are used to estimate the heat load associated with the MP-induced fast-ion losses. The heat load on the FILD detector head and surrounding wall can be up to six times higher with MPs than without 3D fields. When 3D fields are applied and density pump-out is observed, an enhancement of the fast-ion content in the plasma is typically measured by fast-ion D-alpha (FIDA) spectroscopy. The lower density during the MP phase also leads to a deeper beam deposition with an inward radial displacement of ≈2 cm in the maximum of the beam emission. Orbit simulations are used to test different models for 3D

  5. 14 CFR 29.865 - External loads.

    Science.gov (United States)

    2010-01-01

    ... 200 volts per meter. (iii) Be protected against any failure that could be induced by a failure mode of... operational envelope without hazard to the rotorcraft during normal flight conditions. In addition, these...-load combinations to be used for nonhuman external cargo except for the failure of critical structural...

  6. Yeast PAH1-encoded phosphatidate phosphatase controls the expression of CHO1-encoded phosphatidylserine synthase for membrane phospholipid synthesis.

    Science.gov (United States)

    Han, Gil-Soo; Carman, George M

    2017-08-11

    The PAH1 -encoded phosphatidate phosphatase (PAP), which catalyzes the committed step for the synthesis of triacylglycerol in Saccharomyces cerevisiae , exerts a negative regulatory effect on the level of phosphatidate used for the de novo synthesis of membrane phospholipids. This raises the question whether PAP thereby affects the expression and activity of enzymes involved in phospholipid synthesis. Here, we examined the PAP-mediated regulation of CHO1 -encoded phosphatidylserine synthase (PSS), which catalyzes the committed step for the synthesis of major phospholipids via the CDP-diacylglycerol pathway. The lack of PAP in the pah1 Δ mutant highly elevated PSS activity, exhibiting a growth-dependent up-regulation from the exponential to the stationary phase of growth. Immunoblot analysis showed that the elevation of PSS activity results from an increase in the level of the enzyme encoded by CHO1 Truncation analysis and site-directed mutagenesis of the CHO1 promoter indicated that Cho1 expression in the pah1 Δ mutant is induced through the inositol-sensitive upstream activation sequence (UAS INO ), a cis -acting element for the phosphatidate-controlled Henry (Ino2-Ino4/Opi1) regulatory circuit. The abrogation of Cho1 induction and PSS activity by a CHO1 UAS INO mutation suppressed pah1 Δ effects on lipid synthesis, nuclear/endoplasmic reticulum membrane morphology, and lipid droplet formation, but not on growth at elevated temperature. Loss of the DGK1 -encoded diacylglycerol kinase, which converts diacylglycerol to phosphatidate, partially suppressed the pah1 Δ-mediated induction of Cho1 and PSS activity. Collectively, these data showed that PAP activity controls the expression of PSS for membrane phospholipid synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: Involvement of Ca2+ influx

    International Nuclear Information System (INIS)

    Moon, Dong-Oh; Kang, Chang-Hee; Kang, Sang-Hyuck; Choi, Yung-Hyun; Hyun, Jin-Won; Chang, Weon-Young; Kang, Hee-Kyoung; Koh, Young-Sang; Maeng, Young-Hee; Kim, Young-Ree; Kim, Gi-Young

    2012-01-01

    Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various malignant cells, several cancers including human hepatocellular carcinoma (HCC) exhibit potent resistance to TRAIL-induced cell death. The aim of this study is to evaluate the anti-cancer potential of capsaicin in TRAIL-induced cancer cell death. As indicated by assays that measure phosphatidylserine exposure, mitochondrial activity and activation of caspases, capsaicin potentiated TRAIL-resistant cells to lead to cell death. In addition, we found that capsaicin induces the cell surface expression of TRAIL receptor DR5, but not DR4 through the activation Sp1 on its promoter region. Furthermore, we investigated that capsaicin-induced DR5 expression and apoptosis are inhibited by calcium chelator or inhibitors for calmodulin-dependent protein kinase. Taken together, our data suggest that capsaicin sensitizes TRAIL-mediated HCC cell apoptosis by DR5 up-regulation via calcium influx-dependent Sp1 activation. Highlights: ► Capsaicin sensitizes TRAIL-induced apoptosis through activation of caspases. ► Capsaicin induces expression of DR5 through Sp1 activation. ► Capsaicin activates calcium signaling pathway.

  8. Externalities of energy. Swedish implementation of the ExternE methodology

    International Nuclear Information System (INIS)

    Nilsson, Maans; Gullberg, M.

    1998-01-01

    The growing interest for developing economic instruments for efficient environmental policies has opened up a large area of multi-disciplinary research. ExternE is an example of this research, combining disciplines such as engineering, ecology, immunology and economics expertise to create new knowledge about how environmental pressures from energy production affect our nature and society. The ExternE Project aims to identify and, as far as possible quantify the externalities of energy production in Europe. The Stockholm Environment Institute has carried out a preliminary aggregation: -Coal Fuel Cycle: centred around Vaesteraas Kraftvaermeverk, Vaesteraas. This is the largest co-generation plant in Sweden, with four blocks and a maximum co-generation output of 520 MW electricity and 950 MW heat. The analysis is carried out on boiler B4. -Biomass Fuel Cycle: centred around Haendeloeverket, Norrkoeping. This plant predominately burns forestry residues, but a variety of fuels are combusted. Haendeloeverket has an installed capacity of 100 MW electricity and 375 MW heat, in a total of three boilers and two back-pressure turbines. The analysis is carried out on boiler P13. -Hydro Fuel Cycle: Klippens Kraftstation, Storuman. Built in 1990-1994, it is the youngest hydro power station in Sweden. It has been designed and built with significant efforts to account for and protect environmental values. Installed capacity is 28 MW. The environmental impact assessment from the construction of this plant is carried out, but the evaluation is still not finalized. The preliminary aggregation aimed to test whether ExternE results could be used to make estimates for the entire Swedish electricity production system. Hence, national results as well as results from other partner countries in ExternE has been applied

  9. Probabilistic analysis of external events with focus on the Fukushima event

    International Nuclear Information System (INIS)

    Kollasko, Heiko; Jockenhoevel-Barttfeld, Mariana; Klapp, Ulrich

    2014-01-01

    External hazards are those natural or man-made hazards to a site and facilities that are originated externally to both the site and its processes, i.e. the duty holder may have very little or no control over the hazard. External hazards can have the potential of causing initiating events at the plant, typically transients like e.g., loss of offsite power. Simultaneously, external events may affect safety systems required to control the initiating event and, where applicable, also back-up systems implemented for risk-reduction. The plant safety may especially be threatened when loads from external hazards exceed the load assumptions considered in the design of safety-related systems, structures and components. Another potential threat is given by hazards inducing initiating events not considered in the safety demonstration otherwise. An example is loss of offsite power combined with prolonged plant isolation. Offsite support, e.g., delivery of diesel fuel oil, usually credited in the deterministic safety analysis may not be possible in this case. As the Fukushima events have shown, the biggest threat is likely given by hazards inducing both effects. Such hazards may well be dominant risk contributors even if their return period is very high. In order to identify relevant external hazards for a certain Nuclear Power Plant (NPP) location, a site specific screening analysis is performed, both for single events and for combinations of external events. As a result of the screening analysis, risk significant and therefore relevant (screened-in) single external events and combinations of them are identified for a site. The screened-in events are further considered in a detailed event tree analysis in the frame of the Probabilistic Safety Analysis (PSA) to calculate the core damage/large release frequency resulting from each relevant external event or from each relevant combination. Screening analyses of external events performed at AREVA are based on the approach provided

  10. Environmental external effects from wind power based on the EU ExternE methodology

    DEFF Research Database (Denmark)

    Ibsen, Liselotte Schleisner; Nielsen, Per Sieverts

    1998-01-01

    of the Danish part of the project is to implement the framework for externality evaluation, for three different power plants located in Denmark. The paper will focus on the assessment of the impacts of the whole fuel cycles for wind, natural gas and biogas. Priority areas for environmental impact assessment......The European Commission has launched a major study project, ExternE, to develop a methodology to quantify externalities. A “National Implementation Phase”, was started under the Joule II programme with the purpose of implementing the ExternE methodology in all member states. The main objective...

  11. ExternE National Implementation Finland

    Energy Technology Data Exchange (ETDEWEB)

    Pingoud, K; Maelkki, H; Wihersaari, M; Pirilae, P [VTT Energy, Espoo (Finland); Hongisto, M [Imatran Voima Oy, Vantaa (Finland); Siitonen, S [Ekono Energy Ltd, Espoo (Finland); Johansson, M [Finnish Environment Institute, Helsinki (Finland)

    1999-07-01

    ExternE National Implementation is a continuation of the ExternE Project, funded in part by the European Commission's Joule III Programme. This study is the result of the ExternE National Implementation Project for Finland. Three fuel cycles were selected for the Finnish study: coal, peat and wood-derived biomass, which together are responsible for about 40% of total electricity generation in Finland and about 75% of the non-nuclear fuel based generation. The estimated external costs or damages were dominated by the global warming (GW) impacts in the coal and peat fuel cycles, but knowledge of the true GW impacts is still uncertain. From among other impacts that were valued in monetary terms the human health damages due to airborne emissions dominated in all the three fuel cycles. Monetary valuation for ecosystem impacts is not possible using the ExternE methodology at present. The Meri-Pori power station representing the coal fuel cycle is one of the world's cleanest and most efficient coal-fired power plants with a condensing turbine. The coal is imported mainly from Poland. The estimated health damages were about 4 mECU/kWh, crop damages an order of magnitude lower and damages caused to building materials two orders of magnitude lower. The power stations of the peat and biomass fuel cycles are of CHP type, generating electricity and heat for the district heating systems of two cities. Their fuels are of domestic origin. The estimated health damages allocated to electricity generation were about 5 and 6 mECU/kWh, respectively. The estimates were case-specific and thus an generalisation of the results to the whole electricity generation in Finland is unrealistic. Despite the uncertainties and limitations of the methodology, it is a promising tool in the comparison of similar kinds of fuel cycles, new power plants and pollution abatement technologies and different plant locations with each other. (orig.)

  12. ExternE National Implementation Finland

    Energy Technology Data Exchange (ETDEWEB)

    Pingoud, K.; Maelkki, H.; Wihersaari, M.; Pirilae, P. [VTT Energy, Espoo (Finland); Hongisto, M. [Imatran Voima Oy, Vantaa (Finland); Siitonen, S. [Ekono Energy Ltd, Espoo (Finland); Johansson, M. [Finnish Environment Institute, Helsinki (Finland)

    1999-07-01

    ExternE National Implementation is a continuation of the ExternE Project, funded in part by the European Commission's Joule III Programme. This study is the result of the ExternE National Implementation Project for Finland. Three fuel cycles were selected for the Finnish study: coal, peat and wood-derived biomass, which together are responsible for about 40% of total electricity generation in Finland and about 75% of the non-nuclear fuel based generation. The estimated external costs or damages were dominated by the global warming (GW) impacts in the coal and peat fuel cycles, but knowledge of the true GW impacts is still uncertain. From among other impacts that were valued in monetary terms the human health damages due to airborne emissions dominated in all the three fuel cycles. Monetary valuation for ecosystem impacts is not possible using the ExternE methodology at present. The Meri-Pori power station representing the coal fuel cycle is one of the world's cleanest and most efficient coal-fired power plants with a condensing turbine. The coal is imported mainly from Poland. The estimated health damages were about 4 mECU/kWh, crop damages an order of magnitude lower and damages caused to building materials two orders of magnitude lower. The power stations of the peat and biomass fuel cycles are of CHP type, generating electricity and heat for the district heating systems of two cities. Their fuels are of domestic origin. The estimated health damages allocated to electricity generation were about 5 and 6 mECU/kWh, respectively. The estimates were case-specific and thus an generalisation of the results to the whole electricity generation in Finland is unrealistic. Despite the uncertainties and limitations of the methodology, it is a promising tool in the comparison of similar kinds of fuel cycles, new power plants and pollution abatement technologies and different plant locations with each other. (orig.)

  13. ExternE National Implementation Finland

    International Nuclear Information System (INIS)

    Pingoud, K.; Maelkki, H.; Wihersaari, M.; Pirilae, P.; Hongisto, M.; Siitonen, S.; Johansson, M.

    1999-01-01

    ExternE National Implementation is a continuation of the ExternE Project, funded in part by the European Commission's Joule III Programme. This study is the result of the ExternE National Implementation Project for Finland. Three fuel cycles were selected for the Finnish study: coal, peat and wood-derived biomass, which together are responsible for about 40% of total electricity generation in Finland and about 75% of the non-nuclear fuel based generation. The estimated external costs or damages were dominated by the global warming (GW) impacts in the coal and peat fuel cycles, but knowledge of the true GW impacts is still uncertain. From among other impacts that were valued in monetary terms the human health damages due to airborne emissions dominated in all the three fuel cycles. Monetary valuation for ecosystem impacts is not possible using the ExternE methodology at present. The Meri-Pori power station representing the coal fuel cycle is one of the world's cleanest and most efficient coal-fired power plants with a condensing turbine. The coal is imported mainly from Poland. The estimated health damages were about 4 mECU/kWh, crop damages an order of magnitude lower and damages caused to building materials two orders of magnitude lower. The power stations of the peat and biomass fuel cycles are of CHP type, generating electricity and heat for the district heating systems of two cities. Their fuels are of domestic origin. The estimated health damages allocated to electricity generation were about 5 and 6 mECU/kWh, respectively. The estimates were case-specific and thus an generalisation of the results to the whole electricity generation in Finland is unrealistic. Despite the uncertainties and limitations of the methodology, it is a promising tool in the comparison of similar kinds of fuel cycles, new power plants and pollution abatement technologies and different plant locations with each other. (orig.)

  14. Cigarette smoke-induced cell death of a spermatocyte cell line can be prevented by inactivating the Aryl hydrocarbon receptor

    Science.gov (United States)

    Esakky, P; Hansen, D A; Drury, A M; Cusumano, A; Moley, K H

    2015-01-01

    Cigarette smoke exposure causes germ cell death during spermatogenesis. Our earlier studies demonstrated that cigarette smoke condensate (CSC) causes spermatocyte cell death in vivo and growth arrest of the mouse spermatocyte cell line (GC-2spd(ts)) in vitro via the aryl hydrocarbon receptor (AHR). We hypothesize here that inactivation of AHR could prevent the CSC-induced cell death in spermatocytes. We demonstrate that CSC exposure generates oxidative stress, which differentially regulates mitochondrial apoptosis in GC-2spd(ts) and wild type (WT) and AHR knockout (AHR-KO) mouse embryonic fibroblasts (MEFs). SiRNA-mediated silencing of Ahr augments the extent of CSC-mediated cellular damage while complementing the AHR-knockout condition. Pharmacological inhibition using the AHR-antagonist (CH223191) modulates the CSC-altered expression of apoptotic proteins and significantly abrogates DNA fragmentation though the cleavage of PARP appears AHR independent. Pretreatment with CH223191 at concentrations above 50 μM significantly prevents the CSC-induced activation of caspase-3/7 and externalization of phosphatidylserine in the plasma membrane. However, MAPK inhibitors alone or together with CH223191 could not prevent the membrane damage upon CSC addition and the caspase-3/7 activation and membrane damage in AHR-deficient MEF indicates the interplay of multiple cell signaling and cytoprotective ability of AHR. Thus the data obtained on one hand signifies the protective role of AHR in maintaining normal cellular homeostasis and the other, could be a potential prophylactic therapeutic target to promote cell survival and growth under cigarette smoke exposed environment by receptor antagonism via CH223191-like mechanism. Antagonist-mediated inactivation of the aryl hydrocarbon receptor blocks downstream events leading to cigarette smoke-induced cell death of a spermatocyte cell line. PMID:27551479

  15. Nonlinear dynamics of mushy layers induced by external stochastic fluctuations.

    Science.gov (United States)

    Alexandrov, Dmitri V; Bashkirtseva, Irina A; Ryashko, Lev B

    2018-02-28

    The time-dependent process of directional crystallization in the presence of a mushy layer is considered with allowance for arbitrary fluctuations in the atmospheric temperature and friction velocity. A nonlinear set of mushy layer equations and boundary conditions is solved analytically when the heat and mass fluxes at the boundary between the mushy layer and liquid phase are induced by turbulent motion in the liquid and, as a result, have the corresponding convective form. Namely, the 'solid phase-mushy layer' and 'mushy layer-liquid phase' phase transition boundaries as well as the solid fraction, temperature and concentration (salinity) distributions are found. If the atmospheric temperature and friction velocity are constant, the analytical solution takes a parametric form. In the more common case when they represent arbitrary functions of time, the analytical solution is given by means of the standard Cauchy problem. The deterministic and stochastic behaviour of the phase transition process is analysed on the basis of the obtained analytical solutions. In the case of stochastic fluctuations in the atmospheric temperature and friction velocity, the phase transition interfaces (mushy layer boundaries) move faster than in the deterministic case. A cumulative effect of these noise contributions is revealed as well. In other words, when the atmospheric temperature and friction velocity fluctuate simultaneously due to the influence of different external processes and phenomena, the phase transition boundaries move even faster. This article is part of the theme issue 'From atomistic interfaces to dendritic patterns'.This article is part of the theme issue 'From atomistic interfaces to dendritic patterns'. © 2018 The Author(s).

  16. Electronic properties of phosphorene/graphene heterostructures: Effect of external electric field

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Sumandeep; Srivastava, Sunita; Tankeshwar, K. [Department of Physics, Panjab University, Chandigarh-160014 (India); Kumar, Ashok [Centre for Physical Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, India 151001 (India)

    2016-05-23

    We report the electronic properties of electrically gated heterostructures of black and blue phosphorene with graphene. The heterostructure of blue phosphorene with graphene is energetically more favorable than black phospherene/graphene. However, both are bonded by weak interlayer interactions. Graphene induces the Dirac cone character in both heterostructure which shows tunabilities with external electric field. It is found that Dirac cone get shifted depending on the polarity of external electric field that results into the so called self induced p-type or n-type doping effect. These features have importance in the fabrication of nano-electronic devices based on the phosphorene/graphene heterostructures.

  17. Regional Externalities

    NARCIS (Netherlands)

    Heijman, W.J.M.

    2007-01-01

    The book offers practical and theoretical insights in regional externalities. Regional externalities are a specific subset of externalities that can be defined as externalities where space plays a dominant role. This class of externalities can be divided into three categories: (1) externalities

  18. Externalities - an analysis using the EU ExternE-results

    International Nuclear Information System (INIS)

    2003-10-01

    The EU project ExternE quantified the externalities for the different energy technologies. In this work, the ExternE results are used in a MARKAL-analysis for the Nordic countries. The analysis does not go into detail, but gives some interesting indications: The external costs are not fully covered in the Nordic energy systems, the present taxes and charges are not high enough. The emissions from the energy systems would be strongly reduced, if taxes/environmental charges were set at the level ExternE calculate. The emissions from power production would be reduced most. Renewable energy sources and natural gas dominate the energy systems in the ExternE case

  19. ExternE: Externalities of energy Vol. 1. Summary

    International Nuclear Information System (INIS)

    Holland, M.; Berry, J.

    1995-01-01

    There is a growing requirement for policy analysts to take account of the environment in their decision making and to undertake the specified cost-benefit analysis. Within the European Union this is reflected in the 5th Environmental Action Programme, and the Commission's White Paper entitled 'Growth, competitiveness, employment and the ways forward to the 21st century'. This has led to a need for evaluation of environmental externalities. The ExternE Project commenced in 1991 as the European part of a collaborative study between the European Commission and the US Department of Energy. It aims to be the first systematic approach to the evaluation of external costs of a wide range of different fuel cycles. The project will result in an operational accounting framework for the quantification and monetarisation of priority environmental and other externalities. This framework will allow the calculation of the marginal external costs and benefits for specific power plants, at specific sites using specified technologies. There are three major phases in the project. Phase 1 was undertaken in collaboration with the US Department of Energy. In this phase the teams jointly developed the conceptual approach and methodology and shared scientific information for application to a number of fuel cycles. On the European side work concentrated on the nuclear and coal fuel cycles which together were expected to raise many of the fundamental issues in fuel cycle analysis. The project is currently nearing completion of Phase 2. During this phase the methodology has been applied to a wide range of different fossil, nuclear and renewable fuel cycles for power generation and energy conservation options. Also a series of National Implementation Programmes is underway in which the methodology and accounting framework are being applied to reference sites throughout Europe. In addition the general methodology is being extended to address the evaluation of externalities associated with

  20. ExternE: Externalities of energy Vol. 2. Methodology

    International Nuclear Information System (INIS)

    Berry, J.; Holland, M.; Watkiss, P.

    1995-01-01

    This report describes the methodology used by the ExternE Project of the European Commission (DGXII) JOULE Programme for assessment of the external costs of energy. It is one of a series of reports describing analysis of nuclear, fossil and renewable fuel cycles for assessment of the externalities associated with electricity generation. Part I of the report deals with analysis of impacts, and Part II with the economic valuation of those impacts. Analysis is conducted on a marginal basis, to allow the effect of an incremental investment in a given technology to be quantified. Attention has been paid to the specificity of results with respect to the location of fuel cycle activities, the precise technologies used, and the type and source of fuel. The main advantages of this detailed approach are as follows: It takes full and proper account of the variability of impacts that might result from different power projects; It is more transparent than analysis based on hypothetically 'representative' cases for each of the different fuel cycles; It provides a framework for consistent comparison between fuel cycles. A wide variety of impacts have been considered. These include the effects of air pollution on the natural and human environment, consequences of accidents in the workplace, impacts of noise and visual intrusion on amenity, and the effects of climate change arising from the release of greenhouse gases. Wherever possible we have used the 'impact pathway' or 'damage function' approach to follow the analysis from identification of burdens (e.g. emissions) through to impact assessment and then valuation in monetary terms. This has required a detailed knowledge of the technologies involved, pollutant dispersion, analysis of effects on human and environmental health, and economics. In view of this the project brought together a multi-disciplinary team with experts from many European countries and the USA. The spatial and temporal ranges considered in the analysis are

  1. Apoptosis induced by chlormethine and ionizing radiations in normal and tumoral lymphocytes: role of caspase-3

    International Nuclear Information System (INIS)

    Holl, V.P.

    2000-01-01

    Apoptosis can be induced by various stimuli like ionizing radiations or alkylating agents. Recent works have shown that apoptosis due to ionizing radiations can be initiated by DNA and cell membrane alterations, via radical species generation, implying the in fine activation of effector caspases, and in particular caspase-3. The main goal of this work is to clarify the role of caspase-3 in the radio-induced apoptosis mechanisms and to study the effects of apoptosis inhibition on the behaviour of the damaged cells. The effects of activation and caspase-3 activity inhibition on the progress of spontaneous, radio-induced or chlormethine-induced apoptosis have been evaluated for normal and tumoral lymphocytes. A chemical molecule, the ebselen, which can mime the action of the endogenous glutathione peroxidase, and a tetra-peptide inhibitor, AC-DEVD-CHO, selective of effector caspases, have been selected. The results indicate an inhibition by ebselen of all morphological and biochemical characteristics of chlormethine-induced apoptosis and a restoring of the cells viability. This seleno-organic compound also reduces the drop of the intra-cellular glutathione level and the loss of the trans-membrane potential (M) of the mitochondrion in the MOLT-4 tumoral cells treated with chlormethine. In parallel, the AC-DEVD-CHO effect on apoptosis induction has been tested. This inhibitor stops some chlormethine-induced criteria of apoptosis without affecting the final loss of the mitochondrial M and the cells proliferation. AC-DEVD-CHO has been also incubated just before the irradiation of the culture cells. The inhibition of the specific DEVD caspases prevents the inter-nucleosomal fragmentation of DNA and partially delays the externalization of phosphatidylserine without changing the viability of the irradiated cells. Moreover, the analysis of the AC-DEVD-CHO pre-treated irradiated cells floating on the surface shows a strong mitochondrial lactate dehydrogenase activity, which

  2. Phosphatidylserine and Phosphatidylethanolamine Bind to Protein Z Cooperatively and with Equal Affinity.

    Directory of Open Access Journals (Sweden)

    Tanusree Sengupta

    Full Text Available Protein Z (PZ is an anticoagulant that binds with high affinity to Protein Z-dependent protease inhibitor (ZPI and accelerates the rate of ZPI-mediated inhibition of factor Xa (fXa by more than 1000-fold in the presence of Ca2+ and phospholipids. PZ promotion of the ZPI-fXa interaction results from the anchoring of the Gla domain of PZ onto phospholipid surfaces and positioning the bound ZPI in close proximity to the Gla-anchored fXa, forming a ternary complex of PZ/ZPI/fXa. Although interaction of PZ with phospholipid membrane appears to be absolutely crucial for its cofactor activity, little is known about the binding of different phospholipids to PZ. The present study was conceived to understand the interaction of different phospholipids with PZ. Experiments with both soluble lipids and model membranes revealed that PZ binds to phosphatidylserine (PS and phosphatidylethanolamine (PE with equal affinity (Kd~48 μM; further, PS and PE bound to PZ synergistically. Equilibrium dialysis experiments revealed two lipid-binding sites for both PS and PE. PZ binds with weaker affinity to other phospholipids, e.g., phosphatidic acid, phosphatidylglycerol, phosphatidylcholine and binding of these lipids is not synergistic with respect to PS. Both PS and PE -containing membranes supported the formation of a fXa-PZ complex. PZ protection of fXa from antithrombin inhibition were also shown to be comparable in presence of both PS: PC and PE: PC membranes. These findings are particularly important and intriguing since they suggest a special affinity of PZ, in vivo, towards activated platelets, the primary membrane involved in blood coagulation process.

  3. External cervical resorption: diagnostic and treatment tips

    Directory of Open Access Journals (Sweden)

    Alberto Consolaro

    Full Text Available ABSTRACT External cervical resorption is caused, almost exclusively, by dental trauma - especially those characterized by concussion - and is a dental disease to be diagnosed and treated accurately by endodontists. However, the vast majority of the cases is initially diagnosed by an orthodontist, due to the imaging possibilities in standardized documentations. Among the causes of external cervical resorption, it is common to mistakenly attribute it to orthodontic treatment, traumatic occlusion or even to chronic inflammatory periodontal disease. External cervical resorption is associated to dental trauma in several situations mentioned in this paper. In old cases, and eventually still nowadays, it may have been induced by internal tooth bleaching, which is increasingly less frequent in endodontically treated teeth. There are some tips to be followed and some care that must be taken during the diagnosis and treatment of external cervical resorption clinical cases. The present study lists foundations that will allow the professional to perform safely and accurately in each specific case. Some of these tips and care measures are of orthodontic nature.

  4. External PIXE analysis of old inks and papers

    International Nuclear Information System (INIS)

    Hassanzadeh, A.; Lamehi-Rachti, M.; Oliaiy, P.; Rahighi, J.; Shokouhi, F.

    1999-01-01

    Proton Induced X-ray Emission, PIXE is a very well established analytical method. This technique of analysis can equally be applied both in vacuum, internal PIXE, and in atmosphere, external PIXE. External PIXE has been applied to material analysis in Van de Graaff laboratory at AEOI using filters and funny filters. Advantages of using these filters have been studied when analysing ancient written documents such as envelopes, inks, and newspapers. This technique clearly demonstrated the differences between new and old inks and papers. More data is needed to show other features of this technique. (author)

  5. External costs related to power production technologies. ExternE national implementation for Denmark

    Energy Technology Data Exchange (ETDEWEB)

    Schleisner, L; Sieverts Nielsen, P [eds.

    1997-12-01

    The objective of the ExternE National Implementation project has been to establish a comprehensive and comparable set of data on externalities of power generation for all EU member states and Norway. The tasks include the application of the ExternE methodology to the most important fuel cycles for each country as well as to update the already existing results, to aggregate these site- and technology-specific results to more general figures. The current report covers the detailed information concerning the ExternE methodology. Importance is attached to the computer system used in the project and the assessment of air pollution effects on health, materials and ecological effects. Also the assessment of global warming damages are described. Finally the report covers the detailed information concerning the national implementation for Denmark for an offshore wind farm and a wind farm on land, a decentralised CHP plant based on natural gas and a decentralised CHP plant base on biogas. (au) EU-JOULE 3. 79 tabs., 11 ills., 201 refs.

  6. External costs related to power production technologies. ExternE national implementation for Denmark

    International Nuclear Information System (INIS)

    Schleisner, L.; Sieverts Nielsen, P.

    1997-12-01

    The objective of the ExternE National Implementation project has been to establish a comprehensive and comparable set of data on externalities of power generation for all EU member states and Norway. The tasks include the application of the ExternE methodology to the most important fuel cycles for each country as well as to update the already existing results, to aggregate these site- and technology-specific results to more general figures. The current report covers the detailed information concerning the ExternE methodology. Importance is attached to the computer system used in the project and the assessment of air pollution effects on health, materials and ecological effects. Also the assessment of global warming damages are described. Finally the report covers the detailed information concerning the national implementation for Denmark for an offshore wind farm and a wind farm on land, a decentralised CHP plant based on natural gas and a decentralised CHP plant base on biogas. (au) EU-JOULE 3. 79 tabs., 11 ills., 201 refs

  7. Stability properties of a toroidal z-pinch in an external magnetic multipole field

    International Nuclear Information System (INIS)

    Eriksson, H.G.

    1987-01-01

    MHD stability of m=1, axisymmetric, external modes of a toroidal z-pinch immersed in an external multipole field (Extrap configuration) is studied. The description includes the effects of a weak toroidicity, a non-circular plasma cross-section and the influence of induced currents in the external conductors. It is found that the non-circularity of the plasma cross-section always has a destabilizing effect but that the m=1 mode can be stabilized by the external feedback if the non-circularity is small. (author)

  8. Externalities of fuel cycles 'ExternE' project. Summary report

    International Nuclear Information System (INIS)

    Holland, M.; Berry, J.

    1994-01-01

    There is a growing requirement for policy analysts to take account of the environment in their decision making and to undertake the specified cost-benefit analysis. Within the European Union this is reflected in the 5th Environmental Action Programme, and the Commission's White Paper entitled 'Growth, competitiveness, employment and the ways forward to the 21st century'. This has led to a need for evaluation of environmental externalities. The ExternE Project commenced in 1991 as the European part of a collaborative study between the European Commission and the US Department of Energy. It aims to be the first systematic approach to the evaluation of external costs of a wide range of different fuel cycles. The project will result in an operational accounting framework for the quantification and monetarisation of priority environmental and other externalities. This framework will allow the calculation of the marginal external costs and benefits for specific power plants, at specific sites using specified technologies. There are three major phases in the project. Phase I was undertaken in collaboration with the US Department of Energy. In this phase the teams jointly developed the conceptual approach and methodology and shared scientific information for application to a number of fuel cycles. On the European side work concentrated on the nuclear and coal fuel cycles which together were expected to raise many of the fundamental issues in fuel cycle analysis. The project is currently nearing completion of Phase 2. During this phase the methodology has been applied to a wide range of different fossil, nuclear and renewable fuel cycles for power generation and energy conservation options. Also a series of National Implementation Programmes are underway in which the methodology and accounting framework are being applied to reference sites throughout Europe. In addition the general methodology is being extended to address the evaluation of externalities associated with

  9. Formaldehyde sensor based on Ni-doped tetrapod-shaped ZnO nanopowder induced by external magnetic field

    Science.gov (United States)

    Bai, Zikui; Xie, Changsheng; Hu, Mulin; Zhang, Shunping

    2008-12-01

    The sensors based on Ni-doped ZnO nanopowder with tetrapod-shape (T-ZnO) were fabricated by screen-printing technique with external magnetic field in different direction. The morphologies and crystal structures of the thick film were characterized by X-ray diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM), respectively. Gas-sensing property of sensors responded to 100 ppm formaldehyde was also detected. The results show that the direction of magnetic field has crucial effect on the sensor sensitivity. The sensors based on 5 wt% Ni-doped T-ZnO induced by magnetic field in parallel direction to the thick film surface, has the optimization sensitivity, the shortest response and recovery time, which are 10.6, 16 and 15 s, respectively. The magnetic-field induction model and the gas-sensing mechanism of the Ni-doped T-ZnO are proposed.

  10. Involvement of Sac1 phosphoinositide phosphatase in the metabolism of phosphatidylserine in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Tani, Motohiro; Kuge, Osamu

    2014-04-01

    Sac1 is a phosphoinositide phosphatase that preferentially dephosphorylates phosphatidylinositol 4-phosphate. Mutation of SAC1 causes not only the accumulation of phosphoinositides but also reduction of the phosphatidylserine (PS) level in the yeast Saccharomyces cerevisiae. In this study, we characterized the mechanism underlying the PS reduction in SAC1-deleted cells. Incorporation of (32) P into PS was significantly delayed in sac1∆ cells. Such a delay was also observed in SAC1- and PS decarboxylase gene-deleted cells, suggesting that the reduction in the PS level is caused by a reduction in the rate of biosynthesis of PS. A reduction in the PS level was also observed with repression of STT4 encoding phosphatidylinositol 4-kinase or deletion of VPS34 encoding phophatidylinositol 3-kinase. However, the combination of mutations of SAC1 and STT4 or VPS34 did not restore the reduced PS level, suggesting that both the synthesis and degradation of phosphoinositides are important for maintenance of the PS level. Finally, we observed an abnormal PS distribution in sac1∆ cells when a specific probe for PS was expressed. Collectively, these results suggested that Sac1 is involved in the maintenance of a normal rate of biosynthesis and distribution of PS. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm.

    Science.gov (United States)

    Younan, Patrick; Iampietro, Mathieu; Nishida, Andrew; Ramanathan, Palaniappan; Santos, Rodrigo I; Dutta, Mukta; Lubaki, Ndongala Michel; Koup, Richard A; Katze, Michael G; Bukreyev, Alexander

    2017-09-26

    consistently linked with fatal disease outcome. Previous findings have demonstrated that specific T-cell subsets are key contributors to the onset of a cytokine storm. In this study, we investigated the role of Tim-1, a T-cell-receptor-independent trigger of T-cell activation. We first demonstrated that Tim-1-knockout (KO) mice survive lethal Ebola virus challenge. We then used a series of in vitro assays to demonstrate that Ebola virus directly binds primary T cells in a Tim-1-phosphatidylserine-dependent manner. We noted that binding induces a cytokine storm-like phenomenon and that blocking Tim-1-phosphatidylserine interactions reduces viral binding, T-cell activation, and cytokine production. These findings highlight a previously unknown role of Tim-1 in the development of a cytokine storm and "immune paralysis." Copyright © 2017 Younan et al.

  12. Phosphatidylserine targeted single-walled carbon nanotubes for photothermal ablation of bladder cancer

    Science.gov (United States)

    Virani, Needa A.; Davis, Carole; McKernan, Patrick; Hauser, Paul; Hurst, Robert E.; Slaton, Joel; Silvy, Ricardo P.; Resasco, Daniel E.; Harrison, Roger G.

    2018-01-01

    Bladder cancer has a 60%-70% recurrence rate most likely due to any residual tumour left behind after a transurethral resection (TUR). Failure to completely resect the cancer can lead to recurrence and progression into higher grade tumours with metastatic potential. We present here a novel therapy to treat superficial tumours with the potential to decrease recurrence. The therapy is a heat-based approach in which bladder tumour specific single-walled carbon nanotubes (SWCNTs) are delivered intravesically at a very low dose (0.1 mg SWCNT per kg body weight) followed 24 h later by a short 30 s treatment with a 360° near-infrared light that heats only the bound nanotubes. The energy density of the treatment was 50 J cm-2, and the power density that this treatment corresponds to is 1.7 W cm-2, which is relatively low. Nanotubes are specifically targeted to the tumour via the interaction of annexin V (AV) and phosphatidylserine, which is normally internalised on healthy tissue but externalised on tumours and the tumour vasculature. SWCNTs are conjugated to AV, which binds specifically to bladder cancer cells as confirmed in vitro and in vivo. Due to this specific localisation, NIR light can be used to heat the tumour while conserving the healthy bladder wall. In a short-term efficacy study in mice with orthotopic MB49 murine bladder tumours treated with the SWCNT-AV conjugate and NIR light, no tumours were visible on the bladder wall 24 h after NIR light treatment, and there was no damage to the bladder. In a separate survival study in mice with the same type of orthotopic tumours, there was a 50% cure rate at 116 days when the study was ended. At 116 days, no treatment toxicity was observed, and no nanotubes were detected in the clearance organs or bladder.

  13. Anticipated chaos in a nonsymmetric coupled external-cavity-laser system

    International Nuclear Information System (INIS)

    Rees, Paul; Spencer, Paul S.; Pierce, Iestyn; Sivaprakasam, S.; Shore, K. Alan

    2003-01-01

    We explain how the anticipation of chaos in a coupled external cavity laser system described by Sivaprakasam, Shahverdiev, Spencer, and Shore [Phys. Rev. Lett. 87, 154101 (2001)] is obtained. We show that the external cavity induces the required symmetry breaking necessary for the existence of a time delay between the synchronized output of the two laser diodes. The inclusion of a detuning between the two lasers causes one laser to anticipate the chaotic dynamics of the other

  14. Correlation of Vitamin D status and orthodontic-induced external apical root resorption.

    Science.gov (United States)

    Tehranchi, Azita; Sadighnia, Azin; Younessian, Farnaz; Abdi, Amir H; Shirvani, Armin

    2017-01-01

    Adequate Vitamin D is essential for dental and skeletal health in children and adult. The purpose of this study was to assess the correlation of serum Vitamin D level with external-induced apical root resorption (EARR) following fixed orthodontic treatment. In this cross-sectional study, the prevalence of Vitamin D deficiency (defined by25-hydroxyvitamin-D) was determined in 34 patients (23.5% male; age range 12-23 years; mean age 16.63 ± 2.84) treated with fixed orthodontic treatment. Root resorption of four maxillary incisors was measured using before and after periapical radiographs (136 measured teeth) by means of a design-to-purpose software to optimize data collection. Teeth with a maximum percentage of root resorption (%EARR) were indicated as representative root resorption for each patient. A multiple linear regression model and Pearson correlation coefficient were used to assess the association of Vitamin D status and observed EARR. P 0.05). This study suggests that Vitamin D level is not among the clinical variables that are potential contributors for EARR. The prevalence of Vitamin D deficiency does not differ in patients with higher EARR. These data suggest the possibility that Vitamin D insufficiency may not contribute to the development of more apical root resorption although this remains to be confirmed by further longitudinal cohort studies.

  15. IRAK1 variant is protective for orthodontic-induced external apical root resorption.

    Science.gov (United States)

    Pereira, S; Nogueira, L; Canova, F; Lopez, M; Silva, H C

    2016-10-01

    Interleukin-1 beta (IL1B) pathway is a key player in orthodontic-induced external apical root resorption (EARR). The aim of this work was to identify the genes related to the IL1 pathway as possible candidate genes for EARR, which might be included in an integrative predictive model of this complex phenotype. Using a stepwise multiple linear regression model, 195 patients who had undergone orthodontic treatment were assessed for clinical and genetic factors associated with %EARRmax (maximum %EARR value obtained for each patient). The four maxillary incisors and the two maxillary canines were assessed. Three functional single nucleotide polymorphisms (SNPs) were genotyped: rs1143634 in IL1B gene, rs315952 in IL1RN gene, and rs1059703 in X-linked IRAK1 gene. The model showed that four of the nine clinical variables and one SNP explained 30% of the %EARRmax variability. The most significant unique contributions to the model were gender (P = 0.001), treatment duration (P < 0.001), premolar extractions (P = 0.003), Hyrax appliance (P < 0.001), and homozygosity/hemizygosity for variant C from IRAK1 gene (P = 0.018), which proved to be a protective factor. IRAK1 polymorphism is proposed as a protective variant for EARR. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. External costs of energy - do the answers match the questions? Looking back at 10 years of ExternE

    International Nuclear Information System (INIS)

    Krewitt, W.

    2002-01-01

    While the claim for 'getting prices right' is quite popular in conceptual policy papers, the implementation of appropriate internalisation strategies is still hampered by a lack of reliable external cost data. Great expectations were set into the ExternE project, a major research programme launched by the European Commission at the beginning of the 1990s to provide a scientific basis for the quantification of energy related externalities and to give guidance supporting the design of internalisation measures. After more than a decade of research, the ExternE label became a well recognised standard source for external cost data. Looking back into the ExternE history, the paper pursues how emerging new scientific insights and changing background assumptions affected external cost estimates and related recommendations to policy over time. Based on ExternE results, the usefulness and inherent limitations of external cost estimates for impact categories like climate change or nuclear waste disposal is discussed. The paper also gives examples on how external costs in spite of remaining uncertainties are successfully used to support environmental policy. (Author)

  17. Apoptotic abscess imaging with {sup 99m}Tc-HYNIC-rh-Annexin-V

    Energy Technology Data Exchange (ETDEWEB)

    Penn, David L.; Kim, Christopher; Zhang, Kaijun; Mukherjee, Archana; Devakumar, Devadhas; Jungkind, Donald [Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Thakur, Mathew L. [Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107 (United States)], E-mail: mathew.thakur@jefferson.edu

    2010-01-15

    Abscess formation causes systemic and localized up-regulation of neutrophil [polymorphonuclear leukocytes (PMNs)] signaling pathways. In the abscess, following bacterial ingestion or PMN activation by inflammatory mediators, PMN apoptosis is elevated and leads to the externalization of phosphatidylserine. Annexin-V (AnxV) has been shown to have high affinity to externalized phosphatidylserine. We hypothesized that {sup 99m}Tc-AnxV will target high densities of apoptotic PMNs and image abscesses. AnxV, conjugated with hydrazinenicaotinamide (HYNIC), was labeled with reduced {sup 99m}TcO{sub 4}{sup -} and its purity was determined by instant thin-layer chromatography. Apoptosis was induced in isolated human PMNs by incubation in 2% saline for 17 and 22 h at 37 deg. C. PMNs were then incubated with {sup 99m}Tc-HYNIC-AnxV and associated {sup 99m}Tc was determined. Abscesses were induced in mice by intramuscular injection of bacteria or turpentine. Following intravenous administration of {sup 99m}Tc-HYNIC-AnxV, mice were imaged and tissue distribution studied at 4 and 24 h. Radiochemical purity of {sup 99m}Tc-HYNIC-AnxV was 84.9{+-}8.11%. At 17 h, {sup 99m}Tc-HYNIC-AnxV bound to apoptotic PMNs was 71.6{+-}0.01% and 48.6{+-}0.01% for experimental and control cells, respectively (P=.002). At 22 h, experimental cells retained 74.9{+-}0.02% and control cells retained 47.2{+-}0.02% (P=.005). {sup 99m}Tc-HYNIC-AnxV associated with bacterial abscesses was 1.25{+-}0.09 and 3.75{+-}0.83 percent injected dose per gram (%ID/g) at 4 and 24 h compared to turpentine abscesses which was 1.02{+-}0.16 and 0.72{+-}0.17 %ID/g at 4 (P{<=}.05) and 24 h (P{<=}.01). {sup 99m}Tc-HYNIC-AnxV represents a minimally invasive and promising agent to image and potentially distinguish between infectious and inflammatory abscesses.

  18. Fruit extract from a Sechium edule hybrid induce apoptosis in leukaemic cell lines but not in normal cells.

    Science.gov (United States)

    Aguiñiga-Sánchez, Itzen; Soto-Hernández, Marcos; Cadena-Iñiguez, Jorge; Ruíz-Posadas, Lucero del Mar; Cadena-Zamudio, Jorge David; González-Ugarte, Ana Karen; Steider, Benny Weiss; Santiago-Osorio, Edelmiro

    2015-01-01

    The antiproliferative potential of a crude extract from the chayote hybrid H-837-07-GISeM® and its potential for apoptosis induction were assessed in leukaemic cell lines and normal mouse bone marrow mononuclear cells (BM-MNCs). The extract strongly inhibited the proliferation of the P388, J774, and WEHI-3 cell lines (with an IC50 below 1.3 μg·mL(-1)), reduced cell viability, and induced apoptotic body production, phosphatidylserine translocation, and DNA fragmentation. However, the extract had no effect on BM-MNCs. We postulate that these properties make the extract a good candidate for an anti-tumour agent for clinical use.

  19. Phosphatidylserine-stimulated production of N-acyl-phosphatidylethanolamines by Ca2+-dependent N-acyltransferase.

    Science.gov (United States)

    Hussain, Zahir; Uyama, Toru; Kawai, Katsuhisa; Binte Mustafiz, Smriti Sultana; Tsuboi, Kazuhito; Araki, Nobukazu; Ueda, Natsuo

    2018-05-01

    N-acyl-phosphatidylethanolamine (NAPE) is known to be a precursor for various bioactive N-acylethanolamines including the endocannabinoid anandamide. NAPE is produced in mammals through the transfer of an acyl chain from certain glycerophospholipids to phosphatidylethanolamine (PE) by Ca 2+ -dependent or -independent N-acyltransferases. The ε isoform of mouse cytosolic phospholipase A 2 (cPLA 2 ε) was recently identified as a Ca 2+ -dependent N-acyltransferase (Ca-NAT). In the present study, we first showed that two isoforms of human cPLA 2 ε function as Ca-NAT. We next purified both mouse recombinant cPLA 2 ε and its two human orthologues to examine their catalytic properties. The enzyme absolutely required Ca 2+ for its activity and the activity was enhanced by phosphatidylserine (PS). PS enhanced the activity 25-fold in the presence of 1 mM CaCl 2 and lowered the EC 50 value of Ca 2+ >8-fold. Using a PS probe, we showed that cPLA 2 ε largely co-localizes with PS in plasma membrane and organelles involved in the endocytic pathway, further supporting the interaction of cPLA 2 ε with PS in living cells. Finally, we found that the Ca 2+ -ionophore ionomycin increased [ 14 C]NAPE levels >10-fold in [ 14 C]ethanolamine-labeled cPLA 2 ε-expressing cells while phospholipase A/acyltransferase-1, acting as a Ca 2+ -independent N-acyltransferase, was insensitive to ionomycin for full activity. In conclusion, PS potently stimulated the Ca 2+ -dependent activity and human cPLA 2 ε isoforms also functioned as Ca-NAT. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Dipole nano-laser: the effect of an external electric field

    Energy Technology Data Exchange (ETDEWEB)

    Ghannam, T, E-mail: gtalal@hotmail.co [KAIN Institute for Nano-Technology, King Saud University, PO Box 2454, Riyadh 11451 (Saudi Arabia)

    2010-08-14

    Using the Langevin formalism we study the effects an external electromagnetic field induces in a system made of a pumped two-level system (TLS) and a metallic nano-particle (NP) that interact together via their near-fields. The surface plasmons of the NP greatly enhance the scattered light. With the absence of the external EM field the spectral width of the scattered light is broader than that of the system, covering almost the entire optical range. However, with the inclusion the external EM field, a reduction in the spectral width of the scattered light of order of 10-50 times below that of the system is observed for certain parameter regimes.This system exhibits also bistability in the population difference of the TLS with the external field acting as an order parameter, but only for certain values of the noise quanta.

  1. Estimating parameters of chaotic systems synchronized by external driving signal

    International Nuclear Information System (INIS)

    Wu Xiaogang; Wang Zuxi

    2007-01-01

    Noise-induced synchronization (NIS) has evoked great research interests recently. Two uncoupled identical chaotic systems can achieve complete synchronization (CS) by feeding a common noise with appropriate intensity. Actually, NIS belongs to the category of external feedback control (EFC). The significance of applying EFC in secure communication lies in fact that the trajectory of chaotic systems is disturbed so strongly by external driving signal that phase space reconstruction attack fails. In this paper, however, we propose an approach that can accurately estimate the parameters of the chaotic systems synchronized by external driving signal through chaotic transmitted signal, driving signal and their derivatives. Numerical simulation indicates that this approach can estimate system parameters and external coupling strength under two driving modes in a very rapid manner, which implies that EFC is not superior to other methods in secure communication

  2. Attenuated Mycobacterium tuberculosis SO2 vaccine candidate is unable to induce cell death.

    Directory of Open Access Journals (Sweden)

    Adriana Aporta

    Full Text Available It has been proposed that Mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. As part of the characterization of a novel tuberculosis vaccine candidate, the M. tuberculosis phoP mutant SO2, we sought to evaluate its potential to induce host cell death. The parental M. tuberculosis MT103 strain and the current vaccine against tuberculosis Bacillus Calmette-Guérin (BCG were used as comparators in mouse models in vitro and in vivo. Our data reveal that attenuated SO2 was unable to induce apoptotic events neither in mouse macrophages in vitro nor during lung infection in vivo. In contrast, virulent MT103 triggers typical apoptotic events with phosphatidylserine exposure, caspase-3 activation and nuclear condensation and fragmentation. BCG strain behaved like SO2 and did not induce apoptosis. A clonogenic survival assay confirmed that viability of BCG- or SO2-infected macrophages was unaffected. Our results discard apoptosis as the protective mechanism induced by SO2 vaccine and provide evidence for positive correlation between classical apoptosis induction and virulent strains, suggesting apoptosis as a possible virulence determinant during M. tuberculosis infection.

  3. Rationale for a GRAVSAT-MAGSAT mission: A perspective on the problem of external/internal transient field effects

    Science.gov (United States)

    Hermance, J. F.

    1985-01-01

    The Earth's magnetic field at MAGSAT altitudes not only has contributions from the Earth's core and static magnetization in the lithosphere, but also from external electric current systems in the ionosphere and magnetosphere, along with induced electric currents flowing in the conducting earth. Hermance assessed these last two contributions; the external time-varying fields and their associated internal counter-parts which are electromagnetically induced. It is readily recognized that during periods of magnetic disturbance, external currents often contribute from 10's to 100's of nanoteslas (gammas) to observations of the Earth's field. Since static anomalies from lithospheric magnetization are of this same magnitude or less, these external source fields must be taken into account when attempting to delineate gross structural features in the crust.

  4. High-Yield and Sustainable Production of Phosphatidylserine in Purely Aqueous Solutions via Adsorption of Phosphatidylcholine on Triton-X-100-Modified Silica.

    Science.gov (United States)

    Zhang, Xiaoli; Li, Binglin; Wang, Jiao; Li, Huanyu; Zhao, Binxia

    2017-12-13

    Triton X-100 was covalently bound to a surface of silica and acted as an anchor molecule to facilitate the adsorption of phosphatidylcholine (PC) in a purely aqueous solution. The silica-adsorbed PC obtained was successfully used for phospholipase D (PLD)-mediated transphosphatidylation in the production of phosphatidylserine (PS). Organic solvents were completely avoided in the whole production process. The PC loading and PS yield reached 98.9 and 99.0%, respectively. Two adsorption models were studied, and the relevant parameters were calculated to help us understand the adsorption and reaction processes deeply. In addition, the silica-adsorbed PC provides a promising way to continuously biosynthesize PS. A packed-bed reactor was employed to demonstrate the process flow of the continuous production of PS. The recyclability and stability of the Triton-X-100-modified silica were excellent, as demonstrated by its use 30 times during continuous operation without any loss of the productivity.

  5. The ExternE project: methodology, objectives and limitations

    International Nuclear Information System (INIS)

    Rabl, A.; Spadaro, J.V.

    2002-01-01

    This paper presents a summary of recent studies on external costs of energy systems, in particular the ExternE (External Costs of Energy) Project of the European Commission. To evaluate the impact and damage cost of a pollutant, one needs to carry out an impact pathway analysis; this involves the calculation of increased pollutant concentrations in all affected regions due to an incremental emission (e.g. μg/m 3 of particles, using models of atmospheric dispersion and chemistry), followed by the calculation of physical impacts (e.g. number of cases of asthma due to these particles, using a dose-response function). The entire so-called fuel chain (or fuel cycle) is evaluated and compared on the basis of delivered end use energy. Even though the uncertainties are large, the results provide substantial evidence that the classical air pollutants (particles, NO x and SO x ) from the combustion of fossil fuels impose a heavy toll, in addition to the cost of global warming. The external costs are especially large for coal; even for 'good current technology' they may be comparable to the price of electricity. For natural gas the external costs are about a third to a half of coal. The external costs of nuclear are small compared to the price of electricity (at most a few %), and so are the external costs of most renewable energy systems. (authors)

  6. Network and external perturbation induce burst synchronisation in cat cerebral cortex

    Science.gov (United States)

    Lameu, Ewandson L.; Borges, Fernando S.; Borges, Rafael R.; Batista, Antonio M.; Baptista, Murilo S.; Viana, Ricardo L.

    2016-05-01

    The brain of mammals are divided into different cortical areas that are anatomically connected forming larger networks which perform cognitive tasks. The cat cerebral cortex is composed of 65 areas organised into the visual, auditory, somatosensory-motor and frontolimbic cognitive regions. We have built a network of networks, in which networks are connected among themselves according to the connections observed in the cat cortical areas aiming to study how inputs drive the synchronous behaviour in this cat brain-like network. We show that without external perturbations it is possible to observe high level of bursting synchronisation between neurons within almost all areas, except for the auditory area. Bursting synchronisation appears between neurons in the auditory region when an external perturbation is applied in another cognitive area. This is a clear evidence that burst synchronisation and collective behaviour in the brain might be a process mediated by other brain areas under stimulation.

  7. Nanodiamonds activate blood platelets and induce thromboembolism.

    Science.gov (United States)

    Kumari, Sharda; Singh, Manoj K; Singh, Sunil K; Grácio, José J A; Dash, Debabrata

    2014-03-01

    Nanodiamonds (NDs) have been evaluated for a wide range of biomedical applications. Thus, thorough investigation of the biocompatibility of NDs has become a research priority. Platelets are highly sensitive and are one of the most abundant cell types found in blood. They have a central role in hemostasis and arterial thrombosis. In this study, we aim to investigate the direct and acute effects of carboxylated NDs on platelet function. In this study, pro-coagulant parameters such as platelet aggregability, intracellular Ca(2+) flux, mitochondrial transmembrane potential (ΔΨm), generation of reactive oxygen species, surface exposure of phosphatidylserine, electron microscopy, cell viability assay and in vivo thromboembolism were analyzed in great detail. Carboxylated NDs evoked significant activation of human platelets. When administered intravenously in mice, NDs were found to induce widespread pulmonary thromboembolism, indicating the remarkable thrombogenic potential of this nanomaterial. Our findings raise concerns regarding the putative biomedical applications of NDs pertaining to diagnostics and therapeutics, and their toxicity and prothrombotic properties should be critically evaluated.

  8. External costs related to power production technologies. ExternE national implementation for Denmark

    International Nuclear Information System (INIS)

    Schleisner, L.; Sieverts Nielsen, P.

    1997-12-01

    The objective of the ExternE National Implementation project has been to establish a comprehensive and comparable set of data on externalities of power generation for all EU member states and Norway. The tasks include the application of the ExternE methodology to the most important fuel cycles for each country as well as to update the already existing results; to aggregate these site- and technology-specific results to more general figures. The current report covers the results of the national implementation for Denmark. Three different fuel cycles have been chosen as case studies. These are fuel cycles for an offshore wind farm and a wind farm on land, a decentralised CHP plant based on natural gas and a decentralised CHP plant based on biogas. The report covers all the details of the application of the methodology to these fuel cycles aggregation to a national level. (au) EU-JOULE 3. 59 tabs., 25 ills., 61 refs

  9. External costs related to power production technologies. ExternE national implementation for Denmark

    Energy Technology Data Exchange (ETDEWEB)

    Schleisner, L; Sieverts Nielsen, P

    1997-12-01

    The objective of the ExternE National Implementation project has been to establish a comprehensive and comparable set of data on externalities of power generation for all EU member states and Norway. The tasks include the application of the ExternE methodology to the most important fuel cycles for each country as well as to update the already existing results; to aggregate these site- and technology-specific results to more general figures. The current report covers the results of the national implementation for Denmark. Three different fuel cycles have been chosen as case studies. These are fuel cycles for an offshore wind farm and a wind farm on land, a decentralised CHP plant based on natural gas and a decentralised CHP plant based on biogas. The report covers all the details of the application of the methodology to these fuel cycles aggregation to a national level. (au) EU-JOULE 3. 59 tabs., 25 ills., 61 refs.

  10. Environmental externalities related to power production on biogas and natural gas based on the EU ExternE methodology

    DEFF Research Database (Denmark)

    Nielsen, Per Sieverts; Ibsen, Liselotte Schleisner

    1998-01-01

    This paper assesses the environmental impacts and external costs from selected electricity generation systems in Denmark. The assessment is carried out as part of the ExternE National Implementation, which is the second phase of the ExternE project and involves case studies from all Western...... European countries. The project use a “bottom-up” methodology to evaluate the external costs associated with a wide range of different fuel cycles. The project has identified priority impacts, where most are impacts from air emissions. Externalities due to atmospheric emissions are calculated through...

  11. Thrombotic Role of Blood and Endothelial Cells in Uremia through Phosphatidylserine Exposure and Microparticle Release.

    Directory of Open Access Journals (Sweden)

    Chunyan Gao

    Full Text Available The mechanisms contributing to an increased risk of thrombosis in uremia are complex and require clarification. There is scant morphological evidence of membrane-dependent binding of factor Xa (FXa and factor Va (FVa on endothelial cells (EC in vitro. Our objectives were to confirm that exposed phosphatidylserine (PS on microparticle (MP, EC, and peripheral blood cell (PBC has a prothrombotic role in uremic patients and to provide visible and morphological evidence of PS-dependent prothrombinase assembly in vitro. We found that uremic patients had more circulating MP (derived from PBC and EC than controls. Additionally, patients had more exposed PS on their MPs and PBCs, especially in the hemodialysis group. In vitro, EC exposed more PS in uremic toxins or serum. Moreover, reconstitution experiments showed that at the early stages, PS exposure was partially reversible. Using confocal microscopy, we observed that PS-rich membranes of EC and MP provided binding sites for FVa and FXa. Further, exposure of PS in uremia resulted in increased generation of FXa, thrombin, and fibrin and significantly shortened coagulation time. Lactadherin, a protein that blocks PS, reduced 80% of procoagulant activity on PBC, EC, and MP. Our results suggest that PBC and EC in uremic milieu are easily injured or activated, which exposes PS and causes a release of MP, providing abundant procoagulant membrane surfaces and thus facilitating thrombus formation. Blocking PS binding sites could become a new therapeutic target for preventing thrombosis.

  12. Radioiodinated, photoactivatable phosphatidylcholine and phosphatidylserine: transfer properties and differential photoreactive interaction with human erythrocyte membrane proteins

    International Nuclear Information System (INIS)

    Schroit, A.J.; Madsen, J.; Ruoho, A.E.

    1987-01-01

    An isotopically labeled cross-linking reagent, succinimido 3-(3-[ 125 I]iodo-4-azidophenyl)propionate, has been synthesized and coupled to 1-acyl-2-(aminocaproyl)phosphatidylcholine according to previously described procedures. 125 I- and N 3 -labeled phosphatidylserine ( 125 I-N 3 -PS) was produced from the phosphatidylcholine (PC) analog by phospholipase D catalyzed base exchange in the presence of L-serine. These phospholipid analogues are photoactivatable, are labeled with 125 I at high specific activity, completely incorporate into synthetic vesicles, and spontaneously transfer between membranes. When an excess of acceptor vesicles or red blood cells (RBC) was mixed with a population of donor vesicles containing the 125 I-N 3 -phospholipids, approximately 40% of the analogues transferred to the acceptor population. After transfer in the dark to RBC, all of the 125 I-N 3 -PC incorporated into the cells could be removed by washing with serum, whereas the 125 I-N 3 -PS could not. After photolabeling of intact RBC, ∼50% of the PC and 20% of the PS cross-linked to membrane proteins as determined by their insolubility in CHCl 3 /MeOH. Analysis of probe distribution by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that 125 I-N 3 -PS preferentially labeled a M/sub r/ 30,000 peptide which contained ∼30% of the protein-bound label

  13. Internal phase transition induced by external forces in Finsler geometric model for membranes

    Science.gov (United States)

    Koibuchi, Hiroshi; Shobukhov, Andrey

    2016-10-01

    In this paper, we numerically study an anisotropic shape transformation of membranes under external forces for two-dimensional triangulated surfaces on the basis of Finsler geometry. The Finsler metric is defined by using a vector field, which is the tangential component of a three-dimensional unit vector σ corresponding to the tilt or some external macromolecules on the surface of disk topology. The sigma model Hamiltonian is assumed for the tangential component of σ with the interaction coefficient λ. For large (small) λ, the surface becomes oblong (collapsed) at relatively small bending rigidity. For the intermediate λ, the surface becomes planar. Conversely, fixing the surface with the boundary of area A or with the two-point boundaries of distance L, we find that the variable σ changes from random to aligned state with increasing of A or L for the intermediate region of λ. This implies that an internal phase transition for σ is triggered not only by the thermal fluctuations, but also by external mechanical forces. We also find that the frame (string) tension shows the expected scaling behavior with respect to A/N (L/N) at the intermediate region of A (L) where the σ configuration changes between the disordered and ordered phases. Moreover, we find that the string tension γ at sufficiently large λ is considerably smaller than that at small λ. This phenomenon resembles the so-called soft-elasticity in the liquid crystal elastomer, which is deformed by small external tensile forces.

  14. Interaction of the superconducting domains induced by external electric field with electromagnetic waves

    International Nuclear Information System (INIS)

    Shapiro, B.Y.

    1992-01-01

    The behavior of a superconductor in time-independent electric field perpendicular to the surface and in the external electromagnetic wave is theoretically investigated. A new type of the resonance interaction between superconducting domains localized along the magnetic field (if the superconducting phase transition takes place in the external magnetic field perpendicular to the surface) and electromagnetic waves is predicted. The surface impedance of the superconductor with domains is calculated. It is shown that the real part of the impedance has a saturation if the skin length equals the domain size. (orig.)

  15. An analysis of critical heat flux on the external surface of the reactor vessel lower head

    International Nuclear Information System (INIS)

    Yang, Soo Hyung; Baek, Won Pil; Chang, Soon Heung

    1999-01-01

    CHF (Critical heat flux) on the external surface of the reactor vessel lower head is major key in the evaluation on the feasibility of IVR-EVC (In-Vessel Retention through External Vessel Cooling) concept. To identify the CHF on the external surface, considerable works have been performed. Through the review on the previous works related to the CHF on the external surface, liquid subcooling, induced flow along the external surface, ICI (In-Core Instrument) nozzle and minimum gap are identified as major parameters. According to the present analysis, the effects of the ICI nozzle and minimum gap on CHF are pronounced at the upstream of test vessel: on the other hand, the induced flow considerably affects the CHF at downstream of test vessel. In addition, the subcooling effect is shown at all of test vessel, and decreases with the increase in the elevation of test vessel. In the real application of the IVR-EVC concept, vertical position is known as a limiting position, at which thermal margin is the minimum. So, it is very important to precisely predict the CHF at vertical position in a viewpoint of gaining more thermal margins. However, the effects of the liquid subcooling and induced flow do not seem to be adequately included in the CHF correlations suggested by previous works, especially at the downstream positions

  16. O-hexadecyl-dextran entrapped berberine nanoparticles abrogate high glucose stress induced apoptosis in primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Radhika Kapoor

    Full Text Available Nanotized phytochemicals are being explored by researchers for promoting their uptake and effectiveness at lower concentrations. In this study, O-hexadecyl-dextran entrapped berberine chloride nanoparticles (BC-HDD NPs were prepared, and evaluated for their cytoprotective efficacy in high glucose stressed primary hepatocytes and the results obtained compared with bulk berberine chloride (BBR treatment. The nanotized formulation treated primary hepatocytes that were exposed to high glucose (40 mM, showed increased viability compared to the bulk BBR treated cells. BC-HDD NPs reduced the ROS generation by ∼ 3.5 fold during co-treatment, prevented GSH depletion by ∼ 1.6 fold, reduced NO formation by ∼ 5 fold and significantly prevented decline in SOD activity in stressed cells. Lipid peroxidation was also prevented by ∼ 1.9 fold in the presence of these NPs confirming the antioxidant capacity of the formulation. High glucose stress increased Bax/Bcl2 ratio followed by mitochondrial depolarization and activation of caspase-9/-3 confirming involvement of mitochondrial pathway of apoptosis in the exposed cells. Co- and post-treatment of BC-HDD NPs prevented depolarization of mitochondrial membrane, reduced Bax/Bcl2 ratio and prevented externalization of phosphatidyl-serine confirming their anti-apoptotic capacity in those cells. Sub-G1 phase apparent in high glucose stressed cells was not seen in BC-HDD NPs treated cells. The present study reveals that BC-HDD NPs at ∼ 20 fold lower concentration are as effective as BBR in preventing high glucose induced oxidative stress, mitochondrial depolarization and downstream events of apoptotic cell death.

  17. Directed motion generated by heat bath nonlinearly driven by external noise

    International Nuclear Information System (INIS)

    Chaudhuri, J Ray; Barik, D; Banik, S K

    2007-01-01

    Based on the heat bath system approach where the bath is nonlinearly modulated by an external Gaussian random force, we propose a new microscopic model to study directed motion in the overdamped limit for a nonequilibrium open system. Making use of the coupling between the heat bath and the external modulation as a small perturbation, we construct a Langevin equation with multiplicative noise- and space-dependent dissipation and the corresponding Fokker-Planck-Smoluchowski equation in the overdamped limit. We examine the thermodynamic consistency condition and explore the possibility of observing a phase-induced current as a consequence of state-dependent diffusion and, necessarily, nonlinear driving of the heat bath by the external noise

  18. Directed motion generated by heat bath nonlinearly driven by external noise

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhuri, J Ray [Department of Physics, Katwa College, Katwa, Burdwan 713 130, West Bengal (India); Barik, D [Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032 (India); Banik, S K [Department of Physics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0435 (United States)

    2007-12-07

    Based on the heat bath system approach where the bath is nonlinearly modulated by an external Gaussian random force, we propose a new microscopic model to study directed motion in the overdamped limit for a nonequilibrium open system. Making use of the coupling between the heat bath and the external modulation as a small perturbation, we construct a Langevin equation with multiplicative noise- and space-dependent dissipation and the corresponding Fokker-Planck-Smoluchowski equation in the overdamped limit. We examine the thermodynamic consistency condition and explore the possibility of observing a phase-induced current as a consequence of state-dependent diffusion and, necessarily, nonlinear driving of the heat bath by the external noise.

  19. Communication: Polarizable polymer chain under external electric field in a dilute polymer solution.

    Science.gov (United States)

    Budkov, Yu A; Kolesnikov, A L; Kiselev, M G

    2015-11-28

    We study the conformational behavior of polarizable polymer chain under an external homogeneous electric field within the Flory type self-consistent field theory. We consider the influence of electric field on the polymer coil as well as on the polymer globule. We show that when the polymer chain conformation is a coil, application of external electric field leads to its additional swelling. However, when the polymer conformation is a globule, a sufficiently strong field can induce a globule-coil transition. We show that such "field-induced" globule-coil transition at the sufficiently small monomer polarizabilities goes quite smoothly. On the contrary, when the monomer polarizability exceeds a certain threshold value, the globule-coil transition occurs as a dramatic expansion in the regime of first-order phase transition. The developed theoretical model can be applied to predicting polymer globule density change under external electric field in order to provide more efficient processes of polymer functionalization, such as sorption, dyeing, and chemical modification.

  20. ExternE - valuation of hydro power in Klippen. Final report

    International Nuclear Information System (INIS)

    Nilsson, Maans

    1998-08-01

    'true' average willingness to pay for these respondents is within these boundaries. The average willingness to pay was 300-700 SEK/year for Swedes, 600-1900 SEK/year for Locals and 500-2000 SEK/year for Tourists. Total national benefits can be estimated from the average willingness to pay for the three categories. With a total production estimated at 5820 GWh, the externalities are estimated to 54-125 mEcu/kWh from the Swede sample, 0.12-0.33 mEcu/kWh for the locals sample and 1.7-7.7 mEcu/kWh for the tourist sample. The question whether decision-makers should use these CV-results as estimates of the damages induced by a specific project cannot be answered in simple way. There are a number of ethical/philosophical questions as well as methodological pitfalls that must be taken very seriously. It is a challenge to communicate adequate information to a lay audience on a complex phenomenon such as the river ecosystems and impacts of hydro power developments. There is a risk that respondents are ill-informed when they are asked to state a willingness to pay. The results from the Swede sample must be interpreted with serious caution as we see a risk of an embedding effect. We have higher confidence in the samples of Locals and Tourists, who are better informed and familiar with the issue 38 refs, 4 figs, 5 tabs, 1 appendix

  1. Attenuation of Aβ25–35-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways

    International Nuclear Information System (INIS)

    Meng, Xiangbao; Wang, Min; Sun, Guibo; Ye, Jingxue; Zhou, Yanhui; Dong, Xi; Wang, Tingting; Lu, Shan; Sun, Xiaobo

    2014-01-01

    Amyloid-beta (Aβ) has a pivotal function in the pathogenesis of Alzheimer's disease. To investigate Aβ neurotoxicity, we used an in vitro model that involves Aβ 25–35 -induced cell death in the nerve growth factor-induced differentiation of PC12 cells. Aβ 25–35 (20 μM) treatment for 24 h caused apoptotic cell death, as evidenced by significant cell viability reduction, LDH release, phosphatidylserine externalization, mitochondrial membrane potential disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA fragmentation in PC12 cells. Aβ 25–35 treatment led to autophagic cell death, as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and increased LC3-II/LC3-I ratio. Aβ 25–35 treatment induced oxidative stress, as evidenced by intracellular ROS accumulation and increased production of mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG. Phytoestrogens have been proved to be protective against Aβ-induced neurotoxicity and regarded as relatively safe targets for AD drug development. Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10 μM) for 12 h increased estrogen response element reporter activity, activated PI3K/Akt pathways, inhibited GSK-3β, induced Nrf2 nuclear translocation, augmented antioxidant responsive element enhancer activity, upregulated heme oxygenase 1 (HO-1) expression and activity, and provided protective effects against Aβ 25–35 -induced neurotoxicity, including oxidative stress, apoptosis, and autophagic cell death. In conclusion, GP-17 conferred protection against Aβ 25–35 -induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways. This finding might provide novel insights into understanding the mechanism for neuroprotective effects of phytoestrogens or gypenosides

  2. Light Water Reactor Sustainability Program Industry Application External Hazard Analyses Problem Statement

    Energy Technology Data Exchange (ETDEWEB)

    Szilard, Ronaldo Henriques [Idaho National Lab. (INL), Idaho Falls, ID (United States); Coleman, Justin [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis L. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Prescott, Steven [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kammerer, Annie [Annie Kammerer Consulting, Rye, NH (United States); Youngblood, Robert [Idaho National Lab. (INL), Idaho Falls, ID (United States); Pope, Chad [Idaho State Univ., Pocatello, ID (United States)

    2015-07-01

    Risk-Informed Margin Management Industry Application on External Events. More specifically, combined events, seismically induced external flooding analyses for a generic nuclear power plant with a generic site soil, and generic power plant system and structure. The focus of this report is to define the problem above, set up the analysis, describe the methods to be used, tools to be applied to each problem, and data analysis and validation associated with the above.

  3. Conjugated Bilirubin Triggers Anemia by Inducing Erythrocyte Death

    Science.gov (United States)

    Lang, Elisabeth; Gatidis, Sergios; Freise, Noemi F; Bock, Hans; Kubitz, Ralf; Lauermann, Christian; Orth, Hans Martin; Klindt, Caroline; Schuier, Maximilian; Keitel, Verena; Reich, Maria; Liu, Guilai; Schmidt, Sebastian; Xu, Haifeng C; Qadri, Syed M; Herebian, Diran; Pandyra, Aleksandra A; Mayatepek, Ertan; Gulbins, Erich; Lang, Florian; Häussinger, Dieter; Lang, Karl S; Föller, Michael; Lang, Philipp A

    2015-01-01

    Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca2+ influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels. Conclusion: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease. (Hepatology 2015;61:275–284) PMID:25065608

  4. p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression

    Science.gov (United States)

    Tian, Linjie; Choi, Seung-Chul; Murakami, Yousuke; Allen, Joselyn; Morse, Herbert C., III; Qi, Chen-Feng; Krzewski, Konrad; Coligan, John E.

    2014-01-01

    Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment of the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K). CD300f-PI3K association leads to activation of downstream Rac/Cdc42 GTPase and mediates changes of F-actin that drive AC engulfment. Importantly, primary macrophages from CD300f-deficient mice have impaired phagocytosis of ACs. The biological consequence of CD300f deficiency is predisposition to autoimmune disease development, as FcγRIIB-deficient mice develop a systemic lupus erythematosus-like disease at a markedly accelerated rate if CD300f is absent. In this report we identify the mechanism and role of CD300f in AC phagocytosis and maintenance of immune homeostasis.

  5. Regulating multiple externalities

    DEFF Research Database (Denmark)

    Waldo, Staffan; Jensen, Frank; Nielsen, Max

    2016-01-01

    Open access is a well-known externality problem in fisheries causing excess capacity and overfishing. Due to global warming, externality problems from CO2 emissions have gained increased interest. With two externality problems, a first-best optimum can be achieved by using two regulatory instrume......Open access is a well-known externality problem in fisheries causing excess capacity and overfishing. Due to global warming, externality problems from CO2 emissions have gained increased interest. With two externality problems, a first-best optimum can be achieved by using two regulatory...

  6. Levels of Arabidopsis thaliana leaf phosphatidic acids, phosphatidylserines, and most trienoate-containing polar lipid molecular species increase during the dark period of the diurnal cycle

    Directory of Open Access Journals (Sweden)

    Sara eMaatta

    2012-03-01

    Full Text Available Previous work has demonstrated that plant leaf polar lipid fatty acid composition varies during the diurnal (dark-light cycle. Fatty acid synthesis occurs primarily during the light, but fatty acid desaturation continues in the absence of light, resulting in polyunsaturated fatty acids reaching their highest levels toward the end of the dark period. In this work, Arabidopsis thaliana were grown at constant (21°C temperature with 12-h light and 12-h dark periods. Collision induced dissociation time-of-flight mass spectrometry demonstrated that 16:3 and 18:3 fatty acid content in membrane lipids of leaves are higher at the end of the dark than at the end of the light period, while 16:1, 16:2, 18:0, and 18:1 content are higher at the end of the light period. Lipid profiling of membrane galactolipids, phospholipids, and lysophospholipids by electrospray ionization triple quadrupole mass spectrometry indicated that the monogalactosyldiacylglycerol, phosphatidylglycerol, and phosphatidylcholine classes include molecular species whose levels are highest at end of the light period and others that are highest at the end of the dark period. The levels of phosphatidic acid and phosphatidylserine classes were higher at the end of the dark period, and molecular species within these classes either followed the class pattern or were not significantly changed in the diurnal cycle. Phospholipase D (PLD is a family of enzymes that hydrolyzes phospholipids to produce phosphatidic acid. Analysis of several PLD mutant lines suggests that PLDζ2 and possibly PLDα1 may contribute to diurnal cycling of phosphatidic acid. The polar lipid compositional changes are considered in relation to recent data that demonstrate phosphatidylcholine acyl editing.

  7. Joint probability safety assessment for NPP defense infrastructure against extreme external natural hazards

    International Nuclear Information System (INIS)

    Guilin, L.; Defu, L.; Huajun, L.; Fengqing, W.; Tao, Z.

    2012-01-01

    With the increasing tendency of natural hazards, the typhoon, hurricane and tropical Cyclone induced surge, wave, precipitation, flood and wind as extreme external loads menacing Nuclear Power Plants (NPP) in coastal and inland provinces of China. For all of planned, designed And constructed NPP the National Nuclear Safety Administration of China and IAEA recommended Probable Maximum Hurricane /Typhoon/(PMH/T), Probable Maximum Storm Surge (PMSS), Probable Maximum Flood (PMF), Design Basis Flood (DBF) as safety regulations for NPP defense infrastructures. This paper discusses the joint probability analysis of simultaneous occurrence typhoon induced extreme external hazards and compare with IAEA 2006-2009 recommended safety regulation design criteria for some NPP defense infrastructures along China coast. (authors)

  8. Attenuation of Aβ{sub 25–35}-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Xiangbao; Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Sun, Guibo, E-mail: sunguibo@126.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Ye, Jingxue [Jilin Agricultural University, Changchun, Jilin 130021 (China); Zhou, Yanhui [Center of Cardiology, People' s Hospital of Jilin Province, Changchun, 130021, Jilin (China); Dong, Xi [Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Wang, Tingting; Lu, Shan [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Sun, Xiaobo, E-mail: sun_xiaobo163@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China)

    2014-08-15

    Amyloid-beta (Aβ) has a pivotal function in the pathogenesis of Alzheimer's disease. To investigate Aβ neurotoxicity, we used an in vitro model that involves Aβ{sub 25–35}-induced cell death in the nerve growth factor-induced differentiation of PC12 cells. Aβ{sub 25–35} (20 μM) treatment for 24 h caused apoptotic cell death, as evidenced by significant cell viability reduction, LDH release, phosphatidylserine externalization, mitochondrial membrane potential disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA fragmentation in PC12 cells. Aβ{sub 25–35} treatment led to autophagic cell death, as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and increased LC3-II/LC3-I ratio. Aβ{sub 25–35} treatment induced oxidative stress, as evidenced by intracellular ROS accumulation and increased production of mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG. Phytoestrogens have been proved to be protective against Aβ-induced neurotoxicity and regarded as relatively safe targets for AD drug development. Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10 μM) for 12 h increased estrogen response element reporter activity, activated PI3K/Akt pathways, inhibited GSK-3β, induced Nrf2 nuclear translocation, augmented antioxidant responsive element enhancer activity, upregulated heme oxygenase 1 (HO-1) expression and activity, and provided protective effects against Aβ{sub 25–35}-induced neurotoxicity, including oxidative stress, apoptosis, and autophagic cell death. In conclusion, GP-17 conferred protection against Aβ{sub 25–35}-induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways. This finding might provide novel insights into understanding the mechanism for neuroprotective effects of phytoestrogens

  9. Approaches in estimation of external cost for fuel cycles in the ExternE project

    International Nuclear Information System (INIS)

    Afanas'ev, A.A.; Maksimenko, B.N.

    1998-01-01

    The purposes, content and main results of studies realized within the frameworks of the International Project ExternE which is the first comprehensive attempt to develop general approach to estimation of external cost for different fuel cycles based on utilization of nuclear and fossil fuels, as well as on renewable power sources are discussed. The external cost of a fuel cycle is treated as social and environmental expenditures which are not taken into account by energy producers and consumers, i.e. these are expenditures not included into commercial cost nowadays. The conclusion on applicability of the approach suggested for estimation of population health hazards and environmental impacts connected with electric power generation growth (expressed in money or some other form) is made

  10. Application of declarative modeling approaches for external events

    International Nuclear Information System (INIS)

    Anoba, R.C.

    2005-01-01

    Probabilistic Safety Assessments (PSAs) are increasingly being used as a tool for supporting the acceptability of design, procurement, construction, operation, and maintenance activities at Nuclear Power Plants. Since the issuance of Generic Letter 88-20 and subsequent IPE/IPEEE assessments, the NRC has issued several Regulatory Guides such as RG 1.174 to describe the use of PSA in risk-informed regulation activities. Most PSA have the capability to address internal events including internal floods. As the more demands are being placed for using the PSA to support risk-informed applications, there has been a growing need to integrate other eternal events (Seismic, Fire, etc.) into the logic models. Most external events involve spatial dependencies and usually impact the logic models at the component level. Therefore, manual insertion of external events impacts into a complex integrated fault tree model may be too cumbersome for routine uses of the PSA. Within the past year, a declarative modeling approach has been developed to automate the injection of external events into the PSA. The intent of this paper is to introduce the concept of declarative modeling in the context of external event applications. A declarative modeling approach involves the definition of rules for injection of external event impacts into the fault tree logic. A software tool such as the EPRI's XInit program can be used to interpret the pre-defined rules and automatically inject external event elements into the PSA. The injection process can easily be repeated, as required, to address plant changes, sensitivity issues, changes in boundary conditions, etc. External event elements may include fire initiating events, seismic initiating events, seismic fragilities, fire-induced hot short events, special human failure events, etc. This approach has been applied at a number of US nuclear power plants including a nuclear power plant in Romania. (authors)

  11. Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells

    International Nuclear Information System (INIS)

    Cho, Sung-Hee; Chung, Kyung-Sook; Choi, Jung-Hye; Kim, Dong-Hyun; Lee, Kyung-Tae

    2009-01-01

    Compound K [20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC 50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1) the activation of caspases-3, -8, and -9; (2) the loss of mitochondrial membrane potential; (3) the release of cytochrome c and Smac/DIABLO to the cytosol; (4) the translocation of Bid and Bax to mitochondria; and (5) the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation

  12. Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells

    Directory of Open Access Journals (Sweden)

    Choi Jung-Hye

    2009-12-01

    Full Text Available Abstract Background Compound K [20-O-β-(D-glucopyranosyl-20(S-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. Methods We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Results Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1 the activation of caspases-3, -8, and -9; (2 the loss of mitochondrial membrane potential; (3 the release of cytochrome c and Smac/DIABLO to the cytosol; (4 the translocation of Bid and Bax to mitochondria; and (5 the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. Conclusions The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through

  13. Oxidative stress, metabolomics profiling, and mechanism of local anesthetic induced cell death in yeast

    Directory of Open Access Journals (Sweden)

    Cory H.T. Boone

    2017-08-01

    Full Text Available The World Health Organization designates lidocaine as an essential medicine in healthcare, greatly increasing the probability of human exposure. Its use has been associated with ROS generation and neurotoxicity. Physiological and metabolomic alterations, and genetics leading to the clinically observed adverse effects have not been temporally characterized. To study alterations that may lead to these undesirable effects, Saccharomyces cerevisiae grown on aerobic carbon sources to stationary phase was assessed over 6 h. Exposure of an LC50 dose of lidocaine, increased mitochondrial depolarization and ROS/RNS generation assessed using JC-1, ROS/RNS specific probes, and FACS. Intracellular calcium also increased, assessed by ICP-MS. Measurement of the relative ATP and ADP concentrations indicates an initial 3-fold depletion of ATP suggesting an alteration in the ATP:ADP ratio. At the 6 h time point the lidocaine exposed population contained ATP concentrations roughly 85% that of the negative control suggesting the surviving population adapted its metabolic pathways to, at least partially restore cellular bioenergetics. Metabolite analysis indicates an increase of intermediates in the pentose phosphate pathway, the preparatory phase of glycolysis, and NADPH. Oxidative stress produced by lidocaine exposure targets aconitase decreasing its activity with an observed decrease in isocitrate and an increase citrate. Similarly, increases in α-ketoglutarate, malate, and oxaloacetate imply activation of anaplerotic reactions. Antioxidant molecule glutathione and its precursor amino acids, cysteine and glutamate were greatly increased at later time points. Phosphatidylserine externalization suggestive of early phase apoptosis was also observed. Genetic studies using metacaspase null strains showed resistance to lidocaine induced cell death. These data suggest lidocaine induces perpetual mitochondrial depolarization, ROS/RNS generation along with increased

  14. Analysis of External Treatment Methods and Technical Characteristics of External Treatment

    Science.gov (United States)

    Zhang, Rui; Miao, Mingsan; Bai, Ming

    2018-01-01

    Chinese medicine external therapy is a treatment method of Chinese medicine with Chinese characteristics. The effect of traditional Chinese medicine external treatment, convenient operation, external treatment and technology has great prospects for development. The traditional Chinese medicine external treatment method and technical characteristics were analyzed.

  15. WE-D-210-04: Radiation-Induced Polymerization of Ultrasound Contrast Agents in View of Non-Invasive Dosimetry in External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Callens, M; Verboven, E; Van Den Abeele, K [Department of Physics, Wave Propagation and Signal Processing, KU Leuven KULAK, Kortrijk (Belgium); D’Agostino, E [DoseVue NV, Hasselt (Belgium); Pfeiffer, H [Department of Materials Engineering, KU Leuven, Leuven (Belgium); D’hooge, J [Department of Cardiovascular Sciences, Bio-Medical Science Group, KU Leuven, Leuven (Belgium)

    2015-06-15

    Purpose: Ultrasound contrast agents (UCA’s) based on gas-filled microbubbles encapsulated by an amphiphilic shell are well established as safe and effective echo-enhancers in diagnostic imaging. In view of an alternative application of UCA’s, we investigated the use of targeted microbubbles as radiation sensors for external beam radiation therapy. As radiation induces permanent changes in the microbubble’s physico-chemical properties, a robust measure of these changes can provide a direct or indirect estimate of the applied radiation dose. For instance, by analyzing the ultrasonic dispersion characteristics of microbubble distributions before and after radiation treatment, an estimate of the radiation dose at the location of the irradiated volume can be made. To increase the radiation sensitivity of microbubbles, polymerizable diacetylene molecules can be incorporated into the shell. This study focuses on characterizing the acoustic response and quantifying the chemical modifications as a function of radiation dose. Methods: Lipid/diacetylene microbubbles were irradiated with a 6 MV photon beam using dose levels in the range of 0–150 Gy. The acoustic response of the microbubbles was monitored by ultrasonic through-transmission measurements in the range of 500 kHz to 20 MHz, thereby providing the dispersion relations of the phase velocity, attenuation and nonlinear coefficient. In addition, the radiation-induced chemical modifications were quantified using UV-VIS spectroscopy. Results: UV-VIS spectroscopy measurements indicate that ionizing radiation induces the polymerization of diacetylenes incorporated in the microbubble shell. The polymer yield strongly depends on the shell composition and the radiation-dose. The acoustic response is inherently related to the visco-elastic properties of the shell and is strongly influenced by the shell composition and the physico-chemical changes in the environment. Conclusion: Diacetylene-containing microbubbles are

  16. Children's learning of tennis skills is facilitated by external focus instructions

    Directory of Open Access Journals (Sweden)

    Ricardo Hadler

    2014-12-01

    Full Text Available The present study examined the effects of instructions promoting external versus internal foci of attention on the learning of a tennis forehand stroke in 11-year old children. Three groups of participants practiced hitting tennis balls at a target. External focus group participants were instructed to direct their attention to the movement of the racquet, while participants in the internal focus group were asked to direct their attention to the movements of their arm. Participants in a control group did not receive attentional focus instructions. Two days after the practice phase (60 trials, learning was assessed in retention and transfer tests. The results showed that the external focus group demonstrated greater accuracy in hitting a target relative to the two other groups in retention, and relative to the internal focus group in transfer. We conclude that instructions inducing an external focus of attention can enhance children's sport skill learning.

  17. ExternE: Externalities of energy Vol. 5. Nuclear

    International Nuclear Information System (INIS)

    Dreicer, M.; Tort, V.; Manen, P.

    1995-01-01

    Since the early 1970s, there has been increased interest in the environmental impacts that are caused by the generation of electricity. The comparative risk assessment studies at that time used mainly deaths and injuries as impact indicators. By the end of the 1980s studies changed to the assessment of the costs imposed on society and the environment that were not included in the market price of the energy produced, the so-called external costs. The preliminary studies that were published set the conceptual basis, grounded in neo-classical economics, for the valuation of the health and environmental impacts that could be assessed. As a consequence of the many questions raised by the methodologies employed by these early studies, Directorate General XII (DG XII) of the Commission of the European Communities established a collaborative research programme with the United States Department of Energy to identify an appropriate methodology for this type of work. Following the completion of this collaboration, the DG XII programme has continued as the ExternE project. The main objective of the work carried out at CEPN was to develop an impact pathway methodology for the nuclear fuel cycle that would be consistent with the methodologies developed for other fuel cycles, without loosing the nuclear-specific techniques required for a proper evaluation. In this way, comparisons between the different fuel cycles would be possible. This report presents the methodology and demonstration of the results in the context of the French nuclear fuel cycle. The United States team at Oak Ridge National Laboratory has previously issued a draft report on the results of their assessment. The French fuel cycle was broken down into 8 separate stages. Reference sites and 1990s technology were chosen to represent the total nuclear fuel cycle, as it exists today. In addition, the transportation of material between the sites was considered. The facilities are assessed for routine operation, except

  18. ExternE: Externalities of energy Vol. 4. Oil and gas

    International Nuclear Information System (INIS)

    Friedrich, R.; Krewitt, W.; Mayerhofer, P.

    1995-01-01

    Awareness of the environmental damage resulting from human activity, particularly commencing energy use, has grown greatly in recent years. Effects such as global warming, ozone depletion and acid rain are now the subjects of much research and public debate. It is now known that these and other effects damage a wide range of receptors, including human health, forests, crops, freshwater ecosystems and buildings. Such damages are typically not accounted for by the producers and consumers of the good in question (in this case energy). They are thus referred to as 'external costs' or 'externalities', to distinguish them from the private costs which account for the construction of plant, cost of fuel, wages, etc. In recent years there has been a growing interest in the assessment of the environmental and health impacts of energy, and the related external costs. This concern is driven by a number of different factors: the need to integrate environmental concerns in decision making over the choice between different fuels and energy technologies; the need to evaluate the costs and benefits of stricter environmental standards; increased attention to the use of economic instruments for environmental policy, the need to develop overall indicators of environmental performance of different technologies; major changes in the energy sector, including privatisation, liberalisation of markets, reduction of subsidies, etc. An agreed methodology for calculation and integration of external costs has not been established. Earlier work is typically of a preliminary nature and tends to be deficient with respect to both the methods employed and the quality of models and data used. In consequence of this a collaborative project, the EC/US Fuel Cycles Study, was established between Directorate General XLI (Science, Research and Technology) of the European Commission and the United States Department of Energy. This ran for the period 1991 to 1993, and good agreement on a variety of

  19. Kinetics of apoptotic markers in exogeneously induced apoptosis of EL4 cells.

    Science.gov (United States)

    Jessel, Robert; Haertel, Steffen; Socaciu, Carmen; Tykhonova, Svetlana; Diehl, Horst A

    2002-01-01

    We investigated the time-dependence of apoptotic events in EL4 cells by monitoring plasma membrane changes in correlation to DNA fragmentation and cell shrinkage. We applied three apoptosis inducers (staurosporine, tubericidine and X-rays) and we looked at various markers to follow the early-to-late apoptotic events: phospholipid translocation (identified through annexin V-fluorescein assay and propidium iodide), lipid package (via merocyanine assay), membrane fluidity and anisotropy (via fluorescent measurements), DNA fragmentation by the fluorescence-labeling test and cell size measurements. The different apoptotic inducers caused different reactions of the cells: staurosporine induced apoptosis most rapidly in a high number of cells, tubercidine triggered apoptosis only in the S phase cells, while X-rays caused a G2/M arrest and subsequently apoptosis. Loss of lipid asymmetry is promptly detectable after one hour of incubation time. The phosphatidylserine translocation, decrease of lipid package and anisotropy, and the increase of membrane fluidity appeared to be based on the same process of lipid asymmetry loss. Therefore, the DNA fragmentation and the cell shrinkage appear to be parallel and independent processes running on different time scales but which are kinetically inter-related. The results indicate different signal steps to apoptosis dependent on inducer characteristics but the kinetics of "early-to-late" apoptosis appears to be a fixed program.

  20. The Efficacy of Dandelion Root Extract in Inducing Apoptosis in Drug-Resistant Human Melanoma Cells

    Directory of Open Access Journals (Sweden)

    S. J. Chatterjee

    2011-01-01

    Full Text Available Notoriously chemoresistant melanoma has become the most prevalent form of cancer for the 25–29 North American age demographic. Standard treatment after early detection involves surgical excision (recurrence is possible, and metastatic melanoma is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. Characteristic apoptotic morphology of nuclear condensation and phosphatidylserine flipping to the outer leaflet of the plasma membrane of A375 human melanoma cells was observed within 48 hours. DRE-induced apoptosis activates caspase-8 in A375 cells early on, demonstrating employment of an extrinsic apoptotic pathway to kill A375 cells. Reactive Oxygen Species (ROS generated from DRE-treated isolated mitochondria indicates that natural compounds in DRE can also directly target mitochondria. Interestingly, the relatively resistant G361 human melanoma cell line responded to DRE when combined with the metabolism interfering antitype II diabetic drug metformin. Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells.

  1. External representation of argumentation in CSCL and the management of cognitive load

    NARCIS (Netherlands)

    Bruggen, J.M.; Kirschner, P.A.; Jochems, W.

    2002-01-01

    Computer-supported collaborative learning (CSCL) environments, particularly environments where students share external representations, are discussed as an interesting area for the application of cognitive load theory (CLT). CSCL environments share a number of characteristics that will induce

  2. Spin-lattice dynamics simulation of external field effect on magnetic order of ferromagnetic iron

    Directory of Open Access Journals (Sweden)

    C. P. Chui

    2014-03-01

    Full Text Available Modeling of field-induced magnetization in ferromagnetic materials has been an active topic in the last dozen years, yet a dynamic treatment of distance-dependent exchange integral has been lacking. In view of that, we employ spin-lattice dynamics (SLD simulations to study the external field effect on magnetic order of ferromagnetic iron. Our results show that an external field can increase the inflection point of the temperature. Also the model provides a better description of the effect of spin correlation in response to an external field than the mean-field theory. An external field has a more prominent effect on the long range magnetic order than on the short range counterpart. Furthermore, an external field allows the magnon dispersion curves and the uniform precession modes to exhibit magnetic order variation from their temperature dependence.

  3. Development and pharmacokinetic of antimony encapsulated in liposomes of phosphatidylserine using radioisotopes in experimental leishmaniasis; Desenvolvimento e farmacocinetica de antimonio encapsulado em lipossomas de fosfatidilserina utilizando radioisotopos em leishmaniose experimental

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta Etel Treiger

    2010-07-01

    Leishmaniasis are a complex of parasitic diseases caused by intra macrophage protozoa of the genus Leishmania, and is fatal if left untreated. Pentavalent antimonials, though toxic and their mechanism of action being unclear, remain the first-line drugs for treatment. Effective therapy could be achieved by delivering antileishmanial drugs to these sites of infection. Liposomes are phospholipid vesicles that promote improvement in the efficacy and action of drugs in target cell. Liposomes are taken up by the cells of mononuclear phagocytic system (MPS). The purpose of this study was to develop a preparation of meglumine antimonate encapsulated in liposomes of phosphatidylserine and to study its pharmacokinetic in healthy mice to establish its metabolism and distribution. Quantitative analysis of antimony from liposomes demonstrated that Neutron Activation Analysis was the most sensitive technique with almost 100 % of accuracy. All liposome formulations presented a mean diameter size of 150 nm. The determination of IC{sub 50} in infected macrophage showed that liposome formulations were between 10 - 63 fold more effective than the free drug, indicating higher selectivity index. By fluorescence microscopy, an increased uptake of fluorescent-liposomes was seen in infected macrophages during short times of incubation compared with non-infected macrophages. Biodistribution studies showed that meglumine antimonate irradiated encapsulated in liposomes of phosphatidylserine promoted a targeting of antimony for MPS tissues and maintained high doses in organs for a prolonged period. In conclusion, these data suggest that meglumine antimonate encapsulated in liposomes showed higher effectiveness than the non-liposomal drug against Leishmania infection. The development of liposome formulations should be a new alternative for the chemotherapy of infection diseases, especially Leishmaniasis, as they are used to sustain and target pharmaceuticals to the local of infection. (author)

  4. Eupomatenoid-5 Isolated from Leaves of Piper regnellii Induces Apoptosis in Leishmania amazonensis

    Directory of Open Access Journals (Sweden)

    Francielle Pelegrin Garcia

    2013-01-01

    Full Text Available Leishmania spp. are protozoa responsible for leishmaniasis, a neglected disease that kills up to 50,000 people every year. Current therapies mainly rely on antimonial drugs that are inadequate because of their poor efficacy and safety and increased drug resistance. An urgent need exists to find new and more affordable drugs. Our previous study demonstrated the antileishmanial activity of eupomatenoid-5, a neolignan obtained from leaves of Piper regnellii var. pallescens. The aim of the present study was to clarify the mode of action of eupomatenoid-5 against L. amazonensis. We used biochemical and morphological techniques and demonstrated that eupomatenoid-5 induced cell death in L. amazonensis promastigotes, sharing some phenotypic features observed in metazoan apoptosis, including increased reactive oxygen species production, hypopolarization of mitochondrial potential, phosphatidylserine exposure, decreased cell volume, and G0/G1 phase cell cycle arrest.

  5. RELATIVECONTRIBUTIONS OF THE NIGERIAN CAPITALMARKETTO THE GROWTH OF EXTERNAL RESERVES (2005-2014

    Directory of Open Access Journals (Sweden)

    Akaninyene Udo Akpan

    2015-01-01

    Full Text Available Virtually all aspects of human endeavour entail the use of money either selfgenerated or borrowed. In capital market, the stock in trade is money which couldbe raised through various instruments under well governed rules and regulationscarefully administered and followed by different institutions or market operators.External reserves constitute an integral part of the wealth of the nation such thatthe lack of it brings worry to most nations and can limit the ability of the countryto make foreign currency denominated payments and limits its spending abroad.Hence,countries are induced to hold reserves to allow monetary authorities tointervene in markets to control the exchange rate and inflation. Adequate reservesalso allow the country to borrow from abroad and to hedge against instability anduncertainty of external capital flows.Therefore, the objective of this paper is toaccess the relative contribution of the Nigerian capital market if any to the growthof her external reserve.The methodology used is purely descriptive and narrative and the data used is secondary. The evidence provided in the study based on thestatistical analysis, revealed that the Nigerian capital market can induce thegrowthof external reserve but it has not contributed to the growth of externalreserve in Nigeria. Furthermore, the study recommendedamong otherstheneedfor availability of more investment instruments such as derivatives, futures,swaps, options in the market and theexpansion of the Nigerian capital Market bythe government creating an enabling investable environment that will increaseboth the volume of transactions and number of securities traded in the market.This will improve their ability to mobilize resources and efficiently allocate themto the most productive sectors of the economy hence, contributing its portion tothe growth of her external reserve.

  6. Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4.

    Science.gov (United States)

    Tietjen, Gregory T; Gong, Zhiliang; Chen, Chiu-Hao; Vargas, Ernesto; Crooks, James E; Cao, Kathleen D; Heffern, Charles T R; Henderson, J Michael; Meron, Mati; Lin, Binhua; Roux, Benot; Schlossman, Mark L; Steck, Theodore L; Lee, Ka Yee C; Adams, Erin J

    2014-04-15

    Recognition of phosphatidylserine (PS) lipids exposed on the extracellular leaflet of plasma membranes is implicated in both apoptotic cell removal and immune regulation. The PS receptor T cell immunoglobulin and mucin-domain-containing molecule 4 (Tim4) regulates T-cell immunity via phagocytosis of both apoptotic (high PS exposure) and nonapoptotic (intermediate PS exposure) activated T cells. The latter population must be removed at lower efficiency to sensitively control immune tolerance and memory cell population size, but the molecular basis for how Tim4 achieves this sensitivity is unknown. Using a combination of interfacial X-ray scattering, molecular dynamics simulations, and membrane binding assays, we demonstrate how Tim4 recognizes PS in the context of a lipid bilayer. Our data reveal that in addition to the known Ca(2+)-coordinated, single-PS binding pocket, Tim4 has four weaker sites of potential ionic interactions with PS lipids. This organization makes Tim4 sensitive to PS surface concentration in a manner capable of supporting differential recognition on the basis of PS exposure level. The structurally homologous, but functionally distinct, Tim1 and Tim3 are significantly less sensitive to PS surface density, likely reflecting the differences in immunological function between the Tim proteins. These results establish the potential for lipid membrane parameters, such as PS surface density, to play a critical role in facilitating selective recognition of PS-exposing cells. Furthermore, our multidisciplinary approach overcomes the difficulties associated with characterizing dynamic protein/membrane systems to reveal the molecular mechanisms underlying Tim4's recognition properties, and thereby provides an approach capable of providing atomic-level detail to uncover the nuances of protein/membrane interactions.

  7. Radiopharmacological evaluation of 18F-labeled phosphatidylserine-binding peptides for molecular imaging of apoptosis

    International Nuclear Information System (INIS)

    Wuest, Melinda; Perreault, Amanda; Kapty, Janice; Richter, Susan; Foerster, Christian; Bergman, Cody; Way, Jenilee; Mercer, John; Wuest, Frank

    2015-01-01

    Introduction: Radiolabeled phosphatidylserine (PS)-binding peptides represent an innovative strategy for molecular imaging of apoptosis with positron emission tomography (PET). The goal of this study was the radiopharmacological evaluation of radiolabeled peptides for their binding to PS on apoptotic cancer cells, involving metabolic stability, cellular uptake, biodistribution, and dynamic PET imaging experiments. Methods: Binding of peptides LIKKPF, PGDLSR, FBz-LIKKPF, FBz-PGDLSR, FBAM-CLIKKPF and FBAM-CPGDLSR to PS was analyzed in a newly developed radiometric binding assay using 64 Cu-labeled wild-type annexin-V as radiotracer. Radiolabeling of most potent peptides with fluorine-18 was carried out with thiol-selective prosthetic group [ 18 F]FBAM to give [ 18 F]FBAM-CLIKKPF and [ 18 F]FBAM-CPGDLSR. [ 18 F]FBAM-labeled peptides were studied in camptothecin-induced apoptotic human T lymphocyte Jurkat cells, and in a murine EL4 tumor model of apoptosis using dynamic PET imaging and biodistribution. Results: Peptides LIKKPF and PGDLSR inhibited binding of 64 Cu-labeled annexin-V to immobilized PS in the millimolar range (IC 50 10–15 mM) compared to annexin-V (45 nM). Introduction of FBAM prosthetic group slightly increased inhibitory potencies (FBAM-CLIKKPF: IC 50 = 1 mM; FBAM-CPGDLSR: IC 50 = 6 mM). Radiolabeling succeeded in good radiochemical yields of 50–54% using a chemoselective alkylation reaction of peptides CLIKKPF and CPGDLSR with [ 18 F]FBAM. In vivo metabolic stability studies in mice revealed 40–60% of intact peptides at 5 min p.i. decreasing to 25% for [ 18 F]FBAM-CLIKKPF and less than 5% for [ 18 F]FBAM-CPGDLSR at 15 min p.i.. Cell binding of [ 18 F]FBAM-CLIKKPF in drug-treated Jurkat cells was significantly higher compared to untreated cells, but this was not observed for [ 18 F]FBAM-CPGDLSR. Dynamic PET imaging experiments showed that baseline uptake of [ 18 F]FBAM-CLIKKPF in EL4 tumors was higher (SUV 5min 0.46, SUV 60min 0.13) compared to

  8. Fipronil is a powerful uncoupler of oxidative phosphorylation that triggers apoptosis in human neuronal cell line SHSY5Y.

    Science.gov (United States)

    Vidau, Cyril; González-Polo, Rosa A; Niso-Santano, Mireia; Gómez-Sánchez, Rubén; Bravo-San Pedro, José M; Pizarro-Estrella, Elisa; Blasco, Rafael; Brunet, Jean-Luc; Belzunces, Luc P; Fuentes, José M

    2011-12-01

    Fipronil is a phenylpyrazole insecticide known to elicit neurotoxicity via an interaction with ionotropic receptors, namely GABA and glutamate receptors. Recently, we showed that fipronil and other phenylpyrazole compounds trigger cell death in Caco-2 cells. In this study, we investigated the mode of action and the type of cell death induced by fipronil in SH-SY5Y human neuroblastoma cells. Flow cytometric and western blot analyses demonstrated that fipronil induces cellular events belonging to the apoptosis process, such as mitochondrial potential collapse, cytochrome c release, caspase-3 activation, nuclear condensation and phosphatidylserine externalization. In addition, fipronil induces a rapid ATP depletion with concomitant activation of anaerobic glycolysis. This cellular response is characteristic of mitochondrial injury associated with a defect of the respiration process. Therefore, we also investigated the effect of fipronil on the oxygen consumption in isolated mitochondria. Interestingly, we show for the first time that fipronil is a strong uncoupler of oxidative phosphorylation at relative low concentrations. Thus in this study, we report a new mode of action by which the insecticide fipronil could triggers apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. External-strain-induced semimetallic and metallic phase of chlorographene

    Science.gov (United States)

    Puri, Shivam; Bhowmick, Somnath

    2018-04-01

    To overcome the limitations of graphene due to lack of intrinsic band gap, it is generally functionalized with hydrogen or halogen atoms such as fluorine and chlorine. Generally, such functionalization yields a moderate- to high-band-gap material in case of 100% coverage, for example ≈1.5 eV in graphene functionalized with chlorine atoms or chlorographene. In this paper, using ab initio calculations, we report very interesting transformations observed in chlorographene under external strain, driving it to a state with nearly vanishing band gap (under tensile strain) and even converting it to a metal (under compressive strain). We also show the importance of spin-orbit coupling, responsible for the few meV band gap of chlorographene observed under high tensile strain, which would have been a gapless semimetal otherwise.

  10. Regulation of apoptosis by resveratrol through JAK/STAT and mitochondria mediated pathway in human epidermoid carcinoma A431 cells

    International Nuclear Information System (INIS)

    Madan, Esha; Prasad, Sahdeo; Roy, Preeti; George, Jasmine; Shukla, Yogeshwer

    2008-01-01

    Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin present mainly in grapes, red wine and berries, is known to possess strong chemopreventive and anticancer properties. Here, we demonstrated the anti-proliferative and apoptosis-inducing activities of resveratrol in human epidermoid carcinoma A431 cells. Resveratrol has cytotoxic effects through inhibiting cellular proliferation of A431 cells, which leads to the induction of apoptosis, as evident by an increase in the fraction of cells in the sub-G 1 phase of the cell cycle and Annexin-V binding of externalized phosphatidylserine. Results revealed that inhibition of proliferation is associated with regulation of the JAK/STAT pathway, where resveratrol prevents phosphorylation of JAK, thereby inhibiting STAT1 phosphorylation. Furthermore, resveratrol treatment actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. Consequently, an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and subsequent cleavage of PARP, thereby shifting the balance in favor of apoptosis. These observations indicate that resveratrol treatment inhibits JAK/STAT-mediated gene transcription and induce the mitochondrial cell death pathway.

  11. Comprehensive Understanding of Ductility Loss Mechanisms in Various Steels with External and Internal Hydrogen

    Science.gov (United States)

    Takakuwa, Osamu; Yamabe, Junichiro; Matsunaga, Hisao; Furuya, Yoshiyuki; Matsuoka, Saburo

    2017-11-01

    Hydrogen-induced ductility loss and related fracture morphologies are comprehensively discussed in consideration of the hydrogen distribution in a specimen with external and internal hydrogen by using 300-series austenitic stainless steels (Types 304, 316, 316L), high-strength austenitic stainless steels (HP160, XM-19), precipitation-hardened iron-based super alloy (A286), low-alloy Cr-Mo steel (JIS-SCM435), and low-carbon steel (JIS-SM490B). External hydrogen is realized by a non-charged specimen tested in high-pressure gaseous hydrogen, and internal hydrogen is realized by a hydrogen-charged specimen tested in air or inert gas. Fracture morphologies obtained by slow-strain-rate tensile tests (SSRT) of the materials with external or internal hydrogen could be comprehensively categorized into five types: hydrogen-induced successive crack growth, ordinary void formation, small-sized void formation related to the void sheet, large-sized void formation, and facet formation. The mechanisms of hydrogen embrittlement are broadly classified into hydrogen-enhanced decohesion (HEDE) and hydrogen-enhanced localized plasticity (HELP). In the HEDE model, hydrogen weakens interatomic bonds, whereas in the HELP model, hydrogen enhances localized slip deformations. Although various fracture morphologies are produced by external or internal hydrogen, these morphologies can be explained by the HELP model rather than by the HEDE model.

  12. Procoagulant Activity of Blood and Endothelial Cells via Phosphatidylserine Exposure and Microparticle Delivery in Patients with Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Ying Su

    2018-03-01

    Full Text Available Background/Aims: The mechanisms for thrombosis in diabetic retinopathy (DR are complex and need to be further elucidated. The purpose of this study was to test phosphatidylserine (PS exposure on microparticles (MPs and MP-origin cells from the circulation and to analyze cell-/MP-associated procoagulant activity (PCA in DR patients. Methods: PS-positive MPs and cells from healthy controls (n = 20 and diabetic patients (n = 60 were analyzed by flow cytometry and confocal microscopy. Clotting time and purified coagulation complex assays were used to measure PCA. Results: PS exposure on platelets and monocytes was higher in proliferative DR (PDR patients than in non-PDR patients or controls. The highest levels of MPs (derived from platelets [30%], erythrocytes [13%], leukocytes [28%], and endothelial cells [10%] were found in patients with PDR. In addition, PS exposure on blood cells and shed MPs in DR patients led to significantly increased FXa and FIIa generation, fibrin formation, and markedly shortened coagulation time. Moreover, lactadherin reduced 70% of PCA by blocking PS, while an anti-tissue factor antibody had a smaller effect. Conclusion: Our results confirmed that PCA in DR patients may be partly ascribed to PS exposure and MP release from blood and endothelial cells. Lactadherin may act as an efficient anticoagulant factor in this process.

  13. Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

    Science.gov (United States)

    Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

    2018-03-01

    Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

  14. Inside-out: comparing internally generated and externally generated basic emotions.

    Science.gov (United States)

    Salas, Christian E; Radovic, Darinka; Turnbull, Oliver H

    2012-06-01

    A considerable number of mood induction (MI) procedures have been developed to elicit emotion in normal and clinical populations. Although external procedures (e.g., film clips, pictures) are widely used, a number of experiments elicit emotion by using self-generated procedures (e.g., recalling an emotional personal episode). However, no study has directly compared the effectiveness of two types of internal versus external MI across multiple discrete emotions. In the present experiment, 40 undergraduate students watched film clips (external procedure) and recalled personal events (internal procedure) inducing 4 basic emotions (fear, anger, joy, sadness) and later completed a self-report questionnaire. Remarkably, both internal and external procedures elicited target emotions selectively, compared with nontarget emotions. When contrasting the intensity of target emotions, both techniques showed no significant differences, with the exception of Joy, which was more intensely elicited by the internal procedure. Importantly, when considering the overall level of intensity, it was always greater in the internal procedure, for each stimulus. A more detailed investigation of the data suggest that recalling personal events (a type of internal procedure) generates more negative and mixed blends of emotions, which might account for the overall higher intensity of the internal mood induction.

  15. The marine cytotoxin portimine is a potent and selective inducer of apoptosis.

    Science.gov (United States)

    Cuddihy, Sarah L; Drake, Sarah; Harwood, D Tim; Selwood, Andrew I; McNabb, Paul S; Hampton, Mark B

    2016-12-01

    Portimine is a recently discovered member of a class of marine micro-algal toxins called cyclic imines. In dramatic contrast to related compounds in this toxin class, portimine has very low acute toxicity to mice but is highly cytotoxic to cultured cells. In this study we show that portimine kills human Jurkat T-lymphoma cells and mouse embryonic fibroblasts (MEFs), with LC 50 values of 6 and 2.5 nM respectively. Treated cells displayed rapid caspase activation and phosphatidylserine exposure, indicative of apoptotic cell death. Jurkat cells overexpressing the anti-apoptotic protein Bcl-2 or Bax/Bak knockout MEFs were completely protected from portimine. This protection was apparent even at high concentrations of portimine, with no evidence of necrotic cell death, indicating that portimine is a selective chemical inducer of apoptosis. Treatment of the Bcl-2-overexpressing cells with both portimine and the Bcl-2 inhibitor ABT-737 proved a powerful combination, causing >90 % death. We conclude that portimine is one of the most potent naturally derived inducers of apoptosis to be discovered, and it displays strong selectivity for the induction of apoptotic pathways.

  16. Near Infrared Photoimmunotherapy with Combined Exposure of External and Interstitial Light Sources.

    Science.gov (United States)

    Maruoka, Yasuhiro; Nagaya, Tadanobu; Sato, Kazuhide; Ogata, Fusa; Okuyama, Shuhei; Choyke, Peter L; Kobayashi, Hisataka

    2018-02-21

    Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell-specific cancer treatment that induces highly selective necrotic/immunogenic cell death after systemic administration of a photoabsorber antibody conjugate and subsequent NIR light exposure. However, the depth of NIR light penetration in tissue (approximately 2 cm) with external light sources limits the therapeutic effects of NIR-PIT. Interstitial light exposure using cylindrical diffusing optical fibers can overcome this limitation. The purpose in this study was to compare three NIR light delivery methods for treating tumors with NIR-PIT using a NIR laser system at an identical light energy; external exposure alone, interstitial exposure alone, and the combination. Panitumumab conjugated with the photoabsorber IRDye-700DX (pan-IR700) was intravenously administered to mice with A431-luc xenografts which are epithelial growth factor receptor (EGFR) positive. One and 2 days later, NIR light was administered to the tumors using one of three methods. Interstitial exposure alone and in combination with external sources showed the greatest decrease in bioluminescence signal intensity. Additionally, the combination of external and interstitial NIR light exposure showed significantly greater tumor size reduction and prolonged survival after NIR-PIT compared to external exposure alone. This result suggested that the combination of external and interstitial NIR light exposure was more effective than externally applied light alone. Although external exposure is the least invasive means of delivering light, the combination of external and interstitial exposures produces superior therapeutic efficacy in tumors greater than 2 cm in depth from the tissue surface.

  17. First branchial cleft fistula associated with external auditory canal stenosis and middle ear cholesteatoma.

    Science.gov (United States)

    Abdollahi Fakhim, Shahin; Naderpoor, Masoud; Mousaviagdas, Mehrnoosh

    2014-10-01

    First branchial cleft anomalies manifest with duplication of the external auditory canal. This report features a rare case of microtia and congenital middle ear and canal cholesteatoma with first branchial fistula. External auditory canal stenosis was complicated by middle ear and external canal cholesteatoma, but branchial fistula, opening in the zygomatic root and a sinus in the helical root, may explain this feature. A canal wall down mastoidectomy with canaloplasty and wide meatoplasty was performed. The branchial cleft was excised through parotidectomy and facial nerve dissection. It should be considered that canal stenosis in such cases can induce cholesteatoma formation in the auditory canal and middle ear.

  18. Binding of thrombin-activated platelets to a fibrin scaffold through α(IIb)β₃ evokes phosphatidylserine exposure on their cell surface.

    Science.gov (United States)

    Brzoska, Tomasz; Suzuki, Yuko; Mogami, Hideo; Sano, Hideto; Urano, Tetsumei

    2013-01-01

    Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS) and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an α(IIb)β₃ antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment.

  19. Eryptosis in lead-exposed workers.

    Science.gov (United States)

    Aguilar-Dorado, Itzel-Citlalli; Hernández, Gerardo; Quintanar-Escorza, Martha-Angelica; Maldonado-Vega, María; Rosas-Flores, Margarita; Calderón-Salinas, José-Víctor

    2014-12-01

    Eryptosis is a physiological phenomenon in which old and damaged erythrocytes are removed from circulation. Erythrocytes incubated with lead have exhibited major eryptosis. In the present work we found evidence of high levels of eryptosis in lead exposed workers possibly via oxidation. Blood samples were taken from 40 male workers exposed to lead (mean blood lead concentration 64.8μg/dl) and non-exposed workers (4.2μg/dl). The exposure to lead produced an intoxication characterized by 88.3% less δ-aminolevulinic acid dehydratase (δALAD) activity in lead exposed workers with respect to non-lead exposed workers. An increment of oxidation in lead exposed workers was characterized by 2.4 times higher thiobarbituric acid-reactive substance (TBARS) concentration and 32.8% lower reduced/oxidized glutathione (GSH/GSSG) ratio. Oxidative stress in erythrocytes of lead exposed workers is expressed in 192% higher free calcium concentration [Ca(2+)]i and 1.6 times higher μ-calpain activity with respect to non-lead exposed workers. The adenosine triphosphate (ATP) concentration was not significantly different between the two worker groups. No externalization of phosphatidylserine (PS) was found in non-lead exposed workers (lead exposed workers showed 2.82% externalization. Lead intoxication induces eryptosis possibly through a molecular pathway that includes oxidation, depletion of reduced glutathione (GSH), increment of [Ca(2+)], μ-calpain activation and externalization of PS in erythrocytes. Identifying molecular signals that induce eryptosis in lead intoxication is necessary to understand its physiopathology and chronic complications. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Demonstration of immunochemical identity between the nerve growth factor-inducible large external (NILE) glycoprotein and the cell adhesion molecule L1

    DEFF Research Database (Denmark)

    Bock, E; Richter-Landsberg, C; Faissner, A

    1985-01-01

    The nerve growth factor-inducible large external (NILE) glycoprotein and the neural cell adhesion molecule L1 were shown to be immunochemically identical. Immunoprecipitation with L1 and NILE antibodies of [3H]fucose-labeled material from culture supernatants and detergent extracts of NGF......-treated rat PC12 pheochromocytoma cells yielded comigrating bands by SDS-PAGE. NILE antibodies reacted with immunopurified L1 antigen, but not with N-CAM and other L2 epitope-bearing glycoproteins from adult mouse brain. Finally, by sequential immunoprecipitation from detergent extracts of [35S......]methionine-labeled early post-natal cerebellar cell cultures or [3H]fucose-labeled NGF-treated PC12 cells, all immunoreactivity for NILE antibody could be removed by pre-clearing with L1 antibody and vice versa....

  1. Constant external fields in gauge theory and the spin 0, 1/2, 1 path integrals

    International Nuclear Information System (INIS)

    Reuter, M.; Schmidt, M.G.

    1996-10-01

    We investigate the usefulness of the ''string-inspired technique'' for gauge theory calculations in a constant external field background. Our approach is based on Strassler's worldline path integral approach to the Bern-Kosower formalism, and on the construction of worldline (super-) Green's functions incorporating external fields as well as internal propagators. The worldline path integral representation of the gluon loop is reexamined in detail. We calculate the two-loop effective actions induced for a constant external field by a scalar and spinor loop, and the corresponding one-loop effective action in the gluon loop case. (orig.)

  2. Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells.

    Science.gov (United States)

    Inayat-Hussain, S H; Annuar, B O; Din, L B; Ali, A M; Ross, D

    2003-08-01

    Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

  3. Moessbauer radiation dynamical diffraction in crystals being subjected to the action of external variable fields

    International Nuclear Information System (INIS)

    Baryshevskii, V.G.; Skadorov, V.V.

    1986-01-01

    A dynamical theory is developed of the Moessbauer radiation diffraction by crystals being subjected to an variable external field action. Equations describing the dynamical diffraction by nonstationary crystals are obtained. It is shown that the resonant interaction between Moessbauer radiation and shift field induced in the crystal by a variable external field giving rise to an effective conversion of the incident wave into a wave with changed frequency. (author)

  4. [External cephalic version].

    Science.gov (United States)

    Navarro-Santana, B; Duarez-Coronado, M; Plaza-Arranz, J

    2016-08-01

    To analyze the rate of successful external cephalic versions in our center and caesarean sections that would be avoided with the use of external cephalic versions. From January 2012 to March 2016 external cephalic versions carried out at our center, which were a total of 52. We collected data about female age, gestational age at the time of the external cephalic version, maternal body mass index (BMI), fetal variety and situation, fetal weight, parity, location of the placenta, amniotic fluid index (ILA), tocolysis, analgesia, and newborn weight at birth, minor adverse effects (dizziness, hypotension and maternal pain) and major adverse effects (tachycardia, bradycardia, decelerations and emergency cesarean section). 45% of the versions were unsuccessful and 55% were successful. The percentage of successful vaginal delivery in versions was 84% (4% were instrumental) and 15% of caesarean sections. With respect to the variables studied, only significant differences in birth weight were found; suggesting that birth weight it is related to the outcome of external cephalic version. Probably we did not find significant differences due to the number of patients studied. For women with breech presentation, we recommend external cephalic version before the expectant management or performing a cesarean section. The external cephalic version increases the proportion of fetuses in cephalic presentation and also decreases the rate of caesarean sections.

  5. [Synergetic killing effects of external magnetic fields combined with porphyrin-dextran magnetic nanoparticles on the human bladder cancer cells].

    Science.gov (United States)

    Luo, Dao-sheng; Mi, Qi-wu; Meng, Xiang-jun; Gao, Yong; Dai, Yu-ping; Deng, Chun-hua

    2012-08-18

    To study the synergetic killing effects of external magnetic fields combined with the photodynamic action of porphyrin-dextran iron oxide magnetic nanoparticles (PDMN) on human bladder cancer cells in vitro. The PDMN were produced by using the chemical co-precipitation and redox process and the physicochemical properties were characterized. Methyl thiazolyl tetrazolium (MTT) and flow cytometry were used to determine the effects of photodynamic therapy of PDMN combined with external pulsed electromagnetic fields (5 mT) on killing human bladder cancer BIU-87 cells respectively. The diameters of PDMN were 10-15 nm and the saturation magnetization was 0.20 emu/g. Effective diameter of PDMN was 94.8 nm. PDMN could remarkably inhibit the proliferation and induce the obvious apoptosis of BIU-87 cells, and the rates of growth inhibition and apoptosis were (17.61±2.73)% and (24.53±5.74)% respectively. Moreover, external pulsed electromagnetic fields (5 mT) could also suppress the proliferation and induce apoptosis of BIU-87 cells. Furthermore, the photodynamic action of PDMN combined with external magnetic fields significantly inhibited the proliferation and promote apoptosis of BIU-87 cells, and the rates of growth inhibition and apoptosis was (28.11±4.25)% and (24.53±5.74)%, respectively, which were significantly higher than those of other groups (Peffectively inhibit proliferation and induce apoptosis of BIU-87 cells. Moreover, these effects on BIU-87 cells could be strengthened by the combination with external magnetic fields.

  6. Apical External Root Resorption and Repair in Orthodontic Tooth Movement: Biological Events.

    Science.gov (United States)

    Feller, Liviu; Khammissa, Razia A G; Thomadakis, George; Fourie, Jeanine; Lemmer, Johan

    2016-01-01

    Some degree of external root resorption is a frequent, unpredictable, and unavoidable consequence of orthodontic tooth movement mediated by odontoclasts/cementoclasts originating from circulating precursor cells in the periodontal ligament. Its pathogenesis involves mechanical forces initiating complex interactions between signalling pathways activated by various biological agents. Resorption of cementum is regulated by mechanisms similar to those controlling osteoclastogenesis and bone resorption. Following root resorption there is repair by cellular cementum, but factors mediating the transition from resorption to repair are not clear. In this paper we review some of the biological events associated with orthodontically induced external root resorption.

  7. Apical External Root Resorption and Repair in Orthodontic Tooth Movement: Biological Events

    Directory of Open Access Journals (Sweden)

    Liviu Feller

    2016-01-01

    Full Text Available Some degree of external root resorption is a frequent, unpredictable, and unavoidable consequence of orthodontic tooth movement mediated by odontoclasts/cementoclasts originating from circulating precursor cells in the periodontal ligament. Its pathogenesis involves mechanical forces initiating complex interactions between signalling pathways activated by various biological agents. Resorption of cementum is regulated by mechanisms similar to those controlling osteoclastogenesis and bone resorption. Following root resorption there is repair by cellular cementum, but factors mediating the transition from resorption to repair are not clear. In this paper we review some of the biological events associated with orthodontically induced external root resorption.

  8. The CNGRC-GG-D(KLAKLAK)2 peptide induces a caspase-independent, Ca2+-dependent death in human leukemic myeloid cells by targeting surface aminopeptidase N/CD13.

    Science.gov (United States)

    Bouchet, Sandrine; Tang, Ruoping; Fava, Fanny; Legrand, Ollivier; Bauvois, Brigitte

    2016-04-12

    The CD13 antigen's binding site for the Asn-Gly-Arg (NGR) motif enables NGR-containing chemotherapeutic drugs to be delivered to CD13-positive tumours. Human CD13-positive acute myeloid leukemia (AML) cells proliferate abnormally and escape death. Here, we show that the CNGRC-GG-D(KLAKLAK)2 peptide induces death in AML cell lines (U937, THP-1, NB4, HL-60) and primary blood cells from AML patients. Cell death was characterized as a caspase-independent mechanism, without DNA fragmentation, but phosphatidylserine externalization and membrane disruption. Our results demonstrate in U937 cells that (i) the NGR-peptide triggers the loss of mitochondrial potential(ΔΨm) and generates superoxide anion (O2-), (ii) N-acetyl-L-cysteine (NAC) and extra/intracellular Ca2+ chelators (BAPTA) prevent both O2- production and cell death, (iii) the Ca2+-channel blocker nifedipine prevents cell death (indicating that Ca2+ influx is the initial death trigger), and (iv) BAPTA, but not NAC, prevents ΔΨm loss (suggesting O2- is a mitochondrial downstream effector). AML cell lines and primary blasts responding to the lethal action of NGR-peptide express promatrix metalloproteinase-12 (proMMP-12) and its substrate progranulin (an 88 kDa cell survival factor). A cell-free assay highlighted proMMP-12 activation by O2-. Accordingly, NGR-peptide's downregulation of 88 kDa progranulin protein was prevented by BAPTA and NAC. Conversely, AML blast resistance to NGR-peptide is associated with the expression of a distinct, 105 kDa progranulin isoform. These results indicate that CNGRC-GG-D(KLAKLAK)2 induces death in AML cells through the Ca2+-mitochondria-O2.-pathway, and support the link between proMMP-12 activation and progranulin cleavage during cell death. Our findings may have implications for the understanding of tumour biology and treatment.

  9. First Branchial Cleft Fistula Associated with External Auditory Canal Stenosis and Middle Ear Cholesteatoma

    Science.gov (United States)

    Abdollahi fakhim, Shahin; Naderpoor, Masoud; Mousaviagdas, Mehrnoosh

    2014-01-01

    Introduction: First branchial cleft anomalies manifest with duplication of the external auditory canal. Case Report: This report features a rare case of microtia and congenital middle ear and canal cholesteatoma with first branchial fistula. External auditory canal stenosis was complicated by middle ear and external canal cholesteatoma, but branchial fistula, opening in the zygomatic root and a sinus in the helical root, may explain this feature. A canal wall down mastoidectomy with canaloplasty and wide meatoplasty was performed. The branchial cleft was excised through parotidectomy and facial nerve dissection. Conclusion: It should be considered that canal stenosis in such cases can induce cholesteatoma formation in the auditory canal and middle ear. PMID:25320705

  10. First Branchial Cleft Fistula Associated with External Auditory Canal Stenosis and Middle Ear Cholesteatoma

    Directory of Open Access Journals (Sweden)

    shahin abdollahi fakhim

    2014-10-01

    Full Text Available Introduction: First branchial cleft anomalies manifest with duplication of the external auditory canal.   Case Report: This report features a rare case of microtia and congenital middle ear and canal cholesteatoma with first branchial fistula. External auditory canal stenosis was complicated by middle ear and external canal cholesteatoma, but branchial fistula, opening in the zygomatic root and a sinus in the helical root, may explain this feature. A canal wall down mastoidectomy with canaloplasty and wide meatoplasty was performed. The branchial cleft was excised through parotidectomy and facial nerve dissection.   Conclusion:  It should be considered that canal stenosis in such cases can induce cholesteatoma formation in the auditory canal and middle ear.

  11. External radiation surveillance

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, E.J.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report describes how external radiation was measured, how surveys were performed, and the results of these measurements and surveys. External radiation exposure rates were measured at locations on and off the Hanford Site using thermoluminescent dosimeters (TLD). External radiation and contamination surveys were also performed with portable radiation survey instruments at locations on and around the Hanford Site.

  12. External radiation surveillance

    International Nuclear Information System (INIS)

    Antonio, E.J.

    1995-01-01

    This section of the 1994 Hanford Site Environmental Report describes how external radiation was measured, how surveys were performed, and the results of these measurements and surveys. External radiation exposure rates were measured at locations on and off the Hanford Site using thermoluminescent dosimeters (TLD). External radiation and contamination surveys were also performed with portable radiation survey instruments at locations on and around the Hanford Site

  13. Brucella abortus-activated microglia induce neuronal death through primary phagocytosis.

    Science.gov (United States)

    Rodríguez, Ana M; Delpino, M Victoria; Miraglia, M Cruz; Costa Franco, Miriam M; Barrionuevo, Paula; Dennis, Vida A; Oliveira, Sergio C; Giambartolomei, Guillermo H

    2017-07-01

    Inflammation has long been implicated as a contributor to pathogenesis in neurobrucellosis. Many of the associated neurocognitive symptoms of neurobrucellosis may be the result of neuronal dysfunction resulting from the inflammatory response induced by Brucella abortus infection in the central nervous system. In this manuscript, we describe an immune mechanism for inflammatory activation of microglia that leads to neuronal death upon B. abortus infection. B. abortus was unable to infect or harm primary cultures of mouse neurons. However, when neurons were co-cultured with microglia and infected with B. abortus significant neuronal loss occurred. This phenomenon was dependent on TLR2 activation by Brucella lipoproteins. Neuronal death was not due to apoptosis, but it was dependent on the microglial release of nitric oxide (NO). B. abortus infection stimulated microglial proliferation, phagocytic activity and engulfment of neurons. NO secreted by B. abortus-activated microglia induced neuronal exposure of the "eat-me" signal phosphatidylserine (PS). Blocking of PS-binding to protein milk fat globule epidermal growth factor-8 (MFG-E8) or microglial vitronectin receptor-MFG-E8 interaction was sufficient to prevent neuronal loss by inhibiting microglial phagocytosis without affecting their activation. Taken together, our results indicate that B. abortus is not directly toxic to neurons; rather, these cells become distressed and are killed by phagocytosis in the inflammatory surroundings generated by infected microglia. Neuronal loss induced by B. abortus-activated microglia may explain, in part, the neurological deficits observed during neurobrucellosis. © 2017 Wiley Periodicals, Inc.

  14. Flory-type theories of polymer chains under different external stimuli

    Science.gov (United States)

    Budkov, Yu A.; Kiselev, M. G.

    2018-01-01

    In this Review, we present a critical analysis of various applications of the Flory-type theories to a theoretical description of the conformational behavior of single polymer chains in dilute polymer solutions under a few external stimuli. Different theoretical models of flexible polymer chains in the supercritical fluid are discussed and analysed. Different points of view on the conformational behavior of the polymer chain near the liquid-gas transition critical point of the solvent are presented. A theoretical description of the co-solvent-induced coil-globule transitions within the implicit-solvent-explicit-co-solvent models is discussed. Several explicit-solvent-explicit-co-solvent theoretical models of the coil-to-globule-to-coil transition of the polymer chain in a mixture of good solvents (co-nonsolvency) are analysed and compared with each other. Finally, a new theoretical model of the conformational behavior of the dielectric polymer chain under the external constant electric field in the dilute polymer solution with an explicit account for the many-body dipole correlations is discussed. The polymer chain collapse induced by many-body dipole correlations of monomers in the context of statistical thermodynamics of dielectric polymers is analysed.

  15. Phosphatidylserine Sensing by TAM Receptors Regulates AKT-Dependent Chemoresistance and PD-L1 Expression.

    Science.gov (United States)

    Kasikara, Canan; Kumar, Sushil; Kimani, Stanley; Tsou, Wen-I; Geng, Ke; Davra, Viralkumar; Sriram, Ganapathy; Devoe, Connor; Nguyen, Khanh-Quynh N; Antes, Anita; Krantz, Allen; Rymarczyk, Grzegorz; Wilczynski, Andrzej; Empig, Cyril; Freimark, Bruce; Gray, Michael; Schlunegger, Kyle; Hutchins, Jeff; Kotenko, Sergei V; Birge, Raymond B

    2017-06-01

    Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K-dependent endogenous ligands, Protein S (ProS), and growth arrest-specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radioresistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment that can suppress host antitumor immunity. In the present study, we utilized TAM-IFNγR1 reporter lines and expressed TAM receptors in a variety of epithelial cell model systems to show that each TAM receptor has a unique pattern of activation by Gas6 or ProS, as well as unique dependency for PS on apoptotic cells and PS liposomes for activity. In addition, we leveraged this system to engineer epithelial cells that express wild-type TAM receptors and show that although each receptor can promote PS-mediated efferocytosis, AKT-mediated chemoresistance, as well as upregulate the immune checkpoint molecule PD-L1 on tumor cells, Mertk is most dominant in the aforementioned pathways. Functionally, TAM receptor-mediated efferocytosis could be partially blocked by PS-targeting antibody 11.31 and Annexin V, demonstrating the existence of a PS/PS receptor (i.e., TAM receptor)/PD-L1 axis that operates in epithelial cells to foster immune escape. These data provide a rationale that PS-targeting, anti-TAM receptor, and anti-PD-L1-based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to upregulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on cancer cells. Mol Cancer Res; 15(6); 753-64. ©2017 AACR

  16. Some biochemical effects of combined action of external irradiation and strontium 89

    International Nuclear Information System (INIS)

    Khadzhirusev, S.; Kiradzhiev, G.; Lalova, Kh.

    1979-01-01

    An attempt was made to assess the influence of strontium 89 on some biochemical effects, induced by external total X-irradiation of the organism in the early terms after treatment. The serum alkaline and acid phosphatase activities and the serum copper and ceruloplasmin content in rats served as indices. Inference is made that in cases, when either of the two radiation actors is alone responsible for obtaining a definite effects, their combination may integrate the biological effect, their combination may integrate the biological effects. Considerations are adduced on the dose span, within which integration of the effect may be expected. The data of this study indicate, that there is integration, when the effective dose external irradiaton effective dose internal irradiation ratio ranks from 1 : 3 to 1 : 1. No integration of effect was found in case when the effective dose of external irradiation eceeds that of internal irradiation. Data are also presented that, in conformity with the parameters studied, the minimal effective radiostrontium dose, generated in the critical organs, is approximately 3 times higher than the minimal effective dose of external irradiation. (author)

  17. Novel Application of Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging for Diagnosis of External Hydrocephalus.

    Science.gov (United States)

    Nakae, Shunsuke; Murayama, Kazuhiro; Adachi, Kazuhide; Kumai, Tadashi; Abe, Masato; Hirose, Yuichi

    2018-01-01

    Although a subdural fluid collection frequently is observed, diagnostic methods that differentiate between the subdural collection caused by external hydrocephalus and that caused by subdural hygroma have not been established. Here, we report a case of external hydrocephalus caused by Gliadel-induced eosinophilic meningitis that has been previously reported in only 1 case and can be diagnosed by time-spatial labeling inversion pulse magnetic resonance imaging (time-SLIP MRI). A tumor located in the left temporal was detected incidentally in an 81-year-old man by examination of a head injury. The tumor was surgically resected and diagnosed as a high-grade glioma during the surgery; Gliadel wafers subsequently were implanted. Three weeks after the resection, the patient showed disturbed consciousness, and computed tomography revealed a subdural fluid collection. The out-flow of cerebrospinal through the resection cavity was detected by time-SLIP MRI. Cerebrospinal tests indicated high white blood cell counts and high protein levels, with more than 90% of the white blood cell count comprising eosinophils. Therefore, we suspected that the subdural fluid collection was caused by external hydrocephalus because of Gliadel-induced eosinophilic meningitis. We surgically removed the Gliadel wafers and subsequently performed a surgery to insert a ventriculoperitoneal shunt. Histologic examination indicated eosinophilic accumulation around the Gliadel wafers. The patient's symptoms improved after the insertion of a ventriculoperitoneal shunt. In the present case, time-SLIP MRI was a useful and noninvasive method for diagnosing external hydrocephalus which was caused by eosinophilic meningitis because of Gliadel-induced eosinophilic meningitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Hirayama, S; Terasawa, K; Rabeler, R; Hirayama, T; Inoue, T; Tatsumi, Y; Purpura, M; Jäger, R

    2014-04-01

    Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of childhood, affecting 3-5% of school-age children. The present study investigated whether the supplementation of soy-derived phosphatidylserine (PS), a naturally occurring phospholipid, improves ADHD symptoms in children. Thirty six children, aged 4-14 years, who had not previously received any drug treatment related to ADHD, received placebo (n = 17) or 200 mg day(-1) PS (n = 19) for 2 months in a randomised, double-blind manner. Main outcome measures included: (i) ADHD symptoms based on DSM-IV-TR; (ii) short-term auditory memory and working memory using the Digit Span Test of the Wechsler Intelligence Scale for Children; and (iii) mental performance to visual stimuli (GO/NO GO task). PS supplementation resulted in significant improvements in: (i) ADHD (P short-term auditory memory (P short-term auditory memory in children. PS supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

  19. Implementation of PSA models to estimate the probabilities associated with external event combination

    International Nuclear Information System (INIS)

    Burgazzi, Luciano

    2014-01-01

    This note endeavors to address some significant issues revealed by the Fukushima accident in Japan in 2011, such as the analysis of various dependency aspects arisen in the light of the external event PSA framework, as the treatment of the correlated hazards. To this aim some foundational notions to implement the PSA models related to specific aspects, like the external hazard combination, e.g., earthquake and tsunami as at the Fukushima accident, and the external hazard-caused internal events, e.g., seismic induced fire, are proposed and discussed to be incorporated within the risk assessment structure. Risk assessment of external hazards is required and utilized as an integrated part of PRA for operating and new reactor units. In the light of the Fukushima accident, of special interest are correlated events, whose modelling is proposed in the present study, in the form of some theoretical concepts, which lay the foundations for the PSA framework implementation. An applicative example is presented for illustrative purposes, since the analysis is carried out on the basis of generic numerical values assigned to an oversimplified model and results are achieved without any baseline comparison. Obviously the first step aimed at the process endorsement is the analysis of all available information in order to determine the level of applicability of the observed specific plant site events to the envisaged model and the statistical correlation analysis for event occurrence data that can be used as part of this process. Despite these drawbacks that actually do not qualify the achieved results, the present work represents an exploratory study aimed at resolving current open issues to be resolved in the PSA, like topics related to unanticipated scenarios: the combined external hazards of the earthquake and tsunami in Fukushima, external hazards causing internal events, such as seismic induced fire. These topics are to be resolved among the other ones as emerging from the

  20. Radiative decay of coupled states in an external dc field

    International Nuclear Information System (INIS)

    Pal'chikov, V.; Sokolov, Y.; Yakovlev, V.

    2001-01-01

    This paper examines two theoretical aspects of the interference of atomic states in hydrogen which comes from the application of an external electric field F to the 2s metastable state. The radiative corrections to the Bethe-Lamb formula and anisotropy contribution to the angular distribution, which arises from interference between electric-field-induced E1-radiation and forbidden M1-radiation, are analysed

  1. Radiative decay of coupled states in an external dc field

    Energy Technology Data Exchange (ETDEWEB)

    Pal' chikov, V. [National Research Inst. for Physical-Technical and Radiotechnical Measurements (VNIIFTRI), Mendeleevo, Moscow Region (Russian Federation); Sokolov, Y. [Kurchatov Inst., Russian Research Centre, Moscow (Russian Federation); Yakovlev, V. [Moscow Engineering Physics Inst., Moscow (Russian Federation)

    2001-07-01

    This paper examines two theoretical aspects of the interference of atomic states in hydrogen which comes from the application of an external electric field F to the 2s metastable state. The radiative corrections to the Bethe-Lamb formula and anisotropy contribution to the angular distribution, which arises from interference between electric-field-induced E1-radiation and forbidden M1-radiation, are analysed.

  2. Prefrontal Cortex Networks Shift from External to Internal Modes during Learning

    Science.gov (United States)

    Brincat, Scott L.

    2016-01-01

    As we learn about items in our environment, their neural representations become increasingly enriched with our acquired knowledge. But there is little understanding of how network dynamics and neural processing related to external information changes as it becomes laden with “internal” memories. We sampled spiking and local field potential activity simultaneously from multiple sites in the lateral prefrontal cortex (PFC) and the hippocampus (HPC)—regions critical for sensory associations—of monkeys performing an object paired-associate learning task. We found that in the PFC, evoked potentials to, and neural information about, external sensory stimulation decreased while induced beta-band (∼11–27 Hz) oscillatory power and synchrony associated with “top-down” or internal processing increased. By contrast, the HPC showed little evidence of learning-related changes in either spiking activity or network dynamics. The results suggest that during associative learning, PFC networks shift their resources from external to internal processing. SIGNIFICANCE STATEMENT As we learn about items in our environment, their representations in our brain become increasingly enriched with our acquired “top-down” knowledge. We found that in the prefrontal cortex, but not the hippocampus, processing of external sensory inputs decreased while internal network dynamics related to top-down processing increased. The results suggest that during learning, prefrontal cortex networks shift their resources from external (sensory) to internal (memory) processing. PMID:27629722

  3. Development, external validation and clinical usefulness of a practical prediction model for radiation-induced dysphagia in lung cancer patients

    International Nuclear Information System (INIS)

    Dehing-Oberije, Cary; De Ruysscher, Dirk; Petit, Steven; Van Meerbeeck, Jan; Vandecasteele, Katrien; De Neve, Wilfried; Dingemans, Anne Marie C.; El Naqa, Issam; Deasy, Joseph; Bradley, Jeff; Huang, Ellen; Lambin, Philippe

    2010-01-01

    Introduction: Acute dysphagia is a distressing dose-limiting toxicity occurring frequently during concurrent chemo-radiation or high-dose radiotherapy for lung cancer. It can lead to treatment interruptions and thus jeopardize survival. Although a number of predictive factors have been identified, it is still not clear how these could offer assistance for treatment decision making in daily clinical practice. Therefore, we have developed and validated a nomogram to predict this side-effect. In addition, clinical usefulness was assessed by comparing model predictions to physicians' predictions. Materials and methods: Clinical data from 469 inoperable lung cancer patients, treated with curative intent, were collected prospectively. A prediction model for acute radiation-induced dysphagia was developed. Model performance was evaluated by the c-statistic and assessed using bootstrapping as well as two external datasets. In addition, a prospective study was conducted comparing model to physicians' predictions in 138 patients. Results: The final multivariate model consisted of age, gender, WHO performance status, mean esophageal dose (MED), maximum esophageal dose (MAXED) and overall treatment time (OTT). The c-statistic, assessed by bootstrapping, was 0.77. External validation yielded an AUC of 0.94 on the Ghent data and 0.77 on the Washington University St. Louis data for dysphagia ≥ grade 3. Comparing model predictions to the physicians' predictions resulted in an AUC of 0.75 versus 0.53, respectively. Conclusions: The proposed model performed well was successfully validated and demonstrated the ability to predict acute severe dysphagia remarkably better than the physicians. Therefore, this model could be used in clinical practice to identify patients at high or low risk.

  4. The clinical meaning of external cervical resorption in maxillary canine: transoperative dental trauma

    Directory of Open Access Journals (Sweden)

    Alberto Consolaro

    2014-12-01

    Full Text Available External Cervical Resorption in maxillary canines with pulp vitality is frequently associated with dental trauma resulting from surgical procedures carried out to prepare the teeth for further orthodontic traction. Preparation procedures might surgically manipulate the cementoenamel junction or cause luxation of teeth due to applying excessive force or movement tests beyond the tolerance limits of periodontal ligament and cervical tissue structures. Dentin exposure at the cementoenamel junction triggers External Cervical Resorption as a result of inflammation followed by antigen recognition of dentin proteins. External Cervical Resorption is painless, does not induce pulpitis and develops slowly. The lesion is generally associated with and covered by gingival soft tissues which disguise normal clinical aspects, thereby leading to late diagnosis when the process is near pulp threshold. Endodontic treatment is recommended only if surgical procedures are rendered necessary in the pulp space; otherwise, External Cervical Resorption should be treated by conservative means: protecting the dental pulp and restoring function and esthetics of teeth whose pulp will remain in normal conditions. Unfortunately, there is a lack of well-grounded research evincing how often External Cervical Resorption associated with canines subjected to orthodontic traction occurs.

  5. Binding of Thrombin-Activated Platelets to a Fibrin Scaffold through αIIbβ3 Evokes Phosphatidylserine Exposure on Their Cell Surface

    Science.gov (United States)

    Brzoska, Tomasz; Suzuki, Yuko; Mogami, Hideo; Sano, Hideto; Urano, Tetsumei

    2013-01-01

    Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS) and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an αIIbβ3 antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment. PMID:23383331

  6. Binding of thrombin-activated platelets to a fibrin scaffold through α(IIbβ₃ evokes phosphatidylserine exposure on their cell surface.

    Directory of Open Access Journals (Sweden)

    Tomasz Brzoska

    Full Text Available Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an α(IIbβ₃ antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment.

  7. Lipopeptide-Induced Suicidal Erythrocyte Death Correlates with the Degree of Acylation

    Directory of Open Access Journals (Sweden)

    Abdulla Al Mamun Bhuyan

    2017-01-01

    Full Text Available Background/Aims: Consequences of bacterial infection include anemia, which could result from stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Bacterial components known to stimulate eryptosis include lipopeptides. Signaling mediating the triggering of eryptosis include increased cytosolic Ca2+ activity ([Ca2+]i, oxidative stress and cellular accumulation of ceramide. The present study aimed to define the molecular requirements for lipopeptide-induced cell membrane scrambling. Methods: Human erythrocytes were incubated for 48 hours in the absence and presence of 1 or 5 µg/ml of the synthetic lipopeptides Pam1 (lipopeptide with one fatty acid, Pam2 (lipopeptide with two fatty acids, or Pam3 (lipopeptide with three fatty acids. In the following phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ROS formation from DCF dependent fuorescence, and ceramide abundance utilizing specific antibodies. Results: Pam1 (5 µg/ml, Pam2 (5 µg/ml and Pam3 (1 and 5 µg/ml significantly increased the percentage of annexin-V-binding to erythrocytes in a dose dependent manner, which was largely independent of Ca2+. Pam1-3 increased the percentage of both, swollen and shrunken erythrocytes without significantly modifying the average forward scatter. They also increased reactive oxygen species (ROS and ceramide abundance. In all assays the effect on eryptosis increased with increasing number of fatty acids, with Pam3 showing always the strongest effect. In contrast, a comparison of the effect of Pam1-3 on TLR2 dependent immune stimulation showed that not Pam3 but Pam2 displayed the strongest activity, and that immune stimulation was triggered at much lower concentrations than eryptosis. Conclusions: Lipopeptides are not only important

  8. Piezosurgery in External Dacryocystorhinostomy.

    Science.gov (United States)

    Czyz, Craig N; Fowler, Amy M; Dutton, Jonathan J; Cahill, Kenneth V; Foster, Jill A; Hill, Robert H; Everman, Kelly R; Nabavi, Cameron B

    Dacryocystorhinostomy (DCR) can be performed via an external or endoscopic approach. The use of ultrasonic or piezosurgery has been well described for endoscopic DCRs but is lacking for external DCRs. This study presents a case series of external DCRs performed using piezosurgery evaluating results and complications. Prospective, consecutive case series of patients undergoing primary external DCR for lacrimal drainage insufficiency. A standard external DCR technique was used using 1 of 2 piezosurgery systems for all bone incision. All patients received silicone intubation to the lacrimal system. Surgical outcome was measured in terms of patient-reported epiphora as follows: 1) complete resolution, 2) improvement >50%, 3) improvement 50% improvement. There were 4 patients (7%) who had <50% improvement. There was 1 (2%) intraoperative complication and 2 (4%) postoperative complications recorded. Piezourgery is a viable modality for performing external DCRs. The lack of surgical complications shows a potential for decreased soft tissues damage. The surgical success rate based on patient-reported epiphora is similar to those published for mechanical external DCRs. This modality may benefit the novice surgeon in the reduction of soft and mucosal tissue damage.

  9. Magnetic response to applied electrostatic field in external magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Adorno, T.C. [Universidade de Sao Paulo, Instituto de Fisica, Caixa Postal 66318, Sao Paulo, SP (Brazil); University of Florida, Department of Physics, Gainesville, FL (United States); Gitman, D.M. [Universidade de Sao Paulo, Instituto de Fisica, Caixa Postal 66318, Sao Paulo, SP (Brazil); Tomsk State University, Department of Physics, Tomsk (Russian Federation); Shabad, A.E. [P. N. Lebedev Physics Institute, Moscow (Russian Federation)

    2014-04-15

    We show, within QED and other possible nonlinear theories, that a static charge localized in a finite domain of space becomes a magnetic dipole, if it is placed in an external (constant and homogeneous) magnetic field in the vacuum. The magnetic moment is quadratic in the charge, depends on its size and is parallel to the external field, provided the charge distribution is at least cylindrically symmetric. This magneto-electric effect is a nonlinear response of the magnetized vacuum to an applied electrostatic field. Referring to the simple example of a spherically symmetric applied field, the nonlinearly induced current and its magnetic field are found explicitly throughout the space; the pattern of the lines of force is depicted, both inside and outside the charge, which resembles that of a standard solenoid of classical magnetostatics. (orig.)

  10. Role of enzymatic and non enzymatic antioxidant in ameliorating salinity induced damage in nostoc muscorum

    International Nuclear Information System (INIS)

    Hend, A.; Abeer, A.; Allah, A.

    2015-01-01

    Presence of high salt concentration in the growth medium adversely affected the plant growth and productivity by altering its metabolic activities. Experiments were conducted on cyanobacteriaum Nostoc muscorum grown in nitrogen free medium supplemented with 250 mM NaCl to evaluate the salt stress induced changes in growth, antioxidants and lipid composition. Salt stress significantly reduced the growth and physio-biochemical attributes. Salt stress increased malonaldehyde content thereby causing alterations in the lipid fraction. Significant reduction in polyunsaturated fatty acids including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI) and phosphatidylserine (PS) was observed. Where as diacylglycerol, sterol ester and non-esterified fatty acids were increased. Activities of antioxidant enzymes and contents of non-enzymatic antioxidants including glutathione enhanced due to salt stress. An increase in accumulation of proline was also observed. Hence increased activity of antioxidants and altered fatty acid composition was observed in salt stressed Nostoc muscorum. (author)

  11. Distortion of optical feedback signals in microchip Nd:YAG lasers subjected to external multi-beam interference feedback

    International Nuclear Information System (INIS)

    Yi-Dong, Tan; Shu-Lian, Zhang; Zhou, Ren; Cheng, Ren; Yi-Nan, Zhang

    2010-01-01

    This paper proposes a theoretical analysis for the characteristics of an external cavity Nd:YAG laser with feedback of multiple-beam interference, which is induced by the multi-reentrance of the light from the external Fabry–Perot cavity. The theoretical model considers the multiple beam interference of the external Fabry–Perot cavity. It is found that the optical feedback signals are distorted to pulse waveforms instead of the sinusoidal ones in conventional feedback. The experimental results are in good agreement with the theoretical analysis. The obtained theoretical and experimental results can advance the development of a laser feedback interferometer

  12. Neuroprotective Effects of Germinated Brown Rice against Hydrogen Peroxide Induced Cell Death in Human SH-SY5Y Cells

    Directory of Open Access Journals (Sweden)

    Shahid Iqbal

    2012-08-01

    Full Text Available The neuroprotective and antioxidative effects of germinated brown rice (GBR, brown rice (BR and commercially available γ-aminobutyric acid (GABA against cell death induced by hydrogen peroxide (H2O2 in human neuroblastoma SH-SY5Y cells have been investigated. Results show that GBR suppressed H2O2-mediated cytotoxicity and induced G0/G1 phase cell cycle arrest in SH-SY5Y cells. Moreover, GBR reduced mitochondrial membrane potential (MMP and prevented phosphatidylserine (PS translocation in SH-SY5Y cells, key features of apoptosis, and subsequent cell death. GBR exhibited better neuroprotective and antioxidative activities as compared to BR and GABA. These results indicate that GBR possesses high antioxidative activities and suppressed cell death in SH-SY5Y cells by blocking the cell cycle re-entry and apoptotic mechanisms. Therefore, GBR could be developed as a value added functional food to prevent neurodegenerative diseases caused by oxidative stress and apoptosis.

  13. Protein C Inhibitor (PCI) Binds to Phosphatidylserine Exposing Cells with Implications in the Phagocytosis of Apoptotic Cells and Activated Platelets

    Science.gov (United States)

    Rieger, Daniela; Assinger, Alice; Einfinger, Katrin; Sokolikova, Barbora; Geiger, Margarethe

    2014-01-01

    Protein C Inhibitor (PCI) is a secreted serine protease inhibitor, belonging to the family of serpins. In addition to activated protein C PCI inactivates several other proteases of the coagulation and fibrinolytic systems, suggesting a regulatory role in hemostasis. Glycosaminoglycans and certain negatively charged phospholipids, like phosphatidylserine, bind to PCI and modulate its activity. Phosphatidylerine (PS) is exposed on the surface of apoptotic cells and known as a phagocytosis marker. We hypothesized that PCI might bind to PS exposed on apoptotic cells and thereby influence their removal by phagocytosis. Using Jurkat T-lymphocytes and U937 myeloid cells, we show here that PCI binds to apoptotic cells to a similar extent at the same sites as Annexin V, but in a different manner as compared to live cells (defined spots on ∼10–30% of cells). PCI dose dependently decreased phagocytosis of apoptotic Jurkat cells by U937 macrophages. Moreover, the phagocytosis of PS exposing, activated platelets by human blood derived monocytes declined in the presence of PCI. In U937 cells the expression of PCI as well as the surface binding of PCI increased with time of phorbol ester treatment/macrophage differentiation. The results of this study suggest a role of PCI not only for the function and/or maturation of macrophages, but also as a negative regulator of apoptotic cell and activated platelets removal. PMID:25000564

  14. Apoptosis induced by chlormethine and ionizing radiations in normal and tumoral lymphocytes: role of caspase-3; Apoptose induite par la chlormethine et les radiations ionisantes dans les lymphocytes normaux et tumoraux: role de la caspase-3

    Energy Technology Data Exchange (ETDEWEB)

    Holl, V.P

    2000-07-01

    Apoptosis can be induced by various stimuli like ionizing radiations or alkylating agents. Recent works have shown that apoptosis due to ionizing radiations can be initiated by DNA and cell membrane alterations, via radical species generation, implying the in fine activation of effector caspases, and in particular caspase-3. The main goal of this work is to clarify the role of caspase-3 in the radio-induced apoptosis mechanisms and to study the effects of apoptosis inhibition on the behaviour of the damaged cells. The effects of activation and caspase-3 activity inhibition on the progress of spontaneous, radio-induced or chlormethine-induced apoptosis have been evaluated for normal and tumoral lymphocytes. A chemical molecule, the ebselen, which can mime the action of the endogenous glutathione peroxidase, and a tetra-peptide inhibitor, AC-DEVD-CHO, selective of effector caspases, have been selected. The results indicate an inhibition by ebselen of all morphological and biochemical characteristics of chlormethine-induced apoptosis and a restoring of the cells viability. This seleno-organic compound also reduces the drop of the intra-cellular glutathione level and the loss of the trans-membrane potential (M) of the mitochondrion in the MOLT-4 tumoral cells treated with chlormethine. In parallel, the AC-DEVD-CHO effect on apoptosis induction has been tested. This inhibitor stops some chlormethine-induced criteria of apoptosis without affecting the final loss of the mitochondrial M and the cells proliferation. AC-DEVD-CHO has been also incubated just before the irradiation of the culture cells. The inhibition of the specific DEVD caspases prevents the inter-nucleosomal fragmentation of DNA and partially delays the externalization of phosphatidylserine without changing the viability of the irradiated cells. Moreover, the analysis of the AC-DEVD-CHO pre-treated irradiated cells floating on the surface shows a strong mitochondrial lactate dehydrogenase activity, which

  15. ASH External Web Portal (External Portal) -

    Data.gov (United States)

    Department of Transportation — The ASH External Web Portal is a web-based portal that provides single sign-on functionality, making the web portal a single location from which to be authenticated...

  16. An external focus of attention enhances balance learning in older adults.

    Science.gov (United States)

    Chiviacowsky, Suzete; Wulf, Gabriele; Wally, Raquel

    2010-10-01

    Studies with young adults have shown that an external focus of attention (i.e., on the movement effect) results in more effective motor learning and greater automaticity than an internal focus (i.e., on one's own body movements). The present study examined whether instructions inducing an external versus internal attentional focus would differentially affect the learning of a balance task in 32 older adults (24 females and 8 males, mean age: 69.4 years), divided equally, by number and gender, into two groups. The task required participants to stand on a balance platform (stabilometer) tilting to the left and right, and to try to keep the platform as close to horizontal as possible during each 30-s trial. The external focus group was instructed to concentrate on keeping markers on the platform horizontal, while the internal focus group was instructed to concentrate on keeping their feet horizontal. The dependent variable was time in balance (i.e., platform movements within ± 5°). Participants performed 10 practice trials on day 1, with focus reminders given before each trial. Learning was assessed by a retention test, consisting of five trials without instructions, performed 1 day later. The external focus group outperformed the internal focus group in retention [F(4, 120)=3.46, p=.01]. The results demonstrate that the learning benefits of an external attentional focus are generalizable to older learners. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. A combination of p53-activating APR-246 and phosphatidylserine-targeting antibody potently inhibits tumor development in hormone-dependent mutant p53-expressing breast cancer xenografts

    Directory of Open Access Journals (Sweden)

    Liang Y

    2018-03-01

    Full Text Available Yayun Liang,1 Benford Mafuvadze,1 Cynthia Besch-Williford,2 Salman M Hyder1 1Deparment of Biomedical Sciences and Dalton Cardiovascular Research Center, Columbia, MO, USA; 2IDEXX BioResearch, Columbia, MO, USA Background: Between 30 and 40% of human breast cancers express a defective tumor suppressor p53 gene. Wild-type p53 tumor suppressor protein promotes cell-cycle arrest and apoptosis and inhibits vascular endothelial growth factor–dependent angiogenesis, whereas mutant p53 protein (mtp53 lacks these functions, resulting in tumor cell survival and metastasis. Restoration of p53 function is therefore a promising drug-targeted strategy for combating mtp53-expressing breast cancer. Methods: In this study, we sought to determine whether administration of APR-246, a small-molecule drug that restores p53 function, in combination with 2aG4, an antibody that targets phosphatidylserine residues on tumor blood vessels and disrupts tumor vasculature, effectively inhibits advanced hormone-dependent breast cancer tumor growth. Results: APR-246 reduced cell viability in mtp53-expressing BT-474 and T47-D human breast cancer cells in vitro, and significantly induced apoptosis in a dose-dependent manner. However, APR-246 did not reduce cell viability in MCF-7 breast cancer cells, which express wild-type p53. We next examined APR-246’s anti-tumor effects in vivo using BT-474 and T47-D tumor xenografts established in female nude mice. Tumor-bearing mice were treated with APR-246 and/or 2aG4 and tumor volume followed over time. Tumor growth was more effectively suppressed by combination treatment than by either agent alone, and combination therapy completely eradicated some tumors. Immunohistochemistry analysis of tumor tissue sections demonstrated that combination therapy more effectively induced apoptosis and reduced cell proliferation in tumor xenografts than either agent alone. Importantly, combination therapy dramatically reduced the density of blood

  18. The effect of preoperative internal and external biliary drainage on mortality of jaundiced rats

    NARCIS (Netherlands)

    Gouma, D. J.; Coelho, J. C.; Schlegel, J. F.; Li, Y. F.; Moody, F. G.

    1987-01-01

    Mortality following abdominal infection induced by cecal ligation and puncture was studied in rats with obstructive jaundice and after relief of the obstruction by preoperative internal or external biliary drainage. Four groups of adult Sprague-Dawley rats were used: common bile duct ligation (BDL),

  19. Long-term effects of external radiation on the pituitary and thyroid glands

    International Nuclear Information System (INIS)

    Fuks, Z.; Glatstein, E.; Marsa, G.W.; Bagshaw, M.A.; Kaplan, H.S.

    1976-01-01

    Chronic damage following external irradiation of the normal pituitary and thyroid glands, delivered incidentally during radiotherapy of neoplasms of the head and neck may be more common than has been appreciated in the past. A case of a child who developed pituitary dwarfism 5 1 / 2 years after radiation therapy had been delivered for an embryonal rhabdomyosarcoma of the nasopharynx is described. A review of similar cases from the literature is presented. Likewise, external irradiation of the normal thyroid gland produces a spectrum of radiation-induced syndromes. Clinical damage to the pituitary and thyroid glands is usually manifested months to years after treatment and is preceded by a long subclinical phase. A careful exclusion of these glands from radiation treatment fields is recommended whenever possible. An early detection of endocrine function abnormalities in patients receiving radiation to these glands is desirable, since appropriate treatment may prevent the late deleterious effects of external irradiation of the pituitary and thyroid glands

  20. Containment atmosphere response to external sprays

    International Nuclear Information System (INIS)

    Green, J.; Almenas, K.

    1995-01-01

    The application of external sprays to a containment steel shell can be an effective energy removal method and has been proposed in the passive AP-600 design. Reduction of the steel shell temperature in contact with the containment atmosphere enhances both heat and mass transfer driving forces. Large scale experimental data in this area is scarce, therefore the measurements obtained from the E series tests conducted at the German HDR facility deserve special attention. These long term tests simulated various severe accident conditions, including external spraying of the hemispherical steel shell. This investigation focuses upon the integral response of the HDR containment atmosphere during spray periods and upon methods by which lumped parameter system codes, like CONTAIN, model the underlying condensation phenomena. Increases in spray water flowrates above a minimum value were ineffective at improving containment pressure reduction since the limiting resistance for energy transfer lies in the noncondensable-vapor boundary layer at the inner condensing surface. The spray created an unstable condition by cooling the upper layers of a heated atmosphere and thus inducing global natural circulation flows in the facility and subsequently, abrupt changes in lighter-than-air noncondensable (J 2 /He) concentrations. Modeling results using the CONTAIN code are outlined and code limitations are delineated

  1. Containment atmosphere response to external sprays

    Energy Technology Data Exchange (ETDEWEB)

    Green, J.; Almenas, K. [Univ. of Maryland, College Park, MD (United States)

    1995-09-01

    The application of external sprays to a containment steel shell can be an effective energy removal method and has been proposed in the passive AP-600 design. Reduction of the steel shell temperature in contact with the containment atmosphere enhances both heat and mass transfer driving forces. Large scale experimental data in this area is scarce, therefore the measurements obtained from the E series tests conducted at the German HDR facility deserve special attention. These long term tests simulated various severe accident conditions, including external spraying of the hemispherical steel shell. This investigation focuses upon the integral response of the HDR containment atmosphere during spray periods and upon methods by which lumped parameter system codes, like CONTAIN, model the underlying condensation phenomena. Increases in spray water flowrates above a minimum value were ineffective at improving containment pressure reduction since the limiting resistance for energy transfer lies in the noncondensable-vapor boundary layer at the inner condensing surface. The spray created an unstable condition by cooling the upper layers of a heated atmosphere and thus inducing global natural circulation flows in the facility and subsequently, abrupt changes in lighter-than-air noncondensable (J{sub 2}/He) concentrations. Modeling results using the CONTAIN code are outlined and code limitations are delineated.

  2. The effects of phosphatidylserine and omega-3 fatty acid-containing supplement on late life depression

    Directory of Open Access Journals (Sweden)

    Teruhisa Komori

    2015-04-01

    Full Text Available Late life depression is often associated with a poor response to antidepressants; therefore an alternative strategy for therapy is required. Although several studies have reported that phosphatidylserine (PS may be effective for late life depression and that omega-3 fatty acids DHA and EPA have also proven beneficial for many higher mental functions, including depression, no concrete conclusion has been reached. This study was performed to clarify the effect of PS and omega-3 fatty acid-containing supplement for late life depression by not only clinical evaluation but also salivary cortisol levels. Eighteen elderly subjects with major depression were selected for the study. In all, insufficient improvement had been obtained by antidepressant therapy for at least 6 months. The exclusion criteria from prior brain magnetic resonance images (MRI included the presence of structural MRI findings compatible with stroke or other gross brain lesions or malformations, but not white matter hypersensitivities. They took a supplement containing PS 100 mg, DHA 119 mg and EPA 70 mg three times a day for 12 weeks. The effects of the supplement were assessed using the 17-item Hamilton depression scale (HAM-D17 and the basal levels and circadian rhythm of salivary cortisol. The study adopted them as indices because: salivary cortisol levels are high in patients with depression, their circadian rhythm related to salivary cortisol is often irregular, and these symptoms are alleviated as depression improves. The mean HAM-D17 in all subjects taking the supplement was significantly improved after 12 weeks of taking the supplement. These subjects were divided into 10 non-responders and 8 responders. The basal levels and circadian rhythm of salivary cortisol were normalized in the responders while not in non-responders. PS and omega-3 fatty acids, or other elements of the supplement, may be effective for late life depression, associated with the correction of basal

  3. Inducible laryngeal obstruction

    DEFF Research Database (Denmark)

    Halvorsen, Thomas; Walsted, Emil Schwarz; Bucca, Caterina

    2017-01-01

    Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenc...

  4. Coordinated research programme on safety of RBMK type NPPs in relation to external events. V. 1. Working material

    International Nuclear Information System (INIS)

    1999-01-01

    The present volume is a collection of progress reports which have been submitted within the scope of the CRP on safety of RBMK type NPPs in relation to external events including seismic related papers and man-induced events (explosions and airplane crash). It includes papers concerned with experience related to RBMK equipment testing and calculations of seismic resistance, soil-structure interactions analysis, safety assurance, aircraft impact qualification and other external events for RBMK type NPP, seismic stability of NPPs in Eastern Europe, probabilistic assessment of NPP safety under aircraft impact, dynamic analysis of NPPs, screening of external hazards for NPP

  5. Ultrasound-induced cavitation damage to external epithelia of fish skin.

    Science.gov (United States)

    Frenkel, V; Kimmel, E; Iger, Y

    1999-10-01

    Transmission electron microscopy was used to show the effects of therapeutic ultrasound (fish skin. Exposures of up to 90 s produced damage to 5 to 6 of the outermost layers. Negligible temperature elevations and lack of damage observed when using degassed water indicated that the effects were due to cavitation. The minimal intensity was determined for inducing cellular damage, where the extent and depth of damage to the tissues was correlated to the exposure duration. The results may be interpreted as a damage front, advancing slowly from the outer cells inward, presumably in association with the slow replacement of the perforated cell contents with the surrounding water. This study illustrates that a controlled level of microdamage may be induced to the outer layers of the tissues.

  6. External Validation of a Prediction Model for Successful External Cephalic Version

    NARCIS (Netherlands)

    de Hundt, Marcella; Vlemmix, Floortje; Kok, Marjolein; van der Steeg, Jan W.; Bais, Joke M.; Mol, Ben W.; van der Post, Joris A.

    2012-01-01

    We sought external validation of a prediction model for the probability of a successful external cephalic version (ECV). We evaluated the performance of the prediction model with calibration and discrimination. For clinical practice, we developed a score chart to calculate the probability of a

  7. The influence of the N-terminal region of antimicrobial peptide pleurocidin on fungal apoptosis.

    Science.gov (United States)

    Choi, Hyemin; Lee, Dong Gun

    2013-10-28

    In our previous study, the 25-mer antimicrobial peptide pleurocidin (Ple) had been thought to induce apoptosis in Candida albicans. This study demonstrated that reactive oxygen species (ROS) production was a major cause of Ple-induced apoptosis. Four truncated analogs were synthesized to understand the functional roles in the N- and C-terminal regions of Ple on the apoptosis. Ple, Ple (4-25), Ple (1-22), and Ple (1-19) produced ROS, including hydroxyl radicals, on the order of [Ple > Ple (1-22) > Ple (4-25) > Ple (1-19)], whereas Ple (7-25) did not induce any ROS production. The results suggested that the N-terminal deletion affected the ROS-inducing activities much more than that of the C-terminal deletion, and net hydrophobicity [Ple > Ple (1-22) > Ple (4-25) > Ple (1-19) > Ple (7-25)] was related to ROS generation rather than other primary factors like net charge. Hence, we focused on the N-terminal-truncated peptides, Ple (4-25) and Ple (7-25), and examined other apoptotic features, including mitochondrial membrane depolarization, caspase activation, phosphatidylserine externalization, and DNA and nuclear fragmentation. The results also confirmed the disappearance of apoptotic activity of Ple (7-25) by the truncation of the N-terminal region (1-6) and the specific activity patterns between Ple and analogs. In conclusion, the N-terminal region of Ple played an important role in apoptosis.

  8. Stimulus induced bursts in severe postanoxic encephalopathy.

    Science.gov (United States)

    Tjepkema-Cloostermans, Marleen C; Wijers, Elisabeth T; van Putten, Michel J A M

    2016-11-01

    To report on a distinct effect of auditory and sensory stimuli on the EEG in comatose patients with severe postanoxic encephalopathy. In two comatose patients admitted to the Intensive Care Unit (ICU) with severe postanoxic encephalopathy and burst-suppression EEG, we studied the effect of external stimuli (sound and touch) on the occurrence of bursts. In patient A bursts could be induced by either auditory or sensory stimuli. In patient B bursts could only be induced by touching different facial regions (forehead, nose and chin). When stimuli were presented with relatively long intervals, bursts persistently followed the stimuli, while stimuli with short intervals (encephalopathy can be induced by external stimuli, resulting in stimulus-dependent burst-suppression. Stimulus induced bursts should not be interpreted as prognostic favourable EEG reactivity. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. ExternE: Externalities of energy Vol. 3. Coal and lignite

    International Nuclear Information System (INIS)

    Berry, J.; Holland, M.; Lee, D.

    1995-01-01

    Awareness of the environmental damage resulting from human activity, particularly concerning energy use, has grown greatly in recent years. Effects such as global warming, ozone depletion and acid rain are now the subjects of much research and public debate. It is now known that these and other effects damage a wide range of receptors, including human health, forests, crops, freshwater ecosystems and buildings. Such damages are typically not accounted for by the producers and consumers of the good in question (in this case energy). They are thus referred to as 'external costs' or 'externalities', to distinguish them from the private costs which account for the construction of plant, cost of fuel, wages, etc. In recent years there has been a growing interest in the assessment of the environmental and health impacts of energy, and the related external costs. This concern is driven by a number of different factors: the need to integrate environmental concerns in decision making over the choice between different fuels and energy technologies; the need to evaluate the costs and benefits of stricter environmental standards; increased attention to the use of economic instruments for environmental policy; the need to develop overall indicators of environmental performance of different technologies; major changes in the energy sector, including privatisation, liberalisation of markets, reduction of subsidies, etc. An agreed methodology for calculation and integration of external costs has not been established. Earlier work is typically of a preliminary nature and tends to be deficient with respect to both the methods employed and the quality of models and data used. In consequence of this a collaborative project, the EC/US Fuel Cycles Study, was established between Directorate General XII (Science, Research and Technology) of the European Commission and the United States Department of Energy. This ran for the period 1991 to 1993, and good agreement on a variety of

  10. External Shock in a Multi-bursting Gamma-Ray Burst: Energy Injection Phase Induced by the Later Launched Ejecta

    Science.gov (United States)

    Lin, Da-Bin; Huang, Bao-Quan; Liu, Tong; Gu, Wei-Min; Mu, Hui-Jun; Liang, En-Wei

    2018-01-01

    Central engines of gamma-ray bursts (GRBs) may be intermittent and launch several episodes of ejecta separated by a long quiescent interval. In this scenario, an external shock is formed due to the propagation of the first launched ejecta into the circum-burst medium and the later launched ejecta may interact with the external shock at a later period. Owing to the internal dissipation, the later launched ejecta may be observed at a later time (t jet). In this paper, we study the relation of t b and t jet, where t b is the collision time of the later launched ejecta with the formed external shock. It is found that the relation of t b and t jet depends on the bulk Lorentz factor (Γjet) of the later launched ejecta and the density (ρ) of the circum-burst medium. If the value of Γjet or ρ is low, the t b would be significantly larger than t jet. However, the t b ∼ t jet can be found if the value of Γjet or ρ is significantly large. Our results can explain the large lag of the optical emission relative to the γ-ray/X-ray emission in GRBs, e.g., GRB 111209A. For GRBs with a precursor, our results suggest that the energy injection into the external shock and thus more than one external-reverse shock may appear in the main prompt emission phase. According to our model, we estimate the Lorentz factor of the second launched ejecta in GRB 160625B.

  11. Effect of External Electric Field Stress on Gliadin Protein Conformation

    OpenAIRE

    Singh, Ashutosh; Munshi, Shirin; Raghavan, Vijaya

    2013-01-01

    A molecular dynamic (MD) modeling approach was applied to evaluate the effect of external electric field on gliadin protein structure and surface properties. Static electric field strengths of 0.001 V/nm and 0.002 V/nm induced conformational changes in the protein but had no significant effect on its surface properties. The study of hydrogen bond evolution during the course of simulation revealed that the root mean square deviation, radius of gyration and secondary structure formation, all de...

  12. Applications of external PIXE to ancient Egyptian artefacts

    International Nuclear Information System (INIS)

    Moser, M.; Bubb, I.F.; Johnston, N.; El Bouanani, M.; Stannard, W.B.; Short, R.C.

    1998-01-01

    The external Proton Induced X-Ray Emission (PIXE) facility at Royal Melbourne Institute of Technology has been used to analyse ancient Egyptian glass samples, an Egyptian wall paint fragment and soil pigments. A 0.35 mm diameter beam of 1.6 MeV protons, extracted from the vacuum through an 8 μm gold coated Kapton foil was used. Analysis of the spectra was carried out with the analysis package PIXAN. The analysis of two Egyptian glass samples enabled the partial determination of the colouring transition metals and the manufacturing technique, indicating them to be consistent with 'New Kingdom' glasses

  13. External non-white noise and nonequilibrium phase transitions

    International Nuclear Information System (INIS)

    Sancho, J.M.; San Miguel, M.

    1980-01-01

    Langevin equations with external non-white noise are considered. A Fokker Planck equation valid in general in first order of the correlation time tau of the noise is derived. In some cases its validity can be extended to any value of tau. The effect of a finite tau in the nonequilibrium phase transitions induced by the noise is analyzed, by means of such Fokker Planck equation, in general, for the Verhulst equation under two different kind of fluctuations, and for a genetic model. It is shown that new transitions can appear and that the threshold value of the parameter can be changed. (orig.)

  14. Influence of periodic external fields in multiagent models with language dynamics

    Science.gov (United States)

    Palombi, Filippo; Ferriani, Stefano; Toti, Simona

    2017-12-01

    We investigate large-scale effects induced by external fields, phenomenologically interpreted as mass media, in multiagent models evolving with the microscopic dynamics of the binary naming game. In particular, we show that a single external field, broadcasting information at regular time intervals, can reverse the majority opinion of the population, provided the frequency and the effectiveness of the sent messages lie above well-defined thresholds. We study the phase structure of the model in the mean field approximation and in numerical simulations with several network topologies. We also investigate the influence on the agent dynamics of two competing external fields, periodically broadcasting different messages. In finite regions of the parameter space we observe periodic equilibrium states in which the average opinion densities are reversed with respect to naive expectations. Such equilibria occur in two cases: (i) when the frequencies of the competing messages are different but close to each other; (ii) when the frequencies are equal and the relative time shift of the messages does not exceed half a period. We interpret the observed phenomena as a result of the interplay between the external fields and the internal dynamics of the agents and conclude that, depending on the model parameters, the naming game is consistent with scenarios of first- or second-mover advantage (to borrow an expression from the jargon of business strategy).

  15. External Volume Expansion in Irradiated Tissue: Effects on the Recipient Site.

    Science.gov (United States)

    Chin, Michael S; Lujan-Hernandez, Jorge; Babchenko, Oksana; Bannon, Elizabeth; Perry, Dylan J; Chappell, Ava G; Lo, Yuan-Chyuan; Fitzgerald, Thomas J; Lalikos, Janice F

    2016-05-01

    External volume expansion prepares recipient sites to improve outcomes of fat grafting. For patients receiving radiotherapy after mastectomy, results with external volume expansion vary, and the relationship between radiotherapy and expansion remains unexplored. Thus, the authors developed a new translational model to investigate the effects in chronic skin fibrosis after radiation exposure. Twenty-four SKH1-E mice received 50 Gy of β-radiation to each flank and were monitored until fibrosis developed (8 weeks). External volume expansion was then applied at -25 mmHg to one side for 6 hours for 5 days. The opposite side served as the control. Perfusion changes were assessed with hyperspectral imaging. Mice were euthanized at 5 (n = 12) and 15 days (n = 12) after the last expansion application. Tissue samples were analyzed with immunohistochemistry for CD31 and Ki67, Masson trichrome for skin thickness, and picrosirius red to analyze collagen composition. All animals developed skin fibrosis 8 weeks after radiotherapy and became hypoperfused based on hyperspectral imaging. Expansion induced edema on treated sides after stimulation. Perfusion was decreased by 13 percent on the expansion side (p External volume expansion temporarily reduces perfusion, likely because of transient ischemia or edema. Together with mechanotransduction, these effects encourage a proangiogenic and proliferative environment in fibrotic tissue after radiotherapy in the authors' mouse model. Further studies are needed to assess these changes in fat graft retention.

  16. External corners as heat bridges

    Energy Technology Data Exchange (ETDEWEB)

    Berber, J.

    1984-08-01

    The maximum additional heat loss in vertical external corners depending on wall thickness is determined. In order to amire at a low k-value, a much smaller wall thickness is required in externally insulated walls than in monolithic constructions; the greater loss of heat bridge with external insulation stands in contrast to a higher loss in thick, monolithic walls. In relation to total losses, the additional losses through external corners are practically negligible.

  17. (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone inhibits tubulin polymerization, induces G2/M arrest, and triggers apoptosis in human leukemia HL-60 cells

    International Nuclear Information System (INIS)

    Magalhães, Hemerson I.F.; Wilke, Diego V.; Bezerra, Daniel P.; Cavalcanti, Bruno C.; Rotta, Rodrigo; Lima, Dênis P. de; Beatriz, Adilson; Moraes, Manoel O.; Diniz-Filho, Jairo; Pessoa, Claudia

    2013-01-01

    (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a known cytotoxic compound belonging to the phenstatin family. However, the exact mechanism of action of PHT-induced cell death remains to be determined. The aim of this study was to investigate the mechanisms underlying PHT-induced cytotoxicity. We found that PHT displayed potent cytotoxicity in different tumor cell lines, showing IC 50 values in the nanomolar range. Cell cycle arrest in G 2 /M phase along with the augmented metaphase cells was found. Cells treated with PHT also showed typical hallmarks of apoptosis such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of the caspase 3/7 and 8 activation, loss of mitochondrial membrane potential, and internucleosomal DNA fragmentation without affecting membrane integrity. Studies conducted with isolated tubulin and docking models confirmed that PHT binds to the colchicine site and interferes in the polymerization of microtubules. These results demonstrated that PHT inhibits tubulin polymerization, arrests cancer cells in G 2 /M phase of the cell cycle, and induces their apoptosis, exhibiting promising anticancer therapeutic potential. - Highlights: • PHT inhibits tubulin polymerization. • PHT arrests cancer cells in G 2 /M phase of the cell cycle. • PHT induces caspase-dependent apoptosis

  18. Sheared electric field-induced suppression of edge turbulence using externally driven R.F. waves

    International Nuclear Information System (INIS)

    Craddock, G.G.; Diamond, P.H.

    1991-01-01

    Here the authors propose a novel method for active control and suppression of edge turbulence by sheared ExB flows driven by externally launched RF waves. The theory developed addresses the problem of open-quotes flow driveclose quotes, which is somewhat analogous to the problem of plasma current drive. As originally demonstrated for the case of spontaneously driven flows, a net difference in the gradient of the fluid and magnetic Reynolds' stresses produced by radially propagating waves can drive the plasma flow. For the prototypical case of the Alfven wave flow drive considered here, ρ 0 r v θ > - r B θ > is proportional to k perpendicular 2 ρ s 2 in the case of the kinetic Alfven wave, and [(ηk perpendicular 2 -vk perpendicular 2 )/ω] 2 in the case of resistive MHD. Both results reflect the dependence of flow drive on the net stress imbalance. The shear layer width is determined by the waves evanescence length (determined by dissipation) that sets the stress gradient scale length, while the direction of the flow is determined by the poloidal orientation of the launched waves. In particular, it should be noted that both positive and negative E r may be driven, so that enhanced confinement need not be accompanied by impurity accumulation, as commonly encountered in spontaneous H-modes. The efficiency is determined by the criterion that the radial electric field shear be large enough to suppress turbulence. For typical TEXT parameters, and unity efficiency, 300 kW of absorbed power is needed to suppress turbulence over 3 cm radially. For DIII-D, 300 kW over 4 cm is needed. Also, direct transport losses induced by RF have been shown to be small. Extensions of the theory to ICRF are underway and are discussed. They also discuss the analogous problem of current drive using kinetic Alfven waves. 2 refs

  19. Phospholipids chiral at phosphorus. Steric course of the reactions catalyzed by phosphatidylserine synthase from Escherichia coli and yeast

    International Nuclear Information System (INIS)

    Raetz, C.R.H.; Carman, G.M.; Dowhan, W.; Jiang, R.T.; Waszkuc, W.; Loffredo, W.; Tsai, M.D.

    1987-01-01

    The steric courses of the reactions catalyzed by phosphatidylserine (PS) synthase from Escherichia coli and yeast were elucidated by the following procedure. R/sub P/ and S/sub P/ isomers of 1,2-dipalmitoyl-sn-glycero-3-[ 17 O, 18 O]phosphoethanolamine ([ 17 O, 18 O]DPPE) were synthesized and converted to (R/sub P/)- and (S/sub P/)-1,2-dipalmitoyl-sn-glycero-3-[ 16 O, 17 O, 18 O]DPPA), respectively, by incubating with phospholipase D. Condensation of [ 16 O, 17 O, 18 O]DPPA with cytidine 5'-monophosphomorpholidate in pyridine gave the desired substrate for PS synthase, [ 17 O, 18 O]cytidine 5'-diphospho-1,2-dipalmitoyl-sn-glycerol ([ 17 O, 18 O]CDP-DPG), as a mixture of several isotopic and configurational isomers. Incubation of [ 17 O, 18 O]CDP-DPG), as a mixture of several isotopic and configurational isomers. Incubation of [ 17 O, 18 O] CDP-DPG with a mixture of L-serine, PS synthase and PS decarboxylase gave [ 17 O, 18 O]DPPE. The configuration and isotopic enrichments of the starting [ 17 O, 18 O]DPPE and the product were analyzed by 31 P NMR following trimethylsilylation of the DPPE. The results indicate that the reaction of E. coli PS synthase proceeds with retention of configuration at phosphorus, which suggests a two-step mechanism involving a phosphatidyl-enzyme intermediate, while the yeast PS synthase catalyzes the reaction with inversion of configuration, which suggests a single-displacement mechanism. Such results lend strong support to the ping-pong mechanism proposed for the E. coli enzyme and the sequential Bi-Bi mechanism proposed for the yeast enzyme, both based on previous isotopic exchange experiments

  20. Killing of melanoma cells and their metastases by human lactoferricin derivatives requires interaction with the cancer marker phosphatidylserine.

    Science.gov (United States)

    Riedl, Sabrina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar

    2014-10-01

    Despite favorable advancements in therapy cancer is still not curative in many cases, which is often due to inadequate specificity for tumor cells. In this study derivatives of a short cationic peptide derived from the human host defense peptide lactoferricin were optimized in their selective toxicity towards cancer cells. We proved that the target of these peptides is the negatively charged membrane lipid phosphatidylserine (PS), specifically exposed on the surface of cancer cells. We have studied the membrane interaction of three peptides namely LF11-322, its N-acyl derivative 6-methyloctanoyl-LF11-322 and its retro repeat derivative R(etro)-DIM-P-LF11-322 with liposomes mimicking cancerous and non-cancerous cell membranes composed of PS and phosphatidylcholine (PC), respectively. Calorimetric and permeability studies showed that N-acylation and even more the repeat derivative of LF11-322 leads to strongly improved interaction with the cancer mimic PS, whereas only the N-acyl derivative also slightly affects PC. Tryptophan fluorescence of selective peptide R-DIM-P-LF11-322 revealed specific peptide penetration into the PS membrane interface and circular dichroism showed change of its secondary structure by increase of proportion of β-sheets just in the presence of the cancer mimic. Data correlated with in vitro studies with cell lines of human melanomas, their metastases and melanocytes, revealing R-DIM-P-LF11-322 to exhibit strongly increased specificity for cancer cells. This indicates the need of high affinity to the target PS, a minimum length and net positive charge, an adequate but moderate hydrophobicity, and capability of adoption of a defined structure exclusively in presence of the target membrane for high antitumor activity.

  1. Inhibition of Rho - ROCK signaling induces apoptotic and non-apoptotic PS exposure in cardiomyocytes via inhibition of flippase

    NARCIS (Netherlands)

    Krijnen, Paul A. J.; Sipkens, Jessica A.; Molling, Johan W.; Rauwerda, Jan A.; Stehouwer, Coen D. A.; Muller, Alice; Paulus, Walter J.; van Nieuw Amerongen, Geerten P.; Hack, C. Erik; Verhoeven, Arthur J.; van Hinsbergh, Victor W. M.; Niessen, Hans W. M.

    2010-01-01

    Subsequent to myocardial infarction, cardiomyocytes within the infarcted areas and border zones expose phosphatidylserine (PS) in the outer plasma membrane leaflet (flip-flop). We showed earlier that in addition to apoptosis, this flip-flop can be reversible in cardiomyocytes. We now investigated a

  2. External magnetic field induced anomalies of spin nuclear dynamics in thin antiferromagnetic films

    International Nuclear Information System (INIS)

    Tarasenko, S.V.

    1995-01-01

    It is shown that if the thickness of homogeneously magnetized plate of high-axial antiferromagnetic within H external magnetic field becomes lower the critical one, then the effect of dynamic magnetoelastic interaction on Soul-Nakamura exchange of nuclear spins results in formation of qualitatively new types of spreading nuclear spin waves no else compared neither within the model of unrestricted magnetic nor at H = 0 in case of thin plate of high-axial antiferromagnetic. 10 refs

  3. Induction of external abnormalities in offspring of male mice irradiated with 252Cf neutron

    International Nuclear Information System (INIS)

    Kurishita, Akihiro; Ono, Tetsuya; Mori, Yuriko; Okada, Shigefumi; Sawada, Syozo

    1992-01-01

    To assess the genetic effects of fission neutron, the induction of external malformations was studied in F 1 fetuses after F 0 male mice were irradiated. Male mice of the ICR:MCH strain were irradiated with 252 Cf neutron at doses of 0.238, 0.475, 0.95 and 1.9 Gy. They were mated with non-irradiated female mice at 71-120 days after irradiation. Pregnant females were autopsied on day 18 of gestation and their fetuses were examined for deaths and external abnormalities. No increases of pre- and post-implantation losses were noted at any dose. External abnormalities were observed at rates of 1.40% in the 0.238 Gy, 2.23% in the 0.475 Gy, 3.36% in the 0.95 and 3.26% in the 1.9 Gy groups; the rate in the control group was 1.65%. The dose-response curve was linear up to 0.95 Gy, and then flattened out; the induction rate of external abnormalities was 2.7x10 -4 /gamete/cGy based on the linear regression. These results indicated that fission neutron effectively induces external abnormalities in F 1 fetuses after spermatogonial irradiation. (author). 29 refs.; 1 fig.; 2 tabs

  4. Gyrokinetic Simulations with External Resonant Magnetic Perturbations: Island Torque and Nonambipolar Transport with Rotation

    Science.gov (United States)

    Waltz, R. E.; Waelbroeck, F. L.

    2012-03-01

    Static external resonant magnetic perturbations (RMPs) have been added to the δf gyrokinetic code GYRO. This allows nonlinear gyrokinetic simulations of the nonambipolar radial current flow jr and the corresponding plasma torque (density) R[jrBθ/c], induced by islands that break the toroidal symmetry of a tokamak. This extends previous GYRO simulations for the transport of toroidal angular momentum (TAM) [1,2]. The focus is on full torus radial slice electrostatic simulations of induced q=m/n=6/3 islands with widths 5% of the minor radius. The island torque scales with the radial electric field Er the island width w, and the intensity I of the high-n micro-turbulence, as wErI^1/2. The net island torque is null at zero Er rather than at zero toroidal rotation. This means that there is a small co-directed magnetic acceleration to the small diamagnetic co-rotation corresponding to the zero Er which can be called the residual stress [2] from an externally induced island. Finite-beta GYRO simulations of a core radial slice demonstrate island unlocking and the RMP screening. 6pt[1] R.E. Waltz, et al., Phys. Plasmas 14, 122507 (2007). [2] R.E. Waltz, et al., Phys. Plasmas 18, 042504 (2011).

  5. Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.

    Science.gov (United States)

    Kim, Ji Eun; Yoo, Hyun Ju; Gu, Ja Yoon; Kim, Hyun Kyung

    2016-01-01

    The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.

  6. (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone inhibits tubulin polymerization, induces G{sub 2}/M arrest, and triggers apoptosis in human leukemia HL-60 cells

    Energy Technology Data Exchange (ETDEWEB)

    Magalhães, Hemerson I.F. [Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará (Brazil); Centro de Ciências da Saúde, Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa, Paraíba (Brazil); Wilke, Diego V. [Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará (Brazil); Bezerra, Daniel P., E-mail: danielpbezerra@gmail.com [Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia (Brazil); Cavalcanti, Bruno C. [Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará (Brazil); Rotta, Rodrigo; Lima, Dênis P. de; Beatriz, Adilson [Centro de Ciências Exatas e Tecnológicas (Laboratório LP4), Universidade Federal do Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul (Brazil); Moraes, Manoel O.; Diniz-Filho, Jairo [Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará (Brazil); Pessoa, Claudia, E-mail: c_pessoa@yahoo.com [Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará (Brazil)

    2013-10-01

    (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a known cytotoxic compound belonging to the phenstatin family. However, the exact mechanism of action of PHT-induced cell death remains to be determined. The aim of this study was to investigate the mechanisms underlying PHT-induced cytotoxicity. We found that PHT displayed potent cytotoxicity in different tumor cell lines, showing IC{sub 50} values in the nanomolar range. Cell cycle arrest in G{sub 2}/M phase along with the augmented metaphase cells was found. Cells treated with PHT also showed typical hallmarks of apoptosis such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of the caspase 3/7 and 8 activation, loss of mitochondrial membrane potential, and internucleosomal DNA fragmentation without affecting membrane integrity. Studies conducted with isolated tubulin and docking models confirmed that PHT binds to the colchicine site and interferes in the polymerization of microtubules. These results demonstrated that PHT inhibits tubulin polymerization, arrests cancer cells in G{sub 2}/M phase of the cell cycle, and induces their apoptosis, exhibiting promising anticancer therapeutic potential. - Highlights: • PHT inhibits tubulin polymerization. • PHT arrests cancer cells in G{sub 2}/M phase of the cell cycle. • PHT induces caspase-dependent apoptosis.

  7. Performance Targets and External Benchmarking

    DEFF Research Database (Denmark)

    Friis, Ivar; Hansen, Allan; Vámosi, Tamás S.

    Research on relative performance measures, transfer pricing, beyond budgeting initiatives, target costing, piece rates systems and value based management has for decades underlined the importance of external benchmarking in performance management. Research conceptualises external benchmarking...... as a market mechanism that can be brought inside the firm to provide incentives for continuous improvement and the development of competitive advances. However, whereas extant research primarily has focused on the importance and effects of using external benchmarks, less attention has been directed towards...... the conditions upon which the market mechanism is performing within organizations. This paper aims to contribute to research by providing more insight to the conditions for the use of external benchmarking as an element in performance management in organizations. Our study explores a particular type of external...

  8. External Otitis (Swimmer's Ear)

    Science.gov (United States)

    ... otitis. Fungal external otitis (otomycosis), typically caused by Aspergillus niger or Candida albicans, is less common. Boils are ... in the ear. Fungal external otitis caused by Aspergillus niger usually causes grayish black or yellow dots (called ...

  9. How Do Internal and External CSR Affect Employees' Organizational Identification? A Perspective from the Group Engagement Model.

    Science.gov (United States)

    Hameed, Imran; Riaz, Zahid; Arain, Ghulam A; Farooq, Omer

    2016-01-01

    The literature examines the impact of firms' corporate social responsibility (CSR) activities on employees' organizational identification without considering that such activities tend to have different targets. This study explores how perceived external CSR (efforts directed toward external stakeholders) and perceived internal CSR (efforts directed toward employees) activities influence employees' organizational identification. In so doing, it examines the alternative underlying mechanisms through which perceived external and internal CSR activities build employees' identification. Applying the taxonomy prescribed by the group engagement model, the study argues that the effects of perceived external and internal CSR flow through two competing mechanisms: perceived external prestige and perceived internal respect, respectively. Further, it is suggested that calling orientation (how employees see their work contributions) moderates the effects induced by these alternative forms of CSR. The model draws on survey data collected from a sample of 414 employees across five large multinationals in Pakistan. The results obtained using structural equation modeling support these hypotheses, reinforcing the notion that internal and external CSR operate through different mediating mechanisms and more interestingly employees' calling orientation moderates these relationships to a significant degree. Theoretical contributions and practical implications of results are discussed in detail.

  10. Hydropower externalities: A meta-analysis

    International Nuclear Information System (INIS)

    Mattmann, Matteo; Logar, Ivana; Brouwer, Roy

    2016-01-01

    This paper presents a meta-analysis of existing research related to the economic valuation of the external effects of hydropower. A database consisting of 81 observations derived from 29 studies valuing the non-market impacts of hydropower electricity generation is constructed with the main aim to quantify and explain the economic values for positive and negative hydropower externalities. Different meta-regression model specifications are used to test the robustness of significant determinants of non-market values, including different types of hydropower impacts. The explanatory and predictive power of the estimated models is relatively high. Whilst controlling for sample and study characteristics, we find significant evidence for public aversion towards deteriorations of landscape, vegetation and wildlife caused by hydropower projects. There is however only weak evidence of willingness to pay for mitigating these effects. The main positive externality of hydropower generation, the avoidance of greenhouse gas emission, positively influences welfare estimates when combined with the share of hydropower in national energy production. Sensitivity to scope is detected, but not linked to specific externalities or non-market valuation methods. - Highlights: • A global meta-analysis of valuation studies of hydropower externalities is presented. • Positive and negative externalities are distinguished. • Welfare losses due to environmental deteriorations outweigh gains of GHG reductions. • There is only weak evidence of public WTP for mitigating negative externalities. • The non-market values of hydropower externalities are sensitive to scope.

  11. Congenital External Carotid-External Jugular Arteriovenous Fistula: Diagnosis With Contrast-Enhanced Computed Tomography

    International Nuclear Information System (INIS)

    Faghihi Langroudi, Taraneh; Arjmand Shabestari, Abbas; Pourghorban, Ramin; Khalili Pouya, Ensi

    2015-01-01

    Arteriovenous fistula (AVF) between the external carotid artery and external jugular vein is extremely rare, with only few cases reported in the literature so far. Most of these AVFs have been either iatrogenic or secondary to previous trauma. Herein, we report a 42-year-old woman with congenital AVF between the external carotid artery and external jugular vein, presenting with palpitation and dyspnea. The patient was suffering from mitral and tricuspid regurgitation. On physical examination, a thrill on the left side of the neck and an audible bruit over the left mandibular angle were detected. The possibility of abnormal AVF was considered and it was confirmed on contrast-enhanced computed tomography (CT), inferring that this modality is not only fast and non-invasive, but also accurate in detecting vascular abnormalities

  12. New Cooperative Mechanisms of Low Energy Nuclear Reactions Using Superlow Energy External Fields

    OpenAIRE

    Gareev, F. A.; Zhidkova, I. E.

    2005-01-01

    We proposed a new mechanism of LENR: cooperative processes in whole system - nuclei+atoms+condensed matter can occur at smaller threshold then corresponding ones on free constituents. The cooperative processes can be induced and enhanced by low energy external fields. The excess heat is the emission of internal energy and transmutations at LENR are the result of redistribution inner energy of whole system.

  13. Energy policy and externalities

    International Nuclear Information System (INIS)

    Bertel, E.; Fraser, P.

    2002-01-01

    External costs of energy have been assessed in a number of authoritative and reliable studies based upon widely accepted methodologies such as life cycle analysis (LCA). However, although those costs are recognised by most stakeholders and decision makers, results from analytical work on externalities and LCA studies are seldom used in policy making. The International Energy Agency (IEA) and the Nuclear Energy Agency (NEA) convened a joint workshop in November 2001 to offer experts and policy makers an opportunity to present state-of-the-art results from analytical work on externalities and debate issues related to the relevance of external costs and LCA for policy-making purposes. The findings from the workshop highlight the need for further work in the field and the potential rote of international organisations like the IEA and the NEA in this context. (authors)

  14. Externally Verifiable Oblivious RAM

    Directory of Open Access Journals (Sweden)

    Gancher Joshua

    2017-04-01

    Full Text Available We present the idea of externally verifiable oblivious RAM (ORAM. Our goal is to allow a client and server carrying out an ORAM protocol to have disputes adjudicated by a third party, allowing for the enforcement of penalties against an unreliable or malicious server. We give a security definition that guarantees protection not only against a malicious server but also against a client making false accusations. We then give modifications of the Path ORAM [15] and Ring ORAM [9] protocols that meet this security definition. These protocols both have the same asymptotic runtimes as the semi-honest original versions and require the external verifier to be involved only when the client or server deviates from the protocol. Finally, we implement externally verified ORAM, along with an automated cryptocurrency contract to use as the external verifier.

  15. Malignant external otitis: CT evaluation

    International Nuclear Information System (INIS)

    Curtin, H.D.; Wolfe, P.; May, M.

    1982-01-01

    Malignant external otitis is an aggressive infection caused by Pseudomonas aeruginosa that most often occurs in elderly diabetics. Malignant external otitis often spreads inferiorly from the external canal to involve the subtemporal area and progresses medially towards the petrous apex leading to multiple cranial nerve palsies. The computed tomographic (CT) findings in malignant external otitis include obliteration of the normal fat planes in the subtemporal area as well as patchy destruction of the bony cortex of the mastoid. The point of exit of the various cranial nerves can be identified on CT scans, and the extent of the inflammatory mass correlates well with the clinical findings. Four cases of malignant external otitis are presented. In each case CT provided a good demonstration of involvement of the soft tissues at the base of the skull

  16. External costs of electricity; Les couts externes de l'electricite

    Energy Technology Data Exchange (ETDEWEB)

    Rabl, A. [Ecole des Mines de Paris, 75 (France); Spadaro, J.V. [International Atomic Energy Agency (IAEA), Vienna (Austria)

    2005-07-01

    This article presents a synthesis of the ExternE project (External costs of Energy) of the European community about the external costs of power generation. Pollution impacts are calculated using an 'impact pathways' analysis, i.e. an analysis of the emission - dispersion - dose-response function - cost evaluation chain. Results are presented for different fuel cycles (with several technological variants) with their confidence intervals. The environmental impact costs are particularly high for coal: for instance, in France, for coal-fired power plants it is of the same order as the electricity retail price. For natural gas, this cost is about a third of the one for coal. On the contrary, the environmental impact costs for nuclear and renewable energies are low, typically of few per cent of the electricity price. The main part of these costs corresponds to the sanitary impacts, in particular the untimely mortality. In order to avoid any controversy about the cost evaluation of mortality, the reduction of the expectation of life due to the different fuel cycles is also indicated and the risks linked with nuclear energy are presented using several comparisons. (J.S.)

  17. Hydrodynamic interactions induce movement against an external load in a ratchet dimer Brownian motor.

    Science.gov (United States)

    Fornés, José A

    2010-01-15

    We use the Brownian dynamics with hydrodynamic interactions simulation in order to describe the movement of a elastically coupled dimer Brownian motor in a ratchet potential. The only external forces considered in our system were the load, the random thermal noise and an unbiased thermal fluctuation. For a given set of parameters we observe direct movement against the load force if hydrodynamic interactions were considered.

  18. Effects of aqueous humor hydrodynamics on human eye heat transfer under external heat sources.

    Science.gov (United States)

    Tiang, Kor L; Ooi, Ean H

    2016-08-01

    The majority of the eye models developed in the late 90s and early 00s considers only heat conduction inside the eye. This assumption is not entirely correct, since the anterior and posterior chambers are filled aqueous humor (AH) that is constantly in motion due to thermally-induced buoyancy. In this paper, a three-dimensional model of the human eye is developed to investigate the effects AH hydrodynamics have on the human eye temperature under exposure to external heat sources. If the effects of AH flow are negligible, then future models can be developed without taking them into account, thus simplifying the modeling process. Two types of external thermal loads are considered; volumetric and surface irradiation. Results showed that heat convection due to AH flow contributes to nearly 95% of the total heat flow inside the anterior chamber. Moreover, the circulation inside the anterior chamber can cause an upward shift of the location of hotspot. This can have significant consequences to our understanding of heat-induced cataractogenesis. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  19. External beam irradiation inhibits neointimal hyperplasia after injury-induced arterial smooth muscle cell proliferation

    International Nuclear Information System (INIS)

    Schaefer, U.; Micke, O.; Dorszewski, A.; Breithardt, G.; Willich, N.

    1996-01-01

    Purpose/Objective: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by smooth muscle cell proliferation. This study examines the effects of external beam irradiation on neointimal proliferation after external injury to the central artery of the rabbit ear. Materials and Methods: 30 male New Zealand White rabbits were used in this study. Crush lesions were performed on each ear under general anesthesia and bilateral auricular nerve blockade. A single dose of 12 Gy (n=10), 16 Gy (n=10), or 20 Gy (n=10) gamma radiation was delivered to the left or right central artery of the ear 24 hours after injury; the contralateral central artery served as control. All rabbits were sacrificed after twenty-one days and the central arteries of the ear were fixed for morphometric measurements. Results: Mean (± SD) neointimal area was 0.062 ± 0.005 mm 2 (12 Gy), 0.022 ± 0.005 mm 2 (16 Gy) and 0.028 ± 0.006 mm 2 in irradiated arteries compared with 0.081 ± 0.009 mm 2 in the control group. Mean (± SD) luminal area was 0.049 ± 0.004 mm 2 (12 Gy), 0.059 ± 0.002 mm 2 (16 Gy) and 0.072 ± 0.006 mm 2 (24 Gy) in irradiated arteries compared with 0.043 ± 0.008 mm 2 in the control group. The difference in neointimal and luminal area between control and irradiated arteries was significant (p<0.05) only for the 16 and 20 Gy group compared to control. Conclusion: We conclude that in this model, external beam X-ray irradiation was successful in reducing neointimal proliferation after injury of the central artery of the rabbit ear. Marked reductions in neointimal proliferation were demonstrated in vessels subjected to 16 and 20 Gy radiation, a less prominent effect was noted for 12 Gy. Whether this approach can be used successfully to inhibit restenosis in the clinical setting requires further investigation

  20. Technical basis document for external events

    International Nuclear Information System (INIS)

    OBERG, B.D.

    2003-01-01

    This document supports the Tank Farms Documented Safety Analysis and presents the technical basis for the FR-equencies of externally initiated accidents. The consequences of externally initiated events are discussed in other documents that correspond to the accident that was caused by the external event. The external events include aircraft crash, vehicle accident, range fire, and rail accident

  1. Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

    Science.gov (United States)

    van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

    2012-10-01

    The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

  2. Migration and income transfers in the presence of labor quality externalities

    OpenAIRE

    Huizinga, H.P.

    1994-01-01

    In this paper, a worker's productivity is assumed to depend on his own quality and on the average quality of other workers in the same country. The external effects associated with worker quality give rise to increasing returns to average worker quality. As a result, free migration generally reduces world output. Within each country, social benefits that induce low quality workers to leave the labor force can increase national income. Moreover, the operation of such a benefit scheme financed ...

  3. Critical current degradation in superconducting niobium-titanium alloys in external magnetic fields under loading

    International Nuclear Information System (INIS)

    Bojko, V.S.; Lazareva, M.B.; Starodubov, Ya.D.; Chernyj, O.V.; Gorbatenko, V.M.

    1992-01-01

    The effect of external magnetic fields on the stress at which the critical current starts to degrade (the degradation threshold σ 0 e ) under mechanical loads in superconducting Nb-Ti alloys is studied and a possible mechanism of realization of the effect observed is proposed.It is assumed that additional stresses on the transformation dislocation from the external magnetic fields are beneficial for the growth of martensite inclusions whose superconducting parameters (critical current density j k and critical temperature T k ) are lower then those in the initial material.The degradation threshold is studied experimentally in external magnetic fields H up to 7 T.The linear dependence σ 0 e (H) is observed.It is shown that external magnetic fields play an important role in the critical current degradation at the starting stages of deformation.This fact supports the assumption that the degradation of superconducting parameters under loading are due to the phenomenon of superelasticity,i.e. a reversible load-induced change in the martensite inclusions sizes rather than the reversible mechanical twinning.The results obtained are thought to be important to estimating superconducting solenoid stability in a wide range of magnetic fields

  4. The neural correlates of internal and external comparisons: an fMRI study.

    Science.gov (United States)

    Wen, Xue; Xiang, Yanhui; Cant, Jonathan S; Wang, Tingting; Cupchik, Gerald; Huang, Ruiwang; Mo, Lei

    2017-01-01

    Many previous studies have suggested that various comparisons rely on the same cognitive and neural mechanisms. However, little attention has been paid to exploring the commonalities and differences between the internal comparison based on concepts or rules and the external comparison based on perception. In the present experiment, moral beauty comparison and facial beauty comparison were selected as the representatives of internal comparison and external comparison, respectively. Functional magnetic resonance imaging (fMRI) was used to record brain activity while participants compared the level of moral beauty of two scene drawings containing moral acts or the level of facial beauty of two face photos. In addition, a physical size comparison task with the same stimuli as the beauty comparison was included. We observed that both the internal moral beauty comparison and external facial beauty comparison obeyed a typical distance effect and this behavioral effect recruited a common frontoparietal network involved in comparisons of simple physical magnitudes such as size. In addition, compared to external facial beauty comparison, internal moral beauty comparison induced greater activity in more advanced and complex cortical regions, such as the bilateral middle temporal gyrus and middle occipital gyrus, but weaker activity in the putamen, a subcortical region. Our results provide novel neural evidence for the comparative process and suggest that different comparisons may rely on both common cognitive processes as well as distinct and specific cognitive components.

  5. An external focus of attention enhances motor learning in children with intellectual disabilities.

    Science.gov (United States)

    Chiviacowsky, S; Wulf, G; Avila, L T G

    2013-07-01

    The present study examined whether the learning benefits of an external focus of attention (i.e., on the movement effect) relative to an internal focus (i.e. on the movement), found previously in non-disabled children and adults would also be found in children with intellectual disabilities (IDs). Participants (n = 24; average age: 12.2 years) with mild intellectual deficiency (IQ = 51-69) practiced throwing beanbags at a target. In the external focus group, participants were instructed to direct their attention to the movement of the beanbag, while in the internal focus group, participants were asked to direct their attention to the movement of their hand. The practice phase consisted of 40 trials, and attentional focus reminders were given after every third trial. Learning was assessed 1 day later by retention and transfer (greater target distance) tests, each consisting of 10 trials. No focus reminders were given on that day. The external focus group demonstrated more effective learning than the internal focus group, as evidenced by more accurate tosses on the transfer test. The present findings show that instructions that induce an external focus of attention can enhance motor learning in children with IDs. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID.

  6. EDITORIAL: Colloidal dispersions in external fields Colloidal dispersions in external fields

    Science.gov (United States)

    Löwen, Hartmut

    2012-11-01

    third conference in a series that began in 2004 [2] and was continued in 2008 [3]. The CODEF meeting series is held in conjunction with the German Dutch Transregional Collaborative Research Centre SFB TR6 with the title Physics of Colloidal Dispersions in External Fields. Papers from scientists working within this network as well as those from further invited contributors are summarized in this issue. They are organized according to the type of field applied, namely: shear flow electric field laser-optical and magnetic field confinement other fields and active particles To summarize the highlights of this special issue as regards shear fields, the response of depletion-induced colloidal clusters to shear is explored in [4]. Soft particles deform under shear and their structural and dynamical behaviour is studied both by experiment [5] and theory [6]. Transient dynamics after switching on shear is described by a joint venture of theory, simulation and experiment in [7]. Colloids provide the fascinating possibility to drag single particles through the suspension, which gives access to microrheology (as opposed to macrorheology, where macroscopic boundaries are moved). Several theoretical aspects of microrheology are discussed in this issue [8-10]. Moreover, a microscopic theory for shear viscosity is presented [11]. Various aspects of colloids in electric fields are also included in this issue. Electrokinetic phenomena for charged suspensions couple flow and electric phenomena in an intricate way and are intensely discussed both by experiment and simulation in contributions [12-14]. Dielectric phenomena are also influenced by electric fields [15]. Electric fields can induce effective dipolar forces between colloids leading to string formation [16]. Finally, binary mixtures in an electric driving field exhibit laning [17]. Simulation [18] and theoretical [19] studies of this nonequilibrium phenomenon are also discussed in this issue. Laser-optical fields can be used to

  7. Externalizing behaviors in preadolescents: Familial risk to externalizing behaviors and perceived parenting styles

    NARCIS (Netherlands)

    C.J.M. Buschgens (Cathelijne); M.A.G. van Aken (Marcel); S.H.N. Swinkels (Sophie); J. Ormel (Johan Hans); F.C. Verhulst (Frank); J.K. Buitelaar (Jan)

    2010-01-01

    textabstractThe aim was to investigate the contribution of familial risk to externalizing behaviors (FR-EXT), perceived parenting styles, and their interactions to the prediction of externalizing behaviors in preadolescents. Participants were preadolescents aged 10-12 years who participated in

  8. Selectivity of externally facing ion-binding sites in the Na/K pump to alkali metals and organic cations.

    Science.gov (United States)

    Ratheal, Ian M; Virgin, Gail K; Yu, Haibo; Roux, Benoît; Gatto, Craig; Artigas, Pablo

    2010-10-26

    The Na/K pump is a P-type ATPase that exchanges three intracellular Na(+) ions for two extracellular K(+) ions through the plasmalemma of nearly all animal cells. The mechanisms involved in cation selection by the pump's ion-binding sites (site I and site II bind either Na(+) or K(+); site III binds only Na(+)) are poorly understood. We studied cation selectivity by outward-facing sites (high K(+) affinity) of Na/K pumps expressed in Xenopus oocytes, under voltage clamp. Guanidinium(+), methylguanidinium(+), and aminoguanidinium(+) produced two phenomena possibly reflecting actions at site III: (i) voltage-dependent inhibition (VDI) of outwardly directed pump current at saturating K(+), and (ii) induction of pump-mediated, guanidinium-derivative-carried inward current at negative potentials without Na(+) and K(+). In contrast, formamidinium(+) and acetamidinium(+) induced K(+)-like outward currents. Measurement of ouabain-sensitive ATPase activity and radiolabeled cation uptake confirmed that these cations are external K(+) congeners. Molecular dynamics simulations indicate that bound organic cations induce minor distortion of the binding sites. Among tested metals, only Li(+) induced Na(+)-like VDI, whereas all metals tested except Na(+) induced K(+)-like outward currents. Pump-mediated K(+)-like organic cation transport challenges the concept of rigid structural models in which ion specificity at site I and site II arises from a precise and unique arrangement of coordinating ligands. Furthermore, actions by guanidinium(+) derivatives suggest that Na(+) binds to site III in a hydrated form and that the inward current observed without external Na(+) and K(+) represents cation transport when normal occlusion at sites I and II is impaired. These results provide insights on external ion selectivity at the three binding sites.

  9. Foreign direct investment, institutional development, and environmental externalities: evidence from China.

    Science.gov (United States)

    Wang, Danny T; Chen, Wendy Y

    2014-03-15

    The question of how foreign direct investment (FDI) affects a host country's natural environment has generated much debate but little consensus. Building on an institution-based theory, this article examines how the institutional development of a host setting affects the degree of FDI-related environmental externalities in China (specifically, industrial sulfur dioxide emissions). With a panel data set of 287 Chinese cities, over the period 2002-2009, this study reveals that FDI in general induces negative environmental externalities. Investments from OECD countries increase sulfur dioxide emissions, whereas FDI from Hong Kong, Macau, and Taiwan shows no significant effect. Institutional development reduces the impacts of FDI across the board. By focusing on the moderating role of institutions, this study sheds new light on the long-debated relationships among FDI, institutions, and the environments of the host countries. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Comparison of infection between internal-external and external percutaneous transhepatic biliary drainage in treating patients with malignant obstructive jaundice.

    Science.gov (United States)

    Xu, Chuan; Huang, Xin-En; Wang, Shu-Xiang; Lv, Peng-Hua; Sun, Ling; Wang, Fu-An

    2015-01-01

    Percutaneous transhepatic biliary drainage (PTBD) is a form of palliative care for patients with malignant obstructive jaundice. We here compared the infection incidence between internal-external and external drainage for patients with malignant obstructive jaundice. Patients with malignant obstructive jaundice without infection before surgery receiving internal-external or external drainage from January 2008 to July 2014 were recruited. According to percutaneous transhepatic cholangiography (PTC), if the guide wire could pass through the occlusion and enter the duodenum, we recommended internal-external drainage, and external drainage biliary drainage was set up if the occlusion was not crossed. All patients with infection after procedure received a cultivation of blood and a bile bacteriological test. Among 110 patients with malignant obstructive jaundice, 22 (52.4%) were diagnosed with infection after the procedure in the internal-external drainage group, whereas 19 (27.9%) patients were so affected in the external drainage group, the difference being significant (pinternal-external group infection was controlled, as compared to 12 (63.1%) in the external group (pinternal-external group in one month was 42.8%, while this rate in external group was 28.6% (pExternal drainage is a good choice, which could significantly reduce the chance of biliary infection caused by bacteria, and decrease the mortality rate at one month and improve the long-term prognosis.

  11. Externalizing behaviors in preadolescents : familial risk to externalizing behaviors and perceived parenting styles

    NARCIS (Netherlands)

    Buschgens, Cathelijne J. M.; van Aken, Marcel A. G.; Swinkels, Sophie H. N.; Ormel, Johan; Verhulst, Frank C.; Buitelaar, Jan K.

    The aim was to investigate the contribution of familial risk to externalizing behaviors (FR-EXT), perceived parenting styles, and their interactions to the prediction of externalizing behaviors in preadolescents. Participants were preadolescents aged 10-12 years who participated in TRAILS, a large

  12. Externalizing behaviors in preadolescents: familial risk to externalizing behaviors and perceived parenting styles.

    NARCIS (Netherlands)

    Buschgens, C.J.M.; Aken, M.A.G. van; Swinkels, S.H.N.; Ormel, J.; Verhulst, F.C.; Buitelaar, J.K.

    2010-01-01

    The aim was to investigate the contribution of familial risk to externalizing behaviors (FR-EXT), perceived parenting styles, and their interactions to the prediction of externalizing behaviors in preadolescents. Participants were preadolescents aged 10-12 years who participated in TRAILS, a large

  13. Externalizing behaviors in preadolescents: familial risk to externalizing behaviors and perceived parenting styles

    NARCIS (Netherlands)

    Buschgens, C.J.M.; van Aken, M.A.G.; Swinkels, S.H.N.; Ormel, J.; Verhulst, F.C.; Buitelaar, J.K.

    2010-01-01

    The aim was to investigate the contribution of familial risk to externalizing behaviors (FR-EXT), perceived parenting styles, and their interactions to the prediction of externalizing behaviors in preadolescents. Participants were preadolescents aged 10-12 years who participated in TRAILS, a large

  14. Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica

    Science.gov (United States)

    Pais-Morales, Jonnatan; Betanzos, Abigail; García-Rivera, Guillermina; Chávez-Munguía, Bibiana; Shibayama, Mineko; Orozco, Esther

    2016-01-01

    Entamoeba histolytica causes amoebiasis, an infection that kills 100,000 individuals each year. Metronidazole and its derivatives are currently used against this protozoan, but these drugs present adverse effects on human health. Here, we investigated the effect of resveratrol (a natural compound) on E. histolytica trophozoites viability, as well as its influence on the parasite virulence. Trophozoites growth was arrested by 72 μM resveratrol and the IC50 was determined as 220 μM at 48 h. Cells appeared smaller, rounded and in clusters, with debris-containing vacuoles and with abnormally condensed chromatin. Resveratrol triggered reactive oxygen species production. It caused lipid peroxidation and produced phosphatidylserine externalization and DNA fragmentation this latter evidenced by TUNEL assays. It also provoked an increase of intracellular Ca2+ concentration, activated calpain and decreased superoxide dismutase activity, indicating that an apoptosis-like event occurred; however, autophagy was not detected. Cytopathic activity, phagocytosis, encystment and in vivo virulence were diminished dramatically by pre-incubation of trophozoites with resveratrol, evidencing that resveratrol attenuated the trophozoite virulence in vitro. Interestingly, after the inoculation of virulent trophozoites, animals treated with the drug did not develop or developed very small abscesses. Our findings propose that resveratrol could be an alternative to contend amoebiasis. PMID:26731663

  15. Energy policy and externalities: an overview

    International Nuclear Information System (INIS)

    Pearce, D.

    2002-01-01

    Substantial progress has been made in estimating the monetary value of the environmental impacts of different energy systems. Perhaps the best known study in Europe is that sponsored by the European Commission and known as the ExternE programme. In the USA a comparable project is that jointly sponsored by the US Department of Energy and the European Commission. There are many others. In each case what is sought is a monetary value of an environmental impact arising from a unit of energy, usually standardised as a kilowatt hour. These environmental impacts are usually termed 'externalities'. An externality exists if two conditions are met. First, some negative (or positive) impact is generated by an economic activity and imposed on third parties. Second, that impact must not be priced in the market place, i.e. if the effect is negative, no compensation is paid by the generator of the externality to the sufferer. If the effect is positive, the generator of the externality must not appropriate the gains to the third party, e.g. via some price that is charged. In the energy externality literature, the procedure of expressing the externalities in, say, cents or milli-euros (1000 th of an Euro = m-euro) per kWh results in an 'adder'. An adder is simply the unit externality cost added to the standard resource cost of energy. Thus, if an electricity source costs X m/euros to produce or deliver, the final social cost of it is (X+y) m-euros where y is the externality adder. While externality adders have been researched most in the context of energy, they are increasingly being estimated for other economic sectors, notably transport and agriculture. This paper presents the uses of such figures. (author)

  16. Effect of Slow External Flow on Flame Spreading over Solid Material: Opposed Spreading over Polyethylene Wire Insulation

    Science.gov (United States)

    Fujita, O.; Nishizawa, K.; Ito, K.; Olson, S. L.; Kashigawa, T.

    2001-01-01

    The effect of slow external flow on solid combustion is very important from the view of fire safety in space because the solid material in spacecraft is generally exposed to the low air flow for ventilation. Further, the effect of low external flow on fuel combustion is generally fundamental information for industrial combustion system, such as gas turbine, boiler incinerator and so on. However, it is difficult to study the effect of low external flow on solid combustion in normal gravity, because the buoyancy-induced flow strongly disturbs the flow field, especially for low flow velocity. In this research therefore, the effect of slow external flow on opposed flame spreading over polyethylene (PE) wire insulation have been investigated in microgravity. The microgravity environment was provided by Japan Microgravity Center (JAMIC) in Japan and KC-135 at NASA GRC. The tested flow velocity range is 0-30cm/s with different oxygen concentration and inert gas component.

  17. Externality-correcting taxes and regulation

    OpenAIRE

    Christiansen, V.; Smith, S.

    2009-01-01

    Much of the literature on externalities has considered taxes and direct regulation as alternative policy instruments. Both instruments may in practice be imperfect, reflecting informational deficiencies and other limitations. We analyse the use of taxes and regulation in combination, to control externalities arising from individual consumption behaviour. We consider cases where taxes are either imperfectly differentiated to reflect individual differences in externalities, or where some consum...

  18. Cooperative Enhancement Mechanisms of Low Energy Nuclear Reactions Using Superlow Energy External Fields

    OpenAIRE

    Gareev, F. A.; Zhidkova, I. E.

    2006-01-01

    We proposed a new mechanism of LENR: cooperative processes in whole system - nuclei+atoms+condensed matter can occur at smaller threshold energies then corresponding ones on free constituents. The cooperative processes can be induced and enhanced by low energy external fields. The excess heat is the emission of internal energy and transmutations at LENR are the result of redistribution inner energy of whole system.

  19. Human Sound Externalization in Reverberant Environments

    DEFF Research Database (Denmark)

    Catic, Jasmina

    In everyday environments, listeners perceive sound sources as externalized. In listening conditions where the spatial cues that are relevant for externalization are not represented correctly, such as when listening through headphones or hearing aids, a degraded perception of externalization may...... occur. In this thesis, the spatial cues that arise from a combined effect of filtering due to the head, torso, and pinna and the acoustic environment were analysed and the impact of such cues for the perception of externalization in different frequency regions was investigated. Distant sound sources...... were simulated via headphones using individualized binaural room impulse responses (BRIRs). An investigation of the influence of spectral content of a sound source on externalization showed that effective externalization cues are present across the entire frequency range. The fluctuation of interaural...

  20. The dynamics of immunologic reactions in rats affected by repeated external γ-irradiation and internal irradiation with radionuclides

    International Nuclear Information System (INIS)

    Shubik, V.M.; Livshits, R.E.

    1975-01-01

    Nonspecific factors of immunity and formation of autoantibodies in rats exposed to comparable doses of repeated external γ-irradiation and of internal irradiation with Cs 137 , Sr 90 and I 131 chronically administered to animals have been studied comparatively. No essential variations have been found in changes induced in the immunologic reactions by chronic external and even internal γ-irradiation. Certain peculiarities have been revealed in the character of changes in the immunologic reactions depending on biophysical properties of the radionuclides used in the experiments

  1. Malignant external otitis

    International Nuclear Information System (INIS)

    Dupuch, K.M.; Iryboz, T.; Firat, M.; Levy, C.; Tubiana, J.M.

    1991-01-01

    This paper illustrates the value of CT and MR in early diagnosis and spread of malignant external otitis. The authors retrospectively analyzed 15 patients with proved malignant external otitis examined with postcontrast high-resolution CT (15/15) and MR (6/15) (T1- and T2-weighting). Gallium studies were done in 6/15 patients. Early diagnosis was made when CT demonstrated a soft-tissue mass of the external auditory canal associated with scattered zones of cortical bone erosions (13/15). Spread of the disease was better delineated by MR than CT, especially skull base extension (6/15). Temporomandibular joint involvement with extension into parotid or/and masticator spaces 6/15 was as well detected with CT as with MR. If CT remains the first and best procedure for diagnosis, MR - despite its cost - appears a good procedure to depict exact anatomic spread, allowing therapeutic management

  2. Cisplatin combined with hyperthermia kills HepG2 cells in intraoperative blood salvage but preserves the function of erythrocytes.

    Science.gov (United States)

    Yang, Jin-ting; Tang, Li-hui; Liu, Yun-qing; Wang, Yin; Wang, Lie-ju; Zhang, Feng-jiang; Yan, Min

    2015-05-01

    The safe use of intraoperative blood salvage (IBS) in cancer surgery remains controversial. Here, we investigated the killing effect of cisplatin combined with hyperthermia on human hepatocarcinoma (HepG2) cells and erythrocytes from IBS in vitro. HepG2 cells were mixed with concentrated erythrocytes and pretreated with cisplatin (50, 100, and 200 μg/ml) alone at 37 °C for 60 min and cisplatin (25, 50, 100, and 200 μg/ml) combined with hyperthermia at 42 °C for 60 min. After pretreatment, the cell viability, colony formation and DNA metabolism in HepG2 and the Na(+)-K(+)-ATPase activity, 2,3-diphosphoglycerate (2,3-DPG) concentration, free hemoglobin (Hb) level, osmotic fragility, membrane phosphatidylserine externalization, and blood gas variables in erythrocytes were determined. Pretreatment with cisplatin (50, 100, and 200 μg/ml) combined with hyperthermia (42 °C) for 60 min significantly decreased HepG2 cell viability, and completely inhibited colony formation and DNA metabolism when the HepG2 cell concentration was 5×10(4) ml(-1) in the erythrocyte (P2,3-DPG level, phosphatidylserine externalization, and extra-erythrocytic free Hb were significantly altered by hyperthermia plus high concentrations of cisplatin (100 and 200 μg/ml) (P0.05). In conclusion, pretreatment with cisplatin (50 μg/ml) combined with hyperthermia (42 °C) for 60 min effectively eliminated HepG2 cells from IBS but did not significantly affect erythrocytes in vitro.

  3. Assessing Air Pollutant-Induced, Health-Related External Costs in the Context of Nonmarginal System Changes: A Review.

    Science.gov (United States)

    Bachmann, Till M

    2015-08-18

    Marginal analysis is the usual approach to environmental economic assessment, for instance, of health-related external costs due to energy-associated air pollutant emissions. However, nonlinearity exists in all steps of their assessment, i.e., atmospheric dispersion, impact assessment, and monetary valuation. Dedicated assessments thus appear necessary when evaluating large systems or their changes such as in green accounting or the implications of economy-wide energy transitions. Corresponding approaches are reviewed. Tools already exist that allow assessing a marginal change (e.g., one power plant's emissions) for different background emission scenarios that merely need to be defined and implemented. When assessing nonmarginal changes, the top-down approach is considered obsolete, and four variants of the bottom-up approach with different application domains were identified. Variants 1 and 2 use precalculated external cost factors with different levels of sophistication, suitable for energy systems modeling, optimizing for social (i.e., private and external) costs. Providing more reliable results due to more detailed modeling, emission sources are assessed individually or jointly in variants 3 and 4, respectively. Aiming at considering nonlinearity more fully and simultaneously following marginal analysis principles, I propose a variant 3-based approach, subdividing an aggregate (i.e., a nonmarginal change) into several smaller changes. Its strengths and drawbacks, notably the associated effort, are discussed.

  4. Evaluation of radiolabelled annexin A5 for scintigraphic imaging of cell processes (necrosis/apoptosis) in cardiovascular diseases

    International Nuclear Information System (INIS)

    Sarda-Mantel, L.

    2007-03-01

    Annexin A5, a 35KDa protein, specifically binds with high affinity to phosphatidylserine (P.S.) which is actively redistributed to the external leaflet of plasmic membranes in apoptotic cells and activated platelets. Annexin A5 radiolabelled with 99m Tc( 99m Tc-ANX5) was developed by Strauss (stanford, Usa) to image apoptosis in vivo: tumours cells apoptosis induced by chemo-radiotherapy, ischemia/reperfusion lesions in animals and patients, graft rejection. Additionally, many in vitro data suggest that annexin A5 also stains necrosis (membrane disruption), which occurs in all types of cell death. This preclinical work aimed to evaluate the potential interest of 99m Tc-ANX5 imaging as a clinical tool in cardiovascular diseases. Four studies performed in rat models of myocardial infarction by coronary ligation and ischemia-reperfusion, and in rat models of subacute and acute (isoproterenol-induced) myocarditis show the ability of 99m Tc-ANX5 to detect in vivo cardio myocytes death by apoptosis and necrosis. Another study demonstrates that 99m Tc-ANX5 is highly accurate to evaluate in vivo the biological activity of parietal thrombus in a rat model of elastase-induced abdominal aortic aneurysm. These results suggest that 99m Tc-ANX5 imaging could be used in patients for non invasive diagnosis, prognostic evaluation in acute myocarditis and in various thrombotic cardiovascular diseases. (author)

  5. Quantum hacking on a practical continuous-variable quantum cryptosystem by inserting an external light

    Science.gov (United States)

    Qin, Hao; Kumar, Rupesh; Alleaume, Romain

    2015-10-01

    We report here a new side channel attack on a practical continuous-variable (CV) quantum key distribution (QKD) system. Inspired by blinding attack in discrete-variable QKD, we formalize an attack strategy by inserting an external light into a CV QKD system implemented Gaussian-modulated coherent state protocol and show that our attack can compromise its practical security. In this attack, we concern imperfections of a balanced homodyne detector used in CV QKD. According to our analysis, if one inserts an external light into Bob's signal port, due to the imperfect subtraction from the homodyne detector, the leakage of the external light contributes a displacement on the homodyne signal which causes detector electronics saturation. In consequence, Bob's quadrature measurement is not linear with the quadrature sent by Alice. By considering such vulnerability, a potential Eve can launch a full intercept-resend attack meanwhile she inserts an external light into Bob's signal port. By selecting proper properties of the external light, Eve actively controls the induced displacement value from the inserted light which results saturation of homodyne detection. In consequence, Eve can bias the excess noise due to the intercept-resend attack and the external light, such that Alice and Bob believe their excess noise estimation is below the null key threshold and they can still share a secret key. Our attack shows that the detector loopholes also exist in CV QKD, and it seems influence all the CV QKD systems using homodyne detection, since all the practical detectors have finite detection range.

  6. Magnetic field induced incommensurate resonance in cuprate superconductors

    International Nuclear Information System (INIS)

    Zhang Jingge; Cheng Li; Guo Huaiming; Feng Shiping

    2009-01-01

    The influence of a uniform external magnetic field on the dynamical spin response of cuprate superconductors in the superconducting state is studied based on the kinetic energy driven superconducting mechanism. It is shown that the magnetic scattering around low and intermediate energies is dramatically changed with a modest external magnetic field. With increasing the external magnetic field, although the incommensurate magnetic scattering from both low and high energies is rather robust, the commensurate magnetic resonance scattering peak is broadened. The part of the spin excitation dispersion seems to be an hourglass-like dispersion, which breaks down at the heavily low energy regime. The theory also predicts that the commensurate resonance scattering at zero external magnetic field is induced into the incommensurate resonance scattering by applying an external magnetic field large enough

  7. Protection of neuroblastoma Neuro2A cells from hypoxia-induced apoptosis by cyclic phosphatidic acid (cPA.

    Directory of Open Access Journals (Sweden)

    Mari Gotoh

    Full Text Available Cyclic phosphatidic acid (cPA is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We have previously shown that cPA significantly suppresses ischemia-induced delayed neuronal death and the accumulation of glial fibrillary acidic protein in the CA1 region of the rat hippocampus. These results indicated that the systemic administration of cPA can protect hippocampal neurons against ischemia-induced delayed neuronal cell death. In the current study, we investigated the effects of cPA on neuronal cell death caused by hypoxia in vitro and the molecular mechanisms underlying these effects. We used cobalt chloride (CoCl(2 to expose cells to hypoxic conditions in vitro. Treating mouse neuroblastoma (Neuro2A cells with CoCl(2 induced nuclear DNA condensation and phosphatidylserine exposure. However, adding cPA led to the suppression of CoCl(2-induced apoptosis in a cPA dose-dependent manner and attenuated the increase in the Bax/Bcl-2 ratio caused by CoCl(2. Quantitative PCR analysis showed that Neuro2A cells strongly express the LPA(1, LPA(2, and LPA(6, which are G-protein coupled receptors that can be activated by cPA. To date, LPA(1 and LPA(2 have been reported to exhibit antiapoptotic activity. Therefore, to assess the roles of LPA(1 and LPA(2 on cPA-induced neuroprotective functions, Ki16425, a selective LPA(1 and LPA(3 antagonist, was adopted to know the LPA(1 function and siRNA was used to knockdown the expression of LPA(2. On the basis of our results, we propose that cPA-induced protection of Neuro2A cells from CoCl(2-induced hypoxia damage is mediated via LPA(2.

  8. Hodgkin's disease: thyroid dysfunction following external irradiation

    International Nuclear Information System (INIS)

    Tamura, K.; Shimaoka, K.

    1981-01-01

    The thyroid gland is commonly included in the field of radiation therapy for patients with malignant lymphoma and with head and neck tumors. The radiation dose for malignant diseases varies considerably depending on the purpose of treatment and the institutional policies. A substantial number of these patients are developing subclinical and clinical hypothyroidism. The risk of developing hypothyroidism after a moderate radiation dose of 2000 to 4500 rads has been reported to be 10 to 20 percent. In addition, subclinical hypothyroidism is induced further in one third of the patients. There are also suggestions that external irradiation of the thyroid gland in patients with malignant lymphomas, as well as internal irradiation with radioiodine of the normal and hyperthyroid human thyroid glands, would induce elevations of serum antithyroid autoantibody titers. However, only a few cases of Graves disease following irradiation to the thyroid gland have been reported. We encountered a young woman who received radiation therapy to the mantle field for her Hodgkin's disease and developed hypothyroxinemia without overt signs and symptoms of hypothyroidism, followed by appearance of nodular goiter and then full-blown Graves disease

  9. Network evolution induced by asynchronous stimuli through spike-timing-dependent plasticity.

    Directory of Open Access Journals (Sweden)

    Wu-Jie Yuan

    Full Text Available In sensory neural system, external asynchronous stimuli play an important role in perceptual learning, associative memory and map development. However, the organization of structure and dynamics of neural networks induced by external asynchronous stimuli are not well understood. Spike-timing-dependent plasticity (STDP is a typical synaptic plasticity that has been extensively found in the sensory systems and that has received much theoretical attention. This synaptic plasticity is highly sensitive to correlations between pre- and postsynaptic firings. Thus, STDP is expected to play an important role in response to external asynchronous stimuli, which can induce segregative pre- and postsynaptic firings. In this paper, we study the impact of external asynchronous stimuli on the organization of structure and dynamics of neural networks through STDP. We construct a two-dimensional spatial neural network model with local connectivity and sparseness, and use external currents to stimulate alternately on different spatial layers. The adopted external currents imposed alternately on spatial layers can be here regarded as external asynchronous stimuli. Through extensive numerical simulations, we focus on the effects of stimulus number and inter-stimulus timing on synaptic connecting weights and the property of propagation dynamics in the resulting network structure. Interestingly, the resulting feedforward structure induced by stimulus-dependent asynchronous firings and its propagation dynamics reflect both the underlying property of STDP. The results imply a possible important role of STDP in generating feedforward structure and collective propagation activity required for experience-dependent map plasticity in developing in vivo sensory pathways and cortices. The relevance of the results to cue-triggered recall of learned temporal sequences, an important cognitive function, is briefly discussed as well. Furthermore, this finding suggests a potential

  10. Bone scanning in severe external otitis

    International Nuclear Information System (INIS)

    Levin, W.J.; Shary, J.H. III; Nichols, L.T.; Lucente, F.E.

    1986-01-01

    Technetium99 Methylene Diphosphate bone scanning has been considered an early valuable tool to diagnose necrotizing progressive malignant external otitis. However, to our knowledge, no formal studies have actually compared bone scans of otherwise young, healthy patients with severe external otitis to scans of patients with clinical presentation of malignant external otitis. Twelve patients with only severe external otitis were studied with Technetium99 Diphosphate and were compared to known cases of malignant otitis. All scans were evaluated by two neuroradiologists with no prior knowledge of the clinical status of the patients. Nine of the 12 patients had positive bone scans with many scans resembling those reported with malignant external otitis. Interestingly, there was no consistent correlation between the severity of clinical presentation and the amount of Technetium uptake. These findings suggest that a positive bone scan alone should not be interpreted as indicative of malignant external otitis

  11. Lysosomal ceramide generated by acid sphingomyelinase triggers cytosolic cathepsin B-mediated degradation of X-linked inhibitor of apoptosis protein in natural killer/T lymphoma cell apoptosis.

    Science.gov (United States)

    Taniguchi, M; Ogiso, H; Takeuchi, T; Kitatani, K; Umehara, H; Okazaki, T

    2015-04-09

    We previously reported that IL-2 deprivation induced acid sphingomyelinase-mediated (ASM-mediated) ceramide elevation and apoptosis in an NK/T lymphoma cell line KHYG-1. However, the molecular mechanism of ASM-ceramide-mediated apoptosis during IL-2 deprivation is poorly understood. Here, we showed that IL-2 deprivation induces caspase-dependent apoptosis characterized by phosphatidylserine externalization, caspase-8, -9, and -3 cleavage, and degradation of X-linked inhibitor of apoptosis protein (XIAP). IL-2 re-supplementation rescued apoptosis via inhibition of XIAP degradation without affecting caspase cleavage. However, IL-2 deprivation induced ceramide elevation via ASM in lysosomes and activated lysosomal cathepsin B (CTSB) but not cathepsin D. A CTSB inhibitor CA-074 Me and knockdown of CTSB inhibited ceramide-mediated XIAP degradation and apoptosis. Inhibition of ceramide accumulation in lysosomes using an ASM inhibitor, desipramine, decreased cytosolic activation of CTSB by inhibiting its transfer into cytosol from the lysosome. Knockdown of ASM also inhibited XIAP degradation and apoptosis. Furthermore, cell permeable N-acetyl sphingosine (C2-ceramide), which increases mainly endogenous d18:1/16:0 and d18:1/24:1 ceramide-like IL-2 deprivation, induced caspase-dependent apoptosis with XIAP degradation through CTSB. These findings suggest that lysosomal ceramide produced by ASM mediates XIAP degradation by activation of cytosolic CTSB and caspase-dependent apoptosis. The ASM-ceramide-CTSB signaling axis is a novel pathway of ceramide-mediated apoptosis in IL-2-deprived NK/T lymphoma cells.

  12. Metasurface external cavity laser

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Luyao, E-mail: luyaoxu.ee@ucla.edu; Curwen, Christopher A.; Williams, Benjamin S. [Department of Electrical Engineering, University of California, Los Angeles, California 90095 (United States); California NanoSystems Institute, University of California, Los Angeles, California 90095 (United States); Hon, Philip W. C.; Itoh, Tatsuo [Department of Electrical Engineering, University of California, Los Angeles, California 90095 (United States); Chen, Qi-Sheng [Northrop Grumman Aerospace Systems, Redondo Beach, California 90278 (United States)

    2015-11-30

    A vertical-external-cavity surface-emitting-laser is demonstrated in the terahertz range, which is based upon an amplifying metasurface reflector composed of a sub-wavelength array of antenna-coupled quantum-cascade sub-cavities. Lasing is possible when the metasurface reflector is placed into a low-loss external cavity such that the external cavity—not the sub-cavities—determines the beam properties. A near-Gaussian beam of 4.3° × 5.1° divergence is observed and an output power level >5 mW is achieved. The polarized response of the metasurface allows the use of a wire-grid polarizer as an output coupler that is continuously tunable.

  13. Detection of Apoptosis and Necrosis in Normal Human Lung Cells Using 1H NMR Spectroscopy

    Science.gov (United States)

    Shih, Chwen-Ming; Ko, Wun-Chang; Yang, Liang-Yo; Lin, Chien-Ju; Wu, Jui-Sheng; Lo, Tsui-Yun; Wang, Shwu-Huey; Chen, Chien-Tsu

    2005-05-01

    This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their types and the percentage of cell death were assessed on a flow cytometer. Cadmium (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells, respectively, as revealed by phosphatidylserine externalization on a flow cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm) to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the percentage of apoptosis and strongly and positively correlated with PI staining after Cd treatment (r2 = 0.9868, P In contrast, this ratio only increased slightly within 2-h Hg treatment, and longer Hg exposure failed to produce further increase. Following 2-h Hg exposure, the spectral intensity of choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel tool with a quantitative potential to distinguish apoptosis from necrosis as early as the onset of cell death in normal human lung cells.

  14. Ultrasound comparison of external and internal neck anatomy with the LMA Unique.

    Science.gov (United States)

    Lee, Steven M; Wojtczak, Jacek A; Cattano, Davide

    2017-12-01

    Internal neck anatomy landmarks and their relation after placement of an extraglottic airway devices have not been studied extensively by the use of ultrasound. Based on our group experience with external landmarks as well as internal landmarks evaluation with other techniques, we aimed use ultrasound to analyze the internal neck anatomy landmarks and the related changes due to the placement of the Laryngeal Mask Airway Unique. Observational pilot investigation. Non-obese adult patients with no evidence of airway anomalies, were recruited. External neck landmarks were measured based on a validated and standardized method by tape. Eight internal anatomical landmarks, reciprocal by the investigational hypothesis to the external landmarks, were also measured by ultrasound guidance. The internal landmarks were re-measured after optimal placement and inflation of the extraglottic airway devices cuff Laryngeal Mask Airway Unique. Six subjects were recruited. Ultrasound measurements of hyoid-mental distance, thyroid-cricoid distance, thyroid height, and thyroid width were found to be significantly ( p internal neck anatomy. The induced changes and respective specific internal neck anatomy landmarks could help to design devices that would modify their shape accordingly to areas of greatest displacement. Also, while external neck landmark measurements overestimate their respective internal neck landmarks, as we previously reported, the concordance of each measurement and their respective conversion factor could continue to be of help in sizing extraglottic airway devices. Due to the pilot nature of the study, more investigations are warranted.

  15. Antibodies to phosphatidylserine/prothrombin (aPS/PT) enhanced the diagnostic performance in Chinese patients with antiphospholipid syndrome.

    Science.gov (United States)

    Zhang, Shulan; Wu, Ziyan; Zhang, Wen; Zhao, Jiuliang; Norman, Gary L; Zeng, Xiaofeng; Zhang, Fengchun; Li, Yongzhe

    2018-03-21

    Increasing evidence has highlighted the role of non-criteria antiphospholipid antibodies (aPLs) as important supplements to the current criteria aPLs for the diagnosis of antiphospholipid syndrome (APS). In this retrospective study, we evaluated the clinical relevance of antibodies to phosphatidylserine/prothrombin (aPS/PT) in Chinese patients with APS. A total of 441 subjects were tested, including 101 patients with primary APS (PAPS), 140 patients with secondary APS (SAPS), 161 disease controls (DCs) and 39 healthy controls (HCs). Serum IgG/IgM aPS/PT was determined by ELISA. The levels of IgG/IgM aPS/PT were significantly increased in patients with APS compared with DCs and HCs. IgG and IgM aPS/PT were present in 29.7% and 54.5% of PAPS, and 42.1% and 53.6% of SAPS, respectively. For diagnosis of APS, IgG aCL exhibited the highest positive likelihood ratio (LR+) of 21.60, followed by LA (13.84), IgG aβ2GP1 (9.19) and IgG aPS/PT (8.49). aPS/PT was detected in 13.3% of seronegative PAPS patients and 31.3% of seronegative SAPS patients. LA exhibited the highest OR of 3.64 in identifying patients with thrombosis, followed by IgG aCL (OR, 2.63), IgG aPS/PT (OR, 2.55) and IgG aβ2GP1 (OR, 2.33). LA and IgG aCL were correlated with both arterial and venous thrombosis, whereas IgG aPS/PT and IgG aβ2GP1 correlated with venous or arterial thrombosis, respectively. Our findings suggest that the inclusion of IgG/IgM aPS/PT may enhance the diagnostic performance for APS, especially in those in whom APS is highly suspected, but conventional aPLs are repeatedly negative. In addition, IgG aPS/PT may contribute to identify patients at risk of thrombosis.

  16. Stability of aerosol droplets in Bessel beam optical traps under constant and pulsed external forces

    International Nuclear Information System (INIS)

    David, Grégory; Esat, Kıvanç; Hartweg, Sebastian; Cremer, Johannes; Chasovskikh, Egor; Signorell, Ruth

    2015-01-01

    We report on the dynamics of aerosol droplets in optical traps under the influence of additional constant and pulsed external forces. Experimental results are compared with simulations of the three-dimensional droplet dynamics for two types of optical traps, the counter-propagating Bessel beam (CPBB) trap and the quadruple Bessel beam (QBB) trap. Under the influence of a constant gas flow (constant external force), the QBB trap is found to be more stable compared with the CPBB trap. By contrast, under pulsed laser excitation with laser pulse durations of nanoseconds (pulsed external force), the type of trap is of minor importance for the droplet stability. It typically needs pulsed laser forces that are several orders of magnitude higher than the optical forces to induce escape of the droplet from the trap. If the droplet strongly absorbs the pulsed laser light, these escape forces can be strongly reduced. The lower stability of absorbing droplets is a result of secondary thermal processes that cause droplet escape

  17. Stability of aerosol droplets in Bessel beam optical traps under constant and pulsed external forces

    Energy Technology Data Exchange (ETDEWEB)

    David, Grégory; Esat, Kıvanç; Hartweg, Sebastian; Cremer, Johannes; Chasovskikh, Egor; Signorell, Ruth, E-mail: rsignorell@ethz.ch [Laboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, CH-8093 Zürich (Switzerland)

    2015-04-21

    We report on the dynamics of aerosol droplets in optical traps under the influence of additional constant and pulsed external forces. Experimental results are compared with simulations of the three-dimensional droplet dynamics for two types of optical traps, the counter-propagating Bessel beam (CPBB) trap and the quadruple Bessel beam (QBB) trap. Under the influence of a constant gas flow (constant external force), the QBB trap is found to be more stable compared with the CPBB trap. By contrast, under pulsed laser excitation with laser pulse durations of nanoseconds (pulsed external force), the type of trap is of minor importance for the droplet stability. It typically needs pulsed laser forces that are several orders of magnitude higher than the optical forces to induce escape of the droplet from the trap. If the droplet strongly absorbs the pulsed laser light, these escape forces can be strongly reduced. The lower stability of absorbing droplets is a result of secondary thermal processes that cause droplet escape.

  18. Stability of aerosol droplets in Bessel beam optical traps under constant and pulsed external forces.

    Science.gov (United States)

    David, Grégory; Esat, Kıvanç; Hartweg, Sebastian; Cremer, Johannes; Chasovskikh, Egor; Signorell, Ruth

    2015-04-21

    We report on the dynamics of aerosol droplets in optical traps under the influence of additional constant and pulsed external forces. Experimental results are compared with simulations of the three-dimensional droplet dynamics for two types of optical traps, the counter-propagating Bessel beam (CPBB) trap and the quadruple Bessel beam (QBB) trap. Under the influence of a constant gas flow (constant external force), the QBB trap is found to be more stable compared with the CPBB trap. By contrast, under pulsed laser excitation with laser pulse durations of nanoseconds (pulsed external force), the type of trap is of minor importance for the droplet stability. It typically needs pulsed laser forces that are several orders of magnitude higher than the optical forces to induce escape of the droplet from the trap. If the droplet strongly absorbs the pulsed laser light, these escape forces can be strongly reduced. The lower stability of absorbing droplets is a result of secondary thermal processes that cause droplet escape.

  19. Stability of aerosol droplets in Bessel beam optical traps under constant and pulsed external forces

    Science.gov (United States)

    David, Grégory; Esat, Kıvanç; Hartweg, Sebastian; Cremer, Johannes; Chasovskikh, Egor; Signorell, Ruth

    2015-04-01

    We report on the dynamics of aerosol droplets in optical traps under the influence of additional constant and pulsed external forces. Experimental results are compared with simulations of the three-dimensional droplet dynamics for two types of optical traps, the counter-propagating Bessel beam (CPBB) trap and the quadruple Bessel beam (QBB) trap. Under the influence of a constant gas flow (constant external force), the QBB trap is found to be more stable compared with the CPBB trap. By contrast, under pulsed laser excitation with laser pulse durations of nanoseconds (pulsed external force), the type of trap is of minor importance for the droplet stability. It typically needs pulsed laser forces that are several orders of magnitude higher than the optical forces to induce escape of the droplet from the trap. If the droplet strongly absorbs the pulsed laser light, these escape forces can be strongly reduced. The lower stability of absorbing droplets is a result of secondary thermal processes that cause droplet escape.

  20. Autapse-induced multiple stochastic resonances in a modular neuronal network

    Science.gov (United States)

    Yang, XiaoLi; Yu, YanHu; Sun, ZhongKui

    2017-08-01

    This study investigates the nontrivial effects of autapse on stochastic resonance in a modular neuronal network subjected to bounded noise. The resonance effect of autapse is detected by imposing a self-feedback loop with autaptic strength and autaptic time delay to each constituent neuron. Numerical simulations have demonstrated that bounded noise with the proper level of amplitude can induce stochastic resonance; moreover, the noise induced resonance dynamics can be significantly shaped by the autapse. In detail, for a specific range of autaptic strength, multiple stochastic resonances can be induced when the autaptic time delays are appropriately adjusted. These appropriately adjusted delays are detected to nearly approach integer multiples of the period of the external weak signal when the autaptic strength is very near zero; otherwise, they do not match the period of the external weak signal when the autaptic strength is slightly greater than zero. Surprisingly, in both cases, the differences between arbitrary two adjacent adjusted autaptic delays are always approximately equal to the period of the weak signal. The phenomenon of autaptic delay induced multiple stochastic resonances is further confirmed to be robust against the period of the external weak signal and the intramodule probability of subnetwork. These findings could have important implications for weak signal detection and information propagation in realistic neural systems.

  1. Externalities of fuel cycles 'ExternE' project. Hydro fuel cycle. Estimation of physical impacts and monetary valuation for priority impact pathways

    International Nuclear Information System (INIS)

    Navrud, S.; Riise, J.; Strand, J.

    1994-01-01

    The aim of the External Costs of Fuel Cycles (ExternE) study is to develop methods to measure and monetize all the externalities associated with incremental investments in electric power production, taking account of the different stages of the fuel cycles. Since fuel cycle externalities are characterised by being very site-specific, the impact pathway damage function approach, developed in ExternE, has been implemented in different European countries for each of the selected fuel cycles. This is done to demonstrate that this methodological framework can be used at different locations, to motivate further development of the methods, and to look at the sensitivity of the estimates to different locations. Electricite de France (EdF) in France and ENCO Environmental Consultants a.s. in Norway have taken on a joint responsibility for adapting the methodological framework for hydroelectric fuel cycle analyses in Europe. We report the first implementation of the hydroelectric fuel cycle within ExternE. Choice of reference site and technology Two stages of the hydroelectric fuel cycle have been identified: 1. Electricity generation 2. Transmission There are three phases of each of these stages: construction, operation and dismantling. We have assumed a construction period of 5 years (starting in 1990) and an operation period of 40 years. Dismantling after 40 years is not a realistic option. Therefore, we have focused on the construction and operation phases, of both electricity generation and transmission. The Sauda Hydroelectric Development Project (SHDP) was selected, because it illustrates upgrading and extention of an existing hydro power project. Such projects are likely to be the dominating strategy for future hydroelectric development in Norway, many other European countries and in the U.S., due to the lack of new sites available for development. SHDP consists of an extention of a previously developed area (Basis project) and six new diversion projects. The

  2. Structure-independent cross-validation between residual dipolar couplings originating from internal and external orienting media

    International Nuclear Information System (INIS)

    Barbieri, Renato; Bertini, Ivano; Lee, Yong-Min; Luchinat, Claudio; Velders, Aldrik H.

    2002-01-01

    Lanthanide-substituted calcium binding proteins are known to partially orient in high magnetic fields. Orientation provides residual dipolar couplings (rdc's). Two of these systems, Tm 3+ - and Dy 3+ -substituted calbindin D 9k , dissolved in an external orienting medium (nonionic liquid crystalline phase) provide rdc values which are the sum of those induced by the lanthanides and by the liquid crystalline phase on the native calcium binding protein. This structure-independent check shows the innocence of the orienting medium with respect to the structure of the protein in solution. Furthermore, the simultaneous use of lanthanide substitution and external orienting media provides a further effective tool to control and tune the orientation tensor

  3. Externalizing behaviors in preadolescents: familial risk to externalizing behaviors and perceived parenting styles.

    Science.gov (United States)

    Buschgens, Cathelijne J M; van Aken, Marcel A G; Swinkels, Sophie H N; Ormel, Johan; Verhulst, Frank C; Buitelaar, Jan K

    2010-07-01

    The aim was to investigate the contribution of familial risk to externalizing behaviors (FR-EXT), perceived parenting styles, and their interactions to the prediction of externalizing behaviors in preadolescents. Participants were preadolescents aged 10-12 years who participated in TRAILS, a large prospective population-based cohort study in the Netherlands (N = 2,230). Regression analyses were used to determine the relative contribution of FR-EXT and perceived parenting styles to parent and teacher ratings of externalizing behaviors. FR-EXT was based on lifetime parental externalizing psychopathology and the different parenting styles (emotional warmth, rejection, and overprotection) were based on the child's perspective. We also investigated whether different dimensions of perceived parenting styles had different effects on subdomains of externalizing behavior. We found main effects for FR-EXT (vs. no FR-EXT), emotional warmth, rejection, and overprotection that were fairly consistent across rater and outcome measures. More specific, emotional warmth was the most consistent predictor of all outcome measures, and rejection was a stronger predictor of aggression and delinquency than of inattention. Interaction effects were found for FR-EXT and perceived parental rejection and overprotection; other interactions between FR-EXT and parenting styles were not significant. Correlations between FR-EXT and perceived parenting styles were absent or very low and were without clinical significance. Predominantly main effects of FR-EXT and perceived parenting styles independently contribute to externalizing behaviors in preadolescents, suggesting FR-EXT and parenting styles to be two separate areas of causality. The relative lack of gene-environment interactions may be due to the epidemiological nature of the study, the preadolescent age of the subjects, the measurement level of parenting and the measurement level of FR-EXT, which might be a consequence of both genetic and

  4. Ratchet effect on a relativistic particle driven by external forces

    Energy Technology Data Exchange (ETDEWEB)

    Quintero, Niurka R [Departamento de Fisica Aplicada I, Escuela Universitaria Politecnica, Universidad de Sevilla, Calle Virgen de Africa 7, E-41011 Sevilla (Spain); Alvarez-Nodarse, Renato [Departamento de Analisis Matematico, Facultad de Matematicas, Universidad de Sevilla, Apdo 1160, E-41080 Sevilla (Spain); Cuesta, Jose A, E-mail: niurka@us.es, E-mail: ran@us.es, E-mail: cuesta@math.uc3m.es [Grupo Interdisciplinar de Sistemas Complejos (GISC), Departamento de Matematicas, Universidad Carlos III de Madrid, Avenida de la Universidad 30, E-28911 Leganes, Madrid (Spain)

    2011-10-21

    We study the ratchet effect of a damped relativistic particle driven by both asymmetric temporal bi-harmonic and time-periodic piecewise constant forces. This system can be formally solved for any external force, providing the ratchet velocity as a nonlinear functional of the driving force. This allows us to explicitly illustrate the functional Taylor expansion formalism recently proposed for this kind of systems. The Taylor expansion reveals particularly useful to obtain the shape of the current when the force is periodic, piecewise constant. We also illustrate the somewhat counterintuitive effect that introducing damping may induce a ratchet effect. When the force is symmetric under time-reversal and the system is undamped, under symmetry principles no ratchet effect is possible. In this situation increasing damping generates a ratchet current which, upon increasing the damping coefficient eventually reaches a maximum and decreases toward zero. We argue that this effect is not specific of this example and should appear in any ratchet system with tunable damping driven by a time-reversible external force. (paper)

  5. Ratchet effect on a relativistic particle driven by external forces

    International Nuclear Information System (INIS)

    Quintero, Niurka R; Alvarez-Nodarse, Renato; Cuesta, Jose A

    2011-01-01

    We study the ratchet effect of a damped relativistic particle driven by both asymmetric temporal bi-harmonic and time-periodic piecewise constant forces. This system can be formally solved for any external force, providing the ratchet velocity as a nonlinear functional of the driving force. This allows us to explicitly illustrate the functional Taylor expansion formalism recently proposed for this kind of systems. The Taylor expansion reveals particularly useful to obtain the shape of the current when the force is periodic, piecewise constant. We also illustrate the somewhat counterintuitive effect that introducing damping may induce a ratchet effect. When the force is symmetric under time-reversal and the system is undamped, under symmetry principles no ratchet effect is possible. In this situation increasing damping generates a ratchet current which, upon increasing the damping coefficient eventually reaches a maximum and decreases toward zero. We argue that this effect is not specific of this example and should appear in any ratchet system with tunable damping driven by a time-reversible external force. (paper)

  6. Externalities of energy and atomic power

    International Nuclear Information System (INIS)

    2006-09-01

    Energy technology ensures not only energy supply but also has great impacts on society and environments. Economical value and effect evaluation alone doesn't mean appropriate so the evaluation of 'externalities' should be appreciated. In order to assess atomic power in this context, the Atomic Energy Society of Japan set up a research committee on 'externalities of energy and atomic power' from April 2002 to March 2006, whose activities were described in this report. In addition to environmental effects and environmental externalities, four areas were newly studied as follows: (1) biological effects of low dose rate exposure and externalities, (2) externalities as social/economical effects including stable supply and security, (3) energy technologies evaluation and (4) social choice and decision-making. (T. Tanaka)

  7. The External Mind

    DEFF Research Database (Denmark)

    , Extended Mind and Distributed Cognition by Claudio Paolucci pp. 69-96 The Social Horizon of Embodied Language and Material Symbols by Riccardo Fusaroli pp. 97-123 Semiotics and Theories of Situated/Distributed Action and Cognition: a Dialogue and Many Intersections by Tommaso Granelli pp. 125-167 Building......The External Mind: an Introduction by Riccardo Fusaroli, Claudio Paolucci pp. 3-31 The sign of the Hand: Symbolic Practices and the Extended Mind by Massimiliano Cappuccio, Michael Wheeler pp. 33-55 The Overextended Mind by Shaun Gallagher pp. 57-68 The "External Mind": Semiotics, Pragmatism...

  8. In situ analysis of human teeth by external PIXE

    Energy Technology Data Exchange (ETDEWEB)

    Rautray, Tapash R., E-mail: tapash77@hotmail.co [Department of Dental Biomaterials, School of Dentistry, Kyungpook National University, 2-188-1 Samduk-dong, Jung-gu, Daegu (Korea, Republic of); ARASMIN, G. Udayagiri, Kandhamal, Orissa 762100 (India); Das, Saubhagyalaxmi [Institute of Physics, Sachivalaya Marg, Bhubaneswar 751005 (India); Rautray, Alekh C. [ARASMIN, G. Udayagiri, Kandhamal, Orissa 762100 (India)

    2010-07-15

    The elemental profiles of the enamel, cementum and caries of human teeth were analysed by the external proton induced X-ray emission studies. Ten elements namely P, Ca, V, Mn, Fe, Cu, Zn, As, Sr and Pb were estimated in the present study. P and Ca were found to be the major elements whereas all other elements were found in trace level. It was observed that the respective concentrations of elements namely P, Ca, Fe, Zn and Pb in enamel are more than those in cementum. Concentration of P ranged between 6.37% and 25% whereas Ca ranged between 12.94% and 43.36%.

  9. The effect of sodium ions on the light-induced 86Rb release from the isolated crayfish retina

    International Nuclear Information System (INIS)

    Hartung, K.; Stieve, H.

    1980-01-01

    The effect of low external Na + concentrations on the light-induced K + release from crayfish photoreceptor cells was tested by labelling intracellular K + with the isotope 86 Rb. The amount of isotope released per light, stimulus is roughly proportional to the external Na + concentration if the osmolarity is kept constant by replacing Na + with Tris, choline or sucrose. When sucrose is used to replace the depleted Na + the light-induced K + release is a linear function of the external Na + concentration and is reduced by approx. 95% at an external Na + concentration of 5 mmol/l. For choline and Tris substitutions the relationships are less clear but at Na + concentrations + release is smaller in a Tris solution and larger in a choline solution. It is suggested that the light-induced K + release is due mainly to an activation of voltage sensitive K + channels. (orig.)

  10. Effects of external feedback about body tilt: Influence on the Subjective Proprioceptive Horizon.

    Science.gov (United States)

    Bringoux, L; Bourdin, C; Nougier, V; Raphel, C

    2006-11-06

    The present study investigated a cognitive aspect upon spatial perception, namely the impact of a true or false verbal feedback (FB) about the magnitude of body tilt on Subjective Proprioceptive Horizon (SPH) estimates. Subjects were asked to set their extended arm normal to gravity for different pitch body tilts up to 9 degrees . True FB were provided at all body tilt angles, whereas false FB were provided only at 6 degrees backward and 6 degrees forward body tilts for half of the trials. Our data confirmed previous results about the egocentric influence of body tilt itself upon SPH: estimates were linearly lowered with forward tilts and elevated with backward tilts. In addition, results showed a significant effect of the nature of the external FB provided to the subjects. When subjects received a false FB inducing a 3 degrees forward bias relative to physical body tilt, they set their SPH consequently higher than when they received a false FB inducing a 3 degrees backward bias. These findings clearly indicated that false cognitive information about body tilt might significantly modify the judgement of a geocentric direction of space, such as the SPH. This may have deleterious repercussions in aeronautics when pilots have to localize external objects relative to earth-based directions in darkened environments.

  11. Effective response of nonlinear cylindrical coated composites under external AC and DC electric field

    International Nuclear Information System (INIS)

    Yu-Yan, Shen; Xiao-Gang, Chen; Wei, Cui; Yan-Hua, Hao; Qian-Qian, Li

    2009-01-01

    This paper uses the perturbation method to study effective response of nonlinear cylindrical coated composites. Under the external AC and DC electric field E a (1 + sin ωt), the local potentials of composites at all harmonic frequencies are induced. An effective nonlinear response to composite is given for the cylindrical coated inclusions in the dilute limit. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  12. Scattering and radiative properties of semi-external versus external mixtures of different aerosol types

    International Nuclear Information System (INIS)

    Mishchenko, Michael I.; Liu Li; Travis, Larry D.; Lacis, Andrew A.

    2004-01-01

    The superposition T-matrix method is used to compute the scattering of unpolarized light by semi-external aerosol mixtures in the form of polydisperse, randomly oriented two-particle clusters with touching components. The results are compared with those for composition-equivalent external aerosol mixtures, in which the components are widely separated and scatter light in isolation from each other. It is concluded that aggregation is likely to have a relatively weak effect on scattering and radiative properties of two-component tropospheric aerosols and can be replaced by the much simpler external-mixture model in remote sensing studies and atmospheric radiation balance computations

  13. External costs of electricity

    International Nuclear Information System (INIS)

    Rabl, A.; Spadaro, J.V.

    2005-01-01

    This article presents a synthesis of the ExternE project (External costs of Energy) of the European community about the external costs of power generation. Pollution impacts are calculated using an 'impact pathways' analysis, i.e. an analysis of the emission - dispersion - dose-response function - cost evaluation chain. Results are presented for different fuel cycles (with several technological variants) with their confidence intervals. The environmental impact costs are particularly high for coal: for instance, in France, for coal-fired power plants it is of the same order as the electricity retail price. For natural gas, this cost is about a third of the one for coal. On the contrary, the environmental impact costs for nuclear and renewable energies are low, typically of few per cent of the electricity price. The main part of these costs corresponds to the sanitary impacts, in particular the untimely mortality. In order to avoid any controversy about the cost evaluation of mortality, the reduction of the expectation of life due to the different fuel cycles is also indicated and the risks linked with nuclear energy are presented using several comparisons. (J.S.)

  14. Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation.

    Science.gov (United States)

    Rocha, Sandra M; Saraiva, Tatiana; Cristóvão, Ana C; Ferreira, Raquel; Santos, Tiago; Esteves, Marta; Saraiva, Cláudia; Je, Goun; Cortes, Luísa; Valero, Jorge; Alves, Gilberto; Klibanov, Alexander; Kim, Yoon-Seong; Bernardino, Liliana

    2016-06-04

    Histamine is an amine widely known as a peripheral inflammatory mediator and as a neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts as an innate modulator of microglial activity. Herein, we aimed to disclose the role of histamine in microglial phagocytic activity and reactive oxygen species (ROS) production and to explore the consequences of histamine-induced neuroinflammation in dopaminergic (DA) neuronal survival. The effect of histamine on phagocytosis was assessed both in vitro by using a murine N9 microglial cell line and primary microglial cell cultures and in vivo. Cells were exposed to IgG-opsonized latex beads or phosphatidylserine (PS) liposomes to evaluate Fcγ or PS receptor-mediated microglial phagocytosis, respectively. ROS production and protein levels of NADPH oxidases and Rac1 were assessed as a measure of oxidative stress. DA neuronal survival was evaluated in vivo by counting the number of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) of mice. We found that histamine triggers microglial phagocytosis via histamine receptor 1 (H1R) activation and ROS production via H1R and H4R activation. By using apocynin, a broad NADPH oxidase (Nox) inhibitor, and Nox1 knockout mice, we found that the Nox1 signaling pathway is involved in both phagocytosis and ROS production induced by histamine in vitro. Interestingly, both apocynin and annexin V (used as inhibitor of PS-induced phagocytosis) fully abolished the DA neurotoxicity induced by the injection of histamine in the SN of adult mice in vivo. Blockade of H1R protected against histamine-induced Nox1 expression and death of DA neurons in vivo. Overall, our results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson's disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia-induced

  15. Helmet-induced headache among Danish military personnel.

    Science.gov (United States)

    Rahmani, Zakia; Kochanek, Aneta; Astrup, Jesper Johnsen; Poulsen, Jeppe Nørgaard; Gazerani, Parisa

    2017-12-01

    External compression headache is defined as a headache caused by an external physical compression applied on the head. It affects about 4% of the general population; however, certain populations (e.g. construction workers and military personnel) with particular needs of headwear or helmet are at higher risk of developing this type of headache. External compression headache is poorly studied in relation to specific populations. This study aimed to investigate the prevalence and pattern of helmet-induced external compression headache among Danish military personnel of the Northern Jutland region in Denmark. Data acquisition was based on a custom-made questionnaire delivered to volunteers who used helmets in the Danish military service and who agreed to participate in this study. The military of the Northern Jutland region of Denmark facilitated recruitment of the participants. The questionnaires were delivered on paper and the collected (anonymous) answers (total 279) were used for further analysis. About 30% of the study participants reported headache in relation to wearing a military helmet. Headache was defined as a pressing pain predominantly in the front of the head with an average intensity of 4 on a visual analogue scale of 0 (no pain) to 10 (worst pain imaginable). It was also found that helmets with different designs influenced both the occurrence of headache and its characteristics. This study is the first to demonstrate the prevalence and pattern of compression headache among military personnel in North Jutland, Denmark. The findings of this study call for further attention to helmet-induced external compression headache and strategies to minimize the burden.

  16. Intrathecal dihydroergotamine inhibits capsaicin-induced vasodilatation in the canine external carotid circulation via GR127935- and rauwolscine-sensitive receptors.

    Science.gov (United States)

    Marichal-Cancino, Bruno A; González-Hernández, Abimael; Manrique-Maldonado, Guadalupe; Ruiz-Salinas, Inna I; Altamirano-Espinoza, Alain H; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

    2012-10-05

    It has been suggested that during a migraine attack trigeminal nerves release calcitonin gene-related peptide (CGRP), producing central nociception and vasodilatation of cranial arteries, including the extracranial branches of the external carotid artery. Since trigeminal inhibition may prevent this vasodilatation, the present study has investigated the effects of intrathecal dihydroergotamine on the external carotid vasodilatation to capsaicin, α-CGRP and acetylcholine. Anaesthetized vagosympathectomized dogs were prepared to measure blood pressure, heart rate and external carotid conductance. A catheter was inserted into the right common carotid artery for the continuous infusion of phenylephrine (to restore the carotid vascular tone), whereas the corresponding thyroid artery was cannulated for one-min intracarotid infusions of capsaicin, α-CGRP and acetylcholine (which dose-dependently increased the external carotid conductance). Another cannula was inserted intrathecally (C(1)-C(3)) for the administration of dihydroergotamine, the α(2)-adrenoceptor antagonist rauwolscine or the serotonin 5-HT(1B/1D) receptor antagonist GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide hydrochloride monohydrate). Intrathecal dihydroergotamine (10, 31 and 100μg) inhibited the vasodilatation to capsaicin, but not that to α-CGRP or acetylcholine. This inhibition was: (i) unaffected by 10μg GR127935 or 100μg rauwolscine, but abolished by 31μg GR127935 or 310μg rauwolscine at 10μg dihydroergotamine; and (ii) abolished by the combination 10μg GR127935+100μg rauwolscine at 100μg dihydroergotamine. Thus, intrathecal (C(1)-C(3)) dihydroergotamine seems to inhibit the external carotid vasodilatation to capsaicin by spinal activation of serotonin 5-HT(1B/1D) (probably 5-HT(1B)) receptors and α(2) (probably α(2A/2C))-adrenoceptors. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. External effects in Swiss hydropower

    International Nuclear Information System (INIS)

    Hauenstein, W.; Bonvin, J.; Vouillamoz, J.

    1999-01-01

    The article discusses the external costs and benefits of hydropower that are not internalised in normal book-keeping. Several negative and positive effects are discussed. The results of a study that addressed the difficult task of quantifying these external effects are presented. An assessment of the results gained shows that difficulties are to be met regarding system limits, methods of expressing the effects in monetary terms and ethical factors. The report also examines the consideration of external effects as a correction factor for falsified market prices for electricity

  18. Characteristics of anomalous Hall effect in spin-polarized two-dimensional electron gases in the presence of both intrinsic, extrinsic, and external electric-field induced spin—orbit couplings

    International Nuclear Information System (INIS)

    Liu Song; Yan Yu-Zhen; Hu Liang-Bin

    2012-01-01

    The various competing contributions to the anomalous Hall effect in spin-polarized two-dimensional electron gases in the presence of both intrinsic, extrinsic and external electric-field induced spin—orbit coupling were investigated theoretically. Based on a unified semiclassical theoretical approach, it is shown that the total anomalous Hall conductivity can be expressed as the sum of three distinct contributions in the presence of these competing spin—orbit interactions, namely an intrinsic contribution determined by the Berry curvature in the momentum space, an extrinsic contribution determined by the modified Bloch band group velocity and an extrinsic contribution determined by spin—orbit-dependent impurity scattering. The characteristics of these competing contributions are discussed in detail in the paper. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  19. Lumbar lordosis angle and trunk and lower-limb electromyographic activity comparison in hip neutral position and external rotation during back squats.

    Science.gov (United States)

    Oshikawa, Tomoki; Morimoto, Yasuhiro; Kaneoka, Koji

    2018-03-01

    [Purpose] To compare the lumbar lordosis angle and electromyographic activities of the trunk and lower-limb muscles in the hip neutral position and external rotation during back squats. [Subjects and Methods] Ten healthy males without severe low back pain or lower-limb injury participated in this study. The lumbar lordosis angle and electromyographic activities were measured using three-dimensional motion-capture systems and surface electrodes during four back squats: parallel back squats in the hip neutral position and external rotation and full back squats in the hip neutral position and external rotation. A paired t-test was used to compare parallel and full back squats measurements in the hip neutral position and external rotation, respectively. [Results] During parallel back squats, the average lumbar lordosis angle was significantly larger in hip external rotation than in the hip neutral position. During full back squats, lumbar erector spinae and multifidus activities were significantly lower in hip external rotation than in the hip neutral position, whereas gluteus maximus activity was significantly higher in hip external rotation than in the hip neutral position. [Conclusion] The back squat in hip external rotation induced improvement of lumbar kyphosis, an increasing of the gluteus maximus activity and a decrease of both lumbar erector spinae and multifidus activities.

  20. Normal tissue tolerance to external beam radiation therapy: Esophagus

    International Nuclear Information System (INIS)

    Bera, G.; Pointreau, Y.; Denis, F.; Dupuis, O.; Orain, I.; Crehange, G.

    2010-01-01

    The esophagus is a musculo-membranous tube through which food passes from the pharynx to the stomach. Due to its anatomical location, it can be exposed to ionizing radiation in many external radiotherapy indications. Radiation-induced esophageal mucositis is clinically revealed by dysphagia and odynophagia, and usually begins 3 to 4 weeks after the start of radiation treatment. With the rise of multimodality treatments (e.g., concurrent chemoradiotherapy, dose escalation and accelerated fractionation schemes), esophageal toxicity has become a significant dose-limiting issue. Understanding the predictive factors of esophageal injury may improve the optimal delivery of treatment plans. It may help to minimize the risks, hence increasing the therapeutic ratio. Based on a large literature review, our study describes both early and late radiation-induced esophageal injuries and highlights some of the predictive factors for cervical and thoracic esophagus toxicity. These clinical and dosimetric parameters are numerous but none is consensual. The large number of dosimetric parameters strengthens the need of an overall analysis of the dose/volume histograms. The data provided is insufficient to recommend their routine use to prevent radiation-induced esophagitis. Defining guidelines for the tolerance of the esophagus to ionizing radiation remains essential for a safe and efficient treatment. (authors)

  1. Hysteresis-induced bifurcation and chaos in a magneto-rheological suspension system under external excitation

    International Nuclear Information System (INIS)

    Zhang Hailong; Zhang Ning; Wang Enrong; Min Fuhong

    2016-01-01

    The magneto-rheological damper (MRD) is a promising device used in vehicle semi-active suspension systems, for its continuous adjustable damping output. However, the innate nonlinear hysteresis characteristic of MRD may cause the nonlinear behaviors. In this work, a two-degree-of-freedom (2-DOF) MR suspension system was established first, by employing the modified Bouc–Wen force–velocity (F–v) hysteretic model. The nonlinear dynamic response of the system was investigated under the external excitation of single-frequency harmonic and bandwidth-limited stochastic road surface. The largest Lyapunov exponent (LLE) was used to detect the chaotic area of the frequency and amplitude of harmonic excitation, and the bifurcation diagrams, time histories, phase portraits, and power spectrum density (PSD) diagrams were used to reveal the dynamic evolution process in detail. Moreover, the LLE and Kolmogorov entropy (K entropy) were used to identify whether the system response was random or chaotic under stochastic road surface. The results demonstrated that the complex dynamical behaviors occur under different external excitation conditions. The oscillating mechanism of alternating periodic oscillations, quasi-periodic oscillations, and chaotic oscillations was observed in detail. The chaotic regions revealed that chaotic motions may appear in conditions of mid-low frequency and large amplitude, as well as small amplitude and all frequency. The obtained parameter regions where the chaotic motions may appear are useful for design of structural parameters of the vibration isolation, and the optimization of control strategy for MR suspension system. (paper)

  2. Internal and External Readings of Same

    DEFF Research Database (Denmark)

    Hardt, Daniel

    2016-01-01

    Same is an anaphoric element that performs a comparison, which can either be external or internal to a sentence. Hardt and Mikkelsen (2015) show that same, unlike other anaphoric expressions, imposes a parallelism constraint, and they present three types of examples showing that same...... is infelicitous in the absence of parallelism. Hardt and Mikkelsen propose an account that applies uniformly to internal and external readings; however, the evidence they present largely targets external readings – they don’t offer empirical evidence that clearly supports the uniform approach. Furthermore, Barker...... (2007) argues that internal readings must be treated differently than external readings. In this paper, I show that the parallelism effects observed by Hardt and Mikkelsen in fact apply to internal readings as well. This provides support for a uniform treatment of internal and external readings of same...

  3. Externality or sustainability economics?

    International Nuclear Information System (INIS)

    Bergh, Jeroen C.J.M. van den

    2010-01-01

    In an effort to develop 'sustainability economics' Baumgaertner and Quaas (2010) neglect the central concept of environmental economics-'environmental externality'. This note proposes a possible connection between the concepts of environmental externality and sustainability. In addition, attention is asked for other aspects of 'sustainability economics', namely the distinction weak/strong sustainability, spatial sustainability and sustainable trade, distinctive sustainability policy, and the ideas of early 'sustainability economists'. I argue that both sustainability and externalities reflect a systems perspective and propose that effective sustainability solutions require that more attention is given to system feedbacks, notably other-regarding preferences and social interactions, and energy and environmental rebound. The case of climate change and policy is used to illustrate particular statements. As a conclusion, a list of 20 insights and suggestions for research is offered. (author)

  4. Why not to treat the tooth canal to solve external root resorptions? Here are the principles!

    Directory of Open Access Journals (Sweden)

    Alberto Consolaro

    Full Text Available ABSTRACT This paper aims at exposing the foundations or reasons why, in cases of external tooth resorption, including those of orthodontic origin, one should not perform a root canal to treat it. That should be done only to teeth with contamination or pulp necrosis, to remove the periapical inflammation induced by microbial products. When facing cases of external tooth resorption, one's conduct must always respect the following sequence of steps: first of all, identifying the cause accurately; then, planning the therapeutic approach and, finally, adopting the conducts in a very well-founded way. The situations in which endodontic treatment is recommended for tooth resorptions are those when there are: a pulp necrosis with microbial contamination, b aseptic pulp necrosis, c developing calcific metamorphosis of the pulp and d diagnosis of internal resorption. It is not possible, through the pulp, to control the resorption process that is taking place in the external part, after all, the causes are acting in the periodontal ligament. There is no evidence that justifies applying endodontic treatment, by means of root canal, to control external resorption processes, when the pulp shows vitality.

  5. Comfort and acceptability of various immobilization positions using a shoulder external rotation and abduction brace.

    Science.gov (United States)

    Hatta, Taku; Yamamoto, Nobuyuki; Sano, Hirotaka; Itoi, Eiji

    2017-03-01

    Immobilization with shoulder braces is used for conservative treatment of an initial shoulder dislocation. Various arm positions have been investigated to determine optimal position in terms of the anatomical reduction of the Bankart lesion. Recently, the effect of immobilization in shoulder abduction as well as in external rotation has been reported. However, there are few studies assessing subjects' acceptability of the brace in various arm positions. We hypothesized that a certain arm position regarding abduction or external rotation for immobilization would induce significant discomfort during activities of daily living. A dominant arm of 20 healthy participants was immobilized with a shoulder brace in 4 different positions; adduction and internal rotation (Add-IR), adduction and external rotation (Add-ER), 30° of abduction and 30° of external rotation (Abd-30ER), and 30° of abduction and 60° of external rotation (Abd-60ER). After completing immobilization for 24 h, subjects were asked to assess the discomfort of bracing for overall and individual activities, using a visual analogue scale. Data were compared among the four positions. For overall activities and several activities (eating, reading books, and removing and putting on pants), Abd-60ER was significantly more uncomfortable than adducted arm positions. Abd-30ER did not show any differences compared to the other arm positions. Immobilization in abduction and external rotation seems to be acceptable although the arm position in 30° of abduction and 60° of external rotation is less comfortable than the others. Our results might be useful in determining and developing the ideal shoulder brace which could keep patients' compliance and improve their outcomes. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  6. Retrofitting Systems for External Walls

    DEFF Research Database (Denmark)

    Rose, Jørgen

    1997-01-01

    In this report, 9 different external and internal retrofitting systems are analyzed using numerical calculations. The analysis focuses on the thermal bridge effects in the different systems, and on this basis it is discussed whether internal or external retrofitting has the most advantages...

  7. New cooperative mechanisms of low-energy nuclear reactions using super low-energy external field

    International Nuclear Information System (INIS)

    Gareev, F.A.; Zhidkova, I.E.

    2006-01-01

    We propose a new mechanism of LENR: cooperative processes in the whole system, nuclei + atoms + condensed matter, can occur at a smaller threshold energies than the corresponding ones on free constituents. The cooperative processes can be induced and enhanced by low-energy external fields. The excess heat is the emission of internal energy and transmutations at LENR are the result of redistribution of inner energy of the whole system. (author)

  8. New Cooperative Mechanisms of Low-Energy Nuclear Reactions Using Super Low-Energy External Field

    Science.gov (United States)

    Gareev, F. A.; Zhidkova, I. E.

    We propose a new mechanism of LENR: cooperative processes in the whole system, nuclei + atoms + condensed matter, can occur at a smaller threshold energies than the corresponding ones on free constituents. The cooperative processes can be induced and enhanced by low-energy external fields. The excess heat is the emission of internal energy and transmutations at LENR are the result of redistribution of inner energy of the whole system.

  9. Risk analysis of external radiation therapy

    International Nuclear Information System (INIS)

    Arvidsson, Marcus

    2011-09-01

    External radiation therapy is carried out via a complex treatment process in which many different groups of staff work together. Much of the work is dependent on and in collaboration with advanced technical equipment. The purpose of the research task has been to identify a process for external radiation therapy and to identify, test and analyze a suitable method for performing risk analysis of external radiation therapy

  10. Productivity Change and Externalities

    DEFF Research Database (Denmark)

    Kravtsova, Victoria

    2014-01-01

    This paper contributes to the analysis of the impact of externalities on the host country's total factor productivity by taking into account different dimensions of spillover effects. Namely, engagement in exporting and foreign ownership is generally perceived as being beneficial to individual...... firms and the economy as a whole. The approach used in the current research accounts for different internal as well as external factors that individual firms face and evaluates the effect on changes in productivity, technology as well as the efficiency of domestic firms. The empirical analysis focuses...... on Hungary. While the country leads the group of post-socialist countries in the amount of attracted foreign direct investments (FDI) the effect of this policy on the economy remains unclear. The research finds that different externalities play a different role in productivity, technological and efficiency...

  11. Statin-induced autoimmune necrotizing myositis

    Directory of Open Access Journals (Sweden)

    Katarzyna Ząber

    2016-02-01

    Full Text Available Myositides comprise a large group of disorders involving limb muscle weakness. In differential diagnosis we have to consider idiopathic myositides, myositides associated with other diseases, and those induced by external factors, e.g. drug-induced. Statins are commonly used drugs, but many patients experience a broad spectrum of adverse effects including symptoms from skeletal muscle. Physicians should pay special attention to patients reporting muscle weakness lasting longer than 12 weeks, despite statin withdrawal, as well as other symptoms: dysphagia, disturbed grip function, elevated creatinine kinase (CK levels and abnormal electromyography. The reported case deals with the problem of differential diagnosis of drug-induced muscle injury, polymyositis with a recently reported myopathy – statin-induced autoimmune necrotizing myositis, related to anti-HMGCR antibodies.

  12. Externalizing behaviors in preadolescents: familial risk to externalizing behaviors and perceived parenting styles

    OpenAIRE

    2009-01-01

    Abstract The aim was to investigate the contribution of familial risk to externalizing behaviors (FR-EXT), perceived parenting styles, and their interactions to the prediction of externalizing behaviors in preadolescents. Participants were preadolescents aged 10?12 years who participated in TRAILS, a large prospective population-based cohort study in the Netherlands (N = 2,230). Regression analyses were used to determine the relative contribution of FR-EXT and perceived parenting s...

  13. External coating of colonic anastomoses

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Achiam, Michael Patrick; Rosenberg, Jacob

    2012-01-01

    Colon anastomotic leakage remains both a frequent and serious complication in gastrointestinal surgery. External coating of colonic anastomoses has been proposed as a means to lower the rate of this complication. The aim of this review was to evaluate existing studies on external coating of colonic...

  14. Inverse kinetics for subcritical systems with external neutron source

    International Nuclear Information System (INIS)

    Carvalho Gonçalves, Wemerson de; Martinez, Aquilino Senra; Carvalho da Silva, Fernando

    2017-01-01

    Highlights: • It was developed formalism for reactivity calculation. • The importance function is related to the system subcriticality. • The importance function is also related with the value of the external source. • The equations were analyzed for seven different levels of sub criticality. • The results are physically consistent with others formalism discussed in the paper. - Abstract: Nuclear reactor reactivity is one of the most important properties since it is directly related to the reactor control during the power operation. This reactivity is influenced by the neutron behavior in the reactor core. The time-dependent neutrons behavior in response to any change in material composition is important for the reactor operation safety. Transient changes may occur during the reactor startup or shutdown and due to accidental disturbances of the reactor operation. Therefore, it is very important to predict the time-dependent neutron behavior population induced by changes in neutron multiplication. Reactivity determination in subcritical systems driven by an external neutron source can be obtained through the solution of the inverse kinetics equation for subcritical nuclear reactors. The main purpose of this paper is to find the solution of the inverse kinetics equation the main purpose of this paper is to device the inverse kinetics equations for subcritical systems based in a previous paper published by the authors (Gonçalves et al., 2015) and by (Gandini and Salvatores, 2002; Dulla et al., 2006). The solutions of those equations were also obtained. Formulations presented in this paper were tested for seven different values of k eff with external neutrons source constant in time and for a powers ratio varying exponentially over time.

  15. The EPR-a comprehensive design concept against external events

    International Nuclear Information System (INIS)

    Waas, U.; Stoll, U.

    2005-01-01

    The main objective of design provisions against external hazards is to ensure that the safety functions required to bring the plant to safe shutdown are not inadmissible affected. In the design of the EPR particular attention was paid to the following external hazards: Earthquake, Airplane crash, Explosion pressure wave. The design concept for these events is discussed below. The standard EPR covers a large range of possible site conditions, the design earthquake enveloping safe shutdown earthquakes (SSE) to be expected for potential sites. The Basic Design was developed for the seismic loads given in the European Utility Requirements with a horizontal free field Peak Ground Acceleration (PGA) for all site conditions of 0.25 g. The seismic protection is based on a deterministic design approach, with the intention of ensuring the safety functions in case of SSE. The loads for the design basis airplane crash and - if required - for the design extension airplane crash are defined depending on site specific requirements. For the design basis airplane crash as defined in Finland the safety goals are fulfilled for postulated single failure and preventive maintenance as well as for specific unlikely scenarios with local impacts where one redundant train is assumed to be lost. For the design extension airplane crash no single failure and preventive maintenance are assumed. Reactor building (RB), fuel building (FB), safeguard building (SB) 2 and 3 are protected by design against airplane crash. The common base mat of the RB, FB and SBs ensures global stability. To avoid penetration the wall thickness of the outer building structures of RB, FB and SB2/3 is set at 1.80 m (result of an optimization process). To rule out major induced vibrations due to airplane crash the inner building structures are decoupled from the outer walls. The SB 1 and SB4, the main steam and feedwater valve compartments, the diesel buildings and the service water pump buildings are protected against

  16. Development of a real-time internal and external marker tracking system for particle therapy: a phantom study using patient tumor trajectory data.

    Science.gov (United States)

    Cho, Junsang; Cheon, Wonjoong; Ahn, Sanghee; Jung, Hyunuk; Sheen, Heesoon; Park, Hee Chul; Han, Youngyih

    2017-09-01

    Target motion-induced uncertainty in particle therapy is more complicated than that in X-ray therapy, requiring more accurate motion management. Therefore, a hybrid motion-tracking system that can track internal tumor motion and as well as an external surrogate of tumor motion was developed. Recently, many correlation tests between internal and external markers in X-ray therapy have been developed; however, the accuracy of such internal/external marker tracking systems, especially in particle therapy, has not yet been sufficiently tested. In this article, the process of installing an in-house hybrid internal/external motion-tracking system is described and the accuracy level of tracking system was acquired. Our results demonstrated that the developed in-house external/internal combined tracking system has submillimeter accuracy, and can be clinically used as a particle therapy system as well as a simulation system for moving tumor treatment. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  17. The Action of Red Cell Calcium Ions on Human Erythrophagocytosis in Vitro

    Directory of Open Access Journals (Sweden)

    Pedro J. Romero

    2017-12-01

    Full Text Available In the present work we have studied in vitro the effect of increasing red cell Ca2+ ions on human erythrophagocytosis by peripheral monocyte-derived autologous macrophages. In addition, the relative contribution to phagocytosis of phosphatidylserine exposure, autologous IgG binding, complement deposition and Gárdos channel activity was also investigated. Monocytes were obtained after ficoll-hypaque fractionation and induced to transform by adherence to glass coverslips, for 24 h at 37°C in a RPMI medium, containing 10% fetal calf serum. Red blood cells (RBC were loaded with Ca2+ using 10 μM A23187 and 1 mM Ca-EGTA buffers, in the absence of Mg2+. Ca2+-loaded cells were transferred to above coverslips and incubated for 2 h at 37°C under various experimental conditions, after which phagocytosis was assessed by light microscopy. Confirming earlier findings, phagocytosis depended on internal Ca2+. Accordingly; it was linearly raised from about 2–15% by increasing the free Ca2+ content of the loading solution from 0.5 to 20 μM, respectively. Such a linear increase was virtually doubled by the presence of 40% autologous serum. At 7 μM Ca2+, the phagocytosis degree attained with serum was practically equal to that obtained with either 2 mg/ml affinity-purified IgG or 40% IgG-depleted serum. However, phagocytosis was reduced to levels found with Ca2+ alone when IgG-depleted serum was inactivated by heat, implying an involvement of complement. On the other hand, phagocytosis in the absence of serum was markedly reduced by preincubating macrophages with phosphatidylserine-containing liposomes. In contrast, a similar incubation in the presence of serum affected it partially whereas employing liposomes made only of phosphatidylcholine essentially had no effect. Significantly, the Gárdos channel inhibitors clotrimazole (2 μM and TRAM-34 (100 nM fully blocked serum-dependent phagocytosis. These findings show that a raised internal Ca2+ promotes

  18. Current status and issues of external event PSA for extreme natural hazards after Fukushima accident

    International Nuclear Information System (INIS)

    Choi, In-Kil; Hahm, Daegi; Kim, Min Kyu

    2014-01-01

    Extreme external events is emerged as significant risk contributor to the nuclear power plants after Fukushima Daiichi accident due to the catastrophic earthquake followed by great tsunami greater than a design basis. This accident shows that the extreme external events have the potential to simultaneously affect redundant and diverse safety systems and thereby induce common cause failure or common cause initiators. The probabilistic risk assessment methodology has been used for the risk assessment and safety improvement against the extreme natural hazards. The earthquake and tsunami hazard is an important issue for the nuclear industry in Korea. In this paper, the role and application of probabilistic safety assessment for the post Fukushima action will be introduced. For the evaluation of the extreme natural hazard, probabilistic seismic and tsunami hazard analysis is being performed for the safety enhancement. The research activity on the external event PSA and its interim results will be introduced with the issues to be solved in the future for the reliability enhancement of the risk analysis results. (authors)

  19. Socio-economic research on fusion. SERF 1997-98. Macro Tast E2: External costs and benefits. Task 2: Comparison of external costs

    International Nuclear Information System (INIS)

    Schleisner, Lotte; Korhonen, Riitta

    1998-12-01

    This report is part of the SERF (Socio-Economic Research on Fusion) project, Macro Task E2, which covers External Costs and Benefits. The report is the documentation of Task 2, Comparison of External Costs. The aim of Task 2 Comparison of External Costs, has been to compare the external costs of the fusion energy with those from other alternative energy generation technologies. In this task identification and quantification of the external costs for wind energy and photovoltaic have been performed by Risoe, while identification and quantification of the external cost for nuclear fission and fossil fuels have been discussed by VTT. The methodology used for the assessment of the externalities of the fuel cycles selected has been the one developed within the ExternE Project. First estimates for the externalities of fusion energy have been under examination in Macrotask E2. Externalities of fossil fuels and nuclear fission have already been evaluated in the ExternE project and a vast amount of material for different sites in various countries is available. This material is used in comparison. In the case of renewable wind energy and photovoltaic are assessed separately. External costs of the various alternatives may change as new technologies are developed and costs can to a high extent be avoided (e.g. acidifying impacts but also global warming due to carbon dioxide emissions). Also fusion technology can experience major progress and some important cost components probably can be avoided already by 2050. (EG)

  20. Socio-economic research on fusion. SERF 1997-98. Macro Tast E2: External costs and benefits. Task 2: Comparison of external costs

    Energy Technology Data Exchange (ETDEWEB)

    Schleisner, Lotte; Korhonen, Riitta

    1998-12-01

    This report is part of the SERF (Socio-Economic Research on Fusion) project, Macro Task E2, which covers External Costs and Benefits. The report is the documentation of Task 2, Comparison of External Costs. The aim of Task 2 Comparison of External Costs, has been to compare the external costs of the fusion energy with those from other alternative energy generation technologies. In this task identification and quantification of the external costs for wind energy and photovoltaic have been performed by Risoe, while identification and quantification of the external cost for nuclear fission and fossil fuels have been discussed by VTT. The methodology used for the assessment of the externalities of the fuel cycles selected has been the one developed within the ExternE Project. First estimates for the externalities of fusion energy have been under examination in Macrotask E2. Externalities of fossil fuels and nuclear fission have already been evaluated in the ExternE project and a vast amount of material for different sites in various countries is available. This material is used in comparison. In the case of renewable wind energy and photovoltaic are assessed separately. External costs of the various alternatives may change as new technologies are developed and costs can to a high extent be avoided (e.g. acidifying impacts but also global warming due to carbon dioxide emissions). Also fusion technology can experience major progress and some important cost components probably can be avoided already by 2050. (EG) 36 refs.

  1. Proceedings: National conference on environmental externalities

    International Nuclear Information System (INIS)

    1990-01-01

    This report is the proceedings of the National Conference on Environmental Externalities. A environmental externality is the environmental impact of a process or a plant that society must endure. It is a social cost and is paid, but not by the company who produced it or the company's customers who endure it. The main purpose of this report is to gather the many designs and ideas of how and why to internalize the externalities into the pricing systems of the public utility commissions, especially that of the electric utilities. Economic and sociological aspects of the internalization of these externalities are given in these proceedings. Individual papers are processed separately for databases. (MB)

  2. Proceedings: National conference on environmental externalities

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-31

    This report is the proceedings of the National Conference on Environmental Externalities. A environmental externality is the environmental impact of a process or a plant that society must endure. It is a social cost and is paid, but not by the company who produced it or the company`s customers who endure it. The main purpose of this report is to gather the many designs and ideas of how and why to internalize the externalities into the pricing systems of the public utility commissions, especially that of the electric utilities. Economic and sociological aspects of the internalization of these externalities are given in these proceedings. Individual papers are processed separately for databases. (MB)

  3. Polyphenols from evening primrose ( Oenothera paradoxa ) defatted seeds induce apoptosis in human colon cancer Caco-2 cells.

    Science.gov (United States)

    Gorlach, Sylwia; Wagner, Waldemar; Podsedek, Anna; Sosnowska, Dorota; Dastych, Jarosław; Koziołkiewicz, Maria

    2011-07-13

    Polyphenols extracted from evening primrose seeds (industrial waste product) were studied as apoptosis inducers in human colorectal adenocarcinoma Caco-2 and HT-29 cell lines and in rat normal intestinal IEC-6 cells. The extract dose-dependently inhibited the growth of Caco-2, HT-29, and IEC-6 cells. However, nuclear DNA fragmentation characteristic of apoptosis was observed only in Caco-2. After 72 h of incubation with the extract at 150 μM gallic acid equivalents (44.1 μg extract/mL), Caco-2 cell numbers decreased to 19% of control and 48.8% of the cells were identified by flow cytometry as apoptotic. Under the same conditions only 8% of HT-29 cells and 12.6% of IEC-6 cells exhibited hypodiploid DNA content. The effects of the extract and its fractions on phosphatidylserine exposure and cell membrane integrity were assessed by high content screening image cytometry. The fractions strongly and dose-dependently reduced Caco-2 cell numbers, whereas HT-29 and IEC-6 cells were affected to lesser extents.

  4. A remote valency control technique for actinides by external ultrasound irradiation

    International Nuclear Information System (INIS)

    Toraishi, Takashi; Kimura, Takaumi; Arisaka, Makoto

    2006-01-01

    We here report the reduction of Np(V) to Np(IV) induced by external ultrasound irradiation to demonstrate the ability of ultrasound for the valency control of actinide elements. High power ultrasound irradiation to water produces cavitation bubbles. The violent collapse of the bubbles generates 'hot spot' with an instantaneous temperature of thousands degrees and a pressure of thousands atmosphere, and produces H radical and OH radical as a result. Therefore, with scavenging H radical or OH radical, ultrasound irradiation provides either oxidizability or reducibility. 2 ml Np(V) solution in 1 M HCl was irradiated by 600 kHz external ultrasound. 10 vol% of 2-propanol and a Pt black catalyst were added to the test solution. The test solution was kept at 293 K, and bubbled by Ar gas saturated by 2-propanol during irradiation. The reduction was confirmed from the growth of characteristic light absorption of Np(IV) at 725 nm and 960 nm, together with the disappearance of the absorption of Np(V) at 980 nm. Finally, the reduction of Np(V) was completed after 180 min irradiation. (author)

  5. Transient behavior of high-interaction MHD generator following external loading faults

    International Nuclear Information System (INIS)

    Ishikawa, Motoo

    1983-01-01

    Transient behavior consequent to external loading faults is studied numerically on four configurations of high-interaction MHD generators-subsonic Faraday, supersonic Faraday, subsonic diagonal and supersonic diagonal, to provide a variable data base to serve in selecting the type of large-scale MHD generator. Time-dependent one-dimensional Navier-Stokes equations are solved with the 1969 MacCormack method, in combination with the Maxwell equations and the generalized Ohm's law. An artificial viscosity term is added to the Navier-Stokes equations to maintain numerical stability. It is shown that, with both supersonic and subsonic flows, the Faraday generator is liable to sustain more harmful effect from short than from open faults of the external loading circuit. For large-scale diagonal types, on the other hand, open faults are more dangerous. With subsonic flow, a shock wave propagating upstream is induced by short fault in the Faraday, and by open fault in the diagonal-type generator. In the case of supersonic flow, propagation upstream of the disturbance is completely obstructed. Larger electrical stress is foreseen for Faraday than for diagonal configuration. (author)

  6. Gyrokinetic simulations with external resonant magnetic perturbations: Island torque and nonambipolar transport with plasma rotation

    Science.gov (United States)

    Waltz, R. E.; Waelbroeck, F. L.

    2012-03-01

    Static external resonant magnetic field perturbations (RMPs) have been added to the gyrokinetic code GYRO [J. Candy and R. E. Waltz, J. Comp. Phys. 186, 545 (2003)]. This allows nonlinear gyrokinetic simulations of the nonambipolar radial current flow jr, and the corresponding j→×B→ plasma torque (density) R[jrBp/c], induced by magnetic islands that break the toroidal symmetry of a tokamak. This extends the previous GYRO formulation for the transport of toroidal angular momentum (TAM) [R. E. Waltz, G. M. Staebler, J. Candy, and F. L. Hinton, Phys. Plasmas 14, 122507 (2007); errata 16, 079902 (2009)]. The focus is on electrostatic full torus radial slice simulations of externally induced q =m/n=6/3 islands with widths 5% of the minor radius or about 20 ion gyroradii. Up to moderately strong E ×B rotation, the island torque scales with the radial electric field at the resonant surface Er, the island width w, and the intensity I of the high-n micro-turbulence, as Erw√I . The radial current inside the island is carried (entirely in the n =3 component) and almost entirely by the ion E ×B flux, since the electron E ×B and magnetic flutter particle fluxes are cancelled. The net island torque is null at zero Er rather than at zero toroidal rotation. This means that while the expected magnetic braking of the toroidal plasma rotation occurs at strong co- and counter-current rotation, at null toroidal rotation, there is a small co-directed magnetic acceleration up to the small diamagnetic (ion pressure gradient driven) co-rotation corresponding to the zero Er and null torque. This could be called the residual stress from an externally induced island. At zero Er, the only effect is the expected partial flattening of the electron temperature gradient within the island. Finite-beta GYRO simulations demonstrate almost complete RMP field screening and n =3 mode unlocking at strong Er.

  7. Evaluation of external hazards to nuclear power plants in the United States: Other external events

    International Nuclear Information System (INIS)

    Kimura, C.Y.; Prassinos, P.G.

    1989-02-01

    In support of implementation of the Nuclear Regulatory Commission's Severe Accident Policy, the Lawrence Livermore National Laboratory (LLNL) has performed a study of the risk of core damage to nuclear power plants in the United States due to ''other external events.'' The broad objective has been to gain an understanding of whether ''other external events'' (the hazards not covered by previous reports) are among the major potential accident initiators that may pose a threat of severe reactor core damage or of large radioactive release to the environment from the reactor. The ''other external events'' covered in this report are nearby industrial/military facility accidents, on site hazardous material storage accidents, severe temperature transients, severe weather storms, lightning strikes, external fires, extraterrestrial activity, volcanic activity, earth movement, and abrasive windstorms. The analysis was based on two figures-of-merit, one based on core damage frequency and the other based on the frequency of large radioactive releases. 37 refs., 8 tabs

  8. External costs of nuclear-generated electricity

    International Nuclear Information System (INIS)

    Rotaru, I.; Glodeanu, F.; Popescu, D.; Andrei, V.

    2004-01-01

    External costs of nuclear power include: future financial liabilities arising from decommissioning and dismantling of nuclear facilities, health and environmental impacts of radioactivity releases in routine operation, radioactive waste disposal and effects of severe accidents. The nuclear energy industry operates under regulations that impose stringent limits to atmospheric emissions and liquid effluents from nuclear facilities as well as requiring the containment and confinement of solid radioactive waste to ensure its isolation from the biosphere as long as it may be harmful for human health and the environment. The capital and operating costs of nuclear power plants and fuel cycle facilities already internalize a major portion of the above-mentioned potential external costs, and these are reflected in the prices paid by consumers of nuclear-generated electricity. The externality related to potential health and environmental impacts of radioactive releases during routine operations have been assessed in a large number of comprehensive studies, in particular the ExternE project that was created in the framework of the European Commission. With regard to effects of severe nuclear accidents, a special legal regime, the third-party liability system, has been implemented to provide limited third party liability coverage in the event of a nuclear accident. The nuclear plant owners are held liable for some specified first substantial part of damages to third parties, and must secure insurance coverage adequate to cover this part. The Government provides coverage for some specified substantial second part of the damages, with any remaining damages to be considered by the national legislation. Thus, the costs of an incident or accident are fully internalized in the costs borne by the nuclear plant owners. Externalities of energy are not limited to environmental and health related impacts, but may result also from macro-economic, policy or strategic factors not reflected

  9. External effects and social costs of road transport

    NARCIS (Netherlands)

    Verhoef, E.T.

    1994-01-01

    The article contains a welfare economic analysis of road transport's external effects. First, we discuss the definition of external effects. Applying this definition, it is concluded that road transport activities give rise to a wide range of external costs. However, there are no external benefits

  10. Affective decision-making and externalizing behaviors: the role of autonomic activity.

    Science.gov (United States)

    Bubier, Jennifer L; Drabick, Deborah A G

    2008-08-01

    We tested a conceptual model involving the inter-relations among affective decision-making (indexed by a gambling task), autonomic nervous system (ANS) activity, and attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in a largely impoverished, inner city sample of first through third grade children (N=63, 54% male). The present study hypothesized that impaired affective decision-making and decreased sympathetic and parasympathetic activation would be associated with higher levels of ADHD and ODD symptoms, and that low sympathetic and parasympathetic activation during an emotion-inducing task would mediate the relation between affective decision-making and child externalizing symptoms. In support of our model, disadvantageous decision-making on a gambling task was associated with ADHD hyperactivity/impulsivity symptoms among boys, and attenuated sympathetic activation during an emotion-inducing task mediated this relation. Support for the model was not found among girls.

  11. Control of runaway electron energy using externally injected whistler waves

    Science.gov (United States)

    Guo, Zehua; McDevitt, Christopher J.; Tang, Xian-Zhu

    2018-03-01

    One way of mitigating runaway damage of the plasma-facing components in a tokamak fusion reactor is by limiting the runaway electron energy under a few MeV, while not necessarily reducing the runaway current appreciably. Here, we describe a physics mechanism by which such momentum space engineering of the runaway distribution can be facilitated by externally injected high-frequency electromagnetic waves such as whistler waves. The drastic impact that wave-induced scattering can have on the runaway energy distribution is fundamentally the result of its ability to control the runaway vortex in the momentum space. The runaway vortex, which is a local circulation of runaways in momentum space, is the outcome of the competition between Coulomb collisions, synchrotron radiation damping, and runaway acceleration by the parallel electric field. By introducing a wave that resonantly interacts with runaways in a particular range of energies which is mildly relativistic, the enhanced scattering would reshape the vortex by cutting off the part that is highly relativistic. The efficiency of resonant scattering accentuates the requirement that the wave amplitude can be small so the power requirement from external wave injection is practical for the mitigation scheme.

  12. Controlling runaway vortex via externally injected high-frequency electromagnetic waves

    Science.gov (United States)

    Guo, Zehua; McDevitt, Chris; Tang, Xianzhu

    2017-10-01

    One way of mitigating runaway damage of the plasma-facing components in a tokamak fusion reactor is by limiting the runaway electron energy under a few MeV, while not necessarily reducing the runaway current appreciably. Here we describe a physics mechanism by which such momentum space engineering of the runaway distribution can be facilitated by externally injected high-frequency electromagnetic waves such as the whistler waves. The drastic impact that wave-induced scattering can have on the runaway energy distribution is fundamentally the result of its ability to control the runaway vortex in the momentum space. The runaway vortex, which is a local circulation of runaways in momentum space, is the outcome of the competition between Coulomb collisions, synchrotron radiation damping, and runaway acceleration by parallel electric field. By introducing a wave that resonantly interacts with runaways at a particular range of energy that is mildly relativistic, the enhanced scattering would reshape the vortex by cutting off the part that is highly relativistic. The efficiency of resonant scattering accentuates the requirement that the wave amplitude can be small so the power requirement from external wave injection is practical for the mitigation scheme.

  13. External self-gettering of nickel in float zone silicon wafers

    Science.gov (United States)

    Gay, N.; Martinuzzi, S.

    1997-05-01

    During indiffusion of Ni atoms in silicon crystals at 950 °C from a nickel layer source, Ni-Si alloys can be formed close to the surface. Metal solubility in these alloys is higher than in silicon, which induces a marked segregation gettering of the Ni atoms which have diffused in the bulk of the wafers. Consequently, the regions of the wafers covered with the Ni layer are less contaminated than adjacent regions in which Ni atoms have also penetrated, as shown by the absence of precipitates and the higher diffusion length of minority carriers. The results suggest the existence of external self-gettering of Ni atoms by the nickel source.

  14. Solvent effects on ion-receptor interactions in the presence of an external electric field.

    Science.gov (United States)

    Novák, Martin; Foroutan-Nejad, Cina; Marek, Radek

    2016-11-09

    In this work we investigated the influence of an external electric field on the arrangement of the solvent shells around ions interacting with a carbon-based receptor. Our survey reveals that the mechanism of interaction between a monoatomic ion and a π-type ion receptor varies by the variation in the solvent polarity, the nature of the ion, and the strength of the external field. The characteristics of the ion-surface interaction in nonpolar solvents are similar to those observed in a vacuum. However, in water, we identified two mechanisms. Soft and polarizable ions preferentially interact with the π-receptor. In contrast, two bonded states were found for hard ions. A fully solvated ion, weakly interacting with the receptor at weak field, and a strong π-complex at the strong-field regime were identified. An abrupt variation in the potential energy surface (PES) associated with the rearrangement of the solvation shell on the surface of the receptor induced by an external field was observed both in implicit and explicit solvent environments. The electric field at which the solvation shell breaks is proportional to the hardness of the ion as has been suggested recently based on experimental observations.

  15. Effects of Externalities on Patterns of Exchange

    NARCIS (Netherlands)

    Dijkstra, J.; van Assen, M.A.L.M.

    Many real−life examples of exchanges with externalities exist. Externalities of exchange are defined as direct consequences of exchanges for the payoff of actors who are not involved in the exchange. This paper focuses on how externalities influence the partner choice in exchange networks. In an

  16. Accessing external innovation in drug discovery and development.

    Science.gov (United States)

    Tufféry, Pierre

    2015-06-01

    A decline in the productivity of the pharmaceutical industry research and development (R&D) pipeline has highlighted the need to reconsider the classical strategies of drug discovery and development, which are based on internal resources, and to identify new means to improve the drug discovery process. Accepting that the combination of internal and external ideas can improve innovation, ways to access external innovation, that is, opening projects to external contributions, have recently been sought. In this review, the authors look at a number of external innovation opportunities. These include increased interactions with academia via academic centers of excellence/innovation centers, better communication on projects using crowdsourcing or social media and new models centered on external providers such as built-to-buy startups or virtual pharmaceutical companies. The buzz for accessing external innovation relies on the pharmaceutical industry's major challenge to improve R&D productivity, a conjuncture favorable to increase interactions with academia and new business models supporting access to external innovation. So far, access to external innovation has mostly been considered during early stages of drug development, and there is room for enhancement. First outcomes suggest that external innovation should become part of drug development in the long term. However, the balance between internal and external developments in drug discovery can vary largely depending on the company strategies.

  17. Technical review of externalities issues. Final report

    International Nuclear Information System (INIS)

    Niemeyer, V.

    1994-12-01

    Externalities has become the catchword for a major experiment in electric utility regulation. Together with increased competition as a means for economic regulation, this experiment represents a potential revolution in how electric utilities are regulated. It is very important for utilities and policy makers to understand the technical issues and arguments driving the externality experiment. This Technical Review presents four papers covering topics in economics that may play important roles in this revolution. The four papers are: Economic Issues in the Application of Externalities to Electricity Resource Selection; Climate Change, the Marginal Cost of Carbon Dioxide Emissions and the Implications for Carbon Dioxide Emissions Adders; Positive Externalities and Benefits from Electricity; and Socioeconomic Effects of Externality Adders for Electric Utility Emissions

  18. Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Fabien J Cousin

    Full Text Available Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate.A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy.Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.

  19. Two types of external fixators to correct humeral fracture in domestic pigeons

    International Nuclear Information System (INIS)

    Dalmolin, F.; Schossler, J.E.; Bertoletti, B.; Vasconcelos, A.; Muller, D.; Schossler, D.R.; Gomes, K.

    2007-01-01

    This paper was aimed at evaluating two changes in the external fixators for osteosynthesis of the humeral fracture that induce the correction of the humeral fracture in pigeons. The reduction of diaphyseal fracture was made with an intramedulary pin associated to another perpendicular one inserted into the distal segment (Group A - GA); in the Group B (GB) an additional pin was used in the proximal fragment. All the pigeons were evaluated clinically and radiographically up to 60 days, except for four of each group which were submitted to euthanasia at 15, 22, 29 and 36 days for the macro and microscope exams. The flight test was successful in all pigeons. The bone calus was radiografically visible only in the GA; the mean time and the standard deviation for flight was 32.25 ± 6.5 days for the GA and 39.8 ± 3.83 for the GB. The mean time and standard deviation for fracture healing was 36 ± 0 days in the GA and 34 ± 3.4 in the GB. The two types of external fixator evaluated were efficient to stabilized the fracture site allowing complete consolidation and return to function. The use of the external fixator with two perpendicular pins provides more stability at the fracture site although it is necessary more time for the surgery procedure [pt

  20. Evaluation of radiolabelled annexin A5 for scintigraphic imaging of cell processes (necrosis/apoptosis) in cardiovascular diseases; Evaluation de radiotraceurs derives de l'annexine A5 pour l'imagerie scintigraphique de processus cellulaires (apoptose/necrose/thrombose) en pathologie cardiovasculaire (Ressource electronique)

    Energy Technology Data Exchange (ETDEWEB)

    Sarda-Mantel, L

    2007-03-15

    Annexin A5, a 35KDa protein, specifically binds with high affinity to phosphatidylserine (P.S.) which is actively redistributed to the external leaflet of plasmic membranes in apoptotic cells and activated platelets. Annexin A5 radiolabelled with {sup 99m}Tc({sup 99m}Tc-ANX5) was developed by Strauss (stanford, Usa) to image apoptosis in vivo: tumours cells apoptosis induced by chemo-radiotherapy, ischemia/reperfusion lesions in animals and patients, graft rejection. Additionally, many in vitro data suggest that annexin A5 also stains necrosis (membrane disruption), which occurs in all types of cell death. This preclinical work aimed to evaluate the potential interest of {sup 99m}Tc-ANX5 imaging as a clinical tool in cardiovascular diseases. Four studies performed in rat models of myocardial infarction by coronary ligation and ischemia-reperfusion, and in rat models of subacute and acute (isoproterenol-induced) myocarditis show the ability of {sup 99m}Tc-ANX5 to detect in vivo cardio myocytes death by apoptosis and necrosis. Another study demonstrates that {sup 99m}Tc-ANX5 is highly accurate to evaluate in vivo the biological activity of parietal thrombus in a rat model of elastase-induced abdominal aortic aneurysm. These results suggest that {sup 99m}Tc-ANX5 imaging could be used in patients for non invasive diagnosis, prognostic evaluation in acute myocarditis and in various thrombotic cardiovascular diseases. (author)

  1. Externalities of fuel cycles 'ExternE' project. Coal fuel cycle. Estimation of physical impacts and monetary valuation for priority impact pathways

    International Nuclear Information System (INIS)

    Berry, J.E.; Holland, M.R.; Watkiss, P.R.

    1994-01-01

    Background to the ExternE Project Awareness of the environmental damage resulting from human activity, particularly concerning energy use, has grown greatly in recent years. Effects such as global warming, ozone depletion and acid rain are now the subjects of much research and public debate. It is now known that these and other effects damage a wide range of receptors, including human health, forests, crops, freshwater ecosystems and buildings. Such damages are typically not accounted for by the producers and consumers of the good in question (in this case energy). They are thus referred to as 'external costs' or 'externalities', to distinguish them from the private costs which account for the construction of plant, cost of fuel, wages, etc. In recent years there has been a growing interest in the assessment of the environmental and health impacts of energy, and the related external costs. This concern is driven by a number of different factors; The need to integrate environmental concerns in decision making over the choice between different fuels and energy technologies. The need to evaluate the costs and benefits of stricter environmental standards. Increased attention to the use of economic instruments for environmental policy. The need to develop overall indicators of environmental performance of different technologies. Major changes in the energy sector, including privatisation, liberalisation of markets, reduction of subsidies, etc. An agreed methodology for calculation and integration of external costs has not been established. Earlier work is typically of a preliminary nature and tends to be deficient with respect to both the methods employed and the quality of models and data used. In consequence of this a collaborative project, the EC/US Fuel Cycles Study, was established between Directorate General XII (Science, Research and Technology) of the European Commission and the United States Department of Energy. This ran for the period 1991 to 1993, and good

  2. Waveguide based external cavity semiconductor lasers

    NARCIS (Netherlands)

    Oldenbeuving, Ruud; Klein, E.J.; Offerhaus, Herman L.; Lee, Christopher James; Verhaegen, M.; Boller, Klaus J.

    2012-01-01

    We report on progress of the project waveguide based external cavity semiconductor laser (WECSL) arrays. Here we present the latest results on our efforts to mode lock an array of tunable, external cavity semiconductor lasers.

  3. Internal versus external controls on age variability: Definitions, origins and implications in a changing climate

    Science.gov (United States)

    Harman, C. J.

    2015-12-01

    The unsteadiness of stream water age is now well established, but the controls on the age dynamics, and the adequate representation and prediction of those dynamics, are not. A basic distinction can be made between internal variability that arises from changes in the proportions of flow moving through the diverse flow pathways of a hydrologic system, and external variability that arises from the stochasticity of inputs and outputs (such as precipitation and streamflow). In this talk I will show how these two types of age variability can be formally defined and distinguished within the framework of rank StorAge Selection (rSAS) functions. Internal variability implies variations in time in the rSAS function, while external variability does not. This leads naturally to the definition of several modes of internal variability, reflecting generic ways that system flowpaths may be rearranged. This rearrangement may be induced by fluctuations in the system state (such as catchment wetness), or by longer-term changes in catchment structure (such as land use change). One type of change, the 'inverse storage effect' is characterized by an increase in the release of young water from the system in response to an increase in overall system storage. This effect can be seen in many hydrologic settings, and has important implications for the effect of altered hydroclimatic conditions on solute transport through a landscape. External variability, such as increased precipitation, can induce a decrease in mean transit time (and vice versa), but this effect is greatly enhanced if accompanied by an internal shift in flow pathways that increases the relative importance of younger water. These effects will be illustrated using data from field and experimental studies.

  4. The avoided external costs of using wind energy

    Energy Technology Data Exchange (ETDEWEB)

    Markandya, A [Harvard Inst. for International Development, Cambridge, MA (United States)

    1996-12-31

    This article discusses the external costs of electricity generated by conventional fossil fuel sources, such as coal and nuclear power. It compares the costs of electricity generated with coal with that generated with wind. A measure of the benefits of wind energy is the difference between these two external costs. The methodology used for the estimation of the external costs, as well as the estimates of these costs, are taken from the EC ExternE study, financed by DGXII of the European Commission. The present author was a lead economist for that study. (author)

  5. The avoided external costs of using wind energy

    Energy Technology Data Exchange (ETDEWEB)

    Markandya, A. [Harvard Inst. for International Development, Cambridge, MA (United States)

    1995-12-31

    This article discusses the external costs of electricity generated by conventional fossil fuel sources, such as coal and nuclear power. It compares the costs of electricity generated with coal with that generated with wind. A measure of the benefits of wind energy is the difference between these two external costs. The methodology used for the estimation of the external costs, as well as the estimates of these costs, are taken from the EC ExternE study, financed by DGXII of the European Commission. The present author was a lead economist for that study. (author)

  6. The avoided external costs of using wind energy

    International Nuclear Information System (INIS)

    Markandya, A.

    1995-01-01

    This article discusses the external costs of electricity generated by conventional fossil fuel sources, such as coal and nuclear power. It compares the costs of electricity generated with coal with that generated with wind. A measure of the benefits of wind energy is the difference between these two external costs. The methodology used for the estimation of the external costs, as well as the estimates of these costs, are taken from the EC ExternE study, financed by DGXII of the European Commission. The present author was a lead economist for that study. (author)

  7. Parasitic infections of the external eye.

    Science.gov (United States)

    Pahuja, Shivani; Puranik, Charuta; Jelliti, Bechir; Khairallah, Moncef; Sangwan, Virender S

    2013-08-01

    To review the published literature on parasitic infections of external eye. Published articles and case reports on parasitic infections of external eye were reviewed and relevant information was collected. Parasitic infections of the eye are rare. However, being more commonly seen in developing nations, they require active measures for screening, diagnosis, and therapy. Parasites of importance causing external ocular disease are protozoan parasites, such as Leishmania; metazoans, such as nematodes (roundworms), cestodes (tapeworms), and trematodes (flatworms); or ectoparasites, such as Phthirus pubis and Demodex.

  8. Environment and externalization; Environnement et externalisation

    Energy Technology Data Exchange (ETDEWEB)

    Kremlis, G.; Renaud, R. [Association francaise des ingenieurs et techniciens de l' environnement, AFITE, 75 - Paris (France); Touron, M. [Veritas, 75 - Paris (France)] [and others

    2001-07-01

    This document presents the discussions of the 16 may 2000, concerning the externalization and the environment and proposes to answer the following questions: is the externalization a new strategy to better perceive, hopeful engineering department, the technological risks problems, the environment or the land pollution? Does the externalization allow a better organization of the enterprise? To analyse the situation, the document presents the white book of the environmental liability, the administration point of view, some enterprises examples and the importance of the environmental management. (A.L.B.)

  9. Probe branes thermalization in external electric and magnetic fields

    International Nuclear Information System (INIS)

    Ali-Akbari, M.; Ebrahim, H.; Rezaei, Z.

    2014-01-01

    We study thermalization on rotating probe branes in AdS 5 ×S 5 background in the presence of constant external electric and magnetic fields. In the AdS/CFT framework this corresponds to thermalization in the flavour sector in field theory. The horizon appears on the worldvolume of the probe brane due to its rotation in one of the sphere directions. For both electric and magnetic fields the behaviour of the temperature is independent of the probe brane dimension. We also study the open string metric and the fluctuations of the probe brane in such a set-up. We show that the temperatures obtained from open string metric and observed by the fluctuations are larger than the one calculated from the induced metric

  10. Noise-induced chaos and basin erosion in softening Duffing oscillator

    International Nuclear Information System (INIS)

    Gan Chunbiao

    2005-01-01

    It is common for many dynamical systems to have two or more attractors coexist and in such cases the basin boundary is fractal. The purpose of this paper is to study the noise-induced chaos and discuss the effect of noises on erosion of safe basin in the softening Duffing oscillator. The Melnikov approach is used to obtain the necessary condition for the rising of chaos, and the largest Lyapunov exponent is computed to identify the chaotic nature of the sample time series from the system. According to the Melnikov condition, the safe basins are simulated for both the deterministic and the stochastic cases of the system. It is shown that the external Gaussian white noise excitation is robust for inducing the chaos, while the external bounded noise is weak. Moreover, the erosion of the safe basin can be aggravated by both the Gaussian white and the bounded noise excitations, and fractal boundary can appear when the system is only excited by the random processes, which means noise-induced chaotic response is induced

  11. External events analysis of the Ignalina Nuclear Power Plant

    International Nuclear Information System (INIS)

    Liaukonis, Mindaugas; Augutis, Juozas

    1999-01-01

    This paper presents analysis of external events impact on the safe operation of the Ignalina Nuclear Power Plant (INPP) safety systems. Analysis was based on the probabilistic estimation and modelling of the external hazards. The screening criteria were applied to the number of external hazards. The following external events such as aircraft failure on the INPP, external flooding, fire, extreme winds requiring further bounding study were analysed. Mathematical models were developed and event probabilities were calculated. External events analysis showed rather limited external events danger to Ignalina NPP. Results of the analysis were compared to analogous analysis in western NPPs and no great differences were specified. Calculations performed show that external events can not significantly influence the safety level of the Ignalina NPP operation. (author)

  12. External control of the Drosophila melanogaster egg to imago development period by specific combinations of 3D low-frequency electric and magnetic fields.

    Science.gov (United States)

    Makarov, Vladimir I; Khmelinskii, Igor

    2016-01-01

    We report that the duration of the egg-to-imago development period of the Drosophila melanogaster, and the imago longevity, are both controllable by combinations of external 3-dimensional (3D) low-frequency electric and magnetic fields (LFEMFs). Both these periods may be reduced or increased by applying an appropriate configuration of external 3D LFEMFs. We report that the longevity of D. melanogaster imagoes correlates with the duration of the egg-to-imago development period of the respective eggs. We infer that metabolic processes in both eggs and imago are either accelerated (resulting in reduced time periods) or slowed down (resulting in increased time periods). We propose that external 3D LFEMFs induce electric currents in live systems as well as mechanical vibrations on sub-cell, whole-cell and cell-group levels. These external fields induce media polarization due to ionic motion and orientation of electric dipoles that could moderate the observed effects. We found that the longevity of D. melanogaster imagoes is affected by action of 3D LFEMFs on the respective eggs in the embryonic development period (EDP). We interpret this effect as resulting from changes in the regulation mechanism of metabolic processes in D. melanogaster eggs, inherited by the resulting imagoes. We also tested separate effects of either 3D electric or 3D magnetic fields, which were significantly weaker.

  13. Early radiation changes of normal dog brain following internal and external brain irradiation: A preliminary report

    International Nuclear Information System (INIS)

    Chin, H.; Maruyama, Y.; Markesbery, W.; Goldstein, S.; Wang, P.; Tibbs, P.; Young, B.; Feola, J.; Beach, L.

    1984-01-01

    To examine radiation-induced changes in the normal brain, internal or external radiation was given to normal dog brain. Seven medium-sized dogs were used in this study. Two dogs were controls and an ice-pick (plastic implant applicator) was placed in the right frontal lobe for about 5 hours but no irradiation. Two dogs underwent Cs-137 brain implantation for 4 and 5 hours, respectively using an ice-pick technique. Two dogs were given internal neutron irradiation using the same technique of intracerebral ice-pick brachytherapy. One dog received an external photon irradiation using 6-Mev Linear Accelerator. Postmortem microscopic examination was made to study the early cerebral changes to irradiation in three dogs: one control with no irradiation; one received intracerebral Cesium implantation; and one external photon irradiation. Vascular change was the most prominent microscopic finding. There were hemorrhage, endothelial proliferation and fibrinoid changes of small vessel wall. Most of the changes were localized in the white matter and the cortex remained intact. Details (CT, NMR and histological studies) are discussed

  14. Fetomaternal hemorrhage during external cephalic version.

    Science.gov (United States)

    Boucher, Marc; Marquette, Gerald P; Varin, Jocelyne; Champagne, Josette; Bujold, Emmanuel

    2008-07-01

    To estimate the frequency and volume of fetomaternal hemorrhage during external cephalic version for term breech singleton fetuses and to identify risk factors involved with this complication. A prospective observational study was performed including all patients undergoing a trial of external cephalic version for a breech presentation of at least 36 weeks of gestation between 1987 and 2001 in our center. A search for fetal erythrocytes using the standard Kleihauer-Betke test was obtained before and after each external cephalic version. The frequency and volume of fetomaternal hemorrhage were calculated. Putative risk factors for fetomaternal hemorrhage were evaluated by chi(2) test and Mann-Whitney U test. A Kleihauer-Betke test result was available before and after 1,311 trials of external cephalic version. The Kleihauer-Betke test was positive in 67 (5.1%) before the procedure. Of the 1,244 women with a negative Kleihauer-Betke test before external cephalic version, 30 (2.4%) had a positive Kleihauer-Betke test after the procedure. Ten (0.8%) had an estimated fetomaternal hemorrhage greater than 1 mL, and one (0.08%) had an estimated fetomaternal hemorrhage greater than 30 mL. The risk of fetomaternal hemorrhage was not influenced by parity, gestational age, body mass index, number of attempts at version, placental location, or amniotic fluid index. The risk of detectable fetomaternal hemorrhage during external cephalic version was 2.4%, with fetomaternal hemorrhage more than 30 mL in less than 0.1% of cases. These data suggest that the performance of a Kleihauer-Betke test is unwarranted in uneventful external cephalic version and that in Rh-negative women, no further Rh immune globulin is necessary other than the routine 300-microgram dose at 28 weeks of gestation and postpartum. II.

  15. Davidson's Externalism and Swampman's Troublesome Biography

    Directory of Open Access Journals (Sweden)

    André Leclerc

    2005-12-01

    Full Text Available After the seminal works of Putnam (1975, Burge (1979, and Kripke (1982, the next important contribution to externalism is certainly Davidson’s (mainly 1987, 1988, 1989, 2001. By criticizing the posi-tions of these philosophers, Davidson elaborated his own brand of exter-nalism. We shall first present some features of Davidson’s externalism (the importance of historical-causal connections for the foundation of language and thought, for the explanation of how language can be learned, and how attitudes can be identified by the interpreter, and fi-nally how mental content is determined by appealing to the idea of trian-gulation, to prepare the discussion of a few problems. We then discuss two questions in Davidson’s externalism. First, how to reconcile the fact that external factors determine mental content, as Putnam, Burge and Davidson himself argued convincingly, with token-physicalism, the thesis that mental events are identical with physical events occurring “in the head” (or the thesis that mental events supervenes locally on brain ac-tivities? The second main problem is how to reconcile the first person authority with some prima facie consequences of externalism, mainly that we should know the relevant parts of our (natural and social envi-ronment in order to know the content of our own thoughts? We argue that Davidson’s answer to the first question is not successful, while his answer to the second was a breakthrough.

  16. Development of an Intervention for Foster Parents of Young Foster Children with Externalizing Behavior: Theoretical Basis and Program Description

    Science.gov (United States)

    Vanschoonlandt, Femke; Vanderfaeillie, Johan; Van Holen, Frank; De Maeyer, Skrallan

    2012-01-01

    Foster parents are often faced with serious externalizing behaviors of their foster child. These behavioral problems may induce family stress and are related to less effective parenting and often increase. Foster children with behavioral problems are also more at risk of placement breakdown. An intervention to support foster parents of young…

  17. Relaxed plasmas in external magnetic fields

    International Nuclear Information System (INIS)

    Spies, G.O.; Li, J.

    1991-08-01

    The well-known theory of relaxed plasmas (Taylor states) is extended to external magnetic fields whose field lines intersect the conducting toroidal boundary. Application to an axially symmetric, large-aspect-ratio torus with circular cross section shows that the maximum pinch ratio, and hence the phenomenon of current saturation, is independent of the external field. The relaxed state is explicitly given for an external octupole field. In this case, field reversal is inhibited near parts of the boundary if the octupole generates magnetic x-points within the plasma. (orig.)

  18. Stent-induced flow disturbances in the ipsilateral external carotid artery following internal carotid artery stenting: a temporary cause of jaw claudication.

    Science.gov (United States)

    Giurgea, Georgiana-Aura; Haumer, Markus; Mlekusch, Irene; Sabeti-Sandor, Schila; Dick, Petra; Schillinger, Martin; Minar, Erich; Mlekusch, Wolfgang

    2017-07-01

    We hypothesize that stenting of the internal carotid artery can immediately impede blood flow to the external carotid artery by either plaque shift or stent coverage of the ostium, and thereby cause ischemic symptoms like ipsilateral jaw claudication. Thirty-three patients with high-grade asymptomatic stenosis of the internal carotid artery who underwent endovascular treatment were examined by ultrasound of the external carotid artery and performed an exercise test by chewing chewing gum synchronously to an electronic metronome for 3 min. Tests were performed before, the day after, and 1 week after the stenting procedure. Claudication time was defined as the timespan until occurrence of pain of the masseter muscle and/or chewing dyssynchrony to the metronome for more than 15 s. Ten patients with an isolated, atherosclerotic stenosis of the external carotid artery served as controls. A significantly reduced claudication time (in seconds) was recorded in patients who underwent carotid artery stenting compared to baseline values; median 89 (interquartile range, IQR, 57 to 124) vs. median 180 (IQR 153 to 180; p external carotid artery into faster or slower as 200 cm/sec, the effect was even accentuated. Stenting values showed improvement 1 week after but did not return to baseline levels. No respective changes were found in controls. Stenting of the internal carotid artery lead to ipsilateral flow deterioration at the external carotid artery resulting in temporary jaw claudication. This impairment attenuated over the time and was significantly reduced after 1 week.

  19. Estimation of Externalities for Juragua Nuclear Project

    International Nuclear Information System (INIS)

    Mora, H. R.; Carbonell, L. T.

    2002-01-01

    Estimation of externalities allows taking into account environmental impacts due to any activity in total costs calculation. In the present work, the external costs of electricity generation from nuclear energy were calculated considering three scenarios: normal operation (routine releases), accident situation and solid waste disposal. A comparison between these results and those obtained for electricity generation from fossil fuels was made. IAEA proposals of Simplified methodologies were used for externality calculations. The Juragua project was selected as a study case; it is based in two energetic blocks both PWR, VVER 440/318 type with a plant capacity of 417 MWe each. Four impact ways were considered for all scenarios: (1) Inhalation of radionuclides in the air, (2) External irradiation from radionuclides immersed in clouds, (3) External irradiation from deposited radionuclides and (4) Ingestion of radionuclides in agricultural products. Besides, two impact categories (local and regional) for all scenarios were considered. The total cost of externalities was 0.01425 c/kWh, value smaller than the one obtained for electricity generation from fossil fuel (0.256 c/kWh). For the normal operation scenario, the external cost calculated was 0.00112 c/kWh, for accident situation 0.01103 c/kWh, and for the solid wastes management scenario 0.0021 c/kWh. The high value obtained for solid waste disposal scenario is due to repository placement features. (author)

  20. Dynamically induced many-body localization

    Science.gov (United States)

    Choi, Soonwon; Abanin, Dmitry A.; Lukin, Mikhail D.

    2018-03-01

    We show that a quantum phase transition from ergodic to many-body localized (MBL) phases can be induced via periodic pulsed manipulation of spin systems. Such a transition is enabled by the interplay between weak disorder and slow heating rates. Specifically, we demonstrate that the Hamiltonian of a weakly disordered ergodic spin system can be effectively engineered, by using sufficiently fast coherent controls, to yield a stable MBL phase, which in turn completely suppresses the energy absorption from external control field. Our results imply that a broad class of existing many-body systems can be used to probe nonequilibrium phases of matter for a long time, limited only by coupling to external environment.

  1. External effects related to biogas and wind power

    DEFF Research Database (Denmark)

    Ibsen, Liselotte Schleisner; Nielsen, Per Sieverts

    1998-01-01

    Energy produced by wind power and biogas is today more expensive than energy produced by fossil fuels. However, by including external costs related to the technologies, the renewable technologies are expected to result in social benefits compared to the conventional power technologies. The paper...... will focus on estimates of externalities related to wind and biogas energy supplies using the ExternE methodology developed in a major study launched by the European Comission. External costs are the costs imporsed on society that are not included in the market price (e.g. effects of air pollution on health...

  2. Early discharge after external anal sphincter repair

    DEFF Research Database (Denmark)

    Rosenberg, J; Kehlet, H

    1999-01-01

    PURPOSE: The aim of this study was to describe an accelerated-stay program for repair of the external anal sphincter. METHODS: Twenty consecutive patients undergoing overlapping repair of the external anal sphincter were included in the study. Effect parameters were length of hospitalization....... CONCLUSION: We have described a safe accelerated-stay program (24 to 48 hours) for overlapping repair of external anal sphincter....

  3. Initiation but no execution - modulation of peripheral blood lymphocyte apoptosis in rheumatoid arthritis - a potential role for heat shock protein 70

    Directory of Open Access Journals (Sweden)

    Chuturgoon Anil A

    2011-11-01

    Full Text Available Abstract Background Rheumatoid arthritis (RA is a chronic autoimmune disease, which causes synovial damage. Persistence of lymphocyte infiltrates in the rheumatoid synovium has been attributed to abnormal apoptosis. While not comprehensively investigated, perturbations in peripheral blood lymphocyte (PBL apoptosis may also be involved in perpetuation of autoimmune processes in RA. Methods We investigated total, CD4+ and CD19+ PBL apoptosis in our study cohort by monitoring the translocation of phosphatidylserine using the Annexin-V assay. To examine the role of death receptor mediated apoptosis as well as activation-induced-cell-death (AICD, PBLs were labeled with CD95/Fas and CD69 markers and enumerated by flow cytometry. Proteolytic activity of initiator and executioner caspases was determined by luminometry. DNA fragmentation assays were used to examine whether apoptotic signals were transduced to the nucleus. Quantitative PCR arrays were used to investigate apoptotic pathways associated with RA-PBLs. Since heat-shock-protein-70 (HSP70 is an inducible protein which modulates apoptotic signals, we determined HSP70 levels by intra-cellular flow cytometry and western blots. Results The RA-PBLs showed signs of elevated apoptosis whilst in circulation. These include increases in the loss of plasma membrane asymmetry, indicated by increased externalization of phosphatidylserine (especially in B-lymphocytes. RA-PBLs showed a bias to CD95/Fas mediated apoptotic pathways, but low levels of the CD69 marker suggested that this was not associated with immune activation. Although downstream markers of apoptosis such as caspase-3/7 activity, were increased, no DNA fragmentation was observed in RA-PBLs. Interestingly, elevated levels of apoptosis did not correlate with absolute lymphocyte counts in RA patients. Levels of HSP70 were highly elevated in RA-PBLs compared to controls. Conclusion The results suggest that while apoptosis may be initiated in RA

  4. Automated External Defibrillator

    Science.gov (United States)

    ... leads to a 10 percent reduction in survival. Training To Use an Automated External Defibrillator Learning how to use an AED and taking a CPR (cardiopulmonary resuscitation) course are helpful. However, if trained ...

  5. Hysteresis-induced bifurcation and chaos in a magneto-rheological suspension system under external excitation

    Science.gov (United States)

    Hailong, Zhang; Enrong, Wang; Fuhong, Min; Ning, Zhang

    2016-03-01

    The magneto-rheological damper (MRD) is a promising device used in vehicle semi-active suspension systems, for its continuous adjustable damping output. However, the innate nonlinear hysteresis characteristic of MRD may cause the nonlinear behaviors. In this work, a two-degree-of-freedom (2-DOF) MR suspension system was established first, by employing the modified Bouc-Wen force-velocity (F-v) hysteretic model. The nonlinear dynamic response of the system was investigated under the external excitation of single-frequency harmonic and bandwidth-limited stochastic road surface. The largest Lyapunov exponent (LLE) was used to detect the chaotic area of the frequency and amplitude of harmonic excitation, and the bifurcation diagrams, time histories, phase portraits, and power spectrum density (PSD) diagrams were used to reveal the dynamic evolution process in detail. Moreover, the LLE and Kolmogorov entropy (K entropy) were used to identify whether the system response was random or chaotic under stochastic road surface. The results demonstrated that the complex dynamical behaviors occur under different external excitation conditions. The oscillating mechanism of alternating periodic oscillations, quasi-periodic oscillations, and chaotic oscillations was observed in detail. The chaotic regions revealed that chaotic motions may appear in conditions of mid-low frequency and large amplitude, as well as small amplitude and all frequency. The obtained parameter regions where the chaotic motions may appear are useful for design of structural parameters of the vibration isolation, and the optimization of control strategy for MR suspension system. Projects supported by the National Natural Science Foundation of China (Grant Nos. 51475246, 51277098, and 51075215), the Research Innovation Program for College Graduates of Jiangsu Province China (Grant No. KYLX15 0725), and the Natural Science Foundation of Jiangsu Province of China (Grant No. BK20131402).

  6. Tailoring of in-plane magnetic anisotropy in polycrystalline cobalt thin films by external stress

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Dileep, E-mail: dkumar@csr.res.in [UGC-DAE Consortium for Scientic Research, Khandwa Road, Indore 452001 (India); Singh, Sadhana [UGC-DAE Consortium for Scientic Research, Khandwa Road, Indore 452001 (India); Vishawakarma, Pramod [School of Nanotechnology, RGPV, Bhopal 462036 (India); Dev, Arun Singh; Reddy, V.R. [UGC-DAE Consortium for Scientic Research, Khandwa Road, Indore 452001 (India); Gupta, Ajay [Amity Center for Spintronic Materials, Amity University, Sector 125, Noida 201303 (India)

    2016-11-15

    Polycrystalline Co films of nominal thickness ~180 Å were deposited on intentionally curved Si substrates. Tensile and compressive stresses of 100 MPa and 150 MPa were induced in the films by relieving the curvature. It has been found that, within the elastic limit, presence of stress leads to an in-plane magnetic anisotropy in the film and its strength increases with increasing stress. Easy axis of magnetization in the films is found to be parallel/ transverse to the compressive /tensile stresses respectively. The origin of magnetic anisotropy in the stressed films is understood in terms of magneto- elastic coupling, where the stress try to align the magnetic moments in order to minimize the magneto-elastic as well as anisotropy energy. Tensile stress is also found to be responsible for the surface smoothening of the films, which is attributed to the movement of the atoms associated with the applied stress. The present work provides a possible way to tailor the magnetic anisotropy and its direction in polycrystalline and amorphous films using external stress. - Highlights: • Tensile and compressive stresses were induced in Co films by removing the bending force from the substrates after film deposition. • Controlled external mechanical stress is found to be responsible for magnetic anisotropies in amorphous and polycrystalline thin films, where crystalline anisotropy is absent. • Tensile stress leads to surface smoothening of the polycrystalline Co films.

  7. External dosimetry - Applications to radiation protection

    International Nuclear Information System (INIS)

    Faussot, Alain

    2011-01-01

    Dosimetry is the essential component of radiation protection. It allows to determine by calculation and measurement the absorbed dose value, i.e. the energy amounts deposited in matter by ionizing radiations. It deals also with the irradiation effects on living organisms and with their biological consequences. This reference book gathers all the necessary information to understand and master the external dosimetry and the metrology of ionizing radiations, from the effects of radiations to the calibration of radiation protection devices. The first part is devoted to physical dosimetry and allows to obtain in a rigorous manner the mathematical formalisms leading to the absorbed dose for different ionizing radiation fields. The second part presents the biological effects of ionizing radiations on living matter and the determination of a set of specific radiation protection concepts and data to express the 'risk' to develop a radio-induced cancer. The third part deals with the metrology of ionizing radiations through the standardized study of the methods used for the calibration of radiation protection equipments. Some practical exercises with their corrections are proposed at the end of each chapter

  8. Effects of confinement and external fields on structure and transport in colloidal dispersions in reduced dimensionality

    International Nuclear Information System (INIS)

    Wilms, D; Virnau, P; Binder, K; Deutschländer, S; Siems, U; Franzrahe, K; Henseler, P; Keim, P; Schwierz, N; Maret, G; Nielaba, P

    2012-01-01

    In this work, we focus on low-dimensional colloidal model systems, via simulation studies and also some complementary experiments, in order to elucidate the interplay between phase behavior, geometric structures and transport properties. In particular, we try to investigate the (nonlinear!) response of these very soft colloidal systems to various perturbations: uniform and uniaxial pressure, laser fields, shear due to moving boundaries and randomly quenched disorder. We study ordering phenomena on surfaces or in monolayers by Monte Carlo computer simulations of binary hard-disk mixtures, the influence of a substrate being modeled by an external potential. Weak external fields allow a controlled tuning of the miscibility of the mixture. We discuss the laser induced de-mixing for the three different possible couplings to the external potential. The structural behavior of hard spheres interacting with repulsive screened Coulomb or dipolar interaction in 2D and 3D narrow constrictions is investigated using Brownian dynamics simulations. Due to misfits between multiples of the lattice parameter and the channel widths, a variety of ordered and disordered lattice structures have been observed. The resulting local lattice structures and defect probabilities are studied for various cross sections. The influence of a self-organized order within the system is reflected in the velocity of the particles and their diffusive behavior. Additionally, in an experimental system of dipolar colloidal particles confined by gravity on a solid substrate we investigate the effect of pinning on the dynamics of a two-dimensional colloidal liquid. This work contains sections reviewing previous work by the authors as well as new, unpublished results. Among the latter are detailed studies of the phase boundaries of the de-mixing regime in binary systems in external light fields, configurations for shear induced effects at structured walls, studies on the effect of confinement on the structures

  9. Wide area scanning system and carbon microbeams at the external microbeam facility of the INFN LABEC laboratory in Florence

    International Nuclear Information System (INIS)

    Giuntini, L.; Massi, M.; Calusi, S.; Castelli, L.; Carraresi, L.; Fedi, M.E.; Gelli, N.; Liccioli, L.; Mandò, P.A.; Mazzinghi, A.; Palla, L.; Romano, F.P.

    2015-01-01

    Recently, developments have been made to the external scanning microbeam of INFN-LABEC laboratory in Florence. A new system for mechanical sample scanning was implemented. This system allows us to acquire large maps (up to 20 × 20 cm 2 ), of great interest in the Cultural Heritage field. In parallel, the possibility of using carbon microbeams for experiments, such as, for example, ion beam modification of materials and MeV Secondary Ion Mass Spectrometry, has been investigated. As a test application, Particle Induced X-ray Emission with carbon microbeams has been performed on a lapis lazuli stone. First results for both wide area imaging and external carbon microbeams are briefly reported

  10. IMPORTANCE OF DELIVERY CONDITIONS IN THE EXTERNAL PRICE CALCULATION

    Directory of Open Access Journals (Sweden)

    Violeta ISAI

    2005-01-01

    Full Text Available The delivery conditions of the merchandise at export, established by the rules INCOTERMS2000, influence the external price structure. There are some conditions in which the external priceincludes only the value of the merchandise and other conditions in which, besides the value of themerchandise, the price includes also the external transport and insurance. In the case of the exportson commercial credit, when it appears the notion of external interest, this one may be included in theprice or may be invoiced separately, thus defining gross external prices and net external prices.

  11. External Evaluation Measures for Subspace Clustering

    DEFF Research Database (Denmark)

    Günnemann, Stephan; Färber, Ines; Müller, Emmanuel

    2011-01-01

    research area of subspace clustering. We formalize general quality criteria for subspace clustering measures not yet addressed in the literature. We compare the existing external evaluation methods based on these criteria and pinpoint limitations. We propose a novel external evaluation measure which meets...

  12. The external cost of the nuclear fuel cycle

    International Nuclear Information System (INIS)

    Schieber, C.; Schneider, T.

    2002-01-01

    The external cost of the nuclear fuel cycle has been evaluated in the particular context of France as part of the European Commission's ExternE project. All the steps in the fuel cycle which involve the use of cutting edge technology were taken into consideration, from mining of uranium ores to waste disposal, via construction, dismantling of nuclear power plants and the transport of radioactive materials. The general methodology adopted in the study, known as the 'Impact Pathway Analysis', is based on a sequence of evaluations from source terms to the potential= effects on man and the environment, and then to their monetary evaluation, using a single framework devised for all the fuel cycles considered in the ExternE project. The resulting external cost is in the range of 2 to 3 mEuro/kWh when no discount rate is applied, and around 0.1 mEuro/kWh when a discount rate of 3% is considered. Further developments have been made on the external cost of a nuclear accident and on the integration of risk aversion in its evaluation. It appeared that the external cost of a nuclear accident would be about 0.04 mEuro/kWh, instead of 0.002 mEuro/kWh without taking risk aversion into account. (authors)

  13. Cellular and Molecular Pathways Leading to External Root Resorption

    Science.gov (United States)

    Iglesias-Linares, A.; Hartsfield, J.K.

    2016-01-01

    External apical root resorption during orthodontic treatment implicates specific molecular pathways that orchestrate nonphysiologic cellular activation. To date, a substantial number of in vitro and in vivo molecular, genomic, and proteomic studies have supplied data that provide new insights into root resorption. Recent mechanisms and developments reviewed here include the role of the cellular component—specifically, the balance of CD68+, iNOS+ M1- and CD68+, CD163+ M2-like macrophages associated with root resorption and root surface repair processes linked to the expression of the M1-associated proinflammatory cytokine tumor necrosis factor, inducible nitric oxide synthase, the M1 activator interferon γ, the M2 activator interleukin 4, and M2-associated anti-inflammatory interleukin 10 and arginase I. Insights into the role of mesenchymal dental pulp cells in attenuating dentin resorption in homeostasis are also reviewed. Data on recently deciphered molecular pathways are reviewed at the level of (1) clastic cell adhesion in the external apical root resorption process and the specific role of α/β integrins, osteopontin, and related extracellular matrix proteins; (2) clastic cell fusion and activation by the RANKL/RANK/OPG and ATP-P2RX7-IL1 pathways; and (3) regulatory mechanisms of root resorption repair by cementum at the proteomic and transcriptomic levels. PMID:27811065

  14. Initial results of shoulder MRI in external rotation after primary shoulder dislocation and after immobilization in external rotation

    International Nuclear Information System (INIS)

    Pennekamp, W.; Nicolas, V.; Gekle, C.; Seybold, D.

    2006-01-01

    Purpose: A change in the strategy for treating primary anterior traumatic dislocation of the shoulder has occurred. To date, brief fixation of internal rotation via a Gilchrist bandage has been used. Depending on the patient's age, a redislocation is seen in up to 90% of cases. This is due to healing of the internally rotated labrum-ligament tear in an incorrect position. In the case of external rotation of the humerus, better repositioning of the labrum ligament complex is achieved. Using MRI of the shoulder in external rotation, the extent of the improved labrum-ligament adjustment can be documented, and the indication of immobilization of the shoulder in external rotation can be derived. The aim of this investigation is to describe the degree of position changing of the labrum-ligament tear in internal and external rotation. Materials and Methods: 10 patients (9 male, 1 female, mean age 30.4 years, range 15-43 years) with a primary anterior dislocation of the shoulder without hyper laxity of the contra lateral side and labrum-ligament lesion substantiated by MRI were investigated using a standard shoulder MRI protocol (PD-TSE axial fs, PD-TSE coronar fs, T2-TSE sagittal, T1-TSE coronar) by an axial PD-TSE sequence in internal and external rotation. The dislocation and separation of the anterior labrum-ligament complex were measured. The shoulders were immobilized in 10 external rotation for 3 weeks. After 6 weeks a shoulder MRI in internal rotation was performed. Results: In all patients there was a significantly better position of the labrum-ligament complex of the inferior rim in external rotation, because of the tension of the ventral capsule and the subscapular muscle. In the initial investigation, the separation of the labrum-ligament complex in internal rotation was 0.44±0.27 mm and the dislocation was 0.45±0.33 mm. In external rotation the separation was 0.01±0.19 mm and the dislocation was -0.08±0.28 mm. After 6 weeks of immobilization in 10 external

  15. Analysis of ancient Indian silver punch-marked coins by external PIXE

    International Nuclear Information System (INIS)

    Rautray, Tapash R.; Nayak, Suman S.; Tripathy, Bipin B.; Das, Saubhagyalaxmi; Das, Manas R.; Das, Satya R.; Chattopadhyay, Pranab K.

    2011-01-01

    Seven silver punch-marked coins were analysed using external particle induced X-ray emission technique. The main group of elements like Ag, Cu, Au, Pb and Fe were estimated along with a number of trace/minor elements such as K, Ca, Ti, V, Cr, Mn, Co, Ni and Rb in the analysed silver coins. Gold was found in all the coins and varied between 0.7% and 6.2% indicating the better economic condition of that civilisation. - Highlights: → The silver punch-marked coins, in the current study, were in use in India between 6th century BC to 6th century AD and have been analysed by in-air PIXE. → These sets of coins have immense archaeological importance because of their very rare availability. → These coins are distinguished from other coins because of the presence of gold as major element. → While the British period coins were fabricated using modern technologies, the punch-marked coins were shaped manually with developed metal technology. → The analysis of punch-marked coins using external PIXE beam has been done for the first time, which is unique of its kind.

  16. 49 CFR 192.461 - External corrosion control: Protective coating.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false External corrosion control: Protective coating... for Corrosion Control § 192.461 External corrosion control: Protective coating. (a) Each external protective coating, whether conductive or insulating, applied for the purpose of external corrosion control...

  17. Internal and external resorption in a lower molar with an associated endodontic-periodontic lesion: a case report.

    Science.gov (United States)

    Komabayashi, Takashi; Zhu, Qiang

    2012-08-01

    This article describes a unique case in which both internal and external inflammatory resorption and endodontic-periodontic lesions were present at the same time in the patient's left mandibular first molar. Based on clinical and radiographic findings, it was determined that the nature of this case was a pulpal infection-induced inflammatory resorption and furcation lesion. After root canal therapy, the furcation lesion and external inflammatory resorption were completely resolved. This case indicates that the correct diagnosis of the stimulating factor for tooth resorption and determination of the primary origin of endodontic-periodontic lesions are critical for clinical management and success. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

  18. Ultrasound comparison of external and internal neck anatomy with the LMA Unique

    Directory of Open Access Journals (Sweden)

    Steven M. Lee

    2017-12-01

    Full Text Available Introduction: Internal neck anatomy landmarks and their relation after placement of an extraglottic airway devices have not been studied extensively by the use of ultrasound. Based on our group experience with external landmarks as well as internal landmarks evaluation with other techniques, we aimed use ultrasound to analyze the internal neck anatomy landmarks and the related changes due to the placement of the Laryngeal Mask Airway Unique. Methods: Observational pilot investigation. Non-obese adult patients with no evidence of airway anomalies, were recruited. External neck landmarks were measured based on a validated and standardized method by tape. Eight internal anatomical landmarks, reciprocal by the investigational hypothesis to the external landmarks, were also measured by ultrasound guidance. The internal landmarks were re-measured after optimal placement and inflation of the extraglottic airway devices cuff Laryngeal Mask Airway Unique. Results: Six subjects were recruited. Ultrasound measurements of hyoid-mental distance, thyroid-cricoid distance, thyroid height, and thyroid width were found to be significantly (p < 0.05 overestimated using a tape measure. Sagittal neck landmark distances such as thyroid height, sternal-mental distance, and thyroid-cricoid distance significantly decreased after placement of the Laryngeal Mask Airway Unique. Conclusion: The laryngeal mask airway Unique resulted in significant changes in internal neck anatomy. The induced changes and respective specific internal neck anatomy landmarks could help to design devices that would modify their shape accordingly to areas of greatest displacement. Also, while external neck landmark measurements overestimate their respective internal neck landmarks, as we previously reported, the concordance of each measurement and their respective conversion factor could continue to be of help in sizing extraglottic airway devices. Due to the pilot nature of the study, more

  19. Computing betweenness centrality in external memory

    DEFF Research Database (Denmark)

    Arge, Lars; Goodrich, Michael T.; Walderveen, Freek van

    2013-01-01

    Betweenness centrality is one of the most well-known measures of the importance of nodes in a social-network graph. In this paper we describe the first known external-memory and cache-oblivious algorithms for computing betweenness centrality. We present four different external-memory algorithms...

  20. External Beam Radiation Therapy for Cancer

    Science.gov (United States)

    External beam radiation therapy is used to treat many types of cancer. it is a local treatment, where a machine aims radiation at your cancer. Learn more about different types of external beam radiation therapy, and what to expect if you're receiving treatment.

  1. Urban Sprawl and Transportation Externalities

    OpenAIRE

    Holcombe, Randall G.; Williams, DeEdgra W.

    2010-01-01

    One argument in support of minimizing urban sprawl is that sprawl creates transportation externalities. A problem with empirically examining the relationship between sprawl and transportation externalities is that sprawl is a difficult concept to quantify. This paper uses a measure of sprawl designed by Ewing, Pendall, and Chen (2002) to examine the relationship between sprawl and commute times, automobile ownership, miles driven, fatal auto accidents, air pollution, and highway expenditures....

  2. Effect of external volume expansion on the survival of fat grafts

    Directory of Open Access Journals (Sweden)

    Raghuveer Reddy

    2016-01-01

    Full Text Available Introduction: External volume expansion (EVE is one method, which has been utilised for increasing the survival of adipose tissue grafts. EVE releases positive pressure from the graft and also induces intense levels of edema that decreases diffusion of metabolites essential for graft survival initially. The ideal timing of external volume expansion in relation to the injection of the fat to facilitate survival is not yet clear. Aims and Objectives: This study was undertaken to evaluate and compare the efficacy of external volume expansion applied at variable time points in relation to the injection of the fat. Materials and Methods: Athymic mouse was the animal model and human lipo-aspirate mixed with PRP was used as graft. An indigenous dome shaped silicone device was fabricated to deliver a negative pressure of -30 mm of Hg. The EVE was applied at variable time intervals. At the end of 4 weeks visual, histological and radiological features of the injected fat were compared. The adipose tissue was stained with human vimentin to ascertain the origin of the retained fat. Results: All the grafts, which had EVE, had significantly better volume retention and vascularity. The groups which underwent a delayed EVE or prior expansion followed by concomitant graft injection and expansion showed the most optimal vascularity and graft retention. Conclusions: A delayed EVE or prior expansion followed by concomitant graft injection and expansion may be the most ideal combinations to optimize graft take. However, on account of the relatively small sample size, there was a limitation in drawing statistically significant conclusions for certain variables.

  3. Nerve growth factor-inducible large external (NILE) glycoprotein: studies of a central and peripheral neuronal marker.

    Science.gov (United States)

    Salton, S R; Richter-Landsberg, C; Greene, L A; Shelanski, M L

    1983-03-01

    The PC12 clone of pheochromocytoma cells undergoes neuronal differentiation in the presence of nerve growth factor (NGF). Concomitant with this is a significant induction in the incorporation of radiolabeled fucose or glucosamine into a 230,000-dalton cell surface glycoprotein named the NGF-Inducible Large External, or NILE, glycoprotein (GP) (McGuire, J. C., L. A. Greene, and A. V. Furano (1978) Cell 15: 357-365). In the current studies NILE GP was purified from PC12 cells using wheat germ agglutinin-agarose affinity chromatography and SDS-polyacrylamide gel electrophoresis (PAGE). Polyclonal antisera were raised against purified NILE GP and were found to selectively immunoprecipitate a single 230,000-dalton protein from detergent extracts of PC12 cells metabolically labeled with either [3H]fucose, [3H]glucosamine, or [35S]methionine. These antisera stained the surfaces of PC12 cells by indirect immunofluorescence and were cytotoxic to PC12 cells in the presence of complement. Limited treatment of PC12 cells with either trypsin or pronase produced a fucosylated 90,000-dalton immunoreactive fragment of NILE GP which remained in the membrane. Using quantitative immunoelectrophoresis, the action of NGF on NILE GP was represent an increase in the amount of protein, rather than a selective increase in carbohydrate incorporation. Immunofluorescent staining of primary cell cultures and tissue whole mounts revealed that immunologically cross-reactive NILE GP appears to be expressed on the cell surfaces (somas and neurites) of most if not all peripheral and central neurons examined. Immunoprecipitation of radiolabeled cultures showed that the cross-reactive material had an apparent molecular weight by SDS-PAGE of 225,000 to 230,000 in the peripheral nervous system and 200,000 to 210,000 in the central nervous system. NILE-cross-reactive material was also found to a small extent on Schwann cell surfaces, but not at all on a variety of other cell types. These results suggest

  4. External GSM phone calls now made simpler

    CERN Multimedia

    2007-01-01

    On 2 July, the IT/CS Telecom Service introduced a new service making external calls from CERN GSM phones easier. A specific prefix is no longer needed for calls outside CERN. External calls from CERN GSM phones are to be simplified. It is no longer necessary to use a special prefix to call an external number from the CERN GSM network.The Telecom Section of the IT/CS Group is introducing a new system that will make life easier for GSM users. It is no longer necessary to use a special prefix (333) to call an external number from the CERN GSM network. Simply dial the number directly like any other Swiss GSM customer. CERN currently has its own private GSM network with the Swiss mobile operator, Sunrise, covering the whole of Switzerland. This network was initially intended exclusively for calls between CERN numbers (replacing the old beeper system). A special system was later introduced for external calls, allowing them to pass thr...

  5. Energy security externalities and fuel cycle comparisons

    International Nuclear Information System (INIS)

    Bohi, D.; Toman, M.

    1994-01-01

    Externalities related to 'energy security' may be one way in which the full social costs of energy use diverge from the market prices of energy commodities. Such divergences need to be included in reckoning the full costs of different fuel cycles. In this paper we critically examine potential externalities